The role of Mycobacterium tuberculosis complex species on apoptosis and necroptosis state of macrophages derived from active pulmonary tuberculosis patients

The role of Mycobacterium tuberculosis complex species on apoptosis and necroptosis state of macrophages derived from active pulmonary tuberculosis patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research note The role of Mycobacterium tuberculosis complex species on apoptosis and necroptosis state of macrophages derived from active pulmonary tuberculosis patients Budi Yanti, Mulyadi Mulyadi, Muhammad Amin, Harapan Harapan, Ni Made Mertaniasih, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.24644/v4 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Sep, 2020 Read the published version in BMC Research Notes → Version 4 posted 7 You are reading this latest preprint version Show more versions Abstract Objective: The role of Mycobacterium tuberculosis complex (MTBC) species in tuberculosis (TB) infection in human is still questioned. The aim of this study was to determine whether M. tuberculosis and M. bovis is associated with apoptosis and necroptosis by measuring the expression of specific signaling pathways components (Fas-associated protein with death domain (FADD) and receptor interacting protein 3 (RIP3)), and the level of apoptosis. Results: We recruited 30 patients with pulmonary TB; 24 patients were infected with M. tuberculosis Beijing strain and six patients with M. bovis BCG strain. M. tuberculosis-infected patients were more likely to have severe lung damage compared to those infected with M. bovis (odds ratio [OR]: 7.60; 95% confidence interval [CI]: 1.07-54.09). M. tuberculosis infection was associated with lower expression of FADD and lower apoptosis level of macrophages compared to M. bovis. No significant different of RIP3 between MTBC species groups. In conclusion, M. tuberculosis Beijing strain was associated with severe pulmonary damage, inhibited FADD expression and reduced apoptosis level of macrophages derived from pulmonary TB patients. This suggests that the M. tuberculosis Beijing strain is potentially to be used as determinant of disease progressivity and tissue damage in TB cases. General Microbiology Pulmonology Mycobacterium tuberculosis Mycobacterium bovis apoptosis necroptosis FADD RIP3 Figures Figure 1 Introduction Mycobacterium tuberculosis complex (MTBC) continues to significantly impact public health and is associated with one million deaths of tuberculosis (TB) cases annually worldwide [1]. Ability of M. tuberculosis to establish disease is entirely depend on macrophage deaths during infection. Pulmonary macrophages are critical component of the primary innate immune response that have various functions in immune surveillances, removal of cellular debris, microbial clearance, and in resolution of inflammation [2]. There are two pathways of macrophage deaths, apoptosis and necroptosis, that are developed as host antimicrobial defenses in the early TB infection; both of them are programmed cell death [3]. These mechanisms are triggered by tumor necrosis factor alpha (TNFα), oxidative stress, lipopolysaccharide (LPS), and other factors [4]. Apoptosis is characterized by signaling cell through Fas-associated protein with death domain (FADD), a crucial protein that is associated with death receptors (DRs) [5]. Necroptosis can be induced if apoptotic signaling is inhibited through formation of receptor interacting protein 3 (RIP3) [6,7]. MTBC comprises of many members including M. tuberculosis , M. africanum, M. canettii, M. bovis, M. microti, M. orygis, M. caprae, M. pinnipedii, M. suricattae and M. mungi) [8]. These members have different cellular components, the ability of human-to-human transmission, and severity of disease [9]. M. bovis lacks of trehalose-containing glycolipids on its cell walls that could affect the virulence and adaptability within the host cells. The genetic analysis showed that the loss of trehalose-containing glycolipids was related to disturbance surface-exposed acyltrehaloses such sulfatides (SLs), diacyltrehaloses (DATs), triacyltrehaloses (TATs) and pentacyltrehaloses (PATs) and the phoPR component signaling system[10][11] . In M. tuberculosis , this PhoPR system plays a role in the regulation of cell wall complex lipid biosynthesis and the secretion of EsxA / ESAT-6 for modulating the immune response [12]. Reduced this signaling system in M. bovis has been linked to less virulence in humans [11]. Another study showed that MTBC species with dominant PhoP gene expression are hypervirulent and resistant to tuberculosis drugs [13].The role of MTBC species have been proven in various animal models [14], but still be questioned in human [9]. Although some species have 99.9% similarity of nucleotide sequences, they have different abilities to induce macrophages death [15]. Apoptosis and necroptosis play the important roles in innate immune responses against pathogens [16] and are crucial in TB infection [17,18]. In vitro studies showed that the apoptosis of BCG-infected monocytes by the exogenous drug was associated with a reduction of bacillary viability while necrosis was not associated with reduction of BCG viability [19,20]. Another study found that if apoptosis was predominated during a TB infection the bacteria were potentially to be cleared [21]. M tuberculosis Beijing strain with high virulent inhibits apoptosis, and triggers necroptosis because it evades the immune system, induces the necrosis, lyses of the cellular components, and induces the parenchymal destruction and therefore is associated with severe TB [22]. The aim of this study was to assess the role of M. tuberculosis and M. bovis on the state of apoptotic and necroptosis of macrophages isolated from TB patients. Method Study setting and patients Between June and October 2017, a cross-sectional study was conducted. Confirmed new pulmonary TB cases were recruited from Tuberculosis Clinic at Soewandhie Hospital, Surabaya, Indonesia. Bacteriological confirmation was conducted by sputum acid fast staining and GeneXpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA). For the study purpose, the patients underwent fiber optic bronchoscopy to collect bronchoalveolar lavage fluid (BALF) and the macrophages were collected from the BALF. Patients with HIV co-infection, diabetes mellitus, renal abnormality, heart diseases, immune response disorders such as lupus erythematosus and rheumatoid arthritis, non-TB pulmonary diseases, and those who previously received anti-TB treatment were excluded. All samples were tested to identify MTBC species using polymerase chain reaction (PCR) targeting two specific genes: RD9 and TbD1. Assessment of pulmonary damage The degree of pulmonary damage was classified using the NICE Scoring System based on the total lesions in six lung areas [23]. This system assessed four components: the nodule (N), the infiltration or consolidation (I), the cavity (C), and the ectasis (E) based on chest radiograph of three areas of each lung (i.e. six areas of both lungs). For each area, the possible scores were 1 to 4 indicating the lung damage area of 0–25%, >25%–≤50%, >50%–≤75% and >75%, respectively. The pulmonary damage was then categorized as mild if the total score was 8 or less and severe if the total score was more than 8. Samples collection and macrophages isolation BAL was performed using 10 ml of saline solution as described previously [24]. The BALF was centrifuged at 2500rpm for 15 mins, the supernatant was discarded, and cells were resuspended to a cell count of 4x10 5 cells/ml with RPMI 1640 medium. The total cell count was measured using hemocytometer. FADD and RIP3 expression by immunocytochemical staining Pellet cells derived from the centrifugation were applied to glass slides and then washed with PBS three times for 10 mins. Permeabilization was performed with a CA-630-0.5% Igepal solution (Sigma Aldrich, Saint Louis, MO, USA). H 2 O 2 0.3% was then added and incubated for 10 mins before was washed with PBS. The slides were incubated with anti-human monoclonal antibody FADD or RIP3 followed manufacturer’s protocol (Santa Cruz, Oregon, OR, USA). The quantification of the protein expression was conducted according to the previous study [25]. Apoptosis assay The level of apoptosis in infected macrophages was determined by using the Tunel Assay apoptosis kit per manufacturer’s protocol (R&D Systems, Minneapolis, MN, USA). Tunel assay was performed with terminal deoxynucleotidyl transferase enzymes to determine the fragmentation of DNA. The level of apoptosis was measured based on the previous study [26]. MTBC Species identification and sequence confirmation The detection of MTBC species was conducted from the BALF. Briefly, DNA was extracted using DNeasy® Blood & Tissue kit (Ambion Inc., Austin, TX, USA). Amplification of gene-specific M. tuberculosis was conducted using RD9 primers (F: 5’-GTGTAGGTCAGCCCCATCC-3’, I: 5-CAATGTTTGTTGCGCTGC-3’, R: 5’-GCTACCCTCGACCAAGTGTT-3’), while M. bovis was identified using TbD1 primers (F: 5’-AGTGACTGGCCTGGTCAAAC-3’, R: 5’-GAGCTCTGTGCGACGTTATG-3’) [27,28]. The conditions for PCR assays were set up for 30s at 94˚C (denaturation), followed by 35 cycles of denaturation (94˚C, 30s), annealing (56˚C, 1s), and extension (72˚C, 10 min). The confirmation of the strain was conducted by sequencing nine and two of M. tuberculosis and M. bovis samples, respectively and the homology analysis was conducted using Basic Local Alignment Search Tool (BLAST). Statistical analysis Associations between MTBC species and the degree of lung damage including for each subset of NICE component were assessed using chi-squared test. To compare the level of apoptosis, FADD, and RIP3 of macrophages between M. tuberculosis and M. bovis groups, the Man-Whitney test was employed. For all analyses, significance was assessed at α=0.05. Results Characteristics of patients Forty new active pulmonary TB patients were successfully diagnosed and met the inclusion criteria and 30 patients were willing to participate and underwent the BAL procedure. Among 30 patients, majority of them (81.37%) were female and more than half (16/30, 53.3%) aged between 21-40 years old (Table 1). Majority of the patients (75%) were working as laborer and five patients (16.6%) were working as cow slaughters. Based on clinical symptoms, 90%, 86%, 56% and of the patients had anorexia, experienced weight loss, and had persistent fever, respectively. Only 36.6% of patients had low hemoglobin level and 30.0% had low oxygen saturation. Table 1 Detection of MTBC species Based on RD9 gene amplification, 24 (80.0%) M. tuberculosis were identified and nine of them were sequenced for the confirmation. The isolates had 99-100% sequence similarity with the M. tuberculosis Beijing strain 2014 PNGD (Accession no CP022704.2). Six (20.0%) M. bovis were identified and two isolates were sequenced. All of them had 100% sequence similarity with M. bovis BCG strain (Accession no CP033311.1) . Association between MTBC species and lung damage MTBC species had no association with three NICE components (i.e. the presence of nodule, the infiltrate or consolidation, and the cavity of the lungs) (Table 2). Ectasis, however, was more frequent in M. tuberculosis (OR: 10.0; 95%CI: 1.34-74.51). M. tuberculosis was identified in 19 (90.50%) patients with severe lung damage. There was a significant association between M. tuberculosis and severe lung tissue damage, OR: 7.60; 95%CI: 1.07-54.09, p=0.028 (Table 2). Table 2 Association between MTBC species and FADD, RIP3, and apoptosis Our data indicated that the level of FADD was lower in M tuberculosis group compared to M. bovis , 0.208±1.020 vs . 0.667±1.032 cells with p =0.046 (see Fig. 1A&B). The level of RIP3 expression was not different between M tuberculosis group and M. bovis (0.333±0.702 vs 0.500±0.836, p=0.551) . Data from Tunel assay indicated that the level of apoptosis in macrophages derived from M tuberculosis group was significantly lower compared to M. bovis group, 0.875±1.676 vs. 2.500±3.331, p =0.049 (Fig. 1C&D). Discussion The outcome and the disease progression of MTBC species infection are varied; exposure to this mycobacterium can be rapidly cleared by innate immunity or direct progression to active TB. Active TB also has a range of presentations and each form is associated with diverse host responses to the pathogen. Studies have provided evidence that different MTBC species is associated with different virulent [29-31] and would affect host-pathogen interactions [32]. Phenotypic comparisons between M. tuberculosis and M. bovis have been limited to animal studies, which suggested that M. bovis is likely less virulent [9,33,34]. In the present study, 80.0% of TB cases caused by M. tuberculosis and inhibited the cell signaling to apoptosis execution. The previous studies have reported that high virulent M. tuberculosis inhibited apoptosis in TB-cases [35,36]. Virulent M. tuberculosis H37Rv and Erdman for example inhibited apoptosis stronger compared to non-virulent M. bovis BCG strain, H37Ra, and M. kansaii on human alveolar macrophages of healthy nonsmoking volunteers [36]. Other studies found that M. tuberculosis inhibited and suppressed apoptosis of host macrophages on THP-1 [37,38] and J774 cell lines [39]. Data from the present study identified that infection of macrophages with M. tuberculosis was associated with a lower level of FADD compared to M. bovis infection. FADD is an adapter protein to bind caspase 8 and caspase 10 precursors and is simultaneously activated and mediated cell signals with caspases 3, 6, and 7 to induce apoptosis [40]. This suggests that M. tuberculosis is able to inhibit signaling of caspases to execute the apoptosis. A study showed that low FADD expression triggered the necrosis [41] and the necroptosis [42]. Altogether, these explain, in part, the finding of present study that M. tuberculosis infection was significantly associated with severe lung damage. In conclusion, our preeliminary data suggest that M. tuberculosis is associated with more severe lung damage compared to M. bovis infection. M. tuberculosis also inhibits FADD expression and reduces the apoptosis level. Study limitation This was a cross-sectional study at a single health center and included small number of pulmonary TB patients determined to be infected predominantly with M. tuberculosis Beijing strains. Therefore, our study was underpowered, which lessened its internal validity. In this study, the FADD expression was used which may not be the best marker for propensity towards apoptosis or necrosis. Therefore, validation using other standard approaches such as caspase-activity and RIP3 phosphorylation is warrant. Finally, we did not assess the necrosis state of the cells and further study to analysis the role of MTBC species on necrosis is therefore also important. Abbreviations BALF: bronchoalveolar lavage fluid; CI: confidence interval; DRs: death receptors; FADD: Fas-associated protein with death domain; LPS: lipopolysaccharide; MTBC: Mycobacterium tuberculosis complex; OR: odds ratio; PCR: polymerase chain reaction; RIP3: receptor interacting protein 3; TB: tuberculosis; TNFα: tumor necrosis factor alpha. Declarations Author contributions Conceptualization and methodology: BY; Software: MA; Validation: BY, MM; Formal analysis: NMM; Data curation: BY, MA; Writing – original draft preparation: BY, HH; Writing – review & editing: BY, BY, MM, MA, HH, NMM, SS; Supervision: MA, NMM, SS. Acknowledgements The authors would like to thank the support of Dato Prof. Dr. Tahir for his valuable support and encouragement in this study. Competing interests The authors declare that they have no competing interests. Availability of data and materials The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Consent for publication Not applicable. Ethics approval and consent to participate All patients signed an informed consent form prior to study. This study protocol was approved by the Ethics Committee of Dr. Soetomo Hospital Research Committee (388/PANKE/KKE/V/2017). Funding None. References WHO. Global tuberculosis report. Geneva 2019; Oct 19, 2019. https://www.who.int/tb/publications/global_report/en/ (accessed Dec 26, 2019). Byrne A, Mathie S, Gregory L, Lloyd, C. Pulmonary macrophages: key players in the innate defence of the airways. Thorax. 2015; 70: 1189–1196. Ramakrishnan L. Revisiting the role of the granuloma in tuberculosis. Nat Rev Immunol. 2002;12(5): 352-66. Divangahi M, Behar SM, Remld H. 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Tables Table 1 Demographic and clinical characteristics between M. tuberculosis Beijing strain and M. bovis BCG strain Variable MTBC species p-value M. tuberculosis Beijing strain, n (%) M. bovis BCG strain n (%) Gender Female 13 (81.37) 3 (18.8) 0.855 Male 11 (78.6) 3 (21.4) Age (year) 50 4 (100.0) 0(0) Educational attainment Elementary school 8 (89.5) 1 (11.1) 0.466 Junior high school 10 (83.3) 2 (6.7) Senior high school 6 (66.7) 3 (33.3) Occupation Labourer 16 (76.2) 5 (32.8) 0.364 Housewife 6 (100.0) 0 (0) Unemployed 2 (66.7) 1 (33.3) Anorexia Yes 21 (77.7) 6 (22.2) 0.189 No 3 (100.0) 0 (0) Weight loss Yes 21 (80.8) 5 (19.2) 0.364 No 3 (75.0) 1 (25.0) Fever Yes 13 (76.5) 4 (23.5) 0.167 No 11 (84.6) 2 (15.4) Haemoglobin level Normal 8 (72.8) 3 (27.3) 0.750 Low 16 (84.2) 3 (15.8) SaO 2 level Normal 17 (80.9) 4 (19.0) 0.831 Low 7 (77.8) 2 (22.2) Table 2. Severity of pulmonary damage between M. tuberculosis Beijing strain and M. bovis BCG strain Variables n MTBC species OR 95%CI p-value M. tuberculosis Beijing strain, n (%) M. bovis BCG strain, n (%) NICE Score Nodule 4.85 0.72-32.87 0.088 Yes 19 17 (89.5) 2 (10.5) No 11 7 (63.7) 4 (36.4) Infiltrate/consolidation NA NA NA Yes 30 24 (80.0) 6 (20.0) No 0 0 (0.0) 0 (0.0) Cavitas NA NA 0.283 Yes 4 4 (100.0) 0 (0.0) No 26 20 (76.9) 6 (23.1) Ectasis 10.00 1.34-74.51 0.013 Yes 22 20 (90.0) 2 (9.15) No 8 4 (50.0) 4 (50.0) Severity of lung damage 7.60 1.07-54.09 0.028 Mild 9 5 (9.5) 4 (55.6) Severe 21 19 (90.5) 2 (44.4) Cite Share Download PDF Status: Published Journal Publication published 04 Sep, 2020 Read the published version in BMC Research Notes → Version 4 posted Editorial decision: Accept 25 Aug, 2020 Editor assigned by journal 24 Aug, 2020 Reviewers invited by journal 24 Aug, 2020 Reviewer # 1 agreed at journal 24 Aug, 2020 Review # 1 received at journal 24 Aug, 2020 Submission checks completed at journal 23 Aug, 2020 Editor invited by journal 23 Aug, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-15202","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research note","associatedPublications":[],"authors":[{"id":1733296,"identity":"9cd7a00d-0c64-4c74-860d-4c1524b29ab4","order_by":0,"name":"Budi Yanti","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0003-2932-0764","institution":"university","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Budi","middleName":"","lastName":"Yanti","suffix":""},{"id":1733297,"identity":"50f11abf-38ac-495b-8a02-dbf12864ffd7","order_by":1,"name":"Mulyadi Mulyadi","email":"","orcid":"","institution":"Universitas Nahdlatul Ulama Surabaya Fakultas Kedokteran","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mulyadi","middleName":"","lastName":"Mulyadi","suffix":""},{"id":1733298,"identity":"5b622222-f09f-4744-a445-1edcf5bc055a","order_by":2,"name":"Muhammad Amin","email":"","orcid":"","institution":"Universitas Airlangga Fakultas Kedokteran","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"","lastName":"Amin","suffix":""},{"id":1733299,"identity":"ad0ea65e-95d9-4212-93a7-88252a4b5c51","order_by":3,"name":"Harapan Harapan","email":"","orcid":"","institution":"Universitas Syiah Kuala Fakultas Kedokteran","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Harapan","middleName":"","lastName":"Harapan","suffix":""},{"id":1733300,"identity":"ef664262-47fe-48bc-96aa-b6b43f886d0f","order_by":4,"name":"Ni Made Mertaniasih","email":"","orcid":"","institution":"Universitas Airlangga Fakultas Kedokteran","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ni","middleName":"Made","lastName":"Mertaniasih","suffix":""},{"id":1733301,"identity":"4b3d7c9f-ed85-4645-8e65-bec7881fcc9d","order_by":5,"name":"Soetjipto Soetjipto","email":"","orcid":"","institution":"Universitas Airlangga Fakultas Kedokteran","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Soetjipto","middleName":"","lastName":"Soetjipto","suffix":""}],"badges":[],"createdAt":"2020-02-25 13:04:55","currentVersionCode":4,"declarations":"","doi":"10.21203/rs.2.24644/v4","doiUrl":"https://doi.org/10.21203/rs.2.24644/v4","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13104-020-05256-2","type":"published","date":"2020-09-04T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":2115439,"identity":"6bf17c77-4c5c-426f-a7ba-f7ccf48fb75f","added_by":"auto","created_at":"2020-08-27 20:41:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3780035,"visible":true,"origin":"","legend":"FADD expression (A\u0026B) and apoptosis (C\u0026D) of macrophages derived from active pulmonary tuberculosis patients infected with M. bovis BCG strain (A\u0026C) and M. tuberculosis Beijing strain (B\u0026D). ","description":"","filename":"R1Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-15202/v4/R1Figure1.png"},{"id":15668690,"identity":"a5e5862e-e5a9-4a00-8f4b-cca42b6420d9","added_by":"auto","created_at":"2021-11-18 13:49:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2736983,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-15202/v4/3cae7ea1-21c9-43cf-8765-be2eb93c13f8.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eThe role of \u003cem\u003eMycobacterium tuberculosis complex\u003c/em\u003e species on apoptosis and necroptosis state of macrophages derived from active pulmonary tuberculosis patients\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003e\u003cem\u003eMycobacterium tuberculosis \u003c/em\u003ecomplex (MTBC) \u0026nbsp;continues to significantly impact public health and is associated with one million deaths of tuberculosis (TB) cases annually worldwide [1]. Ability of \u003cem\u003eM. tuberculosis \u003c/em\u003eto establish disease is entirely depend on macrophage deaths during infection. Pulmonary macrophages are critical component of the primary innate immune response that have various functions in immune surveillances, removal of cellular debris, microbial clearance, and in resolution of inflammation [2]. There are two pathways of macrophage deaths, apoptosis and necroptosis, that are developed as host antimicrobial defenses in the early TB infection; both of them are programmed cell death [3]. These mechanisms are triggered by tumor necrosis factor alpha (TNF\u0026alpha;), oxidative stress, lipopolysaccharide (LPS), and other factors [4]. Apoptosis is characterized by signaling cell through Fas-associated protein with death domain (FADD), a crucial protein that is associated with death receptors (DRs) [5]. Necroptosis can be induced if apoptotic signaling is inhibited through formation of receptor interacting protein 3 (RIP3) [6,7].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMTBC comprises of many members including \u003cem\u003eM. tuberculosis\u003c/em\u003e, \u003cem\u003eM. africanum, M. canettii, M. bovis, M. microti, M. orygis, M. caprae, M. pinnipedii, M. suricattae \u003c/em\u003eand \u003cem\u003eM. mungi) \u003c/em\u003e[8]. These members \u0026nbsp;have different cellular components, the ability of human-to-human transmission, and severity of disease [9]. \u003cem\u003eM. bovis\u003c/em\u003e lacks of trehalose-containing glycolipids on its cell walls that could affect the virulence and adaptability within the host cells. The genetic analysis showed that the loss of trehalose-containing glycolipids was related to disturbance surface-exposed acyltrehaloses such sulfatides (SLs), diacyltrehaloses (DATs), triacyltrehaloses (TATs) and pentacyltrehaloses (PATs) and the phoPR component signaling system[10][11] . \u003cem\u003eIn M. tuberculosis\u003c/em\u003e, this PhoPR system plays a role in the regulation of cell wall complex lipid biosynthesis and the secretion of EsxA / ESAT-6 for modulating the immune response [12]. Reduced this signaling system in \u003cem\u003eM. bovis\u003c/em\u003e has been linked to less virulence in humans [11]. Another study showed that MTBC species with dominant PhoP gene expression are hypervirulent and resistant to tuberculosis drugs [13].The role of MTBC species have been proven in various animal models [14], but still be questioned in human [9]. Although some species \u0026nbsp;have 99.9% similarity of nucleotide sequences, they have different abilities to induce macrophages death [15]. Apoptosis and necroptosis play the important roles in innate immune responses against pathogens [16] \u0026nbsp;and are crucial in TB infection [17,18]. \u003cem\u003eIn vitro \u003c/em\u003estudies showed that the apoptosis of BCG-infected monocytes by the exogenous drug was associated with a reduction of bacillary viability while necrosis was not associated with reduction of BCG viability [19,20]. Another study found that if apoptosis was predominated during a TB infection the bacteria were potentially to be cleared [21]. \u003cem\u003eM tuberculosis\u003c/em\u003e Beijing strain with high virulent inhibits apoptosis, and triggers necroptosis because it evades the immune system, induces the necrosis, lyses of the cellular components, and induces the parenchymal destruction and therefore is associated with severe TB [22]. The aim of this study was to assess the role of \u003cem\u003eM. tuberculosis \u003c/em\u003eand\u003cem\u003e M. bovis\u003c/em\u003e on the state of apoptotic and necroptosis of macrophages isolated from TB patients.\u003c/p\u003e"},{"header":"Method","content":"\u003ch3\u003e\u003cem\u003eStudy setting and patients \u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eBetween June and October 2017, a cross-sectional study was conducted. Confirmed new pulmonary TB cases were recruited from Tuberculosis Clinic at Soewandhie Hospital, Surabaya, Indonesia. Bacteriological confirmation was conducted by sputum acid fast staining and GeneXpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA). For the study purpose, the patients underwent fiber optic bronchoscopy to collect bronchoalveolar lavage fluid (BALF) and the macrophages were collected from the BALF. Patients with HIV co-infection, diabetes mellitus, renal abnormality, heart diseases, immune response disorders such as lupus erythematosus and rheumatoid arthritis, non-TB pulmonary diseases, and those who previously received anti-TB treatment were excluded. All samples were tested to identify MTBC species using polymerase chain \u0026nbsp;reaction (PCR) targeting two specific genes: RD9 and TbD1.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eAssessment of pulmonary damage\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eThe degree of pulmonary damage was classified using the NICE Scoring System based on the total lesions in six lung areas [23]. This system assessed four components: the nodule (N), the infiltration or consolidation (I), the cavity (C), and the ectasis (E) based on chest radiograph of three areas of each lung (i.e. six areas of both lungs). For each area, the possible scores were 1 to 4 indicating the lung damage area of 0\u0026ndash;25%, \u0026gt;25%\u0026ndash;\u0026le;50%, \u0026gt;50%\u0026ndash;\u0026le;75% and \u0026gt;75%, respectively. The pulmonary damage was then categorized as mild if the total score was 8 or less and severe if the total score was more than 8.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eSamples collection and macrophages isolation \u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eBAL was performed using 10 ml of saline solution as described previously [24]. The BALF was centrifuged at 2500rpm for 15 mins, the supernatant was discarded, and cells were resuspended to a cell count of 4x10\u003csup\u003e5\u003c/sup\u003e cells/ml with RPMI 1640 medium. The total cell count was measured using hemocytometer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eFADD and RIP3 expression by immunocytochemical staining\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003ePellet cells derived from the centrifugation were applied to glass slides and then washed with PBS three times for 10 mins. Permeabilization was performed with a CA-630-0.5% Igepal solution (Sigma Aldrich, Saint Louis, MO, USA). H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e 0.3% was then added and incubated for 10 mins before was washed with PBS. The slides were incubated with anti-human monoclonal antibody FADD or RIP3 followed manufacturer\u0026rsquo;s protocol (Santa Cruz, Oregon, OR, USA). The quantification of the protein expression was conducted according to the previous study [25].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eApoptosis assay\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eThe level of apoptosis in infected macrophages was determined by using the Tunel Assay apoptosis kit per manufacturer\u0026rsquo;s protocol (R\u0026amp;D Systems, Minneapolis, MN, USA). Tunel assay was performed with terminal deoxynucleotidyl transferase enzymes to determine the fragmentation of DNA. The level of apoptosis was measured based on the previous study [26]. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eMTBC \u003cem\u003eSpecies identification and sequence confirmation\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eThe detection of MTBC species \u0026nbsp;was conducted from the BALF. Briefly, DNA was extracted using DNeasy\u0026reg; Blood \u0026amp; Tissue kit (Ambion Inc., Austin, TX, USA). Amplification of gene-specific \u003cem\u003eM. tuberculosis\u003c/em\u003e was conducted using RD9 primers (F: 5\u0026rsquo;-GTGTAGGTCAGCCCCATCC-3\u0026rsquo;, I: 5-CAATGTTTGTTGCGCTGC-3\u0026rsquo;, R: 5\u0026rsquo;-GCTACCCTCGACCAAGTGTT-3\u0026rsquo;), while \u003cem\u003eM. bovis\u003c/em\u003e was identified using TbD1 primers (F: 5\u0026rsquo;-AGTGACTGGCCTGGTCAAAC-3\u0026rsquo;, R: 5\u0026rsquo;-GAGCTCTGTGCGACGTTATG-3\u0026rsquo;) [27,28]. The conditions for PCR assays were set up for 30s at 94˚C (denaturation), followed by 35 cycles of denaturation (94˚C, 30s), annealing (56˚C, 1s), and extension (72˚C, 10 min). The confirmation of the strain was conducted by sequencing nine and two of \u003cem\u003eM. tuberculosis\u003c/em\u003e and \u003cem\u003eM. bovis\u003c/em\u003e samples, respectively and the homology analysis was conducted using Basic Local Alignment Search Tool (BLAST).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eAssociations between MTBC species and the degree of lung damage including for each subset of NICE component were assessed using chi-squared test. To compare the level of apoptosis, FADD, and RIP3 of macrophages between \u003cem\u003eM. tuberculosis\u003c/em\u003e and \u003cem\u003eM. bovis\u003c/em\u003e groups, the Man-Whitney test was employed. For all analyses, significance was assessed at \u0026alpha;=0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003ch3\u003e\u003cem\u003eCharacteristics of patients \u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eForty new active pulmonary TB patients were successfully diagnosed and met the inclusion criteria and 30 patients were willing to participate and underwent the BAL procedure. Among 30 patients, majority of them (81.37%) were female and more than half (16/30, 53.3%) aged between 21-40 years old (Table 1).\u0026nbsp; Majority of the patients (75%) were working as laborer and five patients (16.6%) were working as cow slaughters. Based on clinical symptoms, 90%, 86%, 56% and of the patients had anorexia, experienced weight loss, and had persistent fever, respectively. Only 36.6% of patients had low hemoglobin level and 30.0% had low oxygen saturation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eDetection of MTBC species\u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eBased on RD9 gene amplification, 24 (80.0%) \u003cem\u003eM. tuberculosis\u003c/em\u003e were identified and nine of them were sequenced for the confirmation. The isolates had 99-100% sequence similarity with the \u003cem\u003eM. tuberculosis\u003c/em\u003e Beijing strain 2014 PNGD (Accession no CP022704.2). Six (20.0%) \u003cem\u003eM. bovis\u003c/em\u003e were identified and two isolates were sequenced. All of them had 100% sequence similarity with \u003cem\u003eM. bovis \u003c/em\u003eBCG strain (Accession no CP033311.1)\u003cem\u003e. \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eAssociation between MTBC species and lung damage \u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eMTBC species \u0026nbsp;had no association with three NICE components (i.e. the presence of nodule, the infiltrate or consolidation, and the cavity of the lungs) (Table 2). Ectasis, however, was more frequent in \u003cem\u003eM. tuberculosis\u003c/em\u003e (OR: 10.0; 95%CI: 1.34-74.51). \u003cem\u003eM. tuberculosis\u003c/em\u003e was identified in 19 (90.50%) patients with severe lung damage. There was a significant association between\u003cem\u003e M. tuberculosis\u003c/em\u003e and severe lung tissue damage, OR: 7.60; 95%CI: 1.07-54.09, p=0.028 (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cem\u003eAssociation between MTBC species \u0026nbsp;and\u003c/em\u003e\u003cem\u003e FADD, RIP3, and apoptosis\u0026nbsp; \u003c/em\u003e\u003c/h3\u003e\n\u003cp\u003eOur data indicated that the level of FADD was lower in \u003cem\u003eM tuberculosis \u003c/em\u003egroup compared to \u003cem\u003eM. bovis\u003c/em\u003e, 0.208\u0026plusmn;1.020 \u003cem\u003evs\u003c/em\u003e. 0.667\u0026plusmn;1.032 cells with \u003cem\u003ep\u003c/em\u003e=0.046 \u0026nbsp;(see Fig. 1A\u0026amp;B). The level of RIP3 expression was not different between \u003cem\u003eM tuberculosis \u003c/em\u003egroup and \u003cem\u003eM. bovis \u003c/em\u003e(0.333\u0026plusmn;0.702 \u003cem\u003evs\u003c/em\u003e 0.500\u0026plusmn;0.836, p=0.551)\u003cem\u003e. \u003c/em\u003eData from Tunel assay indicated that the level of apoptosis in macrophages derived from \u003cem\u003eM tuberculosis \u003c/em\u003egroup was significantly lower compared to \u003cem\u003eM. bovis \u003c/em\u003egroup, 0.875\u0026plusmn;1.676 \u003cem\u003evs. \u003c/em\u003e2.500\u0026plusmn;3.331, \u003cem\u003ep\u003c/em\u003e=0.049 (Fig. 1C\u0026amp;D).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe outcome and the disease progression of MTBC species \u0026nbsp;infection are varied; exposure to this mycobacterium \u0026nbsp;can be rapidly cleared by innate immunity or direct progression to active TB. Active TB also has a range of presentations and each form is associated with diverse host responses to the pathogen. Studies have provided evidence that different MTBC species is associated with different virulent [29-31] and would affect host-pathogen interactions [32]. Phenotypic comparisons between \u003cem\u003eM. tuberculosis \u003c/em\u003eand \u003cem\u003eM. bovis \u003c/em\u003ehave been limited to animal studies, which suggested that \u003cem\u003eM. bovis \u003c/em\u003eis likely less virulent [9,33,34]. In the present study, 80.0% of TB cases caused by \u003cem\u003eM. tuberculosis\u003c/em\u003e and inhibited the cell signaling to apoptosis execution. The previous studies have reported that high virulent \u003cem\u003eM. tuberculosis\u003c/em\u003e inhibited apoptosis in TB-cases [35,36]. Virulent \u003cem\u003eM. tuberculosis\u003c/em\u003e H37Rv and Erdman for example inhibited apoptosis stronger compared to non-virulent \u003cem\u003eM. bovis\u003c/em\u003e BCG strain, H37Ra, and \u003cem\u003eM. kansaii\u003c/em\u003e on human alveolar macrophages of healthy nonsmoking volunteers [36]. Other studies found that \u003cem\u003eM. tuberculosis\u003c/em\u003e inhibited and suppressed apoptosis of host macrophages on THP-1 [37,38] and J774 cell lines [39].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData from the present study identified that infection of macrophages with \u003cem\u003eM. tuberculosis\u003c/em\u003e was associated with a lower level of FADD compared to \u003cem\u003eM. bovis \u003c/em\u003einfection. FADD is an adapter protein to bind caspase 8 and caspase 10 precursors and is simultaneously activated and mediated cell signals with caspases 3, 6, and 7 to induce apoptosis [40]. This suggests that \u003cem\u003eM. tuberculosis\u003c/em\u003e is able to inhibit signaling of caspases to execute the apoptosis. A study showed that low FADD expression triggered the necrosis [41] and the necroptosis [42]. Altogether, these explain, in part, the finding of present study that \u003cem\u003eM. tuberculosis \u003c/em\u003einfection was significantly associated with severe lung damage.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, our preeliminary data suggest that \u003cem\u003eM. tuberculosis\u003c/em\u003e is associated with more severe lung damage compared to \u003cem\u003eM. bovis \u003c/em\u003einfection. \u003cem\u003eM. tuberculosis\u003c/em\u003e also inhibits FADD expression and reduces the apoptosis level.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003e\u003cem\u003eStudy limitation \u003c/em\u003e\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThis was a cross-sectional study at a single health center and included small number of pulmonary TB patients determined to be infected predominantly with M. tuberculosis Beijing strains. Therefore, our study was underpowered, which lessened its internal validity. In this study, the FADD expression was used which may not be the best marker for propensity towards apoptosis or necrosis. Therefore, validation using other standard approaches such as caspase-activity and RIP3 phosphorylation is warrant. Finally, we did not assess the necrosis state of the cells and further study to analysis the role of MTBC species on necrosis is therefore also important.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBALF: bronchoalveolar lavage fluid; CI: confidence interval; DRs: death receptors; FADD: Fas-associated protein with death domain; LPS: lipopolysaccharide; MTBC: \u003cem\u003eMycobacterium\u003c/em\u003e \u003cem\u003etuberculosis\u003c/em\u003e complex; OR: odds ratio; PCR: polymerase chain reaction; RIP3: receptor interacting protein 3; TB: tuberculosis; TNF\u0026alpha;: tumor necrosis factor alpha.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization and methodology: BY; Software: MA; Validation: BY, MM; Formal analysis: NMM; Data curation: BY, MA; Writing \u0026ndash; original draft preparation: BY, HH; Writing \u0026ndash; review \u0026amp; editing: BY, BY, MM, MA, HH, NMM, SS; Supervision: MA, NMM, SS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the support of Dato Prof. Dr. Tahir for his valuable support and encouragement in this study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients \u0026nbsp;signed an informed consent form prior to study. This study protocol was approved by the Ethics Committee of Dr. Soetomo Hospital Research Committee (388/PANKE/KKE/V/2017).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWHO. Global tuberculosis report. Geneva 2019; Oct 19, 2019. https://www.who.int/tb/publications/global_report/en/ (accessed Dec 26, 2019).\u003c/li\u003e\n\u003cli\u003eByrne A, Mathie S, Gregory L, Lloyd, C. Pulmonary macrophages: key players in the innate defence of the airways. Thorax. 2015; 70: 1189\u0026ndash;1196.\u003c/li\u003e\n\u003cli\u003eRamakrishnan L. Revisiting the role of the granuloma in tuberculosis. Nat Rev Immunol. 2002;12(5): 352-66.\u003c/li\u003e\n\u003cli\u003eDivangahi M, Behar SM, Remld H. Dying to Live: How the Death Modality of the Infected Macrophage Modulates Immunity to Tuberculosis. In M. Divangahi, ed. The New Paradigm of Immunity to Tuberculosis. 1st ed. New York: Springer; 2013:103-20.\u003c/li\u003e\n\u003cli\u003eDockrell D. The multiple role of FAS ligand in the pathogenesis of infectious disease. Clin Microbiol Infect.2003; 9: 766-779.\u003c/li\u003e\n\u003cli\u003eButler RE, Krishnan N, Garcia-Jimenez W, Francis R, Martyn A, Mendum T, Felemban S, Locker N, Salguero-Bodes J, Robertson B \u0026amp; Stewart GR. Susceptibility of M. tuberculosis-infected host cells to phospho-MLKL driven necroptosis is dependent on cell type and presence of TNFa. Virulence. 2017: 1-38.\u003c/li\u003e\n\u003cli\u003eBerghe TV, Vanlangenakler N, Parthoens E, Deckers W, Devos M, Festjens N, Guerin CJ, Brunk UT, Declarcq W, Vandenabeele P. Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features. Cell Death \u0026amp; Differentiation. 2010; 17(6): 922\u0026ndash;930.\u003c/li\u003e\n\u003cli\u003eCoscolla M, Gagneux S. Consequences of genomic diversity in Mycobacterium tuberculosis. Seminars in immunology. 2014; 26:431-44.\u003c/li\u003e\n\u003cli\u003eCoscolla M, Gagneux S. Does M. tuberculosis genomic diversity explain disease diversity? Drug Discov Today Dis Mech. 2010; 7(1):.e43-59.\u003c/li\u003e\n\u003cli\u003eNobre, A. \u003cem\u003eet al.\u003c/em\u003e (2014) \u0026lsquo;The molecular biology of mycobacterial trehalose in the quest for advanced tuberculosis therapies\u0026rsquo;, \u003cem\u003eMicrobiology (United Kingdom)\u003c/em\u003e, 160(8), pp. 1547\u0026ndash;1570.\u003c/li\u003e\n\u003cli\u003eAsensio, J. G. \u003cem\u003eet al.\u003c/em\u003e (2006) \u0026lsquo;The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis\u0026rsquo;, \u003cem\u003eJournal of Biological Chemistry\u003c/em\u003e, 281(3), pp. 1313\u0026ndash;1316.\u003c/li\u003e\n\u003cli\u003eGonzalo-Asensio, J. \u003cem\u003eet al.\u003c/em\u003e (2014) \u0026lsquo;Evolutionary history of tuberculosis shaped by conserved mutations in the PhoPR virulence regulator.\u0026rsquo;, \u003cem\u003eProceedings of the National Academy of Sciences of the United States of America\u003c/em\u003e. National Academy of Sciences, 111(31), pp. 11491\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eSoto, C. Y. \u003cem\u003eet al.\u003c/em\u003e (2004) \u0026lsquo;IS6110 Mediates Increased Transcription of the phoP Virulence Gene in a Multidrug-Resistant Clinical Isolate Responsible for Tuberculosis Outbreaks\u0026rsquo;, \u003cem\u003eJournal of Clinical Microbiology\u003c/em\u003e, 42(1), pp. 212\u0026ndash;219.\u003c/li\u003e\n\u003cli\u003eTientcheu LD, Koch A, Ndengane M, Andoseh G, Kampmann B, Wilkinson RJ. Immunological consequences of strain variation within the Mycobacterium tuberculosis complex. European Journal of Immunology. 2017; 47: 432\u0026ndash;445.\u003c/li\u003e\n\u003cli\u003eCole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1989;393:537\u0026ndash;544.\u003c/li\u003e\n\u003cli\u003eStuart LM, Alan R, Ezekowitz B. Phagocytosis: Elegant Complexity. Immunity. 2005; \u003cem\u003e22\u003c/em\u003e(5):539\u0026ndash;550.\u003c/li\u003e\n\u003cli\u003eKornfeld H, Mancino G, \u0026amp; Colizzi V. The role of macrophage cell death in tuberculosis. Cell Death and Differentiation. 1999;\u003cem\u003e6\u003c/em\u003e(1):71\u0026ndash;78.\u003c/li\u003e\n\u003cli\u003eLee J, Hartman M, \u0026amp; Kornfeld H. Macrophage apoptosis in tuberculosis. Yonsei Medical Journal\u003cem\u003e. \u003c/em\u003e2009:50(1);1\u0026ndash;11.\u003c/li\u003e\n\u003cli\u003eMolloy A, Laochumroonvorapong P, Kaplan G. Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette-Gu\u0026eacute;rin. J. Exp. Med.1994:180(4);1499-509.\u003c/li\u003e\n\u003cli\u003eChavez-Galan L, Vesin D, Martinvalet D, Garcia I. Low Dose BCG Infection as a Model for Macrophage Activation Maintaining Cell Viability. Journal of Immunology Research. 2016: 2016; 1-18\u003c/li\u003e\n\u003cli\u003eGan H, Lee J, Ren F, Chen M, Kornfeld H, Remold HG. Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence. Nature Immunology. 2008: 9(10); 1189\u0026ndash;1197.\u003c/li\u003e\n\u003cli\u003eBehar S, Divangahi M, Remold H. Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy? Nat Rev Microbiol.2010; 8(9): 668-74.\u003c/li\u003e\n\u003cli\u003eKurashima A, Morimoto K, Horibe M, Hoshino Y, Shiraishi Y, Kudoh S. A Method for visual scoring of pulmonary Mycobacterium avium complex disease: \"NICE scoring system\". Mycobact Dis. 2003;3(1):1\u0026ndash;5.\u003c/li\u003e\n\u003cli\u003ePlacido R, Mancino G, Amendola A, Mariani F, Vendetti S, Piacentini M, Sanduzzi A, Bocchino ML, Zembala M, Colizzi, V. Apoptosis of human monocytes/macrophages in Mycobacterium tuberculosis infection. J Pathol. 1997; 181(1):31-8.\u003c/li\u003e\n\u003cli\u003eRoychowdhury A, Dey RK, Bandyapadhyay A, Bhattacharya P, Mitra RB, Dutta R. Study of mutated p53 protein by immunohistochemistry in urothelial neoplasm of urinary bladder. J Indian Med Assoc. 2010; 110(6): 393-6.\u003c/li\u003e\n\u003cli\u003eDanellishvili L, McGarvey J, Li Y,Bermudez L. Mycobacterium tuberculosis infection causes different levels of apoptosis and necrosis in human macrophages and alveolar epithelial cells. Cellular Microbiology. 2003; 5(9): 649\u0026ndash;660.\u003c/li\u003e\n\u003cli\u003eParsons LM, Brosch R, Cole ST, Somoskovi, A, Loder A, Bretzel G, van Soolingen D, Hale YM, Salfinger M. Rapid and Simple Approach for Identification of Mycobacterium tuberculosis Complex Isolates by PCR-Based Genomic Deletion Analysis. journal of clinical microbiology. 2002;40(7): 2339\u0026ndash;2345.\u003c/li\u003e\n\u003cli\u003eBrosch R, Gordon SV, Marmiesse M, Brodin P, Buchrieser C, Eiglmeimer K, Garnier T, Gutierrez C, Hewinson G, Kremer K, Parsons LM, et al. A new tuberculosis scenario for the Mycobacterium tuberculosis complex. PNAS. 2002; 99(6): 3684-89.\u003c/li\u003e\n\u003cli\u003eComas I, Homolka S, Niemann S, Gagneux S. Genotyping of genetically monomorphic bacteria: DNA sequencing in Mycobacterium tuberculosis highlights the limitations of current methodologies. PLOS One. 2009; 4(11):1-11.\u003c/li\u003e\n\u003cli\u003eHsu T, Hingley-Wilson SM, Chen B, Chen M, Dai AZ, Morin PM, Marks CB, Padiyar J, Goulding C, Gingery M, et al. The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue. Proc Natl Acad Sci U S A. 2003; 14(100): 12420-5.\u003c/li\u003e\n\u003cli\u003eGagneux S, DeRiemer K, Van T, Kato-Maeda M, de Jong BC, Narayanan S, Nicol M, Niemann S, Kremer K, Gutierrez MC, et al. Variable host-pathogen compatibility in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2006.; 103(8): 2869-73.\u003c/li\u003e\n\u003cli\u003eGagneux, S. Host\u0026ndash;pathogen coevolution in human tuberculosis. Phil. Trans. R. Soc. 2012; 367: 850\u0026ndash;859\u003c/li\u003e\n\u003cli\u003eKato-Maeda M, Bifani PJ, Kreiswirth BN, Small, PM. The nature and consequence of genetic variability within Mycobacterium tuberculosis. J Clin Invest. 2001 Mar 1; 107(5): 533\u0026ndash;537.\u003c/li\u003e\n\u003cli\u003ede Jong BC, Hill PC, Brookes RH, Gagneux S, Jeffries DJ, out JK, Donkor SA, Fox A, McAdam KP, Small PM, Adegbola RA. Mycobacterium africanum Elicits an Attenuated T Cell Response to Early Secreted Antigenic Target, 6 kDa, in Patients with Tuberculosis and Their Household Contacts. The Journal of Infectious Diseases. 2006; 193: 1279\u0026ndash;86.\u003c/li\u003e\n\u003cli\u003eBriken V, Miller J., Living on the edge: inhibition of host cell apoptosis by Mycobacterium tuberculosis. Future Microbiol. 2008; 3(4): 15-22.\u003c/li\u003e\n\u003cli\u003eKeane J, Remold HG, Kornfeld H. Virulent Mycobacterium tuberculosis Strains Evade Apoptosis of Infected Alveolar Macrophages. The Journal of Immunology. 2000; 164(4):2016-2020.\u003c/li\u003e\n\u003cli\u003eRiandeau CJ, Kornfeld H. THP-1 Cell Apoptosis in Response to Mycobacterial Infection. Infection and Immunity. 2003; 71(1): 254\u0026ndash;259.\u003c/li\u003e\n\u003cli\u003eDhiman R, Raje M Majmudar S. Differential expression of NF-\u0026kappa;B in mycobacteria infected THP-1 affects apoptosis. Biochimica et Biophysica Acta. 2007; 1770: 649\u0026ndash;658.\u003c/li\u003e\n\u003cli\u003eZhang J, Jiang R, Takayama H, Tanaka Y. Survival of Virulent Mycobacterium tuberculosis Involves Preventing Apoptosis Induced by Bcl-2 Upregulation and Release Resulting from Necrosis. Microbiol Immunol. 2005; 49(9): 845\u0026ndash;852.\u003c/li\u003e\n\u003cli\u003eLi S, Ning L, Lou X, Xu G. Necroptosis in inflammatory bowel disease and other intestinal diseases. World J Clin Cases. 2018; 6(14): 745-752.\u003c/li\u003e\n\u003cli\u003eWelz PS, Wullaert A, Vlantis K, Kandylis V, Fernandez-Majad V, Ermalaeva M, Kirsch P, Sterner-Kock A, Loo GV, Pasparakis M. FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Natur. 2011; 477: 330-335\u003c/li\u003e\n\u003cli\u003eDannapel M, Vlantis K, Kumari S, Polykratis A, Kim C, Wachsmuth L, Eftychi C, Lin J, Corona T, Hermance N, et al. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature. 2014; 513(7516): 90\u0026ndash;94.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; orphans: 2; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: #ffffff; text-decoration-style: initial; text-decoration-color: initial; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica; font-size: 13px; color: #000000;\"\u003eTable 1 Demographic and clinical characteristics between\u0026nbsp;\u003cem style=\"box-sizing: inherit;\"\u003eM. tuberculosis\u003c/em\u003e\u0026nbsp;Beijing strain and\u0026nbsp;\u003cem style=\"box-sizing: inherit;\"\u003eM. bovis\u003c/em\u003e\u0026nbsp;BCG strain\u003c/span\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"box-sizing: inherit; border-collapse: collapse; border-spacing: 0px; color: #4a4a4a; font-family: Roboto, BlinkMacSystemFont, -apple-system, 'Segoe UI', Oxygen, Ubuntu, Cantarell, 'Fira Sans', 'Droid Sans', 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 16px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; orphans: 2; text-align: start; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: #ffffff; text-decoration-style: initial; text-decoration-color: initial; width: 827.778px; border: none;\"\u003e\n\u003ctbody style=\"box-sizing: inherit;\"\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px; border-top: 1pt solid windowtext; border-left: none; border-bottom: 1pt solid windowtext; border-right: none;\" rowspan=\"2\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eVariable\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 478.889px; border-top: 1pt solid windowtext; border-left: none; border-bottom: 1pt solid windowtext; border-right: none;\" colspan=\"2\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eMTBC species\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px; border-top: 1pt solid windowtext; border-left: none; border-bottom: 1pt solid windowtext; border-right: none;\" rowspan=\"2\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003ep-value\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px; border-top: none; border-right: none; border-left: none; border-image: initial; border-bottom: 1pt solid windowtext;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u003cem style=\"box-sizing: inherit;\"\u003eM. tuberculosis\u003c/em\u003e\u0026nbsp;Beijing strain, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px; border-top: none; border-right: none; border-left: none; border-image: initial; border-bottom: 1pt solid windowtext;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u003cem style=\"box-sizing: inherit;\"\u003eM. bovis\u003c/em\u003e\u0026nbsp;BCG strain\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003en (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eGender\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eFemale\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e13 (81.37)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e3 (18.8)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\" rowspan=\"2\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0.855\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eMale\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e11 (78.6)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e3 (21.4)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eAge (year)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026lt;21\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e2 (50.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e2 (50.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\" rowspan=\"4\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0.172\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e21-40\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e12 (75.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e4 (25.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e40-50\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e6 (100.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0 (0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026gt;50\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e4 (100.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0(0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 827.778px;\" colspan=\"4\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eEducational attainment\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eElementary school\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e8 (89.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e1 (11.1)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\" rowspan=\"3\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0.466\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eJunior high school\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e10 (83.3)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e2 (6.7)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eSenior high school\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e6 (66.7)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e3 (33.3)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eOccupation\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eLabourer\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e16 (76.2)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e5 (32.8)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\" rowspan=\"3\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0.364\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eHousewife\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e6 (100.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0 (0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eUnemployed\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e2 (66.7)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e1 (33.3)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eAnorexia\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eYes\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e21 (77.7)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e6 (22.2)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0.189\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eNo\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e3 (100.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0 (0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eWeight loss\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eYes\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e21 (80.8)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e5 (19.2)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0.364\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eNo\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e3 (75.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e1 (25.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eFever\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eYes\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e13 (76.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e4 (23.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0.167\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eNo\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e11 (84.6)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e2 (15.4)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eHaemoglobin level\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eNormal\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e8 (72.8)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e3 (27.3)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0.750\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eLow\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e16 (84.2)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e3 (15.8)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eSaO\u003csub style=\"box-sizing: inherit;\"\u003e2\u0026nbsp;\u003c/sub\u003elevel\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eNormal\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e17 (80.9)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e4 (19.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0.831\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 242.222px; border-top: none; border-right: none; border-left: none; border-image: initial; border-bottom: 1pt solid windowtext;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 15.95pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eLow\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 246.667px; border-top: none; border-right: none; border-left: none; border-image: initial; border-bottom: 1pt solid windowtext;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e7 (77.8)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 232.222px; border-top: none; border-right: none; border-left: none; border-image: initial; border-bottom: 1pt solid windowtext;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e2 (22.2)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 106.667px; border-top: none; border-right: none; border-left: none; border-image: initial; border-bottom: 1pt solid windowtext;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0px; padding: 0px 0px 10px; font-weight: 400; font-size: 0.925rem; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: Roboto, BlinkMacSystemFont, -apple-system, 'Segoe UI', Oxygen, Ubuntu, Cantarell, 'Fira Sans', 'Droid Sans', 'Helvetica Neue', Helvetica, Arial, sans-serif; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; orphans: 2; text-align: start; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: #ffffff; text-decoration-style: initial; text-decoration-color: initial;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; orphans: 2; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: #ffffff; text-decoration-style: initial; text-decoration-color: initial; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica; font-size: 13px; color: #000000;\"\u003eTable 2. \u0026nbsp;Severity of pulmonary damage between\u0026nbsp;\u003cem style=\"box-sizing: inherit;\"\u003eM. tuberculosis\u003c/em\u003e\u0026nbsp;Beijing strain and\u0026nbsp;\u003cem style=\"box-sizing: inherit;\"\u003eM. bovis\u003c/em\u003e\u0026nbsp;BCG strain\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"box-sizing: inherit; border-collapse: collapse; border-spacing: 0px; color: #4a4a4a; font-family: Roboto, BlinkMacSystemFont, -apple-system, 'Segoe UI', Oxygen, Ubuntu, Cantarell, 'Fira Sans', 'Droid Sans', 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 16px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; orphans: 2; text-align: start; text-indent: 0px; text-transform: none; white-space: normal; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; background-color: #ffffff; text-decoration-style: initial; text-decoration-color: initial; width: 776.667px; border: none;\"\u003e\n\u003ctbody style=\"box-sizing: inherit;\"\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 162.222px; border-top: 1pt solid windowtext; border-left: none; border-bottom: 1pt solid windowtext; border-right: none;\" rowspan=\"2\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eVariables\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border-top: 1pt solid windowtext; border-left: none; border-bottom: 1pt solid windowtext; border-right: none;\" rowspan=\"2\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u003cem style=\"box-sizing: inherit;\"\u003en\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border-top: 1pt solid windowtext; border-left: none; border-bottom: 1pt solid windowtext; border-right: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eMTBC species\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 187.778px; border-top: 1pt solid windowtext; border-left: none; border-bottom: 1pt solid windowtext; border-right: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 62.2222px; border-top: 1pt solid windowtext; border-left: none; border-bottom: 1pt solid windowtext; border-right: none;\" rowspan=\"2\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eOR\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 76.6667px; border-top: 1pt solid windowtext; border-left: none; border-bottom: 1pt solid windowtext; border-right: none;\" rowspan=\"2\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e95%CI\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 85.5556px; border-top: 1pt solid windowtext; border-left: none; border-bottom: 1pt solid windowtext; border-right: none;\" rowspan=\"2\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003ep-value\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border-top: none; border-right: none; border-left: none; border-image: initial; border-bottom: 1pt solid windowtext;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u003cem style=\"box-sizing: inherit;\"\u003eM. tuberculosis\u003c/em\u003e\u0026nbsp;Beijing strain, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 187.778px; border-top: none; border-right: none; border-left: none; border-image: initial; border-bottom: 1pt solid windowtext;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u003cem style=\"box-sizing: inherit;\"\u003eM. bovis\u0026nbsp;\u003c/em\u003eBCG strain,\u0026nbsp;n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 162.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eNICE Score \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 187.778px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 62.2222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 76.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 85.5556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 162.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eNodule\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; 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font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 62.2222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; 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padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 85.5556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0.088\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 162.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt -12.4pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Yes\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e19\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e17 (89.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 187.778px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e2 (10.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 62.2222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 76.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 85.5556px; border: none;\" rowspan=\"2\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 162.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt -12.4pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;No\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e11\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e7 (63.7)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 187.778px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e4 (36.4)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 62.2222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 76.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 162.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eInfiltrate/consolidation\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; 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padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0 (0.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 187.778px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; 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font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Yes\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e4\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e4 (100.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 187.778px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0 (0.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 62.2222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 76.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 85.5556px; border: none;\" rowspan=\"2\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 162.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt -12.4pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;No\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e26\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e20 (76.9)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 187.778px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e6 (23.1)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 62.2222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 76.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 162.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eEctasis\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 187.778px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 62.2222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e10.00\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 76.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e1.34-74.51\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 85.5556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0.013\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 162.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt -12.4pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Yes\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e22\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e20 (90.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 187.778px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e2 (9.15)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 62.2222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 76.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 85.5556px; border: none;\" rowspan=\"2\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 162.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt -12.4pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; No\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e8\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e4 (50.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 187.778px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e4 (50.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 62.2222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 76.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 162.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eSeverity of lung damage\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 155.556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 187.778px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: right;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 62.2222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e7.60\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 76.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e1.07-54.09\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 85.5556px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e0.028\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"box-sizing: inherit;\"\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 162.222px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt 8.9pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003eMild\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; padding: 0in 5.4pt; vertical-align: top; text-align: left; width: 46.6667px; border: none;\"\u003e\n\u003cp style=\"box-sizing: inherit; margin: 0in 0in 0.0001pt; padding: 0px 0px 10px; font-weight: 400; font-size: 16px; letter-spacing: 0.35px; line-height: 1.65rem; color: #242c35; font-family: 'Times New Roman', serif; text-align: justify;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; color: #000000;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-size: 13px;\"\u003e\u003cspan style=\"box-sizing: inherit; font-style: inherit; font-weight: inherit; font-family: Helvetica;\"\u003e9\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"box-sizing: inherit; 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The aim of this study was to determine whether M. tuberculosis and M. bovis is associated with apoptosis and necroptosis by measuring the expression of specific signaling pathways components (Fas-associated protein with death domain (FADD) and receptor interacting protein 3 (RIP3)), and the level of apoptosis. \u003c/p\u003e\u003cp\u003eResults: We recruited 30 patients with pulmonary TB; 24 patients were infected with M. tuberculosis Beijing strain and six patients with M. bovis BCG strain. M. tuberculosis-infected patients were more likely to have severe lung damage compared to those infected with\u0026nbsp;M. bovis (odds ratio [OR]: 7.60; 95% confidence interval [CI]: 1.07-54.09). M. tuberculosis infection was associated with lower expression of FADD and lower apoptosis level of macrophages compared to M. bovis. No significant different of RIP3 between MTBC species groups. In conclusion, M. tuberculosis Beijing strain was associated with severe pulmonary damage, inhibited FADD expression and reduced apoptosis level of macrophages derived from pulmonary TB patients. This suggests that the M. tuberculosis Beijing strain is potentially to be used as determinant of disease progressivity and tissue damage in TB cases.\u003c/p\u003e","manuscriptTitle":"The role of Mycobacterium tuberculosis complex species on apoptosis and necroptosis state of macrophages derived from active pulmonary tuberculosis patients","msid":"","msnumber":"","nonDraftVersions":[{"code":4,"date":"2020-08-27 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