Role of Surgery Adjuncts for Overall Survival of Patients with Supratentorial WHO Grade 4 Gliomas.

Role of Surgery Adjuncts for Overall Survival of Patients with Supratentorial WHO Grade 4 Gliomas. | 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 Article Role of Surgery Adjuncts for Overall Survival of Patients with Supratentorial WHO Grade 4 Gliomas. Tomasz Czernicki, Edyta Maj, Przemysław Kunert This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5097905/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background In recent years, numerous advanced techniques supporting surgery (TSS) have been utilized to maximize glioma resection. However, the impact of the multimodal use of TSS, such as awake surgery, intraoperative neurophysiological monitoring, neuronavigation, fluorescence-guided surgery, fMRI, and DTT, on improving OS remains uncertain.. Methods We assessed, in retrospective analysis of 81 patients with supratentorial WHO grade 4 gliomas, the effect of age, gender, tumor location, number of TSS used, EOR, postoperative KPS, IDH-1 status, and use of postoperative adjuvant therapy (PAT) i.e. radiotherapy and chemotherapy on overall survival. Kaplan-Meyer plots with F-Cox test and Cox proportional hazards model were used for univariate and multivariate analysis of survival. Results We used none, one, two, three or four TSS in 30, 20, 15, 9 and 7 patients, respectively. The number of TSS used (none vs. 1–2 vs. 3–4) had a correlation with OS in eloquent areas (P = 0.031, univariate; P = 0.006, multivariate) with median survival of 194, 364, and 674 days, respectively, whereas no correlation was observed in non-eloquent areas. In univariate analysis but not in multivariate analysis, significant factors for OS in gliomas in eloquent areas were younger age (P = 0.025), EOR (gross total vs. subtotal vs. partial resection) (P = 0.015), PAT use (P = 0.00065), and in gliomas in non-eloquent areas were EOR (P = 0.01), postoperative KPS (≥ 70 vs.<70) (P = 0.023), PAT use (P = 0.015). Conclusion The use of multiple techniques supporting surgery simultaneously improves the overall survival of patients with supratentorial WHO grade 4 gliomas in eloquent areas, in contrast to non-eloquent areas. Techniques supporting surgery Awake craniotomy Extent of resection Glioblastoma Intraoperative neuromonitoring Overall survival Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction The treatment of patients with World Health Organization (WHO) Grade 4 gliomas is a complex and multidisciplinary process. Proficient management of these aggressive brain tumors necessitates a combination of surgical, irradiation, and chemotherapy approaches [ 1 , 4 , 17 , 20 , 25 , 27 ]. Maximal safe resection is the primary goal in their surgical management and refers to the amount of tumor that can be safely removed without causing neurological deficits. Many studies have shown that a more extensive resection is associated with better survival outcomes [ 1 , 4 , 6 , 15 , 19 – 21 , 23 , 25 , 28 ]. In recent years, numerous advanced tools have been utilized to maximize gliomas resection and patient outcome [ 1 , 2 , 9 , 17 , 32 ]. However, effect of the use and whether the number of used techniques supporting surgery (TSS) i.e. intraoperative techniques as awake surgery, Intraoperative Neuromonitoring (IONM), neuronavigation, fluorescence-guided surgery (using agents like 5-aminolevulinic acid), and perioperative technique as fMRI and diffusion tensor tractography (DTT) on length of survival remain unclear [ 5 , 6 ]. This study was conducted to evaluate the impact of the use of intraoperative multimodal TSS on the extent of resection (EOR) and its influence on the overall survival (OS) in patients with supratentorial WHO grade 4 gliomas. Material and Methods Patient records and medical histories were retrospectively reviewed to identify eligible participants treated between 2018 and 2020 in Department of Neurosurgery of Medical University of Warsaw. Inclusion criteria encompassed adult patients (age ≥ 18 years) diagnosed with supratentorial WHO Grade 4 gliomas who underwent surgical resection. Exclusion criteria included patients with incomplete medical records, non-supratentorial tumor locations, and those who underwent tumor biopsy. Patients-related variables included age, sex, pre- and postoperative Karnofsky Performance Scale (KPS) status. Tumor-related variables included tumor location (including identification of location as in eloquent or non-eloquent areas, and in dominant or non-dominant hemisphere), tumor volume, and IDH 1 mutation status. In cases of tumors in the eloquent area of motor or language cortex, preoperative fMRI and DTT were performed and used later during surgery. The volume of the tumor was calculated according to the formula: V= ½A x ½B x ½C; where A, B and C are the largest dimensions of the tumor in three perpendicular planes. The extent of tumor resection was assessed by comparing the preoperative MRI image with the postoperative MRI image taken no later than 48 hours after surgery. The EOR was divided into three categories: gross total resection (GTR: 100%), subtotal resection (STR: 80–99%), and partial resection (PR < 80%). All histopathological examinations were conducted in accordance with the 4th edition of the WHO Classification of Tumors of the Central Nervous System from 2016. Postoperative oncological treatment included the use of radiotherapy and/or chemotherapy. All patients were monitored in the Outpatient Clinic and in the Oncology Center and follow-up MRI examinations were performed. The length of survival was determined based on information from the Outpatient Clinic and telephone interviews with patients' families or from the patients themselves if they were still alive at the time of data collection closure (February 20, 2023). Data were analyzed using the Statistica software, version 12.0 (StatSoft). The Shapiro–Wilk test was used to test the normality of the data. Analyses included basic descriptive statistics, the Student t-test, and contingency tables with the Pearson Chi-square test and the exact Fisher test. Survival curves were estimated using the Kaplan–Meier method with F-Cox test for univariate analysis of survival and Cox proportional hazards model was used for multivariate analysis of survival. A P-value of less than 0.05 was considered statistically significant. Results Characteristics and overall outcomes of the study population Eighty-one patients underwent surgery, all of which were performed electiv­ely. In our cohort, the median age was 61 years (interquartile range: 49-68 years), with a male slight predominance - 48 patients (59.26%) compared to 33 females (40.74%). The median tumor volume was 35.28 cm 3 (interquartile range: 16.42–62.37 cm 3 ). Tumors were located in eloquent areas in 36 patients (44.44%) and in the dominant hemisphere in 38 patients (46.91%), respectively. Almost all patients – 78 (96.3%) were independent (KPS ≥70) with only 3 patients (3.7%) being dependent (KPS <70). The number and types of combinations of used TSS are listed in Table 1. Awake surgery was employed in 8 surgeries (9.88%) , ­­IONM in 12 surgeries (14.81%), neuronavigation in 29 surgeries (35.8%), fluorescence-guided surgery ­­in 30 surgeries (37.04%), fMRI and DTT in 26 procedures (32.1%), respectively. For further statistics, we divided the patients into groups: 30 patients (37.04%) without any TSS used, 35 patients (43.21%) with 1-2 TSS used, and the multimodal group - 16 patients (19.75%) with 3-4 used TSS. Gross total resection (GTR) was achieved in 39 cases (49.15%), subtotal resection (STR) in 31 cases (38.27%), and partial resection (PR) in 11 cases (13.58%). No patient died in the postoperative period. Postoperatively, 75 (92.59%) patients were independent (KPS ≥70) and 6 (7.41%) were dependent (KPS <70). Data on the IDH 1 status were available for 41 (50.62%) patients, with 35 (43.21%) having wild-type and 6 (7.41%) having mutated status, respectively. In total, 63 (77,78%) patients received radiotherapy and chemotherapy following surgery, 9 (11.11%) patients received only radiotherapy or chemotherapy, and 9 (11.11%) patients did not receive any postoperative adjuvant therapy. Seventy three (90.12%) of the patients died, while the remaining 8 (9.88%) patients were still alive at the time of data collection closure. The median OS was 406 days (interquartile range: 216-735 days). Table 1. Number and types of combinations of used techniques supporting surgery (TSS) Abbreviations: FGS - Fluorescence-guided surgery; NN – Neuronavigation; AS – Awake surgery; IONM – Intraoperative neuromonitoring Number of used TTS and EOR Number of used TSS had no correlation with EOR in the entire group of gliomas and also in eloquent and non-eloquent subgroups (Chi-Pearson test, P=0.135, P=0.396 and P= 0.062, respectively) (Table 2). Table 2. Number of used TSS and EOR Number of used TSS Entire group patients GTR STR PR 0 20 (66.7%) 7 (23.3% 3 (10%) 1-2 14 (40%) 16 (45.7%) 5 (14.3%) 3-4 5 (31.25%) 8 (50%) 3 (18.75%) Patients with gliomas in the eloquent areas 0 0 1 (100%) 0 1-2 5 (27.8%) 8 (44.4%) 5 (27.8%) 3-4 5 (35.7%) 7 (50%) 2 (14.3%) Patients with gliomas in the non- eloquent areas 0 17 (65.4%) 6 (23.1%) 3 (11.5%) 1-2 9 (52.9%) 8 (47.1%) 0 3-4 0 1 (50%) 1 (50%) The role of TSS use in terms of overall survival in the entire study group of patients The number of used TSS (none vs. 1-2 vs. 3-4) showed no correlation with overall survival (P=0.41). Younger age (below vs. above the median age) (P=0.015), EOR (gross total vs. subtotal vs. partial resection) (P=0.00018) (Figure 1) and the use of postoperative adjuvant therapy (radiotherapy and chemotherapy vs. radiotherapy or chemotherapy vs. none) (P=0.00001) (Figure 2) were correlated with OS in univariate but not in multivariate analysis. Other examined factors, including sex (P=0,32), tumor location in the eloquent vs non-eloquent area (P=0.192), tumor location in the dominant vs. non-dominant hemisphere (P=0.45), tumor volume (below vs. above the median volume) (P=0.182), postoperative KPS status (KPS ≥70 vs. KPS <70) (P=0.147), IDH status (wild-type vs. mutated vs. unknown) (P=0.538), did not correlate with the length of survival. The role of TSS use in terms of overall survival In the subgroup of patients with gliomas restricted to eloquent areas In the subgroup of patients with gliomas restricted to eloquent areas (N=36), once again, younger age (P=0.025) (Figure 3), EOR (P=0.015) (Figure 4) and the use of postoperative adjuvant therapy (P=0.00065) (Figure 5) were correlated with OS. Additionally, the number of used TSS (none vs. 1-2 vs. 3-4) (Figure 6) showed a correlation with median survival of 194, 364 and 674 days, respectively, in univariate analysis (P=0.031). Importantly, it emerged as the only independent prognostic factor in multivariate analysis (P=0.006). Other examined factors, including sex (P=0,32), tumor location in the dominant vs. non-dominant hemisphere (P=0.098), tumor volume (below vs. above the median volume) (P=0.24), postoperative KPS status (KPS ≥70 vs. KPS <70) (P=0.37), IDH 1 status (wild-type vs. mutated vs. unknown) (P=0.864), did not correlate with the length of survival. The role of TSS use in terms of overall survival In the subgroup of patients with gliomas in non-eloquent areas In patients with gliomas in non-eloquent areas (N=45) the use of TSS was not correlated with OS (P=0.25). Postoperative KPS status (≥70 vs.<70) (P=0.023), EOR (P=0.01) (Figure 7) and the use of postoperative adjuvant therapy (P=0.015) (Figure 8) were correlated in univariate but not in multivariate analysis with OS. Other examined factors, including age (P=0.092), sex (P=0.4), tumor location in the dominant vs. non-dominant hemisphere (P=0.08), tumor volume (below vs. above the median volume) (P=0.342), IDH 1 status (wild-type vs. mutated vs. unknown) (P=0.46), did not correlate with the length of survival. Discussion The management of patients with WHO Grade 4 gliomas involves a multidisciplinary approach, necessitating usually a combination of surgical, irradiation, and chemotherapy strategies. The primary objective in surgical management is achieving maximal safe resection, a factor consistently associated with improved OS in various studies [4,6,15,19-21,23,25,28,31]. Considering the incorporation of an increasing number of TSS in the treatment process of brain gliomas in recent decades, we decided to investigate whether the employing a greater number of these adjuncts yields a beneficial effect on both, EOR and OS. These methods include preoperative fMRI and DTT, as well as intraoperative techniques such as neuronavigation, IONM, awake surgery and FGS with 5-ALA [1-5,9,17,32]. Intuitively, combining multimodal pre- and intraoperative adjuncts during the same brain glioma operation should have a greater effect on EOR and OS compared to each modality alone or when used in modest numbers in combination. While numerous studies have been published focusing on the effects of each adjuvant modality [1,5,17], studies comparing the correlation between the use of different numbers of TSS and EOR and OS are scarce [4,32]. Another question worth addressing is whether the application of multimodal TSS has the same rationale in gliomas located in eloquent and non-eloquent areas. Neurosurgeons typically choose adjuncts based on their own expertise with various technologies, suspected tumor histopathology, tumor location, and sometimes on anticipated cost-effectiveness. Awake surgery, employed in procedures involving eloquent brain areas, aims to map and preserve functional regions. It improves the identification of safe access corridors for tumors and provides precise real-time feedback on the function of critical structures, such as motor and language areas [17]. The benefits of brain mapping in gliomas during awake surgery are well demonstrated, improving EOR, PFS and OS, while reducing the rate of postoperative neurological deficits [7,34]. Under the operating microscope, the similarity between tumor appearance and nearby brain parenchyma poses a challenge for achieving a complete tumor resection. Fluorescence-guided surgery with use of 5-ALA significantly enhances the ability to achieve a more extensive tumor resection by revealing residual tumor tissue at the margins [1,10,17,24,36]. Patients who undergo resection with the use of 5-ALA under a blue light microscope exhibit higher EOR, PFS and OS compared to those operated on under a conventional white light microscope [5,10,26]. Neuronavigation guides neurosurgeons in tumor resection, enhancing precision in targeting tumor margins and minimizing damage to the surrounding healthy brai­n [1,30]. A well-known limitation of neuronavigation is challenge associated with brain shift occurring during the surgical resection. A potential solution is the use of intraoperative ultrasound to update the neuronavigation system to account for brain shift [1,30]. The use of neuronavigation improves EOR and OS with an acceptable extension of preparation time for surgery [13,30]. The implementation of preoperative fMRI and DTT in neurosurgical practice enables better planning and guidance for safe resections adjacent to critical regions, offering advantages in mapping without resorting to invasive, time-consuming, intraoperative monitoring techniques. Moreover, it provides an opportunity for integration them with neuronavigation and can be utilized during surgery [1,2,17]. DTT implementation seems to enhance EOR, improve postoperative KPS, and increase OS [31,33]. Intraoperative Neurophysiological Monitoring (IONM) involves monitoring electrical activity during surgery to identify functional brain areas and neural pathways. In glioma surgery, IONM typically begins with mapping of the motor cortex. Subsequently, the simultaneous application of subcortical mapping to detect the distance of corticospinal tracts, along with continuous monitoring of motor evoked potentials (MEP), is believed to be associated with enhanced EOR, fewer severe late functional deficits and better OS [11,12,35]. In assessing overall outcomes, our study revealed that the number of used TSS did not correlate with OS in the entire patient group. It is in contrast to results of Xiong et al. [32], who found in their cohort of 912 patients that the OS was noticeably longer in the group with multimodal use of TSS comparing to the non-multimodal group (21.0 months vs. 16.0 months). It should be noted that in their multimodal group, there were more cases with a better EOR and more IDH-wild type tumors. Cui et al. [4] comparing the multimodal use of TSS including neuronavigation, intraoperative MRI and IONM and singular use of TSS (surgeries guided only by neuronavigation) in removing glioblastoma involving corpus callosum found better EOR, longer median progression-free survival (PFS) and longer median OS in multimodal group in univariate analysis. We found in the entire group of studied patients that factors such as younger age, greater EOR, and use postoperative adjuvant therapy i.e. radiotherapy and/or chemotherapy were significant factors correlated with OS in univariate analysis. It is well-known that younger patients have a more favorable prognosis than their older counterparts [7,14,20,21,25] due to their enhanced response to treatment, including greater tolerance for aggressive surgeries and better response to adjuvant therapies such as radiation and chemotherapy [16,18]. Additionally, younger age is generally associated with better overall health status [22]. The extent of resection is a crucial factor influencing the prognosis of glioblastoma patients. Multiple studies have consistently demonstrated a positive relationship between greater EOR and improved OS [1,4,6,15,19-21,23,25,28]. The rationale behind this association lies in fact that achieving maximal safe resection not only alleviates symptoms but also reduces tumor burden, thereby enhancing the effectiveness of subsequent treatments such as radiation and chemotherapy. The integration of radiotherapy and chemotherapy into treatment regimens of WHO grade 4 gliomas has had established importance for many decades [4,14,17,21,25,28]. The combined modality, known as chemoradiotherapy, aims to enhance the efficacy of both treatments and improve OS, what was proved by Stupp et al. [27] in trial comparing radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy. Interestingly, in the subgroup of patients with gliomas restricted to eloquent areas, the number of used TSS emerged as a notable factor influencing survival [4]. It proved to be the only independent prognostic factor in multivariate analysis. The association between the number of used TSS and OS in the case of gliomas restricted to eloquent areas may arise from the fact that employing various TSS in a multimodal approach enhances the effectiveness of glioma surgeries in critical brain areas. This approach provides neurosurgeons with a more comprehensive understanding of the tumor and its surroundings, leading to improved surgical outcomes. Our results regarding gliomas located in eloquent areas indicate that the use of multimodal TSS during surgeries is justified for such patients and should be considered for implementation into everyday clinical practice. Conversely, in the group of patients with gliomas in non-eloquent areas, we did not observe a similar relationship between the number of TSS used and OS.­­­­­ Our results suggest that there may be no justification for employing multimodal TSS in the case of gliomas located in non-eloquent areas. However, to confirm such a conclusion, prospective studies should be conducted. In addition, it is essential to consider that the unwarranted use of these techniques in such patients may lead to adverse consequences such as prolonged operative time, increased surgical risks including the risk of infection [8], and may have an impact on treatment costs. In the subgroup analysis based on tumor location, i.e., in gliomas restricted to eloquent areas and those in non-eloquent areas, we also observed, in univariate analysis, correlations between EOR and the use of postoperative adjuvant therapy with OS, similar to the results observed in the entire group of patients [1,4,6,15,19-21,23,25,28,32]. However, between these two subgroups of patients we observed one difference: in gliomas located in eloquent areas, the factor correlating with OS was the younger age of the patients, whereas in gliomas located in non-eloquent areas, it was the post-surgery condition of the patients according to KPS scale. Nevertheless, in multivariate analysis, none of these factors retained significance, highlighting the complexity of their individual contributions and interplay between them. We also explored the role of TSS in relation to EOR [4,32]. Contrary to expectations, the number of used TSS did not correlate with EOR in the entire glioma group or in eloquent and non-eloquent subgroups. This finding suggests that while TSS may impact survival in the complex treatment process, its influence on the EOR is more nuanced. Our results contrast to those of other authors who reported associations between multimodal use of TSS and EOR, suggesting it as one of the critical factors influencing OS [3,4,32]. The number of used TSS may influence the neurosurgeon's ability to achieve a maximal safe resection, thereby contributing to improved OS. While the correlation between a greater EOR and improved OS is well-established [1,4,6,15,19-21,23,25,28], challenges persist in balancing the need for maximal tumor removal with the preservation of critical neurological functions. Advances in neurosurgical techniques, imaging modalities, and intraoperative technologies continue to enhance the surgeon's ability to navigate this delicate balance, ultimately contributing to improved prognoses for individuals facing the formidable challenge of glioblastoma. With mounting evidence highlighting the importance of GTR in enhancing patient survival in WHO grade 4 gliomas, recent decades have witnessed the emergence of a myriad of TSS, that allow for improved identification of tumor borders, crucial eloquent cortex and fiber tracts [3,4,32]. These novel adjuncts contribute to achieving higher rates of complete resections in a safe manner [4]. The effective application of these multimodal TSS requires technical proficiency and a thorough understanding of the intricacies associated with each method. Neurosurgeons should undergo specialized training to harness the full potential of these tools, and the learning curve associated with their implementation may impact their efficacy. Several TSS still require additional research to demonstrate their clinical efficacy and cost-effectiveness, preferably through randomized and comparative effectiveness trials. On the other hand, it is important not to overlook classic microsurgical skills, ensuring that the use of TSS does not result in the loss of dexterity and proficiency in tumor removal. Regardless of the surgical adjuncts used, equally important for efficient tumor removal is a thorough knowledge of neuroanatomy, the ability to recognize spatial relations of the tumor to adjacent structures, the ability to feel tumor margins, and the ability to make critical decisions swiftly and accurately. Provided that a neurosurgeon does not possess typical surgical skills, TSS can be misleading during surgery. There were several limitations to the present study. Firstly, it is a retrospective study in which the number and type of TSS used depended largely on the preferences of the operating neurosurgeon. Although we attempted to employ specific TSS combinations for particular tumor locations, the final decision rested with the operating surgeon. Secondly, we did not utilize modalities such as ultrasonography [1,5,29] or iMRI [5,6,9] among the adjuncts. Thirdly, patients were operated on by various neurosurgeons in our department, with different levels of experience, potentially influencing the extent of tumor resection. The varying degrees of experience among neurosurgeons may have also influenced the effectiveness of TSS utilization. Additionally, the relatively small sample size may limit the generalizability of our findings. Further prospective studies with larger cohorts are warranted to validate and expand upon our results. Conclusion In conclusion, our study sheds light on the intricate relationship between TSS, extent of resection, and overall survival in patients with supratentorial WHO Grade 4 gliomas. We observed that the utilization of multimodal pre- and intraoperative TSS, as opposed to using singular or no adjuncts, appears to correlate with overall survival in gliomas located in eloquent areas. However, it does not show a correlation with the extent of resection. On the contrary, in gliomas located in non-eloquent areas, the use of multimodal TSS has no correlation with either the extent of tumor resection and overall survival. Therefore, the use of multimodal adjuncts seems unjustified in such cases. However, to confirm such a conclusion, prospective studies should be conducted. Declarations Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sector. Declarations of interest: none Institutional Review Board Statement: The manuscript does not contain clinical studies or patient data. Our study was a retrospective analysis; all patients were treated according to standard practices, with no experiments or unusual interventions performed. In our institution, this type of research does not require Institutional Review Board (IRB) approval according to national legislation. We obtained a statement from the IRB Committee indicating that the study is exempt from such approval (decision number: AKBE/34/2024). All patients provided written informed consent for the procedures. Patient consent for publication was waived, as no identifiable information is included in the manuscript. Author Contribution Author Contributions: conceptualization, T.C., E.M., P.K.; methodology, T.C., E.M., P.K.; formal analysis, T.C.; investigation, T.C., E.M., P.K.; data curation, T.C., E.M., P.K.; writing—original draft preparation, T.C.; writing—review and editing, E.M., P.K.; visualization, T.C., E.M., P.K.; supervision, P.K.; project administration, T.C.; All authors have read and agreed to the published version of the manuscript. References Bander ED, Magge R, Ramakrishna R (2018) Advances in Glioblastoma Operative Techniques. 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Turk Neurosurg 20:117-125 Wei R, Chen H, Cai Y, Chen J (2023) Application of intraoperative ultrasound in the resection of high-grade gliomas. Front Neurol 14:1240150 Wirtz CR, Albert FK, Schwaderer M, Heuer C, Staubert A, Tronnier VM, Knauth M, Kunze S (2000) The benefit of neuronavigation for neurosurgery analyzed by its impact on glioblastoma surgery. Neurol Res 22:354-360 Wu JS, Zhou LF, Tang WJ, Mao Y, Hu J, Song YY, Hong XN, Du GH (2007) Clinical evaluation and follow-up outcome of diffusion tensor imaging-based functional neuronavigation: a prospective, controlled study in patients with gliomas involving pyramidal tracts. Neurosurgery 61:935-948 Xiong Z, Luo C, Wang P, Hameed NUF, Song S, Zhang X, Wu S, Wu J, Mao Y (2022) The Intraoperative Utilization of Multimodalities Could Improve the Prognosis of Adult Glioblastoma: A Single-Center Observational Study. World Neurosurg 165:e532-e545 Yu CS, Li KC, Xuan Y, Ji XM, Qin W (2005) Diffusion tensor tractography in patients with cerebral tumors: a helpful technique for neurosurgical planning and postoperative assessment. Eur J Radiol 56:197-204 Zhang JJY, Lee KS, Voisin MR, Hervey-Jumper SL, Berger MS, Zadeh G (2020) Awake craniotomy for resection of supratentorial glioblastoma: a systematic review and meta-analysis. Neurooncol Adv2:vdaa111 Zhang N, Yu Z, Hameed NUF, Xu G, Song Y, Wu B, Zhang J, Qiu T, Zhuang D, Lu J, Wu J (2018) Long-Term Functional and Oncologic Outcomes of Glioma Surgery with and without Intraoperative Neurophysiologic Monitoring: A Retrospective Cohort Study in a Single Center. World Neurosurg 119:e94-e105 ­ Zhao S, Wu J, Wang C, Liu H, Dong X, Shi C, Shi C, Liu Y, Teng L, Han D, Chen X, Yang G, Wang L, Shen C, Li H (2013) Intraoperative fluorescence-guided resection of high-grade malignant gliomas using 5-aminolevulinic acid-induced porphyrins: a systematic review and meta-analysis of prospective studies. PLoS One 28:e63682 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-5097905","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":374472213,"identity":"2f360934-aed8-4ce1-87c9-4419596fcdaa","order_by":0,"name":"Tomasz Czernicki","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCUlEQVRIiWNgGAWjYNCDBIYEHn4IkxmEG7Ap4sHQItkA18JIhBaQJoMDBLTYs3cnfvzxh0Fevr332YMHNWkyxjdyTDcwVFgnNkg3YreF5+xmaR4eBsPGnuPmBgnHcnjMbuSY3WA4k57YIHMQuxaJ3A3SDBIMCcwSaWwSiQ0VPGa3gVoY2w4nNgC5OLRs/vnDgCGBTf4ZRIvxbJCWf3i1bJPgAYWUBBtISw6PgTRISwMeLWfObrPmOSBhOIMH6LCEY2k8Evefld1IOJZu3IbDL+ztvZtv/vhjAwyxY2ySP2qS7fl7Dm+78aHGWrZfuvkANi1QIIHGTwBiNnRBIgAZWkbBKBgFo2BYAgD/OlqmVkeBvgAAAABJRU5ErkJggg==","orcid":"","institution":"Medical University of Warsaw","correspondingAuthor":true,"prefix":"","firstName":"Tomasz","middleName":"","lastName":"Czernicki","suffix":""},{"id":374472214,"identity":"2efeb7ef-cb66-4658-ae3c-ed6745ad6807","order_by":1,"name":"Edyta Maj","email":"","orcid":"","institution":"Medical University of Warsaw","correspondingAuthor":false,"prefix":"","firstName":"Edyta","middleName":"","lastName":"Maj","suffix":""},{"id":374472215,"identity":"7dba84cc-c08e-41e4-a4b8-b3bb0af6b8ff","order_by":2,"name":"Przemysław Kunert","email":"","orcid":"","institution":"Medical University of Warsaw","correspondingAuthor":false,"prefix":"","firstName":"Przemysław","middleName":"","lastName":"Kunert","suffix":""}],"badges":[],"createdAt":"2024-09-16 14:00:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5097905/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5097905/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":71937384,"identity":"e906d916-e376-46de-befc-c7d816bce085","added_by":"auto","created_at":"2024-12-20 00:43:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":244653,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of the extent of resection (EOR) (GTR – gross total resection vs. STR – subtotal resection vs. partial resection) with overall survival in the entire group of patients.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5097905/v1/87e73dfdbb1d953f1b62a658.png"},{"id":71937385,"identity":"43e01baa-6e7e-4c00-8dff-d6fbe30e7c02","added_by":"auto","created_at":"2024-12-20 00:43:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":228323,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of the use of postoperative adjuvant therapy (radiotherapy, chemotherapy) with overall survival in the entire group of patients.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5097905/v1/9dbfbe548787bb1776af8789.png"},{"id":71938180,"identity":"83df038b-b516-4076-b649-6e85dd178592","added_by":"auto","created_at":"2024-12-20 00:51:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":202845,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of age with overall survival in patients with gliomas restricted to eloquent areas.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5097905/v1/a58d0c5252da81089dedaf79.png"},{"id":71938933,"identity":"f6942ae1-8f00-45c0-ad04-0917f1d7779b","added_by":"auto","created_at":"2024-12-20 00:59:13","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":216198,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of the extent of resection (EOR) (GTR – gross total resection vs. STR – subtotal resection vs. partial resection) with overall survival in patients with gliomas restricted to eloquent areas.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-5097905/v1/eb2423ec57806ca1d431a964.png"},{"id":71939161,"identity":"a320730f-bbb0-406c-af7c-679d1267dd87","added_by":"auto","created_at":"2024-12-20 01:07:13","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":201912,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of the use of postoperative adjuvant therapy (radiotherapy, chemotherapy) with overall survival in patients with gliomas restricted to eloquent areas.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-5097905/v1/86ed3043013bb98867d8c8fd.png"},{"id":71939762,"identity":"9ac56464-7d63-4115-b7d6-94ce948ec6f8","added_by":"auto","created_at":"2024-12-20 01:15:13","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":214541,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of the number of used techniques supporting surgery (TSS) with overall survival in patients with gliomas restricted to eloquent areas.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-5097905/v1/d5fb279713102f036eea69e3.png"},{"id":71938179,"identity":"a36048e9-e03c-4656-80ed-7019507a0b6a","added_by":"auto","created_at":"2024-12-20 00:51:13","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":217457,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of the extent of resection (EOR) (GTR – gross total resection vs. STR – subtotal resection vs. partial resection) with overall survival in patients with gliomas in non-eloquent areas.\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-5097905/v1/dc868a941810ed6442cd7965.png"},{"id":71937389,"identity":"aa44fa47-cdc6-44f2-83cf-206cf4b113d4","added_by":"auto","created_at":"2024-12-20 00:43:13","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":210256,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of the use of postoperative adjuvant therapy (radiotherapy, chemotherapy) with overall survival in patients with gliomas in non-eloquent areas.\u003c/p\u003e","description":"","filename":"floatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-5097905/v1/e48252e950a63cb40098144c.png"},{"id":75009766,"identity":"e77b1dad-ea71-40d2-9750-88c35322777d","added_by":"auto","created_at":"2025-01-29 11:17:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2084283,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5097905/v1/e4d522ff-db44-45cb-b72e-28642fe279de.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eRole of Surgery Adjuncts for Overall Survival of Patients with Supratentorial WHO Grade 4 Gliomas.\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe treatment of patients with World Health Organization (WHO) Grade 4 gliomas is a complex and multidisciplinary process. Proficient management of these aggressive brain tumors necessitates a combination of surgical, irradiation, and chemotherapy approaches [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Maximal safe resection is the primary goal in their surgical management and refers to the amount of tumor that can be safely removed without causing neurological deficits. Many studies have shown that a more extensive resection is associated with better survival outcomes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In recent years, numerous advanced tools have been utilized to maximize gliomas resection and patient outcome [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. However, effect of the use and whether the number of used techniques supporting surgery (TSS) i.e. intraoperative techniques as awake surgery, Intraoperative Neuromonitoring (IONM), neuronavigation, fluorescence-guided surgery (using agents like 5-aminolevulinic acid), and perioperative technique as fMRI and diffusion tensor tractography (DTT) on length of survival remain unclear [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This study was conducted to evaluate the impact of the use of intraoperative multimodal TSS on the extent of resection (EOR) and its influence on the overall survival (OS) in patients with supratentorial WHO grade 4 gliomas.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cp\u003ePatient records and medical histories were retrospectively reviewed to identify eligible participants treated between 2018 and 2020 in Department of Neurosurgery of Medical University of Warsaw. Inclusion criteria encompassed adult patients (age\u0026thinsp;\u0026ge;\u0026thinsp;18 years) diagnosed with supratentorial WHO Grade 4 gliomas who underwent surgical resection. Exclusion criteria included patients with incomplete medical records, non-supratentorial tumor locations, and those who underwent tumor biopsy. Patients-related variables included age, sex, pre- and postoperative Karnofsky Performance Scale (KPS) status. Tumor-related variables included tumor location (including identification of location as in eloquent or non-eloquent areas, and in dominant or non-dominant hemisphere), tumor volume, and IDH 1 mutation status. In cases of tumors in the eloquent area of motor or language cortex, preoperative fMRI and DTT were performed and used later during surgery. The volume of the tumor was calculated according to the formula: V= \u0026frac12;A x \u0026frac12;B x \u0026frac12;C; where A, B and C are the largest dimensions of the tumor in three perpendicular planes. The extent of tumor resection was assessed by comparing the preoperative MRI image with the postoperative MRI image taken no later than 48 hours after surgery. The EOR was divided into three categories: gross total resection (GTR: 100%), subtotal resection (STR: 80\u0026ndash;99%), and partial resection (PR\u0026thinsp;\u0026lt;\u0026thinsp;80%). All histopathological examinations were conducted in accordance with the 4th edition of the WHO Classification of Tumors of the Central Nervous System from 2016. Postoperative oncological treatment included the use of radiotherapy and/or chemotherapy. All patients were monitored in the Outpatient Clinic and in the Oncology Center and follow-up MRI examinations were performed. The length of survival was determined based on information from the Outpatient Clinic and telephone interviews with patients' families or from the patients themselves if they were still alive at the time of data collection closure (February 20, 2023).\u003c/p\u003e \u003cp\u003eData were analyzed using the Statistica software, version 12.0 (StatSoft). The Shapiro\u0026ndash;Wilk test was used to test the normality of the data. Analyses included basic descriptive statistics, the Student t-test, and contingency tables with the Pearson Chi-square test and the exact Fisher test. Survival curves were estimated using the Kaplan\u0026ndash;Meier method with F-Cox test for univariate analysis of survival and Cox proportional hazards model was used for multivariate analysis of survival. A P-value of less than 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eCharacteristics and overall outcomes of the study population\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEighty-one patients underwent surgery, all of which were performed electiv\u0026shy;ely. In our cohort, the median age was 61 years (interquartile range: 49-68 years), with a male slight predominance - 48 patients (59.26%) compared to 33 females (40.74%).\u0026nbsp;The median tumor volume was 35.28 cm\u003csup\u003e3\u003c/sup\u003e (interquartile range: 16.42\u0026ndash;62.37 cm\u003csup\u003e3\u003c/sup\u003e). Tumors were located in eloquent areas in 36 patients (44.44%) and in the dominant hemisphere in 38 patients (46.91%), respectively. Almost all patients \u0026ndash; 78 (96.3%) were independent (KPS\u0026nbsp;\u0026ge;70) with only 3 patients (3.7%) being dependent (KPS \u0026lt;70). The number and types of combinations of used TSS are listed in Table 1. Awake surgery was employed in 8 surgeries (9.88%) , \u0026shy;\u0026shy;IONM in 12 surgeries (14.81%), neuronavigation in 29 surgeries (35.8%), fluorescence-guided surgery \u0026shy;\u0026shy;in 30 surgeries (37.04%), fMRI and DTT in 26 procedures (32.1%), respectively. For further statistics, we divided the patients into groups: 30 patients (37.04%) without any TSS used, 35 patients (43.21%) with 1-2 TSS used, and the multimodal group - 16 patients (19.75%) with 3-4 used TSS. Gross total resection (GTR) was achieved in 39 cases (49.15%), subtotal resection (STR) in 31 cases (38.27%), and partial resection (PR) in 11 cases (13.58%). No patient died in the postoperative period. Postoperatively, 75 (92.59%) patients were independent (KPS\u0026nbsp;\u0026ge;70) and 6 (7.41%) were dependent (KPS\u0026nbsp;\u0026lt;70). \u0026nbsp;Data on \u0026nbsp;the IDH 1 status were available for 41 (50.62%) patients, with 35 (43.21%) having wild-type and 6 (7.41%) having mutated status, respectively. In total, 63 (77,78%) patients received radiotherapy and chemotherapy following surgery, 9 (11.11%) patients received only radiotherapy or chemotherapy, and 9 (11.11%) patients did not receive any postoperative adjuvant therapy. Seventy three (90.12%) of the patients died, while the remaining 8 (9.88%) patients were still alive at the time of data collection closure. The median OS was 406 days (interquartile range: 216-735 days).\u003c/p\u003e\n\u003cp\u003eTable 1. Number and types of combinations of used techniques supporting surgery (TSS)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cimg 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m9RE1+hz1naGz4NqWeFwTPispj+dPTNpAaUCOw1ru8PlhzWq4fb4/HXqc61pLaDUdtg8xpZl47RtAAAAaHBdwCCaP39++qmrq7W1VVVsPV1zc3PP+Pb2dvfZaD5No+/E5vWXV0Te5VWCXzdenT5X40+rTiqBWM+wrUtsvO1zbD06BupsvE1rNGzf+ccr3JfJkye7YZ/Np86WGw5rG/3t13J8tn5/unAbAQAA0HioqcRdoyaklSAkHequiYu9cEbjTpw44T7PnDnT9e15Qo2PzVPNQC8vphLYub5qZSvBnfu8bt061xd7yY72WTWS999/vxuWb775xvVnzZrl+kVoWbae5cuXu741L47VlurFSTt27EiHutmzk9r2ai9Ksum0L5quEli6YQAAADQ2gkrcVQpoLOgSNTE9depUOtTNgiwZP358+ukO//s8Bnp5tfiBmb2UyIJZqRa4FXXu3Ln0U9IrUJXwuPaXBasKYtUEVvsRBqgAAABoPASVuOv070Z8VotowrfDhmp9Hxro5RVx48YN11ctZFf6kh09p6m34A6E69evp5+636yrYM+eibx69arrD5SwQEDrGohaXgAAAAxvBJW4J6o1naxVk1e0pm+gl1eEXzNqLwrS+vR/OQdaW1tbT+CqbqCDSlGBgNZjVNM8mEE5AAAAhj6CStwT1QKr2bNnp5/i7Hu9AVVBmrpqgU3e5Q0U2xY9v2gBq55vtBrENWvW9PnXJSbWPLcav1lt2Iy37JtZtd0xtjz9j0y/UMBqYwEAANCYCCoxqKrVlqlJqF/rZRS0WDNLe8GN9TXe/vH/pk2bXF+2bduWfuor7/JCftPSWvyX8lhz3ueff971JXy+Mc+yFZyqy/r3JKJjaPumoNX+1YjmUfDaHxY4WjCpbbF/seLX7pZ5wRAAAADqSBcwCOzfT1gX/nsKn/4lhv8vMky4jPDfV/j/fkP/4qKWWsurBGe9vldXbbv9fwti/9bDH/b526pOw/72+NviL9fWHy5fnX/Mwm33169l+N9pODbO6Fj639mx1TaG+5HnuAMAAKC+jdCfSuYQQEF6SY2eKZRKEOf+ZQoAAADQaGj+CgAAAAAojaASAAAAAFAazV+BEvymr2by5MmD8m88AAAAgKGMoBIAAAAAUBrNXwEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQWkMHlQsWLEhGjBjR023dujX9pi/9Cwl/2lrdqlWr0jm7TZkypdf3Z86ccePD6STcLq1bYtMCqB9KF3TNK70A0JddI34Xu17Ce+5wvn8qb+Lvi/IIRWj+ovPUIx2HwT4PwrziUDnvtB3anmr5XKC/GjqoPH78eNLW1pYO5dPR0ZHov7CE/4mlvb29Z/z8+fPTsd10Ifvzqdu0aZMbH9KN8MSJE72m/+abb9y0165dS6cCMNzpeg5v8Pv27XN9Xf9W8DSYKKjCcDNr1ix3X/Tv3bpewqBJ/zNY43U/1vQ7duxIvxl+1q5d6/alDOUpPvzwQ5ffaUR+GqfjqHR3sPJTSs/1/6v1P6vt99q5c+ddSct92o5w/7QdonNhsGl/rTIEjYXmrwXoJjZp0qR0KJt/87JMY2trq+sbJfDNzc3pUDddhEqINN5fj5YXzg9geFPGI7Rs2TLX13fKPA8mZcIpqMJwdf/996efuqkwNiwkyXO/rmcKKJWnUIDdiJT/smDKKO+lgoZY+ttfp06dSj/1PvcGOy33KR+5bt26dOgOy28+//zzrj9YdE954okn0iE0GoLKnJYsWeK6PJSYWGD5008/9er71qxZk37qdv36ddePZfRUwgagPsRaKYjVwgx2JlABpTLhwHCmwla/cFYBBDUk3RRgK6As2hqrXiigjAVXsmHDBtcf6CbBYbptrc3uFp37qimNUZ5U2zKYeUnlXQcjWMfwcc+CSp38ylhZpwQgfFbCavmMPSOhvsSabtk0sfklXMdgmzhxouvrZhcmYH7wKRMmTHB9ZfZsH32N2nwFuBeUfvhpRTiclXn1pwmns/THKNOjYS1b6Zk/X1i45K8/TB/8+ZTO1JrWAkr1bR5j82mctkHLAoYq3UP9jKwy1bWaG+q8tvPcuv6ILc/fhljeRteXDcfyMuLPc+7cuXRsbdoeq6GbMWOG60uYxvjphLqs45aVrwr3y/YjNm14jGJ5nHB5msf4x0tdrWn9gNKmMSq80zmj9C9rn32x39dn22JNXtXXcNay/eOpLvwdYsI8czidjr0fUGr/NE247X5ab7J+33CdGq42bXgd2jziL0ufNa//m6FOdN1DbW1tKsJxXWtra+Y4aW5uduMqF6vr9FnjfDZfe3t7z3L8ZWi8TaNliA2H0+bhz6tlZ/GnqzV95aLsM632BcDdpzTBrkNdm+KnI/61aeMtHfHntetd/aw0TubPn9/znaVRYumfpXn6bNsjliZap+X642w9Wr8/Xuvz2fol3B9gKNH56Z+bdk5bZ9dPeI7bea3O2LC+K8quZ0sL7FpV51/D/nWvTuvyx4XrtvG2XD9tCPcppOOi6fw0wvjbZ8vJsx3+9vrHXeNtGlu2rd+W708jNp2/H7Zs22bbX/8Y+vkjm9fG+cvS+vxpY2z5lqZmCbddbFjf+Wydtg/V+Ntnx9P/bXw23o5FbD3aFtsnf1rRZxvvHyex8Zo/9vvab2mdluWPs/Vofn+8nbdi67djHe4P6sewaf568uRJ1z906JCr4aucjG7YWAlZ5SJzpVBWOueXVunlOKJprL175cR3/cFUOc69SnBEbc5VYhNS84nKRZ8OdbMSH0p1gHvH0g8r5RZrRiX2kh1Lc6zlgZw9e9b1yzxbo9Juq3WwZy6VRigNtFJgn74LmzjZsz611m81mFqupq1kFNwwMNSFeYJ58+aln3pbvny56/v32Uom1/XtuyI++ugj17e0wFonSVbtYiXz3edatDRC/Bogy8v4rZpqses9Vhvos232H+2xdE7y5Kt8SqeU37H0Z+7cua5vx9WOs6VjPqtls2f+bN5t27a5fihsuWVpl+RJZy0PaHnLLAN9vsTY8fKPi38OWPpvx8J+V53zli/Ms8+hor+v8st23Iyd49XWb9PYfuhctmOI+jJsgkq7QehkV4AVNh21hCGWiFoTBEt0aiW0g8HeRBeKbYsSSyXMoTAwBXBv+Dd1M3v2bNcf6OvUz2yOHz8+/dRNb4YeSJZxUgZP+6iMAs9zYzhQnsAvBNG1GTb1Uwbcrtkwcyx+Jj0vC34GMl+R9cKXvMo8k23plj9vnnyVzw8ULLj0j7lRuqLvLTD0l+UXxkmtoK8sC/6r/eaDcb5U46fv/ns4LF32CywGQtHftyy/Cbby7wqYlX8vc25jaBs2QaVOQL+kyNplG7vw7RkhP2P3888/D+iFX4SVBIkuICWkfgKrz3bx+tOKpg2Dy1jNBIB7x9IWlfbrelWmTDdp//mW/vAzF0rXlL5ZAdlAp2vK5FnaqbRJ6xrIzAUg4fNxWV3s+a9qFKyoFtD4tVdy48aN9FO2PNP4FDhZgKRtzqrlKaJMUDhQwvyJZOWr8shzPP1lWcssO47+9txtg3G+5OWn7VbRMHPmTHdswvO6rIH4ffNQ3tcv8NFvO5CFMBg6htXbX3Vh+c1VlfiEmSpdFBaMWZf3ra2DQdsXZsp0gfkJpX/xxoJG7YOxN8QCGBr80lbLLKsJ12A0rdeN2U/brKR/IClD62fMeT08Bpplkmt1Zc5vBXlZTevCmv6YPNOElEHWda9r3r92hiM/sDD9yVf5xzNPIZiOX7iue2Wwzpc8/PuKjpvOL6XFyjv6FSwD4W7km6122s4v7UdYkYLhb9gElXby6UT3AzIrJbKLTN/5CZeCNAV1ukDtZL7bpYCxdvf+9vhNA7JqN2z/VFIF4N6yNMS/uSuNshJkZWyzCoDC/69XizWrFb8prJS5KfuZlZAtT9vvlyznyQwCQ0XYssn4990YfWfXhxUQ1brGNJ3yHZpX+ZPYvw8ryn8etMy1V6YWyPJV/rpr5avy8I+50sfY/vh5IL/pr5RJ46TWMfB/p6w0scj5MhD8Wk8/3bdtUGGJ1peVhy26LQPx+/rCpstGy7IKE227FfpwX6k/9zSo9BMS47/4wqeTz5rC+BeOPRzsz+cnQnrmyKaxB9B1AdkF48+nKvlYTWF/aX26OfnUplzjVSoXJgSaNrzAlRjrQrR9AXB3WVqha1PXrvgFRuGzP3kyl5rGv+HGKKNqmQqlUZY2KJ3znysvwzInlmZqH+yzlcAPdMYJGAi1muepljMWENiLdeylIWKf7Ttdk1ZApO+qZX5tOlNt2rz8/2GtlxOK/8IarbNasGXPedYqQLc8kR9A+C+LyZOvyiP28h+xfJHSFws0tG+WHqofe6lPUfpNwuNlv1NWrbbJc76E7P6Ql72Uxy80tJpC/7cRDecpNFCAWu0ckYH6fWNUqKrfz7ZfFSb22Z4NtfMUdaTrHqsEVe7VwtbFhqVy4fd6tbO6yoXrvjPh9+pCbd6rs9XZ+mw9eVRuVL2W4XfhNs33Xt8cTqvt9Wkfbf5wHdpuAHeXnx6FaVN4TYZpi65lXf827Kcx/rIsjdD1b+Os89OTammCP16dv15/nAnTSqNtCPcDGEp0Tfjnp7pq90f/vDexZfjXmtg1pGuimjBdEP9a1bbF8iaxa9RPI8JttPXE9ifkzxvul5/OhNse5kmkWr4qa79iqi3HhGmgf+xjxys2zuePD/fNfqPYPodqnS+xfVNX7bz0z5HYOeTz91Ofw+3xtyU898SfVp3/G1X7XcJ7gbrYMff30/8N7ffTOjSNP6//26J+jNCfyg8MAAioBNleGFG5KQ74cyYAMBgs7QrTLdVIWU1bJbPfkK2fVGOm5xMrQc6gPJeeh2obK8Gg+0w2HPViWL2oBwAAANXpuejJkycP2Fuo64k1x71XASVQrwgqAQAA6oyeqVRgWebFPfVK7+bQc5tWSwhg4BBUAkCE3/RVVOJvLwsDgOFAgaX+xZHSLr/pq6gJaK2XudQTpel6KZCam97Ll4/5TV9FLyyq9rI2YLjgmUoAAAAAQGnUVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaSO6KtLPvYwYMSL9BAAAAABAtzCEzAwqAQAAAACoheavAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoNJz7dq1ZMmSJe7fqYwZMybZunVr+g3Q7dixY8mUKVPcOaL+7t270296u3nzZrJ+/Xp3HmnaVatWuXEY3vL8/pcuXXLfZ3W1lDl39L22J0yztC0LFixwy9H3Gs6i9Zw5cyYdAgAAyI+gMqVM2bRp01xGrrOzMzl9+nTy1ltvucwdIAooPv744+Sjjz5Kjh49mowePTr561//6saHnn322eTkyZPJ+fPn3fn03Xffucw9hq+8v78CzaampqS1tbVXN3/+fDe+ljLnzurVq5OOjo506I7nnnsuue+++9z/klL69vTTT6ff9LZ///5k4sSJyaxZs9IxAAAABej/VKKrq7m5uauSSeyqZOLSMV1dbW1t+h+eXe3t7ekYNLJdu3aln7pVMvHu/KgECumYbrHzxqatBBfpGAw3eX5/jdPvH1MJ6jK/M2XOHW2XvgunuXjxYq9lqa9hjfdpODyHAQAAiqCmskK1lDt37kzmzZuXjB07Nh2bJDNmzHD9ffv2uT4a28qVK9NP3SZNmuT6kydPdn3zzjvvuFosv9ZH02q6Dz/8MB2D4SbP769xakIfUtN61Tw++eST6Zi4oueOmrN+8cUXydq1a9Mxd/z73/9OP/Xmj1fat27dumT79u3pGAAAgOIIKiu+/fZb13/kkUdc31imUU3RgJCeP1MA8PLLL6djujPpCh6sQMKnZ9o6OjpcgIHhL/b7Z/n666+T5ubmXoVWoaLnjqZX89ZPP/00HdPb7373O9e/ffu268ds3Lgx2bBhQ9XtAgAAqIWgsuKHH35IP8UpMwcYZeb1QpRFixYlR44c6ZUhv3LlSvop240bN9JPGI6q/f5Z9uzZk/zpT39Kh+KKnjt6jlLLzVr/1KlT3XOUeg5UPvjgA1fjabWgPEcJAAAGCkElUNC4ceNck8Fbt265wEKZczSOor+/ahdVMLVw4cJ0TP/pZUBz5sxxgWM1Cjp//fVX9/ZXbcPnn3/uxqvZ7OHDh3uazWofVBuq6Xg5GQAAKIqgEiioq6vLZdD1Rk8FFvy7kMZS9Pc/dOhQ9DnLshQQqguf8YxR0Hn8+HG3zXqLrAWh/nOUCnqXLl2abNq0yb1tVs+X8++UAABAEQSVFRMmTEg/xakJGeDT87aq5bHAwpoujh8/3vWrefDBB9NPGK6yfv8YvWCnVtNXyXvuKCBU4KdaRb8TfafP1f7fpGoiX3zxxZ5mswp6RYGvxumFZbxQCgAAFEFQWWEvxrhw4YLrG/tH4dOnT3d9ILR48eL0Uzd7U+e5c+fSMXdonL7L8wwehofw9w8pDfnll19yNX3Ne+4sX77cBbNhJ/pfmPqcFaDa/9T0t+fUqVPpp256YRnPkQMAgCIIKiuUmdObGfWWV78Z23//93+7/po1a1wfCP3rX/9ybwD1ax/VjFC1V35tkYILjdN3qB+x39938OBBl7ZkCd8EnOfcUY2iaknDTubOnes+K00LaV3vv/9+snnz5nRMN83jU+GaAlgAAIC8CCpTFjjqFfuiTN1rr72WtLS0RDNoaCzKkI8ZM8Y9P2eBgM4RZdI/+eSTXrWPyvSryfRLL73kCik0vf71g8YN5LN1uHuK/P6+AwcOJM8880w61JtetqPgTX0zmOeOtn3Hjh3p0B1W26qX9Wh9Klx7/vnn3TgAAIA8CCpTChxPnz7tMlV6JklNzN58880+pfpoTDo/9KyZnmVTIKA3Ze7bt89l0mNNG/VyFDWb1ptCFRBoXo3D8FT09xdrPp/1htbf//73vfpmMM4de44yVkCmcUePHnX/r1L7pppVq/kEAADIY0SXXgsIAAAAAEAJ1FQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAA3h5s2byfr165MxY8YkI0aMSBYsWJBcunQp/Xbomj59evoJAIaWY8eOua7e7N69Ozlz5kw6hDwIKgEADWH16tXJhAkTkl9++SVpb29Pzp07lzz99NMuwFSnoLOWKVOm9EyvTpkOfzjsFLju378/nfsOjY9NH1LQq6Aya3rr9P2qVauimaBa8/qdbN26NfpdrCPTBdQHBVG6potQId3t27eThQsXpmP6WrJkiUuD8lAarHTM0hfNl6fgL7YOf1kqSIylw0bfKd3zrVy5Mrl8+XLV+dAbQSUAoO4pY3LgwIHkoYcecsOzZs1yweW3337rhmXv3r3ppzhlLjo6Otzn1tbWpKuryy1H/ZaWll7j1SlwVcZm6dKlLvPlO378eHLx4sV0KEmOHj3q5gkdPHgwWbZsmZte6x49erQbr2XbejR+7ty5bvueeOKJPuu67777ek2vz+Jvq5Yxbdq0niBx165dPd+pk/nz5/cMd3Z2Js3NzcnZs2fddwCGL6WPf/3rX9OhfBSEigK6LJpG6W4eSistMFT6om7SpEnJnDlzqgaWWet49913k5MnT7rlvPnmmy4dvnbtWvrtHVr24cOHk7Vr16Zj7lBg+dFHHxFY5lW5OQAAUNcqQZIio65KQJWOuaMSTHVVgjXXVTIg6di+NN3kyZOjy9GwxlcCtXRMNxuvLrZsLVPfZakEcumnbhqOrV8qQarbh3A72tra0k/dqm2runB60fThtki4DADDi9IlpUMtLS1V0yJfR0eHm7Zaeqn0SGmGdbVo/Uq/fFq+xmXNX20dms9Pn7S9ug/4tHzNV20/tK9alvqojppKAEDd++2339JPfY0dOzZ59dVXk1u3bmXWVqoGrxJQuuavRagm01y5ciX9dIfWnUUl6I8++mg6VNvUqVOTI0eOuM/r1q3rKZWvVpPg07aqyzu9xEr3AQwfeizgvffeS0aNGpWOqU0tMyrBWGb6pVrH5557Lvn000/TMbWptnHGjBnpUDctX+nRiRMn+tRW1lqH0vNQeB/YuHFjsmHDhqrpsGpLlfZv27YtHYMsBJUAgLplzzwqyBI1D9Vw+PzMihUrXNPSt956y2VWQps2bUpeeOGFdCg/a06qZfsBZh5q+vrMM8+kQ/loHWrGKl9//bXrA0CMmo4+8sgjhdImFVYpAFST+ywWqFYL1kJqgh9LeydOnOj6//u//+v6ptY6lOZWK0xUk1YtO8++67l2TR/bPtxBUAkAqFvKMHR1dbnnB6U9fbYwrGGzEnGVbofBmJWQF814KROyaNEiN7xjxw7XL+L77793tY9F2dtiqz2HBKCxKX04ffp04dYGesGZPPzww64fUqCq5yCLpJeiwrDz589Hn3uU//mf/0k/5VuHnvlW8KtAUNPL4sWLXV/7nvUcZYyCT90b/Gfw0RdBJQAAFWvWrHF9NYfyKUMSjsuiGlHVhKq5lF4MoYyNSuCLNCkVZXqKNH31Wcl+VuYMQGNToKW0avv27emY/K5fv+76I0eOdH2fBap6wU1Rf//7312/qampJ+3Svyr57LPP3Gd7yVredbz88svJvHnzknHjxiVvv/120tbW5pqyhvuu5akgzt42G6uNtAD6hx9+cH3EEVQCAFChDIcFgfa2P2Vu9AbBvKXuqhFVTaiWY7TcohTIFm36an766SfXL7NeAPVPzxIqrSrSPNWcOnUq/dSbgjG9ZbVMoCr6tyQK/FQjqEI5BXr6dyVKj+XBBx8stA7tm1qIKD2+evVqT8Ge3grrP0epfyuldWk6efbZZ13fFwug0RdBJQAAqbC2Ui9n0POURb3xxhuuOdeWLVtKvY7+u+++K9X0VTSvzJ492/UB1Dd7dtzvsv43pKbduXNn8sc//rHX9PbcebV5q9FLztTcVDWD/nL1kh11+hw+yx5S4KcAUAGepWMKMlVIpyCwv+tQzadYIaGOhYJW/dsmeeqpp9xyaOVRDkElAAAp1e7prYbKaKi2UBmbok1XRRmgPXv2uJdFqBmsmljlpYyPmm2VoUySnkvSep988sl0LIB6Nn78eFfz6HfLly9Pv+0tNq06pXuiz1nzStYLembOnNlnmepU66hOnzVNXqqVXLVqlUvLVEgn/VmHAsX3338/2bx5czom6fN/dq2J7Y0bN1wfBXUBAFDnKpkN93/KYv/fMfz/ZvZ/HCuZmT7/s1HTxpZj8+h/rfk0vy1L/1MtFPs/lc3NzdFpJWv94v+fytj/mjS2rTomeWn68DgBqB+WRtZiaVq1NMandCOWdnRU+b+P9r8zs9LNUNY6fPo+XKelhZae2v8zDqezY3P06NF0DGKoqQQA1DWVeF+4cMF9vnz5susb1QqGzZ3UNKqSAXGf/do+LUdNsyQs4f7qq69c3942aFTLqaZbasKltxX6r6VX7aVqFcX+9YhoW2JNXzXe3rzo03g1+dLytZ5KZq9q7eq+fftcXy/A8Lc1izXfpVkYAPtfkvbCnjKU9qlmMUynlL6ohcgDDzzg0jK9kKfsYwC+9evXJy+++GKf58yV1ms7lCYqLfziiy9c2h9OZ/+a5LHHHnN9ZEiDSwAA6o6VRIddbLxf0q3v/Zo8K6kOu6zl+/Naqbv/vdblD1unknCVloeyprdO36uWtFrpf55tDcWm948TgPpgaVweTU1NudMBTRdOq3RKtZB+yw5No/UrrVQaqHQzr9g6jNLUsAWJTzWhtm71Y+vVNqkFCaoboT+VAwkAAAAAValGUTV8lQCs1BtkhxPtayWodK1KeKN2dTR/BQAAAJCLgqtdu3a5f89R7/QGcP1rEgLK2ggqAQAAAOS2cuVK1y/zL5OGC+2b/jVTmTeANyKavwIAAAAozP7348KFC12/Xmi/Ro4c2fM/LVEbQSUAAAAAoDSavwIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAABAVceOHXNdvdm9e3dy5syZdAhlEVQCAOqSMgkjRozo6RYsWJB+09vWrVt7TRfrsjIc4XRZ6wCAe+XmzZvJqlWreqVTRYOo9evXJ7dv304WLlyYjkmSS5cuuWXZcrWOa9eupd8Ws2TJkmj6OWbMmJ7lh53tg79/mn7//v1ufIy+U5rvW7lyZXL58uWq86G2EV0V6WcAAOqKMhuHDh1K/vrXv7rh5ubmZMeOHe6zT9MpQzNv3rxk8+bNbpwyTM8991xy/vz5ZPTo0cnp06eTqVOnuu98yogoQ6PpJk2alI4FgKFh+vTpydixY5O5c+cmP/30U7Jz5043vr29PZk1a5b7XI1q8q5fv96TNoqCx2nTprlgcOLEicmpU6eSEydOuLTyxx9/dOvLS8tXGj1//vzk+PHj6djutPWdd95J/vKXv6Rjumkf9N0vv/zihhXwHjhwIPn222970vuOjo4+6bHS9DfffDMzeNQ9YPny5W6fUIKCSgAA6lkls6ICVNe1tbWlY3trbW3tqmSy0qFuGrb5Khmors7OzvSb3rR8ABhqlN7t2rUrHeqmYaVpTU1N6ZhsleDMTRumfc3NzV0XL15Mh7ppeZo2XF81WobST+t8SpNjWlpa3PpNJZDtNW1sG7T9Wn5WGi7aVy1LfRRH81cAQEOoZDJcKfrSpUsLNf2qZERcDadqIp999tl0LAAMfaphVPNOn4YnT56c/Prrr+mYbJUAzqWBYc2jaifDlhtbtmxx/d9++831a1ELEbUG+fTTT9Mxva1duzb91JtqJf/0pz+lQ0ly69at9NMd4TZs3Lgx2bBhQ9UaVNVs6rhs27YtHYMiCCoBAA3hoYceSj755BP3edGiRa4pVF5qMqumXmrepaauADAcZAVmU6ZMSe677750KE5NXBXAqdlsKLZca246atQo169l9erVyXvvvVeoqayl2/6znSosrBbIqrmrguA8TX3VVFjTK+BFMQSVAICGoYxIW1ubK9lWCXmRjIOe9VFgqeeRsp7JAYChTumeCsheeOGFdEzcuXPnXP/hhx92/Vr0ZlgFeIsXL07HZNNzlHPmzMkV6PkOHjyYNDU1pUPd1JJEwa/2S8sV2wYFoYcPH84MrkMKPnV/0POZKIagEgDQUPQSBmvOqpLyvFSavmfPnp4mtEVqOgFgqNDLbBSY1Qro1HRWRo4c6fq1fPzxx+5FOLVqHpV26sVnYbPcPBQ8PvPMM+lQt5dfftm9ZG3cuHHJ22+/7QoOVWuqIHPdunXJ9u3b3XRar2oi9ZZYvZQnVqhoAfQPP/zg+siPoBIA0HDUnFXPCSmDojcH5qVniI4cOeI+q5S97OvzAeBeUJr1xRdf9ARa1eiNrnmpllL/zqNWoKhAToFnnvWH7Fn48FlOBbFK07u6upKrV6/2vL313Xff7fUc5dNPP+2CSk0nsWfk8wbQ6IugEgDQkPRyCDVn1cslijRnVem+NaFVaX+stBsA7hYFW/7/b7SauJDSKr14R2lfkecYa1EN4Jdffhn9d02hvXv3usI81Sr626vmuOr0Ofw/kmbfvn19mr5mUZArVhurY6R/M7Js2TI3/NRTT7n1UTA4cAgqAQANSZkqZW6sOeuFCxfSb2pTSbgyZ0Wb0ALAQBs/fnzS2traq9P/WwzpDaivvfZa7oAy9oKekNU8vvHGG+mY6mbOnNlnW9Xpravq9FnTxKjwL2z6GqNA8f333+/1fzXPnj2bfuqmF7fJjRs3XB8DwP1jEQAA6pj+P1n4PyiN/k9aJbB0/9ss9n8qNW8W/a80zVdtGgC41/S/HcP/K1mL/sel0jf1Y/Q/H5UGVvvfj5Ln/z4qDa2Wjh49etT9r+A8tJxwnfY/hy2Nt//VGU5XCWrdeK0PxVBTCQCoaypJ13M2ly9fTsf0pudzspptaR7Nm9XEVaXzakILAEOR0i41hVXTTzX3VNNS6/Tvkao1/Z8xY4br2wt7fGry+thjj7mWHmrS6i9XLTnsRWbqqwbSnnMsS81r9cbuWvSM/Isvvtjz702MmsFqO9SEVsdEz5VWgs8+09m/JtG+oZgRiizTzwAA1BVlcPT2P1/WbU/TqtmVPYOjZ3t8apYVey29MihqAsu/GQEw1OjFNGqmH6OA8Mcff6zaHFbB4K+//ur+pZJR81IVpum58hgFaza9Tas3bvvNUUP2DKi/Hp9eAqT9CINAn56j/Mc//pG5HgW4uh8ouNY2xp4t1fFSl+f5UPRGUAkAAACgDwWFquHr7Owc0Jf7DEUWANcKXhFH81cAAAAAfSi42rVrl/v3HPVu27ZtroaSgLIcgkoAAAAAUfa/J+u5ib/2bfbs2f1+9rOR0fwVAAAAQFX2vx8XLlzo+vVC+zVy5Mie5+lRDkElAAAAAKA0mr8CAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAQL/s3r07uXTpUjrUeLT/Z86cSYcaD0FlQBfDqlWrkgULFqRjgDuOHTuWTJkyJRkxYkQyZsyYZOvWrcnNmzfTb+/QuPXr17tpNK3Oqdh0GF7y/v4+fa95NG1R+/fvT5YsWdJzHvmUVimd0visc8yfRttQ7Wav+evxZugfo2pdbN/1e/vHX52G9btcu3YtOo9+ZztH7He39AAAhgKlSUrHlEZVS/eLTKe08fHHH0+mTp2aju2mtFLpoNLRLP69VX0FZ0VoGy2Nti6852r7p0+f3vO9Pof71N975sqVK5PLly+77WlIXehx9OjRrpaWli4dlvnz56djgW46P0aPHu3OkdbW1q7JkydnnisaN23atK6Ojo6uzs5O91kdhq8iv7+vqanJTad58tI5o+Vqvubm5q729vb0m24XL15027Jr1y43rPPMzjHNazSs9Yv62uaYtra2Qts33Oj46HjpeIZ0LHWc/GOsY+j/bprG6HPWb6rfSuuxZWk5OrYaxz0FwFCg9FD3DqV7SsfC+4vJO50oTdQ9MqT0UulkVvormk/za/n6bOuLLS+L5lEa63f+vVDboWXaPVP0WeP89F3L0baI+mXvmVq/pmk0BJUROsl0QgC+MJHSZwss/ERJCYnG+QmwEmeNq+eMe73L+/v7dNPSb17kt9dydWPTTThruf6Nz+h889djN1E7D+37cJkaDpdVj/T7af9jdGz869WmrZYpUADp/6Z2vGPzaNncUwAMJXZv8tO+mFrTKc3TPamaaumvH+iJ5Zfy3pe0/nAZIRUGx7ZR9/DBuGdaQab6jYTmr0AOar6xfPnyZOzYsemYxH3etGmT+/zvf//b9eWdd95JKolJMmvWrHRMkkyaNCmpJF7Jhx9+mI7BcFLk9zdqNvPFF18ka9euTcfk8+yzzybnz59PTp8+3acZkWhb9P0jjzySjumm803n2FtvveWGY9sk/ng1WVq3bl2yffv2dExj0rGz61XNrk6cOJFUgkbXnCvLG2+8kUyYMCEdunNcr1+/7vo+LfvRRx9NhwCgfqgZ6F/+8pd0qDg1GfUpvyS6n9Wie9iGDRuS1157zaXX1ZroVgI8N73vl19+6UnHB/KeaXm+bdu2pWMaA0ElkIMSiFgG8/7773f93/3ud66vBEcZ/hkzZrhhn9rnK1FTUIDhJe/vb3QePPfcc8mnn36ajslHz2FYQBMLKOXGjRuu/9tvv7m+T+fYrVu33Pptm27fvu36MRs3bnQ3ZD9YbjR6lsf39ttvu36Y0QnpmPnnhAX1ynDEnp/dvHlz+gkA6oPuWbrnzJw5Mx3TfwoMVTD/8ssvp2Oyffvtt25abcOBAweSJ554Ivp+gWeeecZNo+cl7TlJPeeuNNzS8YG+Z+qZTR2fcFvqGUEl0A9fffVVMn/+/J4A4MqVK65fjQUFGP7C39+sXr062bNnT+Fg7aOPPnL9iRMn9rwsQC838F/y8uCDD7q+bqBZfv75Z7dN06ZNSz7++GM37oMPPnBBj9XI6Wan9dhwI1Lm5YcffkiHumuXVfAjWUF9NZ9//nlPYKkAv2Ff1gCgIXzzzTeub/el/lDwpQK5RYsWJUeOHMl1/1y4cGHy3XffqV1t0tbW5tLfnTt3uuDPp/Rc36vQf86cOS6QVA3ljh070im6pxnIe6amVSCrwLdREFQCJSkBVMa+tbU1HYNGkvX7q/mkblplghLVUqrUVTc71XJ2dna6m9+WLVt6AkvdaFtaWlzwYyWy6nTDO3funJvG1q3A9tdff3XBqaZX0CMKng4fPtzTNFfzKgjSdPX+llLto3Uq1fZlNX/y+fNbZ02udNyVgdA5oWZVS5cudcc1rA0FgHpgLa+KFqDGjBs3zhXIKRBTYFm0UE73SqW/CgwVWIZvbtX3SputVlPf697pG8h75sMPP+z6fsFl3et+tBI+HRZeqoBa9OB3+FIOe7A7dv7Yg+q1HorH8BD7/fUAv17gEtLvbi8DyGIvCYidO5PTFwL5LwrS+vUiAI3XSwPsTXa1XpggWoctq3LjdPNpXzROy6y1rcORXX8+7bv/G9r1q84/1iE71vpdsqbTeP1GtrzYeQEA94rSeaVNtfIk1aaz9K2WWPobozTZ1qd7UbV0OIvdS8P7mNJ6pcNapu6Zmkb3yzzrKHPPtPtJ7Lt6RU0lUIJKqVSbZG3xzfjx49NP2QaimQjurazfX6WsKiH1a7HU2Xf6nPUiAXs+M6ZyA3R9v3m1ntFTbVglHXfbY6Wyr7zyiutnUanqiy++2FOyfOjQIdfXvmjcvHnzGuaFUuGzsv61Wa3J0kMPPeT6KqnOKqHXeP1GlQxOT8l5tZdIAEBRai4a3m9iz3QPF0qTVRtYCcRcjWKeR4pC1ozVp9YiehZSzV2VNuueqXcXqDns3r1706niuGfmR1AJFKTMu54jiL3Iw974Zc0QfRqn77IyoRgeqv3+ekOsboZhJ/Pnz3efswoedF6o6evVq1fTMXeMGjXK9cMXAhkFKwpatI4w0PVZM0w9h2JOnTqVfuqmt8qq2U8j0m+gjIa8//77rp+XfgNlVELK4Pz97393n8+ePev6ADAQ9IKc8H4zkC/NqUX3nMGwePHi9FN5/rYpPVchoE8BpqYJ74E+7pnFEFQCBSigOHjwYK+Hu0P6NxMqYfNrJTSfxtm/oMDwVOv3V0CnUtawk7lz57rPKngw4ZuAX331VXdzCmu0Lly44EpeY89papv0/Im+r/a2Wa1LN9bwLaTaLp/WpcKPRqV/FaL91/OtRZ8v1b8TqsYKBwBgIOilMeH95m6+fM3uZwP9Vvt//etfrpA1bNmVZz26J6qA0L9f3nfffdEC22r/6qm/90wrRLRnKxsBQWVAJ6PYyy8Ao1qIp59+2mUM1bzE7/SmTqPAQhn8l156yZ1DSpj07yU0rlotEoa2vL9/Xnqhj25E6psVK1b0nDt289T3J0+edC8Q8CmtUtDzxz/+0f0Lm+PHj1etBddLfWLBsJUIa/+0Tq3r+eefd+PqhfbLWg/EahN9OoY6Bvod9IIk/bb+i3Z03PXW3xg1pQqnVwHB66+/7pY3EKXvADAQFAyJ3hZeTbXpZs+e7frV3mqvfJAFdHZfMxrWG851f7LvlGYqmPvkk0963dNi90zNqzTXn1ePmoQFrC+88IIrsPX/3YjSabXwUdPWmP7eM+3ffj322GOu3xC6H62EzE8fJPY7XqoCOXr0aJ9zw+9agwex9fC2HgjXd3qIWy/syPMwOIamor9/KDaNLVN9n3/uqNMLBfTiAZ//XfiyoBidf+F6fPqucrN2y9S09SSWrqvLQ8dWx1jXsM2nz1qmXtajFzYY3St0HO1lTTaPjivXP4Chwl4g43dK00J5p1Nal3UP1PhwGeG09tIcdUovlX76aauJ3TP9l6FNmzbNLTsrrdX+aBp/+qw8/kDcM7V87UsjGaE/lYMCAAAAALmpxk5N//X/ItFNNZhqnaLWK/4jL/WO5q8AAAAACtNjPWqW6jf7b3Tbtm1zTWcbKaAUaioBAAAAlKLnFFevXp289tpr0RfKNRJ7br8R36FBUAkAAACgX/QSnccff7xhA0vV1o4cOfKuvoF3KCGoBAAAAACUxjOVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAFDIzZs3k927dyfXrl1Lxwxt2s6tW7e67cbAI6gEANQtZSBGjBjRpztz5kw6RTdlMjTt9OnTe6bR5zADovn85SxYsCD9prfYeo8ePZrs37+/Zx3q16JMkL+MrPUBQBHHjh1LpkyZ4tIV9RUcFnHp0qVk9erVyeLFi5NJkyalY7vTvjFjxvSkcWFam0Xr99M6v/PTPX+7NT4rQNT48Htt54oVK9x2Z82HfugCAKCOdXZ2dk2ePLlLt7yWlpZ07B2VYK9r9OjRXfPnz++6ePFiOrZ7/LRp09x3/ngtb9euXW556pqbm9NvetN0mj9cp5Zr87a3t6dj47TsvNMCQB5Kg5qamlyaYumc0hh9zsPSto6OjnRMN6V1ra2tbrltbW0u7VQXThej5Sm90/x+p7Rb6a1oOVqehi1dz0p/NT4rzdR4rU/LwMAhqAQA1D1ldmKBmYY1XgFljGVcwsBSNI8FfMpAxVgGy6dhmzdrvWLrtnUAwECwIM0oWFMao0AzDwVsYWGZ0qswHdSwlhuuL6RgNkxfRcvU/BaUWmGeUfqqtDmk9eq7amL7gP6h+SsAoO6NGjUq/dTb8uXLXb+SAXH90NixY5NNmzYlt27dStatW5eOvaOSyUkqmZpk6dKluZt5ydy5c5NKQJmcOHEic769e/cmf/vb39IhABgYK1euTD91s+arkydPdv1q1Ox1586dyf/9v/83HdNNaeWSJUvSoW7333+/6//+9793/SwLFy5Mpk6dmg7d8fXXXyfTpk3r2b7ffvvN9X1Km33avsOHDydr165Nx8T96U9/SrZs2TJsngcdDggqAQANSc/mdHR0uIxULENjLKOkADDMgDz00EPJJ5984j4vWrTIZWjy2rBhg+sraA3peZ8PP/zQPa8EAINJBVsqHHv55ZfTMdns2ctZs2a5fjVnz551hWcKGstQcPjKK6+kQ3cKB6s9R6nCv+3bt6djsv3hD39w/UOHDrk++o+gEgDQkH744QfX10sfarES/HPnzrm+TxmmtrY2V2L+3HPP5X4BhDJlWm4sWFVG5/nnn3el/wAwGJRW6cU6KhA7cuRIrvTm5MmTrvawGqVnq1atSt56663k008/TccWo207cOBA8uSTT6ZjEvdZwa/SR32vgrfm5ub02yTZuHGjK6zLsx9W+/nZZ5+5PvqPoBIAgBos8Lx+/brrh1SbqczN+fPn3ZsF87Jaym3btrm+2bNnj3tLIQAMlnHjxrmaPRWIKbDU26lrUeuOakGbaj1VWKYmslruY489VqgFh1HT16ampl7rUiColiFvv/2223YFt2+88Yb7Tts+ceLEnhrU9evXu7fQqsvaL82vNBsDg6ASAIAarPbx4Ycfdv2YHTt2uKZeKl1XhiYPBaOWAbPaSvu3I9RSAhhMXV1dLkjUM+UKAFW7WK2lRZ7nxhXUabkXL150QaGWH3sevZaPPvoo+fOf/5wO3aGWIVevXnXrUFqpdFJpp/8cpcYrTT19+rSrgc165p00dmARVAIAGtLMmTNdP9akNWSl2fYcThY19VLpt14AkVU6HgprK9V8a82aNe4zANQS/l9HdXmp9k/BmAWWV65cSb/pHz2nrjTQXkhWhIJEzeM3fa1GwbDSXKOAdMaMGW4bFOSqyey+ffvSbzFYCCoBAA3JnmlURqpaCbxe6CPKHNlzOFlU8q2aSnsj7IULF9JvstlzQipZVyZs3rx5NdcDAEYBYdgVleelYNa0tAh7w3YRsaavWdQq5MUXX+yVZoZBrALM8Ll1DDyCSgBA3Yu9il5Uoi0vvfSS64fUFOz11193QZ+at+ahzI2aXWkeBZi1KOP06quvus8qcaeWEkARqmkMu6L+9a9/uTTrwQcfTMfEqSBOzU/z+uc//+kK5ELVgjw9U/5f//Vf6VA2K/AL3y4brk+tUWIFdQo+a710CPkRVAIA6pq9RVD0inufSt715lY996PnGP0aS2VYFixY4GoyFST6mRItUxmry5cvp2N6U7OrrCD0q6++cm8c9J9d0kt5lKFTibq/Hv8FF3meZwKAahTM6eU1KsCywE5py/vvv+9eglOrdlAtKZRehpRearl6m6ylbWp5obfFhmmhPUsee4GPtknLr/VvSDSdtnnz5s3pmDtUO6pAUsvXdikNX7ZsWfptN9tG7Q8GSBcAAHWqtbW1S7e6sGtvb0+n6FbJxHQ1Nzd3VTI6PdNMmzbNzd/Z2ZlO1S22zCya1talfjifvjf+tDJ//vw+02scAPRHU1NTT5qiNE9pn9LAPC5evOjmi6WhSjNtuVnpp7S0tHSNHj06us5du3a57alFaWG1bda6tQ51bW1t6dg7jh496rYz736jthH6UzmoAAAAAFCVajnVsiJWSzhc1MM+DDUElQAAAAByUdNRPRqgxwpizyoOdWo6qxcBHT9+nH8rMoB4phIAAABALgrE9DKdlpaWXs+GDwfaXv37JgLKgUdNJQAAAIBCFKAdOnTI/Vuk4VBjqRpKvcBH20tAOfAIKgEAAAAApdH8FQAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAN58yZM8n69evToeq2bt2aTJkyJRkxYoTra/jmzZu55weAoWz37t09adyCBQuSS5cupd8A+RFUAgAazqZNm5KdO3e64LCaVatWJW+99Vby0UcfJV1dXcm3336bTJgwIXnggQeS77//Pp0KAIYnFZK99tprPWncpEmTkjlz5iTXrl1LpwDyGVE5gbrSzwAA1D1lliZPnuw+t7a2JmvXrnWfQyqt/+Mf/5i0tbUlS5YsScd2U02nAtPjx4+nYwBgeLG0MEwHVWupjvQNRVBTCQBoKNu2bXOZKFEtZJZ///vfrn/9+nXX982aNSt59NFH0yEAGH727t3r+vPnz3d9M2/evOTEiRPUVqIQgkoAQMNQJunkyZOuVL65uTm5detWsn///vTb3hQ4qhR/3bp1rolYaPPmzeknABh+lBbK1KlTXd9MnDjR9c+dO+f6QB4ElQCAhqFayueff959XrZsmetv2LDB9WM+//zznsBSzcGyAlAAGG7Onz+ffoqLtdIAshBUAgAagl7Ko6BwxYoVblg1kWr21dHRkRw7dsyNC6kEXy/nUXPZX375JVm6dKkLLrOmBwCgERFUAgAagp4fUpPXsWPHpmOSZPny5a7//vvvu36Mpldz2R9//DFpaWlxQej/+3//z70ZFgAAEFQCABqAain1Up4tW7a4/8VmnWoeRS+l0Btdq1FwqecoL168mEybNs39S5Ja8wDA3aL/Memnb+qqpVH2FuwsDz/8cPoJqI2gEgBQ91RLOWPGDPd/2MJOtY/ywQcfuL5RZiz2DKWaxP797393n8+ePev6AHCvqeWFmur73fjx49Nv+9JbXkX/Psl34cIF1//DH/7g+kAe/J9KAEBdUy3lAw884F5KoX/sHbLv9SZY1ULamxAVVL700kvJd99954Z9eqZSTWB37dqVrFy5Mh0LAMNH1v+pHDNmjPvfvDt27EjHALVRUwkAqFsKGDdu3OgySaNGjUrH9qZmrdYM7Lnnnuv1v9kUiKpJmf9iHgWbr7/+umsCu3jx4nQsAAwvKmRTSw09GqDaSqWX9qz4mjVrXB/Ii5pKAEDdUkCo5yVNe3u7e+urT88dhTSd3L59O/k//+f/JLt373ZNYVWbqQC0qakpefnll3u99AcAhiP9H14FlkrflLbp2fNYqw6gGoJKAAAAAEBpNH8FAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCABrCzZs3k/Xr1ydjxoxJRowYkSxYsCC5dOlS+u3QNX369PQTAAxdx44dc1292b17d3LmzJl0CFkIKgEADWH16tXJhAkTkl9++SVpb29Pzp07lzz99NMuwFSnoLOWKVOm9EyvThkNfzjsFLju378/nfsOjY9NH1LQq6Aya3rr9P2qVauiGZ9a8/qdbN26NfpdrBusjFbebdB0IR0zHQv/t9IxVMZQv3Hs91BGWNNoWhU6aP5r1665Qgig3um60Dlv14vSjKLXtq6V27dvJwsXLkzHdF+Lfvpj11UZS5YsccsKWSFhrLN98PdP08fSAKPvwnRl5cqVyeXLl6vOh4ouAADq3MWLF7t0y6sEk+mYbp2dnW68utbW1nRsXFtbW+a0LS0tfcZrXdOmTXPj9X3Itknd0aNH07G9aT7b5o6Ojq7Ro0e76f390Hit174L19XU1NRren3WdP62ahnaVn2n8bt27Uq/6abp58+fnw51H7fm5uY+x6Ga2DGoRuvQOsP9FW1vbP0a1vThPtsxCvdD7Hf191m/h/12QL3Tua7rQteIriud9+rC6y6Lrp3w+rb0yq5Tu5Y1Ttd2EVq+5o1du9p2Ld/vtE6tx2jbJk+e7NZry9L2hZQmK+3IovVrnYgjtQQA1D3LSMQyScqUKANSK7Oj6ZQxiS1HwxqvDI3PxquLLbtW4BJmoixjFtsPZYi0D+F2hJmgatuqLpZp0vThtki4jGpi89ei5Wftr2UQjU2rDGUW7Vu4HTpmsXm0fD9jCtQjXRP+dSSWXlYLsIyCM00bpm+6ppQm+bQ8TRuurxotQ9esdb6s9EdBpH9N6zr2p41tg7Zfy4+l08YC5VhAiq4umr8CAOreb7/9ln7qa+zYscmrr76a3Lp1K9m7d286tjc1o6oElK5JZRGzZs1KPyXJlStX0k93aN1Z1HTs0UcfTYdqmzp1anLkyBH3ed26dT3NzNRsLA9tq7q808vatWvTT3efjp2apYmOlfZZv9GOHTvcuBjt21NPPZUOddPvHmuSp+VXMqbpEFCfrl+/3nMdGQ3rWvr111/TMdkqAVxSCcb6pGUTJ050aZJvy5Ytrl8tPfap2epzzz2XfPrpp+mY3rLSnwMHDiR/+tOf0qHuazwUbsPGjRuTDRs2VE2TJ02a5I7Ltm3b0jHwEVQCAOqWgkE9R6OAQ5544gk3HD4zs2LFimT06NHJW2+9FX22ctOmTckLL7yQDuVnz/Ro2X6AmcfBgweTZ555Jh3KR+uYNm2a+/z111+7fj0KXwai5yXlb3/7m+tXE2agFTieOHHCBZzhb7958+b0E1CfsgIzFaDdd9996VCcCmMUwM2dOzcdc0dsuQrKZNSoUa5fi56Df++996oGeiEVMIn/bKfS32qBrJ6VVBCcJ43Ws9eaPnafaHQElQCAuqVMQldXV9La2uqG29vb3XCY4VGmRUGFSrTDYMwyKUWCQmW2lPFYtGiRG65We5bl+++/71PSn4e9Lda2u97o2H755ZfpUDd7gcZDDz3k+kW88cYbrqZFmeMHHnjAFTiQYUQj0/mvgpZaBWl62Zk8/PDDrl+LCoMU4C1evDgdk00FRXPmzClVGNfU1JQOdVPBka5v7ZcVQNk2KJ08fPhw7lYXCj51n/j222/TMTAElQAAVKxZs8b11QTKp0xIOC6LakRVE6omUkuXLnWZmY6OjkJNSkUZnSJNX33K9EisSefdEnvjrDKp4Th1eVgNszod23DfYs3bfLHtsdpqFSgcP348aWtrc2+G1G9owSXQiA4dOuQCs1oBnZrOysiRI12/lo8//jh58803a9Y8Kv07ffp0n1YFeSh4DFt4vPzyy8m8efOScePGJW+//ba71lVrqiBT1/v27dvddFqvvQVaaUascMkC6B9++MH1cQdBJQAAFcpkWBBoNV8KXk6ePJm7tFw1oqoJ9Z/FsyZfRSiQLdr01fz000+uX2a9A0VBmo6D36k2MBynLg+rYVbX2dnZ57lIo39pEKPtuXjxYjqUuM9hzYQC/6tXrya7du1yw8psKoNJrSUaidK8L774oifQqubUqVPpp9pUS6lCm1qBoq43BZ551h+yxw3CFh4KYtVaROmHrnEr5Hv33Xd7PUepfzGla97SpWeffdb1fXkD6EZEUAkAQCqsrdQLGfQ8ZVFqUqlnG/ViCgtQi/juu+9KNX0VzSuzZ892/XqjDGCYMbXnSP/xj3+4fox/PKsdWy37xx9/dDU158+fz3x5EzAUqYY9q1a+FgV0evGOXoxTqzaxCNUAqsl6nscAdL2ptlG1iv4+qKWDtXbI2p99+/b1afqaxZ7LtgJDBaQqUFy2bJkbVsGV1ncvW3wMNwSVAACkVLunGjVlLlRbqACtaNNVUYZsz5497vkhNYNVpiovZXbUVKsMZYwUCGm9Tz75ZDq2/r3yyiuuv3PnzsI1i/qn6CH9flZTUqQ2BrjXZs6c6VpM+J3G5aE3oL722mu5A8rYC3pCVvOogrY8YtuvTs3e1elz1v6oAC9PCw8Fiu+//36vF3GdPXs2/dTNns++ceOG66M2gkoAADxWS6nMlQUreflvGFRtmJXM64UTscAyFgCpRL9M01ct338x0EDWNAx1CvxVQ6FnK9VkrUhgqYxotdqIWm/ABIYS1bypabff5Wm+v379eldLX6SFxIQJE1z/559/dv2QrkMFqiqgqZYe+ddfbPvV6W206vQ5tj8qjFPQmWf7VZAU1pqGgerly5ddf/z48a5vLPjM+3KiRkJQCQCoa8rYXLhwwX22jIJRRiRs4qQMi2orxa/t03L0PI6EpdpfffWV69sbBo2CHT1fqWBHgaUCGPteQaBqFcWeBRJtSyxjpPH2tkWfxqs5mJav9eglFNVqV9VETD777LNe25rFmu/e7aZg2jarJbRtrkYZVx1rbedjjz3W61hru20/QjpmqhkOp9e/M1CNrwoXgHqlc14vpVHrDF07SkusU/CVdd3IjBkzXN9e2ONT+qbrUNeQmrT6y1X6ZIVs6isYLNMixKfCOP1Py1oUPL/44ot9njlXuq/tUFqjY6LnSnUfCKezgkPtGwJdAADUqfb2dr1xoU8XG1/JQKRzdc/X2tqaDnW5z+H06rKW78/b2dnZNW3atF7fa13+sHVHjx7t2rVrVzrnHVnTW6fvW1pauioZw3SOvvJsayg2vX+cBku1412LpqkEl12VDGKvee0YXbx4MZ2ymx03rdPmqWSEu5qamqoeT6AehGmT3+k6UPpVja6TME3QdaN5Y8tU509v0+o6rEbzVEt7tIxa16vS12rrUdqgddg2xvZdx0vpC/oaoT+VgwcAAAAAualWXzV8eitzvTe5177qpWBqYXIv3649VNH8FQAAAEBhCq70b3j07znqnd4GrmcxCSjjCCoBAAAAlGL/4qfa85fDnfZN/6apv89+1jOavwIAAADoF/vfjwsXLnT9eqH9GjlyZK636DYygkoAAAAAQGk0fwUAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAoCHcvHkzWb9+fTJmzJhkxIgRyYIFC5JLly6l3w5d06dPTz8BwNCiNHT37t3pUP04c+ZMXe7XYCKoBAA0hNWrVycTJkxIfvnll6S9vT05d+5c8vTTT7sAU52CzlqmTJnSM706ZTz84bBT4Lp///507js0PjZ9SBk2BZVZ01un71etWuW2J1RrXr+TrVu3Rr+LdbH1DQR/HSoEiP02tY69uqztC6fTMQIamdKaatdMjNK2gwcPJitXrkzH9LVkyZLc15euc6Vj/nWZp+Avtg5/WUpDYumw0XdK93yzZs1KHn/8cbcM5ENQCQCoe8qYHDhwIHnooYfcsDIMCi6//fZbNyx79+5NP8Up49HR0eE+t7a2Jl1dXW456re0tPQar06BqzI2S5cudTWkvuPHjycXL15Mh5Lk6NGjbp6QMmzLli1z02vdo0ePduO1bFuPxs+dO9dt3xNPPNFnXffdd1+v6fVZ/G3VMqZNm9aTody1a1fPd+pk/vz5PcOdnZ1Jc3NzcvbsWfddHuF2VaN16Jhof2/duuUyjGFgacde26Ft0zZpWMdV+yKLFi2KZko1XVtbm1u+9l3HF2hUurZUwFaErqt33nkn2bx5czqmL9X0Kd3NQ9tggaGuZXWTJk1K5syZUzWwzFrHu+++m5w8edIt580333Tp8LVr19Jv79CyDx8+nKxduzYdc8fUqVOTiRMnEljmVUlYAQCoa5UgSZFRVyWgSsfcUQlAuirBhesqGZB0bF+abvLkydHlaFjjK4FaOqabjVcXW7aWqe+yVIKl9FM3DcfWL5Vgyu1DuB2V4Cn91K3atqoLpxdNH26LhMuoJjZ/LVq+1q2uEjymY3vTNlc77jrGWb9rmW0C6k1TU1PPtaZrJw+lhUePHk2H+lJ6pOvLulpaWlpc+uXTdatxWfNXW4fm89MF7ZvuAz4tX/NVS/el1r6iGzWVAIC699tvv6Wf+ho7dmzy6quvuhqxrNpK1eBVMhau+WsRqk0zV65cST/doXVnUQn6o48+mg7VplL1I0eOuM/r1q3rKZVX07A8tK3q8k4vsdL9gaZaYNU87ty5s08TtWoqmUVXi3n+/Pnk2WefTccC8Kmm75FHHklmzpyZjqlN86iGf+HChemY3lTr+NxzzyWffvppOqY21TbOmDEjHeqm9FHp0YkTJ/rUVtZah9LzUHgf2LhxY7Jhw4aq6bBUgu7kxRdfTIeQhaASAFC37Lk7BVmi5qEaDoOTFStWuKaQb731Vp9mlrJp06bkhRdeSIfys+akWrYfYOZx8ODB5JlnnkmH8tE6FIDJ119/7frD3ahRo1yGU8dQv2O1Z6NCO3bscMdDmVKasAG9KVD74osvChcOvf32267QJoueX3/vvfdqBms+BamxtFfNT+V///d/Xd/UWofSi2qFiUpHtOw86fJ//Md/uO0r8rxpIyKoBADULWUYurq63POD0p4+WxhmoqxEXKXbYTBmJeRFgkLVEirTomf6RMFNUd9//72rfSzK3hYbluwPZ3q26vTp0y6jqOCwyL7peUmr6SwSkAL1TAGcCmmK1CaK0jYFWFmtKFSLqecgixai6RpVq4LYc4/yP//zP+mnfOtQKwUVRmk/Nb0sXrzY9ZV+ZD1HGXP//fe7/ldffeX6iCOoBACgYs2aNa6v5lA+ZUjCcVmUSVNNqJrK6sUQytgoA1akSako01Ok6avPSvazMmd3g164oePgd6otDMepy0sBtoJzBf56qUisViNGBQZ79uxxAal+k3oKtoGyVNOnwrYitYly48YN11cLgpCuLRX+VHsbbJa///3vrq+mppZ2HTt2LPnss8/cZ3vJWt51vPzyy8m8efOScePGuZpVvZhLhVMWTG/fvt1Np+WpIE5pUeyFYPLggw+6vgr6kI2gEgCACmU4LAi0Gi1lbvQGwbyl7sqkqSZUyzFablEKZIs2fTU//fST65dZ70BR7aCOg9+puVw4Tl0RCs51jPUbhf9CoBr/eVPVcNzLgBu415S+/PnPfy7VEiLrjc8KxvSWVQvWitLzmQr8VGikQjkFerdv33bXuiiwK7IOBcsqhFIac/Xq1Z6CPb0V1n+OUgVUWpelRbHnr4sG3o2KoBIAgFRYW7lt2zb3PGVRb7zxhmvOtWXLllJNLr/77rtSGT7RvDJ79mzXrzdqsmYv4CnynKQKBizTqtqQvDWdwFBnz477XbVCl7/+9a+u1t6fXs+biz13XpRecqbmpqoZ9JerFgrWSqHWi7YU+CkAVIBn6ZiuV13vCuz6uw7VfIoVEuq4KWjVv22Sp556yi2HQqdyCCoBAEipdk81aspoqDRfGZuiTVdFGaCyTS6V8VGzrTKUSVKwpfU++eST6dj6Yy/g0XOSH3zwQTq2Nv2WepusjpGa/wH1YPz48a4G3++WL1+efttXOK06a12hvoazZL0lVuPDZapTraM6fS7yhlkV+qjQSGmZCumkP+tQoPj+++/3+r+aYa2rNbG1Jr4oqAsAgDpXyWxk/g82/Z8yn/2Pw0pmps//bNS0seXYPPpfaz7Nb8vS/1QLVQIj972vkqmLTitZ6xf//1SG2+2zbdUxyUvTh8epqDLzaxuztlP/W86OXziN9rHa+nSMB2KfgHph6UIsbfF1dHS46XQN5aFrLHadaTlZ7NrOSjdDWevw6ftwneE+2/8zzpouTN/RGzWVAIC6phLvCxcuuM+XL192faNawbC5k5pGVTIg7rNf26flqGmWhCXc9lZAe9ugUc2YSv7VhEvP8qkprH2v2kvVmIn/qnptS6zpq8afO3cuHbpD49XkS8vXetTEs1rt6r59+1xfL8DwtzWLNd+9F83C9LvZbxfya4ND+p31W2XtnzVPBlCMWnOoVrA/aYHSPi0jTKe0TLUQeeCBB1xaphfylH0MwLd+/Xr3fybD58yV1ms7lCYqrdC/V1HaH06nZzvlP//zP10fGdLgEgCAumMlzGEXG++XdOt7v/ZLn8Pp1WUt35/Xr1GzTuvyh607evSoKy0PZU1vnb5XKXq10v882xqKTe8fp8ES21aNiwl/q3C+rP3T79LU1JQOAY3Nrrms68xnNXp5KL0I0wylU6qF9Gv+LI1TWqnl6/rMK7YOozS1Wg2jakJt3erH1qv5K8FnOoQsI/SnciABAAAAoKYpU6a4ZxT11tZ610j72h80fwUAAACQ2+eff568/vrr6VD9UvN/vTiNgLI2gkoAAAAAuelZx1deecU9r1iv9OznP//5T/e2adRG81cAAAAAhSnw+u///u9k5cqV6Zj6oP26cuVKqX8p1agIKgEAAAAApdH8FQAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAAD65dixY66rN7t3707OnDmTDiELQaVn69atyZgxY5IRI0YkU6ZMSfbv359+A9xx7dq1nnOlGp0/Opf8TvNheMvz++vmM3369J7fXZ+L3JDynDu6cSud0nfaFn1/8+bN9Ntuly5dShYsWOCm0bQazrJq1aq6u2lqf/xjqGMRo2PnTxfrso5NOF3WOvorzzaqC88T0e+u39fOF3U6J5VR0jkTu9fp/LJzWOeX5te5v379+nQKAPXIrnO7/mNpSozmuX37drJw4cJ0TNKTp451Re83S5YsyUxfLR1TGhdbrr5XGqb1apuq5e/1XbjPK1euTC5fvlx1PlR0wWlpaemaPHlyV2trq/s8evToLh0eDQPm4sWL7pyw86OaadOmdc2fP79X19nZmX6L4SjP769p9N2uXbvSMV3us8bpuzxqnTtHjx5126C0StujtEvL13Q+Laepqcl9Vl/TxbS1tdVtWqfjZsdfXXNzc/pNb5pOx0vH1Oj30jjNp+Od9fvp+On7jo6OdEw+/rry0DbqN9b2tLe3p2O7ad3at/B31LCm1+/vz6Pp7bvwvNH+aLx/Duucs2MBoD5ZWqZ7hT7nTdOUVoTpmeZXmqF0xu+UTmkdRVgaHqZVom3U95Y+hWmjaNu0T/79ILZvSuPtnhmj9Wu/EMfdoUInVngSWcaw6ImPxmAZuyxKdPwMGepLtd9fNy/d3EJWaFVLnnNH6/eDTH22wNICH0vD7Aarvv+9qXUTrRf2m6nLyhTo9wkzJHbc1Ol39Y+7T8svqsw82kZtSyzjZBkmY9NmBdKiYxFuh+57sXm0fO6JQH1SWlArvYhRHlrzhWlj1v1O98gi69A9SmmUdVmqpY1Kt/zt0XThfVbbr+VnpfGifdWyYgEpurpo/lpx7ty5ZMuWLelQt6lTpyaVkz65detWOgbIR80sNmzYkLz22muuuUa9NSlEbZUbTp+mqL/88ksyYcKEdCguz7mjpknLly9Pxo4dm45J3OdNmza5z//+97979UP+eK1v3bp1yfbt29Mx9a2SiUgqGYJk6dKlha7LSkbD3Q/Onz+fPPvss+nYoUfngZppiZq86redPHlysmPHDjcuRufZU089lQ51031P51lIy9dxAFBflB4qXWxqaqqaXsRUgkSXRvr3JFm7dm36qbcDBw4kf/rTn9Kh6nSPeu6555JPP/00HVNOLC//22+/pZ+6bdy40d1/w/3wTZo0yaWp27ZtS8fAR1BZoZuqTpTQxIkTXQYEKOLbb791540SMSWeTzzxhGvLHwYZqE/PPPOM++317Ic9w6hnTZTOqKsmz7mjtCq2nPvvv9/1f/e73/Xq6xmXLHluovXkoYceSj755BP3edGiRVWfMQ0pozVt2rTkxIkT7jcZasKXY+h5Sfnb3/7m+tVYIGoUOGo/dZ6F6dbmzZvTTwDqhQoqJaxgqUWFT7pXzZ07Nx1TnaW5/nOX1axevTp57733+n2P0n01DCJ9elZSef5Zs2alY7LpWVNNT56uL4LKKj777LPk1VdfTYeAfJRYfvfdd2obmbS1tblSrZ07d7oMPOqfWjnod1et1pw5c1zGXDWUeUp/+3PufPXVV660WOsX9RUEffzxx274gw8+cMuzm2aRm2g90THWsVXgrhLwIhmD48ePu2Oq32QovbBBGbsvv/wyHepm26dAuqg33njDnUvKLD7wwAPupRVkoID6pFpKta7RNb93796el+soeKpV8KaWfvLwww+7fi0HDx50taF5qGBM99CBuEepoEzpmdIxK3BbvHix62sfDx8+nFmzGtJ9U/cPFQKjN4LKDDrJdNKsWLEiHQMUp4BCCY9lRIvUjGD40u/e2traU+Oo371oprzIuaNlaz1ap2/Pnj3Jr7/+6jIIyjR8/vnnbnx4E1UAYm8GbYS3e+rYWnNWlYTnpdJyHVNrQlvkera38PqdagPDceryUC22Ta/CgrC5qs69amLbY2881H4qgFbwrQymmtFacAmgvpw9e9b177vvPtfSRo9qtLe3u3uGgrpYU3hz/fp11x85cqTr16L7lNZRi9LW06dP92lFUdbLL7+czJs3Lxk3blzy9ttvu7RNrX507/QfAdF67a23SiNj920LoH/44QfXxx0ElRl0kikD1ijNwjB4LCMqykSi/ilI++mnn5LOzk5XKqugMOsGVU3ec+fdd991z1RaLaXRsIID1XyqBtS+92+iyjAoQNL82l5tayMED6o5ttq4IoG0juGRI0fc51oZLp/9Dn6n9Yfj1OWhTJ9Nr98tfC7SZDV/1vZcvHgxHUrc57CkXsH31atX3bOoovNGGa6i5zGAoevChQuu/8ILL/TcI1Q7qDRShVOqvcxy6tSp9FNt9hx7eJ8KKX158803B/RZf91LtT9KL5WmKW0T3Tv9R0Cefvppl8ZZOhx7hj5vAN2ICCoj9LyMSvxrnfhAXjqXVOOE+qdn23ST0g1MNyoFmFYrVu3mnKXWuaPlq3mt3SRrUQD14osv9txEDx065PqaX+NUmvvhhx+6cfVOL3/QsdVzRNZcNA9luKwJrQoN7nWQpd8tLNG3c+Yf//iH68f497hq9zst+8cff3T7WvY8BnB3qFAwqxVCjFo6xDz55JOu//3337t+f+3bty9X01elLyrsU62ivw8qWLXWHQNR8GnPoVvzWmsGvGzZMjesgjqtL2/BIQgq+1Bb69mzZxNQYlCoZgL17f3333dNSX1WK1akVDcUO3fUVOebb77J3UTIbqL+SxLCbXrkkUfcjbURKBhT5sWas1qJfR4KwvXWw6JNaO+WV155xfVV81w06I29iEjHymoO+nMeAxhcM2fOdBUjfqdxWeyt5D///LPrGyt4VLPYLHNzvqBHVHCXp+lrbPvVKfhVp8/V9icPBYq6V/svHrNmwMaeR79x44brozaCSo9O+FGjRuUu8QfyUuZfCTSFFfVPN2A1rwk9+uij6ac78pSAZp07Gn/w4EEXsOYRu4lKmClQYJVVcl2P9FyNnt1RYKkAswgdS3sBxFCj+5hqBVSbqiZcRQJL3QurnZvVMpkA7i3VvKkpu99Ve9mNXlij9O+jjz5Kx3TTPUb+67/+y/VjsgLSkAo0dV/JygP56U1s+9WpsFadPlfbnzxUcBbeO8NA9fLly64/fvx41zcWfOZ9OVEjIahMqUnYO++84x46VrW6dRrfCC+uQH7KnFnQEMt46cUWen7OvlOTCj2L1N//s4Shodbvr+dSVNPn/ysQ3VBVY6Rmp0atInSTtTfRSd5zR5l+PfuhQjA/vVKn+WNiN1GxN+BZIHHy5Mnk+eefd+Pqhf1mlkkIKaOTFZxrHs2bFZTpTal3q2m7tsFqCdWUrBbVLNq/B3nsscfcb2z7od9awzEKRNUMOpxeNbLKfOr/qAKoDyq0VPqndMLuR7re9XZspR/V/v3HjBkzXN9e2JNFb6fW8mIUvOpe2N8KHWtpUivAtUdAwn8lqEBV26G0VeneF1984VoIhdPZvyZRmopAF7paWlr0RG5m197enk6JRtfa2trn/NA4n38+VTKb7vvOzs70WwxneX5/UZqh396m0ecwHTl69Kj7Tn2T59yx+bK62PZouf56QvqucjN182vaehL7zbJoWv93CueLHVvRb9TU1JQODY7YfqjLc3/SNJXMYc9vbF0lw+R+74sXL6ZTdtO4jo4Ot06bpxJMun3UeAD1x78PqJ+V3oWULigtqUbpR1baofH6vta9R+uIrUfpm5+uqcvaHu1jtfUoLdS8toxY3k33ZqWn6GuE/lQOHgAAAADkplrNShDq3kJtz2HWK+1rJah0z9KHNZig+SsAAACAEhRc6d8O6d9z1Ltt27a5psIElHEElQAAAABKsTeQZz2nXQ+0b/rvELzMMxvNXwEAAAD0S+zfVtUD7dfIkSP7/dbZekdQCQAAAAAojeavAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAA0hJs3bybr169PxowZk4wYMSJZsGBBcunSpfTboWv69OnpJwAYWnbv3j0s0tGidK+4du1aOoQ8CCoBAA1h9erVyYQJE5JffvklaW9vT86dO5c8/fTTLsBUp6CzlilTpvRMr+7MmTO9hsNOgev+/fvTue/Q+Nj0IWXWFFRmTW+dvl+1apXbnlCtef1Otm7dGv0u1sXWNxCyjqu2zaffTON0jGwafda48Pf0l6OChdjvHVuvlnXs2LFkyZIlPePKnCvAUKK0xU8blH4UCaJ0DeiaePzxx5OpU6emY7vTDyu40zUQS//y0PZpGWEaoyDWtjnstD9G16xdgxqfdc1qfOz7zZs3J9u2bavLgHnQdAEAUOcuXrzYpVteJZhMx3Tr7Ox049W1tramY+Pa2toyp21paekzXuuaNm2aG6/vQ7ZN6o4ePZqO7U3z2TZ3dHR0jR492k3v74fGa732XbiupqamXtPrs6bzt1XL0LbqO43ftWtX+k03TT9//vx0qPu4NTc39zkO1cSOQS3adlu31unTMdM+6zsdS6Px2hd9548Xm0fL1DThMo32LVznQJ0rwL1maYldwzrXda5qXNY1EdK1GaZbusYnT57slqnPdq0VvQa0DVqO5vXTLtF1a9vtd5re0i3bPw3bsjRPjMaH6zA2b5iOII6gEgBQ95S5iGVQxAKQWhkqTZeV0dFwLPNk49XFlq1l6rssfiAnlvmL7YcyPrFMnAIcX7VtVRdOL5o+3BYJl1FNbP5alGnN2tasbRLLDOp4hBlCLUvzqsvKaGr5sX0biHMFuNd03ofXhRXghAVKMUojdI77FMhpGT6tQ8vU9VKElmPXqX/9KD2IBXi6FjWttkEsvTdaVmwbtB+x69wX21fE0fwVAFD3fvvtt/RTX2PHjk1effXV5NatW8nevXvTsb2pCVYlSHDNqYqYNWtW+ilJrly5kn66Q+vOomZXjz76aDpUm5qgHTlyxH1et25dT1M2NVHLQ9uqLu/0snbt2vTT4Bg5cmT6qbfly5e7fiVD6PohHddNmza531THItTS0pJUMorJzp07+zSprWYwzxXgbpk4cWKvJquyZcsW16+WVho1lf3LX/6SDnXT4wS2DKN1VAJYd73kpeatjzzySDJz5sx0zB0LFy7ss93y9ddfu+t50qRJbji2D+E2KH09fPhwzTTsySefTM6fP1+6GW8jIagEANQte0bOAosnnnjCDYeBxIoVK5LRo0cnb731VvTZGwUoL7zwQjqUnz0PpGX7AWYeBw8eTJ555pl0KB+tQ5krUUarHulZqY6ODhe4xTKYxoLjEydO9HlWbNSoUcmBAwfc76Jzo0iGcbDOFeBuiQVSFpDp2qhG14oCtDDo0/Vmy/ApgNX1kocCvS+++KJwYZWCw1deeSUdurMP1Z6j1HW/ffv2dEw2FSQprfnoo4/SMchCUAkAqFsKsrq6unpqtNrb291wmGlRxkGZImWWwmDMXtRQJChUEKPM16JFi9zwjh07XL+I77//vmrQlMXeFluvL5j44YcfXD9PTaAyg6JalJAywKdPn3YZXtW85D1eA32uAEOBCmt0LSxevDgdE/fNN9+4/oMPPuj6tXz22Weudr8WC/Q+/fTTdEw+mk8FRKpRNPqsfTl06JD7/sMPP3Q1pmbjxo3Jhg0b3LWch9IaFU5lBanoRlAJAEDFmjVrXF+ZDZ+aY4XjsihTpJpQBTNLly51GRnVqhVpUioKToo0ffWpZkDu5evwY2+cVaYsHKduMFngef36ddcPKWhXwK8AUW8CzptpHIhzBRhKPv744+TNN9+sGWhZupInIFM6pmtLtfu16O3cKvzLG+gZFew0NTX1mk8FRp988kny9ttvJ+PGjXOtN9544w33nQr7lEZawY/9myl1WS0WLC2OPcKAOwgqAQCoUEbEgkDLXCgDdfLkydw1T8oUqSbULxWPNQmrRcFJ0aav5qeffnL9MusdKMePH3fHwe/mz5/fZ5y6wWRB4sMPP+z6MQr49bvpd/f/JUE1A3GuAEOFaikVVK1cuTIdk02FQ3mpkO3zzz+vGSgqvfvzn/9cqmWGmqVq3pCev7x69apLY3SNaht0jfrPUWq8nqtWiwU9j66CwPBfmEitJsHoRlAJAEAqrIHS/ynTM3JFqVRcpeN6cUVW6Xc13333XakMlmhemT17tuvXG3uWK9akNaQXbMgf/vAH18+iTKaCRE2vprB5DNS5AvRXrGVALDiKUW3il19+WaqJfjW6jlRYkycd++tf/+oCOn/79fy72HPwMQoSFeT6TV+r0Tb5LxNSQDpjxgy3jSoMUpPZffv2pd+iKIJKAABSqoFSjZpqoFR6rgCtaNNVUan4nj17XCZFmaW8z+uJag3mzZuXDhWjjKQCI603b0ZruFHmT82L1ayuWsZZx1H0e+aptVWm2t4I+8EHH6Rjsw3UuQL0l96GrADO78aPH59+m001+Wryak1D89A5X4uuBxVq5S0YC7ddnbX2UF/DMbGmr1nUzPXFF1/slRaEta4KMK15L4ojqAQAwGM1T6+99lqvNwrm4b/KXhkqK/2fM2dONLCMPcOnWoMyTV+1fP/FQHkyWkPd7du300+92ZsYX3rpJdcP6bi+/vrrLrguUgOjZrsKLPXijzz6c64AA0WFGapt97taBSm6RvTCGr0BtUhaYcvNCr7UMkPNRWsVsPjzh9uubtmyZe479TUco4K7//qv/0qHslkBk5rE+sIAWa0fYsft1KlTrp/35USNiqASAFDXlHm6cOGC+3z58mXXN8psqLTaz+CoJswyG35tn5ajZ3Tk7Nmzrm+++uor11cw4geKylippF21agosleGy7xUEWvNMv8ZN2xIr4df4WJNPjde/SNHytZ62traqGTpr3qW3MvrbmsWa74bH6W7Qy0NEv5+/rfqNtJ+qJdTbbv3jp99UzQF1LPSsVJhJ1LLsfAj5NcyhgTpXgHtNac9jjz3mznP9v1WlH9Yp7ajWssKa1d+4ccP1faoNfOedd9yLsfxlarw6o3WotUG19dSi61DXfxgohjTd+++/n2zevDkdc4dqeJWmajt0fSvNsGDWp+tZhU31UFA3qLoAAKhT7e3tehNMny42vhIcpHN1z9fa2poOdbnP4fTqspbvz9vZ2dlVyZD0+l7r8oetO3r0aNeuXbvSOe/Imt46fd/S0tJVyWSlc/SVZ1tDsen94zRY8m6r9rcStHdVMqg90+hYazodd19smRoXo/H+usL5ypwrwFCga6YSTEbPUXV5rm/NH16LSn9iy7POv9Y0rZaRJ73KukaVTurar0X7U2092g9ti7q2trZ07B1KR7Qdse/Q2wj9qRwsAAAAAKhKrRdUI2kvBatnjbSv/UXzVwAAAAC5WPNVe1axnimgVJN41EZQCQAAACA3veBHzzz357nIoU7PgSqgzPsW20ZH81cAAAAAhenfhzz++ON1F3hpv/TyrVpv0cUdBJUAAAAAgNJo/goAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAhe3evTu5dOlSOlQ/1q9fn1y7di0dQh4ElQCAunTmzJlkxIgRPd2CBQvSb3rbunVrr+linZYVE06XtY7+CvfFOm277+bNm27c9OnTe6bRZ43Tdz5/OWPGjOnzvcTWq2UdO3YsWbJkSc+42LyhKVOm9FoOgHtL1+3+/fvdtZmVxmXRvEoDHn/88WTq1Knp2G4KMletWlU4PVTaorRI6YO2SdsW40+n9C227UqjLM3RdmSlURof+37z5s3Jtm3b6jJgHjRdAADUqc7Ozq5du3Z16Xanrrm5Of2mN003bdq0rpaWlnRMV9fFixfdOM03evRoNxzT1tbmvu/o6EjH5OOvK6+mpia3PfPnz3fb7Dt69KjbDn3nb6vGaz9i+2DzaJmaJlym0XEL16nPdlxbW1vTsXE6RnmnBTD4lF4pbbQ0rr29Pf0mH6VFSj9CGqe0TctUmpGX5pk8ebJLH/TZ0qUwvdB3GqfttbRXnZ/+6rPGaf+UTmm5WWm/xmftu82blfajN4JKAEDdU+bGghplRGIso+LTsM1XLegqknkyZeZRhi2W0bLtzFqmZY6U0QozSFqW7WNWxkvLD9cpFqyqyzo2oum0fq0jKwMH4O6z67/Idak0VNd0NdXSo5CCQAWpPqVTWobSFqM0Jky/rcBKAaSxgkSjffSXYzRvLF3z5dlXdKP5KwCgIVQyGkklY5EsXbq0UFOvSsYoqQRbyfnz55Nnn302HXtvjBw5Mv3U2/Lly12/kkFy/dDYsWOTTZs2Jbdu3UrWrVuXjr2jpaUlqWSckp07d7qmZXlpua+++qpb7t69e9OxvelYVwJK1xQNwPCnpq1/+ctf0qH+O3fuXLJly5Z0qJua1CrdVdpilN6oya3v/vvvd/3f//73ri+//fZb+ukOfzmiZq2HDx9O1q5dm46Je/LJJ13an9UUF3cQVAIAGsJDDz2UfPLJJ+7zokWLCj0rs2PHDhd0nThxwmWohhI9O9TR0eECt/DZJp9lxrQP4QsoRo0alRw4cMAF3Qo6i2SgVqxY4eZ76623os8tKZh94YUX0iEAw5nSBgVoM2fOTMf0n9KmSZMmpUN3TJw40aUt1Zw9e9YV/C1cuDAd052eSbXnKJXObd++PR2TTYGs0taPPvooHYMsBJUAgIahjEdbW5vLFD333HOZmY6Y48eP99TmDaVS6x9++MH189QEKnMkqhkIKVN3+vRpl4lT4Jw36LbaAx3Tr7/+Oh3bzZYxa9Ys1wcwvH3zzTeu/+CDD7r+YPrss89cS4gYFYwpnVJh1qeffpqO7abaRaVjhw4dcmn8hx9+6Go9zcaNG5MNGza4tCsPpa0qjCtyv2hEBJUAgIaiAMias65evTodW5syIHv27HGZFTWhLVLTqbcL2ltPrVMmJRynbjBZ4Hn9+nXXD6mmU7WyChCffvrp3JmoNWvWuL4yaj79u4FwHIDhy1o55A3IylL6qnRILSFC1qReBXya5rHHHuuVHquATK1S3n777WTcuHGuMPCNN95w36lAUDWgVtClfx2iN8mqyyosfPTRR13/ypUrro84gkoAQMNR4KQmU2ryqUxFXgq6jhw54j7PmTMn9/8xUy1nV/fL8Xo6rT8cp24wWZD48MMPu36Mgm49m6kmtXn/JYAycQrUNY9lzHRsTp48SS0lUEdUGHY3qHnq559/Hg1elaYorbx48WLS1NTk0p3wWXG1Srl69aqbTmmSlqM0yX+OUuMVmKqFhtL1rOftrTktqiOoBAA0JDWZUgm2XhCRVUIdowyNNaFVhuZeN4myZ5tiTVpDqp2VP/zhD66fRZkuq83N+wxpWFup//Gm5ykBDK5YS4giLyMbapTmqGCr2jPiou+VdquALk+wq+X6LwTSc5IzZsxwy1G6rlYo+/btS79FUQSVAICGpJJrezmNSqgvXLiQflObavP0xtSiTWgHgzJDagqmILdaRlIv9BFlwGIvxQjZy4lUkv/BBx+kY7NpmVq2ag3U7PW7775zxwnA4NLbnxWE+d348ePTbweWrvHBpLRj9uzZNQNKn739uhq1SHnxxRd7pX1hIKoAM2/rE/RFUAkAaFjKYNjLaRRgFrF582ZXm1d0vv64fft2+qk3ezPhSy+95Poh1aa+/vrrbj8VLOZlLyfKu49WS/naa68lr7zyivsMYHCp8EatC/wuT8FRGbbc/gZfsflV66impkULo/75z39WDXatQM1/Q6yE86i1R+y4nTp1yvXvxsuJhjOCSgBAXVNApWdrLl++nI7pTSXiWYGW5tG8WU1c9fIHBV13y8cff+z6qlX1t8ma5KqWcPr06b1qLJWhUvM41WQqgA4zTVpWVi2t/3KikJarkn4/c6jtsIya3sBo7DcQ/QsAAEODXfs///yz69eiWkS5ceOG68fYS3N03cfSTgWNal3hv1xHNYnvvPOOe4mY/leudRpvz70rzdELdTTelqtAVM9uZ6XhSp/ef/99VwgYUg2nAklth5atNHLZsmXpt3doXUrnB/vlRMNeFwAAdaq1tVVvvunVZdG07e3t6ZB7Y06vTt/HdHZ2djU1NaVDg0PbFW5PbJsqQWVXc3NzVyXD1jNNJTPkptN2+mLL9Pffp/H+usL5KoFk+k3fafU5nF4dgHsndv3713E1o0eP7pP2GC0jXG6YrrS0tLhlKL2y4XAev7P5Nb3SMxuflbb5tD22nhjNr21R19bWlo69Q8vWumLfobcR+lM5WAAAAABQlWoHVauo56brXSPta3/R/BUAAABALtZ81Z5VrGcKKPUIAGojqAQAAACQ2/bt290z3v5zkfVGz3IqoCzyJtpGRvNXAAAAAIXpX4A8/vjjdRd4ab/0srHBeotuPSKoBAAAAACURvNXAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAaws2bN5P169cnY8aMSUaMGJEsWLAguXTpUvrt0DV9+vT0EwAMfbt37x4WaWtR2q8zZ86kQwgRVAIAGsLq1auTCRMmJL/88kvS3t6enDt3Lnn66addgKlOQWctU6ZM6ZlenTIY/nDYKXDdv39/OvcdGh+bPqSMmYLKrOmt0/erVq2KZnhqzet3snXr1uh3sW6wMlj+OlQIEPttah17dVnbF06nYzQYsrZRxzik88T/rXSu6Te9du1aOkW38Pcsso/Hjh1LlixZ0jOuzDmP+qTzor/Xgc4nLefxxx9Ppk6dmo7tTdPonIpdAzFKA/1zXtdErfM2ax3+svR9tcA3lp6uXLkyuXz5cjRNR0UXAAB17uLFi1265VWCyXRMt87OTjdeXWtrazo2rq2tLXPalpaWPuO1rmnTprnx+j5k26Tu6NGj6djeNJ9tc0dHR9fo0aPd9P5+aLzWa9+F62pqauo1vT5rOn9btQxtq77T+F27dqXfdNP08+fPT4e6j1tzc3Of41BN7BhUo2Ni+6Rt0zpjtB3aNvtex9WOu+bXcIx+T32vfS+i6H6IfgM7huF+2PZOnjy513mg8TafttXXn30cqHMe9UPXu35j/xovQ+drVlpm7JzOcz7pvNb5a+mRpVPV0gPJWofm03eivq65GJ331bZPxym8JlG5T6R9AADqlmWa/ODKKKOhjIu6ahkVTadMSGw5sUBNbLy62LK1TH2XJczkaTi2frEMWLgdYean2raqi2WWNH0sw1kt4xUqk2HV8rVudQoeY7TN1Y57tQxomW0qM48y2tqWcDu1XbXOPcsgZ/2OZfZxIM551AelGzpHrCtL56fOl2qUDts1nSft0PIsCDR23mfNn7UO7ad/HttywgIZDYfrDCm41bVTtECq3tH8FQBQ93777bf0U19jx45NXn311eTWrVvJ3r1707G9qRlUJXPtmkwVMWvWrPRTkly5ciX9dIfWnUVNsx599NF0qDY1Nzty5Ij7vG7dup5mk2qOloe2VV3e6WXt2rXpp8HT0tKSVDKXyc6dO3M3mZNKBjmpBKLJ+fPnk2effTYde2+MHDky/dTbxo0b3Xn35ptvZp4LW7Zscf1Ys7+y+ziY5zyGD51Pzz33XPLpp5+mY8rT+fmXv/wlHepL6dkXX3yRO81Q+qXz+pFHHknHdFMapfPyrbfeSsfcUW0d//73v9NPvfnjdTyUdm7fvj0dEzdp0iS3Ddu2bUvHQAgqAQB1y55pU0ZBnnjiCTccBicrVqxIRo8e7TIqsed1Nm3alLzwwgvpUH72TI6W7QeYeRw8eDB55pln0qF8tA4FYPL111+7/nA3atSo5MCBA+4Y6ncs8jzTjh073PE4ceKEy/QOJTrPFCjLk08+6foxysAqeFQAGPtNy+7jYJ3zGD70nPl7771XtXArD12TOj9nzpyZjumtTPB648YN148VCKqgQ+vzz9ta6/jd737n+rdv33b9GBXybNiwIdfx0LPu2u/YtdOoCCoBAHVLQVZXV1fS2trqhtvb291wWJKtTIRq6GIZd3uZQ5GgUKXsynAsWrTIDSvjX9T333+f+bKLauxtsdVeQjHcKLA6ffq0C4IUOBXZt+PHj/fUdA6lF2z4Ndfav2rs+2+++cb1Q2X2caDPeQwvepPpnDlzBuQ3tvPywQcfdP2Qgtc9e/YUCl5tWSpQyvLzzz+nn2qvQ2mprpGPP/7YDX/wwQeuttH2X9fNxIkTcx8PTatr59tvv03HgKASAICKNWvWuL5Kqn3KfIXjsqgmTTWhyqwsXbrUNU3s6Ogo1KRUlKkv0vTVp8yOhG8NvZvCN5SqU01aOE5dXsoUKjhXRk5v7c1bQ6BMpjKbCkj1mxQJSAdjP8qo9ZuW3ceBOOcx/Oj8UCGN3mY6EOy8jAV0FrwWLSDTstT0XemnNf1Wp+BPb+4WW2bedega+fXXX931quV+/vnnbryOx+HDh3sKG7UO1YZqOv0bqpiHH37Y9X/44QfXB0ElAACOaoMsCLTaHmWWTp48mbv0WjWiqgnVckytWqgYZZKKNn01P/30k+uXWe9AUc2ZjoPfqQlnOE5dEQrOdYz1GxX59wfKbNrzpsp85g24B2s/irImgNUKGsrs40Cc8xheFJjpGd5azw0WoYKWGAVr6soGr5s3b3aBpc7NcePGudpIXQsqWFKtoxRZh64Ru6a/++67niDUf45S578KZtT8u7OzM/NZ7qznpBsZQSUAAKmw5kYvYlDmoqg33njDZXr0khXLrBfhZ3iK0rwye/Zs1683qk2wl9MUeYZQQVJbW5vLkDY1Nd3zZ6H8oE2Z4mrUFFr+4z/+w/WzlNnHgTrnce8o6PFrzdVlvdRKL2ZSk1IFaf70CgytFr7IC7GqUbCmoMxfjzr7Tp/D/wUZUmCp/y2sQFBpqV0rr7zyiuv3dx2qiXzxxRd7alkPHTrk+irA0rh58+YlH374oRuH6ggqAQBIqeZGNVGquVFtoQK0ok1XpWxzRNE/qFdGpgxlnhRsab3VXv4y3NnLaZSZ1LNReem3VM2HjpFqPe41q9HOqukRBYb6Pu9vWnQfB+qcx72jF+SoBt/vsl6aE5tWnZrsq9PnrHmz6PyJWb58eZ/1qBPNo8/jx493w3kofdM1r3ntHO3POpTWysKFC11fTp06lX7qprfP6tpADpXIHwCAulbJWPT6H2W+SsYj/dTN/n9ZJRPf538DatrYcmyeSmY+HdNN89uywv+HJpXAyH3vqwQa0Wkla/2iebQefR9ut8+2VcckL00fHqeiysyvbczaTv1/RTt+4TTax2rr0zEuu09l5snzfyorGdd0bG+2reE/le/PPobj7Jwocs6jvuh3rnY+VWPnWtY5HNK0seu62vyWvumar/a/VU3WOozWFdtfzaN5jf5nZSXYTofusOnC67KRUVMJAKhrqum5cOGC+3z58mXXNyqpVi2Q//yZmhBWMhvus18zpOVcvXrVfT579qzrm6+++sr11azMb3Ko0vRKhss1R9Rzbmq+Zd+r9lK1SeI3z9K2xJq+ary9oMKn8WqupuVrPWr+WK2mad++fa7/2Wef9drWLNZ8NzxOd4N+N/vtQn5tcEi/s36rrP2z5sl3i71xUvvib5P2QS9MGTNmjNsev6m0zg/9jhqn39SvTZGy+zhQ5zxgrKm9/RuQMlRLrppS9X26DtRE9Y9//GMyY8YM90ykNVXtDzWdj72Ve/Hixa6v607XiJ4vfv755904nz3n/Nhjj7k+KtLgEgCAumM1MGEXG++XWut7v5TbSqXDLmv5/rx+jZp1Wpc/bJ1KvXft2pXOeUfW9Nbpe9WSVivpz7Otodj0/nEaLLFt1biY8LcK58vaP/0uqoUYTHmPubZF4/zzRLUjqgGK/ab+stTl3cdwvjLnPOqTzoX+XNuqRcw6D0M6j8JprTbfr/mzc07ncLXWFzGxdRilldVqGPWdrj8tI2x9YnSt6vrEHSP0p3LQAAAAAKAw1ey98847PS8Kq2eqwVQrALU0uZdv2R5qaP4KAAAAoDQ11VbzVXv5TT3TG5LVdJaAsjdqKgEAAAD0i57B1RuHX3vttdL/Emmos+eeqz233qgIKgEAAAAMCL1s5/HHH6+7wFK1sCNHjuz1P2ZxB0ElAAAAAKA0nqkEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAKAh3Lx5M1m/fn0yZsyYZMSIEcmCBQuSS5cupd8OXdOnT08/AcDwojR29+7d6VD9OHPmTF3uV38QVAIAGsLq1auTCRMmJL/88kvS3t6enDt3Lnn66addgKlOQWctU6ZM6ZlenTIW/nDYKXDdv39/OvcdGh+bPqQMmYLKrOmt0/erVq1y2xOqNa/fydatW6PfxbrY+gaCvw4VAsR+m1rHXl3W9oXT6RgNhrzHUtOFrBBEv79Np/NP465duxY9r3S+LFmypGd6fdYxOHbs2KD9VqgPOgetwE3nWez8KkrLOHjwYLJy5cp0TPc56qdJSrd0Ppeh8zt27dp+xDq7DnR9ad0ap+mr7a++C6/RWbNmJY8//rhbBlJdAADUuYsXL3bpllcJJtMx3To7O914da2trenYuLa2tsxpW1pa+ozXuqZNm+bG6/uQbZO6o0ePpmN703y2zR0dHV2jR4920/v7ofFar30XrqupqanX9Pqs6fxt1TK0rfpO43ft2pV+003Tz58/Px3qPm7Nzc19jkM1sWNQjY6J7ZO2TeuM0XZo2+x7HVc77ppfwzH6PfW99r2Iovuh7dL2aXv830G07thxtH3Xfuiz7Zv6tt1ank/7qfFann8s9PvH1g0YndOTJ09256E+2/lV5PoO2XXoszTMznm7LjTOztm8lEZpXj9dEl0fWq+W73dap9ZjbJ+1XltWLC2wayiLLRuV+0TaBwCgblmmIZaxVgZEmY1aGRtNp0xIbDka1nhlMHw2Xl1s2VqmvssSZpiyghOxoCLcDmWyfNW2VV04vWj6cFskXEY1sflr0fK1bnVZGTdtc7XjrmOc9buW2ab+7Ie2K2SZWmPbXm277bf2KeOr8zNG2xxbN6BAKgyadH7pHAzPsSJ0LoaFZbqGtWyfFXqEBVnVaBk6p63zZaVJCiL9NET75k8b2wZdf1p+1nVoYvvaiGj+CgCoe7/99lv6qa+xY8cmr776anLr1q1k79696dje1GSqknFwzcKKUBMpc+XKlfTTHVp3FjUTe/TRR9Oh2qZOnZocOXLEfV63bl1PkzI1EctD26ou7/Sydu3a9NPgqWQGk0qAlezcuTPaTDRLJTOYVDKRyfnz55Nnn302HTv06Byw5oFqkrd8+XL3+cCBA5nnh37rN998Mx3q9uuvv7qm3bGmwi+++GL6CehNjwFs2bIlHeqm80vXjtLEMvSsYSVYTRYuXJiO6TZx4kS3bJ+tu1oa7dP5/dxzzyWffvppOqa3rDRJ19Of/vSndCiJ7lu4DRs3bkw2bNhQNZ2WSmDMNVZBUAkAqFsKBvXMjIIseeKJJ9xwGJysWLEiGT16dPLWW29FM+WbNm1KXnjhhXQoP3t+R8v2A8w8Dh48mDzzzDPpUD5ahwIw+frrr11/uBs1apTLEOoY6ncs8qzXjh073PE4ceLEkHz2Sc86+vSbKTOuTOqkSZPSsXH+c2qiYFQZZT1jpgIJnzL3Rc8/NAYVIsXONQWAuubKePvtt12hTigW8Nm6dZ3noWfj33vvvZqBns+uBz/I1b5VC2SVzugY5Llu/uM//sNdt43+3DJBJQCgbilD0NXVlbS2trrh9vZ2NxxmbpRBUeZKmfIwGLMMSZFMub1IZdGiRW5YwU1R33//fZ9S/TzsbbFhYDGcKeN5+vRplxFUcFhk344fP95T01kkIB1sOke+/PLLdKjb4cOHXf+RRx5x/SJ0/qpWVzWzf/zjH/v1AhTgs88+cy04itI5pwArbysLFazoul68eHE6JptqQOfMmVO4gEQFdCqo8akmVoVVKkS0t7jaNih90bWYtyXG/fff7/pfffWV6zcqgkoAACrWrFnj+mru5FOGIxyXRTVpqglVU9mlS5e6jIsyWEWalIoyNUWavvpUui73MqCIvXFWtYXhOHV5KcBWcK7AX2/tjdUox6jAYM+ePS7jqt+kSEA60PthNeXqdI6Ev5GasFajGnZ/ner8t19u3rzZFZyolkhBtNah4DLvsQJE14iuM7XgKOrGjRuun7fm8eOPP3ZNuWvVPGqbVLAU1tDnoeAxbPXx8ssvJ/PmzUvGjRvnalbb2tpc4ZWuFaXj27dvd9NpvfYGZl1rsWvpwQcfdH0VBDYygkoAACqUobAg0Gq0lOk/efJk7pJx1YiqJlTLMbGmZbUokC3a9NX89NNPrl9mvQNFtYM6Dn6nQCccp64IBec6xvqN/GCqFgWk9rypajryBtwDvR9WU66us7Mzeeqpp9JvestqlqeaE82nYFF27drlttGnc1XjtC5Np+DygQceKBRMo7EpqPr8888LNTE1Z8+eTT/VplpK/TuPWoGiAjkFnhboFWFNUsNWH9o3FVLpWrx69WpPwd+7777b6zlKFWApqLRrPPZ8dpnjVI8IKgEASIW1ldu2bXPPUxb1xhtvuCaXeglFmSaX3333Xammr6J5Zfbs2a5fbxRYKWhXM88iz0kq2FJthGpg1BTuXtfeKSMaZqatdloFGVk0n70w6qGHHnL9GO2vMssKwrXP9lwx6ps9R55Vm12LrimdM2XTn7xUyKHm33keDdAL1FTbqFpFf7/UasBaDmS9xGvfvn19mr5msWecrRBRx1IFWMuWLXPDKgTS+u5lK5ChjKASAICUavdUE6WMhGoLFaAVbboqyviXbXKpjI2aZZWhTJCCLa33ySefTMfWH3sBj2rhPvjgg3Rsbf5zh3rhx1BjzQ21fUVf+pEVYCsIt5cVof6NHz/eBYV+Z28UrkVpngqj+hNQzpw5M/2UzWoeVfiWh5YZ7pM61cSr0+es9apQL0+rDwWK77//vmtCbsJaVyvEsSa+6I2gEgAAj9VSvvbaa8krr7ziPuflN1tUxsxK4dXkMhZYxmrLVHpfpumrlu+/GKjem2TZC3hUg1GEMo32ko6hRoUaatIq+i2L1Iho2vBtsj4VNKD+6RxSQYLf5SkYU/Cl5yDLFKL5FNSKNcMPKc3Tv+pQU9ZqaZR/7qvmMNwndaqxV6fPVrvo0/WgoDNPkKxCmbDWNAxUL1++7Pq2j8YKgMo+B18vCCoBAHVNmZgLFy64z5YpMMp0hM2ZlDmx1+H7tX1ajpoTSliCbW/9s7cJGmXQFMCo+aECS2Xc7HsFgaqREr9WStsSywRpvP6nXEjj1fRLy9d61MSzWsZQzcFEb3f0tzWLNd+9F82+9LvZbxfya4ND+p31W2XtnzVPvhu0DadOnXKf7dhXoyaxCiz1W2ob9dvacdeydM7aeRj6//6//6/P9BrWeZanmSEa0/r165N33nknuX79ujtfrNN4dUUoqFUgF0srlOY99thj7ppVk1Z/XUqzrOBNfS2jvwGuCuj0Py1r0T7q/0yGz6HrXqDt0HWra+mLL75w94Zwutu3b7v+f/7nf7p+w+oCAKBOtbe36+0KfbrY+EpmIZ2re77W1tZ0qMt9DqdXl7V8f97Ozs6uSnDQ63utyx+27ujRo12VgCKd846s6a3T9y0tLV0dHR3pHH3l2dZQbHr/OA2W2LZqXEz4W4XzZe2ffpempqZ0aHBUO29q0W+p3zQ8dzTc3NzszhWfptU+tbW19ZpHv1ee9aEx6bzxz6+wK3PuKA3TvD6dz5Vgss/yrfPTFZtW21aN5qmWHmkZ1dJE0XVUbT0XL15067Bt1DUW0vyV4DMdalwj9KdyoAAAAACg39QsVc8oLly4MB1TvxppX6uh+SsAAACAAaN/SfL666+nQ/VLjwfoxWqNHlAKQSUAAACAAaPnwvWis6LPZA4nevbzn//8J88rp2j+CgAAAGDAKfD67//+7z7/k3W4035duXKl3y8TqicElQAAAACA0mj+CgAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAAADbvfu3cmlS5fSofqxfv365Nq1a+kQhKDSs3Xr1mTMmDHJiBEjkunTpydnzpxJvwGyKbFcsGCBO2/UrVq1Krl582b6LeqNbiKWVlSTd7qYgVqHf25OmTKl6o1d5229pXnaH7su1elYxOgY+tPFuqxjE06XtY7+yrON6jRdSL+7fl+dAzad7nHK7Cmt2r9/fzrlHceOHXPTaFqdX5pf55syUoMp/M2sC/dL261xto3q9FnjwvTXX472JZY+x9arZek4LFmypGdcnrTdP87qgOHA0gKdvwNxL9DydO08/vjjydSpU9Ox3SxNKppe6prUNazrStsZS7vEny4rP69r265VbUfWta3xse83b96cbNu2rep9teF0wWlpaelqbW3tam9v72pra+saPXq06zo6OtIpgL4uXrzozpNdu3a5YZ0v06ZNc11nZ6cbh/qh31vphH7zasln3uliBnIdOg+bmprcZ/UnT57sPoeU5mlZ9UjXoa5PHSN1zc3N6Te9aTodL90LjI6xxmk+HWcNx9g9o+j9wl9XHtrG+fPnu+3RvcqndWvfwt9Rw5pev78/j6a377RMn/ZH4y1dk6NHj/Yci6KK7qdoe23bwrRU26Ljre/838S2MfZb2TxapqbJSp91DMN16rPmU1frOrFjl2daYKhQeqDr3a7xMH0pQ9ewrruQxilN0HrCtKcazaN7mK4rfbbrObzO9J3GVcvP67PGaZ91fWu5WfcGjc86HjZv1r2h0RS/O9QhnRQ68XyxmyoQUgJsmXajxIcMRX3TjVC/cS15p4vp7zp0k9N4uxnaeRne/DQcnsP1yI6TujC9N5YR8dlxU1ctGNHyiyozj7ZR2xJup2jb/HuWTZuVWRIdi3A7lNmKzaPl67uiyuynMp7a9jAdtd8ja5mWydN2hue6HY9qx0TLD9cpFqyqyzoHRNNp/VpH7DcChrJq6UsRSld0LVRT7ToOKQgM71N2j/PTJF2befLz+qxxRvsdS9s0byw98OXZ10ZB89eKsWPHuip63/333+/6v//9710fCKkp2Pnz55NHHnkkHdNt1qxZSSVTkbz11lvpGODu+/e//51+6s0fr+Y869atS7Zv356OqW+VjERSyTgkS5cuLdS8q5LxSSpBiLven3322XTs0KN72cqVK91nNcnSb6u0aMeOHW5cjO59Tz31VDrU7datWy59C2n5Og53w8iRI9NPvS1fvtz1Kxk91w9pGzdt2uT2QfsfamlpSSoZwGTnzp2uiVxeWu6rr77qlrt37950bG86p3S81aQOaGRq2vqXv/wlHeq/c+fOJVu2bEmHuqlJrdIjXZMmb37+t99+Sz/d4S9HlIYePnw4Wbt2bTom7sknn3T3hqymuI2EoDLD2bNnXUZi4cKF6Rigtxs3brh+LHFSpkIJVFYbfWCw/e53v3P927dvu37Mxo0bkw0bNrgbcSN46KGHkk8++cR9XrRoUaFnYRSYKRg5ceKEyzANNXo+yKfnJeVvf/ub61djgahRRk37qcxZ7Dmie0X72NHR4QK38Bktn2UqtQ9hcDxq1KjkwIEDrnBBQWeRjOCKFSvcfCowjKXtCmZfeOGFdAhoTLqmlP+ZOXNmOqb/dE1PmjQpHbpj4sSJ7pqsJpafVzogWXm0IgWuun8qTfroo4/SMY2LoDKgG5AyDLppfPrpp+lYoK8HH3zQ9ZVByfLzzz+nn4C7S5luBUEff/yxG/7ggw/cjU816aIbv27INtwolLFoa2tzmZ7nnnuuUMHP8ePHe2q5hlKptO5bX375ZTrUzbZPgXRRb7zxhsuEKW174IEHoi+/uRd++OEH189TE6hzXVTDEVLm9PTp0y4zqvt93sIFqwXRufP111+nY7vZMhrtegJC33zzjetbHmkwffbZZ64FQUy1/LxqF3X9Hzp0yKVtH374Ya9WGEULXJUmqRBrKKST9xJBpcearijDoJvGY489VqgkG41FiY2aUqnkXAmXEhN1ysxZRqZaaTow2Pbs2ZP8+uuv7u12Ok8///xzNz5s1qNz1t6CN9hv9xwKFBhYc9bVq1enY2vTNa9jqsyImtAWuT/o7YE6vn6nTEg4Tl0eTzzxRM/0um+FNXK6h1UT2x5rDqr9VACt4FtvUFSJvQWXtYTLVBfbz6JvfSzKAs/r16+7fkhps2qfdZyefvrp3JnBNWvWuL4ynD7VDIfjgEZkaVHegKwspb+6ftWCIFQrP6+CJbVaefvtt5Nx48a5wkIVpklY4Kp7otJBdVmFiY8++qjrX7lyxfUbFUGlRydQV1dXcvHixaSpqcllwmLPZABGTcEUWCqhUcKkDKqawyoRUyIF3EvKOCs4ULr23Xff9RRy+M16lAFQgKSme52dnYWfNRuuFFBYbVyRQFrH8MiRI+7znDlz+gRzWex38DutPxynLo/29vae6fW7hc9Fmqzmz9oe3euMPofPDin4vnr1qnsWVXTe6PX81QIwfz+si+2n1j+YbBsffvhh14/R/unZTN3r8wa5yoyqQELzWAZT58DJkyeppQQqVIh0Nyg9UkFpLHjNk59XqxWlb5pO17KWo2s5LHDVPVEtG5TuZz2Pb81pGx1BZYQyDTqRdCO8WxcHhi8Flr/88ktPwmSlYa+88orrA0OJAqgXX3yx50as5j+iDLbGzZs3zzUFagRqEqXCH70AwgKEPJRhsSa0yrDkreUaLPrdwucirVDrH//4h+vHWCGD+J9DWvaPP/7o9lW1u1kvqhls9oxWrElrSNspf/jDH1w/izKPVmud91nZsLZS/6tOhTLAUBBrhVDkxWTDga5VFQhVS7ekaH5ey/VfCKTnJGfMmOGWo3RfrVT27duXfosQQWUV9pY5IC8l3CrVUgKmTDowlNjLXPwXFpw6dSr91E1vM1apbiNQMGYvbVEJ9IULF9JvatP1rVYKRZvQ3i1WqKX0qGjQGwuudKysdjs8Z+4WZerUpE3BfLVMsp3nSodjL/cI2UuYdKz07HEtWqaWretEzV7VCoD0HkOF8q4KuPxu/Pjx6beDT9fGYNI1N3v27JoBpS9Pft4KXP00IwxEFWDmbZ3SiAgqq/jnP/856BcH6odqKPVGSWVOeMkT8ribNyet6/333+/z9s65c+emn7opsLKXnDQCZSDspS3VXroVo2OpWq6i890NCnJUs6gATP8GpUhgqZL9aufmfffdl34aPFnNdu0Niy+99JLrh7Sfr7/+uvs9q/0rlZCa4yrtzvtbWi3la6+9RqsUDCm69lUD73d5ClcGiq2rv/e32PxKm9TUtGghTq38fKzAVcJ51EoidiytoO1uvJxoKCOorNDJpAdw/Tfc6cTVMxJFbkpoTAomVcL1xz/+0ZViKXNiTQtRf5RG6DkMqXbTrDWdSlsVvNm/fvAN1Dp8qn2KpWeLFy92fQsklO49//zzbly9sON0+fLldExvKvHOSus1j+bVMmL0cgdrajrYtA2WecnTBEs1iwp6VdquF1XoN7b90G+t4RgFomoGHU6vGlkFawqkBpu9tViFHP6xt6bHqiXU851+jaXu5Wr6p+1XQUGY+dOysmqjlWbbS5hCWq6OoX+NaTssw6k3SRptq12T+lcGwHBi10d/3lyvWkSxf7sWY48J6Xrxr2+joFH3R//lOspnvfPOO+7lW8qvW6fx6qRMfl7XdazAVVTDqUBS26FlK21ZtmxZ+u0dWpfuAw2f9+tCV+Xm1FU5GfR2BNfpc2tra1dnZ2c6BRBn50xTU1NXJaOTjkW9Urpgv7l1GhfKM93Ro0fdePV9A7kO09LS0mc9Pn1XuYG7ZWjaehI7Tlk0bXt7ezp05/q2Luv46l6hNGAwxfZDnb+9WTRNJbjs+Y2tqwRF7ve+ePFiOmU3jdN9Ueu0eSrBlttHjR9M2lZ/G60Lj722I9ynrHt3bJlZx03j/XWF8+mYmXBafQ6nVwcMdbFrxD/Xi1J6EV6zRssN1xVej0qDtAxLbzQczuN3Nn+Z/Ly2p1q6pvm1Lepi+TwtW+siD9jVNUJ/KgcDAAAAAPpFtYOqVdTzxvWukfa1Fpq/AgAAABgQ1nxVTUbrnQJKNZ0HQSUAAACAAaRnuvVstP9cZL3Rs5wKKIu8ibae0fwVAAAAwIDTy+gef/zxugu8tF96SdfdfLPuUEdQCQAAAAAojeavAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAAAAACURlAJAAAAACiNoBIAAAAAUBpBJQAAAACgNIJKAAAAAEBpBJUAAAAAgNIIKgEAAAAApRFUAgAAAABKI6gEAAAAAJRGUAkAAAAAKI2gEgAAAABQGkElAAAAAKA0gkoAAAAAQGkElQAAAACA0ggqAQAAAAClEVQCAAAAAEojqAQAAAAAlEZQCQAAAAAojaASAAAAAFAaQSUAAAAAoDSCSgAAAABAaQSVAAAAAIDSCCoBAAAAAKURVAIAAAAASiOoBAA0hJs3bybr169PxowZk4wYMSJZsGBBcunSpfTboWv69OnpJwAYPo4dO+a6erN79+7kzJkz6RAMQSUAoCGsXr06mTBhQvLLL78k7e3tyblz55Knn37aBZjqFHTWMmXKlJ7p1Slj4Q+HnQLX/fv3p3PfofGx6UMKehVUZk1vnb5ftWpVNKNTa16/k61bt0a/i3WDlbHy16FCgNhvU+vYq8vavnA6HaO7SfuTd53KlOsc0HbqWOh3vnbtmisgAQaTzj2dp0oTitL5efv27WThwoXpmG4695UmKi0tkn4oLfTTMrsOQv50ul60HWH6oWHNb9PE0mij78L9X7lyZXL58uWq8zWkLgAA6tzFixe7dMurBJPpmG6dnZ1uvLrW1tZ0bFxbW1vmtC0tLX3Ga13Tpk1z4/V9yLZJ3dGjR9OxvWk+2+aOjo6u0aNHu+n9/dB4rde+C9fV1NTUa3p91nT+tmoZ2lZ9p/G7du1Kv+mm6efPn58OdR+35ubmPsehmtgxqEbHxPZJ26Z1xmg7tG32vY6rHXfNr+EY/Z76XvteRNH9iNFx0/b5v0uMnXP+76HjYvsHDBadc0o7dJ4Vuc5F88auE11r+s7O31rnv7G0z9IcXe+aX+P8dEHT6TtdI1q2bX+4LRqePHmym1fbo2li6YDSDi0ji9alaxTdSJEAAHXPMg6xTIwyOMqchBmUkKZTRiS2HA1rfJj5svHqYsuuFRz4gZxYZiq2H8oAaR/C7QgzPdW2VV0sk6Tpw22RIpnN2Py1aPlatzplKGO0zdWOu45x1u9aZpvKzBOy86jWsiwjHdL+6DtgMGWlFdUoONM81dJSu661/Dx0DYSFQxYwKm03SrvC9epaC68VDfv7FC5HtBxdn9X2w4LdWEDaiGj+CgCoe7/99lv6qa+xY8cmr776anLr1q1k79696dje1EyrkjlxTbaKmDVrVvopSa5cuZJ+ukPrzqJmXI8++mg6VNvUqVOTI0eOuM/r1q3raRq2ZMkS169F26ou7/Sydu3a9NPgaWlpSSqBYbJz585CzfAqGcKkkhlNzp8/nzz77LPp2HtPTebmzZvnzqcTJ05Ufa5X52SsiZ/OG+0bMNToetW1Vy1tK2rixIkuffNt2bLF9f20XWlXuF6l2brWfLquQuE9YuPGjcmGDRuq7sekSZPcsrdt25aOaWwElQCAumXP3SnIkieeeMINh8HJihUrktGjRydvvfVW9Pm9TZs2JS+88EI6lJ89M6Rl+wFmHgcPHkyeeeaZdCgfrUMBmHz99deuP9yNGjUqOXDggDuG+h2LPMe0Y8cOdzwUvOkZqqFAGdU1a9a4c0r00o8sChy17cosh+fl5s2b00/A0KACEF2rc+fOTccMjFjhlQI6UfqQRdeMnp1/77330jHdlJZUK2hUGqNANk+areedNX3svtFoCCoBAHVLmYKurq6ktbXVDbe3t7vhMJOi0mhl3FWCHQZjVpNUJChU5koZjUWLFrlhBTdFff/9931K5/Owt8VWqwEbbpSBPH36tMsMKjgssm/Hjx/vqeksEpAOBq1fNSfanyeffNLtj7YrVhspb7zxhqv1UUb9gQcecIUhZF4xVCmAk4cfftj1B5NeIqTrZ/HixemY3nStPfbYY64VSph2q7BG15SuJSvUseUobTl8+HDuVhgKPnXf+Pbbb9MxjYugEgCACtUeiWqSfMp0hOOyqCZNNaFqErV06VKXeeno6CjUpFSUsSnS9NWnTI5kBSp3g/+WRutU4xaOU5eXAmwF58rA6a29eYMrFRjs2bPHZUD1mxQJSAd6P955552ec0nbpQyvZDW71jQKitva2txbKnV+WXAJDDXXr193/ZEjR7r+YPr444+TN998M9o8VdetrnWlvbpmwjclv/zyy64J+rhx45K3337bXV8q6FGaoum3b9/uplNaYW9e1jJjaY4F0D/88IPrNzKCSgAAKpSpsCDQarQUmJ08eTJ3LaVqRFUT6j/vZs20ilAgW7Tpq/npp59cv8x6B4oCIR0Hv1ONWzhOXREKznWM9Rspk5eX/7zpnDlzcgfcA7kf1hTaP5esdkS1ldWCZO331atXk127drlhZXyV2c0bWAN3w6lTp9JPg0u1lCpk0b/2iNF129nZ6YJFFSbp+Uv/35coEFUBla5bXVdW6Pfuu+/2eo5ShVe6zuz6jj2bfTcC6OGCoBIAgFRYW6kXMNizb0Wo2aKaXCozU6bJ5XfffVeq6atoXpk9e7br1xs1S1PQrhfwFHlOUsGcMpmq6WxqarrrAZnOI22zX7tpLxDRNmXVVvqUif7xxx/d9mtZeeZBY7Pnyv2uSIHMUKPawy+//LLmIwUKDBUsWmHS2bNnXT+LAlWxQh8dNxVeLVu2zA0/9dRTrpXCvWwBMtQRVAIAkFLt3v+/vft/8aLaHzg+/gGZWj9FV0LrB6lLYVoiJiSk4o24obV1jQ9CoVcN4Va3clXikn1Zr3VBzCwUIiq/VBTSlhoktBZkXzBICmojQvxpNas/YD/7PDtnnZ2deX8Zd1d9v58PGOc98555z5dzZjyvOWfOUhNFYYLaQgK0ZpuuggJN1SaXFG5omlUFBSGCDbbLO3utKnbAQw3f9u3b07n1kZb0Tsk5Wrt2bTp37JEuvG9G7Um2dpOhu7s7LEMnUXlFQTN5KzbPG6+aIV26rrrqqlC7nx1WrFiRfju6RruDnjweBNHklYd2jSJIzPf+mkeguG3btmGdX+WD0Ouvvz6MT506FcYayaBSkqSMWEu5fv365NFHHw2fG5XtUTC+AwiaXBYFlkW1ZTyFr9L0ld/PdgwUm3C1qtgBDx1uNIOCY+yoY7xQS1mWJkuWLAkPMqitzPcESy13rZqRSZMmpZ+kYjwoo3Y/O1R5UNaIqVOnhvHJkyfDuKqiPM+9kj/zwQOVZu5trMdDwrlz56ZzRuLhTb7mM7/8iRMnwpggPSsGn+PROdHFzqBSktTSKFR888034XMsGETUCuabNPFkm0I+srV9/A7v3yD/FPujjz4K49ijYEThjQCGgIHAkiAhfk8QSI0Zsu/7sC9FTV+ZH3tXzGI+Hbfw+2yHJp61Co1vvfVWGL/99tvD9rVMbL57IZp+kW4x7fKytcF5pDNpVXZ8sXnyeCBQ5NzNmDEjnTNS7JSJBxnZvEB6UmudzTekAbWsHDfLS2Ml3i/je9r13HLLLWEcO+wpE6/pouCT+yI1i9l7GPPoyZU8T5Nv7ndxYLn4wI73H2naG6+heK1QO5t9lzmLTnzWrVs34h30WMPJ/ZJr77333gv/L+SXiw8S2b+21y9JUovq6emhh4URQ9H8gQJDutbgegMFkXSqP3zOL89Q9vvZdfv6+voHAphh37Ot7HQcuru7+3fu3JmueU7Z8nHg+87Ozv7e3t50jZEa2de8ouWz52msFO0r84rk0yq/XtnxkS4dHR3p1NjI55uifSlK27hcTFOmBwq44buBgnXY71ppLZ2vfJ5kaAR5s+weUXRd55clX5PHyfvZ6fx6cciuz3USl43XSdl9A9xv43aKHD9+fOj6ZMw9I497++rVq9Op9jaBfwZOliRJkiRVRu0gNXy8P9zqTfA5Vlo80OLkQva2fbGw+askSZKk80ZwxZ++4c9ztDp6B+ddTAPKQQaVkiRJkkZF/PuRVf6c0qWCY+PPNo1Vp0eXIpu/SpIkSRpV8W8/0sNxK+G4Jk6cWNr5T7syqJQkSZIkVWbzV0mSJElSZQaVkiRJkqTKDColSZIkSZUZVEqSJEmSKjOolCRJkiRVZlApSZIkSarMoFKSJEmSVJlBpSRJkiSpMoNKSZIkSVJlBpWSJEmSpMoMKiVJkiRJlRlUSpIkSZIqM6iUJEmSJFVmUClJkiRJqsygUpIkSZJUmUGlJEmSJKkyg0pJkiRJUmUGlZIkSZKkygwqJUmSJEmVGVRKkiRJkiozqJQkSZIkVWZQKUmSJEmqzKBSkiRJklSZQaUkSZIkqTKDSkmSJElSZQaVkiRJkqTKDColSZIkSZUZVEqSJEkaM6+88kry7bffplOtg+M6evRoOtXeDColSS2J/+gnTJgwNCxevDj9ZrgtW7YMW65oKCs05Jcr28b5amQfGVguj4LcmjVrkmuvvXZoudmzZ4fC0OnTp5O9e/emS57z4YcfhmVYdsqUKWH9n3/+OdmwYUO6xPhiPxs9t5yDeKyMmWb9C7Xv0qUu3ie4npoNoFj3vvvuS+bMmZPceOON6dxB3FO4PrnHNIP7U7zGWTde43nZ5Rhzz8vj/si9JS5TK/DlPpg//lWrViUnTpwovI+2nX5JklpUX19f/86dO/v5745h9erV6TfDsdysWbP6Ozs70zn9/cePHw/zWG/y5MlhusiePXvC9729vemcxmS31Qj2cdGiRWF/enp60rmD2DbH1tXVlc4ZxDTLd3R0DFuH5eN3/GYWx8N8zlvU3d09dC6a1exxFon7mj/uPM4BaRGX45zF9Mkfp6T6uFdwL4jXf71rMI97D/ePPO6nXNdcm83cV/gt1uG+wvrTp08P6+evb5aL973s/Su/L8xnOTDm94pwH2F7Zdg+y7Qzg0pJUsuLwRhD2X/8FBjyBSam43oUPghSilQJWKqsUyu4igF0FJctC6TBucjvBwW2onX4fb5rVpXjzCsrOGZRSGWZovTlfI3Gfkjtqta9pwzXIvfNWrgu+d1GsXz2PszneH/IPvjL3gtBcMwyMYBEvGfEY4r3+/wDRKaz6xXh97k/Mm5XNn+VJLWFgUJGMvCffnL//fc31YRroBCTDARZyVdffZUsX748nXvxueKKK0JTLNCE64knnkgGClvJjh07wrwiNEu7++6706lBv/32W2iWlsfvcx7GG83KFi5cGI7l0KFDpc3T/vzzzzD+9ddfwzhr3rx5yc0335xOSRoPNBe955570qnzx31pxYoV4V4U8Xnz5s3hc7wHIN4Lo2nTpoUx95Eou3xWdj7NarmXvvTSS+mcYvw+v71169Z0TvsxqJQktYXrr78+eeONN8Lnu+66q+a7M3kEZrNmzQpBDQWliw3vDmXFd4f+/e9/h3Et+cIXgSPHScCZf0/pmWeeST+Nn40bNyaPPfbYUMGx6L0oEDhSqKMAWPRu6YXYd6ld8TCIB1Rz585N55w/AjfuS3lXX311GF922WVhXIQHiTxUfOSRR9I555b/448/wrjIpk2bwj0oG8iW4T10jrvo/c52YFApSWobS5YsSfbs2RMKOw899FBT//kfPHgwBJYvv/zyRdUpA0/vP/jgg3RqUNw/AulmPf3006F2dt++fcl1111X2gnGeOA46DyDwuQdd9wRCoWc/6KaVLz77rtDgSXrXUzpJLWTTz/9NIxnzJgRxmPpo48+CvesfEdA4N7FPYwHiQcOHBgWHLI89/TXX389TG/fvj3cP3hABe4f11xzzdB0PSzL/y1ffPFFOqe9GFRKktoKT7pjc9a1a9emc+ujMLJr166hJrTN1HTG3gWzA7WB+XkMjbjtttuGlqcQlA+yKNjUUrQ/sXaP4ySAJvimZ0UCtBhc1pP/TYai42y0J9cXXngh1BKA/XryySfD5927d4dxHoVECnRdXV3JmTNnQjoRXOZrciWNrXhPaqSG73wQNPIAjGu+yJVXXhnuYdwTCSzzD5q4p589ezbcl3p7e8ODKXB/f//995PHH388TMcHXCxX1pP0DTfcEMbfffddGLcbg0pJUtuhOWusjWvmT00QtPC0G7fffntpjVkeQVr/YOd4QwPbz89jaERPT8/Q8n19fSPei4zKmnWxP8ePH0+nkvA5Fp4igu+ffvopvIsKCmY076pVa5k9jjgUHSfbrye+95qtJVi2bFkYU1tZth8UYjmWH3/8Mens7AwFxb/97W8XZbNlqVXxMGk8vPjii6FpfFEtJbjfcA8g6CSw5D6QvXewXrw/f/nll0O/w/0uvkfJfZ4HVGyH+y33n6KHbBMnTkw/tSeDSklSW3rzzTdD06dnn322qWaSBDmxCW1HR0fNIGs8EETl34vkuPDZZ5+FcZFsIaysQAZ+mwCNY6V2t6yWcLRRgGN72RpOamXBua+3H5wX3qMkYI7Nlpv9G3tSKyEQyl5PDI20QLhYcd+eOnVq4XuWWTSf50FTDCy///779JtiPGhct27dUC3rO++8E8Zsh3l0HPbqq6+GeTrHoFKS1JYoHFBTGZuzfvPNN+k39VG4oBas2Sa04+XRRx8N41o1emWKavQ4V/Gp/SeffBLGY4ng79ixY6FWIFvDydDd3R2Wef7558M4Yp2ihwMEzP/5z3/C588//zyMpXZEpzkEVtlhNDvSyaKFwliieSrvbeYfqNUSWzrUEpvK8/59lL/nzZw5M9R+ajiDSklS2+IJ9pEjR0JgSYDZDGrBeDez2fXGA0EvNYs8lefPoDQTWBKY1WrWO2nSpPTT2KGWkibKsaYgi8IeBVaOLd8TLO9g1nL55Zenn6T2QysLauyyQ6Od0DSLeysafUWgTNH6BJT79++v+eeSivzwww/hXl/WeRDb2rZt24ieohcsWJB+GsQDyNhqIis+tIrvVrYbg0pJUksjoOLdwBMnTqRzhqMmq6xwwjqsWxaU0VNqbGo61tiH+MT8rbfeCuNaqFmMfx7k1ltvDcFiPA4KT2VNfgnWaN6VX54aWQpk69evD/PGCoEi+1yr18j4NyfZl2yTVmqO6QQo2zEP3z/11FMhnRqpqZA0UmzJcfLkyTCuZ/78+WF86tSpMC4S780oCh65FxC8ZR8ecV9aunRpeEBE093sEDsA47foZIxWF/F3uQ8QMPJnpYoeVoHli/4viPeN+MDt8OHDycqVK8O8rN9//z2Mud+2pX5JklpUV1cXPd8MG8qwbE9PTzrVP2I9vi/S19fX39HRkU6NjaLjYMjubxmWGQgu+wcKZ8PWXbRoUX9nZ2f/8ePH0yUHMa+3tzdsM64zEEyGY2T+WMofZ9E5Z7+zy8TlOM7u7u5wPBwv+8x3HAPHRDpJag7XVf564xpsBNdg0TWM/LXOkF+W65n5jLPTZUN2fe5XcT73AO4Jte5f3CPidorwXbwfsmyRWbNmhe20qwn8M3CCJEmSJGlUULNHk3R6VW111GDSGoLWErHpb7ux+askSZKkUcW73dOnT2+LvxO7devW0HS2XQNKWFMpSZIkadTx3iTvY/P+c60/XXQpi++n1/vTJq3OoFKSJEnSmKGznTlz5rRcYEkt7MSJE8esF91LiUGlJEmSJKky36mUJEmSJFVmUClJkiRJqsygUpIkSZJUmUGlJEmSJKkyg0pJkiRJUmUGlZIkSZKkygwqJUmSJEmVGVRKkiRJkiozqJQkSZIkVWZQKUmSJEmqzKBSkiRJklSZQaUkSZIkqTKDSkmSJElSZQaVkiRJkqTKDColSZIkSZUZVEqSJEmSKjOolCRJkiRVZlApSZIkSarMoFKSJEmSVJlBpSRJkiSpMoNKSZIkSVJlBpWSJEmSpMoMKiVJkiRJlRlUSpIkSZIqM6iUJEmSJFVmUClJkiRJqsygUpIkSZJUmUGlJKktnD59OtmwYUMyZcqUZMKECcnixYuTb7/9Nv324jV79uz0kyRdWl555ZVL4j7bLP4v+fnnn9MpwaBSktQW1q5dm0ydOjU5c+ZM0tPTkxw7dixZunRpCDAZCDrrufbaa4eWZzh69Oiw6fxA4Lp379507XOYX7R8HoUxgsqy5ePA92vWrAn7k1dv3eyALVu2FH5XNBRtbzRkt8FDgKK0qXfuGcr2L78c52gsNHouWS4vPgQh/eNy5L9YmC3KV+SX++67b2h5PnMOPvzwwzFLK5SlRdFxsd/ZPMkxkXfzBfR8vm0mLTne7Hmocm1rMA+SXpybZvMP65IGc+bMSW688cZ07iDSmrzBtd0M0jWmE+vyG0Vpm12OMYFtHtdKzGMsUyvwLbq3PvPMM8nWrVtbMmCurF+SpBZ3/Pjxfv7LGwgm0zmD+vr6wnyGrq6udG6xPXv2lC7b2dk5Yj7bmjVrVpjP93lxnxi6u7vTucOxXtzn3t7e/smTJ4fls8fBfLYbv8tvq6OjY9jyfGa57L7yG+wr3zF/586d6TeDWH7RokXp1OB5W7169YjzUEvROaiFcxKPiX1jm0XYD/Ytfs95jeed9ZkuQnryPcfejGaPg/1i/9ifbDqAbRedx3jsHAef47ExjvvN72VxnMzn97LngvQv2nY9zR4n4ray6RHFdJk+ffqw/J7dR44tK67Dd82mJdtnPYZ6+bTWtd2uOJfcB+L5bzb/kKZF9zXSkHNclIdridcE+ZL1yUesn70vgeXiPY/Pcf/z+8J8lgNjfq8IeaMsT5DHWK8sX7Ybg0pJUsujcFRWMKJwQWGFIV8QzmK5WJDJ/w7TzM8XPuJ8hqLfjgWeMvkCU1lwAgo2saCW3Y98Qb3WvjLklwfL5/cFZYWtIkXr18Pvs20GgqUi7HOt8845LkvXKvt0PsfBfuWxb9kgPu57rf2OaZ1Vq2DMPhdtu5Yqx0nBnX3PpwfHUe8aY/9Ztyy/1jsnRfvL8vW2C5Yru7bbXa28W4Y05JzWQnrxu41i+Wwa8jmmWTaoyz8QIzhmmRhAguWzxxTzWD44ZDq7XpFGjrVd2PxVktTyfv/99/TTSFdccUXy5JNPJr/99luye/fudO5wNH0aKMCEZlLNmDdvXvopSb7//vv00zlsuwzNqm6++eZ0qj6amB04cCB8fuKJJ4aaE9IErRHsK0Ojy+Pxxx9PP42dzs7OZKDQlrz88suFzSnLDBRCk4FANPnqq6+S5cuXp3MvPuSBVatWhc805VuxYkX4vG/fvtL8QVo/99xz6dSgs2fPhqbdRc0B161bl34aWxMnTkw/Dbdp06ZwfbHPZcf07LPPhjFNDfPHUDUtx/LaVjnS8J577kmnzh/3Mq6LbN7h8+bNm8PnP//8M4wRr6Vo2rRpYUwaR9nls7LzyYPcR1966aV0TrE77rgj5Mui5ujtxqBSktSyKDDyzgyFA9x2221hOh+cPPjgg8nkyZOT559/vrBQTuHl4YcfTqcaF9/D4bezAWYj9u/fn9x7773pVGPYBgEYPv744zC+1F1++eUhwOIcko7NFN527NgRzsehQ4dCQfdiw7tfWaRZb29v0tHRMVQYLpMvPFPoJnjiPbH8e15LlixpOv+NFq4nHgiAAngZjpfgkWMoyrtV03Ksrm0V4/okDefOnZvOOX/kjaKHXVdffXUYX3bZZWFchHsw6f/II4+kc84t/8cff4RxER6EbNy4sfQhSMT3BKyvvfZaOqd9GVRKkloWBen+/v6kq6srTPf09ITpfA0bBQMKLUUF2lhAb6ZQHjtSueuuu8I0BeJmff311yM6uGhE7C22lTqQoFB55MiRUDgkoGjm2A4ePDhU03kx1SaQRz744IN0atD7778fxjNnzgzjZpB/qdWl1uSmm24K5ynWVl9I2Rr6eoFy/P7TTz8N47wqaTna17Zqi2k3Y8aMMB5LH330UXgQUXSf5AECDw+5B9OCIxscsjz56PXXXw/T27dvD4FhzAfkrWuuuabhfEEtNw87ih5atBODSkmSBjz22GNhzNPpLHoOzM8rQ00aNaEUUO6///7QZI+ap2aalILCbjNNX7MoDOFCBhT5njsZKHTl5zE0ioIgwTnBAb32NlqAozC5a9euEJCSJs0EpKN9HLGmnIE8kk8jmrDWQiE5u00G9jGiR0oenFDQJvBiGwSX9c7VWKRXFfXybtW0HI1rW42JaZcN4sYCeZoWDPGBYd6VV14Z7sfcLwgs8w8hyEdcb+Rp7tHvvvtumE+e4uFOfPDIegSNLEfPy0XivbroFYd2YlApSdIAakliEBgLIBSQDh8+3PATawo41ITyO1G92pkiFHabbfoa/fLLL2FcZbujhRolzkN2INDJz2NoBsE555g0ygZT9RCQxvdNb7/99oYD7tE+jlhTztDX15fcfffd6TfDlb0DTEGX9QgWsXPnzrCPWeRV5rEtliO4vO6662oGYGOVXs2Kx13rgUqVtByNa1uN4WHEeHjxxRdD0+WiWkqQV0lv7hcElvmHK6wX8/2XX3459DvZ9yjJIzy8YDtcd1xLRe9100RfBpWSJA3J12jwd8hiZxDNePrpp0PzKjofyT8hb0S2kNMs1sX8+fPDuNUQWMVOW5p5t47gYc+ePaGAyTuLF7qpGjU5+fciYzBFsFOG9WKnMtdff30YF+F4f/rpp6FCdXyveLxlg7Z6NYs0+cZf//rXMC5TJS1H69q+FBXVRMf3vS9F3FP5m8P1WoDwMIH7RbwG6tUkUhNJp1axlvWdd94JY7bDvIULFyavvvpqmKeRDColSUpRCKGGhifc1BYSoDXbdBUUQKo2uaTzFgovVVBQJNhiu7U6RbnUxU5bqDngfahGkZbxvcO1a9emcy8edCoD9q/ZQn9ZgE2hmnM1XjVIRWLNfa19IDDk+0bzbrNpOVrX9qWITpwIrLLDVVddlX47ujjHY4l7Ke9t5h/I1LJs2bL0U7nYaRadWkWffPJJ+mkQ7zqTf1TMoFKSpIxYk7F+/frk0UcfDZ8blW22SE1j7KCHZnpFgWVRDQudt1Rp+srvZzsGik/bWxVN1wiWeK+qGbx3SJDT7HrjgcCHJq0gLRttpguWzfcmm0WwNtbKetOk5p7t0wNr2THR2ybeeOONhvNus2l5Ptf2pYzgmYcL2YG8Nhbi7zaTd4sUrc89bv/+/U13fPbDDz+E/FfWeRDb2rZtW8hPWQsWLEg/Dfrmm2+Gmp5nxeBzPDonupgZVEqSWhqBG4UBnDhxIowjCuHUjmQLMDSti0/bszUm/A7NCfH555+HcUQvhKBwmw0UKcxR6KXpFYElzbbi9xSQqGVBtlaKfSlq+sr8Y8eOpVPnMJ/3fPh9tkOzwFo1MG+99VYYv/3228P2tUxsvps/T+OBdItpl5etDc4jnUmrsuOLzZPHA/sQC53x3NdCDQyBJWnJPpK28bzzW+TZmA/zHnjggRHLM00+a7YgXkXsTZM0y5570oree6dMmRKOKdsknOuA/Mo88m62pghV03K0ru12F6+/kydPhnE9sdn9qVOnwrhI9nwX3VOoSSZ4YxyRP+igi/cXydPZIb5fzW+Rx7I9H3NvJWCs9bCC5Yuuj1jDybb5PZqlr1y5MszL4njIg63+IK+ufkmSWlRPTw89i4wYiuYPFDbTtQbX6+rqSqf6w+f88gxlv59dt6+vr3+gwDHse7aVnY5Dd3d3/0BAka55TtnyceD7zs7O/t7e3nSNkRrZ17yi5bPnaawU7SvziuTTKr9e2fGRLh0dHenU2KiVb+ohLUnTfN5hevXq1SGvZLEsxzQQmA1bh/RqZHvnoyi9GPLnnv1jXnb/BoKHcDxFeTf7WwyNpmV+vWyezeeXsjRqd0Vp2ui1P3ny5NK0Kjrf+WXJ28yPeTxOlw3Z9ckHcX6tvBVx3eSvpSy+43f4PZbNI+/xHdddu5vAPwMnQ5IkSZLOCzV7L7zwwlCnYa2snY61Hpu/SpIkSRoVNGem+Wqtd3xbBQElzfBlUClJkiRpFPG3HnnHtqiDslbBnyAhoKz6559ajc1fJUmSJI06OtuZM2dOywVeHBedPY1VL7qXIoNKSZIkSVJlNn+VJEmSJFVmUClJkiRJqsygUpIkSZJUmUGlJEmSJKkyg0pJkiRJUmUGlSX4uzoTJkxIjh49ms6RRor5pGxQ6+MeMXv27KE053OV+8bevXvDH4yeMmVKzbxz+vTp5Nprr022bNmSzhlEXly8eHFYl+9r/W2wNWvWeG+TJEmjxqCyAIW2pUuXplNSOf5OUUdHR9LV1TVsWLRoUZiv1kbgdttttyUPPfRQwl9nYuAz82oFdVncbwgG77///hBQHjhwIPxOmbVr1ya9vb3p1Dlsd9KkSWHdWbNmld7DCF6vueaaZN68eekcSZKk82NQWYBC28qVK9MpqdjPP/+czJ8/PxTSH3/88WEDgcLf//73dEm1qv3794cAbtWqVemcJHyePn16cujQoXROuRhQHjt2LDl+/HiyY8eOmsEeDzFmzpyZTp1DAPvVV18lDz/8cJhmTOCZD2yZfv/990MelSRJGi0GlTmx0DZ37tx0jlRs2rRpobliHsEmBfw77rgjnaNWRvBGcJh15syZZOrUqelUueXLl4e8cuTIkeTGG29M5xYjIHzvvfcKA8I///wz/TRcdj77+MQTTyQvvfRSOkeSJGl0GFRm1Cq0SY36+OOPk9WrVydXXHFFOket6t57701+++23UNsYawU3bNgQHjYUPXDIooab2kzySr2AkoCQ5q1vvvlmOme4yy67LIz/+OOPMC6yadOmZOPGjeZLSZI06gwqU/EpflmhTWrUrl27kjvvvDOdUisjGNyzZ0+obbz99ttDIEkNJc1Y63nttdfCmPcbYwc7vFNJUJpHk3zyVVlAyH7QDPf1118P09u3bw9NcGNTWt+jlCRJY8mgMkWhjQ5WfIqv80HTV5pDLlmyJJ2jVkcgyb2DGst9+/aFGst8c9gi1FJOnjw5BKE8zOrr6wu/9eyzzw4LLGmST8BarzaToPPs2bMhOCUPvvvuu2F+/j1KAkx6h2W5ogBWkiSpWQaVAyi00alKvUKbVM8777xTt9mjWgtB2i+//BKCQnr8ffnll0PNY63AMjaVveWWW0J+4WEWAzWc1DASWLI+yzFkOwIqw/3r4MGDoffXL7/8cuh+ln2Pkoce9DK7efPmsL/sa/5Pk0iSJDXLoHLAP//5z1DQ4sl9HPiTAGDMtNSIV1991aavbeTDDz8M7ykSDBIUEmDyjiTNYXfv3p0uNdLVV1+dfhop/ima77//PgSEBH7Ze1O8H/Edn2v9vUlqItetWzfUAoOHHoiB7MKFC0OelSRJOh8T+mv9QbQ2UfSknpoHCnMUEHkXyc57VA81SjRTpOdPtQdqJEENYVbZ/Czen2T46aef0jmDuB8RMPInRggsf/311/Sbc/iev4W6YMGCZNmyZaEn4jwC3s8++yx55pln0jmD+0Wz23jbj9vyvwFJknQ+DCpL8PSfWsqenh47t1BD4vtp2UK8Whs1ftRK5gND8sLXX389LKik6Wk2+IsBXf4ew2/yTiRNWMtQQ8l7nGUPu9jWmjVrRgS1+SCybP8lSZKaYfNXaZTQSQt/YkLt4+GHHw4BIAFcfIeSGkJaOdDsNOK9bd6VZBw9+OCDocfWf/3rXyEIBN8fPnw4dLpzPtifoh5oqdUEzXTZJttauXJlmCdJklSVQaU0CmLHK3b21F6oYaSmkVrFK6+8MtQgPvXUU8mBAweG9QD8l7/8ZdgYvNNITeLs2bNDwMm6R44cCcP55KP4HmVRk1jmdXd3h/dA2SbN+23aL0mSzpfNXyVJkiRJlVlTKUmSJEmqzKBSkiRJklSZQaUkSZIkqTKDSkmSJElSZQaVkiRJkqTKDColSZIkSZUZVEqSJEmSKjOolCRJkiRVZlApSWoLp0+fTjZs2JBMmTIlmTBhQrJ48eLk22+/Tb+9eM2ePTv9JEmXpg8//DAMreaVV15Jjh49mk61N4NKSVJbWLt2bTJ16tTkzJkzSU9PT3Ls2LFk6dKlIcBkIOis59prrx1anoHCRHY6PxC47t27N137HOYXLZ9H0EtQWbZ8HPh+zZo1hYWbeutmB2zZsqXwu6JhrApT2W3wEKAobeqde4ay/csvxzkaC42eS5bLiw9BSP+4HPmPeT///HNhviK/3HfffUPL85lzQGF+rNKqFo6h0XPLPsZjJc3Jzxwnx6uLQ0yPmE5F+bYI6/zxxx/JkiVL0jnJ0MO9oqHZvEo+L8tn5EGuFa6dot/le/Ia22Wfiq6riO/yx7xq1arkxIkTNddrG/2SJLW448eP9/Nf3kAwmc4Z1NfXF+YzdHV1pXOL7dmzp3TZzs7OEfPZ1qxZs8J8vs+L+8TQ3d2dzh2O9eI+9/b29k+ePDksnz0O5rPd+F1+Wx0dHcOW5zPLZfeV32Bf+Y75O3fuTL8ZxPKLFi1KpwbP2+rVq0ech1qKzkEtnJN4TOwb2yzCfrBv8XvOazzvrM90EdKT7zn2ZjR7HOwX+8f+ZNMBbLvoPMZj5zj4HI+Ncdxvfi+L42Q+v5c9F6R/0bbrafY4i3BcjWw7XlvZfMdxx3TUhRfz3fTp08PnRq8b0jSfl1iftCV/ZAfyLttoBr9PHsnenyL2ke9jPirKh+wbx8Q1E3+r6NjitVSG7XNc7cwrVZLU8mJhoahQQYGDggxDLIwXYTkKH0W/wzTzKRhlxfkMRb9dr9CcLyiVBSeIQUV+P/IFnVr7ylBUMGL5okJb/jdqKVq/Hn6fbTNQ4CzCPtc675zjsnStsk/ncxzsV14szEZx32vtd0zrLAq85M8i7HPRtmupcpx58Xqp91scS1H6cvz549T4455AOpZdg2UIzlgvn4/L7hsEeM1sg+uAvBWHMrWuP/JXdn9YLns9gv3n98uuR3Cs/FajwXYrsvmrJKnl/f777+mnka644orkySefTH777bdk9+7d6dzhaDY1UEAOTaiaMW/evPRTknz//ffpp3PYdhmaMt58883pVH033nhjcuDAgfD5iSeeCE3VQNOwRrCvDI0uj8cffzz9NHYGCprJQICVvPzyyw03t8NAITAZKKAmX331VbJ8+fJ07sWHPEATOtAUb8WKFeHzvn37SvMHaf3cc8+lU4POnj0bmnbzG3nr1q1LP40fmgMuXLgwXDeHDh2q+f4y117Mr1kcP2moC4d73/333590dHQkO3bsSOc2hmuX6zCfj8vuG+T5O++8M52qjXz+0EMPJW+++WY6pxryXl7+/4tNmzYlGzdurHm/njZtWsjrW7duTee0H4NKSVLLokDEuzIEWbjtttvCdD44efDBB5PJkycnzz//fGGhfPPmzcnDDz+cTjUuvsPDb2cDzEbs378/uffee9OpxrANAjB8/PHHYXypu/zyy0Nhk3NIOjbz7hKFYM4HQQ3vTV1s8h2XkGa9vb2hAE8htZYYiEYEoxSQebcsH8DxLluz+e98UQh/7LHHwrUDOjQpQ+BIGvFAI3/9PfPMM+knXQjxIcezzz4bxo3iIQHX7YIFC9I5tcU8m33vshbekf/f//5XM9BrBPeVWg8dud9cc801DV0/vGvK8kX/h7QDg0pJUsuiINDf3590dXWF6Z6enjCdf1JOwYQCLYXyfDAWCzvNFMopUFG4uOuuu8J0s0/48fXXX4caqWZRsEGtmqFLDQHWkSNHQgGQ4LCZYzt48OBQTWczAelYI4988MEH6dSg999/P4xnzpwZxs0g/1IzRM3sTTfdNNTRzYXAeaZWn3S74447Qrpx/sv25+mnnw41WgQh1113XXjo064F84sJD8V4yEHa0Iojdq7DPabeNUhHaLjhhhvCuB4eovEwpRE8oLj99ttH5UEJDzTId+S3+OBj2bJlYcwxck022iKD4JP/Q7744ot0TnsxqJQkaQC1KqCGJYuCRn5eGWrSKHTRDIomYxRYKJQ106QUFGaaafqaRcEGFyqgQFGPs9RE5ecxNIoAm+CcQhu99jYadPDAYNeuXSGwIU2aCUhH+zhiTTkDeSSfRjRhrYVgK7tNhmyvl9Tq8eCEIIAgjm0QXNY7V6N9nC+88MLQNcP5p3k5ypqXswzB/549e0LgwnUUg0tdOJ9//nkYT5o0KbSaiD1nc08jqKt1j/n111/DeOLEiWFcD4FdIy0zuH55wJSvqa/qkUceCc20r7zyyuS///1vyIM8DOGaIR++9NJLYTm2G3u95XopuqZiAP3dd9+FcbsxqJQkaQAFiRgExhotCk2HDx9u+Ik4NaLUhGbfA6vXjLEIgWyzTV+jX375JYyrbHe0ECBwHrIDgU5+HkMzCM45x6RRNpiqJ/u+ab3CcNZoH0esKWfo6+tL7r777vSb4cqa41FjwnoEi9i5c2fYxyzyKvPYFssRXBKg1QqmR/M4Y5Pv7DUTa37Yl1oBLun7008/heMChXoK8o0+QNDo+uabb8KYpv+x1QTpGh/ulD0kwCeffJJ+qi/mmXotM8gHvEscA73RwAMNjoe8Td6LDwBffPHFYe9R8iCLvBivgaL3tBsNoFuVQaUkSal8bSWdLsR3wppBcz6aXPIeUpUml19++WWlpq9gXcyfPz+MWw2BFUE7zTybeU+SwjC1EBSGaWZ3oQMVCqv52pZYO82DjDKsFzuMuv7668O4CMdLIZkgnGMmQBsPXC+kTbZ2MwbB9QKRiPPy448/hnTitxpZR/UV1XTXqg2O6ZZHk2bQRH80vPXWWw01fSUfUKNJrWL2GKhVjzXro1G7Hd91jg9GYjPgf/zjH2Gah0Fs70K2BrkYGVRKkpSido8aGgoQ1BYSoDXbdBUU/Ks2uaRAQ3OsKij8UAhnu7Hg14piBzzUfG3fvj2dWx9pGd87pKOPiw0dRoH9i7U3jSoLsAnCY2dFY4195l06alOztZsM3d3dYRk6w8or2neuoVgj1Uytl8rNnTs3PGTIDswrM3Xq1DA+efJkGEex9o5msWUWNNhBD3jw1kjLjKL9ZyD4ZeBzreNpBIHitm3bhnUQFZsBR/FhzqlTp8JYgwwqJUnKiLWU69evTx599NHwuVHZZovxHUDQ5LIosCyqLaPzlipNX/n9bMdAseDXqmiySbBEzUUzKCzGzjkuNjzUiE0/SctmakJYNt+bbBYPGsYatZRleY9ePXlgQ21l7BAlIqioday1ghc1jpo3HjJkh1gbV4Rmy+Sb1157LZ0zKN7L/u///i+Mi5QFpHnkWQLCspYZ2XxRtP8M1Nwz8LnW8TSCBxzxvh3lA9UTJ06E8VVXXRXGUQw+G+2cqNUYVEqSWhqBW3w3KBYGIgo0+WZMFEoo/CJb28fv0JwQ+SfXH330URjHXgQjasYIYChIE1hSeI7fUzCjRgrZWin2paiAxfzYo2IW82nyxe+zHZp41qpdpakZ3n777cKgNi82370Qzb1It5h2edna4DzSmbQqO77YPHk8sA+xpi2e+1po+klgSVqyj6RtPO/8Fnk25sO8Bx54YMTyTJPP8gXl0UagSB6ZMWNGOmek2LyXBzbZPM+xUjufvT44BmqTSV+W1/jjGiPfkK7xQQDpwt+H5L5W689/3HLLLWEcO+wpw0M0fq8I90gCziqtRbLiPaRegLthw4bwN13z76PzfwL7wfVL/nzvvffC/xH55eJDxVtvvTWM206/JEktqqenh14VRgxF8wcKCelag+t1dXWlU/3hc355hrLfz67b19fXPxAcDPuebWWn49Dd3d0/EFCka55Ttnwc+L6zs7O/t7c3XWOkRvY1r2j57HkaK0X7yrwi+bTKr1d2fKRLR0dHOjU2auWbekhL0jSfd5geKNCHvJLFshzTnj17hq1DejWyvfORP86ic16Uh+NyMe8yPVB4D98NBJMhfWrlaY0P8lpMF8ZF6VuE9Kt3vyCdy9KY+XxP/qiFbRRtp+g+UrY/HGOt7Rw/fnwoDzPmWsuL12a7msA/AydIkiRJkkYFtZrU8PGObas3x+dYB4LK0CrgQva8fSHZ/FWSJEnSqIrvCPPnOVodPYXTVLhdA0oYVEqSJEkadfHP5sR3s1sRx8afcDrfdz8vdTZ/lSRJkjRmYs/EtTr3uRRxXBMnTjzvXmdbgUGlJEmSJKkym79KkiRJkiozqJQkSZIkVWZQKUmSJEmqzKBSkiRJklSZQaUkSZIkqTKDSkmSJElSZQaVkiRJkqTKDColSZIkSZUZVEqSJEmSKjOolCRJkiRVZlApSZIkSarMoFKSJEmSVJlBpSRJkiSpMoNKSZIkSVJlBpWSJEmSpMoMKiVJkiRJlRlUSpIkSZIqM6iUJEmSJFVmUClJkiRJqsygUpIkSZJUmUGlJEmSJKkyg0pJkiRJUmUT+gekn4eZMGFC+kmSJEmSpEH5ENKaSkmSJElSRUny/7rWfmlB4cvXAAAAAElFTkSuQmCC\" width=\"917\" height=\"932\"\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: FGS - Fluorescence-guided surgery; NN \u0026ndash; Neuronavigation; AS \u0026ndash; Awake surgery;\u003c/p\u003e\n\u003cp\u003eIONM \u0026ndash; Intraoperative neuromonitoring\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eNumber of used TTS and EOR\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNumber of used TSS had no correlation with EOR in the entire group of gliomas and also in eloquent and non-eloquent subgroups (Chi-Pearson test, P=0.135, P=0.396 and P= 0.062, respectively) (Table 2).\u003c/p\u003e\n\u003cp\u003eTable 2. Number of used TSS and EOR\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of used TSS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 73.8211%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEntire group patients\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.5528%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGTR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSTR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0894%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.5528%;\"\u003e\n \u003cp\u003e20 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e7 (23.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0894%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;3 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e1-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.5528%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;14 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e\u0026nbsp; 16 (45.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0894%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;5 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e3-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.5528%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;5 (31.25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e8 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0894%;\"\u003e\n \u003cp\u003e\u0026nbsp;3 (18.75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 73.8211%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients with gliomas in the eloquent areas\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.5528%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0894%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e1-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.5528%;\"\u003e\n \u003cp\u003e5 (27.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e8 (44.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0894%;\"\u003e\n \u003cp\u003e5 (27.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e3-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.5528%;\"\u003e\n \u003cp\u003e5 (35.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 7 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0894%;\"\u003e\n \u003cp\u003e2 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 73.8211%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients with gliomas in the non- eloquent areas\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.5528%;\"\u003e\n \u003cp\u003e17 (65.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e6 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0894%;\"\u003e\n \u003cp\u003e3 (11.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e1-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.5528%;\"\u003e\n \u003cp\u003e9 (52.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e8 (47.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0894%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e3-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.5528%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.1789%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 1 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0894%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;1 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eThe role of TSS use in terms of overall survival in the entire study group of patients\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe number of used TSS (none vs. 1-2 vs. 3-4) showed no correlation with overall survival (P=0.41). Younger age (below vs. above the median age) (P=0.015), EOR (gross total vs. subtotal vs. partial resection) (P=0.00018) (Figure 1) and the use of postoperative adjuvant therapy (radiotherapy and chemotherapy vs. radiotherapy or chemotherapy vs. none) (P=0.00001) (Figure 2) were correlated with OS in univariate but not in multivariate analysis. Other examined factors, including sex (P=0,32), tumor location in the eloquent vs non-eloquent area (P=0.192), tumor location in the dominant vs. non-dominant hemisphere (P=0.45), tumor volume (below vs. above the median volume) (P=0.182), postoperative KPS status (KPS \u0026ge;70 vs. KPS \u0026lt;70) (P=0.147), IDH status (wild-type vs. mutated vs. unknown) (P=0.538), did not correlate with the length of survival.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe role of TSS use in terms of overall survival In the subgroup of patients with gliomas restricted to eloquent areas\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn the subgroup of patients with gliomas restricted to eloquent areas (N=36), once again, younger age (P=0.025) (Figure 3), EOR (P=0.015) (Figure 4) and the use of postoperative adjuvant therapy (P=0.00065) (Figure 5) were correlated with OS. Additionally, the number of used TSS (none vs. 1-2 vs. 3-4) (Figure 6) showed a correlation with median survival of 194, 364 and 674 days, respectively, in univariate analysis (P=0.031). Importantly, it emerged as the only independent prognostic factor in multivariate analysis (P=0.006). Other examined factors, including sex (P=0,32), tumor location in the dominant vs. non-dominant hemisphere (P=0.098), tumor volume (below vs. above the median volume) (P=0.24), postoperative KPS status (KPS \u0026ge;70 vs. KPS \u0026lt;70) (P=0.37), IDH 1 status (wild-type vs. mutated vs. unknown) (P=0.864), did not correlate with the length of survival.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe role of TSS use in terms of overall survival In the subgroup of patients with gliomas in non-eloquent areas\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn patients with gliomas in non-eloquent areas (N=45) the use of TSS was not correlated with OS (P=0.25). Postoperative KPS status (\u0026ge;70 vs.\u0026lt;70) (P=0.023), EOR (P=0.01) (Figure 7) and the use of postoperative adjuvant therapy (P=0.015) (Figure 8) were correlated in univariate but not in multivariate analysis with OS. Other examined factors, including age (P=0.092), sex (P=0.4), tumor location in the dominant vs. non-dominant hemisphere (P=0.08), tumor volume (below vs. above the median volume) (P=0.342), IDH 1 status (wild-type vs. mutated vs. unknown) (P=0.46), did not correlate with the length of survival.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe management of patients with WHO Grade 4 gliomas involves a multidisciplinary approach, necessitating usually a combination of surgical, irradiation, and chemotherapy strategies. The primary objective in surgical management is achieving maximal safe resection, a factor consistently associated with improved OS in various studies [4,6,15,19-21,23,25,28,31]. Considering the incorporation of an increasing number of TSS in the treatment process of brain gliomas in recent decades, we decided to investigate whether the employing a greater number of these adjuncts yields a beneficial effect on both, EOR and OS. These methods include preoperative fMRI and DTT, as well as intraoperative techniques such as neuronavigation, IONM, awake surgery and FGS with 5-ALA [1-5,9,17,32]. Intuitively, combining multimodal pre- and intraoperative adjuncts during the same brain glioma operation should have a greater effect on EOR and OS compared to each modality alone or when used in modest numbers in combination. While numerous studies have been published focusing on the effects of each adjuvant modality [1,5,17], studies comparing the correlation between the use of different numbers of TSS and EOR and OS are scarce [4,32]. Another question worth addressing is whether the application of multimodal TSS has the same rationale in gliomas located in eloquent and non-eloquent areas. Neurosurgeons typically choose adjuncts based on their own expertise with various technologies, suspected tumor histopathology, tumor location, and sometimes on anticipated cost-effectiveness.\u003c/p\u003e\n\u003cp\u003eAwake surgery, employed in procedures involving eloquent brain areas, aims to map and preserve functional regions. It improves the identification of safe access corridors for tumors and provides precise real-time feedback on the function of critical structures, such as motor and language areas [17]. The benefits of brain mapping in gliomas during awake surgery are well demonstrated, improving EOR, PFS and OS, while reducing the rate of postoperative neurological deficits [7,34].\u003c/p\u003e\n\u003cp\u003eUnder the operating microscope, the similarity between tumor appearance and nearby brain parenchyma poses a challenge for achieving a complete tumor resection. Fluorescence-guided surgery with use of 5-ALA significantly enhances the ability to achieve a more extensive tumor resection by revealing residual tumor tissue at the margins [1,10,17,24,36]. Patients who undergo resection with the use of 5-ALA under a blue light microscope exhibit higher EOR, PFS and OS compared to those operated on under a conventional white light microscope [5,10,26].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNeuronavigation guides neurosurgeons in tumor resection, enhancing precision in targeting tumor margins and minimizing damage to the surrounding healthy brai\u0026shy;n [1,30]. A well-known limitation of neuronavigation is challenge associated with brain shift occurring during the surgical resection. A potential solution is the use of intraoperative ultrasound to update the neuronavigation system to account for brain shift [1,30]. The use of neuronavigation improves EOR and OS with an acceptable extension of preparation time for surgery [13,30].\u003c/p\u003e\n\u003cp\u003eThe implementation of preoperative fMRI and DTT in neurosurgical practice enables better planning and guidance for safe resections adjacent to critical regions, offering advantages in mapping without resorting to invasive, time-consuming, intraoperative monitoring techniques. Moreover, it provides an opportunity for integration them with neuronavigation and can be utilized during surgery [1,2,17]. DTT implementation seems to enhance EOR, improve postoperative KPS, and increase OS [31,33].\u003c/p\u003e\n\u003cp\u003eIntraoperative Neurophysiological Monitoring (IONM) involves monitoring electrical activity during surgery to identify functional brain areas and neural pathways. In glioma surgery, IONM typically begins with mapping of the motor cortex. Subsequently, the simultaneous application of subcortical mapping to detect the distance of corticospinal tracts, along with continuous monitoring of motor evoked potentials (MEP), is believed to be associated with enhanced EOR, fewer severe late functional deficits and better OS [11,12,35].\u003c/p\u003e\n\u003cp\u003eIn assessing overall outcomes, our study revealed that the number of used TSS did not correlate with OS in the entire patient group. It is in contrast to results of Xiong et al. [32], who found in their cohort of 912 patients that the OS was noticeably longer in the group with multimodal use of TSS comparing to the non-multimodal group (21.0 months vs. 16.0 months). It should be noted that in their multimodal group, there were more cases with a better EOR and more IDH-wild type tumors. Cui et al. [4] comparing the multimodal use of TSS including neuronavigation, intraoperative MRI and IONM and singular use of TSS (surgeries guided only by neuronavigation) in removing glioblastoma involving corpus callosum found better EOR, longer median progression-free survival (PFS) and longer median OS in multimodal group in univariate analysis.\u003c/p\u003e\n\u003cp\u003eWe found in the entire group of studied patients that factors such as younger age, greater EOR, and use postoperative adjuvant therapy i.e. radiotherapy and/or chemotherapy were significant factors correlated with OS in univariate analysis.\u003c/p\u003e\n\u003cp\u003eIt is well-known that younger patients have a more favorable prognosis than their older counterparts [7,14,20,21,25] due to their enhanced response to treatment, including greater tolerance for aggressive surgeries and better response to adjuvant therapies such as radiation and chemotherapy [16,18]. Additionally, younger age is generally associated with better overall health status [22].\u003c/p\u003e\n\u003cp\u003eThe extent of resection is a crucial factor influencing the prognosis of glioblastoma patients. Multiple studies have consistently demonstrated a positive relationship between greater EOR and improved OS [1,4,6,15,19-21,23,25,28]. The rationale behind this association lies in fact that achieving maximal safe resection not only alleviates symptoms but also reduces tumor burden, thereby enhancing the effectiveness of subsequent treatments such as radiation and chemotherapy.\u003c/p\u003e\n\u003cp\u003eThe integration of radiotherapy and chemotherapy into treatment regimens of WHO grade 4 gliomas has had established importance for many decades [4,14,17,21,25,28]. The combined modality, known as chemoradiotherapy, aims to enhance the efficacy of both treatments and improve OS, what was proved by Stupp et al. [27] in trial comparing radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy.\u003c/p\u003e\n\u003cp\u003eInterestingly, in the subgroup of patients with gliomas restricted to eloquent areas, the number of used TSS emerged as a notable factor influencing survival [4]. It proved to be the only independent prognostic factor in multivariate analysis. The association between the number of used TSS and OS in the case of gliomas restricted to eloquent areas may arise from the fact that employing various TSS in a multimodal approach enhances the effectiveness of glioma surgeries in critical brain areas. This approach provides neurosurgeons with a more comprehensive understanding of the tumor and its surroundings, leading to improved surgical outcomes. Our results regarding gliomas located in eloquent areas indicate that the use of multimodal TSS during surgeries is justified for such patients and should be considered for implementation into everyday clinical practice.\u003c/p\u003e\n\u003cp\u003eConversely, in the group of patients with gliomas in non-eloquent areas, we did not observe a similar relationship between the number of TSS used and OS.\u0026shy;\u0026shy;\u0026shy;\u0026shy;\u0026shy; Our results suggest that there may be no justification for employing multimodal TSS in the case of gliomas located in non-eloquent areas. However, to confirm such a conclusion, prospective studies should be conducted. In addition, it is essential to consider that the unwarranted use of these techniques in such patients may lead to adverse consequences such as prolonged operative time, increased surgical risks including the risk of infection [8], and may have an impact on treatment costs.\u003c/p\u003e\n\u003cp\u003eIn the subgroup analysis based on tumor location, i.e., in gliomas restricted to eloquent areas and those in non-eloquent areas, we also observed, in univariate analysis, correlations between EOR and the use of postoperative adjuvant therapy with OS, similar to the results observed in the entire group of patients [1,4,6,15,19-21,23,25,28,32]. However, between these two subgroups of patients we observed one difference: in gliomas located in eloquent areas, the factor correlating with OS was the younger age of the patients, whereas in gliomas located in non-eloquent areas, it was the post-surgery condition of the patients according to KPS scale. Nevertheless, in multivariate analysis, none of these factors retained significance, highlighting the complexity of their individual contributions and interplay between them.\u003c/p\u003e\n\u003cp\u003eWe also explored the role of TSS in relation to EOR [4,32]. Contrary to expectations, the number of used TSS did not correlate with EOR in the entire glioma group or in eloquent and non-eloquent subgroups. This finding suggests that while TSS may impact survival in the complex treatment process, its influence on the EOR is more nuanced.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur results contrast to those of other authors who reported associations between multimodal use of TSS and EOR, suggesting it as one of the critical factors influencing OS [3,4,32]. The number of used TSS may influence the neurosurgeon\u0026apos;s ability to achieve a maximal safe resection, thereby contributing to improved OS. While the correlation between a greater EOR and improved OS is well-established [1,4,6,15,19-21,23,25,28], challenges persist in balancing the need for maximal tumor removal with the preservation of critical neurological functions. Advances in neurosurgical techniques, imaging modalities, and intraoperative technologies continue to enhance the surgeon\u0026apos;s ability to navigate this delicate balance, ultimately contributing to improved prognoses for individuals facing the formidable challenge of glioblastoma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eWith mounting evidence highlighting the importance of GTR in enhancing patient survival in WHO grade 4 gliomas, recent decades have witnessed the emergence of a myriad of TSS, that allow for improved identification of tumor borders, crucial eloquent cortex and fiber tracts [3,4,32]. These novel adjuncts contribute to achieving higher rates of complete resections in a safe manner [4]. The effective application of these multimodal TSS requires technical proficiency and a thorough understanding of the intricacies associated with each method. Neurosurgeons should undergo specialized training to harness the full potential of these tools, and the learning curve associated with their implementation may impact their efficacy. Several TSS still require additional research to demonstrate their clinical efficacy and cost-effectiveness, preferably through randomized and comparative effectiveness trials.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOn the other hand, it is important not to overlook classic microsurgical skills, ensuring that the use of TSS does not result in the loss of dexterity and proficiency in tumor removal. Regardless of the surgical adjuncts used, equally important for efficient tumor removal is a thorough knowledge of neuroanatomy, the ability to recognize spatial relations of the tumor to adjacent structures, the ability to feel tumor margins, and the ability to make critical decisions swiftly and accurately. Provided that a neurosurgeon does not possess typical surgical skills, TSS can be misleading during surgery.\u003c/p\u003e\n\u003cp\u003eThere were several limitations to the present study. Firstly, it is a retrospective study in which the number and type of TSS used depended largely on the preferences of the operating neurosurgeon. Although we attempted to employ specific TSS combinations for particular tumor locations, the final decision rested with the operating surgeon. Secondly, we did not utilize modalities such as ultrasonography [1,5,29] or iMRI [5,6,9] among the adjuncts. Thirdly, patients were operated on by various neurosurgeons in our department, with different levels of experience, potentially influencing the extent of tumor resection. The varying degrees of experience among neurosurgeons may have also influenced the effectiveness of TSS utilization. Additionally, the relatively small sample size may limit the generalizability of our findings. Further prospective studies with larger cohorts are warranted to validate and expand upon our results.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our study sheds light on the intricate relationship between TSS, extent of resection, and overall survival in patients with supratentorial WHO Grade 4 gliomas. We observed that the utilization of multimodal pre- and intraoperative TSS, as opposed to using singular or no adjuncts, appears to correlate with overall survival in gliomas located in eloquent areas. However, it does not show a correlation with the extent of resection. On the contrary, in gliomas located in non-eloquent areas, the use of multimodal TSS has no correlation with either the extent of tumor resection and overall survival. Therefore, the use of multimodal adjuncts seems unjustified in such cases. However, to confirm such a conclusion, prospective studies should be conducted.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sector.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations of interest:\u003c/strong\u003e none\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional Review Board Statement:\u0026nbsp;\u003c/strong\u003eThe manuscript does not contain clinical studies or patient data. Our study was a retrospective analysis; all patients were treated according to standard practices, with no experiments or unusual interventions performed. In our institution, this type of research does not require Institutional Review Board (IRB) approval according to national legislation. We obtained a statement from the IRB Committee indicating that the study is exempt from such approval (decision number: AKBE/34/2024). All patients provided written informed consent for the procedures. Patient consent for publication was waived, as no identifiable information is included in the manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAuthor Contributions: conceptualization, T.C., E.M., P.K.; methodology, T.C., E.M., P.K.; formal analysis, T.C.; investigation, T.C., E.M., P.K.; data curation, T.C., E.M., P.K.; writing\u0026mdash;original draft preparation, T.C.; writing\u0026mdash;review and editing, E.M., P.K.; visualization, T.C., E.M., P.K.; supervision, P.K.; project administration, T.C.; All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBander ED, Magge R, Ramakrishna R (2018) Advances in Glioblastoma Operative Techniques. 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PLoS One 28:e63682\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Techniques supporting surgery, Awake craniotomy, Extent of resection, Glioblastoma, Intraoperative neuromonitoring, Overall survival","lastPublishedDoi":"10.21203/rs.3.rs-5097905/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5097905/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn recent years, numerous advanced techniques supporting surgery (TSS) have been utilized to maximize glioma resection. However, the impact of the multimodal use of TSS, such as awake surgery, intraoperative neurophysiological monitoring, neuronavigation, fluorescence-guided surgery, fMRI, and DTT, on improving OS remains uncertain..\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe assessed, in retrospective analysis of 81 patients with supratentorial WHO grade 4 gliomas, the effect of age, gender, tumor location, number of TSS used, EOR, postoperative KPS, IDH-1 status, and use of postoperative adjuvant therapy (PAT) i.e. radiotherapy and chemotherapy on overall survival. Kaplan-Meyer plots with F-Cox test and Cox proportional hazards model were used for univariate and multivariate analysis of survival.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWe used none, one, two, three or four TSS in 30, 20, 15, 9 and 7 patients, respectively. The number of TSS used (none vs. 1\u0026ndash;2 vs. 3\u0026ndash;4) had a correlation with OS in eloquent areas (P\u0026thinsp;=\u0026thinsp;0.031, univariate; P\u0026thinsp;=\u0026thinsp;0.006, multivariate) with median survival of 194, 364, and 674 days, respectively, whereas no correlation was observed in non-eloquent areas. In univariate analysis but not in multivariate analysis, significant factors for OS in gliomas in eloquent areas were younger age (P\u0026thinsp;=\u0026thinsp;0.025), EOR (gross total vs. subtotal vs. partial resection) (P\u0026thinsp;=\u0026thinsp;0.015), PAT use (P\u0026thinsp;=\u0026thinsp;0.00065), and in gliomas in non-eloquent areas were EOR (P\u0026thinsp;=\u0026thinsp;0.01), postoperative KPS (\u0026ge;\u0026thinsp;70 vs.\u0026lt;70) (P\u0026thinsp;=\u0026thinsp;0.023), PAT use (P\u0026thinsp;=\u0026thinsp;0.015).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe use of multiple techniques supporting surgery simultaneously improves the overall survival of patients with supratentorial WHO grade 4 gliomas in eloquent areas, in contrast to non-eloquent areas.\u003c/p\u003e","manuscriptTitle":"Role of Surgery Adjuncts for Overall Survival of Patients with Supratentorial WHO Grade 4 Gliomas.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-20 00:43:08","doi":"10.21203/rs.3.rs-5097905/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b4b1b540-5e33-4a79-908f-0674870a65a2","owner":[],"postedDate":"December 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-29T11:09:00+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-20 00:43:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5097905","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5097905","identity":"rs-5097905","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}