The CCT-D Trial: Evaluating the efficacy of the app-based cognitive control training de:)press ® as an add-on to standard inpatient care for depression – Study protocol for a randomized controlled trial

The CCT-D Trial: Evaluating the efficacy of the app-based cognitive control training de:)press ® as an add-on to standard inpatient care for depression – Study protocol for a randomized controlled trial | 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 Study protocol The CCT-D Trial: Evaluating the efficacy of the app-based cognitive control training de:)press ® as an add-on to standard inpatient care for depression – Study protocol for a randomized controlled trial Nicole Mauche, Mara Kojcinovic, Jue Huang, Simone Weller, Christian Makiol, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8910222/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 Depression is one of the most common and disabling mental health conditions. Despite evidence-based treatments, fewer than half of affected individuals achieve full remission. This may be due to limited targeting of cognitive vulnerabilities such as impaired control and negative information processing. Cognitive control training offers a promising add-on, with the adaptive Paced Auditory Serial Addition Task designed to activate prefrontal areas and promote neuroplasticity. Digital interventions, especially mobile apps, are increasingly recommended as adjuncts to standard care. This trial tests whether cognitive control training via the app de:)press® added to inpatient care reduces depressive symptoms more effectively and sustainably than a control condition in specialized wards for affective disorders. Methods This randomized, placebo-controlled trial will be conducted at two inpatient centers. A total of 106 adults diagnosed with unipolar depression will be randomly assigned to receive either standard inpatient care alone or standard care plus de:)press® . The app will be provided for six weeks. The primary outcome is clinician-rated symptom severity, measured four weeks after the intervention using the Hamilton Depression Rating Scale. Secondary outcomes include self-rated symptoms, well-being, neuropsychological functioning, and both trait and state rumination. Treatment expectations will be examined in relation to motivation, satisfaction, and outcome. Potential moderators such as age, gender, medication, cognitive style, and illness characteristics will also be analyzed. Discussion This trial examines whether app-based cognitive training can enhance treatment outcomes in inpatient depression care. If effective, it may offer a scalable, low-threshold tool to support recovery. Trial registration : German Clinical Trials Register: DRKS00037075 on 03 June 2025, last updated on 28 July 2025, https://www.drks.de/search/de/trial/DRKS00037075 . Depressive Disorder Cognitive Control Training Mobil Applications Randomized Controlled Trial Paced Auditory Serial Addition Task Gamification Add-on Therapy Treatment Outcome Introduction Background and rationale Major depression (MD) is one of the most prevalent and debilitating mental disorders globally, with a lifetime prevalence of approximately 16–20% worldwide (1, 2) and 11.6% in Germany (3–5). Standard treatments include pharmacotherapy, psychotherapy, and neurostimulation (6) however, many individuals lack timely access to appropriate care, and only a fraction receive depression-specific treatment (7). Internet- and mobile-based interventions (IMIs) have gained importance as adjunct treatments. The German National Clinical Practice Guideline for Unipolar Depression recommends guided IMIs as a first step within a stepped-care approach for mild depressive episodes; for moderate to severe episodes, IMIs may be offered additionally alongside psychotherapy and/or antidepressants (8). While most IMIs are based on cognitive-behavioral principles (9), less evidence exists for cognitive training approaches. Cognitive deficits—particularly in memory, attention, and executive functions—are common in MD and represent a promising target for intervention (10). Dysfunctional cognitive processes in MD are associated with greater disease burden and duration(11), as well as treatment response (12). They are a key predictor of functional impairments and reduced quality of life (13). The neurocognitive model of depression highlights impaired cognitive control (CC) and the related preferential processing of negative information as critical factors in the development and maintenance of MD (14, 15). Neuroimaging studies support this model, showing reduced activity in prefrontal cognitive control regions leading to insufficient regulation of limbic processing of aversive stimuli. Improved control of biased cognitive processes is considered a key mechanism and common behavioral correlate of successful MD interventions (16). Given the persistently high prevalence of MD, existing treatments may inadequately address neuropsychological impairments in attention, memory, executive function, and dysfunctional cognitive processing as vulnerability factors (17, 18). Cognitive control trainings (CCTs) have been proposed to modify cognitive processing biases and reduce depressive symptoms (19–22). CCT leverages neuroplasticity by targeted and repetitive training aimed at strengthening impaired neural circuits and restoring control mechanisms. Recent meta-analyses have shown significant improvements in mood and cognitive symptoms after CCT in MD (20, 23, 24). A commonly used CCT paradigm is the adaptive Paced Auditory Serial Addition Task (aPASAT) (25). Originally developed for neuropsychological assessment of brain injury (26), the task requires continuous serial addition of the two most recent digits (one to nine [1–9]) which are held in working memory and subsequently responding with the result if the addition. The aPASAT demands sustained attention and the ability to overcome distractions and negative feedback. To maintain challenge across participants, the interstimulus interval (ISI) adapts individually based on performance. Growing evidence supports the therapeutic potential of aPASAT in depressed individuals (27). However, evidence for CCT, particularly aPASAT-based training as a blended treatment for inpatients, remains limited. Siegle et al. (25) showed that a two-week aPASAT training (six sessions) added to treatment as usual (TAU) in depressed inpatients reduced rumination and symptom severity compared to TAU alone. These findings were replicated in outpatient samples (28, 29), with follow-up data indicating reduced clinical care needs up to one year post-intervention (29, 30). Contrarily, a recent inpatient study found no significant differences immediately post-intervention between a two-week aPASAT (10 sessions) add-on and a sham training, although exploratory analysis showed significantly higher subjective well-being in the intervention group at one-year follow-up (31). This delayed effect aligns with earlier studies finding significant group differences only at three-month follow-up (28). High dropout rates highlight that IMIs are not equally suitable for all patients: motivation, personal preferences, and technical access play key roles. For optimal effect, CCT must be conducted regularly over several weeks (6). Current studies suggest an optimal dose of 10–15 hours of training distributed over multiple weeks (21). To improve adherence and engagement, our study will utilize a gamified, app-based aPASAT training ( de:)press ® ) that integrates depression-adapted gamification and information elements. A recent pilot study demonstrated the superiority of the gamified version regarding both depressive symptom relief and usage frequency compared to a non-gamified version of the CCT (6). Remarkably, the symptom reduction effect of de:)press ® persisted up to three months post-training. Given the need for accessible adjunctive treatments targeting cognitive dysfunction in depression, this trial tests a gamified, app-based cognitive control training (aPASAT via de:)press ® ) as an add-on to TAU in specialized inpatient units for affective disorders. TAU serves as the comparator to evaluate the specific benefit of the intervention, ensuring both clinical relevance and ethical acceptability, as all participants receive standard care. We expect greater symptom reduction four weeks post-intervention compared to TAU alone. Objectives Primary objective is to evaluate whether six weeks of CCT via the de:)press ® app, in addition to TAU, leads to a greater reduction in depressive symptom severity compared to TAU alone in adults with unipolar depression treated on specialized inpatient units. Secondary objectives are to assess additional benefits of the intervention, including improvements in subjective depressive symptoms, cognitive functioning, and patient-reported outcomes such as rumination, treatment satisfaction, and motivation. The study will also explore potential moderating factors, including treatment expectancy. Potential harms such as reduced adherence due to training burden or negative emotional reactions (e.g., frustration or demotivation) will also be monitored. Methods Patient and public involvement Patients and members of the public were not involved in the design, recruitment, or conduct of this study. However, patient involvement is planned for the dissemination phase. After study completion, participants will be invited to provide feedback on their experience with the intervention and its integration into inpatient care. This feedback will inform future adaptations of the app and its potential broader implementation in clinical practice. Trial design and setting The CCT-D trial is a prospective, randomized, controlled superiority trial with two parallel groups and a 1:1 allocation ratio. The study will be conducted at two urban academic medical centers in Germany: the University Hospital Leipzig and the University Hospital Tübingen. Both sites include specialized inpatient units for affective disorders and operate within the public healthcare system. They provide multiprofessional care with physicians, nurses, psychologists, and therapists. Treatment includes pharmacotherapy, individual and group psychotherapy, digital interventions, and noninvasive neuromodulation (e.g., rTMS), complemented by relaxation, physical, and creative activities. Weekly social visits support discharge planning and ensure coordinated transition to outpatient care. The institutions have established infrastructures for clinical research and comply with national ethics and data protection regulations. Eligibility criteria Eligible participants must be 18 years or older, provide written informed consent, and have a confirmed primary diagnosis of unipolar major depression according to ICD-10 (F32.0, F32.1, F32.2, F33.0, F33.1, F33.2). Additional requirements include sufficient German language skills and the ability to operate a mobile device. Exclusion criteria are acute suicidality, psychotic features (F32.3, F33.3), other major psychiatric conditions (e.g., bipolar disorder, schizophrenia spectrum, organic mental disorders), primary substance dependence (excluding nicotine), intellectual disability, or somatic/neurological disorders affecting cognitive functioning. Individuals currently using other cognitive training interventions, under legal guardianship, institutionalized, with insufficient compliance, or who are pregnant or breastfeeding will also be excluded. Recruitment and data collection will take place locally at the participating university hospitals. Trained clinical staff in accordance with a standardized protocol (Version 1.2, 17. July 2025) will conduct interventions and assessments. Interventions and comparator Participants in the intervention group receive a six-week, app-based cognitive control CCT using the gamified de:)press ® application, which is available for Android devices. The intervention is based on the aPASAT, implemented as a self-administered mobile app. In each session, participants hear a sequence of single-digit numbers (one to nine) via auditory presentation. They are instructed to continuously add the two most recent digits and select the correct sum of each addition (two to eighteen) on a touchscreen. Immediate feedback is provided via a green screen for correct responses and a red screen for incorrect, delayed, or missing inputs. The ISI dynamically adapts based on performance: four consecutive correct responses reduce the ISI by 0.1 seconds; four consecutive errors increase it by 0.1 seconds. The ISI will be carried over from block to block, however it will be reset to the initial 3 s for each new training session. Each training session consists of three 5-minute blocks separated by 30-second breaks. Participants are instructed to complete at least three sessions per week, with a maximum of one session per day, over six weeks. App usage data is automatically recorded; however, the study staff will not monitor adherence or be able to access participants’ performance data during the intervention period. The app includes several gamification elements to enhance motivation and engagement: (a) psychoeducational content on cognitive mechanisms of depression and the rationale for CCT; (b) real-time performance feedback with graphical progress visualization; (c) unlockable levels and audio-guided imagery as adherence rewards; and (d) a virtual coach (animated avatar) providing guidance and encouragement. The app contains all necessary instructions, and no in-person training is required. Technical support is available if needed. Participants may discontinue the intervention at any time or if clinically indicated (e.g., mental health deterioration or safety concerns). Unless consent is fully withdrawn, participation in follow-up assessments remains possible. Control group participants receive standard inpatient TAU, including pharmacotherapy and/or psychotherapy in line with national guidelines (8). No restrictions apply to concomitant care. For ethical reasons, control participants are offered access to the de:)press ® app after their final follow-up assessment. Outcomes Primary outcome To examine whether six weeks of cognitive control training via the de:)press ® in addition to inpatient TAU reduces depressive symptom severity more effectively than standard care alone, the score of the 21-item Hamilton Depression Rating Scale (HAMD-21) at end of study will be collected. Key secondary outcomes The effects of cognitive control training with de:)press ® on response and remission rates of depressive symptoms at four weeks post-intervention, as measured by the HAMD-21. Changes in subjectively reported depressive symptom severity, measured by the Beck Depression Inventory-II (BDI-II), at the end of the intervention and at end of study four weeks later. Changes in general well-being, as assessed by the WHO-5 Well-Being Index, at the end of the intervention and at end of study. Other secondary outcomes Changes in subjective and objective cognitive performance using the app-based THINC‑it ® (32) neuropsychological test battery at end-of-intervention and end of study. Changes in trait and state rumination, as measured by the Rumination subscale of the Rumination-Reflection Questionnaire (RRQ) and an adapted version of the Perseverative Thinking Questionnaire (PTQ). Influence of treatment expectations, operationalized by an adapted version of the “General Treatment Expectation” (BE) subscale of the Questionnaire for Measuring Therapy Motivation (FMP), assessed prior to the start of the intervention. Influence of treatment motivation (indicated by the number of completed training sessions) and satisfaction (measured with an adapted version of the Client Satisfaction Questionnaire, ZUF-8). The role of a distorted cognitive pre-treatment style using the Lübeck Preoperative Thinking Questionnaire (LFPD), assessed before the intervention. Evaluation of the feasibility of implementing de:)press ® into standard inpatient care based on participant uptake, usage rates, and reported barriers to usage. Harms Based on current evidence and prior use, CCT via the CE-certified de:)press ® app is not associated with known adverse effects (AEs). To date, no AEs related to de:)press ® have been reported in previous or ongoing studies. Transient frustration is an expected component of the task and is addressed through integrated psychoeducation and adaptive difficulty adjustment. AEs will be assessed non-systematically via spontaneous self-reports and clinical observation by trained inpatient staff and monitored throughout the intervention period. No ancillary or post-trial care is planned, as all participants are inpatients receiving standard hospital care. Any harm related to trial participation will be managed within the hospital setting, with costs covered according to institutional and legal regulations. Participant timeline Participation in the trial spans a total of 10 weeks per individual and includes three visits: the screening and baseline visit (V0), a visit at the end of the intervention (V1), and an end of study visit (V2), conducted four weeks after the intervention concludes. An overview of the visit schedule is provided in Table 1. The total planned duration of the clinical trial is 12 months. Note . V0, baseline visit; V1, end-of-intervention visit; V2, end-of-study visit; HAMD-21, 21-item Hamilton Depression Rating Scale; BDI-II, Beck Depression Inventory-II; WHO-5, 5-item World Health Organization Well-Being Index; PTQ, Perseverative Thinking Questionnaire; RRQ, Rumination-Reflection Questionnaire; BE, General Treatment Expectation; LFPD, Lübeck Preoperative Thinking Questionnaire; ZUF-8, Client Satisfaction Questionnaire; TAU, treatment as usual; CCT, cognitive control training; IG, intervention group; CG, control group. Sample size The sample size was calculated using G*Power (version 3.1.9.7) based on the primary outcome: depressive symptom severity, measured by the HAMD-21 at four weeks post-intervention. Assuming an effect size of d = 0.7, derived from a previous pilot study of the de:)press ® intervention in outpatients (6), a two-tailed independent samples t -test with 90% power and a significance level of α = 0.05 yielded a required sample size of 44 participants per group. Accounting for an estimated 20% dropout rate, a total of 106 participants will be recruited from the specialized inpatient units for affective disorders at the participating university hospitals. Recruitment Participants will be consecutively approached by staff during their inpatient stay at the participating study sites and are provided with information on the study if interested. Eligible newly admitted patients will be invited to participate, subject to the availability of compatible (personal or provided) mobile devices. Recruitment will be supported through close coordination with clinical teams and ongoing monitoring of enrolment to ensure timely achievement of the target sample size. Randomization Stratified randomization is used to ensure balanced allocation across key demographic variables. Participants are stratified by gender (female, male, diverse; 45%, 45%, 10%) and age group (18–29, 30–49, 50–69, ≥70 years; 30%, 30%, 30%, 10%), resulting in 12 strata. To simulate the expected sample distribution, oversampled randomization matrices (n = 500 each) are created using MATLAB (2023b). Within each stratum, participants are randomly assigned (1:1 ratio) to the intervention or control group using SPSS (version 29, IBM) with a uniform random function (RV.UNIFORM(0,1)); values < 0.5 are assigned to the intervention group, values ≥ 0.5 to the control group. The allocation sequence is embedded in the REDCap database (Research Electronic Data Capture) and automatically triggered upon entry of stratification variables. Allocation concealment is maintained by restricting access to group assignments within the system. Study personnel involved in generating the randomization syntax are not involved in outcome assessments and remained blinded to group assignments. Participants are enrolled and stratification variables entered by trained study staff. Group allocation is disclosed only to the intervention team after eligibility was confirmed. Blinding Due to the nature of the intervention, double-blinding is not feasible. Participants are aware of their group allocation. However, outcome assessors and data analysts responsible for evaluating the primary endpoint remain blinded to group assignment. To maintain blinding, both participants and unblinded study personnel are instructed not to share any information regarding group allocation with the blinded assessors. Unblinding of outcome assessors will occur only after completion of all primary endpoint analyses. Premature unblinding is not planned, as no study procedures or safety monitoring require knowledge of group allocation. Should unblinding become necessary in exceptional cases (e.g., for clinical or organizational reasons), it will be documented and justified in the trial records. Data collection, management, and analysis The above-mentioned outcomes will be assessed using standardized clinician-administered and self-report measures, as well as an app-based neuropsychological test battery, all completed on a mobile device. Data will be collected on-site at three predefined study visits (screening/baseline, end of intervention, and end of study) for both groups. To promote retention, study visits will be scheduled during the inpatient stay whenever possible. After discharge, participants will be contacted in advance and offered flexible scheduling for the follow-up visit. Brief, user-friendly data collection procedures and technical support will be provided as needed. Participants who discontinue or deviate from the intervention will be encouraged to complete outcome assessments; remote completion will be offered if on-site visits are not feasible. All personal and study-related data will be collected and stored in accordance with applicable data protection regulations. Participants will be assigned unique study IDs, with identifying information kept separate from study data. Data will be entered directly into REDCap on a mobile device, which applies range checks and validation rules to ensure data quality. REDCap also maintains a comprehensive audit trail, recording all changes to data entries, including creation, updates, or deletions. Access to the study database is restricted to authorized personnel, and data will be securely stored on institutional servers. Relevant study documents will be retained at each study site for at least 10 years after regular or early study termination and, after the archival period, stored in anonymized form. Any dissemination of results will use anonymized or aggregated data to maintain confidentiality. In case of technical difficulties, the assessments will be provided on paper and later transferred to REDCap. An intention-to-treat (ITT) analysis will be conducted within the full analysis set of all randomized participants with at least one completed intervention. Missing HAMD-21 scores at the follow-up visit four weeks post-intervention will be imputed using multiple imputation. The primary outcome will be analyzed using an Analysis of Covariance (ANCOVA) with study arm as the main factor and baseline score as a covariate. Secondary outcomes will be analyzed similarly, using baseline-adjusted ANCOVAs, logistic regression for categorical variables, or proportional odds models for ordinal variables. Longitudinal trajectories will be evaluated using mixed models and illustrated with line graphs. Descriptive statistics will include means, standard deviations, ranges, medians, quartiles, and absolute and relative frequencies, with two-sided 95% confidence intervals. The number of completed training sessions will be analyzed using a Poisson regression model. Adverse events will be summarized in frequency tables and compared between groups using chi-square tests. Exploratory analyses will examine potential effects of additional therapies and BE. Monitoring Given the low-risk nature of the intervention and the close clinical monitoring inherent to the inpatient setting, no independent Data Monitoring Committee has been established. No interim analyses are planned. Individual participants may withdraw from the study at any time at their own request. Criteria for early termination of the entire study include insufficient recruitment, the emergence of unacceptable risks based on a risk–benefit assessment, or new scientific evidence contradicting continuation. The principal investigator will make decisions regarding study termination. Dissemination plans The results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals, Guideline groups, and to the public via media communications, social networks, presentations at science festivals, charities, family and patient support groups, and clinics. Discussion This randomized controlled trial (RCT) will investigate the feasibility, acceptability, and efficacy of de:)press® , an app-based CCT, as an adjunct to specialized inpatient treatment for unipolar depression. The intervention aims to enhance cognitive control and reduce repetitive negative thought patterns - mechanisms implicated in depressive symptom persistence and relapse ( 11 – 15 ). Outcomes will be compared between CCT plus TAU and TAU alone, with assessments at the end of treatment and four weeks post-intervention. CCT is a computerized cognitive remediation approach that has shown promising effects in remitted depression, particularly on residual symptoms and cognitive control, although findings vary between studies ( 20 , 27 , 33 , 34 ). Evidence for its use in inpatient settings remains scarce ( 31 ). The present trial addresses this gap by integrating a standardized CCT protocol via de:)press® into daily clinical care. de:)press® is a gamified adaptation of the aPASAT, designed to increase engagement and adherence while preserving the core cognitive training mechanisms. This combination of evidence-based task structure and game elements aims to bridge the gap between experimental findings and scalable real-world applications. In Germany, several approved Digital Health Applications (DiGAs) for unipolar depression are listed in the official DiGA directory maintained by the German Federal Institute for Drugs and Medical Devices ( 35 ), but most are grounded in cognitive behavioral therapy and focus on psychoeducation or behavioral activation. Digital interventions specifically designed to remediate cognitive deficits in depression are rare. By targeting cognitive control during acute treatment, this study explores a complementary therapeutic pathway that may improve not only mood but also cognitive functioning and daily life outcomes—domains often still impaired after symptom reduction. In addition to changes in depressive symptoms, the study will examine whether improvements in cognitive performance and rumination can serve as potential mediators of treatment response. Investigating individual differences—such as age, gender, medication, comorbid disorders, pre-existing cognitive distortions, use of neurostimulation, and severity or tendency to relapse—may help identify subgroups most likely to benefit, thus enabling a more individualized application of CCT in clinical practice. From a healthcare perspective, CCT offers potential cost benefits: it is inexpensive to implement, can be standardized and digitally monitored, and could reduce the need for more resource-intensive in-person interventions. Patients’ increasing familiarity with digital tools, accelerated by the COVID-19 pandemic, could further facilitate its adoption. Despite these strengths, some limitations should be noted. Conducting the trial in inpatient units may limit generalizability to outpatient populations. Adherence could be influenced by symptom severity, hospitalization length, and digital literacy. Furthermore, the trial focuses on short-term outcomes; long-term maintenance of benefits remains to be examined. In conclusion, this study will provide important insights into the feasibility and potential effectiveness of app-based CCT as an adjunct to inpatient depression treatment. If positive, the findings could support future large-scale implementation studies and inform clinical guidelines, ultimately contributing to more comprehensive recovery strategies in depression care. Trial status The trial is currently recruiting. Recruitment started in July 2025 and will last until the end of April 2026. Abbreviations AEs Adverse effects ANCOVA Analysis of Covariance aPASAT adaptive Paced Auditory Serial Addition Task BDI-II Beck Depression Inventory-II BE General Treatment Expectation CC Cognitive control CCT Cognitive control training FMP Questionnaire for Measuring Therapy Motivation HAMD-21 21-item Hamilton Depression Rating Scale IMI Internet- and mobile-based intervention ISI Interstimulus interval ITT Intention-to-treat LFPD Lübeck Preoperative Thinking Questionnaire MD Major depression PTQ Perseverative Thinking Questionnaire RCT Randomized controlled trial RRQ Rumination-Reflection Questionnaire TAU Treatment as usual WHO-5 5-item Well-Being Index ZUF-8 Client Satisfaction Questionnaire Declarations Ethics approval and consent to participate The trial protocol and related documents have been reviewed and approved by the Ethics Committee at the Medical Faculty of the University of Leipzig (Ref: 163/23-ek) and the Ethics Committee at the University Hospital Tübingen (Ref: 793/2023BO2). Any substantial protocol amendments have been and will continue to be submitted to both ethics committees, updated in the study registry, and communicated to all investigators, study staff, and other relevant parties prior to implementation. Approvals were obtained prior to the initiation of participant enrollment. Trained study staff (physicians or psychologists) will obtain written informed consent from all participants after providing verbal and written study information. Participants may withdraw at any time without consequences. No ancillary studies or additional data/specimen collection are planned. Consent for publication N/A. Availability of data and material The complete protocol, including the statistical analysis plan, will be registered in the German Clinical Trials Registry (DRKS, https://www.drks.de/search/de/trial/DRKS00037075) and will be updated in the event of any changes. The datasets generated and/or analyzed during the current study are not publicly available due to privacy and ethical restrictions but may be made available from the corresponding author on reasonable request. Competing interests NM, MK, JH, and CM declare that they have no competing interests. SW and CP are founders and shareholders of psykit GmbH, Tübingen, Germany. CP serves as managing director of psykit GmbH. The company developed and distributed the CE-certified medical device de:)press ® with support from the University Hospital Tübingen. MS has received speaker fees from MEDICE Arzneimittel Pütter GmbH & Co. KG, Takeda, and Janssen-Cilag, and has served as an advisory board member for Takeda and Janssen-Cilag. Funding de:)press was provided by psykit GmbH free of charge. No external funding was received for the conduct of this study. Authors contributions MS, NM, JH were responsible for the conception and design of study; NM, JH were responsible for statistics consultation; NM, MK were responsible for drafting the manuscript; MS, CM, JH were responsible for revising the manuscript critically for important intellectual content. All authors have read the manuscript and approval of the version of the manuscript to be published. Acknowledgements N/A. References Bijl RV, Ravelli A, van Zessen G. Prevalence of psychiatric disorder in the general population: results of The Netherlands Mental Health Survey and Incidence Study (NEMESIS). Soc Psychiatry Psychiatr Epidemiol 1998; 33(12):587–95. Ebmeier KP, Donaghey C, Steele JD. Recent developments and current controversies in depression. Lancet 2006; 367(9505):153–67. Jacobi F, Höfler M, Strehle J, Mack S, Gerschler A, Scholl L et al. Erratum zu: Psychische Störungen in der Allgemeinbevölkerung. 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Cognitive control interventions for depression: A systematic review of findings from training studies. Clin Psychol Rev 2017; 53:79–92. Hoorelbeke K, Koster EHW. Internet-delivered cognitive control training as a preventive intervention for remitted depressed patients: Evidence from a double-blind randomized controlled trial study. J Consult Clin Psychol 2017; 85(2):135–46. Siegle GJ, Price RB, Jones NP, Ghinassi F, Painter T, Thase ME. You Gotta Work at It. Clinical Psychological Science 2014; 2(4):455–71. Hoorelbeke K, van den Bergh N, Raedt R de, Wichers M, Koster EHW. Preventing Recurrence of Depression: Long-Term Effects of a Randomized Controlled Trial on Cognitive Control Training for Remitted Depressed Patients. Clinical Psychological Science 2021; 9(4):615–33. Ferrari GRA, Vanderhasselt M-A, Rinck M, Demeyer I, Raedt R de, Beisel S et al. A Cognitive Control Training as Add-On Treatment to Usual Care for Depressed Inpatients. Cogn Ther Res 2021; 45(5):929–43. McIntyre RS, Best MW, Bowie CR, Carmona NE, Cha DS, Lee Y et al. The THINC-Integrated Tool (THINC-it) Screening Assessment for Cognitive Dysfunction: Validation in Patients With Major Depressive Disorder. J Clin Psychiatry 2017; 78(7):873–81. Gefen E, Launder NH, Davey CG, Nahum M, Gilboa Y, Finke C et al. Computerized Cognitive Training in People with Depression: A Systematic Review and Meta-analysis of Randomized Clinical Trials; 2021. Vander Zwalmen Y, Koster EH, Demeester D, Baeken C, Verhaeghe N, Hoorelbeke K. Predicting preventative effects of cognitive control training in remitted depressed individuals: A machine learning approach. Journal of Affective Disorders Reports 2025; 20:100894. Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM). Digitale Gesundheitsanwendungen (DiGA) – Verzeichnis. [cited 2025 Aug 15]. Available from: URL: https://diga.bfarm.de/de. Additional Declarations Competing interest reported. SW and CP are founders and shareholders of psykit GmbH, Tübingen, Germany. CP serves as managing director of psykit GmbH. The company developed and distributed the CE-certified medical device de:)press® with support from the University Hospital Tübingen. MS has received speaker fees from MEDICE Arzneimittel Pütter GmbH & Co. KG, Takeda, and Janssen-Cilag, and has served as an advisory board member for Takeda and Janssen-Cilag. Supplementary Files SPIRIT2025checklist.docx 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-8910222","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":605513070,"identity":"c6d39075-2439-4da3-a731-27481f73b968","order_by":0,"name":"Nicole Mauche","email":"data:image/png;base64,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","orcid":"","institution":"Leipzig University, Faculty of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Nicole","middleName":"","lastName":"Mauche","suffix":""},{"id":605513071,"identity":"bc774a5a-c66b-4b53-bb93-a6623707be58","order_by":1,"name":"Mara Kojcinovic","email":"","orcid":"","institution":"Leipzig University, Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Mara","middleName":"","lastName":"Kojcinovic","suffix":""},{"id":605513072,"identity":"fdb8d365-1aff-4d5c-a671-1425f5fd695d","order_by":2,"name":"Jue Huang","email":"","orcid":"","institution":"Leipzig University, Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jue","middleName":"","lastName":"Huang","suffix":""},{"id":605513073,"identity":"23edc9b2-b47a-41de-afbf-381ffb31514a","order_by":3,"name":"Simone Weller","email":"","orcid":"","institution":"University of Tübingen","correspondingAuthor":false,"prefix":"","firstName":"Simone","middleName":"","lastName":"Weller","suffix":""},{"id":605513074,"identity":"23ef45bf-2f1d-4bcf-8484-26f90c158355","order_by":4,"name":"Christian Makiol","email":"","orcid":"","institution":"Leipzig University, Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Christian","middleName":"","lastName":"Makiol","suffix":""},{"id":605513075,"identity":"2a805342-ca54-4f20-a1a8-9ee297d6502d","order_by":5,"name":"Christian Plewnia","email":"","orcid":"","institution":"University of Tübingen","correspondingAuthor":false,"prefix":"","firstName":"Christian","middleName":"","lastName":"Plewnia","suffix":""},{"id":605513076,"identity":"f174ddb7-e10d-4df0-b30a-90668278a170","order_by":6,"name":"Maria Strauß","email":"","orcid":"","institution":"Leipzig University, Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Strauß","suffix":""}],"badges":[],"createdAt":"2026-02-18 14:23:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8910222/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8910222/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105729255,"identity":"674570fe-d4bd-44a0-8a28-18e86a3704f7","added_by":"auto","created_at":"2026-03-30 11:14:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":754718,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8910222/v1/a9a1b6b1-5ae5-4a83-a0b8-59a227fb7ca4.pdf"},{"id":104720745,"identity":"4fddaa86-b9cc-4f5f-bc50-eb16600cc559","added_by":"auto","created_at":"2026-03-16 12:13:35","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":33896,"visible":true,"origin":"","legend":"","description":"","filename":"SPIRIT2025checklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-8910222/v1/30b05bb255e3ad9ecc5b76b4.docx"}],"financialInterests":"Competing interest reported. SW and CP are founders and shareholders of psykit GmbH, Tübingen, Germany. CP serves as managing director of psykit GmbH. The company developed and distributed the CE-certified medical device de:)press® with support from the University Hospital Tübingen. MS has received speaker fees from MEDICE Arzneimittel Pütter GmbH \u0026 Co. KG, Takeda, and Janssen-Cilag, and has served as an advisory board member for Takeda and Janssen-Cilag.","formattedTitle":"The CCT-D Trial: Evaluating the efficacy of the app-based cognitive control training de:)press ® as an add-on to standard inpatient care for depression – Study protocol for a randomized controlled trial","fulltext":[{"header":"Introduction","content":"\u003ch2\u003eBackground and rationale\u003c/h2\u003e\n\u003cp\u003eMajor depression (MD) is one of the most prevalent and debilitating mental disorders globally, with a lifetime prevalence of approximately 16–20% worldwide (1, 2) and 11.6% in Germany (3–5). Standard treatments include pharmacotherapy, psychotherapy, and neurostimulation (6) however, many individuals lack timely access to appropriate care, and only a fraction receive depression-specific treatment (7).\u003c/p\u003e\n\u003cp\u003eInternet- and mobile-based interventions (IMIs) have gained importance as adjunct treatments. The German National Clinical Practice Guideline for Unipolar Depression recommends guided IMIs as a first step within a stepped-care approach for mild depressive episodes; for moderate to severe episodes, IMIs may be offered additionally alongside psychotherapy and/or antidepressants (8). While most IMIs are based on cognitive-behavioral principles (9), less evidence exists for cognitive training approaches.\u003c/p\u003e\n\u003cp\u003eCognitive deficits—particularly in memory, attention, and executive functions—are common in MD and represent a promising target for intervention (10). Dysfunctional cognitive processes in MD are associated with greater disease burden and duration(11), as well as treatment response (12). They are a key predictor of functional impairments and reduced quality of life (13). The neurocognitive model of depression highlights impaired cognitive control (CC) and the related preferential processing of negative information as critical factors in the development and maintenance of MD (14, 15). Neuroimaging studies support this model, showing reduced activity in prefrontal cognitive control regions leading to insufficient regulation of limbic processing of aversive stimuli. Improved control of biased cognitive processes is considered a key mechanism and common behavioral correlate of successful MD interventions (16).\u003c/p\u003e\n\u003cp\u003eGiven the persistently high prevalence of MD, existing treatments may inadequately address neuropsychological impairments in attention, memory, executive function, and dysfunctional cognitive processing as vulnerability factors (17, 18). Cognitive control trainings (CCTs) have been proposed to modify cognitive processing biases and reduce depressive symptoms (19–22). CCT leverages neuroplasticity by targeted and repetitive training aimed at strengthening impaired neural circuits and restoring control mechanisms. Recent meta-analyses have shown significant improvements in mood and cognitive symptoms after CCT in MD (20, 23, 24).\u003c/p\u003e\n\u003cp\u003eA commonly used CCT paradigm is the adaptive Paced Auditory Serial Addition Task (aPASAT) (25). Originally developed for neuropsychological assessment of brain injury (26), the task requires continuous serial addition of the two most recent digits (one to nine [1–9]) which are held in working memory and subsequently responding with the result if the addition. The aPASAT demands sustained attention and the ability to overcome distractions and negative feedback. To maintain challenge across participants, the interstimulus interval (ISI) adapts individually based on performance.\u003c/p\u003e\n\u003cp\u003eGrowing evidence supports the therapeutic potential of aPASAT in depressed individuals (27). However, evidence for CCT, particularly aPASAT-based training as a blended treatment for inpatients, remains limited. Siegle et al. (25) showed that a two-week aPASAT training (six sessions) added to treatment as usual (TAU) in depressed inpatients reduced rumination and symptom severity compared to TAU alone. These findings were replicated in outpatient samples (28, 29), with follow-up data indicating reduced clinical care needs up to one year post-intervention (29, 30). Contrarily, a recent inpatient study found no significant differences immediately post-intervention between a two-week aPASAT (10 sessions) add-on and a sham training, although exploratory analysis showed significantly higher subjective well-being in the intervention group at one-year follow-up (31). This delayed effect aligns with earlier studies finding significant group differences only at three-month follow-up (28).\u003c/p\u003e\n\u003cp\u003eHigh dropout rates highlight that IMIs are not equally suitable for all patients: motivation, personal preferences, and technical access play key roles. For optimal effect, CCT must be conducted regularly over several weeks (6). Current studies suggest an optimal dose of 10–15 hours of training distributed over multiple weeks (21). To improve adherence and engagement, our study will utilize a gamified, app-based aPASAT training (\u003cem\u003ede:)press\u003csup\u003e®\u003c/sup\u003e\u003c/em\u003e) that integrates depression-adapted gamification and information elements. A recent pilot study demonstrated the superiority of the gamified version regarding both depressive symptom relief and usage frequency compared to a non-gamified version of the CCT (6). Remarkably, the symptom reduction effect of \u003cem\u003ede:)press\u003csup\u003e®\u003c/sup\u003e\u003c/em\u003e persisted up to three months post-training.\u003c/p\u003e\n\u003cp\u003eGiven the need for accessible adjunctive treatments targeting cognitive dysfunction in depression, this trial tests a gamified, app-based cognitive control training (aPASAT via \u003cem\u003ede:)press\u003csup\u003e®\u003c/sup\u003e\u003c/em\u003e) as an add-on to TAU in specialized inpatient units for affective disorders. TAU serves as the comparator to evaluate the specific benefit of the intervention, ensuring both clinical relevance and ethical acceptability, as all participants receive standard care. We expect greater symptom reduction four weeks post-intervention compared to TAU alone.\u003c/p\u003e\n\u003ch2\u003eObjectives\u003c/h2\u003e\n\u003cp\u003ePrimary objective is to evaluate whether six weeks of CCT via the \u003cem\u003ede:)press\u003csup\u003e®\u003c/sup\u003e\u003c/em\u003e app, in addition to TAU, leads to a greater reduction in depressive symptom severity compared to TAU alone in adults with unipolar depression treated on specialized inpatient units.\u003c/p\u003e\n\u003cp\u003eSecondary objectives are to assess additional benefits of the intervention, including improvements in subjective depressive symptoms, cognitive functioning, and patient-reported outcomes such as rumination, treatment satisfaction, and motivation. The study will also explore potential moderating factors, including treatment expectancy. Potential harms such as reduced adherence due to training burden or negative emotional reactions (e.g., frustration or demotivation) will also be monitored.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003ePatient and public involvement\u003c/h2\u003e\n\u003cp\u003ePatients and members of the public were not involved in the design, recruitment, or conduct of this study. However, patient involvement is planned for the dissemination phase. After study completion, participants will be invited to provide feedback on their experience with the intervention and its integration into inpatient care. This feedback will inform future adaptations of the app and its potential broader implementation in clinical practice.\u003c/p\u003e\n\u003ch2\u003eTrial design and setting\u003c/h2\u003e\n\u003cp\u003eThe CCT-D trial is a prospective, randomized, controlled superiority trial with two parallel groups and a 1:1 allocation ratio.\u003c/p\u003e\n\u003cp\u003eThe study will be conducted at two urban academic medical centers in Germany: the University Hospital Leipzig and the University Hospital Tübingen. Both sites include specialized inpatient units for affective disorders and operate within the public healthcare system. They provide multiprofessional care with physicians, nurses, psychologists, and therapists. Treatment includes pharmacotherapy, individual and group psychotherapy, digital interventions, and noninvasive neuromodulation (e.g., rTMS), complemented by relaxation, physical, and creative activities. Weekly social visits support discharge planning and ensure coordinated transition to outpatient care. The institutions have established infrastructures for clinical research and comply with national ethics and data protection regulations.\u003c/p\u003e\n\u003ch2\u003eEligibility criteria\u003c/h2\u003e\n\u003cp\u003eEligible participants must be 18 years or older, provide written informed consent, and have a confirmed primary diagnosis of unipolar major depression according to ICD-10 (F32.0, F32.1, F32.2, F33.0, F33.1, F33.2). Additional requirements include sufficient German language skills and the ability to operate a mobile device.\u003c/p\u003e\n\u003cp\u003eExclusion criteria are acute suicidality, psychotic features (F32.3, F33.3), other major psychiatric conditions (e.g., bipolar disorder, schizophrenia spectrum, organic mental disorders), primary substance dependence (excluding nicotine), intellectual disability, or somatic/neurological disorders affecting cognitive functioning. Individuals currently using other cognitive training interventions, under legal guardianship, institutionalized, with insufficient compliance, or who are pregnant or breastfeeding will also be excluded.\u003c/p\u003e\n\u003cp\u003eRecruitment and data collection will take place locally at the participating university hospitals. Trained clinical staff in accordance with a standardized protocol (Version 1.2, 17. July 2025) will conduct interventions and assessments.\u003c/p\u003e\n\u003ch2\u003eInterventions and comparator\u003c/h2\u003e\n\u003cp\u003eParticipants in the intervention group receive a six-week, app-based cognitive control CCT using the gamified\u0026nbsp;\u003cem\u003ede:)press\u003csup\u003e®\u003c/sup\u003e\u003c/em\u003e application, which is available for Android devices. The intervention is based on the aPASAT, implemented as a self-administered mobile app.\u003c/p\u003e\n\u003cp\u003eIn each session, participants hear a sequence of single-digit numbers (one to nine) via auditory presentation. They are instructed to continuously add the two most recent digits and select the correct sum of each addition (two to eighteen) on a touchscreen. Immediate feedback is provided via a green screen for correct responses and a red screen for incorrect, delayed, or missing inputs. The ISI dynamically adapts based on performance: four consecutive correct responses reduce the ISI by 0.1 seconds; four consecutive errors increase it by 0.1 seconds. The ISI will be carried over from block to block, however it will be reset to the initial 3 s for each new training session. Each training session consists of three 5-minute blocks separated by 30-second breaks. Participants are instructed to complete at least three sessions per week, with a maximum of one session per day, over six weeks. App usage data is automatically recorded; however, the study staff will not monitor adherence or be able to access participants’ performance data during the intervention period.\u003c/p\u003e\n\u003cp\u003eThe app includes several gamification elements to enhance motivation and engagement: (a) psychoeducational content on cognitive mechanisms of depression and the rationale for CCT; (b) real-time performance feedback with graphical progress visualization; (c) unlockable levels and audio-guided imagery as adherence rewards; and (d) a virtual coach (animated avatar) providing guidance and encouragement. The app contains all necessary instructions, and no in-person training is required. Technical support is available if needed.\u003c/p\u003e\n\u003cp\u003eParticipants may discontinue the intervention at any time or if clinically indicated (e.g., mental health deterioration or safety concerns). Unless consent is fully withdrawn, participation in follow-up assessments remains possible.\u003c/p\u003e\n\u003cp\u003eControl group participants receive standard inpatient TAU, including pharmacotherapy and/or psychotherapy in line with national guidelines (8). No restrictions apply to concomitant care. For ethical reasons, control participants are offered access to the\u0026nbsp;\u003cem\u003ede:)press\u003csup\u003e®\u003c/sup\u003e\u003c/em\u003eapp after their final follow-up assessment.\u003c/p\u003e\n\u003ch2\u003eOutcomes\u003c/h2\u003e\n\u003ch3\u003ePrimary outcome\u003c/h3\u003e\n\u003cp\u003eTo examine whether six weeks of cognitive control training via the \u003cem\u003ede:)press\u003csup\u003e®\u0026nbsp;\u003c/sup\u003e\u003c/em\u003ein addition to inpatient TAU reduces depressive symptom severity more effectively than standard care alone, the score of the 21-item Hamilton Depression Rating Scale (HAMD-21) at end of study will be collected.\u003c/p\u003e\n\u003ch3\u003eKey secondary outcomes\u003c/h3\u003e\n\u003cul\u003e\n \u003cli\u003eThe effects of cognitive control training with \u003cem\u003ede:)press\u003csup\u003e®\u0026nbsp;\u003c/sup\u003e\u003c/em\u003eon response and remission rates of depressive symptoms at four weeks post-intervention, as measured by the HAMD-21.\u003c/li\u003e\n \u003cli\u003eChanges in subjectively reported depressive symptom severity, measured by the Beck Depression Inventory-II (BDI-II), at the end of the intervention and at end of study four weeks later.\u003c/li\u003e\n \u003cli\u003eChanges in general well-being, as assessed by the WHO-5 Well-Being Index, at the end of the intervention and at end of study.\u003c/li\u003e\n\u003c/ul\u003e\n\u003ch3\u003eOther secondary outcomes\u003c/h3\u003e\n\u003cul\u003e\n \u003cli\u003eChanges in subjective and objective cognitive performance using the app-based \u003cem\u003eTHINC‑it\u003csup\u003e®\u003c/sup\u003e\u003c/em\u003e (32) neuropsychological test battery at end-of-intervention and end of study.\u003c/li\u003e\n \u003cli\u003eChanges in trait and state rumination, as measured by the Rumination subscale of the Rumination-Reflection Questionnaire (RRQ) and an adapted version of the Perseverative Thinking Questionnaire (PTQ).\u003c/li\u003e\n \u003cli\u003eInfluence of treatment expectations, operationalized by an adapted version of the “General Treatment Expectation” (BE) subscale of the Questionnaire for Measuring Therapy Motivation (FMP), assessed prior to the start of the intervention.\u003c/li\u003e\n \u003cli\u003eInfluence of treatment motivation (indicated by the number of completed training sessions) and satisfaction (measured with an adapted version of the Client Satisfaction Questionnaire, ZUF-8).\u003c/li\u003e\n \u003cli\u003eThe role of a distorted cognitive pre-treatment style using the Lübeck Preoperative Thinking Questionnaire (LFPD), assessed before the intervention.\u003c/li\u003e\n \u003cli\u003eEvaluation of the feasibility of implementing \u003cem\u003ede:)press\u003csup\u003e®\u003c/sup\u003e\u003c/em\u003e into standard inpatient care based on participant uptake, usage rates, and reported barriers to usage.\u003c/li\u003e\n\u003c/ul\u003e\n\u003ch2\u003eHarms\u003c/h2\u003e\n\u003cp\u003eBased on current evidence and prior use, CCT via the CE-certified \u003cem\u003ede:)press\u003csup\u003e®\u003c/sup\u003e\u003c/em\u003eapp is not associated with known adverse effects (AEs). To date, no AEs related to \u003cem\u003ede:)press\u003csup\u003e®\u003c/sup\u003e\u003c/em\u003e have been reported in previous or ongoing studies. Transient frustration is an expected component of the task and is addressed through integrated psychoeducation and adaptive difficulty adjustment.\u003c/p\u003e\n\u003cp\u003eAEs will be assessed non-systematically via spontaneous self-reports and clinical observation by trained inpatient staff and monitored throughout the intervention period.\u003c/p\u003e\n\u003cp\u003eNo ancillary or post-trial care is planned, as all participants are inpatients receiving standard hospital care. Any harm related to trial participation will be managed within the hospital setting, with costs covered according to institutional and legal regulations.\u003c/p\u003e\n\u003ch2\u003eParticipant timeline\u003c/h2\u003e\n\u003cp\u003eParticipation in the trial spans a total of 10 weeks per individual and includes three visits: the screening and baseline visit (V0), a visit at the end of the intervention (V1), and an end of study visit (V2), conducted four weeks after the intervention concludes. An overview of the visit schedule is provided in Table 1. The total planned duration of the clinical trial is 12 months.\u003c/p\u003e\n\u003cp\u003e\u003cimg 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9TxPRVFoOp2W5UzFuGnugQnUzffKBGH3GR5hggWzD0VRlN//NE01n8+VV3pGq8PaqufHpJmXCVaur6/V7XZr58AM2WwafpDneRlQVbdlzlUcxyvHaPa9Whn4G+acANuoNj6aAMLMuapeA821sfo9+Pbtm/I8L9Oqw6Wn0+mdvptV1WHk1e9nNfC5zWg0KvfLXP+r+2Kutd++fSvTzDEWRaG9vT1pWReq7ou5fpne3Or+NV1rq+5zTzH7VB2mhr/XiwkstKxoaHlDMy2K2wyDsudY2JUIm7nZ2n7//m0n1bpK72IwGJQVg12ib3PxaZo3grfDnmPRdNMyadWeN/vzGwRB7fthxuWHYVgOFWq1WuUFfpubnNleNTBvSjPfL3PTaLrZ2y1n1XlbZp+2nUtgeh/soHw+n5c3Y9MjWW28MNeebVQr6OYmruX337i+vq71jFYbNLrdbnne7aEYZh/tc3Kb6t+82lPz9evX8v/V/VHlHLmuW1637OADeC1ms1n5HTWf8+q10XXd8tpzcXFR+16YoU720J4m9hAfp9IDYg8/Mg0P217fVLk2eJ5XuydUGzZUCRDCMKxd/805sIdomoYJu9dhG3e9p1QbfqrD1Lj+/L1eVGBhnm4Sx3H54TNpuzKRsx1pVysUTS101eFP1WFR2zAVmziOicCBJzSfz8vvnB2UV+dxtdttOY5TG8r0HMMO+/1+ub+m5bFpeBWAu7tr42OTxWJRa+hYN7RnG5PJpKy8m32rrvspzefzstfVNGCZwAS4jxcVWLRarfJmaoZB3ecCcBfV4UZxHNe66apffruldxvVyd/3xeRtPCYzQbE6RrdaKa+2ID0U8x23b/bFDk+7slvWTPDQdLNuGo9cld3hQQ3VCeHV+RnV7+unT59qPTfVHkwz7NO0zkVRpG63Wxt60WRTL0Z1+GY1iKoOh3iI4aXAa2C+w9VhkNWhi9VRE2bIUHUIo92yXv1umie2VV+u6+rXr1/Ssl5hrnnVh0hsywxlsq9Z1XqLrOt8tdxoNCp7kj3PKxtd7V6Fqk3XJT3TPQUvy4sKLGR9ie0hDOtUh1Rs20VZVe3BMN2cjuPUJlquG094m+qQqLvKK5O3N33R8fqZ1jHzanpiyX1UK/Jm3dV5QXZr/0MwQ4bs7+19Wv/MjVXL/TfffXNTqw7/kfXUp+pY48IaV73u0YpNTCWj+jeyGySqQwGq5cw1xlRuzPXH87zG64ZJM+euaYK167plg0b1HJtzUh2iALx11Wugt5yLWf3uff36Vbn11Ldq3cB8l7b5bhofPnyQrGvBfVTrF6b3tbouMxSyOiSyWu7nz59lo0e2nKzuOE7jcKx111rbc9xT8LK8uMCiOvTprkOPdrGu+89MxNrFfZ40I6s3hSgfj8F13cbP97p5SA+h2+3WJvPtYjAYlN8Rw/QWBNYjZmXdYO0eSLv3clvrjieKolqDxHQ6bbzGuK670lPTtD7doVVzMBjUWlWNJElWtgW8dUXD0ENvOUnZvoYYJt/Y9rup5TWjet2Komir+aRNFovFyjVQy2My1zjTc2Lb29tTq9Wq9eyGYdjYqNt0rW3yHPcUvCxOwV8awCtiHguZJEnjJHcAAPA4XlyPBQDc12QyUZZl8qynpAAAgMdHjwUAAACAndFjAQAAAGBnG3ss7vukAgAAAABvgwkn6LEAAAAAsLONPRYAAAAAsA16LAAAAADsjMACAAAAwM4ILAAAAADsjMACAAAAwM6eNLDI81yO42z9GNvRaCTHcdTv9+0sAAAAAC/IzoGF7/trg4VqIDEajfTjx48ybzKZ1Mo2OTs7kyTFcWxnAXjD5vO5HMfRfD63s6Q1+eZaRGMF8DQ6nY46nY6dXFqX3+/3+Y7iwZnG6nXs/Oo9w76fYL2dA4vT09Py//ZJrwYSnz9/1ufPn8v33W63/P86x8fHkqQwDMs0U2Hwfb9SEsBb0mq15Hmevn//bmdJkr5//64gCNRqtaTlDSKKIhVFoaIoFMcxFRfgkR0dHSlNU+V5bmcpz3OlaaqTk5MyrdPpyHEcGhPxKEwddF3D9tnZmaIokpbB7Ww2K+8ZSZKo3W43fpZhKXaUZVkhqZBURFFUywuCoJBUBEFQS99FGIaFpMLzPDsLwBsSRVGx7hImqUiSpCiW5ezrRZIka5cF8HCa6gZFw/ey+p0MgqAIw7BSGngYQRA01klns1khqciyzM4qeZ7X+FlG3c49Fq7rKggCqTJ0SZXWCC1bLbSMEpu6lOzuJtOSaFovTO9EtSUjyzI5jtPYjQrg9TOtT3ZPqXlvekUvLy/L3k/j48ePtbIAHkcYhrq8vLSTV76X3W5X/F4vHpvpRbNdX18rCAK5rmtn4Y52DixUCRyyLCu7iW5ubsr8TcOenA3j3QBgHdOoYQ+H+v79e2345GKx0IcPH2plzM3j9+/ftXQAD+vLly8rw6FMw2N1eDTwFEx91B4OdXZ2VtZlm+R5rizL9OnTJzsLlgcJLKqBg5lXcX5+Lkllb0aTamthkiTlWLbxeFwrZxRFUVYYPM9TURSaTqd2MQBvxNHR0cp47DiO9eXLl1oagOdh5kNV51z++PGD1mE8mzAMyzqqlnXRLMs2NoJ7nqcwDMt5e1jvQQILVSZYmy5PexhUk+ofqNfr1YZBAcBtzI3ANFJMJhN5nsfFH3hBjo+Pa8OhbmsdBh6T6UUz7F7uKjOEP4qitY3eqHuwwGJ/f19aBhTVLqZNEaCWvRDVXo04jnniE4CthWFYDoc6Pz9fmU/h+75+/fpVSzPDMt6/f19LB/DwPn/+XA6H2qZ1GHhMphfN1FXX9XL3+331ej1lWabBYGBnY40HCyyqFwnz+Lh1EaBtOp2qKIryMV9ZltlFVmxTBsDr9+XLl3I4VNO47YODg5XJozc3N/RsAE/EzIf68eOHrq+vt64bAI/l+PhY5+fnms/njfeC0Wiki4sLFUXBkL07erDAQpVAwlT6myLAKvObFOY1HA6l5Vi2dfb29sr/81QoAKb1qd/vN47bNq2l1Z7UXq9X+w0eAI/r6OhIl5eXOjs7u7VuADw2c1/4/v37Si+3lsP1uEfcz4MGFtWLRVMEuI0gCLRYLOzk0mAw2DghHMDbc3x8rDiOG8dtu66rLMvKeVyO4yhJEoZiAE+o2+2W49rvUzcAHpLpRYvjeKWXW8sG8uo9w7wYqn87p+DB0QAAAAB29KA9FgAAAADeJgILAAAAADsjsAAAAACwMwILAAAAADvbOHl7+F//q50EAAAAAKXov/936bbAAgAAAAC2wVAoAAAAADsjsAAAAACwMwILAAAAADsjsAAAAACws786sOh0OnIcR77v21kv3nw+l+M4chxHk8nEzgYAAAD+Kg8WWIxGo7KiXH0BwFOrXoP6/b6dDeCB9Pv9Z/uO2fUOGulwV5s+v77vl5+tTqdjZ2ONBwksOp2OhsOhnbzC/IHyPLezAOBBOI6jKIpUFIWKolAcx2tvHADux4wYiOPYzmo0mUwedHRBp9PR5eVl+T0vikLdbtcuBjS67fPr+74ODw/Lz9ZisSC42NLOgcV8PleappJUu5kXRaEgCMpytCQAeGyj0Uie52kwGJRpSZKsvXkAuLvJZKI0TVfu809lMplosVhoOp3aWcCtbvv8TiYTZVmm8Xhcpp2fnytNUxrGt7BzYFH18+fP2nvzpe90Our1emW653nlMKmm4Qrr5k6Y9KZuqeqcheq68jwv05uCG5M3Go1W0qrrMWnz+XwlzbzsD9xkMqnl2/ts6/f7jfsDYDuXl5c6Pj6upX38+FFaXiMA7K7b7eouv61r6gBZlpX3OKN6j153L7Wdn5+vfM+Bbd32+b26ulIYhrW0VqslSbq5uamlY9XOgYU52ZIUx/FK5fuh+L5f9oxIUpqmtfetVquMPC8uLsr0Hz9+SMtgpqmb1CxzeXkpWZUPs55qWqvVKi+ENs/zygviaDSqBVNa7vO64GI+n5etqlEU1VpcAWxnsVjow4cPtTTXdSVJv3//rqUDeBrT6VRJksjzvHJEg5b3Pc/zlCRJmW7KbapHpGmqT58+1YIRhjvioeR5rr29PTtZnufp169fdjIsOwcWkpRlWe19u92uBRjmomJkWbYxWrSZbilZw61sJycn0nL9ZtsmYFjXunF0dCQtKySSdH19XeZlWaY8z8sKiYlgv337Ji2DErMvdp6Zc1K9YGp5QWy6YJr9CIKAoAIA8Oqdnp4qDMNao1+321UYhvr+/XutrGEa79rtdlmXKJZzqejpB57fgwQWrus2Vvbb7fatXZrbqEaI1Up3U1eV53nSMkDI87zs1fj8+XOtrGGGSZgg4vLyUp7nleu+ubnR1dWVJGl/f1+q9GSkaVq2lpjehjzPa4FDr9db6fq1W05PTk7KwIkxowCAtyBNU3358sVO1t7eXm3kQZMkScreSC0bHc/OzmplADy9BwksqkxXpvHU49FMz8TZ2Vm57SAIahegKtd1y2Dk5uZGaZrq8PCwDCKurq7K4MgEIY+pqTcDwHZ831/pqjbf3/fv39fSAfx9zL3c/j5/+PBhZfQEcB+u667MGdayAdoeaotVOwcW8/n8zmMb//z5U/7fVOqrrRPVuRNaXjAMMwE7z/PGJ72Ynoksy3R+fi5Vhhmtc3h4KC0nhGnZM2GCCNPrUQ1OzKTy6lAo85pOp3r37l257upQKPOy53qcnp6Wcz3a7XYtD8D2Dg4OyuGPxs3NjTzPq80HA/D8giCoDT82fv78Wd6XmzQt9+vXr7I+Aexif39/pcfMNPra9Tc0KHY0m80KSWtfm8oVRVGEYbiSbl6e55XL23nryjWt8zb2vmVZVhRFUXieV6ZFUbS2fNOy9j6YVxAEK+tIkqTIsmylDIC7Md+jJEnKNPs9gIcTBEERhqGdvMLc88w9sppW/X4mSbJSzmaXafreA9tY9/mVVe/zPK/2Huvt3GOxrhXQtOYbrVZLURTVykjSeDyutTIkSdL4XGF7/kYURY3lJNXGbNrzMJpUj8HzvLJnotpi8unTp/L/rVbr1i7X8XjceLzruK5blt/09CgA67muqyzLanObkiShlQl4ZubJjdXHzbdaLc1ms9r3tdfrqSiKtcOXtWw1Nk+PchynfLIU33M8lKIoNBwOy8/l8fExD9bZklPYNfZXYD6fl0OKZrPZ2uAHAAAAwMPYucfiJTKPqWNcNQAAAPA0XlWPhe/7tSFK9FYAAAAAT+NV9liIoAIAAAB4Uht7LIb/9b/aSQAAAABQiv77f5duCywAAAAAYBuvdigUAAAAgKdDYAEAAABgZwQWAAAAAHZGYAEAAABgZwQWAAD8hfI8l+M4chxHo9HIzr6X0WhUrtP3fTsba/T7/Qf9O2A98/ns9/t21r1MJpNynY7j2NnPynyuXtp+bUJgAQDAI6lW1O3XSzMajTQcDu3kFZ1OR47jqNPp2FlvVhzHkqSzszM7682Zz+crn3Xzms/ndvFnNZlM1Ov17ORG647rpR3TcyOwAAAAury8lCR5nqeiKLRYLOwiOzOVs7+5N8RUKPM8L9PCMJQkHR8fV0ripbu6uir/XxSF1v0Cw2g0UrvdtpNX+L7/5oMNAgsAAJ5AlmVl5WVdBeY5mUDiMSv9379/t5P+KpPJxE6SJI3HYxVFocFgYGe9aUmS1D7zrVbLLvKsTHDoeZ6dVWN68oIgqB1PFEVlmfl8rizLKku9TQQWAAA8k+rwislkUg4zchrGkFfnVDiOox8/ftTyN6mO1TYvw6zXVIrSNG3c/iampbbT6awds+44TjlkKMuysrxhDxurbr+6TvN/3/fL7drBUNM6TFnzqrYqm/Pu+/7KkBdT+ex0OrVhM57nyVkeX/X4qzadd1nHbP991wUxr4E5xn6/f+u8nuo5ucscFvvzZM6x4TiO0jSV1nwem9i9eIPBQK1WS/1+v9aj0W63y+1VP1uG/Xc3qp8X+1xUPx/2ft7n/DyaAgAAPIooigpJK68gCIqiKIrZbLaSV33NZrOtykVRZG35//E8b6V8df1Zlq2kSyrCMLRXVRRFUQRBUKhyDMUt2zDrsdOr6wjDcCWvumySJCt5nufV0rMsKwrrXJk0e1nzMufXHFPTy+zjujLV49/2nJjtrvt8VNf9t9n0WTXs9OrLfJbXfS7Na93ns9jwt5JUJElSFGv2ofr3q7LXZ3/f1n1+sywrl/U8ryxf/bubz6i9Dftlb8eofgdeAnosAAB4Acwwi9lsVqZdX19Lkk5PT8s0M6QqSZIybZ3RaFT2RFSHpRinp6dyXVdFUZTDQcx+jMfjstxdmP0z67u4uJD+Uesp5yKYeRzT6VR5npc9GbPZTEVRlPscx3GtRVeV/VssFup2u2X6zc2NVBluFQSBXNctW3HNNovKEJbqeTXMPgRBIC17cCRpOp3Wzrk5zibbnHdbFEW1fdOyR+u1s8+Nmevz7du3Ms38TarfjXUmk0n5NzPntPp5PDk5kZbbNX/j6uexyXQ6rQ2XGg6HtR6C8Xhc2zezv67rlmmbzOfzcp/DMFzZZ+Pr16/l/02PlpknYr5bz43AAgCAJ1CdY9FUgTk6OpKk2jj0nz9/SpUhGGEYlpWVaqV6HbO853m18qbyaiozD8VU5iXp8PBQWh73JiYgUGUISbVC9efPn/L/qlQMDVM5NBUsE8iY82kqqma4i+M45Zh5e2iL53nl+T84OCjT7eDmNvc5758/f5Ykffr0qUz7/ft3pcTfx55jYatWhs3f0fxNzDkPgqD8m7RarZXKtu3Xr1/l/6tzXkwwl2XZnf+eWu5XNRjRMsB4iCFr1b9zNXiwHwbguu7K590E5V++fKmVfS4EFgAA4K9lAgjTu2ECmW0CL+CuptNpLViuPlnqKVQ/76ZHqxoQPzcCCwAAXjgzkdO0Tmo53OY2e3t70rKVtjqspvqUm+dQrZi9f/++/L8ZQlJ93VZhqgYQZrJ2tSXc9KBUh0KZl91jcRd2T0rVSz3vfxPzd0vTtOxhmEwmt/aAffjwofx/tTfB9HR5nrf1ECXDnkh9m2oPhNlWtafE9KIZ1e9A9aEMTb8rU/28m14Yu2fjORFYAADwBLzlU4TM6y7j500rpSpPgGmqdNgGg0E5dMQMM3IqTyayhxU9NlPh1vI4Op2OWq1WWdGu7qNzhydTmUDCDDGqDgsxQ0uqQ6Hu8zeQVQE0+9rkpZ3359Lr9Wrne5tg2Kj+Dc13Z5sfs+t2u+Xnqbp9E5A0zW+5jf3ZqQ7HMvv57t27Ms1sN89z7e/vl+nmOOyhcNUhXmb+xrrPlhqG1JlhdC8BgQUAAC9ct9tdmay9zURWLceGN7WQb9Mb8NAGg0Hjvkyn050mn9qV0OpxmcnpD6HVatUmV2/yks7736jVaq18xu3366z7PGVZdq8hck1/R1l/S9d1V76jWn53q/sShmHjZ2ixWNQCljAMG49BViBRndf0EjjFQ33bAAAAADyqPM/LICRJknsFS4+FHgsAAADgL1Gdh/GSggoRWAAAAAAvn/kVbzO/qmno1XMjsAAAAAD+Ii9tCJSxcY7FphnpAAAAAGDCCXosAAAAAOxsY48FAAAAAGyDHgsAAAAAO9vYY8EcCwAAAACbMMcCAAAAwIPZ2GMBAAAAANugxwIAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOzsQQKLTqcjx3FWXp1OR5I0n89r6bbRaLSS1+/3V9Znl7H5vr9SNs/zWpk8z8u80WhUyzOa1uM4jvr9viRpMpk0plfZZcy2qtu3X5PJRLKOvWndZv9Mnr0e++X7vr0KAAAA4EE9SGBxV02V5btwrIDBVOKzLKuVkyTP83be3m3iOLaTdH5+bifdSxzHms/ndjIAAADwojxoYOF5noqiKF/T6dQuIt2jsmzWF0VRmfbjxw9p2QPQ6/VWyhZFoSAIpOX2TG/AXQRBUFvfeDyu5XueV/7fPp40TWv5TaIoqq2/2+3aRSRJR0dHdlJNdR1mm9V9XywW9iIAAADAg3rQwGIbprJ/W2W5yadPn+wkffv2rfy/3WNRDWweqgehKsuy8ni+f/9eppsg5vDwsEy7D8/z5HmesixbO2zrLsyQtYdYFwAAAFD1oIFFlmW1sf1NFdiTk5N7V5arlffPnz9Lki4uLqRlJdx13TLfMBX/NE3trFulaVo7nqZeDxMgVYdDmSBmf3+/TGsyHA5r67fng6iyruFw2Ji/rTzPy3NwdnZmZwMAAAA7edDAYhu/f/+uVZbtIURNTMXbVN6TJFkJItZNULbLPbTq8KXJZFJW4D3P08ePH2tl7yrLMrVaLYVhKO3YA+K6bhlkHR8f29kAAADATh40sLDnWAwGA7uIJNUqy3cdEhVFUeNchHXzCHZp5bfnWDRtV1J5LFdXV+Xcj22CAHuOxbogyMztuE8vT9V0Ot34dwEAAADu60EDi7uoVpaHw6GdXVMUhZIkkZa9HNXKtanAZ1nWGESY4T+mtf4xfPnyRVoOh7q8vKylPZTq8dtzSQAAAIDn9myBhSTNZjM7aa1ut1sGB9X5BtUKvP0UpurwqJOTk1reQ2q1WuW2zTCoVqtlF9tJt9ste0bui8nbAAAAeCwPGljYk7edDT9mJ2tI1DaqT3kyPRWtVqv2GNrqtk3LfhRFjRV9e/K0/XsX9uTtdfM4ZA192nYOw23bt9mPu72L6uRt06sCAAAAPJQHDSzu466VZTMkKMuy8pe9B4OBiqKwSv7DU80pqPacND0W96GY47+r6uTtg4MDOxsAAADYiVOsq5EDAAAAwJaevccCAAAAwN+PwAIAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwAIAAADAzp48sMjzXI7jaD6f195PJhO76Ea+76vf70sN61yn3+/L9/3yve/7Go1GtfdmnW+d4zi1cwMAAABs8iiBheM4K69Op2MXA3AP/X5fjuMoz3M7S77v810DAADPwimKorATd+U4jmazmVqtlp2lPM/led7a/Pu47zp939fx8bEGg4GdJS0rcJI0Ho/tLOBZmeBhOp2WaaPRSGdnZ1osFpWSAAAAT+NReiwAPK7xeKw0TcshhHmeazgc6vz83C4KAADwJJ49sJjP5yvDOsycCfMajUbqdDq1Mf/r5mV0Op1yuep8CpO3aQ5FdZ2O4yiOY8VxXA7lMi/bbXMzqsdi79NkMqnlm/WMRiP5vl/mV7c7Go1qy9hzS8w5Na/qeaue72qZ6rm056yYfbCXsbcr61j7/X75wsNyXVdRFOnk5ERa9q6FYXinHjsAAICH9OyBhc0Ma0qSREVRqCgK/fz5U2ma2kVXtNttnZyclMupMmTkroqiUBiGCsNQRVFoOp3q5ORkZT/yPFeWZfr69Wst3fB9X1EUlft0fHxc5o1GI/V6PWVZVubv7e2V+VmW6erqqty+lhXIy8vLsvxsNlO73S4Ds8lkona7XeYXRaHhcLgShHmeV+YnSaJer9c4Zr/q8PCwXCaKIrXb7Vq+4zi1Y93b21Mcx7UyeDhmCJ/v+0rTlCF7AADgWT1aYNFut9e2iG/y7ds3BUGgbrdbpo3HY3meVyvXJEmSWovt+fm50jS9tcK8rVarJc/zasfy48cPBUEg13VrZY0sy/Tp06fyvakMmqErs9mstqw936NaWczzXHEc18bVt1otBUGgHz9+SJJOTk40m83KfEmKomhliEy1TLfbled5urm5qZWxXVxclP83+2l6LUajkTzPq+3/YDBQEATlezy809NTZVmmJEnsLAAAgCf1aIHFbDartZpXA4VNLi4udHBwYCevDCFq8v79+9p7E2T8+fOnlr6L4+PjWiX97OysHI7SJAxDtdvtlf03lfhNQ1fsYMosUw3YHMdRmqb6+fNn2XtiB3XD4XBlQu+7d+9q7yXp169fdlJNU/D0+/dvSdLl5aUODw/t7MZl8HB6vZ6CIFCv17OzAAAAntSjBRa7+PDhg530Ynz+/LkcDmVa6zcFB+PxWEVRyPd9OdZcCTtw2FY1YDOvas+GHdQVRbESWDyG6jAuPL5Op6MgCDSdThUEAXNZAADAs3pxgYXv+7q6urKTV+Y2NDGt58Y2Ff+7cl1XQRBoMpno+vq6Nmdik+l0qizLlKap5vO5Pn78qCzL7jRMy/TIrFvG9A7Y5+EpuK6ry8tLO7k2fAoPZzKZ1OZVnJycKI7jrYccAgAAPLQXF1gcHR2tVJC2nYBtDwdpt9sKw7CWdhd7e3uNFeOjoyOdn5/r7OxMnz9/trNLeZ7XWpHNkKx3796VAYrda7Hp167NfAp7yFG/3y+DjSiKViZiTyaTR69wfvnyRWma1va/3+8ry7JaOTyMXq+nKIrKYLLVaikMw5XvAAAAwFN5tMDCHufvOI5dpFG32y2fUmSWOzk52WoS8Gw2q20viqKdnpQzGAyUZdnKEKZut6s0TeX7/sY5BK7rlo+rdRxH7Xa7Nll7Op0qDMPaPt82DGw6nZbDqqrn1axzMBgoiiJ5nlc7f9vOcbmvVqul2Wym4XBYbnd/f3+nwA7NHMdZmSivykR/ez4PAADAU3iUX95+DLf9SvZT831fp6enj15h/9t1Oh25rrtTgAcAAICX79F6LB6SedpR9bGtz8nM3SCouF2aptrf37eTAQAA8Mq8uMBiMpmszDM4PDxUEAQPOgl7F6enp1tP2n4r5vP5ylOJOp2OPM8jAAMAAHgDXlxg8fHjx9o4fcdxdHh4WPtRuOfS7/flOI5c130xQ7JeilarVZtPYuZ+PMVjbgEAAPD8/po5FgAAAABerhfXYwEAAADg70NgAQAAAGBnBBYAAAAAdkZgAQAAAGBnBBYAAAAAdkZgAQAAAGBnBBYAAAAAdvbsgYX5MTX7V5tfOt/3NZlM7GQAAADgTXqQwGI0GqnT6djJt+p0OgrDUEVRaDwe29kAGphfgM/z3M6S7/v3+i4CAADs6kECi/taLBba39+3k/GCzOdzOY5jJ+MZjcdjBUGw0ss3Go0kSdPptJYOAADwFJ41sMiyzE4CsIXxeKw0TcvheHmeazgc6vz83C4KAADwJB4lsBiNRvJ9v2ztNi8zdGMymZSt4L1eT47jaD6fS8sKUnUZe8iHya+uO8/zcptm3Y7jlENCRqPRSlpVdRnHcVbmTtjHYeevYx+L7/u1fN/3N67X932NRqNy6EvT/tv7ZrdidzqdWr6d1+/3a+enuo/9fl/tdluqzIVpGn6Dp+e6rqIo0snJibT8W4VhqFarZRcFAAB4Eo8SWGjZG3F6eqqiKFQUhcIw1OHhoSSp2+2qKApJUpIkKopCrVZL8/lcnueVaUVRKEkSeZ5XBh5Gu90uy7iuW27z6uqqTE/TtKwoV9PMkBEtg46Tk5MyP8sy9Xq9cnvz+Vztdluz2awsc3V1dWtvS9OxHB8fl/mO4+jw8HBlu9V9k6ThcKj9/f3G/c/zfGXf9vb2ymV939fBwUGZF0XRSnATx7FUOT9aVlK1bBWfzWa1fHOu8fwGg4G0/Dunaco8JQAA8LyKBxBFUREEQe29veosywpJRZZlZZqkIkmS8n0QBEUYhuV7IwzDMt2sp7pcsWabYRg2plW3Ye+TXWbdPjXtQ5XneUUURXZyUSz31fM8O7lIkqSW7nneyrar53o2m60cn5EkSe1vYkgqZrNZUSyPzS5j78OmbeD5JUly62cRAADgKTxaj4XneXaSJOnPnz92UilNU3358sVO1t7eni4uLmpp79+/r71Xwzb39vYUBEEtTcuWfi17FbRcrjpcKI7jskyapo0TzO1tVeV5rizL9OnTJztLknR5eVnrvTDev3+vLMtqw42qPRDGYrGQJLVarXLf7SFQV1dXStO0dlxmKNTv37/Lck09ELf1xuDl6PV6CoJAvV7PzgIAAHhSjxZY/E2yLCuH+phX9ck6TUHMNt69e2cnPbjFYqGiKBTHsRzHqQ2lCoJg5biKolC3262tA3+nTqejIAg0nU4bnxIFAADwlF5UYBEEga6vr+1k/fz5s5yf8ZBMxX9TL4rneSv7ZHok1nFdV57n6ebmxs6SJB0cHOjy8tJO1u/fv+V5XmMvwm2K5XyU4XAoLXs6TM8GXp/JZFKbV3FycqI4jlceAAAAAPBUXlRgcXJyouFwWKscTSYTxXGsr1+/1so+BNd1FYZh+eQjYzQalcOkjo+PNRwOa5PHtwlyjo+Pa5PAVfmdgcFgoDRNay3MeZ6r1+vp9PS0TLvNZDKpnatfv36VQ7QGg4GyLFtpxbafKnUbE3zZk+fxvHq9nqIoKoPQVqulMAwZEgUAAJ7NiwosWq2WZrNZ+Qhax3HU6/X0mE8jGo/HCsOwNg/h8vKyfGznYDBQFEVqt9tl/sXFxcY5FloulyRJbbmfP3+W+dXhS47jyPM8zWazOw1Tev/+fe1cDYfDWi+FvQ3HcXR0dFRbx22qwZfD42ZfBPN5MU+FMkzvhf3kLwAAgKfgFP94UhAAAAAA3NuL6rEAAAAA8HcisAAAAACwMwILAAAAADsjsAAAAACwMwILAAAAADsjsAAAAACwMwILAAAAADsjsAAAAACwMwILAAAAADsjsAAAAACwMwILAAAAADt7FYFFv9+X7/t28r34vq/JZGInv0l5nstxHM3nczurxnEcjUYjOxkAAABvyJMEFp1OR47jlK+HCgKAt6jf78txHOV5bmfJ9311Oh07GQAA4NE9emDh+75c11VRFOXroQOL8XisxWJhJ+OJFEWhwWBgJ+ORjMdjBUGgfr9fSze9RtPptJYOAADwFB41sJjP58qyTOPxuJZOxQfYzXg8Vpqm5bC9PM81HA51fn5uFwUAAHgSjxpYGE1DNqrMWP7qq2kZMwTEvEylqtPpNLbeVss2DQ+Zz+eN67PZQ7nsvH6/X9s303JcXa5pDoJ9PPYxSNJkMqmVMfts5j1U39v7V13Osc7paDSS7/sr575pP7XseWraz3XzMOxzZudjN67rKooinZycSMvPUhiGarVadlEAAIAn8aiBRavVUhiG8jxvbYV1Pp/L8zwlSVIOlUqSRJ7n1SqjnU5HFxcXZZksy2rrqer3+xoOh7XhV1pWjo35fK52u63ZbFaWubq6Wlmv7/s6ODgoy0RRtDKUK45j7e/vqygKzWYzDYdD+b6vk5OTWtqm4ymKQhcXF7UAaDKZqNfrKcuysszR0VGZX3V0dFQ71slkUjunURTp8PCwtkyWZTo8PCzLmP20A6x2u13u62w2UxzHK2WqzPmprhcPzww/831faZqu9AwCAAA8qeIJzGazQlIhqYiiqJYXBEERhmEtrSiKIgzDMj1JkmLTrlbXkWVZIamYzWZ2sVr6uu1KKpIkKYrldoMgsIusrMcu43leY5pZrzkfWZbVyph9N+me562cL/v4zLqajrfKXncURY3nNAzDct/NMma/jSAIyv2y9yeKosLzvFp5PB7z3bD/RgAAAE/tUXssjFarVWsRr7bKp2mqL1++1MpL0t7eni4uLiRJV1dXCoLALtLo5uZGnuc1DgnxPE/X19fScrv7+/t2EXmeV/7/6upKaZquDCmSpN+/f5flXNct/69KL4ft169fkqTr62sFQbCynHl/c3OjPM+VZZk+ffrUWMb27t07O6k2jKp6XEZT2v7+/spE+Pfv39feS9LPnz/tJEnS5eXlSs8IHk+v11MQBOr1enYWAADAk3qSwMIwAUZ10um21lWod9FUYbYFQVAO6am+ut2uXfRRNAUM26gOxSpuGTr20Pb29uwkPIJOp6MgCDSdThufEgUAAPCUnjSwMKot5UEQlL0IVT9//ixbvvf398vei9t8/PhRWZY1Tv6u9gBUey8M00tg7O3trbTeP4RPnz4pTVM7udznjx8/1novqraZBG2Oo3rO/vz5Uyuj5fmwXV1d7dTjcHBwoMvLSzsZD2wymdTmVZycnNw69wUAAOAxPWpgMZlMViZtTyYTZVmmjx8/SssKkT1heDKZKI5jff36VZLU7XaVZVltCFWe542VKNd1ywnjVaZ11wyROj4+XplQbVeoB4OBsixbaQluesLUXbRaLQVBsDIJ/PDwUGEYlkFFGIbq9Xq1IKndbleW2KwalKyb9F09NnPem4ambevz589K07S23vl8vlVAhO31ej1FUVR+VsyDEhgSBQAAnsujBhaSNBwOa/MTer2eiqKoVYhms5l6vd7aMvrHLGMtFovanAETnNjG47HCMKxt13Xd2u9nDAYDRVGkdrtdlrm4uFgJSIqiUBzHtXWtq6TfxXQ6rT3C1XEcHR8f157sY47D87yyzD/mjm/muq6SJKmd06bfN/A8T/v7+2UZ8wSqpvkp2zI/hlg9Z+12e6d1os5Zfv7tHyU0nx07YAUAAHgKTrFNTRUvRp7n8jxPs9lsp8r6aDTS2dnZowz1AgAAwNvz6D0WeFhmeNMuQQUAAADw0AgsXrB+v1+bm5DneTm2HgAAAHhJCCxesP39/docEPML5fbYegAAAOC5MccCAAAAwM7osQAAAACwMwILAAAAADsjsAAAAACwMwILAAAAADsjsFj+UvFkMrGTtzKZTOQ4zsr7PM9r5Ta5zzLr5Hkux3Fqj6ndxmQy4RebAQAAcG8EFgAAAAB2RmDxwLrdroqikOu6dtZa91nmJdilpwcAAACvC4EFAAAAgJ39VYGF+QVq86rOSRiNRvJ9X/P5fG0ZSSv527a428t1Oh27iFTZD6Pf76vT6ZTzKMxr0zK6ZXudTudex1BVXYe9bcP3/dp2zLwNs29ZlqnX68lxHI1GI6kyX6RpvwEAAPB6/TWBxWQyUZIkKopCRVEoiiIdHh7WymRZptPT07JMGIa1MvP5XO12W7PZrCxzdXWlLMtq67FNJpOV5Q4ODuxia6Vpqqurq3LZIAg2Vrg3bS/Pc7muW6bPZjP1er2VAGoTs22zjouLC/V6vVqZ+Xyu4+PjskySJGq325KkVquloijkeV75NxkMBpKk8/PzcpmiKLRYLMqgAwAAAK9Y8ZfKsqyQVGRZVhRFUURRVNiHY5cJgqAIw7BWpiiKQlKRJImdXNqUnyRJbbtRFBWe55XvwzCsvS+KopjNZhuX2bS9Jp7nleXNMc9mM7tYUVS2bc6JYe9DE3u91e2uE0VREQSBnQwAAIBX5q/psZA1zMbzPDu7MU2S/vz5Iy17Dvb39+3stctp2XIvSR8/frSztrZuqFFTL8M22zOPlDWv23pcqq6vr+V53spE8Q8fPtTeq2E41raqw6yGw6GdDQAAgFforwksfN/XyclJOcTmLpXpqvfv39tJW7Er4o9t3fb6/b48z1OWZeW52BQYNVkX6FR1Oh212+3asKbbmEDk4OCgXCaKIrsYAAAAXqG/IrDI81xZluni4qJMM70Qd+F5nq6vr2tpZt3rtFotqdKT8Nhu297FxYWSJKkFHpv23/bhwwelaWon6+rqqvY+TVPNZrPyfVPviu36+lpBEJTzLSTp58+ftTIAAAB4nf6KwMK4ubkp/390dFTL28bx8bGGw2Gt0m5PAG8ShqHa7fbKU6gey23bqwYB/X6//P82ut2uVJnAreUQsziOK6X+oRqENW3H9/3GgMSYz+eN6wUAAMDr81cEFq7rKkmS8tGmjuPo/PzcLnarwWCgKIrUbrfL9VxcXNw6lGg8HiuKInmed+f5BvexaXsXFxeK47hM39/fv3X/bUVRKE3Tch1XV1dKkqRWZjabaTgclmVOTk5q+ZJ0cnJS7stoNNJgMFAQBOUyp6enDIUCAAB4I5xim8HzAAAAALDBX9FjAQAAAOBlI7AAAAAAsDMCCwAAAAA7I7AAAAAAsDMCCwAAAAA7I7AAAAAAsDMCCwAAAAA7I7AAAAAAsDMCi2eU57kcx9F8PpckzedzOY6jPM/tok/O/Jo2AAAAsA0Ci0c2Go1qwQMAvCSTyUSO42gymdhZ6vf7chzHTgYAoBGBxSM7OztTEAT6/v27nfViNAU+RVFoMBjU0gC8Pt1uV1EUqdfr1dLn87niOFaWZbV0AADWIbB4RKayPh6PFcexnQ0AL8JgMJDneer3+2Xa0dGRoiiS67q1sgAArENg8Yi+f/+u4+Njua4rz/PuPWfBcZzay+5dUGXIlXlVt2Uvb+ZwmCEQktRut8vhEPbcD8P3/dp67KETvu9rNBqVwyccx1Gn06mVAfAynZ+fK45j5XleXj/otQQA3AWBxSOK41ifPn2SJB0fH+vs7MwuspGp4EdRpKIoVBSFZrOZ2u12rVLf7/c1HA7LMkVRlHmTyURJkpTpURTp8PBQWg6BMGVns5mKolC32y2XrXIcR4eHh+V6sixTr9dbCZaGw6H29/fLcmmarpQB8PK0Wi2FYajDw0MNh0Odn5/bRQAA2IjA4pFMJhN5nqdWqyVJ+vz5s7IsW+kF2OTbt28KgqDWathqtRRFUXnTXzcO2izT7XZrwYLZj7s8eWo0GsnzPI3H4zLNdV0lSbISLIVhWNteFEW6vLyslQHwMn39+lVZlikMw/LaBQDAtggsHsn5+bmOj4/L967r3nkS98XFhY6OjuxkffjwQWmaSpKur6/led7GcdBmyJPjOPI8z86+1eXlZe1YjPfv368EKXt7e7UykrRYLOwkAC9Qv99XEASK4/hOjSAAAIjA4nHM53OlaarhcFibk5Cm6aNM4vZ9304q+b6vk5OT2hAmALCNRiOlaarpdKooihobNQAA2ITA4hF8//5dQRDU5jxU5z7Yk57XOTw81NXVlZ2sX79+KQgCSdKnT5/K3gtbnufKskwXFxdl2p8/f2pltnFwcNA4nOn379+39pYAePnyPNdwOFSSJNJyKGWWZbWnRAEAcBsCi0cQx/Ha1r4wDLeeFPn161fFcVyb/DyfzzUcDnVyciIt51x4nrfSa1Fd5ubmpvx/0355nqfr62s7uTQYDJSmaa2Skee5er2eTk9Pa2UB/H3MEKjq/KgkSRgSBQC4EwKLB2Yq9B8/frSzJElfvnxRmqZb3axd11WWZbUhVe12W1mW1SZWLhaLlUfBfvr0qZxg3ev1yvSmoOb09LTcxrrelKIoFMdxba7GbDZb+xQpAH+HTqejNE1rD2fQ8sEPQRCo3W7f6WEPAIC3yynM+BwAAAAAuCd6LAAAAADsjMACAAAAwM4ILAAAAADsjMACAAAAwM4ILAAAAADsjMACAAAAwM4ILAAAAADsjMACAAAAwM4ILAAAAADsjMDigfT7ffX7fTv5UfT7ffm+byc/KMdxNBqN7GQAAACg0asJLDqdjhzHqb06nY5dDABQMZlM5DiOJpOJnaV+vy/HcexkAAAavZrAQpKiKFJRFOVrsVi8yuBiPB5rsVjYyffmOI7m83ktrSgKDQaDWhqA16fb7SqKIvV6vVr6fD5XHMfKsqyWDgDAOq8qsLCdn58rTVM7GQBQMRgM5HlebTjn0dGRoiiS67q1sgAArPOqA4vfv3/L87xamu/7teFS1ZZ6MyQgz/O1ZYxq/rq5FaPRaOPQrNFoJN/3y+1Wy1SXtZfrdDrlNu1tNO2TnZfnuVQ5Xklqt9tylsMhzPHbx22fO3vohO/7Go1G5fAJp2HfAbxM5+fniuNYeZ6X86votQQA3MWrDix6vZ5OT0/L9/P5XMfHx+VQqSRJ1G63a8tI0uHhYVkmiqKVMo7j1IZd7e/vK47jWpl+v6/hcFgbmqVl5bsqyzJdXV2VZdI0LctU09ZNpB4MBrVtRFEkz/M0Ho+lZfCQJEkt//DwUFoOgTD7NZvNVBSFut1ubf2G4zi185JlmXq93sp+DYdD7e/vb7XvAF6OVqulMAx1eHio4XCo8/NzuwgAAJsVr0QQBIWk2msbkorZbFYURVEkSVJIKrIsW1smiqLC87xafrHcfhiGRVEURZZltWWq7HXZ+xmGYWOaWXdhbatqNput3a5h9q16jPYy9v6vO+YkSWrpnuet7FcURUUQBLU0AC+T+e7b32MAALbxqnosqr0IWg4Tss3n89pwniZNY4p///4tSbq8vCxb/Kuqy9zc3MjzPLVarVoZSfI8T9fX17X3VXt7ewqCoJYmqRy+tIkZE21vtzrUyt7eNi4vL3V8fGwn6/3798qyrLZve3t7tTKSHnSiOYDH0+/3FQSB4jheGQoJAMBtXlVgUTWbzTQcDmuV3k6no3a7XQYfJgC5q6bK83Mzv21hj4n2fV8nJye1IUwAYBuNRkrTVNPpVFEU6ejoyC4CAMBGrzawaLVaCoKgNok5TVPNZrPy/Ta9ADbXdXV5eWkn6+Liovz/x48fV1ryjSzL9OnTJzt5J5PJRHEcl/MqjDzPlWVZbd/+/PlTK7ONg4ODxmM2k+ObengA/D3yPNdwOFSSJNJy7laWZWsfTAEAQJNXG1ho+XsPaZrWnl5UHYZ0n5vmly9fViYk9/v9Wk+A67oKw3Bl2FGn01EQBCtDlXbV6/WUJMnaCv7NzU35/6ZWSHt4lm0wGChN09r5yvN8ZXI8gL+TGQJVfXhDkiQMiQIA3MmrDixMBb/X6ynP83J4lJlvcHJyYi9yq1artbKe/f19hWFYKzcejxWGYW0+h+u6mk6ntXK7Mo9z7fV6tW11Oh25rqskSWp5TU96OT09LY/HfoSsURSF4jiuzdWYzWZrnyIF4O/Q6XSUpulKj2e321UQBGq32429rwAA2JzivhMNAAAAAGDpVfdYAAAAAHgaBBYAAAAAdkZgAQAAAGBnG+dYOGt+QA4AAAAAtHzIj+ixAAAAAPAQNvZYAAAAAMA26LEAAAAAsDMCCwAAAAA7I7AAAAAAsDMCCwAAAAA7I7AAAAAAsLMHDywcxylfk8nEzpYkzefzWjnzms/nZZnJZLKS7ziO8jyXJPX7/ZU8x3Hk+35lS5Lv+ytl+v3+1mXsfe10OrVlm8pU19+07mqZ6nHa+67KcZq8Tqezsi77Zc6RvV/mVT3PAAAAwEN40MDCDiSurq5q7yVpNBqp3W7byTX9fl+9Xs9OvpM8z+U4jrIss7NK25SxpWlaVtyN79+/197fV5ZlGo1GdvK9bHOeAQAAgIfyoIHF+fm5JMnzPElSHMdWCWk4HEqSgiBQURTlK4oiaVnZN8uFYVgrE4ZhbV1GtcxisZAkffv2rczPsqzMrwYR25SpMsd1c3NTS7+4uKjlN7GPdzwe20Wk5fmxA5eq6XTaeD6q63Zd99bzDAAAADykBwss8jxXmqZSpaKthl4MwwQAxmAwUKvVqqXZFezxeCzXdWtp2/jz50/5f9d1Gyv125Qxw5FMAKXlcKMsyxQEQaXk/Zh12EO1drHpPJthVg+5PQAAALxNDxZY/PjxQ1q22ruuW1aSq5VwVSrPWZbJcZyVoT+u65Yt/2maytkwV8Oozh8wleT9/f0yv91uN85f2KZM1dHRkWQNhzLDoI6Ojtb2dKhyLObVdEwmmEnTtDH/Lm47z6r0KDX1LAEAAAB38WCBxdnZmSTp+PhYWlMJ13IoT3XI0HA4XKn42q3svV5vbWV8nW63Wxv2YyrY1eBhmzJVHz9+LPfdBFKmUt7tdmtl7+PPnz9KkkRaHrPdY3MX25xnM5Rq3RAzAAAAYFsPEliY4UCS9OnTJ2lZCTdMJdxYLBYqiqI2fGg4HNYCBzMnoFo57vV6jU80Wjd3YTAYqCiKsrKuZfBQfbLTNmWqTOB0eXlZ7u82w6DsuQ7rApFut/tgQ6JuO8/j8XjlnAEAAAD38SCBRfWpSO12W47j1AIC05thm06nteFDTU+RWiwWms1m5fvr6+ta/ja63W6tgm3mgty1jCR9/vxZWuabYV6md+ahVIdEPcQwpW3OMwAAALCLBwksbqv8ZllW9jSsG2Zk5Hm+trfgLvr9fmPvRtU2ZWzV+SMm+FjX+3BfruvWelDu47bzLCZvAwAA4AHtHFhUhy/NZrPacJ9qK7np1TDzGMyr2rPx5csXqWGic/X3GEyPQVW1rFP5gTjTe2JeJhCozinYpozt4OCg/P+mclX2Md1W8a8OibqPbc6zCQirT/ECAAAA7mPnwOLk5KT8v/242GrrvqnErqssF0WhVqtVeypUled5Kpa/0bCN6hOfqpIkKYcabVOmSTW4WbeOh7BpH25z23lWJSg6PDy0SgEAAAB34xRFUdiJAAAAAHAXO/dYAAAAAACBBQAAAICdEVgAAAAA2BmBBQAAAICdEVgAAAAA2BmBBQAAAICdEVgAAAAA2BmBBQAAAICdEVgAAAAA2BmBBQAAAICdEVg8gslkIt/37WRJ0nw+l+M4drK0XM5xHE0mEztLktTpdOQ4jubzuZ1VyvNcjuOo3++XaWa99qvT6dSWvc1oNNp6+U3HCeDl2HTd6ff7fI/xoHzfb7w/mnvXaDSys4BHY65xeZ7bWfJ9f2M9B80ILF6Q8/NzBUGg8/NzO6vm+/fvdlLp27dvdpIkyfM8FUVRe0m6NVAx8jzX5eVlbfnFYlELYFSppLTb7Vo6gJep2+0qiiL1er1a+nw+VxzHyrKslg7sYrFYKMuylQCi3+8rDEMNBoNaOvCYxuOxgiBYqcuYz+d0Oq2lYwsFHlySJIXneXZyURRFMZvNiqbTnmVZmS6pyLLMLlIEQVAEQdC4vCGpCIKgCMOwTNu0P1EUbVzfJkmSrCwrqUiSpDEPwMvleV7tuuF5XhFFUa0M8BDM/cHc57hf4DmZ+leSJLX3s9nMLoot0GPxQvz48UNhGEqSgiBY2/NwcHCgIAhWWnu0jLCDIJDrunbWWqZ1qGkYxH0URaFut2snA3jhzs/PFcex8jwvry+0HuMxdLvd2n2u1+spSRK7GPAkXNdVFEU6OTmRKr1nrVbLLootEFi8EGdnZ9rf35ckHR0dKY5ju0jp5OREZ2dndrLOzs7KL8ZdBEGgX79+2cm3urq6UhAEdjKAv1Cr1VIYhjo8PNRwOLx1SCawi/F4rDiO5fu+giCgQQrPyjSi+L6vNE01Ho/tItgSgcUjybJsZbL0urkH8/lcWZaVF1bz77peBBNFV+dGzOdz+b7/ZBH2aDRSHMd8+YBX5OvXr8qyjNY6PDrXdRWGobIs4z6CF+H09FRZltF7tiMCi0fSNFm6KArNZjO7qL5//14OgzLCMNzYYnh6eqrT09Pa+6Ojo1qZbS0Wi/L/5gkJ5mVPaNIyoh8OhyqK4k7DrgC8bP1+X0EQKI7jrR7qANyXeThA08RZ4Dn0ej0FQbDyIAvcDYHFM8vzXHEcK47jWoU+jmOladr4CDQtezVMfp7nWiwW9+pKzvNcWZbp8+fP0rJ7uhoIVVuSzOMADw8P9Y952gBei9FopDRNNZ1OFUXRvRsqgG20221FUaTpdKo0Tdf20ANPodPpKAgCTadTgt0dEVg8sx8/fqzt3fA8Tz9+/LAXKUVRpB8/fujbt2+13ou7MC2U2/Q8eJ6nJEnotgZemTzPNRwOyyEAg8FAWZZxc8Wj6Pf78jyvHNduHne8riENeEyTyaQ2r+Lk5ERxHBPs3hOBxTM7OzvT8fGxnSxJOj4+bpykbQwGA52dneni4uJevRWO42ixWGz1nObJZCLP8+61HQAvm2lgqH6/kyRhSBQenBkCVR3qOxgM5HkegSyeRa/XUxRFZQOreZAFQ6Luh8DiGU0mE2VZpk+fPtlZkqTPnz8ry7KNUfPh4eHawKSqaTL5bDarza/Y5NevX43rcNb8Yi+Av0On02l8Cop5JGi73aYlGQ9iPp+r3W43Phzg/PxcaZoSXOBJOY5T6z0zzPWw6VfisZlTMFgeAAAAwI7osQAAAACwMwILAAAAADsjsAAAAACwMwILAAAAADsjsAAAAACwMwILAAAAADsjsAAAAACwMwILAAAAADsjsAAAAACwMwKLVybPczmOs/Ky2fnmlee5XVSdTkej0chOXmG2XV2H7/uaTCa1cgBejslkIsdxGr+n/X6/8foB3Jfv+/J9304u7x/b3GuAh2KucU11H9/31el07GTcgsDilcqyTEVRqCgKhWHYeCGfzWZlmaIolCSJPM9Tv9+3iwJ4pbrdrqIoUq/Xq6XP53PFcawsy2rpwC4Wi4WyLFsJIPr9vsIw1GAwqKUDj2k8HisIgpV6j/l8TqfTWjpuR2DxBnz58kVZljVG5FXdbldZlimO48bWSwCv02AwWGlUODo6UhRFcl23VhbYVZIkGg6H5T1pMpkoTVONx2O7KPDoxuOx0jQt6z15nms4HOr8/Nwuii0QWLwh21QQXNdVGIZ8oYA35vz8XHEcK8/zsrWO1mM8hm63qyAI9O3bN0lSr9dTkiR2MeBJuK6rKIp0cnIiVXrPWq2WXRRbILB4A0zL47b29/e1WCzsZACvWKvVUhiGOjw8pLUOj248HiuOY/m+ryAI1O127SLAkzGNKL7v03u2IwKLV8rzvHJCtu/7tDwCuNXXr1+VZRmtdXh0pnc8yzIqcXgRTk9PlWUZvWc7IrB4paqTt4+OjuQ4jubzuV2s0a9fv+ykGt/3a0+SYj4G8Dr0+30FQaA4jre+XgD3YR4O0DRxFngOvV5PQRCsPMgCd0Ng8QaY8azfv3+3sxpdXl7q+PjYTi4tFova06Towgb+fqPRSGmaajqdKooiHR0d2UWAB9NutxVFkabTaW3iLPAcOp2OgiDQdDol2N0RgcUbsre3ZyetME/n+Pz5s50F4JUyT0ExQwAGg4GyLOPmikfR7/fleV45RNc87vi2JxcCj8F+KtnJyQlPx9wBgcUbsG2w0O/31ev1NJvNtnqCFIDXwQyBqvY+JknCkCg8ODMEqvpwgKbHHQNPpdfr1R6tbR5kwZCo+yGweKWqk7d7vZ6yLFsJFtrtdm2uhCQVRcGkTeAN6XQ6jU9BMUMo2+02Lcl4EPP5XO12u/HhAOfn50rTlOACT8pxnFrvmWGuh00/LozNnKIoCjsRAAAAAO6CHgsAAAAAOyOwAAAAALAzAgsAAAAAOyOwAAAAALAzAgsAAAAAOyOwAAAAALAzAgsAAAAAOyOwAAAAALAzAgsAAAAAOyOweIHyPJfjOJpMJnaWRqORHMexk8tl5vO5tPyZevN/m+/7G9ddfTWV28T3/ZV1rNsPAM9vMpms/a73+/3G6w1wX77vy/d9O7m8h41GIzsLeDTmGpfnuZ0l3/fV6XTsZNyCwOIFcl1XQRDo/PzcztLZ2ZkkrVTWf/z4IUlqtVq19G35vq+zszMVRVF79Xq9O32xsizTbDarreO++wTg8XW7XUVRpF6vV0ufz+eK41hZltXSgV0sFgtlWbYSQPT7fYVhqMFgUEsHHtN4PFYQBOr3+7V08/mcTqe1dNyOwOKFOjg4UJqmtbQ8z5VlmTzP0/X1dS3v8vJSYRjW0rbV7/fl+74Wi4WdpaIolKZpY2vmOu/evbOTALxgg8FAnufVbq5HR0eKokiu69bKArtKkkTD4bBsJZ5MJkrTVOPx2C4KPLrxeFyr5+R5ruFw2Ni4i9sRWLxQnz9/lqyeiZubGwVBoOPj47LnwkjTVPv7+7W0beR5rjiOdXJyYmeVoijamG80dSUC+Ducn58rjmPleV621tF6jMfQ7XYVBIG+ffsmSer1ekqSxC4GPAnXdWv1HNN7xmiL+yGweKFc113pmTg/P9fBwYE+f/6sLMvKirwJPj5+/FiW3dafP3+kW4ZQffr0aavhEGZdnucxvwL4y7RaLYVhqMPDQ1rr8OjG47HiOJbv+wqCQN1u1y4CPBnTiOL7Pr1nOyKweMHsnok0TfXp06cy6Li5uZEkXV9fKwiClSEL7XZ7ZSK14zi1IOH379/yPK+23Dq39Ui0Wq3a3IokSdRut+80jArA8/n69auyLKO1Do/OdV2FYagsy6jE4UU4PT1VlmX0nu2IwOIFMz0FeZ5rMpnI87zyZn94eKirqytpOb/i4ODAWlork6jNyw4ktumN0PJGoOUTp7Z56lO321UYhrR8An+Jfr+vIAgUx/Ha7zXwEMzDAZomzgLPodfrKQiClQdZ4G4ILF4wE0Tc3Nzo6upKh4eHZd7+/n45Htr0ZNyHGT61qRJhekQMO1DZ1LK5t7dnJwF4gUajkdI01XQ6VRRFOjo6sosAD6bdbiuKIk2n0zs/IAR4aJ1OR0EQaDqdEuzuiMDihQvDUFdXV7q4uKhNzjbjUb99+1brybgr82jb09NTO6s0HA7vXcm4vLxcGaIF4GUxT0ExQwAGg4GyLOPmikfR7/fleV45rt087vi24bbAY7CfSnZycqI4jgl276vAi5YkSSGpaPpTBUFQeJ5XhGFoZxWSitlsZicXRVEUnucVSZLU0iQVnufV0rIsKyQ1rr9JFEW1bUZRVEgqsiyrlQPwsgRBUARBUEsz15511xHgPmazWePnyvO8lc8g8BQkFVEU1dLCMGysd+F29Fi8cKZnojoUyTg4OFCWZfd6zKytKAodHh7W5k54nqfZbLb1xLoPHz7UJowPh0MVRUGPBfCCdTqdxqegmEeCttttWpLxIObzudrtduPDAc7Pz5WmKb1keFKmrmM/WttcD5t+JR6bOcU/ojUAAAAAuDd6LAAAAADsjMACAAAAwM4ILAAAAADsjMACAAAAwM4ILAAAAADsjMACAAAAwM4ILAAAAADsjMACAAAAwM4ILAAAAADsjMDiDXMcZ+U1n88lSfP5fCWv+ur3+7V1jUajlTKTyaRWBsDLM5lM1n5f+/2+HMexk4F7831fvu/bycrzXI7jaDQa2VnAozHXuDzP7Sz5vq9Op2Mn4xZOURSFnYi3wXEczWYztVotaRlMtNttJUmibre7UrYpXcsvX5Zlsj9KjuMoCAJNp9NaOoCXZTQaaTgc1r7D5nqQZZlc162VB3bhOI6iKNJgMCjTOp2OXNfVeDyulQUemwkeqnWV0Wiks7MzLRaLSklsgx4LlFqtlsIw1Pn5uZ21lum5sIMKk5amKS1QwAs3GAzkeV6tJ/Lo6EhRFBFU4MElSaLhcFi2Ek8mE6VpSlCBZzEej5Wmadlrm+e5hsPhnepC+H8ILFCzt7dnJ62V57niONbp6amdVYqiSGdnZ3YygBfm/PxccRwrz/OyMaDaogw8lG63qyAI9O3bN0lSr9dTkiR2MeBJuK6rKIp0cnIiLRtMwzAsR3PgbggsUPPz58+tWyj//PkjSfr48aOdVfr06ZOyLGscvwjg5TA9loeHh7TW4dGNx2PFcSzf9xUEQeMwW+CpmEYU3/fpPdsRgQVKo9FIcRzr69evdlaj379/S8toH8Df7+vXr8qyjNY6PDrXdRWGobIsoxKHF+H09FRZltF7tiMCizeu3W6XT3EykzfvGijQGwG8Dv1+X0EQKI7j8glxwGOYz+eK41hBEKw8ZRB4Dr1eT0EQqNfr2Vm4AwKLN242m6koivJ1F2YI1M3NjZ1Vur6+lud5dw5WADyt0WikNE01nU4VRZGOjo7sIsCDabfbiqJI0+m0NnEWeA6dTqd8iiXB7m4ILHBvrusqCIJywlOT4XCo4+NjOxnAC2KegmKGAAwGA2VZxs0Vj6Lf78vzvHJcexRF6vV69H7jWdhPJTs5OVEcxwS798TvWLxh9u9YbLLpdywcx5HnebXnPed5Ls/z+B0L4C/Q9Bz3yWSiXq+39TUC2Ib5fRT7c2V+OI/7BZ5a0++q9Pt9xXF855EcoMcCD6AoCh0eHpZzNUygISZ2Ay9ep9NpfAqKeSRou92mJRkPwgQVTQ8HOD8/V5qm9JLhSZn6iv1obXM9bPqVeGxGjwUeleM45f/5BV8AAIDXi8ACAAAAwM4YCgUAAABgZwQWAAAAAHZGYAEAAABgZwQWAAAAAHZGYAEAAABgZwQWAAAAAHZGYAEAAABgZwQWeFCj0aj89e1Op2NnAwAA4JUisMCt5vO5HMfRfD63s2omk4kkqSgKFUWhk5MT9ft9uxgAAABeIQKLB9bv98sW+6aXqZxvqqj7vl9W0rVcZ7WCPplM5DjO2kq7Xb7K9/2Vfcrz3C52L79+/dJgMCjX++7dO+3t7dnFALwg5npSveYY5noGPBTf9+X7vp2sPM/lOI5Go5GdBTwac41rqgf5vs/Ii3sgsHhg4/G4bLFPkkSqtOAXRaFWq2Uvcm9xHK8NTmxmiNLp6Wltf6Io0p8/f+ziNa1Wa2XfNwVGhuu6dhKAF6bb7SqKIvV6vVr6fD5XHMfKsqyWDuxisVgoy7KVAKLf7ysMQw0Gg1o68JjG47GCIFhpjDWfz+l0WkvH7Qgs/lKe5ykMQ7XbbTtrxXw+13A4VJZl6na7tbzBYPBgwc6HDx80Go3KoKXT6ejnz592MQAvzGAwkOd5tZvr0dGRoiiigQAPLkkSDYfDspV4MpkoTVONx2O7KPDoxuOx0jQte23zPNdwONT5+bldFFsgsPiLjcfjlcpAk9PT050qCGaohP3/drtdG0JhghYzFErLfQTw8p2fnyuOY+V5XrbW0XqMx9DtdhUEgb59+yZJ6vV6ZQ8/8NRc11UURTo5OZEqvWcP1ej61hBY/OVMZWDTsKQ0TfXp0yc7+V663a6KopAkzWYzFUVR6wUZDAZljwVdiMDfo9VqKQxDHR4e0lqHRzcejxXHsXzfVxAEK73pwFMyjSi+79N7tiMCi2dkWvzt113GNJvKwNHRkZ0lLbv0JOndu3d2FgDUfP36VVmW0VqHR+e6rsIwVJZlVOLwIpyenirLMnrPdkRg8YxMi7/98jzPLrqRuShvGhJ12wRtNTwxqukpMQBer36/ryAIbu0FBXZlHg7QNHEWeA69Xk9BEKw8yAJ3Q2DxSqwbEuW6rjzP0/X1dS29yWKxqAU4dE0Db8doNFKapppOp4qiaG0vKPAQ2u22oijSdDqtTZwFnkOn01EQBJpOpwS7OyKweCU2DYk6Pj7WcDi0kwFAqjwFxQwBGAwGyrKMmyseRb/fl+d55bh287jjpt8SAB6b/VSyk5MTxXFMsHtPBBaviPlSxHFcSx8MBgqCoPFHYEaj0Uovxza27QUB8PKZIVDVXsokSRp7QYFdmCFQ1YcDND3uGHgqvV6v9uRM01DLkKj7IbB4ZdY9yWU6nSpJEnmeV5tHcXZ2dq9JmqenpxoOh8zFAP5ynU6n8Sko5pGg7XZ7pUECuI/5fK52u934cIDz83OlaUpwgSflOE6t98ww18OmX4nHZk5hnh0KAAAAAPdEjwUAAACAnRFYAAAAANgZgQUAAACAnRFYAAAAANgZgQUAAACAnRFYAAAAANgZgQUAAACAnRFYAAAAANgZgQUAAACAnRFYvEGdTkeO49RenU6nVmY+n6+UcRxH8/m8Vs4YjUYrZSeTiV0MwAszmUzWfl/7/b4cx7GTAQBoRGDxRkVRpKIoytdisVgJLiTVyiRJona7vRJc+L6v4XBYK1sUhXq9XuM6Abwc3W5XURSp1+vV0ufzueI4VpZltXQAANYhsIAk6fz8XGma2sk13W5XQRDo+vq6TOv3+9IyALEVRaE0TTUajewsAC/IYDCQ53nl91mSjo6OFEWRXNetlQUAYB0CC0iSfv/+Lc/z7OQVi8VCHz58kCTlea44jnV6emoXK0VRpLOzMzsZwAtzfn6uOI6V53nZGDAYDOxiAACsRWABSVKv19sYIGg5j0LLngtJ+vPnjyTp48ePtXJVnz59UpZlyvPczgLwgrRaLYVhqMPDQw2HQ52fn9tFAADYiMDijRoOh7WJ1kVRlAFDVbWMlj0Wxu/fvyWJoRLAK/H161dlWaYwDNVqtexsAAA2IrB4o6qTt1XpjbCZMlEUaTgc2tnSckgUgL9fv99XEASK43jlIQ0AANyGwAKazWYaDocbA4TBYKAgCGqTO80QqJubm0rJuuvra3meR68G8MKNRiOlaarpdKooinR0dGQXAQBgIwILqNVqrQQNTU5OTmotma7rKggCnZyc2EVLw+FQx8fHdjKAFyTPcw2HQyVJIi0bErIsu/WaAABAFYEFJEnj8Vhpmjb+SJZhJndWWzKn06myLJPv+7WyeZ7LcRwFQcCTZYAXzgyBqs6zSpKEIVEAgDshsIC07H0Iw1C9Xm/jkCgzubPaklkUhQ4PD2sTvc2jaxkCBbxsnU5HaZpqPB7X0s3v1rTb7Y3XBAAADKdo+mUz4IGYp0lJUpZlBBoAAACvFIEFAAAAgJ0xFAoAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwAJb831fjuPUXvP5vFam0+mslKn++jaAl2UymchxHE0mEztL/X6f7y8AYGsEFriTJElUFIWKolCSJGq328rzvFYmiqKyjHkBeJm63a6iKFKv16ulz+dzxXGsLMtq6QAArENggXvrdruSpJubGzsLwF9kMBjI8zz1+/0y7ejoSFEUyXXdWlkAANYhsMDO3r9/bycB+Mucn58rjmPlea7RaCQtAw4AALZFYIF76/f7CoJArVbLzgLwl2m1WgrDUIeHhxoOhzo/P7eLAACwkVMwAB5b8n1/Zby1/fHpdDpK07SWFoahxuNxLQ3Ay5PnuTzP4zsLALgXeixwJ9XJ21mWyXGcctiEYU/epoIC/B1ML2QcxytPfAMA4DYEFrg313UVRZHOzs7sLAB/mdFopDRNNZ1OFUWRjo6O7CIAAGxEYIGd+b5vJwH4i+R5ruFwqCRJpOWk7SzLak+JAgDgNgQWuDdTGaFlE/i7mSFQ5hHSWg57ZEgUAOAumLyNrTVN3k6SpFYZaZq8LUmz2YynRwEvkPnOZlm28psVm/IAALARWAAAAADYGUOhAAAAAOyMwAIAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwOKVy/NcjuMoz3M7S5LU7/flOM7Ky5TvdDoreaPRqLYO3/dXyjiOo/l8XisH4OWZTCZyHEeTycTOKq8PAABsg8ACCsNQRVHUXq7rlvlRFNXyhsOh+v1+bR1JktTKzGYztdttdTqdWjkAL0u321UURer1erX0+XyuOI6VZVktHQCAdQgscGdJkiiOYzu5ptVqqSgKpWm60sMB4GUZDAbyPK/WYHB0dKQoimqNDAAAbEJggTt7//69nbRWFEU6OzuzkwG8MOfn54rjWHmel40Bg8HALgYAwFoEFriz379/y/M8O7nRp0+fGEoB/AVarZbCMNTh4aGGw6HOz8/tIgAAbERgAcVxXJt0vWlexHw+V6/X0+npqZ0F4C/39etXZVmmMAzVarXsbAAANiKwwMrk7el0WssfDodl0NFutzWbzdTtdmtl1vn9+7edBOCF6vf7CoJAcRzzVDcAwJ0RWOBW9lOh7tKSeXV1pTAM7WQAL8xoNFKapppOp4qiSEdHR3YRAAA2IrDAozGPq/zy5YudBeAFyfNcw+FQSZJIy0nbWZatPFYaAIBNCCzwKEajkdrttpIkuVMPB4CnZ4ZAVYc4msdKMyQKALAtAos3wvO8rSdo30ev16ut//LyUkVRbD0XA8Dz6HQ6StNU4/G4lt7tdhUEgdrttvI8r+UBANDEKYqisBMBAAAA4C7osQAAAACwMwILAAAAADsjsAAAAACwMwILAAAAADsjsAAAAACwMwILAAAAADsjsAAAAACwMwILAAAAADv7qwILx3E0Go3s5I3us8xT6nQ6tf1zHEeTyaRWBgCAxzIajeQ4jp38qoxGI3U6HTv5Xl56vQJ4Tg8aWOR5Lsdx1r4e6ksNAMBrYir31ReVVwB/mwcNLFzXVVEU5cvzPEVRVL6fTqf2IndSFIUGg4GdvNF9lgEA4CmYBrnLy8va/TPLMv38+dMuvrOmlvvBYKCiKGppWI96BbDegwYWAABge4eHh4qiaKXhzXVdjcfjWhoAvHTPElh0Oh31+331+/1ad69539QNbFp15vO5JGk+n8txnJXhV9X5CfdZxqjmm33t9/t2sRrf92vLme0a9nY3dXN3Op2ynN26pIZu8+q2RqORfN/XZDJZWd4+x3me1/I6nU65nHnZ7OPwfb+WXz0Pdh4A4B/MvWfb1u/qdde+7pv8yWRSu39U71u+72s4HCpN09r12Vz7DXOPrt5n7Gu5PT9Qy+Oxy5n7bvVV1bSMlsdSPT773mUfu616H2q6h26z/+a8mPPQ7/d3qlfY+9TUewT87Z4lsJCkOI61v79f61LM87zWDTwcDm+9eHieVy6TJIl6vV6tstzktmUcx6kN4drb21Mcx7V12ObzuY6Pj2vrbbfbZX6e5/I8T0mSlGUkKU3Tylr+odfr6eTkpDwPaZrWLoD9fr/WbT6bzdRut2vHkGWZrq6uVFSGoJkLWHUfPc8rl9Fyf8xyRVEoCILahW8+n68cx/HxcZnvOI5OT0/LvMPDQy6cANDg6upKh4eHdvIKU2mt3pfMdd+uwNr3jziOyzKLxUJRFCkIAhVFocViUVu2ytzzzPa0vPfcxWQyUbvd1mw2K9cTRVFZEd/WaDTSxcVF7dg38X1fh4eHZfmTkxMNh0O72FbMPbooio09SLfVK+x9Ojo6uvc+AS/ZswUWQRCo2+3W0qpdwa7rKggCXV9f18rYqheYbrcrz/N0c3NTK2PbtMxoNJLnebUWpMFgoCAIyvdNWq1WbRlzbCYw+vbt28oxDwaDlYq9JEVRpFarJS3PQxiG5VjbPM8Vx3HtXLVaLQVBoB8/fpRpkmoXwfl8rsViUUszx169MXmeVytzcnJSC36Ojo4URdHKcWh57sIwrOV9/fpVaZre6SYCAG9Bnufa29uzk1eY+0f1HtNqtRRFkc7Pz2tlm+4fV1dXtTLbsLd3enqqi4uLWpnbnJyc1PZHlfupfb/a5OfPn7UArNVq1dZZNZlMlGVZ7T7WarUUhmGt3Lbs+sA6m+oVTfvU7XbvvU/AS/ZsgYXrunaSZHX1NrXm2969e2cn6devX3ZSzaZlLi8vG1uQ1u1vld3lW3VxcaGDg4NampatGLYPHz7YSWXF3Fyoqtsx56o60c8OWK6vr5Vl2cpyWZbVzlfT/mi5/TzPlWWZPn36ZGdLy3MXx3Ft/WY//vz5YxcHgDdvmwnaFxcXOjo6spP14cOHlfvkpvvHXTTd87Iss5PWMveLz58/21lyXVeXl5d28lpfvnwp7y23jWK4urpqbAjcJoBrsu6eaNtUr3jofQJesmcLLGxmDGO1y7Tpi/gU7vNl73Q6arfb5b6bruOqpgv+fVW3Y16bumllddVWX9u0xlQ1XUCNMAxX1l8UxdrWJQB4qw4ODu7cC/AWtVotFZUhxs4tQ6magqLn9hL3CXgMLyawuLy8XOky3TT+87Gsa0m57eKfpmmtK9S+6Pm+39gdbbc23eb9+/dSw/pv8+HDhzu1NjVxXXfjUDPXde+8XwDwVn3+/FlZlq3Mk7AdHh423j9+/fr1bA1wauhtqfZ+b7pf5Hle68G3703r7iPdblfFstHx27dvdra0bBhsul833dc37f9Duss+AX+7FxNYyPqSjUajlYvNU/jy5UvjZOlt9qU6H8Se5HZ0dFSbRKfKZOq7MPMp7OFa5mkV65gxn/Y27fe3OT4+Vq/XW3kKlSrzKewnbdx1GwDwFriuW070ta+beZ6X95GvX78qjuNamfl8ruFwqJOTk8pSt2saPnUf5p5m7jt5nq9MRj49PW28X6RpWvaUmzl59j23yr6HLBaLtSMLTLBWXYfZZtU2+/9Qtt0n4DV4MYHFdDpVunwEnpmf8BwtMa1WS7PZTMPhsNyX/f39WydZ2cvYF/tut1veQKpl7nOM0+m09tg6c75u62pdLBZaLBa15ZrmfWwyGAxq3dGO45StPq7rKls+zau6DftcAAD+wbTC29dNz/P05csXac21td1uK8uyOw8zNY1MTsMjZO/CTD426zo8PFSSJCtl7PvF2dmZCmuo8G33T9d1a+fm8PBw7RBec66q8/20nNRetc3+P5Rt9wl4DZzC/oajUafTkcsPFgEAgAdgRhrYP44I/M1eTI/FS5emqfb39+1kAACAO1v3tEjgb0ZgYZnP543jOz3Pq/0+AwAAwG3yPF+ZJ2Lmbq4b0gX8rRgK1cCMfzSCIKCrEgAA3Ivv+7WHwHie9yxPvgQeG4EFAAAAgJ0xFAoAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwAIAAADAzggsnkGn01n5rYynlOe5HMdRnud2FgAAfz3HcTQajexkAI/szQQWpjI9mUzsLDyCTqcj3/ftZADAE3EcR/P53E4GgEfzZgKLfr+vKIr49ex76nQ6d2r9MT8oeJdlAADPazKZ/HWNQk0BVFEU/Ko18AzeRGAxn8+VpikXmSd2enqqs7MzOxkAAACv0JsILK6vrxWGYS1tMpnIcZzy1el0avm+72s0Gmk0GtXKVecljEYj+b5fDrMyr/u00tvbsfdHywCpWsa0LN02vMte958/f+wi6nQ6K+tWZQhZmqYaDodyHKecH2Lvj93K1e12lWXZSksSAODpmWt79Xpfne/X6XTU6/WUZVmZb9j3uepyJq96T/j//r//b+WeoIY5hvb9qXq/6Pf76nQ6K/drw6RLUrvdlrM8vur+VPm+X1uPfe809/1+v1+WaboXA9igeAOCICiSJFlJq/I8r4iiqPZeUi0tDMOiesqiKCokFZ7nlWmz2ayQtLK9qiAIijAMy/f2ek2ZpvXOZrNamdu2ZfaxyhxblmVFURRFlmW1/THbMvnFclvVc1Es99suU12PSbOXAwA8PvueIamWlmXZyj0kSZLavadYc0+o3jPNeqr3GpNWXcZOC8Owdi+2t2PujdX7ShAEK/dv+zjNduxjr67HlGm671fPh10GwGZvosdisVjo/fv3tTQzB8A4Pj7W5eVlLS0Mw9rwqfF4LC1bSaoWi0X5/1arpTAMdX5+XiuzTp7niuNYs9mslj6dTmut/aenpwrDUK1Wq1bmNsPhUEmS1NLsfXNdtzw2LY/B8zzd3NzUytnG47Fc1y3fHx0d6eLiolbGdV39/PmzlgYAeB5RFJX3Edd1FYahrq6u7GI1p6enSpKkdr1vGupavde4rqsgCPTjx48y7cePHwqCQK7rlve+6n2s1WqtLON5Xu3+dHJyojRNy/fbGI1GK+txXVdJkqwcQxiGtbmYURSt1A0ArPcmAossy/Tu3Ts7udYdPBwO7Wzt7e3ZSQqCQL9+/Srfe55Xy5ek/f39WrCxyc3NjTzPqwUMhud5ur6+liSlaar9/X27SOP2DROUfPz4sZbedC7sbu4sy+wijapdxr1ez87W3t4ej7UFgBfiw4cPdtKt1+g0TdXr9Wr3CDNkqspuwDs6OqpV3M/OznR0dCQt731aDs+qvtI0rTVGNQ2n0hb7XHV5eanj42M7We/fv1eWZbV1Nd33t72fA3gjgYXNjAM9ODhQURQqikJRFNnFXhz7or2taitTk36/L8/zlGVZeT42BSyqBCL6R9+3iqJY6RkBALwOSZKU1/rqaxMzzy7Pc83nc2VZtvJkRnt9RVHUehYA/F3eRGDheV5twvL19bWCIKgNc2oartOUlqapPn36VL63W2wk6erqSoeHh3Zyo48fP660mBhZlpXbqvZeGHmeN27fMD0T9gQ2e4jTxcXFSjf3pvWq0tNSvQFUe3KMnz9/3hrYAABeLs/zGq/v2wjDUD9+/ND19XWtAc80lDXd+x7awcFB43Cm379/y/M87lHAA3oTgYXv+/r9+3ctrTpGcz6fK47jWr4kxXFcq5R3Op3GYUvVJ1xMJhPFcawvX77UyqxjxrjaPQSdTkdBEJTbOj4+1nA4rO3PbcGLGePabrfLtDzPG4csVcfYNv0quOu6KxfmakCU53njcLI8zxu7lgEAL0/T8KDT09OV+898Pt/qCYhfvnzR2dmZzs7O9Pnz5zLdzKew72P9fv/OwUZTw1vVYDBQmqYrT7Lq9Xo6PT2tlQWwmzcRWBwcHNQqzoPBQEEQlGM6T09PG4dCRVGk09PTspwaxlp6nqf9/f2Vcad28LHJeDxWGIa1caau69YmtQ0GA0VRVD5Sz3EcXVxcrAQktul0WjvWw8PDld6Ii4sLxXFcltnf319Z79evX5WmqZzlYwa73W4ZEJn1Ng2Fsnt4AAAvl6nwm2u7lkOakiSp3X/a7fZWvw1l7oW+76/0DEyn05VHwGqL4bs2E/g4DY+QNYqiqN3nPM/TbDZbGZoFYDdOcdsgyVdgPp+r3W7fOh60yvd9HR8fb7xwjkYjnZ2drQQbT8lxHCVJ8iIvjpPJRL1e707nHQAAAH+nN9FjYVpgtum2/Zuse+rTS3FyctLYEwQAAIDX500EFloONxoOh2u7SV+60Wi0su/tdlthGN652/gpmF8r3dTjAwAAgNfjzQQWruuqKIoXOWRoG58+fVp5jngURS/2sXzT6fRZh4gBAADgab2JORYAAAAAHteb6bEAAAAA8HgILAAAAADsjMACAAAAwM4ILAAAAADsjMACAAAAwM4ILP5y8/m89gha+2V+T6Lf75f/t41Go1reZDJZWY/jOCu/o9HE3p9tlgEAvA2+78v3fTtZeZ7LcZxX90O2wFtDYPGXa7VaKopi5WV+8Xo6ndqLbMXzvJV13vYbIPP5XO12W0mSqCgKzWYz9Xo9ggsAgCRpsVgoy7KVAKLf7ysMQ35UFfjLEVi8QvP5XMPhULPZzM56VNfX1wqCoAxAWq2WwjDU1dWVXRQA8EYlSaLhcKg8z6VlL3mapi/2B18BbI/A4hU6OjpSGIZqtVp2FgAAz6rb7SoIAn379k2S1Ov1lCSJXQzAX4jA4pXp9/vKsuxZWn4Gg4HSNC2HPs3nc8VxrK9fv9pFAQBv2Hg8VhzH8n2/1tMN4O9GYPGKmIr8QwyByrJsZfL2NrIsU6/Xk+M4arfbms1mcl3XLgYAeMNc11UYhs/WEAbgcRBYvCIPOQSqafK2YQcc8/lcWj5dyl7u6OhI/X6/smYAwFtnGsKCIOAeAbwiBBavhLkwr2v52dvbs5PuzQ44TCAzHA5Xxsmen58rjuNykh4AAO12W1EUaTqd1obQAvi7EVi8Aqbl5/z83M4qffjwQWma2smSpMvLSx0cHNjJ9/L+/fva+3fv3tXeAwDetn6/L8/zykfLRlGkXq9HAxTwCjhFdYwL/kqO4yiKoluf/21+lGixWJRpo9FIw+GwNtRpMpno5OSkVm4b/X5fcRzX1mV+DOm+v6cBAHg9zO8dzWaz2rBd7hXA60CPxV/ODIEaDocrcx+cyi9vaxlQ+L5fyz87O6sFArsYj8cKw7C2fm4UAABVgoqmuYDn5+dK05T5FsBfjh4LAAAAADujxwIAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwAIAAADAzggsAAAAAOyMwGL5a6CO49jJAAAAALb06gILEySMRiM7CwAAPCPf9+X7vp2sPM+5d+PJ9ft9OY6jPM/tLPm+r06nYyfjFk5RFIWd+Dfr9/vK81yLxUKLxcLObjSfz9Vut/XKTsWTGI1Gury81HQ6tbMAAFjhOI6iKNJgMCjTOp2OXNfVeDyulQUemwkeqvWY0Wiks7OzreuR+H9eXY9FHMflhWk+n9vZAADgGSVJouFwWLYSTyYTpWlKUIFnMR6PlaapJpOJtOw9Gw6HOj8/t4tiC68qsJhMJgqCQK7r6vDwUKenp3YRqdL1ZV5Vo9FoJU3LZapdYqaceVWDmNFoJN/3NZlM5DhOuZx5b152l2+n01m7X01M17F59fv9Wrr5khhmmJi5mK9bvpo3n8/l+37jPvu+r+FwqDRN5ThOrXu7ut6mbm8AwNvU7XYVBIG+ffsmSer1ekqSxC4GPAnXdRVFkU5OTqRlfS8MQ7VaLbsotlG8IkEQFFEUFUVRFLPZrJBUZFlWKxOGYeF5Xi1NUlE9FZKK2Wy2UsakhWFYBEFQ5tnbiqKokFSEYbi2jClneJ5Xex9F0cp+VjWtr7qOMAxr27fTbls+y7LyvJgyZpnquYmiqHYuijXHAgCAYe4xnuet3EOA5+B5XuF5Xq0+iLt7NWfPXKTWVZSrZeygIUmS2gfJrpQnSVJW8s06bNWgxgQWVdV12JIkabywNu2rEQRBkSRJLa26DRMEVFXXd9vy5jjtMtXjLNYEFpv2GwCAYnmvte/bwHMxdUG73oO7eTVDoX78+FEOgzKOj491dnZWvr+5uZGkle6t9+/f195/+fJFcRyX78/Pz3V8fCxV1lEd6uM4jtI01c+fP8tlPM8r/69l12+WZSvDiSTp6uqqHE5UfUnS79+/a2WNNE3V6/Vq5Xu9nrIsk5bH6HleORxqMpnI87zy2G9b3rDPjaTacTYJw1DtdpshUACARvP5XHEcKwiC2jBc4Ln0ej0FQaBer2dn4Q5eTWBRHetvXsPhUFmW1eY/2BX+JqZSPp/Plee50jTV58+fa2WWvT21120Tz4qiUJZlGg6Hcqw5EEEQrKyvKAp1u93aOqqSJFkp/48Og384Pj7W1dWVZAVHxm3L39d4PFZRFOXcDB7XBgCoarfbiqJI0+m0NnEWeA6dTkdBEGg6nRLs7uhVBBbmgmRXkIuiUBAE+v79u7Rsfc+ybOV5xdfX17X3WlbKv3//rpubG4VhWPaEmBZ8ex3bcl1XRVHUJgrt7e3d+ZFmnufp169fdnLN58+fy56XNE1rj/bbZvldTadTZVmmNE15QhcAQFpOjvU8r7wnRVGkXq937/sqsAv7qWQnJyeK45hg977ssVF/oyAIViYqG/b8CTM5xzBzEexTYeYYBEGwMl8gCIKV+RJhGNYmb9v5URTV1mNPAJc12btYbmcdc1zVdc5ms5WJ0kEQNJ6f25ZfNx/FXpd9frMsu3XSOgDgbWp6CEixvDdvuucBj0XSSt3JzP/B3f31Z81cpDZNtrE/NGbWfzVwaPoANQUQRhAE5TrsoKApsDAVcPOy84vlflZfm46paFhn0zE0BRB2XtPy2wYWReV8mmOy12mvAwDw9ph7rX0PuS0PeCzVuottUx7We3W/vA0AAADg6b2KORYAAAAAnheBBQAAAICdEVgAAAAA2NnGORbmR9oAAAAAoIkJJ+ixAAAAALCzjT0WAAAAALANeiwAAAAA7IzAAgAAAMDOCCwAAAAA7IzAAgAAAMDOCCwAAAAA7OxBAotOpyPHcdTpdFbSHMfRaDSqldfyNzJMXp7n5ft1L7Pu6nqb8ufz+UqeeU0mk3L7vu+X6bbq/ty2f2ad/X6/TOv3+/Yqy+2ZPHs99sv3famyXvO+qulYq38DYzQabcxv+vsBALb3r//6rzo/P7eTgUfzz//8z/r586edDDyrBwksbjMcDpXnuZ385Hq9XhnknJ6elunz+bxSSvrx40f5/8+fP9fythHH8co6H1qn01G73baTlaapHMdZu/00TWsBFgDg/v71X/9V//k//2f95//8n/W///f/trOBR/M//+f/1H/4D/9B/+W//BcCDLwYTxJYaNnyvo7ruiqKonwZYRiWadPptLaM53m1Zex8SUqSREVRKMuyMu3s7EyS9PHjxzLt+vq6/L8kXV5eSpKCIJDrurW8KIpq2+12u7V84+joyE6qqa7D8zxpuT2Ttlgs7EVKo9FIaZpK1jmqHmdT0GH0ej07CQBwB9WA4l//9V/tbODJ/PM//zMBBl6MRw8sgiCQnrml3HXdsvJeTTP7ZoINLYdBmUr7bcFBE8/z5HmesixrHAL2EIbDobQ8t+PxuEx3XVdJkpTvm863OeZNgZ4qQ7XW9XwAwFtEQIGXigADL8GjBxZa9hzogVvKsyyrzS3YVImfz+dla/7x8XGZbgKHLMvKoVo3NzdlflNvxHA4rG23aYiXGWf7GEPAqhX9g4ODWp6snpirq6tanqQyENk0XKsakHz//r2WBwBv0TYBxfn5+cq8N168Huv1b//2b/ZHUCLAwDN79MBisVio2+2WLeVPOUG41+vJcZxyWFAQBBoMBmV+NXAw8ypMUGD2966yLFOr1VIYhpKkw8NDu8iD+fDhg520MnSrSRRF0obhUtXz8uXLl1oeALxF//f//l8qafhr/Lt/9+/0b//2b/q///f/2lnAo3r0wMIwLeUPNSTKnmNRDRiaeJ7XOA/DBABmXsVtw6DsORbrKvLmeB9zSNSvX7/spK16SAaDQTk0bN2QKHN8rVbLzgKAN+ef/umf9H/+z//R//pf/0t7e3t2trS8b1TvD7x4PebrP/7H/2h/BPXv/t2/03/6T/9J//Iv/6J/+Zd/aSwDPKYnCyxc1y1byh9ySNQmZvK2lhX8pke27u/vSw0BT9MwqLsyQ8CGw2FtYvUuqhV9EwxVVYdymWNrYnpm4jgugykAwGbbBBjAUyOgwEvxZIGFli3l9x1itAtTwW/qPagGECcnJ1KlF2NX3W73wdZVZdaZpmmtx2E+n5dBm+d5G4OjVqtVBnpNzBjOdfMwAOAtI8DAS0BAgZfmSQMLVYYI7cqevO00/NCdUa3gD4fDlcqyyTO9CpvmFdiTt9cNJTIe6nirxuNxOZQpjuNyX6pzJi4uLipLNKsOiaqq9tzYj+IFAPw/1QDj3//7f29nA4+GgAIv0ZMHFtUhUU+pWsFvt9u1uQjVQMLzvAefV1B9BOxDWSwWjes1v2uxbu6HremXYqs9HZ8+farlAQBW/dM//ZP+23/7b3Yy8Gj+x//4HwQUeHGcwkxCAAAAAIB7evIeCwAAAACvD4EFAAAAgJ0RWAAAAADYGYEFAAAAgJ0RWAAAAADYGYEFAAAAgJ0RWAAAAADYGYEFAAAAgJ0RWAAAAADYGYEFAADYWb/fV6fTsZMBvCF/fWAxGo3kOM7a12QyqZWfz+dyHEej0aiWbvi+vzav0+mszXtITcfUtN1+v79SbjKZNC5vl9mkur1+v69+v28XkZbnyl63KdvpdOT7vr0IAOARmHvbfD63s9Tv9xuvx2aZPM/trBfF7OdzyPO8do8jcAI2++sDi8FgoKIoVBSFZrOZJCnLsjKt2+3Wyn///l1BEOjs7KyW/hKYC9jl5WW5/0VRKMsy/fz5syxXvchWy81mM/369evO56Sq3+8rDEMNBgM7qzSZTOQ4jk5PT1f209ygptOptAySAACPq9VqyfM8ff/+3c5SHMe167Px/ft3eZ4n13Vr6S+Fude02207a611wdV9TCYTeZ5Xu3+aexuAZn99YHFXcRxrPB5Lywr6S3J4eKgoilYuXK7rlvssSe12W0mS1NK0vLFsCghuk+e54jjW169f7azSfD5Xr9dTlmUrAYrrurV9Pz09fZEBHAC8RoeHh7q4uKilmfuc53m6ubmp5V1cXOj4+LiW9pL0ej0lSaIkSeysJ9Hr9TSbzV5s4AW8RG8qsJhMJgqCQK7r6vDwUKenp3aRB9XpdLYOXszwpNsCg9FopCAIVir1D+Hm5qY8P+ucnp4qiqKNZYxut6ssy7Y+BwCA+/vy5ctKz8T19bXCMNTh4aHOz8/L9DzPlWWZPn36VKZp2eK/adiPPQTX7gWpMj0OZj13HVZ0Ww97ldmWlo1vjjXst9Pp1LZ9W2+66a1otVp2FoAN3lRgcX5+roODA2l5AU7TdONF8SldXV3p8PDQTl5xeXlZHsNDu7q6unXdaZqu3Ig2CYJA19fXdjIA4IGZSnC1Z+Ls7Ez7+/vlPc8wZcwyptI/m83KYT9aBhKGCQRMfpIk8jyvzK8yvdtJkpQ92Z7nKUmScvnb7jd30e12y302x2CCEjO/pDp0dzgcrp0/qMo92Q6kAGz2ZgKLPM+Vpqk+f/4sVcaj/vjxwy76LPI8197enp28YrFY6MOHD3byg8jzfOO6TRD27t27Wro9ibvKdd3a/BAAwOMJw7DsmTC9Eh8/fiwDCNODfHV1pTAMy+W+ffumKIpqLfQnJyeK47hcbrFY1IbgdrtdeZ638kCQPM/LIbumcm/uHx8/fizL3dZD/xAmk4myLFsZYjybzcpja2KGBu/t7ZXBSBiGjZPgAfw/byaw+PHjx8own+Pj4wefA1CtZKdpWnbJ2t2yTbatgP/69ctOehCLxULv37+3k1f8+fOn9n6xWJStV7a9vb0X0ysEAK/d/v5+2TNh3/eqPcgXFxfa398vl7u4uNBwOKw1EplJ03me6/r6WlmW1fIdx1GWZbV70mKxKHsmqsOYXNdVEATyPO/WIVAPyQ6gDNNAtmmobhAEteDn69evDO8FbvFmAovhcKg0TWsXxOFwuHKR2LU1wlSyi6JQEAS1buVNY0UPDg5WJt01OTw81OXlpZ38JFzXled5DG0CgBfK9AjM5/OVobMHBwc6OzvTfD4vezKqoiiqDRcyLxOYeJ63klcUxUrPg+d5tfkcxnQ6VVEUWiwWciqPJ3+JXNddmUto3v/+/buWDuD/eROBhekpsC+GxbLyX308n+u6ayvud51fcBefP39WlmW39mqYcbKP0WLi+/6tF8zj42MNh0M7ea2fP3+uXJwBAI/D9AxcX1+v3LPMfcY8dr16bfZ9f2Ov+YcPH5RlmZ28wvd9LRYLpWm6NnBYLBblUKTH7tHe399vbLQzPe/rJmc3LWf2dZuefeCtehOBxfn5eWNXqCQdHR3Vxll+/fq18YLY6XQUBMHai9CuXNdVkiTq9XorT6vI87zcn1arpSiK1G63V4KQ+Xy+suxduK576zCrwWCgMAzl3PI0EGPbuSMAgIdxcHCg4XC48lQj0+t8cXGxMnHazKeo3leq9x4zn8IexmS/N7IsUxzH5fL2/ck0Yj10w5Pdq25GCtj72W63FUVRLa3KPNWwus/9fv9R6wHAq1C8IrPZrJBUZFm2kpYkSa1slaQiiqKVtOorDMNa/mOyty2pmM1mtTJZlq2UsY+9WHNO1kmSpAiCoJYWhmHjsZv12i97P5vSAACPx9wfmq7dYRiuvS43Xdfte4fnebX86r0zDMPaPaS6vqZ7lr3udZIkKbRldcWUlXXft/d7U52gqrqMfX8EsMop/vHFAZTnefkrow/RijSZTNTr9cRHDAAA4PUjsECN6ba2f9X7Pnzf1/Hx8crEPgAAALw+BBZY4TiOoijaKSDodDpaLBZaLBZ2FgAAAF4hAgsAAAAAO3sTT4UCAAAA8LgILAAAAADsjMACAAAAwM4ILAAAAADsjMACAAAAwM4ILAAAwM76/b46nY6dDOANIbB4IpPJRI7jrH2NRiN7ETmOs/Yi3el0yh+zs/X7/bV5Vf1+X77v28nqdDor+zefz+1i8n1/pZzZbqfTaVw3AODhzefztdfqddd6s0ye53bWi2L28znkeV67x627JwP4BwKLJ9LtdlUUhYqiUJZlkqTZbFam2T9GN5lMFASB0jR9lIv+fD5XHMe1H7Azwc/BwUG5X0VRKEkS/f79e6Xc6elprVyWZeW+TqdTSWoMmAAAD6vVasnzPH3//t3OUhzHteuz8f37d3meJ9d1a+kvhbnXtNttO2utdcHVfUwmE3mepyzLyvucubcBaEZg8UKdn5/r6OhIYRjqx48fdvbOTk9PFUVR+T7Pc/V6Pc1ms5Ugp9vtqtvtSsuApNfrKcuyMs1wXbd20T09PdXZ2VmtDADgcRweHuri4qKWZirZnufp5uamlndxcaHj4+Na2kvS6/WUJImSJLGznoS5J77UwAt4iQgsXqA8z5Wmqbrdrvb39zUcDu0iO0vTVJ8/fy7ff/v2TWEYqtVq1crZTECyzYW22+0qy7IHaz0CAKz35cuXlZ6J6+trhWGow8NDnZ+fl+l5nivLMn369KlM07LFf9Own36/Xytj94JUmR4Hs567DisqimKlAWsdsy1JarfbchxHk8mkzLeH+N7Wm256K267JwKoI7B4gX78+KEgCKRl5VzLi9xDmc/nK93fFxcX2t/fr5Vrkqbpyo1okyAIdH19bScDAB6YqQRXeybOzs60v7+vL1++KE3TMt2UMcuYSn91iK6WgYRhAoHqMFnP88r8KtO7nSRJ2ZPteZ6SJCmXPzg4sBe7NzPcWJVhxub+aeaXVIfuDofDjXMRr66udHh4uBJIAdiMwOIFOjs709HRUfk+DMNaS9Oufv/+vTKRL8syvX//vpZmMy1T7969q6Xbk7irXNfVz58/a2kAgMdRvV+YXomPHz+WAYTpQb66ulIYhuVy3759UxRFtRb6k5MTxXFcLrdYLDQej8v8brcrz/NWGr7yPFe73VaSJGXl3tw/Pn78WJazh90+hslkoizLVuZGzGaz8tia5HmuOI61t7dXBiNhGK7cOwHUEVi8MPP5fGX+gmlp2tTlfBe/fv1qHMpUnaC9yZ8/f2rvF4tF2Xpl29vbe7D9BgBstr+/X/ZMmN5vc72v9iDbvdQXFxcaDoe1RiIzaTrPc11fXyvLslq+4zjKsky/fv0q17NYLMqeiep9zHVdBUEgz/NuHQL1kOwAyjANZJuG6gZBUAt+vn79yvBe4BYEFi/M6empZI1zNRf36iTupsBgF0EQ6Orqyk6ucV1XnucxtAkAXijTIzCfz3V5eVkbbnRwcKCzs7OyAavaeyBJURTVhguZl7nfeJ63klc0PNXQ87zGXvbpdKqiKLRYLORUHk/+Ermuu3KfNe+3bYQD3iICixfETNqujnE1ryiKak9Y2tvbW3n6h2G3RNk+fPiw0otwdHSkOI5X0m3Hx8d3mkz+8+fPlYszAOBxmJ6B6+vrlTlxnz9/VpZl+v79e60nQ8shrZuGrX748EHZ8lHpm/i+r8VioTRN1wYOi8WiHIp02z1nV/v7+433StPzvm5ydtNyZl9vGzYMvGUEFi/Ijx8/1j6FwtwQTBfsYDBQlmUrXcrmQr7pSRrv37+v/X6FluXDMJTneSvdvJPJpBxDOxgMFIahnFueBmLkea69vT07GQDwSA4ODjQcDlfuJ6bX+eLiYmXitJlPUZ0vked57Z7SNIzJfm9kWaY4jsvl5/N57UlMptX/oRue7F51cy+097PdbtceuW4zTzWs7nO/31cQBI33aABLBZ5clmWFpGI2m9XSJRVhGNbSqoIgKIIgqKV5nldIKl92/jqSiizL7ORiNpvV1mdetnXlmo7JTgMAPB5zj2m6n4Rh+P9v5w5uJQLiOACPXrTh4jQtaEBCJyoZNTgrQy/e4YV41somdpPN833HGSZzYP5+MTxdl4/W9X2d2NecruvWvqZp/tSg7XjLnM7GfialNIeDOnRkOTaEMKeU1vb9vLd9Z7bnvFpf4c6y+ffG4WZijKEsy4e9se/U932oqiq4xAAA/j/B4qbGcQxFUXz0oT/P81DX9UfDCwAA30GwuLG2bcMwDA/fW7xDjDFM0/SRsQEA+D6CBQAAcJm/QgEAAJedvrHIsmzfBAAAsFrixGmwAAAAeIWtUAAAwGWCBQAAcNkPPLPSZnEknY0AAAAASUVORK5CYII=\" width=\"695\" height=\"622\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNote\u003c/strong\u003e. V0, baseline visit; V1, end-of-intervention visit; V2, end-of-study visit; HAMD-21, 21-item Hamilton Depression Rating Scale; BDI-II, Beck Depression Inventory-II; WHO-5, 5-item World Health Organization Well-Being Index; PTQ, Perseverative Thinking Questionnaire; RRQ, Rumination-Reflection Questionnaire; BE, General Treatment Expectation; LFPD, Lübeck Preoperative Thinking Questionnaire; ZUF-8, Client Satisfaction Questionnaire; TAU, treatment as usual; CCT, cognitive control training; IG, intervention group; CG, control group.\u003c/p\u003e\n\u003ch2\u003eSample size\u003c/h2\u003e\n\u003cp\u003eThe sample size was calculated using G*Power (version 3.1.9.7) based on the primary outcome: depressive symptom severity, measured by the HAMD-21 at four weeks post-intervention. Assuming an effect size of \u003cem\u003ed\u003c/em\u003e = 0.7, derived from a previous pilot study of the\u0026nbsp;\u003cem\u003ede:)press\u003csup\u003e®\u003c/sup\u003e\u003c/em\u003e intervention in outpatients (6), a two-tailed independent samples \u003cem\u003et\u003c/em\u003e-test with 90% power and a significance level of α = 0.05 yielded a required sample size of 44 participants per group. Accounting for an estimated 20% dropout rate, a total of 106 participants will be recruited from the specialized inpatient units for affective disorders at the participating university hospitals.\u003c/p\u003e\n\u003ch2\u003eRecruitment\u003c/h2\u003e\n\u003cp\u003eParticipants will be consecutively approached by staff during their inpatient stay at the participating study sites and are provided with information on the study if interested. Eligible newly admitted patients will be invited to participate, subject to the availability of compatible (personal or provided) mobile devices. Recruitment will be supported through close coordination with clinical teams and ongoing monitoring of enrolment to ensure timely achievement of the target sample size.\u003c/p\u003e\n\u003ch2\u003eRandomization\u003c/h2\u003e\n\u003cp\u003eStratified randomization is used to ensure balanced allocation across key demographic variables. Participants are stratified by gender (female, male, diverse; 45%, 45%, 10%) and age group (18–29, 30–49, 50–69, ≥70 years; 30%, 30%, 30%, 10%), resulting in 12 strata. To simulate the expected sample distribution, oversampled randomization matrices (n = 500 each) are created using MATLAB (2023b). Within each stratum, participants are randomly assigned (1:1 ratio) to the intervention or control group using SPSS (version 29, IBM) with a uniform random function (RV.UNIFORM(0,1)); values \u0026lt; 0.5 are assigned to the intervention group, values ≥ 0.5 to the control group.\u003c/p\u003e\n\u003cp\u003eThe allocation sequence is embedded in the REDCap database (Research Electronic Data Capture) and automatically triggered upon entry of stratification variables. Allocation concealment is maintained by restricting access to group assignments within the system. Study personnel involved in generating the randomization syntax are not involved in outcome assessments and remained blinded to group assignments. Participants are enrolled and stratification variables entered by trained study staff. Group allocation is disclosed only to the intervention team after eligibility was confirmed.\u003c/p\u003e\n\u003ch2\u003eBlinding\u003c/h2\u003e\n\u003cp\u003eDue to the nature of the intervention, double-blinding is not feasible. Participants are aware of their group allocation. However, outcome assessors and data analysts responsible for evaluating the primary endpoint remain blinded to group assignment. To maintain blinding, both participants and unblinded study personnel are instructed not to share any information regarding group allocation with the blinded assessors.\u003c/p\u003e\n\u003cp\u003eUnblinding of outcome assessors will occur only after completion of all primary endpoint analyses. Premature unblinding is not planned, as no study procedures or safety monitoring require knowledge of group allocation. Should unblinding become necessary in exceptional cases (e.g., for clinical or organizational reasons), it will be documented and justified in the trial records.\u003c/p\u003e\n\u003ch2\u003eData collection, management, and analysis\u003c/h2\u003e\n\u003cp\u003eThe above-mentioned outcomes will be assessed using standardized clinician-administered and self-report measures, as well as an app-based neuropsychological test battery, all completed on a mobile device. Data will be collected on-site at three predefined study visits (screening/baseline, end of intervention, and end of study) for both groups. To promote retention, study visits will be scheduled during the inpatient stay whenever possible.\u0026nbsp;After discharge, participants will be contacted in advance and offered flexible scheduling for the follow-up visit. Brief, user-friendly data collection procedures and technical support will be provided as needed. Participants who discontinue or deviate from the intervention will be encouraged to complete outcome assessments; remote completion will be offered if on-site visits are not feasible.\u003c/p\u003e\n\u003cp\u003eAll personal and study-related data will be collected and stored in accordance with applicable data protection regulations. Participants will be assigned unique study IDs, with identifying information kept separate from study data. Data will be entered directly into REDCap on a mobile device, which applies range checks and validation rules to ensure data quality. REDCap also maintains a comprehensive audit trail, recording all changes to data entries, including creation, updates, or deletions. Access to the study database is restricted to authorized personnel, and data will be securely stored on institutional servers. Relevant study documents will be retained at each study site for at least 10 years after regular or early study termination and, after the archival period, stored in anonymized form. Any dissemination of results will use anonymized or aggregated data to maintain confidentiality. In case of technical difficulties, the assessments will be provided on paper and later transferred to REDCap.\u003c/p\u003e\n\u003cp\u003eAn intention-to-treat (ITT) analysis will be conducted within the full analysis set of all randomized participants with at least one completed intervention. Missing HAMD-21 scores at the follow-up visit four weeks post-intervention will be imputed using multiple imputation. The primary outcome will be analyzed using an Analysis of Covariance (ANCOVA) with study arm as the main factor and baseline score as a covariate. Secondary outcomes will be analyzed similarly, using baseline-adjusted ANCOVAs, logistic regression for categorical variables, or proportional odds models for ordinal variables. Longitudinal trajectories will be evaluated using mixed models and illustrated with line graphs. Descriptive statistics will include means, standard deviations, ranges, medians, quartiles, and absolute and relative frequencies, with two-sided 95% confidence intervals. The number of completed training sessions will be analyzed using a Poisson regression model. Adverse events will be summarized in frequency tables and compared between groups using chi-square tests. Exploratory analyses will examine potential effects of additional therapies and BE.\u003c/p\u003e\n\u003ch2\u003eMonitoring\u003c/h2\u003e\n\u003cp\u003eGiven the low-risk nature of the intervention and the close clinical monitoring inherent to the inpatient setting, no independent Data Monitoring Committee has been established. No interim analyses are planned. Individual participants may withdraw from the study at any time at their own request. Criteria for early termination of the entire study include insufficient recruitment, the emergence of unacceptable risks based on a risk–benefit assessment, or new scientific evidence contradicting continuation. The principal investigator will make decisions regarding study termination.\u003c/p\u003e\n\u003ch2\u003eDissemination plans\u003c/h2\u003e\n\u003cp\u003eThe results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals, Guideline groups, and to the public via media communications, social networks, presentations at science festivals, charities, family and patient support groups, and clinics.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis randomized controlled trial (RCT) will investigate the feasibility, acceptability, and efficacy of \u003cem\u003ede:)press\u0026reg;\u003c/em\u003e, an app-based CCT, as an adjunct to specialized inpatient treatment for unipolar depression. The intervention aims to enhance cognitive control and reduce repetitive negative thought patterns - mechanisms implicated in depressive symptom persistence and relapse (\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Outcomes will be compared between CCT plus TAU and TAU alone, with assessments at the end of treatment and four weeks post-intervention.\u003c/p\u003e \u003cp\u003eCCT is a computerized cognitive remediation approach that has shown promising effects in remitted depression, particularly on residual symptoms and cognitive control, although findings vary between studies (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Evidence for its use in inpatient settings remains scarce (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). The present trial addresses this gap by integrating a standardized CCT protocol via \u003cem\u003ede:)press\u0026reg;\u003c/em\u003e into daily clinical care. \u003cem\u003ede:)press\u0026reg;\u003c/em\u003e is a gamified adaptation of the aPASAT, designed to increase engagement and adherence while preserving the core cognitive training mechanisms. This combination of evidence-based task structure and game elements aims to bridge the gap between experimental findings and scalable real-world applications.\u003c/p\u003e \u003cp\u003eIn Germany, several approved Digital Health Applications (DiGAs) for unipolar depression are listed in the official DiGA directory maintained by the German Federal Institute for Drugs and Medical Devices (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e), but most are grounded in cognitive behavioral therapy and focus on psychoeducation or behavioral activation. Digital interventions specifically designed to remediate cognitive deficits in depression are rare. By targeting cognitive control during acute treatment, this study explores a complementary therapeutic pathway that may improve not only mood but also cognitive functioning and daily life outcomes\u0026mdash;domains often still impaired after symptom reduction.\u003c/p\u003e \u003cp\u003eIn addition to changes in depressive symptoms, the study will examine whether improvements in cognitive performance and rumination can serve as potential mediators of treatment response. Investigating individual differences\u0026mdash;such as age, gender, medication, comorbid disorders, pre-existing cognitive distortions, use of neurostimulation, and severity or tendency to relapse\u0026mdash;may help identify subgroups most likely to benefit, thus enabling a more individualized application of CCT in clinical practice.\u003c/p\u003e \u003cp\u003eFrom a healthcare perspective, CCT offers potential cost benefits: it is inexpensive to implement, can be standardized and digitally monitored, and could reduce the need for more resource-intensive in-person interventions. Patients\u0026rsquo; increasing familiarity with digital tools, accelerated by the COVID-19 pandemic, could further facilitate its adoption.\u003c/p\u003e \u003cp\u003eDespite these strengths, some limitations should be noted. Conducting the trial in inpatient units may limit generalizability to outpatient populations. Adherence could be influenced by symptom severity, hospitalization length, and digital literacy. Furthermore, the trial focuses on short-term outcomes; long-term maintenance of benefits remains to be examined.\u003c/p\u003e \u003cp\u003eIn conclusion, this study will provide important insights into the feasibility and potential effectiveness of app-based CCT as an adjunct to inpatient depression treatment. If positive, the findings could support future large-scale implementation studies and inform clinical guidelines, ultimately contributing to more comprehensive recovery strategies in depression care.\u003c/p\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eTrial status\u003c/h2\u003e \u003cp\u003eThe trial is currently recruiting. Recruitment started in July 2025 and will last until the end of April 2026.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eAEs\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eAdverse effects\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eANCOVA\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eAnalysis of Covariance\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eaPASAT\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eadaptive Paced Auditory Serial Addition Task\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eBDI-II\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eBeck Depression Inventory-II\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eBE\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eGeneral Treatment Expectation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eCC\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eCognitive control\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eCCT\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eCognitive control training\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eFMP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eQuestionnaire for Measuring Therapy Motivation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eHAMD-21\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003e21-item Hamilton Depression Rating Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eIMI\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eInternet- and mobile-based intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eISI\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eInterstimulus interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eITT\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eIntention-to-treat\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eLFPD\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eL\u0026uuml;beck Preoperative Thinking Questionnaire\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMD\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eMajor depression\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePTQ\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003ePerseverative Thinking Questionnaire\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eRCT\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eRandomized controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eRRQ\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eRumination-Reflection Questionnaire\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eTAU\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eTreatment as usual\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eWHO-5\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003e5-item Well-Being Index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8462%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eZUF-8\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78.1538%;\"\u003e\n \u003cp\u003eClient Satisfaction Questionnaire\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThe trial protocol and related documents have been reviewed and approved by the Ethics Committee at the Medical Faculty of the University of Leipzig (Ref: 163/23-ek) and the Ethics Committee at the University Hospital Tübingen (Ref: 793/2023BO2). Any substantial protocol amendments have been and will continue to be submitted to both ethics committees, updated in the study registry, and communicated to all investigators, study staff, and other relevant parties prior to implementation. Approvals were obtained prior to the initiation of participant enrollment.\u003c/p\u003e\n\u003cp\u003eTrained study staff (physicians or psychologists) will obtain written informed consent from all participants after providing verbal and written study information. Participants may withdraw at any time without consequences. No ancillary studies or additional data/specimen collection are planned.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eN/A.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and material\u003c/h2\u003e\n\u003cp\u003eThe complete protocol, including the statistical analysis plan, will be registered in the German Clinical Trials Registry (DRKS, https://www.drks.de/search/de/trial/DRKS00037075) and will be updated in the event of any changes. The datasets generated and/or analyzed during the current study are not publicly available due to privacy and ethical restrictions but may be made available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eNM, MK, JH, and CM declare that they have no competing interests. SW and CP are founders and shareholders of psykit GmbH, Tübingen, Germany. CP serves as managing director of psykit GmbH. The company developed and distributed the CE-certified medical device \u003cem\u003ede:)press\u003csup\u003e®\u003c/sup\u003e\u003c/em\u003e with support from the University Hospital Tübingen. MS has received speaker fees from MEDICE Arzneimittel Pütter GmbH \u0026amp; Co. KG, Takeda, and Janssen-Cilag, and has served as an advisory board member for Takeda and Janssen-Cilag.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003ede:)press was provided by psykit GmbH free of charge. No external funding was received for the conduct of this study.\u003c/p\u003e\n\u003ch2\u003eAuthors contributions\u003c/h2\u003e\n\u003cp\u003eMS, NM, JH were responsible for the conception and design of study; NM, JH were responsible for statistics consultation; NM, MK were responsible for drafting the manuscript; MS, CM, JH were responsible for revising the manuscript critically for important intellectual content. All authors have read the manuscript and approval of the version of the manuscript to be published.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eN/A.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBijl RV, Ravelli A, van Zessen G. Prevalence of psychiatric disorder in the general population: results of The Netherlands Mental Health Survey and Incidence Study (NEMESIS). Soc Psychiatry Psychiatr Epidemiol 1998; 33(12):587\u0026ndash;95.\u003c/li\u003e\n\u003cli\u003eEbmeier KP, Donaghey C, Steele JD. Recent developments and current controversies in depression. Lancet 2006; 367(9505):153\u0026ndash;67.\u003c/li\u003e\n\u003cli\u003eJacobi F, H\u0026ouml;fler M, Strehle J, Mack S, Gerschler A, Scholl L et al. Erratum zu: Psychische St\u0026ouml;rungen in der Allgemeinbev\u0026ouml;lkerung. Studie zur Gesundheit Erwachsener in Deutschland und ihr Zusatzmodul \u0026quot;Psychische Gesundheit\u0026quot; (DEGS1-MH). Nervenarzt 2016; 87(1):88\u0026ndash;90.\u003c/li\u003e\n\u003cli\u003eJacobi F, H\u0026ouml;fler M, Strehle J, Mack S, Gerschler A, Scholl L et al. Psychische St\u0026ouml;rungen in der Allgemeinbev\u0026ouml;lkerung : Studie zur Gesundheit Erwachsener in Deutschland und ihr Zusatzmodul Psychische Gesundheit (DEGS1-MH). Nervenarzt 2014; 85(1):77\u0026ndash;87.\u003c/li\u003e\n\u003cli\u003eBusch MA, Maske UE, Ryl L, Schlack R, Hapke U. Pr\u0026auml;valenz von depressiver Symptomatik und diagnostizierter Depression bei Erwachsenen in Deutschland: Ergebnisse der Studie zur Gesundheit Erwachsener in Deutschland (DEGS1). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2013; 56(5-6):733\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eWeller S, Schroeder PA, Plewnia C. Gamification improves antidepressant effects of cognitive control training-A pilot trial. Front Digit Health 2022; 4:994484. Available from: URL: https://pubmed.ncbi.nlm.nih.gov/36339520/.\u003c/li\u003e\n\u003cli\u003eSchneider F, Kratz S, Bermejo I, Menke R, Mulert C, Hegerl U et al. Insufficient depression treatment in outpatient settings. Ger Med Sci 2004; 2:Doc01.\u003c/li\u003e\n\u003cli\u003eArbeitsgemeinschaft f\u0026uuml;r Neuropsychopharmakologie und Pharmakopsychiatrie e.V., Arzneimittelkommission der deutschen \u0026Auml;rzteschaft, Arzneimittelkommission der Deutschen Apotheker, Bundesarbeitsgemeinschaft Selbsthilfe von Menschen mit Behinderung, chronischer Erkrankung und ihren Angeh\u0026ouml;rigen e. V., Bundespsychotherapeutenkammer, Bundesverband der Angeh\u0026ouml;rigen psychisch erkrankter Menschen e. V. et al. Nationale VersorgungsLeitlinie Unipolare Depression - Langfassung. Bundes\u0026auml;rztekammer (B\u0026Auml;K); Kassen\u0026auml;rztliche Bundesvereinigung (KBV); Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF); 2022.\u003c/li\u003e\n\u003cli\u003eEichenberg C, Ott R. Klinisch-psychologische Intervention im Internet. Psychotherapeut 2012; 57(1):58\u0026ndash;69.\u003c/li\u003e\n\u003cli\u003eRock PL, Roiser JP, Riedel WJ, Blackwell AD. Cognitive impairment in depression: a systematic review and meta-analysis. Psychol Med 2014; 44(10):2029\u0026ndash;40.\u003c/li\u003e\n\u003cli\u003eElgamal S, Denburg S, Marriott M, MacQueen G. Clinical factors that predict cognitive function in patients with major depression. Can J Psychiatry 2010; 55(10):653\u0026ndash;61.\u003c/li\u003e\n\u003cli\u003eMorimoto SS, Gunning FM, Wexler BE, Hu W, Ilieva I, Liu J et al. Executive Dysfunction Predicts Treatment Response to Neuroplasticity-Based Computerized Cognitive Remediation (nCCR-GD) in Elderly Patients with Major Depression. Am J Geriatr Psychiatry 2016; 24(10):816\u0026ndash;20.\u003c/li\u003e\n\u003cli\u003eJaeger J, Berns S, Uzelac S, Davis-Conway S. Neurocognitive deficits and disability in major depressive disorder. Psychiatry Res 2006; 145(1):39\u0026ndash;48.\u003c/li\u003e\n\u003cli\u003eDisner SG, Beevers CG, Haigh EAP, Beck AT. Neural mechanisms of the cognitive model of depression. Nat Rev Neurosci 2011; 12(8):467\u0026ndash;77.\u003c/li\u003e\n\u003cli\u003eClark L, Chamberlain SR, Sahakian BJ. Neurocognitive mechanisms in depression: implications for treatment. Annu Rev Neurosci 2009; 32:57\u0026ndash;74.\u003c/li\u003e\n\u003cli\u003eRoiser JP, Elliott R, Sahakian BJ. Cognitive mechanisms of treatment in depression. Neuropsychopharmacology 2012; 37(1):117\u0026ndash;36.\u003c/li\u003e\n\u003cli\u003eRaedt R de, Koster EHW, Joormann J. Attentional control in depression: A translational affective neuroscience approach. Cogn Affect Behav Neurosci 2010; 10(1):1\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eLeMoult J, Gotlib IH. Depression: A cognitive perspective. Clin Psychol Rev 2019; 69:51\u0026ndash;66.\u003c/li\u003e\n\u003cli\u003eVander Zwalmen Y, Hoorelbeke K, Liebaert E, N\u0026egrave;ve de M\u0026eacute;vergnies C, Koster EHW. Cognitive remediation for depression vulnerability: Current challenges and new directions. Front Psychol 2022; 13:903446.\u003c/li\u003e\n\u003cli\u003eMotter JN, Pimontel MA, Rindskopf D, Devanand DP, Doraiswamy PM, Sneed JR. Computerized cognitive training and functional recovery in major depressive disorder: A meta-analysis. J Affect Disord 2016; 189:184\u0026ndash;91.\u003c/li\u003e\n\u003cli\u003eGrinberg A, Egglefield DA, Schiff S, Motter JN, Sneed JR. Computerized Cognitive Training: A Review of Mechanisms, Methodological Considerations, and Application to Research in Depression. J Cogn Enhanc 2021; 5(3):359\u0026ndash;71.\u003c/li\u003e\n\u003cli\u003eGotlib IH, Krasnoperova E, Yue DN, Joormann J. Attentional biases for negative interpersonal stimuli in clinical depression. J Abnorm Psychol 2004; 113(1):121\u0026ndash;35.\u003c/li\u003e\n\u003cli\u003eLegemaat AM, Semkovska M, Brouwer M, Geurtsen GJ, Burger H, Denys D et al. Effectiveness of cognitive remediation in depression: a meta-analysis. Psychol Med 2021; 52(16):1\u0026ndash;16.\u003c/li\u003e\n\u003cli\u003eWoolf C, Lampit A, Shahnawaz Z, Sabates J, Norrie LM, Burke D et al. A Systematic Review and Meta-Analysis of Cognitive Training in Adults with Major Depressive Disorder. Neuropsychol Rev 2022; 32(2):419\u0026ndash;37.\u003c/li\u003e\n\u003cli\u003eSiegle GJ, Ghinassi F, Thase ME. Neurobehavioral Therapies in the 21st Century: Summary of an Emerging Field and an Extended Example of Cognitive Control Training for Depression. Cogn Ther Res 2007; 31(2):235\u0026ndash;62.\u003c/li\u003e\n\u003cli\u003eGronwall DM. Paced auditory serial-addition task: a measure of recovery from concussion. Percept Mot Skills 1977; 44(2):367\u0026ndash;73.\u003c/li\u003e\n\u003cli\u003eKoster EHW, Hoorelbeke K, Onraedt T, Owens M, Derakshan N. Cognitive control interventions for depression: A systematic review of findings from training studies. Clin Psychol Rev 2017; 53:79\u0026ndash;92.\u003c/li\u003e\n\u003cli\u003eHoorelbeke K, Koster EHW. Internet-delivered cognitive control training as a preventive intervention for remitted depressed patients: Evidence from a double-blind randomized controlled trial study. J Consult Clin Psychol 2017; 85(2):135\u0026ndash;46.\u003c/li\u003e\n\u003cli\u003eSiegle GJ, Price RB, Jones NP, Ghinassi F, Painter T, Thase ME. You Gotta Work at It. Clinical Psychological Science 2014; 2(4):455\u0026ndash;71.\u003c/li\u003e\n\u003cli\u003eHoorelbeke K, van den Bergh N, Raedt R de, Wichers M, Koster EHW. Preventing Recurrence of Depression: Long-Term Effects of a Randomized Controlled Trial on Cognitive Control Training for Remitted Depressed Patients. Clinical Psychological Science 2021; 9(4):615\u0026ndash;33.\u003c/li\u003e\n\u003cli\u003eFerrari GRA, Vanderhasselt M-A, Rinck M, Demeyer I, Raedt R de, Beisel S et al. A Cognitive Control Training as Add-On Treatment to Usual Care for Depressed Inpatients. Cogn Ther Res 2021; 45(5):929\u0026ndash;43.\u003c/li\u003e\n\u003cli\u003eMcIntyre RS, Best MW, Bowie CR, Carmona NE, Cha DS, Lee Y et al. The THINC-Integrated Tool (THINC-it) Screening Assessment for Cognitive Dysfunction: Validation in Patients With Major Depressive Disorder. J Clin Psychiatry 2017; 78(7):873\u0026ndash;81.\u003c/li\u003e\n\u003cli\u003eGefen E, Launder NH, Davey CG, Nahum M, Gilboa Y, Finke C et al. Computerized Cognitive Training in People with Depression: A Systematic Review and Meta-analysis of Randomized Clinical Trials; 2021.\u003c/li\u003e\n\u003cli\u003eVander Zwalmen Y, Koster EH, Demeester D, Baeken C, Verhaeghe N, Hoorelbeke K. Predicting preventative effects of cognitive control training in remitted depressed individuals: A machine learning approach. Journal of Affective Disorders Reports 2025; 20:100894.\u003c/li\u003e\n\u003cli\u003eBundesinstitut f\u0026uuml;r Arzneimittel und Medizinprodukte (BfArM). Digitale Gesundheitsanwendungen (DiGA) \u0026ndash; Verzeichnis. [cited 2025 Aug 15]. Available from: URL: https://diga.bfarm.de/de.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"Depressive Disorder, Cognitive Control Training, Mobil Applications, Randomized Controlled Trial, Paced Auditory Serial Addition Task, Gamification, Add-on Therapy, Treatment Outcome","lastPublishedDoi":"10.21203/rs.3.rs-8910222/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8910222/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDepression is one of the most common and disabling mental health conditions. Despite evidence-based treatments, fewer than half of affected individuals achieve full remission. This may be due to limited targeting of cognitive vulnerabilities such as impaired control and negative information processing. Cognitive control training offers a promising add-on, with the adaptive Paced Auditory Serial Addition Task designed to activate prefrontal areas and promote neuroplasticity. Digital interventions, especially mobile apps, are increasingly recommended as adjuncts to standard care. This trial tests whether cognitive control training via the app \u003cem\u003ede:)press\u0026reg;\u003c/em\u003e added to inpatient care reduces depressive symptoms more effectively and sustainably than a control condition in specialized wards for affective disorders.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis randomized, placebo-controlled trial will be conducted at two inpatient centers. A total of 106 adults diagnosed with unipolar depression will be randomly assigned to receive either standard inpatient care alone or standard care plus \u003cem\u003ede:)press\u0026reg;\u003c/em\u003e. The app will be provided for six weeks. The primary outcome is clinician-rated symptom severity, measured four weeks after the intervention using the Hamilton Depression Rating Scale. Secondary outcomes include self-rated symptoms, well-being, neuropsychological functioning, and both trait and state rumination. Treatment expectations will be examined in relation to motivation, satisfaction, and outcome. Potential moderators such as age, gender, medication, cognitive style, and illness characteristics will also be analyzed.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eThis trial examines whether app-based cognitive training can enhance treatment outcomes in inpatient depression care. If effective, it may offer a scalable, low-threshold tool to support recovery.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e \u003cp\u003e: German Clinical Trials Register: DRKS00037075 on 03 June 2025, last updated on 28 July 2025, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.drks.de/search/de/trial/DRKS00037075\u003c/span\u003e\u003cspan address=\"https://www.drks.de/search/de/trial/DRKS00037075\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e","manuscriptTitle":"The CCT-D Trial: Evaluating the efficacy of the app-based cognitive control training de:)press ® as an add-on to standard inpatient care for depression – Study protocol for a randomized controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-16 12:11:36","doi":"10.21203/rs.3.rs-8910222/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":"1078595c-226a-41a1-b10b-5ba60ca4dd0b","owner":[],"postedDate":"March 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-29T17:09:29+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-16 12:11:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8910222","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8910222","identity":"rs-8910222","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}