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The COVID-19 pandemic impacted school-based delivery of special educational supports and therapeutic services. This study describes student receipt of school-based supports/services and parent satisfaction by instruction modalities during the 2020-2021 academic year in the United States. Data were collected through the COVID Experiences Survey from parents of children ages 5-12 years, administered using NORC's AmeriSpeak panel. Most parents reported satisfaction with supports (88.4%) and services (93.2%). Dissatisfaction with special education supports and therapeutic services was more common among parents whose children received supports/ services virtually than in person (special educational supports: aOR=12.00, 95% CI [1.49-96.89], p=0.020; therapeutic services: aOR=15.76, 95% CI [1.01-245.40], p=0.049). These findings suggest opportunities to improve design and delivery of online special education supports and therapeutic services as well as emergency preparedness by considering the needs of students with disabilities and their families.

In the Maximize Project, we are engaging in a research-practice partnership to co-create implementation strategies to facilitate elementary school teachers' use of equity-focused positive behavior supports (EF-PBS). In this paper, we describe the processes used to build an interactive, technology-based platform to enhance teachers' use of EF-PBS via self-reflection, self-assessment, goal setting, and goal review. We describe how we established a multi-disciplinary, multi-state community advisory board to collaborate on Version 1 of platform (Phase 1). We explain how we obtained quantitative and qualitative feedback about the platform from educators in three partnering schools, and how we used those data to produce Version 2 of the platform (Phase 2). Platform use data suggested high utilization in Quarter 1 (August-October) of the school year, when there was protected time to complete activities. However, platform use was moderate in Quarter 2 (October-December) and low in Quarters 3 and 4 (January-May). Educator feedback revealed moderate acceptability, feasibility, and appropriateness of the platform and highlighted ways to improve the user experience (e.g., streamlining steps in goal setting, making resources about strategy implementation easier to find). We discuss lessons learned to inform school mental health co-creation endeavors, including strategies for supporting diverse perspectives, for enhancing advisory board members' voices and confidence, and for creating practical and feasible methods for teachers to benefit from co-created technology-based implementation strategies. Our processes offer guidance for others engaging in research-practice partnerships, developing education technologies and/or supporting teachers' use of equity-focused practices to improve daily school experiences for all students.

Although neurobiologic and genetic factors figure prominently in the development of attention deficit/hyperactivity disorder (ADHD), adverse physical health experiences and conditions encountered during childhood may also play a role. Poor health is known to impact the developing brain with potential lifelong implications for behavioral issues. In attempt to better understand the relationship between childhood physical health and the onset and presence of ADHD symptoms, we summarized international peer-reviewed articles documenting relationships between a select group of childhood diseases or health events (e.g., illnesses, injuries, syndromes) and subsequent ADHD outcomes among children ages 0-17 years. Drawing on a larger two-phase systematic review, 57 longitudinal or retrospective observational studies (1978-2021) of childhood allergies, asthma, eczema, head injury, infection, or sleep problems and later ADHD diagnosis or symptomatology were identified and subjected to meta-analysis. Significant associations were documented between childhood head injuries, infections, and sleep problems with both dichotomous and continuous measures of ADHD, and between allergies with dichotomous measures of ADHD. We did not observe significant associations between asthma or eczema with ADHD outcomes. Heterogeneity detected for multiple associations, primarily among continuously measured outcomes, underscores the potential value of future subgroup analyses and individual studies. Collectively, these findings shed light on the importance of physical health in understanding childhood ADHD. Possible etiologic links between physical health factors and ADHD are discussed, as are implications for prevention efforts by providers, systems, and communities.

Parenting and family environment have significant impact on child development, including development of executive function, attention, and self-regulation, and may affect the risk of developmental disorders including attention-deficit/hyperactivity disorder (ADHD). This paper examines the relationship of parenting and family environment factors with ADHD. A systematic review of the literature was conducted in 2014 and identified 52 longitudinal studies. A follow-up search in 2021 identified 7 additional articles, for a total of 59 studies that examined the association of parenting factors with ADHD outcomes: ADHD overall (diagnosis or symptoms), ADHD diagnosis specifically, or presence of the specific ADHD symptoms of inattention and hyperactivity/impulsivity. For parenting factors that were present in three or more studies, pooled effect sizes were calculated separately for dichotomous or continuous ADHD outcomes, accounting for each study's conditional variance. Factors with sufficient information for analysis were parenting interaction quality (sensitivity/warmth, intrusiveness/reactivity, and negativity/harsh discipline), maltreatment (general maltreatment and physical abuse), parental relationship status (divorce, single parenting), parental incarceration, and child media exposure. All factors showed a significant direct association with ADHD outcomes, except sensitivity/warmth which had an inverse association. Parenting factors predicted diagnosis and overall symptoms as well as inattentive and hyperactive symptoms when measured, but multiple factors showed significant heterogeneity across studies. These findings support the possibility that parenting and family environment influences ADHD symptoms and may affect a child's likelihood of being diagnosed with ADHD. Prevention strategies that support parents, such as decreasing parenting challenges and increasing access to parent training in behavior management, may improve children's long-term developmental health.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by persistent patterns of inattention, hyperactivity, and impulsiveness. Among US children and adolescents aged 3-17 years, 9.4% have a diagnosis of ADHD. Previous research suggests possible links between parental substance use and ADHD among children. We conducted a systematic review and meta-analysis of 86 longitudinal or retrospective studies of prenatal or postnatal alcohol, tobacco, or other parental substance use and substance use disorders and childhood ADHD and its related behavioral dimensions of inattention and hyperactivity-impulsivity. Meta-analyses were grouped by drug class and pre- and postnatal periods with combined sample sizes ranging from 789 to 135,732. Prenatal exposure to alcohol or tobacco and parent substance use disorders were consistently and significantly associated with ADHD among children. Other parental drug use exposures resulted in inconsistent or non-significant findings. Prevention and treatment of parental substance use may have potential for impacts on childhood ADHD.

Abstract Participant management in a lung cancer screening (LCS) depends on the assigned Lung Imaging Reporting and Data System (Lung-RADS) category, which is based on reliable detection and measurement of pulmonary nodules. The aim of this study was to compare the agreement of two AI-based software tools for detection, quantification and categorization of pulmonary nodules in an LCS program in Northern Germany (HANSE-trial). 946 low-dose baseline CT-examinations were analyzed by two AI software tools regarding lung nodule detection, quantification and categorization and compared to the final radiologist read. The relationship between detected nodule volumes by both software tools was assessed by Pearson correlation (r) and tested for significance using Wilcoxon signed-rank test. The consistency of Lung-RADS classifications between Software tool 1 (S1, Aview v2.5, Coreline Soft, Seoul, Korea) and Software tool 2 (S2, Prototype ‘’ChestCTExplore’’, software version ToDo, Siemens Healthineers, Forchheim, Germany) was evaluated by Cohen’s kappa (κ) and percentual agreement (PA).The derived volumes of true positive nodules were strongly correlated (r > 0.95), the volume derived by S2 was significantly higher than by S1 (P

Abstract: Introduction: Physical activity (PA) shows beneficial effects for various mental illnesses, but exercise-prescription has not yet become routine practice in psychiatry. Therefore, this survey addresses attitudes and barriers towards exercise-prescription in health professionals. Methods: We conducted an anonymous online survey among health professionals on the importance of PA in prevention and treatment of mental illness and perceived barriers as part of a larger survey on sports psychiatry. The survey was promoted by societies for sports psychiatry. Results: N = 310 health professionals from Switzerland (86.5%) and other countries responded to the online survey. Sixty percent were physicians (51.1% psychiatrists). Most respondents strongly agreed that PA plays an important role in prevention and treatment of mental (80.2%, 69.8%) and physical (84.5%, 72.0%) illness. Forty-six percent use PA in prevention and 59.4% in treatment of mental illness with lower proportions for physical illness (39.5%, 36.2%). Most mentioned barriers to the use of PA were “insufficient possibilities” in psychiatric institutions (34.8%) and “no reimbursement” (41.9%) in private practice. Participants working in private practice rated barriers in practice significantly higher than those from other workplaces. “No motivation” was found to be the most common barrier for patients (56.5%). PA was used most often for depression (39.5%) followed by substance use disorders (32.1%) and anxiety disorders (30.9%). Conclusions: Health professionals in Switzerland and some extent other European countries show a positive attitude towards the use of PA in mental illness. Current barriers, especially reimbursement in private practice should be addressed to improve prescription-rates of PA.

This mixed-methods study examined how WiseGuyz, a gender-transformative healthy relationships program, can support positive sexual health self-efficacy (SHSE) among adolescents. 570 adolescent boys provided data on SHSE from before to after the program, and 20 adolescent boys participated in interviews and focus groups to discuss their sexual health education needs. Results showed that boys who participated in WiseGuyz reported a significant increase in SHSE from pretest to post-test and that WiseGuyz was different from typical school-based sexual health education in terms of content and facilitation and increasing program engagement. These findings indicate the potential for gender-transformative interventions in supporting positive SHSE.

INTRODUCTION 1956 I. THE DELEGATIONS AND THEIR ELABORATIONS 1959 A. Early Statutes and Institutional Foundations 1960 B. The Statutory Free-Trade and Security Dichotomy 1964 II. CONSTITUTIONALIZING PRESIDENTIAL CONTROL OF 1968 [...], The U.S. Constitution grants Congress the power "[t]o regulate Commerce with foreign Nations," but today the exercise of the foreign commerce power resides primarily with the executive branch. That transfer of control is partly the result of significant delegations of responsibility for managingforeign commerce from Congress to the executive. It is also, however, the result of the securitization of foreign commerce. The executive branch asserts that foreign commerce issues fall under its constitutional powers over foreign affairs, and, thus, that it enjoys authority over foreign commerce that exceeds the scope of congressional delegations. This Article makes three contributions. First, we analyze the development of a trade administrative state charged with managing two sets of broad delegations: to liberalize trade, on the one hand, and to restrict it in the name of "economic security" when the executive deems necessary. Second, we document the way in which the executive branch in recent presidential administrations of both parties has defended those administrations' trade policies in court by arguing that the president's independent constitutional powers over (noncommercial) foreign affairs give him license to exercise power over commerce beyond that delegated by Congress, or that congressional delegations should be construed in his favor. The courts, for their part, have often accepted these claims either directly or indirectly. Third, we propose three statutory reforms that Congress could pass to restore balance to the branches' regulation of foreign commerce: (1) Congress should sunset the president's imposition of tariffs or other trade restrictions pursuant to economic security statutes after 90 or 180 days without the possibility of renewal unless Congress acts; (2) Congress should prohibit the executive branch from relying on any international agreement as the legal basis under which any good or service is imported into the United States, exported from the United States, or regulated while in the United States, unless Congress has either explicitly authorized the agreement in advance or approved it after its conclusion; and (3) Congress should eliminate the Federal Circuit's exclusive jurisdiction over appeals in most trade cases.

Abstract WingAnalogy is a computer tool for automated insect wing morphology and asymmetry analysis. It facilitates project management, enabling users to import pairs of wing images obtained from individual insects, such as left and right, fore- and hindwings. WingAnalogy employs image processing and computer vision to segment wing structures and extract cell boundaries, and junctions. It quantifies essential metrics encompassing cell and wing characteristics, including area, length, width, circularity, and centroid positions. It enables users to scale and superimpose wing images utilizing Particle Swarm Optimization (PSO). WingAnalogy computes regression, Normalized Root Mean Square Error (NRMSE), various cell-based parameters, and distances between cell centroids and junctions. The software generates informative visualizations, aiding researchers in comprehending and interpreting asymmetry patterns. WingAnalogy allows for dividing wings into up to five distinct wing cell sets, facilitating localized comparisons. The software excels in report generation, providing detailed asymmetry measurements in PDF, CSV, and TXT formats.

Claus F Vogelmeier,1 Kai-Michael Beeh,2 Michael Schultze,3 Nils Kossack,4 Lena M Richter,4 Jing Claussen,5 Chris Compton,6 Stephen G Noorduyn,7,8 Afisi S Ismaila,8,9 Gema Requena10 1Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Centre Giessen and Marburg, Philipps-University Marburg, German Center for Lung Research (DZL), Marburg, Germany; 2Insaf Respiratory Research Institute, Wiesbaden, Germany; 3ZEG – Berlin Center for Epidemiology and Health Research GmbH, Berlin, Germany; 4WIG2 GmbH (Wissenschaftliches Institut für Gesundheitsökonomie und Gesundheitssystemforschung) - Scientific Institute for Health Economics and Health System Research, Leipzig, Germany; 5Global Medical Affairs, GSK, Munich, Germany; 6Global Medical, GSK, Brentford, UK; 7Value Evidence and Outcomes, R&D Global Medical, GSK, Mississauga, ON, Canada; 8Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 9Value Evidence and Outcomes, R&D Global Medical, GSK, Collegeville, PA, USA; 10Value Evidence and Outcomes, R&D Global Medical, GSK, Brentford, UKCorrespondence: Gema Requena, GSK, 980 Great West Road, Brentford, Middlesex, TW8 9GS, UK, Tel +44 20 80476893, Email gema.x.requena@gsk.comPurpose: Triple therapy (long-acting muscarinic antagonist/long-acting β2-agonist/inhaled corticosteroid) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. Multiple-inhaler triple therapy (MITT) is associated with poor adherence and persistence. This study assessed comparative adherence and persistence to single-inhaler triple therapy (SITT) versus MITT among patients with COPD in a real-world setting in Germany.Patients and Methods: This retrospective analysis using the WIG2 benchmark database identified patients with COPD newly initiating triple therapy with MITT or SITT (fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or formoterol/beclomethasone/glycopyrronium bromide [FOR/BDP/GLY]) November 2017–June 2019. Eligible patients were ≥ 35 years with 1 year’s continual insurance prior to triple therapy initiation and no previous record of triple therapy. Inverse probability of treatment weighting was used to balance baseline characteristics. Adherence was measured using proportion of days covered (PDC) at 6, 12, and 18 months post-treatment initiation; persistence (time until treatment discontinuation) was measured at 6, 12, and 18 months, with a gap of > 30 days used to define non-persistence.Results: Of 5710 patients included in the analysis (mean age 66 years), 71.4% initiated MITT and 28.6% initiated SITT (FF/UMEC/VI: 41.4%; FOR/BDP/GLY: 58.6%). Mean PDC was higher among SITT versus MITT users at all time points; at each time point, mean PDC was highest among FF/UMEC/VI users. During the first 6 months following treatment initiation, higher adherence was exhibited by FF/UMEC/VI (29%) and FOR/BDP/GLY (19%) users versus MITT users. Over the entire observation period, FF/UMEC/VI users had the highest proportion of persistent patients; at 18 months, 16.5% of FF/UMEC/VI users were persistent versus 2.3% of MITT users.Conclusion: Patients initiating SITT in Germany had significantly higher adherence and persistence compared with patients initiating MITT over 6 to 18 months following treatment initiation. Among SITT, FF/UMEC/VI users had the highest proportion of adherence and persistence.Keywords: comparative, multiple- or single-inhaler triple therapy, new-user, proportion of days covered, real-world analysis, treatment discontinuation

During the early Holocene to mid-Holocene, about 11 500 to 5500 years ago, lakes expanded across the Sahel and Sahara in response to enhanced summer monsoon precipitation. To investigate the effect of these lakes on the West African summer monsoon, previous simulation studies prescribed mid-Holocene lakes from reconstructions. By prescribing mid-Holocene lakes, however, the terrestrial water balance is inconsistent with the size of the lakes. In order to close the terrestrial water cycle, we construct a dynamic endorheic lake (DEL) model and implement it into the atmosphere–land model ICON-JSBACH4. For the first time, this allows us to investigate the dynamic interaction between climate, lakes, and vegetation across northern Africa. Additionally, we investigate the effect of lake depth changes on mid-Holocene precipitation, a neglected aspect in previous simulation studies. A pre-industrial control simulation shows that the DEL model realistically simulates the lake extent across northern Africa. Only in the Ahnet and Chotts basins is the lake area slightly overestimated, which is likely related to the coarse resolution of the simulations. The mid-Holocene simulations reveal that both the lake expansion and the vegetation expansion cause a precipitation increase over northern Africa. The sum of these individual contributions to the precipitation is, however, larger than the combined effect that is generated when lake and vegetation dynamics interact. Thus, the lake–vegetation interaction causes a relative drying response across the entire Sahel. The main reason for this drying response is that the simulated vegetation expansion cools the land surface more strongly than the lake expansion, which is dominated by the expansion of Lake Chad. Accordingly, the surface temperature increases over the region of Lake Chad and causes local changes in the meridional surface-temperature gradient. These changes in the meridional surface-temperature gradient are associated with reduced inland moisture transport from the tropical Atlantic into the Sahel, which causes a drying response in the Sahel. An idealized mid-Holocene experiment shows that a similar drying response is induced when the depth of Lake Chad is decreased by about 1–5 m, without changing the horizontal lake area. By reducing the depth of Lake Chad, the heat storage capacity of the lake decreases, and the lake warms faster during the summer months. Thus, in the ICON-JSBACH4 model, the lake depth significantly influences the simulated surface temperature and the simulated meridional surface-temperature gradient between the simulated lakes and vegetation, thereby affecting mid-Holocene precipitation over northern Africa.

Summary:. Modern approaches to autogenous auricular reconstruction involve a multistage approach where ear elevation is an independent procedure. The goal is to project the reconstructed ear at an anatomically accurate and symmetric auriculocephalic angle, but postoperative scar contraction may adversely affect the long-term outcomes. An ear elevation splint was developed to provide rigid support for the auricle during the acute healing period to promote lasting elevation. The splint is low cost, made from commonly used orthotic materials, and can be conveniently customized for each patient in less than 15 minutes.

Background: Evidence on how decisions regarding escalation to triple therapy and de- or re-escalation are taken and the rationale on which these decisions are based is currently limited in Germany. Objectives: The TETRIS study aims to elucidate influences on treatment decisions surrounding triple therapy in a real-world practice setting in Germany. Design: TETRIS is an ongoing, multicenter, prospective, observational cohort study recruiting patients with chronic obstructive pulmonary disease (COPD) with or without asthma who have already been treated with triple therapy for 2–48 weeks. Methods: For better representation of the treatment reality in Germany, patients are recruited from general practitioners and pulmonologists. Data are collected in two parts. Part 1 involves cross-sectional phenotyping of patients at enrollment. Part 2 involves a 2-year longitudinal follow-up period to monitor/document all visits by the patients during the 24-month observation period per routine clinical practice. Here, we report the demographic and baseline characteristics of 1213 eligible patients recruited to part 1 of the study. Results: The mean patient age was 66.4 years overall, and 29.3% (356/1213) of patients had no comorbidities. The mean CAT score was 19.4; the number of exacerbations and hospitalizations due to exacerbations in the past 3 years before starting triple therapy was 0.6 and 0.1, respectively. Dual bronchodilation with a long-acting muscarinic antagonist (LAMA) plus a long-acting β-2 agonist (LABA) was the most common therapy for COPD before initiation of triple therapy in 58.3% of patients. Conclusion: In this real-world setting in Germany, patients with COPD have a relatively low reported exacerbation rate but high symptom burden, and over 70% are multimorbid. Triple therapy is initiated in patients who are primarily highly symptomatic despite being on LAMA + LABA. Future prospective studies in patients with multimorbidity are warranted to better understand the treatment landscape across the disease spectrum. Trial registration: https://clinicaltrials.gov/study/NCT04657211

Abstract: Introduction: Sports psychiatry is an emerging medical and psychiatric discipline that has experienced significant development in recent years. This growth has been accompanied by an increase in scientific outputs from sports psychiatrists and other academics that address the three fields of activity of sports psychiatry: namely, mental health and disorders in competitive and elite sports, mental health and sport-specific mental disorders in recreational sports, and the use of sport, exercise and physical activity in the prevention and treatment of mental disorders. Conceptual publications have discussed the scope of sports psychiatry and education and training. However, some topics receive more attention than others, with evidence gaps in other key areas of sports psychiatry. Advancing the field towards evidence-based practice requires an assessment of the current state of the literature and the development of a strategic research agenda. Methods: Following the Working Group on Research Gaps, Priorities and Agenda at the Summit on Sports Psychiatry arranged by the International Society for Sports Psychiatry (ISSP), the ISSP Scientific Committee conducted a narrative review of the sports psychiatry literature to benchmark the current academic state of the discipline and further developed the research agenda to provide a strategic framework for future research directions. Results: We discuss a research agenda according to five key areas: sports psychiatry as a discipline, education and training in sports psychiatry, and the three clinical fields of activity of sports psychiatry. Conclusion: This sports psychiatry research agenda provides a framework to guide the strategic development of the scientific literature in the field.

Abstract Background Physical inactivity is a growing risk factor worldwide, therefore getting people into sports is necessary. When prescribing physical activity, it is essential to recommend the correct training intensities. Cardiopulmonary exercise testing (CPX) enables precise determination of individuals’ training intensities but is unavailable for a broad population. Therefore, the Borg scale allows individuals to assess perceived exertion and set their intensity easily and cost-efficiently. In order to transfer CPX to rating of perceived exertion (RPE), previous studies investigated RPE on specific physiological anchors, e.g. blood lactate (bLa) concentrations, but representativeness for a broad population is questionable. Some contradictory findings regarding individual factors influencing RPE occur, whereas univariable analysis has been performed so far. Moreover, a multivariable understanding of individual factors influencing RPE is missing. This study aims to determine RPE values at the individual anaerobic threshold (LT2) and defined bLa concentrations in a large cohort and to evaluate individual factors influencing RPE with multivariable analysis. Methods CPX with bicycle or treadmill ergometer of 6311 participants were analyzed in this cross-sectional study. RPE values at bLa concentrations 2 mmol/l, 3 mmol/l, 4 mmol/l, and LT2 (first rise in bLa over baseline + 1.5 mmol/l) were estimated by spline interpolation. Multivariable cumulative ordinal regression models were performed to assess the influence of sex, age, type of ergometry, VO2max, and duration of exercise testing on RPE. Results Median values [interquartile range (IQR)] of the total population were RPE 13 [11; 14] at 2 mmol/l, RPE 15 [13; 16] at 3 mmol/l, RPE 16 [15; 17] at 4 mmol/l, and RPE 15 [14; 16] at LT2. Main influence of individual factors on RPE were seen especially at 2 mmol/l: male sex (odds ratio (OR) [95%-CI]: 0.65 [0.587; 0.719]), treadmill ergometry (OR 0.754 [0.641; 0.886]), number of stages (OR 1.345 [1.300; 1.394]), age (OR 1.015 [1.012; 1.018]), and VO2max (OR 1.023 [1.015; 1.030]). Number of stages was the only identified influencing factor on RPE at all lactate concentrations/LT2 (3 mmol/l: OR 1.290 [1.244; 1.336]; 4 mmol/l: OR 1.229 [1.187; 1.274]; LT2: OR 1.155 [1.115; 1.197]). Conclusion Our results suggest RPE ≤ 11 for light intensity, RPE 12–14 for moderate intensity, and RPE 15–17 for vigorous intensity, which slightly differs from the current American College of Sports Medicine (ACSM) recommendations. Additionally, we propose an RPE of 15 delineating heavy and severe intensity domain. Age, sex, type of ergometry, duration of exercise, and cardiopulmonary fitness should be considered when recommending individualized intensities with RPE, primarily at lower intensities. Therefore, this study can be used as a new guideline for prescribing individual RPE values in the clinical practice, predominantly for endurance type exercise.

In July 2023, the Center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 pandemic. This report summarizes the rich discussions that occurred during the workshop.The workshop participants discussed multisource data integration and highlighted the benefits of combining traditional surveillance with more novel data sources like mobility data, social media, and wastewater monitoring. Significant advancements were noted in the development of predictive models, with examples from various countries showcasing the use of machine learning and artificial intelligence in detecting and monitoring disease trends. The role of open collaboration between various stakeholders in modelling was stressed, advocating for the continuation of such partnerships beyond the pandemic. A major gap identified was the absence of a common international framework for data sharing, which is crucial for global pandemic preparedness.Overall, the workshop underscored the need for robust, adaptable modelling frameworks and the integration of different data sources and collaboration across sectors, as key elements in enhancing future pandemic response and preparedness.

Abstract Background Differences in immune responses between women and men are leading to a strong sex bias in the incidence of autoimmune diseases that predominantly affect women, such as multiple sclerosis (MS). MS manifests in more than twice as many women, making sex one of the most important risk factor. However, it is incompletely understood which genes contribute to sex differences in autoimmune incidence. To address that, we conducted a gene expression analysis in female and male human spleen and identified the transmembrane protein CD99 as one of the most significantly differentially expressed genes with marked increase in men. CD99 has been reported to participate in immune cell transmigration and T cell regulation, but sex-specific implications have not been comprehensively investigated. Methods In this study, we conducted a gene expression analysis in female and male human spleen using the Genotype-Tissue Expression (GTEx) project dataset to identify differentially expressed genes between women and men. After successful validation on protein level of human immune cell subsets, we assessed hormonal regulation of CD99 as well as its implication on T cell regulation in primary human T cells and Jurkat T cells. In addition, we performed in vivo assays in wildtype mice and in Cd99-deficient mice to further analyze functional consequences of differential CD99 expression. Results Here, we found higher CD99 gene expression in male human spleens compared to females and confirmed this expression difference on protein level on the surface of T cells and pDCs. Androgens are likely dispensable as the cause shown by in vitro assays and ex vivo analysis of trans men samples. In cerebrospinal fluid, CD99 was higher on T cells compared to blood. Of note, male MS patients had lower CD99 levels on CD4+ T cells in the CSF, unlike controls. By contrast, both sexes had similar CD99 expression in mice and Cd99-deficient mice showed equal susceptibility to experimental autoimmune encephalomyelitis compared to wildtypes. Functionally, CD99 increased upon human T cell activation and inhibited T cell proliferation after blockade. Accordingly, CD99-deficient Jurkat T cells showed decreased cell proliferation and cluster formation, rescued by CD99 reintroduction. Conclusions Our results demonstrate that CD99 is sex-specifically regulated in healthy individuals and MS patients and that it is involved in T cell costimulation in humans but not in mice. CD99 could potentially contribute to MS incidence and susceptibility in a sex-specific manner.

Kai-Michael Beeh,1 Kieran J Rothnie,2 Jing Claussen,3 Fränce Hardtstock,4 Rachel K Knapp,4 Thomas Wilke,5 Alexandrosz Czira,2 Chris Compton,6 Afisi S Ismaila7,8 1Insaf Respiratory Research Institute, Wiesbaden, Germany; 2Value Evidence and Outcomes, R&D Global Medical, GSK, Brentford, UK; 3Global Medical Affairs, GSK, Munich, Germany; 4Real World & Advanced Analytics (RWAA), Cytel, Berlin, Germany; 5IPAM e.V., Institute affiliated with University of Wismar, Wismar, Germany; 6Global Medical, GSK, London, UK; 7Value Evidence and Outcomes, R&D Global Medical, GSK, Collegeville, PA, USA; 8Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Afisi S Ismaila, Value Evidence and Outcomes, GSK, 1250 South Collegeville Road, Collegeville, PA, 19426-0989, USA, Tel +1 919 315 8229, Email afisi.s.ismaila@gsk.comPurpose: To assess patient characteristics of users and new initiators of triple therapy for chronic obstructive pulmonary disease (COPD) in Germany.Patients and Methods: Retrospective cohort study of patients with COPD and ≥ 1 prescription for single-inhaler triple therapy (SITT; fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or beclomethasone dipropionate/glycopyrronium bromide/formoterol [BDP/GLY/FOR]) or multiple-inhaler triple therapy (MITT), using data from the AOK PLUS German sickness fund (1 January 2015– 31 December 2019). The index date was the first date of prescription for FF/UMEC/VI or BDP/GLY/FOR (SITT users), or the first date of overlap of inhaled corticosteroid, long-acting β2-agonist, and long-acting muscarinic antagonist (MITT users). Two cohorts were defined: the prevalent cohort included all identified triple therapy users; the incident cohort included patients newly initiating triple therapy for the first time (no prior use of MITT or SITT in the last 2 years). Patient characteristics and treatment patterns were assessed on the index date and during the 24-month pre-index period.Results: In total, 18,630 patients were identified as prevalent triple therapy users (MITT: 17,945; FF/UMEC/VI: 700; BDP/GLY/FOR: 908; non-mutually exclusive) and 2932 patients were identified as incident triple therapy initiators (MITT: 2246; FF/UMEC/VI: 311; BDP/GLY/FOR: 395; non-mutually exclusive). For both the prevalent and incident cohorts, more than two-thirds of patients experienced ≥ 1 moderate/severe exacerbation in the preceding 24 months; in both cohorts more BDP/GLY/FOR users experienced ≥ 1 moderate/severe exacerbation, compared with FF/UMEC/VI and MITT users. Overall, 97.9% of prevalent triple therapy users and 86.4% of incident triple therapy initiators received maintenance treatment in the 24-month pre-index period.Conclusion: In a real-world setting in Germany, triple therapy was most frequently used after maintenance therapy in patients with recent exacerbations, in line with current treatment recommendations.Plain Language Summary: Triple therapy (a combination of three different respiratory inhaled medications) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience repeated short-term symptom flare-ups when taking dual therapy (a combination of two different respiratory medications). Previously, patients had to take triple therapy using two or three separate inhalers. More recently, single-inhaler triple therapies have been developed, meaning patients can take all three different medications at the same time via one single inhaler. This study assessed the characteristics of patients who were already receiving triple therapy, or who started triple therapy (either via multiple inhalers or a single inhaler), in Germany between January 2015 and December 2019.In total, 18,630 patients who were already receiving triple therapy during the study period, and 2932 patients who newly started using triple therapy were included. The study reported that more than two-thirds of included patients had experienced at least one flare-up of COPD symptoms in the 2 years before starting triple therapy. Most patients had also received another therapy for COPD before starting triple therapy. A small proportion of patients started taking triple therapy after receiving no other therapy for COPD in the previous 2 years.The results of the study suggest that triple therapy for COPD in Germany is most often used in accordance with recommendations (patients already receiving therapy and experiencing repeated symptom flare-ups).Keywords: COPD, Germany, MITT, patient characteristics, real-world treatment, SITT

Abstract Highly sensitive vertically aligned carbon nanotube arrays (VANTAs) interdigitated electrode (IDE) arrays are developed for electrochemical biosensing of two cytokines (i.e., interleukin‐10 (IL‐10) and interferon‐gamma (IFN‐γ)) that are useful for early detection Johne's disease (Bovine Paratuberculosis) in cattle. The high aspect ratio VANTA‐IDEs (50–60 µm in height) are grown through a chemical vapor deposition process from an iron (Fe) catalyst that is lithographically patterned on a silicon wafer with equal finger width and inter‐finger spacing of 25 µm. After functionalization with distinct antibodies the VANTA‐IDEs are capable of selective detection of both IL‐10 and IFN‐γ within an actual biological matrix (i.e., diluted bovine implant supernatant) over concentration ranges of 0.1 to 30 pg mL−1 (limit of detection – LOD: 0.0911 pg mL−1) and 50–500 pg mL−1 (LOD: 24.17 pg mL−1), respectively with a response time of

IntroductionValidation of functional free-breathing MRI involves a comparison to more established or more direct measurements. This procedure is cost-intensive, as it requires access to patient cohorts, lengthy protocols, expenses for consumables, and binds working time. Therefore, the purpose of this study is to introduce a synthetic lung model (ASYLUM), which mimics dynamic MRI acquisition and includes predefined lung abnormalities for an alternative validation approach. The model is evaluated with different registration and quantification methods and compared with real data.MethodsA combination of trigonometric functions, deformation fields, and signal combinations were used to create 20 synthetic image time series. Lung voxels were assigned either to normal or one of six abnormality classes. The images were registered with three registration algorithms. The registered images were further analyzed with three quantification methods: deformation-based or signal-based regional ventilation (JVent/RVent) analysis and perfusion amplitude (QA). The registration results were compared with predefined deformations. Quantification methods were evaluated regarding predefined amplitudes and with respect to sensitivity, specificity, and spatial overlap of defects. In addition, 36 patients with chronic obstructive pulmonary disease were included for verification of model interpretations using CT as the gold standard.ResultsOne registration method showed considerably lower quality results (76% correlation vs. 92/97%, p ≤ 0.0001). Most ventilation defects were correctly detected with RVent and QA (e.g., one registration variant with sensitivity ≥78%, specificity ≥88). Contrary to this, JVent showed very low sensitivity for lower lung quadrants (0–16%) and also very low specificity (1–29%) for upper lung quadrants. Similar patterns of defect detection differences between RVent and JVent were also observable in patient data: Firstly, RVent was more aligned with CT than JVent for all quadrants (p ≤ 0.01) except for one registration variant in the lower left region. Secondly, stronger differences in overlap were observed for the upper quadrants, suggesting a defect bias in the JVent measurements in the upper lung regions.ConclusionThe feasibility of a validation framework for free-breathing functional lung imaging using synthetic time series was demonstrated. Evaluating different ventilation measurements, important differences were detected in synthetic and real data, with signal-based regional ventilation assessment being a more reliable method in the investigated setting.

Meat and fish are the most resource-demanding food products with a high carbon footprint. However, worldwide, tons of meat and fish products that are still safe to consume are discarded as waste due to uncertainty about their freshness. This study evaluates the application of a newly developed electronic nose (e-nose) to assess the freshness level of chicken and turkey under regular processing conditions. The device, comprising a micro-cantilever sensor functionalized with a binder selective to the freshness biomarker cadaverine, is crucial in reducing this waste. Upon exposure to cadaverine, the sensor resonance frequency changes as a function of analyte concentration. Standard cadaverine concentrations are measured by High-Performance Liquid Chromatography (HPLC) and associated with the shelf-life estimation determined by sensory and microbial evaluations during an 18-day storage period (5 °C). The findings show that the sensory panel evaluates the meat as unsuitable between days 7 and 9, while bacterial data shows high bacterial levels after day 4. HPLC and e-nose data show increasing cadaverine levels after day 4, correlating well with the bacterial count. The data calibrates the electronic nose, demonstrating its potential as a shelf-life prediction tool, which can assist human sensorial evaluation and significantly reduce food waste.

Objective This cross-sectional study aimed to investigate the role of low energy availability (LEA) in the interplay between depression and disordered eating/eating disorders (DE/EDs) among female athletes. The International Olympic Committee consensus statement on Relative Energy Deficiency in Sport (REDs) identified depression as both an outcome of LEA and a secondary risk factor for REDs. However, the direct link between LEA and depression has yet to be fully established.Methods We assessed 57 female athletes participating in weight-sensitive sports at different levels of competition training at least four times a week. Assessment was conducted using laboratory analyses, clinical interviews and the Patient Health Questionnaire-9 questionnaire. Participants were recruited through various channels, including German sports clubs, Olympic training centres, social media platforms and the distribution of flyers at competitions. Indicators of LEA were defined if at least two of the following three physiological indicators were present: menstrual disturbances, suppressed resting metabolic rate and suppressed thyroid hormones. Logistic and linear regression analysis were used to examine the relationship between LEA, depression and DE/ED.Results The lifetime prevalence of depressive disorders was 29.6%. 19% of the participants were diagnosed with an ED, and an additional 22.6% exhibited DE.LEA was not significantly associated with either lifetime prevalence of depressive disorders or current depressive symptoms. However, a significant association was found between depression and DE/ED in terms of both lifetime prevalence and current depressive symptoms. DE/ED increased the probability of lifetime prevalence of depressive disorders by 34% (19%–49%) compared with normal eating behaviour.Conclusion We found no evidence that LEA is an independent factor for depression in female athletes. Its association with LEA and REDs appears to occur primarily in the presence of DE/ED.

Cochlear implants (CI) represent incredible devices that restore hearing perception for those with moderate to profound sensorineural hearing loss. However, the ability of a CI to restore complex auditory function is limited by the number of perceptually independent spectral channels provided. A major contributor to this limitation is the physical gap between the CI electrodes and the target spiral ganglion neurons (SGNs). In order for CI electrodes to stimulate SGNs more precisely, and thus better approximate natural hearing, new methodologies need to be developed to decrease this gap, (i.e., transitioning CIs from a far-field to near-field device). In this review, strategies aimed at improving the neural-electrode interface are discussed in terms of the magnitude of impact they could have and the work needed to implement them. Ongoing research suggests current clinical efforts to limit the CI-related immune response holds great potential for improving device performance. This could eradicate the dense, fibrous capsule surrounding the electrode and enhance preservation of natural cochlear architecture, including SGNs. In the long term, however, optimized future devices will likely need to induce and guide the outgrowth of the peripheral process of SGNs to be in closer proximity to the CI electrode in order to better approximate natural hearing. This research is in its infancy; it remains to be seen which strategies (surface patterning, small molecule release, hydrogel coating, etc.) will be enable this approach. Additionally, these efforts aimed at optimizing CI function will likely translate to other neural prostheses, which face similar issues.

The CRISPR-Cas13 system has been proposed as an alternative treatment of viral infections. However, for this approach to be adopted as an antiviral, it must be optimized until levels of efficacy rival or exceed the performance of conventional approaches. To take steps toward this goal, we evaluated the influenza viral RNA degradation patterns resulting from the binding and enzymatic activity of mRNA-encoded LbuCas13a and two crRNAs from a prior study, targeting PB2 genomic and messenger RNA. We found that the genome targeting guide has the potential for significantly higher potency than originally detected, because degradation of the genomic RNA is not uniform across the PB2 segment, but it is augmented in proximity to the Cas13 binding site. The PB2 genome targeting guide exhibited high levels (>1 log) of RNA degradation when delivered 24 hours post-infection in vitro and maintained that level of degradation over time, with increasing multiplicity of infection (MOI), and across modern influenza H1N1 and H3N2 strains. Chemical modifications to guides with potent LbuCas13a function, resulted in nebulizer delivered efficacy (>1-2 log reduction in viral titer) in a hamster model of influenza (Influenza A/H1N1/California/04/09) infection given prophylactically or as a treatment (post-infection). Maximum efficacy was achieved with two doses, when administered both pre- and post-infection. This work provides evidence that mRNA-encoded Cas13a can effectively mitigate Influenza A infections opening the door to the development of a programmable approach to treating multiple respiratory infections.

Annual recruitment in fish is undoubtedly impacted by a vast number of biotic and abiotic factors. That is especially the case for fish species such as the black bass (species in the genus Micropterus), where there is extended parental care. Although much focus has been given in the past on determining the roles that many of these factors (e.g., temperatures, wind, flow rates, and habitat change) play in determining recruitment among the back basses, little attention has been given to assessing what role reproductive success plays in that determination. To address this question, we conducted a long-term study on two adjacent smallmouth bass (SMB) Micropterus dolomieu Lacepede, 1802 populations in eastern ON to assess the relationship between annual fry cohort size (FCS) (i.e., population-wide reproductive success) and annual recruitment. To measure population-wide annual FCS, we used snorkel surveys to conduct a complete census of nesting SMB males during the spawn from 1990 to 2015. During those surveys, we quantified mating success, determined which nests were successful or not, and calculated the number of independent fry produced each year by summing those numbers across all successful nests. Summer snorkel surveys from 1991 to 2016 assessed annual recruitment through visual counts of age 1+ juveniles. Results demonstrated a highly significant, positive, linear relationship between annual FCS and annual recruitment. Key words: smallmouth bass, Micropterus dolomieu, annual recruitment, reproductive success, angling, Introduction Smallmouth bass (SMB) Micropterus dolomieu Lacepede, 1802 and largemouth bass M. salmoides (Lacepede, 1802), two of the species in the genus commonly referred to as black bass, are both [...]