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Kristin Kostka,1,2 Talita Duarte-Salles,3 Albert Prats-Uribe,4 Anthony G Sena,5,6 Andrea Pistillo,3 Sara Khalid,4 Lana YH Lai,7 Asieh Golozar,8,9 Thamir M Alshammari,10 Dalia M Dawoud,11 Fredrik Nyberg,12 Adam B Wilcox,13,14 Alan Andryc,5 Andrew Williams,15 Anna Ostropolets,16 Carlos Areia,17 Chi Young Jung,18 Christopher A Harle,19 Christian G Reich,1,2 Clair Blacketer,5,6 Daniel R Morales,20 David A Dorr,21 Edward Burn,3,4 Elena Roel,3,22 Eng Hooi Tan,4 Evan Minty,23 Frank DeFalco,5 Gabriel de Maeztu,24 Gigi Lipori,19 Hiba Alghoul,25 Hong Zhu,26 Jason A Thomas,13 Jiang Bian,19 Jimyung Park,27 Jordi Martínez Roldán,28 Jose D Posada,29 Juan M Banda,30 Juan P Horcajada,31 Julianna Kohler,32 Karishma Shah,33 Karthik Natarajan,16,34 Kristine E Lynch,35,36 Li Liu,37 Lisa M Schilling,38 Martina Recalde,3,22 Matthew Spotnitz,14 Mengchun Gong,39 Michael E Matheny,40,41 Neus Valveny,42 Nicole G Weiskopf,21 Nigam Shah,29 Osaid Alser,43 Paula Casajust,42 Rae Woong Park,27,44 Robert Schuff,21 Sarah Seager,1 Scott L DuVall,35,36 Seng Chan You,45 Seokyoung Song,46 Sergio Fernández-Bertolín,3 Stephen Fortin,5 Tanja Magoc,19 Thomas Falconer,16 Vignesh Subbian,47 Vojtech Huser,48 Waheed-Ul-Rahman Ahmed,33,49 William Carter,38 Yin Guan,50 Yankuic Galvan,19 Xing He,19 Peter R Rijnbeek,6 George Hripcsak,16,34 Patrick B Ryan,5,16 Marc A Suchard,51 Daniel Prieto-Alhambra4 1IQVIA, Cambridge, MA, USA; 2OHDSI Center at The Roux Institute, Northeastern University, Portland, ME, USA; 3Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; 4Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, UK; 5Janssen Research & Development, Titusville, NJ, USA; 6Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands; 7School of Medical Sciences, University of Manchester, Manchester, UK; 8Regeneron Pharmaceuticals, Tarrytown, NY, USA; 9Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 10College of Pharmacy, Riyadh Elm University, Riyadh, Saudi Arabia; 11National Institute for Health and Care Excellence, London, UK; 12School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 13Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA; 14Unviersity of Washington Medicine, Seattle, WA, USA; 15Tufts Institute for Clinical Research and Health Policy Studies, Boston, MA, USA; 16Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA; 17Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 18Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, South Korea; 19University of Florida Health, Gainesville, FL, USA; 20Division of Population Health and Genomics, University of Dundee, Dundee, UK; 21Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA; 22Universitat Autònoma de Barcelona, Barcelona, Spain; 23O’Brien Institute for Public Health, Faculty of Medicine, University of Calgary, Calgary, Canada; 24IOMED, Barcelona, Spain; 25Faculty of Medicine, Islamic University of Gaza, Gaza, Palestine; 26Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 27Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea; 28Director of Innovation and Digital Transformation, Hospital del Mar, Barcelona, Spain; 29Department of Medicine, School of Medicine, Stanford University, Redwood City, CA, USA; 30Georgia State University, Department of Computer Science, Atlanta, GA, USA; 31Department of Infectious Diseases, Hospital del Mar, Institut Hospital del Mar d’Investigació Mèdica (IMIM), Universitat Autònoma de Barcelona, Universitat Pompeu Fabra, Barcelona, Spain; 32United States Agency for International Development, Washington, DC, USA; 33Botnar Research Centre, NDORMS, University of Oxford, Oxford, UK; 34New York-Presbyterian Hospital, New York, NY, USA; 35VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA; 36Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; 37Biomedical Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 38Data Science to Patient Value Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 39Institute of Health Management, Southern Medical University, Guangzhou, People’s Republic of China; 40Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, USA; 41Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA; 42Real-World Evidence, TFS, Barcelona, Spain; 43Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 44Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea; 45Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea; 46Department of Anesthesiology and Pain Medicine, Catholic University of Daegu, School of Medicine, Daegu, South Korea; 47College of Engineering, The University of Arizona, Tucson, AZ, USA; 48National Library of Medicine, National Institutes of Health, Bethesda, MD, USA; 49College of Medicine and Health, University of Exeter, St Luke’s Campus, Exeter, UK; 50DHC Technologies Co. Ltd., Beijing, People’s Republic of China; 51Departments of Biostatistics, Computational Medicine, and Human Genetics, University of California, Los Angeles, CA, USACorrespondence: Daniel Prieto-Alhambra, Botnar Research Centre, Windmill Road, Oxford, OX37LD, UK, Email daniel.prietoalhambra@ndorms.ox.ac.ukPurpose: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.Patients and Methods: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services.Results: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed.Conclusion: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.Keywords: OHDSI, OMOP CDM, descriptive epidemiology, real world data, real world evidence, open science

Importance: Conclusions vary substantially among studies examining associations between area-based social determinants of health (SDOH) and pediatric health disparities based on the selected patient population and SDOH index. Most national studies use zip codes, which encompass a wide distribution of communities, limiting the generalizability of findings., Objectives: To characterize the distributions of composite SDOH indices for pediatric surgical patients within a national sample of academic children's hospitals and to assess SDOH index precision in classifying patients at similar levels of disadvantage., Design, Setting, and Participants: This multicenter retrospective cohort study included patients younger than 18 years who underwent surgery from January 1, 2016, to December 31, 2021, at 8 American College of Surgeons National Surgical Quality Improvement Program Pediatric children's hospitals. Data were analyzed November 15, 2023, to September 25, 2024., Exposures: Exposures included the Social Vulnerability Index (SVI), Area Deprivation Index (ADI), and Child Opportunity Index (COI), which are composite scores of SDOH factors within a geographic area. A standardized, high-fidelity process was developed to link individual patients to SDOH indices at the US census tract and census block group level., Main Outcomes and Measures: The primary outcome was composite SDOH index distribution, which was assessed using interrater reliability scores. Substantial agreement was defined as a Cohen κ statistic higher than 0.60., Results: Of 55 865 included patients, 54.6% were male; 34.8% were infants and toddlers (0-3 years of age), 39.0% were school age (4-12 years), and 26.2% were adolescents (13-17 years). A total of 3468 patients (6.2%) could not be matched to either an SVI, ADI, or COI. Patients with missing geocodes were more likely to be Hispanic (20.1% vs 17.1%; P < .001) and have Medicaid insurance (48.1% vs 44.6%; P < .001) compared with patients with addresses that could be geocoded. With all institutions grouped, SDOH indices showed only minor variations. However, within each institution and among institutions, indices varied considerably, especially the ADI. Indices had low-to-fair interrater reliability within institutions (κ range, 0.15-0.33), indicating that each index classified individual patients differently according to disadvantage., Conclusions and Relevance: In this multicenter retrospective cohort study of 55 865 pediatric surgical patients, 3 different composite measures of SDOH classified disadvantage for individual patients differently. The SDOH index components should be understood and carefully considered prior to inclusion of a composite measure in the analysis of children's surgical outcomes.

Translational magnetic resonance imaging of the rodent brain provides invaluable information for preclinical drug development. However, the automated segmentation of such images for quantitative analyses is limited compared to human brain imaging mainly due to the inferior anatomical contrast and the resulting less advanced registration and atlasing tools. Here, we investigated the potential of deep learning models for the segmentation of magnetic resonance images of rat brains into an entire set of multiple regions of interest (rather than individual loci), focusing on the development of a robust method that accommodates changes in the input based on differences in animal strain (genotype) and size. Manually generated labels are expensive, so we tested the ability of neural networks to learn brain structures from noisy but inexpensive registration-based labels, allowing very large datasets to be leveraged for training. We compared three distinct model architectures (U-Net, Attention-U-Net and DeepLab) by training them on a dataset of >10,000 magnetic resonance images of rat brains and found that each model was able to segment the entire brain into predefined sets of 29 and 58 regions, respectively, with the Attention U-Net achieving the best performance. The models canceled out unstructured label noise in the imperfect training data to provide smoother and more symmetric segmentations than registration-based labeling, and were more robust when presented with input variations, thus outperforming the noisy ground truth. Our pipeline also includes uncertainty estimation and an explainability mechanism, hence providing features essential for anomaly detection and quality assurance. In summary, our study shows that deep learning models do achieve accurate brain segmentation in high-throughput quantitative preclinical imaging without the need for expensive expert-generated labels., Competing Interests: Declaration of competing interest Jonas Kohler was a paid intern of F. Hoffmann-La Roche Ltd, Switzerland, at the time of the project. All other authors are full-time employees of F. Hoffmann-La Roche Ltd, Switzerland., (Copyright © 2024. Published by Elsevier Inc.)

Genetic screens are valuable for identifying novel genes involved in the regulation of developmental processes. To identify genes associated with cell growth regulation in Drosophila melanogaster , a mutagenesis screen was performed. Undergraduate students participating in Fly-CURE phenotypically characterized the E.4.1 mutant which is associated with rough eyes and antennae overgrowth. Following complementation analysis and subsequent genomic sequencing, E.4.1 was identified as a novel mutant allele of GstE14 , a gene involved in ecdysone biosynthesis important for the timing of developmental events. The abnormal eye and antenna phenotypes observed resulting from the loss of GstE14 suggest its role in tissue growth., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Fluorescence correlation spectroscopy (FCS) is a powerful method to measure concentration, mobility, and stoichiometry in solution and in living cells, but quantitative analysis of FCS data remains challenging due to the correlated noise in the autocorrelation function (ACF) of FCS. We demonstrate here that least-squares fitting of the conventional ACF is incompatible with the χ 2 goodness-of-fit test and systematically underestimates the true fit parameter uncertainty. To overcome this challenge, a simple method to fit the ACF is introduced that allows proper calculation of goodness-of-fit statistics and that provides more tightly constrained parameter estimates than the conventional least-squares fitting method, achieving the theoretical minimum uncertainty. Because this method requires significantly more data than the standard method, we further introduce an approximate method that requires fewer data. We demonstrate both these new methods using experiments and simulations of diffusion. Finally, we apply our method to FCS data of the peripheral membrane protein HRas, which has a slow-diffusing membrane-bound population and a fast-diffusing cytoplasmic population. Despite the order-of-magnitude difference of the diffusion times, conventional FCS fails to reliably resolve the two species, whereas the new method identifies the correct model and provides robust estimates of the fit parameters for both species., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The National Collegiate Athletic Association (NCAA) requires schools to provide anti-doping education to student athletes. The purpose of this project was to assess the effectiveness of student pharmacist-led education on NCAA student athletes' knowledge of banned supplements and nutritional/dietary supplements., Educational Activity and Setting: Student athletes at one Midwest public university were provided a 20-min educational presentation on banned substances and nutritional and dietary supplements delivered by two student pharmacists. Student athletes were invited to complete a knowledge assessment at baseline and after the presentation. The assessment consisted of two demographic questions and 13 knowledge questions., Findings: Two hundred thirty-three student athletes provided matched pre- and post-intervention data for analysis. There was an increase in the mean knowledge scores (13 points maximum); 9.8 (75%) before and 11.1 (85%) after the intervention. Student athletes gained more knowledge in the topic areas of stimulant medications and identification of credible drug sources. They gained less knowledge in the topic area of anabolic steroid use., Summary: Student pharmacist-led education resulted in statistically significant increases in student athlete knowledge of banned substances and nutritional/dietary supplements. The educational presentation is adaptable and easily transferable to other universities. Schools of pharmacy should consider implementing student pharmacist-led education to student athletes to meet NCAA education requirements., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study investigates how team cognition occurs in care transitions from operating room (OR) to intensive care unit (ICU). We then seek to understand how the sociotechnical system and team cognition are related., Background: Effective handoffs are critical to ensuring patient safety and have been the subject of many improvement efforts. However, the types of team-level cognitive processing during handoffs have not been explored, nor is it clear how the sociotechnical system shapes team cognition., Method: We conducted this study in an academic, Level 1 trauma center in the Midwestern United States. Twenty-eight physicians (surgery, anesthesia, pediatric critical care) and nurses (OR, ICU) participated in semi-structured interviews. We performed qualitative content analysis and epistemic network analysis to understand the relationships between system factors, team cognition in handoffs and outcomes., Results: Participants described three team cognition functions in handoffs-(1) information exchange, (2) assessment, and (3) planning and decision making; information exchange was mentioned most. Work system factors influenced team cognition. Inter-professional handoffs facilitated information exchange but included large teams with diverse backgrounds communicating, which can be inefficient. Intra-professional handoffs decreased team size and role diversity, which may simplify communication but increase information loss. Participants in inter-professional handoffs reflected on outcomes significantly more in relation to system factors and team cognition ( p < 0.001), while participants in intra-professional handoffs discussed handoffs as a task., Conclusion: Handoffs include team cognition, which was influenced by work system design. Opportunities for handoff improvement include a flexibly standardized process and supportive tools/technologies. We recommend incorporating perspectives of the patient and family in future work.

Understanding how reef-associated sharks use coastal waters through their ontogeny is important for their effective conservation and management. This study used the horizontal movements of acoustically tagged Caribbean reef sharks (Carcharhinus perezi) to examine their use of coastal space around the Cayman Islands between 2009 and 2019. A total of 39 (59.1%) tagged sharks (male = 22, female = 17, immature = 18, mature = 21) were detected on the islands wide network of acoustic receivers. The detection data were used to calculate values of Residency Index (RI), Site-Fidelity Index (SFI) and minimum linear displacement (MLD), as well as for network analysis of individual shark movements to test for differences between demographics, seasons, and diel periods. Sharks were detected for up to 1,598 days post-tagging and some individuals showed resident behaviour but the majority of tagged individuals appear to have been one-off or only occasional transient visitors to the area. Generally, individuals showed strong site-fidelity to different areas displaying linear home ranges of < 20 km. The evidence indicates that there was no pattern of diel behaviour. Tagged sharks generally showed increased movements within and between islands during the summer (April-September), which may be related to breeding activity. Some individuals even made occasional excursions across 110 km of open water > 2,000 m deep between Grand Cayman and Little Cayman. One mature female shark showed a displacement of 148.21 km, the greatest distance reported for this species. The data shows that the distances over which some sharks moved, greatly exceeded the extent of any one of the islands' marine protected areas indicating that this species may be more mobile and dispersive than previously thought. This study provides support for the blanket protection to all sharks throughout Cayman waters, which was incorporated within the National Conservation Act in 2015., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kohler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Health systems are often susceptible to corruption risks. Corruption within health systems has been found to negatively affect the efficacy, safety, and, significantly, equitable distribution of health products. Enforcing effective anti-corruption mechanisms is important to reduce the risks of corruption but requires first an understanding of the ways in which corruption manifests. When there are public health crises, such as the COVID-19 pandemic, corruption risks can increase due to the need for accelerated rates of resource deployment that may result in the bypassing of standard operating procedures., Main Body: A rapid review was conducted to examine factors that increased corruption risks during the COVID-19 pandemic as well as potential anti-corruption, transparency and accountability (ACTA) mechanisms to reduce these risks. A search was conducted including terms related to corruption, COVID-19, and health systems from January 2020 until January 2022. In addition, relevant grey literature websites were hand searched for items. A single reviewer screened the search results removing those that did not meet the inclusion criteria. This reviewer then extracted data relevant to the research objectives from the included articles. 20 academic articles and 17 grey literature pieces were included in this review. Majority of the included articles described cases of substandard and falsified products. Several papers attributed shortages of these products as a major factor for the emergence of falsified versions. Majority of described corruption instances occurred in low- and middle-income countries. The main affected products identified were chloroquine tablets, personal protective equipment, COVID-19 vaccine, and diagnostic tests. Half of the articles were able to offer potential anti-corruption strategies., Conclusion: Shortages of health products during the COVID-19 pandemic seemed to be associated with increased corruption risks. We found that low- and middle-income countries are particularly vulnerable to corruption during global emergencies. Lastly, there is a need for additional research on effective anti-corruption mechanisms., (© 2023. The Author(s).)

Background: Public health emergencies raise significant concerns about corruption and accountability; however, these concerns can manifest in different ways across diverse locations. For instance, more developed countries with a stronger rule of law may experience more corruption in vaccine procurement, whereas developing countries may experience more corruption at the point of distribution and delivery to end users. This research focuses on corruption concerns in Nigeria, specifically examining the procurement and distribution of COVID-19 vaccines., Methods: This paper utilizes a scoping review and a qualitative research approach. Key informants (n = 40) involved in the procurement and distribution of COVID-19 vaccines across two states in Nigeria were interviewed. Findings from the scoping review were summarized, and collected data were inductively coded and analysed in themes, revealing clear examples of implementation irregularities and corruption in the country's COVID-19 vaccination processes., Results: Vaccination programme budgeting processes were unclear, and payment irregularities were frequently observed, resulting in vaccinators soliciting informal payments while in the field. Recruitment and engagement of vaccination personnel was opaque, while target vaccination rates incentivized data falsification during periods of vaccine hesitancy. Accountability mechanisms, such as health worker supervision, vaccination data review, and additional technical support provided by donors were implemented but not effective at preventing corruption among frontline workers., Conclusions: Future accountability measures should be evidence-driven based on findings from this research. Personnel recruitment, contracting, budgeting, and remuneration should focus on transparency and accountability., (© 2023. The Author(s).)

Background: Mosquitoes and the diseases they transmit pose a significant public health threat worldwide, causing more fatalities than any other animal. To effectively combat this issue, there is a need for increased public awareness and mosquito control. However, traditional surveillance programs are time-consuming, expensive, and lack scalability. Fortunately, the widespread availability of mobile devices with high-resolution cameras presents a unique opportunity for mosquito surveillance. In response to this, the Global Mosquito Observations Dashboard (GMOD) was developed as a free, public platform to improve the detection and monitoring of invasive and vector mosquitoes through citizen science participation worldwide., Methods: GMOD is an interactive web interface that collects and displays mosquito observation and habitat data supplied by four datastreams with data generated by citizen scientists worldwide. By providing information on the locations and times of observations, the platform enables the visualization of mosquito population trends and ranges. It also serves as an educational resource, encouraging collaboration and data sharing. The data acquired and displayed on GMOD is freely available in multiple formats and can be accessed from any device with an internet connection., Results: Since its launch less than a year ago, GMOD has already proven its value. It has successfully integrated and processed large volumes of real-time data (~ 300,000 observations), offering valuable and actionable insights into mosquito species prevalence, abundance, and potential distributions, as well as engaging citizens in community-based surveillance programs., Conclusions: GMOD is a cloud-based platform that provides open access to mosquito vector data obtained from citizen science programs. Its user-friendly interface and data filters make it valuable for researchers, mosquito control personnel, and other stakeholders. With its expanding data resources and the potential for machine learning integration, GMOD is poised to support public health initiatives aimed at reducing the spread of mosquito-borne diseases in a cost-effective manner, particularly in regions where traditional surveillance methods are limited. GMOD is continually evolving, with ongoing development of powerful artificial intelligence algorithms to identify mosquito species and other features from submitted data. The future of citizen science holds great promise, and GMOD stands as an exciting initiative in this field., (© 2023. The Author(s).)

Few studies have focused on the conditions in which individuals perceive hypocrisy in others. The current study introduces and tests the Motivated Appeal to Hypocrisy (MAtH) hypothesis. This hypothesis examines core social psychological motivational threats and asks (a) whether these are related to the accounts of individuals in charging others with hypocrisy, and (b) whether these perceptions of hypocrisy are associated with reductions in the persuasiveness of persons targeted as hypocrites. Study 1 ( N = 201 ) was based on qualitative coding of stories and revealed, as expected, that violations of core social motives involving belongingness, understanding, control, self-enhancement, and trust are involved in participants' stories of hypocrisy. Study 2 ( N = 237 ) used a multilevel correlational approach and demonstrated that violations of core social motives significantly predict perceptions of hypocrisy and the rejection of a person's message or advice. The relation between social motive violations and message rejection was mediated by perceptions of hypocrisy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pillow, Hale, Kohler, Mills and Soler.)

Background: Haemostasis is a crucial process by which the body stops bleeding. It is achieved by the formation of a platelet plug, which is strengthened by formation of a fibrin mesh mediated by the coagulation cascade. In proinflammatory and prothrombotic conditions, multiple interactions of the complement system and the coagulation cascade are known to aggravate thromboinflammatory processes and increase the risk of arterial and venous thrombosis. Whether those interactions also play a relevant role during the physiological process of haemostasis is not yet completely understood. The aim of this study was to investigate the potential role of complement components and activation during the haemostatic response to mechanical vessel injury., Methods: We used a microvascular bleeding model that simulates a blood vessel, featuring human endothelial cells, perfusion with fresh human whole blood, and an inducible mechanical injury to the vessel. We studied the effects of complement inhibitors against components of the lectin (MASP-1, MASP-2), classical (C1s), alternative (FD) and common pathways (C3, C5), as well as a novel triple fusion inhibitor of all three complement pathways (TriFu). Effects on clot formation were analysed by recording of fibrin deposition and the platelet activation marker CD62P at the injury site in real time using a confocal microscope., Results: With the inhibitors targeting MASP-2 or C1s, no significant reduction of fibrin formation was observed, while platelet activation was significantly reduced in the presence of the FD inhibitor. Both common pathway inhibitors targeting C3 or C5, respectively, were associated with a substantial reduction of fibrin formation, and platelet activation was also reduced in the presence of the C3 inhibitor. Triple inhibition of all three activation pathways at the C3-convertase level by TriFu reduced both fibrin formation and platelet activation. When several complement inhibitors were directly compared in two individual donors, TriFu and the inhibitors of MASP-1 and C3 had the strongest effects on clot formation., Conclusion: The observed impact of complement inhibition on reducing fibrin clot formation and platelet activation suggests a role of the complement system in haemostasis, with modulators of complement initiation, amplification or effector functions showing distinct profiles. While the interactions between complement and coagulation might have evolved to support haemostasis and protect against bleeding in case of vessel injury, they can turn harmful in pathological conditions when aggravating thromboinflammation and promoting thrombosis., Competing Interests: Author DR is the inventor of patents or patent applications that describe complement inhibitors for therapeutic purposes, some of which are developed by Amyndas Pharmaceuticals; has provided paid consulting services to Roche Pharma, Sobi, and Greenovation; and has provided scientific lectures sponsored by Roche and Alexion. Author CS has received Honoria for speaking at symposia as well as research funding from pharmaceutical industry. He is a named inventor of a patent application that describes the use of TriFu as a potential therapeutic agent EP3474883B1. Author AD looks into developing TriFu as a therapeutic agent. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Golomingi, Kohler, Lamers, Pouw, Ricklin, Dobó, Gál, Pál, Kiss, Dopler, Schmidt, Hardy, Lam and Schroeder.)

From the onset of the pandemic in the United States, racial disparities in COVID-19 outcomes have been evident. In April 2020, several events prompted a concerned group of colleagues to form the Black Equity Coalition (BEC), a Black-led coalition in Allegheny County, Pennsylvania, which brings together professionals from multiple sectors who aim to ensure an equitable response to the COVID-19 pandemic. Several significant milestones have been achieved, and this article describes the development, functioning, and outcomes of the Coalition in the first 15 months of operation (April 2020-June 2021). COVID-19 was the reason for such an unprecedented effort, but this BEC infrastructure will be needed long after COVID-19 is controlled. In addition to short-term activities and reactive measures to prevent and mitigate COVID-19 in Black populations, the BEC is serving as a crucial link between government, health care stakeholders, and communities to produce long-term systemic change.

Purpose: Next-generation sequencing (NGS) has revolutionized the diagnostic process for rare/ultrarare conditions. However, diagnosis rates differ between analytical pipelines. In the National Institutes of Health-Undiagnosed Diseases Network (UDN) study, each individual's NGS data are concurrently analyzed by the UDN sequencing core laboratory and the clinical sites. We examined the outcomes of this practice., Methods: A retrospective review was performed at 2 UDN clinical sites to compare the variants and diagnoses/candidate genes identified with the dual analyses of the NGS data., Results: In total, 95 individuals had 100 diagnoses/candidate genes. There was 59% concordance between the UDN sequencing core laboratories and the clinical sites in identifying diagnoses/candidate genes. The core laboratory provided more diagnoses, whereas the clinical sites prioritized more research variants/candidate genes (P < .001). The clinical sites solely identified 15% of the diagnoses/candidate genes. The differences between the 2 pipelines were more often because of variant prioritization disparities than variant detection., Conclusion: The unique dual analysis of NGS data in the UDN synergistically enhances outcomes. The core laboratory provided a clinical analysis with more diagnoses and the clinical sites prioritized more research variants/candidate genes. Implementing such concurrent dual analyses in other genomic research studies and clinical settings can improve both variant detection and prioritization., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

The experimental autocorrelation function of fluorescence correlation spectroscopy calculated from finite-length data is a biased estimator of the theoretical correlation function. This study presents a new theoretical framework that explicitly accounts for the data length to allow for unbiased analysis of experimental autocorrelation functions. To validate our theory, we applied it to experiments and simulations of diffusion and characterized the accuracy and precision of the resulting parameter estimates. Because measurements in living cells are often affected by instabilities of the fluorescence signal, autocorrelation functions are typically calculated on segmented data to improve their robustness. Our reformulated theory extends the range of usable segment times down to timescales approaching the diffusion time. This flexibility confers unique advantages for live-cell data that contain intensity variations and instabilities. We describe several applications of short segmentation to analyze data contaminated with unwanted fluctuations, drifts, or spikes in the intensity that are not suited for conventional fluorescence correlation analysis. These results demonstrate the potential of our theoretical framework to significantly expand the experimental systems accessible to fluorescence correlation spectroscopy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Hereditary sensory and autonomic neuropathy type IV (HSAN) is a rare and debilitating disorder highlighted by congenital absence of pain and anhidrosis. Orthopedic sequelae include physeal fractures, Charcot joint development, excessive joint laxity, soft tissue infections and recurrent painless dislocations, all of which often present in a delayed fashion. While there is no accepted guideline on management of these patients, several case studies have highlighted the importance of early diagnosis and cautioned against surgical intervention in these patients due to their inability to perceive pain and comply with post-operative restriction. The purpose of this case report is to present the clinical course of a patient with HSAN IV and the unique orthopedic challenges it presented. While some of her orthopedic injuries healed appropriately following treatment, others have gone on to have devastating complications and progressive joint destruction. Level of Evidence: IV., (Copyright © The Iowa Orthopaedic Journal 2023.)

Objectives: Corruption undermines the quality of healthcare and leads to inequitable access to essential health products. WHO, Global Fund, United Nations Development Programme (UNDP) and World Bank are engaged in anti-corruption in health sectors globally. Throughout the COVID-19 pandemic, weakened health systems and overlooked regulatory processes have increased corruption risks. The objective of this study is thus to explore the strengths and weaknesses of these organisations' anti-corruption mechanisms and their trajectories since the pandemic began., Design, Setting and Participants: 25 semistructured key informant interviews with a total of 27 participants were conducted via Zoom between April and July 2021 with informants from WHO, World Bank, Global Fund and UNDP, other non-governmental organisations involved in anti-corruption and academic institutions. Key informant selection was guided by purposive and snowball sampling. Detailed interview notes were qualitatively coded by three researchers. Data analysis followed an inductive-deductive hybrid thematic analysis framework., Results: The findings demonstrate that WHO, World Bank, Global Fund and UNDP have shifted from criminalisation/punitive approaches to anti-corruption to preventative ones and that anti-corruption initiatives are strong when they are well funded, explicitly address corruption and are complemented by strong monitoring and evaluation mechanisms. Weaknesses in the organisations' approaches to anti-corruption include one-size-fits-all approaches, lack of political will to address corruption and zero-tolerance policies for corruption. The COVID-19 pandemic has highlighted the necessity of improving anti-corruption by promoting strong accountability and transparency in health systems., Conclusions: Results from this study highlight the strengths, weaknesses and recent trajectories of anti-corruption in the Global Fund, World Bank, UNDP and WHO. This study underscores the importance of implementing strong and robust anti-corruption mechanisms specifically geared towards corruption prevention that remain resilient even in times of emergency., Competing Interests: Competing interests: JK is the Director of WHO Collaborating Centre for Governance, Accountability, and Transparency in the Pharmaceutical Sector. AB is a research assistants there and AG and GS were research assistants there when the research was conducted., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Breastfeeding is less prevalent among African American women than their white peers. Moreover, breastfeeding rates in the South lag behind those in other regions of the U.S. Consequently, various efforts have been undertaken to promote breastfeeding among groups for which this practice is less common. This study examines African American and white racial disparities concerning (1) exposure to breastfeeding promotional information and (2) reported prevalence of breastfeeding in primary social networks. The survey combines a randomly selected sample of adults representative of the population and a non-random oversample of African Americans in a predominantly rural tri-county area on the Mississippi Gulf Coast. An initial wave of 2019 Mississippi REACH Social Climate Survey data collected under the auspices of the CDC-funded REACH program (Mississippi's Healthy Families, Mothers, and Babies Initiative; 2018-2023) is used to examine racial disparities in these two key outcomes for Mississippians in Hancock, Harrison, and Jackson counties. The results show that African American respondents are more likely to be exposed to breastfeeding promotional messages than their white counterparts. However, the reported prevalence of breastfeeding in African American respondents' primary social networks is significantly lower than that indicated by their white peers. These paradoxical results underscore the limitations of promotional efforts alone to foster breastfeeding. While breastfeeding promotion is important, the reduction of racial disparities in this practice likely requires a multi-pronged effort that involves structural breastfeeding supports (e.g., lactation spaces, peer networking groups, and pro-breastfeeding employment policies and workplaces). This study provides a promising model of innovative methodological approaches to the study of breastfeeding while underscoring the complex nature of racial disparities in lactation prevalence.

Throughout the COVID-19 pandemic, international access to COVID-19 vaccines and other health technologies has remained highly asymmetric. This inequity has had a particularly deleterious impact on low- and middle-income countries, engaging concerns about the human rights to health and to the equal enjoyment of the benefits of scientific progress enshrined under articles 12 and 15 of the International Covenant on Economic, Social and Cultural Rights. In response, the relationship between intellectual property rights and public health has reemerged as a subject of global interest. In October 2020, a wholesale waiver of the copyright, patent, industrial design, and undisclosed information sections of the Agreement on Trade-Related Aspects of Intellectual Property (TRIPS Agreement) was proposed by India and South Africa as a legal mechanism to increase access to affordable COVID-19 medical products. Here, we identify and evaluate the TRIPS waiver positions of World Trade Organization (WTO) members and other key stakeholders throughout the waiver's 20-month period of negotiation at the WTO. In doing so, we find that most stakeholders declined to explicitly contextualize the TRIPS waiver within the human right to health and that historical stakeholder divisions on the relationship between intellectual property and access to medicines appear largely unchanged since the early 2000s HIV/AIDS crisis. Given the WTO's consensus-based decision-making process, this illuminates key challenges faced by policy makers seeking to leverage the international trading system to improve equitable access to health technologies., Competing Interests: Competing interests: None declared., (Copyright © 2022 Kohler, Wong, and Tailor.)

Competing Interests: Competing interests: During the conduct of the study: KP reports grants from Unitaid; VW reports grants from the Center for Emerging Infectious Diseases Policy & Research, Gilead, UCB, the Fleming Fund, the World Health Organization Southeast Asia Office, the Rockefeller Brothers Foundation, the United States Pharmacopeia, Management Sciences for Health and the National Institute for Allergy and Infectious Diseases; and JK reports grants from the Leslie Dan Faculty of Pharmacy, University of Toronto CSAP Award and the Connaught Global Challenge Award from the University of Toronto. AW and VR have nothing to disclose. The funders had no role in the conception, analysis or writing of this analysis.

Introduction: Disparities in surgical management have been documented across a range of disease processes. The objective of this study was to investigate sociodemographic disparities in young females undergoing excision of a breast mass., Methods: A retrospective study of females aged 10-21 y who underwent surgery for a breast lesion across eleven pediatric hospitals from 2011 to 2016 was performed. Differences in patient characteristics, workup, management, and pathology by race/ethnicity, insurance status, median neighborhood income, and urbanicity were evaluated with bivariate and multivariable regression analyses., Results: A total of 454 females were included, with a median age of 16 y interquartile range (IQR: 3). 44% of patients were nonHispanic (NH) Black, 40% were NH White, and 7% were Hispanic. 50% of patients had private insurance, 39% had public insurance, and 9% had other/unknown insurance status. Median neighborhood income was $49,974, and 88% of patients resided in a metropolitan area. NH Whites have 4.5 times the odds of undergoing preoperative fine needle aspiration or core needle biopsy compared to NH Blacks (CI: 2.0, 10.0). No differences in time to surgery from the initial imaging study, size of the lesion, or pathology were observed on multivariable analysis., Conclusions: We found no significant differences by race/ethnicity, insurance status, household income, or urbanicity in the time to surgery after the initial imaging study. The only significant disparity noted on multivariable analysis was NH White patients were more likely to undergo preoperative biopsy than were NH Black patients; however, the utility of biopsy in pediatric breast masses is not well established., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Missense variants in COL4A genes are often found in patients with an Alport syndrome-like presentation, but their pathogenicity is not always clear. We encountered a woman with microscopic hematuria and proteinuria at 33 years of age with a diagnosis of thin basement membrane disease who was approaching end stage kidney disease at 59 years of age. We hypothesized that this patient's kidney disease was within the spectrum of Alport syndrome., Methods: We used histologic, genetic, and biochemical approaches to investigate the mechanisms of kidney disease. By immunofluorescence, we investigated collagen IV chain composition of the glomerular basement membrane (GBM). We employed targeted sequencing to search for pathogenic variants in COL4A and other relevant genes. We utilized N- and C-terminal split NanoLuciferase assays to determine the effect of a novel COL4A4 variant of uncertain significance (VUS) on collagen IV heterotrimer formation in vitro . We transfected COL4A4 expression constructs with split NanoLuciferase fragment-fused COL4A3 and COL4A5 constructs into human embryonic kidney 293T cells. To assay for α 3 α 4 α 5(IV) heterotrimer formation and secretion, we measured luminescence in cell lysates and culture supernatants from transfected cells., Results: Immunostaining suggested that the collagen α 3 α 4 α 5(IV) network was present throughout the patient's GBMs. DNA sequencing revealed a novel homozygous VUS: COL4A4 c.1180G>A (p. Gly394Ser). In the C-terminal split luciferase-based α 3 α 4 α 5(IV) heterotrimer formation assays, luminescence levels for G394S were comparable to WT, but in the N-terminal tag assays, the extracellular luminescence levels for G394S were decreased by approximately 50% compared with WT., Conclusions: Our cell-based assay provides a platform to test COL4 VUS and shows that G394S impairs assembly of the α 3 α 4 α 5(IV) N-terminus and subsequent trimer secretion. These data suggest that the COL4A4-G394S variant is pathogenic and causes an atypical mild form of autosomal recessive Alport syndrome., Competing Interests: V. Bhalla reports consultancy for Bayer Pharmaceuticals, CareDx, Guidepoint LLC, Janssen Pharmaceuticals, LEK Consulting, and Reata; ownership interest in Pyrames Health and Viscira LLC; research funding from CareDx (spouse); honoraria from Bayer Pharmaceuticals and CareDx (spouse); an advisory or leadership role for the American Journal of Physiology—Renal Physiology (editorial board; July 2007–present), CareDx (scientific advisory board; spouse), Physiologic Reports (April 2018–present), Pyrames (scientific advisory board), and Relypsa (scientific advisory board); participation in a speakers’ bureau for CareDx (spouse); and other interests or relationships with the American Medical Association, Validated Device Listing-Blood Pressure Measurement Devices, Hypertension Council, American Heart Association (member), and Kidney and Cardiovascular Disease Council, American Heart Association (immediate past-chair). J.H. Miner reports consultancy for Alpha Insights, AstraZeneca, Bridge Bio, Deerfield Management, Guidepoint, Janssen Biotech, Inc., Mantra Bio, National Institutes of Health, and The Planning Shop; research funding from Cadre/Myonid Therapeutics, Chinook Therapeutics, and Lung Therapeutics, Inc.; honoraria from Pfizer; patents or royalties from Angion, Genentech, Kerafast, and Maze Therapeutics; an advisory or leadership role for the American Society for Matrix Biology (president), Journal of Clinical Investigation (consulting editor), Kidney International (editorial board), Matrix Biology (editorial board), Matrix Biology Plus (editorial board); and other interests or relationships with the Alport Syndrome Foundation (scientific advisory research network). All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Yellow fever virus (YFV) is a potentially lethal, zoonotic, blood-borne flavivirus transmitted to humans and non-human primates by mosquitoes. Owing to multiple deadly epidemics, the WHO classifies YFV as a "high impact, high threat disease" with resurgent epidemic potential. At present, there are no approved antiviral therapies to combat YFV infection. Herein we report on 2'-halogen-modified nucleoside analogs as potential anti-YFV agents. Of 11 compounds evaluated, three showed great promise with low toxicity, high intracellular metabolism into the active nucleoside triphosphate form, and sub-micromolar anti-YFV activity. Notably, we investigated a 2'-fluoro,2'-bromouridine phosphate prodrug (C9), a known anti-HCV agent with good stability in human blood and favorable metabolism. Predictive modeling revealed that C9 could readily bind the active site of the YFV RdRp, conferring its anti-YFV activity. C9 displayed potent anti-YFV activity in primary human macrophages, 3D hepatocyte spheroids, and in mice. In an A129 murine model, shortly after infection, C9 significantly reduced YFV replication and protected against YFV-induced liver inflammation and pathology with no adverse effects. Collectively, this work identifies a potent new anti-YFV agent with strong therapeutic promise.

The radial arm maze (RAM) is a common behavioral test to quantify spatial learning and memory in rodents. Prior attempts to refine the standard experimental setup have been insufficient. Previously, we demonstrated the feasibility of a fully automated, voluntary, and stress-free eight-arm RAM not requiring food or water deprivation. Here, we compared this newly developed refined RAM to a classic manual experimental setup using 24 female 10-12 weeks old C57BL/6J mice. We used a lipopolysaccharide (LPS)-induced model of systemic inflammation to examine long-term cognitive impairment for up to 13 weeks following LPS injection. Both mazes demonstrated robust spatial learning performance during the working memory paradigm. The refined RAM detected spatial learning and memory deficits among LPS-treated mice in the working memory paradigm, whereas the classic RAM detected spatial learning and memory deficits only in the combined working/reference memory paradigm. In addition, the refined RAM allowed for quantification of an animal's overall exploratory behavior and day/night activity pattern. While our study highlights important aspects of refinement of the new setup, our comparison of methods suggests that both RAMs have their respective merits depending on experimental requirements., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kohler, Mei, Banneke, Winter, Endres and Emmrich.)

The Radar Imager for Mars Subsurface Experiment instrument has conducted the first rover-mounted ground-penetrating radar survey of the Martian subsurface. A continuous radar image acquired over the Perseverance rover's initial ~3-kilometer traverse reveals electromagnetic properties and bedrock stratigraphy of the Jezero crater floor to depths of ~15 meters below the surface. The radar image reveals the presence of ubiquitous strongly reflecting layered sequences that dip downward at angles of up to 15 degrees from horizontal in directions normal to the curvilinear boundary of and away from the exposed section of the Séitah formation. The observed slopes, thicknesses, and internal morphology of the inclined stratigraphic sections can be interpreted either as magmatic layering formed in a differentiated igneous body or as sedimentary layering commonly formed in aqueous environments on Earth. The discovery of buried structures on the Jezero crater floor is potentially compatible with a history of igneous activity and a history of multiple aqueous episodes.

Background: Complement lectin pathway components, in particular mannan-binding lectin (MBL) and MBL-associated serine proteases (MASPs) have been shown to interact with coagulation factors and contribute to clot formation. Here we investigated the role of MBL and MASP-1 in the haemostatic response following mechanical vessel injury in a human microfluidic bleeding model., Methods: We studied haemostasis in a microvascular bleeding model in the presence of human endothelial cells and human whole blood under flow conditions. We monitored incorporation of proteins into the clot with fluorescently labelled antibodies and studied their effects on clot formation, platelet activation, and bleeding time with specific inhibitors. Platelet activation was also studied by flow cytometry., Results: Upon vessel injury, MBL accumulated at the injury site in a well-defined wall-like structure. MBL showed partial colocalisation with fibrin, and strong colocalisation with von Willebrand factor and (activated) platelets. Flow cytometry ruled out direct binding of MBL to platelets, but confirmed a PAR4- and thrombin-dependent platelet-activating function of MASP-1. Inhibiting MBL during haemostasis reduced platelet activation, while inhibiting MASP-1 reduced platelet activation, fibrin deposition and prolonged bleeding time., Conclusion: We show in a microvascular human bleeding model that MBL and MASP-1 have important roles in the haemostatic response triggered by mechanical vessel injury: MBL recognises the injury site, while MASP-1 increases fibrin formation, platelet activation and shortens bleeding time. While the complement lectin pathway may be harmful in the context of pathological thrombosis, it appears to be beneficial during the physiological coagulation response by supporting the crucial haemostatic system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Golomingi, Kohler, Jenny, Hardy, Dobó, Gál, Pál, Kiss, Lam and Schroeder.)

Background: Subscapularis tendon failure after anatomic total shoulder arthroplasty can lead to pain, dysfunction, and early component failure. The purpose of this study was to report on the results of pectoralis major tendon transfer for treatment of irreparable subscapularis tendon failure in the setting of prior shoulder arthroplasty., Methods: Patients who underwent pectoralis major muscle transfer for treatment of subscapularis failure in the setting of prior total shoulder arthroplasty or hemiarthroplasty were included in the study. The entirety of the pectoralis major tendon was transferred superficial to the conjoined tendon and placed lateral to the bicipital groove., Results: Eight patients were included in the study. All 7 patient who experienced pain in their shoulder had improvement in their pain postoperatively. Those patients with preserved active motion were able to regain that motion postoperatively. Radiographically, anterior translation was found to be temporarily improved; however, anterior instability would later recur in most cases, though this did not correlate with increased pain or decreased function., Discussion: Management options ranging from continued observation, revision repair, pectoralis muscle transfer, or revision to reverse total shoulder arthroplasty should be considered in a setting of subscapularis failure after shoulder arthroplasty. Decision-making should be based on physiological age of the patient as well as symptoms present as well as the position and stability of the arthroplasty components., Conclusion: Pectoralis muscle transfer can provide pain relief, improve subjective instability, and preserve function in physiological young patients with an irreparable subscapularis who have well-positioned and well-fixed anatomic shoulder arthroplasty components., (© 2022 The Authors.)

We present herein the design, synthesis, and optimization of gut-restricted inhibitors of Na + /H + exchanger isoform 3 (NHE3). NHE3 is predominantly expressed in the kidney and gastrointestinal tract where it acts as the major absorptive sodium transporter. We desired minimally systemic agents that would block sodium absorption in the gastrointestinal tract but avoid exposure in the kidney. Starting with a relatively low-potency highly bioavailable hit compound ( 1 ), potent and minimally absorbed NHE3 inhibitors were designed, culminating with the discovery of tenapanor ( 28 ). Tenapanor has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of irritable bowel syndrome with constipation in adults., Competing Interests: The authors declare the following competing financial interest(s): J.W.J., M.R.L., L.H., K.K., M.N., and A.G.S. were employed by and own stock in Ardelyx, Inc. N.B., S.K.M., C.W.C., J.K., E.D.L., and D.C. were employed by Ardelyx, Inc., (© 2022 The Authors. Published by American Chemical Society.)

Introduction:  Gastroschisis feeding practices vary. Standardized neonatal feeding protocols have been demonstrated to improve nutritional outcomes. We report outcomes of infants with gastroschisis that were fed with and without a protocol., Materials and Methods:  A retrospective study of neonates with uncomplicated gastroschisis at 11 children's hospitals from 2013 to 2016 was performed.Outcomes of infants fed via institutional-specific protocols were compared with those fed without a protocol. Subgroup analyses of protocol use with immediate versus delayed closure and with sutured versus sutureless closure were conducted., Results:  Among 315 neonates, protocol-based feeding was utilized in 204 (65%) while no feeding protocol was used in 111 (35%). There were less surgical site infections (SSI) in those fed with a protocol (7 vs. 16%, p  = 0.019). There were no differences in TPN duration, time to initial oral intake, time to goal feeds, ventilator use, peripherally inserted central catheter line deep venous thromboses, or length of stay. Of those fed via protocol, less SSIs occurred in those who underwent sutured closure (9 vs. 19%, p  = 0.026). Further analyses based on closure timing or closure method did not demonstrate any significant differences., Conclusion:  Across this multi-institutional cohort of infants with uncomplicated gastroschisis, there were more SSIs in those fed without an institutional-based feeding protocol but no differences in other outcomes., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Weak governance over public sector pharmaceutical policy and practice limits access to essential medicines, inflates pharmaceutical prices, and wastes scarce health system resources. Pharmaceutical systems are technically complex and involve extensive interactions between the private and public sectors. For members of public sector pharmaceutical committees, relationships with the private sector can result in conflicts of interest, which may introduce commercial biases into decision-making, potentially compromising public health objectives and health system sustainability. We conducted a descriptive, qualitative study of conflict of interest policies and practices in the public pharmaceutical sector in ten countries in the World Health Organization (WHO) South-East Asia Region (SEAR) (Bangladesh, Bhutan, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, and Timor-Leste) between September 2020 and March 2021., Results: We identified 45 policy and regulatory documents and triangulated documentary data with 21 expert interviews. Key informants articulated very different governance priorities and conflict of interest concerns depending on the features of their country's pharmaceutical industry, market size, and national economic objectives related to the domestic pharmaceutical industry. Public sector pharmaceutical policies and regulations consistently contained provisions for pharmaceutical committee members to disclose relevant interests, but contained little detail about what should be declared, when, and how often, nor whether disclosures are evaluated and by whom. Processes for preventing or managing conflicts of interest were less well developed than those for disclosure except for a few key procurement processes. Where processes for managing conflicts of interest were specified, the dominant strategy was to recuse committee members with a conflict of interest from relevant work. Policies rarely specified that committee members should divest or otherwise be free from conflicts of interest., Conclusions: Robust processes for conflict of interest prevention and management could ensure the integrity of decision-making and build public trust in pharmaceutical processes to achieve public health objectives. Upstream approaches including supportive legislative frameworks, the creation of oversight bodies, and strengthening regulatory institutions can also contribute to building cultures of transparency, accountability, and trust., (© 2022. The Author(s).)

The melting of glaciers and ice caps accounts for about one-third of current sea-level rise 1-3 , exceeding the mass loss from the more voluminous Greenland or Antarctic Ice Sheets 3,4 . The Arctic archipelago of Svalbard, which hosts spatial climate gradients that are larger than the expected temporal climate shifts over the next century 5,6 , is a natural laboratory to constrain the climate sensitivity of glaciers and predict their response to future warming. Here we link historical and modern glacier observations to predict that twenty-first century glacier thinning rates will more than double those from 1936 to 2010. Making use of an archive of historical aerial imagery 7 from 1936 and 1938, we use structure-from-motion photogrammetry to reconstruct the three-dimensional geometry of 1,594 glaciers across Svalbard. We compare these reconstructions to modern ice elevation data to derive the spatial pattern of mass balance over a more than 70-year timespan, enabling us to see through the noise of annual and decadal variability to quantify how variables such as temperature and precipitation control ice loss. We find a robust temperature dependence of melt rates, whereby a 1 °C rise in mean summer temperature corresponds to a decrease in area-normalized mass balance of -0.28 m yr -1 of water equivalent. Finally, we design a space-for-time substitution 8 to combine our historical glacier observations with climate projections and make first-order predictions of twenty-first century glacier change across Svalbard., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

While care transitions influence quality of care, less work studies transitions between hospital units. We studied care transitions from the operating room (OR) to pediatric and adult intensive critical care units (ICU) using Systems Engineering Initiative for Patient Safety (SEIPS)-based process modeling. We interviewed twenty-nine physicians (surgery, anesthesia, pediatric critical care) and nurses (OR, ICU) and administered the AHRQ Hospital Survey on Patient Safety Culture items about handoffs, care transitions and teamwork. Care transitions are complex, spatio-temporal processes and involve work during the transition (i.e., handoff and transport) and preparation and follow up activities (i.e., articulation work). Physicians defined the transition as starting earlier and ending later than nurses. Clinicians in the OR to adult ICU transition without a team handoff reported significantly less information loss and better cooperation, despite positive interview data. A team handoff and supporting articulation work should increase awareness, improving quality and safety of care transitions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)