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Background: Humanitarian mine action (HMA) stakeholders have an organized presence with well-resourced medical capability in many conflict and post-conflict settings. Humanitarian mine action has the potential to positively augment local trauma care capacity for civilian casualties of explosive ordnance (EO) and explosive weapons (EWs). Yet at present, few strategies exist for coordinated engagement between HMA and the health sector to support emergency care system strengthening to improve outcomes among EO/EW casualties., Methods: A scoping literature review was conducted to identify records that described trauma care interventions pertinent to civilian casualties of EO/EW in resource-constrained settings using structured searches of indexed databases and grey literature. A 2017 World Health Organization (WHO) review on trauma systems components in low- and middle-income countries (LMICs) was updated with additional eligible reports describing trauma care interventions in LMICs or among civilian casualties of EO/EWs after 2001., Results: A total of 14,195 non-duplicative records were retrieved, of which 48 reports met eligibility criteria. Seventy-four reports from the 2017 WHO review and 16 reports identified from reference lists yielded 138 reports describing interventions in 47 countries. Intervention efficacy was assessed using heterogenous measures ranging from trainee satisfaction to patient outcomes; only 39 reported mortality differences. Interventions that could feasibly be supported by HMA stakeholders were synthesized into a bundle of opportunities for HMA engagement designated links in a Civilian Casualty Care Chain (C-CCC)., Conclusions: This review identified trauma care interventions with the potential to reduce mortality and disability among civilian EO/EW casualties that could be feasibly supported by HMA stakeholders. In partnership with local and multi-lateral health authorities, HMA can leverage their medical capabilities and expertise to strengthen emergency care capacity to improve trauma outcomes in settings affected by EO/EWs.

Introduction: Access to essential medicines is limited in developing countries mainly due to inefficiencies in health supply chain management, such as the absence of standard monitoring frameworks and poorly designed Logistics Management Information Systems (LMIS). Health supply chain managers need accurate and timely data for decision-making. However, routine health information systems suffer from poor data quality, reliance on paper-based reports, insufficient logistic formats, inadequate infrastructure, and limited human resources., Objective: This study evaluates the data quality of LMIS for health commodities in public health facilities in the Amhara National Regional State of Ethiopia., Methods: The study was conducted in Ethiopia's Amhara National Regional State. The study employed an institution-based concurrent mixed-methods design. Data collection involved 102 facilities selected through multi-stage stratified random sampling, adhering to sampling criteria set by USAID's Logistics Indicators Assessment Tool (LIAT). Data abstraction checklists were used to collect data., Results: Of the seven tracer medicines selected to evaluate data quality, there was substantial variability in inventory accuracy rates. Inventory discrepancies were significant, highlighting potential issues with manual and digital record-keeping systems, with overall mean physical and electronic inventory accuracy rates of 74.7% and 70.6%, respectively. Additionally, the Report and Requisition Form (RRF) showed trends of timely submission, with the overall mean percentage completeness for the seven tracer medicines at 90.2%. However, the data quality experienced fluctuations, with the overall average percentage of legality (authorization of LMIS reports) and the accuracy of the RRF at 77.2% and 76%, respectively., Conclusion and Recommendation: The evaluation of data quality revealed significant discrepancies in physical and electronic records, with notable fluctuations in completeness, legality, legibility, and accuracy within the health LMIS. To rectify these issues, robust data quality verification processes, clear guidelines, targeted interventions, strengthened monitoring systems, regular audits, and comprehensive training for health supply chain staff are needed., Competing Interests: All authors declared that there are no competing interests., (© 2025 Mekonen et al.)

Objective: Retention to complete follow-up surveys in extensive longitudinal epidemiological cohort studies is vital yet challenging. All of Us developed pilot interventions to improve response rates for follow-up surveys., Study Design and Setting: The pilot interventions occurred from April 27, 2020, to August 3, 2020. The three arms were: (1) telephone appointment [staff members calling participants offering appointments to complete surveys over phone] (2) postal [mail reminder to complete surveys through U.S. Postal Service], and (3) combination of telephone appointment and postal. Controls received digital-only reminders [program-level digital recontact via email or through the participant portal]. Study sites chose their study arm and participants were not randomized., Results: A total of 50 sites piloted interventions with 17,593 participants, while 47,832 participants comprised controls during the same period. Of all participants, 6,828 (10.4%) completed any follow-up surveys (1448: telephone; 522: postal; 486: combination; 4372: controls). Follow-up survey completions were 24% higher in the telephone appointment arm than in controls in bivariate analyses. When controlling for confounders, telephone appointment and combination arms increased rates of completion similarly compared to controls, while the postal arm had no significant effect (odds ratio [95% Confidence Interval], telephone appointment:2.01[1.81-2.23]; combination:1.91[1.66-2.20]; postal:0.92[0.79-1.07]). Although the effects of the telephone appointment and combination arms were similar, differential effects were observed across sub-populations., Conclusion: Telephone appointments appeared to be the most successful intervention in our study. Lessons learned about retention interventions, and improvement in follow-up survey completion rates provide generalizable knowledge for similar cohort studies and demonstrate the potential value of precision reminders and engagement with sub-populations of a cohort., Competing Interests: NO authors have competing interests., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Objectives: This study aimed to evaluate the performance of vaccine logistics management information systems at public health facilities in Amhara Region, Ethiopia., Methods: An institution-based concurrent explanatory mixed design was used at public health facilities in Amhara Region, Ethiopia. In total, 102 health facilities were selected using the multi-stage, stratified, random-sampling proportionate-to-size method. Data were collected using a structured data abstraction checklist from vaccine logistics management information system records. Additionally, experiences of Expanded Program for Immunization focal persons were gathered through interviewer-administered questionnaires., Results: Among the 102 health facilities surveyed, 99 (97.1%) provided vaccination services during the study period. On the day of the visit, the average availability and utilization rates of 15 vaccine logistics management information system forms were 44.1% and 40.5%, respectively. The mean inventory accuracy for tracer vaccines stood at 58.3% ± 45.1%. The overall average accuracy percentages for urban and rural vaccine request form reports were 73.4% and 69.6%, respectively., Conclusions: The performance of vaccine logistics management information systems in these public health facilities was suboptimal. Key issues identified include inconsistent use of recording forms, shortages of reporting forms, lack of digitalization, poor data quality, and a shortage of qualified staff. These findings underscore the urgent need for standardization of the vaccine logistics management information system and enhancement of data quality.

Lung transplantation (LTx) outcomes are impeded by ischemia/reperfusion injury (IRI) and subsequent chronic lung allograft dysfunction (CLAD). We examined the undefined role of receptor Mer tyrosine kinase (MerTK) on monocytic myeloid-derived suppressor cells (M-MDSCs) in efferocytosis to facilitate resolution of lung IRI. Single-cell RNA sequencing of lung tissue and bronchoalveolar lavage (BAL) from patients after LTx were analyzed. Murine lung hilar ligation and allogeneic orthotopic LTx models of IRI were used with BALB/c (WT), Cebpb-/- (MDSC-deficient), Mertk-/-, or MerTK-cleavage-resistant mice. A significant downregulation in MerTK-related efferocytosis genes in M-MDSC populations of patients with CLAD was observed compared with healthy individuals. In the murine IRI model, a significant increase in M-MDSCs, MerTK expression, and efferocytosis and attenuation of lung dysfunction was observed in WT mice during injury resolution that was absent in Cebpb-/- and Mertk-/- mice. Adoptive transfer of M-MDSCs in Cebpb-/- mice significantly attenuated lung dysfunction and inflammation. Additionally, in a murine orthotopic LTx model, increases in M-MDSCs were associated with resolution of lung IRI in the transplant recipients. In vitro studies demonstrated the ability of M-MDSCs to efferocytose apoptotic neutrophils in a MerTK-dependent manner. Our results suggest that MerTK-dependent efferocytosis by M-MDSCs can substantially contribute to the resolution of post-LTx IRI.

Background: The COVID-19 pandemic led to the most substantial health crisis in the 21st Century. This pandemic interrupted the supply of essential commodities for human beings. Among the essential commodities for human survival, disruption of the supply of essential health commodities has become a global concern., Objective: The study aimed to systematically analyze published articles on the challenges, impacts, and prospects of the global health commodities' supply chain in the era of the COVID-19 pandemic., Methods: A standard searching strategy was conducted in seven research databases to retrieve pertinent articles. Finally, 459 articles were retrieved for further screening, and only 13 articles were selected for final synthesis., Results: Almost 38.5% of the studies targeted the supply chain of health commodities used to treat HIV, TB, and malaria. Lockdown policies, travel restrictions, lack of transportation, low manufacturing capacity, and rising costs were the significant challenges indicated for the supply interruption of essential health commodities and COVID-19 vaccines. Findings indicated that the supply interruption of essential health commodities leads to a devastating impact on global health., Conclusion: Global medicine shortages due to the pandemic crisis can have a devastatingly harmful impact on patient outcomes and might result in a devastatingly long-lasting effect on the health of the world community. Supply-related challenges of the COVID-19 vaccine affect countries' ambitions for achieving herd immunity quickly. Monitoring the pandemic's effect on the health commodities' supply system and designing a short-term and long-term resilient health supply chain system that can cope with current and future health catastrophes is pivotal., Competing Interests: All authors have declared that they have no competing interests in this work., (© 2024 Mekonen et al.)

Rationale: Patients with end stage lung diseases require lung transplantation (LTx) that can be impeded by ischemia-reperfusion injury (IRI) leading to subsequent chronic lung allograft dysfunction (CLAD) and inadequate outcomes., Objectives: We examined the undefined role of MerTK (receptor Mer tyrosine kinase) on monocytic myeloid-derived suppressor cells (M-MDSCs) in efferocytosis (phagocytosis of apoptotic cells) to facilitate resolution of lung IRI., Methods: Single-cell RNA sequencing of lung tissue and BAL from post-LTx patients was analyzed. Murine lung hilar ligation and allogeneic orthotopic LTx models of IRI were used with Balb/c (WT), cebpb -/- (MDSC-deficient), Mertk -/- or MerTK-CR (cleavage resistant) mice. Lung function, IRI (inflammatory cytokine and myeloperoxidase expression, immunohistology for neutrophil infiltration), and flow cytometry of lung tissue for efferocytosis of apoptotic neutrophils were assessed in mice., Measurements and Main Results: A significant downregulation in MerTK-related efferocytosis genes in M-MDSC populations of CLAD patients compared to healthy subjects was observed. In the murine IRI model, significant increase in M-MDSCs, MerTK expression and efferocytosis was observed in WT mice during resolution phase that was absent in cebpb -/- Land Mertk -/- mice. Adoptive transfer of M-MDSCs in cebpb -/- mice significantly attenuated lung dysfunction, and inflammation leading to resolution of IRI. Additionally, in a preclinical murine orthotopic LTx model, increases in M-MDSCs were associated with resolution of lung IRI in the transplant recipients. In vitro studies demonstrated the ability of M-MDSCs to efferocytose apoptotic neutrophils in a MerTK-dependent manner., Conclusions: Our results suggest that MerTK-dependent efferocytosis by M-MDSCs can significantly contribute to the resolution of post-LTx IRI.

Over 200 million SARS-CoV-2 patients have or will develop persistent symptoms (long COVID). Given this pressing research priority, the National COVID Cohort Collaborative (N3C) developed a machine learning model using only electronic health record data to identify potential patients with long COVID. We hypothesized that additional data from health surveys, mobile devices, and genotypes could improve prediction ability. In a cohort of SARS-CoV-2 infected individuals (n=17,755) in the All of Us program, we applied and expanded upon the N3C long COVID prediction model, testing machine learning infrastructures, assessing model performance, and identifying factors that contributed most to the prediction models. For the survey/mobile device information and genetic data, extreme gradient boosting and a convolutional neural network delivered the best performance for predicting long COVID, respectively. Combined survey, genetic, and mobile data increased specificity and the Area Under Curve the Receiver Operating Characteristic score versus the original N3C model., Competing Interests: Declarations The authors declared no competing interests for this work.

In response to the rapidly evolving coronavirus disease 2019 (COVID-19) pandemic, the All of Us Research Program longitudinal cohort study developed the COVID-19 Participant Experience (COPE) survey to better understand the pandemic experiences and health impacts of COVID-19 on diverse populations within the United States. Six survey versions were deployed between May 2020 and March 2021, covering mental health, loneliness, activity, substance use, and discrimination, as well as COVID-19 symptoms, testing, treatment, and vaccination. A total of 104,910 All of Us Research Program participants, of whom over 73% were from communities traditionally underrepresented in biomedical research, completed 275,201 surveys; 9,693 completed all 6 surveys. Response rates varied widely among demographic groups and were lower among participants from certain racial and ethnic minority populations, participants with low income or educational attainment, and participants with a Spanish language preference. Survey modifications improved participant response rates between the first and last surveys (13.9% to 16.1%, P < 0.001). This paper describes a data set with longitudinal COVID-19 survey data in a large, diverse population that will enable researchers to address important questions related to the pandemic, a data set that is of additional scientific value when combined with the program's other data sources., (© Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Many epidemiologic studies have identified important relationships between leukocyte telomere length (LTL) with genetics and health. Most of these studies have been significantly limited in scope by focusing predominantly on individual diseases or restricted to GWAS analysis. Using two large patient populations derived from Vanderbilt University and Marshfield Clinic biobanks linked to genomic and phenomic data from medical records, we investigated the inter-relationship between LTL, genomics, and human health. Our GWAS confirmed 11 genetic loci previously associated with LTL and two novel loci in SCNN1D and PITPNM1 . PheWAS of LTL identified 67 distinct clinical phenotypes associated with both short and long LTL. We demonstrated that several diseases associated with LTL were related to one another but were largely independent from LTL genetics. Age of death was correlated with LTL independent of age. Those with very short LTL (<-1.5 standard deviation [SD]) died 10.4 years (p < 0.0001) younger than those with average LTL (±0.5 SD; mean age of death = 74.2 years). Likewise, those with very long LTL (>1.5 SD) died 1.9 years (p = 0.0175) younger than those with average LTL. This is consistent with the PheWAS results showing diseases associating with both short and long LTL. Finally, we estimated that the genome (12.8%) and age (8.5%) explain the largest proportion of LTL variance, whereas the phenome (1.5%) and sex (0.9%) explained a smaller fraction. In total, 23.7% of LTL variance was explained. These observations provide the rationale for expanded research to understand the multifaceted correlations between TL biology and human health over time, leading to effective LTL usage in medical applications., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Introduction: There is little systematic tracking or detailed analysis of investments in research and development for blast injury to support decision-making around research future funding., Methods: This study examined global investments into blast injury-related research from public and philanthropic funders across 2000-2019. Research databases were searched using keywords, and open data were extracted from funder websites. Data collected included study title, abstract, award amount, funder and year. Individual awards were categorised to compare amounts invested into different blast injuries, the scientific approaches taken and analysis of research investment into blast traumatic brain injury (TBI)., Results: A total of 806 awards were identified into blast injury-related research globally, equating to US$902.1 million (m, £565.9m GBP). There was a general increase in year-on-year investment between 2003 and 2009 followed by a consistent decline in annual funding since 2010. Pre-clinical research received $671.3 m (74.4%) of investment. Brain-related injury research received $427.7 m (47.4%), orthopaedic injury $138.6 m (15.4%), eye injury $63.7 m (7.0%) and ear injury $60.5m (6.7%). Blast TBI research received a total investment of $384.3 m, representing 42.6% of all blast injury-related research. The U.S. Department of Defense funded $719.3 m (80%)., Conclusions: Investment data suggest that blast TBI research has received greater funding than other blast injury health areas. The funding pattern observed can be seen as reactive, driven by the response to the War on Terror, the rising profile of blast TBI and congressionally mandated research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study was to analyze a publicly available sample of rule-based phenotype definitions to characterize and evaluate the variability of logical constructs used., Materials and Methods: A sample of 33 preexisting phenotype definitions used in research that are represented using Fast Healthcare Interoperability Resources and Clinical Quality Language (CQL) was analyzed using automated analysis of the computable representation of the CQL libraries., Results: Most of the phenotype definitions include narrative descriptions and flowcharts, while few provide pseudocode or executable artifacts. Most use 4 or fewer medical terminologies. The number of codes used ranges from 5 to 6865, and value sets from 1 to 19. We found that the most common expressions used were literal, data, and logical expressions. Aggregate and arithmetic expressions are the least common. Expression depth ranges from 4 to 27., Discussion: Despite the range of conditions, we found that all of the phenotype definitions consisted of logical criteria, representing both clinical and operational logic, and tabular data, consisting of codes from standard terminologies and keywords for natural language processing. The total number and variety of expressions are low, which may be to simplify implementation, or authors may limit complexity due to data availability constraints., Conclusions: The phenotype definitions analyzed show significant variation in specific logical, arithmetic, and other operators but are all composed of the same high-level components, namely tabular data and logical expressions. A standard representation for phenotype definitions should support these formats and be modular to support localization and shared logic., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

While dietary fiber has been shown to influence the composition of gut microbiota and cognitive function in adults, much less is known about the fiber-microbiome-cognition association in children. We profiled gut microbiota using quantitative PCR (qPCR) and evaluated cognitive function using the Corsi block-tapping test (CBT) and the psychomotor vigilance test (PVT) before, during, and after the dietary intervention of 127 school-aged children in northern Thailand. While we found that Sinlek rice (SLR) consumption did not significantly alter the abundance of gut microbiota or the cognitive performance of school-aged children, we did find age to be associated with variations in both the gut microbiota profiles and cognitive outcomes. Gammaproteobacteria was significantly lower in the control and SLR groups during the middle time points of both phases (Weeks 4 and 61), and its abundance was associated with age. Cognitive performance using CBT and PVT were also found to be age-sensitive, as older children outperformed younger children on both of these cognitive assessments. Finally, a multiple factor analysis (MFA) revealed that age and cognitive performance best explain individual variation in this study. Collectively, these findings further describe the influence of host variables on the microbial profiles and cognitive outcomes of school-aged children consuming Sinlek rice in Thailand.

Competing Interests: None disclosed.

Purpose: The goal of Electronic Medical Records and Genomics (eMERGE) Phase III Network was to return actionable sequence variants to 25,084 consenting participants from 10 different health care institutions across the United States. The purpose of this study was to evaluate system-based issues relating to the return of results (RoR) disclosure process for clinical grade research genomic tests to eMERGE3 participants., Methods: RoR processes were developed and approved by each eMERGE institution's internal review board. Investigators at each eMERGE3 site were surveyed for RoR processes related to the participant's disclosure of pathogenic or likely pathogenic variants and engagement with genetic counseling. Standard statistical analysis was performed., Results: Of the 25,084 eMERGE participants, 1444 had a pathogenic or likely pathogenic variant identified on the eMERGEseq panel of 67 genes and 14 single nucleotide variants. Of these, 1077 (74.6%) participants had results disclosed, with 562 (38.9%) participants provided with variant-specific genetic counseling. Site-specific processes that either offered or required genetic counseling in their RoR process had an effect on whether a participant ultimately engaged with genetic counseling (P = .0052)., Conclusion: The real-life experience of the multiarm eMERGE3 RoR study for returning actionable genomic results to consented research participants showed the impact of consent, method of disclosure, and genetic counseling on RoR., Competing Interests: Conflicts of Interest R.C.G. receives compensation for advising AIA, Applied Therapeutics, Humanity, and Verily and is a cofounder of Genome Medical, Inc, a technology and services company providing genetics expertise to patients, providers, employers, and care systems. All other authors declare no conflicts of interest., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: Birth delivery method and breastfeeding practices contribute to microbiota colonization. Other factors including diet and demographic factors structure the gut microbiome assembly and diversity through childhood development. The exploration of these factors, especially in Southeast Asian children, remains limited., Methods: We investigated the fecal microbiota of 127 school-aged children in Thailand using quantitative PCR (qPCR) to assess the influence of diet and demographic factors on the gut microbiota. Multivariate analysis (multiple factor analysis (MFA) and Partial Least Squares Discriminant Analysis (PLS-DA)) were used to link particular gut microbes to diet and demographic factors., Results: Diet and demographic factors were associated with variation among gut microbiota. The abundance of Gammaproteobacteria increased in children with infrequent intake of high fat foods. Obese children possessed a lower level of Firmicutes and Ruminococcus . Bifidobacterium was enriched in pre-teen aged children and detected at lower levels among formula-fed children. Prevotella was more abundant in children who were delivered vaginally. While ethnicity explained a small amount of variation in the gut microbiota, it nonetheless was found to be significantly associated with microbiome composition., Conclusions: Exogenous and demographic factors associate with, and possibly drive, the assembly of the gut microbiome of an understudied population of school-aged children in Thailand., Competing Interests: Kongkiat Kespechara is the founder of Sooksatharana (Social Enterprise) Co., Ltd., (©2022 Gruneck et al.)

Background: Sequencing Mendelian arrhythmia genes in individuals without an indication for arrhythmia genetic testing can identify carriers of pathogenic or likely pathogenic (P/LP) variants. However, the extent to which these variants are associated with clinically meaningful phenotypes before or after return of variant results is unclear. In addition, the majority of discovered variants are currently classified as variants of uncertain significance, limiting clinical actionability., Methods: The eMERGE-III study (Electronic Medical Records and Genomics Phase III) is a multicenter prospective cohort that included 21 846 participants without previous indication for cardiac genetic testing. Participants were sequenced for 109 Mendelian disease genes, including 10 linked to arrhythmia syndromes. Variant carriers were assessed with electronic health record-derived phenotypes and follow-up clinical examination. Selected variants of uncertain significance (n=50) were characterized in vitro with automated electrophysiology experiments in HEK293 cells., Results: As previously reported, 3.0% of participants had P/LP variants in the 109 genes. Herein, we report 120 participants (0.6%) with P/LP arrhythmia variants. Compared with noncarriers, arrhythmia P/LP carriers had a significantly higher burden of arrhythmia phenotypes in their electronic health records. Fifty-four participants had variant results returned. Nineteen of these 54 participants had inherited arrhythmia syndrome diagnoses (primarily long-QT syndrome), and 12 of these 19 diagnoses were made only after variant results were returned (0.05%). After in vitro functional evaluation of 50 variants of uncertain significance, we reclassified 11 variants: 3 to likely benign and 8 to P/LP., Conclusions: Genome sequencing in a large population without indication for arrhythmia genetic testing identified phenotype-positive carriers of variants in congenital arrhythmia syndrome disease genes. As the genomes of large numbers of people are sequenced, the disease risk from rare variants in arrhythmia genes can be assessed by integrating genomic screening, electronic health record phenotypes, and in vitro functional studies., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier; NCT03394859.

Etiologies of HIV disparities are multifaceted; anti-LGBTQ stigma and social marginalization are contributory factors. A city health department developed a program, #ProjectPresence, exhibiting professional photos of Black LGBTQ persons in public spaces. An academic partner explored the relationship of the program to visibility, anti-LGBTQ stigma and social marginalization of Black LGBTQ persons, i.e. models, directly involved in the program and their perceptions of these relationships more broadly for community members. Brief self-administered surveys and semi-structured, in-depth interviews with #ProjectPresence models (n = 15) were conducted after the program to gather their experiences before, during and after the program. Descriptive analyses of survey responses were conducted using Stata 15.1. Interviews were audio-recorded, transcribed and analyzed in NVivo10 using categorical analysis. Surveys indicated prevalent experiences of enacted stigma (73 %) and perceptions of poor local acceptance of LGBTQ people (53 %). Interviews suggested that the program may have influenced positive individual- and community-level changes by increasing visibility of LGBTQ communities and improving acceptance among non-LGBTQ persons, inspiring personal growth and self-acceptance among models, and providing opportunities to foster new connections among LGBTQ subpopulations. Our findings suggest similar programs may present promising approaches for the reduction of stigma and social marginalization affecting LGBTQ persons and communities., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To describe the use of robotic-assisted transplant ureteral repair (RATUR) for treating transplant ureteral stricture (TUS) in 3 patients who had undergone robot assisted kidney transplant (RAKT)., Method: We reviewed the medical records of 3 patients who experienced TUS after RAKT and who underwent RATUR between 2017 and 2020. The patients' RAKT, post-transplant clinical course, endourological interventions, reoperation, and recovery were assessed., Results: All patients diagnosed with TUS presented with deterioration of kidney function after RAKT. Method of diagnosis included ultrasound, antegrade ureterogram, and CT scan. All 3 patients had a short (<1 cm) area of TUS and underwent RATUR. For 2 patients, distal strictures were bypassed with modified Lich-Gregoir ureteroneocystostomy reimplantation. One patient was treated with pyelo-ureterostomy to the contralateral native ureter. No intraoperative complications, conversions to open surgery, or significant operative blood loss requiring blood transfusion for any patient were observed. Also, no patients had urine leaks in the immediate or late postoperative period. After RATUR, 2 patients developed Clavien grade II complications with rectus hematoma or urinary tract infection., Conclusion: RATUR is a technically feasible operation for kidney transplant patients with TUS after RAKT. This procedure may provide the same benefits of open operation without promoting certain comorbidities that may occur from open surgical procedures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Blast injuries remain a serious threat to defence and civilian populations around the world. 'Primary' blast injuries (PBIs) are caused by direct blast wave interaction with the human body, particularly affecting air-containing organs. Work to define blast loading conditions for injury research has received relatively little attention, though with a continued experimental focus on PBIs and idealised explosion assumptions, meaningful test outcomes and subsequent clinical applications, rely on appropriate simulated conditions. This paper critically evaluates and combines existing PBI criteria (grouped into those affecting the auditory system, pulmonary injuries and brain trauma) as a function of idealised blast wave parameters. For clinical blast injury researchers, analysis of the multi-injury criteria indicates zones of appropriate loading conditions for human-scale test items and demonstrates the importance of simulating blast conditions that are both realistic and relevant to the injury type. For certain explosive scenarios, spatial interpretation of the 'zones of relevance' could support emergency response and hazard preparedness by informing triage, patient management and resource allocation, thus leading to improved health outcomes. This work will prove useful to clinical blast injury researchers, blast protection engineers and clinical practitioners involved in the triage, diagnosis, and treatment of PBIs., (Copyright © 2021. Published by Elsevier Ltd.)

Background & Aims: In contrast to most other common diseases, few genetic variants have been identified that impact risk of cirrhosis. We aimed to identify new genetic variants that predispose to cirrhosis, to test whether such variants, aggregated into a polygenic score, enable genomic risk stratification, and to test whether alcohol intake or body mass index interacts with polygenic predisposition., Methods: We conducted a multi-trait genome-wide association study combining cirrhosis and alanine aminotransferase levels performed in 5 discovery studies (UK Biobank, Vanderbilt BioVU, Atherosclerosis Risk in Communities study, and 2 case-control studies including 4829 individuals with cirrhosis and 72,705 controls and 362,539 individuals with alanine aminotransferase levels). Identified variants were replicated in 3 studies (Partners HealthCare Biobank, FinnGen, and Biobank Japan including 3554 individuals with cirrhosis and 343,826 controls). A polygenic score was tested in Partners HealthCare Biobank., Results: Five previously reported and 7 newly identified genetic variants were associated with cirrhosis in both the discovery studies multi-trait genome-wide association study (P < 5 × 10 -8 ) and the replication studies (P < .05), including a missense variant in the APOE gene and a noncoding variant near EFN1A. These 12 variants were used to generate a polygenic score. Among Partners HealthCare Biobank individuals, high polygenic score-defined as the top quintile of the distribution-was associated with significantly increased risk of cirrhosis (odds ratio, 2.26; P < .001) and related comorbidities compared with the lowest quintile. Risk was even more pronounced among those with extreme polygenic risk (top 1% of the distribution, odds ratio, 3.16; P < .001). The impact of extreme polygenic risk was substantially more pronounced in those with elevated alcohol consumption or body mass index. Modeled as risk by age 75 years, probability of cirrhosis with extreme polygenic risk was 13.7%, 20.1%, and 48.2% among individuals with no or modest, moderate, and increased alcohol consumption, respectively (P interaction < .001). Similarly, probability among those with extreme polygenic risk was 6.5%, 10.3%, and 19.5% among individuals with normal weight, overweight, and obesity, respectively (P interaction < .001)., Conclusions: Twelve independent genetic variants, 7 of which are newly identified in this study, conferred risk for cirrhosis. Aggregated into a polygenic score, these variants identified a subset of the population at substantially increased risk who are most susceptible to the hepatotoxic effects of excess alcohol consumption or obesity., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Dacarbazine chemotherapy has been the mainstay of melanoma treatment for >30 years. In the early 2000s, carboplatin (with or without other agents, such as paclitaxel) was the most commonly used second-line therapy in the UK. The aim of the present study was to report a significant response rate to second-line carboplatin in patients from three UK institutions who had been previously treated and failed to respond to dacarbazine, and investigate whether sequential therapy may be more effective compared with combination therapy. A total of 104 patients were identified, the majority of whom were treated with carboplatin (area under the curve 5-6) every 3 weeks for a maximum of 6 cycles. A total of 102 patients were evaluable for response, among whom 11 patients had an objective response (1 complete response and 10 partial responses) and 15 had stable disease, giving an overall response rate of 11% and disease control rate of 26%. The median progression-free survival was 1.8 months (range, 0.2-36+ months) and the median overall survival was 4.6 months (range, 0.2-36+ months). Surprisingly, the majority of the patients who benefited from second-line carboplatin therapy were those with visceral metastases, the survival of whom would not be expected to exceed 6 months after first-line treatment., (Copyright © 2020, Spandidos Publications.)

Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability., Methods: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease., Results: Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24-1.66]; P =1.6×10 -6 ), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97-1.15]; P =0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratio PRS , 1.26 [95% CI, 1.18-1.36]; P PRS =2.7×10 -11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratio PRS+family history+smoking , 1.24 [95% CI, 1.14-1.35]; P PRS =1.27×10 -6 ). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines., Conclusions: We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.

Analyzing 12,361 all-cause cirrhosis cases and 790,095 controls from eight cohorts, we identify a common missense variant in the Mitochondrial Amidoxime Reducing Component 1 gene (MARC1 p.A165T) that associates with protection from all-cause cirrhosis (OR 0.91, p = 2.3*10-11). This same variant also associates with lower levels of hepatic fat on computed tomographic imaging and lower odds of physician-diagnosed fatty liver as well as lower blood levels of alanine transaminase (-0.025 SD, 3.7*10-43), alkaline phosphatase (-0.025 SD, 1.2*10-37), total cholesterol (-0.030 SD, p = 1.9*10-36) and LDL cholesterol (-0.027 SD, p = 5.1*10-30) levels. We identified a series of additional MARC1 alleles (low-frequency missense p.M187K and rare protein-truncating p.R200Ter) that also associated with lower cholesterol levels, liver enzyme levels and reduced risk of cirrhosis (0 cirrhosis cases for 238 R200Ter carriers versus 17,046 cases of cirrhosis among 759,027 non-carriers, p = 0.04) suggesting that deficiency of the MARC1 enzyme may lower blood cholesterol levels and protect against cirrhosis., Competing Interests: CAE reports consulting fees from Navitor Pharma, Novartis and Deerfield Management. AVK has received research grants from IBM Research and the Novartis Institute for Biomedical Research and has served as a consultant to or received honoraria from Color Genomics, Illumina, Novartis, Maze Therapeutics, and Navitor Pharmaceuticals; and has a patent related to a genetic risk predictor (20190017119). SK is an employee of Verve Therapeutics and has received a research grant from Bayer Healthcare; and consulting fees from Merck, Novartis, Sanofi, AstraZeneca, Alnylam Pharmaceuticals, Leerink Partners, Noble Insights, MedGenome, Aegerion Pharmaceuticals, Regeneron Pharmaceuticals, Quest Diagnostics, Color Genomics, Genomics PLC, and Eli Lilly and Company; and holds equity in San Therapeutics, Catabasis Pharmaceuticals, Verve Therapeutics and Maze Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Patients with end-stage renal disease are at increased risk for psychiatric and cognitive pathologies. Despite this, there is little standardization of the psychosocial and/or psychiatric evaluation of renal transplant candidates. The purpose of this study is to report the frequency of psychiatric and cognitive pathologies and corresponding psychiatric recommendations in a sample of patients actively listed for kidney transplant., Methods: We performed a retrospective chart review of 104 patients listed for kidney transplant who underwent semistructured psychiatric assessments as part of a novel clinical protocol. Transplant psychiatry routinely administers brief screeners of cognitive functioning and health literacy, also collected from patients' charts., Results: There were a number of primary psychiatric disorders, including active substance abuse. Even using a conservative cutoff, 52.4% of patients' charts indicated evidence of cognitive impairment, and 28.9% indicated limited health literacy. In addition, there were numerous additional recommendations made within every category (educational, psychotherapeutic/psychiatric, cognitive, cessation of substance use, substance abuse treatment, and mobilizing support for transplant). With the exclusion of the recommendation for more education regarding the transplant process, most patients had at least 1 to 3 recommendations (n = 72, 69.2%)., Conclusions: We have identified a number of concerning psychosocial and psychiatric factors in patients who were evaluated and listed for kidney transplantation that can adversely impact transplant outcomes. The findings provide support for more in-depth and ongoing psychiatric assessments as standard clinical protocol for kidney transplant candidates., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: With its increasingly widespread adoption, electronic health records (EHR) have enabled phenotypic information extraction at an unprecedented granularity and scale. However, often a medical concept (e.g. diagnosis, prescription, symptom) is described in various synonyms across different EHR systems, hindering data integration for signal enhancement and complicating dimensionality reduction for knowledge discovery. Despite existing ontologies and hierarchies, tremendous human effort is needed for curation and maintenance - a process that is both unscalable and susceptible to subjective biases. This paper aims to develop a data-driven approach to automate grouping medical terms into clinically relevant concepts by combining multiple up-to-date data sources in an unbiased manner., Methods: We present a novel data-driven grouping approach - multi-view banded spectral clustering (mvBSC) combining summary data from multiple healthcare systems. The proposed method consists of a banding step that leverages the prior knowledge from the existing coding hierarchy, and a combining step that performs spectral clustering on an optimally weighted matrix., Results: We apply the proposed method to group ICD-9 and ICD-10-CM codes together by integrating data from two healthcare systems. We show grouping results and hierarchies for 13 representative disease categories. Individual grouping qualities were evaluated using normalized mutual information, adjusted Rand index, and F 1 -measure, and were found to consistently exhibit great similarity to the existing manual grouping counterpart. The resulting ICD groupings also enjoy comparable interpretability and are well aligned with the current ICD hierarchy., Conclusion: The proposed approach, by systematically leveraging multiple data sources, is able to overcome bias while maximizing consensus to achieve generalizability. It has the advantage of being efficient, scalable, and adaptive to the evolving human knowledge reflected in the data, showing a significant step toward automating medical knowledge integration., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: Postcraniotomy pain protocols use opioids, which are considered suboptimal analgesia following this procedure. Multimodal analgesia components are sparse. Our null hypothesis states that sumatriptan is not different to placebo in addition to usual intravenous opioids, for the treatment of acute postcraniotomy pain., Methods and Analysis: This is a prospective single-centre randomised double-blinded placebo-controlled phase III clinical trial comparing subcutaneous sumatriptan injection in the recovery area with placebo for the treatment of postcraniotomy pain. Eligible adult patients (18 years and older) undergoing craniotomy will be identified preoperatively. Both patient groups will receive a subcutaneous injection at a point where recovery-nursing staff would initiate the usual intravenous opioid analgesia as per standardised pain management protocol. In both groups, further pain management will be followed by the usual intravenous opioid administration. Primary outcome will consist of the difference in pain experienced by the two groups of patients in recovery area 60 min after the study drug administration. Postcraniotomy pain will be measured at regular intervals using the Visual Analogue Scale (VAS) in recovery area. The minimal clinically important difference of 10 mm on the VAS between the two groups will be considered as statistically significant. We will include selected clinical and patient-reported outcomes as secondary endpoints. Univariate regression will be conducted on each one of the clinically plausible potential confounders. We will enrol a total 136 patients, with the study duration of 2 years. This trial will commence recruitment on the 1 July 2019., Ethics and Dissemination: This trial protocol has achieved approval by the Austin Health Research Committee, HREC/17/Austin/596. This trial was prospectively registered with Australian New Zealand Clinical Trials Registry on the 10/05/2018 with a unique trial identifier U1111-1209-9072 and registration Number ACTRN12618000793213P. Findings of this study will be disseminated in peer-reviewed academic journals., Trial Registration Number: U1111-1209-9072, ACTRN12618000793213P., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare, chronic, inflammatory disorder with cutaneous and osteoarticular manifestations. 1 The aetiology of SAPHO syndrome is unknown and therefore treatment is tailored towards the individual. Non-steroidal anti-inflammatory drugs, bisphosphonates, corticosteriods, antibiotics, disease modifying anti-rheumatic drugs and biologics have all been used with variable success., (© Royal College of Physicians 2019. All rights reserved.)

Background: There is an urgent need for biomarkers to better stratify patients with idiopathic pulmonary fibrosis by risk for lung transplantation allocation who have the same clinical presentation. We aimed to investigate whether a specific immune cell type from patients with idiopathic pulmonary fibrosis could identify those at higher risk of poor outcomes. We then sought to validate our findings using cytometry and electronic health records., Methods: We first did a discovery analysis with transcriptome data from the Gene Expression Omnibus at the National Center for Biotechnology Information for 120 peripheral blood mononuclear cell (PBMC) samples of patients with idiopathic pulmonary fibrosis. We estimated percentages of 13 immune cell types using statistical deconvolution, and investigated the association of these cell types with transplant-free survival. We validated these results using PBMC samples from patients with idiopathic pulmonary fibrosis in two independent cohorts (COMET and Yale). COMET profiled monocyte counts in 45 patients with idiopathic pulmonary fibrosis from March 12, 2010, to March 10, 2011, using flow cytometry; we tested if increased monocyte count was associated with the primary outcome of disease progression. In the Yale cohort, 15 patients with idiopathic pulmonary fibrosis (with five healthy controls) were classed as high risk or low risk from April 28, 2014, to Aug 20, 2015, using a 52-gene signature, and we assessed whether monocyte percentage (measured by cytometry by time of flight) was higher in high-risk patients. We then examined complete blood count values in the electronic health records (EHR) of 45 068 patients with idiopathic pulmonary fibrosis, systemic sclerosis, hypertrophic cardiomyopathy, or myelofibrosis from Stanford (Jan 01, 2008, to Dec 31, 2015), Northwestern (Feb 15, 2001 to July 31, 2017), Vanderbilt (Jan 01, 2008, to Dec 31, 2016), and Optum Clinformatics DataMart (Jan 01, 2004, to Dec 31, 2016) cohorts, and examined whether absolute monocyte counts of 0·95 K/μL or greater were associated with all-cause mortality in these patients., Findings: In the discovery analysis, estimated CD14+ classical monocyte percentages above the mean were associated with shorter transplant-free survival times (hazard ratio [HR] 1·82, 95% CI 1·05-3·14), whereas higher percentages of T cells and B cells were not (0·97, 0·59-1·66; and 0·78, 0·45-1·34 respectively). In two validation cohorts (COMET trial and the Yale cohort), patients with higher monocyte counts were at higher risk for poor outcomes (COMET Wilcoxon p=0·025; Yale Wilcoxon p=0·049). Monocyte counts of 0·95 K/μL or greater were associated with mortality after adjusting for forced vital capacity (HR 2·47, 95% CI 1·48-4·15; p=0·0063), and the gender, age, and physiology index (HR 2·06, 95% CI 1·22-3·47; p=0·0068) across the COMET, Stanford, and Northwestern datasets). Analysis of medical records of 7459 patients with idiopathic pulmonary fibrosis showed that patients with monocyte counts of 0·95 K/μL or greater were at increased risk of mortality with lung transplantation as a censoring event, after adjusting for age at diagnosis and sex (Stanford HR=2·30, 95% CI 0·94-5·63; Vanderbilt 1·52, 1·21-1·89; Optum 1·74, 1·33-2·27). Likewise, higher absolute monocyte count was associated with shortened survival in patients with hypertrophic cardiomyopathy across all three cohorts, and in patients with systemic sclerosis or myelofibrosis in two of the three cohorts., Interpretation: Monocyte count could be incorporated into the clinical assessment of patients with idiopathic pulmonary fibrosis and other fibrotic disorders. Further investigation into the mechanistic role of monocytes in fibrosis might lead to insights that assist the development of new therapies., Funding: Bill & Melinda Gates Foundation, US National Institute of Allergy and Infectious Diseases, and US National Library of Medicine., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Competing interests: None declared.

In systemic lupus erythematosus (SLE), dsDNA antibodies are associated with renal disease. Less is known about comorbidities in patients without dsDNA or other autoantibodies. Using an electronic health record (EHR) SLE cohort, we employed a phenome-wide association study (PheWAS) that scans across billing codes to compare comorbidities in SLE patients with and without autoantibodies. We used our validated algorithm to identify SLE subjects. Autoantibody status was defined as ever positive for dsDNA, RNP, Smith, SSA and SSB. PheWAS was performed in antibody positive vs. negative SLE patients adjusting for age and race and using a false discovery rate of 0.05. We identified 1097 SLE subjects. In the PheWAS of dsDNA positive vs. negative subjects, dsDNA positive subjects were more likely to have nephritis ( p = 2.33 × 10 -9 ) and renal failure ( p = 1.85 × 10 -5 ). After adjusting for sex, race, age and other autoantibodies, dsDNA was independently associated with nephritis and chronic kidney disease. Those patients negative for dsDNA, RNP, SSA and SSB negative subjects were all more likely to have billing codes for sleep, pain and mood disorders. PheWAS uncovered a hierarchy within SLE-specific autoantibodies with dsDNA having the greatest impact on major organ involvement.

This study investigates the inter-tester repeatability of an upper limb direct kinematic (ULDK) model specifically for the reporting of elbow flexion-extension (FE) during overhead sporting movements, such as cricket bowling. The ULDK model consists of an upper arm and a forearm connected with a 6° of freedom elbow joint. The ULDK model was assessed for inter-tester repeatability by calculating elbow FE during cricket bowling in two sessions, with unique testers applying the kinematic marker set in each session. Analysis of both elbow FE time-varying waveforms (statistical parametric mapping = 0% time different) and extracted discrete events (no statistical differences, strong correlations > 0.9) support that this model is inter-tester repeatable at assessing elbow FE within the context of cricket bowling. This model is recommended as a framework in future studies for measuring elbow kinematics during other overhead sporting tasks, with recommendations for further participant-specific considerations. Graphical abstract ᅟ.

Hyperemesis gravidarum is a common condition characterised by severe nausea and vomiting. The referral process from the emergency department (ED) to obstetrics and gynaecology (O&G) can lead to treatment delays before the gynaecology team review the patient, resulting in unnecessary prolonged inpatient stays in O&G. This quality improvement project created a clinical pathway which optimised care of patients presenting with hyperemesis gravidarum in the ED at the Princess Royal University Hospital using a treatment protocol. Two audits were carried out to assess improvements in patient care and reduction in admissions to O&G. Overall, admissions to O&G were reduced by 68.7% (cycle 1) and 70.5% (cycle 2) compared with admission rates before the proforma, saving the trust an estimated £265 700 and 235 bed days over a year., Competing Interests: Competing interests: None declared.

Crowdsourcing services like Amazon Mechanical Turk allow researchers to ask questions to crowds of workers and quickly receive high quality labeled responses. However, crowds drawn from the general public are not suitable for labeling sensitive and complex data sets, such as medical records, due to various concerns. Major challenges in building and deploying a crowdsourcing system for medical data include, but are not limited to: managing access rights to sensitive data and ensuring data privacy controls are enforced; identifying workers with the necessary expertise to analyze complex information; and efficiently retrieving relevant information in massive data sets. In this paper, we introduce a crowdsourcing framework to support the annotation of medical data sets. We further demonstrate a workflow for crowdsourcing clinical chart reviews including (1) the design and decomposition of research questions; (2) the architecture for storing and displaying sensitive data; and (3) the development of tools to support crowd workers in quickly analyzing information from complex data sets.

Less than 3% of protein-coding genetic variants are predicted to result in loss of protein function through the introduction of a stop codon, frameshift, or the disruption of an essential splice site; however, such predicted loss-of-function (pLOF) variants provide insight into effector transcript and direction of biological effect. In >400,000 UK Biobank participants, we conduct association analyses of 3759 pLOF variants with six metabolic traits, six cardiometabolic diseases, and twelve additional diseases. We identified 18 new low-frequency or rare (allele frequency < 5%) pLOF variant-phenotype associations. pLOF variants in the gene GPR151 protect against obesity and type 2 diabetes, in the gene IL33 against asthma and allergic disease, and in the gene IFIH1 against hypothyroidism. In the gene PDE3B, pLOF variants associate with elevated height, improved body fat distribution and protection from coronary artery disease. Our findings prioritize genes for which pharmacologic mimics of pLOF variants may lower risk for disease.

The yeast Candida parapsilosis is an increasingly common cause of systemic fungal infections among immunocompromised individuals, including premature infants. Adhesion to host surfaces is an important step in pathogenesis, but this process has not been extensively studied in this organism. A microfluidics assay was developed to test the ability of C. parapsilosis to adhere to immobilized host extracellular matrix proteins under physiological fluid shear conditions. Growth in mammalian tissue culture medium at 37°C for 3 to 6 h led to the induction of an adhesive phenotype at shear forces of 1 to 5 dynes/cm 2 in some isolates of C. parapsilosis Glutamic acid, proline, and calcium appeared to be the minimally necessary requirements for increased adhesion in these assays. To determine whether genes homologous to the ALS gene family of C. albicans were important for the adhesive phenotype, the expression levels of 5 homologous C. parapsilosis genes were quantified by using quantitative PCR (qPCR) under conditions leading to increased adhesion. CPAR2&#95;404800 ( CpALS7 ) and CPAR2&#95;404780 showed increased expression levels compared to those in control yeast. The extent of adhesion was variable among different isolates, and linear regression identified the expression of CpALS7 but not CPAR2&#95;404780 as having a strong positive correlation with adhesion. A homozygous CpALS7 deletion strain was deficient in adhesion, whereas the expression of CpALS7 in Saccharomyces cerevisiae resulted in increased adhesion. Together, these data provide strong evidence that CpAls7 aids in the adherence of C. parapsilosis to the extracellular matrix under shear forces and support its previously reported role in virulence., (Copyright © 2018 American Society for Microbiology.)

Objective: Birth month and climate impact lifetime disease risk, while the underlying exposures remain largely elusive. We seek to uncover distal risk factors underlying these relationships by probing the relationship between global exposure variance and disease risk variance by birth season., Material and Methods: This study utilizes electronic health record data from 6 sites representing 10.5 million individuals in 3 countries (United States, South Korea, and Taiwan). We obtained birth month-disease risk curves from each site in a case-control manner. Next, we correlated each birth month-disease risk curve with each exposure. A meta-analysis was then performed of correlations across sites. This allowed us to identify the most significant birth month-exposure relationships supported by all 6 sites while adjusting for multiplicity. We also successfully distinguish relative age effects (a cultural effect) from environmental exposures., Results: Attention deficit hyperactivity disorder was the only identified relative age association. Our methods identified several culprit exposures that correspond well with the literature in the field. These include a link between first-trimester exposure to carbon monoxide and increased risk of depressive disorder (R = 0.725, confidence interval [95% CI], 0.529-0.847), first-trimester exposure to fine air particulates and increased risk of atrial fibrillation (R = 0.564, 95% CI, 0.363-0.715), and decreased exposure to sunlight during the third trimester and increased risk of type 2 diabetes mellitus (R = -0.816, 95% CI, -0.5767, -0.929)., Conclusion: A global study of birth month-disease relationships reveals distal risk factors involved in causal biological pathways that underlie them., (© The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

A recent quantitative review in the area of stigma and help seeking in the armed forces has questioned the association between these factors (Sharp et al. 2015). To date, the contribution of qualitative literature in this area has largely been ignored, despite the value this research brings to the understanding of complex social constructs such as stigma. The aim of the current systematic review of qualitative studies was to identify appropriate literature, assess the quality and synthesize findings across studies regarding evidence of stigma-related barriers and facilitators to help seeking for mental health issues within the armed forces. A multi-database text word search incorporating searches of PsycINFO, MEDLINE, Social Policy and Practice, Social Work Abstracts, EMBASE, ERIC and EBM Review databases between 1980 and April 2015 was conducted. Literature was quality assessed using the Critical Appraisal Skills Programme tool. Thematic synthesis was conducted across the literature. The review identified eight studies with 1012 participants meeting the inclusion criteria. Five overarching themes were identified across the literature: (1) non-disclosure; (2) individual beliefs about mental health; (3) anticipated and personal experience of stigma; (4) career concerns; and (5) factors influencing stigma. The findings from the current systematic review found that unlike inconsistent findings in the quantitative literature, there was substantial evidence of a negative relationship between stigma and help seeking for mental health difficulties within the armed forces. The study advocates for refinement of measures to accurately capture the complexity of stigma and help seeking in future quantitative studies.

Objectives: Electronic health records (EHRs) have increasingly emerged as a powerful source of clinical data that can be leveraged for reuse in research and in modular health apps that integrate into diverse health information technologies. A key challenge to these use cases is representing the knowledge contained within data from different EHR systems in a uniform fashion. Method: We reviewed several recent studies covering the knowledge representation in the common data models for the Observational Medical Outcomes Partnership (OMOP) and its Observational Health Data Sciences and Informatics program, and the United States Patient Centered Outcomes Research Network (PCORNet). We also reviewed the Health Level 7 Fast Healthcare Interoperability Resource standard supporting app-like programs that can be used across multiple EHR and research systems. Results: There has been a recent growth in high-impact efforts to support quality-assured and standardized clinical data sharing across different institutions and EHR systems. We focused on three major efforts as part of a larger landscape moving towards shareable, transportable, and computable clinical data. Conclusion: The growth in approaches to developing common data models to support interoperable knowledge representation portends an increasing availability of high-quality clinical data in support of research. Building on these efforts will allow a future whereby significant portions of the populations in the world may be able to share their data for research., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart.)

Electronic health records (EHRs) linked with biobanks have been recognized as valuable data sources for pharmacogenomic studies, which require identification of patients with certain adverse drug reactions (ADRs) from a large population. Since manual chart review is costly and time-consuming, automatic methods to accurately identify patients with ADRs have been called for. In this study, we developed and compared different informatics approaches to identify ADRs from EHRs, using clopidogrel-induced bleeding as our case study. Three different types of methods were investigated: 1) rule-based methods; 2) machine learning-based methods; and 3) scoring function-based methods. Our results show that both machine learning and scoring methods are effective and the scoring method can achieve a high precision with a reasonable recall. We also analyzed the contributions of different types of features and found that the temporality information between clopidogrel and bleeding events, as well as textual evidence from physicians' assertion of the adverse events are helpful. We believe that our findings are valuable in advancing EHR-based pharmacogenomic studies.

Addressing minority health and health disparities has been a missing piece of the puzzle in Big Data science. This article focuses on three priority opportunities that Big Data science may offer to the reduction of health and health care disparities. One opportunity is to incorporate standardized information on demographic and social determinants in electronic health records in order to target ways to improve quality of care for the most disadvantaged populations over time. A second opportunity is to enhance public health surveillance by linking geographical variables and social determinants of health for geographically defined populations to clinical data and health outcomes. Third and most importantly, Big Data science may lead to a better understanding of the etiology of health disparities and understanding of minority health in order to guide intervention development. However, the promise of Big Data needs to be considered in light of significant challenges that threaten to widen health disparities. Care must be taken to incorporate diverse populations to realize the potential benefits. Specific recommendations include investing in data collection on small sample populations, building a diverse workforce pipeline for data science, actively seeking to reduce digital divides, developing novel ways to assure digital data privacy for small populations, and promoting widespread data sharing to benefit under-resourced minority-serving institutions and minority researchers. With deliberate efforts, Big Data presents a dramatic opportunity for reducing health disparities but without active engagement, it risks further widening them., Competing Interests: Competing Interests: None declared.