Protein-S Deficiency Diagnosed Post-ACL Injury in a Collegiate Track and Field Athlete

OBJECTIVES 1.Summarize details of unique case involving undiagnosed clotting disorder in a collegiate athlete. 2.Present overview regarding mechanism and epidemiology of protein S deficiency. 3.Identify the role of the certified athletic trainer in the evaluation and treatment process, and as a patient advocate. 4.Emphasize importance of trust and communication between athlete, certified athletic trainer, and team physician throughout evaluation and treatment

Minimum Description Length Control

We propose a novel framework for multitask reinforcement learning based on the minimum description length (MDL) principle. In this approach, which we term MDL-control (MDL-C), the agent learns the common structure among the tasks with which it is faced and then distills it into a simpler representation which facilitates faster convergence and generalization to new tasks. In doing so, MDL-C naturally balances adaptation to each task with epistemic uncertainty about the task distribution. We motivate MDL-C via formal connections between the MDL principle and Bayesian inference, derive theoretical performance guarantees, and demonstrate MDL-C's empirical effectiveness on both discrete and high-dimensional continuous control tasks

Evidence-Based Genetics and Identification of Key Human Alzheimer’s Disease Alleles with Co-morbidities

Advancements in biomedical research have contributed to increasing the life expectancy of humans, but we now observe an increase in age-related diseases such as Alzheimer’s disease. Genome-Wide Association Studies (GWAS) and linkage studies have identified human genes associated with Alzheimer’s disease (referred to as AD genes). A previous study by Vahdati in 2017 has revealed the human AD genes and counterparts in model species [1]. Thus, we further investigate the co-morbidity genes and alleles. Using ontology analysis combined with cluster analysis, the study identified functional pathways enriched among the human AD genes, including 179 genes out of 695 human AD genes (26%) that were associated with one or more of the four neurological diseases including Amyotrophic lateral sclerosis, Multiple sclerosis, Parkinson’s disease, and Schizophrenia [1]. More importantly, the results indicate co-morbidities with Late-Onset Alzheimer’s Disease (LOAD) and other neurological conditions, implying the complexity of the phenotypes in the human AD. The co-morbidity genes may account for mixed symptoms for human AD as well as age-related risks of infections. Of them, the three genes are well conserved (Angiotensin I Converting Enzyme gene, ACE; Methylenetetrahydrofolate Reductase gene, MTHFR; and tumor necrosis factor gene, TNF). In this study, we confirmed the comorbidity of the three genes associated with AD. We further identified the comorbidity of two alleles in the MTHFR gene, C677T and A222V, significantly associated with Alzheimer’s disease. This study provides an example of evidencebased analysis that is cost-effective and may be an effective approach to develop cure-alls for multiple diseases

Guideline concordance for timely chest imaging after new presentations of dyspnoea or haemoptysis in primary care: a retrospective cohort study

BACKGROUND: Guidelines recommend urgent chest X-ray for newly presenting dyspnoea or haemoptysis but there is little evidence about their implementation. METHODS: We analysed linked primary care and hospital imaging data for patients aged 30+ years newly presenting with dyspnoea or haemoptysis in primary care during April 2012 to March 2017. We examined guideline-concordant management, defined as General Practitioner-ordered chest X-ray/CT carried out within 2 weeks of symptomatic presentation, and variation by sociodemographic characteristic and relevant medical history using logistic regression. Additionally, among patients diagnosed with cancer we described time to diagnosis, diagnostic route and stage at diagnosis by guideline-concordant status. RESULTS: In total, 22 560/162 161 (13.9%) patients with dyspnoea and 4022/8120 (49.5%) patients with haemoptysis received guideline-concordant imaging within the recommended 2-week period. Patients with recent chest imaging pre-presentation were much less likely to receive imaging (adjusted OR 0.16, 95% CI 0.14-0.18 for dyspnoea, and adjusted OR 0.09, 95% CI 0.06-0.11 for haemoptysis). History of chronic obstructive pulmonary disease/asthma was also associated with lower odds of guideline concordance (dyspnoea: OR 0.234, 95% CI 0.225-0.242 and haemoptysis: 0.88, 0.79-0.97). Guideline-concordant imaging was lower among dyspnoea presenters with prior heart failure; current or ex-smokers; and those in more socioeconomically disadvantaged groups.The likelihood of lung cancer diagnosis within 12 months was greater among the guideline-concordant imaging group (dyspnoea: 1.1% vs 0.6%; haemoptysis: 3.5% vs 2.7%). CONCLUSION: The likelihood of receiving urgent imaging concords with the risk of subsequent cancer diagnosis. Nevertheless, large proportions of dyspnoea and haemoptysis presenters do not receive prompt chest imaging despite being eligible, indicating opportunities for earlier lung cancer diagnosis

HOIL1 regulates group 2 innate lymphoid cell numbers and type 2 inflammation in the small intestine

Patients with mutations in HOIL1 experience a complex immune disorder including intestinal inflammation. To investigate the role of HOIL1 in regulating intestinal inflammation, we employed a mouse model of partial HOIL1 deficiency. The ileum of HOIL1-deficient mice displayed features of type 2 inflammation including tuft cell and goblet cell hyperplasia, and elevated expression of Il13, Il5 and Il25 mRNA. Inflammation persisted in the absence of T and B cells, and bone marrow chimeric mice revealed a requirement for HOIL1 expression in radiation-resistant cells to regulate inflammation. Although disruption of IL-4 receptor alpha (IL4Rα) signaling on intestinal epithelial cells ameliorated tuft and goblet cell hyperplasia, expression of Il5 and Il13 mRNA remained elevated. KLRG

Does clinical management improve outcomes following self-Harm? Results from the multicentre study of self-harm in England

Background Evidence to guide clinical management of self-harm is sparse, trials have recruited selected samples, and psychological treatments that are suggested in guidelines may not be available in routine practice. Aims To examine how the management that patients receive in hospital relates to subsequent outcome. Methods We identified episodes of self-harm presenting to three UK centres (Derby, Manchester, Oxford) over a 10 year period (2000 to 2009). We used established data collection systems to investigate the relationship between four aspects of management (psychosocial assessment, medical admission, psychiatric admission, referral for specialist mental health follow up) and repetition of self-harm within 12 months, adjusted for differences in baseline demographic and clinical characteristics. Results 35,938 individuals presented with self-harm during the study period. In two of the three centres, receiving a psychosocial assessment was associated with a 40% lower risk of repetition, Hazard Ratios (95% CIs): Centre A 0.99 (0.90–1.09); Centre B 0.59 (0.48–0.74); Centre C 0.59 (0.52–0.68). There was little indication that the apparent protective effects were mediated through referral and follow up arrangements. The association between psychosocial assessment and a reduced risk of repetition appeared to be least evident in those from the most deprived areas. Conclusion These findings add to the growing body of evidence that thorough assessment is central to the management of self-harm, but further work is needed to elucidate the possible mechanisms and explore the effects in different clinical subgroups

Deep learning quantification of percent steatosis in donor liver biopsy frozen sections

BACKGROUND: Pathologist evaluation of donor liver biopsies provides information for accepting or discarding potential donor livers. Due to the urgent nature of the decision process, this is regularly performed using frozen sectioning at the time of biopsy. The percent steatosis in a donor liver biopsy correlates with transplant outcome, however there is significant inter- and intra-observer variability in quantifying steatosis, compounded by frozen section artifact. We hypothesized that a deep learning model could identify and quantify steatosis in donor liver biopsies. METHODS: We developed a deep learning convolutional neural network that generates a steatosis probability map from an input whole slide image (WSI) of a hematoxylin and eosin-stained frozen section, and subsequently calculates the percent steatosis. Ninety-six WSI of frozen donor liver sections from our transplant pathology service were annotated for steatosis and used to train (n = 30 WSI) and test (n = 66 WSI) the deep learning model. FINDINGS: The model had good correlation and agreement with the annotation in both the training set (r of 0.88, intraclass correlation coefficient [ICC] of 0.88) and novel input test sets (r = 0.85 and ICC=0.85). These measurements were superior to the estimates of the on-service pathologist at the time of initial evaluation (r = 0.52 and ICC=0.52 for the training set, and r = 0.74 and ICC=0.72 for the test set). INTERPRETATION: Use of this deep learning algorithm could be incorporated into routine pathology workflows for fast, accurate, and reproducible donor liver evaluation. FUNDING: Mid-America Transplant Society

Cost-effectiveness of Different Advanced Life Support Providers for Victims of Out-of-hospital Cardiac Arrests

Background/purposeThe survival rate of out-of-hospital cardiac arrest (OHCA) is only about 1.4% in Taiwan. The best configuration to achieve optimal outcomes in OHCA is still uncertain for many communities. The purpose of this study was to investigate the cost-effectiveness of two models of providing advanced life support (ALS) services, emergency medical technicians (EMTs) vs. emergency physicians (EPs), in a two-tiered emergency medical services (EMS) system.MethodsThis was a prospective, observational, multicenter study comparing ALS provided by EMTs vs. EPs for the management of victims of OHCA. The study population consisted of patients experiencing OHCA of non-traumatic origin in Taipei city, Taiwan, between November 1999 and December 2000, for whom ALS was activated. We performed a cost-effectiveness analysis to determine the economic attractiveness of these two ALS provider programs. The outcome measurements were aggregate costs, survival and incremental cost per life saved. Sensitivity analyses were performed on all variables.ResultsThe expected total cost per OHCA patient was US$2248.19 and US$832.07 for the EMT and EP programs, respectively. The overall survival rate was 4.4%. The survival rate was 9.3% for the EMT program and 2.6% for the EP program. The incremental cost-effectiveness ratio (ICER) of EMTs vs. EPs was US$21,136 per life saved. The ICER was sensitive to hospital admission cost changes and the probability of survival to discharge in patients admitted to hospital in the EMT program. The increased survival rate of OHCA patients in the EMT program may be attributable to the services of the hospital and/or the EMT program.ConclusionThe use of EMTs as ALS care providers for OHCA patients in the two-tiered EMS system resulted in a reasonable cost-effectiveness ratio. EMTs could be considered as the second tier of EMS systems in urban areas in Taiwan

Planned Parenthood: LGBTQ Healthcare in Southern New England

The LGBTQ community experiences health disparities related to access to care, utilization of care, experiences of discrimination, perceptions of injustice, healthcare neglect, and inappropriate care. In addition, statistics often cite higher rates of some health outcomes, such as higher rates of mental illness and substance use in the LGBTQ community at large and HIV/AIDS for transgender women and gay and queer men (Alvy et al., 2011; Cochran et al., 2003; Coulter et al., 2015). These disparities in health and healthcare stand as an emergency beacon to both community members and organizations aimed to serve them. Organizations throughout Connecticut and Rhode Island, such as AIDS Project New Haven, True Colors in Hartford, Triangle Community Center in Norwalk, and SAGE in Providence advocate and work toward the better health of these organizations. But the question of what healthcare needs and desires among LGBTQ community members are not being met by local organizations remains uncertain. This report highlights health disparities and needs among the LGBTQ community using both previous research and the voices of community members. Through highlighting the health care experiences of community members, we illuminate some key factors that influence the health outcomes and thoughts around healthcare within the LGBTQ community. Several of the recommendations and thoughts regarding the expansion and changes to PPSNE are simple, yet poignant fixes to strengthen the comfort and confidence levels of PPSNE staff and providers into the highly comfortable strata found in the survey. This cyclical relationship between providers and patients offers a new and expansive market and community access to Planned Parenthood, with another, often expansive healthcare organization to provide care to community members. Other Planned Parenthood locations throughout the United States offer services and amplify access through specific marketing campaigns to LGBTQ community members. Utilizing these models and heeding the suggestions of community members can offer potential success to both parties, as well as potentially working toward intangible goals, like reducing stigma, increasing awareness, and spreading positive health outcomes throughout the LGBTQ community and the general community. We encourage Planned Parenthood of Southern New England to consider these these steps, and believe that doing so will improve the health status of many LGBTQ community members by dramatically increasing both accessibility and demand for high quality clinical services at PPSNE.https://elischolar.library.yale.edu/ysph_pbchrr/1051/thumbnail.jp