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The design of heliostats throughout a concentrated solar power (CSP) plant are currently of uniform design, however, research into the variation in heliostat wind loading within a radially staggered field array can provide insight into potential material cost savings in heliostat field design. Experimental investigation was carried out on a field array model in the University of Adelaide large wind tunnel. A total of 64 heliostat models of size 0.1 × 0.1 m were radially arranged over four surround rows. Four 3-axis load cells were utilized to analyze field array cases of morning (0700 hours), noon (1200 hours), and evening (1700 hours) configurations. Angle calculations for beam reflection were made for the 21st March (equinox). Results show mean and peak drag force coefficients reduce with distance into the field for a 1700 hour case due to high upstream blockage. Comparing the downstream drag and lift force coefficients against each test configuration, when heliostats are at steep elevation angles, high flow blockage leads to a reduction of coefficients downstream (0700 hour and 1700 hour cases). When elevation angles are reduced (1200 hours), drag and lift coefficients increase with distance from the central tower in the downstream direction. Results also show the central tower increases load coefficients on downstream heliostats, and therefore should be considered in heliostat wind loading and field design.

This study analyses the turbulent wind properties in the lower 10 m of the atmospheric surface layer close to the ground where heliostats are located. Power spectral densities of streamwise and vertical components of wind are analysed, and the frequencies associated with the peak of the spectra are determined using field data collected at two open-country terrains in addition to spectral models of ESDU85020. Variations of the peak frequencies with height from the ground, terrain type and average wind speed are discussed and the impact on heliostat wind loads are described. It is found that while the peak frequency of the streamwise turbulence is between 0.01–0.1 Hz, the peak of the vertical turbulence occurs at frequencies in the range of 0.1–1 Hz. It is shown that smaller heliostats that are located closer to the ground are exposed to turbulent wind fluctuations at a higher frequency and are thus expected to experience wind loads with a higher dominant frequency compared to larger heliostats located higher above the ground. These frequencies need to be considered in design of heliostat drives and structural components

The Heliostat Consortium (HelioCon) Wind Load Subtask was initiated with the aim of bringing research work pertaining to wind load measurement, characterization, and prediction taking place across several tasks, including Advanced Manufacturing, Components and Controls, and Field Deployment. The cross-cutting wind load subtopic in the HelioCon roadmap report [1] highlighted standardized methods and tools that are needed for a more detailed understanding of the static and dynamic loads on a heliostat. This will enable cost reduction of wind-dependent heliostat components to avoid unnecessarily conservative, overly constrained designs and increase field efficiency/reliability, to reduce the risk of component failures due to high-wind events (>15 m/s). Gaps related to heliostat wind load include site characterization for wind measurements, critical load cases for heliostat design, turbulence impacts on heliostat tracking error, testing of heliostat array configurations, understanding spatial variation of maximum loads across the solar field, and heliostat field layout and operating strategies. The recommended highest-priority pathway as first steps taken by HelioCon to address these gaps are to develop site characterization guidelines for heliostat design and field load measurements.

This study investigated high-frequency load fluctuations on a rectangular heliostat model in a boundary layer wind tunnel experiment. Statistical methods for peak wind load predictions were compared with load distributions through load cell and surface pressure measurements on the heliostat model placed in two simulated atmospheric boundary layers (ABLs) representing a flat desert terrain and open country terrain. It was found that statistical peak predictions based on horizontal wind gust velocity amplitude underestimates the load coefficients in stow and at oblique azimuth angles for maximum azimuth moments. In addition, it was shown that the distributions of the centre of pressure position and the hinge moment in stow position are non-Gaussian. It is therefore recommended that the frequency and amplitude of the vertical wind velocity component must be considered for peak load predictions of hinge moments and azimuth moments.

Compassion towards oneself and towards others has been associated with positive psychological outcomes, however, research is limited by the availability of valid psychometric measures, particularly in languages other than English. The current study translated (English to French) and validated the following measures: the Compassionate Engagement and Action Scales (CEAS), assessing self-compassion (CEAS-SC), compassion to others (CEAS-TO), and compassion from others (CEAS-FROM); the Compassion Scale (CS); and the Sussex-Oxford Compassion Scales for Self (SOCS-S) and Others (SOCS-O). French-speaking participants were recruited online (N = 384) and completed the translated measures as well as questionnaires assessing self-compassion, depression, anxiety, stress, insecure attachment, mindfulness, and well-being. Confirmatory Factor Analysis supports the original factor structures proposed for the CEAS-FROM (two-factor hierarchical), CS (four-factor hierarchical), SOCS-S and SOCS-O (five-factor hierarchical), with alternate factor structures proposed for CEAS-SC (three-factor) and CEAS-TO (two-factor). Results showed good internal consistency and convergent validity for all scales, supporting the use of total scores for the translated measures.

In the article [CEGS20b], we introduced various moduli stacks of two-dimensional tamely potentially Barsotti–Tate representations of the absolute Galois group of a p-adic local field, as well as related moduli stacks of Breuil–Kisin modules with descent data. We study the irreducible components of these stacks, establishing, in particular, that the components of the former are naturally indexed by certain Serre weights.

The University of Adelaide has recently commissioned a facility dedicated to investigating the atmospheric boundary layer (ABL) for the analysis of wind loads on full-scale heliostats. Wind tunnel testing is an affordable way to analyse loads on a scaled structure before committing to a full-scale design. Scale testing however has its challenges as most cases in literature fail to correctly scale the ABL when scaling a model due to the differences between the ratio of the heliostat chord to the boundary layer depth in a wind tunnel and ABL. There is a lack of direct comparison between wind tunnel and full-scale heliostat wind loads. The Atmospheric Boundary Layer Research Facility (ABLRF) consists of arrays of ultrasonic anemometers and a 1.5 aspect ratio heliostat, mounted on a 6-axis load cell, for the comparison of loads measured in the wind tunnel with a full-scale model. Preliminary results categorise the site to have a roughness of 0.01 m to 0.03 m indicating open country farmland, when compared to standards. Comparison between coefficients of lift force, drag force, and hinge moment on the heliostat model at a single elevation angle at the ABLRF and wind tunnel models in literature verify the commissioning of the site, allowing for further in-depth analysis of wind load coefficients at varying elevation and azimuth angles.

ABSTRACTBackground The Michigan State College of Human Medicine began as an experiment to teach medical students in community-based settings and to create a primary care workforce for the state. Decades later, CHM faced internal and external challenges that spurred creation of a new curriculum – the Share Discovery Curriculum – founded on learning by doing and other learning theories.Methods A curricular design group (CDG) developed guiding principles for reform. Based on this, pedagogies and structures were selected to achieve this vision and developed into a curricular structure. Components of the first-year curriculum were piloted with a group of students and faculty members.Results Six guiding principles were endorsed, grounded in learning theories such as Dewey’s Learning by Doing. Based upon these, several key features of the new curriculum emerged: learning communities; one-on-one coaches for students; symptom-based presentations for content; simulation, authentic clinical tasks, flipped classrooms, and modified practice-based learning as primary teaching modalities; early, integrated clinical and scientific learning; milestones as course learning objectives; and a multidimensional, competency-based assessment system.Discussion The process and outcomes described here are intended as an exemplar for schools undertaking curricular change. Early stakeholder engagement, faculty development, sustainable administrative systems, and managing complexity are core to the success of such endeavors.

Abstract Aims People experiencing homelessness (PEH) have been identified as being increasingly susceptible to Coronavirus disease (COVID-19), with policies enacted to test, isolate, increase hygiene practices and prioritise vaccines among this population. Here, we conduct a scoping review of the current evidence-base pertaining to the prevalence and presentation of COVID-19 in PEH, COVID-vaccine hesitancy rates and government interventions enacted within the first year of the pandemic for PEH. Materials and methods A systematic search was conducted on Pubmed, Cochrane, Embase and MedRxiv databases for studies reporting primary data on COVID-19 prevalence and clinical characteristics in PEH, vaccine uptake for PEH and policies enacted targeting PEH. Study qualities were assessed with The National Heart, Lung and Blood Institute’s set of Study Quality. Results Eighty-three studies were included in our final analysis. The overall prevalence of symptomatic COVID-19 infection in PEH is estimated at 35%. The most common symptoms found were cough and shortness of breath, followed by fever. Concerns regarding vaccine hesitancy amongst PEH related to thoroughness of COVID-19 vaccine clinical trials, side effects and mistrust of the government. The main strategies implemented by governments were mass testing, adaption of healthcare service provision, provision of alternative housing, encouraging personal hygiene (hand sanitation and mask wearing), and inter-organisational communication. Discussion In our meta-analysis, 35% of PEH with a COVID-19 infection presented symptomatically; the low prevalence of symptomatic COVID-19 infection suggests widespread testing following outbreaks would be beneficial for this group of individuals. Temporary recuperation units and measures for housing stability in the pandemic, namely provision of alternative housing and stopping evictions, were found to be highly effective. High rates of vaccine hesitancy means that education and encouragement towards vaccination would be beneficial for this vulnerable population, where comorbidities are common. Finally increased focus in research should be placed on the mental health burden of COVID-19 and the pandemic on PEH moving forwards.

**Background:** The US population includes 24 million to 29 million people with diagnosed and undiagnosed chronic obstructive pulmonary disease (COPD). Studies have demonstrated the safety and efficacy of single-inhaler triple therapy (SITT) in reducing COPD exacerbations. Long-term population implications of SITT use have not been quantified. **Objectives:** This simulation-based projection aimed to estimate the potential impact of widespread SITT use on the US COPD population. **Methods:** Exacerbation and all-cause mortality reductions reported in the Efficacy and Safety of Triple Therapy in Obstructive Lung Disease trial (ETHOS; NCT02465567) were used to project clinical outcomes in US patients meeting ETHOS trial eligibility criteria (ETHOS-Eligible) and patients meeting a practical definition of SITT eligibility (Expanded ETHOS-Eligible). The US COPD population was modeled with 1000 simulations of patient progression over 10 years. Agent characteristics were based on literature and claims analysis of the 2016-2018 Medicare 100% fee-for-service and IBM MarketScan^®^ databases. Agent annual characteristics reflected incident cases, changes in COPD severity, treatment, mortality, and exacerbations under status quo treatment patterns and scenarios for the adoption of SITT. The scenarios assumed the reduced exacerbation and mortality rates associated with SITT according to ETHOS trial outcomes mean values. **Results:** Higher than current SITT adoption over 10 years would be expected to substantially reduce COPD exacerbation-associated hospitalizations by 2 million. Applying mean improvements reported in ETHOS for SITT would extend average patient life expectancy 2.2 years for ETHOS-Eligible patients and 1.7 years for Expanded ETHOS-Eligible patients. The number needed to treat to extend the average patient life by 1 year was 8 for the ETHOS-Eligible population and 10 for the Expanded ETHOS-Eligible population. **Discussion:** Widespread SITT adoption may be impeded by competitive pressures from generic treatments and nonadherence, and efficacy observed in clinical trials may not occur in real-world populations. **Conclusions:** Assuming ETHOS treatment effects and adherence translate to clinical practice, higher than current use of SITT can substantially reduce COPD exacerbations and hospitalizations and extend survival. These results should be viewed cautiously, because the improved outcomes for SITT in the ETHOS final retrieved vital statistics data were not statistically significant for all comparator therapy groups.

Background Despite unprecedented benefit from immune checkpoint inhibitors (ICIs) in patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI-H) advanced gastrointestinal cancers, a relevant proportion of patients shows primary resistance or short-term disease control. Since malignant effusions represent an immune-suppressed niche, we investigated whether peritoneal involvement with or without ascites is a poor prognostic factor in patients with dMMR/MSI-H metastatic colorectal cancer (mCRC) and gastric cancer (mGC) receiving ICIs.Methods We conducted a global multicohort study at Tertiary Cancer Centers and collected clinic-pathological data from a cohort of patients with dMMR/MSI-H mCRC treated with anti-PD-(L)1 ±anti-CTLA-4 agents at 12 institutions (developing set). A cohort of patients with dMMR/MSI-high mGC treated with anti-PD-1 agents±chemotherapy at five institutions was used as validating dataset.Results The mCRC cohort included 502 patients. After a median follow-up of 31.2 months, patients without peritoneal metastases and those with peritoneal metastases and no ascites had similar outcomes (adjusted HR (aHR) 1.15, 95% CI 0.85 to 1.56 for progression-free survival (PFS); aHR 0.96, 95% CI 0.65 to 1.42 for overall survival (OS)), whereas inferior outcomes were observed in patients with peritoneal metastases and ascites (aHR 2.90, 95% CI 1.70 to 4.94; aHR 3.33, 95% CI 1.88 to 5.91) compared with patients without peritoneal involvement. The mGC cohort included 59 patients. After a median follow-up of 17.4 months, inferior PFS and OS were reported in patients with peritoneal metastases and ascites (aHR 3.83, 95% CI 1.68 to 8.72; aHR 3.44, 95% CI 1.39 to 8.53, respectively), but not in patients with only peritoneal metastases (aHR 1.87, 95% CI 0.64 to 5.46; aHR 2.15, 95% CI 0.64 to 7.27) when compared with patients without peritoneal involvement.Conclusions Patients with dMMR/MSI-H gastrointestinal cancers with peritoneal metastases and ascites should be considered as a peculiar subgroup with highly unfavorable outcomes to current ICI-based therapies. Novel strategies to target the immune-suppressive niche in malignant effusions should be investigated, as well as next-generation ICIs or intraperitoneal approaches.

Abstract Until recently, China's Belt and Road Initiative (BRI) has overlooked many of the social and environmental dimensions of its projects and actions in favor of more immediate economic and sociopolitical considerations. The main focus of investments under BRI has largely been to improve transport, telecommunication, and energy infrastructures. However, in Central Asia, biodiversity is not only foundational for the livelihoods and socioeconomic wellbeing of communities, it also shapes people's culture and identities. Furthermore, ecosystem services derived from functioning landscapes bring enormous benefit for millions of people downstream through integrated and transboundary water systems. Already under pressure from climate‐induced melting of glaciers, the fate of ecologically important areas is considered in light of the potential harm arising from large‐scale linear infrastructure projects and related investments under China‐led BRI. Following review of some of the anticipated impacts of BRI on mountain environments and societies in the region, we highlight several emerging opportunities and then offer recommendations for development programs—aiming fundamentally to enhance the sustainability of BRI investments. Leveraging new opportunities to strengthen partner countries’ priority Sustainable Development Goals and enhancing their agency in the selection of collaborations and the standards to use in environmental impact and risk assessments are recommended.

Abstract Background Vast volumes of data, coded through hierarchical terminologies (e.g., International Classification of Diseases, Tenth Revision–Clinical Modification [ICD10-CM], Medical Subject Headings [MeSH]), are generated routinely in electronic health record systems and medical literature databases. Although graphic representations can help to augment human understanding of such data sets, a graph with hundreds or thousands of nodes challenges human comprehension. To improve comprehension, new tools are needed to extract the overviews of such data sets. We aim to develop a visual interactive analytic tool for filtering and summarizing large health data sets coded with hierarchical terminologies (VIADS) as an online, and publicly accessible tool. The ultimate goals are to filter, summarize the health data sets, extract insights, compare and highlight the differences between various health data sets by using VIADS. The results generated from VIADS can be utilized as data-driven evidence to facilitate clinicians, clinical researchers, and health care administrators to make more informed clinical, research, and administrative decisions. We utilized the following tools and the development environments to develop VIADS: Django, Python, JavaScript, Vis.js, Graph.js, JQuery, Plotly, Chart.js, Unittest, R, and MySQL. Results VIADS was developed successfully and the beta version is accessible publicly. In this paper, we introduce the architecture design, development, and functionalities of VIADS. VIADS includes six modules: user account management module, data sets validation module, data analytic module, data visualization module, terminology module, dashboard. Currently, VIADS supports health data sets coded by ICD-9, ICD-10, and MeSH. We also present the visualization improvement provided by VIADS in regard to interactive features (e.g., zoom in and out, customization of graph layout, expanded information of nodes, 3D plots) and efficient screen space usage. Conclusions VIADS meets the design objectives and can be used to filter, summarize, compare, highlight and visualize large health data sets that coded by hierarchical terminologies, such as ICD-9, ICD-10 and MeSH. Our further usability and utility studies will provide more details about how the end users are using VIADS to facilitate their clinical, research or health administrative decision making.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and terminal interstitial lung disease (ILD) with a median survival of 3–5 years. The British Thoracic Society (BTS) established the UK IPF Registry in 2013 as a platform to collect data on clinical characteristics, treatments and outcomes for this cohort in the UK. Between 1 January 2013 and 31 October 2019, 2474 cases were registered. Most patients were male (79%) with a mean±sd age of 74±8.3 years and 66% were ex-smokers. Over time we observed an increase in the number of patients aged over 70 years. However, we have not seen a trend towards earlier presentation as symptoms of breathless and/or cough were present for >12 months in 63% of the cohort. At presentation, mean±sd % predicted forced vital capacity (FVC) was 78.2±18.3%, median 76.2% (interquartile range (IQR) 22.4%) and transfer factor of the lung for carbon monoxide (TLCO) 48.4±16.0, median 47.5 (IQR 20.1). Most cases were discussed at an ILD multidisciplinary meeting, with an increase over this time in the number of cases reported as having possible usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) thorax. We noted a reduction in the number of patients undergoing surgical lung biopsy or bronchoalveolar lavage. Although more patients were prescribed anti-fibrotic therapies from 2013 to 2019, 43% were ineligible for treatment based upon National Institute for Health and Care Excellence (NICE) prescribing criteria. Hypertension, ischaemic heart disease, diabetes mellitus and gastro-oesophageal reflux were the most common comorbidities. In conclusion, we have presented baseline demographics as well as diagnostic and treatment strategies from the largest single-country IPF registry, reflecting changes in UK practices over this period.

An incomplete ascertainment of genetic variation within the highly polymorphic immunoglobulin heavy chain locus (IGH) has hindered our ability to define genetic factors that influence antibody-mediated processes. Due to locus complexity, standard high-throughput approaches have failed to accurately and comprehensively capture IGH polymorphism. As a result, the locus has only been fully characterized two times, severely limiting our knowledge of human IGH diversity. Here, we combine targeted long-read sequencing with a novel bioinformatics tool, IGenotyper, to fully characterize IGH variation in a haplotype-specific manner. We apply this approach to eight human samples, including a haploid cell line and two mother-father-child trios, and demonstrate the ability to generate high-quality assemblies (>98% complete and >99% accurate), genotypes, and gene annotations, identifying 2 novel structural variants and 15 novel IGH alleles. We show multiplexing allows for scaling of the approach without impacting data quality, and that our genotype call sets are more accurate than short-read (>35% increase in true positives and >97% decrease in false-positives) and array/imputation-based datasets. This framework establishes a desperately needed foundation for leveraging IG genomic data to study population-level variation in antibody-mediated immunity, critical for bettering our understanding of disease risk, and responses to vaccines and therapeutics.

Background This study evaluates the generalizability of an eight-station progress clinical skills examination and assesses the growth in performance for six clinical skills domains among first- and second-year medical students over four time points during the academic year. Methods We conducted a generalizability study for longitudinal and cross-sectional comparisons and assessed growth in six clinical skill domains via repeated measures ANOVA over the first and second year of medical school. Results The generalizability of the examination domain scores was low but consistent with previous studies of data gathering and communication skills. Variations in case difficulty across administrations of the examination made it difficult to assess longitudinal growth. It was possible to compare students at different training levels and the interaction of training level and growth. Second-year students outperformed first-year students, but first-year students’ clinical skills performance grew faster than second-year students narrowing the gap in clinical skills over the students’ first year of medical school. Conclusions Case specificity limits the ability to assess longitudinal growth in clinical skills through progress testing. Providing students with early clinical skills training and authentic clinical experiences appears to result in the rapid growth of clinical skills during the first year of medical school.

The Mountain Societies Research Institute (MSRI) operates at the interface of science and society in Central Asia. As part of the University of Central Asia and the wider Aga Khan Development Network, MSRI engages in transdisciplinary research for development and regularly seeks to strengthen regional capacities, to inform policy and practice, and to promote open dialogue among key stakeholders about development issues. MSRI thus aims to improve the well-being and resilience of mountain communities in the context of rapidly changing economic, sociocultural, political, and environmental conditions. MSRI's integrated approach to research, both with and for the benefit of mountain societies, demands simultaneous understanding of social and ecological factors operating at multiple spatial and temporal scales. Broadly embedded within the framework of the Sustainable Development Goals, and more specifically the Sustainable Mountain Development agenda, the research and affiliated activities at MSRI also aim to elucidate and highlight the development challenges and opportunities of a long-neglected part of the world, greater Central Asia, extending from the Caucasus to western China.

We construct, over any CM field, compatible systems of $l$-adic Galois representations that appear in the cohomology of algebraic varieties and have (for all $l$) algebraic monodromy groups equal to the exceptional group of type $E_{6}$.

Introduction: There is great variation in the knowledge base of Emergency Medicine (EM) interns in July. The first objective knowledge assessment during residency does not occur until eight months later, in February, when the American Board of EM (ABEM) administers the in-training examination (ITE). In 2013, the National Board of Medical Examiners (NBME) released the EM Advanced Clinical Examination (EM-ACE), an assessment intended for fourth-year medical students. Administration of the EM-ACE to interns at the start of residency may provide an earlier opportunity to assess the new EM residents’ knowledge base. The primary objective of this study was to determine the correlation of the NBME EM-ACE, given early in residency, with the EM ITE. Secondary objectives included determination of the correlation of the United States Medical Licensing Examination (USMLE) Step 1 or 2 scores with early intern EM-ACE and ITE scores and the effect, if any, of clinical EM experience on examination correlation. Methods: This was a multi-institutional, observational study. Entering EM interns at six residencies took the EM-ACE in July 2013 and the ABEM ITE in February 2014. We collected scores for the EMACE and ITE, age, gender, weeks of clinical EM experience in residency prior to the ITE, and USMLE Step 1 and 2 scores. Pearson’s correlation and linear regression were performed. Results: Sixty-two interns took the EM-ACE and the ITE. The Pearson’s correlation coefficient between the ITE and the EM-ACE was 0.62. R-squared was 0.5 (adjusted 0.4). The coefficient of determination was 0.41 (95% CI [0.3-0.8]). For every increase of one in the scaled EM-ACE score, we observed a 0.4% increase in the EM in-training score. In a linear regression model using all available variables (EM-ACE, gender, age, clinical exposure to EM, and USMLE Step 1 and Step 2 scores), only the EM-ACE score was significantly associated with the ITE (p

Let $p$ be a prime number and $F$ a totally real number field. For each prime $\mathfrak{p}$ of $F$ above $p$ we construct a Hecke operator $T_{\mathfrak{p}}$ acting on $(\text{mod}\,p^{m})$ Katz Hilbert modular classes which agrees with the classical Hecke operator at $\mathfrak{p}$ for global sections that lift to characteristic zero. Using these operators and the techniques of patching complexes of Calegari and Geraghty we prove that the Galois representations arising from torsion Hilbert modular classes of parallel weight $\mathbf{1}$ are unramified at $p$ when $[F:\mathbb{Q}]=2$ . Some partial and some conjectural results are obtained when $[F:\mathbb{Q}]>2$ .

The past 25 years have seen a rapid growth of knowledge about brain mechanisms involved in visual mental imagery. These advances have largely been made independently of the long history of philosophical – and even psychological – reckoning with imagery and its parent concept ‘imagination’. We suggest that the view from these empirical findings can be widened by an appreciation of imagination’s intellectual history, and we seek to show how that history both created the conditions for – and presents challenges to – the scientific endeavour. We focus on the neuroscientific literature’s most commonly used task - imagining a concrete object – and, after sketching what is known of the neurobiological mechanisms involved, we examine the same basic act of imagining from the perspective of several key positions in the history of philosophy and psychology. We present positions that, firstly, contextualise and inform the neuroscientific account, and secondly, pose conceptual and methodological challenges to the scientific analysis of imagery. We conclude by reflecting on the intellectual history of visualisation in the light of contemporary science, and the extent to which such science may resolve long-standing theoretical debates.

Objective. With improving rates of initial survival in severe sepsis, second-hit infections that occur following resolution of the primary insult carry an increasing burden of morbidity. However, despite the clinical relevance of these infections, no data are available on differential outcomes in patients with first and second-hit infections depending on the nature of the causative organism. This study aims to explore any differences in these subgroups.Design. In a retrospective, observational cohort study, the United Kingdom Intensive Care National Audit and Research Centre (ICNARC) database was used to explore the outcomes of patient with first-hit infections leading to sepsis, and sepsis patients with second-hit infections grouped according to the Gram status of the causative organism.Setting. General critical care units in England, Wales, and Northern Ireland participating in the ICNARC programme between 1 January 2007 – 30 June 2012. Patients. Patient groups analysed included 2119 patients with and 1319 patients without sepsis who developed an intensive care unit acquired infection in blood. Subgroups included patients with trauma, emergency neurosurgical, elective surgical, and cardiogenic shock.Measurements and main results. Gram-negative organisms were associated with poorer outcomes in first-hit infections. The 90-day mortality of patients who developed a Gram-negative infection was 43.6% following elective surgery and 27.9% following trauma. This compared with a mortality of 25.6% and 20.6%, respectively, in Gram-positive infections. Unexpectedly, an inverse relationship between Gram status and mortality was observed in second-hit infections. Patients with an initial diagnosis of sepsis who developed secondary infections caused by Gram-negative organisms had a 90-day mortality of 40.4%, compared with 43.6% in Gram-positive infections.Conclusions. Our study identifies a fundamental difference in patient outcomes between first-hit and second-hit bacterial infections, which may be due to genetic, microbiological, immunological, and environmental factors. This finding has direct implications for risk stratification and defines future research priorities.

Huntington’s Disease (HD) is a progressive neurodegenerative disorder that causes motor, cognitive, and psychiatric symptoms. In these experiments, we tested if operant training at an early age affected adult cognitive deficits in the zQ175 KI Het (zQ175) mouse model of HD. In Experiment 1 we trained zQ175 mice in a fixed-ratio/progressive ratio (FR/PR) task to assay learning and motivational deficits. We found pronounced deficits in response rates and task engagement in naïve adult zQ175 mice (32-33 weeks age), while deficits in zQ175 mice trained from 6-7 weeks age were either absent or less severe. When those mice were re-tested as adults, FR/PR performance deficits were absent or otherwise less severe than deficits observed in naïve adult zQ175 relative to wild type (WT) mice. In Experiment 2, we used a Go/No-go operant task to assess the effects of early cognitive testing on response inhibition deficits in zQ175 mice. We found that zQ175 mice that began testing at 7-8 weeks did not exhibit deficits in Go/No-go testing, but when re-tested at 28-29 weeks age exhibited an initial impairment that diminished with training. These transient deficits were nonetheless mild relative to deficits observed among adult zQ175 mice without prior testing experience. In Experiment 3 we trained mice in a two-choice visual discrimination test to evaluate cognitive flexibility. As in prior experiments, we found performance deficits were mild or absent in mice that started training at 6-9 weeks of age, while deficits in naive mice exposed to training at 28-29 weeks were severe. Re-testing mice at 28-29 weeks age, were previously trained starting at 6-9 weeks, revealed that deficits in learning and cognitive flexibility were absent or reduced relative to effects observed in naive adults. In Experiment 4, we tested working memory deficits with a delayed non-match to position (DNMTP) test. Mice with prior experience exhibited mild working memory deficits, with males zQ175 exhibiting no deficits, and females performing significantly worse than WT mice at a single delay interval, whereas naive zQ175 exhibited severe delay-dependent deficits at all intervals exceeding 1 s. In sum, these experiments indicate that CAG-dependent impairments in motivation, motor control,

The exponential increase in data over the last decade presents a significant challenge to analytics efforts that seek to process and interpret such data for various applications. Neural-inspired computing approaches are being developed in order to leverage the computational advantages of the analog, low-power data processing observed in biological systems. Analog resistive memory crossbars can perform a parallel read or a vector-matrix multiplication as well as a parallel write or a rank-1 update with high computational efficiency. For an NxN crossbar, these two kernels are at a minimum O(N) more energy efficient than a digital memory-based architecture. If the read operation is noise limited, the energy to read a column can be independent of the crossbar size (O(1)). These two kernels form the basis of many neuromorphic algorithms such as image, text, and speech recognition. For instance, these kernels can be applied to a neural sparse coding algorithm to give an O(N) reduction in energy for the entire algorithm. Sparse coding is a rich problem with a host of applications including computer vision, object tracking, and more generally unsupervised learning.

Background: Residents’ funduscopy skill is an important topic for medical education.Objective: To provide a snapshot of the performance of direct funduscopy (DF) as part of the initial clinical assessment among different faculty physicians and residents from Internal Medicine (IM), Emergency Medicine (EM) and Neurology (N).Methods: Retrospective study of 200 randomly reviewed charts of patients (> 18 years) presenting either to the ED, inpatient units or outpatient clinics from January 2001 to July 2013, with corresponding ICD-9 codes for headaches, altered mental status and visual changes.Results: Whereas the Neurology Service was the one who performed most DF upon initial evaluation, DF is infrequently done throughout services independent of inpatient or outpatient location. More than half of patients (66%) presenting with visual symptoms had evaluation done by Ophthalmology. Conclusions: A more robust teaching of DF should be included among the basic clinical competencies during Medical School and Neurology Residency training.

The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies, such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some muscular dystrophies. The biology of muscle stem cells varies depending on their embryologic origins and the muscles with which they are associated. Here we review the biology of skeletal muscle stem cell populations of eight different muscle groups. Understanding the biological variation of skeletal muscles and their resident stem cells could provide valuable insight into mechanisms underlying the susceptibility of certain muscles to myopathic disease.

Evidence for Fe(II) oxidation and deposition of Fe(III)-bearing minerals from anoxic or redox-stratified Precambrian oceans has received support from decades of sedimentological and geochemical investigation of Banded Iron Formations (BIF). While the exact mechanisms of Fe(II) oxidation remains equivocal, reaction with O2 in the marine water column, produced by cyanobacteria or early oxygenic phototrophs, was likely. In order to understand the role of cyanobacteria in the deposition of Fe(III) minerals to BIF, we must first know how planktonic marine cyanobacteria respond to ferruginous (anoxic and Fe(II)-rich) waters in terms of growth, Fe uptake and homeostasis, and Fe mineral formation. We therefore grew the common marine cyanobacterium Synechococcus PCC 7002 in closed bottles that began anoxic, and contained Fe(II) concentrations that span the range of possible concentrations in Precambrian seawater. These results, along with cell suspension experiments, indicate that Fe(II) is likely oxidized by this strain via chemical oxidation with oxygen produced during photosynthesis, and not via any direct enzymatic or photosynthetic pathway. Imaging of the cell-mineral aggregates with scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) are consistent with extracellular precipitation of Fe(III) (oxyhydr)oxide minerals, but that >10% of Fe(III) sorbs to cell surfaces rather than precipitating. Proteomic experiments support the role of reactive oxygen species (ROS) in Fe(II) toxicity to Synechococcus PCC 7002. The proteome expressed under low Fe conditions included multiple siderophore biosynthesis and siderophore and Fe transporter proteins, but most siderophores are not expressed during growth with Fe(II). These results provide a mechanistic and quantitative framework for evaluating the geochemical consequences of perhaps life’s greatest metabolic innovation, i.e. the evolution and activity of oxygenic photosynthesis, in ferruginous Precambrian oceans.

The International Pseudomonas aeruginosa Consortium is sequencing over 1000 genomes and building an analysis pipeline for the study of Pseudomonas genome evolution, antibiotic resistance and virulence genes. Metadata, including genomic and phenotypic data for each isolate of the collection, are available through the International Pseudomonas Consortium Database (http://ipcd.ibis.ulaval.ca/). Here, we present our strategy and the results that emerged from the analysis of the first 389 genomes. With as yet unmatched resolution, our results confirm that P. aeruginosa strains can be divided into three major groups that are further divided into subgroups, some not previously reported in the literature. We also provide the first snapshot of P. aeruginosa strain diversity with respect to antibiotic resistance. Our approach will allow us to draw potential links between environmental strains and those implicated in human and animal infections, understand how patients become infected and how the infection evolves over time as well as identify prognostic markers for better evidence-based decisions on patient care.

We report a case of pathologically confirmed tumefactive multiple sclerosis (MS) followed shortly thereafter by the diagnosis of an oligoastrocytoma. The complexity of diagnosis and management of concomitant presence of tumefactive MS and glial cell tumors is discussed.

Accuracy in localizing the brain areas that generate neuromagnetic activity in magnetoencephalography (MEG) is dependent on properly co-registering MEG data to the participant’s structural magnetic resonance image (MRI). Effective MEG-MRI co-registration is, in turn, dependent on how accurately we can digitize anatomical landmarks on the surface of the head. In this study, we compared the performance of three devices —Polhemus electromagnetic system, NextEngine laser scanner and Microsoft Kinect for Windows — for source localization accuracy and MEG-MRI co-registration. A calibrated phantom was used for verifying the source localization accuracy. The Kinect improved source localization accuracy over the Polhemus and the laser scanner by 2.23 mm (137%) and 0.81 mm (50%), respectively. MEG-MRI co-registration accuracy was verified on data from five healthy human participants, who received the digitization process using all three devices. The Kinect device captured approximately 2000 times more surface points than the Polhemus in one third of the time (one minute compared to three minutes) and thrice as many points as the NextEngine laser scanner. Following automated surface matching, the calculated mean MEG-MRI co-registration error for the Kinect was improved by 2.85 mm with respect to the Polhemus device, and equivalent to the laser scanner. Importantly, the Kinect device automatically aligns 20-30 images per second in real-time, reducing the limitations on participant head movement during digitization that are implicit in NextEngine laser scan (~1 minute). We conclude that the Kinect scanner is an effective device for head digitization in MEG, providing the necessary accuracy in source localization and MEG-MRI co-registration, while reducing digitization time.

This population-based study investigates genotype-phenotype correlations of low-normal CGG repeats in the fragile X mental retardation 1 (FMR1) gene. FMR1 plays an important role in brain development and function, and encodes FMRP (fragile X mental retardation protein), an RNA-binding protein that regulates protein synthesis impacting activity-dependent synaptic development and plasticity. Most past research has focused on CGG premutation expansions (41 to 200 CGG repeats) and on fragile X syndrome (200+ CGG repeats), with considerably less attention on the other end of the spectrum of CGG repeats. Using existing data, older adults with 23 or fewer CGG repeats (2 SDs below the mean) were compared with age-peers who have normal numbers of CGGs (24-40) with respect to cognition, mental health, cancer, and having children with disabilities. Men (n = 341 with an allele in the low-normal range) and women (n = 46 with two low-normal alleles) had significantly more difficulty with their memory and ability to solve day to day problems. Women with both FMR1 alleles in the low-normal category had significantly elevated odds of feeling that they need to drink more to get the same effect as in the past. These women also had two and one-half times the odds of having had breast cancer and four times the odds of uterine cancer. Men and women with low-normal CGGs had higher odds of having a child with a disability, either a developmental disability or a mental health condition. These findings are in line with the hypothesis that there is a need for tight neuronal homeostatic control mechanisms for optimal cognitive and behavioral functioning, and more generally that low numbers as well as high numbers of CGG repeats may be problematic for health.

In addition to their role in protein degradation and digestion, proteases can also function as hormone-like signaling molecules that regulate vital patho-physiological processes, including inflammation, hemostasis, pain and repair mechanisms. Certain proteases can signal to cells by cleaving protease-activated receptors (PARs), a family of four G protein-coupled receptors. PARs are expressed by almost all cell types, control important physiological and disease-relevant processes, and are an emerging therapeutic target for major diseases. Most information about PAR activation and function derives from studies of a few proteases, for example thrombin in the case of PAR1, PAR3 and PAR4, and trypsin in the case of PAR2 and PAR4. These proteases cleave PARs at established sites with the extracellular N-terminal domains, and expose tethered ligands that stabilize conformations of the cleaved receptors that activate the canonical pathways of G protein- and/or β-arrestin-dependent signaling. However, a growing number of proteases have been identified that cleave PARs at divergent sites to activate distinct patterns of receptor signaling and trafficking. The capacity of these proteases to trigger distinct signaling pathways is referred to as biased signaling, and can lead to unique patho-physiological outcomes. Given that a different repertoire of proteases are activated in various patho-physiological conditions that may activate PARs by different mechanisms, signaling bias may account for the divergent actions of proteases and PARs. Moreover, therapies that target disease-relevant biased signaling pathways may be more effective and selective approaches for the treatment of protease- and PAR-driven diseases. Thus, rather than mediating the actions of a few proteases, PARs may integrate the biological actions of a wide spectrum of proteases in different patho-physiological conditions.Keywords: PARs, proteases, biased signaling, G proteins, β-arrestins, signal transduction

The slick hair coat (SLICK) is a dominantly inherited trait typically associated with tropically adapted cattle that are from Criollo descent through Spanish colonization of cattle into the New World. The trait is of interest relative to climate change, due to its association with improved thermo-tolerance and subsequent increased productivity. Previous studies localized the SLICK locus to a 4 cM region on chromosome (Chr) 20 and identified signatures of selection in this region derived from Senepol cattle. The current study compares three slick-haired Criollo-derived breeds including Senepol, Carora, and Romosinuano and three additional slick-haired cross-bred lineages to non-slick ancestral breeds. Genome-wide association (GWA), haplotype analysis, signatures of selection, runs of homozygosity, and identity by state (IBS) calculations were used to identify a 0.8Mb (37.7-38.5Mb) consensus region for the SLICK locus on Chr 20 in which contains SKP2 and SPEF2 as possible candidate genes. Three specific haplotype patterns are identified in slick individuals, all with zero frequency in non-slick individuals. Admixture analysis identified common genetic patterns between the three slick breeds at the SLICK locus. Principle component analysis and admixture results show Senepol and Romosinuano sharing a higher degree of genetic similarity to one another with a much lesser degree of similarity to Carora. Variation in GWA, haplotype analysis, and IBS calculations with accompanying population structure information supports potentially two mutations, one common to Senepol and Romosinuano and another in Carora, effecting genes contained within our refined location for the SLICK locus.

For scientific, clinical, and machine learning purposes alike, it is desirable to quantify the verbal reports of high-level visual percepts. Methods to do this simply do not exist at present. Here we propose a novel methodological principle to help fill this gap, and provide empirical evidence designed to serve as the initial ‘proof’ of this principle. In the proposed method, subjects view images real-world scenes and describe, in their own words, what they saw. The verbal description is independently evaluated by several evaluators. Each evaluator assigns a rank score to the subject’s description of each visual object in each image using a novel ranking principle, which takes advantage of the well-known fact that semantic descriptions of real-life objects and scenes can usually be rank-ordered. Thus, for instance, ‘animal’, ‘dog’, and ‘retriever’ can be regarded as increasingly finer-level, and therefore higher-ranking, descriptions of a given object. These numeric scores can preserve the richness of the original verbal description, and can be subsequently evaluated using conventional statistical procedures. We describe an exemplar implementation of this method and empirical data that show its feasibility. With appropriate future standardization and validation, this novel method can serve as an important tool to help quantify the subjective experience of the visual world. In addition to being a novel, potentially powerful testing tool, our method also represents, to our knowledge, the only available method for numerically representing verbal accounts of real-world experience. Given that its minimal requirements, i.e., a verbal description and the ground truth that elicited the description, our method has a wide variety of potential real-world applications.

Background: The annual number of emergency department (ED) visits in the United States increased 23% between 1997 and 2007. The uninsured and those with chronic medical conditions are high users of emergency care. Objective: We sought to determine whether access to comprehensive outpatient primary and specialty care and care coordination provided by The Access Partnership (TAP) reduced ED utilization among uninsured patients relative to patients who chose not to enroll. Methods: Multiple time series analysis was performed to examine rates of ED utilization and inpatient admission among TAP patients and a comparison group of eligible patients who did not join (non-TAP patients). Monthly ED utilization and inpatient admission rates for both groups were examined prior to and subsequent to referral to TAP, within a study period 2007-2011. Results: During the study period, 623 patients were eligible to enroll, and 374 joined the program. Rates of ED visits per month increased in both groups. Compared with non-TAP patients, TAP patients had 2.0 fewer ED visits not leading to admission per 100 patient-months post-TAP ( P = .03, 95% confidence interval = 0.2-3.9). TAP status was a moderate predictor of ED visits not leading to admission, after controlling for age, gender, and zip code ( P = .04, 95% confidence interval = 0.1-3.9). Conclusions: Although overall ED utilization did not change significantly between program participants and nonparticipants, TAP patients had a lower rate of ED visits not resulting in inpatient admission relative to the comparison group.

There are significant limitations among the few prior studies that have examined the development and implementation of interprofessional education (IPE) experiences to accommodate a high volume of students from several disciplines and from different institutions. The present study addressed these gaps by seeking to determine the extent to which a single, large, inter-institutional, and IPE simulation event improves student perceptions of the importance and relevance of IPE and simulation as a learning modality, whether there is a difference in students’ perceptions among disciplines, and whether the results are reproducible. A total of 290 medical, nursing, pharmacy, and physical therapy students participated in one of two large, inter-institutional, IPE simulation events. Measurements included student perceptions about their simulation experience using the Attitude Towards Teamwork in Training Undergoing Designed Educational Simulation (ATTITUDES) Questionnaire and open-ended questions related to teamwork and communication. Results demonstrated a statistically significant improvement across all ATTITUDES subscales, while time management, role confusion, collaboration, and mutual support emerged as significant themes. Results of the present study indicate that a single IPE simulation event can reproducibly result in significant and educationally meaningful improvements in student perceptions towards teamwork, IPE, and simulation as a learning modality.

Microsatellite (MS) markers have recently been used for parental verification and are still the international standard despite higher cost, error rate, and turnaround time compared with Single Nucleotide Polymorphisms (SNP)-based assays. Despite domestic and international interest from producers and research communities, no viable means currently exist to verify parentage for an individual unless all familial connections were analyzed using the same DNA marker type (MS or SNP). A simple and cost-effective method was devised to impute MS alleles from SNP haplotypes within breeds. For some MS, imputation results may allow inference across breeds. A total of 347 dairy cattle representing 4 dairy breeds (Brown Swiss, Guernsey, Holstein, and Jersey) were used to generate reference haplotypes. This approach has been verified (>98% accurate) for imputing the International Society of Animal Genetics (ISAG) recommended panel of 12 MS for cattle parentage verification across a validation set of 1,307 dairy animals.. Implementation of this method will allow producers and breed associations to transition to SNP-based parentage verification utilizing MS genotypes from historical data on parents where SNP genotypes are missing. This approach may be applicable to additional cattle breeds and other species that wish to migrate from MS- to SNP- based parental verification.

The use of structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI) in animals models of neuropathology is of increasing interest to the neuroscience community. In this work, we present our approach to create optimal translational studies that include both animal and human neuroimaging data within the frameworks of a study of postnatal neuro-development in intra-uterine cocaine exposure. We propose the use of non-invasive neuroimaging to study developmental brain structural and white matter pathway abnormalities via sMRI and DTI, as advanced MR imaging technology is readily available and automated image analysis methodology have recently been transferred from the human to animal imaging setting. For this purpose, we developed a synergistic, parallel approach to imaging and image analysis for the human and the rodent branch of our study. We propose an equivalent design in both the selection of the developmental assessment stage and the neuroimaging setup. This approach brings significant advantages to study neurobiological features of early brain development that are common to animals and humans but also preserve analysis capabilities only possible in animal research. This paper presents the main framework and individual methods for the proposed cross-species study design, as well as preliminary DTI cross-species comparative results in the intra-uterine cocaine exposure study.

High resolution diffusion tensor imaging (DTI) can provide important information on brain development, yet it is challenging in live neonatal rats due to the small size of neonatal brain and motion-sensitive nature of DTI. Imaging in live neonatal rats has clear advantages over fixed brain scans, as longitudinal and functional studies would be feasible to understand neuro-developmental abnormalities. In this study, we developed imaging strategies that can be used to obtain high resolution 3D DTI images in live neonatal rats at postnatal day 5 (PND5) and postnatal day 14 (PND14), using only 3 hours of imaging acquisition time. An optimized 3D DTI pulse sequence and appropriate animal setup to minimize physiological motion artifacts are the keys to successful high resolution 3D DTI imaging. Thus, a 3D RARE DTI sequence with twin navigator echoes was implemented to accelerate imaging acquisition time and minimize motion artifacts. It has been suggested that neonatal mammals possess a unique ability to tolerate mild to moderate hypothermia and hypoxia without long term impact. Thus, we additionally utilized this ability to minimize motion artifacts in MR images by carefully suppressing the respiratory rate to around 15/min for PND5 and 30/min for PND14 using mild to moderate hypothermia. These imaging strategies have been successfully implemented to study how the effect of cocaine exposure in dams might affect brain development in their rat pups. Image quality resulting from this in vivo DTI study was comparable to ex vivo scans. FA values were also similar between the live and fixed brain scans. The capability of acquiring high quality in vivo DTI imaging offers a valuable opportunity to study many neurological disorders in brain development in an authentic living environment.

Background: Rapidly reversible weakness with neck flexion (McArdle sign) is common in patients with multiple sclerosis (MS). The pathophysiology is unknown., Objective: To evaluate changes in central motor conduction time (CMCT) in patients with and without McArdle sign., Methods: We measured McArdle sign with a torque cell and CMCT with neck flexed and extended in patients with MS, other causes of myelopathy, and healthy controls., Results: CMCT was prolonged with neck flexion disproportionately in those with MS-associated myelopathy (MSAM) with prominent McArdle sign compared to MS patients with lesser degrees of McArdle sign, and to controls., Conclusion: McArdle sign may result from stretch-induced slowing of conduction due to demyelination., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Diapause regulates seasonal insect life cycles and may be highly variable within and among populations due to genetic and environmental variability. Both types of variation may influence how populations respond plastically or evolutionarily to changing climates. We assessed diapause variability in spruce beetle Dendroctonus rufipennis Kirby (Coleoptera: Curculionidae, Scolytinae), a major forest pest whose life cycle timing is regulated by both prepupal and adult diapauses. Using mating studies and ovary dissections, we tested for variability in adult diapause within and between collection sites in Colorado and Wyoming, USA. Ovary morphology suggested that most females from both sites enter diapause prior to egg formation (oogenesis) when reared at warm temperatures. Though previous studies suggested that adult diapause is obligate, we found that a small proportion of females from both populations terminated diapause without winter chilling in the lab. Moreover, we found that most female beetles sampled at the Colorado field site had mature ovaries relatively early in the fall, suggesting that transient exposure to low temperatures may potentiate pre-winter reproductive development. Adult diapause may act primarily as a block to prevent offspring production late in the season but not necessarily as an overwintering phenotype. Overall, our data do not suggest imminent life cycle shifts mediated by adult diapause, but if the observed variability is heritable, diapause regulation may evolve in response to changing environmental conditions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Dysfunctional adipose tissue is believed to promote the development of hepatic steatosis and systemic insulin resistance, but many of the mechanisms involved are still unclear. Lipin 1 catalyzes the conversion of phosphatidic acid to diacylglycerol (DAG), the penultimate step of triglyceride synthesis, which is essential for lipid storage. Herein we found that adipose tissue LPIN1 expression is decreased in people with obesity compared to lean subjects, and low LPIN1 expression correlated with multi-tissue insulin resistance and increased rates of hepatic de novo lipogenesis. Comprehensive metabolic and multi-omic phenotyping demonstrated that adipocyte-specific Lpin1-/- mice had a metabolically-unhealthy phenotype, including liver and skeletal muscle insulin resistance, hepatic steatosis, increased hepatic de novo lipogenesis, and transcriptomic signatures of metabolically associated steatohepatitis that was exacerbated by high-fat diets. We conclude that adipocyte lipin 1-mediated lipid storage is vital for preserving adipose tissue and systemic metabolic health, and its loss predisposes mice to metabolically associated steatohepatitis.

Identifying dormancy traits is important for predicting insect population success, particularly in a changing climate that could disrupt evolved traits. The mountain pine beetle (Dendroctonus ponderosae Hopkins) is native to North America, is responsible for millions of acres of tree mortality, and is expanding northward in Canada. Research has identified thermal traits important to epidemic-phase ecology that vary among populations. Genomic research identified 3 mountain pine beetle haplogroups representing Pleistocene glacial refugia. Significant variation in generation timing aligning with the haplogroups has been observed. The adult stage was previously identified as the likely cause of differences among populations, although the mechanism(s) remain unclear. We tested for an adult summer diapause that varies among populations from 2 haplogroups, southern Colorado (CO) (central haplogroup) and southern Idaho (ID) (eastern haplogroup) using respirometry and reproduction experiments. Warm temperatures (25 °C) resulted in reduced respiration rates of central haplogroup mountain pine beetle compared to a cool temperature treatment (15 °C), whereas respiration of the eastern haplogroup did not differ between the treatments. Mated pairs of central haplogroup mountain pine beetle reared/held at 15 °C were more likely to be classified with a higher reproductive success rating compared to pairs reared/held at 25 °C. These results support a facultative summer adult diapause in southern CO central haplogroup mountain pine beetle. Manifestation of this diapause was low/absent among adults from the northerly ID location. This diapause likely serves to maintain univoltinism shown to be important for mountain pine beetle epidemic-phase ecology. The variation occurring among haplogroups highlights the long-term, evolved processes driving local adaptations in mountain pine beetle., (Published by Oxford University Press on behalf of Entomological Society of America 2024.)

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide, primarily affecting the heart and blood vessels, with atherosclerosis being a major contributing factor to their onset. Epidemiological and clinical studies have linked high levels of low-density lipoprotein (LDL) emanating from distorted cholesterol homeostasis as its major predisposing factor. Cholesterol homeostasis, which involves maintaining the balance in body cholesterol level, is mediated by several proteins or receptors, transcription factors, and even genes, regulating cholesterol influx (through dietary intake or de novo synthesis) and efflux (by their conversion to bile acids). Previous knowledge about CVDs management has evolved around modulating these receptors' activities through synthetic small molecules/antibodies, with limited interest in natural products. The central roles of the cholesteryl ester transfer protein (CETP), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cytochrome P450 family 7 subfamily A member 1 (CYP7A1), among other proteins or receptors, have fostered growing scientific interests in understanding more on their regulatory activities and potential as drug targets. We present up-to-date knowledge on the contributions of CETP, PCSK9, and CYP7A1 toward CVDs, highlighting the clinical successes and failures of small molecules/antibodies to modulate their activities. In recommendation for a new direction to improve cardiovascular health, we have presented recent findings on natural products (including functional food, plant extracts, phytochemicals, bioactive peptides, and therapeutic carbohydrates) that also modulate the activities of CETP, PCSK-9, and CYP7A1, and emphasized the need for more research efforts redirected toward unraveling more on natural products potentials even at clinical trial level for CVD management., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background This study aims to investigate the potential association of the Chief Executive Officer (CEO)'s educational background on hospital safety metrics, specifically the Leapfrog safety grades. Methods A total of 172 academic and university-affiliated hospitals across the United States were included in the study. Information regarding a CEO's background was obtained through hospital websites, while the Leapfrog safety scores were found through the Leapfrog safety grade website. Hospital sizes were also noted. Results A total of 67 hospitals were led by Doctors of Medicine (MDs), 16 were led by Masters in Business Administration (MBAs), 14 were led by Masters in Healthcare Administration (MHAs), and 62 were led by CEOs with various other degree types. Of the 42 A-rated hospitals included, 17 were led by physicians and 25 by nonphysicians. The average Leapfrog grade point average was similar regardless of the CEO's background, ranging from 2.6 to 3.1. Conclusion The findings suggest that a CEO's educational background has less of an impact on the overall hospital safety performance than what may have previously been hypothesized., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Razick et al.)

The main obstacle for the electrocatalytic production of "green hydrogen" is finding suitable electrocatalysts which operate highly efficiently over extended periods of time. The topic of this study is the oxygen evolution reaction (OER), one of the half-reactions of water splitting. It is complex and has intricate kinetics, which impairs the reaction efficiency. Transition metal oxides have shown potential as electrocatalysts for this reaction, but much remains unknown about the atomic scale processes. We have investigated structure-composition-reactivity correlations for Co 3 O 4 , CoFe 2 O 4 , and Fe 3 O 4 epitaxial thin-film electrocatalysts exposing either the (001) or (111) surface facets. We found that for Co 3 O 4 , the (001) facet is more reactive, while for the other oxides, the (111) facet is more active. A Tafel-like evaluation reveals systematically smaller "Tafel" slopes for the (001) facets. Furthermore, the slopes are smaller for the iron-containing films. Additionally, we found that the oxyhydroxide skin layer which forms under OER reaction conditions is thicker on the cobalt oxides than on the other oxides, which we attribute to either a different density of surface defects or to iron hindering the growth of the skin layers. All studied skin layers were thinner than 1 nm.

Background: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of immunotherapeutic opportunities to extend patient survival., Methods: Multiplex immunohistochemistry (mIHC) and automated image analysis based on novel computational imaging technology were used to decipher the abundance and spatial distribution of T cells, macrophages, and tumor cells, relative to K17 expression in 235 PDACs., Results: K17 expression had profound effects on the exclusion of intratumoral CD8+ T cells and was also associated with decreased numbers of peritumoral CD8+ T cells, CD16+ macrophages, and CD163+ macrophages (p < 0.0001). The differences in the intratumor and peritumoral CD8+ T cell abundance were not impacted by neoadjuvant therapy, tumor stage, grade, lymph node status, histologic subtype, nor KRAS, p53, SMAD4, or CDKN2A mutations., Conclusions: Thus, K17 expression correlates with major differences in the immune microenvironment that are independent of any tested clinicopathologic or tumor intrinsic variables, suggesting that targeting K17-mediated immune effects on the immune system could restore the innate immunologic response to PDAC and might provide novel opportunities to restore immunotherapeutic approaches for this most deadly form of cancer., (© 2024. The Author(s).)