Search

Abstract Alzheimer’s disease (AD) is a multifactorial disease with both genetic and environmental factors contributing to its etiology. Previous evidence has implicated disturbed insulin signaling as a key mechanism that plays a role in both neurodegenerative diseases such as AD and comorbid somatic diseases such as diabetes mellitus type 2 (DM2). In this study, we analysed available genome-wide association studies (GWASs) of AD and somatic insulin-related diseases and conditions (SID), i.e., DM2, metabolic syndrome and obesity, to identify genes associated with both AD and SID that could increase our insights into their molecular underpinnings. We then performed functional enrichment analyses of these genes. Subsequently, using (additional) GWAS data, we conducted shared genetic etiology analyses between AD and SID, on the one hand, and blood and cerebrospinal fluid (CSF) metabolite levels on the other hand. Further, integrating all these analysis results with elaborate literature searches, we built a molecular landscape of the overlap between AD and SID. From the landscape, multiple functional themes emerged, including insulin signaling, estrogen signaling, synaptic transmission, lipid metabolism and tau signaling. We also found shared genetic etiologies between AD/SID and the blood/CSF levels of multiple metabolites, pointing towards “energy metabolism” as a key metabolic pathway that is affected in both AD and SID. Lastly, the landscape provided leads for putative novel drug targets for AD (including MARK4, TMEM219, FKBP5, NDUFS3 and IL34) that could be further developed into new AD treatments.

Background: Wild-type transthyretin amyloidosis (ATTRwt amyloidosis) is primarily diagnosed in elderly men but diagnoses in younger patients and women have recently increased. Objectives: The purpose of this study was to examine age- and sex-related differences in patients with ATTRwt amyloidosis enrolled in the THAOS (Transthyretin Amyloidosis Outcomes Survey). Methods: THAOS was a global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic transthyretin gene variants. Patient characteristics at enrollment were analyzed by age at enrollment and sex (data cutoff date: August 1, 2022). Results: Of 1,251 patients with ATTRwt amyloidosis, 13.7%, 49.1%, 34.5%, and 2.8% were aged

Terminal Aerodrome Forecasts (TAFs) are essential components of aviation meteorology, providing critical information for flight safety and operational decision-making. This study conducts a comprehensive analysis of TAF for European airports during the years 2022 and 2023, leveraging Python functions accessible via a dedicated GitHub repository. The complexity inherent in TAF, characterized by diverse change groups, header formats, and regional variations, presents challenges for accurate interpretation. The analysis focuses on key parameters within TAF, including the count of corrected messages and the frequency and types of change groups. The count of corrected messages serves as a metric for evaluating the quality of service provided, while the examination of change group utilization reveals distinct patterns and tendencies specific to each airport. The findings underscore the significance of regional regulations, meteorologist decision-making, and adherence to International Civil Aviation Organization (ICAO) standards in shaping TAF. The GitHub repository and associated Python functions presented in this study provide valuable resources for meteorologists, researchers, and aviation personnel to conduct in-depth analyses and derive insights from TAF. Ultimately, this study identifies local differences and inconsistencies in the publication of TAF, laying the groundwork for enhancing their consistency and uniformity.

Aviation forecasters, recognized for their consistent professionalism and rigorous training, typically exhibit unwavering focus on their responsibilities. Despite this, acknowledging the human element, this research explores the potential impact of external social and psychological influences on their forecasting accuracy. Utilizing standard Terminal Aerodrome Forecasts (TAF) and Meteorological Aerodrome Reports (METAR) observations, the study assesses forecast quality, emphasizing significant events like the COVID-19 pandemic, Nordic storm, tornado, and ice hockey world cup finals. Instances of decreased forecast accuracy during these events prompt an investigation into the role of social and psychological factors. This paper introduces a novel approach, employing variance from the long-term average, to gauge the influence of social and psychological factors on professional performance. Beyond highlighting the daily impacts of the social environment on highly routinized and professional activities, the study underscores an often-overlooked prospect. It posits that professional and technical assessment metrics can robustly indicate the severity of social and natural events. The research thus contributes to a deeper understanding of the intricate interplay between meteorological expertise and external influences, emphasizing the potential for utilizing professional performance metrics as indicators of broader societal events.

Abstract Background Growth hormone deficiency (GHD) has been implicated in increased cardiovascular and cerebrovascular disease risk seen in hypopituitarism, however the mechanism remains speculative. We hypothesise that platelet abnormalities may play a contributory role. Herein we examined platelet behaviour in GHD hypopituitary patients, pre- and post-growth hormone (GH) replacement. Methods This study utilizes a physiological flow-based assay to quantify platelet function in whole blood from patient cohorts under arterial shear. Thirteen GH Naïve hypopituitary adults with GHD and thirteen healthy matched controls were studied. Patients were assessed before and after GH treatment. All other pituitary replacements were optimised before the study. In addition to a full endocrine profile, whole blood was labelled and perfused over immobilised von Willibrand factor (vWF). Seven parameters of dynamic platelet-vWF interactions were recorded using digital image microscopy and analysed by customised platelet tracking software. Results We found a significantly altered profile of platelet-vWF interactions in GHD individuals compared to healthy controls. Specifically, we observed a marked increase in platelets shown to form associations such as tethering, rolling and adherence to immobilized vWF, which were reduced post GH treatment. Speed and distance platelets travelled across vWF was similar between controls and pre-therapy GHD patients, however, this was considerably increased post treatment. This may indicate reduced platelet signaling resulting in less stable adhesion of platelets post GH treatment. Conclusions Taken together observed differences in platelet behaviour may contribute to an increased risk of thrombosis in GHD which can in part be reversed by GH therapy.

In medical imaging, access to data is commonly limited due to patient privacy restrictions, and it can be difficult to acquire enough data in the case of rare diseases. The purpose of this investigation was to develop a reusable open-source synthetic image-generation pipeline, the GAN Image Synthesis Tool (GIST), that is easy to use as well as easy to deploy. The pipeline helps to improve and standardize AI algorithms in the digital health space by generating high quality synthetic image data that is not linked to specific patients. Its image generation capabilities include the ability to generate imaging of pathologies or injuries with low incidence rates. This improvement of digital health AI algorithms could improve diagnostic accuracy, aid in patient care, decrease medicolegal claims, and ultimately decrease the overall cost of healthcare. The pipeline builds on existing Generative Adversarial Networks (GANs) algorithms, and preprocessing and evaluation steps were included for completeness. For this work, we focused on ensuring the pipeline supports radiography, with a focus on synthetic knee and elbow X-ray images. In designing the pipeline, we evaluated the performance of current GAN architectures, studying the performance on available X-ray data. We show that the pipeline is capable of generating high-quality and clinically relevant images based on a lay person’s evaluation and the Fréchet Inception Distance (FID) metric.

Abstract Challenges in social communication is one of the core symptom domains in autism spectrum disorder (ASD). Novel therapies are under development to help individuals with these challenges, however the ability to show a benefit is dependent on a sensitive and reliable measure of treatment effect. Currently, measuring these deficits requires the use of time-consuming and subjective techniques. Objective measures extracted from natural conversations could be more ecologically relevant, and administered more frequently—perhaps giving them added sensitivity to change. While several studies have used automated analysis methods to study autistic speech, they require manual transcriptions. In order to bypass this time-consuming process, an automated speaker diarization algorithm must first be applied. In this paper, we are testing whether a speaker diarization algorithm can be applied to natural conversations between autistic individuals and their conversational partner in a natural setting at home over the course of a clinical trial. We calculated the average duration that a participant would speak for within their turn. We found a significant correlation between this feature and the Vineland Adaptive Behaviour Scales (VABS) expressive communication score (r = 0.51, p = 7 × 10–5). Our results show that natural conversations can be used to obtain measures of talkativeness, and that this measure can be derived automatically, thus showing the promise of objectively evaluating communication challenges in ASD.

ABSTRACT Objective Recent studies have found that human Friedreich ataxia patients have dysfunction of transmission in the auditory neural pathways. Here, we characterize hearing deficits in a mouse model of Friedreich ataxia and compare these to a clinical population. Methods Sixteen mice with a C57BL/6 background were evaluated. Eight were YG8Pook/J animals (Friedreich ataxia phenotype) and eight wild‐type mice served as controls. Auditory function was assessed between ages 6 and 12 months using otoacoustic emissions and auditory steady‐state responses. At study end, motor deficit was assessed using Rotorod testing and inner ear tissue was examined. Thirty‐seven individuals with Friedreich ataxia underwent auditory steady‐state evoked potential assessment and response amplitudes were compared with functional hearing ability (speech perception‐in‐noise) and disease status was measured by the Friedreich Ataxia Rating Scale. Results The YG8Pook/J mice showed anatomic and functional abnormality. While otoacoustic emission responses from the cochlear hair cells were mildly affected, auditory steady‐state responses showed exaggerated amplitude reductions as the animals aged with Friedreich ataxia mice showing a 50–60% decrease compared to controls who showed only a 20–25% reduction (F(2,94) = 17.90, p

Abstract This observational claims-linked survey study assessed the prevalence of and risk factors for suboptimal asthma control and healthcare utilization in adults with asthma receiving fixed-dose combination (FDC) inhaled corticosteroid/long-acting β2-agonist (ICS/LABA). Commercially insured adults from the Optum Research Database were invited to complete the Asthma Control Test (ACT) and Asthma Control Questionnaire-6 (ACQ-6). Among participants (N = 428), 36.4% (ACT-assessed) and 55.6% (ACQ-6-assessed) had inadequately controlled asthma. Asthma-related quality of life was worse and asthma-related healthcare resource utilization was higher in poorly controlled asthma. Factors associated with ACT-defined suboptimal asthma control in multivariate analysis included: frequent short-acting β2-agonist (SABA) use, asthma-related outpatient visits, lower treatment adherence, and lower education levels. During follow-up, factors associated with asthma exacerbations and/or high SABA use included: inadequately controlled asthma (ACT-assessed), body mass index ≥30 kg/m2, and high-dose ICS/LABA. Approximately 35–55% of adults with asthma were inadequately controlled despite FDC ICS/LABA; poor control was associated with worse disease outcomes.

Abstract Background We sought to identify features that distinguish osteoarthritis (OA) and rheumatoid arthritis (RA) hematoxylin and eosin (H&E)-stained synovial tissue samples. Methods We compared fourteen pathologist-scored histology features and computer vision-quantified cell density (147 OA and 60 RA patients) in H&E-stained synovial tissue samples from total knee replacement (TKR) explants. A random forest model was trained using disease state (OA vs RA) as a classifier and histology features and/or computer vision-quantified cell density as inputs. Results Synovium from OA patients had increased mast cells and fibrosis (p < 0.001), while synovium from RA patients exhibited increased lymphocytic inflammation, lining hyperplasia, neutrophils, detritus, plasma cells, binucleate plasma cells, sub-lining giant cells, fibrin (all p < 0.001), Russell bodies (p = 0.019), and synovial lining giant cells (p = 0.003). Fourteen pathologist-scored features allowed for discrimination between OA and RA, producing a micro-averaged area under the receiver operating curve (micro-AUC) of 0.85±0.06. This discriminatory ability was comparable to that of computer vision cell density alone (micro-AUC = 0.87±0.04). Combining the pathologist scores with the cell density metric improved the discriminatory power of the model (micro-AUC = 0.92±0.06). The optimal cell density threshold to distinguish OA from RA synovium was 3400 cells/mm2, which yielded a sensitivity of 0.82 and specificity of 0.82. Conclusions H&E-stained images of TKR explant synovium can be correctly classified as OA or RA in 82% of samples. Cell density greater than 3400 cells/mm2 and the presence of mast cells and fibrosis are the most important features for making this distinction.

In an increasingly complex world there is a real, urgent need for methodologies to enable engineers to model complex sociotechnical systems, as these now seem to describe the majority of systems in use today. This is, of course, exacerbated by the increasing involvement and augmentation with “black box” AI contributions. Hollnagel produced a methodology (FRAM) which did allow the analyst insights into these systems’ behaviour, but the model-based system engineering applications demand numbers and a quantitative approach. In the last 10 years, this original approach, developed to model systems as sets of interactive, interdependent “functions” (abstracted from agent or component details), has been further developed to the point where it can take the basic data and structures from the current component-focussed system engineering “models”, and can pull them all together into dynamic models (as opposed to the static, fixed System Theoretic Process Accimaps) from which analysts can discern how they really work in practice, and predict the emergent behaviours characteristic of complex systems. This paper describes how the FRAM methodology has now been extended to provide these extra, essential attributes. It also describes its implementation using an open-source software, freely available for use and verification on the GitHub site.

Objective This study aims to leverage natural language processing (NLP) and machine learning clustering analyses to (1) identify co-occurring symptoms of patients undergoing catheter ablation for atrial fibrillation (AF) and (2) describe clinical and sociodemographic correlates of symptom clusters.Methods We conducted a cross-sectional retrospective analysis using electronic health records data. Adults who underwent AF ablation between 2010 and 2020 were included. Demographic, comorbidity and medication information was extracted using structured queries. Ten AF symptoms were extracted from unstructured clinical notes (n=13 416) using a validated NLP pipeline (F-score=0.81). We used the unsupervised machine learning approach known as Ward’s hierarchical agglomerative clustering to characterise and identify subgroups of patients representing different clusters. Fisher’s exact tests were used to investigate subgroup differences based on age, gender, race and heart failure (HF) status.Results A total of 1293 patients were included in our analysis (mean age 65.5 years, 35.2% female, 58% white). The most frequently documented symptoms were dyspnoea (64%), oedema (62%) and palpitations (57%). We identified six symptom clusters: generally symptomatic, dyspnoea and oedema, chest pain, anxiety, fatigue and palpitations, and asymptomatic (reference). The asymptomatic cluster had a significantly higher prevalence of male, white and comorbid HF patients.Conclusions We applied NLP and machine learning to a large dataset to identify symptom clusters, which may signify latent biological underpinnings of symptom experiences and generate implications for clinical care. AF patients’ symptom experiences vary widely. Given prior work showing that AF symptoms predict adverse outcomes, future work should investigate associations between symptom clusters and postablation outcomes.

A 52-year-old male presented with multiple tender, plum-coloured facial plaques following the treatment with acitretin 50 mg/day for his psoriasis. The lesions subsided over 3 months. Acitretin was restarted at 20 mg/day as psoriasis flared. A week later, the patient presented with fever and a symmetrically distributed, tender, livid, hemorrhagic papulopustular eruption and large violaceous ulcerated plaques on both soles. Within a week, the patient developed abdominal pain and distension. CT scans of the abdomen showed segments of small bowel wall thickening. Chest X-ray showed consolidation and nodularity of the lung bases. Histopathology demonstrated findings consistent with a diagnosis of Sweet’s syndrome. The diagnosis of drug-induced Sweet’s Syndrome was established. The patient was treated with a combination of intravenous methylprednisolone and cyclophosphamide. Drug-induced SS has been reported to be associated with many drugs, especially granulocyte-monocyte-colony-stimulating-factor and all-trans-retinoic acid. Although very rare, acitretin-induced SS should be considered in a patient who develops pustulonecrotic skin lesions and systemic upset after intake of acitretin.

Este estudio es sobre los movimientos sociales de Latinoamerica a través de los que se ubicaban en el Perú, luego de su experiencia en Dar es Salaam (Tanzania) el autor (Slater) nos introduce a los estudios del desarrollo desde la geografía radical, es la exploración del poder de los movimientos sociales campesinos, contrario a lo que la mayoría de científicos sociales estudiaban como los movimientos obreros desde los países centrales. Al tener una posición postcolonial desde la geografía radical también explora las territorialidades de los asalariados de las ciudades costeras y de los movimientos regionales campesinos del interior del Perú, estudiaba las contradicciones del capital y el trabajo asalariado y registro el trabajo no asalariado que existía antes de la reforma agraria del gobierno militar de Velasco Alvarado. También registro las “otras” formas de producción no capitalistas que persistían como territorialidades alternativas desde la democracia, participación ciudadana y lucha al hegemónico y desordenado capitalismo peruano, además identifico los vacíos o errores de la intervención estatal en los territorios provincianos desde la hegemónica ciudad capital peruana de un régimen militar que se declaró revolucionario, que tampoco se atrevió a decirle reformista. Se centro en dos movimientos sociales uno al sur del Perú en Arequipa y el otro al oriente del país en Pucalpa.

Abstract Background There is limited information available on the impact of moderate asthma exacerbations, often called “asthma attacks” (i.e., those not requiring hospitalisation or treatment with systemic corticosteroids) on patients’ lives. This multi-country qualitative study explored the patient experience of these events. Methods Semi-structured concept elicitation interviews were conducted in the USA and Germany with adult patients with asthma who had experienced a moderate asthma exacerbation in the prior 30 days. Physicians with experience in managing patients with asthma were also interviewed. Interviews explored patients’ experience of symptoms and impact of moderate exacerbations and associated exacerbation triggers and treatment patterns. Physicians were also asked about their interpretation of a clinical definition and treatment of a moderate exacerbation. Results Twenty-eight patient (n = 20 in the USA, n = 8 in Germany) and six physician (n = 3 in the USA, n = 3 in Germany) interviews were conducted. During their moderate exacerbation, all patients reported experiencing shortness of breath, which many considered to be severe and the most bothersome symptom. Wheezing was also reported by all patients and considered severe by two thirds of patients. Most patients also reported coughing and chest tightness. All or almost all patients reported that moderate exacerbation caused fatigue/tiredness and impacted their physical functioning, emotional functioning, activities of daily living and work/school life. Most patients reported using rescue or maintenance inhalers to alleviate symptoms of the exacerbation. Conceptual saturation (i.e., the point at which no new concepts are likely to emerge with continued data collection) was achieved. Findings were used to develop a patient-focused conceptual model of the experience of moderate asthma exacerbations, outlining concepts related to triggers, symptoms, impact, and treatment from the patient perspective. Physician data was consistent with patient reports and complemented the conceptual model. Conclusions Findings from concept elicitation interviews highlight the increased frequency, duration and severity of asthma symptoms and increased rescue medication use during moderate asthma exacerbations compared with the typical daily asthma experience, which have a substantial impact on patients’ lives.

Background: Cardiac implantable electronic devices (CIEDs) may enable early identification of COVID-19 to facilitate timelier intervention. Objective: To characterize early physiologic changes associated with the onset of acute COVID-19 infection, as well as during and after acute infection, among patients with CIEDs. Methods: CIED sensor data from March 2020 to February 2021 from 286 patients with a CIED were linked to clinical data from electronic health records. Three cohorts were created: known COVID-positive (n = 20), known COVID-negative (n = 166), and a COVID-untested control group (n = 100) included to account for testing bias. Associations between changes in CIED sensors from baseline (including HeartLogic index, a composite index predicting worsening heart failure) and COVID-19 status were evaluated using logistic regression models, Wilcoxon signed rank tests, and Mann-Whitney U tests. Results: Significant differences existed between the cohorts by race, ethnicity, CIED device type, and medical admissions. Several sensors changed earlier for COVID-positive vs COVID-negative patients: HeartLogic index (mean 16.4 vs 9.2 days [P = .08]), respiratory rate (mean 8.5 vs 3.9 days [P = .01], and activity (mean 8.2 vs 3.5 days [P = .008]). Respiratory rate during the 7 days before testing significantly predicted a positive vs negative COVID-19 test, adjusting for age, sex, race, and device type (odds ratio 2.31 [95% confidence interval 1.33–5.13]). Conclusion: Physiologic data from CIEDs could signal early signs of infection that precede clinical symptoms, which may be used to support early detection of infection to prevent decompensation in this at-risk population.

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated. Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54–74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11–1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p

Objectives While procedure length is considered an important metric for cardiothoracic surgical procedures, the relationship between procedure length and adverse events (AEs) in congenital cardiac catheterizations has little published data available. Furthermore, most existing congenital cardiac catheterization risk prediction models are built on logistic regression models. This study aimed to characterize the relationship between case length and AE occurrence in congenital cardiac catheterization while adjusting for known risk factors and to investigate the potential role of non-linear analysis in risk modeling.Design Age, case type, and procedure duration were evaluated for relationships with the primary outcome using logistic regression. Non-linearity of the associations with continuous risk factors was assessed using restricted cubic spline transformations.Setting and participants All diagnostic and interventional congenital cardiac catheterization cases performed at Boston Children’s Hospital between January 1, 2014 and October 31, 2019 were analyzed.Main outcome measure The primary outcome was defined as the occurrence of any clinically significant (level 3/4/5) AE.Results A total of 7011 catheterization cases met inclusion criteria, with interventional procedures accounting for 68% of cases. Median case duration was 97 min. A multivariable model including age, procedure type, and case duration showed a significant relationship between case duration and AE occurrence (OR 1.07 per 10 min increase, 95% CI 1.06 to 1.09, p

Measurement(s) Shark bite incidents Technology Type(s) survey Factor Type(s) none Sample Characteristic - Organism Elasmobranchii Sample Characteristic - Environment ocean Sample Characteristic - Location Australia

Abstract Objective To describe common intraoperative and pathologic findings of atypical parathyroid tumors (APTs) and evaluate clinical outcomes in patients undergoing parathyroidectomy. Methods In this multi‐institutional retrospective case series, data were collected from patients who underwent parathyroidectomy from 2000 to 2018 from three tertiary care institutions. APTs were defined according to the AJCC eighth edition guidelines and retrospective chart review was performed to evaluate the incidence of recurrent laryngeal nerve injury, recurrence of disease, and disease‐specific mortality. Results Twenty‐eight patients were identified with a histopathologic diagnosis of atypical tumor. Mean age was 56 years (range, 23–83) and 68% (19/28) were female. All patients had an initial diagnosis of primary hyperparathyroidism with 21% (6/28) exhibiting clinical loss of bone density and 32% (9/28) presenting with nephrolithiasis or renal dysfunction. Intraoperatively, 29% (8/28) required thyroid lobectomy, 29% (8/28) had gross adherence to adjacent structures and 46% (13/28) had RLN adherence. The most common pathologic finding was fibrosis 46% (13/28). Postoperative complications include RLN paresis/paralysis in 14% (4/28) and hungry bone syndrome in 7% (2/28). No patients with a diagnosis of atypical tumor developed recurrent disease, however there was one patient that had persistent disease and hypercalcemia that is being observed. There were 96% (27/28) patients alive at last follow‐up, with one death unrelated to disease. Conclusion Despite the new AJCC categorization of atypical tumors staged as Tis, we observed no recurrence of disease after resection and no disease‐specific mortality. However, patients with atypical tumors may be at increased risk for recurrent laryngeal nerve injury and incomplete resection.

Introduction: The epidemic of gun violence in the United States (US) is exacerbated by frequent mass shootings. In 2021, there were 698 mass shootings in the US, resulting in 705 deaths and 2,830 injuries. This is a companion paper to a publication in JAMA Network Open, in which the nonfatal outcomes of victims of mass shootings have been only partially described. Methods: We gathered clinical and logistic information from 31 hospitals in the US about 403 survivors of 13 mass shootings, each event involving greater than 10 injuries, from 2012–19. Local champions in emergency medicine and trauma surgery provided clinical data from electronic health records within 24 hours of a mass shooting. We organized descriptive statistics of individual-level diagnoses recorded in medical records using International Classification of Diseases codes, according to the Barell Injury Diagnosis Matrix (BIDM), a standardized tool that classifies 12 types of injuries within 36 body regions. Results: Of the 403 patients who were evaluated at a hospital, 364 sustained physical injuries—252 by gunshot wound (GSW) and 112 by non-ballistic trauma—and 39 were uninjured. Fifty patients had 75 psychiatric diagnoses. Nearly 10% of victims came to the hospital for symptoms triggered by, but not directly related to, the shooting, or for exacerbations of underlying conditions. There were 362 gunshot wounds recorded in the Barell Matrix (1.44 per patient). The Emergency Severity Index (ESI) distribution was skewed toward higher acuity than typical for an emergency department (ED), with 15.1% ESI 1 and 17.6% ESI 2 patients. Semi-automatic firearms were used in 100% of these civilian public mass shootings, with 50 total weapons for 13 shootings (Route 91 Harvest Festival, Las Vegas. 24). Assailant motivations were reported to be associated with hate crimes in 23.1%. Conclusion: Survivors of mass shootings have substantial morbidity and characteristic injury distribution, but 37% of victims had no GSW. Law enforcement, emergency medical systems, and hospital and ED disaster planners can use this information for injury mitigation and public policy planning. The BIDM is useful to organize data regarding gun violence injuries. We call for additional research funding to prevent and mitigate interpersonal firearm injuries, and for the National Violent Death Reporting System to expand tracking of injuries, their sequelae, complications, and societal costs.

Widespread and substantial diversification of current agroecosystems appears fundamental to meeting many grand challenges in agriculture. Despite urgent calls for diversification on regional scales, particularly in regions dominated by industrialized, low-diversity agriculture, strategies for diversification on such scales are in early stages of development, conceptually and practically. We outline such a strategy, and its implementation by the Forever Green Partnership, a public-private-NGO coalition in support of agricultural diversification in the U.S. Midwest region. Our strategy supports introduction and scaling of multiple novel crops in a region, which requires development of many interdependent supporting elements, including supportive markets, infrastructure, policy, finance, and R&D. The core of our strategy is development of sustainable supply chains (SSCs) for a set of novel crops. We define SSCs as rudimentary systems of these supporting elements for novel crops, linking on-farm crop production to end-use markets while advancing economic, environmental, and social sustainability criteria that are demanded by stakeholders. SSCs provide a scaffold upon which fully-developed support systems for multiple novel crops can be constructed, thus driving regional diversification. SSCs cannot be “built in a day”; rather they must evolve as production of novel crops expands over time and space, and as new challenges and opportunities emerge. Therefore, regional diversification requires a system to sustain this evolutionary process across time and multiple novel crops. We posit that an effective system can be built from two crucial elements: a process of conscious and concerted cultural evolution, and a polycentric network that organizes and supports that process. We outline this system and its conceptual basis, and its implementation by the Forever Green Partnership, and associated challenges and accomplishments. Three years after its inception, the Partnership has attracted substantial resources, developed a polycentric network, and some elements of the cultural-evolution process are in place. However, node development is uneven across the network, hindering its operation. In addition to advancing strategies for regional-scale diversification, the Partnership is seeking to advance conceptual and practical understanding of sustainability transitions in agriculture, and to explore the potential value of conscious cultural evolution in such transitions.

The Dobbs v. Jackson decision by the United States Supreme Court has rescinded the constitutional guarantee of abortion across the United States. As a result, at least 13 states have banned abortion access with unknown effects. Using “Texas” SB8 law that similarly restricted abortions in Texas, we provide insight into how individuals respond to these restrictions using aggregated and anonymized human mobility data. We find that “Texas” SB 8 law reduced mobility near abortion clinics in Texas by people who live in Texas and those who live outside the state. We also find that mobility from Texas to abortion clinics in other states increased, with notable increases in Missouri and Arkansas, two states that subsequently enacted post-Dobbs bans. These results highlight the importance of out-of-state abortion services for women living in highly restrictive states.

The goal of this paper is to share an analytic framework for understanding Students’ Ways of Thinking (SWoT) in STEM-rich learning environments. Before revealing our refined coding framework, we detail the nature of our collaborations and the various analytic decisions that led to its formation. These collaborations supported our collective ability to make sense of SWoT and produce a more coherent perspective that can be operationalized in STEM contexts. Our analytic framework foregrounds student claim-making and the related evidence and reasoning used in support. Specific commentary about the development and application of each coding category is provided, including examples of student data and rationale for related coding decisions. Our analytic framework, and discussion of its formation, can help educators, curriculum makers, and policymakers make use of SWoT in the development of meaningful and effective STEM education.

Objective We quantified inflammatory burden in rheumatoid arthritis (RA) synovial tissue by using computer vision to automate the process of counting individual nuclei in hematoxylin and eosin images. Methods We adapted and applied computer vision algorithms to quantify nuclei density (count of nuclei per unit area of tissue) on synovial tissue from arthroplasty samples. A pathologist validated algorithm results by labeling nuclei in synovial images that were mislabeled or missed by the algorithm. Nuclei density was compared with other measures of RA inflammation such as semiquantitative histology scores, gene‐expression data, and clinical measures of disease activity. Results The algorithm detected a median of 112,657 (range 8,160‐821,717) nuclei per synovial sample. Based on pathologist‐validated results, the sensitivity and specificity of the algorithm was 97% and 100%, respectively. The mean nuclei density calculated by the algorithm was significantly higher (P

Aims Slipped upper femoral epiphysis (SUFE) has well documented biochemical and mechanical risk factors. Femoral and acetabular morphologies seem to be equally important. Acetabular retroversion has a low prevalence in asymptomatic adults. Hips with dysplasia, osteoarthritis, and Perthes’ disease, however, have higher rates, ranging from 18% to 48%. The aim of our study was to assess the prevalence of acetabular retroversion in patients presenting with SUFE using both validated radiological signs and tomographical measurements. Methods A retrospective review of all SUFE surgical cases presenting to the Royal Children’s Hospital, Melbourne, Australia, from 2012 to 2019 were evaluated. Preoperative plain radiographs were assessed for slip angle, validated radiological signs of retroversion, and standardized postoperative CT scans were used to assess cranial and mid-acetabular version. Results In all, 116 SUFEs presented in 107 patients who underwent surgical intervention; 47 (52%) were male, with a mean age of 12.7 years (7.5 to 16.6). Complete radiological data was available for 91 patients (99 hips) with adequate axial CT imaging of both hips. Overall, 82 patients (82%) underwent pinning in situ (PIS), with subcapital realignment surgery (SRS) performed in 17 patients (18%) (slip angles > 75°). Contralateral prophylactic PIS was performed in 72 patients (87%). On the slip side, 62 patients (68%) had one or more radiological sign of retroversion. Tomographical acetabular retroversion was more pronounced cranially than caudally of the acetabulum on both the affected side and the contralateral side (p < 0.001) as expected in the normal population. Increasing severity of the slip was found to be directly proportional to the degree of reduction in cranial and central acetabular version (p < 0.05) in the SUFE hips. Conclusion Acetabular retroversion is more prevalent in patients with SUFE than previously reported, and have been shown be correlated to the severity of the slip presentation. The presence of radiological signs of acetabular retroversion could be used to justify prophylactic contralateral pinning. Cite this article: Bone Jt Open 2022;3(2):158–164.

Visibility observations and accurate forecasts are essential in meteorology, requiring a dense network of observation stations. This paper investigates image processing techniques for object detection and visibility determination using static cameras. It proposes a comprehensive method that includes image preprocessing, landmark identification, and visibility estimation, mirroring the observation process of professional meteorological observers. This study validates the visibility observation procedure using the k-nearest neighbors machine learning method across six locations, including four in the Czech Republic, one in the USA, and one in Germany. By comparing our results with professional observations, the paper demonstrates the suitability of the proposed method for operational application, particularly in foggy and low visibility conditions. This versatile method holds potential for adoption by meteorological services worldwide.

Background:. Closed reduction and internal fixation (CRIF) of closed hand fractures in the main operating room (OR) is much more expensive than outside of the OR. However, there is a reluctance to fix fractures out of the OR due to the perceived increase in infections. Our goal was to prospectively analyze the infection rates of performing CRIF of closed metacarpal and phalangeal fractures in these two settings. Methods:. A multicenter prospective analysis of patients undergoing CRIF of metacarpal or phalangeal fractures inside or outside the OR was performed. Demographic data, injury characteristics, surgery information and postoperative infectious complications were recorded, including cellulitis, frank pus, and osteomyelitis. Results:. The study involved 1042 patients with a total of 2265 Kirschner-wires (K-wires). Infection rates were not statistically higher in the 719 patients who had CRIF outside of the OR (cellulitis 2.5%, frank pus 1.4%) compared with the 323 patients with CRIF in the OR group (cellulitis 3.4%, frank pus 2.5%). The OR group had a longer time to operation and a longer procedure time, but a shorter time with the K-wires in place. Conclusion:. K-wire fixation of closed hand fractures outside of the OR under field sterility is safe because it does not increase infectious complications compared to CRIF in the main OR under full sterility.

Coastal pelagic ecosystems are highly variable in space and time, with environmental conditions and the distribution of biomass being driven by complex processes operating at multiple scales. The emergent properties of these processes and their interactive effects result in complex and dynamic environmental mosaics referred to as “seascapes”. Mechanisms that link large-scale oceanographic processes and ecological variability in coastal environments remain poorly understood, despite their importance for predicting how ecosystems will respond to climate change. Here we assessed seascape variability along the path of the rapidly intensifying East Australian Current (EAC) Southern Extension in southeast Australia, a hotspot of ocean warming and ecosystem tropicalisation. Using satellite and in situ measures of temperature, salinity and current velocity coupled with contemporaneous measurements of pelagic biomass distribution from nine boat-based active acoustic surveys in five consecutive years, we investigated relationships between the physical environment and the distribution of pelagic biomass (zooplankton and fish) at multiple timescales. Survey periods were characterised by high variability in oceanographic conditions, with variation in coastal conditions influenced by meso-to-large scale processes occurring offshore, including the position and strength of eddies. Intra-annual variability was often of a similar or greater magnitude to inter-annual variability, suggesting highly dynamic conditions with important variation occurring at scales of days to weeks. Two seascape categories were identified being characterised by (A) warmer, less saline water and (B) cooler, more saline water, with the former indicating greater influence of the EAC on coastal processes. Warmer waters were also associated with fewer, deeper and less dense biological aggregations. As the EAC continues to warm and penetrate further south, it is likely that this will have substantial effects on biological activity in coastal pelagic ecosystems, including a potential reduction in the accessibility of prey aggregations to surface-feeding predators and to fisheries. These results highlight the import role of offshore oceanographic processes in driving coastal seascape variability and biological activity in a region undergoing rapid oceanic warming and ecological change.

The aim of this work was to determine the dependence of the heart rate of operators of forwarding machines on the activities performed during the working day within the framework of timber forwarding and to compare individual activities in terms of the level of physical workload. For this purpose, the work shift of operators carrying out timber forwarding was divided into individual activities: driving, maintenance, forwarding, and break. During these work activities, the heart rate of each operator was taken for subsequent evaluation. A portable device, a Garmin smartwatch, was used to measure their heart rate. The results show that the highest pulse rates of the operators occurred during the maintenance of the entrusted machine, while the highest pulse fluctuations were recorded during forwarding. During this activity, the highest heart rate of the entire measurement process was recorded (132.0000 bpm), but also the lowest (42.0000 bpm). Furthermore, it was proven that both the operator and the activity he performs affect the pulse rate. The activities themselves did not differ from each other in only one of the six cases of comparison, specifically, between driving and forwarding.

Abstract Background Adherence to chronic obstructive pulmonary disease (COPD) maintenance medication is important for managing symptoms and exacerbation risk, and is associated with reduced mortality, hospitalizations, and costs. This study compared on-treatment exacerbations, medical costs, and medication adherence in patients with COPD initiating treatment with umeclidinium/vilanterol (UMEC/VI) or tiotropium (TIO). Methods This retrospective matched cohort study selected patients from Optum’s de-identified Clinformatics Data Mart database who initiated maintenance treatment with UMEC/VI or TIO between 01/01/2014 and 12/31/2017 (index date defined as the first dispensing). Eligible patients were ≥ 40 years of age and had ≥ 12 months continuous health plan coverage pre- and post-index; ≥ 1 medical claim for COPD pre-index or on the index date; no moderate/severe COPD-related exacerbations on the index date; no asthma diagnosis pre- or post-index; no maintenance medication fills containing inhaled corticosteroids, long-acting β2-agonists, or long-acting muscarinic antagonists pre-index or on the index date; and no fills for both UMEC/VI and TIO on the index date. Outcomes included time-to-first (Kaplan–Meier analysis) and rates of on-treatment COPD-related moderate/severe exacerbations, medication adherence (proportion of days covered [PDC] and proportion of adherent patients [PDC ≥ 0.8]), and COPD-related medical costs per patient per month (PPPM). Propensity score matching was used to adjust for potential confounders. Results Each cohort included 3929 matched patients. Kaplan–Meier rates of on-treatment COPD-related exacerbations were similar between cohorts (hazard ratio at 12 months; overall: 0.93, moderate: 0.92, severe: 1.07; all p > 0.05). UMEC/VI versus TIO initiators had significantly higher adherence (mean PDC: 0.44 vs 0.37; p

Abstract Objectives With ever increasingly complex healthcare settings, technology enhanced simulation (TES) is well positioned to explore all perspectives to enhance patient safety and patient outcomes. Analysis from a Safety-II stance requires identification of human adjustments in daily work that are key to maintaining safety. The aim of this paper is to describe an approach to explore the consequences of human variability from a Safety-II perspective and describe the added value of this to TES. Methods The reader is guided through a novel application of functional resonance analysis methodology (FRAM), a method to analyse how a system or activity is affected by human variability, to explore human adaptations observed in in situ simulations (ISS). The structured applicability of this novel approach to TES is described by application to empirical data from the standardised ISS management of paediatric time critical head injuries (TCHI). Results A case series is presented to illustrate the step-wise observation of key timings during ISSs, the construction of FRAM models and the visualisation of the propagation of human adaptations through the FRAM models. The key functions/actions that ensure the propagation are visible, as are the sequelae of the adaptations. Conclusions The approach as described in this paper is a first step to illuminating how to explore, analyse and observe the consequences of positive and negative human adaptations within simulated complex systems. This provides TES with a structured methodology to visualise and reflect upon both Safety-I and Safety-II perspectives to enhance patient safety and patient outcomes.

Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 0.7–2.0 cases/million/year. A majority of patients present with steroid hormone excess or abdominal mass effects, and in 15% of patients ACC is discovered incidentally. We present a case of 30-year-old otherwise asymptomatic Caucasian male who presented with a testicular swelling. Subsequent imaging and investigations revealed disseminated sarcoidosis and an 11 cm adrenal lesion. An adrenalectomy was performed. Histological examination of the resected specimen confirmed an ACC and also demonstrated a thin rim of adrenal tissue containing non-caseating granulomas, consistent with adrenal sarcoid.

Abstract This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society describes the current status of mobile health (“mHealth”) technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self‐management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored.

Calls for more integrated approaches to STEM have reached every sector of education, including formal and nonformal spaces, from early childhood to tertiary levels. The goal of STEM education as an integrated effort shifts beyond acquiring knowledge in any one or combination of STEM disciplines and, instead, focuses on designing solutions to complex, contextual problems that transcend disciplinary boundaries. To realize this goal, we first need to understand what transdisciplinary STEM might actually look and sound like in action, particularly in regard to the nature of student thinking. This paper addresses that need by investigating student reasoning during nonformal STEM-focused learning experiences. We chose four learning episodes, all involving elementary students working on engineering design tasks, to highlight the various ways transdisciplinary thinking might arise or not. In our analysis, we highlight factors that may have supported or hindered the integration of mathematical, scientific, technological, and engineering ways of thinking. For example, the nature of the task, materials provided, and level of adult support influenced the nature of student reasoning. Based on our findings, we provide suggestions for how to promote transdisciplinary thinking in both formal and nonformal spaces.

The anti-Müllerian hormone (AMH) is a glycoprotein that plays an important role in prenatal sex differentiation. It is used as a biomarker in polycystic ovary syndrome (PCOS) diagnostics, as well as for estimating an individual’s ovarian reserve and the ovarian response to hormonal stimulation during in vitro fertilization (IVF). The aim of this study was to test the stability of AMH during various preanalytical conditions that are in accordance with the ISBER (International Society for Biological and Environmental Repositories) protocol. Plasma and serum samples were taken from each of the 26 participants. The samples were then processed according to the ISBER protocol. AMH levels were measured in all the samples simultaneously using the chemiluminescent kit ACCESS AMH in a UniCel® DxI 800 Immunoassay System (Beckman Coulter, Brea, CA, USA). The study proved that AMH retains a relatively high degree of stability during repeated freezing and thawing in serum. AMH was shown to be less stable in plasma samples. Room temperature proved to be the least suitable condition for the storage of samples before performing the biomarker analysis. During the testing of storage stability at 5–7 °C, the values decreased over time for all the plasma samples but remained stable in the serum samples. We proved that AMH is highly stable under various stress conditions. The anti-Müllerian hormone retained the greatest stability in the serum samples.

Introduction Nearly one-quarter of patients discharged from the hospital with heart failure (HF) are readmitted within 30 days, placing a significant burden on patients, families and health systems. The objective of the ‘Using Mobile Integrated Health and Telehealth to support transitions of care among patients with Heart failure’ (MIGHTy-Heart) study is to compare the effectiveness of two postdischarge interventions on healthcare utilisation, patient-reported outcomes and healthcare quality among patients with HF.Methods and analysis The MIGHTy-Heart study is a pragmatic comparative effectiveness trial comparing two interventions demonstrated to improve the hospital to home transition for patients with HF: mobile integrated health (MIH) and transitions of care coordinators (TOCC). The MIH intervention bundles home visits from a community paramedic (CP) with telehealth video visits by emergency medicine physicians to support the management of acute symptoms and postdischarge care coordination. The TOCC intervention consists of follow-up phone calls from a registered nurse within 48–72 hours of discharge to assess a patient’s clinical status, identify unmet clinical and social needs and reinforce patient education (eg, medication adherence and lifestyle changes). MIGHTy-Heart is enrolling and randomising (1:1) 2100 patients with HF who are discharged to home following a hospitalisation in two New York City (NY, USA) academic health systems. The coprimary study outcomes are all-cause 30-day hospital readmissions and quality of life measured with the Kansas City Cardiomyopathy Questionnaire 30 days after hospital discharge. The secondary endpoints are days at home, preventable emergency department visits, unplanned hospital admissions and patient-reported symptoms. Data sources for the study outcomes include patient surveys, electronic health records and claims submitted to Medicare and Medicaid.Ethics and dissemination All participants provide written or verbal informed consent prior to randomisation in English, Spanish, French, Mandarin or Russian. Study findings are being disseminated to scientific audiences through peer-reviewed publications and presentations at national and international conferences. This study has been approved by: Biomedical Research Alliance of New York (BRANY #20-08-329-380), Weill Cornell Medicine Institutional Review Board (20-08022605) and Mt. Sinai Institutional Review Board (20-01901).Trial registration number Clinicaltrials.gov, NCT04662541.

Background: Free mobile applications (apps) that use photoplethysmography (PPG) waveforms may extend atrial fibrillation (AF) detection to underserved populations, but they have not been rigorously evaluated. Objective: The purpose of this study was to systematically review and evaluate the quality, functionality, and adherence to self-management behaviors of existing mobile apps for AF. Methods: We systematically searched 3 app stores for apps that were free, available in English, and intended for use by patients to detect and manage AF. A minimum of 2 reviewers evaluated (1) app quality, using the Mobile Application Rating Scale (MARS); (2) functionality using published criteria; and (3) features that support 4 self-management behaviors (including PPG waveform monitoring) identified using evidence-based guidelines. Interrater reliability between the reviewers was calculated. Results: Of 12 included apps, 5 (42%) scored above average for quality (MARS score ≥3.0). App quality was highest for their ease of use, navigation, layout, and visual appeal (eg, functionality and aesthetics) and lowest for their behavioral change support and subjective impressions of quality. The most common app functionalities were capturing and graphically displaying user-entered data (n = 9 [75%]). Nearly all apps (n = 11 [92%]) supported PPG waveform monitoring, but only 2 (17%) supported all 4 self-management behaviors. Interrater reliability was high (0.75–0.83). Conclusion: The reviewed apps had wide variability in quality, functionality, and adherence to self-management behaviors. Given the accessibility of these apps to underserved populations and the tremendous potential they hold for improving AF detection and management, high priority should be given to improving app quality and functionality.

Abstract Background Impaired thrombin generation (TG) in patients with acquired coagulopathy, is due to low coagulation factors and thrombocytopenia. The latter is typically treated with platelet transfusions and the former with plasma and occasionally with prothrombin complex concentrates (PCCs). We hypothesized that manipulating the concentrations of coagulation factors might result in restoration of platelet‐dependent TG over and above that of simple replacement therapy. Objective To investigate the influence of PCCs on impaired TG secondary to thrombocytopenia. Methods TG was evaluated by thrombin generation assay using a thrombocytopenia model in which normal plasma samples with varying platelet counts (20‐300 × 109/L) were spiked with PCCs (25%‐150% increase in plasma PCC levels). Results PCCs and platelets significantly increased TG in a dose‐dependent manner in vitro. Two‐way repeated measures of analysis of variance showed variance in peak height, area under the curve, time to peak, and velocity. This variance explained, respectively, by levels of PCC was 47, 59, 25 and 53%; by platelet count was 45, 28, 44, and 14%; by the combination was 80, 67, 70, and 62% variance; and a combination with additional interaction was 91, 84, 76, and 68%. TG at a platelet count 40 × 109/L with an approximate 25% increase in PCC concentration was similar to TG at 150 × 109/L. Similarly, patient samples spiked ex vivo with PCCs also showed highly significant improvements in TG. Conclusions Impaired TG of thrombocytopenia is improved by PCCs, supporting the need for additional studies in complex coagulopathies characterized by mild to moderate thrombocytopenia and abnormal coagulation.

Introduction: Lactobacillus rhamnosus is an anaerobic or facultative anaerobic Gram-positive rod that is commonly found in the human gastrointestinal tract and vaginal tract. Infections secondary to L. rhamnosus have not been well illustrated in the literature. The purpose of this study was to describe the clinical courses of patients with L. rhamnosus infection in our institution. Materials and Methods: A retrospective chart review was performed on patients with the growth of L. rhamnosus or L. rhamnosus/casei from January 1, 2013, to December 31, 2017. Results: Forty-seven patients had growth of L. rhamnosus or L. rhamnosus/casei. Of these, 35 patients were included in the study who received therapy. Twenty patients (57.1%) presented with leukocytosis, 17 (48.5%) with fever, and 15 (42.8%) with abdominal pain. Twenty-three (66.1%) had intra-abdominal infection, 8 (22.3%) were bacteremic, and 4 (11.4%) had mediastinitis. Thirty-three patients (94.3%) had a polymicrobial infection. Eighteen (51.4%) patients had disruption of the gastrointestinal tract, 14 (40.0%) had underlying malignancy, and 11 (31.4%) had prior antibiotic exposure. Twenty (57.1%) patients clinically improved after therapy. However, the overall mortality rate was 56.2%, all of whom died of unrelated causes. Conclusion: Lactobacilli are organisms thought to have low pathogenicity. Our study identified cases of L. rhamnosus infections in a population of patients with serious underlying medical conditions.

The attenuated total reflection (ATR) apparatus, with an added partial reflection/partial transmission mode, was used to demonstrate a novel way of characterizing water-based substances at 0.7 to 10.0 THz at the Australian Synchrotron THz-far infrared beamline. The technique utilized a diamond-crystal-equipped ATR to track temperature-dependent changes in reflectance. A “crossover flare” feature in the spectral scan was noted, which appeared to be a characteristic of water and water-dominated compounds. A “quiet zone” feature was also seen, where no temperature-dependent variation in reflectance exists. The variation in these spectral features can be used as a signature for the presence of bound and bulk water. The method can also potentially identify the presence of fats and oils in a biological specimen. The technique requires minimal sample preparation and is non-destructive. The presented method has the promise to provide a novel, real-time, low-preparation, analytical method for investigating biological material, which offers avenues for rapid medical diagnosis and industrial analysis.