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After more than three months of lava dome extrusion, La Soufrière (St. Vincent) transitioned to a series of explosive eruptions in April 2021. Here we present a time-series petrologic analysis of the phenocryst and microlite populations during the first ∼48 hours of explosivity to constrain ascent conditions and processes that drove changes in behavior. Primary eruptive products were crystal-rich (45-50 vol%) basaltic andesites with similar phenocryst phase assemblages and compositions. The change in eruptive style is consistent with overpresurization as a consequence of second boiling from anhydrous microlite crystallization. The microlites display variation between the explosive phases, with two populations: 1) “inherited” - normally zoned high-An plagioclase (>An70) + olivine (Fo62-79) + clinopyroxene + titanomagnetite, inferred to have crystallized at depths >15 km and high water pressures; 2) “juvenile” - unzoned plagioclase (An45-65) + clinopyroxene + orthopyroxene + intermediate pyroxene (Wo12-38) + titanomagnetite, inferred to have crystallized upon ascent due to decompression and degassing. Scoria from the first explosions featured extensive groundmass crystallization and a significant “inherited” microlite population. Later explosions had a more abundant “juvenile” microlite population and lower crystallinity, consistent with more rapid ascent from depth, initiated by decompression following initial blasts and destruction of the lava dome. Supplementary material at https://doi.org/10.6084/m9.figshare.c.6534864

This study describes the cell-free biomanufacturing of a broad-spectrum antiviral protein, griffithsin (GRFT) such that it can be produced with consistent purity and potency in less than 24 hours. We demonstrate GRFT production using two independent cell-free systems, one plant and one microbial. Griffithsin purity and quality were verified using standard regulatory metrics. Efficacy was demonstratedin vitroagainst SARS-CoV-2 and HIV-1 and was nearly identical to that of GRFT expressedin vivo. The proposed production process is efficient and can be readily scaled up and deployed anywhere in the world where a viral pathogen might emerge. The current emergence of viral variants has resulted in frequent updating of existing vaccines and loss of efficacy for front-line monoclonal antibody therapies. Proteins such as GRFT with its efficacious and broad virus neutralizing capability provide a compelling pandemic mitigation strategy to promptly suppress viral emergence at the source of an outbreak.

Background: Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide.Methods: A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected.Results: We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity.Conclusions: Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes. Background: Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide.Methods: A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected.Results: We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity.Conclusions: Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes.

© 2023 Elsevier B.V. All rights reserved., Background: The possibility of atypical antipsychotics (AA) to induce manic symptoms has been raised by several articles. The objective of this study was to describe whether exposure to AA may induce mania in mood disorders. Methods: We performed a systematic review following the preferred reporting items for systematic reviews and meta-analysis guidelines. The systematic search encompassed all relevant studies published until April 4th, 2022. A meta-analysis testing whether treatment emergent mania (TEM) is more frequent with the use of AA compared with placebo was performed. Results: A total of 52 studies were included in the systematic review. We found 24 case reports or case series describing 40 manic/hypomanic episodes allegedly induced by AA. Twenty-one placebo-controlled trials were included in a meta-analysis including 4823 individuals treated with AA and 3252 individuals receiving placebo. Our meta-analysis showed that the use of AA protects against the development of TEM (OR: 0.68 [95 % CI: 0.52-0.89], p = 0.005). Limitations: AA-induced mania/hypomania was not the primary outcome in any of the observational or interventional studies. TEM was not homogeneously defined across studies. In most case reports it was not possible to establish causality between the use of AA and the development of manic symptoms. Conclusions: TEM is more frequent with placebo than with AA, which suggests that AA exposure does not represent a relevant risk for TEM. Mania/hypomania induced by an AA seems to be rare events, since anecdotal evidence from case reports and case series were not observed in observational prospective and interventional studies.

Background: Established randomized trial-based parameters for acute ischemic stroke group patients into generic treatment groups, leading to attempts using various artificial intelligence (AI) methods to directly correlate patient characteristics to outcomes and thereby provide decision support to stroke clinicians. We review AI-based clinical decision support systems in the development stage, specifically regarding methodological robustness and constraints for clinical implementation. Methods: Our systematic review included full-text English language publications proposing a clinical decision support system using AI techniques for direct decision support in acute ischemic stroke cases in adult patients. We (1) describe data and outcomes used in those systems, (2) estimate the systems’ benefits compared with traditional stroke diagnosis and treatment, and (3) reported concordance with reporting standards for AI in healthcare. Results: One hundred twenty-one studies met our inclusion criteria. Sixty-five were included for full extraction. In our sample, utilized data sources, methods, and reporting practices were highly heterogeneous. Conclusions: Our results suggest significant validity threats, dissonance in reporting practices, and challenges to clinical translation. We outline practical recommendations for the successful implementation of AI research in acute ischemic stroke treatment and diagnosis.

BACKGROUND: Post-stroke arm impairment at rehabilitation admission as predictor of discharge arm impairment was consistently reported as extremely useful. Several models for acute prediction exist (e.g. the Scandinavian), though lacking external validation and larger time-window admission assessments. OBJECTIVES: (1) use the 33 Fugl-Meyer Assessment-Upper Extremity (FMA-UE) individual items to predict total FMA-UE score at discharge of patients with ischemic stroke admitted to rehabilitation within 90 days post-injury, (2) use eight individual items (seven from the Scandinavian study plus the top predictor item from objective 1) to predict mild impairment (FMA-UE≥48) at discharge and (3) adjust the top three models from objective 2 with known confounders. METHODS: This was an observational study including 287 patients (from eight settings) admitted to rehabilitation (2009-2020). We applied regression models to candidate predictors, reporting adjusted R 2, odds ratios and ROC-AUC using 10-fold cross-validation. RESULTS: We achieved good predictive power for the eight item-level models (AUC: 0.70-0.82) and for the three adjusted models (AUC: 0.85-0.88). We identified finger mass flexion as new item-level top predictor (AUC:0.88) and time to admission (OR = 0.9(0.9;1.0)) as only common significant confounder. CONCLUSION: Scandinavian item-level predictors are valid in a different context, finger mass flexion outperformed known predictors, days-to-admission predict discharge mild arm impairment.

Identifying alien species is important to ensure the early detection of biological invasions and survey shifts in species distributions in the context of global change. Here, we report on three alien bark and ambrosia beetles newly detected in Switzerland: Cyclorhipidion distinguendum (Eggers, 1930), C. pelliculosum (Eichhoff, 1878), and Hypothenemus eruditus (Westwood, 1834). These species were recorded for the first time during a comprehensive survey of saproxylic beetles accross major forest types and along an altitudinal gradient during the entire growing season in the southern Alps, in the canton of Ticino. Their local abundance and number of occurrences accross different lowland forest habitats, including alluvial forests of national importance, indicates that all three species are already naturalized. Given their polyphagy, it is likely that all three species will become more extensively distributed across Switzerland, with a yet unknown environmental impact.

The National Weather Service plays a critical role in alerting the public when dangerous weather occurs. Tornado warnings are one of the most publicly visible products the NWS issues given the large societal impacts tornadoes can have. Understanding the performance of these warnings is crucial for providing adequate warning during tornadic events and improving overall warning performance. This study aims to understand warning performance during the lifetimes of individual storms (specifically in terms of probability of detection and lead time). For example, does probability of detection vary based on if the tornado was the first produced by the storm, or the last? We use tornado outbreak data from 2008 to 2014, archived NEXRAD radar data, and the NWS verification database to associate each tornado report with a storm object. This approach allows for an analysis of warning performance based on the chronological order of tornado occurrence within each storm. Results show that the probability of detection and lead time increase with later tornadoes in the storm; the first tornadoes of each storm are less likely to be warned and on average have less lead time. Probability of detection also decreases overnight, especially for first tornadoes and storms that only produce one tornado. These results are important for understanding how tornado warning performance varies during individual storm life cycles and how upstream forecast products (e.g., Storm Prediction Center tornado watches, mesoscale discussions, etc.) may increase warning confidence for the first tornado produced by each storm. Significance Statement In this study, we focus on better understanding real-time tornado warning performance on a storm-by-storm basis. This approach allows us to examine how warning performance can change based on the order of each tornado within its parent storm. Using tornado reports, warning products, and radar data during tornado outbreaks from 2008 to 2014, we find that probability of detection and lead time increase with later tornadoes produced by the same storm. In other words, for storms that produce multiple tornadoes, the first tornado is generally the least likely to be warned in advance; when it is warned in advance, it generally contains less lead time than subsequent tornadoes. These findings provide important new analyses of tornado warning performance, particularly for the first tornado of each storm, and will help inform strategies for improving warning performance.

Focused Clinical Question: Does the application of kinesiotape compared with standard treatments result in greater/faster postoperative edema reduction after total knee replacement or anterior cruciate ligament repair?Clinical Bottom Line: There was sufficient evidence to support the application of kinesiotape to reduce postoperative edema brought on by a total knee replacement or anterior cruciate ligament repair. Patients who received kinesiotaping, applied to the skin with a pattern to enhance lymphatic drainage, showed significant decreases in postoperative knee circumference measurements and pain levels. Kinesiotaping application under these acute conditions offers an evidence-based approach for clinicians to optimize the physiological environment and promote progress through a patient’s phases of healing.

This study provides evidence that hypothalamic gliosis is a key early event through which androgen deficiency in combination with a Western-style diet might lead to cardiometabolic dysregulation in males. Furthermore, this work provides the first evidence in humans of a positive association between hypothalamic gliosis and LDL-cholesterol, advancing our knowledge of CNS influences on CVD risk progression.

It is unclear how often adolescents with persistent asthma know when to use different inhaled medications (as-needed rescue vs. daily controller; 'accurate use'), or whether this knowledge is associated with clinical asthma outcomes. This study aimed to characterize adolescent knowledge of accurate use; examine whether accurate use is associated with controller medication adherence, asthma symptoms, or exacerbations requiring acute health care services; and determine whether knowledge of accurate use improves following regular exposure to controller medications with school-based directly observed therapy (DOT).We analyzed baseline and 7-month data from the School-Based Asthma Care for Teens trial. Adolescents (12-16 years) identified inhaled medications on a chart and stated when each is used. We compared accurate use with adolescent-reported adherence, recent symptoms, and asthma-related acute health care visits; and exposure to DOT. Analyses were limited to subjects with controller medication.Of 430 participants, 252 had controller medication at baseline. Knowledge of accurate use was described by 62%, and associated with adherence (odds ratio [OR]: 2.06, 95% confidence interval [CI]: 1.12-3.83). By 7 months, 313 adolescents had controller medication; 75% described accurate use, which was associated with adherence (OR: 3.46, 95% CI: 1.83-6.54), health care (OR: 0.39, 95% CI: 0.20-0.79), and DOT exposure (OR: 1.83, 95% CI: 1.10-3.32). Associations with adherence and health care at 7 months persisted in adjusted analyses.Adolescent knowledge of accurate medication use was linked with greater adherence (baseline, 7 months), less acute health care (7 months), and exposure to in-school DOT. Interventions to support adolescents with persistent asthma should consider school-based care strategies and facilitate adolescent understanding of when to use different medications.

Because of its antiarrhythmic potency and due to the lack of alternatives, amiodarone is often used for antiarrhythmic therapy in patients with ICD or CRT-D systems. To date, robust data on the safety and clinical benefit of amiodarone therapy in these patients are missing OBJECTIVE: This study was designed to assess the periprocedural and post-procedural outcome of combined therapy with beta-blockers plus amiodarone compared to treatment with single beta-blockers in this "real life" cohort of ICD recipients of the German DEVICE registry.4,499 patients who underwent ICD implantation, revision, or upgrade in 49 centers participating in the German DEVICE Registry were enrolled 03/2007-02/2014.Amiodarone had no significant effect on the success of defibrillation testing. Early implantation-associated complications were similar between the groups. One-year overall mortality was, however, significantly higher in the beta-blocker plus amiodarone cohort (adjusted HR 2.09; p0.001). Interestingly, amongst the surviving patients, amiodarone was not associated with a significantly reduced risk of ICD discharges, syncopal events. Further, the occurrence of VT storm or incessant VTs and the number of patients scheduled for intracardiac ablation did not differ among both groups while the rate of rehospitalization was lower in the cohort with sole beta-blockers.While amiodarone has no adverse effect on the success of defibrillation testing, our data suggest an increased all-cause mortality under amiodarone therapy, especially in the subgroups of patients with sinus rhythm or severely reduced left ventricular function. In surviving patients, rates of arrhythmic events were comparable.

Elevated pulmonary vascular resistance (PVR) is broadly accepted as an imminent risk factor for mortality after heart transplantation (HTx). However, no current HTx recipient risk score includes PVR or other hemodynamic parameters. This study examined the utility of various hemodynamic parameters for risk stratification in a contemporary HTx population.Patients from seven German HTx centers undergoing HTx between 2011 and 2015 were included retrospectively. Established risk factors and complete hemodynamic datasets before HTx were analyzed. Outcome measures were overall all-cause mortality, 12-month mortality, and right heart failure (RHF) after HTx.The final analysis included 333 patients (28% female) with a median age of 54 (IQR 46-60) years. The median mean pulmonary artery pressure was 30 (IQR 23-38) mm Hg, transpulmonary gradient 8 (IQR 5-10) mm Hg, and PVR 2.1 (IQR 1.5-2.9) Wood units. Overall mortality was 35.7%, 12-month mortality was 23.7%, and the incidence of early RHF was 22.8%, which was significantly associated with overall mortality (log-rank HR 4.11, 95% CI 2.47-6.84; log-rank p.0001). Pulmonary arterial elastance (Ea) was associated with overall mortality (HR 1.74, 95% CI 1.25-2.30; p.001) independent of other non-hemodynamic risk factors. Ea values below a calculated cutoff represented a significantly reduced mortality risk (HR 0.38, 95% CI 0.19-0.76; p.0001). PVR with the established cutoff of 3.0 WU was not significant. Ea was also significantly associated with 12-month mortality and RHF.Ea showed a strong impact on post-transplant mortality and RHF and should become part of the routine hemodynamic evaluation in HTx candidates.

Objectives The growing demand for palliative care has been accelerated due to the COVID-19 pandemic. However, providing community-based palliative care was also more difficult to do safely and faced several challenges. The goal of this integrative review was to identify, describe, and synthesize previous studies on the challenges for health professionals delivering palliative care in the community during the COVID-19 pandemic. Methods Searches were carried out on the Ovid MEDLINE, CINAHL, PsycINFO, Social Care Online, PubMed, Embase, and Expanded Academic databases. Journals typically reporting palliative care and community health studies were also searched (Palliative Medicine, Journal of Pain and Symptom Management, and Health & Social Care in the Community). All articles were peer-reviewed and published in English between December 2019 and September 2022. Results Database and hand searches identified 1231 articles. After duplicates were removed and the exclusion criteria applied, 27 articles were included in the final review. Themes in the research findings centered on 6 interconnected categories. The challenges imposed by the pandemic (lack of resources, communication difficulties, access to education and training, and interprofessional coordination), as well as the varying levels of success of the health-care responses, impacted the well-being of health professionals and, in turn, the well-being and care of patients and families. Significance of results The pandemic has provided the impetus for rethinking flexible and innovative approaches to overcome the challenges of delivering community palliative care. However, existing governmental and organizational policies require revision to improve communication and effective interprofessional collaboration, and additional resources are needed. A blended model of virtual and in-person palliative care delivery may provide the best solution to community palliative care delivery moving forward.

Community integration (CI) is often regarded as the foundation of rehabilitation endeavors after stroke; nevertheless, few studies have investigated the relationship between inpatient rehabilitation (clinical and demographic) variables and long-term CI. To identify novel classes of patients having similar temporal patterns in CI and relate them to baseline features. Retrospective observational cohort study analyzing (n = 287) adult patients with stroke admitted to rehabilitation between 2003 and 2018, including baseline Functional Independence Measure (FIM) at discharge, follow-ups (m = 1264) of Community Integration Questionnaire (CIQ) between 2006 and 2022. Growth mixture models (GMMs) were fitted to identify CI trajectories, and baseline predictors were identified using multivariate logistic regression (reporting AUC) with 10-fold cross validation. Each patient was assessed at 2.7 (2.2–3.7), 4.4 (3.7–5.6), and 6.2 (5.4–7.4) years after injury, 66% had a fourth assessment at 7.9 (6.8–8.9) years. GMM identified three classes of trajectories: Lowest CI (n=105, 36.6%): The lowest mean total CIQ; highest proportion of dysphagia (47.6%) and aphasia (46.7%), oldest at injury, largest length of stay (LOS), largest time to admission, and lowest FIM. Highest CI (n=63, 21.9%): The highest mean total CIQ, youngest, shortest LOS, highest education (27% university) highest FIM, and Intermediate CI (n=119, 41.5%): Intermediate mean total CIQ and FIM scores. Age at injury OR: 0.89 (0.85–0.93), FIM OR: 1.04 (1.02–1.07), hypertension OR: 2.86 (1.25–6.87), LOS OR: 0.98 (0.97–0.99), and high education OR: 3.05 (1.22–7.65) predicted highest CI, and AUC was 0.84 (0.76–0.93). Novel clinical (e.g. hypertension) and demographic (e.g. education) variables characterized and predicted long-term CI trajectories.

Laser powder bed fusion of metals (PBF-LB/M) is advantageous for manufacturing bulk metallic glasses with size and geometrical freedom. However, the oxygen uptake along the production chain can negatively impact the generation of high-quality, amorphous parts. In this context, Cu–Ti-based alloys were gas-atomised and additively manufactured using commercial- (CP) and high-purity (HP) feedstocks. The oxygen absorption in each processing step was tracked and related to the amorphous phase formation and glass-forming ability (GFA) of alloys. Results show an increasing oxygen absorption, considerably influenced by the starting feedstock, especially for CP. In HP material, the most contribution is inherent from the powder oxygen content. Results reveal the lack of influence of the oxygen content in the GFA. TEM analysis of commercial powder and PBF-LB/M sample show uniform and featureless micrographs, displaying the absence of oxygen-induced nucleation. The present contribution enhances the qualification and economic processability of amorphous metals by PBF-LB/M. in press

In the era of blood group genomics, reference collections of complete and fully resolved blood group gene alleles have gained high importance. For most blood groups, however, such collections are currently lacking, as resolving full-length gene sequences as haplotypes (ie, separated maternal/paternal origin) remains exceedingly difficult with both Sanger and short-read next-generation sequencing. Using the latest third-generation long-read sequencing, we generated a collection of fully resolved sequences for all 6 main ABO allele groups: ABO∗A1/A2/B/O.01.01/O.01.02/O.02. We selected 77 samples from an ABO genotype data set (n = 25 200) of serologically typed Swiss blood donors. The entire ABO gene was amplified in 2 overlapping long-range polymerase chain reactions (covering ∼23.6 kb) and sequenced by long-read Oxford Nanopore sequencing. For quality validation, 2 samples per ABO group were resequenced using Illumina and Pacific Biosciences technology. All 154 full-length ABO sequences were resolved as haplotypes. We observed novel, distinct sequence patterns for each ABO group. Most genetic diversity was found between, not within, ABO groups. Phylogenetic tree and haplotype network analyses highlighted distinct clades of each ABO group. Strikingly, our data uncovered 4 genetic variants putatively specific for ABO∗A1, for which direct diagnostic targets are currently lacking. We validated A1-diagnostic potential using whole-genome data (n = 4872) of a multiethnic cohort. Overall, our sequencing strategy proved powerful for producing high-quality ABO haplotypes and holds promise for generating similar collections for other blood groups. The publicly available collection of 154 haplotypes will serve as a valuable resource for molecular analyses of ABO, as well as studies about the function and evolutionary history of ABO.

Background Platelets are key players in the pathophysiology of coronary artery disease (CAD) and platelet hyperreactivity leads to increased risk of developing adverse cardiovascular events. Further, significant changes in the platelet lipidome occur in patients with acute coronary syndrome (ACS) and critically regulated lipids lead to platelet hyperresponsiveness. Statin treatment is crucial in the treatment and prevention of patients with CAD by remodeling lipid metabolism. Objective In this study, we investigate the platelet lipidome of CAD patients by untargeted lipidomics, highlighting significant changes between statin-treated and naïve patients. Methods We characterized the platelet lipidome in a CAD cohort (n = 105) by an untargeted lipidomics approach using liquid chromatography coupled to mass spectrometry. Results Among the annotated lipids, 41 lipids were significantly upregulated in statin-treated patients, whereas 6 lipids were downregulated compared to naïve patients. The most prominent upregulated lipids in statin-treated patients belong to the class of triglycerides, cholesteryl esters, palmitic acid, and oxidized phospholipids, whereas mainly glycerophospholipids were downregulated compared to untreated patients. A more pronounced effect of statin treatment on the platelet lipidome was observed in ACS patients. We further highlight a dose-dependent influence on the platelet lipidome. Conclusion Our results reveal that the platelet lipidome is altered in CAD patients with statin treatment and upregulated lipids embody mainly characteristic triglycerides, whereas downregulated lipids mostly compromise glycerophospholipids, which may play a role in the pathophysiology of CAD. Results of this study may contribute to the understanding of statin treatment softening the lipid phenotype.

This paper aims to identify all of the unexploited potentialities of sports activities with regard to sustainability by answering the following question: Considering the priorities that the 2030 Agenda identified with regard to sustainability, what does sport contribute to the process of transition towards a more sustainable global scenario? According to the European Union Council, sport and physical activity play a strategic role in the global challenge toward sustainability and achieving the 17 SDGs. The contribution of sport to the 2030 Agenda is indeed strategic. However, through a non-systematic review, the authors have observed almost a complete absence of SDGs within sports literature. Discussing the results through the lens of the SDGs, the authors have identified a series of qualitative and quantitative research opportunities connected with the 17 SDGs and related targets. The authors have also identified a total of 27 research hypotheses. This evidence could support academics, sports managers, professionals, and practitioners in identifying their contribution to the global priorities towards sustainability.