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9 páginas.- 5 figuras.- 51 referencias.- Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41561-023-01170-x, Soil mosses are among the most widely distributed organisms on land. Experiments and observations suggest that they contribute to terrestrial soil biodiversity and function, yet their ecological contribution to soil has never been assessed globally under natural conditions. Here we conducted the most comprehensive global standardized field study to quantify how soil mosses influence 8 ecosystem services associated with 24 soil biodiversity and functional attributes across wide environmental gradients from all continents. We found that soil mosses are associated with greater carbon sequestration, pool sizes for key nutrients and organic matter decomposition rates but a lower proportion of soil-borne plant pathogens than unvegetated soils. Mosses are especially important for supporting multiple ecosystem services where vascular-plant cover is low. Globally, soil mosses potentially support 6.43 Gt more carbon in the soil layer than do bare soils. The amount of soil carbon associated with mosses is up to six times the annual global carbon emissions from any altered land use globally. The largest positive contribution of mosses to soils occurs under a high cover of mat and turf mosses, in less-productive ecosystems and on sandy and salty soils. Our results highlight the contribution of mosses to soil life and functions and the need to conserve these important organisms to support healthy soils., The study work associated with this paper was funded by a Large Research Grant from the British Ecological Society (no. LRB17\1019; MUSGONET). D.J.E. is supported by the Hermon Slade Foundation. M.D.-B. was supported by a Ramón y Cajal grant from the Spanish Ministry of Science and Innovation (RYC2018-025483-I), a project from the Spanish Ministry of Science and Innovation for the I + D + i (PID2020-115813RA-I00 funded by MCIN/AEI/10.13039/501100011033a) and a project PAIDI 2020 from the Junta de Andalucía (P20_00879). E.G. is supported by the European Research Council grant agreement 647038 (BIODESERT). M.B. is supported by a Ramón y Cajal grant from Spanish Ministry of Science (RYC2021-031797-I). A.d.l.R is supported by the AEI project PID2019-105469RB-C22. L.W. and Jianyong Wang are supported by the Program for Introducing Talents to Universities (B16011) and the Ministry of Education Innovation Team Development Plan (2013-373). The contributions of T.G. and T.U.N. were supported by the Research Program in Forest Biology, Ecology and Technology (P4-0107) and the research projects J4-3098 and J4-4547 of the Slovenian Research Agency. The contribution of P.B.R. was supported by the NSF Biological Integration Institutes grant DBI-2021898. J. Durán and A. Rodríguez acknowledge support from the FCT (2020.03670.CEECIND and SFRH/BDP/108913/2015, respectively), as well as from the MCTES, FSE, UE and the CFE (UIDB/04004/2021) research unit financed by FCT/MCTES through national funds (PIDDAC).

Sport coaches can play an influential role in athletes’ mental health help seeking through purposeful communication, destigmatization of mental health concerns, and supportive relationships. To positively engage in these behaviors, coaches require mental health knowledge (or literacy), positive attitudes about that knowledge, and self-efficacy to use that knowledge. Guided by a multidimensional health literacy framework, we conducted a content analysis of web content and scholarly literature to identify health education programming for coaches that addressed athlete mental health. A purposive sample of Olympic National Governing Bodies, collegiate athletic associations, high school sport associations, youth sport governing bodies, and the scholarly literature were analyzed. We found inconsistent programming regarding a range of mental health disorders, behaviors critical to mental health promotion, and critical components of mental health literacy. Implications and next steps for mental health literacy support for coaches are discussed.

In spatial statistics, a common objective is to predict values of a spatial process at unobserved locations by exploiting spatial dependence. Kriging provides the best linear unbiased predictor using covariance functions and is often associated with Gaussian processes. However, when considering non-linear prediction for non-Gaussian and categorical data, the Kriging prediction is no longer optimal, and the associated variance is often overly optimistic. Although deep neural networks (DNNs) are widely used for general classification and prediction, they have not been studied thoroughly for data with spatial dependence. In this work, we propose a novel DNN structure for spatial prediction, where the spatial dependence is captured by adding an embedding layer of spatial coordinates with basis functions. We show in theory and simulation studies that the proposed DeepKriging method has a direct link to Kriging in the Gaussian case, and it has multiple advantages over Kriging for non-Gaussian and non-stationary data, i.e., it provides non-linear predictions and thus has smaller approximation errors, it does not require operations on covariance matrices and thus is scalable for large datasets, and with sufficiently many hidden neurons, it provides the optimal prediction in terms of model capacity. We further explore the possibility of quantifying prediction uncertainties based on density prediction without assuming any data distribution. Finally, we apply the method to predicting PM2.5 concentrations across the continental United States.

Traditionally, multiple sclerosis has been categorised by distinct clinical descriptors—relapsing-remitting, secondary progressive, and primary progressive—for patient care, research, and regulatory approval of medications. Accumulating evidence suggests that the clinical course of multiple sclerosis is better considered as a continuum, with contributions from concurrent pathophysiological processes that vary across individuals and over time. The apparent evolution to a progressive course reflects a partial shift from predominantly localised acute injury to widespread inflammation and neurodegeneration, coupled with failure of compensatory mechanisms, such as neuroplasticity and remyelination. Ageing increases neural susceptibility to injury and decreases resilience. These observations encourage a new consideration of the course of multiple sclerosis as a spectrum defined by the relative contributions of overlapping pathological and reparative or compensatory processes. New understanding of key mechanisms underlying progression and measures to quantify progressive pathology will potentially have important and beneficial implications for clinical care, treatment targets, and regulatory decision-making.

Polymicrobial syndromes such as Bacterial Vaginosis (BV), where there is a great diversity of microorganisms and causal connotations, turn it into a disease with complex dynamics in the bacteria’s coexistence in groups of patients. The main aim of this study was to explore a dataset of patients with BV to determine a more informed number of groups to create for further analysis of bacteria’s coexistence. The Agglomerative Hierarchical Clustering (AHC) algorithm was applied to a BV dataset from an urban population in southeastern Mexico consisting of 201 patient records with 59 patient attributes and three classes (BV-positive, BV-negative, BV-indeterminate). In the clustering results obtained, it is possible to identify different remarkable groups of patients. The most prevalent coexisting bacteria among patients with BV were Atopobium + Gardnerella vaginalis with 37.50%, Atopobium + Megasphaera with 15.68% in the first experiment. Whereas, in the second experiment, the coexisting bacteria were Atopobium + Megasphaera + Mycoplasma hominis with 33.33% and Atopobium + Gardnerella vaginalis + Mycoplasma hominis with 25%. Finally, we provided evidence that via the AHC algorithm, it was possible to identify an optimal number of clusters with high intra-similarity and inter-dissimilarity. Furthermore, this approach allowed us to create a clustering model that helps analyze the complex dynamics between bacteria in groups of patients with BV.

SummaryZink ist ein wichtiges Spurenelement im menschlichen Körper. Zu den Folgen von Zinkmangel gehören unter anderem eine erhöhte Infektanfälligkeit, Hauterkrankungen sowie Wachstums- und Fruchtbarkeitsstörungen. Das Spurenelement spielt eine wichtige Rolle für die Immunabwehr: Zink ist für die humorale und zelluläre Immun­antwort wichtig, unterstützt Bereiche der angeborenen und erworbenen Immunabwehr und führt zu einer direkten Aktivierung von Makrophagen. Typische Symptome, eine Patientenanamnese sowie Laborbefunde weisen einen Zinkmangel nach. Dieser wird durch den Einsatz hoch dosierter Zinkpräparate behoben.

We present existence and controllability results for mild solutions to the Atangana–Baleanu fractional evolution equations. We prove our results by applying bounded integral contractors and a sequencing technique. In contrast to the papers available in the literature, in order to establish our controllability results, we need not define the induced inverse of the controllability operator, and the pertinent nonlinear function need not necessarily satisfy a Lipschitz condition. In addition, we also establish trajectory controllability results. Finally, we discuss an application, which illustrates our results.

The induction of partial tolerance toward pancreatic autoantigens in the treatment of type 1 diabetes mellitus (T1DM) can be attained by autologous hematopoietic stem cell transplantation (HSCT). However, most patients treated by autologous HSCT eventually relapse. Furthermore, allogeneic HSCT which could potentially provide a durable non-autoimmune T-cell receptor (TCR) repertoire is associated with a substantial risk for transplant-related mortality. We have previously demonstrated an effective approach for attaining engraftment without graft versus host disease (GVHD) of allogeneic T-cell depleted HSCT, following non-myeloablative conditioning, using donor-derived anti-3rd party central memory CD8 veto T cells (Tcm). In the present study, we investigated the ability of this relatively safe transplant modality to eliminate autoimmune T-cell clones in the NOD mouse model which spontaneously develop T1DM. Our results demonstrate that using this approach, marked durable chimerism is attained, without any transplant-related mortality, and with a very high rate of diabetes prevention. TCR sequencing of transplanted mice showed profound changes in the T-cell repertoire and decrease in the prevalence of specific autoimmune T-cell clones directed against pancreatic antigens. This approach could be considered as strategy to treat people destined to develop T1DM but with residual beta cell function, or as a platform for prevention of beta cell destruction after transplantation of allogenic beta cells.

The study focuses on the analysis of Middle Neolithic burial complexes of the Baikal-Yenisey Siberia. Based on a series of reliable radiocarbon dates, their age lies within the range of 6190–5900 cal BP. It partly corresponds to the end of the hiatus in the mortuary traditions of Cis-Baikal. Features of the burial rite and funerary offerings are analyzed and compared with those of neighboring territories. One of the most frequent images in the art of the Middle Neolithic Baikal-Yenisey Siberia is that of the waterfowl, rendered as fi gurines. The common grave goods are leaf-shaped stone arrowheads, shell beads, and pendants made of animal bones and teeth. The funerary rite included the use of fi re and reddish mineral pigment, as well as disrupting the anatomical integrity of the skeletons, possibly due to partial burial (the data are tentative). Most burials of the late stage of the hiatus are evidently those of hunter-gatherers manufacturing the Ust-Belaya ceramics, which were found in certain burials. A bone arrowhead with a biconical point and fi gurines representing waterfowl suggest cultural ties with the Urals and Western Siberia; but their nature has yet to be clarifi ed, which requires large-scale AMS-dating and paleogenetic analysis.

Introduction: Concerns of the persistence and severity of the adverse effects of fluoroquinolones, mainly involving the nervous system, muscles and joints, resulted in the 2018 referral procedure led by the European Medicines Agency (EMA). They advised to stop prescribing fluoroquinolones for infections of mild severity or of a presumed self-limiting course and for prevention of infections, plus to restrict prescriptions in cases of milder infections where other treatment options are available, and restrict in at-risk populations. We aimed to examine whether the impact of EMA regulatory interventions implemented throughout 2018–2019 had an impact on fluoroquinolone prescribing rates. Methods: A retrospective population-based cohort study was conducted using electronic health care records from six European countries between 2016 and 2021. We analysed monthly incident fluoroquinolone use rates overall and for each fluoroquinolone active substance through flexible modelling via segmented regression to detect time points of trend changes, in monthly percentage change (MPC). Results: The incidence of fluoroquinolone use ranged from 0.7 to 8.0/1000 persons per month over all calendar years. While changes in fluoroquinolone prescriptions were observed over time across countries, these were inconsistent and did not seem to be temporally related to EMA interventions (e.g., Belgium: February/May 2018, MPC − 33.3%, 95% confidence interval [CI] − 35.9 to − 30.7; Germany: February/May 2019, MPC − 12.6%, 95% CI − 13.7 to − 11.6]; UK: January/April 2016, MPC − 4.9%, 95% CI − 6.2 to − 3.6). Conclusion: The regulatory action associated with the 2018 referral did not seem to have relevant effects on fluoroquinolone prescribing in primary care.

The COVID-19 pandemic has greatly altered family life, and research among adults and families has found increases financial stress, mental health problems, screen time, parental conflict, and child behavior problems. Given these patterns, we sought to replicate these findings with a younger and largely non-white sample. Using the Family Stress Model, we consider how these constructs might relate to each other during the pandemic. From surveys of 247 predominately Latine mothers and fathers of children under 4 years of age in the U.S., we found that financial strain was related to children’s media exposure and use, largely through impacts on parents’ mental health and coparenting relationship. Interestingly, only use of television in the background and during mealtimes were associated with increases in parents’ perception of increases in children’s behavior problems. Such findings better capture how stress may operate in a family system and offer a way to counsel parents about healthier media habits for young children. Prior State of Knowledge: The COVID-19 pandemic increased families’ feelings of financial and emotional strain as well as screen time, though most research is with affluent families and those with older children. Novel Contributions: Among economically and ethnically diverse families with young children, we find relationships between financial strain, parental mental health, coparenting relationship quality, and parenting around media. Of children’s media use, only background TV is associated with increases in behavior problems. Practical Implications: The findings underscore the importance of supporting parents through pandemic-related stressors and consideration of how passive media viewing might relate to problematic behaviors for young children.

We examine patterns of county participation in immigration enforcement across the Obama and Trump administrations and responses to the Trump administration’s efforts to mandate local compliance with Immigration and Customs Enforcement (ICE) directives. We focus on the policy that directly speaks to local discretion in enforcing federal law—namely, the willingness of local officials to render immigrant detainees to ICE. We find that underlying patterns of detainee transfers from counties to ICE were largely consistent between the Obama and Trump administrations. Nonetheless, the rate of detainee transfers increased during the Trump administration, an outcome associated with county support for Trump in the 2016 election. The findings suggest that partisanship is an entrenched source of diverging county enforcement practices, increasing intergovernmental conflict and undermining the “steam valve” potential of immigration federalism.

Reduction of the microbial load of soiled carcasses is essential in the production of game meat. Rinsing with water is a common practice in handling game carcasses to remove any visible contamination. In this study, microbiological investigations were performed on carcasses of roe deer (Capreolus capreolus), inoculated with a mixture of gastrointestinal content and then either rinsed (n = 3) or unrinsed (n = 3). Water rinsing may have short-term effects on bacterial contamination related to soiling. However, introducing water into the body cavity may promote bacterial growth during cold storage.

Introduction Iron oxide nanoparticles have been used in preclinical and clinical research as imaging agents for decades because of their magnetic properties and their known safety profile. We have been developing the MagSense® HER2 Test Reagent (MSH2TR), a formulation of anti-human epidermal growth factor receptor 2 (HER2) conjugated iron oxide nanoparticles, for the noninvasive detection of metastatic lymph nodes to aid in staging of HER2 positive (HER2+) breast cancer patients. Currently, nodal staging requires a patient’s lymph nodes to be surgically removed or biopsied for histopathological examination. MSH2TR is currently being investigated in a first-in-human phase I study in subjects with HER2+ primary breast cancer who, in the judgment of the investigator, have a likelihood of lymph node metastasis. Methods This phase I study is designed to be a preliminary proof-of-principle study with the primary objective of achieving an initial assessment of the safety and tolerability of the MSH2TR injectable imaging agent. A secondary objective of the study is the confirmation that the route of administration is effective in allowing the imaging agent to reach the patient’s lymph nodes. The exploratory objectives of the study include a comparison of the two imaging modalities: magnetic resonance imaging (MRI) and a novel proprietary technology called magnetic relaxometry (MRX), to standard clinical tissue histopathology. The exploratory objectives are expected to provide a preliminary assessment as to whether the MagSense® HER2 imaging agent, when used with one or both imaging modalities, might be able to provide a non-invasive alternative to nodal biopsy. All eligible subjects receive a 30mg injection of MSH2TR into the subareolar interstitial tissue or area near and around the primary tumor. MRI of the axilla are performed before and 24 to 72 hours after MSH2TR injection followed by core biopsy or dissection of the suspected lymph node tissue as per standard of care (SOC) procedures for histopathology assessments and also for ex vivo MRX measurements using the MagSense® Relaxometry Instrument. Review of the MRI scans and histopathology are performed in respective central laboratories. The study is currently enrolling in 4 clinical sites in Australia. Results From an interim evaluation of the first five patients that have completed the study, MSH2TR appears to be safe and well tolerated and no safety issues reported related to the imaging agent. The imaging agent, as administered, is reaching the lymph nodes. The study intends to enroll approximately 15 patients for the preliminary efficacy assessment. Safety and efficacy results from available patients’ data will be presented. Conclusion Available data to date from the ongoing phase I study show that the MagSense® HER2 imaging agent, as administered, appear to be safe and drains to the axillary lymph nodes within the timeframe of interest. Further data collection is ongoing for the preliminary evaluation of efficacy. Citation Format: Yalia Jayalakshmi, Jane Fox, Natalie Yang, Marie Zhang, Robert Proulx, Steven Reich. Noninvasive Detection of Lymph Node Involvement in Subjects with Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer using the MagSense® HER2 Test Reagent – A First-In-Human Phase 1 Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-09-02.

Mitochondria generate energy through oxidative phosphorylation (OXPHOS). The function of key OXPHOS proteins can be altered by variation in mitochondria-related genes, which may increase the risk of mental illness. We investigated the association of mitochondria-related genes and their genetic risk burden with cognitive performance.We leveraged cross-sectional data from 1320 individuals with a severe psychiatric disorder and 466 neurotypical individuals from the PsyCourse Study. The cognitive tests analyzed were the Trail-Making Test, Verbal Digit Span Test, Digit-Symbol Test, and Multiple Choice Vocabulary Intelligence Test. Association analyses between the cognitive tests, and single-nucleotide polymorphisms (SNPs) mapped to mitochondria-related genes, and their polygenic risk score (PRS) for schizophrenia (SCZ) were performed with PLINK 1.9 and R program.We found a significant association (FDR-adjusted p < 0.05) in the Cytochrome C Oxidase Assembly Factor 8 (COA8) gene locus of the OXPHOS pathway with the Verbal Digit Span (forward) test. Mitochondrial PRS was not significantly associated with any of the cognitive tests.Moderate statistical power due to relatively small sample size.COA8 encodes a poorly characterized mitochondrial protein involved in apoptosis. Here, this gene was associated with the Verbal Digit Span (forward) test, which evaluates short-term memory. Our results warrant replication and may lead to better understanding of cognitive impairment in mental disorders.

[Abstract] Here we provide the ‘Global Spectrum of Plant Form and Function Dataset’, containing species mean values for six vascular plant traits. Together, these traits –plant height, stem specific density, leaf area, leaf mass per area, leaf nitrogen content per dry mass, and diaspore (seed or spore) mass – define the primary axes of variation in plant form and function. The dataset is based on ca. 1 million trait records received via the TRY database (representing ca. 2,500 original publications) and additional unpublished data. It provides 92,159 species mean values for the six traits, covering 46,047 species. The data are complemented by higher-level taxonomic classification and six categorical traits (woodiness, growth form, succulence, adaptation to terrestrial or aquatic habitats, nutrition type and leaf type). Data quality management is based on a probabilistic approach combined with comprehensive validation against expert knowledge and external information. Intense data acquisition and thorough quality control produced the largest and, to our knowledge, most accurate compilation of empirically observed vascular plant species mean traits to date. The study has been supported by the TRY initiative on plant traits (https://www.try-db.org). TRY is an initiative of the Max Planck Institute for Biogeochemistry, bioDISCOVERY/Future Earth (ICSU), the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig and Núcleo DiverSus (CONICET- Universidad Nacional de Córdoba, Argentina). The Global Spectrum of Plant Form and Function study has been supported by the European BACI project (Towards a Biosphere Atmosphere change Index, EU grant ID 640176), and grants to SD by FONCyT, CONICET, Universidad Nacional de Córdoba, the Inter-American Institute for Global Change Research, and The Newton Fund (NERC UK – CONICET ARG). VO thanks RSF (#19-14-00038p). Open Access funding enabled and organized by Projekt DEAL

Objectives In 2012, onetime hepatitis C virus (HCV) screening was recommended for all baby boomers (people born during 1945-1965) in the United States, but only 4.0%-12.9% of baby boomers have ever had a screening ordered by a health care provider. This study examined the HCV screening prevalence among adult patients in a large academic health care system and assessed factors associated with the completion of screening when ordered for baby boomers. Methods We defined HCV screening completion as the completion of an HCV antibody test when it was ordered. We used electronic health records to examine HCV screening completion rates among adults (N = 106 630) from August 1, 2015, through July 31, 2020, by birth cohort. Among baby boomers whose health care provider ordered HCV screening, we examined frequency and percentages of HCV screening completion by sociodemographic and clinical characteristics. We conducted univariate and multivariable logistic regression analyses to assess factors associated with HCV screening completion among baby boomers. Results During the study period, 73.0% of baby boomers completed HCV screening when it was ordered. HCV completion did not differ by sex or race and ethnicity among baby boomers. Baby boomers with Medicare supplemental health insurance compared with commercial health insurance (adjusted odds ratio [aOR] = 1.87) and those seeing only advanced practice professionals compared with specialty care physicians (aOR = 2.24) were more likely to complete HCV screening when it was ordered. Conclusions Noncompletion of HCV screening is one of many barriers along the HCV treatment continuum. Our findings suggest a need for interventions targeting systems, health care providers, and patients to increase HCV screening rates in the United States.

Introduction: Emerging evidence suggests that Chemotherapy (CT) treated breast cancer survivors (BCS) who have “risk variants” in genes may be more susceptible to cognitive impairment (CI) and/or poor cardiac phenotypes. The objective of this preliminary study was to examine whether there is a relationship between genetic variants and objective/subjective cognitive or cardiac phenotypes. Methods and Analysis: BCS were recruited from Moffitt Cancer Center, Morsani College of Medicine, AdventHealth Tampa and Sarasota Memorial Hospital. Genomic DNA were collected at baseline for genotyping analysis. A total of 16 single nucleotide polymorphisms (SNPs) from 14 genes involved in cognitive or cardiac function were evaluated. Three genetic models (additive, dominant, and recessive) were used to test correlation coefficients between genetic variants and objective/subjective measures of cognitive functioning and cardiac outcomes (heart rate, diastolic blood pressure, systolic blood pressure, respiration rate, and oxygen saturation). Results: BCS (207 participants) with a mean age of 56 enrolled in this study. The majority were non-Hispanic white (73.7%), married (63.1%), and received both CT and radiation treatment (77.3%). Three SNPs in genes related to cognitive functioning (rs429358 in APOE, rs1800497 in ANKK1, rs10119 in TOMM40) emerged with the most consistent significant relationship with cognitive outcomes. Among five candidate SNPs related to cardiac functioning, rs8055236 in CDH13 and rs1801133 in MTHER emerged with potential significant relationships with cardiac phenotype. Conclusions: These preliminary results provide initial targets to further examine whether BCS with specific genetic profiles may preferentially benefit from interventions designed to improve cognitive and cardiac functioning following CT.

In this essay, we discuss some urgent challenges for democracy and education in the Deweyan sense in connection with current developments of technologies and questions of sustainability. We proceed in four major parts, following the systematic distinction of four mutually interrelated levels of technologies in culture found in the late work of Michel Foucault. In part 1, we focus on the technologies of production. We connect Foucault’s perspective with more recent research on questions of social inequality and the production and distribution of wealth. In part 2, we address the level of technologies of sign systems, connecting Foucault’s perspective with critical approaches like Chomsky and Zuboff. In part 3, we turn to the level of technologies of power and domination. We use Crouch’s approach to post-democracy in order to examine some crucial dangers for democracy. In part 4, we look at the level of technologies of the self. We consider connections with contemporary constructivist as well as Deweyan perspectives in education that emphasize the role of relationships and processes of social self-creation. The essay closes with a summary of the most important conclusions of our discussion.

Objective: We aimed to investigate whether ibuprofen use, compared with other non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs), cyclooxygenase-2 inhibitors (COX-2i) or paracetamol, increases the risk of coronavirus disease 2019 (COVID-19) diagnosis or hospitalisation. Design: A prevalent user and active comparator cohort study. Setting: Two US claims databases (Open Claims and PharMetrics Plus) mapped to the Observational Medical Outcomes Partnership Common Data Model. Participants: Insured patients with a history of osteoarthritis or back pain and receiving ibuprofen, other ns-NSAIDs, COX-2i or paracetamol between 1 November, 2019 and 31 January, 2020 (study enrolment window 1) or between 1 February, 2020 and 31 October, 2020 (study enrolment window 2). Main Outcome Measures: Large-scale propensity score matching and empirical calibration were used to minimise confounding. Incidence and hazard ratios of COVID-19 diagnosis and hospitalisation according to drug/s use were estimated and pooled in the same study period across data sources using a fixed-effects meta-analysis. Index treatment episode was the primary risk evaluation window, censored at the time of discontinuation. Results: A total of 633,562 and 1,063,960 participants were included in periods 1 and 2, respectively, for the ibuprofen versus ns-NSAIDs comparison, 311,669 and 524,470 for ibuprofen versus COX-2i, and 492,002 and 878,598 for ibuprofen versus paracetamol. Meta-analyses of empirically calibrated hazard ratios revealed no significantly differential risk of COVID-19 outcomes in users of ibuprofen versus any of the other studied analgesic classes: hazard ratios were 1.13 (0.96–1.33) for the ibuprofen-ns-NSAIDs comparison, 1.03 (0.83–1.28) for the ibuprofen-COX-2i comparison and 1.13 (0.74–1.73) for ibuprofen-paracetamol comparison on COVID-19 diagnosis in the February 2020–October 2020 window. Similar hazard ratios were found on COVID-19 hospitalisation and across both study periods. Conclusions: In patients with osteoarthritis or back pain, we found no differential risks of incident COVID-19 diagnosis or COVID-19 hospitalisation for ibuprofen users compared with other ns-NSAIDs, COX-2i or paracetamol. Our findings support regulatory recommendations that NSAIDs, including ibuprofen, should be prescribed as indicated in the same way as before the COVID-19 pandemic, especially for those who rely on ibuprofen or NSAIDs to manage chronic arthritis or musculoskeletal pain symptoms. Graphical abstract: [Figure not available: see fulltext.].

The association between postictal electroencephalogram (EEG) suppression (PES), autonomic dysfunction, and Sudden Unexpected Death in Epilepsy (SUDEP) remains poorly understood. We compared PES on simultaneous intracranial and scalp-EEG and evaluated the association of PES with postictal heart rate variability (HRV) and SUDEP outcome.Convulsive seizures were analyzed in patients with drug-resistant epilepsy at 5 centers. Intracranial PES was quantified using the Hilbert transform. HRV was quantified using root mean square of successive differences of interbeat intervals, low-frequency to high-frequency power ratio, and RR-intervals.There were 64 seizures from 63 patients without SUDEP and 11 seizures from 6 SUDEP patients. PES occurred in 99% and 87% of seizures on intracranial-EEG and scalp-EEG, respectively. Mean PES duration in intracranial and scalp-EEG was similar. Intracranial PES was regional (90% of channels) in 46% of seizures; scalp PES was generalized in all seizures. Generalized PES showed greater decrease in postictal parasympathetic activity than regional PES. PES duration and extent were similar between patients with and without SUDEP.Regional intracranial PES can be present despite scalp-EEG demonstrating generalized or no PES. Postictal autonomic dysfunction correlates with the extent of PES.Intracranial-EEG demonstrates changes in autonomic regulatory networks not seen on scalp-EEG.

Achieving Magnet® recognition with help from international colleagues.

The 'Rotor Hub Flow Prediction Workshops' have been productive collaborations between experimental and computational efforts in the important area of high-Reynolds number model testing of rotor hubs and associated complex interactional aerodynamics in the long-age wake as relevant to current and future rotorcraft. As such the hub flow workshops have joined the ranks of past successful collaborations such as the UH-60 Airloads and HART-II workshops. This paper begins by describing the basic physics of rotor hub flows and gives a brief summary of recent water-tunnel test campaigns. Following, the evolution of the hub flow workshops is summarized, with emphasis on the productive interactions between experimentalists and computational participants. A compilation of computational blind comparison results against measured data for all three workshops thus far is presented. Challenges associated with uncertainties in both experiments and computations and their effect on quantitative comparisons are discussed. In particular, emphasis is given to the "lessons learned" on both sides and an outlook on remaining challenges and next research steps in the area of rotor hub flows is provided.

OX40 is crucial for T-cell differentiation and memory induction. The anti-OX40 antibody, rocatinlimab inhibits the OX40 pathway. We evaluated the efficacy and safety of rocatinlimab in adults with moderate-to-severe atopic dermatitis.This multicentre, double-blind, placebo-controlled phase 2b study was done at 65 secondary and tertiary sites in the USA, Canada, Japan, and Germany. Eligible patients were adults (aged 18 years or older) with confirmed atopic dermatitis (American Academy of Dermatology Consensus Criteria or local diagnostic criteria) with moderate-to-severe disease activity, as defined by an Eczema Area and Severity Index (EASI) score of 16 or more, validated Investigator's Global Assessment for Atopic Dermatitis score of 3 (moderate) or 4 (severe), and affected body surface area 10% or higher at both screening and baseline, with documented history (within 1 year) of inadequate response to topical medications or if topical treatments were medically inadvisable. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous rocatinlimab every 4 weeks (150 mg or 600 mg) or every 2 weeks (300 mg or 600 mg) or subcutaneous placebo up to week 18, with an 18-week active-treatment extension and 20-week follow-up. Percentage change from baseline in EASI score was assessed as the primary endpoint at week 16 and during the active extension and follow-up in all randomly assigned patients exposed to study drug with a post-baseline EASI score at week 16 or earlier according to the group they were randomly assigned to. Safety was assessed in all randomly assigned patients exposed to study drug; patients were analysed according to the group they were randomly assigned to. The study is registered with ClinicalTrials.gov, NCT03703102.Between Oct 22, 2018, and Oct 21, 2019, 274 patients (114 [42%] women, 160 [58%] men; mean age 38·0 years [SD 14·5]) were randomly assigned to one of the rocatinlimab groups (217 [79%] patients) or to the placebo group (57 [21%] patients). Compared with placebo (-15·0 [95% CI -28·6 to -1·4]), significant least-squares mean percent reductions in EASI score at week 16 were observed in all rocatinlimab groups (rocatinlimab 150 mg every 4 weeks -48·3 [-62·2 to -34·0], p=0·0003; rocatinlimab 600 mg every 4 weeks -49·7 [-64·3 to -35·2], p=0·0002; rocatinlimab 300 mg every 2 weeks -61·1 [-75·2 to -47·0], p0·0001; and rocatinlimab 600 mg every 2 weeks -57·4 [-71·3 to -43·4], p0·0001). The most common adverse events during the double-blind period in patients receiving rocatinlimab (adverse events ≥5% of patients in the total rocatinlimab group and more common than the placebo group) were pyrexia (36 [17%] patients), nasopharyngitis (30 [14%] patients), chills (24 [11%] patients), headache (19 [9%] patients), aphthous ulcer (15 [7%] patients), and nausea (13 [6%] patients). There were no deaths.Patients treated with rocatinlimab had progressive improvements in atopic dermatitis, which was maintained in most patients after treatment discontinuation. Treatment was well tolerated.Kyowa Kirin.