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Spread by Hyalomma genus ticks, Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic disease endemic throughout Southern and Eastern Europe, Asia, and Africa. To date, there are no widely approved vaccines for CCHFV and treatment for disease is largely supportive. Due to this lack of intervention, the WHO lists CCHFV as a high-priority pathogen. Recently, we described a highly efficacious self-replicating RNA vaccine which is protective against CCHFV disease in mice and non-human primates. This vaccine induces high titers of non-neutralizing anti-nucleoprotein (NP) antibodies and a robust T-cell response against the viral glycoprotein. Here, we assess the durability of this vaccine in mice by monitoring the immunogenicity and efficacy of this vaccine up to 1 year post vaccination. We found that while glycoprotein-specific T-cell responses and anti-NP antibody titers waned over time, mice remained protected against lethal CCHFV challenge for at least 1 year post vaccination., Competing Interests: Competing interests: J.E. has an equity interest in HDT Bio. J.E. and A.K. are a co-inventor on U.S. patent application no. 62/993,307 “Compositions and methods for delivery of RNA” pertaining to formulations for RNA delivery. D.W.H., J.E., and H.F. are inventors on U.S. patent application number 63/365,015 “Replicating RNA vaccine for Crimean-Congo hemorrhagic fever virus” regarding the repRNA for use against CCHFV. All other authors declare no competing interests., (© 2024. The Author(s).)

Importance: Lipodermatosclerosis (LDS) stems from vascular dysfunction and dermal inflammation and thereby is mechanistically similar to systemic sclerosis (SSc). The association of LDS with SSc in the clinical setting has not been well characterized in the literature., Objective: To evaluate the prevalence of LDS in SSc and the association of LDS with vascular complications, particularly pulmonary hypertension, in patients with SSc., Design, Setting, and Participants: This retrospective cohort study used prospectively collected longitudinal data from a cohort of patients from the multidisciplinary rheumatology and dermatology clinic at a single tertiary care center from November 2004 to November 2022. Adult patients (aged ≥18 years at the time of cohort entry) with SSc were included., Exposure: Clinical diagnosis of LDS based on expert opinion or histopathologic findings., Main Outcomes and Measures: The main outcomes included prevalence of LDS, the association of LDS with the macrovascular complications, including pulmonary hypertension, digital gangrene and/or scleroderma renal crisis. Disease complications, including cardiac arrhythmias and heart failure, were compared among patients with and without LDS., Results: Among 567 patients with SSc (494 [87.1%] female; mean [SD] age, 53.4 [14.4] years), 25 (4.4%) had LDS and 542 (95.6%) did not have LDS. Skin ulceration occurred in 8 patients with LDS (32.0%). Patients with LDS had higher frequencies of cardiac arrhythmia (11 of 24 [45.8%] vs 145 of 539 [26.9%]), heart failure (7 [28.0%] vs 55 [10.1%]), and pulmonary hypertension (12 [48.0%] vs 137 of 541 [25.3%]) compared with patients without LDS. Frequency of scleroderma renal crisis and digital gangrene did not differ significantly between patients with and without LDS (0 vs 37 [6.8%] and 4 [16.0%] vs 69 of 538 [12.8%], respectively). Among patients with LDS, 9 (36.0%) were either discharged to hospice or died during follow-up compared with 115 patients without LDS (21.2%). Lipodermatosclerosis was associated with pulmonary hypertension (adjusted prevalence odds ratio, 3.10; 95% CI, 1.33-7.25)., Conclusions and Relevance: In this cohort study, LDS was a rare clinical manifestation in patients with SSc but was associated with pulmonary hypertension. Therefore, patients with LDS should be closely monitored and screened for pulmonary hypertension.

Importance: In the US, there are more than 1.5 million adults living with congenital heart disease (CHD). The Congenital Heart Initiative (CHI) is a digital, online, patient-empowered registry that was created to advance multicenter research and improve clinical care by gathering patient-reported outcomes (PROs) in adults with CHD., Objective: To report the initial findings of the PROs for adults with CHD from the first 3 years of the CHI., Design, Setting, and Participants: The CHI was launched nationally on December 7, 2020, as an observational cohort (survey) study. Data were collected virtually through December 31, 2023, and stored on Health Insurance Portability and Accountability Act-compliant cloud-based servers with restricted access. Adults with CHD were recruited through email, social media, general advertising through advocacy organizations, and targeted outreach (telephone and in-clinic recruitment) by clinical centers., Main Outcomes and Measures: Demographics and validated survey tools on quality of life, mental health, physical activity, and health care utilization were collected at baseline and every 4 months. Descriptive statistics were used to understand the associations between various factors, including the complexity of heart defects, physical activity levels, mental health comorbidities, and socioeconomic and health care access variables. All categorical variables were analyzed using χ2 or Fischer exact test as appropriate., Results: By December 31, 2023, the CHI had enrolled 4558 participants (2530 female [56%]) with a mean (SD) age of 38.5 (13.9) years, representing all 50 states. Approximately 88% of participants (3998 participants) completed at least 1 electronic visit as of December 31, 2023. The most prevalent CHD anatomy included tetralogy of Fallot (883 participants [22%]), transposition of great arteries (452 participants [11%]), and coarctation of the aorta (429 participants [11%]). Approximately 88% of participants (3998 participants) reported at least 1 comorbidity, with arrhythmia (1300 participants [33%]) as the most common cardiac comorbidity and mood disorder (1326 participants [35%]) as the most common noncardiac comorbidity. Among female participants, 45% (1147 participants) reported having had a pregnancy, with 38% (967 participants) resulting in biological children. Participants with complex CHD were less likely than those with moderate CHD to meet recommended physical activity guidelines (χ22 = 15.9; n = 3320; P < .001), a factor that was more pronounced among female participants. Overall health-related quality of life was rated as good or better by 84% of participants who completed the quality of life PROs (2882 participants), with no difference by CHD complexity., Conclusions and Relevance: In this cohort study of adults living with CHD, many patients reported mood disorders, but most reported good health-related quality of life. The CHI, the largest registry of adults with CHD, is poised to facilitate multicenter research with the goal of improving clinical outcomes for all adults with CHD.

Environmental DNA (eDNA) is widely used in biodiversity, conservation, and ecological studies but despite its successes, similar approaches have not yet been regularly applied to assist in wildlife crime investigations. The purpose of this paper is to review current eDNA methods and assess their potential forensic application in freshwater environments considering collection, transport and persistence, analysis, and interpretation, while identifying additional research required to present eDNA evidence in court. An extensive review of the literature suggests that commonly used collection methods can be easily adapted for forensic frameworks providing they address the appropriate investigative questions and take into consideration the uniqueness of the target species, its habitat, and the requirements of the end user. The use of eDNA methods to inform conservationists, monitor biodiversity and impacts of climate change, and detect invasive species and pathogens shows confidence within the scientific community, making the acceptance of these methods by the criminal justice system highly possible. To contextualise the potential application of eDNA on forensic investigations, two test cases are explored involving i) species detection and ii) species localisation. Recommendations for future work within the forensic eDNA discipline include development of suitable standardised collection methods, considered collection strategies, forensically validated assays and publication of procedures and empirical research studies to support implementation within the legal system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Breast cancer clinical stage and nodal status are the most clinically significant drivers of patient management, in combination with other pathological biomarkers, such as estrogen receptor (ER), progesterone receptor or human epidermal growth factor receptor 2 (HER2) receptor status and tumor grade. Accurate prediction of such parameters can help avoid unnecessary intervention, including unnecessary surgery. The objective was to investigate the role of magnetic resonance imaging (MRI) radiomics for yielding virtual prognostic biomarkers (ER, HER2 expression, tumor grade, molecular subtype, and T-stage)., Materials and Methods: Patients with primary invasive breast cancer who underwent dynamic contrast-enhanced (DCE) breast MRI between July 2013 and July 2016 in a single center were retrospectively reviewed. Age, N-stage, grade, ER and HER2 status, and Ki-67 (%) were recorded. DCE images were segmented and Haralick texture features were extracted. The Bootstrap Lasso feature selection method was used to select a small subset of optimal texture features. Classification of the performance of the final model was assessed with the area under the receiver operating characteristic curve (AUC)., Results: Median age of patients (n = 209) was 49 (21-79) years. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the model for differentiating N0 vs N1-N3 was: 71%, 79%, 76%, 74%, 75% [AUC = 0.78 (95% confidence interval (CI) 0.72-0.85)], N0-N1 vs N2-N3 was 81%, 59%, 24%, 95%, 62% [AUC = 0.74 (95% CI 0.63-0.85)], distinguishing HER2(+) from HER2(-) was 79%, 48%, 34%, 87%, 56% [AUC = 0.64 (95% CI 0.54-0.73)], high nuclear grade (grade 2-3) vs low grade (grades 1) was 56%, 88%, 96%, 29%, 61% [AUC = 0.71 (95% CI 0.63-0.80)]; and for ER (+) vs ER(-) status the [AUC=0.67 (95% CI 0.59-0.76)]. Radiomics performance in distinguishing triple-negative vs other molecular subtypes was [0.60 (95% CI 0.49-0.71)], and Luminal A [0.66 (95% CI 0.56-0.76)]., Conclusion: Quantitative radiomics using MRI contrast texture shows promise in identifying aggressive high grade, node positive triple negative breast cancer, and correlated well with higher nuclear grades, higher T-stages, and N-positive stages., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (©Copyright 2024 by the Turkish Federation of Breast Diseases Societies / European Journal of Breast Health published by Galenos Publishing House.)

Introduction: The aim of this retrospective study was to firstly assess the stability of surgical advancement using inter-molar mandibular distraction osteogenesis (IMDO) and secondly to assess the impact of the surgical intervention on subsequent mandibular growth in patients with residual growth., Methods: The sample consisted of 17 (13F and 4M) consecutively treated patients who underwent IMDO and orthodontic treatment. Cephalometric analysis was performed at three time points: T0 prior to distraction; T1 post-distraction immediately prior to surgical removal of the distractors; and T2 following completion of orthodontic treatment when the final lateral cephalogram was taken (0.86-4.37 years after T1). Statistical comparison of lower facial height, mandibular length, growth, condylar position and anterior mandibular rotation was performed., Results: No association was found between changes in any of the cephalometric measurements and the length of the follow-up interval. The anterior mandibular segment underwent clockwise rotation during distraction and recovered to near its pre-distraction angulation during remodelling. An increase in the lower facial height of 1.88 ± 2.81mm also occurred during distraction (T0-T1) and was maintained during the follow-up period (T1-T2). Post-distraction (T1-T2) growth of lower facial height (p value 0.872) and mandibular length (p value 0.251) showed no association when compared to an untreated control group and an overall reduction in growth was reported., Conclusions: IMDO was highly stable within a follow-up period of 2.3 ± 0.9 years; however, growth appears to have been inhibited., (© 2024. Crown.)

There is increased recognition that people with lived-experience of mental ill-health ought to be centred in research design, implementation and translation, and quality improvement and program evaluation of services. There is also an increased focus on ways to ensure that co-design processes can be led by people with lived-experience of mental ill-health. Despite this, there remains limited explanation of the physical, social, human, and economic infrastructure needed to create and sustain such models in research and service settings. This is particularly pertinent for all health service sectors (across mental and physical health and social services) but more so across tertiary education settings where research generation occurs for implementation and translation activities with policy and services. The Co-Design Living Labs program was established in 2017 as an example of a community-based embedded approach to bring people living with trauma and mental ill-health and carers/family and kinship group members together with university-based researchers to drive end-to-end research design to translation in mental healthcare and research sectors. The program's current membership is near to 2000 people. This study traces the evolution of the program in the context of the living labs tradition of open innovation. It overviews the philosophy of practice for working with people with lived-experience and carer/family and kinship group members-togetherness by design. Togetherness by design centres on an ethical relation of being-for that moves beyond unethical and transactional approaches of being-aside and being-with , as articulated by sociologist Zygmunt Bauman. The retrospective outlines how an initial researcher-driven model can evolve and transform to become one where people with lived-experience of mental ill-health and carer/family kinship group members hold clear decision-making roles, share in power to enact change, and move into co-researcher roles within research teams. Eight mechanisms are presented in the context of an explanatory theoretical model of change for co-design and coproduction, which are used to frame research co-design activities and provide space for continuous learning and evolution of the Co-Design Living Labs program., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Palmer, Bibb, Lewis, Densley, Kritharidis, Dettmann, Sheehan, Daniell, Harding, Schipp, Dost and McDonald.)

Background: Primary care is essential to address the unmet physical health needs of people with severe mental ill-health. Continued poor cardiovascular health demands improved screening and preventive care. No previous reviews have examined primary care cardiovascular screening rates for people living with severe mental ill-health; termed in the literature "severe mental illness"., Methods: A scoping review following Joanna Briggs Institute methodology was conducted. Cardiovascular risk factor screening rates in adults with severe mental ill-health were examined in general or family practices (as the main delivery sites of primary care). Literature published between 2001 and 2023 was searched using electronic databases including Medline, Embase, Web of Science, PsychINFO and CINAHL. Two reviewers independently screened titles and abstracts and conducted a full-text review. The term "severe mental illness" was applied as the term applied in the literature over the past decades. Study information, participant details and cardiovascular risk factor screening rates for people with 'severe mental illness' were extracted and synthesised., Results: Thirteen studies were included. Nine studies were from the United Kingdom and one each from Canada, Spain, New Zealand and the Netherlands. The general and/or family practice cardiovascular disease screening rates varied considerably across studies, ranging from 0 % to 75 % for people grouped within the term "severe mental illness". Lipids and blood pressure were the most screened risk factors., Conclusions: Cardiovascular disease screening rates in primary care settings for adults living with severe mental ill-health varied considerably. Tailored and targeted cardiovascular risk screening will enable more comprehensive preventive care to improve heart health outcomes and address this urgent health inequity., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The biodiversity of coral reef habitats is rapidly declining due to the effects of anthropogenic climate change, prompting the use of active restoration as a mitigation strategy. Sexual propagation can maintain or enhance genetic diversity in restoration of these ecosystems, but these approaches suffer from a range of inefficiencies in rearing and husbandry. Algal overgrowth of juveniles is a major bottleneck in the production of sexually propagated corals that may be alleviated by co-culture with herbivores. We reared juvenile Montipora capitata alongside juvenile native Hawaiian collector urchins, Tripneustes gratilla , for 15 weeks and documented significant ecological benefits of co-culture. Urchin treatments significantly increased the survivorship of coral aggregates (14%) and individual settlers (24%). We also documented a significant increase in coral growth in the presence of urchins. These results demonstrate the utility of microherbivory in promoting coral growth and survivorship in ex situ conditions, providing valuable insight for restoration pipelines of native Hawaiian coral species., Competing Interests: The authors declare that they have no competing interests., (© 2023 Barrows et al.)

Objective: To evaluate a facilitated, 90-min session, delivered for four weeks, Online Carer Wellbeing and Connection Program in Victoria, Australia., Methods: One hundred and three carers took part in the evaluation. Eighty-six completed both pre- and post-program surveys evaluating program impacts on psychological distress, perceived loneliness, and social support. Qualitative interviews were conducted ( n  = 76) post-program for experiential data., Findings: Paired samples t -tests showed significant decreases between pre- and post-program for psychological distress ( M  = 25.10, SD  = 7.08; M  = 22.00, SD  = 6.57; t (85) = 4.88, p  = 0.000), perceived loneliness ( M  = 6.69, SD  = 1.89; M  = 6.14, SD  = 1.76; t (85) = 3.45, p  = 0.000) and perceived social support ( M  = 8.31, SD  = 2.48; M  = 8.83, SD  = 2.21; t (85) = -2.54, p  = 0.013). Thematic analysis identified positive experiences and the mechanisms of action (or the ingredients for program success) as: 1. Delivery by a trained facilitator; 2. Provision of respite for person being cared for during meetings; 3. Technical assistance; 4. Online modality; 5. Inclusivity; 6. Diversity of experience; 7. Shared understanding; 8. Safety; 9. Emotional release; 10. Reflection, and; 11. Self-care practices., Innovation: A model illustrating the mechanisms of action based on the findings of the mixed-methods evaluation is presented to support wider implementation and translation., Conclusion: The online program effectively reduced psychological distress and loneliness and improved carer wellbeing., Competing Interests: We have no known conflict of interest to disclose., (© 2023 The Authors.)

Inflammation in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection drives severity of coronavirus disease 2019 (COVID-19) and is influenced by host genetics. To understand mechanisms of inflammation, animal models that reflect genetic diversity and clinical outcomes observed in humans are needed. We report a mouse panel comprising the genetically diverse Collaborative Cross (CC) founder strains crossed to human ACE2 transgenic mice (K18-hACE2) that confers susceptibility to SARS-CoV-2. Infection of CC x K18-hACE2 resulted in a spectrum of survival, viral replication kinetics, and immune profiles. Importantly, in contrast to the K18-hACE2 model, early type I interferon (IFN-I) and regulated proinflammatory responses were required for control of SARS-CoV-2 replication in PWK x K18-hACE2 mice that were highly resistant to disease. Thus, virus dynamics and inflammation observed in COVID-19 can be modeled in diverse mouse strains that provide a genetically tractable platform for understanding anti-coronavirus immunity., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Cyanoacrylate glue closure was first used in humans 10 years ago to treat venous reflux of the axial veins. Studies have since shown its clinical efficacy in vein closure. However, great need exists to elucidate further the types of specific adverse reactions that cyanoacrylate glue can cause for better patient selection and to minimize these events. In the present study, we systematically reviewed the literature to identify the types of reported reactions. In addition, we explored the pathophysiology contributing to these reactions and proposed the mechanistic pathway with inclusion of actual cases., Methods: We searched the literature for reports of reactions following cyanoacrylate glue use in patients with venous diseases between 2012 and 2022. The search was performed using MeSH (medical subject headings) terms. The terms included cyanoacrylate, venous insufficiency, chronic venous disorder, varicose veins, vein varicosities, venous ulcer, venous wound, CEAP (clinical, etiologic, anatomic, pathophysiologic), vein, adverse events, phlebitis, hypersensitivity, foreign body granuloma, giant cell, endovenous glue-induced thrombosis, and allergy. The search was limited to the literature reported in English. These studies were evaluated for the type of product used and the reactions noted. A systematic review, in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) method, was performed. Covidence software (Melbourne, VC, Australia) was used for full-text screening and data extraction. Two reviewers reviewed the data, and the content expert served as the tiebreaker., Results: We identified 102, of which, 37 reported on cyanoacrylate use other than in the context of chronic venous diseases and were excluded. Fifty-five reports were determined appropriate for data extraction. The adverse reactions to cyanoacrylate glue were phlebitis, hypersensitivity, foreign body granuloma, and endovenous glue-induced thrombosis., Conclusions: Although cyanoacrylate glue closure for venous reflux is generally a safe and clinically effective treatment choice for patients with symptomatic chronic venous disease and axial reflux, some adverse events could be specific to the properties of the cyanoacrylate product. We propose mechanisms for how such reactions can occur based on histologic changes, published reports, and case examples; however, further exploration is necessary to confirm these theories., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Ebstein's anomaly is a rare congenital heart malformation for which surgical and medical management are still controversial. The cone repair has transformed surgical outcomes in many of these patients. We aimed to present our results on the outcomes of patients with Ebstein's anomaly who underwent a cone repair or tricuspid valve replacement., Methods: A total of 85 patients who underwent a cone repair (mean age, 16.5 years) or tricuspid valve replacement (mean age, 40.8 years) between 2006 and 2021 were included. Univariate, multivariate, and Kaplan-Meier analyses were used to evaluate operative and long-term outcomes., Results: Residual/recurrent greater than mild-to-moderate tricuspid regurgitation at discharge was higher after cone repair compared with tricuspid valve replacement (36% vs 5%; P  = .010). However, at last follow-up, the risk of greater than mild-to-moderate tricuspid regurgitation was not different between groups (35% in the cone group vs 37% in the tricuspid valve replacement group; P  = .786). The tricuspid valve replacement group had a higher risk of tricuspid valve reoperation (37% vs 9%; P  = .005) and tricuspid stenosis (21% vs 0%; P  = .002) compared with the cone repair group. Kaplan-Meier freedom from reintervention was 97%, 91%, and 91% at 2, 4, and 6 years after cone repair, respectively, and 84%, 74%, and 68% at 2, 4, and 6 years after tricuspid valve replacement, respectively ( P  = .0191). At last follow-up, right ventricular function was significantly worse from baseline in the tricuspid valve replacement group ( P  = .0294). There were no statistical differences between age-stratified cohorts or surgeon volume in the cone repair group., Conclusions: The cone procedure offers excellent results, with stable tricuspid valve function and low reintervention and death rates at last follow-up. The rate of greater than mild-to-moderate residual tricuspid regurgitation at discharge was higher after cone repair compared with tricuspid valve replacement, but this did not expose the patient to a higher risk of reoperation or death at last follow-up. Tricuspid valve replacement was associated with a significantly higher risk of tricuspid valve reoperation and tricuspid valve stenosis, and worse right ventricular function at last follow-up., (© 2023 The Author(s).)

Background: Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients., Methods: Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination., Findings: Forty-three infliximab-treated patients with IBD were recruited (30 Crohn's disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.037). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R 2 X 0.25, R 2 Y 0.26, Q 2 0.15; CV-ANOVA p = 0.038). Trimethylamine, isobutyrate and omega-muricholic acid were associated with better response, while succinate, phenylalanine, taurolithocholate and taurodeoxycholate were associated with poorer response., Interpretation: Our data suggest that there is an association between the gut microbiota and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine may be important in mitigating anti-TNF-induced attenuation of the immune response., Funding: JLA is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-502), funded by Imperial College London and The Joyce and Norman Freed Charitable Trust. BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002). The Division of Digestive Diseases at Imperial College London receives financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. Metabolomics studies were performed at the MRC-NIHR National Phenome Centre at Imperial College London; this work was supported by the Medical Research Council (MRC), the National Institute of Health Research (NIHR) (grant number MC&#95;PC&#95;12025) and infrastructure support was provided by the NIHR Imperial Biomedical Research Centre (BRC). The NIHR Exeter Clinical Research Facility is a partnership between the University of Exeter Medical School College of Medicine and Health, and Royal Devon and Exeter NHS Foundation Trust. This project is supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care., Competing Interests: Declaration of interests Dr Saifuddin has received travel expense support from Janssen. Dr Lin reports non-financial support from Pfizer, non-financial support from Ferring, outside the submitted work. Dr. Kennedy reports grants from AbbVie, Biogen, Celgene, Celtrion, Galapagos, MSD, Napp, Pfizer, Pharmacosmos, Roche and Takeda, consulting fees from Amgen, Bristol-Myers Squibb, Falk, Janssen, Mylan, Pharmacosmos, Galapagos, Takeda and Tillotts, personal fees from Allergan, Celltrion, Falk, Ferring, Janssen, Pharmacosmos, Takeda, Tilllotts, Galapagos, and support for attending meetings from AbbVie, Falk and Janssen outside the submitted work. Prof. Sebastian reports grants from Takeda, Abbvie, Tillots Pharma, Janssen, Pfizer, Biogen and personal fees from Takeda, Abbvie, Janssen, Pharmacocosmos, Biogen, Pfizer, Tillots Pharma and Falk Pharma, outside the submitted work. Dr Hart reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, AZ, Atlantic, Bristol-Myers Squibb, Celltrion, Falk, Galapogos, Janssen, MSD, Napp Pharmaceuticals, Pfizer, Pharmacosmos, Shire and Takeda and Global Steering Committee for Genentech, support for attending meetings from Abbvie, Takeda and Janssen, and Participation on a Data Safety Monitoring Board or Advisory Board for AbbVie, AZ, Atlantic, Bristol-Myers Squibb, Galapogos, Janssen, Pfizer and Takeda. Prof. Lees reports a Future Leaders Fellow award from UKRI, personal consulting fees from Galapagos, Abbvie, Takeda, Pfizer, Janssen, Iterative Scopes and institutional consulting fees from Trellus Health, personal fees from Galapagos, Abbvie, Takeda, Pfizer, Janssen, GSK, Gilead, Fresnius Kabi, Ferring and Dr Falk, and support for attending meetings from Galapagos, Abbvie, Takeda, Pfizer, Janssen, GSK, Gilead, Fresnius Kabi, Ferring and Dr Falk. Dr. Goodhand reports grants from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study. Prof. Ahmad reports grant funding from Pfizer to his institution to deliver this study, grants from Celltrion, Roche, Takeda, Biogen and Galapagos and honoraria for lectures from Takeda and Roche, outside the submitted work. Dr Powell has received research grant(s) from Bristol Myers Squibb outside the submitted work. Dr. Powell reports personal fees from Takeda, Janssen, Pfizer, Bristol-Myers Squibb, Abbvie, Roche, Lilly, Allergan, and Celgene, outside the submitted work; Dr. Powell has served as a speaker/advisory board member for Abbvie, Allergan, Bristol Myers Squibb, Celgene, Falk, Ferring, Janssen, Pfizer, Tillotts, Takeda and Vifor Pharma. The following authors have nothing to declare: Dr Alexander, Dr Ibraheim, Claire Bewshea, Rachel Nice, Dr Liu, Dr Mullish, Dr Danckert, Melissa Torkizadeh, Jesús Miguéns Blanco, Lauren A Roberts, Hemanth Prabhudev, Caroline Sands, Verena Horneffer-van der Sluis, Matthew Lewis, Professor Teare, Martin Olbei, Tamas Korcsmaros and Professor Marchesi., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Gut-brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease-modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide., Methods: We characterised 77 participants with diagnosed-PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time. Complete-linkage hierarchical cluster analysis of metabolites discriminant for PD-status was performed., Results: Longer colonic transit was linked to deficits in faecal short-chain-fatty acids outside PD, to a 'tryptophan-containing metabolite cluster' overall. Phenotypic cluster analysis aggregated colonic transit with brady/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan-cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole-ring compound (anti-fungals) and vitamin B3 (anti-inflammatory) and with higher serum CCL20 (chemotactic for lymphocytes/dendritic cells towards mucosal epithelium). The faster pulse in PD was irrespective of postural hypotension. The benzoic acid-cluster deficit was linked to (well-recognised) lower caffeine and alcohol intakes, tryptophan-cluster deficit to higher maltose intake. Free-sugar intake was increased in PD, maltose intake being 63% higher (p = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [p = .001, adjusted for proton-pump inhibitors (p = .001)], with 16% of PD-probands exceeding a cut-point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut-point., Conclusions: Emerging picture is of (i) clinical phenotype being described by deficits in microbial metabolites essential to gut health; (ii) intestinal inflammation; (iii) a systemic inflammatory response syndrome., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Since the emergence of SARS-CoV-2, five different variants of concern (VOCs) have been identified: Alpha, Beta, Gamma, Delta, and Omicron. Because of confounding factors in the human population, such as preexisting immunity, comparing severity of disease caused by different VOCs is challenging. Here, we investigate disease progression in the rhesus macaque model upon inoculation with the Delta, Omicron BA.1, and Omicron BA.2 VOCs. Disease severity in rhesus macaques inoculated with Omicron BA.1 or BA.2 was lower than those inoculated with Delta and resulted in significantly lower viral loads in nasal swabs, bronchial cytology brush samples, and lung tissue in rhesus macaques. Cytokines and chemokines were up-regulated in nasosorption samples of Delta animals compared to Omicron BA.1 and BA.2 animals. Overall, these data suggest that, in rhesus macaques, Omicron replicates to lower levels than the Delta VOC, resulting in reduced clinical disease.

Objective: Pandemics negatively impact healthcare workers' (HCW's) mental health and well-being causing additional feelings of anxiety, depression, moral distress and post-traumatic stress. A comprehensive review and evidence synthesis of HCW's mental health and well-being interventions through pandemics reporting mental health outcomes was conducted addressing two questions: (1) What mental health support interventions have been reported in recent pandemics, and have they been effective in improving the mental health and well-being of HCWs? (2) Have any mobile apps been designed and implemented to support HCWs' mental health and well-being during pandemics?, Design: A narrative evidence synthesis was conducted using Cochrane criteria for synthesising and presenting findings when systematic review and pooling data for statistical analysis are not suitable due to the heterogeneity of the studies., Data Sources: Evidence summary resources, bibliographic databases, grey literature sources, clinical trial registries and protocol registries were searched., Eligibility Criteria: Subject heading terms and keywords covering three key concepts were searched: SARS-CoV-2 coronavirus (or similar infectious diseases) epidemics, health workforce and mental health support interventions. Searches were limited to English-language items published from 1 January 2000 to 14 June 2022. No publication-type limit was used., Data Extraction and Synthesis: Two authors determined eligibility and extracted data from identified manuscripts. Data was synthesised into tables and refined by coauthors., Results: 2694 studies were identified and 27 papers were included. Interventions were directed at individuals and/or organisations and most were COVID-19 focused. Interventions had some positive impacts on HCW's mental health and well-being, but variable study quality, low sample sizes and lack of control conditions were limitations. Two mobile apps were identified with mixed outcomes., Conclusion: HCW interventions were rapidly designed and implemented with few comprehensively described or evaluated. Tailored interventions that respond to HCWs' needs using experience co-design for mental health and well-being are required with process and outcome evaluation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In late 2021, the SARS-CoV-2 Omicron (B.1.1.529) variant of concern (VoC) was reported with many mutations in the viral spike protein that were predicted to enhance transmissibility and allow viral escape of neutralizing antibodies. Within weeks of the first report of B.1.1.529, this VoC has rapidly spread throughout the world, replacing previously circulating strains of SARS-CoV-2 and leading to a resurgence in COVID-19 cases even in populations with high levels of vaccine- and infection-induced immunity. Studies have shown that B.1.1.529 is less sensitive to protective antibody conferred by previous infections and vaccines developed against earlier lineages of SARS-CoV-2. The ability of B.1.1.529 to spread even among vaccinated populations has led to a global public health demand for updated vaccines that can confer protection against B.1.1.529., Methods: We rapidly developed a replicating RNA vaccine expressing the B.1.1.529 spike and evaluated immunogenicity in mice and hamsters. We also challenged hamsters with B.1.1.529 and evaluated whether vaccination could protect against viral shedding and replication within respiratory tissue., Findings: We found that mice previously immunized with A.1-specific vaccines failed to elevate neutralizing antibody titers against B.1.1.529 following B.1.1.529-targeted boosting, suggesting pre-existing immunity may impact the efficacy of B.1.1.529-targeted boosters. Furthermore, we found that our B.1.1.529-targeted vaccine provides superior protection compared to the ancestral A.1-targeted vaccine in hamsters challenged with the B.1.1.529 VoC after a single dose of each vaccine., Interpretation: Our data suggest that B.1.1.529-targeted vaccines may provide superior protection against B.1.1.529 but pre-existing immunity and timing of boosting may need to be considered for optimum protection., Funding: This research was supported in part by the Intramural Research Program, NIAID/NIH, Washington Research Foundation and by grants 27220140006C (JHE), AI100625, AI151698, and AI145296 (MG)., Competing Interests: Declaration of interests JHE, APK, KK, JA, PB, MG, and DHF have equity interest in HDT Bio Corp. JHE and APK are inventors on U.S. patent application no. 62/993,307 pertaining to the LION formulation. DHF has consulted with Orlance Inc (co-founder and advisory board), HDT Bio (consultant), Abacus Inc (consultant), SQZ Biotech (consultant), GLG (consultant), WilmerHale (consultant, expert witness). AG has grants and contracts to their institution from Abbott, Merck, Gilead, Pfizer, Novavax, Janssen, Cepheid and Hologic., (Published by Elsevier B.V.)

Objectives: Tricuspid valve (TV) surgery remains understudied and little data exist describing the surgical indications, outcomes, and prognostic factors for pediatric patients with non-Ebstein 2-ventricle congenital TV lesions. This study aims to describe early and late outcomes of pediatric patients with non-Ebstein congenital TV lesions undergoing isolated TV procedures at a single institution., Methods: All patients who underwent TV surgery for non-Ebstein congenital TV disease between 2006 and 2018 were included. Patients who had missing preoperative data, patients with single-ventricle physiology, congenitally corrected transposition of the great arteries, and patients undergoing TV intervention as part of repair of an atrioventricular canal defect were excluded. The primary end point was the occurrence of TV reintervention or TV regurgitation (TR) ≥ moderate., Results: A total of 85 patients were included. The tricuspid lesion was isolated TR in 80 (94.1%), isolated tricuspid stenosis in 3 (3.5%) and mixed disease in 2 (2.4%) patients. Median age at surgery was 33 years (interquartile range, 12-53 years). TV repair and TV replacement were performed in 66 (77.6%) and 19 (22.4%) patients, respectively. One (1.2%) patient underwent TV reoperation during the same admission. There was no in-hospital mortality. Median follow-up was 3.3 years (interquartile range, 0.1-4.7 years). The overall cumulative incidence of TV reintervention or TR deemed moderate or greater at 1, 3, and 5 years was 3% ± 2%, 11% ± 4%, and 20% ± 8%. In multivariable analysis, age younger than 12 years ( P  = .04) and mitral valve regurgitation deemed moderate or greater ( P  = .01) were independent risk factors for TV reintervention or recurrent TR deemed to be moderate or greater at last follow-up., Conclusions: TV surgery in patients with non-Ebstein congenital TV disease can be performed with good outcomes. TV reintervention or TR deemed moderate or greater occurred in 20% of patients on midterm follow-up. Patients younger than age 12 years are at higher risk for recurrent TR or TV reintervention, whereas preoperative MR deemed moderate or greater increases this risk, especially in patients older than age 12 years. There was no difference in outcomes between TV replacement and repair., (© 2022 The Author(s).)

Purpose: Blood loss (BL) during posterior spinal fusion for adolescent idiopathic scoliosis (AIS) may be estimated using a variety of unproven techniques. Patient care and research on BL are likely impacted by a lack of standardization. A novel FDA-approved blood volume (BV) analysis system (BVA-100 Blood Volume Analyzer) allows rapid processing with > 97% accuracy. The purpose of this study was to investigate common methods for BL estimation., Methods: BV assessment was performed with the BVA-100. After obtaining a baseline sample of 5 mL of blood, 1 mL of I-131-labeled albumin was injected intravenously over 1 min. Five milliliter blood samples were then collected at 12, 18, 24, 30, and 36 min post-injection. Intravenous fluid was minimized to maintain euvolemia. Salvaged blood was not administered during surgery. BL was estimated using several common techniques and compared to the BV measurements provided by the BVA-100 (BVABL)., Results: Thirty AIS patients were prospectively enrolled with major curves of 54° and underwent fusions of 10 levels. BL based on the BVA-100 (BVABL) was 519.2 [IQR 322.9, 886.2] mL. Previously published formulas all failed to approximate BVABL. Multiplying the cell saver volume return by 3 (CS3) approximates BVABL well with a Spearman correlation coefficient and ICC of 0.80 and 0.72, respectively. An extrapolated cell salvage-based estimator also showed high intraclass correlation coefficient (ICC) and Spearman coefficients with less bias than CS3., Conclusion: Published formulaic approaches do not approximate true blood loss. Multiplying the cell saver volume by 3 or using the cell salvage-based estimator had the highest correlation coefficient and ICC., Level of Evidence: Prospective cohort Level 2., (© 2021. The Author(s), under exclusive licence to Scoliosis Research Society.)

A model of the RESET melting process in conventional phase-change memory (PCM) devices is constructed in which the Gibbs-Thomson (GT) effect, representing local equilibrium at the solid-liquid interface, is included as an interfacial condition for the electro-thermal model of the PCM device. A comparison is made between the GT model and a commonly used model in which the interfacial temperature is fixed at the bulk melting temperature of the PCM material. The model is applied to conventional PCM designs in which a dome-shaped liquid/amorphous region is formed. Two families of solutions are computed representing steady state liquid regions, distinguished by their thermodynamic aspects. There is a family of solutions representing a hypothetical liquid nucleation process, and a family of larger steady-state liquid solutions representing the limit of the melting process. These 'melting limits' enable calculation of minima in voltage and corresponding current required for the RESET process. In this PCM configuration, the GT effect constrains the equilibrium solid-liquid interface temperature to remain above the bulk melting temperature during melting. The magnitude of this temperature difference increases with decreasing device size scale, thus requiring an increase in the required voltage and current needed for RESET compared to the case in which the interface temperature is approximated by the bulk melting temperature. This increase becomes substantial for active device dimensions in the <20 nm range. The impact of this phenomena on PCM device design is discussed., (© 2022 IOP Publishing Ltd.)

Background: Larval connectivity between distinct benthic populations is essential for their persistence. Although connectivity is difficult to measure in situ, it can be predicted via models that simulate biophysical interactions between larval behaviour and ocean currents. The blue mussel (Mytilus Edulis L.) is widespread throughout the northern hemisphere and extensively commercialised worldwide. In the Irish Sea, this industry represents ~ 50% of Welsh shellfisheries, where cultivation is mainly based on wild spat. However, the main sources and amount of spat varied interannually (1100 tonnes harvest in 2014 against zero in 2018). The aim of this study is to characterise the structure and dynamics of the blue mussel metapopulation within the northern part of the Irish Sea., Methods: We develop a Lagrangian particle tracking model, driven by a high-resolution (from 30 to 5000 m) validated unstructured coastal hydrodynamic model of the Irish Sea, to simulate spatial and temporal variability of larval dispersal and connectivity between distinct mussel populations and potential settlement areas., Results: Our results showed that: (1) larvae positioned near the surface were strongly influenced by wind-driven currents suggesting that connectivity networks had the potential to span hundreds of kilometres; (2) in contrast, larvae positioned deeper in the water column were driven by tidal currents, producing intricate spatial patterns of connectivity between mussel beds over tens of kilometres that were consistent over time., Conclusions: Dispersal of mussel larvae in the tidally energetic Irish Sea during the April-May spawning season is potentially driven by wind-driven surface currents, as confirmed by fisherman observations of inter-annual variability in wild spat collection. These results have important implications for metapopulation dynamics within the context of climate change and sustainable shellfisheries management (i.e. gain and loss of populations and harvest areas according to wind conditions)., (© 2022. The Author(s).)

Background: Travelers to tropical areas may be susceptible to illness or injuries. This study aims to assess morbidity among travelers during their travel and compare those who became ill or were injured with those who did not., Methods: This prospective study included 400 travelers who were counselled by a physician in pre-travel clinics in central Israel between 2017 and 2018. Participants were interviewed within a month after their return regarding morbidity during travel, including health problems that started one week following their return., Results: Most travelers (N = 320, 80%) reported at least one illness or injury. Illnesses/injuries were more common among females than males (84.9% vs. 75.1%, p = 0.01), travel periods longer than 30 days (87.7% vs. 77.2%, p = 0.03), and travelers accompanied by their friends or solo travelers compared with those who traveled with their family/partner (83.8% and 70.0%, respectively, p = 0.002). The most common complaint was diarrhea (N = 159, 49.6%), followed by high-altitude sickness (N = 118, 36.9%) and fever (N = 100, 31.2%). Altitude sickness symptoms were more common in females than in males (58.9% vs. 41.0%, p = 0.006) and in those who ascended rapidly in comparison to those who ascended gradually (58.7% vs. 44.6%, p = 0.04). Animal injury was reported by 30 (7.5%) participants yet only eight (27.0%) received medical care, seven of whom (23.3%) were vaccinated against rabies., Conclusions: Being a female, traveling with friends or alone and longer travel periods were associated with illness/injury. Practitioners at pre-travel clinics should inform travelers of the possible risks including the potential severe consequences of rabies and altitude sickness., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background : Evidence indicates that the more traditional and behavioural parenting strategies are ineffective when parenting a child who has experienced developmental trauma. Recognising the need to parent with an attachment focus, the current paper evaluates the effectiveness of running the [Enfys] Nurturing Attachments Group, virtually, within the context of the COVID-19 pandemic. Method : A pilot feasibility study evaluated eight bespoke groups. Consenting professionals and co-professionals completed the Brief Parental Self-Efficacy Scale (BFSS), Care Questionnaire (CQ) and the Parental Reflective Functioning Questionnaire (PRFQ). Results : One hundred forty individuals attended the groups, with 51 (36%) completing both pre-and post-measures. The results provide evidence that professionals and co-professionals reported statistically significant positive increases on both the BPSS ( d = .55) and CQ ( d = .62). For the PRFQ, the results showed a statistically significant decrease on the Pre-mentalising sub scale, a non-significant mid-range score for Certainty about Mental States and a non-significant increase for Parental Interest and Curiosity in Mental States . Conclusion : The study has demonstrated initial viability of effectively facilitating the [Enfys] Nurturing Attachments Group, virtually. Importantly, it has also shown that the group can be run with professionals alongside co-professionals.

To meet the ambitious objectives of biodiversity and climate conventions, the international community requires clarity on how these objectives can be operationalized spatially and how multiple targets can be pursued concurrently. To support goal setting and the implementation of international strategies and action plans, spatial guidance is needed to identify which land areas have the potential to generate the greatest synergies between conserving biodiversity and nature's contributions to people. Here we present results from a joint optimization that minimizes the number of threatened species, maximizes carbon retention and water quality regulation, and ranks terrestrial conservation priorities globally. We found that selecting the top-ranked 30% and 50% of terrestrial land area would conserve respectively 60.7% and 85.3% of the estimated total carbon stock and 66% and 89.8% of all clean water, in addition to meeting conservation targets for 57.9% and 79% of all species considered. Our data and prioritization further suggest that adequately conserving all species considered (vertebrates and plants) would require giving conservation attention to ~70% of the terrestrial land surface. If priority was given to biodiversity only, managing 30% of optimally located land area for conservation may be sufficient to meet conservation targets for 81.3% of the terrestrial plant and vertebrate species considered. Our results provide a global assessment of where land could be optimally managed for conservation. We discuss how such a spatial prioritization framework can support the implementation of the biodiversity and climate conventions., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

This review provides a critical, multi-faceted assessment of the practical contribution tidal stream energy can make to the UK and British Channel Islands future energy mix. Evidence is presented that broadly supports the latest national-scale practical resource estimate, of 34 TWh/year, equivalent to 11% of the UK's current annual electricity demand. The size of the practical resource depends in part on the economic competitiveness of projects. In the UK, 124 MW of prospective tidal stream capacity is currently eligible to bid for subsidy support (MeyGen 1C, 80 MW; PTEC, 30 MW; and Morlais, 14 MW). It is estimated that the installation of this 124 MW would serve to drive down the levelized cost of energy (LCoE), through learning, from its current level of around 240   £ / MWh to below 150   £ / MWh , based on a mid-range technology learning rate of 17%. Doing so would make tidal stream cost competitive with technologies such as combined cycle gas turbines, biomass and anaerobic digestion. Installing this 124 MW by 2031 would put tidal stream on a trajectory to install the estimated 11.5 GW needed to generate 34 TWh/year by 2050. The cyclic, predictable nature of tidal stream power shows potential to provide additional, whole-system cost benefits. These include reductions in balancing expenditure that are not considered in conventional LCoE estimates. The practical resource is also dependent on environmental constraints. To date, no collisions between animals and turbines have been detected, and only small changes in habitat have been measured. The impacts of large arrays on stratification and predator-prey interaction are projected to be an order of magnitude less than those from climate change, highlighting opportunities for risk retirement. Ongoing field measurements will be important as arrays scale up, given the uncertainty in some environmental and ecological impact models. Based on the findings presented in this review, we recommend that an updated national-scale practical resource study is undertaken that implements high-fidelity, site-specific modelling, with improved model validation from the wide range of field measurements that are now available from the major sites. Quantifying the sensitivity of the practical resource to constraints will be important to establish opportunities for constraint retirement. Quantification of whole-system benefits is necessary to fully understand the value of tidal stream in the energy system., (© 2021 The Authors.)

Dysregulated inflammation dominated by chemokine expression is a key feature of disease following infection with the globally important human pathogens Zika virus (ZIKV) and dengue virus, but a mechanistic understanding of how pro-inflammatory responses are initiated is lacking. Mitophagy is a quality-control mechanism that regulates innate immune signaling and cytokine production through selective degradation of damaged mitochondria. Here, we demonstrate that ZIKV nonstructural protein 5 (NS5) antagonizes mitophagy by binding to the host protein Ajuba and preventing its translocation to depolarized mitochondria where it is required for PINK1 activation and downstream signaling. Consequent mitophagy suppression amplifies the production of pro-inflammatory chemokines through protein kinase R (PKR) sensing of mitochondrial RNA. In Ajuba -/- mice, ZIKV induces early expression of pro-inflammatory chemokines associated with significantly enhanced dissemination to tissues. This work identifies Ajuba as a critical regulator of mitophagy and demonstrates a role for mitophagy in limiting systemic inflammation following infection by globally important human viruses., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Molecular identification is increasingly used to speed up biodiversity surveys and laboratory experiments. However, many groups of organisms cannot be reliably identified using standard databases such as GenBank or BOLD due to lack of sequenced voucher specimens identified by experts. Sometimes a large number of sequences are available, but with too many errors to allow identification. Here, we address this problem for parasitoids of Drosophila by introducing a curated open-access molecular reference database, DROP (Drosophila parasitoids). Identifying Drosophila parasitoids is challenging and poses a major impediment to realize the full potential of this model system in studies ranging from molecular mechanisms to food webs, and in biological control of Drosophila suzukii. In DROP, genetic data are linked to voucher specimens and, where possible, the voucher specimens are identified by taxonomists and vetted through direct comparison with primary type material. To initiate DROP, we curated 154 laboratory strains, 856 vouchers, 554 DNA sequences, 16 genomes, 14 transcriptomes, and six proteomes drawn from a total of 183 operational taxonomic units (OTUs): 114 described Drosophila parasitoid species and 69 provisional species. We found species richness of Drosophila parasitoids to be heavily underestimated and provide an updated taxonomic catalogue for the community. DROP offers accurate molecular identification and improves cross-referencing between individual studies that we hope will catalyse research on this diverse and fascinating model system. Our effort should also serve as an example for researchers facing similar molecular identification problems in other groups of organisms., (© 2021 John Wiley & Sons Ltd.)

As a high-impact educational practice, cooperative learning uses a structured group study to promote students' active learning. Currently, it lacks economical yet effective tools to facilitate the interactive nature of structured cooperative learning in regular classrooms. Here, we have established a mobile technology-based cooperative learning (MBCL) platform that comprises the 2018 iPad, Apple Pencil, LiveBoard, Google Forms, and Google Drive. We tested the MBCL platform in multiple undergraduate biology courses. During semester-long MBCL studies, the students engaged in cooperative learning to discuss a real-life issue or chapter-based contents. With the MBCL platform, the students' group study processes were shown on shared, visible electronic whiteboards that were updated in real-time, generating visible thinking and instant, interactive communication. The instructor was able to guide the students promptly to conduct knowledge integration and knowledge synthesis using tables and diagrams. The deep learning outcome was evident in the examples and quantitative analyses of students' whiteboard study results and team presentations. Thus, integrating innovative mobile technologies into high-impact teaching practices, exemplified by the MBCL platform, promotes deep learning in higher education., (© 2021 The Authors. Biochemistry and Molecular Biology Education published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Background: The COVID-19 pandemic has highlighted the importance of health care workers' mental health and well-being for the successful function of the health care system. Few targeted digital tools exist to support the mental health of hospital-based health care workers, and none of them appear to have been led and co-designed by health care workers., Objective: RMHive is being led and developed by health care workers using experience-based co-design (EBCD) processes as a mobile app to support the mental health challenges posed by the COVID-19 pandemic to health care workers. We present a protocol for the impact evaluation for the rapid design and delivery of the RMHive mobile app., Methods: The impact evaluation will adopt a mixed methods design. Qualitative data from photo interviews undertaken with up to 30 health care workers and semistructured interviews conducted with up to 30 governance stakeholders will be integrated with qualitative and quantitative user analytics data and user-generated demographic and mental health data entered into the app. Analyses will address three evaluation questions related to engagement with the mobile app, implementation and integration of the app, and the impact of the app on individual mental health outcomes. The design and development will be described using the Mobile Health Evidence Reporting and Assessment guidelines. Implementation of the app will be evaluated using normalization process theory to analyze qualitative data from interviews combined with text and video analysis from the semistructured interviews. Mental health impacts will be assessed using the total score of the 4-item Patient Health Questionnaire (PHQ4) and subscale scores for the 2-item Patient Health Questionnaire for depression and the 2-item Generalized Anxiety Scale for anxiety. The PHQ4 will be completed at baseline and at 14 and 28 days., Results: The anticipated average use period of the app is 30 days. The rapid design will occur over four months using EBCD to collect qualitative data and develop app content. The impact evaluation will monitor outcome data for up to 12 weeks following hospital-wide release of the minimal viable product release. The study received funding and ethics approvals in June 2020. Outcome data is expected to be available in March 2021, and the impact evaluation is expected to be published mid-2021., Conclusions: The impact evaluation will examine the rapid design, development, and implementation of the RMHive app and its impact on mental health outcomes for health care workers. Findings from the impact evaluation will provide guidance for the integration of EBCD in rapid design and implementation processes. The evaluation will also inform future development and rollout of the app to support the mental health needs of hospital-based health care workers more widely., International Registered Report Identifier (irrid): DERR1-10.2196/26168., (©Matthew Lewis, Victoria J Palmer, Aneta Kotevski, Konstancja Densley, Meaghan L O'Donnell, Caroline Johnson, Franz Wohlgezogen, Kathleen Gray, Kate Robins-Browne, Luke Burchill. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.03.2021.)

Understanding the ecological factors that drive animal density patterns in time and space is key to devising effective conservation strategies. In Tanzania, most chimpanzees (~75%) live outside national parks where human activities threaten their habitat's integrity and connectivity. Mahale Mountains National Park (MMNP), therefore, is a critical area for chimpanzees (Pan troglodytes schweinfurthii) in the region due to its location and protective status. Yet, despite its importance and long history of chimpanzee research (>50 years), a park-wide census of the species has never been conducted. The park is categorized as a savanna-woodland mosaic, interspersed with riparian forest, wooded grassland, and bamboo thicket. This heterogeneous landscape offers an excellent opportunity to assess the ecological characteristics associated with chimpanzee density, a topic still disputed, which could improve conservation plans that protect crucial chimpanzee habitat outside the park. We examined the influence of fine-scale vegetative characteristics and topographical features on chimpanzee nest density, modeling nest counts using hierarchical distance sampling. We counted 335 nests in forest and woodland habitats across 102 transects in 13 survey sites. Nests were disproportionately found more in or near evergreen forests, on steep slopes, and in feeding tree species. We calculated chimpanzee density in MMNP to be 0.23 ind/km2, although density varied substantially among sites (0.09-3.43 ind/km2). Density was associated with factors related to the availability of food and nesting trees, with topographic heterogeneity and the total basal area of feeding tree species identified as significant positive predictors. Species-rich habitats and floristic diversity likely play a principal role in shaping chimpanzee density within a predominately open landscape with low food abundance. Our results provide valuable baseline data for future monitoring efforts in MMNP and enhance our understanding of this endangered species' density and distribution across Tanzania., Competing Interests: No authors have competing interests.

Background: While atypical antipsychotic medications are widely used for treating depressive disorders, their long-term effects on the risk of subsequent dementia have not been studied adequately., Objective: To investigate whether the risk of dementia differs according to the use of atypical antipsychotic drugs, and compare the effects of antipsychotic agents on dementia risk in individuals with late-life depressive disorders., Methods: A nationwide population-based retrospective cohort study was conducted using data from the National Health Insurance Service-Senior Cohort of South Korea. Atypical antipsychotic dosages were standardized using a defined daily dose, and the cumulative dosage was calculated. Participants were observed from January 2008 to December 2015. Cox proportional hazard regression analysis was used to estimate the hazard ratios., Results: The cohort included 43,788 elderly adults with depressive disorders: 9,901 participants (22.6%) were diagnosed with dementia. Findings showed that atypical antipsychotics were prescribed to 1,967 participants (4.5%). Compared with non-users, users of atypical antipsychotics experienced a significantly higher risk for dementia with an adjusted hazard ratio (aHR) of 1.541 (95% confidence interval [CI], 1.415-1.678). A cumulative dose-response relationship was observed (test for trend, p < 0.0001). Among atypical antipsychotics, risperidone displayed the highest risk for dementia (aHR 1.767, [95% CI, 1.555-2.009])., Conclusion: In this study of elderly individuals with depressive disorders, atypical antipsychotic use was associated with a significantly higher risk of subsequent dementia. Healthcare professionals should be aware of this potential long-term risk. A limitation that should be mentioned is that we could not exclude patients with bipolar depression.

In March 2010, a sequence of three major rainfall events in New England (United States) led to a record-breaking flooding event in the Pawtuxet River Watershed with a peak flow discharge of about 500-year return period. After development of hydrological and hydraulic models, a number of factors that played important roles in the impact of this flooding and other extreme events including river structures (reservoirs, historical textile mill dams, and bridges) were investigated. These factors are currently omitted within risk assessments tools such as flood insurance rate maps. Some management strategies that should be considered for future flood risk mitigation were modeled and discussed. Furthermore, to better understand possible future risks in a warmer climate, another extreme flood event was simulated. The synthetic/hypothetical storm (Hurricane Rhody with two landfalls) was created based on the characteristics of the historical hurricanes that severely impacted this region in the past. It was shown that while the first landfall of this hurricane did not lead to significant flood risk, the second landfall could generate more rain and flooding equivalent to a 500-year event. Results and the methodology of this study can be used to better understand and assess future flood risk in similar watersheds., (© 2020 The Authors. Journal of Flood Risk Management published by Chartered Institution of Water and Environmental Management and John Wiley & Sons Ltd.)