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This report describes the moral phenomena that students in an intensive Arabic study abroad program encountered as they tried to find speaking opportunities for themselves outside of institutional arrangements. The ways that participants went about speaking activities were accompanied by tensions that they had to deal with throughout the program. They found themselves obliged to consider values such as decisiveness, independence, and fairness as they tried to become better conversationalists, cultural insiders, and friends with the people they met. Additional research using the same analytic framework could reveal deeply practical insights for the benefit of language learners and practitioners.

BACKGROUND: Cardiac function of critically ill patients with COVID-19 generally has been reported from clinically obtained data. Echocardiographic deformation imaging can identify ventricular dysfunction missed by traditional echocardiographic assessment. RESEARCH QUESTION: What is the prevalence of ventricular dysfunction and what are its implications for the natural history of critical COVID-19? STUDY DESIGN AND METHODS: This is a multicenter prospective cohort of critically ill patients with COVID-19. We performed serial echocardiography and lower extremity vascular ultrasound on hospitalization days 1, 3, and 8. We defined left ventricular (LV) dysfunction as the absolute value of longitudinal strain of < 17% or left ventricle ejection fraction (LVEF) of < 50%. Primary clinical outcome was inpatient survival. RESULTS: We enrolled 110 patients. Thirty-nine (35.5%) died before hospital discharge. LV dysfunction was present at admission in 38 patients (34.5%) and in 21 patients (36.2%) on day 8 (P = .59). Median baseline LVEF was 62% (interquartile range [IQR], 52%-69%), whereas median absolute value of baseline LV strain was 16% (IQR, 14%-19%). Survivors and nonsurvivors did not differ statistically significantly with respect to day 1 LV strain (17.9% vs 14.4%; P = .12) or day 1 LVEF (60.5% vs 65%; P = .06). Nonsurvivors showed worse day 1 right ventricle (RV) strain than survivors (16.3% vs 21.2%; P = .04). INTERPRETATION: Among patients with critical COVID-19, LV and RV dysfunction is common, frequently identified only through deformation imaging, and early (day 1) RV dysfunction may be associated with clinical outcome.

Abstract Background Abdominal aortic aneurysm (AAA) is an important cardiovascular health problem. Ultrasound screening is proven to reduce AAA mortality and programmes have been implemented in some healthcare systems. Those who are identified as having a small AAA in screening enter into a surveillance programme to monitor AAA size. Individuals in AAA surveillance are at elevated risk of cardiovascular events, which is not currently addressed sufficiently. We aimed to develop a simple intervention to reduce cardiovascular risk, which could be embedded in AAA surveillance pathways. Methods Intervention mapping methods were used to co-develop the intervention with individuals with AAA, families/carers, and healthcare staff. We identified “targets for change” by synthesising research evidence and international guidelines and consulting with patients, caregivers and health service providers. We conducted a series of workshops to identify barriers to and facilitators of change and used taxonomies of behaviour change theories and techniques to match intervention strategies to each target. Further stakeholder involvement work helped refine the intervention. Results The developed intervention focusses on assessment and individually tailored discussion of risk factors, exchanging information, building motivation and action planning, followed by review of progress and problem-solving. Workbooks covering physical activity, diet, stress management, alcohol, smoking, blood pressure and mental health are provided to support behaviour change. The intervention is facilitated by trained healthcare professionals during the patient’s AAA screening appointment for the duration that they are in surveillance. Discussion The developed intervention will now be tested to assess whether it can be integrated with the current AAA screening programme. The developed intervention is a novel approach to reducing cardiovascular disease in the AAA population, it is also the first intervention which tries to do this in this population. Trial registration International Clinical Trial Registration: ISRCTN93993995.

Biomedical science students need to learn to code. Graduates face a future where they will be better prepared for research higher degrees and the workforce if they can code. Embedding coding in a biomedical curriculum comes with challenges. First, biomedical science students often experience anxiety learning quantitative and computational thinking skills and second biomedical faculty often lack expertise required to teach coding. In this study, we describe a creative coding approach to building coding skills in students using the packages of Processing and Arduino. Biomedical science students were taught by an interdisciplinary faculty team from Medicine and Health, Science and Architecture, Design and Planning. We describe quantitative and qualitative responses of students to this approach. Cluster analysis revealed a diversity of student responses, with a large majority of students who supported creative coding in the curriculum, a smaller but vocal cluster, who did not support creative coding because either the exercises were not sufficiently challenging or were too challenging and believed coding should not be in a Biomedical Science curriculum. We describe how two creative coding platforms, Processing and Arduino, embedded and used to visualize human physiological data, and provide responses to students, including those minority of students, who are opposed to coding in the curriculum This study found a variety of students responses in a final year capstone course of an undergraduate Biomedical Science degree where future pathways for students are either in research higher degrees or to the workforce with a future which will be increasingly data driven.

Museum education is a dynamic and evolving field, requiring a commitment to continuous professional growth and the integration of best practices as they develop. As the field has shifted towards creating participant-centered experiences that encourage active learning and dialogue, museum educators have been seeking new ways to enhance their practice and provide visitors with meaningful experiences. One such approach is the adoption of a coaching mindset, drawing on core competencies from the professional field of performance coaching to support museum educators. This article will explore how the effective application of five key coaching competencies, alongside a coaching mindset, can empower museum educators in their practice, improve their museum teaching, and enhance the visitor experience. By exploring the impact of coaching competencies and mindset on museum education practice, this article aims to contribute to a broader understanding of the potential benefits of utilizing coaching approaches in the field of museum education.

We evaluated the performance of 12 lateral flow devices by assessing their analytical sensitivity for SARS-CoV-2 variant BA.2.86. Kits from ACON, Orient Gene, Xiamen Biotime, Getein, and SureScreen detected variant BA.2.86 to sufficient sensitivity levels, comparable to those observed with previous Omicron variants. The stocks of lateral flow devices currently held by the UK government do not currently need changing for deployment for this variant.

Arable field margins provide important floral resources for insect foragers. This study assessed the significance of cultivated margins and floristically enhanced margins, both English agri-environment scheme (AES) options, to foraging bumble bees (Bombus species). We examined plant foraging preferences in each habitat according to species and caste. Additionally, detailed botanical surveys were carried out to determine vascular plant densities on the study margins. Overall, our results emphasised the importance of spontaneous (Asteraceae) species emerging from the seed bank in the provision of forage across Bombus species and castes, and highlighted that Bombus foraging preferences appeared to be only weakly related to floral species densities. Although found only occasionally in high densities, the popularity of these dicots was likely due to high nectar sugar mass. Bombus queens were recorded relatively infrequently, implying that these habitats are failing to provide the preferred floral resources of all Bombus spp. queens. Queens that were observed were found to favour earlier-flowering species (e.g. Anchusa arvensis) and species with longer corollas (e.g. Vicia sativa). Worker bees across Bombus spp. showed high overlap in plant preferences (e.g. Cirsium arvense, Ononis spinosa). However, some variability in preferences between castes within a species were noted, for example, only B. terrestris/lucorum drones were found to forage on Crepis vesicaria in cultivated margins. Additionally, bumble bee abundance was only found to increase as dicot cover increased. Overall, our findings highlight the importance of continuing to utilise multiple AES types in order to fully support Bombus and other pollinating insect populations on farmland.

The notion of language learners as informed consumers developed by Cohen and White (2008) takes up the issue of how best to develop the knowledge, skills and awareness of language learners given the infinite variety of language learning opportunities. The informed consumer approach focused not only on developing awareness of both formal and informal learning environments, but also on enhancing the ability to critically appraise those opportunities and to optimise language learning within them. In this article we trace how the notion of language learners as informed consumers has been drawn on in innovative studies of technology-mediated language learning; a common focus of those studies has been on ways of fostering awareness of the potential of particular technology-mediated learning environments and the relevant knowledge and skills which would support the active and effective use of those environments. We show how strands of the informed consumer approach have been used to investigate expertise and affordances in electronic dictionary use (Levy & Steel, 2015) and the trajectories of distance learners of Chinese (Tasker, 2010). In the latter part of the article we consider the experiences and reflections of learners of Arabic in a study abroad context in Jordan as part of Project Perseverance; findings from that project open up new dimensions of what it means to be an informed consumer of language instruction in relation to specific situational and cultural norms and constraints. To conclude the article identifies not only the distinctive contribution of the informed consumer approach but also how it sheds light on the ways in which individuals seek out and curate personally meaningful sites for language learning within their life worlds.

The cognitive, educational and economic benefits of learning a second language have been well documented in the literature. This paper reports findings on perspectives of 13 stakeholders on the benefits of a case study about teaching Vietnamese to preschoolers in a regional early childhood context in Tasmania, Australia in 2017. Using a thematic approach in analysing 13 semi-structured interviews, five main themes on the benefits of the programme for the children identified were language development, cultural and global awareness, numeracy enhancement, reading engagement, and personal development. The results showed that participating educators and parents all had positive attitudes towards the early Vietnamese language programme, believed that there were many benefits and expressed a desire for its continuity. These findings suggest that there is a need and desire for second language education in early childhood in the Tasmanian context. Therefore, policy makers, educators and researchers should provide preschools access to learning and teaching resources of a language of their choice to benefit children's overall development and learning in early childhood, adolescence and beyond.

Onion center rot is caused by at least four species of genus Pantoea (P. ananatis, P. agglomerans, P. allii, and P. stewartii subsp. indologenes). Critical onion pathogenicity determinants for P. ananatis were recently described, but whether those determinants are common among other onion-pathogenic Pantoea species remains unknown. In this work, we report onion pathogenicity determinants in P. stewartii subsp. indologenes and P. allii. We identified two distinct secondary metabolite biosynthetic gene clusters present separately in different strains of onion-pathogenic P. stewartii subsp. indologenes. One cluster is similar to the previously described HiVir phosphonate biosynthetic cluster identified in P. ananatis and another is a novel putative phosphonate biosynthetic gene cluster, which we named Halophos. The Halophos gene cluster was also identified in P. allii strains. Both clusters are predicted to be phosphonate biosynthetic clusters based on the presence of a characteristic phosphoenolpyruvate phosphomutase (pepM) gene. The deletion of the pepM gene from either HiVir or Halophos clusters in P. stewartii subsp. indologenes caused loss of necrosis on onion leaves and red onion scales and resulted in significantly lower bacterial populations compared with the corresponding wild-type and complemented strains. Seven (halB to halH) of 11 genes (halA to halK) in the Halophos gene cluster are required for onion necrosis phenotypes. The onion nonpathogenic strain PNA15-2 (P. stewartii subsp. indologenes) gained the capacity to cause foliar necrosis on onion via exogenous expression of a minimal seven-gene Halophos cluster (genes halB to halH). Furthermore, cell-free culture filtrates of PNA14-12 expressing the intact Halophos gene cluster caused necrosis on onion leaves consistent with the presence of a secreted toxin. Based on the similarity of proteins to those with experimentally determined functions, we are able to predict most of the steps in Halophos biosynthesis. Together, these observations indicate that production of the toxin phosphonate seems sufficient to account for virulence of a variety of different Pantoea strains, although strains differ in possessing a single but distinct phosphonate biosynthetic cluster. Overall, this is the first report of onion pathogenicity determinants in P. stewartii subsp. indologenes and P. allii. [Graphic: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.

The end-Cretaceous bolide impact triggered the devastation of marine ecosystems. However, the specific kill mechanism(s) are still debated, and how primary production subsequently recovered remains elusive. We used marine plankton microfossils and eco-evolutionary modeling to determine strategies for survival and recovery, finding that widespread phagotrophy (prey ingestion) was fundamental to plankton surviving the impact and also for the subsequent reestablishment of primary production. Ecological selectivity points to extreme post-impact light inhibition as the principal kill mechanism, with the marine food chain temporarily reset to a bacteria-dominated state. Subsequently, in a sunlit ocean inhabited by only rare survivor grazers but abundant small prey, it was mixotrophic nutrition (autotrophy and heterotrophy) and increasing cell sizes that enabled the eventual reestablishment of marine food webs some 2 million years later.

Continuous-cover forestry (CCF), which maintains a relatively intact forest cover through selective harvesting, has emerged over the last few decades as a popular alternative to rotational forest management (RFM). Coast redwood, which is native to the western United States, grows rapidly in New Zealand and is well suited to CCF as it has high shade tolerance, an ability to coppice from the cut stem, and resistance to pests, diseases, wind and fire. A forest estate model was used to compare the carbon sequestration, timber production and profitability of redwood CCF, RFM and permanent carbon forestry (PCF) regimes at a regional level within New Zealand. Through linear programming, this model optimised carbon accumulation and harvesting decisions across a large forest to meet a series of constraints associated with each regime. All three regimes represented good investment decisions, but CCF had the highest soil expectation value (SEV) within most North Island regions while PCF had a slightly higher SEV within the South Island regions. Under the transitional CCF (CCFt), revenue from carbon initially increased before levelling out at 40 years, after which time a sustainable harvest of high-value timber commenced in perpetuity without additional revenue from carbon. The CCFt regime transitioned to a steady-state condition, with a uniform age class distribution from year 150 onwards (CCFs), after which time a very high SEV was attained that exceeded that of CCFt by four-fold in the North Island (NZD 136,126/ha vs. NZD 34,430/ha) and seven-fold (NZD 44,714 vs. NZD 6267/ha) in the South Island. This study highlights the profitability of managing redwood under CCF and how initial carbon revenue can be used to finance the transition of the forest to a steady-state condition that produces a stream of valuable timber with a very high rate of return.

Successful restoration measures need a good understanding of how the composition, structure, and functioning of ecosystems change with degradation and what the best indicators of these changes are. To answer these questions, we worked on four ecosystem types in the Mediterranean Andes mountains in central Chile (from sclerophyllous forest to Andean shrublands), which represent an elevational gradient from 700 to 3,250 m. We sampled three plots on each of the three degradation levels (low, medium, and high) for each ecosystem at increasing distances from goat corrals. We measured 35 indicators that describe vegetation (14), soil (15), and ecosystem processes (6) for one growing season. Degradation caused a decrease in shrub cover, shrub productivity, the Normalized Community Structure Integrity Index (CSIIn), litter depth, total soil nitrogen and C/N ratio, and an increase in clay content. Plant species indicating low degradation were consistently native woody species. When comparing ecosystems (i.e., at different elevations) against the type of variable, process-based indicators showed more statistically significant differences. Based on their consistency across ecosystems and ease of measurement, we recommend using shrub cover and litter depth as indicators of degradation. Finally, we concluded that ecosystems are highly degraded when vegetation- and process-based indicators change ∼ 60% or when soil indicators change ∼ 25%. These results could also be used to set goals for restoration projects in these mountain ecosystems.

Introduction Liver resection carries a high risk for extensive bleeding and need for blood transfusions, which is associated with significant negative impact on outcome. In malignant disease, the most common indication for surgery, it also includes increased risk for recurrence of cancer. Argipressin decreases liver and portal blood flow and may have the potential to reduce bleeding during liver surgery, although this has not been explored.Method and analysis ARG-01 is a prospective, randomised, placebo-controlled, double-blinded study on 248 patients undergoing liver resection at Sahlgrenska University Hospital, Sweden. Patients will be randomised to one of two parallel groups, infusion of argipressin or normal saline administered peroperatively. The primary endpoint is peroperative blood loss. Secondary outcomes include need for blood transfusion, perioperative variables, length of hospital stay, the inflammatory response, organ damage markers and complications at 30 days.Ethics and dissemination The study is enrolling patients since March 2022. The trial is approved by the Swedish Ethical Review Authority (Dnr 2021-03557) and the Swedish Medical Product Agency (Dnr 5.1-2021-90115). Results will be announced at scientific meetings and in international peer-reviewed journals.Trial registration number ClinicalTrials.gov, NCT05293041 and EudraCT, 2021-001806-32

The cause of the end-Cretaceous mass extinction is vigorously debated, owing to the occurrence of a very large bolide impact and flood basalt volcanism near the boundary. Disentangling their relative importance is complicated by uncertainty regarding kill mechanisms and the relative timing of volcanogenic outgassing, impact, and extinction. We used carbon cycle modeling and paleotemperature records to constrain the timing of volcanogenic outgassing. We found support for major outgassing beginning and ending distinctly before the impact, with only the impact coinciding with mass extinction and biologically amplified carbon cycle change. Our models show that these extinction-related carbon cycle changes would have allowed the ocean to absorb massive amounts of carbon dioxide, thus limiting the global warming otherwise expected from postextinction volcanism.

Health care personnel (HCP) caring for patients with coronavirus disease 2019 (COVID-19) might be at high risk for contracting SARS-CoV-2, the virus that causes COVID-19. Understanding the prevalence of and factors associated with SARS-CoV-2 infection among frontline HCP who care for COVID-19 patients are important for protecting both HCP and their patients. During April 3-June 19, 2020, serum specimens were collected from a convenience sample of frontline HCP who worked with COVID-19 patients at 13 geographically diverse academic medical centers in the United States, and specimens were tested for antibodies to SARS-CoV-2. Participants were asked about potential symptoms of COVID-19 experienced since February 1, 2020, previous testing for acute SARS-CoV-2 infection, and their use of personal protective equipment (PPE) in the past week. Among 3,248 participants, 194 (6.0%) had positive test results for SARS-CoV-2 antibodies. Seroprevalence by hospital ranged from 0.8% to 31.2% (median = 3.6%). Among the 194 seropositive participants, 56 (29%) reported no symptoms since February 1, 2020, 86 (44%) did not believe that they previously had COVID-19, and 133 (69%) did not report a previous COVID-19 diagnosis. Seroprevalence was lower among personnel who reported always wearing a face covering (defined in this study as a surgical mask, N95 respirator, or powered air purifying respirator [PAPR]) while caring for patients (5.6%), compared with that among those who did not (9.0%) (p = 0.012). Consistent with persons in the general population with SARS-CoV-2 infection, many frontline HCP with SARS-CoV-2 infection might be asymptomatic or minimally symptomatic during infection, and infection might be unrecognized. Enhanced screening, including frequent testing of frontline HCP, and universal use of face coverings in hospitals are two strategies that could reduce SARS-CoV-2 transmission.

Numerical models have been highly successful in simulating global carbon and nutrient cycles in today's ocean, together with observed spatial and temporal patterns of chlorophyll and plankton biomass at the surface. With this success has come some confidence in projecting the century-scale response to continuing anthropogenic warming. There is also increasing interest in using such models to understand the role of plankton ecosystems in past oceans. However, today's marine environment is the product of billions of years of continual evolution-a process that continues today. In this paper, we address the questions of whether an assumption of species invariance is sufficient, and if not, under what circumstances current model projections might break down. To do this, we first identify the key timescales and questions asked of models. We then review how current marine ecosystem models work and what alternative approaches are available to account for evolution. We argue that for timescales of climate change overlapping with evolutionary timescales, accounting for evolution may to lead to very different projected outcomes regarding the timescales of ecosystem response and associated global biogeochemical cycling. This is particularly the case for past extinction events but may also be true in the future, depending on the eventual degree of anthropogenic disruption. The discipline of building new numerical models that incorporate evolution is also hugely beneficial in itself, as it forces us to question what we know about adaptive evolution, irrespective of its quantitative role in any specific event or environmental changes.

Antibacterial foam dressing has been developed in recent years based on polymeric membranes and silver ions or silver nanoparticles as antibacterial components. However, silver ions or silver nanoparticles have cytotoxicity to humans. Herein, we used biocompatible multi-branched gold nanoparticles as an antimicrobial agent in polyurethane foam wound dressings. This study described a rapid and surfactant-free method for the preparation of multi-branched gold nanoparticles using hydroquinone as a reducing agent and chitosan as a stabilizer as well as assisted irradiation. The optimal procedure of polyurethane foam fabricated with high water absorption and small average pore size, achieved nearly 500% of absorptivity and 98 nm of pore size. The antibacterial effects of the multi-branched gold nanoparticles containing polyurethane foam against both Escherichia coli and Staphylococcus aureus were investigated. The results demonstrated that multi-branched gold nanoparticles can be used as a viable alternative to conventional antibiotics in wound dressings.

Many higher education students across the world are studying in situations where a high proportion of the academic materials they encounter are online reading texts written in their second language. While the online medium presents a number of challenges to L2 readers, it also enables the provision of a range of support mechanisms, such as instant feedback. This quasi-experimental study investigated the use of two types of feedback, elaborative and knowledge of response, and compares their effectiveness for enhancing online second language reading comprehension. The participants were 113 Emirati students of L2 English at a higher education college in the United Arab Emirates. Data were collected using a pre-test and a post-test measure of reading comprehension and an online reading comprehension exercise containing either elaborative or knowledge of response feedback. The results of the quasi-experiment showed no significant difference between the effects of the two feedback types on comprehension of an online reading text for the sample as a whole. Equally, for the high-proficiency readers, feedback type had no significant effect on text comprehension. However, with regard to the low-proficiency readers, those receiving elaborative feedback performed significantly better on the post-test than those who received knowledge of response feedback. The findings suggest that elaborative feedback can enhance online L2 reading comprehension but that it needs to be tailored specifically to the needs of the L2 readers it is intended to support.

Abstract Background Cardiovascular disease is a major contributor to poor health in the UK and the leading cause of death in England. Peripheral arterial disease and high blood pressure are conditions that identify individuals at high cardiovascular disease risk, likely to benefit from cardiovascular risk management. Both conditions remain considerably underdiagnosed and untreated. The National Health Service abdominal aortic aneurysm (AAA) screening programmes represent an opportunity to screen for these conditions with potentially minimal additional effort or cost. We explored AAA screening programme staff views on the proposed introduction of such additional screening within AAA screening. Methods Nine focus groups and seven follow-on interviews were undertaken with 38 AAA screening staff. Our study methods were oriented broadly towards a grounded theory methodology, and data were analysed using thematic analysis. Results Three themes were identified: (i) ‘Perceptions of patient experience and health-related outcomes’, (ii) ‘Opportunities and challenges for programme staff’, and (iii) ‘Maintaining and improving programme standards’. Staff talked about the high uptake of AAA screening, staff experience and skills in their role, and the programme’s high quality standards as both opportunities and potential challenges linked to the proposed additions to AAA screening. While positive about the potential to improve patients’ health outcomes, participants had questions about the practicalities of incorporating additional procedures within their time- and resource-constrained context, and how this may reconfigure work processes, roles and relationships. Conclusions The proposed additions to the programme require taking staff’s views into account. Key areas that need to be addressed relate to ensuring follow-up support for patients, clarity around staff responsibilities, and availability of sufficient resources for the programme.

The COVID-19 pandemic has affected millions of people worldwide. Because of the challenges associated with the pandemic, universal levels of happiness have likely depleted. We know little about how those with prior existing mental health concerns have responded to the pandemic. Using cross-sectional (study 1; N = 1,366) and longitudinal (study 2; N = 262) data, we utilized a stress and resilience perspective to explore mental health symptoms and happiness among older adults before and after the declaration of the pandemic. Results for both studies indicated higher levels of depression and anxiety symptoms predicted lower levels of happiness; however, for those who indicated higher levels of mental health symptoms, post-pandemic declaration happiness levels were higher than pre-pandemic happiness levels. Findings suggest that resilience may be learned throughout a lifetime, and that experiences from prior stressors may show benefits in responding to future ones, even among vulnerable populations.

ObjectiveIn a large-scale population cardiovascular screening programme, peripheral artery disease (PAD) and hypertension would ideally be rapidly assessed using a single device. The ankle-brachial pressure index (ABPI) is calculated by comparing the ankle and brachial blood pressure (BP). However, it is currently unclear whether brachial BP measurements provided by automated PAD screening systems are sufficiently accurate for simultaneous hypertension screening.MethodsTwo portable PAD screening devices, the MESI ABPI MD and Huntleigh's Dopplex ABIlity, were evaluated following the European Society of Hypertension International Protocol (ESH-IP) Revision 2010 using a mercury-free sphygmomanometer as a reference device.ResultsOn average, the MESI slightly underestimated brachial systolic blood pressure (BP) with a bias and standard deviation (SD) of -3.5 (SD: 3.3) mmHg and diastolic BP with a bias of -1.5 (SD: 2.3) mmHg. For systolic BP estimates, the Dopplex was more accurate than the MESI with a lower bias of -0.5 (SD: 4.2) mmHg but less precise. The MESI successfully fulfilled all the requirements of the ESH-IP for hypertension screening. The Dopplex device failed the ESH-IP due to the absence of DBP measurements.ConclusionsThe MESI device appears to be suitable for simultaneous PAD and hypertension screening as part of a preventative care programme. Huntleigh's Dopplex ABIlity failed to pass the ESH-IP validation test. Further clinical trials are underway to assess the use of the MESI for simultaneous screening for hypertension and PAD in a population screening setting.

Chronic lymphocytic leukemia (CLL) is a genetically and clinically heterogeneous malignancy affecting older individuals. There are a number of current treatment options for CLL, including monoclonal antibodies, targeted drugs, chemotherapy, and different combinations of these. However, for those patients who are intrinsically treatment resistant, or relapse following initial responses, novel targeted therapies are still needed. Targeting the mouse double-minute-2 human homolog (MDM2), a primary negative regulator of p53, is an appealing therapeutic strategy for non-genotoxic reactivation of p53, since the TP53 gene is in its wild-type state at diagnosis in approximately 90% of patients. Mutated SF3B1 and TP53 are both associated with more aggressive disease, resistance to therapies and poorer overall survival for CLL. In this study, we performed a screen for SF3B1 and TP53 mutations and tested RG7388 (idasanutlin), a second-generation MDM2 inhibitor, in a cohort of CLL primary patient samples. SF3B1 mutations were detected in 24 of 195 cases (12.3%) and found associated with poor overall survival (hazard ratio [HR] 2.12, p = 0.032) and high CD38 expression (median CD38 (%) 32 vs. 5; p = 0.0087). The novel striking finding of this study was an independent link between SF3B1 mutational status and poor response to RG7388. Overall, SF3B1 mutations in CLL patient samples were associated with resistance to treatment with RG7388 ex vivo, and patients with the wild type for both SF3B1 and TP53 are more likely to benefit from treatment with MDM2 inhibitors.

Foreign language houses, on-campus residences in which students pledge to speak in their target language, offer valuable opportunities for language and culture learning. Scores of such programs exist at universities across North America (Dewey, Baker, Bown, & Martinsen, 2011), yet little is written about them in the research literature. This article details a foreign language residence at a large private university in the Western United States, describing the history of the program as well as the design of the foreign language house -- from the physical space to the curriculum and social programming. It is hoped that this article provides insights into how to initiate or improve existing programs.

Less than 3% of protein-coding genetic variants are predicted to result in loss of protein function through the introduction of a stop codon, frameshift, or the disruption of an essential splice site; however, such predicted loss-of-function (pLOF) variants provide insight into effector transcript and direction of biological effect. In >400,000 UK Biobank participants, we conduct association analyses of 3759 pLOF variants with six metabolic traits, six cardiometabolic diseases, and twelve additional diseases. We identified 18 new low-frequency or rare (allele frequency

Abstract Background Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms. Methods MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05). Discussion Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design. Trial registration Australian Clinical Trials ACTRN12618001707257 . Registered on 16 October 2018

Abstract Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). Methods In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

Background: Patients with peripheral artery disease (PAD) often do not receive optimal best medical therapy (BMT). Through interaction with patients and haealthcare-professionals (HCPs) we developed the LEaflet Gp letter Structured checklist (LEGS) complex clinical intervention to support HCPs provide guideline-compliant PAD BMT. Methods: This was a prospective multicentre study assessing the feasibility and fidelity of delivering the LEGS intervention in primary and secondary care over 6 months. Intervention fidelity was scored based on the proportion of intervention components used correctly at discharge, 30 days, and 6 months. Results: Overall, 129 individuals were screened and 120 took part (33% female, 74% with chronic limb threatening ischaemia; 93% recruitment rate). Of those, 118 (98% retention rate) completed follow-up. Mean intervention fidelity score at discharge (primary outcome measure) was 63% [95% Confidence Interval (CI): 39-68%, SD: 5%], exceeding the success criteria set at 60% by a panel of HCPs and patients. This, however, declined to 51% at 6 months. Eight patients (6.7%) died (all cardiovascular deaths), 4 (3.3%) had a major lower limb amputation, 12 (10%) had a cardiovascular event, and 13 (11%) were admitted due to limb ischaemia at 6 months. Incomplete lipid therapy prescriptions and LEGS intervention documents not received by primary care CHPs were the most common reasons for not complying with the LEGS intervention. Conclusion: The LEGS intervention can be delivered in PAD care pathways across different hospitals, primary, and community healthcare settings with acceptable fidelity, to streamline and improve PAD BMT short and medium term.

Abstract Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemizygous knockout mice (Col4a1/a2 +/− , 129Svj background) we show that partial Col4a1/a2 deficiency augmented AAA formation. Although unchallenged aortas were morphometrically and biomechanically unaffected by genotype, explorative proteomic analyses of aortas revealed a clear reduction in BM components and contractile vascular smooth muscle cell (VSMC) proteins, suggesting a central effect of the BM in maintaining VSMCs in the contractile phenotype. These findings were translated to human arteries by showing that COL4A1/A2 correlated to BM proteins and VSMC markers in non-lesioned internal mammary arteries obtained from coronary artery bypass procedures. Moreover, in human AAA tissue, MYH11 (VSMC marker) was depleted in areas of reduced COL4 as assessed by immunohistochemistry. Finally, circulating COL4A1 degradation fragments correlated with AAA progression in the largest Danish AAA cohort, suggesting COL4A1/A2 proteolysis to be an important feature of AAA formation. In sum, we identify COL4A1/A2 as a critical regulator of VSMC phenotype and a protective factor in AAA formation.