The dune effect on sand-transporting winds on Mars

Wind on Mars is a significant agent of contemporary surface change, yet the absence of in situ meteorological data hampers the understanding of surface–atmospheric interactions. Airflow models at length scales relevant to landform size now enable examination of conditions that might activate even small-scale bedforms (ripples) under certain contemporary wind regimes. Ripples have the potential to be used as modern ‘wind vanes’ on Mars. Here we use 3D airflow modelling to demonstrate that local dune topography exerts a strong influence on wind speed and direction and that ripple movement likely reflects steered wind direction for certain dune ridge shapes. The poor correlation of dune orientation with effective sand-transporting winds suggests that large dunes may not be mobile under modelled wind scenarios. This work highlights the need to first model winds at high resolution before inferring regional wind patterns from ripple movement or dune orientations on the surface of Mars today

Bioavailability and kidney responses to Diclofenac in the fathead minnow (Pimephales promelas)

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Diclofenac is one of the most widely prescribed nonsteroidal anti-inflammatory drugs worldwide. It is frequently detected in surface waters; however, whether this pharmaceutical poses a risk to aquatic organisms is debated. Here we quantified the uptake of diclofenac by the fathead minnow (Pimephales promelas) following aqueous exposure (0.2-25.0 μg L(-1)) for 21 days, and evaluated the tissue and biomolecular responses in the kidney. Diclofenac accumulated in a concentration- and time-dependent manner in the plasma of exposed fish. The highest plasma concentration observed (for fish exposed to 25 μg L(-1) diclofenac) was within the therapeutic range for humans. There was a strong positive correlation between exposure concentration and the number of developing nephrons observed in the posterior kidney. Diclofenac was not found to modulate the expression of genes in the kidney associated with its primary mode of action in mammals (prostaglandin-endoperoxide synthases) but modulated genes associated with kidney repair and regeneration. There were no significant adverse effects following 21 days exposure to concentrations typical of surface waters. The combination of diclofenac's uptake potential, effects on kidney nephrons and relatively small safety margin for some surface waters may warrant a longer term chronic health effects analysis for diclofenac in fish.This work was funded by Knowledge Transfer Partnership (KTP): Use of ‘omic’ technologies in the environmental risk assessment of pharmaceuticals (KTP007650) and AstraZeneca’s Safety, Health and Environment (SHE) Research Programme. We thank Lina Gunnarsson, Matt Winter and James Cresswell (Exeter University), and former members of the Brixham Environmental Laboratory for their advice and assistance. Authors declare no competing financial interest

Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The Hidden Curriculum of Veterinary Education: Mediators and Moderators of Its Effects

The “hidden curriculum” has long been supposed to have an effect on students' learning during their clinical education, and in particular in shaping their ideas of what it means to be a professional. Despite this, there has been little evidence linking specific changes in professional attitudes to the individual components of the hidden curriculum. This study aimed to recognize those components that led to a change in students' professional attitudes at a UK veterinary school, as well as to identify the attitudes most affected. Observations were made of 11 student groups across five clinical rotations, followed by semi-structured interviews with 23 students at the end of their rotation experience. Data were combined and analyzed thematically, taking both an inductive and deductive approach. Views about the importance of technical competence and communication skills were promoted as a result of students' interaction with the hidden curriculum, and tensions were revealed in relation to their attitudes toward compassion and empathy, autonomy and responsibility, and lifestyle ethic. The assessment processes of rotations and the clinical service organization served to communicate the messages of the hidden curriculum, bringing about changes in student professional attitudes, while student-selected role models and the student rotation groups moderated the effects of these influences

Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

Funding: HRS and MF are supported by the Medical Research Council [MR/R008345/1]. CJ’s salary came through MRC core funding MC_UU_12023/26. SJS is funded by the Wellcome Trust [WT 209560/Z/17/Z]. CRS has received funding from the Medical Research Council [MR/R008345/1], the National Institute for Health Research [11/46/23] and the New Zealand Health Research Council [20/1018] and Ministry for Business, Innovation and Employment. EV is funded by the Medical Research Council [MR/R008345/1] through the EAVE II grant and supported by the Scottish Government. We also acknowledge the support of HDR UK. The views and opinions expressed here are those of the authors and do not necessarily reflect those of the Health Technology Assessment programme, NIHR, NHS, or the UK Department of Health.Background Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected.Publisher PDFPeer reviewe

Development and Validation of the Behavioral Tendencies Questionnaire

At a fundamental level, taxonomy of behavior and behavioral tendencies can be described in terms of approach, avoid, or equivocate (i.e., neither approach nor avoid). While there are numerous theories of personality, temperament, and character, few seem to take advantage of parsimonious taxonomy. The present study sought to implement this taxonomy by creating a questionnaire based on a categorization of behavioral temperaments/tendencies first identified in Buddhist accounts over fifteen hundred years ago. Items were developed using historical and contemporary texts of the behavioral temperaments, described as “Greedy/Faithful”, “Aversive/Discerning”, and “Deluded/Speculative”. To both maintain this categorical typology and benefit from the advantageous properties of forced-choice response format (e.g., reduction of response biases), binary pairwise preferences for items were modeled using Latent Class Analysis (LCA). One sample (n1 = 394) was used to estimate the item parameters, and the second sample (n2 = 504) was used to classify the participants using the established parameters and cross-validate the classification against multiple other measures. The cross-validated measure exhibited good nomothetic span (construct-consistent relationships with related measures) that seemed to corroborate the ideas present in the original Buddhist source documents. The final 13-block questionnaire created from the best performing items (the Behavioral Tendencies Questionnaire or BTQ) is a psychometrically valid questionnaire that is historically consistent, based in behavioral tendencies, and promises practical and clinical utility particularly in settings that teach and study meditation practices such as Mindfulness Based Stress Reduction (MBSR)

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

The social and healthcare professional support drawn upon by women antenatally during the COVID-19 pandemic: A recurrent, cross-sectional, thematic analysis

Objective: To explore antenatal experiences of social and healthcare professional support during different phases of social distancing restriction implementation in the UK. Design: Semi-structured interviews were conducted via telephone or video-conferencing software between 13 July 2020 – 2 September 2020. Interviews were transcribed and a recurrent, cross-sectional, thematic analysis was conducted. Participants: Twelve antenatal women were interviewed during UK social distancing restrictions (Timepoint 1; T1) and a separate sample of twelve women were interviewed in the initial easing of these restrictions (Timepoint 2; T2). Findings: T1 themes were: ‘Maternity care as non-essential’ and ‘Pregnancy is cancelled’. T2 themes were: ‘Technology is a polarised tool’ and ‘Clinically vulnerable, or not clinically vulnerable? That is the question’. Key conclusions: At T1, anxieties were ascribed to the exclusion of partners from routine care, and to perceived insensitivity and aggression from the public. For T2, insufficient Governmental transparency led to disillusionment, confusion, and anger. Covert workplace discrimination also caused distress at T2. Across timepoints: deteriorated mental wellbeing was attributed to depleted opportunities to interact socially and scaled back maternity care. Implications for practice: Recommendations are made to: protect maternal autonomy; improve quality of mental health and routine care signposting; prioritise parental community support in the re-opening of ‘non-essential’ services; prioritise the option for face-to-face appointments when safe and legal; and protecting the rights of working mothers

Organizational factors and depression management in community-based primary care settings

Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe

The antenatal psychological experiences of women during two phases of the COVID-19 pandemic: A recurrent, cross-sectional, thematic analysis

Initial COVID-19-related social distancing restrictions, imposed in the UK in March 2020, and the subsequent lifting of restrictions in May 2020 caused antenatal disruption and stress which exceeded expected vulnerabilities associated with this lifecourse transition. The current study aimed to explore the antenatal psychological experiences of women during different phases of pandemic-related lockdown restrictions in the UK. Semi-structured interviews were held with 24 women about their antenatal experiences: twelve were interviewed after the initial lockdown restrictions (Timepoint 1; T1), and a separate twelve women were interviewed after the subsequent lifting of those restrictions (Timepoint 2; T2). Interviews were transcribed and a recurrent, cross-sectional thematic analysis was conducted. Two themes were identified for each timepoint, and each theme contained sub-themes. T1 themes were: ‘A Mindful Pregnancy’ and ‘It’s a Grieving Process’, and T2 themes were: ‘Coping with Lockdown Restrictions’ and ‘Robbed of Our Pregnancy’. COVID-19 related social distancing restrictions had an adverse effect on women’s mental health during the antenatal period. Feeling trapped, anxious, and abandoned were common at both timepoints. Actively encouraging conversations about mental wellbeing during routine care and adopting a prevention opposed to cure attitude toward implementing additional support provisions may serve to improve antenatal psychological wellbeing during health crises