Covid-19 is an unfolding health and financial crisis for US local governments

With disputes between the US federal and state governments as to how best to respond to the Covid-19 pandemic ongoing, many local governments have had to respond to the crisis on their own. Bruce D. McDonald, III and Sarah E. Larson write that for many of these local governments, Covid-19 is a double crisis. Not only is it a public health emergency, it is also a financial crisis as sales tax revenues plummet because of stay at home policies at the same time as health expenditures are on the rise

Multimodal perioperative pain protocol for Gynecologic Oncology laparotomy reduces length of hospital stay

Our primary objective was to evaluate the impact of a multimodal perioperative pain regimen on length of hospital stay for patients undergoing laparotomy with a gynecologic oncologist

What is Microbial Dormancy?

Life can be stressful. One way to deal with stress is to simply wait it out. Microbes do this by entering a state of reduced activity and increased resistance commonly called ‘dormancy’. But what is dormancy? Different scientific disciplines emphasize distinct traits and phenotypic ranges in defining dormancy for their microbial species and system-specific questions of interest. Here, we propose a unified definition of microbial dormancy, using a broad framework to place earlier discipline-specific definitions in a new context. We then discuss how this new definition and framework may improve our ability to investigate dormancy using multi-omics tools. Finally, we leverage our framework to discuss the diversity of genomic mechanisms for dormancy in an extreme environment that challenges easy definitions – the permafrost

Risk of Fetal Death Associated With Maternal Drug Dependence and Placental Abruption: A Population-Based Study

Abstract Objective: Substance use in pregnancy is associated with placental abruption, but the risk of fetal death independent of abruption remains undetermined. Our objective was to examine the effect of maternal drug dependence on placental abruption and on fetal death in association with abruption and independent of it. Methods: To examine placental abruption and fetal death, we performed a retrospective population-based study of 1 854 463 consecutive deliveries of liveborn and stillborn infants occurring between January 1, 1995 and March 31, 2001, using the Canadian Institute for Health Information Discharge Abstract Database. Results: Maternal drug dependence was associated with a tripling of the risk of placental abruption in singleton pregnancies (adjusted odds ratio [OR] 3.1; 95% confidence intervals [CI] 2.6-3.7), but not in multiple gestations (adjusted OR 0.88; 95% CI 0.12-6.4). Maternal drug dependence was associated with an increased risk of fetal death independent of abruption (adjusted OR 1.6: 95% CI 1.1-2.2) in singleton pregnancies, but not in multiples. Risk of fetal death was increased with placental abruption in both singleton and multiple gestations, even after controlling for drug dependence (adjusted OR 11.4 in singleton pregnancy; 95% CI 10.6-12.2, and 3.4 in multiple pregnancy; 95% CI 2.4-4.9). Conclusion: Maternal drug use is associated with an increased risk of intrauterine fetal death independent of placental abruption. In singleton pregnancies, maternal drug dependence is associated with an increased risk of placental abruption. Résumé Objectif : Bien que la consommation d'alcool et de drogues au cours de la grossesse soit associée au décollement placentaire, le risque de mort foetale n'étant pas associé à ce dernier demeure indéterminé. Notre objectif était d'examiner l'effet de la dépendance de la mère aux drogues sur le décollement placentaire, ainsi que sur la mort foetale attribuable à ce dernier et sur la mort foetale n'y étant pas attribuable. Résultats : La dépendance de la mère aux drogues a été associée à un risque triplé de décollement placentaire dans le cas des grossesses monofoetales (rapport de cotes [RC] corrigé, 3,1; intervalle de confiance [IC] à 95 %, 2,6-3,7), mais non pas dans celui des grossesses multiples (RC corrigé, 0,88; IC à 95 %, 0,12-6,4). La dépendance de la mère aux drogues a été associée à une hausse du risque de mort foetale n'étant pas attribuable au décollement (RC corrigé, 1,6; IC à 95 %, 1,1-2,2) dans le cas des grossesses monofoetales, mais non pas dans celui des grossesses multiples. Le risque de mort foetale connaissait une hausse en présence d'un décollement placentaire, tant dans le cas des grossesses monofoetales que dans celui des grossesses multiples, et ce, même à la suite de la neutralisation de l'effet de la dépendance aux drogues (dans le cas des grossesses monofoetales : RC corrigé, 11,4; IC à 95 %, 10,6-12,2; dans celui des grossesses multiples : RC corrigé, 3,4; IC à 95 %, 2,4-4,9). Méthodes Conclusion : La consommation de drogues par la mère est associée à une hausse du risque de mort foetale intra-utérine, peu importe la présence ou non d'un décollement placentaire. Dans le cas des grossesses monofoetales, la dépendance de la mère aux drogues est associée à une hausse du risque de décollement placentaire

Internal construct validity of the Warwick-Edinburgh Mental Well-being Scale (WEMWBS): a Rasch analysis using data from the Scottish Health Education Population Survey

Background: The Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) was developed to meet demand for instruments to measure mental well-being. It comprises 14 positively phrased Likert-style items and fulfils classic criteria for scale development. We report here the internal construct validity of WEMWBS from the perspective of the Rasch measurement model. Methods: The model was applied to data collected from 779 respondents in Wave 12 (Autumn 2006) of the Scottish Health Education Population Survey. Respondents were aged 16–74 (average 41.9) yrs. Results: Initial fit to model expectations was poor. The items 'I've been feeling good about myself', 'I've been interested in new things' and 'I've been feeling cheerful' all showed significant misfit to model expectations, and were deleted. This led to a marginal improvement in fit to the model. After further analysis, more items were deleted and a strict unidimensional seven item scale (the Short Warwick Edinburgh Mental Well-Being Scale (SWEMWBS)) was resolved. Many items deleted because of misfit with model expectations showed considerable bias for gender. Two retained items also demonstrated bias for gender but, at the scale level, cancelled out. One further retained item 'I've been feeling optimistic about the future' showed bias for age. The correlation between the 14 item and 7 item versions was 0.954. Given fit to the Rasch model, and strict unidimensionality, SWEMWBS provides an interval scale estimate of mental well-being. Conclusion: A short 7 item version of WEMWBS was found to satisfy the strict unidimensionality expectations of the Rasch model, and be largely free of bias. This scale, SWEMWBS, provides a raw score-interval scale transformation for use in parametric procedures. In terms of face validity, SWEMWBS presents a more restricted view of mental well-being than the 14 item WEMWBS, with most items representing aspects of psychological and eudemonic well-being, and few covering hedonic well-being or affect. However, robust measurement properties combined with brevity make SWEMWBS preferable to WEMWBS at present for monitoring mental well-being in populations. Where face validity is an issue there remain arguments for continuing to collect data on the full 14 item WEMWBS

Efficient generation of vesicular stomatitis virus (VSV)-pseudotypes bearing morbilliviral glycoproteins and their use in quantifying virus neutralising antibodies

Morbillivirus neutralising antibodies are traditionally measured using either plaque reduction neutralisation tests (PRNTs) or live virus microneutralisation tests (micro-NTs). While both test formats provide a reliable assessment of the strength and specificity of the humoral response, they are restricted by the limited number of viral strains that can be studied and often present significant biological safety concerns to the operator. In this study, we describe the adaptation of a replication-defective vesicular stomatitis virus (VSVΔG) based pseudotyping system for the measurement of morbillivirus neutralising antibodies. By expressing the haemagglutinin (H) and fusion (F) proteins of canine distemper virus (CDV) on VSVΔG pseudotypes bearing a luciferase marker gene, neutralising antibody titres could be measured rapidly and with high sensitivity. Further, by exchanging the glycoprotein expression construct, responses against distinct viral strains or species may be measured. Using this technique, we demonstrate cross neutralisation between CDV and peste des petits ruminants virus (PPRV). As an example of the value of the technique, we demonstrate that UK dogs vary in the breadth of immunity induced by CDV vaccination; in some dogs the neutralising response is CDV-specific while, in others, the neutralising response extends to the ruminant morbillivirus PPRV. This technique will facilitate a comprehensive comparison of cross-neutralisation to be conducted across the morbilliviruses

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis

Abstract (provisional) Background Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. Methods This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. Discussion This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747

BMP9 Mutations Cause a Vascular-Anomaly Syndrome with Phenotypic Overlap with Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, is caused by mutations in genes involved in the transforming growth factor beta (TGF-β) signaling pathway (ENG, ACVRL1, and SMAD4). Yet, approximately 15% of individuals with clinical features of HHT do not have mutations in these genes, suggesting that there are undiscovered mutations in other genes for HHT and possibly vascular disorders with overlapping phenotypes. The genetic etiology for 191 unrelated individuals clinically suspected to have HHT was investigated with the use of exome and Sanger sequencing; these individuals had no mutations in ENG, ACVRL1, and SMAD4. Mutations in BMP9 (also known as GDF2) were identified in three unrelated probands. These three individuals had epistaxis and dermal lesions that were described as telangiectases but whose location and appearance resembled lesions described in some individuals with RASA1-related disorders (capillary malformation-arteriovenous malformation syndrome). Analyses of the variant proteins suggested that mutations negatively affect protein processing and/or function, and a bmp9-deficient zebrafish model demonstrated that BMP9 is involved in angiogenesis. These data confirm a genetic cause of a vascular-anomaly syndrome that has phenotypic overlap with HHT