Dates of birth and seasonal changes in well-being among 4904 subjects completing the seasonal pattern assessment questionnaire

Background: Abnormal distributions of birthdates, suggesting intrauterine aetiological factors, have been found in several psychiatric disorders, including one study of out-patients with Seasonal Affective Disorder (S.A.D.). We investigated birthdate distribution in relation to seasonal changes in well-being among a cohort who had completed the Seasonal Pattern Assessment Questionnaire (SPAQ). Method: A sample of 4904 subjects, aged 16 to 64, completed the SPAQ. 476 were cases of S.A.D. on the SPAQ and 580 were cases of sub-syndromal S.A.D. (S-S.A.D.). 92 were interview confirmed cases of S.A.D. Months and dates of birth were compared between S.A.D. cases and all others, between S.A.D. and S-S.A.D. cases combined and all others, and between interview confirmed cases and all others. Seasonality, as measured through seasonal fluctuations in well-being on the Global Seasonality Scores (GSS) of the SPAQ, was compared for all subjects by month and season of birth. Results: There was no evidence of an atypical pattern of birthdates for subjects fulfilling criteria for S.A.D., for the combined S.A.D. / S-S.A.D. group or for interview confirmed cases. There was also no relationship between seasonality on the GSS and month or season of birth. Limitations: Diagnoses of S.A.D. made by SPAQ criteria are likely to be overinclusive. Conclusion: Our findings differ from studies of patients with more severe mood disorders, including psychiatric out-patients with S.A.D. The lack of association between seasonality and birthdates in our study adds credence to the view that the aetiology of S.A.D. relates to separable factors predisposing to affective disorders and to seasonality

Immuno-fluorescent Labeling of Microtubules and Centrosomal Proteins in Ex Vivo Intestinal Tissue and 3D In Vitro Intestinal Organoids.

The advent of 3D in vitro organoids that mimic the in vivo tissue architecture and morphogenesis has greatly advanced the ability to study key biological questions in cell and developmental biology. In addition, organoids together with recent technical advances in gene editing and viral gene delivery promises to advance medical research and development of new drugs for treatment of diseases. Organoids grown in vitro in basement matrix provide powerful model systems for studying the behavior and function of various proteins and are well suited for live-imaging of fluorescent-tagged proteins. However, establishing the expression and localization of the endogenous proteins in ex vivo tissue and in in vitro organoids is important to verify the behavior of the tagged proteins. To this end we have developed and modified tissue isolation, fixation, and immuno-labeling protocols for localization of microtubules, centrosomal, and associated proteins in ex vivo intestinal tissue and in in vitro intestinal organoids. The aim was for the fixative to preserve the 3D architecture of the organoids/tissue while also preserving antibody antigenicity and enabling good penetration and clearance of fixative and antibodies. Exposure to cold depolymerizes all but stable microtubules and this was a key factor when modifying the various protocols. We found that increasing the ethylenediaminetetraacetic acid (EDTA) concentration from 3 mM to 30 mM gave efficient detachment of villi and crypts in the small intestine while 3 mM EDTA was sufficient for colonic crypts. The developed formaldehyde/methanol fixation protocol gave very good structural preservation while also preserving antigenicity for effective labeling of microtubules, actin, and the end-binding (EB) proteins. It also worked for the centrosomal protein ninein although the methanol protocol worked more consistently. We further established that fixation and immuno-labeling of microtubules and associated proteins could be achieved with organoids isolated from or remaining within the basement matrix

A road map for reliable power electronics for more electric aircraft

The gradual evolution from hydro-pneumatic to electrical disposition of power in aircraft has placed stringent requirements on the reliability of power electronic components in current and future aerospace applications. This paper examines the prevalent state-of-the-art in power electronics and provides an analytical overview of power electronics in More Electric Aircraft (MEA) vis-à-vis the generation and distribution of power within these aircraft. The types of power devices currently employed for multiple conversion topologies are analysed and weighed according to their respective reliability characteristics. Beginning with an in-depth review of failure modes in the currently available devices, the paper highlights the salient emerging state-of-the-art Wide Band Gap (WBG) technologies such as Gallium Nitride (GaN) and Silicon Carbide (SiC) and draws an extensive comparison with their Silicon counterparts. A comprehensive examination of techniques employed for the estimation of the reliability of WBG power devices has revealed a number of areas that merit due consideration. For instance, the physics-based models that have been developed to assess the operational lifetime of silicon-based devices for given failure modes require revamping in light of the new materials and the unique electrical and physical characteristics the WBG devices possess. Similarly, the condition monitoring techniques, with respect to the primary and secondary parameters, require further investigation to determine highly representative feature vectors that best describe the degradation within these devices. More significantly, optimisation of the proposed techniques for the health assessment of these devices needs to be pursued through the optimal use of vital parameters. Keeping these critical findings in perspective, a road map highlighting various avenues for power electronics optimisation in MEA is put forth to apprise the aerospace fraternity of its growing significance

PRimary care rEsponse to domestic violence and abuse in the COvid-19 panDEmic (PRECODE): protocol of a rapid mixed-methods study in the UK

BACKGROUND: The implementation of lockdowns in the UK during the COVID-19 pandemic resulted in a system switch to remote primary care consulting at the same time as the incidence of domestic violence and abuse (DVA) increased. Lockdown-specific barriers to disclosure of DVA reduced the opportunity for DVA detection and referral. The PRECODE (PRimary care rEsponse to domestic violence and abuse in the COvid-19 panDEmic) study will comprise quantitative analysis of the impact of the pandemic on referrals from IRIS (Identification and Referral to Improve Safety) trained general practices to DVA agencies in the UK and qualitative analysis of the experiences of clinicians responding to patients affected by DVA and adaptations they have made transitioning to remote DVA training and patient support. METHODS/DESIGN: Using a rapid mixed method design, PRECODE will explore and explain the dynamics of DVA referrals and support before and during the pandemic on a national scale using qualitative data and over four years of referrals time series data. We will undertake interrupted-time series and non-linear regression analysis, including sensitivity analyses, on time series of referrals to DVA services from routinely collected data to evaluate the impact of the pandemic and associated lockdowns on referrals to the IRIS Programme, and analyse key determinants associated with changes in referrals. We will also conduct an interview- and observation-based qualitative study to understand the variation, relevance and feasibility of primary care responses to DVA before and during the pandemic and its aftermath. The triangulation of quantitative and qualitative findings using rapid analysis and synthesis will enable the articulation of multiscale trends in primary care responses to DVA and complex mechanisms by which these responses have changed during the pandemic. DISCUSSION: Our findings will inform the implementation of remote primary care and DVA service responses as services re-configure. Understanding the adaptation of clinical and service responses to DVA during the pandemic is crucial for the development of evidence-based, effective remote support and referral beyond the pandemic. TRIAL REGISTRATION: PRECODE is an observational epidemiologic study, not an intervention evaluation or trial. We will not be reporting results of an intervention on human participants

Genome Characterization of a Novel Wastewater Bacteroides fragilis Bacteriophage (vB_BfrS_23) and its Host GB124

Bacteroides spp. are part of the human intestinal microbiota but can under some circumstances become clinical pathogens. Phages are a potentially valuable therapeutic treatment option for many pathogens, but phage therapy for pathogenic Bacteroides spp. including Bacteroides fragilis is currently limited to three genome-sequenced phages. Here we describe the isolation from sewage wastewater and genome of a lytic phage, vB_BfrS_23, that infects and kills B. fragilis strain GB124. Transmission electron microscopy identified this phage as a member of the Siphoviridae family. The phage is stable when held at temperatures of 4 and 60°C for 1 h. It has a very narrow host range, only infecting one host from a panel of B. fragilis strains (n = 8). Whole-genome sequence analyses of vB_BfrS_23 determined it is double-stranded DNA phage and is circularly permuted, with a genome of 48,011 bp. The genome encodes 73 putative open reading frames. We also sequenced the host bacterium, B. fragilis GB124 (5.1 Mb), which has two plasmids of 43,923 and 4,138 bp. Although this phage is host specific, its isolation together with the detailed characterization of the host B. fragilis GB124 featured in this study represent a useful starting point from which to facilitate the future development of highly specific therapeutic agents. Furthermore, the phage could be a novel tool in determining water (and water reuse) treatment efficacy, and for identifying human fecal transmission pathways within contaminated environmental waters and foodstuffs

Health psychology interventions to improve adherence to maintenance therapies in asthma

© 2018 The Cochrane Collaboration. This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: Main objectives To determine the effectiveness of theory-based and non-theory based health psychology interventions for improving adherence to maintenance therapy in adults with asthma Secondary objectives To compare the effectiveness of adherence interventions which are based on theory, as defined by the Theory Coding Scheme (TCS), to interventions which are not theory-based To identify and describe, using the TSC and Theoretical Domain Framework (TDF), the different health psychology theories which have been used in interventions to improve adherence to maintenance therapy in adults with asthma To evaluate the extent to which health psychology theory has been applied to the development of adherence interventions in asthm

The TANDEM trial: protocol for the process evaluation of a randomised trial of a complex intervention for anxiety and/or depression in people living with chronic obstructive pulmonary disease (COPD)

Background: TANDEM is a randomised controlled trial of a complex healthcare intervention to improve the psychological and physical health of people living with chronic obstructive pulmonary disease (COPD) and anxiety and/or depression. Based on health psychology theory set out in a logic model, respiratory health professionals were recruited and trained to deliver a cognitive behavioural approach intervention (The TANDEM intervention) under the supervision of senior cognitive behavioural practitioners. Here, we describe the protocol for the process evaluation commissioned alongside the trial. A realist approach that includes attention to describing contexts and mechanisms has been adopted. Methods: We set up a multi-disciplinary team to develop and deliver the process evaluation. The mixed-methods design incorporates quantitative process data; monitoring of intervention fidelity; qualitative interviews with patients, carers, health professionals (facilitators) and clinical supervisors about their perspectives on acceptability of the intervention; and exploration with all stakeholders (including management/policy-makers) on future implementation. Normalisation process theory (NPT) will inform data collection and interpretation with a focus on implementation. Quantitative process data will be analysed descriptively. Qualitative interview data will be analysed before the trial outcomes are known using analytic induction and constant comparison to develop themes. Findings from the different elements will be reported separately and then integrated. Conclusion: Detailed description and analysis of study processes in a research trial such as TANDEM enables research teams to describe study contexts and mechanisms and to examine the relationship with outcomes. In this way, learning from the trial goes beyond the randomised control trial (RCT) model where effectiveness is prioritised and makes it possible to explore issues arising for post-trial study implementation. Trial registration: ISRCTN ISRCTN59537391. Registered on 20 March 2017. Trial protocol version 6.0, 22 April 2018. Process evaluation protocol version 4.0, 1 November 2020

Ninein is essential for apico-basal microtubule formation and CLIP-170 facilitates its redeployment to non-centrosomal microtubule organizing centres.

Differentiation of columnar epithelial cells involves a dramatic reorganization of the microtubules (MTs) and centrosomal components into an apico-basal array no longer anchored at the centrosome. Instead, the minus-ends of the MTs become anchored at apical non-centrosomal microtubule organizing centres (n-MTOCs). Formation of n-MTOCs is critical as they determine the spatial organization of MTs, which in turn influences cell shape and function. However, how they are formed is poorly understood. We have previously shown that the centrosomal anchoring protein ninein is released from the centrosome, moves in a microtubule-dependent manner and accumulates at n-MTOCs during epithelial differentiation. Here, we report using depletion and knockout (KO) approaches that ninein expression is essential for apico-basal array formation and epithelial elongation and that CLIP-170 is required for its redeployment to n-MTOCs. Functional inhibition also revealed that IQGAP1 and active Rac1 coordinate with CLIP-170 to facilitate microtubule plus-end cortical targeting and ninein redeployment. Intestinal tissue and in vitro organoids from the Clip1/Clip2 double KO mouse with deletions in the genes encoding CLIP-170 and CLIP-115, respectively, confirmed requirement of CLIP-170 for ninein recruitment to n-MTOCs, with possible compensation by other anchoring factors such as p150Glued and CAMSAP2 ensuring apico-basal microtubule formation despite loss of ninein at n-MTOCs

Adapting domestic abuse training to remote delivery during the COVID-19 pandemic: perspectives from general practice and support services

BACKGROUND: Identifying and responding to patients affected by domestic violence and abuse (DVA) is vital in primary care. There may have been a rise in the reporting of DVA cases during the COVID-19 pandemic and associated lockdown measures. Concurrently general practice adopted remote working that extended to training and education. IRIS (Identification and Referral to Improve Safety) is an example of an evidence-based UK healthcare training support and referral programme, focusing on DVA. IRIS transitioned to remote delivery during the pandemic. AIM: To understand the adaptations and impact of remote DVA training in IRIS-trained general practices by exploring perspectives of those delivering and receiving training. DESIGN AND SETTING: Qualitative interviews and observation of remote training of general practice teams in England were undertaken. METHOD: Semi-structured interviews were conducted with 21 participants (three practice managers, three reception and administrative staff, eight general practice clinicians, and seven specialist DVA staff), alongside observation of eight remote training sessions. Analysis was conducted using a framework approach. RESULTS: Remote DVA training in UK general practice widened access to learners. However, it may have reduced learner engagement compared with face-to-face training and may challenge safeguarding of remote learners who are domestic abuse survivors. DVA training is integral to the partnership between general practice and specialist DVA services, and reduced engagement risks weakening this partnership. CONCLUSION: The authors recommend a hybrid DVA training model for general practice, including remote information delivery alongside a structured face-to-face element. This has broader relevance for other specialist services providing training and education in primary care