A pragmatic effectiveness study of 10-session cognitive behavioural therapy (CBT-T) for eating disorders: Targeting barriers to treatment provision

Objective Ten‐session cognitive behavioural therapy (CBT‐T) for transdiagnostic eating disorders targets several barriers to treatment, including cost, therapist expertise, and lengthy wait lists. Method We used a case series design to investigate the effectiveness of CBT‐T delivered by trainee psychologists in a postgraduate training clinic. Participants were randomly allocated to commence treatment either immediately or after a 4‐week waitlist period. CBT‐T was delivered to 52 patients, by six different trainees under supervision. Measures of eating disorder cognitions and behaviours, quality of life, and general psychopathology were examined in completer and intention‐to‐treat analyses using multilevel modelling. Last observation carried forward was applied for abstinence, remission, and good outcome analyses to aid comparison with prior studies. Results Significant improvements, associated with medium to large effect sizes, were found for eating disorder cognitions, behaviours quality of life, and negative affect from baseline to posttreatment, and at 1‐ and 3‐month follow‐up. Attrition (38.5%) was comparable with other treatment studies. Conclusion Results provide evidence for the effectiveness of CBT‐T delivered by trainee psychologists for transdiagnostic eating disorder patients, thus tackling some important barriers for treatment. Longer follow‐up, randomised controlled trial designs, and moderator analyses will provide more robust evidence about which patients do best with a shorter therapy

Cdk1 Targets Srs2 to Complete Synthesis-Dependent Strand Annealing and to Promote Recombinational Repair

Cdk1 kinase phosphorylates budding yeast Srs2, a member of UvrD protein family, displays both DNA translocation and DNA unwinding activities in vitro. Srs2 prevents homologous recombination by dismantling Rad51 filaments and is also required for double-strand break (DSB) repair. Here we examine the biological significance of Cdk1-dependent phosphorylation of Srs2, using mutants that constitutively express the phosphorylated or unphosphorylated protein isoforms. We found that Cdk1 targets Srs2 to repair DSB and, in particular, to complete synthesis-dependent strand annealing, likely controlling the disassembly of a D-loop intermediate. Cdk1-dependent phosphorylation controls turnover of Srs2 at the invading strand; and, in absence of this modification, the turnover of Rad51 is not affected. Further analysis of the recombination phenotypes of the srs2 phospho-mutants showed that Srs2 phosphorylation is not required for the removal of toxic Rad51 nucleofilaments, although it is essential for cell survival, when DNA breaks are channeled into homologous recombinational repair. Cdk1-targeted Srs2 displays a PCNA–independent role and appears to have an attenuated ability to inhibit recombination. Finally, the recombination defects of unphosphorylatable Srs2 are primarily due to unscheduled accumulation of the Srs2 protein in a sumoylated form. Thus, the Srs2 anti-recombination function in removing toxic Rad51 filaments is genetically separable from its role in promoting recombinational repair, which depends exclusively on Cdk1-dependent phosphorylation. We suggest that Cdk1 kinase counteracts unscheduled sumoylation of Srs2 and targets Srs2 to dismantle specific DNA structures, such as the D-loops, in a helicase-dependent manner during homologous recombinational repair

Effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified: study protocol of a randomized controlled trial

Background: Disordered eating behavior and body dissatisfaction affect a large proportion of the Dutch population and account for severe psychological, physical and social morbidity. Yet, the threshold for seeking professional care is still high. In the Netherlands, only 7.5% of patients with bulimia nervosa and 33% of patients with anorexia nervosa are treated within the mental health care system. Easily accessible and low-threshold interventions, therefore, are needed urgently. The internet has great potential to offer such interventions. The aim of this study is to determine whether a web-based treatment program for patients with eating disorders can improve eating disorder psychopathology among female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified. Methods/design: This randomized controlled trial will compare the outcomes of an experimental treatment group to a waiting list control group. In the web-based treatment program, participants will communicate personally and asynchronously with their therapists exclusively via the internet. The first part of the program will focus on analyzing eating attitudes and behaviors. In the second part of the program participants will learn how to change their attitudes and behaviors. Participants assigned to the waiting list control group will receive no-reply email messages once every two weeks during the waiting period of 15 weeks, after which they can start the program. The primary outcome measure is an improvement in eating disorder psychopathology as determined by the Eating Disorder Examination Questionnaire. Secondary outcomes include improvements in body image, physical and mental health, body weight, self-esteem, quality of life, and social contacts. In addition, the participants’ motivation for treatment and their acceptability of the program and the therapeutic alliance will be measured. The study will follow the recommendations in the CONSORT statement relating to designing and reporting on RCTs. Discussion: This study protocol presents the design of a RCT for evaluating the effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Impact of electrical contacts design and materials on the stability of Ti superconducting transition shape

The South Pole Telescope SPT-3G camera utilizes Ti/Au transition edge sensors (TESs). A key requirement for these sensors is reproducibility and long-term stability of the superconducting (SC) transitions. Here, we discuss the impact of electrical contacts design and materials on the shape of the SC transitions. Using scanning electron microscope, atomic force microscope, and optical differential interference contrast microscopy, we observed the presence of unexpected defects of morphological nature on the titanium surface and their evolution in time in proximity to Nb contacts. We found direct correlation between the variations of the morphology and the SC transition shape. Experiments with different diffusion barriers between TES and Nb leads were performed to clarify the origin of this problem. We have demonstrated that the reproducibility of superconducting transitions can be significantly improved by preventing diffusion processes in the TES–leads contact areas