Lensing Magnification: A novel method to weigh high-redshift clusters and its application to SpARCS

We introduce a novel method to measure the masses of galaxy clusters at high redshift selected from optical and IR Spitzer data via the red-sequence technique. Lyman-break galaxies are used as a well understood, high-redshift background sample allowing mass measurements of lenses at unprecedented high redshifts using weak lensing magnification. By stacking a significant number of clusters at different redshifts with average masses of ~1-3x10^14M_sun, as estimated from their richness, we can calibrate the normalisation of the mass-richness relation. With the current data set (area: 6 deg^2) we detect a magnification signal at the >3-sigma level. There is good agreement between the masses estimated from the richness of the clusters and the average masses estimated from magnification, albeit with large uncertainties. We perform tests that suggest the absence of strong systematic effects and support the robustness of the measurement. This method - when applied to larger data sets in the future - will yield an accurate calibration of the mass-observable relations at z>~1 which will represent an invaluable input for cosmological studies using the galaxy cluster mass function and astrophysical studies of cluster formation. Furthermore this method will probably be the least expensive way to measure masses of large numbers of z>1 clusters detected in future IR-imaging surveys.Comment: 5 pages, 1 figure, 1 table, accepted by ApJL, minor revision

Presumptive TRP channel CED-11 promotes cell volume decrease and facilitates degradation of apoptotic cells in

Apoptotic cells undergo a series of morphological changes. These changes are dependent on caspase cleavage of downstream targets, but which targets are signifi cant and how they facilitate the death process are not well understood. In Caenorhabditis elegans an increase in the refractility of the dying cell is a hallmark morphological change that is caspase dependent. We identify a presumptive transient receptor potential (TRP) cation channel, CED-11, that acts in the dying cell to promote the increase in apoptotic cell refractility. CED-11 is required for multiple other morphological changes during apoptosis, including an increase in electron density as visualized by electron microscopy and a decrease in cell volume. In ced-11 mutants, the degradation of apoptotic cells is delayed. Mutation of ced-11 does not cause an increase in cell survival but can enhance cell survival in other cell-death mutants, indicating that ced-11 facilitates the death process. In short, ced-11 acts downstream of caspase activation to promote the shrinkage, death, and degradation of apoptotic cells. Keywords: TRP channel; apoptosis; C. elegans; cell volume; apoptotic volume decreaseNational Institutes of Health (U.S.) (Grant T32GM007287

Therapeutic alliance in psychological therapy for posttraumatic stress disorder: A systematic review and meta‐analysis

From Wiley via Jisc Publications RouterHistory: received 2021-02-06, rev-recd 2021-06-21, accepted 2021-06-24, pub-electronic 2021-07-21Article version: VoRPublication status: PublishedAbstract: Background: Therapeutic alliance is a key element of successful therapy. Despite being particularly relevant in people with posttraumatic stress disorder (PTSD), due to fear, mistrust and avoidance, there has not yet been a comprehensive systematic review of therapeutic alliance in this population. This review explored (a) variables which may predict alliance and (b) whether alliance predicts PTSD outcomes. Method: Following the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines, the review identified 34 eligible studies. Studies were subjected to a quality assessment. Predictors of alliance were considered in a narrative synthesis. Twelve studies were entered into a meta‐analysis of the association between therapeutic alliance and PTSD outcomes. Results: There was some evidence for individual variables including attachment, coping styles and psychophysiological variables predicting the alliance. Therapy variables did not predict alliance. The therapeutic alliance was found to significantly predict PTSD outcomes, with an aggregated effect size of r = −.34, across both in‐person and remote therapies. Limitations: Included studies were restricted to peer‐reviewed, English language studies. Quality of included studies was mostly rated weak to moderate, primarily reflecting issues with selection bias in this area of research. Conclusions: This is the first review to demonstrate that therapeutic alliance is a consistent predictor of PTSD outcomes, in both in‐person and remote therapies, and the effect appears at least as strong as in other populations. This is of relevance to clinicians working with traumatized populations. The review identified a need for further research to determine variables predicting alliance in therapy for PTSD

Child educational progress in Born in Bradford pregnancies affected by gestational diabetes and also exposed to maternal common mental disorders

Abstract Gestational diabetes and the maternal mental disorders of anxiety and depression have been implicated in adverse offspring neuro-behavioural outcomes but these exposures have only been studied in isolation. 1051 children whose mothers were diagnosed with gestational diabetes in UK’s Born in Bradford cohort had linkage to maternal primary care records, providing diagnostic and treatment codes for depression and anxiety. Education record linkage provided results of the Early Years Foundation Stage Profile from the first year of school, aged five. Risk of not attaining a ‘Good level of development’ was analysed using multivariable Poisson regression within a generalised estimating equation framework. Multiple imputation was implemented for missing data. There was limited evidence of increased risk of failure to attain a ‘good level of development’ in those additionally exposed to maternal mental disorders (adjusted RR 1.21; 95% CI 0.94, 1.55). However, there was more evidence in children of Pakistani maternal ethnicity (adjusted RR 1.36; 95% CI 1.04, 1.77) than White British; this may have been driven by English not being the primary language spoken in the home. Therefore there may be groups with GDM in whom it is particularly important to optimise both maternal physical and mental health to improve child outcomes

Minocycline 200 mg or 400 mg versus placebo for mild Alzheimer's disease: the MADE Phase II, three-arm RCT

Background: Minocycline is an anti-inflammatory drug and protects against the toxic effects of β-amyloid in vitro and in animal models of Alzheimer’s disease. To the best of our knowledge, no randomised placebo-controlled clinical trials in patients with Alzheimer’s disease looking at the efficacy and tolerability of minocycline have been carried out. Objectives: The trial investigated whether or not minocycline was superior to placebo in slowing down the rate of decline in cognitive and functional ability over 2 years. The safety and tolerability of minocycline were also assessed. Design: A Phase II, three-arm, randomised, double-blind, multicentre trial with a semifactorial design. Participants continued on trial treatment for up to 24 months. Setting: Patients were identified from memory services, both within the 32 participating NHS trusts and within the network of memory services supported by the Dementias and Neurodegenerative Diseases Research Network (also known as DeNDRoN). Participants: Patients with standardised Mini Mental State Examination scores of > 23 points and with Alzheimer’s disease assessed by the National Institute on Aging–Alzheimer’s Association’s criteria were identified from memory services. Intervention: Patients with mild Alzheimer’s disease were randomly allocated 1 : 1 : 1 to receive one of three treatments: arm 1 – 400 mg per day of minocycline; arm 2 – 200 mg per day of minocycline; or arm 3 – placebo. Patients continued treatment for 24 months. Participants, investigators and outcome assessors were blind to treatment allocation. Main outcome measures: Primary outcome measures were decline in standardised Mini Mental State Examination and Bristol Activities of Daily Living Scale scores of combined minocycline treatment arms versus placebo, as analysed by intention-to-treat repeated measures regression. Results: Between 23 May 2014 and 14 April 2016, 554 participants were randomised. Of the 544 eligible participants, the mean age was 74.3 years and the average standardised Mini Mental State Examination score was 26.4 points. A total of 252 serious adverse events were reported, with the most common categories being neuropsychiatric and cardiocirculatory. Significantly fewer participants completed treatment with 400 mg of minocycline [29% (53/184)] than 200 mg [62% (112/181)] or placebo [64% (114/179)] (p < 0.0001), mainly because of gastrointestinal symptoms (p = 0.0008), dermatological side effects (p = 0.02) and dizziness (p = 0.01). Assessment rates were also lower in the 400-mg treatment arm: 68% (119 of 174 expected) for standardised Mini Mental State Examination scores at 24 months, compared with 82% (144/176) for the 200-mg treatment arm and 84% (140/167) for the placebo arm. Decline in standardised Mini Mental State Examination scores over the 24-month study period in the combined minocycline arms was similar to that in the placebo arm (4.1- vs. 4.3-point reduction; p = 0.9), as was the decline in the 400- and 200-mg treatment arms (3.3 vs. 4.7 points; p = 0.08). Likewise, worsening of Bristol Activities of Daily Living Scale scores over 24 months was similar in all trial arms (5.7, 6.6 and 6.2 points in the 400-mg treatment arm, 200-mg treatment arm and placebo arm, respectively; a p-value of 0.57 for minocycline vs. placebo and a p-value of 0.77 for 400 vs. 200 mg of minocycline). Results were similar in different patient subgroups and in sensitivity analyses adjusting for missing data. Limitations: Potential limitations of the study include that biomarkers were not used to confirm the diagnosis of Alzheimer’s disease, as these and apolipoprotein E (APOE) genotyping are not routinely available within the NHS. Compliance was also worse than expected and differential follow-up rates were observed, with fewer assessments obtained for the 400-mg treatment arm than for the 200-mg treatment and placebo arms. Conclusions: Minocycline does not delay the progress of cognitive or functional impairment in people with mild Alzheimer’s disease over a 2-year period. Minocycline at a dose of 400 mg is poorly tolerated in this population. Future work: The Minocycline in mild Alzheimer’s DiseasE (MADE) study provides a framework for a streamlined trial design that can be usefully applied to test other disease-modifying therapies

Clusters of Galaxies at 1 < z < 2 : The Spitzer Adaptation of the Red-Sequence Cluster Survey

As the densest galaxy environments in the universe, clusters are vital to our understanding of the role that environment plays in galaxy formation and evolution. Unfortunately, the evolution of high-redshift cluster galaxies is poorly understood because of the “cluster desert” that exists at 1 2 to the quiescent population at z < 1. The existing seven-passband Spitzer data (3.6, 4.5, 5.8, 8.0, 24, 70, 160 μm) will allow us to make the first measurements of the evolution of the cluster red-sequence, IR luminosity function, and the mid-IR dust-obscured star-formation rate for 1 < z < 2 clusters