Behavioural activation by mental health nurses for late-life depression in primary care: a randomized controlled trial

Background: Depressive symptoms are common in older adults. The effectiveness of pharmacological treatments and the availability of psychological treatments in primary care are limited. A behavioural approach to depression treatment might be beneficial to many older adults but such care is still largely unavailable. Behavioural Activation (BA) protocols are less complicated and more easy to train than other psychological therapies, making them very suitable for delivery by less specialised therapists. The recent introduction of the mental health nurse in primary care centres in the Netherlands has created major opportunities for improving the accessibility of psychological treatments for late-life depression in primary care. BA may thus address the needs of older patients while improving treatment outcome and lowering costs.The primary objective of this study is to compare the effectiveness and cost-effectiveness of BA in comparison with treatment as usual (TAU) for late-life depression in Dutch primary care. A secondary goal is to explore several potential mechanisms of change, as well as predictors and moderators of treatment outcome of BA for late-life depression. Methods/design: Cluster-randomised controlled multicentre trial with two parallel groups: a) behavioural activation, and b) treatment as usual, conducted in primary care centres with a follow-up of 52 weeks. The main inclusion criterion is a PHQ-9 score > 9. Patients are excluded from the trial in case of severe mental illness that requires specialized treatment, high suicide risk, drug and/or alcohol abuse, prior psychotherapy, change in dosage or type of prescribed antidepressants in the previous 12 weeks, or moderate to severe cognitive impairment. The intervention consists of 8 weekly 30-min BA sessions delivered by a trained mental health nurse. Discussion: We expect BA to be an effective and cost-effective treatment for late-life depression compared to TAU. BA delivered by mental health nurses could increase the availability and accessibility of non-pharmacological treatments for late-life depression in primary care. Trial registration: This study is retrospectively registered in the Dutch Clinical Trial Register NTR6013on August 25th 2016. © 2017 The Author(s)

Psychometric Properties of Measuring Antiretroviral Therapy Adherence Among Young Latino Sexual Minority Men With HIV: Ecological Momentary Assessment and Electronic Pill Dispenser Study.

BACKGROUND: Increasing HIV rates among young Latino sexual minority men (YLSMM) warrant innovative and rigorous studies to assess prevention and treatment strategies. Ecological momentary assessments (EMAs) and electronic pill dispensers (EPDs) have been used to measure antiretroviral therapy (ART) adherence repeatedly in real time and in participants natural environments, but their psychometric properties among YLSMM are unknown. OBJECTIVE: The studys objective was to assess the concurrent validity, acceptability, compliance, and behavioral reactivity of EMAs and EPDs among YLSMM with HIV. METHODS: A convenience sample of 56 YLSMM with HIV with suboptimal ART adherence, aged 18-34 years, was recruited into a 28-consecutive-day EMA study. Concurrent validity was analyzed by comparing median ART adherence rates and calculating Spearman correlations between ART adherence measured by EMA, EPD, and baseline retrospective validated 3-item and single-item measures. Acceptability was assessed in exit interviews asking participants to rate EMA and EPD burden. Compliance was assessed by computing the percent lost to follow-up, the percent of EMAs missed, and the percentage of days the EPD was not opened that had corresponding EMA data self-reporting adherence to ARTs. Behavioral reactivity was assessed by computing the median change in ART adherence during the study period, using generalized mixed models to assess whether the cumulative number of EMAs completed and days of EPD use predicted ART adherence over time, and by asking participants to rate perceived reactivity using a Likert scale. RESULTS: EMA ART adherence was significantly correlated with baseline validated 3-item (r=0.41, P=.003) and single-item (r=0.52, P<.001) measures, but correlations were only significant for participants that reported EMA was not burdensome. Correlations for EPD ART adherence were weaker but significant (r=0.36, P=.009; r=0.34, P=.01, respectively). Acceptability was high for EMAs (48/54, 89%) and EPDs (52/54, 96%) per self-report. Loss to follow-up was 4% (2/56), with the remaining participants completing 88.6% (1339/1512) of study-prompted EMAs. The percentage of missed EMA surveys increased from 5.8% (22/378) in week 1 of the study to 16.7% (63/378) in week 4. Of 260 days when EPDs were not opened, 68.8% (179) had a corresponding EMA survey self-reporting ART adherence. Reactivity inferred from the median change in ART adherence over time was 8.8% for EMAs and -0.8% for EPDs. Each completed EMA was associated with 1.03 odds (95% CI 1-1.07) of EMA ART adherence over time, and each day of EPD use with 0.97 odds (95% CI 0.96-0.99) of EPD ART adherence over time. Self-reported perceived behavioral reactivity was 39% for EMAs and 35% for EPDs. CONCLUSIONS: This study provides evidence of concurrent validity with retrospective validated measures for EMA- and EPD-measured ART adherence among YLSMM, when participant burden is carefully considered, without significant behavioral reactivity. While acceptability and compliance of EMAs and EPDs were high overall, noncompliance increased over time, suggesting respondent fatigue

Improving Fluid Intelligence With Training on Working Memory: A Meta-Analysis

Working memory (WM), the ability to store and manipulate information for short periods of time, is an important predictor of scholastic aptitude and a critical bottleneck underlying higher-order cognitive processes, including controlled attention and reasoning. Recent interventions targeting WM have suggested plasticity of the WM system by demonstrating improvements in both trained and untrained WM tasks. However, evidence on transfer of improved WM into more general cognitive domains such as fluid intelligence (Gf) has been more equivocal. Therefore, we conducted a meta-analysis focusing on one specific training program, n-back. We searched PubMed and Google Scholar for all n-back training studies with Gf outcome measures, a control group, and healthy participants between 18 and 50 years of age. In total, we included 20 studies in our analyses that met our criteria and found a small but significant positive effect of n-back training on improving Gf. Several factors that moderate this transfer are identified and discussed. We conclude that short-term cognitive training on the order of weeks can result in beneficial effects in important cognitive functions as measured by laboratory tests

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

A protocol for the conduct of a multicentre, prospective, randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures: the HUmeral SHaft (HUSH) fracture study

Aims: Fractures of the humeral shaft represent 3% to 5% of all fractures. The most common treatment for isolated humeral diaphysis fractures in the UK is non-operative using functional bracing, which carries a low risk of complications, but is associated with a longer healing time and a greater risk of nonunion than surgery. There is an increasing trend to surgical treatment, which may lead to quicker functional recovery and lower rates of fracture nonunion than functional bracing. However, surgery carries inherent risk, including infection, bleeding, and nerve damage. The aim of this trial is to evaluate the clinical and cost-effectiveness of functional bracing compared to surgical fixation for the treatment of humeral shaft fractures. Methods: The HUmeral SHaft (HUSH) fracture study is a multicentre, prospective randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures in adult patients. Participants will be randomized to receive either functional bracing or surgery. With 334 participants, the trial will have 90% power to detect a clinically important difference for the Disabilities of the Arm, Shoulder and Hand questionnaire score, assuming 20% loss to follow-up. Secondary outcomes will include function, pain, quality of life, complications, cost-effectiveness, time off work, and ability to drive. Discussion: The results of this trial will provide evidence regarding clinical and cost-effectiveness between surgical and non-surgical treatment of humeral shaft fractures. Ethical approval has been obtained from East of England – Cambridge Central Research Ethics Committee. Publication is anticipated to occur in 2024

Proteome analysis of peroxisomes from dark‐treated senescent Arabidopsis leaves

Peroxisomes compartmentalize a dynamic suite of biochemical reactions and play a central role in plant metabolism, such as the degradation of hydrogen peroxide, metabolism of fatty acids, photorespiration, and the biosynthesis of plant hormones. Plant peroxisomes have been traditionally classified into three major subtypes, and in‐depth mass spectrometry (MS)‐based proteomics has been performed to explore the proteome of the two major subtypes present in green leaves and etiolated seedlings. Here, we carried out a comprehensive proteome analysis of peroxisomes from Arabidopsis leaves given a 48‐h dark treatment. Our goal was to determine the proteome of the third major subtype of plant peroxisomes from senescent leaves, and further catalog the plant peroxisomal proteome. We identified a total of 111 peroxisomal proteins and verified the peroxisomal localization for six new proteins with potential roles in fatty acid metabolism and stress response by in vivo targeting analysis. Metabolic pathways compartmentalized in the three major subtypes of peroxisomes were also compared, which revealed a higher number of proteins involved in the detoxification of reactive oxygen species in peroxisomes from senescent leaves. Our study takes an important step towards mapping the full function of plant peroxisomes.Peroxisomes are important to development and stress response. Here we report a comprehensive proteome analysis of peroxisomes from Arabidopsis leaves treated with extended darkness, which identified new proteins with potential roles in fatty acid metabolism and stress response, thus taking an important step towards defining the full function of plant peroxisomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146507/1/jipb12670-sup-0001-SuppFigs-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146507/2/jipb12670.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146507/3/jipb12670_am.pd

Specialization along the Left Superior Temporal Sulcus for Auditory Categorization

The affinity and temporal course of functional fields in middle and posterior superior temporal cortex for the categorization of complex sounds was examined using functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) recorded simultaneously. Data were compared before and after subjects were trained to categorize a continuum of unfamiliar nonphonemic auditory patterns with speech-like properties (NP) and a continuum of familiar phonemic patterns (P). fMRI activation for NP increased after training in left posterior superior temporal sulcus (pSTS). The ERP P2 response to NP also increased with training, and its scalp topography was consistent with left posterior superior temporal generators. In contrast, the left middle superior temporal sulcus (mSTS) showed fMRI activation only for P, and this response was not affected by training. The P2 response to P was also independent of training, and its estimated source was more anterior in left superior temporal cortex. Results are consistent with a role for left pSTS in short-term representation of relevant sound features that provide the basis for identifying newly acquired sound categories. Categorization of highly familiar phonemic patterns is mediated by long-term representations in left mSTS. Results provide new insight regarding the function of ventral and dorsal auditory streams

The Protein Maker: an automated system for high-throughput parallel purification

The Protein Maker instrument addresses a critical bottleneck in structural genomics by allowing automated purification and buffer testing of multiple protein targets in parallel with a single instrument. Here, the use of this instrument to (i) purify multiple influenza-virus proteins in parallel for crystallization trials and (ii) identify optimal lysis-buffer conditions prior to large-scale protein purification is described

Risk factors and prognosis of young stroke. The FUTURE study: A prospective cohort study. Study rationale and protocol

Contains fulltext : 98322.pdf (postprint version ) (Open Access)BACKGROUND: Young stroke can have devastating consequences with respect to quality of life, the ability to work, plan or run a family, and participate in social life. Better insight into risk factors and the long-term prognosis is extremely important, especially in young stroke patients with a life expectancy of decades. To date, detailed information on risk factors and the long-term prognosis in young stroke patients, and more specific risk of mortality or recurrent vascular events, remains scarce. METHODS/DESIGN: The FUTURE study is a prospective cohort study on risk factors and prognosis of young ischemic and hemorrhagic stroke among 1006 patients, aged 18-50 years, included in our study database between 1-1-1980 and 1-11-2010. Follow-up visits at our research centre take place from the end of 2009 until the end of 2011. Control subjects will be recruited among the patients' spouses, relatives or social environment. Information on mortality and incident vascular events will be retrieved via structured questionnaires. In addition, participants are invited to the research centre to undergo an extensive sub study including MRI. DISCUSSION: The FUTURE study has the potential to make an important contribution to increase the knowledge on risk factors and long-term prognosis in young stroke patients. Our study differs from previous studies by having a maximal follow-up of more than 30 years, including not only TIA and ischemic stroke but also hemorrhagic stroke, the addition of healthy controls and prospectively collect data during an extensive follow-up visit. Completion of the FUTURE study may provide better information for treating physicians and patients with respect to the prognosis of young stroke.8 p

Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476)

Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 years after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomised patients 1:1 to SOC-alone with or without daily abiraterone acetate 1000 mg + prednisolone 5 mg (SOC + AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards and flexible parametric models, accounting for baseline stratification factors. One thousand and three patients were contemporaneously randomised (November 2011 to January 2014): median age 67 years; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% unassessable; median PSA 97 ng/mL. At 6.1 years median follow-up, 329 SOC-alone deaths (118 low-risk, 178 high-risk) and 244 SOC + AAP deaths (75 low-risk, 145 high-risk) were reported. Adjusted HR = 0.60 (95% CI: 0.50-0.71; P = 0.31 × 10−9) favoured SOC + AAP, with 5-years survival improved from 41% SOC-alone to 60% SOC + AAP. This was similar in low-risk (HR = 0.55; 95% CI: 0.41-0.76) and high-risk (HR = 0.54; 95% CI: 0.43-0.69) patients. Median and current maximum time on SOC + AAP was 2.4 and 8.1 years. Toxicity at 4 years postrandomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group