Anxious to see you: Neuroendocrine mechanisms of social vigilance and anxiety during adolescence.

Social vigilance is a behavioral strategy commonly used in adverse or changing social environments. In animals, a combination of avoidance and vigilance allows an individual to evade potentially dangerous confrontations while monitoring the social environment to identify favorable changes. However, prolonged use of this behavioral strategy in humans is associated with increased risk of anxiety disorders, a major burden for human health. Elucidating the mechanisms of social vigilance in animals could provide important clues for new treatment strategies for social anxiety. Importantly, during adolescence the prevalence of social anxiety increases significantly. We hypothesize that many of the actions typically characterized as anxiety behaviors begin to emerge during this time as strategies for navigating more complex social structures. Here, we consider how the social environment and the pubertal transition shape neural circuits that modulate social vigilance, focusing on the bed nucleus of the stria terminalis and prefrontal cortex. The emergence of gonadal hormone secretion during adolescence has important effects on the function and structure of these circuits, and may play a role in the emergence of a notable sex difference in anxiety rates across adolescence. However, the significance of these changes in the context of anxiety is still uncertain, as not enough studies are sufficiently powered to evaluate sex as a biological variable. We conclude that greater integration between human and animal models will aid the development of more effective strategies for treating social anxiety

KH domains with impaired nucleic acid binding as a tool for functional analysis

In eukaryotes, RNA-binding proteins that contain multiple K homology (KH) domains play a key role in coordinating the different steps of RNA synthesis, metabolism and localization. Understanding how the different KH modules participate in the recognition of the RNA targets is necessary to dissect the way these proteins operate. We have designed a KH mutant with impaired RNA-binding capability for general use in exploring the role of individual KH domains in the combinatorial functional recognition of RNA targets. A double mutation in the hallmark GxxG loop (GxxG-to-GDDG) impairs nucleic acid binding without compromising the stability of the domain. We analysed the impact of the GDDG mutations in individual KH domains on the functional properties of KSRP as a prototype of multiple KH domain-containing proteins. We show how the GDDG mutant can be used to directly link biophysical information on the sequence specificity of the different KH domains of KSRP and their role in mRNA recognition and decay. This work defines a general molecular biology tool for the investigation of the function of individual KH domains in nucleic acid binding proteins

A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive-compulsive disorder in children/adolescents and adults

BACKGROUND: Obsessive-compulsive disorder (OCD) is a relatively common and disabling condition. OBJECTIVES: To determine the clinical effectiveness, acceptability and cost-effectiveness of pharmacological and psychological interventions for the treatment of OCD in children, adolescents and adults. DATA SOURCES: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Trials Registers, which includes trials from routine searches of all the major databases. Searches were conducted from inception to 31 December 2014. REVIEW METHODS: We undertook a systematic review and network meta-analysis (NMA) of the clinical effectiveness and acceptability of available treatments. Outcomes for effectiveness included mean differences in the total scores of the Yale-Brown Obsessive-Compulsive Scale or its children's version and total dropouts for acceptability. For the cost-effectiveness analysis, we developed a probabilistic model informed by the results of the NMA. All analyses were performed using OpenBUGS version 3.2.3 (members of OpenBUGS Project Management Group; see www.openbugs.net ). RESULTS: We included 86 randomised controlled trials (RCTs) in our systematic review. In the NMA we included 71 RCTs (54 in adults and 17 in children and adolescents) for effectiveness and 71 for acceptability (53 in adults and 18 in children and adolescents), comprising 7643 and 7942 randomised patients available for analysis, respectively. In general, the studies were of medium quality. The results of the NMA showed that in adults all selective serotonin reuptake inhibitors (SSRIs) and clomipramine had greater effects than drug placebo. There were no differences between SSRIs, and a trend for clomipramine to be more effective did not reach statistical significance. All active psychological therapies had greater effects than drug placebo. Behavioural therapy (BT) and cognitive therapy (CT) had greater effects than psychological placebo, but cognitive-behavioural therapy (CBT) did not. BT and CT, but not CBT, had greater effects than medications, but there are considerable uncertainty and methodological limitations that should be taken into account. In children and adolescents, CBT and BT had greater effects than drug placebo, but differences compared with psychological placebo did not reach statistical significance. SSRIs as a class showed a trend for superiority over drug placebo, but the difference did not reach statistical significance. However, the superiority of some individual drugs (fluoxetine, sertraline) was marginally statistically significant. Regarding acceptability, all interventions except clomipramine had good tolerability. In adults, CT and BT had the highest probability of being most cost-effective at conventional National Institute for Health and Care Excellence thresholds. In children and adolescents, CBT or CBT combined with a SSRI were more likely to be cost-effective. The results are uncertain and sensitive to assumptions about treatment effect and the exclusion of trials at high risk of bias. LIMITATIONS: The majority of psychological trials included patients who were taking medications. There were few studies in children and adolescents. CONCLUSIONS: In adults, psychological interventions, clomipramine, SSRIs or combinations of these are all effective, whereas in children and adolescents, psychological interventions, either as monotherapy or combined with specific SSRIs, were more likely to be effective. Future RCTs should improve their design, in particular for psychotherapy or combined interventions. STUDY REGISTRATION: The study is registered as PROSPERO CRD42012002441. FUNDING DETAILS: The National Institute for Health Research Health Technology Assessment programme

The utility of diagnostic selective nerve root blocks in the management of patients with lumbar radiculopathy: a systematic review.

OBJECTIVE: Lumbar radiculopathy (LR) often manifests as pain in the lower back radiating into one leg (sciatica). Unsuccessful back surgery is associated with significant healthcare costs and risks to patients. This review aims to examine the diagnostic accuracy of selective nerve root blocks (SNRBs) to identify patients most likely to benefit from lumbar decompression surgery. DESIGN: Systematic review of diagnostic test accuracy studies. ELIGIBILITY CRITERIA: Primary research articles using a patient population with low back pain and symptoms in the leg, SNRB administered under radiological guidance as index test, and any reported reference standard for the diagnosis of LR. INFORMATION SOURCES: MEDLINE (Ovid), MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Science Citation Index, Biosis, LILACS, Dissertation abstracts and National Technical Information Service from inception to 2018. METHODS: Risk of bias and applicability was assessed using the QUADAS-2 tool. We performed random-effects logistic regression to meta-analyse studies grouped by reference standard. RESULTS: 6 studies (341 patients) were included in this review. All studies were judged at high risk of bias. There was substantial heterogeneity across studies in sensitivity (range 57%-100%) and specificity (10%-86%) estimates. Four studies were diagnostic cohort studies that used either intraoperative findings during surgery (pooled sensitivity: 93.5% [95% CI 84.0 to 97.6]; specificity: 50.0% [16.8 to 83.2]) or 'outcome following surgery' as the reference standard (pooled sensitivity: 90.9% [83.1 to 95.3]; specificity 22.0% [7.4 to 49.9]). Two studies had a within-patient case-control study design, but results were not pooled because different types of control injections were used. CONCLUSIONS: We found limited evidence which was of low methodological quality indicating that the diagnostic accuracy of SNRB is uncertain and that specificity in particular may be low. SNRB is a safe test with a low risk of clinically significant complications, but it remains unclear whether the additional diagnostic information it provides justifies the cost of the test.National Institute for Health Research Health Technology Assessment programme grant (project number 09/111/01)

Offering self-sampling to cervical screening non-attenders in primary care

Objectives To assess the feasibility and acceptability of offering self-sampling for Human Papillomavirus (HPV) testing to cervical screening non-attenders when they consult primary care for any reason. Methods In a pilot implementation study, six general practices in London, UK, offered self-sampling kits during consultation to women aged 25–64 who were at least six months overdue for cervical screening (no cytology test recorded in the past 3.5 years if aged 25–49, or 5.5 years if aged 50–64). Eligible women were identified using an automated real-time search (during consultation) of the general practice electronic medical record system. Women collected samples either in clinic or at home (dry flocked swabs analysed using Roche Cobas®4800). Results Of approximately 5000 eligible women, 3131 consulted primary care between January and December 2014 (mean recruitment period 9.5 months). Of these, 21% (652) were offered kits, 14% (443) accepted, and 9% (292) returned a self-sample. The proportion of eligible women offered kits varied considerably among practices (11–36%). Sample return rates increased with kit offered rates ( r = 0.8, p = 0.04). Of 39 HPV positive women 85% (33) attended follow-up, including two with invasive cancers (stage 2A1 and 1A1). Conclusions Offering self-sampling to cervical screening non-attenders opportunistically in primary care is feasible. Return rates could be increased if more women were offered kits. A large trial is needed to identify how self-sampling is best integrated into the national screening programme, and to identify determinants of uptake. </jats:sec

Interactive Sensory Objects Developed for and by People with Learning Disabilities

This paper describes a project that aims to help improve the accessibility of museums and heritage sites by creating a series of interactive, multisensory objects. The objects will be developed collaboratively by artists, technologists, people with an interest in heritage sites, and people with disabilities and their carers in a series of sensory art and electronics workshops. The workshops and the sensory objects will explore aspects of physicality and how to appeal to the entire range of senses for both control and feedback. In addition to creating new interactive objects, the project aims to learn more about how to engage people with disabilities as participant researchers in designing art objects, and how to make heritage sites more accessible generally