Re: Recognition and management of psychosis and schizophrenia in children and young people : summary of NICE guidance.

The publication of NICE guidelines relating to the Recognition and management of Psychosis and Schizophrenia in children and young people 1 is to be welcomed given the lack of published guidance in this area, especially concerning the management of young people deemed to be at high risk of psychosis 2,3. However, we feel that the working group may have missed an opportunity to incorporate the views of current adolescent service users. The guideline development process included service-user representation at all stages. However, there was a dearth of published literature in relation to the experiences and treatment preferences of child and adolescent service users with psychosis to draw on 4 although we note the guidelines did not reference our recently published study in this area 5. Indeed, this is a patient group rarely consulted, possibly due to a perception that young people may find it difficult to articulate hallucinatory experiences or have inaccurate recall of events 6,7. However, there is a growing acceptance that eliciting and learning from service users' views is an important means of improving the quality of future health care and research within the NHS 8,9. Indeed, where the evidence base is uncertain, as in the present case, patient preferences may play a more significant role in treatment selection 10. In response to our concerns we are working with our local Early Intervention in Psychosis service to address this issue by offering information to young people describing possible therapeutic options and asking them to state their preferences

Correspondence between T. Melden, George C. Stokes, and John Shary

Correspondence regarding lot 282, Shary Subdivision between November 1, 1930 and October 15, 1942 between T. Melden, George C. Stokes, John Shary, Pearl Stokes, and attorneys for the United Irrigation Company.https://scholarworks.utrgv.edu/johnshary/1024/thumbnail.jp

Association between Sex-Biased Gene Expression and Mutations with Sex-Specific Phenotypic Consequences in Drosophila

Genome-wide mRNA transcription profiles reveal widespread molecular sexual dimorphism or “sex-biased” gene expression, yet the relationship between molecular and phenotypic sexual dimorphism remains unclear. A major unresolved question is whether sex-biased genes typically perform male- and female-specific functions (whether these genes have sex-biased phenotypic or fitness consequences) or have similar functional importance for both sexes. To elucidate the relationship between sex-biased transcription and sex-biased fitness consequences, we analyzed a large data set of lethal, visible, and sterile mutations that have been mapped to the Drosophila melanogaster genome. The data permitted us to classify genes according to their sex-specific mutational effects and to infer the relationship between sex-biased transcription level and sex-specific fitness consequences. We find that mutations in female-biased genes are (on average) more deleterious to females than to males and that mutations in male-biased genes tend to be more deleterious to males than to females. Nevertheless, mutations in most sex-biased genes have similar phenotypic consequences for both sexes, which suggests that sex-biased transcription is not necessarily associated with functional genetic differentiation between males and females. These results have interesting implications for the evolution of sexual dimorphism and sex-specific adaptation

Effects of a Water-Soluble Cinnamon Extract on Body Composition and Features of the Metabolic Syndrome in Pre-Diabetic Men and Women

Purpose: The purpose of this study was to determine the effects of supplementation with a water-soluble cinnamon extract (Cinnulin PF®) on body composition and features of the metabolic syndrome. Methods: Twenty-two subjects with prediabetes and the metabolic syndrome (mean ± SD: age, BMI, systolic blood pressure [SBP], fasting blood glucose [FBG]: 46.0 ± 9.7 y; 33.2 ± 9.3 kg/m 2; 133 ± 17 mm Hg; 114.3 ± 11.6 mg/dL) were randomly assigned to supplement their diet with either Cinnulin PF ® (500 mg/d) or a placebo for 12-weeks. Main outcome measures were changes in FBG, SBP, and body composition measured after 12-weeks of supplementation. The primary statistical analyses consisted of two factor (group x time), repeated-measures ANOVA for between group differences over time. In all analyses, an intent-to-treat approach was used and significance was accepted at P<0.05. Results: Subjects in the Cinnulin PF ® group had significant decreases in FBG (-8.4%: 116.3 ± 12.8 mg/dL [pre] to 106.5 ± 20.1 mg/dL [post], p<0.01), SBP (-3.8%: 133 ± 14 mm Hg [pre] to 128 ± 18 mm Hg [post], p<0.001), and increases in lean mass (+1.1%: 53.7 ± 11.8 kg [pre] to 54.3 ± 11.8 kg [post], p<0.002) compared with the placebo group. Additionally, within-group analyses uncovered small, but statistically significant decreases in body fat (-0.7%: 37.9 ± 9.2 % [pre] to 37.2 ± 8.9 % [post], p<0.02) in the Cinnulin PF ® group. No significant changes in clinical blood chemistries were observed betwee

Protocol for the proactive or reactive telephone smoking cessation support (PORTSSS) trial

Background: Telephone quit lines are accessible to many smokers and are used to engage motivated smokers to make quit attempts. Smoking cessation counselling provided via telephone can either be reactive (i.e. primarily involving the provision of evidence-based information), or proactive (i.e. primarily involving repeated, sequenced calls from and interaction with trained cessation counsellors). Some studies have found proactive telephone counselling more effective and this trial will investigate whether or not proactive telephone support for smoking cessation, delivered through the National Health Service (NHS) Smoking Helpline is more effective or cost-effective than reactive support. It will also investigate whether or not providing nicotine replacement therapy (NRT), in addition to telephone counselling, has an adjunctive impact on smoking cessation rates and whether or not this is cost effective. Methods: This will be a parallel group, factorial design RCT, conducted through the English national NHS Smoking Helpline which is run from headquarters in Glasgow. Participants will be smokers who call the helpline from any location in England and who wish to stop smoking. If 644 participants are recruited to four equally-sized trial groups (total sample size = 2576), the trial will have 90% power for detecting a treatment effect (Odds Ratio) of 1.5 for each of the two interventions: i) proactive versus reactive support and ii) the offer of NRT versus no offer. The primary outcome measure for the study is self-reported, prolonged abstinence from smoking for at least six months following an agreed quit date. A concurrent health economic evaluation will investigate the cost effectiveness of the two interventions when delivered via a telephone helpline. Discussion: The PORTSSS trial will provide high quality evidence to determine the most appropriate kind of counselling which should be provided via the NHS Smoking Helpline and also whether or not an additional offer of cost-free NRT is effective and cost effective for smoking cessation. Trial Registration: (clinicaltrials.gov): NCT0077594

Practitioner review: Treatments for Tourette syndrome in children and young people: a systematic review

Background:Tourette syndrome (TS) and chronic tic disorder (CTD) affect 1–2% of children and young people, but the most effective treatment is unclear. To establish the current evidence base, we conducted a systematic review of interventions for children and young people. Methods:Databases were searched from inception to 1 October 2014 for placebo-controlled trials of pharmacological, behavioural, physical or alternative interventions for tics in children and young people with TS or CTD. Certainty in the evidence was assessed with the GRADE approach. Results: Forty trials were included [pharmacological (32), behavioural (5), physical (2), dietary (1)]. For tics/global score there was evidence favouring the intervention from four trials of a2-adrenergic receptor agonists [clonidine and guanfacine, standardised mean difference (SMD) = -0.71; 95% CI -1.03, -0.40; N = 164] and two trials of habit reversal training (HRT)/comprehensive behavioural intervention (CBIT) (SMD = -0.64; 95% CI -0.99, -0.29; N = 133). Certainty in the effect estimates was moderate. A post hoc analysis combining oral clonidine/guanfacine trials with a clonidine patch trial continued to demonstrate benefit (SMD = -0.54; 95% CI -0.92, -0.16), but statistical heterogeneity was high. Evidence from four trials suggested that antipsychotic drugs improved tic scores (SMD = -0.74; 95% CI -1.08, -0.40; N = 76), but certainty in the effect estimate was low. The evidence for other interventions was categorised as low or very low quality, or showed no conclusive benefit. Conclusions: When medication is considered appropriate for the treatment of tics, the balance of clinical benefits to harm favours a2-adrenergic receptor agonists (clonidine and guanfacine) as first-line agents. Antipsychotics are likely to be useful but carry the risk of harm and so should be reserved for when a2-adrenergic receptor agonists are either ineffective or poorly tolerated. There is evidence that HRT/CBIT is effective, but there is no evidence for HRT/CBIT alone relative to combining medication and HRT/CBIT. There is currently no evidence to suggest that the physical and dietary interventions reviewed are sufficiently effective and safe to be considered as treatments

GENCODE: reference annotation for the human and mouse genomes in 2023.

GENCODE produces high quality gene and transcript annotation for the human and mouse genomes. All GENCODE annotation is supported by experimental data and serves as a reference for genome biology and clinical genomics. The GENCODE consortium generates targeted experimental data, develops bioinformatic tools and carries out analyses that, along with externally produced data and methods, support the identification and annotation of transcript structures and the determination of their function. Here, we present an update on the annotation of human and mouse genes, including developments in the tools, data, analyses and major collaborations which underpin this progress. For example, we report the creation of a set of non-canonical ORFs identified in GENCODE transcripts, the LRGASP collaboration to assess the use of long transcriptomic data to build transcript models, the progress in collaborations with RefSeq and UniProt to increase convergence in the annotation of human and mouse protein-coding genes, the propagation of GENCODE across the human pan-genome and the development of new tools to support annotation of regulatory features by GENCODE. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org

Garotas de loja, história social e teoria social [Shop Girls, Social History and Social Theory]

Shop workers, most of them women, have made up a significant proportion of Britain’s labour force since the 1850s but we still know relatively little about their history. This article argues that there has been a systematic neglect of one of the largest sectors of female employment by historians and investigates why this might be. It suggests that this neglect is connected to framings of work that have overlooked the service sector as a whole as well as to a continuing unease with the consumer society’s transformation of social life. One element of that transformation was the rise of new forms of aesthetic, emotional and sexualised labour. Certain kinds of ‘shop girls’ embodied these in spectacular fashion. As a result, they became enduring icons of mass consumption, simultaneously dismissed as passive cultural dupes or punished as powerful agents of cultural destruction. This article interweaves the social history of everyday shop workers with shifting representations of the ‘shop girl’, from Victorian music hall parodies, through modernist social theory, to the bizarre bombing of the Biba boutique in London by the Angry Brigade on May Day 1971. It concludes that progressive historians have much to gain by reclaiming these workers and the service economy that they helped create

The theory of expanded, extended, and enhanced opportunities for youth physical activity promotion

Background Physical activity interventions targeting children and adolescents (≤18 years) often focus on complex intra- and inter-personal behavioral constructs, social-ecological frameworks, or some combination of both. Recently published meta-analytical reviews and large-scale randomized controlled trials have demonstrated that these intervention approaches have largely produced minimal or no improvements in young people\u27s physical activity levels. Discussion In this paper, we propose that the main reason for previous studies\u27 limited effects is that fundamental mechanisms that lead to change in youth physical activity have often been overlooked or misunderstood. Evidence from observational and experimental studies is presented to support the development of a new theory positing that the primary mechanisms of change in many youth physical activity interventions are approaches that fall into one of the following three categories: (a) the expansion of opportunities for youth to be active by the inclusion of a new occasion to be active, (b) the extension of an existing physical activity opportunity by increasing the amount of time allocated for that opportunity, and/or (c) the enhancement of existing physical activity opportunities through strategies designed to increase physical activity above routine practice. Their application and considerations for intervention design and interpretation are presented. Summary The utility of these mechanisms, referred to as the Theory of Expanded, Extended, and Enhanced Opportunities (TEO), is demonstrated in their parsimony, logical appeal, support with empirical evidence, and the direct and immediate application to numerous settings and contexts. The TEO offers a new way to understand youth physical activity behaviors and provides a common taxonomy by which interventionists can identify appropriate targets for interventions across different settings and contexts. We believe the formalization of the TEO concepts will propel them to the forefront in the design of future intervention studies and through their use, lead to a greater impact on youth activity behaviors than what has been demonstrated in previous studies

The Toll-Like Receptor 4 (TLR4) Variant rs2149356 and Risk of Gout in European and Polynesian Sample Sets

Deposition of crystallized monosodium urate (MSU) in joints as a result of hyperuricemia is a central risk factor for gout. However other factors must exist that control the progression from hyperuricaemia to gout. A previous genetic association study has implicated the toll-like receptor 4 (TLR4) which activates the NLRP3 inflammasome via the nuclear factor-κB signaling pathway upon stimulation by MSU crystals. The T-allele of single nucleotide polymorphism rs2149356 in TLR4 is a risk factor associated with gout in a Chinese study. Our aim was to replicate this observation in participants of European and New Zealand Polynesian (Māori and Pacific) ancestry. A total of 2250 clinically-ascertained prevalent gout cases and 13925 controls were used. Non-clinically-ascertained incident gout cases and controls from the Health Professional Follow-up (HPFS) and Nurses Health Studies (NHS) were also used. Genotypes were derived from genome-wide genotype data or directly obtained using Taqman. Logistic regression analysis was done including age, sex, diuretic exposure and ancestry as covariates as appropriate. The T-allele increased the risk of gout in the clinically-ascertained European samples (OR = 1.12, P = 0.012) and decreased the risk of gout in Polynesians (OR = 0.80, P = 0.011). There was no evidence for association in the HPFS or NHS sample sets. In conclusion TLR4 SNP rs2143956 associates with gout risk in prevalent clinically-ascertained gout in Europeans, in a direction consistent with previously published results in Han Chinese. However, with an opposite direction of association in Polynesians and no evidence for association in a non-clinically-ascertained incident gout cohort this variant should be analysed in other international gout genetic data sets to determine if there is genuine evidence for association