Lateral stress evolution in chromium sulfide cermets with varying excess chromium

The shock response of chromium sulfide-chromium, a cermet of potential interest as a matrix material for ballistic applications, has been investigated at two molar ratios. Using a combustion synthesis technique allowed for control of the molar ratio of the material, which was investigated under near-stoichiometric (cermet) and excess chromium (interpenetrating composite) conditions, representing chromium:sulfur molar ratios of 1.15:1 and 4:1, respectively. The compacts were investigated via the plate-impact technique, which allowed the material to be loaded under a onedimensional state of strain. Embedded manganin stress gauges were employed to monitor the temporal evolution of longitudinal and lateral components of stress in both materials. Comparison of these two components has allowed assessment of the variation of material shear strength both with impact pressure/strain-rate and time for the two molar ratio conditions. The two materials exhibited identical material strength despite variations in their excess chromium content

Understanding the barriers to accessing symptom-specific cognitive behavior therapy (CBT) for distressing voices: reflecting on and extending the lessons learnt from the CBT for psychosis literature

The experience of hearing voices ('auditory hallucinations') can cause significant distress and disruption to quality of life for people with a psychosis diagnosis. Psychological therapy in the form of Cognitive Behavior Therapy for psychosis is recommended for the treatment of positive symptoms, including distressing voices, but is rarely available to patients in the UK. Cognitive Behavior Therapy for psychosis has recently evolved with the development of symptom-specific therapies that focus upon only one symptom of psychosis at a time. Preliminary findings from randomized controlled trials suggest that these symptom-specific therapies can be more effective for distressing voices than the use of broad CBT protocols, and have the potential to target voices trans-diagnostically. Whilst this literature is evolving, consideration must be given to the potential for a symptom-specific approach to overcome some of the barriers to delivery of evidence-based psychological therapies within clinical services. These barriers are discussed in relation to the UK mental health services, and we offer suggestions for future research to enhance our understanding of these barriers

A mixed mixed-methods investigation of mental health stigma, absenteeism and presenteeism among UK postgraduate researchers

Purpose Postgraduate researchers (PGRs) appear to be particularly vulnerable to mental health problems. Mental health-related stigma and discrimination may be endemic within universities, creating a threatening environment that undermines PGRs’ health and well-being. These environmental characteristics may increase PGRs’ absenteeism and presenteeism, attendance behaviours that have great personal and institutional consequences. The study of this issue, however, has been limited to date. Design/methodology/approach This was a mixed methods psychological study using cross-sectional data provided by 3,352 UK-based PGRs. Data were collected in a new national survey (U-DOC) led by a British University in 2018–2019. We used structural equation modelling techniques to test associations between workplace mental health-related stigma and discrimination, presenteeism, absenteeism and demographic characteristics. The authors analysed qualitative survey data with framework analysis to deductively and inductively explore associations between workplace culture, stigma and discrimination, and attendance behaviours. Findings The authors found that some PGRs report positive perceptions and experiences of the academic mental health-related workplace culture. However, experiences of mental health stigma and discrimination appear widespread. Both quantitative and qualitative results show that experiences of mental health-related stigma are associated with greater absenteeism and presenteeism. People with mental health problems appear especially vulnerable to experiencing stigma and its impacts. Practical implications Key implications include recommendations for universities to improve support for PGR mental health, and to encourage taking annual leave and necessary sickness absences, by providing a more inclusive environment with enhanced mental health service provision and training for faculty and administrative staff. Originality/value This study presents the first large-scale survey of PGR experiences of mental health-related stigma and discrimination, and their associations with absenteeism and presenteeism

The Enthusiast’s Eye: The Value of Unsanctioned Knowledge in Design Historical Scholarship

If design history research relies solely on institutionalized documentation and academic scholarship – that is, sanctioned knowledge – not only will its purview be limited to a very narrow segment of design culture, it will also lose out on a vast array of sources to valuable knowledge about our material environment produced by amateurs, collectors, and enthusiasts – what we in this article define as “unsanctioned knowledge.” Because of its dissociation with professional institutions and academic protocols and their – albeit admittedly utopian, but nonetheless upheld – ideals of objectivity, this type of knowledge is typically considered fundamentally subjective in nature and therefore of little or no relevance and value to academic scholarship. In this article, we argue that, to the contrary, design historical scholarship has much to gain from engaging more seriously with the unsanctioned knowledge represented by the enthusiast's eye

Nationwide assessment of the mental health of UK doctoral researchers

Doctoral Researchers (DRs) are an important part of the academic community and, after graduating, make substantial social and economic contributions. Despite this importance, DR wellbeing has long been of concern. Recent studies have concluded that DRs may be particularly vulnerable to mental health problems, yet direct comparisons of the prevalence of mental health problems between this population and control groups are lacking. Here, by comparing DRs with educated working controls, we show that DRs report significantly greater anxiety and depression, and that this difference is not explained by a higher rate of pre-existing mental health problems. Moreover, most DRs perceive poor mental health as a ‘normal’ part of the PhD process. Thus, our findings suggest a hazardous impact of PhD study on mental health, with DRs being particularly at risk of developing common mental health problems. This provides an evidence-based mandate for universities and funders to reflect upon practices related to DR training and mental health. Our attention should now be directed towards understanding what factors may explain heightened anxiety and depression among DRs so as to inform preventative measures and interventions

Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis

Background Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people. Methods We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefined data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy (change in depressive symptoms) and tolerability (discontinuations due to adverse events). We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023. Findings We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more effective than placebo (standardised mean difference −0·51, 95% credible interval [CrI] −0·99 to −0·03). In terms of tolerability, fluoxetine was also better than duloxetine (odds ratio [OR] 0·31, 95% CrI 0·13 to 0·95) and imipramine (0·23, 0·04 to 0·78). Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo (5·49, 1·96 to 20·86; 3·19, 1·01 to 18·70; and 2·80, 1·20 to 9·42, respectively). In terms of heterogeneity, the global I2 values were 33·21% for efficacy and 0% for tolerability. Interpretation When considering the risk–benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated. Funding National Basic Research Program of China (973 Program)

Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue

Although thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias is inherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g., 6 mm biopsy), which becomes grossly under-powered as tumor volume scales. Here, we demonstrate representative sequencing (Rep-Seq) as a new method to achieve unbiased tumor tissue sampling. Rep-Seq uses fixed residual tumor material, which is homogenized and subjected to next-generation sequencing. Analysis of intratumor tumor mutation burden (TMB) variability shows a high level of misclassification using current single-biopsy methods, with 20% of lung and 52% of bladder tumors having at least one biopsy with high TMB but low clonal TMB overall. Misclassification rates by contrast are reduced to 2% (lung) and 4% (bladder) when a more representative sampling methodology is used. Rep-Seq offers an improved sampling protocol for tumor profiling, with significant potential for improved clinical utility and more accurate deconvolution of clonal structure

The Contribution of National Spontaneous Reporting Systems to Detect Signals of Torsadogenicity: Issues Emerging from the ARITMO Project

Introduction: Spontaneous reporting systems (SRSs) are pivotal for signal detection, especially for rare events with a high drug-attributable component, such as torsade de pointes (TdP). Use of different national SRSs is rarely attempted because of inherent difficulties, but should be considered on the assumption that rare events are diluted in international databases. Objective: The aim was to describe TdP-related events associated with antipsychotics, H1-antihistamines and anti-infectives in three national SRSs (in Italy, Germany and France) and highlight potential signals of torsadogenicity through a combined literature evaluation. Methods: A common search strategy was applied to extract TdP-related events: (1) TdP, (2) QT interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. Signals of disproportionate reporting (SDRs) were calculated for TdP + QT interval abnormalities and defined by a lower limit of the 95 % confidence interval of the reporting odds ratio (ROR) >1. Among SDRs with at least three cases without concomitant pro-arrhythmic drugs, we defined potential new signal of torsadogenicity as drugs with no published evidence from (a) the crediblemeds® website (http://www.crediblemeds.com, as of November 1st, 2014); (b) studies on the FDA Adverse Event Reporting System (FAERS); and (c) safety trials or pharmaco-epidemiological studies (as of December 16th, 2014). Results: Overall, 3505 cases were retrieved (1372, 1468, and 801 for France, Germany and Italy, respectively). Antipsychotics were mainly recorded in Germany (792 cases), whereas antibiotics peaked at 515 and 491 (France and Italy, respectively). Forty-one drugs met criteria for SDRs in at least one single source, of which 31 were detected only from one single SRS: 18, ten and three (French, German and Italian SRS, respectively). By contrast, only five SDRs were detected in all national data sources (amisulpride, aripiprazole, haloperidol, olanzapine, risperidone). Overall, five potential new signals of torsadogenicity were identified: flupentixol, ganciclovir, levocetirizine, oxatomide and tiapride. Conclusions: We found differences across and within national SRSs in the reporting of drug-induced TdP, which finally resulted in five potential new signals of torsadogenicity. These findings warrant targeted pharmacovigilance studies to formally assess the existence of actual drug–event associations

Atomically dispersed Pt-N-4 sites as efficient and selective electrocatalysts for the chlorine evolution reaction

Chlorine evolution reaction (CER) is a critical anode reaction in chlor-alkali electrolysis. Although precious metal-based mixed metal oxides (MMOs) have been widely used as CER catalysts, they suffer from the concomitant generation of oxygen during the CER. Herein, we demonstrate that atomically dispersed Pt-N-4 sites doped on a carbon nanotube (Pt-1/CNT) can catalyse the CER with excellent activity and selectivity. The Pt-1/CNT catalyst shows superior CER activity to a Pt nanoparticle-based catalyst and a commercial Ru/Ir-based MMO catalyst. Notably, Pt-1/CNT exhibits near 100% CER selectivity even in acidic media, with low Cl- concentrations (0.1M), as well as in neutral media, whereas the MMO catalyst shows substantially lower CER selectivity. In situ electrochemical X-ray absorption spectroscopy reveals the direct adsorption of Cl- on Pt-N-4 sites during the CER. Density functional theory calculations suggest the PtN4C12 site as the most plausible active site structure for the CER

Treatment response and remission in a double-blind, randomized, head-to-head study of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit hyperactivity disorder

The Author(s) 2014. This article is published with open access at Springerlink.com Objectives A secondary objective of this head-to-head study of lisdexamfetamine dimesylate (LDX) and ato-moxetine (ATX) was to assess treatment response rates in children and adolescents with attention-deficit hyperactiv-ity disorder (ADHD) and an inadequate response to methylphenidate (MPH). The primary efficacy and safety outcomes of the study, SPD489-317 (ClinicalTrials.gov NCT01106430), have been published previously. Methods In this 9-week, double-blind, active-controlled study, patients aged 6–17 years with a previous inadequate response to MPH were randomized (1:1) to dose-optimized LDX (30, 50 or 70 mg/day) or ATX (patients \70 kg: 0.5–1.2 mg/kg/day, not to exceed 1.4 mg/kg/day; patients C70 kg: 40, 80 or 100 mg/day). Treatment response was a secondary efficacy outcome and was predefined as a reduction from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score of at least 25, 30 or 50 %. Sustained response was predefined as a reduction from baseline in ADHD-RS-IV total score (C25, C30 or C50 %) or a Clinical Global Impressions (CGI)–Improvement (CGI–I) score of 1 or 2 throughout weeks 4–9. CGI– Severity (CGI–S) scores were also assessed, as an indicator of remission. Results A total of 267 patients were enrolled (LDX, n = 133; ATX, n = 134) and 200 completed the study (LDX, n = 99; ATX, n = 101). By week 9, significantly (p \ 0.01) greater proportions of patients receiving LDX than ATX met the response criteria of a reduction from baseline in ADHD-RS-IV total score of at least 25 % (90.5 vs. 76.7 %), 30 % (88.1 vs. 73.7 %) or 50 % (73.0 vs. 50.4 %). Sustained response rates were also signifi-cantly (p \ 0.05) higher among LDX-treated patient