On the dynamic tensile strength of Zirconium

Despite its fundamental nature, the process of dynamic tensile failure (spall) is poorly understood. Spall initiation via cracks, voids, etc, before subsequent coalesce, is known to be highly microstructure-dependant. In particular, the availability of slip planes and other methods of plastic deformation controls the onset (or lack thereof) of spall. While studies have been undertaken into the spall response of BCC and FCC materials, less attention has paid to the spall response of highly anisotropic HCP materials. Here the dynamic behaviour of zirconium is investigated via plate-impact experiments, with the aim of building on an ongoing in-house body of work investigating these highly complex materials. In particular, in this paper the effect of impact stress on spall in a commercially sourced Zr rod is considered, with apparent strain-rate softening highlighted

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

Helping parents to help children overcome fear: the influence of a short video tutorial

Objectives Anxiety runs in families, and its transmission is largely environmental. However, studies rarely explore this process in clinically anxious parents or ask participants to face a genuine fear. We also do not know whether this process is modifiable. This study will explore these questions using a sample of clinically anxious parents. Design Experimental design comparing clinically anxious parents with non‐anxious parents, and exploring the effects of a tutorial intervention versus a control group. Methods Parents with and without anxiety disorders and their children (5–9 years) participated (N = 72). Children chose two fearful animal stimuli. Parents helped the child approach the first in graded steps. The following parental behaviours were recorded: positive/negative verbal information; positive/negative modelling; encouragement/praising of approach/avoidance behaviours. Half the parents were then randomly assigned to a short video tutorial advising how to help children cope with fearful situations. The remainder watched a control video. The approach task was repeated with the second stimulus. Results Parenting behaviours fell into two categories: ‘approach parenting’ (encouraging/praising/modelling approach; positive verbal information) and ‘avoidance parenting’ (encouraging/praising/modelling avoidance; negative verbal information). The parenting tutorial increased ‘approach parenting’ and decreased ‘avoidance parenting’ and was associated with increased child approach towards fearful stimuli. This was not moderated by parent or child anxiety. Conclusions Parenting, particularly ‘avoidance parenting’, is associated with children's approach and avoidance. A short video tutorial modified these parenting behaviours and reduced avoidance. These effects were apparent regardless of parent or child anxiety level

Index insurance and climate risk management: addressing social equity

Motivation Fair distribution of benefits from index insurance matters. Lack of attention to social equity can reinforce inequalities and undermine the potential index insurance holds as a tool for climate risk management that is also pro-poor. Purpose The aims are to: (i) examine social equity concerns raised by index insurance in the context of climate risk management; (ii) consider how greater attention can be given to social equity in index insurance initiatives; and (iii) reflect on the policy challenges raised by seeking to take social equity into account as a mechanism for climate risk reduction. Approach and methods The article draws on learning from the CGIAR’s Research Program on Climate Change, Agriculture and Food Security (CCAFS) and presents the cases of the Index Based Livelihoods Insurance (IBLI) and Agriculture and Climate Risk Enterprise Ltd. (ACRE) in East Africa. It proposes a framework for unpacking social equity related to equitable access, procedures, representation and distribution within index insurance schemes Findings Systematically addressing social equity raises hard policy choices for index insurance initiatives without straightforward solutions. Attention to how benefits and burdens of index insurance are distributed raises the unpalateable truth for development policy that the poorest members of rural society can be excluded. Nevertheless, a focus on social equity may open up opportunities to ensure index insurance is linked to more socially just climate risk management. At the very least, it may prevent index insurance from generating greater inequality. Taking social equity into account thus, shifts the focus from agricultural systems in transition per se to systems with potential to incorporate societal transformation through distributive justice. Policy implications A framework is presented for unpacking different dimensions of social equity in index insurance schemes. It is intended to facilitate identification of opportunities for building outcomes that are more equitable, with greater potential for inclusion and fairer distribution

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

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)

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

Selection of metastasis competent subclones in the tumour interior

The genetic evolutionary features of solid tumour growth are becoming increasingly well described, but the spatial and physical nature of subclonal growth remains unclear. Here, we utilize 102 macroscopic whole-tumour images from clear cell renal cell carcinoma patients, with matched genetic and phenotypic data from 756 biopsies. Utilizing a digital image processing pipeline, a renal pathologist marked the boundaries between tumour and normal tissue and extracted positions of boundary line and biopsy regions to X and Y coordinates. We then integrated coordinates with genomic data to map exact spatial subclone locations, revealing how genetically distinct subclones grow and evolve spatially. We observed a phenotype of advanced and more aggressive subclonal growth in the tumour centre, characterized by an elevated burden of somatic copy number alterations and higher necrosis, proliferation rate and Fuhrman grade. Moreover, we found that metastasizing subclones preferentially originate from the tumour centre. Collectively, these observations suggest a model of accelerated evolution in the tumour interior, with harsh hypoxic environmental conditions leading to a greater opportunity for driver somatic copy number alterations to arise and expand due to selective advantage. Tumour subclone growth is predominantly spatially contiguous in nature. We found only two cases of subclone dispersal, one of which was associated with metastasis. The largest subclones spatially were dominated by driver somatic copy number alterations, suggesting that a large selective advantage can be conferred to subclones upon acquisition of these alterations. In conclusion, spatial dynamics is strongly associated with genomic alterations and plays an important role in tumour evolution