The Electrochemical Kinetics of the Evolution of Isotopically Enriched Gases and the Mechanism of the Oxygen Evolution Reaction

This work describes a method which follows, by mass spectrometry, the kinetics of gas evolution from an isotopically enriched electrode surface. The mechanisms of both 18O16O and 4D 2 evolution were investigated by this technique. 34O 2 evolution was studied on platinum, NiCo2O4 and lithiated CO3O4 electrodes in alkaline electrolyte, and additionally on platinum electrodes in acid electrolyte. The kinetics were found to be consistent with a mechanism of oxygen evolution which involved successive oxidations on a single site or reaction via a bridge structure. It was found, in all cases, that the total number of sites responsible for oxygen evolution were less than the total number of sites at the surface. Additionally, on NiCo2O4 electrodes the number of sites which showed enrichment decreased with aging of the electrode, in agreement with evidence from its cyclic voltammogram. Tafel slopes and cyclic voltammograms are reported for each electrode. On each substrate the amount of enrichment detected was less than would have been expected from the degree of enrichment of the electrolyte. This is most readily explained on consideration of the proposed mechanism of oxygen evolution, where the first step involving oxide formation is rate determining on platinum and NiCo2O4 (high overpotential). The intermediate oxide species formed being rapidly removed as oxygen was evolved. On materials in which the metal was initially in a trivalent state, a mechanism involving a bridge structure between this trivalent site and a second site is postulated; its formation being rate determining at low overpotential on NiCo2O4. This method was extended to follow the mechanism of hydrogen evolution on both platinum and platinised hydrogen tungsten bronzeelectrodes. The kinetics of the removal of an adsorbed deuteron were consistent with a second order recombination and found to be fast (k = 0.02 +/- 0.02 s-1 at 25&deg;C on platinum). Experiments on platinised hydrogen tungsten bronze electrodes confirmed the existence of a synergistic effect in this system. <p

The Role of Multiple Sclerosis as a Risk Factor for the Development of Osteoporosis

Background: Osteoporosis is the most common bone disease in the United States, and it is particularly common among women with multiple sclerosis (MS). However, despite this association, the temporal relationship between these two conditions has not been previously studied. Data from the Women’s Health Initiative provides a unique opportunity to examine the risk of developing osteoporosis over time in individuals diagnosed with MS. Objective: The purpose of this study is to refine the relationship between MS and osteoporosis, clarifying the impact of environmental and pharmacologic factors on each condition, as well as addressing treatment and preventative efforts for a patient population at a greater potential risk for osteoporosis. Methods: The study sample, derived from the Women’s Health Initiative, included 449 women who reported an MS diagnosis at baseline and 161,359 women without MS who comprised a control group. Baseline measures of self-reported osteoporosis, age, smoking status, steroid and anti-inflammatory use, and supplementary as well as dietary calcium and vitamin D were compared. MS patients reporting osteoporosis at baseline were removed, resulting in 355 women with MS to monitor for time to incident osteoporosis. Survival analyses were performed on follow-up data gathered annually between 1993 and 2005 to factor out significant associations of additional factors. Proportions of participants on osteoporosis-related medications as well as latency to use were compared between the multiple sclerosis and control cohorts. Results: At baseline, women with MS are nearly three times as likely to report osteoporosis (p Conclusions: A higher prevalence of osteoporosis at baseline suggests MS may significantly increase the risk of osteoporosis in premenopausal women. In contrast, environmental and pharmacologic variables appear to have a more significant role in the post-menopausal population. While osteoporosis was treated similarly between both groups, the point for intervention or prevention of osteoporosis in MS patients may be earlier in the disease course

Interventions for preventing type 2 diabetes in adults with mental disorders in low and middle income countries

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of pharmacological, behaviour change, and organisational interventions compared to comparator intervention in preventing diabetes among people with mental illness in LMICs

Clinical Trials and Medical Care: Defining the Therapeutic Misconception

A key component of informed consent to participate in medical research includes understanding that research is not the same as treatment

Genetic architecture of heart mitochondrial proteome influencing cardiac hypertrophy.

Mitochondria play an important role in both normal heart function and disease etiology. We report analysis of common genetic variations contributing to mitochondrial and heart functions using an integrative proteomics approach in a panel of inbred mouse strains called the Hybrid Mouse Diversity Panel (HMDP). We performed a whole heart proteome study in the HMDP (72 strains, n=2-3 mice) and retrieved 848 mitochondrial proteins (quantified in ≥50 strains). High- resolution association mapping on their relative abundance levels revealed three trans-acting genetic loci on chromosomes (chr) 7, 13 and 17 that regulate distinct classes of mitochondrial proteins as well as cardiac hypertrophy. DAVID enrichment analyses of genes regulated by each of the loci revealed that the chr13 locus was highly enriched for complex-I proteins (24 proteins, P=2.2E-61), the chr17 locus for mitochondrial ribonucleoprotein complex (17 proteins, P=3.1E-25) and the chr7 locus for ubiquinone biosynthesis (3 proteins, P=6.9E-05). Follow-up high resolution regional mapping identified NDUFS4, LRPPRC and COQ7 as the candidate genes for chr13, chr17 and chr7 loci, respectively, and both experimental and statistical analyses supported their causal roles. Furthermore, a large cohort of Diversity Outbred mice was used to corroborate Lrpprc gene as a driver of mitochondrial DNA (mtDNA)-encoded gene regulation, and to show that the chr17 locus is specific to heart. Variations in all three loci were associated with heart mass in at least one of two independent heart stress models, namely, isoproterenol-induced heart failure and diet-induced obesity. These findings suggest that common variations in certain mitochondrial proteins can act in trans to influence tissue-specific mitochondrial functions and contribute to heart hypertrophy, eluci- dating mechanisms that may underlie genetic susceptibility to heart failure in human populations

Interventions for Complex Traumatic Events (INCiTE): Systematic review and research prioritisation exercise

Background: People with a history of complex traumatic events typically experience trauma and stressor disorders and additional mental comorbidities. It is not known if existing evidence-based treatments are effective and acceptable for this group of people. Objective: To identify candidate psychological and non-pharmacological treatments for future research. Design: Mixed-methods systematic review. Participants: Adults aged 65 18 years with a history of complex traumatic events. Interventions: Psychological interventions versus control or active control; pharmacological interventions versus placebo. Main outcome measures: Post-traumatic stress disorder symptoms, common mental health problems and attrition. Data sources: Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 onwards); Cochrane Central Register of Controlled Trials (CENTRAL) (from inception); EMBASE (1974 to 2017 week 16); International Pharmaceutical Abstracts (1970 onwards); MEDLINE and MEDLINE Epub Ahead of Print and In-Process &amp; Other Non-Indexed Citations (1946 to present); Published International Literature on Traumatic Stress (PILOTS) (1987 onwards); PsycINFO (1806 to April week 2 2017); and Science Citation Index (1900 onwards). Searches were conducted between April and August 2017. Review methods: Eligible studies were singly screened and disagreements were resolved at consensus meetings. The risk of bias was assessed using the Cochrane risk-of-bias tool and a bespoke version of a quality appraisal checklist used by the National Institute for Health and Care Excellence. A meta-analysis was conducted across all populations for each intervention category and for population subgroups. Moderators of effectiveness were assessed using metaregression and a component network meta-analysis. A qualitative synthesis was undertaken to summarise the acceptability of interventions with the relevance of findings assessed by the GRADE-CERQual checklist. Results: One hundred and four randomised controlled trials and nine non-randomised controlled trials were included. For the qualitative acceptability review, 4324 records were identified and nine studies were included. The population subgroups were veterans, childhood sexual abuse victims, war affected, refugees and domestic violence victims. Psychological interventions were superior to the control post treatment for reducing post-traumatic stress disorder symptoms (standardised mean difference -0.90, 95% confidence interval -1.14 to -0.66; number of trials = 39) and also for associated symptoms of depression, but not anxiety. Trauma-focused therapies were the most effective interventions across all populations for post-traumatic stress disorder and depression. Multicomponent and trauma-focused interventions were effective for negative self-concept. Phase-based approaches were also superior to the control for post-traumatic stress disorder and depression and showed the most benefit for managing emotional dysregulation and interpersonal problems. Only antipsychotic medication was effective for reducing post-traumatic stress disorder symptoms; medications were not effective for mental comorbidities. Eight qualitative studies were included. Interventions were more acceptable if service users could identify benefits and if they were delivered in ways that accommodated their personal and social needs. Limitations: Assessments about long-term effectiveness of interventions were not possible. Studies that included outcomes related to comorbid psychiatric states, such as borderline personality disorder, and populations from prisons and humanitarian crises were under-represented. Conclusions: Evidence-based psychological interventions are effective and acceptable post treatment for reducing post-traumatic stress disorder symptoms and depression and anxiety in people with complex trauma. These interventions were less effective in veterans and had less of an impact on symptoms associated with complex post-traumatic stress disorder. Future work: Definitive trials of phase-based versus non-phase-based interventions with long-term follow-up for post-traumatic stress disorder and associated mental comorbidities. Study registration: This study is registered as PROSPERO CRD42017055523. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 43. See the NIHR Journals Library website for further project information

QTL mapping in autotetraploids using SNP dosage information

Dense linkage maps derived by analysing SNP dosage in autotetraploids provide detailed information about the location of, and genetic model at, quantitative trait loci. Recent developments in sequencing and genotyping technologies enable researchers to generate high-density single nucleotide polymorphism (SNP) genotype data for mapping studies. For polyploid species, the SNP genotypes are informative about allele dosage, and Hackett et al. (PLoS ONE 8:e63939, 2013) presented theory about how dosage information can be used in linkage map construction and quantitative trait locus (QTL) mapping for an F1 population in an autotetraploid species. Here, QTL mapping using dosage information is explored for simulated phenotypic traits of moderate heritability and possibly non-additive effects. Different mapping strategies are compared, looking at additive and more complicated models, and model fitting as a single step or by iteratively re-weighted modelling. We recommend fitting an additive model without iterative re-weighting, and then exploring non-additive models for the genotype means estimated at the most likely position. We apply this strategy to re-analyse traits of high heritability from a potato population of 190 F1 individuals: flower colour, maturity, height and resistance to late blight (Phytophthora infestans (Mont.) de Bary) and potato cyst nematode (Globodera pallida), using a map of 3839 SNPs. The approximate confidence intervals for QTL locations have been improved by the detailed linkage map, and more information about the genetic model at each QTL has been revealed. For several of the reported QTLs, candidate SNPs can be identified, and used to propose candidate trait genes. We conclude that the high marker density is informative about the genetic model at loci of large effects, but that larger populations are needed to detect smaller QTLs

The process and delivery of CBT for depression in adults: a systematic review and network meta-analysis

Cognitive-behavioural therapy (CBT) is an effective treatment for depressed adults. CBT interventions are complex, as they include multiple content components and can be delivered in different ways. We compared the effectiveness of different types of therapy, different components and combinations of components and aspects of delivery used in CBT interventions for adult depression. We conducted a systematic review of randomised controlled trials in adults with a primary diagnosis of depression, which included a CBT intervention. Outcomes were pooled using a component-level network meta-analysis. Our primary analysis classified interventions according to the type of therapy and delivery mode. We also fitted more advanced models to examine the effectiveness of each content component or combination of components. We included 91 studies and found strong evidence that CBT interventions yielded a larger short-term decrease in depression scores compared to treatment-as-usual, with a standardised difference in mean change of −1.11 (95% credible interval −1.62 to −0.60) for face-to-face CBT, −1.06 (−2.05 to −0.08) for hybrid CBT, and −0.59 (−1.20 to 0.02) for multimedia CBT, whereas wait list control showed a detrimental effect of 0.72 (0.09 to 1.35). We found no evidence of specific effects of any content components or combinations of components. Technology is increasingly used in the context of CBT interventions for depression. Multimedia and hybrid CBT might be as effective as face-to-face CBT, although results need to be interpreted cautiously. The effectiveness of specific combinations of content components and delivery formats remain unclear. Wait list controls should be avoided if possible

Efficacy and acceptability of psychosocial interventions in asylum seekers and refugees: systematic review and meta-analysis

Abstract Aims. In the past few years, there has been an unprecedented increase in the number of forcibly displaced migrants worldwide, of which a substantial proportion is refugees and asylum seekers. Refugees and asylum seekers may experience high levels of psychological distress, and show high rates of mental health conditions. It is therefore timely and particularly relevant to assess whether current evidence supports the provision of psychosocial interventions for this population. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the efficacy and acceptability of psychosocial interventions compared with control conditions (treatment as usual/no treatment, waiting list, psychological placebo) aimed at reducing mental health problems in distressed refugees and asylum seekers. Methods. We used Cochrane procedures for conducting a systematic review and meta-analysis of RCTs. We searched for published and unpublished RCTs assessing the efficacy and acceptability of psychosocial interventions in adults and children asylum seekers and refugees with psychological distress. Post-traumatic stress disorder (PTSD), depressive and anxiety symptoms at post-intervention were the primary outcomes. Secondary outcomes include: PTSD, depressive and anxiety symptoms at follow-up, functioning, quality of life and dropouts due to any reason. Results. We included 26 studies with 1959 participants. Meta-analysis of RCTs revealed that psychosocial interventions have a clinically significant beneficial effect on PTSD (standardised mean difference [SMD] = −0.71; 95% confidence interval [CI] −1.01 to −0.41; I2 = 83%; 95% CI 78–88; 20 studies, 1370 participants; moderate quality evidence), depression (SMD = −1.02; 95% CI −1.52 to −0.51; I2 = 89%; 95% CI 82–93; 12 studies, 844 participants; moderate quality evidence) and anxiety outcomes (SMD = −1.05; 95% CI −1.55 to −0.56; I2 = 87%; 95% CI 79–92; 11 studies, 815 participants; moderate quality evidence). This beneficial effect was maintained at 1 month or longer follow-up, which is extremely important for populations exposed to ongoing post-migration stressors. For the other secondary outcomes, we identified a non-significant trend in favour of psychosocial interventions. Most evidence supported interventions based on cognitive behavioural therapies with a trauma-focused component. Limitations of this review include the limited number of studies collected, with a relatively low total number of participants, and the limited available data for positive outcomes like functioning and quality of life. Conclusions. Considering the epidemiological relevance of psychological distress and mental health conditions in refugees and asylum seekers, and in view of the existing data on the effectiveness of psychosocial interventions, these interventions should be routinely made available as part of the health care of distressed refugees and asylum seekers. Evidence-basedguidelines and implementation packages should be developed accordingly