Systematic review of global functioning and quality of life in people with psychotic disorders

Aims People with psychotic disorders face impairments in their global functioning and their quality of life (QoL). The relationship between the two outcomes has not been systematically investigated. Through a systematic review, we aim to explore the presence and extent of associations between global functioning and QoL and establish whether associations depend on the instruments employed.Methods In May 2016, ten electronic databases were searched using a two-phase process to identify articles in which associations between global functioning and QoL were assessed. Basic descriptive data and correlation coefficients between global functioning and QoL instruments were extracted, with the strength of the correlation assessed according to the specifications of Cohen 1988. Results were reported with reference to the Meta-analysis of Observational Studies in Epidemiology guidelines and PRISMA standards. A narrative synthesis was performed due to heterogeneity in methodological approaches.Results Of an initial 15 183 non-duplicate articles identified, 756 were deemed potentially relevant, with 40 studies encompassing 42 articles included. Fourteen instruments for measuring global functioning and 22 instruments for measuring QoL were used. Twenty-nine articles reported linear associations while 19 assessed QoL predictors. Correlations between overall scores varied in strength, primarily dependent on the QoL instrument employed, and whether QoL was objectively or subjectively assessed. Correlations observed for objective QoL measures were consistently larger than those observed for subjective measures, as were correlations for an interviewer than self-assessed QoL. When correlations were assessed by domains of QoL, the highest correlations were found for social domains of QoL, for which most correlations were moderate or higher. Global functioning consistently predicted overall QoL as did depressive and negative symptoms.Conclusions This review is the first to explore the extent of associations between global functioning and QoL in people with psychotic disorders. We consistently found a positive association between global functioning and QoL. The strength of the association was dependent on the QoL instrument employed. QoL domains strongly associated with global functioning were highlighted. The review illustrates the extensive array of instruments used for the assessment of QoL and to a lesser extent global functioning in people with psychotic disorders and provides a framework to understand the different findings reported in the literature. The findings can also inform the future choice of instruments by researchers and/or clinicians. The observed associations reassure that interventions for improving global functioning will have a positive impact on the QoL of people living with a psychotic disorder

Health-related quality of life, functioning and social experiences in people with psychotic disorders

To inform development of a model for health-related quality of life (HRQoL) in people with psychotic disorders, we aimed to assess correlations between utilities and dimension scores for the Assessment of Quality of Life (AQoL)-4D with functioning and social experiences; ascertain if patient housing and clinical status affected correlations; and determine aspects of functioning that jointly predict HRQoL. We analyzed data for 1642 people with an ICD-10 psychotic disorder from the 2010 Australian National Survey of Psychosis. Global functioning was measured with the Personal and Social Performance scale, independent functioning with the Multidimensional Scale of Independent Functioning and social functioning through level of social dysfunction. Social experiences comprised perceived loneliness and experienced stigma. We assessed Spearman’s rank correlation coefficients and undertook linear regression analyses. Moderate associations were found between AQoL-4D utilities and all variables, except experienced stigma. Perceived loneliness had the strongest association. The AQoL-4D social relationships dimension was most strongly associated with social variables; its independent living dimension with global and independent functioning. Correlations between utilities and all variables, except for social dysfunction, were modified by housing. Course of disorder impacted correlations with utilities and independent functioning. Global functioning and social dysfunction were found to jointly predict HRQoL. In conclusion, as the AQoL-4D can differentiate between functioning and social experiences individually and when categorized by housing and clinical status in people with psychosis, predictive models of HRQoL in this population are feasible, and only need include select aspects of functioning and social experiences, particularly perception of loneliness

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

La educación inclusiva frente a las desigualdades sociales: un estado de la cuestion y algunas reflexiones geograficas

Este artículo establece un estado de la cuestión e la educación inclusiva en el mundo y sugiere algunas reflexiones al respecto. El primer apartado recuerda las conexiones ineludibles entre las preocupaciones educativas por la educación inclusiva y las preocupaciones más generales por la desigualdad. El segundo consigna los criterios de búsqueda de las publicaciones académicas, y observa dos grandes temas en sus contenidos: sobre todo, el cambio interno de las escuelas atrae las miradas, pero en segundo plano también el entorno territorial despierta algunas inquietudes. El tercero anota los criterios de búsqueda de la documentación del Banco Mundial, la OCDE y la UNESCO. En este ámbito los simposios de la Oficina Internacional de la Educación de UNESCO revelan una interpretación dispar, aunque convergente, del concepto de educación inclusiva en las distintas regiones mundiales. Asimismo, todas las publicaciones oficiales muestran una atención prioritaria a las dinámicas internas de las escuelas, puesto que apenas algunas esbozan ciertas relaciones entre la educación inclusiva y las políticas públicas. El último apartado adelanta varios argumentos a favor de una mayor consideración de las escalas local y estatal de la educación inclusiva. Las principales razones para atender a la dimensión local provienen de la causalidad acumulativa de las privaciones sociales, de la necesidad de articular la acción de las escuelas y de la posibilidad de abrir un espacio significativo para la participación ciudadana. Asimismo, las principales razones para atender a la dimensión estatal surgen de las posibles sinergias entre la educación inclusiva y la expansión educativa (p. ej. ¿es correlativo el avance de la escolarización en los distintos ciclos escolares?) como también entre la educación inclusiva y la protección social (p. ej. ¿tienen una implicación pedagógica consistente las abundantes condiciones educativas de las transferencias sociales?

Expression of a Serine Protease Gene prC Is Up-Regulated by Oxidative Stress in the Fungus Clonostachys rosea: Implications for Fungal Survival

BACKGROUND: Soil fungi face a variety of environmental stresses such as UV light, high temperature, and heavy metals. Adaptation of gene expression through transcriptional regulation is a key mechanism in fungal response to environmental stress. In Saccharomyces cerevisiae, the transcription factors Msn2/4 induce stress-mediated gene expression by binding to the stress response element. Previous studies have demonstrated that the expression of extracellular proteases is up-regulated in response to heat shock in fungi. However, the physiological significance of regulation of these extracellular proteases by heat shock remains unclear. The nematophagous fungus Clonostachys rosea can secret an extracellular serine protease PrC during the infection of nematodes. Since the promoter of prC has three copies of the stress response element, we investigated the effect of environmental stress on the expression of prC. METHODOLOGY/PRINCIPAL FINDINGS: Our results demonstrated that the expression of prC was up-regulated by oxidants (H(2)O(2) or menadione) and heat shock, most likely through the stress response element. After oxidant treatment or heat shock, the germination of conidia in the wild type strain was significantly higher than that in the prC mutant strain in the presence of nematode cuticle. Interestingly, the addition of nematode cuticle significantly attenuated the production of reactive oxygen species (ROS) induced by oxidants and heat shock in the wild type strain, but not in prC mutant strain. Moreover, low molecule weight (<3 kD) degradation products of nematode cuticle suppressed the inhibitory effect of conidial germination induced by oxidants and heat shock. CONCLUSIONS/SIGNIFICANCE: These results indicate that PrC plays a protective role in oxidative stress in C. rosea. PrC degrades the nematode cuticle to produce degradation products, which in turn offer a protective effect against oxidative stress by scavenging ROS. Our study reveals a novel strategy for fungi to adapt to environmental stress

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation

A reflective perspective on the challenges facing research-led teaching in the performing and creative arts

This article provides a reflective perspective on the role that research-led teaching plays in the development of future arts workers in higher education. It explores the challenges faced by lecturers developing curricula in the performing and creative arts and argues that the increasing focus on employability can conflict with universities’ traditional aim of developing conceptual and critical thinkers. The article charges that the UK’s higher education sector is rapidly transforming itself into a two-tier system, which is serving to dichotomise vocational and academic learning even further. It concludes with a call for universities, students and employers to reject the false dichotomy between vocational and academic learning and perceive education in a more holistic, longitudinal sense, which might in turn develop more balanced graduates who excel in networked knowledge, conceptual and theoretical imagination and critical, lateral thinking

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)