The OPERA trial : a protocol for the process evaluation of a randomised trial of an exercise intervention for older people in residential and nursing accommodation

Background: The OPERA trial is large cluster randomised trial testing a physical activity intervention to address depression amongst people living in nursing and residential homes for older people. A process evaluation was commissioned alongside the trial and we report the protocol for this process evaluation. Challenges included the cognitive and physical ability of the participants, the need to respect the privacy of all home residents, including study non-participants, and the physical structure of the homes. Evaluation activity had to be organised around the structured timetable of homes, leaving limited opportunities for data collection. The aims of this process evaluation are to provide findings that will assist in the interpretation of the clinical trial results, and to inform potential implementation of the physical activity intervention on a wider scale. Methods/design: Quantitative data on recruitment of homes and individuals is being collected. For homes in the intervention arm, data on dose and fidelity of the intervention delivered; including individual rates of participation in exercise classes are collected. In the control homes, uptake and delivery of depression awareness training is monitored. These data will be combined with qualitative data from an in-depth study of a purposive sample of eight homes (six intervention and two control). Discussion: Although process evaluations are increasingly funded alongside trials, it is still rare to see the findings published, and even rarer to see the protocol for such an evaluation published. Process evaluations have the potential to assist in interpreting and understanding trial results as well as informing future roll-outs of interventions. If such evaluations are funded they should also be reported and reviewed in a similar way to the trial outcome evaluation

Editing reality in the brain

Recent information technologies such as virtual reality (VR) and augmented reality (AR) allow the creation of simulated sensory worlds with which we can interact. Using programming language, digital details can be overlaid onto displays of our environment, confounding what is real and what has been artificially engineered. Natural language, particularly the use of direct verbal suggestion (DVS) in everyday and hypnotic contexts, can also manipulate the meaning and significance of objects and events in ourselves and others. In this review, we focus on how socially rewarding language can construct and influence reality. Language is symbolic, automatic and flexible and can be used to augment bodily sensations e.g. feelings of heaviness in a limb or suggest a colour that is not there. We introduce the term ‘suggested reality’ (SR) to refer to the important role that language, specifically DVS, plays in constructing, maintaining and manipulating our shared reality. We also propose the term edited reality to encompass the wider influence of information technology and linguistic techniques that results in altered subjective experience and review its use in clinical settings, while acknowledging its limitations. We develop a cognitive model indicating how the brain’s central executive structures use our personal and linguistic-based narrative in subjective awareness, arguing for a central role for language in DVS. A better understanding of the characteristics of VR, AR and SR and their applications in everyday life, research and clinical settings can help us to better understand our own reality and how it can be edited

Early breastfeeding practices: Descriptive analysis of recent Demographic and Health Surveys.

The aim of this study was to describe early breastfeeding practices (initiation within 1 hr of birth, no prelacteal feeding, and a combination of both-"optimal" early breastfeeding) according to childbirth location in low- and middle-income countries. Using data from the most recent Demographic and Health Survey (2000-2013) for 57 countries, we extracted information on the most recent birth for women aged 15-49 with a live birth in the preceding 24 months. Childbirth setting was self-reported by location (home or facility) and subtype (home delivery with or without a skilled birth attendant; public or private facility). We produced overall world and four region-level summary statistics by applying national population adjusted survey weights. Overall, 39% of children were breastfed within 1 hr of birth (region range 31-60%), 49% received no prelacteal feeding (41-65%), and 28% benefited from optimal early breastfeeding (21-46%). In South/Southeast Asia and Sub-Saharan Africa, early breastfeeding outcomes were more favourable for facility births compared to home births; trends were less consistent in Latin America and Middle East/Europe. Among home deliveries, there was a higher prevalence of positive breastfeeding practices for births with a skilled birth attendant across all regions other than Latin America. For facility births, breastfeeding practices were more favourable among those taking place in the public sector. This study is the most comprehensive assessment to date of early breastfeeding practices by childbirth location. Our results suggest that skilled delivery care-particularly care delivered in public sector facilities-appears positively correlated with favourable breastfeeding practices

A web-based tool for eliciting probability distributions from experts

We present a web-based probability distribution elicitation tool: The MATCH Uncertainty Elicitation Tool. The Tool is designed to help elicit probability distributions about uncertain model parameters from experts, in situations where suitable data is either unavailable or sparse. The Tool is free to use, and offers five different techniques for eliciting univariate probability distributions. A key feature of the Tool is that users can log in from different sites and view and interact with the same graphical displays, so that expert elicitation sessions can be conducted remotely (in conjunction with tele- or videoconferencing). This will make probability elicitation easier in situations where it is difficult to interview experts in person. Even when conducting elicitation remotely, interviewers will be able to follow good elicitation practice, advise the experts, and provide instantaneous feedback and assistance

Giving up on consciousness as the ghost in the machine

Consciousness as used here, refers to the private, subjective experience of being aware of our perceptions, thoughts, feelings, actions, memories (psychological contents) including the intimate experience of a unified self with the capacity to generate and control actions and psychological contents. This compelling, intuitive consciousnesscentric account has, and continues to shape folk and scientific accounts of psychology and human behavior. Over the last 30 years, research from the cognitive neurosciences has challenged this intuitive social construct account when providing a neurocognitive architecture for a human psychology. Growing evidence suggests that the executive functions typically attributed to the experience of consciousness are carried out competently, backstage and outside subjective awareness by a myriad of fast, efficient non-conscious brain systems. While it remains unclear how and where the experience of consciousness is generated in the brain, we suggested that the traditional intuitive explanation that consciousness is causally efficacious is wrong-headed when providing a cognitive neuroscientific account of human psychology. Notwithstanding the compelling 1st-person experience (inside view) that convinces us that subjective awareness is the mental curator of our actions and thoughts, we argue that the best framework for building a scientific account is to be consistent with the biophysical causal dependency of prior neural processes. From a 3rd person perspective, (outside view), we propose that subjective awareness lacking causal influence, is (no more) than our experience of being aware, our awareness of our psychological content, knowing that we are aware, and the belief that that such experiences are evidence of an agentive capacity shared by others. While the human mind can be described as comprising both conscious and nonconscious aspects, both ultimately depend on neural process in the brain. In arguing for the counter-intuitive epiphenomenal perspective, we suggest that a scientific approach considers all mental aspects of mind including consciousness in terms of their underlying, preceding (causal) biological changes, in the realization that most brain processes are not accompanied by any discernible change in subjective awareness

Identification and molecular genetic analysis of the cichorine gene cluster in Aspergillus nidulans

We recently demonstrated that the phytotoxin cichorine is produced by Aspergillus nidulans. Through a set of targeted deletions, we have found a cluster of seven genes that are required for its biosynthesis. Two of the deletions yielded molecules that give information about the biosynthesis of this metabolite

Novel Compound Heterozygous Mutations Expand the Recognized Phenotypes of \u3cem\u3eFARS2\u3c/em\u3e-linked Disease

Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins

The c-Rel Subunit of NF-κB Regulates Epidermal Homeostasis and Promotes Skin Fibrosis in Mice

The five subunits of transcription factor NF-κB have distinct biological functions. NF-κB signaling is important for skin homeostasis and aging, but the contribution of individual subunits to normal skin biology and disease is unclear. Immunohistochemical analysis of the p50 and c-Rel subunits within lesional psoriatic and systemic sclerosis skin revealed abnormal epidermal expression patterns, compared with healthy skin, but RelA distribution was unaltered. The skin of Nfkb1−/− and c-Rel−/− mice is structurally normal, but epidermal thickness and proliferation are significantly reduced, compared with wild-type mice. We show that the primary defect in both Nfkb1−/− and c-Rel−/− mice is within keratinocytes that display reduced proliferation both in vitro and in vivo. However, both genotypes can respond to proliferative stress, with 12-O-tetradecanoylphorbol-13-acetate–induced epidermal hyperproliferation and closure rates of full-thickness skin wounds being equivalent to those of wild-type controls. In a model of bleomycin-induced skin fibrosis, Nfkb1−/− and c-Rel−/− mice displayed opposite phenotypes, with c-Rel−/− mice being protected and Nfkb1−/− developing more fibrosis than wild-type mice. Taken together, our data reveal a role for p50 and c-Rel in regulating epidermal proliferation and homeostasis and a profibrogenic role for c-Rel in the skin, and identify a link between epidermal c-Rel expression and systemic sclerosis. Modulating the actions of these subunits could be beneficial for treating hyperproliferative or fibrogenic diseases of the skin

Sequential design of computer experiments for the estimation of a probability of failure

This paper deals with the problem of estimating the volume of the excursion set of a function $f:\mathbb{R}^d \to \mathbb{R}$ above a given threshold, under a probability measure on $\mathbb{R}^d$ that is assumed to be known. In the industrial world, this corresponds to the problem of estimating a probability of failure of a system. When only an expensive-to-simulate model of the system is available, the budget for simulations is usually severely limited and therefore classical Monte Carlo methods ought to be avoided. One of the main contributions of this article is to derive SUR (stepwise uncertainty reduction) strategies from a Bayesian-theoretic formulation of the problem of estimating a probability of failure. These sequential strategies use a Gaussian process model of $f$ and aim at performing evaluations of $f$ as efficiently as possible to infer the value of the probability of failure. We compare these strategies to other strategies also based on a Gaussian process model for estimating a probability of failure.Comment: This is an author-generated postprint version. The published version is available at http://www.springerlink.co

Motherhood on ice? A media framing analysis of older mothers in the UK news

Changing gender roles and increased sexual and economic freedom have created opportunities for women to give birth relatively late in life. However, stigma and misplaced fears about physical capacity are often reported as sources of anxiety among older, and in vitro fertilisation-induced mothers. In this study, we apply a specially adapted method for analysing news media content to a week's selection of material in the British media following the dissemination of research at an international medical conference. Our findings suggest, despite some positive commentaries, that much negative discourse is circulated by the media about older mothers, from implied claims of selfishness (older mothers as 'delaying' conception) to violations of the 'natural order'. These latter claims reflect the long-standing ambivalence by the media generally towards scientific advancement, but they also reveal continuing resistance towards unorthodox lifestyles