Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells

Wolbachia are intracellular maternally inherited bacteria that can spread through insect populations and block virus transmission by mosquitoes, providing an important approach to dengue control. To better understand the mechanisms of virus inhibition, we here perform proteomic quantification of the effects of Wolbachia in Aedes aegypti mosquito cells and midgut. Perturbations are observed in vesicular trafficking, lipid metabolism and in the endoplasmic reticulum that could impact viral entry and replication. Wolbachia-infected cells display a differential cholesterol profile, including elevated levels of esterified cholesterol, that is consistent with perturbed intracellular cholesterol trafficking. Cyclodextrins have been shown to reverse lipid accumulation defects in cells with disrupted cholesterol homeostasis. Treatment of Wolbachia-infected Ae. aegypti cells with 2-hydroxypropyl-β-cyclodextrin restores dengue replication in Wolbachia-carrying cells, suggesting dengue is inhibited in Wolbachia-infected cells by localised cholesterol accumulation. These results demonstrate parallels between the cellular Wolbachia viral inhibition phenotype and lipid storage genetic disorders

The Psychopathology and Neuroanatomical Markers of Depression in Early Psychosis

Depression frequently occurs in first-episode psychosis (FEP) and predicts longer-term negative outcomes. It is possible that this depression is seen primarily in a distinct subgroup, which if identified could allow targeted treatments. We hypothesize that patients with recent-onset psychosis (ROP) and comorbid depression would be identifiable by symptoms and neuroanatomical features similar to those seen in recent-onset depression (ROD). Data were extracted from the multisite PRONIA study: 154 ROP patients (FEP within 3 months of treatment onset), of whom 83 were depressed (ROP+D) and 71 who were not depressed (ROP-D), 146 ROD patients, and 265 healthy controls (HC). Analyses included a (1) principal component analysis that established the similar symptom structure of depression in ROD and ROP+D, (2) supervised machine learning (ML) classification with repeated nested cross-validation based on depressive symptoms separating ROD vs ROP+D, which achieved a balanced accuracy (BAC) of 51%, and (3) neuroanatomical ML-based classification, using regions of interest generated from ROD subjects, which identified BAC of 50% (no better than chance) for separation of ROP+D vs ROP-D. We conclude that depression at a symptom level is broadly similar with or without psychosis status in recent-onset disorders; however, this is not driven by a separable depressed subgroup in FEP. Depression may be intrinsic to early stages of psychotic disorder, and thus treating depression could produce widespread benefit

Soft systems methodology: a context within a 50-year retrospective of OR/MS

Soft systems methodology (SSM) has been used in the practice of operations research and management science OR/MS) since the early 1970s. In the 1990s, it emerged as a viable academic discipline. Unfortunately, its proponents consider SSM and traditional systems thinking to be mutually exclusive. Despite the differences claimed by SSM proponents between the two, they have been complementary. An extensive sampling of the OR/MS literature over its entire lifetime demonstrates the richness with which the non-SSM literature has been addressing the very same issues as does SSM

Stakeholder perspectives on shale gas fracking: A Q-method study of environmental discourses

The rapid expansion of shale gas exploration worldwide is a significant source of environmental controversy. Successful shale gas policymaking is dependent upon a clear understanding of the dynamics of competing stakeholder perspectives on these issues, and so methods are needed to delineate the areas of agreement and conflict that emerge. This empirical study, based in the United Kingdom, examines emergent perspectives on a range of environmental, health and socio-economic impacts associated with shale gas fracking using Q- methodology: a combined qualitative-quantitative approach. The analysis reveals three typologies of perspectives amongst key industry, civil society and non-affiliated citizen stakeholders; subsequently contextualised in relation to Dryzek’s typology of environmental discourses. These are labelled A) “Don’t trust the fossil fuels industry: campaign for renewables” (mediating between sustainable development and democratic pragmatism discourses); B) “Shale gas is a bridge fuel: economic growth and environmental scepticism” (mediating between economic rationalism and ecological modernisation discourses); and C) “Take place protective action and legislate in the public interest” (reflecting a discourse of administrative rationalism). The implications of these competing discourses for nascent shale gas policy in the UK are discussed in light of recent Government public consultation on changes to national planning policy

Self-management of chronic low back pain: Four viewpoints from patients and healthcare providers

A move towards self-management is central to health strategy around chronic low back pain, but its concept and meaning for those involved are poorly understood. In the reported study, four distinct and shared viewpoints on self-management were identified among people with pain and healthcare providers using Q methodology. Each construes self-management in a distinctive manner and articulates a different vision of change. Identification of similarities and differences among the viewpoints holds potential for enhancing communication between patients and healthcare providers and for better understanding the complexities of self-management in practice

General psychopathology links burden of recent life events and psychotic symptoms in a network approach

Recent life events have been implicated in the onset and progression of psychosis. However, psychological processes that account for the association are yet to be fully understood. Using a network approach, we aimed to identify pathways linking recent life events and symptoms observed in psychosis. Based on previous literature, we hypothesized that general symptoms would mediate between recent life events and psychotic symptoms. We analyzed baseline data of patients at clinical high risk for psychosis and with recent-onset psychosis (n = 547) from the Personalised Prognostic Tools for Early Psychosis Management (PRONIA) study. In a network analysis, we modeled links between the burden of recent life events and all individual symptoms of the Positive and Negative Syndrome Scale before and after controlling for childhood trauma. To investigate the longitudinal associations between burden of recent life events and symptoms, we analyzed multiwave panel data from seven timepoints up to month 18. Corroborating our hypothesis, burden of recent life events was connected to positive and negative symptoms through general psychopathology, specifically depression, guilt feelings, anxiety and tension, even after controlling for childhood trauma. Longitudinal modeling indicated that on average, burden of recent life events preceded general psychopathology in the individual. In line with the theory of an affective pathway to psychosis, recent life events may lead to psychotic symptoms via heightened emotional distress. Life events may be one driving force of unspecific, general psychopathology described as characteristic of early phases of the psychosis spectrum, offering promising avenues for interventions

Risk perception of women during high risk pregnancy: A systematic review

Risk perception in women with high risk pregnancies can affect their attitude to medical care and therefore influence the wellbeing of mother and baby. This article reviews quantitative measures of risk perception in women with high risk pregnancies. A systematic search of eight electronic databases was conducted. Additional articles were obtained through searching references of identified articles. Seven studies were identified that reported quantitative measures of risk perception in relation to high risk pregnancy. The main findings were that women with high risk pregnancies perceive themselves and the pregnancies to be at risk. However, mean risk scores consistently fall below the midpoint on risk perception measures suggesting women do not perceive this risk as extreme. Women with high risk pregnancies consistently rated their risk as being greater than that of women with low risk pregnancies. Results were inconsistent for the association between women's risk perception and that of healthcare professionals. Women with higher socio-economic status were more likely to be concerned about risk, although lower socio-economic status is associated with increased risk in pregnancy. There was a consistent association between high risk pregnancy and higher levels of anxiety. This review indicates that women at high risk during pregnancy do not perceive this risk to be extreme and that there is poor agreement between women's and healthcare professionals’ perceptions of risk. This is likely to have implications for medical care and pregnancy outcomes

An Alternative Ethics? Justice and Care as Guiding Principles for Qualitative Research

The dominant conception of social research ethics is centred on deontological and consequentialist principles. In place of this, some qualitative researchers have proposed a very different approach. This appeals to a range of commitments that transform the goal of research as well as framing how it is pursued. This new ethics demands a participatory form of inquiry, one in which the relationship between researchers and researched is equalized. In this paper we examine this alternative approach, focusing in particular on two of the principles that are central to it: justice and care. We argue that there are some significant defects and dangers associated with this new conception of research ethics

How service‐users with intellectual disabilities understand challenging behaviour and approaches to managing it

Background This study explored understandings that service‐users with intellectual disabilities and challenging behaviour held around their behaviour, what shaped these understandings, and the relationship between how behaviours are managed and well‐being. Methods Eight participants (three female, five male) partook in individual semi‐structured qualitative interviews. Interviews were transcribed and analysed using interpretative phenomenological analysis. Results Three master themes emerged from this analysis: (a) challenging behaviour can be explained via an internal or external frame of reference, with each framework having different implications for how participants attempted to manage behaviour. (b) Positive relationships provide a long‐term buffer to challenging behaviour, with positive relationships with family, staff and peers operating through different mechanisms to achieve this. (c) A greater ability to exert power and control in day‐to‐day life was perceived to reduce challenging behaviour in the long term. Conclusions Implications for practice are discussed

Growing up beside you: a relational sociology of early childhood

This article will begin by outlining influential attempts by historians and sociologists to develop a more adequate theoretical understanding of past and contemporary childhoods, focusing on the major problems that stem from the pivotal role that ‘developmentalism’ plays in their arguments. I will argue that sociologists can overcome some of their deepest fears about the role of developmental psychology by developing a relational approach that integrates the biological and social aspects of children’s development. In the development of a relational sociology of early childhood we need to make important connections with closely related disciplines, but at the same time draw on and integrate research findings from relevant areas within the social and natural sciences. An alternative perspective drawn from the writings of Norbert Elias will be put forward and illustrated by discussing some of the key concepts that Elias and Vygotsky used to explain the language development of young children