Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome

Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis

Revisiting the distribution of oceanic N₂ fixation and estimating diazotrophic contribution to marine production

Marine N2 fixation supports a significant portion of oceanic primary production by making N2 bioavailable to planktonic communities, in the process influencing atmosphere-ocean carbon fluxes and our global climate. However, the geographical distribution and controlling factors of marine N2 fixation remain elusive largely due to sparse observations. Here we present unprecedented high-resolution underway N2 fixation estimates across over 6000 kilometers of the western North Atlantic. Unexpectedly, we find increasing N2 fixation rates from the oligotrophic Sargasso Sea to North America coastal waters, driven primarily by cyanobacterial diazotrophs. N2 fixation is best correlated to phosphorus availability and chlorophyll-a concentration. Globally, intense N2 fixation activity in the coastal oceans is validated by a meta-analysis of published observations and we estimate the annual coastal N2 fixation flux to be 16.7 Tg N. This study broadens the biogeography of N2 fixation, highlights the interplay of regulating factors, and reveals thriving diazotrophic communities in coastal waters with potential significance to the global nitrogen and carbon cycles

From Research Evidence to “Evidence by Proxy”? Organizational Enactment of Evidence-Based Health Care in Four High-Income Countries

Public Administration Review published by Wiley Periodicals, Inc. on behalf of The American Society for Public Administration. Drawing on multiple qualitative case studies of evidence-based health care conducted in Sweden, Canada, Australia, and the United Kingdom, the authors systematically explore the composition, circulation, and role of codified knowledge deployed in the organizational enactment of evidence-based practice. The article describes the “chain of codified knowledge,” which reflects the institutionalization of evidence-based practice as organizational business as usual, and shows that it is dominated by performance standards, policies and procedures, and locally collected (improvement and audit) data. These interconnected forms of “evidence by proxy,” which are informed by research partly or indirectly, enable simplification, selective reinforcement, and contextualization of scientific knowledge. The analysis reveals the dual effects of this codification dynamic on evidence-based practice and highlights the influence of macro-level ideological, historical, and technological factors on the composition and circulation of codified knowledge in the organizational enactment of evidence-based health care in different countries

Mobilising evidence to improve nursing practice: A qualitative study of leadership roles and processes in four countries

© 2018 Elsevier Ltd Background: The approach and style of leaders is known to be an important factor influencing the translation of research evidence into nursing practice. However, questions remain as to what types of roles are most effective and the specific mechanisms through which influence is achieved. Objectives: The aim of the study was to enhance understanding of the mechanisms by which key nursing roles lead the implementation of evidence-based practice across different care settings and countries and the contextual factors that influence them. Design: The study employed a qualitative descriptive approach. Settings: Data collection was undertaken in acute care and primary/community health care settings in Australia, Canada, England and Sweden. Participants: 55 individuals representing different levels of the nursing leadership structure (executive to frontline), roles (managers and facilitators), sectors (acute and primary/community) and countries. Methods: Individual semi-structured interviews were conducted with all participants exploring their roles and experiences of leading evidence-based practice. Data were analysed through a process of qualitative content analysis. Results: Different countries had varying structural arrangements and roles to support evidence-based nursing practice. At a cross-country level, three main themes were identified relating to different mechanisms for enacting evidence-based practice, contextual influences at a policy, organisational and service delivery level and challenges of leading evidence-based practice. Conclusions: National policies around quality and performance shape priorities for evidence-based practice, which in turn influences the roles and mechanisms for implementation that are given prominence. There is a need to maintain a balance between the mechanisms of managing and monitoring performance and facilitating critical questioning and reflection in and on practice. This requires a careful blending of managerial and facilitative leadership. The findings have implications for theory, practice, education and research relating to implementation and evidence-based practice

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

Revisiting the distribution of oceanic N 2 fixation and estimating diazotrophic contribution to marine production

Marine N 2 fixation supports a significant portion of oceanic primary production by making N 2 bioavailable to planktonic communities, in the process influencing atmosphere-ocean carbon fluxes and our global climate. However, the geographical distribution and controlling factors of marine N 2 fixation remain elusive largely due to sparse observations. Here we present unprecedented high-resolution underway N 2 fixation estimates across over 6000 kilometers of the western North Atlantic. Unexpectedly, we find increasing N 2 fixation rates from the oligotrophic Sargasso Sea to North America coastal waters, driven primarily by cyanobacterial diazotrophs. N 2 fixation is best correlated to phosphorus availability and chlorophyll-a concentration. Globally, intense N 2 fixation activity in the coastal oceans is validated by a meta-analysis of published observations and we estimate the annual coastal N 2 fixation flux to be 16.7 Tg N. This study broadens the biogeography of N 2 fixation, highlights the interplay of regulating factors, and reveals thriving diazotrophic communities in coastal waters with potential significance to the global nitrogen and carbon cycles

Racism, anti-racist practice and social work: articulating the teaching and learning experiences of Black social workers

In the mid 1990s a Black practice teacher programme was established in Manchester and Merseyside with the primary aim to increase the number of Black practice teachers in social work organisations, and in turn provide a supportive and encouraging learning environment for Black student social workers whilst on placement. In the north‐west of England research has been undertaken, to establish the quality of the practice teaching and student learning taking place with Black practice teachers and students. This paper is an exploration of the ideas generated within the placement process that particularly focused on the discourse of racism and ant‐racist practice. Black students and practice teachers explain their understanding of racism and anti‐racist practice within social work. From the research, the paper will critique some of the ideas concerning anti‐racism. In particular, it will question whether anti‐racist social work practice needs to be re‐evaluated in the light of a context with new migrants, asylum seekers and refugees. It will concluded, by arguing that whilst the terms anti‐racism, Black and Minority Ethnic have resonance as a form of political strategic essentialism, it is important to develop more positive representations in the future