Sublethal exposure to copper supresses the ability to acclimate to hypoxia in a model fish species

This is the final version. Available on open access from Elsevier via the DOI in this recordHypoxia is one of the major threats to biodiversity in aquatic systems. The association of hypoxia with nutrient-rich effluent input into aquatic systems results in scenarios where hypoxic waters could be contaminated with a wide range of chemicals, including metals. Despite this, little is known about the ability of fish to respond to hypoxia when exposures occur in the presence of environmental toxicants. We address this knowledge gap by investigating the effects of exposures to different levels of oxygen in the presence or absence of copper using the three-spined sticklebacks (Gasterosteus aculeatus) model. Fish were exposed to different air saturations (AS; 100%, 75% and 50%) in combination with copper (20 μg/L) over a 4 day period. The critical oxygen level (Pcrit), an indicator of acute hypoxia tolerance, was 54.64 ± 2.51% AS under control conditions, and 36.21 ± 2.14% when fish were chronically exposed to hypoxia (50% AS) for 4 days, revealing the ability of fish to acclimate to low oxygen conditions. Importantly, the additional exposure to copper (20 μg/L) prevented this improvement in Pcrit, impairing hypoxia acclimation. In addition, an increase in ventilation rate was observed for combined copper and hypoxia exposure, compared to the single stressors or the controls. Interestingly, in the groups exposed to copper, a large increase in variation in the measured Pcrit was observed between individuals, both under normoxic and hypoxic conditions. This variation, if observed in wild populations, may lead to selection for a tolerant phenotype and alterations in the gene pool of the populations, with consequences for their sustainability. Our findings provide strong evidence that copper reduces the capacity of fish to respond to hypoxia by preventing acclimation and will inform predictions of the consequences of global increases of hypoxia in water systems affected by other pollutants worldwide.University of ExeterCentre for Environment Fisheries and Aquaculture Science (Cefas)Biotechnology and Biological Sciences Research Council (BBSRC)ONICYT-FONDECY

Hypoxia modifies the response to flutamide and linuron in male three-spined stickleback (Gasterosteus aculeatus)

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordHypoxia is a major stressor in aquatic environments and it is frequently linked with excess nutrients resulting from sewage effluent discharges and agricultural runoff, which often also contain complex mixtures of chemicals. Despite this, interactions between hypoxia and chemical toxicity are poorly understood. We exposed male three-spined stickleback during the onset of sexual maturation to a model anti-androgen (flutamide; 250μg/L) and a pesticide with anti-androgenic activity (linuron; 250μg/L), under either 97% or 56% air saturation (AS). We assessed the effects of each chemical, alone and in combination with reduced oxygen concentration, by measuring the transcription of spiggin in the kidney, as a marker of androgen signalling, and 11 genes in the liver involved in some of the molecular pathways hypothesised to be affected by the exposures. Spiggin transcription was strongly inhibited by flutamide under both AS conditions. In contrast, for linuron, a strong inhibition of spiggin was observed under 97% AS, but this effect was supressed under reduced air saturation, likely due to interactions between the hypoxia inducible factor and the aryl hydrocarbon receptor (AhR) pathways. In the liver, hypoxia inducible factor 1α was induced following exposure to both flutamide and linuron, however this was independent of the level of air saturation. This work illustrates the potential for interactions between hypoxia and pollutants with endocrine or AhR agonist activity to occur, with implications for risk assessment and management.Centre for Environment, Fisheries and Aquaculture Scienc

Feasibility of neuromuscular training in patients with severe hip or knee OA: The individualized goal-based NEMEX-TJR training program

<p>Abstract</p> <p>Background</p> <p>Although improvements are achieved by general exercise, training to improve sensorimotor control may be needed for people with osteoarthritis (OA). The aim was to apply the principles of neuromuscular training, which have been successfully used in younger and middle-aged patients with knee injuries, to older patients with severe hip or knee OA. We hypothesized that the training program was feasible, determined as: 1) at most acceptable self-reported pain following training; 2) decreased or unchanged pain during the training period; 3) few joint specific adverse events related to training, and 4) achieved progression of training level during the training period.</p> <p>Methods</p> <p>Seventy-six patients, between 60 and 77 years, with severe hip (n = 38, 55% women) or knee OA (n = 38, 61% women) underwent an individualized, goal-based neuromuscular training program (NEMEX-TJR) in groups for a median of 11 weeks (quartiles 7 to 15) prior to total joint replacement (TJR). Pain was self-reported immediately after each training session on a 0 to 10 cm, no pain to pain as bad as it could be, scale, where 0-2 indicates safe, > 2 to 5 acceptable and > 5 high risk pain. Joint specific adverse events were: not attending or ceasing training because of increased pain/problems in the index joint related to training, and self-reported pain > 5 after training. The level of difficulty of training was registered.</p> <p>Results</p> <p>Patients with severe OA of the hip or knee reported safe pain (median 2 cm) after training. Self-reported pain was lower at training sessions 10 and 20 (p = 0.04) and unchanged at training sessions 5 and 15 (p = 0.170, p = 0.161) compared with training session 1. There were no joint specific adverse events in terms of not attending or ceasing training. Few patients (n = 17, 22%) reported adverse events in terms of self-reported pain > 5 after one or more training sessions. Progression of training level was achieved over time (p < 0.001).</p> <p>Conclusions</p> <p>The NEMEX-TJR training program is feasible in patients with severe hip or knee OA, in terms of safe self-reported pain following training, decreased or unchanged pain during the training period, few joint specific adverse events, and achieved progression of training level during the training period.</p

Alcohol brief interventions practice following training for multidisciplinary health and social care teams: a qualitative interview study

Introduction and Aims: Few studies of the implementation of alcohol brief interventions (ABI) have been conducted in community settings such as mental health, social work and criminal justice teams. This qualitative interview study sought to explore the impact of training on ABI delivery by staff from a variety of such teams. Design and Methods: Fifteen semi-structured telephone interviews were carried out with trained practitioners and with managers to explore the use of, perceived need for and approaches to ABI delivery and recording with clients, and compatibility of ABIs with current practice. Interviews were analysed thematically using an inductive approach. Results: Very few practitioners reported delivery of any ABIs following training primarily because they felt ABIs to be inappropriate for their clients. According to practitioners, this was either because they drank too much or too little to benefit. Practitioners reported a range of current activities relating to alcohol, and some felt that their knowledge and confidence were improved following training. One practitioner reported ABI delivery and was considered a training success, while expectations of ABIs did not fit with current practice including assessment procedures for the remainder. Discussion and Conclusions: Identified barriers to ABI delivery included issues relating to individual practitioners, their teams, current practice and the ABI model. They are likely to be best addressed by strategic team- and setting-specific approaches to implementation, of which training is only one part

Understanding innovators' experiences of barriers and facilitators in implementation and diffusion of healthcare service innovations: A qualitative study

This article is made available through the Brunel Open Access Publishing Fund - Copyright @ 2011 Barnett et al.Background: Healthcare service innovations are considered to play a pivotal role in improving organisational efficiency and responding effectively to healthcare needs. Nevertheless, healthcare organisations encounter major difficulties in sustaining and diffusing innovations, especially those which concern the organisation and delivery of healthcare services. The purpose of the present study was to explore how healthcare innovators of process-based initiatives perceived and made sense of factors that either facilitated or obstructed the innovation implementation and diffusion. Methods: A qualitative study was designed. Fifteen primary and secondary healthcare organisations in the UK, which had received health service awards for successfully generating and implementing service innovations, were studied. In-depth, semi structured interviews were conducted with the organisational representatives who conceived and led the development process. The data were recorded, transcribed and thematically analysed. Results: Four main themes were identified in the analysis of the data: the role of evidence, the function of inter-organisational partnerships, the influence of human-based resources, and the impact of contextual factors. "Hard" evidence operated as a proof of effectiveness, a means of dissemination and a pre-requisite for the initiation of innovation. Inter-organisational partnerships and people-based resources, such as champions, were considered an integral part of the process of developing, establishing and diffusing the innovations. Finally, contextual influences, both intra-organisational and extra-organisational were seen as critical in either impeding or facilitating innovators' efforts. Conclusions: A range of factors of different combinations and co-occurrence were pointed out by the innovators as they were reflecting on their experiences of implementing, stabilising and diffusing novel service initiatives. Even though the innovations studied were of various contents and originated from diverse organisational contexts, innovators' accounts converged to the significant role of the evidential base of success, the inter-personal and inter-organisational networks, and the inner and outer context. The innovators, operating themselves as important champions and being often willing to lead constructive efforts of implementation to different contexts, can contribute to the promulgation and spread of the novelties significantly.This research was supported financially by the Multidisciplinary Assessment of Technology Centre for Healthcare (MATCH)

Prescribing practices of primary-care veterinary practitioners in dogs diagnosed with bacterial pyoderma

Concern has been raised regarding the potential contributions of veterinary antimicrobial use to increasing levels of resistance in bacteria critically important to human health. Canine pyoderma is a frequent, often recurrent diagnosis in pet dogs, usually attributable to secondary bacterial infection of the skin. Lesions can range in severity based on the location, total area and depth of tissue affected and antimicrobial therapy is recommended for resolution. This study aimed to describe patient signalment, disease characteristics and treatment prescribed in a large number of UK, primary-care canine pyoderma cases and to estimate pyoderma prevalence in the UK vet-visiting canine population

Making sense of evidence in management decisions: the role of research-based knowledge on innovation adoption and implementation in healthcare. study protocol

<p>Abstract</p> <p>Background</p> <p>We know that patient care can be improved by implementing evidence-based innovations and applying research findings linked to good practice. Successfully implementing innovations in complex organisations, such as the UK's National Health Service (NHS), is often challenging as multiple contextual dynamics mediate the process. Research studies have explored the challenges of introducing innovations into healthcare settings and have contributed to a better understanding of why potentially useful innovations are not always implemented in practice, even if backed by strong evidence. Mediating factors include health policy and health system influences, organisational factors, and individual and professional attitudes, including decision makers' perceptions of innovation evidence. There has been limited research on how different forms of evidence are accessed and utilised by organisational decision makers during innovation adoption. We also know little about how diverse healthcare professionals (clinicians, administrators) make sense of evidence and how this collective sensemaking mediates the uptake of innovations.</p> <p>Methods</p> <p>The study will involve nine comparative case study sites of acute care organisations grouped into three regional clusters across England. Each of the purposefully selected sites represents a variety of trust types and organisational contexts. We will use qualitative methods, in-depth interviews, observation of key meetings, and systematic analysis of relevant secondary data to understand the rationale and challenges involved in sourcing and utilising innovation evidence in the empirical setting of infection prevention and control. We will use theories of innovation adoption and sensemaking in organisations to interpret the data. The research will provide lessons for the uptake and continuous use of innovations in the English and international health systems.</p> <p>Discussion</p> <p>Unlike most innovation studies, which involve single-level analysis, our study will explore the innovation-adoption process at multiple embedded levels: micro (individual), meso (organisational), and macro (interorganisational). By comparing and contrasting across the nine sites, each with different organisational contexts, local networks, leadership styles, and different innovations considered for adoption, the findings of the study will have wide relevance. The research will produce actionable findings responding to the political and economic need for healthcare organisations to be innovation-ready.</p

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

Modulation of emotional appraisal by false physiological feedback during fMRI

BACKGROUND James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined. METHODOLOGY/PRINCIPAL FINDINGS We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level. CONCLUSIONS/SIGNIFICANCE Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state

Visualizing the Effects of rTMS in a Patient Sample: Small N vs. Group Level Analysis

The use of transcranial magnetic stimulation (TMS) to assess changes in cortical excitability is a tool used with increased prevalence in healthy and impaired populations. One factor of concern with this technique is how to achieve adequate statistical power given constraints of a small number of subjects and variability in responses. This paper compares a single pulse excitability measure using traditional group-level statistics vs single subject analyses in a patient population of subjects with focal hand dystonia, pre and post repetitive TMS (rTMS). Results show significant differences in cortical excitability for 4/5 subjects using a split middle line analysis on plots of individual subject data. Group level statistics (ANOVA), however, did not detect any significant findings. The consideration of single subject statistics for TMS excitability measures may assist researchers in describing the variably of rTMS outcome measures