Collaborative working within UK NHS secondary care and across sectors for COPD and the impact of peer review : qualitative findings from the UK National COPD Resources and Outcomes Project

Introduction: We investigated the effects on collaborative work within the UK National Health Service (NHS) of an intervention for service quality improvement: informal, structured, reciprocated, multidisciplinary peer review with feedback and action plans. The setting was care for chronic obstructive pulmonary disease (COPD). Theory and methods: We analysed semi-structured interviews with 43 hospital respiratory consultants, nurses and general managers at 24 intervention and 11 control sites, as part of a UK randomised controlled study, the National COPD Resources and Outcomes Project (NCROP), using Scott’s conceptual framework for action (inter-organisational, intra-organisational, inter-professional and inter-individual). Three areas of care targeted by NCROP involved collaboration across primary and secondary care. Results: Hospital respiratory department collaborations with commissioners and hospital managers varied. Analysis suggested that this is related to team responses to barriers. Clinicians in unsuccessful collaborations told ‘atrocity stories’ of organisational, structural and professional barriers to service improvement. The others removed barriers by working with government and commissioner agendas to ensure continued involvement in patients’ care. Multidisciplinary peer review facilitated collaboration between participants, enabling them to meet, reconcile differences and exchange ideas across boundaries. Conclusions: The data come from the first randomised controlled trial of organisational peer review, adding to research into UK health service collaborative work, which has had a more restricted focus on inter-professional relations. NCROP peer review may only modestly improve collaboration but these data suggest it might be more effective than top-down exhortations to change when collaboration both across and within organisations is required

Dissecting interferon-induced transcriptional programs in human peripheral blood cells

Interferons are key modulators of the immune system, and are central to the control of many diseases. The response of immune cells to stimuli in complex populations is the product of direct and indirect effects, and of homotypic and heterotypic cell interactions. Dissecting the global transcriptional profiles of immune cell populations may provide insights into this regulatory interplay. The host transcriptional response may also be useful in discriminating between disease states, and in understanding pathophysiology. The transcriptional programs of cell populations in health therefore provide a paradigm for deconvoluting disease-associated gene expression profiles.We used human cDNA microarrays to (1) compare the gene expression programs in human peripheral blood mononuclear cells (PBMCs) elicited by 6 major mediators of the immune response: interferons alpha, beta, omega and gamma, IL12 and TNFalpha; and (2) characterize the transcriptional responses of purified immune cell populations (CD4+ and CD8+ T cells, B cells, NK cells and monocytes) to IFNgamma stimulation. We defined a highly stereotyped response to type I interferons, while responses to IFNgamma and IL12 were largely restricted to a subset of type I interferon-inducible genes. TNFalpha stimulation resulted in a distinct pattern of gene expression. Cell type-specific transcriptional programs were identified, highlighting the pronounced response of monocytes to IFNgamma, and emergent properties associated with IFN-mediated activation of mixed cell populations. This information provides a detailed view of cellular activation by immune mediators, and contributes an interpretive framework for the definition of host immune responses in a variety of disease settings

Heterogeneity in treatment outcomes and incomplete recovery in first episode psychosis:does one size fit all?

The heterogeneity in recovery outcomes for individuals with First Episode Psychosis (FEP) calls for a strong evidence base to inform practice at an individual level. Between 19–89% of young people with FEP have an incomplete recovery despite gold-standard evidence-based treatments, suggesting current service models, which adopt a ‘one-size fits all’ approach, may not be addressing the needs of many young people with psychosis. The lack of consistent terminology to define key concepts such as recovery and treatment resistance, the multidimensional nature of these concepts, and common comorbid symptoms are some of the challenges faced by the field in delineating heterogeneity in recovery outcomes. The lack of robust markers for incomplete recovery also results in potential delay in delivering prompt, and effective treatments to individuals at greatest risk. There is a clear need to adopt a stratified approach to care where interventions are targeted at subgroups of patients, and ultimately at the individual level. Novel machine learning, using large, representative data from a range of modalities, may aid in the parsing of heterogeneity, and provide greater precision and sophistication in identifying those on a pathway to incomplete recovery

Prevalence and impact of chronic widespread pain in the Bangladeshi and White populations of Tower Hamlets, East London

The prevalence and impact of chronic pain differ between ethnic groups. We report a study of the comparative prevalence and impact of chronic pain in Bangladeshi, British Bangladeshi and White British/Irish people. We posted a short questionnaire to a random sample of 4,480 patients registered with 16 general practices in the London Borough of Tower Hamlets and conducted a longer questionnaire with patients in the waiting areas at those practices. We distinguished between Bangladeshi participants who were born in the UK or had arrived in the UK at the age of 14 or under (British Bangladeshi) and those who arrived in UK at the age of over 14 (Bangladeshi). We obtained 1,223/4,480 (27 %) responses to the short survey and 600/637 (94 %) to the long survey. From the former, the prevalence of chronic pain in the White, British Bangladeshi and Bangladeshi groups was 55, 54 and 72 %, respectively. The corresponding figures from the long survey were 49, 45 and 70 %. Chronic widespread pain was commoner in the Bangladeshi (16 %) than in the White (10 %) or British Bangladeshi (9 %) groups. People with chronic pain experienced poorer quality of life (odds ratio for scoring best possible health vs. good health (or good vs. poor health) 5.6 (95 % confidence interval 3.4 to 9.8)), but we found no evidence of differences between ethnic groups in the impact of chronic pain on the quality of life. Chronic pain is commoner and, of greater severity, in Bangladeshis than in Whites. On most measures in this study, British Bangladeshis resembled the Whites more than the Bangladeshis

Understanding the power requirements of autonomous underwater systems, Part I: An analytical model for optimum swimming speeds and cost of transport

Many marine species exhibit capabilities that would be desirable for manmade systems operating in the maritime environment. However, without detracting from the potential, if bioinspiration is to prove beneficial, it is important to have a consistent set of metrics that allow fair comparison, without bias, when comparing the performance of engineered and biological systems. In this study we focus on deriving an unbiased metric of performance applicable to marine animals and engineered subsea vehicles for one of the most fundamental of properties; that of the energy cost of locomotion. We present a rational analytical model of the physics behind the total energy cost of locomotion applicable to both biological and engineered autonomous underwater marine systems. This model proposes the use of an equivalent spheroid efficiency as a fair metric to compare engineered and biological systems. The model is then utilised to identify how changes in mass, speed, spheroid efficiency and hotel load impact the performance of the system

Single Nucleotide Polymorphism in hsa-mir-196a-2 and Breast Cancer Risk: A Case Control Study

microRNAs are small, non-coding RNAs that influence gene expression on a post-transcriptional level. They participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. As they may have an effect on thousands of target mRNAs, single-nucleotide polymorphisms in microRNA genes might have major functional consequences, because the microRNA's properties and/or maturation may change. miR-196a has been reported to be aberrantly expressed in breast cancer tissue. Additionally, the SNP rs11614913 in hsa-mir-196a-2 has been found to be associated with breast cancer risk in some studies although not in others. This study evaluated the association between rs11614913 and breast cancer risk in a Caucasian case-control cohort in Queensland, Australia. Results do not support an association of the tested hsa-mir-196a-2 polymorphism with breast cancer susceptibility in this cohort. As there is a discrepancy between our results and previous findings, it is important to assess the role of rs11614913 in breast cancer by further larger studies investigating different ethnic group

Laser writing of individual atomic defects in a crystal with near-unity yield

Atomic defects in wide band gap materials show great promise for development of a new generation of quantum information technologies, but have been hampered by the inability to produce and engineer the defects in a controlled way. The nitrogen-vacancy (NV) color center in diamond is one of the foremost candidates, with single defects allowing optical addressing of electron spin and nuclear spin degrees of freedom with potential for applications in advanced sensing and computing. Here we demonstrate a method for the deterministic writing of individual NV centers at selected locations with high positioning accuracy using laser processing with online fluorescence feedback. This method provides a new tool for the fabrication of engineered materials and devices for quantum technologies and offers insight into the diffusion dynamics of point defects in solids.Comment: 16 pages, 8 figure

Circumventricular organ apelin receptor knockdown decreases blood pressure and sympathetic drive responses in the spontaneously hypertensive rat

The central site(s) mediating the cardiovascular actions of the apelin-apelin receptor (APJ) system remains a major question. We hypothesized that the sensory circumventricular organs (CVOs), interfacing between the circulation and deeper brain structures, are sites where circulating apelin acts as a signal in the central nervous system to decrease blood pressure (BP). We show that APJ gene (aplnr) expression was elevated in the CVOs of spontaneously hypertensive rats (SHRs) compared to normotensive Wistar Kyoto (WKY) controls, and that there was a greater mean arterial BP (MABP) decrease following microinjection of [Pyr(1)]apelin-13 to the CVOs of SHRs compared to WKY rats. Lentiviral APJ-specific-shRNA (LV-APJ-shRNA) was used to knockdown aplnr expression, both collectively in three CVOs and discretely in individual CVOs, of rats implanted with radiotelemeters to measure arterial pressure. LV-APJ-shRNA-injection decreased aplnr expression in the CVOs and abolished MABP responses to microinjection of [Pyr(1)]apelin-13. Chronic knockdown of aplnr in any of the CVOs, collectively or individually, did not affect basal MABP in SHR or WKY rats. Moreover, knockdown of aplnr in any of the CVOs individually did not affect the depressor response to systemic [Pyr(1)]apelin-13. By contrast, multiple knockdown of aplnr in the three CVOs reduced acute cardiovascular responses to peripheral [Pyr(1)]apelin-13 administration in SHR but not WKY rats. These results suggest that endogenous APJ activity in the CVOs has no effect on basal BP but that functional APJ in the CVOs is required for an intact cardiovascular response to peripherally administered apelin in the SHR

Development of quantum perspectives in modern physics

Introductory undergraduate courses in classical physics stress a perspective that can be characterized as realist; from this perspective, all physical properties of a classical system can be simultaneously specified and thus determined at all future times. Such a perspective can be problematic for introductory quantum physics students, who must develop new perspectives in order to properly interpret what it means to have knowledge of quantum systems. We document this evolution in student thinking in part through pre- and post-instruction evaluations using the Colorado Learning Attitudes about Science Survey. We further characterize variations in student epistemic and ontological commitments by examining responses to two essay questions, coupled with responses to supplemental quantum attitude statements. We find that, after instruction in modern physics, many students are still exhibiting a realist perspective in contexts where a quantum-mechanical perspective is needed. We further find that this effect can be significantly influenced by instruction, where we observe variations for courses with differing learning goals. We also note that students generally do not employ either a realist or a quantum perspective in a consistent manner.Comment: 18 pages, plus references; 3 figures; 9 tables. PACS: 01.40.Fk, 03.65._

Increased apelin receptor gene expression in the subfornical organ of spontaneously hypertensive rats.

The vascular organ of the lamina terminalis, subfornical organ (SFO), and area postrema comprise the sensory circumventricular organs (CVO) which are central structures that lie outside the blood brain barrier and are thought to provide an interface between peripherally circulating signals and the brain through their projections to central autonomic structures. The SFO expresses mRNA for the G protein-coupled apelin receptor (APJ, gene name aplnr) and exogenous microinjection of the neuropeptide apelin (apln) to the SFO elicits a depressor effect. Here we investigated the expression and cellular distribution of aplnr, apln and the recently described ligand apela (apela) in the CVOs and investigated whether differences in the levels of expression of apelinergic gene transcripts in these regions might underlie the chronic elevated blood pressure seen in hypertension. We carried out multiplex in situ hybridization histochemistry on CVO tissue sections from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) controls. Confocal immunofluorescent images indicated strong aplnr expression, with lower levels of apln and modest apela expression, in the CVOs of both WKY rats and SHRs, in both neurons and glia. The expression level of aplnr transcripts was increased in the SFO of SHRs compared to WKY rats. Our data may highlight a potential dysfunction in the communication between CVOs and downstream signalling pathways in SHRs, which may contribute to its different phenotype/s