Adaptive response and enlargement of dynamic range

Many membrane channels and receptors exhibit adaptive, or desensitized, response to a strong sustained input stimulus, often supported by protein activity-dependent inactivation. Adaptive response is thought to be related to various cellular functions such as homeostasis and enlargement of dynamic range by background compensation. Here we study the quantitative relation between adaptive response and background compensation within a modeling framework. We show that any particular type of adaptive response is neither sufficient nor necessary for adaptive enlargement of dynamic range. In particular a precise adaptive response, where system activity is maintained at a constant level at steady state, does not ensure a large dynamic range neither in input signal nor in system output. A general mechanism for input dynamic range enlargement can come about from the activity-dependent modulation of protein responsiveness by multiple biochemical modification, regardless of the type of adaptive response it induces. Therefore hierarchical biochemical processes such as methylation and phosphorylation are natural candidates to induce this property in signaling systems.Comment: Corrected typos, minor text revision

Beyond the ostensible: an exploration of barriers to lean implementation and sustainability in healthcare

The barriers to implement lean have been well researched and have generated consistent results; this study identifies these as ostensible barriers. There is a dearth of research that focus on understanding the causes of these ostensible barriers. Thus, this study aims to empirically investigate the deeper causes that produce ostensible barriers to implement lean in emergency areas of the healthcare. To achieve this aim, the paper draws on rich, qualitative data from four different sources of data, using exploratory case studies as the main approach. Undertaking thematic analysis, six main underlying barriers emerge as the root cause of ostensible barriers. The results suggest that addressing each of the underlying barriers in healthcare is likely to support lean implementation and sustainability, by reducing the impact of restraining forces that come from stakeholders and the public healthcare system

The BRAIN Initiative: developing technology to catalyse neuroscience discovery

The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated dramatically in the past decade. Capitalizing on this momentum, the United States launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop and apply new tools and technologies for revolutionizing our understanding of the brain. In this article, we review the scientific vision for this initiative set forth by the National Institutes of Health and discuss its implications for the future of neuroscience research. Particular emphasis is given to its potential impact on the mapping and study of neural circuits, and how this knowledge will transform our understanding of the complexity of the human brain and its diverse array of behaviours, perceptions, thoughts and emotions

Comparing nuclear power trajectories in Germany and the UK: from ‘regimes' to ‘democracies’ in sociotechnical transitions and Discontinuities

This paper focuses on arguably the single most striking contrast in contemporary major energy politics in Europe (and even the developed world as a whole): the starkly differing civil nuclear policies of Germany and the UK. Germany is seeking entirely to phase out nuclear power by 2022. Yet the UK advocates a ‘nuclear renaissance’, promoting the most ambitious new nuclear construction programme in Western Europe.Here,this paper poses a simple yet quite fundamental question: what are the particular divergent conditions most strongly implicated in the contrasting developments in these two countries. With nuclear playing such an iconic role in historical discussions over technological continuity and transformation, answering this may assist in wider understandings of sociotechnical incumbency and discontinuity in the burgeoning field of‘sustainability transitions’. To this end, an ‘abductive’ approach is taken: deploying nine potentially relevant criteria for understanding the different directions pursued in Germany and the UK. Together constituted by 30 parameters spanning literatures related to socio-technical regimes in general as well as nuclear technology in particular, the criteria are divided into those that are ‘internal’ and ‘external’ to the ‘focal regime configuration’ of nuclear power and associated ‘challenger technologies’ like renewables. It is ‘internal’ criteria that are emphasised in conventional sociotechnical regime theory, with ‘external’ criteria relatively less well explored. Asking under each criterion whether attempted discontinuation of nuclear power would be more likely in Germany or the UK, a clear picture emerges. ‘Internal’ criteria suggest attempted nuclear discontinuation should be more likely in the UK than in Germany– the reverse of what is occurring. ‘External’ criteria are more aligned with observed dynamics –especially those relating to military nuclear commitments and broader ‘qualities of democracy’. Despite many differences of framing concerning exactly what constitutes ‘democracy’, a rich political science literature on this point is unanimous in characterising Germany more positively than the UK. Although based only on a single case,a potentially important question is nonetheless raised as to whether sociotechnical regime theory might usefully give greater attention to the general importance of various aspects of democracy in constituting conditions for significant technological discontinuities and transformations. If so, the policy implications are significant. A number of important areas are identified for future research, including the roles of diverse understandings and specific aspects of democracy and the particular relevance of military nuclear commitments– whose under-discussion in civil nuclear policy literatures raises its own questions of democratic accountability

Improving the effectiveness of psychological interventions for depression and anxiety in the cardiac rehabilitation pathway using group-based metacognitive therapy (PATHWAY Group MCT) : study protocol for a randomised controlled trial

BACKGROUND: Anxiety and depression are prevalent among cardiac rehabilitation patients but pharmacological and psychological treatments have limited effectiveness in this group. Furthermore, psychological interventions have not been systematically integrated into cardiac rehabilitation services despite being a strategic priority for the UK National Health Service. A promising new treatment, metacognitive therapy, may be well-suited to the needs of cardiac rehabilitation patients and has the potential to improve outcomes. It is based on the metacognitive model, which proposes that a thinking style dominated by rumination, worry and threat monitoring maintains emotional distress. Metacognitive therapy is highly effective at reducing this thinking style and alleviating anxiety and depression in mental health settings. This trial aims to evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy for cardiac rehabilitation patients with elevated anxiety and/or depressive symptoms. METHODS/DESIGN: The PATHWAY Group-MCT trial is a multicentre, two-arm, single-blind, randomised controlled trial comparing the clinical- and cost-effectiveness of group-based metacognitive therapy plus usual cardiac rehabilitation to usual cardiac rehabilitation alone. Cardiac rehabilitation patients (target sample n = 332) with elevated anxiety and/or depressive symptoms will be recruited across five UK National Health Service Trusts. Participants randomised to the intervention arm will receive six weekly sessions of group-based metacognitive therapy delivered by either cardiac rehabilitation professionals or research nurses. The intervention and control groups will both be offered the usual cardiac rehabilitation programme within their Trust. The primary outcome is severity of anxiety and depressive symptoms at 4-month follow-up measured by the Hospital Anxiety and Depression Scale total score. Secondary outcomes are severity of anxiety/depression at 12-month follow-up, health-related quality of life, severity of post-traumatic stress symptoms and strength of metacognitive beliefs at 4- and 12-month follow-up. Qualitative interviews will help to develop an account of barriers and enablers to the effectiveness of the intervention. DISCUSSION: This trial will evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy in alleviating anxiety and depression in cardiac rehabilitation patients. The therapy, if effective, offers the potential to improve psychological wellbeing and quality of life in this large group of patients. TRIAL REGISTRATION: UK Clinical Trials Gateway, ISRCTN74643496 , Registered on 8 April 2015

Recent Advances in Childhood Arterial Ischemic Stroke

Although many underlying diseases have been reported in the setting of childhood arterial ischemic stroke, emerging research demonstrates that non-atherosclerotic intracerebral arteriopathies in otherwise healthy children are prevalent. Minor infections may play a role in arteriopathies that have no other apparent underlying cause. Although stroke in childhood differs in many aspects from adult stroke, few systematic studies specific to pediatrics are available to inform stroke management. Treatment trials of pediatric stroke are required to determine the best strategies for acute treatment and secondary stroke prevention. The high cost of pediatric stroke to children, families, and society demands further study of its risk factors, management, and outcomes. This review focuses on the recent findings in childhood arterial ischemic stroke

Der Konflikt in Afghanistan : Historischer und gesellschaftlicher Hintergrund, Evolution und Lageentwicklung – ein Positionspapier

This study is part of a larger project, the aim of which is to elucidate “mental health nurses” attitudes towards their patients'. In this study, nurses' and patients' attitudes are described from the perspective of both parties using a qualitative approach. The informants were selected from a rehabilitation unit for young adults, below 40, suffering from psychosis at a psychiatric clinic that provides acute psychiatric care. The informant group consisted of three dyads: three patients with various diagnoses and three nurses with primary responsibility for the patients' daily care. The aim of this particular study was to extend our preliminary understanding of nurses' attitudes towards psychiatric patients in the context of psychiatric in-patient care, by elucidating the patient's “inner” picture of her/his past, present and future and the nurse's picture of the same patient's past, present and future. Data were collected and analysed using a phenomenological-hermeneutic approach and the narrative picturing technique. For each picture and group, 15 related sub-themes emerged, on the basis of which six themes were formulated. The findings show that the nurses overrate their own importance when it comes to the patient's well-being on the ward. All the nurses emphasize confirmation and safety as the basis of their nursing care, while in the patient's picture the nurses represent a replication of childhood demands, which probably means that nursing care risks becoming a continuation of the patient's childhood estrangement

Functional Contribution of Elevated Circulating and Hepatic Non-Classical CD14+CD16+ Monocytes to Inflammation and Human Liver Fibrosis

BACKGROUND: Monocyte-derived macrophages critically perpetuate inflammatory responses after liver injury as a prerequisite for organ fibrosis. Experimental murine models identified an essential role for the CCR2-dependent infiltration of classical Gr1/Ly6C(+) monocytes in hepatic fibrosis. Moreover, the monocyte-related chemokine receptors CCR1 and CCR5 were recently recognized as important fibrosis modulators in mice. In humans, monocytes consist of classical CD14(+)CD16(-) and non-classical CD14(+)CD16(+) cells. We aimed at investigating the relevance of monocyte subpopulations for human liver fibrosis, and hypothesized that 'non-classical' monocytes critically exert inflammatory as well as profibrogenic functions in patients during liver disease progression. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed circulating monocyte subsets from freshly drawn blood samples of 226 patients with chronic liver disease (CLD) and 184 healthy controls by FACS analysis. Circulating monocytes were significantly expanded in CLD-patients compared to controls with a marked increase of the non-classical CD14(+)CD16(+) subset that showed an activated phenotype in patients and correlated with proinflammatory cytokines and clinical progression. Correspondingly, CD14(+)CD16(+) macrophages massively accumulated in fibrotic/cirrhotic livers, as evidenced by immunofluorescence and FACS. Ligands of monocyte-related chemokine receptors CCR2, CCR1 and CCR5 were expressed at higher levels in fibrotic and cirrhotic livers, while CCL3 and CCL4 were also systemically elevated in CLD-patients. Isolated monocyte/macrophage subpopulations were functionally characterized regarding cytokine/chemokine expression and interactions with primary human hepatic stellate cells (HSC) in vitro. CD14(+)CD16(+) monocytes released abundant proinflammatory cytokines. Furthermore, CD14(+)CD16(+), but not CD14(+)CD16(-) monocytes could directly activate collagen-producing HSC. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the expansion of CD14(+)CD16(+) monocytes in the circulation and liver of CLD-patients upon disease progression and suggest their functional contribution to the perpetuation of intrahepatic inflammation and profibrogenic HSC activation in liver cirrhosis. The modulation of monocyte-subset recruitment into the liver via chemokines/chemokine receptors and their subsequent differentiation may represent promising approaches for therapeutic interventions in human liver fibrosis