2,816 research outputs found

    Expression of Ki-67 and Bcl-2 in gastric epithelial cells: role of antralization in gastric carcinogenesis

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    Cardiac Calcitropes, Myotropes, and Mitotropes: JACC Review Topic of the Week.

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    The term "inotrope" is familiar and intimately connected with pharmaceuticals clinically used for treatment of low cardiac output with cardiogenic shock. Traditional inotropic agents exert their effect by modulating calcium signaling in the myocardium. Their use is associated with poor long-term outcomes. Newer molecules in development intend to break from calcium mediation and the associated detrimental long-term effects by targeting distinct mechanisms of action to improve cardiac performance. Thus, "inotropy" does not sufficiently describe the range of potential novel pharmaceutical products. To enhance communication around and evaluation of current, emerging, and potential therapies, this review proposes a novel nuanced and holistic framework to categorize pharmacological agents that improve myocardial performance based on 3 myocardial mechanisms: calcitropes, which alter intracellular calcium concentrations; myotropes, which affect the molecular motor and scaffolding; and mitotropes, which influence energetics. Novel chemical entities can easily be incorporated into this structure, distinguishing themselves based on their mechanisms and clinical outcomes

    The unseen and unacceptable face of digital libraries

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    The social and organizational aspects of digital libraries are often overlooked but this paper reviews how they can affect users' awareness and acceptance of digital libraries. An analysis of research conducted within two contrasting domains (Clinical and Academic) is presented which highlights issues of user interactions, work practices and the organizational social structures. The combined study comprises an analysis of 98 in-depth interviews and focus groups with lecturers, librarians and hospital clinicians. The importance of current and past roles of the library, and how users interacted with it, are revealed. Web-based digital libraries, while alleviating most library resource and interaction problems, require a change in librarians' and DL designers' roles and interaction patterns if they are to be implemented acceptably and effectively. Without this role change, users will at best be unaware of these digital resources and at worst feel threatened by them. The findings of this paper highlight the importance on DL design and implementation of the social context and supporting user communication (i.e. collaboration and consultation) in their information search and usage activities

    New Sum Rules from Low Energy Compton Scattering on Arbitrary Spin Target

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    We derive two sum rules by studying the low energy Compton scattering on a target of arbitrary (nonzero) spin j. In the first sum rule, we consider the possibility that the intermediate state in the scattering can have spin |j \pm 1| and the same mass as the target. The second sum rule applies if the theory at hand possesses intermediate narrow resonances with masses different from the mass of the scatterer. These sum rules are generalizations of the Gerasimov-Drell-Hearn-Weinberg sum rule. Along with the requirement of tree level unitarity, they relate different low energy couplings in the theory. Using these sum rules, we show that in certain cases the gyromagnetic ratio can differ from the "natural" value g=2, even at tree level, without spoiling perturbative unitarity. These sum rules can be used as constraints applicable to all supergravity and higher-spin theories that contain particles charged under some U(1) gauge field. In particular, applied to four dimensional N=8 supergravity in a spontaneously broken phase, these sum rules suggest that for the theory to have a good ultraviolet behavior, additional massive states need to be present, such as those coming from the embedding of the N=8 supergravity in type II superstring theory. We also discuss the possible implications of the sum rules for QCD in the large-N_c limit.Comment: 18 pages, v2: discussion on black hole contribution is included, references added; v3: extended discussion in introduction, version to appear in JHE

    Apoptosis and the activity of ceramide, Bax and Bcl-2 in the lungs of neonatal rats exposed to limited and prolonged hyperoxia

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    BACKGROUND: The aim of the study is to examine the effect of limited and prolonged hyperoxia on neonatal rat lung. This is done by examining the morphologic changes of apoptosis, the expression of ceramide, an important mediator of apoptosis, the expression of inflammatory mediators represented by IL-1β and the expression of 2 proto-oncogenes that appear to modulate apoptosis (Bax and Bcl-2). METHODS: Newborn rats were placed in chambers containing room air or oxygen above 90% for 7 days. The rats were sacrificed at 3, 7 or 14 days and their lungs removed. Sections were fixed, subjected to TUNEL, Hoechst, and E-Cadherin Staining. Sections were also incubated with anti-Bcl-2 and anti-Bax antisera. Bcl-2 and Bax were quantitated by immunohistochemistry. Lipids were extracted, and ceramide measured through a modified diacylglycerol kinase assay. RT-PCR was utilized to assess IL-1β expression. RESULTS: TUNEL staining showed significant apoptosis in the hyperoxia-exposed lungs at 3 days only. Co-staining of the apoptotic cells with Hoechst, and E-Cadherin indicated that apoptotic cells were mainly epithelial cells. The expression of Bax and ceramide was significantly higher in the hyperoxia-exposed lungs at 3 and 14 days of age, but not at 7 days. Bcl-2 was significantly elevated in the hyperoxia-exposed lungs at 3 and 14 days. IL-1β expression was significantly increased at 14 days. CONCLUSION: Exposure of neonatal rat lung to hyperoxia results in early apoptosis documented by TUNEL assay. The early rise in Bax and ceramide appears to overcome the anti-apoptotic activity of Bcl-2. Further exposure did not result in late apoptotic changes. This suggests that apoptotic response to hyperoxia is time sensitive. Prolonged hyperoxia results in acute lung injury and the shifting balance of ceramide, Bax and Bcl-2 may be related to the evolution of the inflammatory process

    An elementary stringy estimate of transport coefficients of large temperature QCD

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    Modeling QCD at large temperature with a simple holographic five dimensional theory encoding minimal breaking of conformality, allows for the calculation of all the transport coefficients, up to second order, in terms of a single parameter. In particular, the shear and bulk relaxation times are provided. The result follows by deforming the AdS background with a scalar dual to a marginally relevant operator, at leading order in the deformation parameter.Comment: 11 pages; v2: comments and references adde

    REFERQUAL: A pilot study of a new service quality assessment instrument in the GP Exercise Referral scheme setting

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    Background The development of an instrument accurately assessing service quality in the GP Exercise Referral Scheme (ERS) industry could potentially inform scheme organisers of the factors that affect adherence rates leading to the implementation of strategic interventions aimed at reducing client drop-out. Methods A modified version of the SERVQUAL instrument was designed for use in the ERS setting and subsequently piloted amongst 27 ERS clients. Results Test re-test correlations were calculated via Pearson's 'r' or Spearman's 'rho', depending on whether the variables were Normally Distributed, to show a significant (mean r = 0.957, SD = 0.02, p < 0.05; mean rho = 0.934, SD = 0.03, p < 0.05) relationship between all items within the questionnaire. In addition, satisfactory internal consistency was demonstrated via Cronbach's 'α'. Furthermore, clients responded favourably towards the usability, wording and applicability of the instrument's items. Conclusion REFERQUAL is considered to represent promise as a suitable tool for future evaluation of service quality within the ERS community. Future research should further assess the validity and reliability of this instrument through the use of a confirmatory factor analysis to scrutinise the proposed dimensional structure

    The Precursors and Products of Justice Climates: Group Leader Antecedents and Employee Attitudinal Consequences

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    Drawing on the organizational justice, organizational climate, leadership and personality, and social comparison theory literatures, we develop hypotheses about the effects of leader personality on the development of three types of justice climates (e.g., procedural, interpersonal, and informational), and the moderating effects of these climates on individual level justice- attitude relationships. Largely consistent with the theoretically-derived hypotheses, the results showed that leader (a) agreeableness was positively related to procedural, interpersonal and informational justice climates, (b) conscientiousness was positively related to a procedural justice climate, and (c) neuroticism was negatively related to all three types of justice climates. Further, consistent with social comparison theory, multilevel data analyses revealed that the relationship between individual justice perceptions and job attitudes (e.g., job satisfaction, commitment) was moderated by justice climate such that the relationships were stronger when justice climate was high

    Which older people decline participation in a primary care trial of physical activity and why: insights from a mixed methods approach

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    This article is available through the Brunel Open Access Publishing Fund. Copyright 2014 Rogers et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Physical activity is of vital importance to older peoples’ health. Physical activity intervention studies with older people often have low recruitment, yet little is known about non-participants. Methods: Patients aged 60–74 years from three UK general practices were invited to participate in a nurse-supported pedometer-based walking intervention. Demographic characteristics of 298 participants and 690 non-participants were compared. Health status and physical activity of 298 participants and 183 non-participants who completed a survey were compared using age, sex adjusted odds ratios (OR) (95% confidence intervals). 15 non-participants were interviewed to explore perceived barriers to participation. Results: Recruitment was 30% (298/988). Participants were more likely than non-participants to be female (54% v 47%; p = 0.04) and to live in affluent postcodes (73% v 62% in top quintile; p < 0.001). Participants were more likely than non-participants who completed the survey to have an occupational pension OR 2.06 (1.35-3.13), a limiting longstanding illness OR 1.72 (1.05-2.79) and less likely to report being active OR 0.55 (0.33-0.93) or walking fast OR 0.56 (0.37-0.84). Interviewees supported general practice-based physical activity studies, particularly walking, but barriers to participation included: already sufficiently active, reluctance to walk alone or at night, physical symptoms, depression, time constraints, trial equipment and duration. Conclusion: Gender and deprivation differences suggest some selection bias. However, trial participants reported more health problems and lower activity than non-participants who completed the survey, suggesting appropriate trial selection in a general practice population. Non-participant interviewees indicated that shorter interventions, addressing physical symptoms and promoting confidence in pursuing physical activity, might increase trial recruitment and uptake of practice-based physical activity endeavours.The National Institute for Health Research (NIHR) under its Research for Patient Benefit Programme (Grant Reference Number PB-PG-0909-20055)

    Drinking behaviour and alcohol-related harm amongst older adults: analysis of existing UK datasets.

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    Older adults experience age-related physiological changes that increase sensitivity and decrease tolerance to alcohol and there are a number of age-related harms such as falls, social isolation and elder abuse, which are compounded by alcohol misuse. Despite this unique vulnerability and the fact that the number of older adults is increasing, the literature on drinking behaviour and alcohol-related harm in older adults is sparse. This article describes a secondary analysis of UK data to address this knowledge gap
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