Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

Cardiovascular disease in a cohort exposed to the 1940-45 Channel Islands occupation

BACKGROUND To clarify the nature of the relationship between food deprivation/undernutrition during pre- and postnatal development and cardiovascular disease (CVD) in later life, this study examined the relationship between birth weight (as a marker of prenatal nutrition) and the incidence of hospital admissions for CVD from 1997–2005 amongst 873 Guernsey islanders (born in 1923–1937), 225 of whom had been exposed to food deprivation as children, adolescents or young adults (i.e. postnatal undernutrition) during the 1940–45 German occupation of the Channel Islands, and 648 of whom had left or been evacuated from the islands before the occupation began. METHODS Three sets of Cox regression models were used to investigate (A) the relationship between birth weight and CVD, (B) the relationship between postnatal exposure to the occupation and CVD and (C) any interaction between birth weight, postnatal exposure to the occupation and CVD. These models also tested for any interactions between birth weight and sex, and postnatal exposure to the occupation and parish of residence at birth (as a marker of parish residence during the occupation and related variation in the severity of food deprivation). RESULTS The first set of models (A) found no relationship between birth weight and CVD even after adjustment for potential confounders (hazard ratio (HR) per kg increase in birth weight: 1.12; 95% confidence intervals (CI): 0.70 – 1.78), and there was no significant interaction between birth weight and sex (p = 0.60). The second set of models (B) found a significant relationship between postnatal exposure to the occupation and CVD after adjustment for potential confounders (HR for exposed vs. unexposed group: 2.52; 95% CI: 1.54 – 4.13), as well as a significant interaction between postnatal exposure to the occupation and parish of residence at birth (p = 0.01), such that those born in urban parishes (where food deprivation was worst) had a greater HR for CVD than those born in rural parishes. The third model (C) found no interaction between birth weight and exposure to the occupation (p = 0.43). CONCLUSION These findings suggest that the levels of postnatal undernutrition experienced by children, adolescents and young adults exposed to food deprivation during the 1940–45 occupation of the Channel Islands were a more important determinant of CVD in later life than the levels of prenatal undernutrition experienced in utero prior to the occupatio

Evaluating the successful implementation of evidence into practice using the PARiHS framework : theoretical and practical challenges

Background The PARiHS framework (Promoting Action on Research Implementation in Health Services) has proved to be a useful practical and conceptual heuristic for many researchers and practitioners in framing their research or knowledge translation endeavours. However, as a conceptual framework it still remains untested and therefore its contribution to the overall development and testing of theory in the field of implementation science is largely unquantified. Discussion This being the case, the paper provides an integrated summary of our conceptual and theoretical thinking so far and introduces a typology (derived from social policy analysis) used to distinguish between the terms conceptual framework, theory and model – important definitional and conceptual issues in trying to refine theoretical and methodological approaches to knowledge translation. Secondly, the paper describes the next phase of our work, in particular concentrating on the conceptual thinking and mapping that has led to the generation of the hypothesis that the PARiHS framework is best utilised as a two-stage process: as a preliminary (diagnostic and evaluative) measure of the elements and sub-elements of evidence (E) and context (C), and then using the aggregated data from these measures to determine the most appropriate facilitation method. The exact nature of the intervention is thus determined by the specific actors in the specific context at a specific time and place. In the process of refining this next phase of our work, we have had to consider the wider issues around the use of theories to inform and shape our research activity; the ongoing challenges of developing robust and sensitive measures; facilitation as an intervention for getting research into practice; and finally to note how the current debates around evidence into practice are adopting wider notions that fit innovations more generally. Summary The paper concludes by suggesting that the future direction of the work on the PARiHS framework is to develop a two-stage diagnostic and evaluative approach, where the intervention is shaped and moulded by the information gathered about the specific situation and from participating stakeholders. In order to expedite the generation of new evidence and testing of emerging theories, we suggest the formation of an international research implementation science collaborative that can systematically collect and analyse experiences of using and testing the PARiHS framework and similar conceptual and theoretical approaches. We also recommend further refinement of the definitions around conceptual framework, theory, and model, suggesting a wider discussion that embraces multiple epistemological and ontological perspectives

On the use of parataxonomy in biodiversity monitoring: a case study on wild flora

International audienceMonitoring programs that assess species-richness and turnover are now regarded as essential to document biodiversity loss worldwide. Implementation of such programs is impeded by a general decrease in the number of skilled naturalists. Here we studied how morphotypes, instead of species, might be used by unskilled participants (referred to as “volunteers”) to survey common plant communities. Our main questions were: (1) Can morphotypes be used as a robust estimator of species-richness (alpha-diversity) and assemblage turnover (Beta-diversity)? and (2) What is the robustness (reproducibility and repeatability) of such methods? Double inventories were performed on 150 plots in arable Weld margins, one by a non-expert using morphotypes, the other by a taxonomist using species. To test the robustness of morphotype identiWcation among participants, 20 additional plots were surveyed by eight volunteers using the same protocol. We showed that (1) the number of morphotypes identiWed by unskilled volunteers in a plot was always strongly correlated with species-richness. (2) Morphotypes were sensitive to diVerences among habitats but were less accurate than species to detect these diVerences. (3) Morphotype identiWcation varied signiWcantly within and between volunteers. Due to this lack of repeatability and reproducibility, parataxonomy cannot be considered a good surrogate for taxonomy. Nevertheless, assuming that morphotypes are identiWed with standardized methods, and that results are used only to evaluate gross species-richness but not species turnover, parataxonomy might be a valuable tool for rapid biodiversity assessment of common wild flora

Effects of an interactive CD-program on 6 months readmission rate in patients with heart failure – a randomised, controlled trial [NCT00311194]

BACKGROUND: Disease-management programmes including patient education have promoted improvement in outcome for patients with heart failure. However, there is sparse evidence concerning which component is essential for success, and very little is known regarding the validity of methods or material used for the education. METHODS: Effects of standard information to heart failure patients given prior to discharge from hospital were compared with additional education by an interactive program on all-cause readmission or death within 6 months. As a secondary endpoint, patients' general knowledge of heart failure and its treatment was tested after 2 months. RESULTS: Two hundred and thirty patients were randomised to standard information (S) or additional CD-ROM education (E). In (S) 52 % reached the endpoint vs. 49 % in (E). This difference was not significant. Of those who completed the questionnaire (37 %), patients in (E) achieved better knowledge and a marginally better outcome. CONCLUSION: The lack of effect on the readmission rate could be due to an insufficient sample size but might also indicate that in pharmacologically well-treated patients there is little room for altering the course of the condition. As there was some indication that patients who knew more about their condition might fare better, the place for intensive education and support of heart failure patients has yet to be determined

Interventions aimed at increasing research use in nursing: a systematic review

<p>Abstract</p> <p>Background</p> <p>There has been considerable interest recently in developing and evaluating interventions to increase research use by clinicians. However, most work has focused on medical practices; and nursing is not well represented in existing systematic reviews. The purpose of this article is to report findings from a systematic review of interventions aimed at increasing research use in nursing.</p> <p>Objective</p> <p>To assess the evidence on interventions aimed at increasing research use in nursing.</p> <p>Methods</p> <p>A systematic review of research use in nursing was conducted using databases (Medline, CINAHL, Healthstar, ERIC, Cochrane Central Register of Controlled Trials, and Psychinfo), grey literature, ancestry searching (Cochrane Database of Systematic Reviews), key informants, and manual searching of journals. Randomized controlled trials and controlled before- and after-studies were included if they included nurses, if the intervention was explicitly aimed at increasing research use or evidence-based practice, and if there was an explicit outcome to research use. Methodological quality was assessed using pre-existing tools. Data on interventions and outcomes were extracted and categorized using a pre-established taxonomy.</p> <p>Results</p> <p>Over 8,000 titles were screened. Three randomized controlled trials and one controlled before- and after-study met the inclusion criteria. The methodological quality of included studies was generally low. Three investigators evaluated single interventions. The most common intervention was education. Investigators measured research use using a combination of surveys (three studies) and compliance with guidelines (one study). Researcher-led educational meetings were ineffective in two studies. Educational meetings led by a local opinion leader (one study) and the formation of multidisciplinary committees (one study) were both effective at increasing research use.</p> <p>Conclusion</p> <p>Little is known about how to increase research use in nursing, and the evidence to support or refute specific interventions is inconclusive. To advance the field, we recommend that investigators: (1) use theoretically informed interventions to increase research use, (2) measure research use longitudinally using theoretically informed and psychometrically sound measures of research use, as well as, measuring patient outcomes relevant to the intervention, and (3) use more robust and methodologically sound study designs to evaluate interventions. If investigators aim to establish a link between using research and improved patient outcomes they must first identify those interventions that are effective at increasing research use.</p

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Geographical variation in cardiovascular incidence: results from the British Women's Heart and Health Study

BACKGROUND: Prevalence of cardiovascular disease (CVD) in women shows regional variations not explained by common risk factors. Analysis of CVD incidence will provide insight into whether there is further divergence between regions with increasing age. METHODS: Seven-year follow-up data on 2685 women aged 59-80 (mean 69) at baseline from 23 towns in the UK were available from the British Women's Heart and Health Study. Time to fatal or non-fatal CVD was analyzed using Cox regression with adjustment for risk factors, using multiple imputation for missing values. RESULTS: Compared to South England, CVD incidence is similar in North England (HR 1.05 (95% CI 0.84, 1.31)) and Scotland (0.93 (0.68, 1.27)), but lower in Midlands/Wales (0.85 (0.64, 1.12)). Event severity influenced regional variation, with South England showing lower fatal incident CVD than other regions, but higher non-fatal incident CVD. Kaplan-Meier plots suggested that regional divergence in CVD occurred before baseline (before mean baseline age of 69). CONCLUSIONS: In women, regional differences in CVD early in adult life do not further diverge in later life. This may be due to regional differences in early detection, survivorship of women entering the study, or event severity. Targeting health care resources for CVD by geographic variation may not be appropriate for older age-groups