302 research outputs found

    Equation of state and high-pressure/high-temperature phase diagram of magnesium

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    The phase diagram of magnesium has been investigated to 211 GPa at 300 K, and to 105 GPa at 4500 K, by using a combination of x-ray diffraction and resistive and laser heating. The ambient pressure hcp structure is found to start transforming to the bcc structure at ∼45 GPa, with a large region of phase-coexistence that becomes smaller at higher temperatures. The bcc phase is stable to the highest pressures reached. The hcp-bcc phase boundary has been studied on both compression and decompression, and its slope is found to be negative and steeper than calculations have previously predicted. The laser-heating studies extend the melting curve of magnesium to 105 GPa and suggest that, at the highest pressures, the melting temperature increases more rapidly with pressure than previously reported. Finally, we observe some evidence of a new phase in the region of 10 GPa and 1200 K, where previous studies have reported a double-hexagonal-close-packed (dhcp) phase. However, the additional diffraction peaks we observe cannot be accounted for by the dhcp phase alone

    Using molecular data for epidemiological inference: assessing the prevalence of Trypanosoma brucei rhodesiense in Tsetse in Serengeti, Tanzania

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    Background: Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude. Methodology/Principal Findings: Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0–0.085) for G. swynnertoni and 0% (0–0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0–0.054) and 0.0089% (0–0.059) respectively, and by model inference 0.0064% and 0.00085% respectively. Conclusions/Significance: The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data

    The Evolution of Bat Vestibular Systems in the Face of Potential Antagonistic Selection Pressures for Flight and Echolocation

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    PMCID: PMC3634842This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

    IAP Display: A Simple Method to Identify Mouse Strain Specific IAP Insertions

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    Intracisternal A-type particle (IAP) elements are high copy number long terminal repeat (LTR) rodent retrotransposons. Some IAP elements can transpose, and are responsible for ~12% of spontaneous mouse mutations. Inbred mouse strains show variation in genomic IAP distribution, contributing to inter-strain genetic variability. Additionally IAP elements can influence the transcriptional regulation of neighbouring genes through their strong LTR promoter, effecting phenotypic variation. This genetic and phenotypic variability can translate into experimental variability between mouse strains. For example, it has been demonstrated that strain-specific genetic/epigenetic factors can interact to yield variable responses to drugs. Therefore, in experimental contexts it is essential to unequivocally identify mouse strains. Recently it was estimated that any two inbred strains share only ~40% of their IAP insertions. Of the remaining 60%, some insertions will be strain specific, fixed during inbreeding. These fixed insertions can be exploited as genetic markers to identify inbred strains, if they can be identified simply and efficiently. Here, we report the development of a PCR-based system allowing direct acquisition of strain-specific IAP insertions. In a pilot study, we identified 21 IAP loci, genotyped IAP insertions at 9 loci, and discovered two strain-specific insertions that could reliably identify these strains

    The systematic guideline review: method, rationale, and test on chronic heart failure

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    Background: Evidence-based guidelines have the potential to improve healthcare. However, their de-novo-development requires substantial resources-especially for complex conditions, and adaptation may be biased by contextually influenced recommendations in source guidelines. In this paper we describe a new approach to guideline development-the systematic guideline review method (SGR), and its application in the development of an evidence-based guideline for family physicians on chronic heart failure (CHF). Methods: A systematic search for guidelines was carried out. Evidence-based guidelines on CHF management in adults in ambulatory care published in English or German between the years 2000 and 2004 were included. Guidelines on acute or right heart failure were excluded. Eligibility was assessed by two reviewers, methodological quality of selected guidelines was appraised using the AGREE instrument, and a framework of relevant clinical questions for diagnostics and treatment was derived. Data were extracted into evidence tables, systematically compared by means of a consistency analysis and synthesized in a preliminary draft. Most relevant primary sources were re-assessed to verify the cited evidence. Evidence and recommendations were summarized in a draft guideline. Results: Of 16 included guidelines five were of good quality. A total of 35 recommendations were systematically compared: 25/35 were consistent, 9/35 inconsistent, and 1/35 un-rateable (derived from a single guideline). Of the 25 consistencies, 14 were based on consensus, seven on evidence and four differed in grading. Major inconsistencies were found in 3/9 of the inconsistent recommendations. We re-evaluated the evidence for 17 recommendations (evidence-based, differing evidence levels and minor inconsistencies) - the majority was congruent. Incongruity was found where the stated evidence could not be verified in the cited primary sources, or where the evaluation in the source guidelines focused on treatment benefits and underestimated the risks. The draft guideline was completed in 8.5 man-months. The main limitation to this study was the lack of a second reviewer. Conclusion: The systematic guideline review including framework development, consistency analysis and validation is an effective, valid, and resource saving-approach to the development of evidence-based guidelines

    A pragmatic, multicentre, randomised controlled trial comparing stapled haemorrhoidopexy to traditional excisional surgery for haemorrhoidal disease (eTHoS): study protocol for a randomised controlled trial

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    Background: Current interventions for haemorrhoidal disease include traditional haemorrhoidectomy (TH) and stapled haemorrhoidopexy (SH) surgery. However, uncertainty remains as to how they compare from a clinical, quality of life (QoL) and economic perspective. The study is therefore designed to determine whether SH is more effective and more cost-effective, compared with TH. Methods/Design: eTHoS (either Traditional Haemorrhoidectomy or Stapled Haemorrhoidopexy for Haemorrhoidal Disease) is a pragmatic, multicentre, randomised controlled trial. Currently, 29 secondary care centres are open to recruitment. Patients, aged 18 year or older, with circumferential haemorrhoids grade II to IV, are eligible to take part. The primary clinical and economic outcomes are QoL profile (area under the curve derived from the EuroQol Group’s 5 Dimension Health Status Questionnaire (EQ-5D) at all assessment points) and incremental cost per quality adjusted life year (QALY) based on the responses to the EQ-5D at 24 months. The secondary outcomes include a comparison of the SF-36 scores, pain and symptoms sub-domains, disease recurrence, complication rates and direct and indirect costs to the National Health Service (NHS). A sample size of n =338 per group has been calculated to provide 90% power to detect a difference in the mean area under the curve (AUC) of 0.25 standard deviations derived from EQ-5D score measurements, with a two-sided significance level of 5%. Allowing for non-response, 400 participants will be randomised per group. Randomisation will utilise a minimisation algorithm that incorporates centre, grade of haemorrhoidal disease, baseline EQ-5D score and gender. Blinding of participants and outcome assessors is not attempted. Discussion: This is one of the largest trials of its kind. In the United Kingdom alone, 29,000 operations for haemorrhoidal disease are done annually. The trial is therefore designed to give robust evidence on which clinicians and health service managers can base management decisions and, more importantly, patients can make informed choices. Trial registration: Current Controlled Trials ISRCTN80061723 (assigned 8 March 2010

    Impacts of climate change on plant diseases – opinions and trends

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    There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

    Methodological quality of systematic reviews of animal studies: a survey of reviews of basic research

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    BACKGROUND: Systematic reviews can serve as a tool in translation of basic life sciences research from laboratory to human research and healthcare. The extent to which reviews of animal research are systematic and unbiased is not known. METHODS: We searched, without language restrictions, Medline, Embase, bibliographies of known reviews (1996–2004) and contacted experts to identify citations of reviews of basic science literature which, as a minimum, performed search of a publicly available resource. From these we identified reviews of animal studies where laboratory variables were measured or where treatments were administered to live animals to examine their effects, and compared them with reviews of bench studies in which human or animal tissues, cell systems or organ preparations were examined in laboratories to better understand mechanisms of diseases. RESULTS: Systematic reviews of animal studies often lacked methodological features such as specification of a testable hypothesis (9/30, 30%); literature search without language restriction (8/30, 26.6%); assessment of publication bias (5/30, 16.6%), study validity (15/30, 50%) and heterogeneity (10/30, 33.3%); and meta-analysis for quantitative synthesis (12/30, 40%). Compared to reviews of bench studies, they were less prone to bias as they specified the question (96.6% vs. 80%, p = 0.04), searched multiple databases (60% vs. 26.6%, p = 0.01), assessed study quality (50% vs. 20%, p = 0.01), and explored heterogeneity (33.3% vs. 2.2%, p = 0.001) more often. CONCLUSION: There seems to be a gradient of frequency of methodological weaknesses among reviews: Attempted systematic reviews of whole animal research tend to be better than those of bench studies, though compared to systematic reviews of human clinical trials they are apparently poorer. There is a need for rigour when reviewing animal research

    Role of the general practitioner during the active breast cancer treatment phase: an analysis of health care use

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    PURPOSE: Little is known about the actual involvement of the general practitioner (GP) during the active breast cancer treatment phase. Therefore, this study explored (disease-specific) primary health care use among women undergoing active treatment for breast cancer compared with women without breast cancer. METHODS: A total of 185 women with a first diagnosis of early-stage breast cancer between 1998 and 2007 were identified in the primary care database of the Registration Network Groningen and matched with a reference population of 548 women without breast cancer on birth year and GP. RESULTS: Since diagnosis, patients with breast cancer had twice as many face-to-face contacts compared with women from the reference population (median 6.0 vs 3.0/year, Mann-Whitney (M-W) test p < 0.001). The median number of drug prescriptions and referrals was also significantly higher among patients than among the reference population (11.0 vs 7.0/year, M-W test p < 0.001 and 1.0 vs 0.0/year, M-W test p < 0.001). More patients than women from the reference population had face-to-face contacts or were prescribed drugs for reasons related to breast cancer and its treatment, including gastrointestinal problems, psychological reasons and endocrine therapy. CONCLUSIONS: During the active breast cancer treatment phase, GPs are involved in the management of treatment-related side effects and psychological symptoms, as well as in the administration of endocrine therapy. Based on the findings of this study, interventions across the primary/secondary interface can be planned to improve quality of life and other outcomes in patients undergoing breast cancer treatment

    Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

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    We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
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