Rapid field-cycling MRI using fast spin-echo

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Micrococcal Nuclease Does Not Substantially Bias Nucleosome Mapping

We have mapped sequence-directed nucleosome positioning on genomic DNA molecules using high-throughput sequencing. Chromatins, prepared by reconstitution with either chicken or frog histones, were separately digested to mononucleosomes using either micrococcal nuclease (MNase) or caspase-activated DNase (CAD). Both enzymes preferentially cleave internucleosomal (linker) DNA, although they do so by markedly different mechanisms. MNase has hitherto been very widely used to map nucleosomes, although concerns have been raised over its potential to introduce bias. Having identified the locations and quantified the strength of both the chicken or frog histone octamer binding sites on each DNA, the results obtained with the two enzymes were compared using a variety of criteria. Both enzymes displayed sequence specificity in their preferred cleavage sites, although the nature of this selectivity was distinct for the two enzymes. In addition, nucleosomes produced by CAD nuclease are 8–10 bp longer than those produced with MNase, with the CAD cleavage sites tending to be 4–5 bp further out from the nucleosomal dyad than the corresponding MNase cleavage sites. Despite these notable differences in cleavage behaviour, the two nucleases identified essentially equivalent patterns of nucleosome positioning sites on each of the DNAs tested, an observation that was independent of the histone type. These results indicate that biases in nucleosome positioning data collected using MNase are, under our conditions, not significant

Simple algorithm for the correction of MRI image artefacts due to random phase fluctuations

Grant support: This work was supported by EPSRC [grant numbers EP/E036775/1, EP/K020293/1] and received funding from the European Union's Horizon 2020 research and innovation programme [grant agreement No 668119, project “IDentIFY”]Peer reviewedPublisher PD

Provider-initiated testing and counselling programmes in sub-Saharan Africa: a systematic review of their operational implementation.

OBJECTIVE: The routine offer of an HIV test during patient-provider encounters is gaining momentum within HIV treatment and prevention programmes. This review examined the operational implementation of provider-initiated testing and counselling (PITC) programmes in sub-Saharan Africa. DESIGN AND METHODS: PUBMED, EMBASE, Global Health, COCHRANE Library and JSTOR databases were searched systematically for articles published in English between January 2000 and November 2010. Grey literature was explored through the websites of international and nongovernmental organizations. Eligibility of studies was based on predetermined criteria applied during independent screening by two researchers. RESULTS: We retained 44 studies out of 5088 references screened. PITC polices have been effective at identifying large numbers of previously undiagnosed individuals. However, the translation of policy guidance into practice has had mixed results, and in several studies of routine programmes the proportion of patients offered an HIV test was disappointingly low. There were wide variations in the rates of acceptance of the test and poor linkage of those testing positive to follow-up assessments and antiretroviral treatment. The challenges encountered encompass a range of areas from logistics, to data systems, human resources and management, reflecting some of the weaknesses of health systems in the region. CONCLUSIONS: The widespread adoption of PITC provides an unprecedented opportunity for identifying HIV-positive individuals who are already in contact with health services and should be accompanied by measures aimed at strengthening health systems and fostering the normalization of HIV at community level. The resources and effort needed to do this successfully should not be underestimated

The epidemiology of HIV among young people in sub-Saharan Africa: know your local epidemic and its implications for prevention.

BACKGROUND: Broad patterns of HIV epidemiology are frequently used to design generic HIV programs in sub-Saharan Africa. METHODS: We reviewed the epidemiology of HIV among young people in sub-Saharan Africa, and explored the unique dynamics of infection in its different regions. RESULTS: In 2009, HIV prevalence among youth in sub-Saharan Africa was an estimated 1.4% in males and 3.4% in females, but these values mask wide variation at regional and national levels. Within countries there are further major differences in HIV prevalence, such as by sex, urban/rural location, economic status, education, or ethnic group. Within this highly nuanced context, HIV prevention programs targeting youth must consider both where new infections are occurring and where they are coming from. CONCLUSIONS: Given the epidemiology, one-size-fits-all HIV prevention programs are usually inappropriate at regional and national levels. Consideration of local context and risk associated with life transitions, such as leaving school or getting married, is imperative to successful programming for young people

Can Small Firms Find and Defend Strategic Niches? A Test of the Porter Hypothesis

A number of studies have found a positive relation between market share and profitability. Michael Porter argues that this need not hold when small firms find strategic niches protected by mobility barriers. This paper examines that hypothesis by comparing the profitability of large and small lines of business when the activities of the two groups (proxied by the allocation of sales across submarkets) differ on average. We find that in heterogeneous product mix industries profits of large LBs are no longer significantly greater than profits of smaller rivals, except that market leaders maintain their advantage regardless of product mix

Software for interpreting cardiopulmonary exercise tests

<p>Abstract</p> <p>Background</p> <p>Cardiopulmonary exercise testing (CPET) has become an important modality for the evaluation and management of patients with a diverse array of medical problems. However, interpreting these tests is often difficult and time consuming, requiring significant expertise.</p> <p>Methods</p> <p>We created a computer software program (XINT) that assists in CPET interpretation. The program uses an integrative approach as recommended in the Official Statement of the American Thoracic Society/American College of Chest Physicians (ATS/ACCP) on Cardiopulmonary Exercise Testing. In this paper we discuss the principles behind the software. We also provide the detailed logic in an accompanying file (Additional File <supplr sid="S1">1</supplr>). The actual program and the open source code are also available free over the Internet at <url>http://www.xint.org</url>. For convenience, the required download files can also be accessed from this article.</p> <suppl id="S1"> <title> <p>Additional file 1</p> </title> <text> <p>XINTlogic. This file provides the detailed logic used by the XINT program. The variable names are described in Table <tblr tid="T1">1</tblr>. The actual source code may also be read directly simply by opening the source code with a text editor.</p> </text> <file name="1471-2466-7-15-S1.doc"> <p>Click here for file</p> </file> </suppl> <p>Results</p> <p>To test the clinical usefulness of XINT, we present the computer generated interpretations of the case studies discussed in the ATS/ACCP document in another accompanying file (Additional File <supplr sid="S2">2</supplr>). We believe the interpretations are consistent with the document's criteria and the interpretations given by the expert panel.</p> <suppl id="S2"> <title> <p>Additional file 2</p> </title> <text> <p>XINTinterpretations. These are the XINT generated reports based on the five examples provided in the ATS/ACCP statement on cardiopulmonary exercise testing <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>.</p> </text> <file name="1471-2466-7-15-S2.doc"> <p>Click here for file</p> </file> </suppl> <p>Conclusion</p> <p>Computers have become an integral part of modern life. Peer-reviewed scientific journals are now able to present not just medical concepts and experimental studies, but actual functioning medical interpretive software. This has enormous potential to improve medical diagnoses and patient care. We believe XINT is such a program that will give clinically useful interpretations when used by the medical community at large.</p