Challenges to generating political prioritization for adolescent sexual and reproductive health in Kenya: A qualitative study.

BackgroundDespite the high burden of adverse adolescent sexual and reproductive health (SRH) outcomes, it has remained a low political priority in Kenya. We examined factors that have shaped the lack of current political prioritization of adolescent SRH service provision.MethodsWe used the Shiffman and Smith policy framework consisting of four categories-actor power, ideas, political contexts, and issue characteristics-to analyse factors that have shaped political prioritization of adolescent SRH. We undertook semi-structured interviews with 14 members of adolescent SRH networks between February and April 2019 at the national level and conducted thematic analysis of the interviews.FindingsSeveral factors hinder the attainment of political priority for adolescent SRH in Kenya. On actor power, the adolescent SRH community was diverse and united in adoption of international norms and policies, but lacked policy entrepreneurs to provide strong leadership, and policy windows were often missed. Regarding ideas, community members lacked consensus on a cohesive public positioning of the problem. On issue characteristics, the perception of adolescents as lacking political power made politicians reluctant to act on the existing data on the severity of adolescent SRH. There was also a lack of consensus on the nature of interventions to be implemented. Pertaining to political contexts, sectoral funding by donors and government treasury brought about tension within the different government ministries resulting in siloed approaches, lack of coordination and overall inefficiency. However, the SRH community has several strengths that augur well for future political support. These include the diverse multi-sectoral background of its members, commitment to improving adolescent SRH, and the potential to link with other health priorities such as maternal health and HIV/AIDS.ConclusionIn order to increase political attention to adolescent SRH in Kenya, there is an urgent need for policy actors to: 1) create a more cohesive community of advocates across sectors, 2) develop a clearer public positioning of adolescent SRH, 3) agree on a set of precise approaches that will resonate with the political system, and 4) identify and nurture policy entrepreneurs to facilitate the coupling of adolescent SRH with potential solutions when windows of opportunity arise

Vergence eye movements in patients with schizophrenia

AbstractPrevious studies have shown that smooth pursuit eye movements are impaired in patients with schizophrenia. However, under normal viewing conditions, targets move not only in the frontoparallel plane but also in depth, and tracking them requires both smooth pursuit and vergence eye movements. Although previous studies in humans and non-human primates suggest that these two eye movement subsystems are relatively independent of one another, to our knowledge, there have been no prior studies of vergence tracking behavior in patients with schizophrenia. Therefore, we have investigated these eye movements in patients with schizophrenia and in healthy controls. We found that patients with schizophrenia exhibited substantially lower gains compared to healthy controls during vergence tracking at all tested speeds (e.g. 0.25Hz vergence tracking mean gain of 0.59 vs. 0.86). Further, consistent with previous reports, patients with schizophrenia exhibited significantly lower gains than healthy controls during smooth pursuit at higher target speeds (e.g. 0.5Hz smooth pursuit mean gain of 0.64 vs. 0.73). In addition, there was a modest (r≈0.5), but significant, correlation between smooth pursuit and vergence tracking performance in patients with schizophrenia. Our observations clearly demonstrate substantial vergence tracking deficits in patients with schizophrenia. In these patients, deficits for smooth pursuit and vergence tracking are partially correlated suggesting overlap in the central control of smooth pursuit and vergence eye movements

An Automated Procedure to Identify Biomedical Articles that Contain Cancer-associated Gene Variants

The proliferation of biomedical literature makes it increasingly difficult for researchers to find and manage relevant information. However, identifying research articles containing mutation data, a requisite first step in integrating large and complex mutation data sets, is currently tedious, time-consuming and imprecise. More effective mechanisms for identifying articles containing mutation information would be beneficial both for the curation of mutation databases and for individual researchers. We developed an automated method that uses information extraction, classifier, and relevance ranking techniques to determine the likelihood of MEDLINE abstracts containing information regarding genomic variation data suitable for inclusion in mutation databases. We targeted the CDKN2A (p16) gene and the procedure for document identification currently used by CDKN2A Database curators as a measure of feasibility. A set of abstracts was manually identified from a MEDLINE search as potentially containing specific CDKN2A mutation events. A subset of these abstracts was used as a training set for a maximum entropy classifier to identify text features distinguishing relevant from not relevant abstracts. Each document was represented as a set of indicative word, word pair, and entity tagger-derived genomic variation features. When applied to a test set of 200 candidate abstracts, the classifier predicted 88 articles as being relevant; of these, 29 of 32 manuscripts in which manual curation found CDKN2A sequence variants were positively predicted. Thus, the set of potentially useful articles that a manual curator would have to review was reduced by 56%, maintaining 91% recall (sensitivity) and more than doubling precision (positive predictive value). Subsequent expansion of the training set to 494 articles yielded similar precision and recall rates, and comparison of the original and expanded trials demonstrated that the average precision improved with the larger data set. Our results show that automated systems can effectively identify article subsets relevant to a given task and may prove to be powerful tools for the broader research community. This procedure can be readily adapted to any or all genes, organisms, or sets of documents

Improved nuclear localization of DNA-binding polyamides

Regulation of endogenous genes by DNA-binding polyamides requires effective nuclear localization. Previous work employing confocal microscopy to study uptake of fluorophore-labeled polyamides has demonstrated the difficulty of predicting a priori the nuclear uptake of a given polyamide. The data suggest that dye identity influences uptake sufficiently such that a dye-conjugate cannot be used as a proxy for unlabeled analogs. Polyamides capable of nuclear localization unaided by fluorescent dyes are desirable due to size and other limitations of fluorophores. Recently, a polyamide-fluorescein conjugate targeted to the hypoxia response element (HRE) was found to inhibit vascular endothelial growth factor (VEGF) expression in cultured HeLa cells. The current study uses inhibition of VEGF expression as a biological read-out for effective nuclear localization of HRE-targeted polyamides. We synthesized a focused library of non-fluorescent, HRE-targeted polyamides in which the C-terminus ‘tail’ has been systematically varied. Members of this library bind the HRE with affinities comparable or superior to that of the fluorescein-labeled analog. Although most library members demonstrate modest or no biological activity, two non-fluorescent polyamides are reported with activity rivaling that of the previously reported fluorescein-labeled polyamide. We also show evidence that promoter occupancy by HIF-1, the transcription factor that binds the HRE, is inhibited by HRE-targeted polyamides

Stroke Induces Prolonged Changes in Lipid Metabolism, the Liver and Body Composition in Mice

Acknowledgements We would like to thank the Biological Services Facility at the University of Manchester for expert animal husbandry and Karen Davies who helped with the MRI. The Histology Facility equipment that was used in this study was purchased by the University of Manchester Strategic Fund. Special thanks goes to Peter Walker for their help with the histology. Funding information This work was supported by the Kohn Foundation, an Edward Bonham Carter Doctoral Scholarship, an EPSRC/MRC Centre for Doctoral Training in Regenerative Medicine studentship grant (EP/L014904/1), and the Medical Research Council (MR/K501311/1).Peer reviewedPublisher PD

A molecular insight into algal-oomycete warfare : cDNA analysis of Ectocarpus siliculosus infected with the basal oomycete Eurychasma dicksonii

Peer reviewedPublisher PD

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

How to analyse longitudinal data from multiple sources in qualitative health research : the pen portrait analytic technique

BACKGROUND: Longitudinal qualitative research is starting to be used in applied health research, having been popular in social research for several decades. There is potential for a large volume of complex data to be captured, over a span of months or years across several different methods. How to analyse this volume of data - with its inherent complexity - represents a problem for health researchers. There is a previous dearth of methodological literature which describes an appropriate analytic process which can be readily employed. METHODS: We document a worked example of the Pen Portrait analytic process, using the qualitative dataset for which the process was originally developed. RESULTS: Pen Portraits are recommended as a way in which longitudinal health research data can be concentrated into a focused account. The four stages of undertaking a pen portrait are: 1) understand and define what to focus on 2) design a basic structure 3) populate the content 4) interpretation. Instructive commentary and guidance is given throughout with consistent reference to the original study for which Pen Portraits were devised. The Pen Portrait analytic process was developed by the authors, borne out of a need to effectively integrate multiple qualitative methods collected over time. Pen Portraits are intended to be adaptable and flexible, in order to meet the differing analytic needs of qualitative longitudinal health studies. CONCLUSIONS: The Pen Portrait analytic process provides a useful framework to enable researchers to conduct a robust analysis of multiple sources of qualitative data collected over time

Tracing the wider impacts of biomedical research: A literature search to develop a novel citation categorisation technique

There is an increasing need both to understand the translation of biomedical research into improved healthcare and to assess the range of wider impacts from health research such as improved health policies, health practices and healthcare. Conducting such assessments is complex and new methods are being sought. Our new approach involves several steps. First, we developed a qualitative citation analysis technique to apply to biomedical research in order to assess the contribution that individual papers made to further research. Second, using this method, we then proposed to trace the citations to the original research through a series of generations of citing papers. Third, we aimed eventually to assess the wider impacts of the various generations. This article describes our comprehensive literature search to inform the new technique. We searched various databases, specific bibliometrics journals and the bibliographies of key papers. After excluding irrelevant papers we reviewed those remaining for either general or specific details that could inform development of our new technique. Various characteristics of citations were identified that had been found to predict their importance to the citing paper including the citation’s location; number of citation occasions and whether the author(s) of the cited paper were named within the citing paper. We combined these objective characteristics with subjective approaches also identified from the literature search to develop a citation categorisation technique that would allow us to achieve the first of the steps above, i.e., being able routinely to assess the contribution that individual papers make to further research.Medical Research Council as part of the MRC-NIHR Methodology Research Programme, and Professor Martin Buxton