Showing papers by "University of Leicester published in 2011"

Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials

Abstract: Funnel plots, and tests for funnel plot asymmetry, have been widely used to examine bias in the results of meta-analyses. Funnel plot asymmetry should not be equated with publication bias, because it has a number of other possible causes. This article describes how to interpret funnel plot asymmetry, recommends appropriate tests, and explains the implications for choice of meta-analysis model

TRY - a global database of plant traits

Abstract: Plant traits – the morphological, anatomical, physiological, biochemical and phenological characteristics of plants and their organs – determine how primary producers respond to environmental factors, affect other trophic levels, influence ecosystem processes and services and provide a link from species richness to ecosystem functional diversity. Trait data thus represent the raw material for a wide range of research from evolutionary biology, community and functional ecology to biogeography. Here we present the global database initiative named TRY, which has united a wide range of the plant trait research community worldwide and gained an unprecedented buy-in of trait data: so far 93 trait databases have been contributed. The data repository currently contains almost three million trait entries for 69 000 out of the world's 300 000 plant species, with a focus on 52 groups of traits characterizing the vegetative and regeneration stages of the plant life cycle, including growth, dispersal, establishment and persistence. A first data analysis shows that most plant traits are approximately log-normally distributed, with widely differing ranges of variation across traits. Most trait variation is between species (interspecific), but significant intraspecific variation is also documented, up to 40% of the overall variation. Plant functional types (PFTs), as commonly used in vegetation models, capture a substantial fraction of the observed variation – but for several traits most variation occurs within PFTs, up to 75% of the overall variation. In the context of vegetation models these traits would better be represented by state variables rather than fixed parameter values. The improved availability of plant trait data in the unified global database is expected to support a paradigm shift from species to trait-based ecology, offer new opportunities for synthetic plant trait research and enable a more realistic and empirically grounded representation of terrestrial vegetation in Earth system models.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Abstract: Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

Abstract: We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 - 10'8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.

The Anthropocene: From Global Change to Planetary Stewardship

Abstract: Over the past century, the total material wealth of humanity has been enhanced. However, in the twenty-first century, we face scarcity in critical resources, the degradation of ecosystem services, and the erosion of the planet’s capability to absorb our wastes. Equity issues remain stubbornly difficult to solve. This situation is novel in its speed, its global scale and its threat to the resilience of the Earth System. The advent of the Anthropence, the time interval in which human activities now rival global geophysical processes, suggests that we need to fundamentally alter our relationship with the planet we inhabit. Many approaches could be adopted, ranging from geo-engineering solutions that purposefully manipulate parts of the Earth System to becoming active stewards of our own life support system. The Anthropocene is a reminder that the Holocene, during which complex human societies have developed, has been a stable, accommodating environment and is the only state of the Earth System that we know for sure can support contemporary society. The need to achieve effective planetary stewardship is urgent. As we go further into the Anthropocene, we risk driving the Earth System onto a trajectory toward more hostile states from which we cannot easily return.

Global and regional importance of the tropical peatland carbon pool

Abstract: Accurate inventory of tropical peatland is important in order to (a) determine the magnitude of the carbon pool; (b) estimate the scale of transfers of peat-derived greenhouse gases to the atmosphere resulting from land use change; and (c) support carbon emissions reduction policies. We review available information on tropical peatland area and thickness and calculate peat volume and carbon content in order to determine their best estimates and ranges of variation. Our best estimate of tropical peatland area is 441 025 km2 (?11% of global peatland area) of which 247 778 km2 (56%) is in Southeast Asia. We estimate the volume of tropical peat to be 1758 Gm3 (?18–25% of global peat volume) with 1359 Gm3 in Southeast Asia (77% of all tropical peat). This new assessment reveals a larger tropical peatland carbon pool than previous estimates, with a best estimate of 88.6 Gt (range 81.7–91.9 Gt) equal to 15–19% of the global peat carbon pool. Of this, 68.5 Gt (77%) is in Southeast Asia, equal to 11–14% of global peat carbon. A single country, Indonesia, has the largest share of tropical peat carbon (57.4 Gt, 65%), followed by Malaysia (9.1 Gt, 10%). These data are used to provide revised estimates for Indonesian and Malaysian forest soil carbon pools of 77 and 15 Gt, respectively, and total forest carbon pools (biomass plus soil) of 97 and 19 Gt. Peat carbon contributes 60% to the total forest soil carbon pool in Malaysia and 74% in Indonesia. These results emphasize the prominent global and regional roles played by the tropical peat carbon pool and the importance of including this pool in national and regional assessments of terrestrial carbon stocks and the prediction of peat-derived greenhouse gas emissions.

Design concepts for the Cherenkov Telescope Array CTA: An advanced facility for ground-based high-energy gamma-ray astronomy

Abstract: Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.

Human metabolic individuality in biomedical and pharmaceutical research

Abstract: Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.

Acute Exacerbations of Chronic Obstructive Pulmonary Disease: Identification of Biologic Clusters and Their Biomarkers

Abstract: Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology. Objectives: Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation. Methods: Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated. Measurements and Main Results: A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed "pauciinflammatory." Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1 beta, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83-0.95); serum CXCL10, 0.83 (95% CI, 0.70-0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78-0.93), respectively. Conclusions: The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1 beta, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.

Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility

Abstract: Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 x 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 x 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.

Epidemiology of Autism Spectrum Disorders in Adults in the Community in England

Abstract: Context To our knowledge, there is no published information on the epidemiology of autism spectrum disorders (ASDs) in adults. If the prevalence of autism is increasing, rates in older adults would be expected to be lower than rates among younger adults. Objective To estimate the prevalence and characteristics of adults with ASD living in the community in England. Design A stratified, multiphase random sample was used in the third national survey of psychiatric morbidity in adults in England in 2007. Survey data were weighted to take account of study design and nonresponse so that the results were representative of the household population. Setting General community (ie, private households) in England. Participants Adults (people 16 years or older). Main Outcome Measures Autism Diagnostic Observation Schedule, Module 4 in phase 2 validated against the Autism Diagnostic Interview–Revised and Diagnostic Interview for Social and Communication Disorders in phase 3. A 20-item subset of the Autism-Spectrum Quotient self-completion questionnaire was used in phase 1 to select respondents for phase 2. Respondents also provided information on sociodemographics and their use of mental health services. Results Of 7461 adult participants who provided a complete phase 1 interview, 618 completed phase 2 diagnostic assessments. The weighted prevalence of ASD in adults was estimated to be 9.8 per 1000 (95% confidence interval, 3.0-16.5). Prevalence was not related to the respondent's age. Rates were higher in men, those without educational qualifications, and those living in rented social (government-financed) housing. There was no evidence of increased use of services for mental health problems. Conclusions Conducting epidemiologic research on ASD in adults is feasible. The prevalence of ASD in this population is similar to that found in children. The lack of an association with age is consistent with there having been no increase in prevalence and with its causes being temporally constant. Adults with ASD living in the community are socially disadvantaged and tend to be unrecognized.

Phages in nature.

Abstract: Phages are the most abundant organisms in the biosphere and they are a ubiquitous feature of prokaryotic existence. A bacteriophage is a virus which infects a bacterium. Archaea are also infected by viruses, whether these should be referred to as ‘phages’ is debatable, but they are included as such in the scope this article. Phage have been of interest to scientists as tools to understand fundamental molecular biology, as vectors of horizontal gene transfer and drivers of bacterial evolution, as sources of diagnostic and genetic tools, and as novel therapeutic agents. Unraveling the biology of phages and their relationship with their hosts is key to understanding microbial systems and their exploitation. In this article we describe the roles of phages in different host systems and show how modeling, microscopy, isolation, genomic and metagenomic based approaches have come together recently to provide unparalleled insights into these small but vital constituents of the microbial world.

Matters of care in technoscience: assembling neglected things. .

Abstract: This paper aims to encourage an ethos of care in the study of science and technology. It starts with a reading of Bruno Latour's notion of'matters of concern' as favouring an awareness of the ethico-political effects of constructivist accounts in STS. Introducing attention to concern brings us closer to a notion of care. However, there is a'critical' edge to care that Latour's politics of things tends to disregard. Drawing upon feminist knowledge politics, I propose to treat matters of fact and sociotechnical assemblages as 'matters of care' and argue that engaging with care requires a speculative commitment to neglected things.

The Spitzer-WISE Survey of the Ecliptic Poles

Abstract: We have carried out a survey of the north and south ecliptic poles, EP-N and EP-S, respectively, with the Spitzer Space Telescope and the Wide-field Infrared Survey Explorer (WISE). The primary objective was to cross-calibrate WISE with the Spitzer and Midcourse Space Experiment (MSX) photometric systems by developing a set of calibration stars that are common to these infrared missions. The ecliptic poles were continuous viewing zones for WISE due to its polar-crossing orbit, making these areas ideal for both absolute and internal calibrations. The Spitzer IRAC and MIPS imaging survey covers a complete area of 0.40 deg^2 for the EP-N and 1.28 deg^2 for the EP-S. WISE observed the whole sky in four mid-infrared bands, 3.4, 4.6, 12, and 22 μm, during its eight-month cryogenic mission, including several hundred ecliptic polar passages; here we report on the highest coverage depths achieved by WISE, an area of ~1.5 deg^2 for both poles. Located close to the center of the EP-N, the Sy-2 galaxy NGC 6552 conveniently functions as a standard calibrator to measure the red response of the 22 μm channel of WISE. Observations from Spitzer-IRAC/MIPS/IRS-LL and WISE show that the galaxy has a strong red color in the mid-infrared due to star-formation and the presence of an active galactic nucleus (AGN), while over a baseline >1 year the mid-IR photometry of NGC 6552 is shown to vary at a level less than 2%. Combining NGC 6552 with the standard calibrator stars, the achieved photometric accuracy of the WISE calibration, relative to the Spitzer and MSX systems, is 2.4%, 2.8%, 4.5%, and 5.7% for W1 (3.4 μm), W2 (4.6 μm), W3 (12 μm), and W4 (22 μm), respectively. The WISE photometry is internally stable to better than 0.1% over the cryogenic lifetime of the mission. The secondary objective of the Spitzer-WISE Survey was to explore the poles at greater flux-level depths, exploiting the higher angular resolution Spitzer observations and the exceptionally deep (in total coverage) WISE observations that potentially reach down to the confusion limit of the survey. The rich Spitzer and WISE data sets were used to study the Galactic and extragalactic populations through source counts, color-magnitude and color-color diagrams. As an example of what the data sets facilitate, we have separated stars from galaxies, delineated normal galaxies from power-law-dominated AGNs, and reported on the different fractions of extragalactic populations. In the EP-N, we find an AGN source density of ~260 deg^(–2) to a 12 μm depth of 115 μJy, representing 15% of the total extragalactic population to this depth, similar to what has been observed for low-luminosity AGNs in other fields.

A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease

Abstract: Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). ...

A possible relativistic jetted outburst from a massive black hole fed by a tidally disrupted star.

Abstract: Gas accretion onto some massive black holes (MBHs) at the centers of galaxies actively powers luminous emission, but most MBHs are considered dormant. Occasionally, a star passing too near an MBH is torn apart by gravitational forces, leading to a bright tidal disruption flare (TDF). Although the high-energy transient Sw 1644+57 initially displayed none of the theoretically anticipated (nor previously observed) TDF characteristics, we show that observations suggest a sudden accretion event onto a central MBH of mass about 106 to 107 solar masses. There is evidence for a mildly relativistic outflow, jet collimation, and a spectrum characterized by synchrotron and inverse Compton processes; this leads to a natural analogy of Sw 1644+57 to a temporary smaller-scale blazar.

Relativistic jet activity from the tidal disruption of a star by a massive black hole

Abstract: Two groups report observations of the X-ray source Swift J164449.3+573451, which was discovered when it triggered the Swift Burst Alert Telescope on 28 March 2011. Burrows et al. report that the source has increased in brightness in the X-ray band more than 10,000-fold since 1990, and by more than 100-fold since early 2010. They conclude that we are observing the onset of relativistic jet activity from a supermassive black hole. Zauderer et al. arrive at a similar conclusion based on their observation of a radio transient associated with the source, and extensive monitoring at centimetre to millimetre wavelengths during the first month of its evolution. They estimate the mass of the black hole at around 106 solar masses. Supermassive black holes have powerful gravitational fields with strong gradients that can destroy stars that get too close1,2, producing a bright flare in ultraviolet and X-ray spectral regions from stellar debris that forms an accretion disk around the black hole3,4,5,6,7. The aftermath of this process may have been seen several times over the past two decades in the form of sparsely sampled, slowly fading emission from distant galaxies8,9,10,11,12,13,14, but the onset of the stellar disruption event has not hitherto been observed. Here we report observations of a bright X-ray flare from the extragalactic transient Swift J164449.3+573451. This source increased in brightness in the X-ray band by a factor of at least 10,000 since 1990 and by a factor of at least 100 since early 2010. We conclude that we have captured the onset of relativistic jet activity from a supermassive black hole. A companion paper15 comes to similar conclusions on the basis of radio observations. This event is probably due to the tidal disruption of a star falling into a supermassive black hole, but the detailed behaviour differs from current theoretical models of such events.

Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data

Abstract: Objective To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease. Design Mendelian randomisation meta-analysis of ind ...

Explaining Michigan: Developing an Ex Post Theory of a Quality Improvement Program

Abstract: Context: Understanding how and why programs work—not simply whether they work—is crucial. Good theory is indispensable to advancing the science of improvement. We argue for the usefulness of ex post theorization of programs. Methods: We propose an approach, located within the broad family of theory-oriented methods, for developing ex post theories of interventional programs. We use this approach to develop an ex post theory of the Michigan Intensive Care Unit (ICU) project, which attracted international attention by successfully reducing rates of central venous catheter bloodstream infections (CVC-BSIs). The procedure used to develop the ex post theory was (1) identify program leaders’ initial theory of change and learning from running the program; (2) enhance this with new information in the form of theoretical contributions from social scientists; (3) synthesize prior and new information to produce an updated theory. Findings: The Michigan project achieved its effects by (1) generating isomorphic pressures for ICUs to join the program and conform to its requirements; (2) creating a densely networked community with strong horizontal links that exerted normative pressures on members; (3) reframing CVC-BSIs as a social problem and addressing it through a professional movement combining “grassroots” features with a vertically integrating program structure; (4) using several interventions that functioned in different ways to shape a culture of commitment to doing better in practice; (5) harnessing data on infection rates as a disciplinary force; and (6) using “hard edges.” Conclusions: Updating program theory in the light of experience from program implementation is essential to improving programs’ generalizability and transferability, although it is not a substitute for concurrent evaluative fieldwork. Future iterations of programs based on the Michigan project, and improvement science more generally, may benefit from the updated theory present here.

Early Identification and Management of Psychological Risk Factors (“Yellow Flags”) in Patients With Low Back Pain: A Reappraisal

Abstract: Originally the term "yellow flags" was used to describe psychosocial prognostic factors for the development of disability following the onset of musculoskeletal pain. The identification of yellow flags through early screening was expected to prompt the application of intervention guidelines to achieve secondary prevention. In recent conceptualizations of yellow flags, it has been suggested that their range of applicability should be confined primarily to psychological risk factors to differentiate them from other risk factors, such as social and environmental variables. This article addresses 2 specific questions that arise from this development: (1) Can yellow flags influence outcomes in people with acute or subacute low back pain? and (2) Can yellow flags be targeted in interventions to produce better outcomes? Consistent evidence has been found to support the role of various psychological factors in prognosis, although questions remain about which factors are the most important, both individually and in combination, and how they affect outcomes. Published early interventions have reported mixed results, but, overall, the evidence suggests that targeting yellow flags, particularly when they are at high levels, does seem to lead to more consistently positive results than either ignoring them or providing omnibus interventions to people regardless of psychological risk factors. Psychological risk factors for poor prognosis can be identified clinically and addressed within interventions, but questions remain in relation to issues such as timing, necessary skills, content of treatments, and context. In addition, there is still a need to elucidate mechanisms of change and better integrate this understanding into the broader context of secondary prevention of chronic pain and disability.

Glycaemic control in type 1 diabetes during real time continuous glucose monitoring compared with self monitoring of blood glucose: meta-analysis of randomised controlled trials using individual patient data

Abstract: Objective To determine the clinical effectiveness of real time continuous glucose monitoring compared with self monitoring of blood glucose in type 1 diabetes. Design Meta-analysis of randomised controlled trials. Data sources Cochrane database for randomised controlled trials, Ovid Medline, Embase, Google Scholar, lists of papers supplied by manufacturers of continuous glucose monitors, and cited literature in retrieved articles. Studies reviewed Randomised controlled trials of two or more months’ duration in men and non-pregnant women with type 1 diabetes that compared real time continuous glucose monitoring with self monitoring of blood glucose and where insulin delivery was the same in both arms. Analysis Two step meta-analysis of individual patient data with the primary outcome of final glycated haemoglobin (HbA 1c ) percentage and area under the curve of hypoglycaemia (glucose concentration 1c and hypoglycaemia. Results Six trials were identified, consisting of 449 patients randomised to continuous glucose monitoring and 443 to self monitoring of blood glucose. The overall mean difference in HbA 1c for continuous glucose monitoring versus self monitoring of blood glucose was −0.30% (95% confidence interval −0.43% to −0.17%) (−3.0, −4.3 to −1.7 mmol/mol). A best fit regression model of determinants of final HbA 1c showed that for every one day increase of sensor usage per week the effect of continuous glucose monitoring versus self monitoring of blood glucose increased by 0.150% (95% credibility interval −0.194% to −0.106%) (1.5, −1.9 to −1.1 mmol/mol) and every 1% (10 mmol/mol) increase in baseline HbA 1c increased the effect by 0.126% (−0.257% to 0.0007%) (1.3, −2.6 to 0.0 mmol/mol). The model estimates that, for example, a patient using the sensor continuously would experience a reduction in HbA 1c of about 0.9% (9 mmol/mol) when the baseline HbA 1c is 10% (86 mmol/mol). The overall reduction in area under the curve of hypoglycaemia was −0.28 (−0.46 to −0.09), corresponding to a reduction in median exposure to hypoglycaemia of 23% for continuous glucose monitoring compared with self monitoring of blood glucose. In a best fit regression model, baseline area under the curve of hypoglycaemia was only weakly related to the effect of continuous glucose monitoring compared with self monitoring of blood glucose on hypoglycaemia outcome, and sensor usage was unrelated to hypoglycaemia at outcome. Conclusions Continuous glucose monitoring was associated with a significant reduction in HbA 1c percentage, which was greatest in those with the highest HbA 1c at baseline and who most frequently used the sensors. Exposure to hypoglycaemia was also reduced during continuous glucose monitoring. The most cost effective or appropriate use of continuous glucose monitoring is likely to be when targeted at people with type 1 diabetes who have continued poor control during intensified insulin therapy and who frequently use continuous glucose monitoring.

Preterm birth and childhood psychiatric disorders.

Abstract: Epidemiologic studies have, for many years, identified preterm birth as a significant risk factor for psychiatric disorders. There has been a recent resurgence of interest in neurobehavioral outcomes after preterm birth. In this article, we review clinical cohort studies of the prevalence, etiology, and risk factors for psychiatric sequelae in ex-preterm children. Studies using diagnostic psychiatric evaluations are few in number but typically report a 3- to 4-fold increased risk for disorders in middle childhood. Our review of studies reveals a "preterm behavioral phenotype" characterized by an increased risk for symptoms and disorders associated with inattention, anxiety, and social difficulties. The most contemporary studies have also reported a markedly increased prevalence of autism spectrum disorders (ASD) in preterm populations. Our examination of the correlates and comorbidities of psychiatric disorders is indicative of a different causative pathway that may be associated with altered brain development after preterm birth. Despite the low population attributable risk, the frequency of these symptoms and disorders means that psychiatric screening is likely to be beneficial in this vulnerable population.

LINE-1 Elements in Structural Variation and Disease

Abstract: The completion of the human genome reference sequence ushered in a new era for the study and discovery of human transposable elements. It now is undeniable that transposable elements, historically dismissed as junk DNA, have had an instrumental role in sculpting the structure and function of our genomes. In particular, long interspersed element-1 (LINE-1 or L1) and short interspersed elements (SINEs) continue to affect our genome, and their movement can lead to sporadic cases of disease. Here, we briefly review the types of transposable elements present in the human genome and their mechanisms of mobility. We next highlight how advances in DNA sequencing and genomic technologies have enabled the discovery of novel retrotransposons in individual genomes. Finally, we discuss how L1-mediated retrotransposition events impact human genomes.

Management of hypertension: summary of NICE guidance

Abstract: Hypertension is one of the most important preventable causes of death worldwide and one of the commonest conditions treated in primary care in the United Kingdom, where it affects more than a quarter of all adults and over half of those over the age of 65 years.1 This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the management of hypertension,2 which updates the 2004 and 2006 clinical guidelines.3 4 5 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Diagnosing hypertension (Updated recommendation) [ Based on the experience and opinion of the Guideline Development Group (GDG) ]