Prebiotic fructans have greater impact on luminal microbiology and CD3+ T cells in healthy siblings than patients with Crohn’s disease : a pilot study investigating the potential for primary prevention of inflammatory bowel disease

Funding This work was supported by a clinical research fellowship granted by the charity Core (Guts UK) (CRH). FMF and PL received financial support from the Scottish Government Rural and Environment Science and Analytical Services. Acknowledgments The authors would like to acknowledge BENEO-Orafti, Teinen, Belgium who provided the oligofructose-enriched inulin. The authors would like to thank the patients and the siblings who generously participated in this study.Peer reviewedPostprin

Self-Screening and Non-Physician Screening for Hypertension in Communities: A Systematic Review.

BACKGROUND: Community-based self-screening may provide opportunities to increase detection of hypertension, and identify raised blood pressure (BP) in populations who do not access healthcare. This systematic review aimed to evaluate the effectiveness of non-physician screening and self-screening of BP in community settings. METHODS: We searched the Cochrane Central Trials Register, Medline, Embase, CINAHL, and Science Citation Index & Conference Proceedings Citation Index-Science to November 2013 to identify studies reporting community-based self-screening or non-physician screening for hypertension in adults. Results were stratified by study site, screener, and the cut-off used to define high screening BP. RESULTS: We included 73 studies, which described screening in 9 settings, with pharmacies (22%) and public areas/retail (15%) most commonly described. We found high levels of heterogeneity in all analyses, despite stratification. The highest proportions of eligible participants screened were achieved by mobile units (range 21%-88%) and pharmacies (range 40%-90%). Self-screeners had similar median rates of high BP detection (25%-35%) to participants in studies using other screeners. Few (16%) studies reported referral to primary care after screening. However, where participants were referred, a median of 44% (range 17%-100%) received a new hypertension diagnosis or antihypertensive medication. CONCLUSIONS: Community-based non-physician or self-screening for raised BP can detect raised BP, which may lead to the identification of new cases of hypertension. However, current evidence is insufficient to recommend specific approaches or settings. Studies with good follow-up of patients to definitive diagnosis are needed.This article presents independent research funded by a National Institute for Health Research Programme Grant RP-PG-1209–10051.This is the final version of the article. It was first available from Oxford University Press via http://dx.doi.org/10.1093/ajh/hpv02

Considering the impact of situation-specific motivations and constraints in the design of naturally ventilated and hybrid buildings

A simple logical model of the interaction between a building and its occupants is presented based on the principle that if free to do so, people will adjust their posture, clothing or available building controls (windows, blinds, doors, fans, and thermostats) with the aim of achieving or restoring comfort and reducing discomfort. These adjustments are related to building design in two ways: first the freedom to adjust depends on the availability and ease-of-use of control options; second the use of controls affects building comfort and energy performance. Hence it is essential that these interactions are considered in the design process. The model captures occupant use of controls in response to thermal stimuli (too warm, too cold etc.) and non-thermal stimuli (e.g. desire for fresh air). The situation-specific motivations and constraints on control use are represented through trigger temperatures at which control actions occur, motivations are included as negative constraints and incorporated into a single constraint value describing the specifics of each situation. The values of constraints are quantified for a range of existing buildings in Europe and Pakistan. The integration of the model within a design flow is proposed and the impact of different levels of constraints demonstrated. It is proposed that to minimise energy use and maximise comfort in naturally ventilated and hybrid buildings the designer should take the following steps: 1. Provide unconstrained low energy adaptive control options where possible, 2. Avoid problems with indoor air quality which provide motivations for excessive ventilation rates, 3. Incorporate situation-specific adaptive behaviour of occupants in design simulations, 4. Analyse the robustness of designs against variations in patterns of use and climate, and 5. Incorporate appropriate comfort standards into the operational building controls (e.g. BEMS)

The SCottish Alcoholic Liver disease Evaluation: a population-level matched cohort study of hospital-based costs, 1991-2011

Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission. 5 matched controls for every incident case were identified from the Scottish population level primary care database. Hospital costs were calculated for both cases and controls using length of stay from morbidity records and hospital-specific daily rates by specialty. Remaining lifetime costs were estimated using parametric survival models and predicted annual costs. 35,208 incident alcoholic liver disease hospitalisations were identified. Mean annual hospital costs for cases were 2.3 times that of controls pre diagnosis (£804 higher) and 10.2 times (£12,774 higher) post diagnosis. Mean incident admission cost was £6,663. Remaining lifetime cost for a male, 50-59 years old, living in the most deprived area diagnosed with acoholic liver disease was estimated to be £65,999 higher than the matched controls (£12,474 for 7.43 years remaining life compared to £1,224 for 21.8 years). In Scotland, alcoholic liver disease diagnosis is associated with significant increases in admissions to hospital both before and after diagnosis. Our results provide robust population level estimates of costs of alcoholic liver disease for the purposes of health-care delivery, planning and future cost-effectiveness analyses

Comparative significance of invasive measures of microvascular injury in acute myocardial infarction

Background: The resistive reserve ratio (RRR) expresses the ratio between basal and hyperemic microvascular resistance. RRR measures the vasodilatory capacity of the microcirculation. We compared RRR, index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) for predicting microvascular obstruction (MVO), myocardial hemorrhage, infarct size, and clinical outcomes, after ST-segment–elevation myocardial infarction. Methods: In the T-TIME trial (Trial of Low-Dose Adjunctive Alteplase During Primary PCI), 440 patients with acute ST-segment–elevation myocardial infarction from 11 UK hospitals were prospectively enrolled. In a subset of 144 patients, IMR, CFR, and RRR were measured post-primary percutaneous coronary intervention. MVO extent (% left ventricular mass) was determined by cardiovascular magnetic resonance imaging at 2 to 7 days. Infarct size was determined at 3 months. One-year major adverse cardiac events, heart failure hospitalizations, and all-cause death/heart failure hospitalizations were assessed. Results: In these 144 patients (mean age, 59±11 years, 80% male), median IMR was 29.5 (interquartile range: 17.0–55.0), CFR was 1.4 (1.1–2.0), and RRR was 1.7 (1.3–2.3). MVO occurred in 41% of patients. IMR>40 was multivariably associated with more MVO (coefficient, 0.53 [95% CI, 0.05–1.02]; P=0.031), myocardial hemorrhage presence (odds ratio [OR], 3.20 [95% CI, 1.25–8.24]; P=0.016), and infarct size (coefficient, 5.05 [95% CI, 0.84–9.26]; P=0.019), independently of CFR≤2.0, RRR≤1.7, myocardial perfusion grade≤1, and Thrombolysis in Myocardial Infarction frame count. RRR was multivariably associated with MVO extent (coefficient, −0.60 [95% CI, −0.97 to −0.23]; P=0.002), myocardial hemorrhage presence (OR, 0.34 [95% CI, 0.15–0.75]; P=0.008), and infarct size (coefficient, −3.41 [95% CI, −6.76 to −0.06]; P=0.046). IMR>40 was associated with heart failure hospitalization (OR, 5.34 [95% CI, 1.80–15.81] P=0.002), major adverse cardiac events (OR, 4.46 [95% CI, 1.70–11.70] P=0.002), and all-cause death/ heart failure hospitalization (OR, 4.08 [95% CI, 1.55–10.79] P=0.005). RRR was associated with heart failure hospitalization (OR, 0.44 [95% CI, 0.19–0.99] P=0.047). CFR was not associated with infarct characteristics or clinical outcomes. Conclusions: In acute ST-segment–elevationl infarction, IMR and RRR, but not CFR, were associated with MVO, myocardial hemorrhage, infarct size, and clinical outcomes

Improving ultrasound video classification: an evaluation of novel deep learning methods in echocardiography

Echocardiography is the commonest medical ultrasound examination, but automated interpretation is challenging and hinges on correct recognition of the ‘view’ (imaging plane and orientation). Current state-of-the-art methods for identifying the view computationally involve 2-dimensional convolutional neural networks (CNNs), but these merely classify individual frames of a video in isolation, and ignore information describing the movement of structures throughout the cardiac cycle. Here we explore the efficacy of novel CNN architectures, including time-distributed networks and two-stream networks, which are inspired by advances in human action recognition. We demonstrate that these new architectures more than halve the error rate of traditional CNNs from 8.1% to 3.9%. These advances in accuracy may be due to these networks’ ability to track the movement of specific structures such as heart valves throughout the cardiac cycle. Finally, we show the accuracies of these new state-of-the-art networks are approaching expert agreement (3.6% discordance), with a similar pattern of discordance between views

One-year outcomes after low-dose intracoronary alteplase during primary percutaneous coronary intervention. The T-TIME randomized trial

No abstract available

Epigenome-Wide Association Study of Kidney Function Identifies Trans-Ethnic and Ethnic-Specific Loci

BACKGROUND: DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. METHODS: The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. RESULTS: We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. CONCLUSIONS: We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context