Three decades of post-logging tree community recovery in naturally regenerating and actively restored dipterocarp forest in Borneo

Selective logging has affected large areas of tropical forests and there is increasing interest in how to manage selectively logged forests to enhance recovery. However, the impacts of logging and active restoration, by liberation cutting and enrichment planting, on tree community composition are poorly understood compared to trajectories of biomass recovery. Here, we assess the long-term impacts of selective logging and active restoration for biomass recovery on tree species diversity, community composition, and forest structure. We censused all stems ≥2 cm diameter at breast height (DBH) on 46 permanent plots in unlogged, primary forest in the Danum Valley Conservation Area (DVCA; 12 plots, totalling 0.6 ha) and in sites logged 23–35 years prior to the census in the Ulu Segama Forest Reserve adjacent to DVCA (34 plots, totalling 1.7 ha) in Sabah, Malaysian Borneo. Active restoration treatments, including enrichment planting and climber cutting, were implemented on 17 of the logged forest plots 12–24 years prior to the census. Total plot-level basal area and pole (5–10 cm DBH) stem density were lower in logged than unlogged forests, however no difference was found in stem density amongst saplings (2–5 cm DBH) or established trees (≥10 cm DBH). Neither basal area, nor plot-level stem density varied with time since logging at any size class, although sapling and pole stem densities were lower in actively restored than naturally regenerating logged forest. Sapling species diversity was lower in logged than unlogged forest, however there were no other significant effects of logging on tree species richness or diversity indices. Tree species composition, however, differed between logged and unlogged forests across all stem size classes (PERMANOVA), reflected by 23 significant indicator species that were only present in unlogged forest. PERMANOVA tests revealed no evidence that overall species composition changed with time since logging or with active restoration treatments at any size class. However, when naturally regenerating and actively restored communities were compared, two indicator species were identified in naturally regenerating forest and three in actively restored forests. Together our results suggest that selective logging has a lasting effect on tree community composition regardless of active restoration treatments and, even when species richness and diversity are stable, species composition remains distinct from unlogged forest for more than two decades post-harvest. Active restoration efforts should be targeted, monitored, and refined to try to ensure positive outcomes for multiple metrics of forest recovery

Increased risk of A(H1N1)pdm09 influenza infection in UK pig industry workers compared to a general population cohort

Background: Pigs are mixing vessels for influenza viral reassortment but the extent of influenza transmission between swine and humans is not well understood. Objectives: To assess whether occupational exposure to pigs is a risk factor for human infection with human and swine-adapted influenza viruses. Methods: UK pig industry workers were frequency-matched on age, region, sampling month, and gender with a community-based comparison group from the Flu Watch study. HI assays quantified antibodies for swine and human A(H1) and A(H3) influenza viruses (titres≥40 considered seropositive and indicative of infection). Virus-specific associations between seropositivity and occupational pig exposure were examined using multivariable regression models adjusted for vaccination. Pigs on the same farms were also tested for seropositivity. Results: 42% of pigs were seropositive to A(H1N1)pdm09. Pig industry workers showed evidence of increased odds of A(H1N1)pdm09 seropositivity compared to the comparison group, albeit with wide confidence intervals (CI), Adjusted Odds Ratio after accounting for possible cross reactivity with other swine A(H1) viruses (aOR) 25.30, 95% CI [1.44-536.34], p=0.028. Conclusion: The results indicate that A(H1N1)pdm09 virus was common in UK pigs during the pandemic and subsequent period of human A(H1N1)pdm09 circulation, and occupational exposure to pigs was a risk factor for human infection. Influenza immunization of pig industry workers may reduce transmission and the potential for virus reassortment

Increased risk of A(H1N1)pdm09 influenza infection in UK pig industry workers compared to a general population cohort.

BACKGROUND: Pigs are mixing vessels for influenza viral reassortment, but the extent of influenza transmission between swine and humans is not well understood. OBJECTIVES: To assess whether occupational exposure to pigs is a risk factor for human infection with human and swine-adapted influenza viruses. METHODS: UK pig industry workers were frequency-matched on age, region, sampling month, and gender with a community-based comparison group from the Flu Watch study. HI assays quantified antibodies for swine and human A(H1) and A(H3) influenza viruses (titres ≥ 40 considered seropositive and indicative of infection). Virus-specific associations between seropositivity and occupational pig exposure were examined using multivariable regression models adjusted for vaccination. Pigs on the same farms were also tested for seropositivity. RESULTS: Forty-two percent of pigs were seropositive to A(H1N1)pdm09. Pig industry workers showed evidence of increased odds of A(H1N1)pdm09 seropositivity compared to the comparison group, albeit with wide confidence intervals (CIs), adjusted odds ratio after accounting for possible cross-reactivity with other swine A(H1) viruses (aOR) 25·3, 95% CI (1·4-536·3), P = 0·028. CONCLUSION: The results indicate that A(H1N1)pdm09 virus was common in UK pigs during the pandemic and subsequent period of human A(H1N1)pdm09 circulation, and occupational exposure to pigs was a risk factor for human infection. Influenza immunisation of pig industry workers may reduce transmission and the potential for virus reassortment.This work was supported by joint funding from the Biotechnology and Biological Sciences Research Council (BBSRC), the Medical Research Council (MRC), and the Wellcome Trust (WT) [(BBSRC/MRC/WT) BB/H014306/1; (MRC/WT) MC_U122785833; (MRC) G0800767 and G0600511]; Alborada Trust (to J.L.N.W.); the RAPIDD programme of the Science & Technology Directorate (to J.L.N.W.); US Department of Homeland Security (to J.L.N.W.); and the Fogarty International Center at the National Institutes of Health (to J.L.N.W.). DAI is supported by a fellowship from the National Institute for Health Research (NIHR) (PDF-2012-05-305) (this research is independent and the views expressed in this publication are those of the authors and not necessarily those of the Department of Health or NIHR).This is the final version of the article. It first appeared from Wiley via https://doi.org//10.1111/irv.12364/abstract

A facilitated home-based cardiac rehabilitation intervention for people with heart failure and their caregivers:a research programme including the REACH-HF RCT

Background: Rates of participation in centre (hospital)-cardiac rehabilitation by patients with heart failure are suboptimal. Heart failure has two main phenotypes differing in underlying pathophysiology: Heart failure with reduced ejection fraction is characterised by depressed left ventricular systolic function (‘reduced ejection fraction’), whereas heart failure with preserved ejection fraction is diagnosed after excluding other causes of dyspnoea with normal ejection fraction. This programme aimed to develop and evaluate a facilitated home-based cardiac rehabilitation intervention that could increase the uptake of cardiac rehabilitation while delivering the clinical benefits of centre-based cardiac rehabilitation. Objectives: To develop an evidence-informed, home-based, self-care cardiac rehabilitation programme for patients with heart failure and their caregivers [the REACH-HF (Rehabilitation Enablement in Chronic Heart Failure) intervention]. To conduct a pilot randomised controlled trial to assess the feasibility of a full trial of the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with preserved ejection fraction. To assess the short- and long-term clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with reduced ejection fraction and their caregivers. Design: Intervention mapping to develop the REACH-HF intervention; uncontrolled feasibility study; pilot randomised controlled trial in those with heart failure with preserved ejection fraction; randomised controlled trial with a trial-based cost-effectiveness analysis in those with heart failure with reduced ejection fraction; qualitative studies including process evaluation; systematic review of cardiac rehabilitation in heart failure; and modelling to assess long-term cost-effectiveness (in those with heart failure with reduced ejection fraction). Setting: Four centres in England and Wales (Birmingham, Cornwall, Gwent and York); one centre in Scotland (Dundee) for a pilot randomised controlled trial. Participants: Adults aged ≥ 18 years with heart failure with reduced ejection fraction (left ventricular ejection fraction &lt; 45%) for the main randomised controlled trial (n = 216), and those with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥ 45%) for the pilot randomised controlled trial (n = 50). Intervention: A self-care, facilitated cardiac rehabilitation manual was offered to patients (and participating caregivers) at home over 12 weeks by trained health-care professionals in addition to usual care or usual care alone. Main outcome measures: The primary outcome was disease-specific health-related quality of life measured using the Minnesota Living with Heart Failure Questionnaire at 12 months. Secondary outcomes included deaths and hospitalisations. Results: The main randomised controlled trial recruited 216 participants with heart failure with reduced ejection fraction and 97 caregivers. A significant and clinically meaningful between-group difference in the Minnesota Living with Heart Failure Questionnaire score (primary outcome) at 12 months (–5.7 points, 95% confidence interval –10.6 to –0.7 points) favoured the REACH-HF intervention (p = 0.025). Eight (4%) patients (four in each group) had died at 12 months. There was no significant difference in hospital admissions, at 12 months, with 19 participants in the REACH-HF intervention group having at least one hospital admission, compared with 24 participants in the control group (odds ratio 0.72, 95% confidence interval 0.35 to 1.51; p = 0.386). The mean cost of the intervention was £418 per participant with heart failure with reduced ejection fraction. The costs at 12 months were, on average, £401 higher in the intervention group than in the usual care alone group. Model-based economic evaluation, extrapolating from the main randomised controlled trial in those with heart failure with reduced ejection fraction over 4 years, found that adding the REACH-HF intervention to usual care had an estimated mean cost per participant of £15,452 (95% confidence interval £14,240 to £16,780) and a mean quality-adjusted lifeyear gain of 4.47 (95% confidence interval 3.83 to 4.91) years, compared with £15,051 (95% confidence interval £13,844 to £16,289) and 4.24 (95% confidence interval 4.05 to 4.43) years, respectively, for usual care alone. This gave an incremental cost per quality-adjusted life-year of £1721. The probabilistic sensitivity analysis indicated 78% probability that the intervention plus usual care versus usual care alone has a cost-effectiveness below the willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained. The intervention was well received by participants with heart failure with reduced ejection fraction and those with heart failure with preserved ejection fraction, as well as their caregivers. Both randomised controlled trials recruited to target, with &gt; 85% retention at follow-up. Limitations: Key limitations included (1) lack of blinding – given the nature of the intervention and the control we could not mask participants to treatments, so our results may reflect participant expectation bias; (2) that we were not able to capture consistent participant-level data on level of intervention adherence; (3) that there may be an impact on the generalisability of findings due to the demographics of the trial patients, as most were male (78%) and we recruited only seven people from ethnic minorities. Conclusions: Evaluation of the comprehensive, facilitated, home-based REACH-HF intervention for participants with heart failure with reduced ejection fraction and caregivers indicated clinical effectiveness in terms of health-related quality of life and patient self-care but no other secondary outcomes. Although the economic analysis conducted alongside the full randomised controlled trial did not produce significant differences on the EuroQol-5 Dimensions or in quality-adjusted life-years, economic modelling suggested greater cost-effectiveness of the intervention than usual care. Our REACH-HF intervention offers a new evidence-based cardiac rehabilitation option that could increase uptake of cardiac rehabilitation in patients with heart failure not attracted to or able to access hospital-based programmes. Future work: Systematic collection of real-world data would track future changes in uptake of and adherence to alternative cardiac rehabilitation interventions in heart failure with reduced ejection fraction and increase understanding of how changes in service delivery might affect clinical and health economic outcomes. The findings of our pilot randomised controlled trial in patients with heart failure with preserved ejection fraction support progression to a full multicentre randomised controlled trial. </p

A facilitated home-based cardiac rehabilitation intervention for people with heart failure and their caregivers:a research programme including the REACH-HF RCT

Background: Rates of participation in centre (hospital)-cardiac rehabilitation by patients with heart failure are suboptimal. Heart failure has two main phenotypes differing in underlying pathophysiology: Heart failure with reduced ejection fraction is characterised by depressed left ventricular systolic function (‘reduced ejection fraction’), whereas heart failure with preserved ejection fraction is diagnosed after excluding other causes of dyspnoea with normal ejection fraction. This programme aimed to develop and evaluate a facilitated home-based cardiac rehabilitation intervention that could increase the uptake of cardiac rehabilitation while delivering the clinical benefits of centre-based cardiac rehabilitation. Objectives: To develop an evidence-informed, home-based, self-care cardiac rehabilitation programme for patients with heart failure and their caregivers [the REACH-HF (Rehabilitation Enablement in Chronic Heart Failure) intervention]. To conduct a pilot randomised controlled trial to assess the feasibility of a full trial of the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with preserved ejection fraction. To assess the short- and long-term clinical effectiveness and cost-effectiveness of the REACH-HF intervention in addition to usual care in patients with heart failure with reduced ejection fraction and their caregivers. Design: Intervention mapping to develop the REACH-HF intervention; uncontrolled feasibility study; pilot randomised controlled trial in those with heart failure with preserved ejection fraction; randomised controlled trial with a trial-based cost-effectiveness analysis in those with heart failure with reduced ejection fraction; qualitative studies including process evaluation; systematic review of cardiac rehabilitation in heart failure; and modelling to assess long-term cost-effectiveness (in those with heart failure with reduced ejection fraction). Setting: Four centres in England and Wales (Birmingham, Cornwall, Gwent and York); one centre in Scotland (Dundee) for a pilot randomised controlled trial. Participants: Adults aged ≥ 18 years with heart failure with reduced ejection fraction (left ventricular ejection fraction &lt; 45%) for the main randomised controlled trial (n = 216), and those with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥ 45%) for the pilot randomised controlled trial (n = 50). Intervention: A self-care, facilitated cardiac rehabilitation manual was offered to patients (and participating caregivers) at home over 12 weeks by trained health-care professionals in addition to usual care or usual care alone. Main outcome measures: The primary outcome was disease-specific health-related quality of life measured using the Minnesota Living with Heart Failure Questionnaire at 12 months. Secondary outcomes included deaths and hospitalisations. Results: The main randomised controlled trial recruited 216 participants with heart failure with reduced ejection fraction and 97 caregivers. A significant and clinically meaningful between-group difference in the Minnesota Living with Heart Failure Questionnaire score (primary outcome) at 12 months (–5.7 points, 95% confidence interval –10.6 to –0.7 points) favoured the REACH-HF intervention (p = 0.025). Eight (4%) patients (four in each group) had died at 12 months. There was no significant difference in hospital admissions, at 12 months, with 19 participants in the REACH-HF intervention group having at least one hospital admission, compared with 24 participants in the control group (odds ratio 0.72, 95% confidence interval 0.35 to 1.51; p = 0.386). The mean cost of the intervention was £418 per participant with heart failure with reduced ejection fraction. The costs at 12 months were, on average, £401 higher in the intervention group than in the usual care alone group. Model-based economic evaluation, extrapolating from the main randomised controlled trial in those with heart failure with reduced ejection fraction over 4 years, found that adding the REACH-HF intervention to usual care had an estimated mean cost per participant of £15,452 (95% confidence interval £14,240 to £16,780) and a mean quality-adjusted lifeyear gain of 4.47 (95% confidence interval 3.83 to 4.91) years, compared with £15,051 (95% confidence interval £13,844 to £16,289) and 4.24 (95% confidence interval 4.05 to 4.43) years, respectively, for usual care alone. This gave an incremental cost per quality-adjusted life-year of £1721. The probabilistic sensitivity analysis indicated 78% probability that the intervention plus usual care versus usual care alone has a cost-effectiveness below the willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained. The intervention was well received by participants with heart failure with reduced ejection fraction and those with heart failure with preserved ejection fraction, as well as their caregivers. Both randomised controlled trials recruited to target, with &gt; 85% retention at follow-up. Limitations: Key limitations included (1) lack of blinding – given the nature of the intervention and the control we could not mask participants to treatments, so our results may reflect participant expectation bias; (2) that we were not able to capture consistent participant-level data on level of intervention adherence; (3) that there may be an impact on the generalisability of findings due to the demographics of the trial patients, as most were male (78%) and we recruited only seven people from ethnic minorities. Conclusions: Evaluation of the comprehensive, facilitated, home-based REACH-HF intervention for participants with heart failure with reduced ejection fraction and caregivers indicated clinical effectiveness in terms of health-related quality of life and patient self-care but no other secondary outcomes. Although the economic analysis conducted alongside the full randomised controlled trial did not produce significant differences on the EuroQol-5 Dimensions or in quality-adjusted life-years, economic modelling suggested greater cost-effectiveness of the intervention than usual care. Our REACH-HF intervention offers a new evidence-based cardiac rehabilitation option that could increase uptake of cardiac rehabilitation in patients with heart failure not attracted to or able to access hospital-based programmes. Future work: Systematic collection of real-world data would track future changes in uptake of and adherence to alternative cardiac rehabilitation interventions in heart failure with reduced ejection fraction and increase understanding of how changes in service delivery might affect clinical and health economic outcomes. The findings of our pilot randomised controlled trial in patients with heart failure with preserved ejection fraction support progression to a full multicentre randomised controlled trial. </p

A Randomised Controlled Trial of a Facilitated Home-Based Rehabilitation Intervention in Patients with Heart Failure with Preserved Ejection Fraction and their Caregivers:The REACH-HFpEF Pilot Study

Abstract Introduction Home-based cardiac rehabilitation may overcome suboptimal rates of participation. The overarching aim of this study was to assess the feasibility and acceptability of the novel Rehabilitation EnAblement in CHronic Hear Failure (REACH-HF) rehabilitation intervention for patients with heart failure with preserved ejection fraction (HFpEF) and their caregivers. Methods and results Patients were randomised 1:1 to REACH-HF intervention plus usual care (intervention group) or usual care alone (control group). REACH-HF is a home-based comprehensive self-management rehabilitation programme that comprises patient and carer manuals with supplementary tools, delivered by trained healthcare facilitators over a 12 week period. Patient outcomes were collected by blinded assessors at baseline, 3 months and 6 months postrandomisation and included health-related quality of life (primary) and psychological well-being, exercise capacity, physical activity and HF-related hospitalisation (secondary). Outcomes were also collected in caregivers. We enrolled 50 symptomatic patients with HF from Tayside, Scotland with a left ventricular ejection fraction ≥45% (mean age 73.9 years, 54% female, 100% white British) and 21 caregivers. Study retention (90%) and intervention uptake (92%) were excellent. At 6 months, data from 45 patients showed a potential direction of effect in favour of the intervention group, including the primary outcome of Minnesota Living with Heart Failure Questionnaire total score (between-group mean difference −11.5, 95% CI −22.8 to 0.3). A total of 11 (4 intervention, 7 control) patients experienced a hospital admission over the 6 months of follow-up with 4 (control patients) of these admissions being HF-related. Improvements were seen in a number intervention caregivers' mental health and burden compared with control. Conclusions Our findings support the feasibility and rationale for delivering the REACH-HF facilitated home-based rehabilitation intervention for patients with HFpEF and their caregivers and progression to a full multicentre randomised clinical trial to test its clinical effectiveness and cost-effectiveness

Quantifying the extent to which index event biases influence large genetic association studies

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.As genetic association studies increase in size to 100,000s of individuals, subtle biases may influence conclusions. One possible bias is "index event bias" (IEB) that appears due to the stratification by, or enrichment for, disease status when testing associations between genetic variants and a disease-associated trait. We aimed to test the extent to which IEB influences some known trait associations in a range of study designs and provide a statistical framework for assessing future associations. Analysing data from 113,203 non-diabetic UK Biobank participants, we observed three (near TCF7L2, CDKN2AB and CDKAL1) overestimated (BMI-decreasing) and one (near MTNR1B) underestimated (BMI-increasing) associations among 11 type 2 diabetes risk alleles (at P  500,000 if the prevalence of those diseases differs by > 10% from the background population. In conclusion, IEB may result in false positive or negative genetic associations in very large studies stratified or strongly enriched for/against disease cases.H.Y., A.R.W. and T.M.F. are supported by the European Research Council grant: 323195; SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC. S.E.J. is funded by the Medical Research Council (grant: MR/M005070/1). M.A.T., M.N.W. and A.M. are supported by the Wellcome Trust Institutional Strategic Support Award (WT097835MF). R.M.F. is a Sir Henry Dale Fellow (Wellcome Trust and Royal Society grant: 104150/Z/14/Z). R.B. is funded by the Wellcome Trust and Royal Society grant: 104150/Z/14/Z. J.T. is funded by a Diabetes Research and Wellness Foundation Fellowship. Z.K. received financial support from the Leenaards Foundation, the Swiss Institute of Bioinformatics and the Swiss National Science Foundation (31003A-143914) and SystemsX.ch (39). The work of M.P.B was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award no. T32HL007779. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. E.R.P. holds a WT New investigator award 102820/Z/13/Z

Genetic Evidence for a Link Between Favorable Adiposity and Lower Risk of Type 2 Diabetes, Hypertension, and Heart Disease.

Recent genetic studies have identified some alleles that are associated with higher BMI but lower risk of type 2 diabetes, hypertension, and heart disease. These "favorable adiposity" alleles are collectively associated with lower insulin levels and higher subcutaneous-to-visceral adipose tissue ratio and may protect from disease through higher adipose storage capacity. We aimed to use data from 164,609 individuals from the UK Biobank and five other studies to replicate associations between a genetic score of 11 favorable adiposity variants and adiposity and risk of disease, to test for interactions between BMI and favorable adiposity genetics, and to test effects separately in men and women. In the UK Biobank, the 50% of individuals carrying the most favorable adiposity alleles had higher BMIs (0.120 kg/m(2) [95% CI 0.066, 0.174]; P = 1E-5) and higher body fat percentage (0.301% [0.230, 0.372]; P = 1E-16) compared with the 50% of individuals carrying the fewest alleles. For a given BMI, the 50% of individuals carrying the most favorable adiposity alleles were at lower risk of type 2 diabetes (odds ratio [OR] 0.837 [0.784, 0.894]; P = 1E-7), hypertension (OR 0.935 [0.911, 0.958]; P = 1E-7), and heart disease (OR 0.921 [0.872, 0.973]; P = 0.003) and had lower blood pressure (systolic -0.859 mmHg [-1.099, -0.618]; P = 3E-12 and diastolic -0.394 mmHg [-0.534, -0.254]; P = 4E-8). In women, these associations could be explained by the observation that the alleles associated with higher BMI but lower risk of disease were also associated with a favorable body fat distribution, with a lower waist-to-hip ratio (-0.004 cm [95% CI -0.005, -0.003] 50% vs. 50%; P = 3E-14), but in men, the favorable adiposity alleles were associated with higher waist circumference (0.454 cm [0.267, 0.641] 50% vs. 50%; P = 2E-6) and higher waist-to-hip ratio (0.0013 [0.0003, 0.0024] 50% vs. 50%; P = 0.01). Results were strengthened when a meta-analysis with five additional studies was conducted. There was no evidence of interaction between a genetic score consisting of known BMI variants and the favorable adiposity genetic score. In conclusion, different molecular mechanisms that lead to higher body fat percentage (with greater subcutaneous storage capacity) can have different impacts on cardiometabolic disease risk. Although higher BMI is associated with higher risk of diseases, better fat storage capacity could reduce the risk.This is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/db15-167

Epigenetic scores for the circulating proteome as tools for disease prediction

Protein biomarkers have been identified across many age-related morbidities. However, characterising epigenetic influences could further inform disease predictions. Here, we leverage epigenome-wide data to study links between the DNA methylation (DNAm) signatures of the circulating proteome and incident diseases. Using data from four cohorts, we trained and tested epigenetic scores (EpiScores) for 953 plasma proteins, identifying 109 scores that explained between 1% and 58% of the variance in protein levels after adjusting for known protein quantitative trait loci (pQTL) genetic effects. By projecting these EpiScores into an independent sample (Generation Scotland; n = 9537) and relating them to incident morbidities over a follow-up of 14 years, we uncovered 137 EpiScore-disease associations. These associations were largely independent of immune cell proportions, common lifestyle and health factors, and biological aging. Notably, we found that our diabetes-associated EpiScores highlighted previous top biomarker associations from proteome-wide assessments of diabetes. These EpiScores for protein levels can therefore be a valuable resource for disease prediction and risk stratification