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Abstract Background Forests are a key component of the global carbon cycle, and research is needed into the effects of human-driven and natural processes on their carbon pools. Airborne laser scanning (ALS) produces detailed 3D maps of forest canopy structure from which aboveground carbon density can be estimated. Working with a ALS dataset collected over the 8049-km2 Wellington Region of New Zealand we create maps of indigenous forest carbon and evaluate the influence of wind by examining how carbon storage varies with aspect. Storms flowing from the west are a common cause of disturbance in this region, and we hypothesised that west-facing forests exposed to these winds would be shorter than those in sheltered east-facing sites. Methods The aboveground carbon density of 31 forest inventory plots located within the ALS survey region were used to develop estimation models relating carbon density to ALS information. Power-law models using rasters of top-of-the-canopy height were compared with models using tree-level information extracted from the ALS dataset. A forest carbon map with spatial resolution of 25 m was generated from ALS maps of forest height and the estimation models. The map was used to evaluate the influences of wind on forests. Results Power-law models were slightly less accurate than tree-centric models (RMSE 35% vs 32%) but were selected for map generation for computational efficiency. The carbon map comprised 4.5 million natural forest pixels within which canopy height had been measured by ALS, providing an unprecedented dataset with which to examine drivers of carbon density. Forests facing in the direction of westerly storms stored less carbon, as hypothesised. They had much greater above-ground carbon density for a given height than any of 14 tropical forests previously analysed by the same approach, and had exceptionally high basal areas for their height. We speculate that strong winds have kept forests short without impeding basal area growth. Conclusion Simple estimation models based on top-of-the canopy height are almost as accurate as state-of-the-art tree-centric approaches, which require more computing power. High-resolution carbon maps produced by ALS provide powerful datasets for evaluating the environmental drivers of forest structure, such as wind.

Abstract Background In 2012, as a pilot for Botswana’s national Xpert MTB/RIF (Xpert) rollout plans, intensified tuberculosis (TB) case finding (ICF) activities were strengthened at 22 HIV treatment clinics prior to phased activation of 13 Xpert instruments. Together, the strengthened ICF intervention and Xpert activation are referred to as the “Xpert package”. Methods The evaluation, called the Xpert Package Rollout Evaluation using a Stepped-wedge design (XPRES), has two key objectives: (1) to compare sensitivity of microscopy-based and Xpert-based pulmonary TB diagnostic algorithms in diagnosing sputum culture-positive TB; and (2) to evaluate impact of the “Xpert package” on all-cause, 6-month, adult antiretroviral therapy (ART) mortality. A pragmatic, stepped-wedge cluster-randomized trial design was chosen. The design involves enrollment of three cohorts: (1) cohort R, a retrospective cohort of all study clinic ART enrollees in the 24 months before study initiation (July 31, 2012); (2) cohort A, a prospective cohort of all consenting patients presenting to study clinics after study initiation, who received the ICF intervention and the microscopy-based TB diagnostic algorithm; and (3) cohort B, a prospective cohort of all consenting patients presenting to study clinics after Xpert activation, who received the ICF intervention and the Xpert-based TB diagnostic algorithm. TB diagnostic sensitivity will be compared between TB culture-positive enrollees in cohorts A and B. All-cause, 6-month ART-mortality will be compared between cohorts R and B. With anticipated cohort R, A, and B sample sizes of about 10,131, 1,878, and 4,258, respectively, the study is estimated to have >80 % power to detect differences in pre-versus post-Xpert TB diagnostic sensitivity if pre-Xpert sensitivity is ≤52.5 % and post-Xpert sensitivity ≥82.5 %, and >80 % power to detect a 40 % reduction in all-cause, 6-month, ART mortality between cohorts R and B if cohort R mortality is ≥13/100 person-years. Discussion Only one small previous trial (N = 424) among ART enrolees in Zimbabwe evaluated, in a secondary analysis, Xpert impact on all-cause 6-month ART mortality. No mortality impact was observed. This Botswana trial, with its larger sample size and powered specifically to detect differences in all-cause 6-month ART mortality, remains well-positioned to contribute understanding of Xpert impact. Trial registration Retrospectively registered at ClinicalTrials.gov: NCT02538952 .

The endemic New Zealand kauri trees (Agathis australis) are under threat by the deadly kauri dieback disease (Phytophthora agathidicida (PA)). This study aimed to identify spectral index combinations for characterising visible stress symptoms in the kauri canopy. The analysis is based on an aerial AISA hyperspectral image mosaic and 1258 reference crowns in three study sites in the Waitakere Ranges west of Auckland. A field-based assessment scheme for canopy stress symptoms (classes 1−5) was further optimised for use with RGB aerial images. A combination of four indices with six bands in the spectral range 450−1205 nm resulted in a correlation of 0.93 (mean absolute error 0.27, RMSE 0.48) for all crown sizes. Comparable results were achieved with five indices in the 450−970 nm region. A Random Forest (RF) regression gave the most accurate predictions while a M5P regression tree performed nearly as well and a linear regression resulted in slightly lower correlations. Normalised Difference Vegetation Indices (NDVI) in the near-infrared / red spectral range were the most important index combinations, followed by indices with bands in the near-infrared spectral range from 800 to 1205 nm. A test on different crown sizes revealed that stress symptoms in smaller crowns with denser foliage are best described in combination with pigment-sensitive indices that include bands in the green and blue spectral range. A stratified approach with individual models for pre-segmented low and high forest stands improved the overall performance. The regression models were also tested in a pixel-based analysis. A manual interpretation of the resulting raster map with stress symptom patterns observed in aerial imagery indicated a good match. With bandwidths of 10 nm and a maximum number of six bands, the selected index combinations can be used for large-area monitoring on an airborne multispectral sensor. This study establishes the base for a cost-efficient, objective monitoring method for stress symptoms in kauri canopies, suitable to cover large forest areas with an airborne multispectral sensor.

A modular system for performing Geographic Object-Based Image Analysis (GEOBIA), using entirely open source (General Public License compatible) software, is presented based around representing objects as raster clumps and storing attributes as a raster attribute table (RAT). The system utilizes a number of libraries, developed by the authors: The Remote Sensing and GIS Library (RSGISLib), the Raster I/O Simplification (RIOS) Python Library, the KEA image format and TuiView image viewer. All libraries are accessed through Python, providing a common interface on which to build processing chains. Three examples are presented, to demonstrate the capabilities of the system: (1) classification of mangrove extent and change in French Guiana; (2) a generic scheme for the classification of the UN-FAO land cover classification system (LCCS) and their subsequent translation to habitat categories; and (3) a national-scale segmentation for Australia. The system presented provides similar functionality to existing GEOBIA packages, but is more flexible, due to its modular environment, capable of handling complex classification processes and applying them to larger datasets.

Niemann-Pick C1-like 1 protein (NPC1L1) plays a critical role in intestinal cholesterol absorption. Our objective was to examine whether five variants (-133A>G, -18A>C, L272L, V1296V, and U3_28650A>G) at the NPC1L1 gene have effects on lipid levels, prevalence, and incidence of coronary heart disease (CHD) and lipid-lowering response to pravastatin. We studied 5,804 elderly participants from the PROSPER study, who were randomized to prava­statin 40 mg/day or placebo and were followed on average for 3.2 years. In the adjusted gender-pooled analyses, homozygous carriers of the minor alleles at four NPC1L1 sites (-18A>C, L272L, V1296V, and U3_28650A>G, minor allele frequencies 0.15–0.33) had 2–8% higher LDL-cholesterol (LDL-C) levels at baseline than homozygous carriers of the common alleles (P < 0.05). Homozygotes for the rare alleles also had a significant increase in the risk of CHD events on trial (range of hazard ratios 1.50–1.67; P < 0.02), regardless of the treatment regimen. The -133 A>G polymorphism and not other variants was associated with 6 month LDL-C lowering (P = 0.02). Our data indicate that variation in the NPC1L1 gene is associated with plasma total and LDL-C levels and CHD risk.

Cholesterol homeostasis, defined as the balance between absorption and synthesis, influences circulating cholesterol concentrations and subsequent coronary heart disease (CHD) risk. Statin therapy targets the rate-limiting enzyme in cholesterol biosynthesis and is efficacious in lowering CHD events and mortality. Nonetheless, CHD events still occur in some treated patients. To address differences in outcome during pravastatin therapy (40 mg/day), plasma markers of cholesterol synthesis (desmosterol, lathosterol) and fractional cholesterol absorption (campesterol, sitosterol) were measured, baseline and on treatment, in the Prospective Study of Pravastatin in the Elderly at Risk trial participants with (cases, n = 223) and without (controls, n = 257) a CHD event. Pravastatin therapy decreased plasma LDL-cholesterol and triglycerides and increased HDL-cholesterol concentrations to a similar extent in cases and controls. Decreased concentrations of the cholesterol synthesis markers desmosterol (−12% and −11%) and lathosterol (−50% and −56%) and increased concentrations of the cholesterol absorption markers campesterol (48% and 51%) and sitosterol (25% and 26%) were observed on treatment, but the magnitude of change was similar between cases and controls. These data suggest that decreases in cholesterol synthesis in response to pravastatin treatment were accompanied by modest compensatory increases in fractional cholesterol absorption. The magnitude of these alterations were similar between cases and controls and do not explain differences in outcomes with pravastatin treatment.

Several plasma non-lipid biomarkers have been shown to predict major cardiovascular events (MCVEs) in population studies. Our objective was to investigate the relationship between lipid and non-lipid biomarkers levels achieved during statin therapy and the incidence of MCVEs in patients with stable coronary heart disease (CHD). We conducted a substudy of the TNT (Treating to New Targets) study, which was a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of CHD. Fasting plasma levels of standard lipids and of 18 non-lipid biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in 157 patients who experienced MCVEs during the 4.9 years of study follow-up and in 1349 controls. MCVE was defined as CHD death, nonfatal, non-procedure-related myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke. After adjusting for age, sex and treatment arm, plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), insulin, neopterin, N-terminal pro-brain natriuretic peptide (BNP), lipoprotein(a) [Lp(a)], and the soluble receptor for advanced glycation end products (sRAGE) were predictive of recurrent MCVEs (P ≤ 0.02 for each doubling of plasma concentration). However, no significant association was observed between the risk of recurrent MCVEs and plasma levels of low-density lipoprotein cholesterol, adiponectin, cystatin C, lipoprotein-associated phospholipase A2, monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, osteopontin, soluble CD40 ligand, soluble intercellular adhesion molecule-1, or soluble vascular cell adhesion molecule-1. After further adjustment for diabetes, hypertension, smoking, and BMI, the relationship between hsCRP, insulin and MCVE were no longer significant, while the relationship between Lp(a), neopterin, NT-proBNP and sRAGE and MCVE remained statistically significant. In conclusion, in patients with CHD treated with atorvastatin, plasma levels of Lp(a), neopterin, NT-proBNP, and sRAGE are associated with the risk of recurrent MCVEs.ClinicalTrials.gov NCT00327691.

The St. Thomas' mixed hyperlipidemic (SMHL) rabbit (previously St. Thomas' Hospital rabbit) is a putative model of familial combined hyperlipidemia (FCH). When fed a low (0.08%) cholesterol diet, it exhibits elevations in both plasma cholesterol and triglyceride compared to New Zealand White (NZW) controls. To determine the mechanism for this hyperlipidemia we studied the secretion of apolipoprotein B (apoB)-containing lipoproteins from perfused livers of both young and mature rabbits. During a 3-h perfusion we measured the total cholesterol and triglyceride content of the medium and the cholesterol, triglyceride, and apoB content of very low density lipoprotein (VLDL)1 (Sf 60–400), VLDL2 (Sf 20–60), intermediate (Sf 12–20), and low (Sf 0–12) density lipoproteins (IDL, LDL). Lipoprotein concentrations increased linearly throughout the perfusion period. The rate of cholesterol output was 3-fold higher (459 vs. 137 ng/g liver/min, P = 0.003) in SMHL versus NZW rabbits whilst that of triglyceride was similar (841 vs. 662 ng/g liver/min, NS). VLDL1 cholesterol output was elevated 2-fold (232 vs. 123 ng/g liver/min, P < 0.05) and VLDL2 + IDL + LDL cholesterol output, 4.5-fold (106 vs. 23 ng/g liver/min, P < 0.005) in SMHL versus NZW rabbits. ApoB output in VLDL1 was 38 ng/g liver per min in SMHL and 14 ng/g liver per min in NZW (NS). In SMHL VLDL2 + IDL + LDL apoB was increased 9-fold at 53 versus 6 ng/g liver per min in NZW (P < 0.001). We conclude that the SMHL rabbit overproduces apoB-containing lipoproteins particularly in the VLDL2 + IDL + LDL fraction, a characteristic consistent with its use as a model of FCH.—Ardern, H. A., G. M. Benson, K. E. Suckling, M. J. Caslake, J. Shepherd, and C. J. Packard. Apolipoprotein B overproduction by the perfused liver of the St. Thomas' mixed hyperlipidemic (SMHL) rabbit.

BACKGROUND: Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke. METHODS AND FINDINGS: In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70-82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44-2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04-1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p

BACKGROUND: Reduced glomerular filtration rate (GFR) is associated with increased cardiovascular risk in young and middle aged individuals. Associations with cardiovascular disease and mortality in older people are less clearly established. We aimed to determine the predictive value of the GFR for mortality and morbidity using data from the 5,804 participants randomized in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). METHODS AND FINDINGS: Glomerular filtration rate was estimated (eGFR) using the Modification of Diet in Renal Disease equation and was categorized in the ranges ([20-40], [40-50], [50-60]) >or= 60 ml/min/1.73 m(2). Baseline risk factors were analysed by category of eGFR, with and without adjustment for other risk factors. The associations between baseline eGFR and morbidity and mortality outcomes, accrued after an average of 3.2 y, were investigated using Cox proportional hazard models adjusting for traditional risk factors. We tested for evidence of an interaction between the benefit of statin treatment and baseline eGFR status. Age, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index, fasting glucose, female sex, histories of hypertension and vascular disease were associated with eGFR (p = 0.001 or less) after adjustment for other risk factors. Low eGFR was independently associated with risk of all cause mortality, vascular mortality, and other noncancer mortality and with fatal and nonfatal coronary and heart failure events (hazard ratios adjusted for CRP and other risk factors (95% confidence intervals [CIs]) for eGFR < 40 ml/min/1.73m(2) relative to eGFR >or= 60 ml/min/1.73m(2) respectively 2.04 (1.48-2.80), 2.37 (1.53-3.67), 3.52 (1.78-6.96), 1.64 (1.18-2.27), 3.31 (2.03-5.41). There were no nominally statistically significant interactions (p < 0.05) between randomized treatment allocation and eGFR for clinical outcomes, with the exception of the outcome of coronary heart disease death or nonfatal myocardial infarction (p = 0.021), with the interaction suggesting increased benefit of statin treatment in subjects with impaired GFRs. CONCLUSIONS: We have established that, in an elderly population over the age of 70 y, impaired GFR is associated with female sex, with presence of vascular disease, and with levels of other risk factors that would be associated with increased risk of vascular disease. Further, impaired GFR is independently associated with significant levels of increased risk of all cause mortality and fatal vascular events and with composite fatal and nonfatal coronary and heart failure outcomes. Our analyses of the benefits of statin treatment in relation to baseline GFR suggest that there is no reason to exclude elderly patients with impaired renal function from treatment with a statin.

Majority of human long non-coding RNAs (lncRNAs) are not conserved in mouse. Here the authors identify metabolic trait-associated lncRNA genes and show a functional role of a non-conserved human lncRNA, LINC01018, in lipid metabolism using a humanized mouse model.