Detecting Inter-Annual Variations in the Phenology of Evergreen Conifers Using Long-Term MODIS Vegetation Index Time Series

Long-term observations of vegetation phenology can be used to monitor the response of terrestrial ecosystems to climate change. Satellite remote sensing provides the most efficient means to observe phenological events through time series analysis of vegetation indices such as the Normalized Difference Vegetation Index (NDVI). This study investigates the potential of a Photochemical Reflectance Index (PRI), which has been linked to vegetation light use efficiency, to improve the accuracy of MODIS-based estimates of phenology in an evergreen conifer forest. Timings of the start and end of the growing season (SGS and EGS) were derived from a 13-year-long time series of PRI and NDVI based on a MAIAC (multi-angle implementation of atmospheric correction) processed MODIS dataset and standard MODIS NDVI product data. The derived dates were validated with phenology estimates from ground-based flux tower measurements of ecosystem productivity. Significant correlations were found between the MAIAC time series and ground-estimated SGS (R-2 = 0.36-0.8), which is remarkable since previous studies have found it difficult to observe inter-annual phenological variations in evergreen vegetation from satellite data. The considerably noisier NDVI product could not accurately predict SGS, and EGS could not be derived successfully from any of the time series. While the strongest relationship overall was found between SGS derived from the ground data and PRI, MAIAC NDVI exhibited high correlations with SGS more consistently (R-2 > 0.6 in all cases). The results suggest that PRI can serve as an effective indicator of spring seasonal transitions, however, additional work is necessary to confirm the relationships observed and to further explore the usefulness of MODIS PRI for detecting phenology.Peer reviewe

Levonorgestrel-releasing intrauterine system vs. usual medical treatment for menorrhagia: An economic evaluation alongside a randomised controlled trial

Objective: To undertake an economic evaluation alongside the largest randomised controlled trial comparing Levonorgestrel-releasing intrauterine device ('LNG-IUS') and usual medical treatment for women with menorrhagia in primary care; and compare the cost-effectiveness findings using two alternative measures of quality of life. Methods: 571 women with menorrhagia from 63 UK centres were randomised between February 2005 and July 2009. Women were randomised to having a LNG-IUS fitted, or usual medical treatment, after discussing with their general practitioner their contraceptive needs or desire to avoid hormonal treatment. The treatment was specified prior to randomisation. For the economic evaluation we developed a state transition (Markov) model with a 24 month follow-up. The model structure was informed by the trial women's pathway and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per Quality Adjusted Life Year (QALY) estimated using both EQ-5D and SF-6D. Results: Using EQ-5D, LNG-IUS was the most cost-effective treatment for menorrhagia. LNG-IUS costs £100 more than usual medical treatment but generated 0.07 more QALYs. The incremental cost-effectiveness ratio for LNG-IUS compared to usual medical treatment was £1600 per additional QALY. Using SF-6D, usual medical treatment was the most cost-effective treatment. Usual medical treatment was both less costly (£100) and generated 0.002 more QALYs. Conclusion: Impact on quality of life is the primary indicator of treatment success in menorrhagia. However, the most costeffective treatment differs depending on the quality of life measure used to estimate the QALY. Under UK guidelines LNG-IUS would be the recommended treatment for menorrhagia. This study demonstrates that the appropriate valuation of outcomes in menorrhagia is crucial. Copyright: © 2014 Sanghera et al

Review of the life history and conservation of federally endangered plant species of the Lower Rio Grande Valley, Texas, USA

This review aims to summarize information critical to the conservation of the federally listed endangered species of South Texas, which occur along the border of Texas and Mexico. This paper describes the characteristics, habitat, population status, distribution, life history, threats, and restoration of endangered plant species of the Lower Rio Grande Valley, Texas, which includes Cameron, Willacy, Hidalgo, and Starr County. Seven federally listed species are considered including Ambrosia cheiranthifolia, Asclepias prostrata, Astrophytum asterias, Ayenia limitaris, Manihot walkerae, Lesquerella thamnophila (syn. Physaria thamnophila), and Thymophylla tephroleuca. An eighth species, Physostegia correllii is under consideration for federal listing by the U.S. Fish and Wildlife Service. This paper assembles information on the background, biological status, major threats, and conservation to aid managers and the scientific community in restoring and managing these species. - El objetivo de esta revisión es resumir la información crítica para la conservación de las especies en peligro de extinción incluidas en la lista federal del sur de Texas, que se encuentran a lo largo de la frontera entre Texas y México. En este documento se describen las características, el hábitat, el estado de la población, la distribución, el ciclo biológico, las amenazas y la restauración de las especies vegetales en peligro de extinción del Valle Inferior del Río Grande, Texas, que incluye los condados de Cameron, Willacy, Hidalgo y Starr. Se consideran siete especies incluidas en la lista federal, entre ellas Ambrosia cheiranthifolia, Asclepias prostrata, Astrophytum asterias, Ayenia limitaris, Manihot walkerae, Lesquerella thamnophila (syn. Physaria thamnophila) y Thymophylla tephroleuca. Una octava especie, Physostegia correllii, está siendo considerada por el Servicio de Pesca y Vida Silvestre de EE.UU. para su inclusión en la lista federal. Este documento reúne información sobre los antecedentes, el estado biológico, las principales amenazas y la conservación para ayudar a los gestores y a la comunidad científica a restaurar y gestionar estas especies

Promoting Optimal Physical Exercise for Life: An Exercise and Self-Management Program to Encourage Participation in Physical Activity after Discharge from Stroke Rehabilitation—A Feasibility Study

People with stroke do not achieve adequate levels of physical exercise following discharge from rehabilitation. We developed a group exercise and self-management program (PROPEL), delivered during stroke rehabilitation, to promote uptake of physical activity after discharge. This study aimed to establish the feasibility of a larger study to evaluate the effect of this program on participation in self-directed physical activity. Participants with subacute stroke were recruited at discharge from one of three rehabilitation hospitals; one hospital offered the PROPEL program whereas the other two did not (comparison group; COMP). A high proportion (11/16) of eligible PROPEL program participants consented to the study. Fifteen COMP participants were also recruited. Compliance with wearing an accelerometer for 6 weeks continuously and completing physical activity questionnaires was high (>80%), whereas only 34% of daily heart rate data were available. Individuals who completed the PROPEL program seemed to have higher outcome expectations for exercise, fewer barriers to physical activity, and higher participation in physical activity than COMP participants (Hedge’s g≥0.5). The PROPEL program delivered during stroke rehabilitation shows promise for reducing barriers to exercise and increasing participation in physical activity after discharge. This study supports feasibility of a larger randomized trial to evaluate this program

C-STICH2: emergency cervical cerclage to prevent miscarriage and preterm birth—study protocol for a randomised controlled trial

Abstract Background Cervical cerclage is a recognised treatment to prevent late miscarriage and pre-term birth (PTB). Emergency cervical cerclage (ECC) for cervical dilatation with exposed unruptured membranes is less common and the potential benefits of cerclage are less certain. A randomised control trial is needed to accurately assess the effectiveness of ECC in preventing pregnancy loss compared to an expectant approach. Methods C-STICH2 is a multicentre randomised controlled trial in which women presenting with cervical dilatation and unruptured exposed membranes at 16 + 0 to 27 + 6 weeks gestation are randomised to ECC or expectant management. Trial design includes 18 month internal pilot with embedded qualitative process evaluation, minimal data set and a within-trial health economic analysis. Inclusion criteria are ≥16 years, singleton pregnancy, exposed membranes at the external os, gestation 16 + 0–27 + 6 weeks, and informed consent. Exclusion criteria are contraindication to cerclage, cerclage in situ or previous cerclage in this pregnancy. Randomisation occurs via an online service in a 1:1 ratio, using a minimisation algorithm to reduce chance imbalances in key prognostic variables (site, gestation and dilatation). Primary outcome is pregnancy loss; a composite including miscarriage, termination of pregnancy and perinatal mortality defined as stillbirth and neonatal death in the first week of life. Secondary outcomes include all core outcomes for PTB. Two-year development outcomes will be assessed using general health and Parent Report of Children’s Abilities-Revised (PARCA-R) questionnaires. Intended sample size is 260 participants (130 each arm) based on 60% rate of pregnancy loss in the expectant management arm and 40% in the ECC arm, with 90% power and alpha 0.05. Analysis will be by intention-to-treat. Discussion To date there has been one small trial of ECC in 23 participants which included twin and singleton pregnancies. This small trial along with the largest observational study (n = 161) found ECC to prolong pregnancy duration and reduce deliveries before 34 weeks gestation. It is important to generate high quality evidence on the effectiveness of ECC in preventing pregnancy loss, and improve understanding of the prevalence of the condition and frequency of complications associated with ECC. An adequately powered RCT will provide the highest quality evidence regarding optimum care for these women and their babies. Trial registration ISRCTN Registry ISRCTN12981869 . Registered on 13th June 2018

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

In Children with Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis is Associated with Advanced Fibrosis

Background & Aims Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. Methods We performed a cross-sectional study of baseline data from 813 children (age <18 years; mean age, 12.8 ± 2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Results Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P < .001) and a significantly higher proportion had any fibrosis (81% vs 51%; P < .001) or advanced fibrosis (13% vs 5%; P < .001) compared with children with zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P < .001). Conclusions Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis

Cross-cutting principles for planetary health education

Since the 2015 launch of the Rockefeller Foundation Lancet Commission on planetary health,1 an enormous groundswell of interest in planetary health education has emerged across many disciplines, institutions, and geographical regions. Advancing these global efforts in planetary health education will equip the next generation of scholars to address crucial questions in this emerging field and support the development of a community of practice. To provide a foundation for the growing interest and efforts in this field, the Planetary Health Alliance has facilitated the first attempt to create a set of principles for planetary health education that intersect education at all levels, across all scales, and in all regions of the world—ie, a set of cross-cutting principles

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year