PEAT-CLSM : A Specific Treatment of Peatland Hydrology in the NASA Catchment Land Surface Model

Peatlands are poorly represented in global Earth system modeling frameworks. Here we add a peatland-specific land surface hydrology module (PEAT-CLSM) to the Catchment Land Surface Model (CLSM) of the NASA Goddard Earth Observing System (GEOS) framework. The amended TOPMODEL approach of the original CLSM that uses topography characteristics to model catchment processes is discarded, and a peatland-specific model concept is realized in its place. To facilitate its utilization in operational GEOS efforts, PEAT-CLSM uses the basic structure of CLSM and the same global input data. Parameters used in PEAT-CLSM are based on literature data. A suite of CLSM and PEAT-CLSM simulations for peatland areas between 40 degrees N and 75 degrees N is presented and evaluated against a newly compiled data set of groundwater table depth and eddy covariance observations of latent and sensible heat fluxes in natural and seminatural peatlands. CLSM's simulated groundwater tables are too deep and variable, whereas PEAT-CLSM simulates a mean groundwater table depth of -0.20 m (snow-free unfrozen period) with moderate temporal fluctuations (standard deviation of 0.10 m), in significantly better agreement with in situ observations. Relative to an operational CLSM version that simply includes peat as a soil class, the temporal correlation coefficient is increased on average by 0.16 and reaches 0.64 for bogs and 0.66 for fens when driven with global atmospheric forcing data. In PEAT-CLSM, runoff is increased on average by 38% and evapotranspiration is reduced by 19%. The evapotranspiration reduction constitutes a significant improvement relative to eddy covariance measurements.Peer reviewe

Adherence with statins in a real-life setting is better when associated cardiovascular risk factors increase: a cohort study

<p>Abstract</p> <p>Background</p> <p>While the factors for poor adherence for treatment with statins have been highlighted, the impact of their combination on adherence is not clear.</p> <p>Aims</p> <p>To estimate adherence for statins and whether it differs according to the number of cardiovascular risk factors.</p> <p>Methods</p> <p>A cohort study was conducted using data from the main French national health insurance system reimbursement database. Newly treated patients with statins between September 1 and December 31, 2004 were included. Patients were followed up 15 months. The cohort was split into three groups according to their number of additional cardiovascular risk factors that included age and gender, diabetes mellitus and cardiovascular disease (using co-medications as a <it>proxy</it>). Adherence was assessed for each group by using four parameters: <it>(i) </it>proportion of days covered by statins, <it>(ii) </it>regularity of the treatment over time, <it>(iii) </it>persistence, and <it>(iv) </it>the refill delay.</p> <p>Results</p> <p>16,397 newly treated patients were identified. Of these statin users, 21.7% did not have additional cardiovascular risk factors. Thirty-one percent had two cardiovascular risk factors and 47% had at least three risk factors. All the parameters showed a sub-optimal adherence whatever the group: days covered ranged from 56% to 72%, regularity ranged from 23% to 33% and persistence ranged from 44% to 59%, but adherence was better for those with a higher number of cardiovascular risk factors.</p> <p>Conclusions</p> <p>The results confirm that long-term drug treatments are a difficult challenge, particularly in patients at lower risk and invite to the development of therapeutic education.</p

Variations in TcdB Activity and the Hypervirulence of Emerging Strains of Clostridium difficile

Hypervirulent strains of Clostridium difficile have emerged over the past decade, increasing the morbidity and mortality of patients infected by this opportunistic pathogen. Recent work suggested the major C. difficile virulence factor, TcdB, from hypervirulent strains (TcdBHV) was more cytotoxic in vitro than TcdB from historical strains (TcdBHIST). The current study investigated the in vivo impact of altered TcdB tropism, and the underlying mechanism responsible for the differences in activity between the two forms of this toxin. A combination of protein sequence analyses, in vivo studies using a Danio rerio model system, and cell entry combined with fluorescence assays were used to define the critical differences between TcdBHV and TcdBHIST. Sequence analysis found that TcdB was the most variable protein expressed from the pathogenicity locus of C. difficile. In line with these sequence differences, the in vivo effects of TcdBHV were found to be substantially broader and more pronounced than those caused by TcdBHIST. The increased toxicity of TcdBHV was related to the toxin's ability to enter cells more rapidly and at an earlier stage in endocytosis than TcdBHIST. The underlying biochemical mechanism for more rapid cell entry was identified in experiments demonstrating that TcdBHV undergoes acid-induced conformational changes at a pH much higher than that of TcdBHIST. Such pH-related conformational changes are known to be the inciting step in membrane insertion and translocation for TcdB. These data provide insight into a critical change in TcdB activity that contributes to the emerging hypervirulence of C. difficile

Heparin Induces Harmless Fibril Formation in Amyloidogenic W7FW14F Apomyoglobin and Amyloid Aggregation in Wild-Type Protein In Vitro

Glycosaminoglycans (GAGs) are frequently associated with amyloid deposits in most amyloid diseases, and there is evidence to support their active role in amyloid fibril formation. The purpose of this study was to obtain structural insight into GAG-protein interactions and to better elucidate the molecular mechanism underlying the effect of GAGs on the amyloid aggregation process and on the related cytotoxicity. To this aim, using Fourier transform infrared and circular diochroism spectroscopy, electron microscopy and thioflavin fluorescence dye we examined the effect of heparin and other GAGs on the fibrillogenesis and cytotoxicity of aggregates formed by the amyloidogenic W7FW14 apomyoglobin mutant. Although this protein is unrelated to human disease, it is a suitable model for in vitro studies because it forms amyloid-like fibrils under physiological conditions of pH and temperature. Heparin strongly stimulated aggregation into amyloid fibrils, thereby abolishing the lag-phase normally detected following the kinetics of the process, and increasing the yield of fibrils. Moreover, the protein aggregates were harmless when assayed for cytotoxicity in vitro. Neutral or positive compounds did not affect the aggregation rate, and the early aggregates were highly cytotoxic. The surprising result that heparin induced amyloid fibril formation in wild-type apomyoglobin and in the partially folded intermediate state of the mutant, i.e., proteins that normally do not show any tendency to aggregate, suggested that the interaction of heparin with apomyoglobin is highly specific because of the presence, in protein turn regions, of consensus sequences consisting of alternating basic and non-basic residues that are capable of binding heparin molecules. Our data suggest that GAGs play a dual role in amyloidosis, namely, they promote beneficial fibril formation, but they also function as pathological chaperones by inducing amyloid aggregation

A randomized trial to assess the impact of opinion leader endorsed evidence summaries on the use of secondary prevention strategies in patients with coronary artery disease: the ESP-CAD trial protocol [NCT00175240]

BACKGROUND: Although numerous therapies have been shown to be beneficial in the prevention of myocardial infarction and/or death in patients with coronary disease, these therapies are under-used and this gap contributes to sub-optimal patient outcomes. To increase the uptake of proven efficacious therapies in patients with coronary disease, we designed a multifaceted quality improvement intervention employing patient-specific reminders delivered at the point-of-care, with one-page treatment guidelines endorsed by local opinion leaders ("Local Opinion Leader Statement"). This trial is designed to evaluate the impact of these Local Opinion Leader Statements on the practices of primary care physicians caring for patients with coronary disease. In order to isolate the effects of the messenger (the local opinion leader) from the message, we will also test an identical quality improvement intervention that is not signed by a local opinion leader ("Unsigned Evidence Statement") in this trial. METHODS: Randomized trial testing three different interventions in patients with coronary disease: (1) usual care versus (2) Local Opinion Leader Statement versus (3) Unsigned Evidence Statement. Patients diagnosed with coronary artery disease after cardiac catheterization (but without acute coronary syndromes) will be randomly allocated to one of the three interventions by cluster randomization (at the level of their primary care physician), if they are not on optimal statin therapy at baseline. The primary outcome is the proportion of patients demonstrating improvement in their statin management in the first six months post-catheterization. Secondary outcomes include examinations of the use of ACE inhibitors, anti-platelet agents, beta-blockers, non-statin lipid lowering drugs, and provision of smoking cessation advice in the first six months post-catheterization in the three treatment arms. Although randomization will be clustered at the level of the primary care physician, the design effect is anticipated to be negligible and the unit of analysis will be the patient. DISCUSSION: If either the Local Opinion Leader Statement or the Unsigned Evidence Statement improves secondary prevention in patients with coronary disease, they can be easily modified and applied in other communities and for other target conditions

Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

Evaluation of a self-management patient education program for patients with fibromyalgia syndrome: study protocol of a cluster randomized controlled trial

Background Fibromyalgia syndrome (FMS) is a complex chronic condition that makes high demands on patients’ self-management skills. Thus, patient education is considered an important component of multimodal therapy, although evidence regarding its effectiveness is scarce. The main objective of this study is to assess the effectiveness of an advanced self-management patient education program for patients with FMS as compared to usual care in the context of inpatient rehabilitation. Methods/Design We conducted a multicenter cluster randomized controlled trial in 3 rehabilitation clinics. Clusters are groups of patients with FMS consecutively recruited within one week after admission. Patients of the intervention group receive the advanced multidisciplinary self-management patient education program (considering new knowledge on FMS, with a focus on transfer into everyday life), whereas patients in the control group receive standard patient education programs including information on FMS and coping with pain. A total of 566 patients are assessed at admission, at discharge and after 6 and 12 months, using patient reported questionnaires. Primary outcomes are patients’ disease- and treatment-specific knowledge at discharge and self-management skills after 6 months. Secondary outcomes include satisfaction, attitudes and coping competences, health-promoting behavior, psychological distress, health impairment and participation. Treatment effects between groups are evaluated using multilevel regression analysis adjusting for baseline values. Discussion The study evaluates the effectiveness of a self-management patient education program for patients with FMS in the context of inpatient rehabilitation in a cluster randomized trial. Study results will show whether self-management patient education is beneficial for this group of patients

Heart rate variability in critical care medicine: a systematic review.

BACKGROUND: Heart rate variability (HRV) has been used to assess cardiac autonomic activity in critically ill patients, driven by translational and biomarker research agendas. Several clinical and technical factors can interfere with the measurement and/or interpretation of HRV. We systematically evaluated how HRV parameters are acquired/processed in critical care medicine. METHODS: PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (1996-2016) were searched for cohort or case-control clinical studies of adult (>18 years) critically ill patients using heart variability analysis. Duplicate independent review and data abstraction. Study quality was assessed using two independent approaches: Newcastle-Ottowa scale and Downs and Black instrument. Conduct of studies was assessed in three categories: (1) study design and objectives, (2) procedures for measurement, processing and reporting of HRV, and (3) reporting of relevant confounding factors. RESULTS: Our search identified 31/271 eligible studies that enrolled 2090 critically ill patients. A minority of studies (15; 48%) reported both frequency and time domain HRV data, with non-normally distributed, wide ranges of values that were indistinguishable from other (non-critically ill) disease states. Significant heterogeneity in HRV measurement protocols was observed between studies; lack of adjustment for various confounders known to affect cardiac autonomic regulation was common. Comparator groups were often omitted (n = 12; 39%). This precluded meaningful meta-analysis. CONCLUSIONS: Marked differences in methodology prevent meaningful comparisons of HRV parameters between studies. A standardised set of consensus criteria relevant to critical care medicine are required to exploit advances in translational autonomic physiology.GLA is supported by a British Journal of Anaesthesia and Royal College of Anaesthetists Basic Science fellowship, British Oxygen Company grant from the Royal College of Anaesthetists and British Heart Foundation programme grant (RG/14/4/3073