Effect of obesity on the population pharmacokinetics of meropenem in critically ill patients

Severe pathophysiological changes in critical illness can lead to dramatically altered antimicrobial pharmacokinetics (PK). The additional effect of obesity on PK potentially increases the challenge for effective dosing. The aim of this prospective study was to describe the population PK of meropenem for a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients prescribed meropenem were recruited into the following three body mass index (BMI) groups: nonobese (18.5 to 29.9 kg/m(2)), obese (30.0 to 39.9 kg/m(2)), and morbidly obese (>= 40 kg/m(2)). Serial plasma samples were taken, and meropenem concentrations were determined using a validated chromatographic method. Population PK analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Nineteen critically ill patients with different BMI categories were enrolled. The patients' mean +/- standard deviation (SD) age, weight, and BMI were 49 +/- 15.9 years, 95 +/- 22.0 kg, and 33 +/- 7.0 kg/m(2), respectively. A two-compartment model described the data adequately. The mean +/- SD parameter estimates for the final covariate model were as follows: clearance (CL), 15.5 +/- 6.0 liters/h; volume of distribution in the central compartment (V-1), 11.7 +/- 5.8 liters; intercompartmental clearance from the central compartment to the peripheral compartment, 25.6 +/- 35.1 liters h(-1); and intercompartmental clearance from the peripheral compartment to the central compartment, 8.32 +/- 12.24 liters h(-1). Higher creatinine clearance (CLCR) was associated with a lower probability of target attainment, with BMI having little effect. Although obesity was found to be associated with an increased V-1, dose adjustment based on CLCR appears to be more important than patient BMI

Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal

The canonical Wnt/β-catenin signaling pathway governs diverse developmental, homeostatic and pathologic processes. Palmitoylated Wnt ligands engage cell surface Frizzled (Fzd) receptors and Lrp5/6 co-receptors enabling β-catenin nuclear translocation and Tcf/Lef-dependent gene transactivation1–3. Mutations in Wnt downstream signaling components have revealed diverse functions presumptively attributed to Wnt ligands themselves, although direct attribution remains elusive, as complicated by redundancy between 19 mammalian Wnts and 10 Fzds1 and Wnt hydrophobicity2,3. For example, individual Wnt ligand mutations have not revealed homeostatic phenotypes in the intestinal epithelium4, an archetypal canonical Wnt pathway-dependent rapidly self-renewing tissue whose regeneration is fueled by proliferative crypt Lgr5+ intestinal stem cells (ISCs)5–9. R-spondin ligands (Rspo1–4) engage distinct Lgr4-6 and Rnf43/Znrf3 receptor classes10–13, markedly potentiate canonical Wnt/β-catenin signaling and induce intestinal organoid growth in vitro and Lgr5+ ISCs in vivo8,14–17. However, the interchangeability, functional cooperation and relative contributions of Wnt versus Rspo ligands to in vivo canonical Wnt signaling and ISC biology remain unknown. Here, we deconstructed functional roles of Wnt versus Rspo ligands in the intestinal crypt stem cell niche. We demonstrate that the default fate of Lgr5+ ISCs is lineage commitment, escape from which requires both Rspo and Wnt ligands. However, gain-of-function studies using Rspo versus a novel non-lipidated Wnt analog reveal qualitatively distinct, non-interchangeable roles for these ligands in ISCs. Wnts are insufficient to induce Lgr5+ ISC self-renewal, but rather confer a basal competency by maintaining Rspo receptor expression that enables Rspo to actively drive and specify the extent of stem cell expansion. This functionally non-equivalent yet cooperative interplay between Wnt and Rspo ligands establishes a molecular precedent for regulation of mammalian stem cells by distinct priming and self-renewal factors, with broad implications for precision control of tissue regeneration

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Evaluación financiera de un sistema de visión computarizado que determine el grado de fermentación de granos de cacao.

Este proyecto realiza un estudio en la industria del cacao con el objetivo de mejorar la exactitud en la clasificación de la fermentación de los granos mediante la implementación de un prototipo de control automático usando imágenes hiperespectrales. Para realizar la evaluación del proyecto se dividió el estudio en cuatro etapas: estudio de mercado, estudio técnico, estudio organizacional y estudio financiero, y mediante herramientas como encuestas y entrevistas se recopiló información primaria y secundaria y se determinó la viabilidad de un plan de negocio para comercializar el sistema de visión por computador.GuayaquilIngeniería en Negocios Internacionales

The future of coffee and cocoa agroforestry in a warmer Mesoamerica

Climate change threatens coffee production and the livelihoods of thousands of families in Mesoamerica that depend on it. Replacing coffee with cocoa and integrating trees in combined agroforestry systems to ameliorate abiotic stress are among the proposed alternatives to overcome this challenge. These two alternatives do not consider the vulnerability of cocoa and tree species commonly used in agroforestry plantations to future climate conditions. We assessed the suitability of these alternatives by identifying the potential changes in the distribution of coffee, cocoa and the 100 most common agroforestry trees found in Mesoamerica. Here we show that cocoa could potentially become an alternative in most of coffee vulnerable areas. Agroforestry with currently preferred tree species is highly vulnerable to future climate change. Transforming agroforestry systems by changing tree species composition may be the best approach to adapt most of the coffee and cocoa production areas. Our results stress the urgency for land use planning considering climate change effects and to assess new combinations of agroforestry species in coffee and cocoa plantations in Mesoamerica

Aquatic communities in arid landscapes: Local conditions, dispersal traits and landscape configuration determine local biodiversity

AimTo understand how environmental conditions and landscape structure interact at different spatial scales to shape the community composition of arid zone aquatic invertebrates with different dispersal abilities.LocationAustralia.MethodsFor each of five drainage basins and for their encompassing region (Pilbara), we built matrices of dissimilarities in presence–absence patterns of aquatic invertebrate community composition. This was carried out for all taxa collectively and separately for five dispersal trait groups: obligate aquatics, passive aerial dispersers, animals moving by aerial phoresy, weak and strong fliers. We analysed correlations between community dissimilarities and (1) dissimilarities in local environmental conditions, (2) geographic distances and (3) landscape resistance distances among the sites from which invertebrates were sampled. Calculation of landscape resistances accounted for longitudinal connectivity along the river channels (least-cost-path), lateral connectivity between streams and the potential effects of rugged topography on invertebrate dispersal.ResultsLocal environmental factors and landscape resistances explained differences in community composition at the regional scale. In basins with complex topography, local environmental conditions were the main factor explaining community dissimilarities in most dispersal groups. Conversely, in basins where flatter topography meant that moderate to high lateral connectivity between streams is possible, the spatial configuration of the dendritic network determined the community composition of most dispersal trait groups. Geographic and least-cost-path distances were poor predictors of community composition. None of the groups showed a consistent correlation with environmental factors alone, or just landscape resistances, across all basins.Main conclusionsLocal environmental conditions, hydrological connectivity and landscape resistance to dispersal are all important influences on community composition of arid zone aquatic invertebrates. The impact of each of these factors varies with dispersal trait group and spatial configuration of basins: the importance of lateral connectivity for explaining a substantial proportion of community composition points to a major role of flooding regimes in maintaining biological communities

An LC-MS/MS method to determine vancomycin in plasma (total and unbound), urine and renal replacement therapy effluent

Aim: Critical illness and medical interventions, such as renal replacement therapy, can cause changes to vancomycin pharmacokinetics and lead to suboptimal dosing. To comprehensively characterize vancomycin pharmacokinetic a method must measure vancomycin in a range of clinical matrices. Results: A LC–MS/MS method was developed using hydrophilic interaction liquid chromatography and microsample volumes, where possible. For all matrices, the linear concentration range was 1–100 μg/ml, interassay accuracy and precision was within 15%, and recovery above 80%. No matrix effects were observed. Calibration equivalence may be applied for some matrix combinations. Conclusion: A method for the analysis of vancomycin in plasma (total, unbound), urine and renal replacement therapy effluent, suitable for use in any patient pharmacokinetic study, has been developed and validated. </jats:p

Global quantification of contrasting leaf life span strategies for deciduous and evergreen species in response to environmental conditions

Aim: Species with deciduous and evergreen leaf habits typically differ in leaf life span (LLS). Yet quantification of the response of LLS, within each habit, to key environmental conditions is surprisingly lacking. The aim of this study is to quantify LLS strategies of the two leaf habits under varying temperature, moisture and nutrient conditions, using a global database. We hypothesize that deciduous LLS reflects the length of the growing season, avoiding unfavourable conditions regardless of the cause. Evergreen species adjust to unfavourable periods and amortize lower net carbon gains over several growing seasons, with increasing LLS associated with increasingly short favourable versus unfavourable season lengths. Location: Global. Methods: Data on LLS and environmental variables were compiled from global datasets for 189 deciduous and 506 evergreen species across 83 study locations. Individual and combined effects of measures of seasonality of temperature, water and nutrient availability on length of the growing season and on LLS were quantified using linear mixed models. The best models for predicting LLS were obtained using Akaike's information criterion (AIC) and ΔAIC. Results: The LLS of deciduous and evergreen species showed opposite responses to changes in environmental conditions. Under unfavourable conditions, deciduous LLS decreases while evergreen LLS increases. A measure of temperature alone was the best predictor of the growing season. The LLS of deciduous species was independent of environmental conditions after expressing LLS in relation to the number of growing seasons. Evergreen species, on the other hand, adjusted to unfavourable conditions by increasing LLS up to four growing seasons. Contrary to expectations, variation in LLS was best explained solely by temperature, instead of by combined measures of temperature, moisture and nutrient availability. Shifts in the photosynthesis to respiration balance might provide a physiological explanation. Main conclusions: Temperature, and not drought or nutrient availability, is the primary driver of contrasting responses of LLS for different leaf habit types