Biases in southern hemisphere climate trends induced by coarsely specifying the temporal resolution of stratospheric ozone

Global climate models that do not include interactive middle atmosphere chemistry, such as most of those contributing to the Coupled Model Intercomparison Project Phase 5, typically specify stratospheric ozone using monthly mean, zonal mean values and linearly interpolate to the time resolution of the model. We show that this method leads to significant biases in the simulated climate of the southern hemisphere (SH) over the late twentieth century. Previous studies have attributed similar biases in simulated SH climate change to the effect of the spatial smoothing of the specified ozone, i.e., to using zonal mean concentrations. We here show that the bias in climate trends due to undersampling of the rapid temporal changes in ozone during the seasonal evolution of the Antarctic ozone hole is considerable and reaches all the way into the troposphere. Our results suggest that the bias can be substantially reduced by specifying daily ozone concentrations

Attitudes toward and experiences of gender issues among physician teachers: A survey study conducted at a university teaching hospital in Sweden

<p>Abstract</p> <p>Background</p> <p>Gender issues are important to address during medical education, however research about the implementation of gender in medical curricula reports that there are obstacles. The aim of this study was to explore physician teachers' attitudes to gender issues.</p> <p>Methods</p> <p>As part of a questionnaire, physician teachers at Umeå University in Sweden were given open-ended questions about explanations for and asked to write examples why they found gender important or not. The 1 469 comments from the 243 respondents (78 women, 165 men) were analyzed by way of content analysis. The proportion of comments made by men and women in each category was compared.</p> <p>Results</p> <p>We found three themes in our analysis: Understandings of gender, problems connected with gender and approaches to gender. Gender was associated with differences between women and men regarding behaviour and disease, as well as with inequality of life conditions. Problems connected with gender included: delicate situations involving investigations of intimate body parts or sexual attraction, different expectations on male and female physicians and students, and difficulty fully understanding the experience of people of the opposite sex. The three approaches to gender that appeared in the comments were: 1) avoidance, implying that the importance of gender in professional relationships was recognized but minimized by comparing gender with aspects, such as personality and neutrality; 2) simplification, implying that gender related problems were easy to address, or already solved; and 3) awareness, implying that the respondent was interested in gender issues or had some insights in research about gender. Only a few individuals described gender as an area of competence and knowledge. There were comments from men and women in all categories, but there were differences in the relative weight for some categories. For example, recognizing gender inequities was more pronounced in the comments from women and avoidance more common in comments from men.</p> <p>Conclusion</p> <p>The surveyed physician teachers gave many examples of gender-related problems in medical work and education, but comments describing gender as an area of competence and knowledge were few. Approaches to gender characterized by avoidance and simplification suggest that faculty development programs on gender need to address and reflect on attitudes as well as knowledge.</p

Short-Course, High-Dose Rifampicin Achieves Wolbachia Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic Filariasis and Onchocerciasis

Lymphatic filariasis (LF) and onchocerciasis are priority neglected tropical diseases targeted for elimination. The only safe drug treatment with substantial curative activity against the filarial nematodes responsible for LF (Brugia malayi, Wuchereria bancrofti) or onchocerciasis (Onchocerca volvulus) is doxycycline. The target of doxycycline is the essential endosymbiont, Wolbachia. Four to six weeks doxycycline therapy achieves >90% depletion of Wolbachia in worm tissues leading to blockade of embryogenesis, adult sterility and premature death 18–24 months post-treatment. Long treatment length and contraindications in children and pregnancy are obstacles to implementing doxycycline as a public health strategy. Here we determine, via preclinical infection models of Brugia malayi or Onchocerca ochengi that elevated exposures of orally-administered rifampicin can lead to Wolbachia depletions from filariae more rapidly than those achieved by doxycycline. Dose escalation of rifampicin achieves >90% Wolbachia depletion in time periods of 7 days in B. malayi and 14 days in O. ochengi. Using pharmacokinetic-pharmacodynamic modelling and mouse-human bridging analysis, we conclude that clinically relevant dose elevations of rifampicin, which have recently been determined as safe in humans, could be administered as short courses to filariasis target populations with potential to reduce anti-Wolbachia curative therapy times to between one and two weeks

Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection

© 2014 Gironès et al. Chagas disease is caused by Trypanosoma cruzi infection, being cardiomyopathy the more frequent manifestation. New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy. There is growing evidence linking immune response and metabolism in inflammatory processes and specifically in Chagas disease. Thus, some metabolites are able to enhance and/or inhibit the immune response. Metabolite levels found in the host during an ongoing infection could provide valuable information on the pathogenesis and/or identify deregulated metabolic pathway that can be potential candidates for treatment and being potential specific biomarkers of the disease. To gain more insight into those aspects in Chagas disease, we performed an unprecedented metabolomic analysis in heart and plasma of mice infected with T. cruzi. Many metabolic pathways were profoundly affected by T. cruzi infection, such as glucose uptake, sorbitol pathway, fatty acid and phospholipid synthesis that were increased in heart tissue but decreased in plasma. Tricarboxylic acid cycle was decreased in heart tissue and plasma whereas reactive oxygen species production and uric acid formation were also deeply increased in infected hearts suggesting a stressful condition in the heart. While specific metabolites allantoin, kynurenine and p-cresol sulfate, resulting from nucleotide, tryptophan and phenylalanine/tyrosine metabolism, respectively, were increased in heart tissue and also in plasma. These results provide new valuable information on the pathogenesis of acute Chagas disease, unravel several new metabolic pathways susceptible of clinical management and identify metabolites useful as potential specific biomarkers for monitoring treatment and clinical severity in patients.This work was supported by ‘‘Ministerio de Ciencia e Innovación’’ (SAF2010-17833); ‘‘Fondo de Investigaciones Sanitarias’’ (PS09/00538 and PI12/00289); ‘‘Red de Investigación de Centros de Enfermedades Tropicales’’ (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet);‘‘Universidad Autónoma de Madrid’’ and ‘‘Comunidad de Madrid’’ (CC08-UAM/SAL-4440/08); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD-2332) and ‘‘Fundación Ramón Areces’Peer Reviewe

Changing Patterns of Microhabitat Utilization by the Threespot Damselfish, Stegastes planifrons, on Caribbean Reefs

Background: The threespot damselfish, Stegastes planifrons (Cuvier), is important in mediating interactions among corals, algae, and herbivores on Caribbean coral reefs. The preferred microhabitat of S. planifrons is thickets of the branching staghorn coral Acropora cervicornis. Within the past few decades, mass mortality of A. cervicornis from white-band disease and other factors has rendered this coral a minor ecological component throughout most of its range. Methodology/Principal Findings: Survey data from Jamaica (heavily fished), Florida and the Bahamas (moderately fished), the Cayman Islands (lightly to moderately fished), and Belize (lightly fished) indicate that distributional patterns of S. planifrons are positively correlated with live coral cover and topographic complexity. Our results suggest that speciesspecific microhabitat preferences and the availability of topographically complex microhabitats are more important than the abundance of predatory fish as proximal controls on S. planifrons distribution and abundance. Conclusions/Significance: The loss of the primary microhabitat of S. planifrons—A. cervicornis—has forced a shift in the distribution and recruitment of these damselfish onto remaining high-structured corals, especially the Montastraea annulari

How do parents manage irritability, challenging behavior, non-compliance and anxiety in children with Autism Spectrum Disorders? A meta-synthesis

Although there is increasing research interest in the parenting of children with ASD, at present, little is known about everyday strategies used to manage problem behaviour. We conducted a meta-synthesis to explore what strategies parents use to manage irritability, non-compliance, challenging behaviour and anxiety in their children with ASD. Approaches included: (1) accommodating the child; (2) modifying the environment; (3) providing structure, routine and occupation; (4) supervision and monitoring; (5) managing non-compliance with everyday tasks; (6) responding to problem behaviour; (7) managing distress; (8) maintaining safety and (9) analysing and planning. Results suggest complex parenting demands in children with ASD and problem behaviour. Findings will inform the development of a new measure to quantify parenting strategies relevant to ASD

Abiotic ammonium formation in the presence of Ni-Fe metals and alloys and its implications for the Hadean nitrogen cycle

Experiments with dinitrogen-, nitrite-, nitrate-containing solutions were conducted without headspace in Ti reactors (200°C), borosilicate septum bottles (70°C) and HDPE tubes (22°C) in the presence of Fe and Ni metal, awaruite (Ni80Fe20) and tetrataenite (Ni50Fe50). In general, metals used in this investigation were more reactive than alloys toward all investigated nitrogen species. Nitrite and nitrate were converted to ammonium more rapidly than dinitrogen, and the reduction process had a strong temperature dependence. We concluded from our experimental observations that Hadean submarine hydrothermal systems could have supplied significant quantities of ammonium for reactions that are generally associated with prebiotic synthesis, especially in localized environments. Several natural meteorites (octahedrites) were found to contain up to 22 ppm Ntot. While the oxidation state of N in the octahedrites was not determined, XPS analysis of metals and alloys used in the study shows that N is likely present as nitride (N3-). This observation may have implications toward the Hadean environment, since, terrestrial (e.g., oceanic) ammonium production may have been supplemented by reduced nitrogen delivered by metal-rich meteorites. This notion is based on the fact that nitrogen dissolves into metallic melts

Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies

Biological and Non-Biological Methods for Lignocellulosic Biomass Deconstruction

Owing to their abundance and cost-effectiveness, lignocellulosic materials have attracted increasing attention in clean energy technologies over the last decade. However, the complex polymer structure in these residues makes it difficult to extract the fermentable sugars. Therefore, various pretreatment regimes have been used resulting in the breaking of lignocelluloses’ physical and chemical structures, thereby enhancing the availability of the polysaccharides which are subsequently hydrolysed into different biocommodities. This chapter provides an evaluation of some of the latest exploited methodologies that are used in the pretreatment of lignocellulosic materials. Moreover, the chapter discusses the advantages and disadvantages of each method