Compensated right ventricular function of the onset of pulmonary hypertension in a rat model depends on chamber remodeling and contractile augmentation.

Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geometric remodeling and intrinsic changes in myocardial mechanical properties in a monocrotaline (MCT) animal model. In a longitudinal study of PAH, ventricular morphology and function were assessed weekly during the first four weeks after MCT exposure. Using invasive measurements of RV pressure and volume, heart performance was evaluated at end of systole and diastole to quantify contractility (end-systolic elastance) and chamber stiffness (end-diastolic elastance). To distinguish between morphological and intrinsic mechanisms, a computational model of the RV was developed and used to determine the level of prediction when accounting for wall masses and unloaded volume measurements changes. By four weeks, mean pulmonary arterial pressure and elastance rose significantly. RV pressures rose significantly after the second week accompanied by significant RV hypertrophy, but RV stroke volume and cardiac output were maintained. The model analysis suggested that, after two weeks, this compensation was only possible due to a significant increase in the intrinsic inotropy of RV myocardium. We conclude that this MCT-PAH rat is a model of RV compensation during the first month after treatment, where geometric remodeling on EDPVR and increased myocardial contractility on ESPVR are the major mechanisms by which stroke volume is preserved in the setting of elevated pulmonary arterial pressure. The mediators of this compensation might themselves promote longer-term adverse remodeling and decompensation in this animal model

Vertical Field Effect Transistor based on Graphene-WS2 Heterostructures for flexible and transparent electronics

The celebrated electronic properties of graphene have opened way for materials just one-atom-thick to be used in the post-silicon electronic era. An important milestone was the creation of heterostructures based on graphene and other two-dimensional (2D) crystals, which can be assembled in 3D stacks with atomic layer precision. These layered structures have already led to a range of fascinating physical phenomena, and also have been used in demonstrating a prototype field effect tunnelling transistor - a candidate for post-CMOS technology. The range of possible materials which could be incorporated into such stacks is very large. Indeed, there are many other materials where layers are linked by weak van der Waals forces, which can be exfoliated and combined together to create novel highly-tailored heterostructures. Here we describe a new generation of field effect vertical tunnelling transistors where 2D tungsten disulphide serves as an atomically thin barrier between two layers of either mechanically exfoliated or CVD-grown graphene. Our devices have unprecedented current modulation exceeding one million at room temperature and can also operate on transparent and flexible substrates

Exploring forest structural complexity by multi-scale segmentation of VHR imagery

Forests are complex ecological systems, characterised by multiple-scale structural and dynamical patterns which are not inferable from a system description that spans only a narrow window of resolution; this makes their investigation a difficult task using standard field sampling protocols. We segment a QuickBird image covering a beech forest in an initial stage of old-growthness – showing, accordingly, a good degree of structural complexity – into three segmentation levels. We apply field-based diversity indices of tree size, spacing, species assemblage to quantify structural heterogeneity amongst forest regions delineated by segmentation. The aim of the study is to evaluate, on a statistical basis, the relationships between spectrally delineated image segments and observed spatial heterogeneity in forest structure, including gaps in the outer canopy. Results show that: some 45% of the segments generated at the coarser segmentation scale (level 1) are surrounded by structurally different neighbours; level 2 segments distinguish spatial heterogeneity in forest structure in about 63% of level 1 segments; level 3 image segments detect better canopy gaps, rather than differences in the spatial pattern of the investigated structural indices. Results support also the idea of a mixture of macro and micro structural heterogeneity within the beech forest: large size populations of trees homogeneous for the examined structural indices at the coarser segmentation level, when analysed at a finer scale, are internally heterogeneous; and vice versa. Findings from this study demonstrate that multiresolution segmentation is able to delineate scale-dependent patterns of forest structural heterogeneity, even in an initial stage of old-growth structural differentiation. This tool has therefore a potential to improve the sampling design of field surveys aimed at characterizing forest structural complexity across multiple spatio-temporal scales.L'articolo è disponibile sul sito dell'editore www.sciencedirect.co

Balancing the dilution and oddity effects: Decisions depend on body size

Background Grouping behaviour, common across the animal kingdom, is known to reduce an individual's risk of predation; particularly through dilution of individual risk and predator confusion (predator inability to single out an individual for attack). Theory predicts greater risk of predation to individuals more conspicuous to predators by difference in appearance from the group (the ‘oddity’ effect). Thus, animals should choose group mates close in appearance to themselves (eg. similar size), whilst also choosing a large group. Methodology and Principal Findings We used the Trinidadian guppy (Poecilia reticulata), a well known model species of group-living freshwater fish, in a series of binary choice trials investigating the outcome of conflict between preferences for large and phenotypically matched groups along a predation risk gradient. We found body-size dependent differences in the resultant social decisions. Large fish preferred shoaling with size-matched individuals, while small fish demonstrated no preference. There was a trend towards reduced preferences for the matched shoal under increased predation risk. Small fish were more active than large fish, moving between shoals more frequently. Activity levels increased as predation risk decreased. We found no effect of unmatched shoal size on preferences or activity. Conclusions and Significance Our results suggest that predation risk and individual body size act together to influence shoaling decisions. Oddity was more important for large than small fish, reducing in importance at higher predation risks. Dilution was potentially of limited importance at these shoal sizes. Activity levels may relate to how much sampling of each shoal was needed by the test fish during decision making. Predation pressure may select for better decision makers to survive to larger size, or that older, larger fish have learned to make shoaling decisions more efficiently, and this, combined with their size relative to shoal-mates, and attractiveness as prey items influences shoaling decisions

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

The influence of portfolio aims and structure on student attitudes towards portfolios as a learning tool: A Scoping Review

Background: Portfolios are widely used in undergraduate health professional education, however the majority of literature suggests that these are poorly received by students, in terms of being an effective learning tool. Objectives: to evaluate whether the aims/purpose or structure/level of standardisation/content of student portfolios influences their attitudes to and perceptions of its use as a learning tool. Major Findings: Aims/purpose and structure/level of standardisation/content of portfolios were analysed in relation to student responses in order to determine any relationship between these. The level of information provided in the studies was variable, making analysis difficult, however there appeared to be no clear link between any of these factors and student responses. The interplay of level of support and guidance, the time required for completion of the portfolio, and the role of assessment appear to have the greatest influence on student views. Conclusions: Considering the wide use of portfolios in health professional education, student support for these is limited, and further research is required to determine if alternative approaches to portfolio learning can positively influence student attitudes and perceptions

A comparative, randomized clinical trial of artemisinin/naphtoquine twice daily one day versus artemether/lumefantrine six doses regimen in children and adults with uncomplicated falciparum malaria in Côte d'Ivoire

<p>Abstract</p> <p>Background</p> <p>Drug resistance in <it>Plasmodium falciparum </it>poses a major threat to malaria control. Combination anti-malarial therapy, including artemisinins, has been advocated to improve efficacy and limit the spread of resistance. The fixed combination of oral artemether-lumefantrine (AL) is highly effective and well-tolerated. Artemisinin/naphtoquine (AN) is a fixed-dose ACT that has recently become available in Africa.</p> <p>The objectives of the study were to compare the efficacy and safety of AN and AL for the treatment of uncomplicated <it>falciparum </it>malaria in a high transmission-intensity site in Ivory Coast.</p> <p>Methods</p> <p>We enrolled 122 participants aged 6 months or more with uncomplicated <it>falciparum </it>malaria. Participants were randomized to receive either artemisinin/naphtoquine or artemether/lumefantrine with variable dose according to their weight. Primary endpoints were the risks of treatment failure within 28 days, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infection.</p> <p>Results</p> <p>Among 125 participants enrolled, 123 (98.4%) completed follow-up. Clinical evaluation of the 123 participants showed that cumulative PCR-uncorrected cure rate on day 28 was 100% for artemisinin/naphtoquine and 98.4% for artemether/lumefantrine. Both artemisinin-based combinations effected rapid fever and parasite clearance.</p> <p>Interpretation</p> <p>These data suggest that Arco^®could prove to be suitable for use as combination antimalarial therapy. Meanwhile, pharmacokinetic studies and further efficacy assessment should be conducted before its widespread use can be supported.</p