Ecdysteroid Hormones Link the Juvenile Environment to Alternative Adult Life Histories in a Seasonal Insect

The conditional expression of alternative life strategies is a widespread feature of animal life and a pivotal adaptation to life in seasonal environments. To optimally match suites of traits to seasonally changing ecological opportunities, animals living in seasonal environments need mechanisms linking information on environmental quality to resource allocation decisions. The butterfly Bicyclus anynana expresses alternative adult life histories in the alternating wet and dry seasons of its habitat as endpoints of divergent developmental pathways triggered by seasonal variation in preadult temperature. Pupal ecdysteroid hormone titers are correlated with the seasonal environment, but whether they play a functional role in coordinating the coupling of adult traits in the alternative life histories is unknown. Here, we show that manipulating pupal ecdysteroid levels is sufficient to mimic in direction and magnitude the shifts in adult reproductive resource allocation normally induced by seasonal temperature. Crucially, this allocation shift is accompanied by changes in ecologically relevant traits, including timing of reproduction, life span, and starvation resistance. Together, our results support a functional role for ecdysteroids during development in mediating strategic reproductive investment decisions in response to predictive indicators of environmental quality. This study provides a physiological mechanism for adaptive developmental plasticity, allowing organisms to cope with variable environments.European Union’s FP6 Programme (Network of Excellence LifeSpan FP6/036894), FCT fellowship (SFRH/BD/45486/2008)

Clinical decision support improves the appropriateness of laboratory test ordering in primary care without increasing diagnostic error : the ELMO cluster randomized trial

Background: Inappropriate laboratory test ordering poses an important burden for healthcare. Clinical decision support systems (CDSS) have been cited as promising tools to improve laboratory test ordering behavior. The objectives of this study were to evaluate the effects of an intervention that integrated a clinical decision support service into a computerized physician order entry (CPOE) on the appropriateness and volume of laboratory test ordering, and on diagnostic error in primary care. Methods: This study was a pragmatic, cluster randomized, open-label, controlled clinical trial. Setting: Two hundred eighty general practitioners (GPs) from 72 primary care practices in Belgium. Patients: Patients aged >= 18 years with a laboratory test order for at least one of 17 indications: cardiovascular disease management, hypertension, check-up, chronic kidney disease (CKD), thyroid disease, type 2 diabetes mellitus, fatigue, anemia, liver disease, gout, suspicion of acute coronary syndrome (ACS), suspicion of lung embolism, rheumatoid arthritis, sexually transmitted infections (STI), acute diarrhea, chronic diarrhea, and follow-up of medication. Interventions: The CDSS was integrated into a computerized physician order entry (CPOE) in the form of evidence-based order sets that suggested appropriate tests based on the indication provided by the general physician. Measurements: The primary outcome of the ELMO study was the proportion of appropriate tests over the total number of ordered tests and inappropriately not-requested tests. Secondary outcomes of the ELMO study included diagnostic error, test volume, and cascade activities. Results: CDSS increased the proportion of appropriate tests by 0.21 (95% CI 0.16-0.26, p < 0.0001) for all tests included in the study. GPs in the CDSS arm ordered 7 (7.15 (95% CI 3.37-10.93, p = 0.0002)) tests fewer per panel. CDSS did not increase diagnostic error. The absolute difference in proportions was a decrease of 0.66% (95% CI 1.4% decrease-0.05% increase) in possible diagnostic error. Conclusions: A CDSS in the form of order sets, integrated within the CPOE improved appropriateness and decreased volume of laboratory test ordering without increasing diagnostic error

Proving full-system security properties under multiple attacker models on capability machines

International audienceAssembly-level protection mechanisms (virtual memory, trusted execution environments, virtualization) make it possible to guarantee security properties of a full system in the presence of arbitrary attacker provided code. However, they typically only support a single trust boundary: code is either trusted or untrusted, and protection cannot be nested. Capability machines provide protection mechanisms that are more fine-grained and that do support arbitrary nesting of protection. We show in this paper how this enables the formal verification of full-system security properties under multiple attacker models: different security objectives of the full system can be verified under a different choice of trust boundary (i.e. under a different attacker model). The verification approach we propose is modular, and is robust: code outside the trust boundary for a given security objective can be arbitrary, unverified attacker-provided code. It is based on the use of universal contracts for untrusted adversarial code: sound, conservative contracts which can be combined with manual verification of trusted components in a compositional program logic. Compositionality of the program logic also allows us to reuse common parts in the analyses for different attacker models. We instantiate the approach concretely by extending an existing capability machine model with support for memory-mapped I/O and we obtain full system, machine-verified security properties about external effect traces while limiting the manual verification effort to a small trusted computing base relevant for the specific property under study

The 1st Verified Software Competition, Extended Experience Report

We, the organizers and participants, report our experiences from the 1st Veried Software Competition, held in August 2010 in Edinburgh at the VSTTE 2010 conferenc

The 1st Verified Software Competition, Extended Experience Report

We, the organizers and participants, report our experiences from the 1st Veried Software Competition, held in August 2010 in Edinburgh at the VSTTE 2010 conferenc

Beyond climate envelopes: effects of weather on regional population trends in butterflies

Although the effects of climate change on biodiversity are increasingly evident by the shifts in species ranges across taxonomical groups, the underlying mechanisms affecting individual species are still poorly understood. The power of climate envelopes to predict future ranges has been seriously questioned in recent studies. Amongst others, an improved understanding of the effects of current weather on population trends is required. We analysed the relation between butterfly abundance and the weather experienced during the life cycle for successive years using data collected within the framework of the Dutch Butterfly Monitoring Scheme for 40 species over a 15-year period and corresponding climate data. Both average and extreme temperature and precipitation events were identified, and multiple regression was applied to explain annual changes in population indices. Significant weather effects were obtained for 39 species, with the most frequent effects associated with temperature. However, positive density-dependence suggested climatic independent trends in at least 12 species. Validation of the short-term predictions revealed a good potential for climate-based predictions of population trends in 20 species. Nevertheless, data from the warm and dry year of 2003 indicate that negative effects of climatic extremes are generally underestimated for habitat specialists in drought-susceptible habitats, whereas generalists remain unaffected. Further climatic warming is expected to influence the trends of 13 species, leading to an improvement for nine species, but a continued decline in the majority of species. Expectations from climate envelope models overestimate the positive effects of climate change in northwestern Europe. Our results underline the challenge to include population trends in predicting range shifts in response to climate change

Lymphangiogenesis and Lymphatic Remodeling Induced by Filarial Parasites: Implications for Pathogenesis

Even in the absence of an adaptive immune system in murine models, lymphatic dilatation and dysfunction occur in filarial infections, although severe irreversible lymphedema and elephantiasis appears to require an intact adaptive immune response in human infections. To address how filarial parasites and their antigens influence the lymphatics directly, human lymphatic endothelial cells were exposed to filarial antigens, live parasites, or infected patient serum. Live filarial parasites or filarial antigens induced both significant LEC proliferation and differentiation into tube-like structures in vitro. Moreover, serum from patently infected (microfilaria positive) patients and those with longstanding chronic lymphatic obstruction induced significantly increased LEC proliferation compared to sera from uninfected individuals. Differentiation of LEC into tube-like networks was found to be associated with significantly increased levels of matrix metalloproteases and inhibition of their TIMP inhibitors (Tissue inhibitors of matrix metalloproteases). Comparison of global gene expression induced by live parasites in LEC to parasite-unexposed LEC demonstrated that filarial parasites altered the expression of those genes involved in cellular organization and development as well as those associated with junction adherence pathways that in turn decreased trans-endothelial transport as assessed by FITC-Dextran. The data suggest that filarial parasites directly induce lymphangiogenesis and lymphatic differentiation and provide insight into the mechanisms underlying the pathology seen in lymphatic filariasis