Travel risk, malaria importation and malaria transmission in Zanzibar

The prevalence of Plasmodium falciparum malaria in Zanzibar has reached historic lows. Improving control requires quantifying malaria importation rates, identifying high-risk travelers, and assessing onwards transmission

Thermodynamic analysis of black hole solutions in gravitating nonlinear electrodynamics

We perform a general study of the thermodynamic properties of static electrically charged black hole solutions of nonlinear electrodynamics minimally coupled to gravitation in three space dimensions. The Lagrangian densities governing the dynamics of these models in flat space are defined as arbitrary functions of the gauge field invariants, constrained by some requirements for physical admissibility. The exhaustive classification of these theories in flat space, in terms of the behaviour of the Lagrangian densities in vacuum and on the boundary of their domain of definition, defines twelve families of admissible models. When these models are coupled to gravity, the flat space classification leads to a complete characterization of the associated sets of gravitating electrostatic spherically symmetric solutions by their central and asymptotic behaviours. We focus on nine of these families, which support asymptotically Schwarzschild-like black hole configurations, for which the thermodynamic analysis is possible and pertinent. In this way, the thermodynamic laws are extended to the sets of black hole solutions of these families, for which the generic behaviours of the relevant state variables are classified and thoroughly analyzed in terms of the aforementioned boundary properties of the Lagrangians. Moreover, we find universal scaling laws (which hold and are the same for all the black hole solutions of models belonging to any of the nine families) running the thermodynamic variables with the electric charge and the horizon radius. These scale transformations form a one-parameter multiplicative group, leading to universal "renormalization group"-like first-order differential equations. The beams of characteristics of these equations generate the full set of black hole states associated to any of these gravitating nonlinear electrodynamics...Comment: 51 single column pages, 19 postscript figures, 2 tables, GRG tex style; minor corrections added; final version appearing in General Relativity and Gravitatio

The Geographic Synchrony of Seasonal Influenza: A Waves across Canada and the United States

BACKGROUND: As observed during the 2009 pandemic, a novel influenza virus can spread globally before the epidemic peaks locally. As consistencies in the relative timing and direction of spread could form the basis for an early alert system, the objectives of this study were to use the case-based reporting system for laboratory confirmed influenza from the Canadian FluWatch surveillance program to identify the geographic scale at which spatial synchrony exists and then to describe the geographic patterns of influenza A virus across Canada and in relationship to activity in the United States (US). METHODOLOGY/PRINCIPAL FINDINGS: Weekly laboratory confirmations for influenza A were obtained from the Canadian FluWatch and the US FluView surveillance programs from 1997/98 to 2006/07. For the six seasons where at least 80% of the specimens were antigenically similar, we identified the epidemic midpoint of the local/regional/provincial epidemics and analyzed trends in the direction of spread. In three out of the six seasons, the epidemic appeared first in Canada. Regional epidemics were more closely synchronized across the US (3-5 weeks) compared to Canada (5-13 weeks), with a slight gradient in timing from the southwest regions in the US to northeast regions of Canada and the US. Cities, as well as rural areas within provinces, usually peaked within a couple of weeks of each other. The anticipated delay in peak activity between large cities and rural areas was not observed. In some mixed influenza A seasons, lack of synchronization sub-provincially was evident. CONCLUSIONS/SIGNIFICANCE: As mixing between regions appears to be too weak to force a consistency in the direction and timing of spread, local laboratory-based surveillance is needed to accurately assess the level of influenza activity in the community. In comparison, mixing between urban communities and adjacent rural areas, and between some communities, may be sufficient to force synchronization

Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewedPublisher PD

Transit Photometry as an Exoplanet Discovery Method

Photometry with the transit method has arguably been the most successful exoplanet discovery method to date. A short overview about the rise of that method to its present status is given. The method's strength is the rich set of parameters that can be obtained from transiting planets, in particular in combination with radial velocity observations; the basic principles of these parameters are given. The method has however also drawbacks, which are the low probability that transits appear in randomly oriented planet systems, and the presence of astrophysical phenomena that may mimic transits and give rise to false detection positives. In the second part we outline the main factors that determine the design of transit surveys, such as the size of the survey sample, the temporal coverage, the detection precision, the sample brightness and the methods to extract transit events from observed light curves. Lastly, an overview over past, current and future transit surveys is given. For these surveys we indicate their basic instrument configuration and their planet catch, including the ranges of planet sizes and stellar magnitudes that were encountered. Current and future transit detection experiments concentrate primarily on bright or special targets, and we expect that the transit method remains a principal driver of exoplanet science, through new discoveries to be made and through the development of new generations of instruments.Comment: Review chapte

An elaborated feeding cycle model for reductions in vectorial capacity of night-biting mosquitoes by insecticide-treated nets

BACKGROUND: Insecticide Treated Nets (ITNs) are an important tool for malaria control. ITNs are effective because they work on several parts of the mosquito feeding cycle, including both adult killing and repelling effects. METHODS: Using an elaborated description of the classic feeding cycle model, simple formulas have been derived to describe how ITNs change mosquito behaviour and the intensity of malaria transmission, as summarized by vectorial capacity and EIR. The predicted changes are illustrated as a function of the frequency of ITN use for four different vector populations using parameter estimates from the literature. RESULTS: The model demonstrates that ITNs simultaneously reduce mosquitoes' lifespans, lengthen the feeding cycle, and by discouraging human biting divert more bites onto non-human hosts. ITNs can substantially reduce vectorial capacity through small changes to all of these quantities. The total reductions in vectorial capacity differ, moreover, depending on baseline behavior in the absence of ITNs. Reductions in lifespan and vectorial capacity are strongest for vector species with high baseline survival. Anthropophilic and zoophilic species are affected differently by ITNs; the feeding cycle is lengthened more for anthrophilic species, and the proportion of bites that are diverted onto non-human hosts is higher for zoophilic species. CONCLUSION: This model suggests that the efficacy of ITNs should be measured as a total reduction in transmission intensity, and that the quantitative effects will differ by species and by transmission intensity. At very high rates of ITN use, ITNs can generate large reductions in transmission intensity that could provide very large reductions in transmission intensity, and effective malaria control in some areas, especially when used in combination with other control measures. At high EIR, ITNs will probably not substantially reduce the parasite rate, but when transmission intensity is low, reductions in vectorial capacity combine with reductions in the parasite rate to generate very large reductions in EIR

What Should Vaccine Developers Ask? Simulation of the Effectiveness of Malaria Vaccines

A number of different malaria vaccine candidates are currently in pre-clinical or clinical development. Even though they vary greatly in their characteristics, it is unlikely that any of them will provide long-lasting sterilizing immunity against the malaria parasite. There is great uncertainty about what the minimal vaccine profile should be before registration is worthwhile; how to allocate resources between different candidates with different profiles; which candidates to consider combining; and what deployment strategies to consider.We use previously published stochastic simulation models, calibrated against extensive epidemiological data, to make quantitative predictions of the population effects of malaria vaccines on malaria transmission, morbidity and mortality. The models are fitted and simulations obtained via volunteer computing. We consider a range of endemic malaria settings with deployment of vaccines via the Expanded program on immunization (EPI), with and without additional booster doses, and also via 5-yearly mass campaigns for a range of coverages. The simulation scenarios account for the dynamic effects of natural and vaccine induced immunity, for treatment of clinical episodes, and for births, ageing and deaths in the cohort. Simulated pre-erythrocytic vaccines have greatest benefits in low endemic settings (<EIR of 10.5) where between 12% and 14% of all deaths are averted when initial efficacy is 50%. In some high transmission scenarios (>EIR of 84) PEV may lead to increased incidence of severe disease in the long term, if efficacy is moderate to low (<70%). Blood stage vaccines (BSV) are most useful in high transmission settings, and are comparable to PEV for low transmission settings. Combinations of PEV and BSV generally perform little better than the best of the contributing components. A minimum half-life of protection of 2–3 years appears to be a precondition for substantial epidemiological effects. Herd immunity effects can be achieved with even moderately effective (>20%) malaria vaccines (either PEV or BSV) when deployed through mass campaigns targeting all age-groups as well as EPI, and especially if combined with highly efficacious transmission-blocking components.We present for the first time a stochastic simulation approach to compare likely effects on morbidity, mortality and transmission of a range of malaria vaccines and vaccine combinations in realistic epidemiological and health systems settings. The results raise several issues for vaccine clinical development, in particular appropriateness of vaccine types for different transmission settings; the need to assess transmission to the vector and duration of protection; and the importance of deployment additional to the EPI, which again may make the issue of number of doses required more critical. To test the validity and robustness of our conclusions there is a need for further modeling (and, of course, field research) using alternative formulations for both natural and vaccine induced immunity. Evaluation of alternative deployment strategies outside EPI needs to consider the operational implications of different approaches to mass vaccination

Inhibition of Progenitor Dendritic Cell Maturation by Plasma from Patients with Peripartum Cardiomyopathy: Role in Pregnancy-associated Heart Disease

Dendritic cells (DCs) play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM) is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births) provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder. Plasma samples from two groups (n = 12) of age- and parity-matched Haitian women with or without evidence of PPCM were tested for levels of biomarkers of cardiac tissue remodeling and immune activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of TGF- were measured in PPCM subjects relative to controls. Yet despite these findings, in vitro maturation of normal human cord blood derived progenitor dendritic cells (CBDCs) was significantly reduced (p < 0.001) in the presence of plasma from PPCM patients relative to plasma from post-partum control subjects as determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs to induce allo-responses in PBMCs. These results represent the first findings linking inhibition of DC maturation to the dysregulation of normal physiologic cardiac tissue remodeling during pregnancy and the pathogenesis of PPCM

The Role of Age and Exposure to Plasmodium falciparum in the Rate of Acquisition of Naturally Acquired Immunity: A Randomized Controlled Trial

Background: The rate of acquisition of naturally acquired immunity (NAI) against malaria predominantly depends on transmission intensity and age, although disentangling the effects of these is difficult. We used chemoprophylaxis to selectively control exposure to P. falciparum during different periods in infancy and explore the effect of age in the build-up of NAI, measured as risk of clinical malaria.\ud \ud Methods and Findings: A three-arm double-blind randomized placebo-controlled trial was conducted in 349 infants born to Mozambican HIV-negative women. The late exposure group (LEG) received monthly Sulfadoxine-Pyrimethamine (SP) plus Artesunate (AS) from 2.5–4.5 months of age and monthly placebo from 5.5–9.5 months; the early exposure group (EEG) received placebo from 2.5–4.5 months and SP+AS from 5.5–9.5 months; and the control group (CG) received placebo from 2.5–9.5 months. Active and passive case detection (PCD) were conducted from birth to 10.5 and 24 months respectively. The primary endpoint was time to first or only episode of malaria in the second year detected by PCD. The incidence of malaria during the second year was of 0.50, 0.51 and 0.35 episodes/PYAR in the LEG, EEG and CG respectively (p = 0.379 for the adjusted comparison of the 3 groups). The hazard ratio of the adjusted comparison between the LEG and the CG was 1.38 (0.83–2.28, p = 0.642) and that between the EEG and the CG was 1.35 (0.81–2.24, p = 0.743).\ud \ud Conclusions: After considerably interfering with exposure during the first year of life, there was a trend towards a higher risk of malaria in the second year in children who had received chemoprophylaxis, but there was no significant rebound. No evidence was found that the age of first exposure to malaria affects the rate of acquisition of NAI. Thus, the timing of administration of antimalarial interventions like malaria vaccines during infancy does not appear to be a critical determinant

Wire Marking Results in a Small but Significant Reduction in Avian Mortality at Power Lines: A BACI Designed Study

10 paginas, 4 figuras y 4 tablesBackground: Collision with electric power lines is a conservation problem for many bird species. Although the implementation of flight diverters is rapidly increasing, few well-designed studies supporting the effectiveness of this costly conservation measure have been published. Methodology/Principal Findings: We provide information on the largest worldwide marking experiment to date, including carcass searches at 35 (15 experimental, 20 control) power lines totalling 72.5 km, at both transmission (220 kV) and distribution (15 kV-45 kV) lines. We found carcasses of 45 species, 19 of conservation concern. Numbers of carcasses found were corrected to account for carcass losses due to removal by scavengers or being overlooked by researchers, resulting in an estimated collision rate of 8.2 collisions per km per month. We observed a small (9.6%) but significant decrease in the number of casualties after line marking compared to before line marking in experimental lines. This was not observed in control lines. We found no influence of either marker size (large vs. small spirals, sample of distribution lines only) or power line type (transmission vs. distribution, sample of large spirals only) on the collision rate when we analyzed all species together. However, great bustard mortality was slightly lower when lines were marked with large spirals and in transmission lines after marking. Conclusions: Our results confirm the overall effectiveness of wire marking as a way to reduce, but not eliminate, bird collisions with power lines. If raw field data are not corrected by carcass losses due to scavengers and missed observations, findings may be biased. The high cost of this conservation measure suggests a need for more studies to improve its application, including wire marking with non-visual devices. Our findings suggest that different species may respond differently to marking, implying that species-specific patterns should be explored, at least for species of conservation concern.We thank A. Garcıa Fernandez and M. Carrasco for their assistance during the field work. We also thank J. Camaño and J. Velasco of HENARSA, and the electric companies Iberdrola, Union Fenosa and Red Electrica de España for their cooperation. S. Young reviewed the English. RB was contracted within the project CGL2008-02567 of the Direccion General de Investigacion, Spanish Ministry of Science and Innovation and later supported by a postdoctoral grant from Junta de Comunidades de Castilla-La Mancha. C. Ponce, C. Palacın, CM and BM were supported by contracts CSICHENARSA. This study was carried out within the Preventive, corrective and compensatory measures to balance the impact of the M-50 and R-2 highways on the population of great bustards and other steppe-land birds in the Important Bird Area Talamanca-Camarma and the Site of Community Importance Cuenca de los rıos Jarama y Henares, supported by a contract HENARSA-CSIC. Additional financial support was provided by project GL2008-02567 of the Direccion General de Investigacion, Spanish Ministry of Science and Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe