Dengue human infection models supporting drug development.

Dengue is a arboviral infection that represents a major global health burden. There is an unmet need for effective dengue therapeutics to reduce symptoms, duration of illness and incidence of severe complications. Here, we consider the merits of a dengue human infection model (DHIM) for drug development. A DHIM could allow experimentally controlled studies of candidate therapeutics in preselected susceptible volunteers, potentially using smaller sample sizes than trials that recruited patients with dengue in an endemic country. In addition, the DHIM would assist the conduct of intensive pharmacokinetic and basic research investigations and aid in determining optimal drug dosage. Furthermore, a DHIM could help establish proof of concept that chemoprophylaxis against dengue is feasible. The key challenge in developing the DHIM for drug development is to ensure the model reliably replicates the typical clinical and laboratory features of naturally acquired, symptomatic dengue

Chytrid epidemics may increase genetic diversity of a diatom spring-bloom

Contrary to expectation, populations of clonal organisms are often genetically highly diverse. In phytoplankton, this diversity is maintained throughout periods of high population growth (that is, blooms), even though competitive exclusion among genotypes should hypothetically lead to the dominance of a few superior genotypes. Genotype-specific parasitism may be one mechanism that helps maintain such high-genotypic diversity of clonal organisms. Here, we present a comparison of population genetic similarity by estimating the beta-dispersion among genotypes of early and peak bloom populations of the diatom Asterionella formosa for three spring-blooms under high or low parasite pressure. The Asterionella population showed greater beta-dispersion at peak bloom than early bloom in the 2 years with high parasite pressure, whereas the within group dispersion did not change under low parasite pressure. Our findings support that high prevalence parasitism can promote genetic diversification of natural populations of clonal hosts

Lowering IceCube's energy threshold for point source searches in the Southern Sky

Observation of a point source of astrophysical neutrinos would be a "smoking gun" signature of a cosmic-ray accelerator. While IceCube has recently discovered a diffuse flux of astrophysical neutrinos, no localized point source has been observed. Previous IceCube searches for point sources in the southern sky were restricted by either an energy threshold above a few hundred TeV or poor neutrino angular resolution. Here we present a search for southern sky point sources with greatly improved sensitivities to neutrinos with energies below 100 TeV. By selecting charged-current ν μ interacting inside the detector, we reduce the atmospheric background while retaining efficiency for astrophysical neutrino-induced events reconstructed with sub-degree angular resolution. The new event sample covers three years of detector data and leads to a factor of 10 improvement in sensitivity to point sources emitting below 100 TeV in the southern sky. No statistically significant evidence of point sources was found, and upper limits are set on neutrino emission from individual sources. A posteriori analysis of the highest-energy (~100 TeV) starting event in the sample found that this event alone represents a 2.8σ deviation from the hypothesis that the data consists only of atmospheric background.Fil: Aartsen, M. G.. University of Adelaide; AustraliaFil: Abraham, K.. Technische Universität München; AlemaniaFil: Ackermann, M.. Deutsches Elektronen-Synchrotron; AlemaniaFil: Adams, J.. University Of Canterbury; Nueva ZelandaFil: Aguilar, J. A.. Université Libre de Bruxelles; BélgicaFil: Golup, Geraldina Tamara. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Wallace, A.. University of Adelaide; AustraliaFil: Wallraff, M.. Rwth Aachen University; AlemaniaFil: Wandkowsky, N.. University of Wisconsin; Estados UnidosFil: Weaver, Ch.. University of Alberta; CanadáFil: Wendt, C.. University of Wisconsin; Estados UnidosFil: Westerhoff, S.. University of Wisconsin; Estados UnidosFil: Whelan, B. J.. University of Adelaide; AustraliaFil: Whitehorn, N.. University of California at Berkeley; Estados UnidosFil: Wickmann, S.. Rwth Aachen University; AlemaniaFil: Wiebe, K.. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Wiebusch, C. H.. Rwth Aachen University; AlemaniaFil: Wille, L.. University of Wisconsin; Estados UnidosFil: Williams, D. R.. University of Alabama at Birmingahm; Estados UnidosFil: Wills, L.. Drexel University; Estados UnidosFil: Wissing, H.. University of Maryland; Estados UnidosFil: Wolf, M.. Stockholms Universitet; SueciaFil: Wood, T. R.. University of Alberta; CanadáFil: Woschnagg, K.. University of California at Berkeley; Estados UnidosFil: Xu, D. L.. University of Wisconsin; Estados UnidosFil: Xu, X. W.. Southern University; Estados UnidosFil: Xu, Y.. Stony Brook University; Estados UnidosFil: Yanez, J. P.. Deutsches Elektronen-Synchrotron; AlemaniaFil: Yodh, G.. University of California at Irvine; Estados UnidosFil: Yoshida, S.. Chiba University; JapónFil: Zoll, M.. Stockholms Universitet; Sueci

Mainstreaming biodiversity: A review of national strategies

Biodiversity is suffering dramatic declines across the globe, threatening the ability of ecosystems to provide the services on which humanity depends. Mainstreaming biodiversity into the plans, strategies and policies of different economic sectors is key to reversing these declines. The importance of this mainstreaming is recognized by the Convention on Biological Diversity (CBD) and its Aichi targets. Individual countries can implement the goals of the CBD through their National Biodiversity Strategies and Action Plans (NBSAPs), which aim to, inter alia, support the mainstreaming of biodiversity into the policies of key economic sectors, such as agriculture, forestry and fisheries. This paper investigates the performance of countries at incorporating biodiversity mainstreaming into their post-2010 NBSAPs. We conduct a large-scale review of 144 NBSAPs against five criteria and calculate a national-level indicator for comparing levels of mainstreaming among countries. Our results show that developing countries, particularly those in Africa, have higher scores, indicating that they have a higher awareness of the importance of biodiversity mainstreaming. Developing nations were also more likely to involve a greater range of stakeholders in the NBSAP development process, whilst developed nations were less likely to give specific details about the monetary contributions of biodiversity to their economies. Overall, our findings suggest that biodiversity mainstreaming remains a challenge across much of the world, but that progress in some areas can provide direction and momentum in the future

Genetic variants of MICB and PLCE1 and associations with the laboratory features of dengue

Background: A previous genome-wide association study identified 2 susceptibility loci for severe dengue at MICB rs3132468 and PLCE1 rs3740360 and further work showed these mutations to be also associated with less severe clinical presentations. The aim of this study was to determine if these specific loci were associated with laboratory features of dengue that correlate with clinical severity with the aim of elucidating the functional basis of these genetic variants. Methods: This was a case-only analysis of laboratory-confirmed dengue patients obtained from 2 prospective cohort studies and 1 randomised clinical trial in Vietnam (Trial registration: ISRCTN ISRCTN03147572. Registered 24th July 2012). 2742 dengue cases were successfully genotyped at MICB rs3132468 and PLCE1 rs3740360. Laboratory variables were compared between genotypes and stratified by DENV serotype. Results: The analysis showed no association between MICB and PLCE1 genotype and early viraemia level, platelet nadir, white cell count nadir, or maximum haematocrit in both overall analysis and in analysis stratified by serotype. Discussion: The lack of an association between genotype and viremia level may reflect the sampling procedures within the included studies. The study findings mean that the functional basis of these mutations remains unclear. Trial registration: ISRCTN ISRCTN03147572. Registered 24th July 2012

Measurements of Sub-degree B-mode Polarization in the Cosmic Microwave Background from 100 Square Degrees of SPTpol Data

We present a measurement of the $B$-mode polarization power spectrum (the $BB$ spectrum) from 100 $\mathrm{deg}^2$ of sky observed with SPTpol, a polarization-sensitive receiver currently installed on the South Pole Telescope. The observations used in this work were taken during 2012 and early 2013 and include data in spectral bands centered at 95 and 150 GHz. We report the $BB$ spectrum in five bins in multipole space, spanning the range $300 \le \ell \le 2300$, and for three spectral combinations: 95 GHz $\times$ 95 GHz, 95 GHz $\times$ 150 GHz, and 150 GHz $\times$ 150 GHz. We subtract small ($< 0.5 \sigma$ in units of statistical uncertainty) biases from these spectra and account for the uncertainty in those biases. The resulting power spectra are inconsistent with zero power but consistent with predictions for the $BB$ spectrum arising from the gravitational lensing of $E$-mode polarization. If we assume no other source of $BB$ power besides lensed $B$ modes, we determine a preference for lensed $B$ modes of $4.9 \sigma$. After marginalizing over tensor power and foregrounds, namely polarized emission from galactic dust and extragalactic sources, this significance is $4.3 \sigma$. Fitting for a single parameter, $A_\mathrm{lens}$, that multiplies the predicted lensed $B$-mode spectrum, and marginalizing over tensor power and foregrounds, we find $A_\mathrm{lens} = 1.08 \pm 0.26$, indicating that our measured spectra are consistent with the signal expected from gravitational lensing. The data presented here provide the best measurement to date of the $B$-mode power spectrum on these angular scales.Comment: 21 pages, 4 figure

CMB Polarization B-mode Delensing with SPTpol and Herschel

We present a demonstration of delensing the observed cosmic microwave background (CMB) B-mode polarization anisotropy. This process of reducing the gravitational-lensing generated B-mode component will become increasingly important for improving searches for the B modes produced by primordial gravitational waves. In this work, we delens B-mode maps constructed from multi-frequency SPTpol observations of a 90 deg$^2$ patch of sky by subtracting a B-mode template constructed from two inputs: SPTpol E-mode maps and a lensing potential map estimated from the $\textit{Herschel}$ $500\,\mu m$ map of the CIB. We find that our delensing procedure reduces the measured B-mode power spectrum by 28% in the multipole range $300 < \ell < 2300$; this is shown to be consistent with expectations from theory and simulations and to be robust against systematics. The null hypothesis of no delensing is rejected at $6.9 \sigma$. Furthermore, we build and use a suite of realistic simulations to study the general properties of the delensing process and find that the delensing efficiency achieved in this work is limited primarily by the noise in the lensing potential map. We demonstrate the importance of including realistic experimental non-idealities in the delensing forecasts used to inform instrument and survey-strategy planning of upcoming lower-noise experiments, such as CMB-S4.Comment: 17 pages, 10 figures. Comments are welcome

A Measurement of the Cosmic Microwave Background Gravitational Lensing Potential from 100 Square Degrees of SPTpol Data

We present a measurement of the cosmic microwave background (CMB) gravitational lensing potential using data from the first two seasons of observations with SPTpol, the polarization-sensitive receiver currently installed on the South Pole Telescope (SPT). The observations used in this work cover 100 deg$^2$ of sky with arcminute resolution at 150 GHz. Using a quadratic estimator, we make maps of the CMB lensing potential from combinations of CMB temperature and polarization maps. We combine these lensing potential maps to form a minimum-variance (MV) map. The lensing potential is measured with a signal-to-noise ratio of greater than one for angular multipoles between $100< L <250$. This is the highest signal-to-noise mass map made from the CMB to date and will be powerful in cross-correlation with other tracers of large-scale structure. We calculate the power spectrum of the lensing potential for each estimator, and we report the value of the MV power spectrum between $100< L <2000$ as our primary result. We constrain the ratio of the spectrum to a fiducial $\Lambda$CDM model to be $A_{\rm MV}=0.92 \pm 0.14 {\rm\, (Stat.)} \pm 0.08 {\rm\, (Sys.)}$. Restricting ourselves to polarized data only, we find $A_{\rm POL}=0.92 \pm 0.24 {\rm\, (Stat.)} \pm 0.11 {\rm\, (Sys.)}$. This measurement rejects the hypothesis of no lensing at $5.9 \sigma$ using polarization data alone, and at $14 \sigma$ using both temperature and polarization data.Comment: 16 pages, 8 figure

Measurements of the Temperature and E-Mode Polarization of the CMB from 500 Square Degrees of SPTpol Data

We present measurements of the $E$-mode polarization angular auto-power spectrum ($EE$) and temperature-$E$-mode cross-power spectrum ($TE$) of the cosmic microwave background (CMB) using 150 GHz data from three seasons of SPTpol observations. We report the power spectra over the spherical harmonic multipole range $50 < \ell \leq 8000$, and detect nine acoustic peaks in the $EE$ spectrum with high signal-to-noise ratio. These measurements are the most sensitive to date of the $EE$ and $TE$ power spectra at $\ell > 1050$ and $\ell > 1475$, respectively. The observations cover 500 deg$^2$, a fivefold increase in area compared to previous SPTpol analyses, which increases our sensitivity to the photon diffusion damping tail of the CMB power spectra enabling tighter constraints on \LCDM model extensions. After masking all sources with unpolarized flux $>50$ mJy we place a 95% confidence upper limit on residual polarized point-source power of $D_\ell = \ell(\ell+1)C_\ell/2\pi <0.107\,\mu{\rm K}^2$ at $\ell=3000$, suggesting that the $EE$ damping tail dominates foregrounds to at least $\ell = 4050$ with modest source masking. We find that the SPTpol dataset is in mild tension with the $\Lambda CDM$ model ($2.1\,\sigma$), and different data splits prefer parameter values that differ at the $\sim 1\,\sigma$ level. When fitting SPTpol data at $\ell < 1000$ we find cosmological parameter constraints consistent with those for $Planck$ temperature. Including SPTpol data at $\ell > 1000$ results in a preference for a higher value of the expansion rate (H_0 = 71.3 \pm 2.1\,\mbox{km}\,s^{-1}\mbox{Mpc}^{-1} ) and a lower value for present-day density fluctuations ($\sigma_8 = 0.77 \pm 0.02$).Comment: Updated to match version accepted to ApJ. 34 pages, 17 figures, 6 table