Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis: The EVOLVE Trial

Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%–29%

Multiple Insecticide Resistance: An Impediment to Insecticide-Based Malaria Vector Control Program

BACKGROUND: Indoor Residual Spraying (IRS), insecticide-treated nets (ITNs) and long-lasting insecticidal nets (LLINs) are key components in malaria prevention and control strategy. However, the development of resistance by mosquitoes to insecticides recommended for IRS and/or ITNs/LLINs would affect insecticide-based malaria vector control. We assessed the susceptibility levels of Anopheles arabiensis to insecticides used in malaria control, characterized basic mechanisms underlying resistance, and evaluated the role of public health use of insecticides in resistance selection. METHODOLOGY/PRINCIPAL FINDINGS: Susceptibility status of An. arabiensis was assessed using WHO bioassay tests to DDT, permethrin, deltamethrin, malathion and propoxur in Ethiopia from August to September 2009. Mosquito specimens were screened for knockdown resistance (kdr) and insensitive acetylcholinesterase (ace-1(R)) mutations using AS-PCR and PCR-RFLP, respectively. DDT residues level in soil from human dwellings and the surrounding environment were determined by Gas Chromatography with Electron Capture Detector. An. arabiensis was resistant to DDT, permethrin, deltamethrin and malathion, but susceptible to propoxur. The West African kdr allele was found in 280 specimens out of 284 with a frequency ranged from 95% to 100%. Ace-1(R) mutation was not detected in all specimens scored for the allele. Moreover, DDT residues were found in soil samples from human dwellings but not in the surrounding environment. CONCLUSION: The observed multiple-resistance coupled with the occurrence of high kdr frequency in populations of An. arabiensis could profoundly affect the malaria vector control programme in Ethiopia. This needs an urgent call for implementing rational resistance management strategies and integrated vector control intervention

Anonymous Traitor Tracing: How to Embed Arbitrary Information in a Key

In a traitor tracing scheme, each user is given a different decryption key. A content distributor can encrypt digital content using a public encryption key and each user in the system can decrypt it using her decryption key. Even if a coalition of users combines their decryption keys and constructs some ``pirate decoder\u27\u27 that is capable of decrypting the content, there is a public tracing algorithm that is guaranteed to recover the identity of at least one of the users in the coalition given black-box access to such decoder. In prior solutions, the users are indexed by numbers $1,\ldots,N$ and the tracing algorithm recovers the index $i$ of a user in a coalition. Such solutions implicitly require the content distributor to keep a record that associates each index $i$ with the actual identifying information for the corresponding user (e.g., name, address, etc.) in order to ensure accountability. In this work, we construct traitor tracing schemes where all of the identifying information about the user can be embedded directly into the user\u27s key and recovered by the tracing algorithm. In particular, the content distributor does not need to separately store any records about the users of the system, and honest users can even remain anonymous to the content distributor. The main technical difficulty comes in designing tracing algorithms that can handle an exponentially large universe of possible identities, rather than just a polynomial set of indices $i \in [N]$. We solve this by abstracting out an interesting algorithmic problem that has surprising connections with seemingly unrelated areas in cryptography. We also extend our solution to a full ``broadcast-trace-and-revoke\u27\u27 scheme in which the traced users can subsequently be revoked from the system. Depending on parameters, some of our schemes can be based only on the existence of public-key encryption while others rely on indistinguishability obfuscation

Environmental dependence of the galaxy stellar mass function in the Dark Energy Survey Science Verification Data

Measurements of the galaxy stellar mass function are crucial to understand the formation of galaxies in the Universe. In a hierarchical clustering paradigm it is plausible that there is a connection between the properties of galaxies and their environments. Evidence for environmental trends has been established in the local Universe. The Dark Energy Survey (DES) provides large photometric datasets that enable further investigation of the assembly of mass. In this study we use ~3.2 million galaxies from the (South Pole Telescope) SPT-East field in the DES science verification (SV) dataset. From grizY photometry we derive galaxy stellar masses and absolute magnitudes, and determine the errors on these properties using Monte-Carlo simulations using the full photometric redshift probability distributions. We compute galaxy environments using a fixed conical aperture for a range of scales. We construct galaxy environment probability distribution functions and investigate the dependence of the environment errors on the aperture parameters. We compute the environment components of the galaxy stellar mass function for the redshift range 0.15<z<1.05. For z<0.75 we find that the fraction of massive galaxies is larger in high density environment than in low density environments. We show that the low density and high density components converge with increasing redshift up to z~1.0 where the shapes of the mass function components are indistinguishable. Our study shows how high density structures build up around massive galaxies through cosmic time

The STRong lensing Insights into the Dark Energy Survey (STRIDES) 2016 follow-up campaign - I. Overview and classification of candidates selected by two techniques

The primary goals of the STRong lensing Insights into the Dark Energy Survey (STRIDES) collaboration are to measure the dark energy equation of state parameter and the free streaming length of dark matter. To this aim, STRIDES is discovering strongly lensed quasars in the imaging data of the Dark Energy Survey and following them up to measure time delays, high resolution imaging, and spectroscopy sufficient to construct accurate lens models. In this paper, we first present forecasts for STRIDES. Then, we describe the STRIDES classification scheme, and give an overview of the Fall 2016 follow-up campaign. We continue by detailing the results of two selection methods, the Outlier Selection Technique and a morphological algorithm, and presenting lens models of a system, which could possibly be a lensed quasar in an unusual configuration. We conclude with the summary statistics of the Fall 2016 campaign. Including searches presented in companion papers (Anguita et al.; Ostrovski et al.), STRIDES followed up 117 targets identifying 7 new strongly lensed systems, and 7 nearly identical quasars (NIQs), which could be confirmed as lenses by the detection of the lens galaxy. 76 candidates were rejected and 27 remain otherwise inconclusive, for a success rate in the range 6-35\%. This rate is comparable to that of previous searches like SQLS even though the parent dataset of STRIDES is purely photometric and our selection of candidates cannot rely on spectroscopic information

Dengue-2 Structural Proteins Associate with Human Proteins to Produce a Coagulation and Innate Immune Response Biased Interactome

<p>Abstract</p> <p>Background</p> <p>Dengue virus infection is a public health threat to hundreds of millions of individuals in the tropical regions of the globe. Although Dengue infection usually manifests itself in its mildest, though often debilitating clinical form, dengue fever, life-threatening complications commonly arise in the form of hemorrhagic shock and encephalitis. The etiological basis for the virus-induced pathology in general, and the different clinical manifestations in particular, are not well understood. We reasoned that a detailed knowledge of the global biological processes affected by virus entry into a cell might help shed new light on this long-standing problem.</p> <p>Methods</p> <p>A bacterial two-hybrid screen using DENV2 structural proteins as bait was performed, and the results were used to feed a manually curated, global dengue-human protein interaction network. Gene ontology and pathway enrichment, along with network topology and microarray meta-analysis, were used to generate hypothesis regarding dengue disease biology.</p> <p>Results</p> <p>Combining bioinformatic tools with two-hybrid technology, we screened human cDNA libraries to catalogue proteins physically interacting with the DENV2 virus structural proteins, Env, cap and PrM. We identified 31 interacting human proteins representing distinct biological processes that are closely related to the major clinical diagnostic feature of dengue infection: haemostatic imbalance. In addition, we found dengue-binding human proteins involved with additional key aspects, previously described as fundamental for virus entry into cells and the innate immune response to infection. Construction of a DENV2-human global protein interaction network revealed interesting biological properties suggested by simple network topology analysis.</p> <p>Conclusions</p> <p>Our experimental strategy revealed that dengue structural proteins interact with human protein targets involved in the maintenance of blood coagulation and innate anti-viral response processes, and predicts that the interaction of dengue proteins with a proposed human protein interaction network produces a modified biological outcome that may be behind the hallmark pathologies of dengue infection.</p

Dark Energy Survey year 1 results: Joint analysis of galaxy clustering, galaxy lensing, and CMB lensing two-point functions

We perform a joint analysis of the auto and cross-correlations between three cosmic fields: the galaxy density field, the galaxy weak lensing shear field, and the cosmic microwave background (CMB) weak lensing convergence field. These three fields are measured using roughly 1300 sq. deg. of overlapping optical imaging data from first year observations of the Dark Energy Survey and millimeter-wave observations of the CMB from both the South Pole Telescope Sunyaev-Zel'dovich survey and Planck. We present cosmological constraints from the joint analysis of the two-point correlation functions between galaxy density and galaxy shear with CMB lensing. We test for consistency between these measurements and the DES-only two-point function measurements, finding no evidence for inconsistency in the context of flat $\Lambda$CDM cosmological models. Performing a joint analysis of five of the possible correlation functions between these fields (excluding only the CMB lensing autospectrum) yields $S_{8}\equiv \sigma_8\sqrt{\Omega_{\rm m}/0.3} = 0.782^{+0.019}_{-0.025}$ and $\Omega_{\rm m}=0.260^{+0.029}_{-0.019}$. We test for consistency between these five correlation function measurements and the Planck-only measurement of the CMB lensing autospectrum, again finding no evidence for inconsistency in the context of flat $\Lambda$CDM models. Combining constraints from all six two-point functions yields $S_{8}=0.776^{+0.014}_{-0.021}$ and $\Omega_{\rm m}= 0.271^{+0.022}_{-0.016}$. These results provide a powerful test and confirmation of the results from the first year DES joint-probes analysis

Dark Energy Survey Year 1 Results: Cross-correlation between Dark Energy Survey Y1 galaxy weak lensing and South Pole Telescope +Planck CMB weak lensing

We cross-correlate galaxy weak lensing measurements from the Dark Energy Survey (DES) year-one data with a cosmic microwave background (CMB) weak lensing map derived from South Pole Telescope (SPT) and Planck data, with an effective overlapping area of 1289 deg2. With the combined measurements from four source galaxy redshift bins, we obtain a detection significance of 5.8σ. We fit the amplitude of the correlation functions while fixing the cosmological parameters to a fiducial ΛCDM model, finding A=0.99±0.17. We additionally use the correlation function measurements to constrain shear calibration bias, obtaining constraints that are consistent with previous DES analyses. Finally, when performing a cosmological analysis under the ΛCDM model, we obtain the marginalized constraints of ωm=0.261-0.051+0.070 and S8σ8ωm/0.3=0.660-0.100+0.085. These measurements are used in a companion work that presents cosmological constraints from the joint analysis of two-point functions among galaxies, galaxy shears, and CMB lensing using DES, SPT, and Planck data

Dark energy survey year 1 results: Redshift distributions of the weak-lensing source galaxies

We describe the derivation and validation of redshift distribution estimates and their uncertainties for the populations of galaxies used as weak-lensing sources in the Dark Energy Survey (DES) Year 1 cosmological analyses. The Bayesian Photometric Redshift (BPZ) code is used to assign galaxies to four redshift bins between z ≈ 0.2 and ≈1.3, and to produce initial estimates of the lensing-weighted redshift distributions nPZi(z) ∝ dni/dz for members of bin i. Accurate determination of cosmological parameters depends critically on knowledge of ni, but is insensitive to bin assignments or redshift errors for individual galaxies. The cosmological analyses allow for shifts ni (z) = nPZi(z - Δzi) to correct themean redshift of ni(z) for biases in nPZi. The Δzi are constrained by comparison of independently estimated 30-band photometric redshifts of galaxies in the Cosmic Evolution Survey (COSMOS) field to BPZ estimates made from the DES griz fluxes, for a sample matched in fluxes, pre-seeing size, and lensing weight to the DES weak-lensing sources. In companion papers, the Δzi of the three lowest redshift bins are further constrained by the angular clustering of the source galaxies around red galaxies with secure photometric redshifts at 0.15 &lt; z &lt; 0.9. This paper details the BPZ and COSMOS procedures, and demonstrates that the cosmological inference is insensitive to details of the ni(z) beyond the choice of Δzi. The clustering and COSMOS validation methods produce consistent estimates of Δzi in the bins where both can be applied, with combined uncertainties of σΔzi = 0.015, 0.013, 0.011, and 0.022 in the four bins. Repeating the photo-z procedure instead using the Directional Neighbourhood Fitting algorithm, or using the ni(z) estimated from the matched sample in COSMOS, yields no discernible difference in cosmological inferences

Cosmic Voids and Void Lensing in the Dark Energy Survey Science Verification Data

Galaxies and their dark matter halos populate a complicated filamentary network around large, nearly empty regions known as cosmic voids. Cosmic voids are usually identified in spectroscopic galaxy surveys, where 3D information about the large-scale structure of the Universe is available. Although an increasing amount of photometric data is being produced, its potential for void studies is limited since photometric redshifts induce line-of-sight position errors of $\sim50$ Mpc/$h$ or more that can render many voids undetectable. In this paper we present a new void finder designed for photometric surveys, validate it using simulations, and apply it to the high-quality photo-$z$ redMaGiC galaxy sample of the Dark Energy Survey Science Verification (DES-SV) data. The algorithm works by projecting galaxies into 2D slices and finding voids in the smoothed 2D galaxy density field of the slice. Fixing the line-of-sight size of the slices to be at least twice the photo-$z$ scatter, the number of voids found in these projected slices of simulated spectroscopic and photometric galaxy catalogs is within 20% for all transverse void sizes, and indistinguishable for the largest voids of radius $\sim 70$ Mpc/$h$ and larger. The positions, radii, and projected galaxy profiles of photometric voids also accurately match the spectroscopic void sample. Applying the algorithm to the DES-SV data in the redshift range $0.2<z<0.8$, we identify 87 voids with comoving radii spanning the range 18-120 Mpc/$h$, and carry out a stacked weak lensing measurement. With a significance of $4.4\sigma$, the lensing measurement confirms the voids are truly underdense in the matter field and hence not a product of Poisson noise, tracer density effects or systematics in the data. It also demonstrates, for the first time in real data, the viability of void lensing studies in photometric surveys