Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia

Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle-cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM (Novel use Of Hydroxyurea in an African Region with Malaria) was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2.5 mg/kg per day for 12 months. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events (AEs), clinical and laboratory effects, and hematological toxicities. Children received either hydroxyurea (N = 104) or placebo (N = 103). Malaria incidence did not differ between children on hydroxyurea (0.05 episodes per child per year; 95% confidence interval [0.02, 0.13]) vs placebo (0.07 episodes per child per year [0.03, 0.16]); the hydroxyurea/placebo malaria incidence rate ratio was 0.7 ([0.2, 2.7]; P = .61). Time to infection also did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%; P = .001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious AEs, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria). Hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or AEs. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined. This trial was registered at www.clinicaltrials.gov as #NCT01976416

The Transit Light Curve Project. IX. Evidence for a Smaller Radius of the Exoplanet XO-3b

We present photometry of 13 transits of XO-3b, a massive transiting planet on an eccentric orbit. Previous data led to two inconsistent estimates of the planetary radius. Our data strongly favor the smaller radius, with increased precision: R_p = 1.217 +/- 0.073 R_Jup. A conflict remains between the mean stellar density determined from the light curve, and the stellar surface gravity determined from the shapes of spectral lines. We argue the light curve should take precedence, and revise the system parameters accordingly. The planetary radius is about 1 sigma larger than the theoretical radius for a hydrogen-helium planet of the given mass and insolation. To help in planning future observations, we provide refined transit and occultation ephemerides.Comment: To appear in ApJ [22 pages

The relationship between irrigation-induced electrical loads and antecedent weather conditions in Tasmania, Australia

Over the past decade in Australia, there has been a general trend towards the introduction of electrical motors to operate irrigation pumps. While electrical motors provide many advantages over the alternatives, electrical loads can aggregate in some areas to become large peaks, which challenge the existing electrical distribution networks. This is especially true during extreme hot or dry periods, when irrigators collectively demand significant electrical resources at the same time. While there is an inherent link between weather conditions and the amount of electricity used for irrigation, this relationship is poorly understood. Previous studies have either focused on localised data related to concurrent temperature, rainfall and soil moisture, or they have annualised summaries over large areas. In this study, we compare intensive irrigation periods with the drought factor at a case study irrigation scheme in Tasmania, Australia, finding a strong relationship between electrical load and periods when the drought factor is > 6. This relatively simple relationship may be useful for managers of electricity supply and distribution, managers of water resources, and irrigators, as it may be used to minimise the risk of exceeding the capacity of the electricity network, improve water availability and optimise irrigation scheduling

The Interannual variability of hurricane activity in the Atlantic and east pacific regions

The investigation of the interannual and interdecadal variations in hurricane activity has been an important topic of study lately, especially with regard to their implications for climate change issues. On the interannual time-scale, the El Niño and Southern Oscillation (ENSO) phase has been correlated with hurricane activity in the Atlantic and Eastern Pacific Ocean Basins. For example, various atmospheric and oceanic parameters that influence hurricane development become significantly altered during an El Niño event, leading to suppressed easterly wave development and growth in the Atlantic, but more activity in the Eastern Pacific Ocean Basin. This study examined the interannual variability of hurricane intensity (measured as wind speed and interpreted through the Saffir-Simpson Scale) from 1938 through 2007 in the Atlantic and 1970 through 2007 in the Pacific basins, respectively. These data were then compared with the occurrence of El Niño/La Niña events as defined using the Japan Meteorological Association (JMA) index. El Niño/La Niña variability superimposed on variability associated with the Pacific Decadal Oscillation (PDO) was also examined here. Not surprisingly, during an El Niño year the intensity of Atlantic hurricanes was found to be weaker than during a neutral year or a La Niña year, but these conclusions were opposite in the Eastern Pacific Ocean Basin. There were also significant differences found in hurricane intensity between El Niño and La Niña years when the PDO was in phase 1 (warm phase), rather than when the PDO was in phase 2 (cool phase). This study also examined the interannual variation in hurricane intensity by genesis region (i.e. Atlantic: the eastern and western Atlantic Ocean Basins, the Caribbean, and the Gulf of Mexico; Eastern Pacific: divided into quadrants using 20o N and 125o W as the quadrant intersection point). Finally, the utility of this information in a long-range forecast application is demonstrated

The Absolute Magnitude of RRc Variables From Statistical Parallax

We present the first definitive measurement of the absolute magnitude of RR Lyrae c-type variable stars (RRc) determined purely from statistical parallax. We use a sample of 247 RRc selected from the All Sky Automated Survey (ASAS) for which high-quality light curves, photometry and proper motions are available. We obtain high-resolution echelle spectra for these objects to determine radial velocities and abundances as part of the Carnegie RR Lyrae Survey (CARRS). We find that M_(V,RRc) = 0.52 +/- 0.11 at a mean metallicity of [Fe/H] = -1.59. This is to be compared with previous estimates for RRab stars (M_(V,RRab) = 0.75 +/- 0.13 and the only direct measurement of an RRc absolute magnitude (RZ Cephei, M_(V, RRc) = 0.27 +/- 0.17). We find the bulk velocity of the halo to be (W_pi, W_theta, W_z) = (10.9,34.9,7.2) km/s in the radial, rotational and vertical directions with dispersions (sigma_(W_pi), sigma_(W_theta), sigma_(W_z)) = (154.7, 103.6, 93.8) km/s. For the disk, we find (W_pi, W_theta, W_z) = (8.5, 213.2, -22.1) km/s with dispersions (sigma_(W_pi), sigma_(W_theta), sigma_(W_z)) = (63.5, 49.6, 51.3) km/s. Finally, we suggest that UCAC2 proper motion errors may be overestimated by about 25%Comment: Submitted to ApJ. 11 pages including 6 figure

Late-Life Exercise Mitigates Skeletal Muscle Epigenetic Aging

There are functional benefits to exercise in muscle, even when performed late in life, but the contributions of epigenetic factors to late-life exercise adaptation are poorly defined. Using reduced representation bisulfite sequencing (RRBS), ribosomal DNA (rDNA) and mitochondrial-specific examination of methylation, targeted high-resolution methylation analysis, and DNAge™ epigenetic aging clock analysis with a translatable model of voluntary murine endurance/resistance exercise training (progressive weighted wheel running, PoWeR), we provide evidence that exercise may mitigate epigenetic aging in skeletal muscle. Late-life PoWeR from 22–24 months of age modestly but significantly attenuates an age-associated shift toward promoter hypermethylation. The epigenetic age of muscle from old mice that PoWeR-trained for eight weeks was approximately eight weeks younger than 24-month-old sedentary counterparts, which represents ~8% of the expected murine lifespan. These data provide a molecular basis for exercise as a therapy to attenuate skeletal muscle aging

Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health

Vitamin D is an essential nutrient for the maintenance of skeletal muscle and bone health. The vitamin D receptor (VDR) is present in muscle, as is CYP27B1, the enzyme that hydroxylates 25(OH)D to its active form, 1,25(OH)D. Furthermore, mounting evidence suggests that vitamin D may play an important role during muscle damage and regeneration. Muscle damage is characterized by compromised muscle fiber architecture, disruption of contractile protein integrity, and mitochondrial dysfunction. Muscle regeneration is a complex process that involves restoration of mitochondrial function and activation of satellite cells (SC), the resident skeletal muscle stem cells. VDR expression is strongly upregulated following injury, particularly in central nuclei and SCs in animal models of muscle injury. Mechanistic studies provide some insight into the possible role of vitamin D activity in injured muscle. In vitro and in vivo rodent studies show that vitamin D mitigates reactive oxygen species (ROS) production, augments antioxidant capacity, and prevents oxidative stress, a common antagonist in muscle damage. Additionally, VDR knockdown results in decreased mitochondrial oxidative capacity and ATP production, suggesting that vitamin D is crucial for mitochondrial oxidative phosphorylation capacity; an important driver of muscle regeneration. Vitamin D regulation of mitochondrial health may also have implications for SC activity and self-renewal capacity, which could further affect muscle regeneration. However, the optimal timing, form and dose of vitamin D, as well as the mechanism by which vitamin D contributes to maintenance and restoration of muscle strength following injury, have not been determined. More research is needed to determine mechanistic action of 1,25(OH)D on mitochondria and SCs, as well as how this action manifests following muscle injury in vivo. Moreover, standardization in vitamin D sufficiency cut-points, time-course study of the efficacy of vitamin D administration, and comparison of multiple analogs of vitamin D are necessary to elucidate the potential of vitamin D as a significant contributor to muscle regeneration following injury. Here we will review the contribution of vitamin D to skeletal muscle regeneration following injury

Planetary Candidates Observed by Kepler. VIII. A Fully Automated Catalog with Measured Completeness and Reliability Based on Data Release 25

We present the Kepler Object of Interest (KOI) catalog of transiting exoplanets based on searching 4 yr of Kepler time series photometry (Data Release 25, Q1–Q17). The catalog contains 8054 KOIs, of which 4034 are planet candidates with periods between 0.25 and 632 days. Of these candidates, 219 are new, including two in multiplanet systems (KOI-82.06 and KOI-2926.05) and 10 high-reliability, terrestrial-size, habitable zone candidates. This catalog was created using a tool called the Robovetter, which automatically vets the DR25 threshold crossing events (TCEs). The Robovetter also vetted simulated data sets and measured how well it was able to separate TCEs caused by noise from those caused by low signal-to-noise transits. We discuss the Robovetter and the metrics it uses to sort TCEs. For orbital periods less than 100 days the Robovetter completeness (the fraction of simulated transits that are determined to be planet candidates) across all observed stars is greater than 85%. For the same period range, the catalog reliability (the fraction of candidates that are not due to instrumental or stellar noise) is greater than 98%. However, for low signal-to-noise candidates between 200 and 500 days around FGK-dwarf stars, the Robovetter is 76.7% complete and the catalog is 50.5% reliable. The KOI catalog, the transit fits, and all of the simulated data used to characterize this catalog are available at the NASA Exoplanet Archive