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Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function. © 2013 The American Society of Human Genetics.

International audience; ObjectivesSeveral automated algorithms for epidemiological surveillance in hospitals have been proposed. However, the usefulness of these methods to detect nosocomial outbreaks remains unclear. The goal of this review was to describe outbreak detection algorithms that have been tested within hospitals, consider how they were evaluated, and synthesize their results.MethodsWe developed a search query using keywords associated with hospital outbreak detection and searched the MEDLINE database. To ensure the highest sensitivity, no limitations were initially imposed on publication languages and dates, although we subsequently excluded studies published before 2000. Every study that described a method to detect outbreaks within hospitals was included, without any exclusion based on study design. Additional studies were identified through citations in retrieved studies.ResultsTwenty-nine studies were included. The detection algorithms were grouped into 5 categories: simple thresholds (n = 6), statistical process control (n = 12), scan statistics (n = 6), traditional statistical models (n = 6), and data mining methods (n = 4). The evaluation of the algorithms was often solely descriptive (n = 15), but more complex epidemiological criteria were also investigated (n = 10). The performance measures varied widely between studies: e.g., the sensitivity of an algorithm in a real world setting could vary between 17 and 100%.ConclusionEven if outbreak detection algorithms are useful complementary tools for traditional surveillance, the heterogeneity in results among published studies does not support quantitative synthesis of their performance. A standardized framework should be followed when evaluating outbreak detection methods to allow comparison of algorithms across studies and synthesis of results.

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P= 2.1 x 10(-12) and LGR6, P = 1.4 x 10(-8)), 2p24.1 (P = 4.6 x 10(-8)) and 16q12.2 (FTO, P = 4.0 x 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P> 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

PURPOSE: Atezolizumab is an established treatment option for pretreated urothelial carcinoma, demonstrating efficacy in phase II/III trials. The SAUL study enrolled a broader patient population to determine safety and efficacy in underrepresented subgroups. MATERIALS AND METHODS: Patients with metastatic urinary tract carcinoma received atezolizumab 1,200 mg every 3 weeks until disease progression, unacceptable toxicity, loss of clinical benefit, or patient/physician decision. The primary endpoint was safety. Efficacy was a secondary endpoint. Analyses by programmed cell death ligand-1 (PD-L1) status, age, Eastern Cooperative Oncology Group performance status (ECOG PS) and renal impairment were prespecified; post hoc analyses explored outcomes by tumor location. RESULTS: A total of 1,004 patients were enrolled. Subgroup analyses in patients with older age, renal impairment, or upper tract urothelial carcinoma showed safety and efficacy similar to those in patients without these characteristics. Patients with ECOG PS 2 had clinical features typically associated with aggressive disease; median overall survival was 2.3 months versus 10.0 months in patients with ECOG PS0/1. Patients with PD-L1 expression on ≥5% of tumor-infiltrating immune cells tended to have better outcomes than those with <5% PD-L1 expression, although conclusions on the relative efficacy of atezolizumab cannot be drawn from this single-arm study. CONCLUSIONS: The understudied populations included in the SAUL study had similar outcomes to those in more selected populations included in phase II/III trials of atezolizumab, except for those with ECOG PS 2. Age ≥80 years and/or creatinine clearance <30 ml/minute does not preclude administration of atezolizumab; however, treatment risk versus benefit must be carefully assessed in patients with ECOG PS 2.

We present the discovery of a co-moving planetary-mass companion ~42" (~2000 AU) from a young M3 star, GU Psc, likely member of the young AB Doradus Moving Group (ABDMG). The companion was first identified via its distinctively red i - z color (> 3.5) through a survey made with Gemini-S/GMOS. Follow-up Canada-France-Hawaii Telescope/WIRCam near-infrared (NIR) imaging, Gemini-N/GNIRS NIR spectroscopy and Wide-field Infrared Survey Explorer photometry indicate a spectral type of T3.5+-1 and reveal signs of low gravity which we attribute to youth. Keck/Adaptive Optics NIR observations did not resolve the companion as a binary. A comparison with atmosphere models indicates Teff = 1000-1100 K and logg = 4.5-5.0. Based on evolution models, this temperature corresponds to a mass of 9-13 MJup for the age of ABDMG (70-130 Myr). The relatively well-constrained age of this companion and its very large angular separation to its host star will allow its thorough characterization and will make it a valuable comparison for planetary-mass companions that will be uncovered by forthcoming planet-finder instruments such as Gemini Planet Imager and SPHERE. 18 p., 10 fig., published in ApJ. May 20th, 2014: Small corrections compared to the journal version: 1) addition of the an important reference to 1RSX 1609-2105b from Lafreni\`ere et al. 2008, 2010, 2) update of the url for Andrew Mann metallicity calibration, 3) correction of a few factual mistakes in section 2.2.4), 4) aesthetic reformatting of urls

This work was supported by the U.S. Department of Energy and National Science Foundation; the Italian Istituto Nazionale di Fisica Nucleare; the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Natural Sciences and Engineering Research Council of Canada; the National Science Council of the Republic of China; the Swiss National Science Foundation; the A. P. Sloan Foundation; the Bundesministerium für Bildung und Forschung, Germany; the Korean World Class University Program, the National Research Foundation of Korea; the Science and Technology Facilities Council and the Royal Society, United Kingdom; the Russian Foundation for Basic Research; the Ministerio de Ciencia e Innovación, and Programa Consolider-Ingenio 2010, Spain; the Slovak R&D Agency; the Academy of Finland; the Australian Research Council (ARC); and the EU community Marie Curie Fellowship Contract No. 302103. This work was also supported by the Shrum Foundation, the Weizman Institute of Science and the Israel Science Foundation. Results of a study of the substructure of the highest transverse momentum (pT) jets observed by the CDF Collaboration are presented. Events containing at least one jet with pT>400 GeV/c in a sample corresponding to an integrated luminosity of 5.95 fb−1, collected in 1.96 TeV proton-antiproton collisions at the Fermilab Tevatron collider, are selected. A study of the jet mass, angularity, and planar-flow distributions is presented, and the measurements are compared with predictions of perturbative quantum chromodynamics. A search for boosted top-quark production is also described, leading to a 95% confidence level upper limit of 38 fb on the production cross section of top quarks with pT>400 GeV/c. Peer Reviewed et al.

International audience; Different protein sources, such as canola meal (CM) or dried distillers grains (DDG), are currently used in dairy rations to replace soybean meal (SBM). However, little data exists comparing their rumen degradation in a single study. Therefore, the objective of this study was to compare the ruminal degradation of dry matter (DM), crude protein (CP), and AA of SBM, CM, high-protein corn DDG (HPDDG), and wheat DDG plus solubles (WDDGS). In situ studies were conducted with 4 rumen-fistulated lactating Holstein cows fed a diet containing 38% grass hay and 62% corn-based concentrate. Each protein source was incubated in the rumen of each cow in nylon bags for 0, 2, 4, 8, 16, 24, and 48 h to determine DM and CP rumen degradation kinetics, whereas additional bags were also incubated for 16 h to evaluate AA ruminal disappearance. Rumen DM and CP degradability was calculated from rumenundegraded residues corrected or not for small particle loss. Data were fitted to an exponential model to estimate degradation parameters and effective degradability (ED) was calculated with a passage rate of 0.074 h(-1). The WDDGS and SBM had higher uncorrected ED (DM =- 75.0 and 72.6%; CP = 84.8 and 66.0%, respectively) than CM and HPDDG (DM = 57.2 and 55.5%; CP = 59.3 and 48.2%, respectively), due to higher soluble fraction in WDDGS and a combination of higher potentially degradable fraction and rate of degradation in SBM. Correction for small particle loss from bags, higher for WDDGS than for the other protein sources, decreased estimated ED but did not alter feed ranking. The ruminal disappearance of AA after 16 h of incubation reflected the overall pattern of CP degradation between protein supplements, but the ruminal disappearance of individual AA differed between protein supplements. Overall, these results indicate that, in the current study, (1) SBM and WDDGS were more degradable in the rumen than CM and HPDDG, and (2) that small particle loss correction is relevant but does not alter this ranking.

International audience; This study investigated prey captures in free-ranging adult female Australian fur seals (Arctocephalus pusillus doriferus) using head-mounted 3-axis accelerometers and animal-borne video cameras. Acceleration data was used to identify individual attempted prey captures (APC), and video data were used to independently verify APC and prey types. Results demonstrated that head-mounted accelerometers could detect individual APC but were unable to distinguish among prey types (fish, cephalopod, stingray) or between successful captures and unsuccessful capture attempts. Mean detection rate (true positive rate) on individual animals in the testing subset ranged from 67-100%, and mean detection on the testing subset averaged across 4 animals ranged from 82-97%. Mean False positive (FP) rate ranged from 15-67% individually in the testing subset, and 26-59% averaged across 4 animals. Surge and sway had significantly greater detection rates, but also conversely greater FP rates compared to heave. Video data also indicated that some head movements recorded by the accelerometers were unrelated to APC and that a peak in acceleration variance did not always equate to an individual prey item. The results of the present study indicate that head-mounted accelerometers provide a complementary tool for investigating foraging behaviour in pinnipeds, but that detection and FP correction factors need to be applied for reliable field application.

Creee lors du Forum UNESCO de 2002 sur l'impact des didacticiels libres, l’expression « ressources educatives libres » (REL) designe « des materiels d'enseignement, d'apprentissage et de recherche sur tout support, numerique ou autre, existant dans le domaine public ou publies sous une licence ouverte permettant l'acces, l'utilisation, l’adaptation et la redistribution gratuits par d'autres, sans restrictions ou avec des restrictions limitees » (Declaration de Paris sur les REL, 2012). Par le...

The results of gamma-ray observations of the binary system HESS J0632 + 057 collected during 450 hr over 15 yr, between 2004 and 2019, are presented. Data taken with the atmospheric Cherenkov telescopes H.E.S.S., MAGIC, and VERITAS at energies above 350 GeV were used together with observations at X-ray energies obtained with Swift-XRT, Chandra, XMM-Newton, NuSTAR, and Suzaku. Some of these observations were accompanied by measurements of the H�� emission line. A significant detection of the modulation of the very high-energy gamma-ray fluxes with a period of 316.7 �� 4.4 days is reported, consistent with the period of 317.3 �� 0.7 days obtained with a refined analysis of X-ray data. The analysis of data from four orbital cycles with dense observational coverage reveals short-timescale variability, with flux-decay timescales of less than 20 days at very high energies. Flux variations observed over a timescale of several years indicate orbit-to-orbit variability. The analysis confirms the previously reported correlation of X-ray and gamma-ray emission from the system at very high significance, but cannot find any correlation of optical H�� parameters with fluxes at X-ray or gamma-ray energies in simultaneous observations. The key finding is that the emission of HESS J0632 + 057 in the X-ray and gamma-ray energy bands is highly variable on different timescales. The ratio of gamma-ray to X-ray flux shows the equality or even dominance of the gamma-ray energy range. This wealth of new data is interpreted taking into account the insufficient knowledge of the ephemeris of the system, and discussed in the context of results reported on other gamma-ray binary systems. The astrophysical journal 923(2), 241 (2021). doi:10.3847/1538-4357/ac29b7 Published by Univ., Chicago, Ill. [u.a.]