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We recently contributed to the description of eight individuals with a novel condition caused by 16p13.3 microdeletions encompassing TBC1D24, ATP6V0C, and PDPK1 and resulting in epilepsy, microcephaly and neurodevelopmental problems. The phenotypic spectrum, the minimum overlapping region and the underlying disease mechanism for this disorder remain to be clarified. Here we report a 3.5‐year‐old male, with microcephaly, autism spectrum disorder and a de novo 16p13.3 microdeletion. We performed detailed in silico analysis to show that the minimum overlapping region for the condition is ~80Kb encompassing five protein coding genes. Analysis of loss of function constraint metrics, transcript‐aware evaluation of the population variants, GeVIR scores, analysis of reported pathogenic point variants, detailed review of the known functions of gene products and their animal models showed that the haploinsufficiency of ATP6V0C likely underlies the phenotype of this condition. Protein–protein interaction network, gene phenology and analysis of topologically associating domain showed that it was unlikely that the disorder has an epistatic or regulatory basis. 16p13.3 deletions encompassing ATP6V0C cause a neurodevelopmental disorder. Our results broaden the phenotypic spectrum of this disorder and clarify the likely underlying disease mechanism for the condition.

A. Leauthaud et al., Lensing without borders is a cross-survey collaboration created to assess the consistency of galaxy–galaxy lensing signals (ΔΣ) across different data sets and to carry out end-to-end tests of systematic errors. We perform a blind comparison of the amplitude of ΔΣ using lens samples from BOSS and six independent lensing surveys. We find good agreement between empirically estimated and reported systematic errors which agree to better than 2.3σ in four lens bins and three radial ranges. For lenses with zL > 0.43 and considering statistical errors, we detect a 3–4σ correlation between lensing amplitude and survey depth. This correlation could arise from the increasing impact at higher redshift of unrecognized galaxy blends on shear calibration and imperfections in photometric redshift calibration. At zL > 0.54, amplitudes may additionally correlate with foreground stellar density. The amplitude of these trends is within survey-defined systematic error budgets that are designed to include known shear and redshift calibration uncertainty. Using a fully empirical and conservative method, we do not find evidence for large unknown systematics. Systematic errors greater than 15 per cent (25 per cent) ruled out in three lens bins at 68 per cent (95 per cent) confidence at z < 0.54. Differences with respect to predictions based on clustering are observed to be at the 20–30 per cent level. Our results therefore suggest that lensing systematics alone are unlikely to fully explain the ‘lensing is low’ effect at z < 0.54. This analysis demonstrates the power of cross-survey comparisons and provides a promising path for identifying and reducing systematics in future lensing analyses., We acknowledge use of the lux supercomputer at UC Santa Cruz, funded by NSF MRI grant AST 1828315. This material is based on work supported by the U.D Department of Energy, Office of Science, Office of High Energy Physics under Award Number DE-SC0019301. AL acknowledges support from the David and Lucille Packard foundation, and from the Alfred.P Sloan foundation. CH acknowledges support from the European Research Council under grant number 647112, and support from the Max Planck Society and the Alexander von Humboldt Foundation in the framework of the Max Planck-Humboldt Research Award endowed by the Federal Ministry of Education and Research. KK acknowledges support from the Royal Society and Imperial College. HH is supported by a Heisenberg grant of the Deutsche Forschungsgemeinschaft (Hi 1495/5-1), as well as an ERC Consolidator Grant (no. 770935). AHW is supported by an European Research Council Consolidator Grant (no. 770935). Funding for the DES Projects has been provided by the U.S. Department of Energy; the U.S. National Science Foundation; the Ministry of Science and Education of Spain; the Science and Technology Facilities Council of the United Kingdom; the Higher Education Funding Council for England; the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign; the Kavli Institute of Cosmological Physics at the University of Chicago; the Center for Cosmology and Astro-Particle Physics at the Ohio State University; the Mitchell Institute for Fundamental Physics and Astronomy at Texas A&M University; Financiadora de Estudos e Projetos; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro; Conselho Nacional de Desenvolvimento Científico e Tecnológico and the Ministério da Ciência; Tecnologia e Inovação; the Deutsche Forschungsgemeinschaft; and the Collaborating Institutions in the Dark Energy Survey. The Collaborating Institutions are Argonne National Laboratory; the University of California at Santa Cruz; the University of Cambridge; Centro de Investigaciones Energéticas; Medioambientales y Tecnológicas-Madrid; the University of Chicago; University College London; the DES-Brazil Consortium; the University of Edinburgh; the Eidgenössische Technische Hochschule (ETH) Zürich; Fermi National Accelerator Laboratory; the University of Illinois at Urbana-Champaign; the Institut de Ciències de l’Espai (IEEC/CSIC); the Institut de Física d’Altes Energies; Lawrence Berkeley National Laboratory; the Ludwig-Maximilians Universität München and the associated Excellence Cluster Universe; the University of Michigan; NFS’s NOIRLab; the University of Nottingham; The Ohio State University; the University of Pennsylvania; the University of Portsmouth; SLAC National Accelerator Laboratory; Stanford University; the University of Sussex; Texas A&M University; and the OzDES Membership Consortium. Based in part on observations at Cerro Tololo Inter-American Observatory at NSF’s NOIRLab (NOIRLab Prop. ID 2012B-0001; PI: J. Frieman), which is managed by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. The DES data management system is supported by the National Science Foundation under grant numbers AST-1138766 and AST-1536171. The DES participants from Spanish institutions are partially supported by MICINN under grants ESP2017-89838, PGC2018-094773, PGC2018-102021, SEV-2016-0588, SEV-2016-0597, and MDM-2015-0509, some of which include ERDF funds from the European Union. IFAE is partially funded by the CERCA program of the Generalitat de Catalunya. Research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Program (FP7/2007-2013) including ERC grant agreements 240672, 291329, and 306478. We acknowledge support from the Brazilian Instituto Nacional de Ciência e Tecnologia (INCT) do e-Universo (CNPq grant 465376/2014-2). This manuscript has been authored by Fermi Research Alliance, LLC under Contract No. DE-AC02-07CH11359 with the U.S. Department of Energy, Office of Science, Office of High Energy Physics. The Hyper Suprime-Cam (HSC) collaboration includes the astronomical communities of Japan and Taiwan, and Princeton University. The HSC instrumentation and software were developed by the National Astronomical Observatory of Japan (NAOJ), the Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU), the University of Tokyo, the High Energy Accelerator Research Organisation (KEK), the Academia Sinica Institute for Astronomy and Astrophysics in Taiwan (ASIAA), and Princeton University. Funding was contributed by the FIRST program from the Japanese Cabinet Office, the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), the Japan Society for the Promotion of Science (JSPS), Japan Science and Technology Agency (JST), the Toray Science Foundation, NAOJ, Kavli IPMU, KEK, ASIAA, and Princeton University. This paper makes use of software developed for the Large Synoptic Survey Telescope. We thank the LSST Project for making their code available as free software at http://dm.lsst.org This paper is based [in part] on data collected at the Subaru Telescope and retrieved from the HSC data archive system, which is operated by Subaru Telescope and Astronomy Data Center (ADC) at NAOJ. Data analysis was in part carried out with the cooperation of Center for Computational Astrophysics (CfCA), NAOJ. The Pan-STARRS1 Surveys (PS1) and the PS1 public science archive have been made possible through contributions by the Institute for Astronomy, the University of Hawaii, the Pan-STARRS Project Office, the Max Planck Society and its participating institutes, the Max Planck Institute for Astronomy, Heidelberg, and the Max Planck Institute for Extraterrestrial Physics, Garching, The Johns Hopkins University, Durham University, the University of Edinburgh, the Queen’s University Belfast, the Harvard-Smithsonian Center for Astrophysics, the Las Cumbres Observatory Global Telescope Network Incorporated, the National Central University of Taiwan, the Space Telescope Science Institute, the National Aeronautics and Space Administration under grant No. NNX08AR22G issued through the Planetary Science Division of the NASA Science Mission Directorate, the National Science Foundation grant no. AST-1238877, the University of Maryland, Eotvos Lorand University (ELTE), the Los Alamos National Laboratory, and the Gordon and Betty Moore Foundation. Based on observations made with ESO Telescopes at the La Silla Paranal Observatory under programme IDs 177.A-3016, 177.A-3017, 177.A-3018, and 179.A-2004, and on data products produced by the KiDS consortium. The KiDS production team acknowledges support from: Deutsche Forschungsgemeinschaft, ERC, NOVA, and NWO-M grants; Target; the University of Padova, and the University Federico II (Naples). This work was supported by the Department of Energy, Laboratory Directed Research and Development program at SLAC National Accelerator Laboratory, under contract DE-AC02-76SF00515 and as a part of the Panofsky Fellowship awarded to DG. MM is partially funded by FAPERJ, CNPq, and CONICET. BM acknowledges support from the Brazilian funding agency FAPERJ.

Human enteric adenovirus species F (HAdV-F) is one of the most common pathogens responsible for acute gastroenteritis worldwide. Brazil is a country with continental dimensions where continuous multiregional surveillance is vital to establish a more complete picture of the epidemiology of HAdV-F. The aim of the current study was to investigate the molecular epidemiology of HAdV-F using full-genome data in rural and low-income urban areas in northern Brazil. This will allow a genetic comparison between Brazilian and global HAdV-F strains. The frequency of HAdV-F infections in patients with gastroenteritis and molecular typing of positive samples within this period was also analysed. A total of 251 stool samples collected between 2010 and 2016 from patients with acute gastroenteritis were screened for HAdV-F using next-generation sequencing techniques. HAdV-F infection was detected in 57.8 % (145/251) of samples. A total of 137 positive samples belonged to HAdV-F41 and 7 to HAdV-F40. HAdV-F40/41 dual infection was found in one sample. Detection rates did not vary significantly according to the year. Single HAdV-F infections were detected in 21.9 % (55/251) of samples and mixed infections in 37.4 % (94/251), with RVA/HAdV-F being the most frequent association (21.5 %; 54/251). Genetic analysis indicated that the HAdV-F strains circulating in Brazil were closely related to worldwide strains, and the existence of some temporal order was not observed. This is the first large-scale HAdV-F study in Brazil in which whole-genome data and DNA sequence analyses were used to characterize HAdV-F strains. Expanding the viral genome database could improve overall genotyping success and assist the National Center for Biotechnology Information (NCBI)/GenBank in standardizing the HAdV genome records by providing a large set of annotated HAdV-F genomes.

A 63-year-old woman was referred to neurology with bilateral severe progressive pain and stiffness in her thighs. The patient had a 3-year history of injecting intramuscular cyclizine into the anterior thigh to treat nausea associated with a longstanding pan-enteric dysmotility syndrome. MRI of the thighs demonstrated fibrotic appearances. A biopsy of the left vastus lateralis and surrounding fascia identified pathology consistent with a fibrous myopathy. The patient was advised to stop intramuscular injections of cyclizine and undergo physiotherapy but she still remained in considerable pain. Although fibrous myopathy occurring as a consequence of recurrent intramuscular drug injections, particularly heroin, has been previously described, this is the first report of fibrous myopathy associated with the use of intramuscular cyclizine. We highlight this rare association and suggest that the long-term use of intramuscular cyclizine be avoided.

Diarrhea remains one of the most common causes of deaths in children. Although many studies have investigated the prevalence of enteric pathogens around the globe some diarrheal episodes remain unexplained. It is possible that some yet-unidentified viral agents could be related to these cases of gastroenteritis. By using viral metagenomics techniques, we screened 251 fecal samples of children between 0.5 to 2.5-year-old with acute diarrhea not associated with common pathogens. These children live in rural areas and have different levels of contact with animals such as pigs, cows and bats. Here we report a complete genome of one mammalian orthoreovirus (MRV) type 3, denoted TO-151/BR, detected in a female child in the state of Tocantins (north of Brazil). Brazilian TO-151/BR strain was classified as MRV-3 based on S1 phylogeny and was closely related to porcine Asian strains. Phylogenetic analyses showed that other segments were more similar to MRV-3s of different geographic locations and hosts, including human and bats, highlighting genome reassortment and lack of host-specific barriers. This is the first report of MRV-3 in South America and a hypothesis of a silent long-term circulation of this virus in Brazil has been raised.

Whilst stroke-associated pneumonia (SAP) is common and associated with poor outcomes, less is known about the determinants of these adverse clinical outcomes in SAP. To identify the factors that influence mortality and morbidity in SAP. Data for patients with SAP (n = 854) were extracted from a regional Hospital Stroke Register in Norfolk, UK (2003–2015). SAP was defined as pneumonia occurring within 7 days of admission by the treating clinicians. Mutlivariable regression models were constructed to assess factors influencing survival and the level of disability at discharge using modified Rankin Scale [mRS]. Mean (SD) age was 83.0 (8.7) years and ischaemic stroke occurred in 727 (85.0%). Mortality was 19.0% at 30 days and 44.0% at 6 months. Stroke severity assessment using National Institutes of Health Stroke Scale was not recorded in the data set although Oxfordshire Community Stroke Project was Classification. In the multivariable analyses, 30-day mortality was independently associated with age (OR 1.04, 95% CI 1.01–1.07, p = 0.01), haemorrhagic stroke (2.27, 1.07–4.78, p = 0.03) and pre-stroke disability (mRS 4–5 v 0–1: 6.45, 3.12–13.35, p p p p = 0.017) and previous transient ischemic attack (1.94, 1.12–3.36, p = 0.019). Disability defined by mRS at discharge was independently associated with age (1.10, 1.05–1.16, p p = 0.012). We have identified non-modifiable determinants of poor prognosis in patients with SAP. Further studies are required to identify modifiable factors which may guide areas for intervention to improve the prognosis in SAP in these patients.

Human Adenovirus species C (HAdV-C) is the most common etiologic agent of respiratory disease. In the present study, we characterized the nearly full-length genome of one potential new HAdV-C recombinant strain constituted by Penton and Fiber proteins belonging to type 89 and a chimeric Hexon protein of types 1 and 89. By using viral metagenomics techniques, we screened out, in the states of Tocantins and Par&aacute, Northern and North regions of Brazil, from 2010 to 2016, 251 fecal samples of children between 0.5 to 2.5 years old. These children were presenting acute diarrhea not associated with common pathogens (i.e., rotavirus, norovirus). We identified two HAdV-C strains in two distinct patients. Phylogenetic analysis performed using all complete genomes available at GenBank database indicated that one strain (HAdV-C BR-245) belonged to type 1. The phylogenetic analysis also indicated that the second strain (HAdV-C BR-211) was located at the base of the clade formed by the newly HAdV-C strains type 89. Recombination analysis revealed that strain HAdV-C BR-211 is a chimera in which the variable regions of Hexon gene combined HAdV-C1 and HAdV-C89 sequences. Therefore, HAdV-C BR-211 strain possesses a genomic backbone of type HAdV-C89 and a unique insertion of HAdV-C1 in the Hexon sequence. Recombination may play an important driving force in HAdV-C diversity and evolution. Studies employing complete genomic sequencing on circulating HAdV-C strains in Brazil are needed to understand the clinical significance of the presented data.

We present a measurement of the quasar luminosity function in the range 0.682.15. Using pure luminosity evolution models, we fitted our LF measurements, and predicted quasar number counts as a function of redshift and observed magnitude. These predictions are useful inputs for future cosmology surveys such as those relying on the observation of quasars to measure baryon acoustic oscillations., Comment: 15 pages, 14 figs, accepted for publication in A&A

This report is based on the BigBOSS proposal submission to NOAO in October 2010, and reflects the project status at that time with minor updates; BigBOSS is a Stage IV ground-based dark energy experiment to study baryon acoustic oscillations (BAO) and the growth of structure with a wide-area galaxy and quasar redshift survey over 14,000 square degrees. It has been conditionally accepted by NOAO in response to a call for major new instrumentation and a high-impact science program for the 4-m Mayall telescope at Kitt Peak. The BigBOSS instrument is a robotically-actuated, fiber-fed spectrograph capable of taking 5000 simultaneous spectra over a wavelength range from 340 nm to 1060 nm, with a resolution R = 3000-4800. Using data from imaging surveys that are already underway, spectroscopic targets are selected that trace the underlying dark matter distribution. In particular, targets include luminous red galaxies (LRGs) up to z = 1.0, extending the BOSS LRG survey in both redshift and survey area. To probe the universe out to even higher redshift, BigBOSS will target bright [OII] emission line galaxies (ELGs) up to z = 1.7. In total, 20 million galaxy redshifts are obtained to measure the BAO feature, trace the matter power spectrum at smaller scales, and detect redshift space distortions. BigBOSS will provide additional constraints on early dark energy and on the curvature of the universe by measuring the Ly-alpha forest in the spectra of over 600,000 2.2 < z < 3.5 quasars. BigBOSS galaxy BAO measurements combined with an analysis of the broadband power, including the Ly-alpha forest in BigBOSS quasar spectra, achieves a FOM of 395 with Planck plus Stage III priors. This FOM is based on conservative assumptions for the analysis of broad band power (kmax = 0.15), and could grow to over 600 if current work allows us to push the analysis to higher wave numbers (kmax = 0.3). BigBOSS will also place constraints on theories of modified gravity and inflation, and will measure the sum of neutrino masses to 0.024 eV accuracy.

The aim of this paper is to present a large international field experiment that took place in March-April 2008 on the French Aquitanian coast. During this field experiment, both very small and large spatial and temporal scales have been explored concerning hydrodynamic, sedimentary and morphodynamic processes in the surf and swash zones using innovative methods. This field experiment, one of the largest to take place in Europe (with the COAST 3D project), will provide a unique data set to explore surf zone and swash processes and improve numerical models in presence of very energetic events (5 storms with Hs > 5m) on macrotidal multi-barred sandy beaches. Mots-cles : Experimental – plage sableuse – meso, macrotidal -processus hydrodynamiques – processus sedimentaires – morphodynamique – zones de surf et jet de rive 636 Instrumentation, mesures, imagerie et teledetection

Patients with duodenal ulcer were given intravenous injections of 0.1, 0.2, and 0.4 U per kg of insulin on different days. In each of 8 patients the peak acid output was higher after 0.2 U per kg than after 0.1 U per kg and the difference was significant. In 19 patients the peak acid output after 0.2 U per kg was significantly higher than after 0.4 U per kg. The mean lowest blood glucose concentration was significantly lower after the larger dose of insulin. These results support the concept that insulin-stimulated acid secretion is not an all or none phenomenon but is dose-related and also hypoglycemia-related. An optimum dose of insulin is proposed for gastric function tests and defined as "That dose which in most subjects lowers the blood glucose concentration sufficiently to allow near-maximum vagal stimulation to occur without producing so low a blood glucose concentration that acid secretion is depressed. The desirable range of blood glucose concentration is probably about 15 to 25 mg per 100 ml."

Without a medical miracle, it seems inevitable that the Acquired Immune Deficiency Syndrome (AIDS) pandemic will become not only the most serious public health problem of this generation but a dominating issue in 3rd world development. As a present-day killer, AIDS in developing countries is insignificant compared to malaria, tuberculosis, or infant diarrhea, but this number is misleading in 3 ways. First, it fails to reflect the per capita rate of AIDS cases. On this basis, Bermuda, French Guyana, and the Bahamas have much higher rates than the US. Second, there is extensive underreporting of AIDS cases in most developing nations. Finally, the number of AIDS cases indicates where the epidemic was 5-7 years ago, when these people became infected. Any such projections of the growth of 3rd world AIDS epidemics are at this time based on epidemiologic data from the industrialized rations of the north and on the assumption that the virus acts similarly in the south as it does in the US and Europe. Yet, 3rd world conditions differ. Sexually transmitted diseases usually are more prevalent, and people have a different burden of other diseases and of other stresses to the immune system. In Africa, AIDS already is heavily affecting the mainstream population in some nations. Some regions will approach net population declines over the next decade. How far their populations eventually could decline because of AIDS is unclear and will depend crucially on countermeasures taken or not taken over the next 1-2 years. In purely economic terms, AIDS will affect the direct costs of health care, expenses which are unrealistic for most 3rd world countries. Further, the vast majority of deaths from AIDS in developing countries will occur among those in the sexually active age groups -- the wage earners and food producers. Deaths in this age group also will reduce the labor available for farming and industry. AIDS epidemics also may have significant effects on foreign investment in the 3rd world as well as negative effects on tourism. The global underclass will be disproportionately affected by AIDS as the blacks and Hispanics already are in New York and Miami. Thus far, the reaction of donor countries to the World Health Organization's (WHO) appeal for funds to fight the battle against AIDS has been excellent. The global strategy of WHO places priority on national campaigns, but none of the national campaigns will be effective unless linked to similar actions in other nations to form a vigorous international program. The US has a special responsibility to provide international leadership on AIDS. The US is the world leader in AIDS research and has the bulk of the virus research capacity. Further, no country can come close to matching US experience in dealing with AIDS through "safe sex" education campaigns.

Paroxysmal hypertension after cardiac surgery is a phenomenon of physiological and clinical significance. The possible preoperative and intraoperative factors that may predict its occurrence were studied in 81 consecutive patients undergoing coronary artery surgery (n = 58) or valve replacement (n = 27), of whom 45 (56%) developed postoperative hypertension. Hypertension occurred significantly more often in those patients who received beta adrenergic blocking agents preoperatively and who underwent coronary artery surgery. Patients with hypertension had significantly higher mean left ventricular ejection fractions preoperatively (52%) than those without (41%) and required phentolamine significantly more often and isoprenaline significantly less often intraoperatively. It is suggested that the significance of preoperative beta adrenergic blockade, the type of operation, and the intraoperative requirement for phentolamine in patients who developed post-operative hypertension may indicate the role of enhanced sympathetic activity and disturbance of cardiac receptors during surgery. Preoperative myocardial performance and the method of myocardial protection during surgery are likely to influence the occurrence of the hypertensive phenomenon.

Investigations were carried out in man and dog to study the validity of Cannon's law of denervation supersensitivity in relation to parasympathetic denervation of the stomach. Subthreshold doses of carbachol did not accelerate gastric emptying before vagotomy but caused a significant increase in the rate of gastric emptying after vagotomy. These findings may be relevant to aberrations of gastrointestinal motility after vagotomy and may provide the basis of a test for completeness of gastric vagotomy.