Clinical spectrum, prognosis and estimated prevalence of DNAJB11-kidney disease

Monoallelic mutations of DNAJB11 were recently described in seven pedigrees with atypical clinical presentations of autosomal dominant polycystic kidney disease. DNAJB11 encodes one of the main cofactors of the endoplasmic reticulum chaperon BiP, a heat-shock protein required for efficient protein folding and trafficking. Here we conducted an international collaborative study to better characterize the DNAJB11-associated phenotype. Thirteen different loss-of-function variants were identified in 20 new pedigrees (54 affected individuals) by targeted next-generation sequencing, whole-exome sequencing or whole-genome sequencing. Amongst the 77 patients (27 pedigrees) now in total reported, 32 reached end stage kidney disease (range, 55-89 years, median age 75); without a significant difference between males and females. While a majority of patients presented with non-enlarged polycystic kidneys, renal cysts were inconsistently identified in patients under age 45. Vascular phenotypes, including intracranial aneurysms, dilatation of the thoracic aorta and dissection of a carotid artery were present in four pedigrees. We accessed Genomics England 100,000 genomes project data, and identified pathogenic variants of DNAJB11 in nine of 3934 probands with various kidney and urinary tract disorders. The clinical diagnosis was cystic kidney disease for eight probands and nephrocalcinosis for one proband. No additional pathogenic variants likely explaining the kidney disease were identified. Using the publicly available GnomAD database, DNAJB11 genetic prevalence was calculated at 0.85/10.000 individuals. Thus, establishing a precise diagnosis in atypical cystic or interstitial kidney disease is crucial, with important implications in terms of follow-up, genetic counseling, prognostic evaluation, therapeutic management, and for selection of living kidney donors

Time calibration of the ANTARES neutrino telescope

The ANTARES deep-sea neutrino telescope comprises a three-dimensional array of photomultipliers to detect the Cherenkov light induced by upgoing relativistic charged particles originating from neutrino interactions in the vicinity of the detector. The large scattering length of light in the deep sea facilitates an angular resolution of a few tenths of a degree for neutrino energies exceeding 10 TeV. In order to achieve this optimal performance, the time calibration procedures should ensure a relative time calibration between the photomultipliers at the level of similar to 1 ns. The methods developed to attain this level of precision are described

The positioning system of the ANTARES Neutrino Telescope

The ANTARES neutrino telescope, located 40km off the coast of Toulon in the Mediterranean Sea at a mooring depth of about 2475m, consists of twelve detection lines equipped typically with 25 storeys. Every storey carries three optical modules that detect Cherenkov light induced by charged secondary particles (typically muons) coming from neutrino interactions. As these lines are flexible structures fixed to the sea bed and held taut by a buoy, sea currents cause the lines to move and the storeys to rotate. The knowledge of the position of the optical modules with a precision better than 10cm is essential for a good reconstruction of particle tracks. In this paper the ANTARES positioning system is described. It consists of an acoustic positioning system, for distance triangulation, and a compass-tiltmeter system, for the measurement of the orientation and inclination of the storeys. Necessary corrections are discussed and the results of the detector alignment procedure are described

Performance of the front-end electronics of the ANTARES neutrino telescope

ANTARES is a high-energy neutrino telescope installed in the Mediterranean Sea at a depth of 2475 m. It consists of a three-dimensional array of optical modules, each containing a large photomultiplier tube. A total of 2700 front-end ASICs named Analogue Ring Samplers (ARS) process the phototube signals, measure their arrival time, amplitude and shape as well as perform monitoring and calibration tasks. The ARS chip processes the analogue signals from the optical modules and converts information into digital data. All the information is transmitted to shore through further multiplexing electronics and an optical link. This paper describes the performance of the ARS chip; results from the functionality and characterization tests in the laboratory are summarized and the long-term performance in the apparatus is illustrated.Comment: 20 pages, 22 figures, published in Nuclear Instruments and Methods

Investigations of the Mars Upper Atmosphere with ExoMars Trace Gas Orbiter

The Martian mesosphere and thermosphere, the region above about 60 km, is not the primary target of the ExoMars 2016 mission but its Trace Gas Orbiter (TGO) can explore it and address many interesting issues, either in-situ during the aerobraking period or remotely during the regular mission. In the aerobraking phase TGO peeks into thermospheric densities and temperatures, in a broad range of latitudes and during a long continuous period. TGO carries two instruments designed for the detection of trace species, NOMAD and ACS, which will use the solar occultation technique. Their regular sounding at the terminator up to very high altitudes in many different molecular bands will represent the first time that an extensive and precise dataset of densities and hopefully temperatures are obtained at those altitudes and local times on Mars. But there are additional capabilities in TGO for studying the upper atmosphere of Mars, and we review them briefly. Our simulations suggest that airglow emissions from the UV to the IR might be observed outside the terminator. If eventually confirmed from orbit, they would supply new information about atmospheric dynamics and variability. However, their optimal exploitation requires a special spacecraft pointing, currently not considered in the regular operations but feasible in our opinion. We discuss the synergy between the TGO instruments, specially the wide spectral range achieved by combining them. We also encourage coordinated operations with other Mars-observing missions capable of supplying simultaneous measurements of its upper atmosphere

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Search for chargino-neutralino production in ppbar collisions at sqrt(s) = 1.96 TeV

We present the results of a search for associated production of the chargino and neutralino supersymmetric particles using up to 1.1 fb-1 of integrated luminosity collected by the CDF II experiment at the Tevatron ppbar collider at a center-of-mass energy of 1.96 TeV. The search is conducted by analyzing events with a large transverse momentum imbalance and either three charged leptons or two charged leptons of the same electric charge. The numbers of observed events are found to be consistent with standard model expectations. Upper limits on the production cross section are derived in different theoretical models. In one of these models a lower limit on the mass of the chargino is set at 129 GeV/c^2 at the 95% confidence level.Comment: To be submitted to Phys.Rev.Let

Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features

The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom’s 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia