Showing papers by "Pierre-and-Marie-Curie University published in 2020"
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F. Kyle Satterstrom1, F. Kyle Satterstrom2, Jack A. Kosmicki, Jiebiao Wang3 +198 more•Institutions (53)
TL;DR: The largest exome sequencing study of autism spectrum disorder (ASD) to date, using an enhanced analytical framework to integrate de novo and case-control rare variation, identifies 102 risk genes at a false discovery rate of 0.1 or less, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.
1,169 citations
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Romina Ahumada1, Carlos Allende Prieto2, Carlos Allende Prieto3, Andres Almeida4 +342 more•Institutions (94)
TL;DR: The most recent data release from the Sloan Digital Sky Surveys (SDSS-IV) is DR16 as mentioned in this paper, which is the fourth and penultimate from the fourth phase of the survey.
Abstract: This paper documents the sixteenth data release (DR16) from the Sloan Digital Sky Surveys; the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the southern hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey (TDSS) and new data from the SPectroscopic IDentification of ERosita Survey (SPIDERS) programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).
803 citations
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TL;DR: The current status of the Standard Model calculation of the anomalous magnetic moment of the muon is reviewed in this paper, where the authors present a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice approach.
801 citations
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TL;DR: The current status of the Standard Model calculation of the anomalous magnetic moment of the muon has been reviewed in this paper, where the authors present a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice-QCD approach.
Abstract: We review the present status of the Standard Model calculation of the anomalous magnetic moment of the muon. This is performed in a perturbative expansion in the fine-structure constant $\alpha$ and is broken down into pure QED, electroweak, and hadronic contributions. The pure QED contribution is by far the largest and has been evaluated up to and including $\mathcal{O}(\alpha^5)$ with negligible numerical uncertainty. The electroweak contribution is suppressed by $(m_\mu/M_W)^2$ and only shows up at the level of the seventh significant digit. It has been evaluated up to two loops and is known to better than one percent. Hadronic contributions are the most difficult to calculate and are responsible for almost all of the theoretical uncertainty. The leading hadronic contribution appears at $\mathcal{O}(\alpha^2)$ and is due to hadronic vacuum polarization, whereas at $\mathcal{O}(\alpha^3)$ the hadronic light-by-light scattering contribution appears. Given the low characteristic scale of this observable, these contributions have to be calculated with nonperturbative methods, in particular, dispersion relations and the lattice approach to QCD. The largest part of this review is dedicated to a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice-QCD approach. The final result reads $a_\mu^\text{SM}=116\,591\,810(43)\times 10^{-11}$ and is smaller than the Brookhaven measurement by 3.7$\sigma$. The experimental uncertainty will soon be reduced by up to a factor four by the new experiment currently running at Fermilab, and also by the future J-PARC experiment. This and the prospects to further reduce the theoretical uncertainty in the near future-which are also discussed here-make this quantity one of the most promising places to look for evidence of new physics.
420 citations
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TL;DR: In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone.
Abstract: Background In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown. Methods In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of Results A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials. Conclusions In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN ClinicalTrials.gov number, NCT01639339.).
395 citations
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University of Colorado Denver1, Boston University2, Paris Diderot University3, University of Texas System4, University of Zurich5, McMaster University6, University of Texas Health Science Center at San Antonio7, Pierre-and-Marie-Curie University8, University Health Network9, Bellvitge University Hospital10, Duke University11, Radboud University Nijmegen12, University of Freiburg13, Oregon Health & Science University14
TL;DR: This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, MycOBacterium kansasii, and Myc Cobacterium xenopi among the slowly growing NTM and MyCobacterius abscessus among the rapidly growing N TM.
Abstract: Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
329 citations
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University of Colorado Denver1, Boston University2, Paris Diderot University3, University of Texas System4, University of Zurich5, McMaster University6, University of Texas Health Science Center at San Antonio7, Pierre-and-Marie-Curie University8, University Health Network9, Bellvitge University Hospital10, Duke University11, Radboud University Nijmegen12, University of Freiburg13, Oregon Health & Science University14
TL;DR: This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, MycOBacterium kansasii, and Myc Cobacterium xenopi among the slowly growing NTM and MyCobacteria abscessus among the rapidly growing N TM.
Abstract: Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
297 citations
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TL;DR: A 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI is found in patients with cancer.
Abstract: Importance Limited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after an immune-related adverse event (irAE). Objective To identify the recurrence rate of the same irAE that prompted discontinuation of ICI therapy after an ICI rechallenge in patients with cancer and to identify the clinical features associated with such recurrences. Design, Setting, and Participants This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase, which contains case reports from more than 130 countries. Case reports were extracted from database inception (1967) to September 1, 2019. All consecutive ICI cases with at least 1 associated irAE were included. Main Outcomes and Measures The primary outcome was the rate of recurrence of the initial irAE after an ICI rechallenge. Secondary outcomes included the factors associated with the recurrence after a rechallenge among informative rechallenges, the recurrence rate according to the ICI regimen (anti–programmed cell death 1 or anti–programmed cell death ligand 1 monotherapy, anti–cytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy), and the rate of occurrence of a different irAE after a rechallenge. Results A total of 24 079 irAE cases associated with at least 1 ICI were identified. Among the irAEs, 452 of 6123 irAEs associated with ICI rechallenges (7.4%) were informative rechallenges. One hundred thirty recurrences (28.8%; 95% CI, 24.8-33.1) of the initial irAE were observed. In a rechallenge, colitis (reporting odds ratio [OR], 1.77; 95% CI, 1.14-2.75;P = .01), hepatitis (reporting OR, 3.38; 95% CI, 1.31-8.74;P = .01), and pneumonitis (reporting OR, 2.26; 95% CI, 1.18-4.32;P = .01) were associated with a higher recurrence rate, whereas adrenal events were associated with a lower recurrence rate (reporting OR, 0.33; 95% CI, 0.13-0.86;P = .03) compared with other irAEs. Conclusions and Relevance This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI. Resuming ICI therapy could be considered for select patients, with appropriate monitoring and use of standard treatment algorithms to identify and treat toxic effects.
255 citations
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Juliette Alimena1, James Baker Beacham2, Martino Borsato3, Yangyang Cheng4 +213 more•Institutions (105)
TL;DR: In this paper, the authors present a survey of the current state of LLP searches at the Large Hadron Collider (LHC) and chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC.
Abstract: Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton–proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments—as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER—to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
218 citations
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University of Colorado Denver1, Boston University2, Paris Diderot University3, University of Texas System4, University of Zurich5, McMaster University6, University of Texas Health Science Center at San Antonio7, Pierre-and-Marie-Curie University8, University Health Network9, Bellvitge University Hospital10, Duke University11, Radboud University Nijmegen12, University of Freiburg13, Oregon Health & Science University14
TL;DR: This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, MycOBacterium kansasii, and Myc Cobacterium xenopi among the slowly growing NTM and MyCobacterius abscessus among the rapidly growing N TM.
Abstract: Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
217 citations
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TL;DR: A subset of membranous nephropathy that is associated with accumulation and co-localization of NELL-1 and IgG along the glomerular basement membrane, and with anti-NELL- 1 antibodies in the serum, is defined.
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University of São Paulo1, Spanish National Research Council2, Fermilab3, Stanford University4, Autonomous University of Madrid5, University of Portsmouth6, University of Wisconsin-Madison7, University of Sussex8, University of Pennsylvania9, Institut d'Astrophysique de Paris10, Pierre-and-Marie-Curie University11, Argonne National Laboratory12, Ludwig Maximilian University of Munich13, University College London14, University of Illinois at Urbana–Champaign15, University of Chicago16, University of Michigan17, Ohio State University18, University of Queensland19, Indian Institute of Technology, Hyderabad20, Carnegie Mellon University21, University of Arizona22, California Institute of Technology23, University of California, Santa Cruz24, University of Oslo25, University of Cambridge26, ETH Zurich27, Max Planck Society28, Harvard University29, Lowell Observatory30, Macquarie University31, Carnegie Institution for Science32, Princeton University33, Australian National University34, Texas A&M University35, University of Trieste36, Duke University37, Brookhaven National Laboratory38, Austin Peay State University39, University of Southampton40, Oak Ridge National Laboratory41, Stony Brook University42, University of Edinburgh43
TL;DR: In this paper, a joint analysis of the counts and weak lensing signal of redMaPPer clusters selected from the DES Year 1 dataset was performed using the same shear and source photometric redshifts estimates as were used in the DES combined probes analysis.
Abstract: We perform a joint analysis of the counts and weak lensing signal of redMaPPer clusters selected from the Dark Energy Survey (DES) Year 1 dataset. Our analysis uses the same shear and source photometric redshifts estimates as were used in the DES combined probes analysis. Our analysis results in surprisingly low values for S-8 = sigma(8)(Omega(m)/0.3)(0.5) = 0.65 0.04, driven by a low matter density parameter, Omega(m) = 0.179(-0.038)(+0.031), with sigma(8) - Omega(m) posteriors in 2.4 sigma tension with the DES Y1 3x2pt results, and in 5.6 sigma with the Planck CMB analysis. These results include the impact of post-unblinding changes to the analysis, which did not improve the level of consistency with other data sets compared to the results obtained at the unblinding. The fact that multiple cosmological probes (supernovae, baryon acoustic oscillations, cosmic shear, galaxy clustering and CMB anisotropies), and other galaxy cluster analyses all favor significantly higher matter densities suggests the presence of systematic errors in the data or an incomplete modeling of the relevant physics. Cross checks with x-ray and microwave data, as well as independent constraints on the observable -mass relation from Sunyaev-Zeldovich selected clusters, suggest that the discrepancy resides in our modeling of the weak lensing signal rather than the cluster abundance. Repeating our analysis using a higher richness threshold (lambda >= 30) significantly reduces the tension with other probes, and points to one or more richness -dependent effects not captured by our model.
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TL;DR: It is shown that leukocytes cannot only migrate under low adhesion but can also transmit forces in the complete absence of transmembrane force coupling.
Abstract: Eukaryotic cells migrate by coupling the intracellular force of the actin cytoskeleton to the environment. While force coupling is usually mediated by transmembrane adhesion receptors, especially those of the integrin family, amoeboid cells such as leukocytes can migrate extremely fast despite very low adhesive forces1. Here we show that leukocytes cannot only migrate under low adhesion but can also transmit forces in the complete absence of transmembrane force coupling. When confined within three-dimensional environments, they use the topographical features of the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton follows the texture of the substrate, creating retrograde shear forces that are sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent migration are not mutually exclusive, but rather are variants of the same principle of coupling retrograde actin flow to the environment and thus can potentially operate interchangeably and simultaneously. As adhesion-free migration is independent of the chemical composition of the environment, it renders cells completely autonomous in their locomotive behaviour.
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TL;DR: In this article, the authors demonstrate the feasibility of incorporating optical fibre Bragg grating sensors into commercial 18650 cells to monitor the dynamic chemical and thermal state of a cell during operation.
Abstract: Monitoring the dynamic chemical and thermal state of a cell during operation is crucial to making meaningful advancements in battery technology as safety and reliability cannot be compromised. Here we demonstrate the feasibility of incorporating optical fibre Bragg grating sensors into commercial 18650 cells. By adjusting fibre morphologies, wavelength changes associated with both temperature and pressure are decoupled with high accuracy, which allows tracking of chemical events such as solid electrolyte interphase formation and structural evolution. We also demonstrate how multiple sensors are used to determine the heat generated by the cell without resorting to microcalorimetry. Unlike with conventional isothermal calorimetry, the cell’s heat capacity contribution is readily assessed, allowing for full parametrization of the thermal model. Collectively, these findings offer a scalable solution for screening electrolyte additives, rapidly identifying the best formation processes of commercial cells and designing battery thermal management systems with enhanced safety. Tracking a battery’s chemical and thermal states during operation offers important information on its reliability and lifetime. Here the authors develop optical fibre sensors and decouple temperature and pressure variations in the measurements inside of batteries, allowing chemical and thermal events to be monitored with high accuracy.
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Serbian Academy of Sciences and Arts1, University of Belgrade2, Wrocław Medical University3, University of Cyprus4, National and Kapodistrian University of Athens5, Medical University of Vienna6, British Heart Foundation7, Pierre-and-Marie-Curie University8, Marmara University9, Karolinska University Hospital10, University of Perugia11, University of Brescia12, Hannover Medical School13, University Medical Center Groningen14, University of Hasselt15, The Volgograd State Medical University16, Queen's University Belfast17, National Institutes of Health18, Charité19, Vita-Salute San Raffaele University20
TL;DR: Type 2 diabetes mellitus is common in patients with heart failure (HF) and associated with considerable morbidity and mortality and there is evidence of several new glucose‐lowering medications showing either neutral or beneficial cardiovascular effects.
Abstract: Type 2 diabetes mellitus (T2DM) is common in patients with heart failure (HF) and associated with considerable morbidity and mortality. Significant advances have recently occurred in the treatment of T2DM, with evidence of several new glucose-lowering medications showing either neutral or beneficial cardiovascular effects. However, some of these agents have safety characteristics with strong practical implications in HF [i.e. dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose co-transporter type 2 (SGLT-2) inhibitors]. Regarding safety of DPP-4 inhibitors, saxagliptin is not recommended in HF because of a greater risk of HF hospitalisation. There is no compelling evidence of excess HF risk with the other DPP-4 inhibitors. GLP-1 RAs have an overall neutral effect on HF outcomes. However, a signal of harm suggested in two small trials of liraglutide in patients with reduced ejection fraction indicates that their role remains to be defined in established HF. SGLT-2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) have shown a consistent reduction in the risk of HF hospitalisation regardless of baseline cardiovascular risk or history of HF. Accordingly, SGLT-2 inhibitors could be recommended to prevent HF hospitalisation in patients with T2DM and established cardiovascular disease or with multiple risk factors. The recently completed trial with dapagliflozin has shown a significant reduction in cardiovascular mortality and HF events in patients with HF and reduced ejection fraction, with or without T2DM. Several ongoing trials will assess whether the results observed with dapagliflozin could be extended to other SGLT-2 inhibitors in the treatment of HF, with either preserved or reduced ejection fraction, regardless of the presence of T2DM. This position paper aims to summarise relevant clinical trial evidence concerning the role and safety of new glucose-lowering therapies in patients with HF.
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Stanford University1, University of Wisconsin-Madison2, Rutgers University3, University of Pittsburgh4, Max Planck Society5, Fermilab6, University of Chicago7, Carnegie Mellon University8, Texas A&M University9, Carnegie Institution for Science10, University of São Paulo11, Autonomous University of Madrid12, University of Pennsylvania13, Pierre-and-Marie-Curie University14, University of Paris15, University College London16, National Center for Supercomputing Applications17, Indian Institute of Technology, Hyderabad18, University of Michigan19, Spanish National Research Council20, ETH Zurich21, University of Queensland22, Ohio State University23, University of Arizona24, Macquarie University25, Lowell Observatory26, University of Illinois at Urbana–Champaign27, Princeton University28, University of Sussex29, Universidade Federal do Rio Grande do Sul30, University of Southampton31, Brandeis University32, Oak Ridge National Laboratory33, University of Portsmouth34, Ludwig Maximilian University of Munich35
TL;DR: In this article, a model of the galaxy-halo connection was combined with newly derived observational selection functions based on searches for satellites in photometric surveys over nearly the entire high Galactic latitude sky.
Abstract: The population of Milky Way (MW) satellites contains the faintest known galaxies and thus provides essential insight into galaxy formation and dark matter microphysics. Here we combine a model of the galaxy-halo connection with newly derived observational selection functions based on searches for satellites in photometric surveys over nearly the entire high Galactic latitude sky. In particular, we use cosmological zoom-in simulations of MW-like halos that include realistic Large Magellanic Cloud (LMC) analogs to fit the position-dependent MW satellite luminosity function. We report decisive evidence for the statistical impact of the LMC on the MW satellite population due to an estimated 6 2 observed LMC-associated satellites, consistent with the number of LMC satellites inferred from Gaia proper-motion measurements, confirming the predictions of cold dark matter models for the existence of satellites within satellite halos. Moreover, we infer that the LMC fell into the MW within the last 2 Gyr at high confidence. Based on our detailed full-sky modeling, we find that the faintest observed satellites inhabit halos with peak virial masses below at 95% confidence, and we place the first robust constraints on the fraction of halos that host galaxies in this regime. We predict that the faintest detectable satellites occupy halos with peak virial masses above, highlighting the potential for powerful galaxy formation and dark matter constraints from future dwarf galaxy searches.
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20 Apr 2020TL;DR: The authors' cross sectional study in both COVID-19 out- and inpatients strongly suggests that daily smokers have a very much lower probability of developing symptomatic or severe SARS-CoV-2 infection as compared to the general population.
Abstract: Importance: As the pandemic of COVID-19 is still under progression, identification of prognostic factors remains a global challenge. The role of cigarette smoking has been suggested among the disease’s epidemiological risk factors, although it is highly controversial. Objective: To evaluate the correlation of daily smoking with the susceptibility to develop SARS-CoV-2 infection. Participants: We estimated the rates of daily current smokers in COVID-19-infected patients in a large French university hospital between February 28th , 2020 and March 30th , 2020 for outpatients and from March 23rd , till April 9th , 2020 for inpatients. Design: The rates from both groups were compared to those of daily current smokers in the 2018 French general population, established in 2018, after standardization of the data for sex and age. Results: The inpatient group was composed of 343 patients, median age 65 yr: 206 men (601%, median age 66 years) and 137 women (39.9%, median age 65 years) with a rate of daily smokers of 4.4% (5.4% of men and 2.9% of women).The outpatient group was composed of 139 patients, median age 44 years: 62 men (44.6 %, median age 43 years, and 77 women (55.4 %, median age 44 years). The daily smokers rate was 5.3% (5.1% of men and 5.5 % of women). In the French population, the daily smokers rate was 25.4% (28.2% of men and 22.9% of women). The rate of current daily smokers was significantly lower in COVID-19 outpatients and inpatients (80.3% and 75.4%, respectively), as compared to that in the French general population with standardized incidence ratios according to sex and age of 0.197 [0.094 - 0.41] and 0.246 [0.148 - 0.408]. These ratios did not significantly differ between the two groups (P=0.63). Conclusions and relevance: Our cross sectional study in both COVID-19 out- and inpatients strongly suggests that daily smokers have a very much lower probability of developing symptomatic or severe SARS-CoV-2 infection as compared to the general population.
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Kyung Hee University1, Max Planck Society2, Spanish National Research Council3, Instituto Nacional de Técnica Aeroespacial4, Centre national de la recherche scientifique5, Technical University of Madrid6, University of Valencia7, Kiepenheuer Institut für Sonnenphysik8, University of Barcelona9, Braunschweig University of Technology10, University of Göttingen11, Pierre-and-Marie-Curie University12, European Space Research and Technology Centre13
TL;DR: The Polarimetric and Helioseismic Imager on the Solar Orbiter mission (SO/PHI) as discussed by the authors is the first magnetograph and helio-physics instrument to observe the Sun from outside the Sun-Earth line.
Abstract: Aims. This paper describes the Polarimetric and Helioseismic Imager on the Solar Orbiter mission (SO/PHI), the first magnetograph and helioseismology instrument to observe the Sun from outside the Sun-Earth line. It is the key instrument meant to address the top-level science question: How does the solar dynamo work and drive connections between the Sun and the heliosphere? SO/PHI will also play an important role in answering the other top-level science questions of Solar Orbiter, while hosting the potential of a rich return in further science.Methods. SO/PHI measures the Zeeman effect and the Doppler shift in the Fe I 617.3 nm spectral line. To this end, the instrument carries out narrow-band imaging spectro-polarimetry using a tunable LiNbO3 Fabry-Perot etalon, while the polarisation modulation is done with liquid crystal variable retarders. The line and the nearby continuum are sampled at six wavelength points and the data are recorded by a 2k × 2k CMOS detector. To save valuable telemetry, the raw data are reduced on board, including being inverted under the assumption of a Milne-Eddington atmosphere, although simpler reduction methods are also available on board. SO/PHI is composed of two telescopes; one, the Full Disc Telescope, covers the full solar disc at all phases of the orbit, while the other, the High Resolution Telescope, can resolve structures as small as 200 km on the Sun at closest perihelion. The high heat load generated through proximity to the Sun is greatly reduced by the multilayer-coated entrance windows to the two telescopes that allow less than 4% of the total sunlight to enter the instrument, most of it in a narrow wavelength band around the chosen spectral line.Results. SO/PHI was designed and built by a consortium having partners in Germany, Spain, and France. The flight model was delivered to Airbus Defence and Space, Stevenage, and successfully integrated into the Solar Orbiter spacecraft. A number of innovations were introduced compared with earlier space-based spectropolarimeters, thus allowing SO/PHI to fit into the tight mass, volume, power and telemetry budgets provided by the Solar Orbiter spacecraft and to meet the (e.g. thermal) challenges posed by the mission’s highly elliptical orbit.
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TL;DR: In this paper, the authors perform Bayesian model selection on a wide range of theoretical predictions for the neutron star equation of state, and find that all scenarios from prompt collapse to long-lived or even stable remnants are possible.
Abstract: GW170817 is the very first observation of gravitational waves originating from the coalescence of two compact objects in the mass range of neutron stars, accompanied by electromagnetic counterparts, and offers an opportunity to directly probe the internal structure of neutron stars. We perform Bayesian model selection on a wide range of theoretical predictions for the neutron star equation of state. For the binary neutron star hypothesis, we find that we cannot rule out the majority of theoretical models considered. In addition, the gravitational-wave data alone does not rule out the possibility that one or both objects were low-mass black holes. We discuss the possible outcomes in the case of a binary neutron star merger, finding that all scenarios from prompt collapse to long-lived or even stable remnants are possible. For long-lived remnants, we place an upper limit of 1.9 kHz on the rotation rate. If a black hole was formed any time after merger and the coalescing stars were slowly rotating, then the maximum baryonic mass of non-rotating neutron stars is at most 3.05M⊙, and three equations of state considered here can be ruled out. We obtain a tighter limit of 2.67M⊙ for the case that the merger results in a hypermassive neutron star.
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TL;DR: The Hepamet fibrosis scoring system had the greatest net benefit in identifying patients who should undergo liver biopsy analysis and led to significant improvements in reclassification, reducing the number of patients with undetermined results to 20% from 30% for the FIB-4 and NFS systems.
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Shanghai Jiao Tong University1, Columbia University2, Chinese Ministry of Education3, Peking University4, Istanbul University5, University of Parma6, University of Milan7, University of Michigan8, Medical University of Warsaw9, Polish Academy of Sciences10, Autonomous University of Barcelona11, University of Bern12, Uludağ University13, Marmara University14, University of Messina15, University of Chieti-Pescara16, University of Bari17, Charles University in Prague18, Vita-Salute San Raffaele University19, University of Turin20, University of Verona21, Katholieke Universiteit Leuven22, Seoul National University Hospital23, New Generation University College24, Juntendo University25, Toronto General Hospital26, Mayo Clinic27, University of Manchester28, University College London29, Royal London Hospital30, Icahn School of Medicine at Mount Sinai31, Mount Sinai Hospital32, University of Freiburg33, Charité34, University of Erlangen-Nuremberg35, Radboud University Nijmegen36, University of Washington37, Boston University38, French Institute of Health and Medical Research39, Pierre-and-Marie-Curie University40, University of Hamburg41, University of Brescia42
TL;DR: The findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk.
Abstract: Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 ( rs230540, OR = 1.25, P = 3.4 × 10−12) and IRF4 ( rs9405192, OR = 1.29, P = 1.4 × 10−14), fine-map the PLA2R1 locus ( rs17831251, OR = 2.25, P = 4.7 × 10−103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10−49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10−93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10−23 and OR = 3.39, P = 5.2 × 10−82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20–37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk. Membranous nephropathy (MN) is a rare autoimmune disease of podocyte-directed antibodies, such as anti-phospholipase A2 receptor. Here, the authors report a genome-wide association study for MN and identify two previously unreported loci encompassing the NFKB1 and IRF4 genes and additional ancestry-specific effects.
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TL;DR: In this article, the future potential of the LISA mission in the area of fundamental physics was further delineated and sharpen the potential of LISA data in a broad range of topics.
Abstract: In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA,we present here a sample of what we view as particularly promising fundamental physics directions. We organize these directions through a “science-first” approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.
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Washington University in St. Louis1, Rockefeller University2, Yale University3, St. Joseph's Hospital and Medical Center4, University of Arizona5, University of Adelaide6, University College London7, University of Toronto8, National and Kapodistrian University of Athens9, Monash University10, Zhengzhou University11, Pierre-and-Marie-Curie University12, GeneDx13, Fudan University14, University of Texas Southwestern Medical Center15, Harvard University16, Kennedy Krieger Institute17, University of New Mexico18, Boston Children's Hospital19, University of Sydney20, University of Gothenburg21, University of Wisconsin-Madison22
TL;DR: Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen, providing evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.
Abstract: In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.
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TL;DR: LiteBIRD as mentioned in this paper, the Lite (Light) satellite for the study of B-mode polarization and inflation from cosmic background radiation detection, is a space mission for primordial cosmology and fundamental physics.
Abstract: LiteBIRD, the Lite (Light) satellite for the study of B-mode polarization and Inflation from cosmic background Radiation Detection, is a space mission for primordial cosmology and fundamental physics. JAXA selected LiteBIRD in May 2019 as a strategic large-class (L-class) mission, with its expected launch in the late 2020s using JAXA's H3 rocket. LiteBIRD plans to map the cosmic microwave background (CMB) polarization over the full sky with unprecedented precision. Its main scientific objective is to carry out a definitive search for the signal from cosmic inflation, either making a discovery or ruling out well-motivated inflationary models. The measurements of LiteBIRD will also provide us with an insight into the quantum nature of gravity and other new physics beyond the standard models of particle physics and cosmology. To this end, LiteBIRD will perform full-sky surveys for three years at the Sun-Earth Lagrangian point L2 for 15 frequency bands between 34 and 448 GHz with three telescopes, to achieve a total sensitivity of 2.16 μK-arcmin with a typical angular resolution of 0.5° at 100 GHz. We provide an overview of the LiteBIRD project, including scientific objectives, mission requirements, top-level system requirements, operation concept, and expected scientific outcomes.
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TL;DR: In this article, a search for continuous gravitational waves from five radio pulsars, comprising three recycled pulsars (PSR J0437-4715, PSR J0711-6830, and PSRJ0737-3039A), was presented.
Abstract: We present a search for continuous gravitational waves from five radio pulsars, comprising three recycled pulsars (PSR J0437-4715, PSR J0711-6830, and PSR J0737-3039A) and two young pulsars: the Crab pulsar (J0534+2200) and the Vela pulsar (J0835-4510). We use data from the third observing run of Advanced LIGO and Virgo combined with data from their first and second observing runs. For the first time, we are able to match (for PSR J0437-4715) or surpass (for PSR J0711-6830) the indirect limits on gravitational-wave emission from recycled pulsars inferred from their observed spin-downs, and constrain their equatorial ellipticities to be less than 10-8. For each of the five pulsars, we perform targeted searches that assume a tight coupling between the gravitational-wave and electromagnetic signal phase evolution. We also present constraints on PSR J0711-6830, the Crab pulsar, and the Vela pulsar from a search that relaxes this assumption, allowing the gravitational-wave signal to vary from the electromagnetic expectation within a narrow band of frequencies and frequency derivatives.
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TL;DR: In this article, the authors consider the estimation of a signal from the knowledge of its noisy linear random Gaussian projections and show that approximate message-passing always reaches the minimal-mean-square error.
Abstract: We consider the estimation of a signal from the knowledge of its noisy linear random Gaussian projections. A few examples where this problem is relevant are compressed sensing, sparse superposition codes, and code division multiple access. There has been a number of works considering the mutual information for this problem using the replica method from statistical physics. Here we put these considerations on a firm rigorous basis. First, we show, using a Guerra-Toninelli type interpolation, that the replica formula yields an upper bound to the exact mutual information. Secondly, for many relevant practical cases, we present a converse lower bound via a method that uses spatial coupling, state evolution analysis and the I-MMSE theorem. This yields a single letter formula for the mutual information and the minimal-mean-square error for random Gaussian linear estimation of all discrete bounded signals. In addition, we prove that the low complexity approximate message-passing algorithm is optimal outside of the so-called hard phase, in the sense that it asymptotically reaches the minimal-mean-square error. In this work spatial coupling is used primarily as a proof technique. However our results also prove two important features of spatially coupled noisy linear random Gaussian estimation. First there is no algorithmically hard phase. This means that for such systems approximate message-passing always reaches the minimal-mean-square error. Secondly, in the limit of infinitely long coupled chain, the mutual information associated to spatially coupled systems is the same as the one of uncoupled linear random Gaussian estimation.
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TL;DR: It is demonstrated that highly polyploid tumours are associated with a poor prognosis and underline the importance of quantification of cellular and nuclear ploidy spectra during HCC tumorigenesis.
Abstract: Objectives Polyploidy is a fascinating characteristic of liver parenchyma. Hepatocyte polyploidy depends on the DNA content of each nucleus (nuclear ploidy) and the number of nuclei per cell (cellular ploidy). Which role can be assigned to polyploidy during human hepatocellular carcinoma (HCC) development is still an open question. Here, we investigated whether a specific ploidy spectrum is associated with clinical and molecular features of HCC. Design Ploidy spectra were determined on surgically resected tissues from patients with HCC as well as healthy control tissues. To define ploidy profiles, a quantitative and qualitative in situ imaging approach was used on paraffin tissue liver sections. Results We first demonstrated that polyploid hepatocytes are the major components of human liver parenchyma, polyploidy being mainly cellular (binuclear hepatocytes). Across liver lobules, polyploid hepatocytes do not exhibit a specific zonation pattern. During liver tumorigenesis, cellular ploidy is drastically reduced; binuclear polyploid hepatocytes are barely present in HCC tumours. Remarkably, nuclear ploidy is specifically amplified in HCC tumours. In fact, nuclear ploidy is amplified in HCCs harbouring a low degree of differentiation and TP53 mutations. Finally, our results demonstrated that highly polyploid tumours are associated with a poor prognosis. Conclusions Our results underline the importance of quantification of cellular and nuclear ploidy spectra during HCC tumorigenesis.
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TL;DR: The care of multiple sclerosis in France is based on two complementary interlinked networks: MS expert centers in university hospitals and regional networks of neurologists.
Abstract: The care of multiple sclerosis (MS) in France is based on two complementary interlinked networks: MS expert centers in university hospitals and regional networks of neurologists. The routine use of...
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TL;DR: In this article, the authors performed single-cell RNA-sequencing to establish an exhaustive high-resolution map of blood antigen-presenting cells (APC) in 7 COVID-19 patients with moderate or severe pneumonia, at day-1 and day-4 post-admission, and two healthy donors.
Abstract: COVID-19 can lead to life-threatening acute respiratory failure, characterized by simultaneous increase in inflammatory mediators and viral load. The underlying cellular and molecular mechanisms remain unclear. We performed single-cell RNA-sequencing to establish an exhaustive high-resolution map of blood antigen-presenting cells (APC) in 7 COVID-19 patients with moderate or severe pneumonia, at day-1 and day-4 post-admission, and two healthy donors. We generated a unique dataset of 31,513 high quality APC, including monocytes and rare dendritic cell (DC) subsets. We uncovered multiprocess and previously unrecognized defects in anti-viral immune defense in specific APC compartments from severe patients: i) increase of pro-apoptotic genes exclusively in pDC, which are key effectors of antiviral immunity, ii) sharp decrease of innate sensing receptors, TLR7 and DHX9, in pDC and cDC1, respectively, iii) down-regulation of antiviral effector molecules, including Interferon stimulated genes (ISG) in all monocyte subsets, and iv) decrease of MHC class II-related genes, and MHC class II transactivator (CIITA) activity in cDC2, suggesting a viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore defective immune defense.