The pathogenic c.1171A>G (p.Arg391Gly) and c.2359G>A (p.Val787Ile) ABCC6 variants display incomplete penetrance causing pseudoxanthoma elasticum in a subset of individuals

ABCC6 promotes ATP efflux from hepatocytes to bloodstream. ATP is metabolized to pyrophosphate, an inhibitor of ectopic calcification. Pathogenic variants of ABCC6 cause pseudoxanthoma elasticum, a highly variable recessive ectopic calcification disorder. Incomplete penetrance may initiate disease heterogeneity, hence symptoms may not, or differently manifest in carriers. Here, we investigated whether incomplete penetrance is a source of heterogeneity in pseudoxanthoma elasticum. By integrating clinical and genetic data of 589 patients, we created the largest European cohort. Based on allele frequency alterations, we identified two incomplete penetrant pathogenic variants, c.2359G>A (p.Val787Ile) and c.1171A>G (p.Arg391Gly), with 6.5% and 2% penetrance, respectively. However, when penetrant, the c.1171A>G (p.Arg391Gly) manifested a clinically unaltered severity. After applying in silico and in vitro characterization, we suggest that incomplete penetrant variants are only deleterious if a yet unknown interacting partner of ABCC6 is mutated simultaneously. The low penetrance of these variants should be contemplated in genetic counseling

Complex pleural empyema can be safely treated with vacuum-assisted closure

<p>Abstract</p> <p>Objective</p> <p>For patients with postoperative pleural empyema, open window thoracostomy (OWT) is often necessary to prevent sepsis. Vacuum-assisted closure (VAC) is a well-known therapeutic option in wound treatment. The efficacy and safety of intrathoracal VAC therapy, especially in patients with pleural empyema with bronchial stump insufficiency or remain lung, has not yet been investigated.</p> <p>Methods</p> <p>Between October 2009 and July 2010, eight consecutive patients (mean age of 66.1 years) with multimorbidity received an OWT with VAC for the treatment of postoperative or recurrent pleural empyema. Two of them had a bronchial stump insufficiency (BPF).</p> <p>Results</p> <p>VAC therapy ensured local control of the empyema and control of sepsis. The continuous suction up to 125 mm Hg cleaned the wound and thoracic cavity and supported the rapid healing. Additionally, installation of a stable vacuum was possible in the two patients with BPF. The smaller bronchus stump fistula closed spontaneously due to the VAC therapy, but the larger remained open.</p> <p>The direct contact of the VAC sponge did not create any air leak or bleeding from the lung or the mediastinal structures. The VAC therapy allowed a better re-expansion of remaining lung.</p> <p>One patient died in the late postoperative period (day 47 p.o.) of multiorgan failure. In three cases, VAC therapy was continued in an outpatient service, and in four patients, the OWT was treated with conventional wound care. After a mean time of three months, the chest wall was closed in five of seven cases. However, two patients rejected the closure of the OWT. After a follow-up at 7.7 months, neither recurrent pleural empyema nor BPF was observed.</p> <p>Conclusion</p> <p>VAC therapy was effective and safe in the treatment of complicated pleural empyema. The presence of smaller bronchial stump fistula and of residual lung tissue are not a contraindication for VAC therapy.</p

Working paper analysing the economic implications of the proposed 30% target for areal protection in the draft post-2020 Global Biodiversity Framewor

58 pages, 5 figures, 3 tables- The World Economic Forum now ranks biodiversity loss as a top-five risk to the global economy, and the draft post-2020 Global Biodiversity Framework proposes an expansion of conservation areas to 30% of the earth’s surface by 2030 (hereafter the “30% target”), using protected areas (PAs) and other effective area-based conservation measures (OECMs). - Two immediate concerns are how much a 30% target might cost and whether it will cause economic losses to the agriculture, forestry and fisheries sectors. - Conservation areas also generate economic benefits (e.g. revenue from nature tourism and ecosystem services), making PAs/Nature an economic sector in their own right. - If some economic sectors benefit but others experience a loss, high-level policy makers need to know the net impact on the wider economy, as well as on individual sectors. [...]A. Waldron, K. Nakamura, J. Sze, T. Vilela, A. Escobedo, P. Negret Torres, R. Button, K. Swinnerton, A. Toledo, P. Madgwick, N. Mukherjee were supported by National Geographic and the Resources Legacy Fund. V. Christensen was supported by NSERC Discovery Grant RGPIN-2019-04901. M. Coll and J. Steenbeek were supported by EU Horizon 2020 research and innovation programme under grant agreement No 817578 (TRIATLAS). D. Leclere was supported by TradeHub UKRI CGRF project. R. Heneghan was supported by Spanish Ministry of Science, Innovation and Universities, Acciones de Programacion Conjunta Internacional (PCIN-2017-115). M. di Marco was supported by MIUR Rita Levi Montalcini programme. A. Fernandez-Llamazares was supported by Academy of Finland (grant nr. 311176). S. Fujimori and T. Hawegawa were supported by The Environment Research and Technology Development Fund (2-2002) of the Environmental Restoration and Conservation Agency of Japan and the Sumitomo Foundation. V. Heikinheimo was supported by Kone Foundation, Social Media for Conservation project. K. Scherrer was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under grant agreement No 682602. U. Rashid Sumaila acknowledges the OceanCanada Partnership, which funded by the Social Sciences and Humanities Research Council of Canada (SSHRC). T. Toivonen was supported by Osk. Huttunen Foundation & Clare Hall college, Cambridge. W. Wu was supported by The Environment Research and Technology Development Fund (2-2002) of the Environmental Restoration and Conservation Agency of Japan. Z. Yuchen was supported by a Ministry of Education of Singapore Research Scholarship Block (RSB) Research FellowshipPeer reviewe

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| &lt; 0.03 at 95% confidence level. [Figure not available: see fulltext.

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe