Showing papers by "University of Valencia published in 2021"

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

ERA5-Land: a state-of-the-art global reanalysis dataset for land applications

Abstract: . Framed within the Copernicus Climate Change Service (C3S) of the European Commission, the European Centre for Medium-Range Weather Forecasts (ECMWF) is producing an enhanced global dataset for the land component of the fifth generation of European ReAnalysis (ERA5), hereafter referred to as ERA5-Land. Once completed, the period covered will span from 1950 to the present, with continuous updates to support land monitoring applications. ERA5-Land describes the evolution of the water and energy cycles over land in a consistent manner over the production period, which, among others, could be used to analyse trends and anomalies. This is achieved through global high-resolution numerical integrations of the ECMWF land surface model driven by the downscaled meteorological forcing from the ERA5 climate reanalysis, including an elevation correction for the thermodynamic near-surface state. ERA5-Land shares with ERA5 most of the parameterizations that guarantees the use of the state-of-the-art land surface modelling applied to numerical weather prediction (NWP) models. A main advantage of ERA5-Land compared to ERA5 and the older ERA-Interim is the horizontal resolution, which is enhanced globally to 9 km compared to 31 km (ERA5) or 80 km (ERA-Interim), whereas the temporal resolution is hourly as in ERA5. Evaluation against independent in situ observations and global model or satellite-based reference datasets shows the added value of ERA5-Land in the description of the hydrological cycle, in particular with enhanced soil moisture and lake description, and an overall better agreement of river discharge estimations with available observations. However, ERA5-Land snow depth fields present a mixed performance when compared to those of ERA5, depending on geographical location and altitude. The description of the energy cycle shows comparable results with ERA5. Nevertheless, ERA5-Land reduces the global averaged root mean square error of the skin temperature, taking as reference MODIS data, mainly due to the contribution of coastal points where spatial resolution is important. Since January 2020, the ERA5-Land period available has extended from January 1981 to the near present, with a 2- to 3-month delay with respect to real time. The segment prior to 1981 is in production, aiming for a release of the whole dataset in summer/autumn 2021. The high spatial and temporal resolution of ERA5-Land, its extended period, and the consistency of the fields produced makes it a valuable dataset to support hydrological studies, to initialize NWP and climate models, and to support diverse applications dealing with water resource, land, and environmental management. The full ERA5-Land hourly ( Munoz-Sabater , 2019 a ) and monthly ( Munoz-Sabater , 2019 b ) averaged datasets presented in this paper are available through the C3S Climate Data Store at https://doi.org/10.24381/cds.e2161bac and https://doi.org/10.24381/cds.68d2bb30 , respectively.

In the realm of the Hubble tension - a review of solutions

Abstract: The $\Lambda$CDM model provides a good fit to a large span of cosmological data but harbors areas of phenomenology. With the improvement of the number and the accuracy of observations, discrepancies among key cosmological parameters of the model have emerged. The most statistically significant tension is the $4-6\sigma$ disagreement between predictions of the Hubble constant $H_0$ by early time probes with $\Lambda$CDM model, and a number of late time, model-independent determinations of $H_0$ from local measurements of distances and redshifts. The high precision and consistency of the data at both ends present strong challenges to the possible solution space and demand a hypothesis with enough rigor to explain multiple observations--whether these invoke new physics, unexpected large-scale structures or multiple, unrelated errors. We present a thorough review of the problem, including a discussion of recent Hubble constant estimates and a summary of the proposed theoretical solutions. Some of the models presented are formally successful, improving the fit to the data in light of their additional degrees of freedom, restoring agreement within $1-2\sigma$ between {\it Planck} 2018, using CMB power spectra data, BAO, Pantheon SN data, and R20, the latest SH0ES Team measurement of the Hubble constant ($H_0 = 73.2 \pm 1.3{\rm\,km\,s^{-1}\,Mpc^{-1}}$ at 68\% confidence level). Reduced tension might not simply come from a change in $H_0$ but also from an increase in its uncertainty due to degeneracy with additional physics, pointing to the need for additional probes. While no specific proposal makes a strong case for being highly likely or far better than all others, solutions involving early or dynamical dark energy, neutrino interactions, interacting cosmologies, primordial magnetic fields, and modified gravity provide the best options until a better alternative comes along.[Abridged]

Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial.

Abstract: Summary Background Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. Methods In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 × 5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m2 orally twice daily on days 1–14, oxaliplatin 130 mg/m2 intravenously on day 1, and a chemotherapy-free interval between days 15–21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m2 intravenously and fluorouracil 600 mg/m2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3–14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov , NCT01558921 , and is now complete. Findings Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5–5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8–27·6) in the experimental group versus 30·4% (26·1–34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60–0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). Interpretation The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer. Funding Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.

State of the Art and Prospects for Halide Perovskite Nanocrystals.

Abstract: Metal-halide perovskites have rapidly emerged as one of the most promising materials of the 21st century, with many exciting properties and great potential for a broad range of applications, from photovoltaics to optoelectronics and photocatalysis. The ease with which metal-halide perovskites can be synthesized in the form of brightly luminescent colloidal nanocrystals, as well as their tunable and intriguing optical and electronic properties, has attracted researchers from different disciplines of science and technology. In the last few years, there has been a significant progress in the shape-controlled synthesis of perovskite nanocrystals and understanding of their properties and applications. In this comprehensive review, researchers having expertise in different fields (chemistry, physics, and device engineering) of metal-halide perovskite nanocrystals have joined together to provide a state of the art overview and future prospects of metal-halide perovskite nanocrystal research.

Population Properties of Compact Objects from the Second LIGO-Virgo Gravitational-Wave Transient Catalog

Abstract: We report on the population of 47 compact binary mergers detected with a false-alarm rate of 0.01 are dynamically assembled. Third, we estimate merger rates, finding RBBH = 23.9-+8.614.3 Gpc-3 yr-1 for BBHs and RBNS = 320-+240490 Gpc-3 yr-1 for binary neutron stars. We find that the BBH rate likely increases with redshift (85% credibility) but not faster than the star formation rate (86% credibility). Additionally, we examine recent exceptional events in the context of our population models, finding that the asymmetric masses of GW190412 and the high component masses of GW190521 are consistent with our models, but the low secondary mass of GW190814 makes it an outlier.

Comprehensive defect suppression in perovskite nanocrystals for high-efficiency light-emitting diodes

Abstract: Electroluminescence efficiencies of metal halide perovskite nanocrystals (PNCs) are limited by a lack of material strategies that can both suppress the formation of defects and enhance the charge carrier confinement. Here we report a one-dopant alloying strategy that generates smaller, monodisperse colloidal particles (confining electrons and holes, and boosting radiative recombination) with fewer surface defects (reducing non-radiative recombination). Doping of guanidinium into formamidinium lead bromide PNCs yields limited bulk solubility while creating an entropy-stabilized phase in the PNCs and leading to smaller PNCs with more carrier confinement. The extra guanidinium segregates to the surface and stabilizes the undercoordinated sites. Furthermore, a surface-stabilizing 1,3,5-tris(bromomethyl)-2,4,6-triethylbenzene was applied as a bromide vacancy healing agent. The result is highly efficient PNC-based light-emitting diodes that have current efficiency of 108 cd A−1 (external quantum efficiency of 23.4%), which rises to 205 cd A−1 (external quantum efficiency of 45.5%) with a hemispherical lens. Guanidinium doping is shown to enhance the operation of perovskite nanocrystal light-emitting diodes.

Global epidemiology of atrial fibrillation: An increasing epidemic and public health challenge.

Abstract: BackgroundAtrial fibrillation is the most frequent cardiac arrhythmia. It has been estimated that 6–12 million people worldwide will suffer this condition in the US by 2050 and 17.9 million people ...

2020 global reassessment of the neutrino oscillation picture

Abstract: We present an updated global fit of neutrino oscillation data in the simplest three-neutrino framework In the present study we include up-to-date analyses from a number of experiments Concerning the atmospheric and solar sectors, besides the data considered previously, we give updated analyses of IceCube DeepCore and Sudbury Neutrino Observatory data, respectively We have also included the latest electron antineutrino data collected by the Daya Bay and RENO reactor experiments, and the long-baseline T2K and NOνA measurements, as reported in the Neutrino 2020 conference All in all, these new analyses result in more accurate measurements of θ13, θ12, $$ \Delta {m}_{21}^2 $$ and $$ \left|\Delta {m}_{31}^2\right| $$ The best fit value for the atmospheric angle θ23 lies in the second octant, but first octant solutions remain allowed at ∼ 24σ Regarding CP violation measurements, the preferred value of δ we obtain is 108π (158π) for normal (inverted) neutrino mass ordering The global analysis still prefers normal neutrino mass ordering with 25σ statistical significance This preference is milder than the one found in previous global analyses These new results should be regarded as robust due to the agreement found between our Bayesian and frequentist approaches Taking into account only oscillation data, there is a weak/moderate preference for the normal neutrino mass ordering of 200σ While adding neutrinoless double beta decay from the latest Gerda, CUORE and KamLAND-Zen results barely modifies this picture, cosmological measurements raise the preference to 268σ within a conservative approach A more aggressive data set combination of cosmological observations leads to a similar preference for normal with respect to inverted mass ordering, namely 270σ This very same cosmological data set provides 2σ upper limits on the total neutrino mass corresponding to Σmν < 012 (015) eV in the normal (inverted) neutrino mass ordering scenario The bounds on the neutrino mixing parameters and masses presented in this up-to-date global fit analysis include all currently available neutrino physics inputs

Observation of Gravitational Waves from Two Neutron Star–Black Hole Coalescences

Abstract: We report the observation of gravitational waves from two compact binary coalescences in LIGO’s and Virgo’s third observing run with properties consistent with neutron star–black hole (NSBH) binaries. The two events are named GW200105_162426 and GW200115_042309, abbreviated as GW200105 and GW200115; the first was observed by LIGO Livingston and Virgo and the second by all three LIGO–Virgo detectors. The source of GW200105 has component masses 8.9−1.5+1.2 and 1.9−0.2+0.3M⊙ , whereas the source of GW200115 has component masses 5.7−2.1+1.8 and 1.5−0.3+0.7M⊙ (all measurements quoted at the 90% credible level). The probability that the secondary’s mass is below the maximal mass of a neutron star is 89%–96% and 87%–98%, respectively, for GW200105 and GW200115, with the ranges arising from different astrophysical assumptions. The source luminosity distances are 280−110+110 and 300−100+150Mpc , respectively. The magnitude of the primary spin of GW200105 is less than 0.23 at the 90% credible level, and its orientation is unconstrained. For GW200115, the primary spin has a negative spin projection onto the orbital angular momentum at 88% probability. We are unable to constrain the spin or tidal deformation of the secondary component for either event. We infer an NSBH merger rate density of 45−33+75Gpc−3yr−1 when assuming that GW200105 and GW200115 are representative of the NSBH population or 130−69+112Gpc−3yr−1 under the assumption of a broader distribution of component masses.

First M87 Event Horizon Telescope Results. VIII. Magnetic Field Structure near the Event Horizon

Abstract: Full list of authors: Akiyama, Kazunori; Algaba, Juan Carlos; Alberdi, Antxon; Alef, Walter; Anantua, Richard; Asada, Keiichi; Azulay, Rebecca; Baczko, Anne-Kathrin; Ball, David; Balokovic, Mislav; Barrett, John; Benson, Bradford A.; Bintley, Dan; Blackburn, Lindy; Blundell, Raymond; Boland, Wilfred; Bouman, Katherine L.; Bower, Geoffrey C.; Boyce, Hope Bremer, Michael; Brinkerink, Christiaan D.; Brissenden, Roger; Britzen, Silke; Broderick, Avery E.; Broguiere, Dominique; Bronzwaer, Thomas; Byun, Do-Young; Carlstrom, John E.; Chael, Andrew; Chan, Chi-kwan; Chatterjee, Shami; Chatterjee, Koushik; Chen, Ming-Tang; Chen, Yongjun; Chesler, Paul M.; Cho, Ilje; Christian, Pierre; Conway, John E.; Cordes, James M.; Crawford, Thomas M.; Crew, Geoffrey B.; Cruz-Osorio, Alejandro; Cui, Yuzhu; Davelaar, Jordy; De Laurentis, Mariafelicia; Deane, Roger; Dempsey, Jessica; Desvignes, Gregory; Dexter, Jason; Doeleman, Sheperd S.; Eatough, Ralph P.; Falcke, Heino; Farah, Joseph; Fish, Vincent L.; Fomalont, Ed; Ford, H. Alyson; Fraga-Encinas, Raquel; Friberg, Per; Fromm, Christian M.; Fuentes, Antonio; Galison, Peter; Gammie, Charles F.; Garcia, Roberto; Gelles, Zachary; Gentaz, Olivier; Georgiev, Boris; Goddi, Ciriaco; Gold, Roman; Gomez, Jose L.; Gomez-Ruiz, Arturo I.; Gu, Minfeng; Gurwell, Mark; Hada, Kazuhiro; Haggard, Daryl; Hecht, Michael H.; Hesper, Ronald; Himwich, Elizabeth; Ho, Luis C.; Ho, Paul; Honma, Mareki; Huang, Chih-Wei L.; Huang, Lei; Hughes, David H.; Ikeda, Shiro; Inoue, Makoto; Issaoun, Sara; James, David J.; Jannuzi, Buell T.; Janssen, Michael; Jeter, Britton; Jiang, Wu; Jimenez-Rosales, Alejandra; Johnson, Michael D.; Jorstad, Svetlana; Jung, Taehyun; Karami, Mansour; Karuppusamy, Ramesh; Kawashima, Tomohisa; Keating, Garrett K.; Kettenis, Mark; Kim, Dong-Jin; Kim, Jae-Young; Kim, Jongsoo; Kim, Junhan; Kino, Motoki; Koay, Jun Yi; Kofuji, Yutaro; Koch, Patrick M.; Koyama, Shoko; Kramer, Michael; Kramer, Carsten; Krichbaum, Thomas P.; Kuo, Cheng-Yu; Lauer, Tod R.; Lee, Sang-Sung; Levis, Aviad; Li, Yan-Rong; Li, Zhiyuan; Lindqvist, Michael; Lico, Rocco; Lindahl, Greg; Liu, Jun; Liu, Kuo; Liuzzo, Elisabetta; Lo, Wen-Ping; Lobanov, Andrei P.; Loinard, Laurent; Lonsdale, Colin; Lu, Ru-Sen; MacDonald, Nicholas R.; Mao, Jirong; Marchili, Nicola; Markoff, Sera; Marrone, Daniel P.; Marscher, Alan P.; Marti-Vidal, Ivan; Matsushita, Satoki; Matthews, Lynn D.; Medeiros, Lia; Menten, Karl M.; Mizuno, Izumi; Mizuno, Yosuke; Moran, James M.; Moriyama, Kotaro; Moscibrodzka, Monika; Muller, Cornelia; Musoke, Gibwa; Mus Mejias, Alejandro; Michalik, Daniel; Nadolski, Andrew; Nagai, Hiroshi; Nagar, Neil M.; Nakamura, Masanori; Narayan, Ramesh; Narayanan, Gopal; Natarajan, Iniyan; Nathanail, Antonios; Neilsen, Joey; Neri, Roberto; Ni, Chunchong; Noutsos, Aristeidis; Nowak, Michael A.; Okino, Hiroki; Olivares, Hector; Ortiz-Leon, Gisela N.; Oyama, Tomoaki; Ozel, Feryal; Palumbo, Daniel C. M.; Park, Jongho; Patel, Nimesh; Pen, Ue-Li; Pesce, Dominic W.; Pietu, Vincent; Plambeck, Richard; PopStefanija, Aleksandar; Porth, Oliver; Potzl, Felix M.; Prather, Ben; Preciado-Lopez, Jorge A.; Psaltis, Dimitrios; Pu, Hung-Yi; Ramakrishnan, Venkatessh; Rao, Ramprasad; Rawlings, Mark G.; Raymond, Alexander W.; Rezzolla, Luciano; Ricarte, Angelo; Ripperda, Bart; Roelofs, Freek; Rogers, Alan; Ros, Eduardo; Rose, Mel; Roshanineshat, Arash; Rottmann, Helge; Roy, Alan L.; Ruszczyk, Chet; Rygl, Kazi L. J.; Sanchez, Salvador; Sanchez-Arguelles, David; Sasada, Mahito; Savolainen, Tuomas; Schloerb, F. Peter; Schuster, Karl-Friedrich; Shao, Lijing; Shen, Zhiqiang; Small, Des; Sohn, Bong Won; SooHoo, Jason; Sun, He; Tazaki, Fumie; Tetarenko, Alexandra J.; Tiede, Paul; Tilanus, Remo P. J.; Titus, Michael; Toma, Kenji; Torne, Pablo; Trent, Tyler; Traianou, Efthalia; Trippe, Sascha; van Bemmel, Ilse; van Langevelde, Huib Jan; van Rossum, Daniel R.; Wagner, Jan; Ward-Thompson, Derek; Wardle, John; Weintroub, Jonathan; Wex, Norbert; Wharton, Robert; Wielgus, Maciek; Wong, George N.; Wu, Qingwen; Yoon, Doosoo; Young, Andre; Young, Ken; Younsi, Ziri; Yuan, Feng; Yuan, Ye-Fei; Zensus, J. Anton; Zhao, Guang-Yao; Zhao, Shan-Shan; Event Horizon Telescope Collaboration.-- This is an open access article, original content from this work may be used under the terms of the Creative Commons Attribution 4.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Abstract: Following its emergence in late 2019, the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1,2 has been tracked via phylogenetic analysis of viral genome sequences in unprecedented detail3–5. While the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, within Europe travel resumed in the summer of 2020. Here we report on a novel SARS-CoV-2 variant, 20E (EU1), that emerged in Spain in early summer, and subsequently spread across Europe. We find no evidence of increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate 20E (EU1) was introduced hundreds of times to European countries by summertime travelers, likely undermining local efforts to keep SARS-CoV-2 cases low. Our results demonstrate how a variant can rapidly become dominant even in absence of a substantial transmission advantage in favorable epidemiological settings. Genomic surveillance is critical to understanding how travel can impact SARS-CoV-2 transmission, and thus for informing future containment strategies as travel resumes.

The burden of heat-related mortality attributable to recent human-induced climate change

Abstract: Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018. Across all study countries, we find that 37.0% (range 20.5-76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change.

First M87 Event Horizon Telescope Results. VII. Polarization of the Ring

Abstract: Full list of authors: Akiyama, Kazunori; Algaba, Juan Carlos; Alberdi, Antxon; Alef, Walter; Anantua, Richard; Asada, Keiichi; Azulay, Rebecca; Baczko, Anne-Kathrin; Ball, David; Balokovic, Mislav; Barrett, John; Benson, Bradford A.; Bintley, Dan; Blackburn, Lindy; Blundell, Raymond; Boland, Wilfred; Bouman, Katherine L.; Bower, Geoffrey C.; Boyce, Hope Bremer, Michael; Brinkerink, Christiaan D.; Brissenden, Roger; Britzen, Silke; Broderick, Avery E.; Broguiere, Dominique; Bronzwaer, Thomas; Byun, Do-Young; Carlstrom, John E.; Chael, Andrew; Chan, Chi-kwan; Chatterjee, Shami; Chatterjee, Koushik; Chen, Ming-Tang; Chen, Yongjun; Chesler, Paul M.; Cho, Ilje; Christian, Pierre; Conway, John E.; Cordes, James M.; Crawford, Thomas M.; Crew, Geoffrey B.; Cruz-Osorio, Alejandro; Cui, Yuzhu; Davelaar, Jordy; De Laurentis, Mariafelicia; Deane, Roger; Dempsey, Jessica; Desvignes, Gregory; Dexter, Jason; Doeleman, Sheperd S.; Eatough, Ralph P.; Falcke, Heino; Farah, Joseph; Fish, Vincent L.; Fomalont, Ed; Ford, H. Alyson; Fraga-Encinas, Raquel; Freeman, William T.; Friberg, Per; Fromm, Christian M.; Fuentes, Antonio; Galison, Peter; Gammie, Charles F.; Garcia, Roberto; Gentaz, Olivier; Georgiev, Boris; Goddi, Ciriaco; Gold, Roman; Gomez, Jose L.; Gomez-Ruiz, Arturo I.; Gu, Minfeng; Gurwell, Mark; Hada, Kazuhiro; Haggard, Daryl; Hecht, Michael H.; Hesper, Ronald; Ho, Luis C.; Ho, Paul; Honma, Mareki; Huang, Chih-Wei L.; Huang, Lei; Hughes, David H.; Ikeda, Shiro; Inoue, Makoto; Issaoun, Sara; James, David J.; Jannuzi, Buell T.; Janssen, Michael; Jeter, Britton; Jiang, Wu; Jimenez-Rosales, Alejandra; Johnson, Michael D.; Jorstad, Svetlana; Jung, Taehyun; Karami, Mansour; Karuppusamy, Ramesh; Kawashima, Tomohisa; Keating, Garrett K.; Kettenis, Mark; Kim, Dong-Jin; Kim, Jae-Young; Kim, Jongsoo; Kim, Junhan; Kino, Motoki; Koay, Jun Yi; Kofuji, Yutaro; Koch, Patrick M.; Koyama, Shoko; Kramer, Michael; Kramer, Carsten; Krichbaum, Thomas P.; Kuo, Cheng-Yu; Lauer, Tod R.; Lee, Sang-Sung; Levis, Aviad; Li, Yan-Rong; Li, Zhiyuan; Lindqvist, Michael; Lico, Rocco; Lindahl, Greg; Liu, Jun; Liu, Kuo; Liuzzo, Elisabetta; Lo, Wen-Ping; Lobanov, Andrei P.; Loinard, Laurent; Lonsdale, Colin; Lu, Ru-Sen; MacDonald, Nicholas R.; Mao, Jirong; Marchili, Nicola; Markoff, Sera; Marrone, Daniel P.; Marscher, Alan P.; Marti-Vidal, Ivan; Matsushita, Satoki; Matthews, Lynn D.; Medeiros, Lia; Menten, Karl M.; Mizuno, Izumi; Mizuno, Yosuke; Moran, James M.; Moriyama, Kotaro; Moscibrodzka, Monika; Muller, Cornelia; Musoke, Gibwa; Mejias, Alejandro Mus; Michalik, Daniel; Nadolski, Andrew; Nagai, Hiroshi; Nagar, Neil M.; Nakamura, Masanori; Narayan, Ramesh; Narayanan, Gopal; Natarajan, Iniyan; Nathanail, Antonios; Neilsen, Joey; Neri, Roberto; Ni, Chunchong; Noutsos, Aristeidis; Nowak, Michael A.; Okino, Hiroki; Olivares, Hector; Ortiz-Leon, Gisela N.; Oyama, Tomoaki; Ozel, Feryal; Palumbo, Daniel C. M.; Park, Jongho; Patel, Nimesh; Pen, Ue-Li; Pesce, Dominic W.; Pietu, Vincent; Plambeck, Richard; PopStefanija, Aleksandar; Porth, Oliver; Potzl, Felix M.; Prather, Ben; Preciado-Lopez, Jorge A.; Psaltis, Dimitrios; Pu, Hung-Yi; Ramakrishnan, Venkatessh; Rao, Ramprasad; Rawlings, Mark G.; Raymond, Alexander W.; Rezzolla, Luciano; Ricarte, Angelo; Ripperda, Bart; Roelofs, Freek; Rogers, Alan; Ros, Eduardo; Rose, Mel; Roshanineshat, Arash; Rottmann, Helge; Roy, Alan L.; Ruszczyk, Chet; Rygl, Kazi L. J.; Sanchez, Salvador; Sanchez-Arguelles, David; Sasada, Mahito; Savolainen, Tuomas; Schloerb, F. Peter; Schuster, Karl-Friedrich; Shao, Lijing; Shen, Zhiqiang; Small, Des; Sohn, Bong Won; SooHoo, Jason; Sun, He; Tazaki, Fumie; Tetarenko, Alexandra J.; Tiede, Paul; Tilanus, Remo P. J.; Titus, Michael; Toma, Kenji; Torne, Pablo; Trent, Tyler; Traianou, Efthalia; Trippe, Sascha; van Bemmel, Ilse; van Langevelde, Huib Jan; van Rossum, Daniel R.; Wagner, Jan; Ward-Thompson, Derek; Wardle, John; Weintroub, Jonathan; Wex, Norbert; Wharton, Robert; Wielgus, Maciek; Wong, George N.; Wu, Qingwen; Yoon, Doosoo; Young, Andre; Young, Ken; Younsi, Ziri; Yuan, Feng; Yuan, Ye-Fei; Zensus, J. Anton; Zhao, Guang-Yao; Zhao, Shan-Shan; Event Horizon Telescope Collaboration.-- This is an open access article, original content from this work may be used under the terms of the Creative Commons Attribution 4.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.

Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer.

Abstract: Novel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.

A gravitational-wave measurement of the Hubble constant following the second observing run of Advanced LIGO and Virgo

Abstract: This paper presents the gravitational-wave measurement of the Hubble constant (H 0) using the detections from the first and second observing runs of the Advanced LIGO and Virgo detector network. The presence of the transient electromagnetic counterpart of the binary neutron star GW170817 led to the first standard-siren measurement of H 0. Here we additionally use binary black hole detections in conjunction with galaxy catalogs and report a joint measurement. Our updated measurement is H 0 = km s−1 Mpc−1 (68.3% of the highest density posterior interval with a flat-in-log prior) which is an improvement by a factor of 1.04 (about 4%) over the GW170817-only value of km s−1 Mpc−1. A significant additional contribution currently comes from GW170814, a loud and well-localized detection from a part of the sky thoroughly covered by the Dark Energy Survey. With numerous detections anticipated over the upcoming years, an exhaustive understanding of other systematic effects are also going to become increasingly important. These results establish the path to cosmology using gravitational-wave observations with and without transient electromagnetic counterparts.

Evaluation of deep learning algorithms for national scale landslide susceptibility mapping of Iran

Abstract: The identification of landslide-prone areas is an essential step in landslide hazard assessment and mitigation of landslide-related losses. In this study, we applied two novel deep learning algorithms, the recurrent neural network (RNN) and convolutional neural network (CNN), for national-scale landslide susceptibility mapping of Iran. We prepared a dataset comprising 4069 historical landslide locations and 11 conditioning factors (altitude, slope degree, profile curvature, distance to river, aspect, plan curvature, distance to road, distance to fault, rainfall, geology and land-sue) to construct a geospatial database and divided the data into the training and the testing dataset. We then developed RNN and CNN algorithms to generate landslide susceptibility maps of Iran using the training dataset. We calculated the receiver operating characteristic (ROC) curve and used the area under the curve (AUC) for the quantitative evaluation of the landslide susceptibility maps using the testing dataset. Better performance in both the training and testing phases was provided by the RNN algorithm (AUC=0.88) than by the CNN algorithm (AUC=0.85). Finally, we calculated areas of susceptibility for each province and found that 6% and 14% of the land area of Iran is very highly and highly susceptible to future landslide events, respectively, with the highest susceptibility in Chaharmahal and Bakhtiari Province (33.8%). About 31% of cities of Iran are located in areas with high and very high landslide susceptibility. The results of the present study will be useful for the development of landslide hazard mitigation strategies.

Upper limits on the isotropic gravitational-wave background from Advanced LIGO and Advanced Virgo’s third observing run

Abstract: We report results of a search for an isotropic gravitational-wave background (GWB) using data from Advanced LIGO’s and Advanced Virgo’s third observing run (O3) combined with upper limits from the earlier O1 and O2 runs. Unlike in previous observing runs in the advanced detector era, we include Virgo in the search for the GWB. The results of the search are consistent with uncorrelated noise, and therefore we place upper limits on the strength of the GWB. We find that the dimensionless energy density Ω GW ≤ 5.8 × 10 − 9 at the 95% credible level for a flat (frequency-independent) GWB, using a prior which is uniform in the log of the strength of the GWB, with 99% of the sensitivity coming from the band 20–76.6 Hz; Ω GW ( f ) ≤ 3.4 × 10 − 9 at 25 Hz for a power-law GWB with a spectral index of 2 / 3 (consistent with expectations for compact binary coalescences), in the band 20–90.6 Hz; and Ω GW ( f ) ≤ 3.9 × 10 − 10 at 25 Hz for a spectral index of 3, in the band 20–291.6 Hz. These upper limits improve over our previous results by a factor of 6.0 for a flat GWB, 8.8 for a spectral index of 2 / 3 , and 13.1 for a spectral index of 3. We also search for a GWB arising from scalar and vector modes, which are predicted by alternative theories of gravity; we do not find evidence of these, and place upper limits on the strength of GWBs with these polarizations. We demonstrate that there is no evidence of correlated noise of magnetic origin by performing a Bayesian analysis that allows for the presence of both a GWB and an effective magnetic background arising from geophysical Schumann resonances. We compare our upper limits to a fiducial model for the GWB from the merger of compact binaries, updating the model to use the most recent data-driven population inference from the systems detected during O3a. Finally, we combine our results with observations of individual mergers and show that, at design sensitivity, this joint approach may yield stronger constraints on the merger rate of binary black holes at z ≳ 2 than can be achieved with individually resolved mergers alone.

Self-care of heart failure patients: practical management recommendations from the Heart Failure Association of the European Society of Cardiology

Abstract: Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion.

Chemical Aspects of Human and Environmental Overload with Fluorine

Abstract: Over the last 100-120 years, due to the ever-increasing importance of fluorine-containing compounds in modern technology and daily life, the explosive development of the fluorochemical industry led to an enormous increase of emission of fluoride ions into the biosphere. This made it more and more important to understand the biological activities, metabolism, degradation, and possible environmental hazards of such substances. This comprehensive and critical review focuses on the effects of fluoride ions and organofluorine compounds (mainly pharmaceuticals and agrochemicals) on human health and the environment. To give a better overview, various connected topics are also discussed: reasons and trends of the advance of fluorine-containing pharmaceuticals and agrochemicals, metabolism of fluorinated drugs, withdrawn fluorinated drugs, natural sources of organic and inorganic fluorine compounds in the environment (including the biosphere), sources of fluoride intake, and finally biomarkers of fluoride exposure.