Life span and reproductive cost explain interspecific variation in the optimal onset of reproduction.

Fitness can be profoundly influenced by the age at first reproduction (AFR), but to date the AFR-fitness relationship only has been investigated intraspecifically. Here, we investigated the relationship between AFR and average lifetime reproductive success (LRS) across 34 bird species. We assessed differences in the deviation of the Optimal AFR (i.e., the species-specific AFR associated with the highest LRS) from the age at sexual maturity, considering potential effects of life history as well as social and ecological factors. Most individuals adopted the species-specific Optimal AFR and both the mean and Optimal AFR of species correlated positively with life span. Interspecific deviations of the Optimal AFR were associated with indices reflecting a change in LRS or survival as a function of AFR: a delayed AFR was beneficial in species where early AFR was associated with a decrease in subsequent survival or reproductive output. Overall, our results suggest that a delayed onset of reproduction beyond maturity is an optimal strategy explained by a long life span and costs of early reproduction. By providing the first empirical confirmations of key predictions of life-history theory across species, this study contributes to a better understanding of life-history evolution

PDA-Based Glyconanomicelles for Hepatocellular Carcinoma Cells Active Targeting Via Mannose and Asialoglycoprotein Receptors

Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the fourth most common cause of cancer-related mortality worldwide. Sorafenib is the first-line molecular therapy for patients in an advanced stage of HCC. However, the recommended clinical dose of Sorafenib is associated with several complications, which derive from its lack of cell specificity and its very low water solubility. To circumvent these drawbacks, in the present study we developed two sugar-coated polydiacetylene-based nanomicelles-Sorafenib carriers targeting mannose and asialoglycoprotein receptors (MR and ASGPR, respectively). The strategies allowed the inducement of apoptosis and reduction of cell proliferation at a nanomolar, instead of micromolar, range in liver cancer cells. The study showed that, contrary to literature data, Sorafenib included into the pMicMan (Man = mannose) vector (targeting MR) is more efficient than pMicGal (Gal = galactose) (targeting ASGPR). Indeed, pMicMan increased the endosomal incorporation with an increased intracellular Sorafenib concentration that induced apoptosis and reduced cell proliferation at a low concentration range (10-20 nM).Financial support was provided by the Spanish Ministry of Economy and Competitiveness (CTQ2016-78580-C2-1-R to N.K.) and the Institute of Health Carlos III (ISCIII) (PI13/00021, PI16/00090, and PI19/01266 to J.M.) both cofinanced by the European Regional Development Fund (ERDF) from FEDER and the European Social Fund (ESF), as well by the Andalusian Ministry of Economy, Science and Innovation (P07-FQM-2774 to N.K., CV20-04221 to N.K. P20_00882 to N.K. and CTS-6264 to J.M.), the PAIDI Program from the Andalusian Government (FQM-313 to N.K., CV20-04221 to N.K., P20_00882 to N.K., P20_00882 to N.K., and CTS-0664 to J.M.), the Andalusian Ministry of Health (PI-00025-2013, and PI-0198-2016 to J.M.), and the CSIC (CSIC–COV19-047). We thank the Biomedical Research Network Center for Liver and Digestive Diseases founded by the ISCIII and cofinanced by FEDER “A way to achieve Europe” and ERDF for their financial support. The COST action CA-18132 “Functional Glyconanomaterials for the Development of Diagnostic and Targeted Therapeutic Probe” is also acknowledged. E.R.B., C.C.A., and P. de la C.-O. were supported by FPU predoctoral fellowship (FPU15/04267, FPU17/00190, and FPU17/00026) from Spanish Ministry of Education, Culture and Sports. E.N.-V. was supported by the predoctoral i-PFIS IIS-enterprise contract in science and technologies in health (IFI18/00014) from ISCiii.Peer reviewe

Heat-related cardiorespiratory mortality: effect modification by air pollution across 482 cities from 24 countries

Background Evidence on the potential interactive effects of heat and ambient air pollution on cause-specific mortality is inconclusive and limited to selected locations. Objectives We investigated the effects of heat on cardiovascular and respiratory mortality and its modification by air pollution during summer months (six consecutive hottest months) in 482 locations across 24 countries. Methods Location-specific daily death counts and exposure data (e.g., particulate matter with diameters ≤ 2.5 µm [PM2.5]) were obtained from 2000 to 2018. We used location-specific confounder-adjusted Quasi-Poisson regression with a tensor product between air temperature and the air pollutant. We extracted heat effects at low, medium, and high levels of pollutants, defined as the 5th, 50th, and 95th percentile of the location-specific pollutant concentrations. Country-specific and overall estimates were derived using a random-effects multilevel meta-analytical model. Results Heat was associated with increased cardiorespiratory mortality. Moreover, the heat effects were modified by elevated levels of all air pollutants in most locations, with stronger effects for respiratory than cardiovascular mortality. For example, the percent increase in respiratory mortality per increase in the 2-day average summer temperature from the 75th to the 99th percentile was 7.7% (95% Confidence Interval [CI] 7.6-7.7), 11.3% (95%CI 11.2-11.3), and 14.3% (95% CI 14.1-14.5) at low, medium, and high levels of PM2.5, respectively. Similarly, cardiovascular mortality increased by 1.6 (95%CI 1.5-1.6), 5.1 (95%CI 5.1-5.2), and 8.7 (95%CI 8.7-8.8) at low, medium, and high levels of O3, respectively. Discussion We observed considerable modification of the heat effects on cardiovascular and respiratory mortality by elevated levels of air pollutants. Therefore, mitigation measures following the new WHO Air Quality Guidelines are crucial to enhance better health and promote sustainable development

Comparison of weather station and climate reanalysis data for modelling temperature-related mortality

Epidemiological analyses of health risks associated with non-optimal temperature are traditionally based on ground observations from weather stations that offer limited spatial and temporal coverage. Climate reanalysis represents an alternative option that provide complete spatio-temporal exposure coverage, and yet are to be systematically explored for their suitability in assessing temperature-related health risks at a global scale. Here we provide the first comprehensive analysis over multiple regions to assess the suitability of the most recent generation of reanalysis datasets for health impact assessments and evaluate their comparative performance against traditional station-based data. Our findings show that reanalysis temperature from the last ERA5 products generally compare well to station observations, with similar non-optimal temperature-related risk estimates. However, the analysis offers some indication of lower performance in tropical regions, with a likely underestimation of heat-related excess mortality. Reanalysis data represent a valid alternative source of exposure variables in epidemiological analyses of temperature-related risk. © 2022, The Author(s).The original version of this Article contained an error in Affiliation 25, which was incorrectly given as ‘Faculty of Medicine ArqFuturo INSPER, University of São Paulo, São Paulo, Brazil’. The correct affiliation is listed below. Faculty of Medicine, University of São Paulo, São Paulo, Brazil The original Article has been corrected. © The Author(s) 2022.The study was primarily supported by Grants from the European Commission’s Joint Research Centre Seville (Research Contract ID: JRC/SVQ/2020/MVP/1654), Medical Research Council-UK (Grant ID: MR/R013349/1), Natural Environment Research Council UK (Grant ID: NE/R009384/1), European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655). The following individual Grants also supported this work: J.K and A.U were supported by the Czech Science Foundation, project 20-28560S. A.T was supported by MCIN/AEI/10.13039/501100011033, Grant CEX2018-000794-S. V.H was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant agreement No 101032087. This work was generated using Copernicus Climate Change Service (C3S) information [1985–2019]

Fluctuating temperature modifies heat-mortality association around the globe

Studies have investigated the effects of heat and temperature variability (TV) on mortality. However, few assessed whether TV modifies the heat-mortality association. Data on daily temperature and mortality in the warm season were collected from 717 locations across 36 countries. TV was calculated as the standard deviation of the average of the same and previous days’ minimum and maximum temperatures. We used location-specific quasi-Poisson regression models with an interaction term between the cross-basis term for mean temperature and quartiles of TV to obtain heat-mortality associations under each quartile of TV, and then pooled estimates at the country, regional, and global levels. Results show the increased risk in heat-related mortality with increments in TV, accounting for 0.70% (95% confidence interval [CI]: −0.33 to 1.69), 1.34% (95% CI: −0.14 to 2.73), 1.99% (95% CI: 0.29–3.57), and 2.73% (95% CI: 0.76–4.50) of total deaths for Q1–Q4 (first quartile–fourth quartile) of TV. The modification effects of TV varied geographically. Central Europe had the highest attributable fractions (AFs), corresponding to 7.68% (95% CI: 5.25–9.89) of total deaths for Q4 of TV, while the lowest AFs were observed in North America, with the values for Q4 of 1.74% (95% CI: −0.09 to 3.39). TV had a significant modification effect on the heat-mortality association, causing a higher heat-related mortality burden with increments of TV. Implementing targeted strategies against heat exposure and fluctuant temperatures simultaneously would benefit public health. © 2022 The Author(s)Funding text 1: This study was supported by the Australian Research Council (DP210102076) and the Australian National Health and Medical Research Council (APP2000581). Y.W and B.W. were supported by the China Scholarship Council (nos. 202006010044 and 202006010043); S.L. was supported by an Emerging Leader Fellowship of the Australian National Health and Medical Research Council (no. APP2009866); Y.G. was supported by Career Development Fellowship (no. APP1163693) and Leader Fellowship (no. APP2008813) of the Australian National Health and Medical Research Council; J.K. and A.U. were supported by the Czech Science Foundation (project no. 20–28560S); N.S. was supported by the National Institute of Environmental Health Sciences-funded HERCULES Center (no. P30ES019776); Y.H. was supported by the Environment Research and Technology Development Fund (JPMEERF15S11412) of the Environmental Restoration and Conservation Agency; M.d.S.Z.S.C. and P.H.N.S. were supported by the São Paulo Research Foundation (FAPESP); H.O. and E.I. were supported by the Estonian Ministry of Education and Research (IUT34–17); J.M. was supported by a fellowship of Fundação para a Ciência e a Tecnlogia (SFRH/BPD/115112/2016); A.G. and F.S. were supported by the Medical Research Council UK (grant ID MR/R013349/1), the Natural Environment Research Council UK (grant ID NE/R009384/1), and the EU's Horizon 2020 project, Exhaustion (grant ID 820655); A.S. and F.d.D. were supported by the EU's Horizon 2020 project, Exhaustion (grant ID 820655); V.H. was supported by the Spanish Ministry of Economy, Industry and Competitiveness (grant ID PCIN-2017–046); and A.T. by MCIN/AEI/10.13039/501100011033 (grant CEX2018-000794-S). Statistics South Africa kindly provided the mortality data, but had no other role in the study. Y.G. A.G. M.H. and B. Armstrong set up the collaborative network. Y.G. S.L. and Y.W. designed the study. Y.G. S.L. and A.G. developed the statistical methods. Y.W. B.W. S.L. and Y.G. took the lead in drafting the manuscript and interpreting the results. Y.W. B.W. Y.G. A.G. S.T. A.O. A.U. A.S. A.E. A.M.V.-C. A. Zanobetti, A.A. A. Zeka, A.T. B. Alahmad, B. Armstrong, B.F. C.Í. C. Ameling, C.D.l.C.V. C. Åström, D.H. D.V.D. D.R. E.I. E.L. F.M. F.A. F.D. F.S. G.C.-E. H. Kan, H.O. H. Kim, I.-H.H. J.K. J.M. J.S. K.K. M.H.-D. M.S.R. M.H. M.P. M.d.S.Z.S.C. N.S. P.M. P.G. P.H.N.S. R.A. S.O. T.N.D. V.C. V.H. W.L. X.S. Y.H. M.L.B. and S.L. provided the data and contributed to the interpretation of the results and the submitted version of the manuscript. Y.G. S.L. and Y.W. accessed and verified the data. All of the authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication. The authors declare no competing interests.; Funding text 2: This study was supported by the Australian Research Council ( DP210102076 ) and the Australian National Health and Medical Research Council ( APP2000581 ). Y.W and B.W. were supported by the China Scholarship Council (nos. 202006010044 and 202006010043 ); S.L. was supported by an Emerging Leader Fellowship of the Australian National Health and Medical Research Council (no. APP2009866 ); Y.G. was supported by Career Development Fellowship (no. APP1163693) and Leader Fellowship (no. APP2008813) of the Australian National Health and Medical Research Council ; J.K. and A.U. were supported by the Czech Science Foundation (project no. 20–28560S ); N.S. was supported by the National Institute of Environmental Health Sciences -funded HERCULES Center (no. P30ES019776 ); Y.H. was supported by the Environment Research and Technology Development Fund ( JPMEERF15S11412 ) of the Environmental Restoration and Conservation Agency; M.d.S.Z.S.C. and P.H.N.S. were supported by the São Paulo Research Foundation (FAPESP); H.O. and E.I. were supported by the Estonian Ministry of Education and Research ( IUT34–17 ); J.M. was supported by a fellowship of Fundação para a Ciência e a Tecnlogia ( SFRH/BPD/115112/2016 ); A.G. and F.S. were supported by the Medical Research Council UK (grant ID MR/R013349/1 ), the Natural Environment Research Council UK (grant ID NE/R009384/1 ), and the EU’s Horizon 2020 project, Exhaustion (grant ID 820655 ); A.S. and F.d.D. were supported by the EU’s Horizon 2020 project, Exhaustion (grant ID 820655 ); V.H. was supported by the Spanish Ministry of Economy, Industry and Competitiveness (grant ID PCIN-2017–046 ); and A.T. by MCIN/AEI/10.13039/501100011033 (grant CEX2018-000794-S). Statistics South Africa kindly provided the mortality data, but had no other role in the study

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE