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This paper describes the GISS‐E2.1 contribution to the Coupled Model Intercomparison Project, Phase 6 (CMIP6). This model version differs from the predecessor model (GISS‐E2) chiefly due to parameterization improvements to the atmospheric and ocean model components, while keeping atmospheric resolution the same. Model skill when compared to modern era climatologies is significantly higher than in previous versions. Additionally, updates in forcings have a material impact on the results. In particular, there have been specific improvements in representations of modes of variability (such as the Madden‐Julian Oscillation and other modes in the Pacific) and significant improvements in the simulation of the climate of the Southern Oceans, including sea ice. The effective climate sensitivity to 2xCO2 is slightly higher than previously at 2.7‐‐3.1°C (depending on version), and is a result of lower CO2 radiative forcing and stronger positive feedbacks.

This paper presents the response to anthropogenic forcing in the GISS-E2.1 climate models for the 21st century Shared Socioeconomic Pathways emission scenarios within the Coupled Model Intercomparison Project Phase 6 (CMIP6). The experiments were performed using an updated and improved version of the NASA Goddard Institute for Space Studies (GISS) coupled general circulation model that includes two different versions for atmospheric composition: A non-interactive version (NINT) with prescribed composition and a tuned aerosol indirect effect and the One-Moment Aerosol model (OMA) version with fully interactive aerosols which includes a parameterized first indirect aerosol effect on clouds. The effective climate sensitivities are 3.0°C and 2.9°C for the NINT and OMA models, respectively. Each atmospheric version is coupled to two different ocean general circulation models: The GISS ocean model (E2.1-G) and HYCOM (E2.1-H). We describe the global mean responses for all future scenarios and spatial patterns of change for surface air temperature and precipitation for four of the marker scenarios: SSP1-2.6, SSP2-4.5, SSP4-6.0, and SSP5-8.5. By 2100, global mean warming ranges from 1.5°C to 5.2°C relative to 1,850–1,880 mean temperature. Two high-mitigation scenarios SSP1-1.9 and SSP1-2.6 limit the surface warming to below 2°C by the end of the 21st century, except for the NINT E2.1-H model that simulates 2.2°C of surface warming. For the high emission scenario SSP5-8.5, the range is 4.6–5.2°C at 2100. Due to about 15% larger effective climate sensitivity and stronger transient climate response in both NINT and OMA CMIP6 models compared to CMIP5 versions, there is a stronger warming by 2100 in the SSP emission scenarios than in the comparable Representative Concentration Pathway (RCP) scenarios in CMIP5. Changes in sea ice area are highly correlated to global mean surface air temperature anomalies and show steep declines in both hemispheres, with the largest sea ice area decreases occurring during September in the Northern Hemisphere in both E2.1-G (−1.21 × 106 km2/°C) and E2.1-H models (−0.94 × 106 km2/°C). Both coupled models project decreases in the Atlantic overturning stream function by 2100. The largest decrease of 56%–65% in the 21st century overturning stream function is produced in the warmest scenario SSP5-8.5 in the E2.1-G model, comparable to the reduction in the corresponding CMIP5 GISS-E2 RCP8.5 simulation. Both low-end scenarios SSP1-1.9 and SSP1-2.6 also simulate substantial reductions of the overturning (9%–37%) with slow recovery of about 10% by the end of the 21st century (relative to the maximum decrease at the middle of the 21st century).

Simulations of the CMIP6 historical period 1850‐‐2014, characterized by the emergence of anthropogenic climate drivers like greenhouse gases, are presented for different configurations of the NASA Goddard Institute for Space Studies (GISS) Earth System ModelE2.1. The GISS‐E2.1 ensembles are more sensitive to forcing than their CMIP5 predecessors (GISS‐E2), but warm less during recent decades due to reduced total forcing. This forcing reduction is attributed to an increase in longwave opacity in pre‐industrial simulations, resulting in an atmosphere less sensitive to further increases in opacity that result from rising greenhouse gas concentrations. This demonstrates the importance of the base climatology to forcing and forced climate trends. Most model versions match observed temperature trends since 1979 from the ocean to the stratosphere. The choice of ocean model is important to the transient climate response, as found in CMIP5 GISS‐E2: the model that more efficiently exports heat to the deep ocean shows a smaller rise in tropospheric temperature. Model sea level rise over the historical period is traced to excessive drawdown of aquifers to meet irrigation demand with a smaller contribution from thermal expansion. This shows how fully coupled models can provide indirect observational constraints upon forcing, in this case, constraining irrigation rates with observed sea level changes. The overall agreement of GISS‐E2.1 with observed trends is familiar from evaluation of its predecessors, as is the conclusion that these trends are almost entirely anthropogenic in origin.

Cardiac fibrosis is central to the pathology of heart failure, particularly heart failure with preserved ejection fraction (HFpEF). Irrespective of the underlying profibrotic condition (e.g. ageing, diabetes, hypertension), maladaptive cardiac fibrosis is defined by the transformation of resident fibroblasts to matrix‐secreting myofibroblasts. Numerous profibrotic factors have been identified at the molecular level (e.g. TGFβ, IL11, AngII), which activate gene expression programs for myofibroblast activation. A number of existing HF therapies indirectly target fibrotic pathways; however, despite multiple clinical trials in HFpEF, a specific clinically effective antifibrotic therapy remains elusive. Therapeutic inhibition of TGFβ, the master‐regulator of fibrosis, has unfortunately proven toxic and ineffective in clinical trials to date, and new approaches are needed. In this review, we discuss the pathophysiology and clinical implications of interstitial fibrosis in HFpEF. We provide an overview of trials targeting fibrosis in HFpEF to date and discuss the promise of potential new therapeutic approaches and targets in the context of underlying molecular mechanisms. Graphical Abstract This review discusses recent advances in novel therapeutic approaches against cardiac fibrosis in heart failure with preserved ejection fraction and their underlying molecular mechanisms.

Severe and persistent 21st-century drought in southwestern North America (SWNA) motivates comparisons to medieval megadroughts and questions about the role of anthropogenic climate change. We use hydrological modeling and new 1200-year tree-ring reconstructions of summer soil moisture to demonstrate that the 2000–2018 SWNA drought was the second driest 19-year period since 800 CE, exceeded only by a late-1500s megadrought. The megadrought-like trajectory of 2000–2018 soil moisture was driven by natural variability superimposed on drying due to anthropogenic warming. Anthropogenic trends in temperature, relative humidity, and precipitation estimated from 31 climate models account for 47% (model interquartiles of 35 to 105%) of the 2000–2018 drought severity, pushing an otherwise moderate drought onto a trajectory comparable to the worst SWNA megadroughts since 800 CE.

One classical version of cosmological argument, defended famously by Thomas Aquinas and Duns Scotus, deduces the existence of a First Cause from the existence of a particular sort of causal series: one that is ‘essentially ordered’. This argument has received renewed defence in recent work by Feser (2013), Cohoe (2013), and Kerr (2015). I agree with these philosophers that the argument is sound. I believe, however, that the standard defence given of the ECA in these philosophers can be complemented by a formulation that appeals to the powers theory of possibility. This approach to possibility has been defended in recent years by, for example, Pruss (2002), Jacobs (2010), and Vetter (2015). In this article, I show how this modal theory allows us to defend the ECA in a way that is dialectically advantageous as well as clarifying.

The assessment of competitive movement demands in team sports has traditionally relied upon global positioning system (GPS) analyses presented as fixed-time epochs (e.g., 5-40 min). More recently, presenting game data as a rolling average has become prevalent due to concerns over a loss of sampling resolution associated with the windowing of data over fixed periods. Accordingly, this study compared rolling average (ROLL) and fixed-time (FIXED) epochs for quantifying the peak movement demands of international rugby union match-play as a function of playing position. Elite players from three different squads (n = 119) were monitored using 10 Hz GPS during 36 matches played in the 2014-2017 seasons. Players categorised broadly as forwards and backs, and then by positional sub-group (FR: front row, SR: second row, BR: back row, HB: half back, MF: midfield, B3: back three) were monitored during match-play for peak values of high-speed running (>5 m·s-1; HSR) and relative distance covered (m·min-1) over 60-300 s using two types of sample-epoch (ROLL, FIXED). Irrespective of the method used, as the epoch length increased, values for the intensity of running actions decreased (e.g., For the backs using the ROLL method, distance covered decreased from 177.4 ± 20.6 m·min-1 in the 60 s epoch to 107.5 ± 13.3 m·min-1 for the 300 s epoch). For the team as a whole, and irrespective of position, estimates of fixed effects indicated significant between-method differences across all time-points for both relative distance covered and HSR. Movement demands were underestimated consistently by FIXED versus ROLL with differences being most pronounced using 60 s epochs (95% CI HSR: -6.05 to -4.70 m·min-1, 95% CI distance: -18.45 to -16.43 m·min-1). For all HSR time epochs except one, all backs groups increased more (p < 0.01) from FIXED to ROLL than the forward groups. Linear mixed modelling of ROLL data highlighted that for HSR (except 60 s epoch), SR was the only group not significantly different to FR. For relative distance covered all other position groups were greater than the FR (p < 0.05). The FIXED method underestimated both relative distance (~11%) and HSR values (up to ~20%) compared to the ROLL method. These differences were exaggerated for the HSR variable in the backs position who covered the greatest HSR distance; highlighting important consideration for those implementing the FIXED method of analysis. The data provides coaches with a worst-case scenario reference on the running demands required for periods of 60-300 s in length. This information offers novel insight into game demands and can be used to inform the design of training games to increase specificity of preparation for the most demanding phases of matches.

The use of pesticides within agricultural ecosystems has led to wide concern regarding negative effects on the environment. One possible alternative is the use of predators of pest species that naturally occur within agricultural ecosystems. However, the mechanistic basis for how species can be manipulated in order to maximize pest control remains unclear. We carried out a meta-analysis of 51 studies that manipulated predator species richness in reference to suppression of herbivore prey to determine which components of predator diversity affect pest control. Overall, functional diversity (FD) based on predator’s habitat domain, diet breadth and hunting strategy was ranked as the most important variable. Our analysis showed that increases in FD in polycultures led to greater prey suppression compared to both the mean of the component predator species, and the most effective predator species, in monocultures. Further analysis of individual traits indicated these effects are likely to be driven by broad niche differentiation and greater resource exploitation in functionally diverse predator communities. A decoupled measure of phylogenetic diversity, whereby the overlap in variation with FD was removed, was not found to be an important driver of prey suppression. Our results suggest that increasing FD in predatory invertebrates will help maximize pest control ecosystem services in agricultural ecosystems, with the potential to increase suppression above that of the most effective predator species.

For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark 1 – 7 . Here we examined whether IL-11, a pro-inflammatory cytokine of the IL-6 family, has a negative effect on age-associated disease and lifespan. As mice age, IL-11 is upregulated across cell types and tissues to regulate an ERK–AMPK–mTORC1 axis to modulate cellular, tissue- and organismal-level ageing pathologies. Deletion of Il11 or Il11ra1 protects against metabolic decline, multi-morbidity and frailty in old age. Administration of anti-IL-11 to 75-week-old mice for 25 weeks improves metabolism and muscle function, and reduces ageing biomarkers and frailty across sexes. In lifespan studies, genetic deletion of Il11 extended the lives of mice of both sexes, by 24.9% on average. Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%. Together, these results demonstrate a role for the pro-inflammatory factor IL-11 in mammalian healthspan and lifespan. We suggest that anti-IL-11 therapy, which is currently in early-stage clinical trials for fibrotic lung disease, may provide a translational opportunity to determine the effects of IL-11 inhibition on ageing pathologies in older people. IL-11 is identified as a key regulator of ERK–AMPK–mTORC1 signalling, metabolism, inflammation and age-related disease and lifespan in mouse and human.

Streamflow often increases after fire, but the persistence of this effect and its importance to present and future regional water resources are unclear. This paper addresses these knowledge gaps for the western United States (WUS), where annual forest fire area increased by more than 1,100% during 1984 to 2020. Among 72 forested basins across the WUS that burned between 1984 and 2019, the multibasin mean streamflow was significantly elevated by 0.19 SDs (P < 0.01) for an average of 6 water years postfire, compared to the range of results expected from climate alone. Significance is assessed by comparing prefire and postfire streamflow responses to climate and also to streamflow among 107 control basins that experienced little to no wildfire during the study period. The streamflow response scales with fire extent: among the 29 basins where > 20% of forest area burned in a year, streamflow over the first 6 water years postfire increased by a multibasin average of 0.38 SDs, or 30%. Postfire streamflow increases were significant in all four seasons. Historical fire–climate relationships combined with climate model projections suggest that 2021 to 2050 will see repeated years when climate is more fire-conducive than in 2020, the year currently holding the modern record for WUS forest area burned. These findings center on relatively small, minimally managed basins, but our results suggest that burned areas will grow enough over the next 3 decades to enhance streamflow at regional scales. Wildfire is an emerging driver of runoff change that will increasingly alter climate impacts on water supplies and runoff-related risks.