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The undifferentiated clonal cell line, H9c2, derived from left ventricular rat heart tissue, has been extensively used in cardiovascular research. In the present study, 2 independent laboratories aimed to investigate the cells’ capacity to differentiate into distinct cardiac-like cells. Undifferentiated H9c2 cells were supplemented daily for a period of 6 - 12 days, with varying concentrations of retinoic acid (RA) (10nM, 30nM and 1μM), in standard cell culture medium containing either 1% foetal bovine, or horse serum, in order to stimulate differentiation of the cells into a more cardiac-specific phenotype. Light microscopy confirmed some degree of morphological change associated with differentiation, and a significant increase in oxidative phosphorylation following RA treatment was observed. However, Western blot probing for the cardiac-specific markers Cardiac Troponin T (cTnT) and Myosin Light Chain-2v (MLC2v) indicated little to no differentiation, although immunocytochemistry indicated the presence of cTnT expression. Thus, it was found that the differentiation protocol induced differentiation in some, but not all cells, thereby generating a heterogeneous cell population. Our findings suggest that the H9c2 cell line may display some degree of resistance to differentiation. This should be kept in mind when considering to use this model for cardiovascular research.

This research proposes a parametric design process model to improve the structural engineering project team performance by automating the design and three-dimensional modelling procedures of box culverts. Although standardised design procedures can reduce the design time of repetitive structures such as box culverts, the increased time and effort required for revising construction drawings negatively impacts a project's performance. A literature review was conducted to develop a theoretical process model to improve the current structural design optimisation and three-dimensional modelling procedures of box culverts. The proposed process model was validated using structured interviews with professionally registered structural engineers for appropriateness to box culverts and the potential to improve project performance. The data analysis revealed that the interviewed engineers were in favour of automating the design optimisation and three-dimensional modelling procedures of box culverts. Moreover, parametric design automation would result in improved project performance when encountering an inevitable design change. However, the user's control over the output of each process should not be discarded. This study can help readers understand the transformation of the structural design and three-dimensional modelling procedures of repetitive structures, such as box culverts, into an algorithmic form to achieve improved project performance. [ABSTRACT FROM AUTHOR]

Limiting warming to well below 2°C requires rapid and complete decarbonisation of energy systems. We compare economy-wide modelling of 1.5°C and 2°C scenarios with sector-focused analyses of four critical sectors that are difficult to decarbonise: aviation, shipping, road freight transport, and industry. We develop and apply a novel framework to analyse and track mitigation progress in these sectors. We find that emission reductions in the 1.5°C and 2°C scenarios of the IMAGE model come from deep cuts in CO2 intensities and lower energy intensities, with minimal demand reductions in these sectors' activity. We identify a range of additional measures and policy levers that are not explicitly captured in modelled scenarios but could contribute significant emission reductions. These are demand reduction options, and include less air travel (aviation), reduced transportation of fossil fuels (shipping), more locally produced goods combined with high load factors (road freight), and a shift to a circular economy (industry). We discuss the challenges of reducing demand both for economy-wide modelling and for policy. Based on our sectoral analysis framework, we suggest modelling improvements and policy recommendations, calling on the relevant UN agencies to start tracking mitigation progress through monitoring key elements of the framework (CO2 intensity, energy efficiency, and demand for sectoral activity, as well as the underlying drivers), as a matter of urgency. Key policy insights Four critical sectors (aviation, shipping, road freight, and industry) cannot cut their CO2 emissions to zero rapidly with technological supply-side options alone. Without large-scale negative emissions, significant demand reductions for those sectors' activities are needed to meet the 1.5–2°C goal. Policy priorities include affordable alternatives to frequent air travel; smooth connectivity between low-carbon travel modes; speed reductions in shipping and reduced demand for transporting fossil fuels; distributed manufacturing and local storage; and tightening standards for material use and product longevity. The COVID-19 crisis presents a unique opportunity to enact lasting CO2 emissions reductions, through switching from frequent air travel to other transport modes and online interactions. Policies driving significant demand reductions for the critical sectors' activities would reduce reliance on carbon removal technologies that are unavailable at scale. [ABSTRACT FROM AUTHOR]

There is a need for further integrated research on developing a set of sustainable development objectives, based on the proposed framework of planetary boundaries indicators. The relevant research questions are divided in this paper into four key categories, related to the underlying processes and selection of key indicators, understanding the impacts of different exposure levels and influence of connections between different types of impacts, a better understanding of different response strategies and the available options to implement changes. Clearly, different categories of scientific disciplines and associated models exist that can contribute to the necessary analysis, noting that the distinctions between them are fuzzy. In the paper, we both indicate how different models relate to the four categories of questions but also how further insights can be obtained by connecting the different disciplines (without necessarily fully integrating them). Research on integration can support planetary boundary quantification in a credible way, linking human drivers and social and biophysical impacts. [ABSTRACT FROM AUTHOR]

Efforts to limit climate change below a given temperature level require that global emissions of CO2 cumulated over time remain below a limited quota. This quota varies depending on the temperature level, the desired probability of staying below this level and the contributions of other gases. In spite of this restriction, global emissions of CO2 from fossil fuel combustion and cement production have continued to grow by 2.5% per year on average over the past decade. Two thirds of the CO2 emission quota consistent with a 2 °C temperature limit has already been used, and the total quota will likely be exhausted in a further 30 years at the 2014 emissions rates. We show that CO2 emissions track the high end of the latest generation of emissions scenarios, due to lower than anticipated carbon intensity improvements of emerging economies and higher global gross domestic product growth. In the absence of more stringent mitigation, these trends are set to continue and further reduce the remaining quota until the onset of a potential new climate agreement in 2020. Breaking current emission trends in the short term is key to retaining credible climate targets within a rapidly diminishing emission quota. [ABSTRACT FROM AUTHOR]

Projections of the deployment of Carbon Capture and Storage (CCS) technologies vary considerably. Cumulative emission reductions by CCS until 2100 vary in the majority of projections of the IPCC-TAR scenarios from 220 to 2200 GtCO2. This variation is a result of uncertainty in key determinants of the baselines of different models, such as, technological development (IPCC Special Report on Carbon Dioxide Capture and Storage. Prepared by Working Group III of the Intergovernmental Panel on Climate Change. Cambridge University Press, Cambridge, United Kingdom and New York). Technological key parameters of CCS deployment are power plant efficiency and investment cost, capture cost, transport cost and storage capacity. This study provides insights in how uncertain the key parameters are and how this influences CCS deployment projections. For each parameter, ranges are determined on the basis of the existing literature. CCS deployment is systematically assessed for all of these parameter ranges in a global energy system model (TIMER). The results show that investment cost uncertainty causes the largest range in cumulative CO2 captured from global electricity production (13-176 GtCO2 in 2050) in a scenario with a medium fossil fuel price level. The smallest, but still significant range of 65-91 GtCO2 cumulatively captured until 2050, is caused by the uncertainty in the efficiency of the power plant and capture unit. [ABSTRACT FROM AUTHOR]

We decompose the rise of self-employment in the Netherlands in the period 1992 to 2006. Using Logit estimates we identify the most important determinants of the recent upturn, separately for women and for men. In contrast with findings for the United States, we find that changes in the industrial composition only play a small role. For women, we find that intra-sectoral developments have been important in spurring self-employment. In particular, it has become more common for women to be self-employed in the Trade and Culture sectors. The ageing of society (older people are more often self-employed) is an important cause of the observed increase. This effect is partly compensated by the negative effect of a higher educated labour force. The estimation results imply that both policies to foster self-employment and a socio-cultural trend have been important. We postulate that generic policy effects have been the most important cause of the increase in self-employment. The largest effects were seen just in the last few years of our sample (2004–2006), which appears to be inconsistent with the notion of a longer lasting socio-cultural trend. [ABSTRACT FROM AUTHOR]

This paper presents a set of multi-gas mitigation scenarios that aim for stabilisation of greenhouse gas radiative forcing in 2150 at levels from 3.7 to 5.3 W/m². At the moment, non-CO2 gasses (methane, nitrous oxide, PFCs, HFCs and SF2) contribute to about a quarter of the global emissions. The analysis shows that including these non-CO2 gases in mitigation analysis is crucial in formulating a cost-effective response. For stabilisation at 4.5 W/m², a multi-gas approach leads to 40% lower costs than an approach that would focus at CO2-only. Within the assumptions used in this study, the non-CO2 gasses contribution to total reduction is very large under less stringent targets (up to 60%), but declines under stringent targets. While stabilising at 3.7 W/m² obviously leads to larger environmental benefits than the 4.5 W/m² case (temperature increase in 2100 are 1.9 and 2.3°C, respectively), the costs of the lower target are higher (0.80% and 0.34% of GDP in 2100, respectively). Improving knowledge on how future reduction potential for non-CO2 gasses could develop is shown to be a crucial research question. [ABSTRACT FROM AUTHOR]

The consumption of media -- especially radio and television -- by children has been a topic of research for decades now. Although extensive research has been published on the effects of the media, also in South Africa, very few (if any) publications address the issue of when and what children are viewing in South Africa, and if something should be done about this behaviour. In this article, specific examples of the viewing patterns of children between the ages of 7 and 15 are presented in the context of unacceptable material to which they are exposed. The different roles of parents, broadcasters and legislators are discussed, against the backdrop of recent literature, in an attempt to suggest a way forward. [ABSTRACT FROM AUTHOR]

[1] We explored the climate impacts for two land-use change scenarios, aimed at mitigating the buildup of greenhouse gases in the atmosphere. Using the integrated assessment model IMAGE 2.2, we found that the large-scale implementation in the extratropics of either carbon-sequestration or modern-biomass plantations decreases the CO2 concentration with 70–80 ppmv by the year 2100 compared to a nonmitigation baseline. In a coupled land/atmosphere/ocean/sea-ice model this moderates global warming over the 21st century by 10%. However, the carbon-sequestration option raises the absorption of solar radiation due to a lower albedo compared to the scenario involving modem-biomass plantations (for biofuels production). The albedo-induced difference in global mean temperature is as large as the mitigation by CO2 changes in the two scenarios compared to the baseline. Further, an atmospheric circulation change in the carbon-plantation scenario weakens the supply of moisture from the oceans to North Africa and central Eurasia. In our model this decreases annual mean precipitation over North Africa by up to 10% and further increases summer temperatures over Eurasia. These findings lead us to conclude that other climate impacts than just CO2 changes have to be taken into account when discussing climate-change mitigation options that involve land-use changes. [ABSTRACT FROM AUTHOR]

Competing Interests: Declaration of interests We declare no competing interests.

Targets can distort competition in favor of incumbent firms.

The therapeutic properties of flavonoids are reported to offer cardioprotective benefits against doxorubicin (Dox)-induced cardiotoxicity (DIC). In the current study, we aimed to investigate the prophylactic properties of 7-hydroxyflavanone (7H), a flavonoid with antioxidative properties, against DIC. An in vitro model of DIC was established by exposing H9c2 cardiomyoblasts to Dox for 6 days. Similarly, cells were also co-treated with 7H to assess its ability to mitigate DIC. The data obtained indicate that 7H, as a co-treatment, alleviates Dox-induced oxidative stress by enhancing total glutathione content ( p ≤ 0.001) and superoxide dismutase activity ( p ≤ 0.001) whilst decreasing ROS ( p ≤ 0.001), malondialdehyde production ( p ≤ 0.001) and the secretion of interleukin-6 ( p ≤ 0.001). The data also showed an improvement in mitochondrial function as shown via enhanced bioenergetics, mitochondrial membrane potential, and PGC1-alpha ( p ≤ 0.05) and pAMPK ( p ≤ 0.001) expression. The cardioprotective potential of 7H was further highlighted by its ability attenuate Dox-induced caspase 3/7 activity ( p ≤ 0.001), apoptosis ( p ≤ 0.001) and necrosis ( p ≤ 0.05). In conclusion, our findings demonstrated the cardioprotective benefits of 7H and thus suggests that it could be a suitable candidate cardioprotective agent against DIC.

Environmental risks are a substantial factor in the current burden of disease, and their role is likely to increase in the future. Model-based scenario analysis is used extensively in environmental sciences to explore the potential effects of human activities on the environment. In this Review, we examine the literature on scenarios modelling environmental effects on health to identify the most relevant findings, common methods used, and important research gaps. Health outcomes and measures related to climate change (n=106) and air pollution (n=30) were most frequently studied. Studies examining future disease burden due to changes or policies related to dietary risks were much less common (n=10). Only a few studies assessed more than two environmental risks (n=3), even though risks can accumulate and interact with each other. Studies predominantly covered high-income countries and Asia. Sociodemographic, vulnerability, and health-system changes were rarely accounted for; thus, assessing the full effect of future environmental changes in an integrative way is not yet possible. We recommend that future models incorporate a broader set of determinants of health to more adequately capture their effect, as well as the effect of mitigation and adaptation efforts., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The stability and resilience of the Earth system and human well-being are inseparably linked 1-3 , yet their interdependencies are generally under-recognized; consequently, they are often treated independently 4,5 . Here, we use modelling and literature assessment to quantify safe and just Earth system boundaries (ESBs) for climate, the biosphere, water and nutrient cycles, and aerosols at global and subglobal scales. We propose ESBs for maintaining the resilience and stability of the Earth system (safe ESBs) and minimizing exposure to significant harm to humans from Earth system change (a necessary but not sufficient condition for justice) 4 . The stricter of the safe or just boundaries sets the integrated safe and just ESB. Our findings show that justice considerations constrain the integrated ESBs more than safety considerations for climate and atmospheric aerosol loading. Seven of eight globally quantified safe and just ESBs and at least two regional safe and just ESBs in over half of global land area are already exceeded. We propose that our assessment provides a quantitative foundation for safeguarding the global commons for all people now and into the future., (© 2023. The Author(s).)

Despite its projected crucial role in stringent, future global climate policy, non-CO 2 greenhouse gas (NCGG) mitigation remains a large uncertain factor in climate research. A revision of the estimated mitigation potential has implications for the feasibility of global climate policy to reach the Paris Agreement climate goals. Here, we provide a systematic bottom-up estimate of the total uncertainty in NCGG mitigation, by developing 'optimistic', 'default' and 'pessimistic' long-term NCGG marginal abatement cost (MAC) curves, based on a comprehensive literature review of mitigation options. The global 1.5-degree climate target is found to be out of reach under pessimistic MAC assumptions, as is the 2-degree target under high emission assumptions. In a 2-degree scenario, MAC uncertainty translates into a large projected range in relative NCGG reduction (40-58%), carbon budget (±120 Gt CO 2 ) and policy costs (±16%). Partly, the MAC uncertainty signifies a gap that could be bridged by human efforts, but largely it indicates uncertainty in technical limitations., (© 2023. The Author(s).)

Doxorubicin (Dox)-induced cardiotoxicity (DIC) remains a serious health burden, especially in developing countries. Unfortunately, the high cost of current preventative strategies has marginalized numerous cancer patients because of socio-economic factors. In addition, the efficacy of these strategies, without reducing the chemotherapeutic properties of Dox, is frequently questioned. These limitations have widened the gap and necessity for alternative medicines, like flavonoids, to be investigated. However, new therapeutics may also present their own shortcomings, ruling out the idea of "natural is safe". The U.S. Food and Drug Administration (FDA) has stipulated that the concept of drug-safety be considered in all pre-clinical and clinical studies, to explore the pharmacokinetics and potential interactions of the drugs being investigated. As such our studies on flavonoids, as cardio-protectants against DIC, have been centered around cardiac and cancer models, to ensure that the efficacy of Dox is preserved. Our findings thus far suggest that flavonoids of Galenia africana could be suitable candidates for the prevention of DIC. However, this still requires further investigation, which would focus on drug-interactions as well as in vivo experimental models to determine the extent of cardioprotection., Competing Interests: RB is employed by BioPharm. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sangweni, van Vuuren, Mabasa, Gabuza, Huisamen, Naidoo, Barry and Johnson.)

A breakthrough in oncology research was the discovery of doxorubicin (Dox) in the 1960's. Unlike other chemotherapy drugs, Dox was determined to have a greater therapeutic index. Since its discovery, Dox has, in part, contributed to the 5-10-year survival increase in cancer patient outcomes. Unfortunately, despite its efficacy, both in adult and pediatric cancers, the clinical significance of Dox is tainted by its adverse side effects, which usually manifest as cardiotoxicity. The issue stems from Dox's lack of specificity which prevents it from accurately distinguishing between cancer cells and healthy cell lines, like cardiomyocytes. In addition, the high binding affinity of Dox to topoisomerases, which are abundantly found in cancer and cardiac cells in different isoforms, potentiates DNA damage. In both cell lines, Dox induces cytotoxicity by stimulating the production of pro-oxidants whilst inhibiting antioxidant enzymatic activity. Given that the cardiac muscle has an inherently low antioxidant capacity makes it susceptible to oxidative damage thereby, allowing the accumulation of Dox within the myocardium. Subsequently, Dox drives the activation of cell death pathways, such as ferroptosis, necroptosis and apoptosis by triggering numerous cellular responses that have been implicated in diseases. To date, the exact mechanism by which Dox induces the cardiotoxicity remains an aspect of much interest in cardio-oncology research. Hence, the current review summarizes the proposed mechanisms that are associated with the onset and progression of DIC., (© 2022. The Author(s).)

Background: Modeling suggests that climate change mitigation actions can have substantial human health benefits that accrue quickly and locally. Documenting the benefits can help drive more ambitious and health-protective climate change mitigation actions; however, documenting the adverse health effects can help to avoid them. Estimating the health effects of mitigation (HEM) actions can help policy makers prioritize investments based not only on mitigation potential but also on expected health benefits. To date, however, the wide range of incompatible approaches taken to developing and reporting HEM estimates has limited their comparability and usefulness to policymakers., Objective: The objective of this effort was to generate guidance for modeling studies on scoping, estimating, and reporting population health effects from climate change mitigation actions., Methods: An expert panel of HEM researchers was recruited to participate in developing guidance for conducting HEM studies. The primary literature and a synthesis of HEM studies were provided to the panel. Panel members then participated in a modified Delphi exercise to identify areas of consensus regarding HEM estimation. Finally, the panel met to review and discuss consensus findings, resolve remaining differences, and generate guidance regarding conducting HEM studies., Results: The panel generated a checklist of recommendations regarding stakeholder engagement: HEM modeling, including model structure, scope and scale, demographics, time horizons, counterfactuals, health response functions, and metrics; parameterization and reporting; approaches to uncertainty and sensitivity analysis; accounting for policy uptake; and discounting., Discussion: This checklist provides guidance for conducting and reporting HEM estimates to make them more comparable and useful for policymakers. Harmonization of HEM estimates has the potential to lead to advances in and improved synthesis of policy-relevant research that can inform evidence-based decision making and practice. https://doi.org/10.1289/EHP6745.

Background: The clinical use of Doxorubicin (Dox) is significantly limited by its dose-dependent cardiotoxic side effect. Accumulative evidence suggests that the use of flavonoids, such as the antioxidative Pinocembrin (Pin), could be effective in the prevention of Dox-induced cardiotoxicity. Accordingly, we investigated the ability of pinocembrin (Pin) to attenuate Dox-induced cardiotoxicity in an in vitro H9c2 cardiomyoblast model., Methodology: The cardioprotective potential of Pin was established in H9c2 cells. Here, cells were treated with Dox (2μM), Dox (2μM) + Pin (1μM), and Dox (2μM) + Dexrazoxane (20μM) for 6 days. Thereafter, the safe co-administration of Pin with Dox, in a cancer environment, was investigated in MCF-7 breast cancer cells subjected to the same experimental conditions. Untreated cells served as the control. Subsequently, Pin's ability to attenuate Dox-mediated oxidative stress, impaired mitochondrial bioenergetics and potential, as well as aggravated apoptosis was quantified using biochemical assays., Results: The results demonstrated that co-treatment with Pin mitigates Dox-induced oxidative stress by alleviating the antioxidant enzyme activity of the H9c2 cells. Pin further reduced the rate of apoptosis and necrosis inferred by Dox by improving mitochondrial bioenergetics. Interestingly, Pin did not decrease the efficacy of Dox but, rather increased the rate of apoptosis and necrosis in Dox-treated MCF-7 cells., Conclusion: The findings presented in this study showed, for the first time, that Pin attenuates Dox-induced cardiotoxicity without reducing its chemotherapeutic effect. We propose that additional studies, using in vivo models, should be conducted to further investigate Pin as a suitable candidate in the prevention of the cardiovascular dysfunction inferred by Dox administration., (Copyright © 2020 Sangweni, Moremane, Riedel, van Vuuren, Huisamen, Mabasa, Barry and Johnson.)

Long-term global scenarios have underpinned research and assessment of global environmental change for four decades. Over the past ten years, the climate change research community has developed a scenario framework combining alternative futures of climate and society to facilitate integrated research and consistent assessment to inform policy. Here we assess how well this framework is working and what challenges it faces. We synthesize insights from scenario-based literature, community discussions and recent experience in assessments, concluding that the framework has been widely adopted across research communities and is largely meeting immediate needs. However, some mixed successes and a changing policy and research landscape present key challenges, and we recommend several new directions for the development and use of this framework., Competing Interests: Competing interestsThe authors declare no competing interests., (© Springer Nature Limited 2020.)

A rapid and deep decarbonization of power supply worldwide is required to limit global warming to well below 2 °C. Beyond greenhouse gas emissions, the power sector is also responsible for numerous other environmental impacts. Here we combine scenarios from integrated assessment models with a forward-looking life-cycle assessment to explore how alternative technology choices in power sector decarbonization pathways compare in terms of non-climate environmental impacts at the system level. While all decarbonization pathways yield major environmental co-benefits, we find that the scale of co-benefits as well as profiles of adverse side-effects depend strongly on technology choice. Mitigation scenarios focusing on wind and solar power are more effective in reducing human health impacts compared to those with low renewable energy, while inducing a more pronounced shift away from fossil and toward mineral resource depletion. Conversely, non-climate ecosystem damages are highly uncertain but tend to increase, chiefly due to land requirements for bioenergy.

Scenarios that limit global warming to below 2 °C by 2100 assume significant land-use change to support large-scale carbon dioxide (CO 2 ) removal from the atmosphere by afforestation/reforestation, avoided deforestation, and Biomass Energy with Carbon Capture and Storage (BECCS). The more ambitious mitigation scenarios require even greater land area for mitigation and/or earlier adoption of CO 2 removal strategies. Here we show that additional land-use change to meet a 1.5 °C climate change target could result in net losses of carbon from the land. The effectiveness of BECCS strongly depends on several assumptions related to the choice of biomass, the fate of initial above ground biomass, and the fossil-fuel emissions offset in the energy system. Depending on these factors, carbon removed from the atmosphere through BECCS could easily be offset by losses due to land-use change. If BECCS involves replacing high-carbon content ecosystems with crops, then forest-based mitigation could be more efficient for atmospheric CO 2 removal than BECCS.

Hopes are high that removing fossil fuel subsidies could help to mitigate climate change by discouraging inefficient energy consumption and levelling the playing field for renewable energy. In September 2016, the G20 countries re-affirmed their 2009 commitment (at the G20 Leaders' Summit) to phase out fossil fuel subsidies and many national governments are using today's low oil prices as an opportunity to do so. In practical terms, this means abandoning policies that decrease the price of fossil fuels and electricity generated from fossil fuels to below normal market prices. However, whether the removal of subsidies, even if implemented worldwide, would have a large impact on climate change mitigation has not been systematically explored. Here we show that removing fossil fuel subsidies would have an unexpectedly small impact on global energy demand and carbon dioxide emissions and would not increase renewable energy use by 2030. Subsidy removal would reduce the carbon price necessary to stabilize greenhouse gas concentration at 550 parts per million by only 2-12 per cent under low oil prices. Removing subsidies in most regions would deliver smaller emission reductions than the Paris Agreement (2015) climate pledges and in some regions global subsidy removal may actually lead to an increase in emissions, owing to either coal replacing subsidized oil and natural gas or natural-gas use shifting from subsidizing, energy-exporting regions to non-subsidizing, importing regions. Our results show that subsidy removal would result in the largest CO 2 emission reductions in high-income oil- and gas-exporting regions, where the reductions would exceed the climate pledges of these regions and where subsidy removal would affect fewer people living below the poverty line than in lower-income regions.

Aim: The aim of this study was to evaluate the effects of the sphingosine analogue, FTY720 (Fingolimod), on the outcomes of myocardial ischaemia/reperfusion (I/R) injury., Methods: Two concentrations of FTY720 (1 or 2.5 µM were administered either prior to (PreFTY), or following (PostFTY) 20 minutes' global (GI) or 35 minutes' regional ischaemia (RI) in the isolated, perfused, working rat heart. Functional recovery during reperfusion was assessed following both models of ischaemia, while infarct size (IFS) was determined following RI., Results: FTY720 at 1 µM exerted no effect on functional recovery, while 2.5 µM significantly impaired aortic output (AO) recovery when administered prior to GI (% recovery: control: 33.88 ± 6.12% vs PreFTY: 0%, n = 6-10; p < 0.001), as well as before and after RI ( % recovery: control: 27.86 ± 13.22% vs PreFTY: 0.62% ; p < 0.05; and PostFTY: 2.08%; p = 0.0585, n = 6). FTY720 at 1 µM administered during reperfusion reduced IFS (% of area at risk (AAR): control: 39.89 ± 3.93% vs PostFTY: 26.56 ± 4.32%, n = 6-8; p < 0.05), while 2.5 µM FTY720 reduced IFS irrespective of the time of administration ( % of AAR: control: 39.89 ± 3.93% vs PreFTY: 29.97 ± 1.03% ; and PostFTY: 30.45 ± 2.16%, n = 6; p < 0.05)., Conclusion: FTY720 exerted divergent outcomes on function and tissue survival depending on the concentration administered, as well as the timing of administration.

The 17 Sustainable Development Goals (SDGs) call for a comprehensive new approach to development rooted in planetary boundaries, equity, and inclusivity. The wide scope of the SDGs will necessitate unprecedented integration of siloed policy portfolios to work at international, regional, and national levels toward multiple goals and mitigate the conflicts that arise from competing resource demands. In this analysis, we adopt a comprehensive modeling approach to understand how coherent policy combinations can manage trade-offs among environmental conservation initiatives and food prices. Our scenario results indicate that SDG strategies constructed around Sustainable Consumption and Production policies can minimize problem-shifting, which has long placed global development and conservation agendas at odds. We conclude that Sustainable Consumption and Production policies (goal 12) are most effective at minimizing trade-offs and argue for their centrality to the formulation of coherent SDG strategies. We also find that alternative socioeconomic futures-mainly, population and economic growth pathways-generate smaller impacts on the eventual achievement of land resource-related SDGs than do resource-use and management policies. We expect that this and future systems analyses will allow policy-makers to negotiate trade-offs and exploit synergies as they assemble sustainable development strategies equal in scope to the ambition of the SDGs.