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Griggs et al. (2013) redefine sustainable development as “development that meets the needs of the present while safeguarding Earth’s life-support system, on which the welfare of current and future generations depend.” We recommend this as the end goal that the United Nations sustainable development goals (SDGs) should strive to achieve. Integration across the SDGs is less than what is required from a science perspective. Effective implementation of the SDGs will require States to attend to trade-offs and overlaps. We argue that continuous failure to address integration within the SDGs will jeopardize realization of this ultimate end goal. Therefore, we adopt a systems approach to identify gaps and connections across the goals and targets of the SDGs as well as leverage points for effective intervention. We triangulate across methods of critical analysis, conceptual modeling, and keyword network analysis to draw out seven “overarching directions” that could provide a prioritization framework to enhance efficient implementation of the SDGs. Our results identify main gaps as exclusion of key actors (e.g., corporations) and issues (e.g., intergenerational equity and population); inadequate reconciliation of economic growth with maintaining the Earth system; and deficient consideration of the relationship with international law. Conceptual mapping identifies education and innovation; governance and implementation; sustainable consumption and production; and addressing the key drivers of climate change as key leverage points. The keyword analysis highlights greater integration within the SDGs than what appears at face value. Keywords “access,” “women,” “resources,” and “finance” feature across the SDGs and provide further leverage points. Targeting these issues will facilitate realization of a high proportion of SDGs and correspondingly could have a disproportional impact on effective SDG implementation. We conclude that the success of the SDGs needs to be evaluated by the extent to which it contributes to human development while advancing protection of “planetary must-haves” for current and future generations.

An increasing number of patients with heart failure receive implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation defibrillators (CRT-Ds) with telemonitoring function. Early detection of worsening heart failure, or upstream factors predisposing to worsening heart failure, by implant-based telemonitoring might enable pre-emptive intervention and improve outcomes, but the evidence is weak. We investigated this possibility in IN-TIME, a clinical trial. We did this randomised, controlled trial at 36 tertiary clinical centres and hospitals in Australia, Europe, and Israel. We enrolled patients with chronic heart failure, NYHA class II–III symptoms, ejection fraction of no more than 35%, optimal drug treatment, no permanent atrial fibrillation, and a recent dual-chamber ICD or CRT-D implantation. After a 1 month run-in phase, patients were randomly assigned (1:1) to either automatic, daily, implant-based, multiparameter telemonitoring in addition to standard care or standard care without telemonitoring. Investigators were not masked to treatment allocation. Patients were masked to allocation unless they were contacted because of telemonitoring findings. Follow-up was 1 year. The primary outcome measure was a composite clinical score combining all-cause death, overnight hospital admission for heart failure, change in NYHA class, and change in patient global self-assessment, for the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT00538356. We enrolled 716 patients, of whom 664 were randomly assigned (333 to telemonitoring, 331 to control). Mean age was 65·5 years and mean ejection fraction was 26%. 285 (43%) of patients had NYHA functional class II and 378 (57%) had NYHA class III. Most patients received CRT-Ds (390; 58·7%). At 1 year, 63 (18·9%) of 333 patients in the telemonitoring group versus 90 (27·2%) of 331 in the control group (p=0·013) had worsened composite score (odds ratio 0·63, 95% CI 0·43–0·90). Ten versus 27 patients died during follow-up. Automatic, daily, implant-based, multiparameter telemonitoring can significantly improve clinical outcomes for patients with heart failure. Such telemonitoring is feasible and should be used in clinical practice. Biotronik SE & Co. KG.

The Anthropocene biosphere constitutes an unprecedented phase in the evolution of life on Earth with one species, humans, exerting extensive control. The increasing intensity of anthropogenic forces in the twenty-first century has widespread implications for attempts to govern both human-dominated ecosystems and the last remaining wild ecosystems. Here, we review how evolutionary biology can inform governance and policies in the Anthropocene, focusing on five governance challenges that span biodiversity, environmental management, food and other biomass production, and human health. The five challenges are: ( a ) evolutionary feedbacks, ( b ) maintaining resilience, ( c ) alleviating constraints, ( d ) coevolutionary disruption, and ( e ) biotechnology. Strategies for governing these dynamics will themselves have to be coevolutionary, as eco-evolutionary and social dynamics change in response to each other.

Kawasaki disease has well-described cardiovascular complications. However, the association to autoimmunity and cancer in the long term is not well described. We investigated theses associations using a registry-based matched cohort follow-up study of patients diagnosed with Kawasaki disease. Patients with Kawasaki disease were included and matched 1:5 to a population control group, matched by birth year, sex and incident month of the Kawasaki disease diagnosis. A total of 820 cases < 21 years of age were identified. Median age at diagnosis was 3 years. Median follow-up time was 12 years. Patients with KD were at higher risk of being diagnosed with ischaemic heart disease at 10 years (HR 39.94 (95% CI 5.00–319.28)) and 30 years (HR 8.33 (95% CI 3.03–22.91)). The 10-, 20- and 30-year risks of developing autoimmune disorders were HR 4.23 (95% CI 3.01–5.94), HR 3.23 (95% CI 2.44–4.29) and 2.83 (95% CI, 2.17–3.68), all p < 0.001. Cancer risk was increased after 30 years (HR 2.42 (95% CI, 1.09–5.34)). All-cause mortality after 35 years was also significantly increased (HR 3.14 (95% CI, 1.03–9.60)). Children with KD have increased long-term risks of ischaemic heart disease also of autoimmune disease and cancer, as well as an increased all-cause mortality. The surprisingly increased risk of autoimmunity must be investigated further.What is known:• Kawasaki disease is characterized by acute vasculitis and inflammation that can affect the coronary arteries.• Anti-inflammatory medicine is effective in the acute stages of the disease.What is new:• Children with Kawasaki disease have an increased risk of developing autoimmune disease in the long term.• Kawasaki disease is associated with a slightly increased mortality rate driven by non-cardiovascular causes.

BackgroundSustainable development goals (SDGs) may play a pivotal role in mitigating antimicrobial resistance (AMR). This study examines how countries can integrate AMR mitigation with sustainable development strategies, providing evidence on the prioritisation of AMR-related efforts within both agendas.MethodsWe conducted a comparative analysis of the international global action plan (GAP) and national action plan (NAP) on AMR and SDGs across 10 countries in Africa and Asia. We employed content analysis to map actions to AMR drivers, descriptive statistics to summarise the coverage and focus of the actions and inferential statistics to explore factors associated with the level of policy alignment.ResultsOur findings highlight gaps in the current AMR policy landscape, where drivers are at risk of being redundantly addressed, narrowly focused or entirely overlooked. At the international level, over 50% of AMR drivers are addressed by both frameworks, but national-level overlap is lower (10.5%–47.4%), with Asian countries showing stronger alignment than African countries. Asian countries show a higher proportion of shared drivers than African countries. A considerable proportion of drivers are addressed solely by AMR-NAPs (23.7%–60.5%) or SDG-NAPs (13.2%–31.6%), raising concerns that actions may benefit either sustainable development or AMR at the expense of the other. Finally, 10.5%–26.3% of drivers, mostly distal, are not acknowledged by either framework, highlighting potential policy blind spots.ConclusionsThe Agenda 2030 includes ambitious and cross-cutting goals with GAP-AMR, therefore it can facilitate intersectoral collaboration in addressing AMR. The effective implementation of both agendas will depend on national governments’ capacity to ensure that efforts in combating AMR also contribute to sustainable development.

Non-Technical SummarySeveral transnational corporations, investors, international organizations, and philanthropies have formed coalitions to respond to global social and environmental challenges. Do these coalitions, consisting of large-scale actors, have the capacity to contribute to the sustainability transformations that are needed, or do they perpetuate the same systemic dynamics that created the problems in the first place? We investigate this question by comparing publicly available information from five coalitions working on financial and food systems sustainability.Technical SummaryThis paper examines whether large-scale actor coalitions (LSACs) may contribute to transformations toward equitable and sustainable futures. We use a ‘rapid assessment’ 20-variable framework to collect and analyze empirical data from five food and finance coalitions to identify their roles and capacities for transformative change. Our results indicate that LSACs implement distinct strategies to reach their goals. More specifically, due to their diverse set-ups, LSACs have the ability to raise awareness of sustainability issues, utilize ties to push forward agendas, engage in institutional policy-shaping processes, experiment with solutions, and showcase promising niche initiatives. We identify ways that LSACs’ actions can enable efforts of other change-makers who aim to change the food and finance systems and contribute to systems with high and diverse capacities for transformative change. We also discuss why the roles and lack of certain capacities of LSACs might hinder the creation of enabling conditions for transformative change within the food and finance sectors.Social Media SummaryCoalitions consisting of powerful actors have a range of transformative capacities that, under certain conditions, can support systemic transformations within their sectors.

1. Insect responses to recent climate change are well documented, but the role of resource specialization in determining species vulnerability remains poorly understood. Uncovering local ecological effects of temperature change with high-quality, standardized data provides an important first opportunity for predictions about responses of resource specialists, and long-term time series are essential in revealing these responses. 2. Here, we investigate temperature-related changes in local insect communities, using a sampling site with more than a quarter-million records from two decades (1992–2009) of full-season, quantitative light trapping of 1543 species of moths and beetles. 3. We investigated annual as well as long-term changes in fauna composition, abundance and phenology in a climate-related context using species temperature affinities and local temperature data. Finally, we explored these local changes in the context of dietary specialization. 4. Across both moths and beetles, temperature affinity of specialists increased through net gain of hot-dwelling species and net loss of cold-dwelling species. The climate-related composition of generalists remained constant over time. We observed an increase in species richness of both groups. Furthermore, we observed divergent phenological responses between cold- and hot-dwelling species, advancing and delaying their relative abundance, respectively. Phenological advances were particularly pronounced in cold-adapted specialists. 5. Our results suggest an important role of resource specialization in explaining the compositional and phenological responses of insect communities to local temperature increases. We propose that resource specialists in particular are affected by local temperature increase, leading to the distinct temperature-mediated turnover seen for this group. We suggest that the observed increase in species number could have been facilitated by dissimilar utilization of an expanded growing season by cold- and hot-adapted species, as indicated by their oppositely directed phenological responses. An especially pronounced advancement of cold-adapted specialists suggests that such phenological advances might help minimize further temperature-induced loss of resource specialists. 6. Although limited to a single study site, our results suggest several local changes in the insect fauna in concordance with expected change of larger-scale temperature increases.

The risk of hyperkalemia in relation to different combinations of antihypertensive therapy remains to be elucidated. In this Danish register-based study, we aimed to investigate the risk of developing hyperkalemia in relation to different combinations of antihypertensive therapy. Using incidence density matching, we matched a hyperkalemic patient to five normokalemic patients on eGFR groups, age, sex, and time between study entry and date of potassium measurement. Combination therapies were subdivided into eight groups: beta blockers (BB) + calcium channel blockers (CCB), BB + renin angiotensin system inhibitors (RASi), BB + RASi + mineralocorticoid receptor antagonists (MRA), CCB + RASi, CCB + RASi + thiazides, CCB + thiazides, RASi + thiazides, and other combinations. Multivariable conditional logistic regression was used to estimate the odds of hyperkalemia within 90 days for each of the eight antihypertensive combination therapies. A total of 793 patients with hyperkalemia were matched to 3598 normokalemic patients. In multivariable analysis, odds of developing hyperkalemia when being treated with BB + RASi + MRA was 1.95 (95% CI, 1.39–2.72) compared to RASi + thiazides (reference). CCB + thiazides (OR, 0.76 [95% CI, 0.45–1.28]) and CCB + RASi + Thiazid (OR 0.81 [95% CI, 0.51–1.28]) were among the others not significantly associated with hyperkalemia. Combinations of BB + RASi + MRA were significantly associated with an increased risk of developing hyperkalemia within 90 days of initiating treatment. Patients treated with BB + RASi + MRA within 90 days of treatment initiation, were associated with an increased hyperkalemia risk. When treating hypertensive patients with combination antihypertensive therapy, identifying and monitoring patients with a high risk of dyskalemias is a crucial goal to avoid serious adverse effects and detrimental outcomes related to dyskalemia.

With increased use of transcatheter aortic valve implantation (TAVI) in treatment of aortic stenosis, it is important to evaluate real life data trends in outcomes. This nationwide register-based study aimed to present an outlook on temporal trends in characteristics and outcomes, including mortality. First-time consecutive Danish patients who underwent TAVI from 2010 to 2019 were included in this study. The chi-square and Kruskal–Wallis tests were performed to assess the differences in the characteristics over time and Cochrane–Armitage trend tests were used to examine changes in complications and mortality. Between 2010 and 2019, 4,847 patients (54.6% men, median age 82 [quartile 1 to quartile 3: 77 to 85] years) underwent first-time TAVI. A statistically significant decrease over time was observed for preprocedural hypertension, ischemic heart disease, and heart failure, whereas preexisting chronic obstructive lung disease and preprocedural pacemaker remained stable. We observed a significant decrease in 30- and 90-day postoperative preprocedural pacemaker implantation from 2011 to 2017, with 15.1% and 15.9% in 2011 and 8.6% and 8.9% in 2017, respectively. The incidence of for 30- and 90-day heart failure significantly decreased from 19.3% and 20.3% to 8.5% and 9.1%, respectively. We observed significant changes for 30-day atrial fibrillation, whereas the changes over time for 90-day atrial fibrillation and 30- and 90-day stroke/transient ischemic attack remained insignificant. The all-cause mortality within 30- and 90 days significantly decreased over time from 6.7% and 9.2% in 2011 to 1.5% and 2.7% in 2019 and 2016, respectively. In conclusion, this national study provides general insight on the trends of complications and mortality of TAVI, demonstrating significant reductions over time.

Background The BIO|GUARD-MI study was an unblinded trial that investigated the clinical effect of continuous arrhythmia monitoring with an implantable cardiac monitor in patients after myocardial infarction. Unexpectedly, a pre-specified interim analysis identified a higher incidence of non-cardiovascular adverse events in the treatment group. This was assumed due to a performance bias and ultimately led to premature study termination. By study protocol, participants were expected to visit the study site only when invited after detected arrhythmias. Here, we provide a secondary analysis of participant initiated contacts to the investigational site, which may be the basis of the presumed bias, and employ it to identify a subgroup of participants that may be responsible for the bias. Methods We compare the numbers of participants with self-initiated contacts between the study groups in the total cohort and in 24 subgroups, 14 of them based on the country and 10 on clinical or demographic characteristics. Results In the total cohort, similar percentages of participants of the treatment and control groups visited the investigational site on their own initiative (13.3% vs. 9.7%; P  = 0.12). However, the subgroup analysis revealed a statistically significant difference in participants from Denmark (24.4% vs. 2.3%) after correction for multiple testing ( P  = 0.0004). Other variables support the assumption that this affected the reporting of adverse events. Conclusions In the BIO|GUARD-MI trial, a performance bias is evident in participants from Denmark. In the Danish health system, the general practitioner acts as a gate keeper for secondary and tertiary care, which treatment group participants could bypass. This led to more clinical events being reported in them. When conducting an unblinded diagnostic trial, continuous assessment of characteristics that indicate unexpected participant behaviour is important. Such differences may be driven by characteristics of national health systems. Trial registration https://www.clinicaltrials.gov/ct2/show/NCT02341534 , First registered at ClinicalTrials.gov on January 14, 2015.