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Deliberately removing carbon dioxide from the atmosphere is an important element of bringing mitigation pathways in line with the climate goals of the Paris Agreement. To reach global net-zero CO2 emissions and limit global warming to 1.5°C with no or limited overshoot, global mitigation pathways assessed by IPCC’s Sixth Assessment Report require some world regions to achieve net-negative CO2 emissions with large-scale carbon dioxide removal (CDR) deployment. This raises important questions about the availability and feasibility of CDR deployment in different societal and political contexts. This paper therefore combines an analysis of CDR deployment in a sample of scenarios from the IPCC AR6 database with a bottom-up analysis of the state of CDR governance and policy in countries considered key in scaling up CDR capacity and not yet covered by existing research. In particular, the paper focuses on Brazil, China, and India as important emerging economies and large emitters. We highlight the expected use of CDR methods in those regions in scenarios and systematically assess and compare the level of CDR regulation and innovation across these countries. This comparative perspective has the potential to broaden the understanding of existing and emerging CDR policies and politics. The synthesis of the case studies provides three key contributions to existing literature: First, we explore the state of CDR governance and policymaking in key emerging economies. As in OECD countries, there is a notable lack of CDR regulation and innovation to enable the scale of CDR required in the short- and medium term. Second, we identify that repurposing policies is a key type of emerging CDR policymaking in these countries targeting CDR methods in the land use, land use change and forestry (LULUCF) sector. We find that the repurposing efforts strengthen the level of regulation and innovation for this group of methods. Third, we explore three building blocks (regional differentiation, de

AIMS: Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. Our objective was to examine if modifiable anthropometric obesity indices show putatively causal association with kidney health and disease and highlight biological mechanisms of potential relevance to the association between obesity and the kidney. METHODS AND RESULTS: We performed observational, one-sample, two-sample Mendelian randomization (MR) and multivariable MR studies in ∼300 000 participants of white-British ancestry from UK Biobank and participants of predominantly European ancestry from genome-wide association studies. The MR analyses revealed that increasing values of genetically predicted body mass index and waist circumference were causally associated with biochemical indices of renal function, kidney health index (a composite renal outcome derived from blood biochemistry, urine analysis, and International Classification of Disease-based kidney disease diagnoses), and both acute and chronic kidney diseases of different aetiologies including hypertensive renal disease and diabetic nephropathy. Approximately 13-16% and 21-26% of the potentially causal effect of obesity indices on kidney health were mediated by blood pressure and type 2 diabetes, respectively. A total of 61 pathways mapping primarily onto transcriptional/translational regulation, innate and adaptive immunity, and extracellular matrix and metabolism were associated with obesity measures in gene set enrichment analysis in up to 467 kidney transcriptomes. CONCLUSIONS: Our data show that a putatively causal association of obesity with renal health is largely independent of blood pressure and type 2 diabetes and uncover the signatures of obesity on the transcriptome of human kidney.

The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension.

Interpersonal touch behavior differs across cultures, yet no study to date has systematically tested for cultural variation in affective touch, nor examined the factors that might account for this variability. Here, over 14,000 individuals from 45 countries were asked whether they embraced, stroked, kissed, or hugged their partner, friends, and youngest child during the week preceding the study. We then examined a range of hypothesized individual-level factors (sex, age, parasitic history, conservatism, religiosity, and preferred interpersonal distance) and cultural-level factors (regional temperature, parasite stress, regional conservatism, collectivism, and religiosity) in predicting these affective-touching behaviors. Our results indicate that affective touch was most prevalent in relationships with partners and children, and its diversity was relatively higher in warmer, less conservative, and religious countries, and among younger, female, and liberal people. This research allows for a broad and integrated view of the bases of cross-cultural variability in affective touch.

BACKGROUND: The WHO estimates a global shortage of 2.8 million physicians, with severe deficiencies especially in low and middle-income countries (LMIC). The unequitable distribution of physicians worldwide is further exacerbated by the migration of physicians from LMICs to high-income countries (HIC). This large-scale migration has numerous economic consequences which include increased mortality associated with inadequate physician supply in LMICs. METHODS: We estimate the economic cost for LMICs due to excess mortality associated with physician migration. To do so, we use the concept of a value of statistical life and marginal mortality benefit provided by physicians. Uncertainty of our estimates is evaluated with Monte Carlo analysis. RESULTS: We estimate that LMICs lose US$15.86 billion (95% CI $3.4 to $38.2) annually due to physician migration to HICs. The greatest total costs are incurred by India, Nigeria, Pakistan and South Africa. When these costs are considered as a per cent of gross national income, the cost is greatest in the WHO African region and in low-income countries. CONCLUSION: The movement of physicians from lower to higher income settings has substantial economic consequences. These are not simply the result of the movement of human capital, but also due to excess mortality associated with loss of physicians. Valuing these costs can inform international and domestic policy discussions that are meant to address this issue.

AIMS: Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)-the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. METHODS AND RESULTS: We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. CONCLUSION: Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.

The Lancet Commission on Global Surgery defined six surgical indicators and a framework for a national surgical plan that aimed to incorporate surgical care as a part of global public health. Multiple countries have since begun national surgical planning; each faces unique challenges in doing so. Implementation science can be used to more systematically explain this heterogeneous process, guide implementation efforts and ultimately evaluate progress. We describe our intervention using the Consolidated Framework for Implementation Research. This framework requires identifying characteristics of the intervention, the individuals involved, the inner and outer setting of the intervention, and finally describing implementation processes. By hosting a consultative symposium with clinicians and policy makers from around the world, we are able to specify key aspects of each element of this framework. We define our intervention as the incorporation of surgical care into public health planning, identify local champions as the key individuals involved, and describe elements of the inner and outer settings. Ultimately we describe top-down and bottom-up models that are distinct implementation processes. With the Consolidated Framework for Implementation Research, we are able to identify specific strategic models that can be used by implementers in various settings. While the integration of surgical care into public health throughout the world may seem like an insurmountable challenge, this work adds to a growing effort that seeks to find a way forward.

The Millennium Development Goals have ended and the Sustainable Development Goals have begun, marking a shift in the global health landscape. The frame of reference has changed from a focus on 8 development priorities to an expansive set of 17 interrelated goals intended to improve the well-being of all people. In this time of change, several groups, including the Lancet Commission on Global Surgery, have brought a critical problem to the fore: 5 billion people lack access to safe, affordable surgical and anaesthesia care when needed. The magnitude of this problem and the world's new focus on strengthening health systems mandate reimagined roles for and renewed commitments from high income country actors in global surgery. To discuss the way forward, on 6 May 2015, the Commission held its North American launch event in Boston, Massachusetts. Panels of experts outlined the current state of knowledge and agreed on the roles of surgical colleges and academic medical centres; trainees and training programmes; academia; global health funders; the biomedical devices industry, and news media and advocacy organisations in building sustainable, resilient surgical systems. This paper summarises these discussions and serves as a consensus statement providing practical advice to these groups. It traces a common policy agenda between major actors and provides a roadmap for maximising benefit to surgical patients worldwide. To close the access gap by 2030, individuals and organisations must work collectively, interprofessionally and globally. High income country actors must abandon colonial narratives and work alongside low and middle income country partners to build the surgical systems of the future.