Editorial

In the years leading to the handover on 1 July 1997, there were both pessimists and optimists among the observers of the process of decolonisation and the establishment of the so-called “One Country, Two systems” arrangement in Hong Kong. For the pessimists, their main concerns were two. First, the socialist system in China could hardly accommodate a free market, capitalist Hong Kong; conflict was inevitable. Second, the encounter between an authoritarian China and a highly liberalised Hong Kong would also be a source of conflict and contention; personal freedom in Hong Kong would quickly be contained. For the optimists, with China eager to carry out market reform and Hong Kong being well placed to facilitate its economic reform and modernisation, capitalism would continue to prosper in the former British colony. The return of Hong Kong to China would therefore be no more than business as usual. Changes, if any, would be minimal. Both the pessimists and the optimists failed to anticipate the kind of problems encountered by Hong Kong since 1997.

Éditorial

Dans les années qui ont précédé la rétrocession de Hong Kong à la Chine le 1er juillet 1997, les observateurs du processus de décolonisation du territoire et de l’instauration de la formule « un pays, deux systèmes » étaient partagés en optimistes et pessimistes. Les pessimistes avaient deux inquiétudes principales. Ils pensaient tout d’abord que le système socialiste chinois pourrait difficilement intégrer le capitalisme de marché de Hong Kong et que le conflit était donc inévitable. Ensuite, la rencontre entre un pays autoritaire et une ville très libérale serait également une source de tension et de conflit, qui entrainerait rapidement la limitation des libertés individuelles à Hong Kong. Pour les optimistes, Hong Kong était en revanche bien placé pour faciliter les réformes économiques et la modernisation que la Chine était impatiente de renforcer et poursuivre. En conséquence, le capitalisme allait pour eux continuer à prospérer dans l’ancienne colonie britannique et la rétrocession ne provoquerait que peu de changements. En réalité, ni les pessimistes ni les optimistes n’ont anticipé les nouveaux défis qui se posent à Hong Kong depuis 1997

Editorial

In the years leading to the handover on 1 July 1997, there were both pessimists and optimists among the observers of the process of decolonisation and the establishment of the so-called “One Country, Two systems” arrangement in Hong Kong. For the pessimists, their main concerns were two. First, the socialist system in China could hardly accommodate a free market, capitalist Hong Kong; conflict was inevitable. Second, the encounter between an authoritarian China and a highly liberalised Hong Kong would also be a source of conflict and contention; personal freedom in Hong Kong would quickly be contained. For the optimists, with China eager to carry out market reform and Hong Kong being well placed to facilitate its economic reform and modernisation, capitalism would continue to prosper in the former British colony. The return of Hong Kong to China would therefore be no more than business as usual. Changes, if any, would be minimal. Both the pessimists and the optimists failed to anticipate the kind of problems encountered by Hong Kong since 1997.

Wilson Loops, Geometric Transitions and Bubbling Calabi-Yau's

Motivated by recent developments in the AdS/CFT correspondence, we provide several alternative bulk descriptions of an arbitrary Wilson loop operator in Chern-Simons theory. Wilson loop operators in Chern-Simons theory can be given a description in terms of a configuration of branes or alternatively anti-branes in the resolved conifold geometry. The representation of the Wilson loop is encoded in the holonomy of the gauge field living on the dual brane configuration. By letting the branes undergo a new type of geometric transition, we argue that each Wilson loop operator can also be described by a bubbling Calabi-Yau geometry, whose topology encodes the representation of the Wilson loop. These Calabi-Yau manifolds provide a novel representation of knot invariants. For the unknot we confirm these identifications to all orders in the genus expansion.Comment: 26 pages; v.2 typos corrected, explanations clarified; v.3 typos corrected, reference adde

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Genetic insights into resting heart rate and its role in cardiovascular disease.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.</p

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol�which is a marker of cardiovascular risk�changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95 credible interval 3.7 million�4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world. © 2020, The Author(s), under exclusive licence to Springer Nature Limited

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)