Quantified Assertions in Eiffel

This paper discusses extensions to the language Eiffel, required to write more comprehensive software specifications, where a specification in Eiffel is a collection of class interfaces with features specified using an assertion language (i.e. a BON static model). The focus of the paper is the extension of the assertion language with quantification. Two forms of quantification are identified, which are distinguished according to whether the quantified variable is of reference or expanded type. A semantics for each of the two forms is described, and the consequences for assertion checking at run-time considered

Encapsulation and Aggregation

A notion of object ownership is introduced as a solution to difficult problems of specifying and reasoning about complex linked structures and of modeling aggregates (composit objects). Syntax and semantics are provided for extending Eiffel with language support for object ownership annotation and checking. The ideas also apply to other OOPLs such as C++

A meta-QTL analysis highlights genomic hotspots associated with phosphorus use efficiency in rice (Oryza sativa L.)

Phosphorus use efficiency (PUE) is a complex trait, governed by many minor quantitative trait loci (QTLs) with small effects. Advances in molecular marker technology have led to the identification of QTLs underlying PUE. However, their practical use in breeding programs remains challenging due to the unstable effects in different genetic backgrounds and environments, interaction with soil status, and linkage drag. Here, we compiled PUE QTL information from 16 independent studies. A total of 192 QTLs were subjected to meta-QTL (MQTL) analysis and were projected into a high-density SNP consensus map. A total of 60 MQTLs, with significantly reduced number of initial QTLs and confidence intervals (CI), were identified across the rice genome. Candidate gene (CG) mining was carried out for the 38 MQTLs supported by multiple QTLs from at least two independent studies. Genes related to amino and organic acid transport and auxin response were found to be abundant in the MQTLs linked to PUE. CGs were cross validated using a root transcriptome database (RiceXPro) and haplotype analysis. This led to the identification of the eight CGs (OsARF8, OsSPX-MFS3, OsRING141, OsMIOX, HsfC2b, OsFER2, OsWRKY64, and OsYUCCA11) modulating PUE. Potential donors for superior PUE CG haplotypes were identified through haplotype analysis. The distribution of superior haplotypes varied among subspecies being mostly found in indica but were largely scarce in japonica. Our study offers an insight on the complex genetic networks that modulate PUE in rice. The MQTLs, CGs, and superior CG haplotypes identified in our study are useful in the combination of beneficial alleles for PUE in rice

An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients.

The Association of Cancer Physicians in the United Kingdom has developed a strategy to improve outcomes for cancer patients and identified the goals and commitments of the Association and its members.The ACP is very grateful to all of its members who have expressed views on the development of the strategy and to the sponsors of our workshops and publications, especially Cancer Research UK and Macmillan Cancer SupportThis is the final version of the article. It was first available from Cancer Intelligence via http://dx.doi.org/10.3332/ecancer.2016.60

The timing of strike-slip shear along the Ranong and Khlong Marui faults, Thailand

The timing of shear along many important strike-slip faults in Southeast Asia, such as the Ailao Shan-Red River, Mae Ping and Three Pagodas faults, is poorly understood. We present 40Ar/39Ar, U-Pb SHRIMP and microstructural data from the Ranong and Khlong Marui faults of Thailand to show that they experienced a major period of ductile dextral shear during the middle Eocene (48–40 Ma, centered on 44 Ma) which followed two phases of dextral shear along the Ranong Fault, before the Late Cretaceous (>81 Ma) and between the late Paleocene and early Eocene (59–49 Ma). Many of the sheared rocks were part of a pre-kinematic crystalline basement complex, which partially melted and was intruded by Late Cretaceous (81–71 Ma) and early Eocene (48 Ma) tin-bearing granites. Middle Eocene dextral shear at temperatures of ~300–500°C formed extensive mylonite belts through these rocks and was synchronous with granitoid vein emplacement. Dextral shear along the Ranong and Khlong Marui faults occurred at the same time as sinistral shear along the Mae Ping and Three Pagodas faults of northern Thailand, a result of India-Burma coupling in advance of India-Asia collision. In the late Eocene (<37 Ma) the Ranong and Khlong Marui faults were reactivated as curved sinistral branches of the Mae Ping and Three Pagodas faults, which were accommodating lateral extrusion during India-Asia collision and Himalayan orogenesis

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) 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 health(4,5). 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 riskchanged 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.Peer reviewe

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.Peer reviewe

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks