Rational policymaking during a pandemic.

Policymaking during a pandemic can be extremely challenging. As COVID-19 is a new disease and its global impacts are unprecedented, decisions are taken in a highly uncertain, complex, and rapidly changing environment. In such a context, in which human lives and the economy are at stake, we argue that using ideas and constructs from modern decision theory, even informally, will make policymaking a more responsible and transparent process.

National trends and disparities in retail food environments in the USA between 1990 and 2014.

OBJECTIVE: To describe national disparities in retail food environments by neighbourhood composition (race/ethnicity and socio-economic status) across time and space. DESIGN: We examined built food environments (retail outlets) between 1990 and 2014 for census tracts in the contiguous USA (n 71 547). We measured retail food environment as counts of all food stores, all unhealthy food sources (including fast food, convenience stores, bakeries and ice cream) and healthy food stores (including supermarkets, fruit and vegetable markets) from National Establishment Time Series business data. Changes in food environment were mapped to display spatial patterns. Multi-level Poisson models, clustered by tract, estimated time trends in counts of food stores with a land area offset and independent variables population density, racial composition (categorised as predominantly one race/ethnicity (>60 %) or mixed), and inflation-adjusted income tertile. SETTING: The contiguous USA between 1990 and 2014. PARTICIPANTS: All census tracts (n 71 547). RESULTS: All food stores and unhealthy food sources increased, while the subcategory healthy food remained relatively stable. In models adjusting for population density, predominantly non-Hispanic Black, Hispanic, Asian and mixed tracts had significantly more destinations of all food categories than predominantly non-Hispanic White tracts. This disparity increased over time, predominantly driven by larger increases in unhealthy food sources for tracts which were not predominantly non-Hispanic White. Income and food store access were inversely related, although disparities narrowed over time. CONCLUSIONS: Our findings illustrate a national food landscape with both persistent and shifting spatial patterns in the availability of establishments across neighbourhoods with different racial/ethnic and socio-economic compositions.

Changes in household food and drink purchases following restrictions on the advertisement of high fat, salt, and sugar products across the Transport for London network: A controlled interrupted time series analysis.

BACKGROUND: Restricting the advertisement of products with high fat, salt, and sugar (HFSS) content has been recommended as a policy tool to improve diet and tackle obesity, but the impact on HFSS purchasing is unknown. This study aimed to evaluate the impact of HFSS advertising restrictions, implemented across the London (UK) transport network in February 2019, on HFSS purchases. METHODS AND FINDINGS: Over 5 million take-home food and drink purchases were recorded by 1,970 households (London [intervention], n = 977; North of England [control], n = 993) randomly selected from the Kantar Fast Moving Consumer Goods panel. The intervention and control samples were similar in household characteristics but had small differences in main food shopper sex, socioeconomic position, and body mass index. Using a controlled interrupted time series design, we estimated average weekly household purchases of energy and nutrients from HFSS products in the post-intervention period (44 weeks) compared to a counterfactual constructed from the control and pre-intervention (36 weeks) series. Energy purchased from HFSS products was 6.7% (1,001.0 kcal, 95% CI 456.0 to 1,546.0) lower among intervention households compared to the counterfactual. Relative reductions in purchases of fat (57.9 g, 95% CI 22.1 to 93.7), saturated fat (26.4 g, 95% CI 12.4 to 40.4), and sugar (80.7 g, 95% CI 41.4 to 120.1) from HFSS products were also observed. Energy from chocolate and confectionery purchases was 19.4% (317.9 kcal, 95% CI 200.0 to 435.8) lower among intervention households than for the counterfactual, with corresponding relative reductions in fat (13.1 g, 95% CI 7.5 to 18.8), saturated fat (8.7 g, 95% CI 5.7 to 11.7), sugar (41.4 g, 95% CI 27.4 to 55.4), and salt (0.2 g, 95% CI 0.1 to 0.2) purchased from chocolate and confectionery. Relative reductions are in the context of secular increases in HFSS purchases in both the intervention and control areas, so the policy was associated with attenuated growth of HFSS purchases rather than absolute reduction in HFSS purchases. Study limitations include the lack of out-of-home purchases in our analyses and not being able to assess the sustainability of observed changes beyond 44 weeks. CONCLUSIONS: This study finds an association between the implementation of restrictions on outdoor HFSS advertising and relative reductions in energy, sugar, and fat purchased from HFSS products. These findings provide support for policies that restrict HFSS advertising as a tool to reduce purchases of HFSS products.

The impact of shelf tags with Nutri-Score on consumer purchases: a difference-in-difference analysis of a natural experiment in supermarkets of a major retailer in Belgium.

BACKGROUND: Delhaize, a major Belgian retailer, started implementing electronic shelf labels (ESL) with Nutri-Score since May 2019. Nutri-Score rates the healthfulness of packaged foods with five colours/letters from red/E (least healthy) to green/A (most healthy). This study evaluated the impact of ESL on consumer purchases, overall, and by food category. METHODS: For 43 intervention stores (implementing ESL in the period 27 May 2019-19 June 2019), a control store, from the same province and retailer-assigned cluster was matched. There were 14 unique control stores. By store, weekly non-food and food sales for 2018 and 2019 were received by Nutri-Score (A/B/C/D/E) and food category according to a retailer-assigned classification system. The primary outcomes were the proportion of food sales for Nutri-Score A,B,C,D,E. Difference-in-differences regression analysis was conducted to estimate the effect of the ESL intervention on proportion of overall food and food category sales for Nutri-Score A,B,C,D,E, using linear mixed models to account for clustering at store-level. We controlled for store characteristics (region, cluster, non-food sales) and week of the year. Analyses were weighted to re-balance discrepancy between the number of intervention and control stores. To account for multiple testing, a Bonferroni adjustment was applied. RESULTS: Comparing pre- and post-intervention periods, difference-in-differences for the proportion of Nutri-Score B and C product sales were more favourable in intervention than control stores (0.11 ± 0.04%, p = 0.007 and - 0.06 ± 0.03%, p = 0.026 respectively), while difference-in-differences for the proportion of Nutri-Score D product sales were less favourable in intervention than control stores (0.12 ± 0.04%, p = 0.002). For 17/58 food categories (representing 29% of total food sales) a positive impact [increase in healthier (Nutri-Score A, B) and/or decrease in less healthy (Nutri-Score D, E) food sales], and for 16/58 categories (representing 24% of total food sales) a negative impact was found. Positive impacts were found for vegetable, fruit and dairy products and confectionery. Negative impacts were found for bread and bakery products. CONCLUSION: The impact of ESL on consumer purchases was mixed. Favourable difference-in-differences were found for Nutri-Score B and C products and unfavourable difference-in-differences for Nutri-Score D products. Shelf labeling on its own is unlikely to significantly influence consumer behaviours.

Have socio-economic inequalities in sugar purchasing widened? A longitudinal analysis of food and beverage consumer data from British households, 2014-2017.

OBJECTIVE: To examine socio-economic inequalities in decreases in household sugar purchasing in Great Britain (GB). DESIGN: Longitudinal, population-based study. SETTING: Data were obtained from the GB Kantar Fast-Moving Consumer Goods (FMCG) panel (2014-2017), a nationally representative panel study of food and beverages bought and brought into the home. We estimated changes in daily sugar purchases by occupational social grade from twenty-three food groups, using generalised estimating equations (household-level clustering). PARTICIPANTS: British households who regularly reported food and beverages to the GB Kantar FMCG (n 28 033). RESULTS: We found that lower social grades obtained a lower proportion of sugar from healthier foods and a greater proportion of sugar from less healthy foods and beverages. In 2014, differences in daily sugar purchased between the lowest and the highest social grades were 3·9 g/capita/d (95 % CI 2·9, 4·8) for table sugar, 2·4 g (95 % CI 1·8, 3·1) for sugar-sweetened beverages, 2·2 g (95 % CI 1·5, 2·8) for chocolate and confectionery and 1·0 g (95 % CI 0·7, 1·3) for biscuits. Conversely, the lowest social grade purchased less sugar from fruits (2·1 g (95 % CI 1·5, 2·8)) and vegetables (0·7 g (95 % CI 0·5, 0·8)) than the highest social grade. We found little evidence of change in social grade differences between 2014 and 2017. These results suggest that recent overall declines in sugar purchases are largely equally distributed across socio-economic groups. CONCLUSIONS: This suggests that recent population-level policy activity to reduce sugar consumption in GB does not appear to exacerbate or reduce existing socio-economic inequalities in sugar purchasing. Low agency, population-level policies may be the best solution to improving population diet without increasing inequalities.

Teaching life cycle assessment in higher education.

Purpose: Scientific Life Cycle Assessment (LCA) literature provides some examples of LCA teaching in higher education, but not a structured overview of LCA teaching contents and related competencies. Hence this paper aims at assessing and highlighting trends in LCA learning outcomes, teaching approaches and developed content used to equip graduates for their future professional practices in sustainability. Methods: Based on a literature review on teaching LCA in higher education and a collaborative consensus building approach through expert group panel discussions, an overview of LCA learning and competency levels with related teaching contents and corresponding workload is developed. The levels are built on the European Credit Transfer and Accumulation System (ECTS) and Bloom's taxonomy of learning. Results and discussion: The paper frames five LCA learning and competency levels that differ in terms of study program integration, workload, cognitive domain categories, learning outcomes, and envisioned professional skills. It furthermore provides insights into teaching approaches and content, including software use, related to these levels. Conclusions and recommendations: This paper encourages and supports higher educational bodies to implement a minimum of 'life cycle literacy' into students' curriculum across various domains by increasing the availability, visibility and quality of their teaching on life cycle thinking and LCA.

Patterns of beverage purchases amongst British households: A latent class analysis.

BACKGROUND: Beverages, especially sugar-sweetened beverages (SSBs), have been increasingly subject to policies aimed at reducing their consumption as part of measures to tackle obesity. However, precision targeting of policies is difficult as information on what types of consumers they might affect, and to what degree, is missing. We fill this gap by creating a typology of beverage consumers in Great Britain (GB) based on observed beverage purchasing behaviour to determine what distinct types of beverage consumers exist, and what their socio-demographic (household) characteristics, dietary behaviours, and weight status are. METHODS AND FINDINGS: We used cross-sectional latent class analysis to characterise patterns of beverage purchases. We used data from the 2016 GB Kantar Fast-Moving Consumer Goods (FMCG) panel, a large representative household purchase panel of food and beverages brought home, and restricted our analyses to consumers who purchase beverages regularly (i.e., >52 l per household member annually) (n = 8,675). Six categories of beverages were used to classify households into latent classes: SSBs; diet beverages; fruit juices and milk-based beverages; beer and cider; wine; and bottled water. Multinomial logistic regression and linear regression were used to relate class membership to household characteristics, self-reported weight status, and other dietary behaviours, derived from GB Kantar FMCG. Seven latent classes were identified, characterised primarily by higher purchases of 1 or 2 categories of beverages: 'SSB' (18% of the sample; median SSB volume = 49.4 l/household member/year; median diet beverage volume = 38.0 l), 'Diet' (16%; median diet beverage volume = 94.4 l), 'Fruit & Milk' (6%; median fruit juice/milk-based beverage volume = 30.0 l), 'Beer & Cider' (7%; median beer and cider volume = 36.3 l; median diet beverage volume = 55.6 l), 'Wine' (18%; median wine volume = 25.5 l; median diet beverage volume = 34.3 l), 'Water' (4%; median water volume = 46.9 l), and 'Diverse' (30%; diversity of purchases, including median SSB volume = 22.4 l). Income was positively associated with being classified in the Diverse class, whereas low social grade was more likely for households in the classes SSB, Diet, and Beer & Cider. Obesity (BMI > 30 kg/m2) was more prevalent in the class Diet (41.2%, 95% CI 37.7%-44.7%) despite households obtaining little energy from beverages in that class (17.9 kcal/household member/day, 95% CI 16.2-19.7). Overweight/obesity (BMI > 25 kg/m2) was above average in the class SSB (66.8%, 95% CI 63.7%-69.9%). When looking at all groceries, households from the class SSB had higher total energy purchases (1,943.6 kcal/household member/day, 95% CI 1,901.7-1,985.6), a smaller proportion of energy from fruits and vegetables (6.0%, 95% CI 5.8%-6.3%), and a greater proportion of energy from less healthy food and beverages (54.6%, 95% CI 54.0%-55.1%) than other classes. A greater proportion of energy from sweet snacks was observed for households in the classes SSB (18.5%, 95% CI 18.1%-19.0%) and Diet (18.8%, 95% CI 18.3%-19.3%). The main limitation of our analyses, in common with other studies, is that our data do not include information on food and beverage purchases that are consumed outside the home. CONCLUSIONS: Amongst households that regularly purchase beverages, those that mainly purchased high volumes of SSBs or diet beverages were at greater risk of obesity and tended to purchase less healthy foods, including a high proportion of energy from sweet snacks. These households might additionally benefit from policies targeting unhealthy foods, such as sweet snacks, as a way of reducing excess energy intake.

Longitudinal associations between perceptions of the neighbourhood environment and physical activity in adolescents: evidence from the Olympic Regeneration in East London (ORiEL) study.

BACKGROUND: Most UK adolescents do not achieve recommended levels of physical activity. Previous studies suggested that perceptions of the neighbourhood environment could contribute to explain differences in physical activity behaviours. We aimed to examine whether five measures of perceptions - perceived bus stop proximity, traffic safety, street connectivity, enjoyment of the neighbourhood for walking/cycling, and personal safety - were longitudinally associated with common forms of physical activity, namely walking to school, walking for leisure, and a composite measure of outdoor physical activity. We further aimed to investigate the moderating role of gender. METHODS: We used longitudinal data from the Olympic Regeneration in East London (ORiEL) study, a prospective cohort study. In 2012, 3106 adolescents aged 11 to 12 were recruited from 25 schools in 4 deprived boroughs of East London. Adolescents were followed-up in 2013 and 2014. The final sample includes 2260 adolescents surveyed at three occasions. We estimated logistic regression models using Generalised Estimating Equations to test the plausibility of hypotheses on the nature of the longitudinal associations (general association, cumulative effect, co-varying trajectories), adjusting for potential confounders. Item non-response was handled using multiple imputation. RESULTS: Longitudinal analyses indicate little evidence that perceptions of the neighbourhood are important predictors of younger adolescent physical activity. There was weak evidence that greater perceived proximity to bus stops is associated with a small decrease in the probability of walking for leisure. Results also indicate that poorer perception of personal safety decreases the probability of walking for leisure. There was some indication that better perception of street connectivity is associated with more outdoor physical activity. Finally, we found very little evidence that the associations between perceptions of the neighbourhood and physical activity differed by gender. CONCLUSIONS: This study suggests that younger adolescents' perceptions of their neighbourhood environment, and changes in these perceptions, did not consistently predict physical activity in a deprived and ethnically diverse urban population. Future studies should use situation-specific measures of the neighbourhood environment and physical activity to better capture the hypothesised processes and explore the relative roles of the objective environment, parental and adolescents' perceptions in examining differences in types of physical activity.

Sustained low rotavirus activity and hospitalisation rates in the post-vaccination era in Belgium, 2007 to 2014.

In 2006, Belgium was the first country in the European Union to recommend rotavirus vaccination in the routine infant vaccination schedule and rapidly achieved high vaccine uptake (86-89% in 2007). We used regional and national data sources up to 7 years post-vaccination to study the impact of vaccination on laboratory-confirmed rotavirus cases and rotavirus-related hospitalisations and deaths. We showed that (i) from 2007 until 2013, vaccination coverage remained at 79-88% for a complete course, (ii) in children 0-2 years, rotavirus cases decreased by 79% (95% confidence intervals (CI): 68--89%) in 2008-2014 compared to the pre-vaccination period (1999--2006) and by 50% (95% CI: 14-82%) in the age group ≥ 10 years, (iii) hospitalisations for rotavirus gastroenteritis decreased by 87% (95% CI: 84-90%) in 2008--2012 compared to the pre-vaccination period (2002--2006), (iv) median age of rotavirus cases increased from 12 months to 17 months and (v) the rotavirus seasonal peak was reduced and delayed in all post-vaccination years. The substantial decline in rotavirus gastroenteritis requiring hospitalisations and in rotavirus activity following introduction of rotavirus vaccination is sustained over time and more pronounced in the target age group, but with evidence of herd immunity.

Combined RNAi and localization for functionally dissecting long noncoding RNAs.

Whereas methods to comprehensively study cellular roles of protein-coding genes are available, techniques to systematically investigate long noncoding RNAs (lncRNAs), which have been implicated in diverse biological pathways, are limited. Here we report combined knockdown and localization analysis of noncoding RNAs (c-KLAN) that merges functional characterization and localization approaches to study lncRNAs. Using this technique we identified transcripts that regulate mouse embryonic stem cell identity.

Assessing the validity of the Global Activity Limitation Indicator in fourteen European countries.

BACKGROUND: The Global Activity Limitation Indicator (GALI), the measure underlying the European indicator Healthy Life Years (HLY), is widely used to compare population health across countries. However, the comparability of the item has been questioned. This study aims to further validate the GALI in the adult European population. METHODS: Data from the European Health Interview Survey (EHIS), covering 14 European countries and 152,787 individuals, were used to explore how the GALI was associated with other measures of disability and whether the GALI was consistent or reflected different disability situations in different countries. RESULTS: When considering each country separately or all combined, we found that the GALI was significantly associated with measures of activities of daily living, instrumental activity of daily living, and functional limitations (P < 0.001 in all cases). Associations were largest for activity of daily living and lowest though still high for functional limitations. For each measure, the magnitude of the association was similar across most countries. Overall, however, the GALI differed significantly between countries in terms of how it reflected each of the three disability measures (P < 0.001 in all cases). We suspect cross-country differences in the results may be due to variations in: the implementation of the EHIS, the perception of functioning and limitations, and the understanding of the GALI question. CONCLUSION: The study both confirms the relevance of this indicator to measure general activity limitations in the European population and the need for caution when comparing the level of the GALI from one country to another.

Vika/vox, a novel efficient and specific Cre/loxP-like site-specific recombination system.

Targeted genome engineering has become an important research area for diverse disciplines, with site-specific recombinases (SSRs) being among the most popular genome engineering tools. Their ability to trigger excision, integration, inversion and translocation has made SSRs an invaluable tool to manipulate DNA in vitro and in vivo. However, sophisticated strategies that combine different SSR systems are ever increasing. Hence, the demand for additional precise and efficient recombinases is dictated by the increasing complexity of the genetic studies. Here, we describe a novel site-specific recombination system designated Vika/vox. Vika originates from a degenerate bacteriophage of Vibrio coralliilyticus and shares low sequence similarity to other tyrosine recombinases, but functionally carries out a similar type of reaction. We demonstrate that Vika is highly specific in catalyzing vox recombination without recombining target sites from other SSR systems. We also compare the recombination activity of Vika/vox with other SSR systems, providing a guideline for deciding on the most suitable enzyme for a particular application and demonstrate that Vika expression does not cause cytotoxicity in mammalian cells. Our results show that Vika/vox is a novel powerful and safe instrument in the 'genetic toolbox' that can be used alone or in combination with other SSRs in heterologous hosts.

Activity limitations predict health care expenditures in the general population in Belgium.

BACKGROUND: Disability and chronic conditions both have an impact on health expenditures and although they are conceptually related, they present different dimensions of ill-health. Recent concepts of disability combine a biological understanding of impairment with the social dimension of activity limitation and resulted in the development of the Global Activity Limitation Indicator (GALI). This paper reports on the predictive value of the GALI on health care expenditures in relation to the presence of chronic conditions. METHODS: Data from the Belgian Health Interview Survey 2008 were linked with data from the compulsory national health insurance (n = 7,286). The effect of activity limitation on health care expenditures was assessed via cost ratios from multivariate linear regression models. To study the factors contributing to the difference in health expenditure between persons with and without activity limitations, the Blinder-Oaxaca decomposition method was used. RESULTS: Activity limitations are a strong determinant of health care expenditures. People with severe activity limitations (5.1%) accounted for 16.9% of the total health expenditure, whereas those without activity limitations (79.0%), were responsible for 51.5% of the total health expenditure. These observed differences in health care expenditures can to some extent be explained by chronic conditions, but activity limitations also contribute substantially to higher health care expenditures in the absence of chronic conditions (cost ratio 2.46; 95% CI 1.74-3.48 for moderate and 4.45; 95% CI 2.47-8.02 for severe activity limitations). The association between activity limitation and health care expenditures is stronger for reimbursed health care costs than for out-of-pocket payments. CONCLUSION: In the absence of chronic conditions, activity limitations appear to be an important determinant of health care expenditures. To make projections on health care expenditures, routine data on activity limitations are essential and complementary to data on chronic conditions.

Contribution of chronic diseases to the disability burden in a population 15 years and older, Belgium, 1997-2008.

BACKGROUND: Age-associated disability reduces quality of life in older populations and leads to wide-range implications for social and health policy. The identification of diseases that contribute to the disability burden is crucial to the development of prevention and intervention strategies to reduce disability. In this study, we assessed the contribution of chronic diseases to the prevalence of disability in Belgium. METHODS: Data from 35,837 individuals aged 15 years or older who participated in the 1997, 2001, 2004, or 2008 Belgian Health Interview Surveys were used. Disability was defined as difficulties in doing at least one of six activities of daily living (transfer in and out of bed, transfer in and out of chair, dressing, washing hands and face, feeding, and going to the toilet) and/or mobility limitations (ability to walk without stopping less than 200 m). Multiple additive regression models were fitted separately for men and women to estimate the age-specific background disability rate (experienced by everyone, independent of the presence of specific diseases) and disease-specific disability rates (disability rate in subjects who reported selected chronic diseases). RESULTS: Musculoskeletal, cardiovascular, and respiratory diseases were the main contributors to the disability burden in Belgium. Musculoskeletal diseases were the most prevalent diseases in men and women in all age groups. Neurological diseases and stroke were the most disabling diseases, i.e. caused the highest level of disability among the diseased individuals, in all age groups for men and women, respectively. Back pain was the main cause of disability in men aged 15 to 64 years, while heart attack was the major contributor to the disability prevalence in men aged 65 or older. Likewise, arthritis was the main cause of disability among women across all age groups. Depression was also an important contributor in young subjects (15-54 years). Cancer was not an important contributor to the disability prevalence in Belgium. CONCLUSIONS: To reduce the burden of disability in Belgium, interventions should target musculoskeletal, cardiovascular and respiratory diseases especially among elderly. Furthermore, attention should also be given to depression in young individuals.

Using mortality follow-up of surveys to estimate social inequalities in healthy life years.

BACKGROUND: The estimation of healthy life years (HLY) by socio-economic status (SES) requires two types of data: the prevalence of activity limitation by SES generally extracted from surveys and mortality rates by SES generally derived from a linkage between the SES information in population databases (census, register) and mortality records. In some situations, no population-wide databases are available to produce mortality rates by SES, and therefore some alternatives must be explored. This paper assesses the validity of calculating HLY by SES using mortality rates derived from a linkage between surveys and mortality records. METHODS: TWO SURVEYS WERE CHOSEN TO EXPLORE THE VALIDITY OF THE PROPOSED APPROACH: The Belgian Health Interview Survey (HIS) and the Belgian Survey on Income and Living Conditions (SILC). The mortality follow-up of these surveys were used to calculate HLY by educational level at age 25. These HLY were compared with HLY estimates calculated using the mortality follow-up of the 2001 census. The validity of this approach was evaluated against two criteria. First, the HLY calculated using the census and those calculated using the surveys must not be significantly different. Second, survey-based HLY must show significant social inequalities since such inequalities have been consistently reported with census-based HLY. RESULTS: Both criteria were met. First, for each educational category, no statistically significant difference was found when comparing census-based and survey-based HLY estimates. For instance, men in the lowest educational category have shown a HLY of 34 years according to the HIS, and while this figure was 35.5 years according to the census, this difference was not statistically significant. Second, the survey-based HLY have shown a significant social gradient. For instance, men in the highest educational category are expected to live 9.5 more HLY than their counterparts in the lowest educational category based on the HIS estimates, compared with 7.3 HLY based on the census estimates. CONCLUSIONS: This article suggests that using the mortality follow-up of a nationally representative cross-sectional survey is a valid approach to monitor social inequalities in HLY in the absence of population-wide data.

The effect of smoking on the duration of life with and without disability, Belgium 1997-2011.

BACKGROUND: Smoking is the single most important health threat yet there is no consistency as to whether non-smokers experience a compression of years lived with disability compared to (ex-)smokers. The objectives of the manuscript are (1) to assess the effect of smoking on the average years lived without disability (Disability Free Life Expectancy (DFLE)) and with disability (Disability Life Expectancy (DLE)) and (2) to estimate the extent to which these effects are due to better survival or reduced disability in never smokers. METHODS: Data on disability and mortality were provided by the Belgian Health Interview Survey 1997 and 2001 and a 10 years mortality follow-up of the survey participants. Disability was defined as difficulties in activities of daily living (ADL), in mobility, in continence or in sensory (vision, hearing) functions. Poisson and multinomial logistic regression models were fitted to estimate the probabilities of death and the prevalence of disability by age, gender and smoking status adjusted for socioeconomic position. The Sullivan method was used to estimate DFLE and DLE at age 30. The contribution of mortality and of disability to smoking related differences in DFLE and DLE was assessed using decomposition methods. RESULTS: Compared to never smokers, ex-smokers have a shorter life expectancy (LE) and DFLE but the number of years lived with disability is somewhat larger. For both sexes, the higher disability prevalence is the main contributing factor to the difference in DFLE and DLE. Smokers have a shorter LE, DFLE and DLE compared to never smokers. Both higher mortality and higher disability prevalence contribute to the difference in DFLE, but mortality is more important among males. Although both male and female smokers experience higher disability prevalence, their higher mortality outweighs their disability disadvantage resulting in a shorter DLE. CONCLUSION: Smoking kills and shortens both life without and life with disability. Smoking related disability can however not be ignored, given its contribution to the excess years with disability especially in younger age groups.

High-intensity interval training attenuates impairment in regulatory protein machinery of mitochondrial quality control in skeletal muscle of diet-induced obese mice.

Mitochondrial quality control processes are essential in governing mitochondrial integrity and function. The purpose of the study was to examine the effects of 10 weeks of high-intensity interval training (HIIT) on the regulatory protein machinery of skeletal muscle mitochondrial quality control and whole-body glucose homeostasis in diet-induced obese mice. Male C57BL/6 mice were assigned to low-fat diet (LFD) or high-fat diet (HFD) group. After 10 weeks, HFD-fed mice were divided into sedentary and HIIT (HFD + HIIT) groups for another 10 weeks (n = 9/group). Graded exercise test, glucose and insulin tolerance tests, mitochondrial respiration, and protein markers of mitochondrial quality control processes were determined. HFD-fed mice exhibited lower ADP-stimulated mitochondrial respiration (p < 0.05). However, 10 weeks of HIIT prevented this impairment (p < 0.05). Importantly, the ratio of Drp1(Ser616) over Drp1(Ser637) phosphorylation, an indicator of mitochondrial fission, was significantly higher in HFD-fed mice (p < 0.05), but such increase was attenuated in HFD-HIIT compared to HFD (-35.7%, p < 0.05). Regarding autophagy, skeletal muscle p62 content was lower in the HFD group than the LFD group (-35.1%, p < 0.05); however, such reduction was disappeared in the HFD + HIIT group. In addition, LC3B II/I ratio was higher in the HFD group than the LFD group (15.5%, p < 0.05) but was ameliorated in the HFD + HIIT group (-29.9%, p < 0.05). Overall, our study demonstrated that 10 weeks of HIIT was effective in improving skeletal muscle mitochondrial respiration and the regulatory protein machinery of mitochondrial quality control in diet-induced obese mice through the alterations of mitochondrial fission protein Drp1 phosphorylations and p62/LC3B-mediated regulatory machinery of autophagy.

Limits of Ultra: Towards an Interdisciplinary Understanding of Ultra-Endurance Running Performance.

Ultra-endurance running (UER) poses extreme mental and physical challenges that present many barriers to completion, let alone performance. Despite these challenges, participation in UER events continues to increase. With the relative paucity of research into UER training and racing compared with traditional endurance running distance (e.g., marathon), it follows that there are sizable improvements still to be made in UER if the limitations of the sport are sufficiently understood. The purpose of this review is to summarise our current understanding of the major limitations in UER. We begin with an evolutionary perspective that provides the critical background for understanding how our capacities, abilities and limitations have come to be. Although we show that humans display evolutionary adaptations that may bestow an advantage for covering large distances on a daily basis, these often far exceed the levels of our ancestors, which exposes relative limitations. From that framework, we explore the physiological and psychological systems required for running UER events. In each system, the factors that limit performance are highlighted and some guidance for practitioners and future research are shared. Examined systems include thermoregulation, oxygen delivery and utilisation, running economy and biomechanics, fatigue, the digestive system, nutritional and psychological strategies. We show that minimising the cost of running, damage to lower limb tissue and muscle fatigability may become crucial in UER events. Maintaining a sustainable core body temperature is critical to performance, and an even pacing strategy, strategic heat acclimation and individually calculated hydration all contribute to sustained performance. Gastrointestinal issues affect almost every UER participant and can be due to a variety of factors. We present nutritional strategies for different event lengths and types, such as personalised and evidence-based approaches for varying types of carbohydrate, protein and fat intake in fluid or solid form, and how to avoid flavour fatigue. Psychology plays a vital role in UER performance, and we highlight the need to be able to cope with complex situations, and that specific long and short-term goal setting improves performance. Fatigue in UER is multi-factorial, both physical and mental, and the perceived effort or level of fatigue have a major impact on the ability to continue at a given pace. Understanding the complex interplay of these limitations will help prepare UER competitors for the different scenarios they are likely to face. Therefore, this review takes an interdisciplinary approach to synthesising and illuminating limitations in UER performance to assist practitioners and scientists in making informed decisions in practice and applicable research.

Perceptions of Cheating and Doping in E-Cycling.

E-cycling is a growing area of cycling appealing to competitive cyclists and fitness enthusiasts. Zwift is the most popular e-cycling platform, with approx. 1 million subscribers and is a virtual environment that hosts regular races, including the UCI e-cycling world championships. The popularity of Zwift has given rise to cases of cheating and hacking the system to gain an advantage in e-racing. As a result, some high-profile professional riders have faced bans. We set out to understand the thoughts and concerns e-cyclists have about cheating, hacking, and doping in e-cycling. A total of 337 females and 1130 males were recruited over a 7-week period via social networking sites to complete an online survey. Forty-four per cent had experienced cheating during e-racing, which made them feel angry, annoyed, disappointed, and cheated. However, 15% of those who experienced cheating said they did not care, possibly because many see e-racing as a game or training tool rather than a competitive event. Eighty-seven per cent of participants were in favour of enforcing a ban on cheaters in e-cycling, while 34% wanted cheaters to be banned during in-person cycling events too. Results indicate that many e-cyclists have experienced cheating and would like clearer rules and bans for cheaters during e-races.

Partial skeletal muscle-specific Drp1 knockout enhances insulin sensitivity in diet-induced obese mice, but not in lean mice.

OBJECTIVE: Dynamin-related protein 1 (Drp1) is the key regulator of mitochondrial fission. We and others have reported a strong correlation between enhanced Drp1 activity and impaired skeletal muscle insulin sensitivity. This study aimed to determine whether Drp1 directly regulates skeletal muscle insulin sensitivity and whole-body glucose homeostasis. METHODS: We employed tamoxifen-inducible skeletal muscle-specific heterozygous Drp1 knockout mice (mDrp1+/-). Male mDrp1+/- and wildtype (WT) mice were fed with either a high-fat diet (HFD) or low-fat diet (LFD) for four weeks, followed by tamoxifen injections for five consecutive days, and remained on their respective diet for another four weeks. In addition, we used primary human skeletal muscle cells (HSkMC) from lean, insulin-sensitive, and severely obese, insulin-resistant humans and transfected the cells with either a Drp1 shRNA (shDrp1) or scramble shRNA construct. Skeletal muscle and whole-body insulin sensitivity, skeletal muscle insulin signaling, mitochondrial network morphology, respiration, and H2O2 production were measured. RESULTS: Partial deletion of the Drp1 gene in skeletal muscle led to improved whole-body glucose tolerance and insulin sensitivity (P < 0.05) in diet-induced obese, insulin-resistant mice but not in lean mice. Analyses of mitochondrial structure and function revealed that the partial deletion of the Drp1 gene restored mitochondrial dynamics, improved mitochondrial morphology, and reduced mitochondrial Complex I- and II-derived H2O2 (P < 0.05) under the condition of diet-induced obesity. In addition, partial deletion of Drp1 in skeletal muscle resulted in elevated circulating FGF21 (P < 0.05) and in a trend towards increase of FGF21 expression in skeletal muscle tissue (P = 0.095). In primary myotubes derived from severely obese, insulin-resistant humans, ShRNA-induced-knockdown of Drp1 resulted in enhanced insulin signaling, insulin-stimulated glucose uptake and reduced cellular reactive oxygen species (ROS) content compared to the shScramble-treated myotubes from the same donors (P < 0.05). CONCLUSION: These data demonstrate that partial loss of skeletal muscle-specific Drp1 expression is sufficient to improve whole-body glucose homeostasis and insulin sensitivity under obese, insulin-resistant conditions, which may be, at least in part, due to reduced mitochondrial H2O2 production. In addition, our findings revealed divergent effects of Drp1 on whole-body metabolism under lean healthy or obese insulin-resistant conditions in mice.