True interindividual variability exists in postprandial appetite responses in healthy men but is not moderated by the FTO genotype

Background: After meal ingestion, a series of coordinated hormone responses occur concomitantly with changes in perceived appetite. It is not known whether interindividual variability in appetite exists in response to a meal. Objectives: This study aimed to 1) assess the reproducibility of appetite responses to a meal; 2) quantify individual differences in responses; and 3) explore any moderating influence of the fat mass and obesity associated (FTO) gene. Methods: Using a replicated crossover design, 18 healthy men (mean ± SD 28.5 ± 9.8 years, 27.0 ± 5.0 kg·m-2 ) recruited according to FTO genotype (9 AA, 9 TT) completed two identical control and two identical standardized meal conditions (5025 kJ) in randomized sequences. Perceived appetite and plasma acylated ghrelin, total peptide YY (PYY), insulin and glucose concentrations were measured before and after interventions as primary outcomes. Interindividual differences were explored using Pearson’s product-moment correlations between the first and second replicate of the control-adjusted meal response. Within-participant covariate-adjusted linear mixed models were used to quantify participant by-condition and genotype-by-condition interactions. Results: The meal suppressed acylated ghrelin and appetite perceptions (standardized effect sizes (ES): 0.18-4.26) and elevated total PYY, insulin and glucose (ES: 1.96-21.60). For all variables, SD of change scores was greater in the meal versus control conditions. Moderate-to-large positive correlations were observed between the two replicates of control-adjusted meal responses for all variables (r=0.44-0.86, P≤0.070). Participant-by-condition interactions were present for all variables (P≤0.056). FTO genotype-by-condition interactions were not significant (P≥0.19) and treatment effect differences between genotype groups were small (ES≤0.27) for all appetite parameters. Conclusions: Reproducibility of postprandial appetite responses is generally good. True interindividual variability is present beyond any random within-subject variation in healthy men but is not moderated by the FTO genotype. These findings highlight the 3 importance of exploring individual differences in appetite for the prevention and/or treatment of obesity. Clinical trial registry number: NCT03771690 (ClinicalTrials.gov)

The Big Society and the Conjunction of Crises: Justifying Welfare Reform and Undermining Social Housing

The idea of the “Big Society” can be seen as culmination of a long-standing debate about the regulation of welfare. Situating the concept within governance theory, the article considers how the UK coalition government has justified a radical restructuring of welfare provision, and considers its implications for housing provision. Although drawing on earlier modernization processes, the article contends that the genesis for welfare reform was based on an analysis that the government was forced to respond to a unique conjunction of crises: in morality, the state, ideology and economics. The government has therefore embarked upon a programme, which has served to undermine the legitimacy of the social housing sector (most notably in England), with detrimental consequences for residents and raising significant dilemmas for those working in the housing sector

Promoting responsibility, shaping behaviour: housing management, mixed communities and the construction of citizenship

This article examines housing policies aimed at establishing mixed income communities. Based on stakeholder interviews and case study analysis in England and Scotland, the article pays particular attention to the impact of interventions in housing management. The first part of the article considers the policy context for mixed communities and considers the conceptual basis underlying contemporary housing management through discourses of culture and social control. The second part considers how this agenda has resulted in the adoption of intensive management strategies within mixed communities; illustrated in the development of allocation policies, initiatives designed to tackle anti-social behaviour and proposals to develop sustainable communities. The main argument is given that the concept of mixed communities is based on the premise of social housing failure, citizenship has been defined largely in response to private sector interests. This approach to management has been a contributory factor in the construction of social housing as a form of second-class citizenship

Individual variation in hunger, energy intake and ghrelin responses to acute exercise

Purpose This study aimed to characterize the immediate and extended effect of acute exercise on hunger, energy intake, and circulating acylated ghrelin concentrations using a large data set of homogenous experimental trials and to describe the variation in responses between individuals. Methods Data from 17 of our group's experimental crossover trials were aggregated yielding a total sample of 192 young, healthy males. In these studies, single bouts of moderate to high-intensity aerobic exercise (69% ± 5% V˙O2 peak; mean ± SD) were completed with detailed participant assessments occurring during and for several hours postexercise. Mean hunger ratings were determined during (n = 178) and after (n = 118) exercise from visual analog scales completed at 30-min intervals, whereas ad libitum energy intake was measured within the first hour after exercise (n = 60) and at multiple meals (n = 128) during the remainder of trials. Venous concentrations of acylated ghrelin were determined at strategic time points during (n = 118) and after (n = 89) exercise. Results At group level, exercise transiently suppressed hunger (P < 0.010, Cohen's d = 0.77) but did not affect energy intake. Acylated ghrelin was suppressed during exercise (P < 0.001, Cohen's d = 0.10) and remained significantly lower than control (no exercise) afterward (P < 0.024, Cohen's d = 0.61). Between participants, there were notable differences in responses; however, a large proportion of this spread lay within the boundaries of normal variation associated with biological and technical assessment error. Conclusion In young men, acute exercise suppresses hunger and circulating acylated ghrelin concentrations with notable diversity between individuals. Care must be taken to distinguish true interindividual variation from random differences within normal limits

Where Two Are Fighting, the Third Wins: Stronger Selection Facilitates Greater Polymorphism in Traits Conferring Competition-Dispersal Tradeoffs

A major conundrum in evolution is that, despite natural selection, polymorphism is still omnipresent in nature: Numerous species exhibit multiple morphs, namely several abundant values of an important trait. Polymorphism is particularly prevalent in asymmetric traits, which are beneficial to their carrier in disruptive competitive interference but at the same time bear disadvantages in other aspects, such as greater mortality or lower fecundity. Here we focus on asymmetric traits in which a better competitor disperses fewer offspring in the absence of competition. We report a general pattern in which polymorphic populations emerge when disruptive selection increases: The stronger the selection, the greater the number of morphs that evolve. This pattern is general and is insensitive to the form of the fitness function. The pattern is somewhat counterintuitive since directional selection is excepted to sharpen the trait distribution and thereby reduce its diversity (but note that similar patterns were suggested in studies that demonstrated increased biodiversity as local selection increases in ecological communities). We explain the underlying mechanism in which stronger selection drives the population towards more competitive values of the trait, which in turn reduces the population density, thereby enabling lesser competitors to stably persist with reduced need to directly compete. Thus, we believe that the pattern is more general and may apply to asymmetric traits more broadly. This robust pattern suggests a comparative, unified explanation to a variety of polymorphic traits in nature.ope

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Urban space and the social control of incivilities: perceptions of space influencing the regulationof anti-social behaviour

Contemporary cities are increasingly governed through space. In this article,we examine how urban space and perceptions thereof can influence the social control inthe area of incivilities. To this end, we first inspect the existing literature, in particularthe socio-spatial studies that emphasise the importance of culture and values in theinteraction with social control. Partly drawing on examples from our previous studies,we suggest that people’s perceptions of urban space (influenced by cultural symbols,social and media representations, aesthetics and other values) affect their perceptions ofincivilities, while the latter often determine or at least importantly contribute to theshaping of the social control of incivilities. We further highlight the role of gentrifica-tion as a medium and a tool of social control. The paper concludes by discussingimplications of this for the possible future, more integrated and interdisciplinaryresearch on the social control of incivilities in the city