Modelling the impact of lockdown-easing measures on cumulative COVID-19 cases and deaths in England.

OBJECTIVES: To assess the potential impacts of successive lockdown-easing measures in England, at a point in the COVID-19 pandemic when community transmission levels were relatively high. DESIGN: We developed a Bayesian model to infer incident cases and reproduction number (R) in England, from incident death data. We then used this to forecast excess cases and deaths in multiple plausible scenarios in which R increases at one or more time points. SETTING: England. PARTICIPANTS: Publicly available national incident death data for COVID-19 were examined. PRIMARY OUTCOME: Excess cumulative cases and deaths forecast at 90 days, in simulated scenarios of plausible increases in R after successive easing of lockdown in England, compared with a baseline scenario where R remained constant. RESULTS: Our model inferred an R of 0.75 on 13 May when England first started easing lockdown. In the most conservative scenario modelled where R increased to 0.80 as lockdown was eased further on 1 June and then remained constant, the model predicted an excess 257 (95% CI 108 to 492) deaths and 26 447 (95% CI 11 105 to 50 549) cumulative cases over 90 days. In the scenario with maximal increases in R (but staying ≤1), the model predicts 3174 (95% CI 1334 to 6060) excess cumulative deaths and 421 310 (95% CI 177 012 to 804 811) cases. Observed data from the forecasting period aligned most closely to the scenario in which R increased to 0.85 on 1 June, and 0.9 on 4 July. CONCLUSIONS: When levels of transmission are high, even small changes in R with easing of lockdown can have significant impacts on expected cases and deaths, even if R remains ≤1. This will have a major impact on population health, tracing systems and healthcare services in England. Following an elimination strategy rather than one of maintenance of R ≤1 would substantially mitigate the impact of the COVID-19 epidemic within England

Sugar addiction: the state of the science.

PURPOSE: As obesity rates continue to climb, the notion that overconsumption reflects an underlying 'food addiction' (FA) has become increasingly influential. An increasingly popular theory is that sugar acts as an addictive agent, eliciting neurobiological changes similar to those seen in drug addiction. In this paper, we review the evidence in support of sugar addiction. METHODS: We reviewed the literature on food and sugar addiction and considered the evidence suggesting the addictiveness of highly processed foods, particularly those with high sugar content. We then examined the addictive potential of sugar by contrasting evidence from the animal and human neuroscience literature on drug and sugar addiction. RESULTS: We find little evidence to support sugar addiction in humans, and findings from the animal literature suggest that addiction-like behaviours, such as bingeing, occur only in the context of intermittent access to sugar. These behaviours likely arise from intermittent access to sweet tasting or highly palatable foods, not the neurochemical effects of sugar. CONCLUSION: Given the lack of evidence supporting it, we argue against a premature incorporation of sugar addiction into the scientific literature and public policy recommendations.Wellcome Trust (Senior Fellowship award)This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00394-016-1229-

Disrupted iron regulation in the brain and periphery in cocaine addiction

Stimulant drugs acutely increase dopamine neurotransmission in the brain, and chronic use leads to neuroadaptive changes in the mesolimbic dopamine system and morphological changes in basal ganglia structures. Little is known about the mechanisms underlying these changes but preclinical evidence suggests that iron, a coenzyme in dopamine synthesis and storage, may be a candidate mediator. Iron is present in high concentrations in the basal ganglia and stimulant drugs may interfere with iron homeostasis. We hypothesised that morphological brain changes in cocaine addiction relate to abnormal iron regulation in the brain and periphery. We determined iron concentration in the brain, using quantitative susceptibility mapping, and in the periphery, using iron markers in circulating blood, in 44 patients with cocaine addiction and 44 healthy controls. Cocaine-addicted individuals showed excess iron accumulation in the globus pallidus, which strongly correlated with duration of cocaine use, and mild iron deficiency in the periphery, which was associated with low iron levels in the red nucleus. Our findings show that iron dysregulation occurs in cocaine addiction and suggest that it arises consequent to chronic cocaine use. Putamen enlargement in these individuals was unrelated to iron concentrations, suggesting that these are co-occurring morphological changes that may respectively reflect predisposition to, and consequences of cocaine addiction. Understanding the mechanisms by which cocaine affects iron metabolism may reveal novel therapeutic targets, and determine the value of iron levels in the brain and periphery as biomarkers of vulnerability to, as well as progression and response to treatment of cocaine addiction.This work was supported by the NIHR Cambridge Biomedical Research Centre and the Behavioural and Clinical Neuroscience Institute (which was supported by a joint award from the Medical Research Council and the Wellcome Trust). The Food Frequency Questionnaire and related analysis software were used in the study. These instruments were initially developed as part of the EPIC-Norfolk Study, which was supported by Cancer Research UK programme grant (C864/A8257)

Studying food reward and motivation in humans

A key challenge in studying reward processing in humans is to go beyond subjective self-report measures and quantify different aspects of reward such as hedonics, motivation, and goal value in more objective ways. This is particularly relevant for the understanding of overeating and obesity as well as their potential treatments. In this paper are described a set of measures of food-related motivation using handgrip force as a motivational measure. These methods can be used to examine changes in food related motivation with metabolic (satiety) and pharmacological manipulations and can be used to evaluate interventions targeted at overeating and obesity. However to understand food-related decision making in the complex food environment it is essential to be able to ascertain the reward goal values that guide the decisions and behavioral choices that people make. These values are hidden but it is possible to ascertain them more objectively using metrics such as the willingness to pay and a method for this is described. Both these sets of methods provide quantitative measures of motivation and goal value that can be compared within and between individuals

Birth weight, family history of diabetes and diabetes onset in schizophrenia.

INTRODUCTION:The prevalence of diabetes in schizophrenia is twice that in the general population, but there are few reliable predictors of which individuals will develop glucose dysregulation. OBJECTIVE:To test if abnormal birth weight (either too low or too high) and parental diabetes, both variables that can be ascertained in the clinic, can predict diabetes onset in patients with schizophrenia. RESEARCH DESIGN AND METHODS:Electronic records of a cohort of 190 clozapine-treated patients (37% treated for more than 20 years) and Cox regression survival analysis (with any type of glucose dysregulation as the event) to account for differences in length of treatment before the event and age at clozapine treatment initiation. RESULTS:Age at clozapine initiation (Exp(B)=1.098; p<0.001), family history of diabetes (Exp(B)=2.299; p=0.049) and birth weight2 (Exp(B)=0.999; p=0.013) were significant predictors of glucose dysregulation onset, while gender was not (Exp(B)=0.1.350; p=0.517). Among individuals with 10 years of follow-up, 80% of those with both abnormal birth weight and a family history of diabetes developed diabetes compared with 56% with only abnormal birth weight, 40% with only a family history of diabetes and 20% in those with neither. CONCLUSIONS:Since 48% of cases had at least one risk factor and 6% had both risk factors, there is a substantial proportion of patients for whom preventive strategies could be implemented

Eating at food outlets and leisure places and "on the go" is associated with less-healthy food choices than eating at home and in school in children: cross-sectional data from the UK National Diet and Nutrition Survey Rolling Program (2008-2014).

BACKGROUND: Where children eat has been linked to variations in diet quality, including the consumption of low-nutrient, energy-dense food, a recognized risk factor for obesity. OBJECTIVE: The aim of this study was to provide a comprehensive analysis of consumption patterns and nutritional intake by eating location in British children with the use of a nationally representative survey. DESIGN: Cross-sectional data from 4636 children (80,075 eating occasions) aged 1.5-18 y from the UK National Diet and Nutrition Survey Rolling Program (2008-2014) were analyzed. Eating locations were categorized as home, school, work, leisure places, food outlets, and "on the go." Foods were classified into core (considered important or acceptable within a healthy diet) and noncore (all other foods). Other variables included the percentage of meals eaten at home, sex, ethnicity, body mass index, income, frequency of eating out, takeaway meal consumption, alcohol consumption, and smoking. RESULTS: The main eating location across all age groups was at home (69-79% of eating occasions), with the highest energy intakes. One-third of children from the least-affluent families consumed ≤25% of meals at home. Eating more at home was associated with less sugar and takeaway food consumption. Eating occasions in leisure places, food outlets, and "on the go" combined increased with age, from 5% (1.5-3 y) to 7% (11-18 y), with higher energy intakes from noncore foods in these locations. The school environment was associated with higher intakes of core foods and reduced intakes of noncore foods in children aged 4-10 y who ate school-sourced foods. CONCLUSIONS: Home and school eating are associated with better food choices, whereas other locations are associated with poor food choices. Effective, sustained initiatives targeted at behaviors and improving access to healthy foods in leisure centers and food outlets, including food sold to eat "on the go," may improve food choices. Home remains an important target for intervention through family and nutrition education, outreach, and social marketing campaigns. This trial was registered with the ISRTCN registry (https://www.isrctn.com) as ISRCTN17261407

Dopamine modulates the neural representation of subjective value of food in hungry subjects.

Although there is a rich literature on the role of dopamine in value learning, much less is known about its role in using established value estimations to shape decision-making. Here we investigated the effect of dopaminergic modulation on value-based decision-making for food items in fasted healthy human participants. The Becker-deGroot-Marschak auction, which assesses subjective value, was examined in conjunction with pharmacological fMRI using a dopaminergic agonist and an antagonist. We found that dopamine enhanced the neural response to value in the inferior parietal gyrus/intraparietal sulcus, and that this effect predominated toward the end of the valuation process when an action was needed to record the value. Our results suggest that dopamine is involved in acting upon the decision, providing additional insight to the mechanisms underlying impaired decision-making in healthy individuals and clinical populations with reduced dopamine levels.This is the author's accepted manuscript. The final version is available from the Society for Neuroscience in the Journal of Neuroscience at http://www.jneurosci.org/content/34/50/16856.abstract

Covid-19 in the UK: policy on children and schools

Key messagesPandemic policy on children and schools reflected UK based scientific narratives that did not align with global scientific consensusGovernment relied on evidence that downplayed the seriousness of covid-19 in children, underestimated the benefits of precautionary measures, and overestimated the harms of vaccinationReturn to school in September 2020 with minimal emphasis on masking and air quality, and inadequate support for isolation may have accelerated community transmissionThe public inquiry should explore why the UK was an international outlier in its approach to protecting children and making schools and communities safe

Oxytocin administration suppresses hypothalamic activation in response to visual food cues

The aim of this study was to use functional neuroimaging to investigate whether oxytocin modulates the neural response to visual food cues in brain regions involved in the control of food intake. Twenty-four normal weight volunteers received intranasal oxytocin (24 IU) or placebo in a double-blind, randomized crossover study. Measurements were made forty-five minutes after dosing. On two occasions, functional MRI (fMRI) scans were performed in the fasted state; the blood oxygen level-dependent (BOLD) response to images of high-calorie foods versus low-calorie foods was measured. Given its critical role in eating behaviour, the primary region of interest was the hypothalamus. Secondary analyses examined the parabrachial nuclei and other brain regions involved in food intake and food reward. Intranasal oxytocin administration suppressed hypothalamic activation to images of high-calorie compared to low-calorie food (P = 0.0125). There was also a trend towards suppression of activation in the parabrachial nucleus (P = 0.0683). No effects of intranasal oxytocin were seen in reward circuits or on ad libitum food intake. Further characterization of the effects of oxytocin on neural circuits in the hypothalamus is needed to establish the utility of targeting oxytocin signalling in obesity