Heterochromatin and the molecular mechanisms of 'parent-of-origin' effects in animals.

Twenty five years ago it was proposed that conserved components of constitutive heterochromatin assemble heterochromatinlike complexes in euchromatin and this could provide a general mechanism for regulating heritable (cell-to-cell) changes in gene expressibility. As a special case, differences in the assembly of heterochromatin-like complexes on homologous chromosomes might also regulate the parent-of-origin-dependent gene expression observed in placental mammals. Here, the progress made in the intervening period with emphasis on the role of heterochromatin and heterochromatin-like complexes in parent-of-origin effects in animals is reviewed

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health

Risks of airborne pollution accidents in a major conurbation: Case study of Zhangjiakou, a host city for the 2022 Winter Olympics

The number of airborne pollution accidents is second only to that of water-borne pollution accidents, in recorded environmental disasters. Acute casualties and public health costs have prompted many airborne pollution risk analyses. To date, few assessment methods have been carried out at regional-scale to quantify acute airborne pollution risk. Herein, a Hybrid Simulation and Risk Analysis approach, involving a systematic combination of simulation, risk ranking, and standardized analysis, is proposed at regional scale. Gaussian and heavy-gas models are utilized in the simulation process, and acute exposure limits preferentially adopted in the risk analysis. The case study shows that 34 of 243 townships in Zhangjiakou City of north China, one of the twin cities selected to host the 2022 Winter Olympics, are threatened by airborne risk sources. It is found that the accidental air pollution risk is comparatively higher in the Xuanhua and Wanquan conurbations. High-risk chemical enterprises (312–432 risk scores) are mostly located near urban areas with high population density where many people are vulnerable receptors to potential air pollution accidents. The resulting risk map indicates that acute airborne pollution from Zhangjiakou would not be a threat either to the proposed Olympic site at Chongli or to downwind Beijing

Gambling disorder and substance-related disorders: Similarities and differences

Gambling disorder (GD) has important similarities with substance use disorders (SUDs) in terms of both diagnostic criteria and underlying mechanisms of action. With regard to diagnostic criteria, only craving is not present as a formal criterion in DSM-5 GD, and chasing losses is not present in SUDs. All other major diagnostic criteria such as loss of control over gambling, tolerance, withdrawal, and negative consequences due to gambling overlap with those of SUD. With regard to underlying mechanisms and vulnerability factors, higher impulsivity, abnormalities in decision-making, deficient executive functions, and related fronto-striatal brain circuitry abnormalities are related to the development and course of both SUD and GD. However, there are also differences between GD and SUD. In gambling, cognitive factors such as risk-taking and decision-making are intrinsically related to the addictive behavior itself, whereas in SUD these effects can also be associated with the pharmacological effect or the neurotoxicity related to (chronic) substance use. Moreover misperceptions with regard to gambling, the experience and interpretation of near misses, and the processing of (potential) rewards and losses influence the experience of gambling, which is not true for SUD. Importantly, these aspects also differ between disordered gamblers and non-problematic gamblers and are thus unique for GD and consitute a risk for relapse. Both shared and unique mechanisms are relevant as targets for the treatment of GD. This chapter concludes with a discussion on novel treatment methods that target some of the working mechanisms shared by GD and SUDs