A rapid evidence review of the effectiveness and cost-effectiveness of alcohol control policies: an English perspective.

This paper reviews the evidence for the effectiveness and cost-effectiveness of policies to reduce alcohol-related harm. Policies focus on price, marketing, availability, information and education, the drinking environment, drink-driving, and brief interventions and treatment. Although there is variability in research design and measured outcomes, evidence supports the effectiveness and cost-effectiveness of policies that address affordability and marketing. An adequate reduction in temporal availability, particularly late night on-sale availability, is effective and cost-effective. Individually-directed interventions delivered to at-risk drinkers and enforced legislative measures are also effective. Providing information and education increases awareness, but is not sufficient to produce long-lasting changes in behaviour. At best, interventions enacted in and around the drinking environment lead to small reductions in acute alcohol-related harm. Overall, there is a rich evidence base to support the decisions of policy makers in implementing the most effective and cost-effective policies to reduce alcohol-related harm.

JBP1 and JBP2 are two distinct thymidine hydroxylases involved in J biosynthesis in genomic DNA of African trypanosomes.

Genomic DNA of African trypanosomes contains a hypermodified thymidine residue termed base J (beta-d-glucosyl-HOMedU). This modified base is localized primarily to repetitive DNA, namely the telomeres, and is implicated in the regulation of antigenic variation. The base is synthesized in a two-step pathway. Initially, a thymidine residue in DNA is hydroxylated by a thymidine hydroxylase (TH). This intermediate (HOMedU) is then glucosylated to form base J. Two proteins involved in J synthesis, JBP1 (J binding protein 1) and JBP2, contain a putative TH domain related to the family of Fe(2+)/2-oxoglutarate-dependent hydroxylases. We have previously shown that mutations in the TH domain of JBP1 kill its ability to stimulate J synthesis. Here we show that mutation of key residues in the TH domain of JBP2 ablate its ability to induce de novo J synthesis. While the individual JBP1 null and JBP2 null trypanosomes have reduced J levels, the deletion of both JBP1 and JBP2 generates a cell line that completely lacks base J but still contains glucosyl-transferase activity. Reintroduction of JBP2 in the J-null trypanosome stimulates HOMedU formation and site-specific synthesis of base J. We conclude that JBP2 and JBP1 are the TH enzymes involved in J biosynthesis.

The protein that binds to DNA base J in trypanosomatids has features of a thymidine hydroxylase.

Trypanosomatids contain an unusual DNA base J (beta-d-glucosylhydroxymethyluracil), which replaces a fraction of thymine in telomeric and other DNA repeats. To determine the function of base J, we have searched for enzymes that catalyze J biosynthesis. We present evidence that a protein that binds to J in DNA, the J-binding protein 1 (JBP1), may also catalyze the first step in J biosynthesis, the conversion of thymine in DNA into hydroxymethyluracil. We show that JBP1 belongs to the family of Fe(2+) and 2-oxoglutarate-dependent dioxygenases and that replacement of conserved residues putatively involved in Fe(2+) and 2-oxoglutarate-binding inactivates the ability of JBP1 to contribute to J synthesis without affecting its ability to bind to J-DNA. We propose that JBP1 is a thymidine hydroxylase responsible for the local amplification of J inserted by JBP2, another putative thymidine hydroxylase.

Alcohol-related harm to others in England: a cross-sectional analysis of national survey data.

OBJECTIVES: To estimate the prevalence, the frequency and the perpetrators of alcohol-related harm to others (AHTO) and identify factors associated with experiencing harm and aggressive harm. DESIGN: Cross-sectional survey. SETTING: England. PARTICIPANTS: Adults (general population) aged 16 and over. OUTCOME MEASURES: Percentage of respondents who experienced harm. Socioeconomic and demographic factors associated with the outcomes. Outcomes were (1) experienced harm/did not experience harm and (2) experienced aggressive harm (physically threatened, physically hurt and forced/pressured into something sexual)/did not experience an aggressive harm (no aggressive harm plus no harm at all). RESULTS: Data to support a response rate calculation were not collected; 96.3% of people surveyed completed the AHTO questions. The weighted sample was 4874; 20.1% (95% CI 18.9 to 21.4, N=980) reported experiencing harm in the previous 12 months and 4.6% (95% CI 4.0 to 5.4, N=225) reported experiencing an aggressive harm. Friends and strangers were the dominant perpetrators. Most harms (74.8%) occurred less than monthly. Factors associated with experiencing harm were: younger age (p<0.001), drinking harmfully/hazardously (p<0.001), white British (p<0.001 compared to other white groups and Asian groups and p=0.017 compared to black groups), having a disability (p<0.001), being educated (p<0.001 compared to no education) and living in private rented accommodation (p=0.004 compared with owned outright). Being in the family stage of life (defined as having children in the household) had significantly lower odds of harm (p=0.006 compared to being single), as did being retired (p<0.001 compared to being employed). Factors associated with experiencing an aggressive harm were similar. CONCLUSIONS: This exploratory study, using data collected through the Alcohol Toolkit Survey, shows that AHTO affects 20.1% of the population of England. Even apparently minor harms, like being kept awake, can have a negative impact on health, while aggressive harms are clearly of concern. Using a standard methodology to measure harm across studies would be advantageous. Policies that focus on alcohol must take into consideration the impact of drinking on those other than the drinker.

Crisis decision theory: decisions in the face of negative events.

How do people respond to negative life events? Crisis decision theory combines the strengths of coping theories with research on decision making to predict the responses people choose under negative circumstances. The theory integrates literatures on coping, health behavior, and decision making, among others, into 3 stages that describe the process of responding to negative events: (a) assessing the severity of the negative event, (b) determining response options, and (c) evaluating response options. The author reviews and organizes the relevant research on factors that shape information processing at each stage and that ultimately predict decisions in the face of negative events. Finally, the author presents a critique of crisis decision theory and discusses areas for future research.

JBP2, a SWI2/SNF2-like protein, regulates de novo telomeric DNA glycosylation in bloodstream form Trypanosoma brucei.

Synthesis of the modified thymine base, beta-d-glucosyl-hydroxymethyluracil or J, within telomeric DNA of Trypanosoma brucei correlates with the bloodstream form specific epigenetic silencing of telomeric variant surface glycoprotein genes involved in antigenic variation. In order to analyze the function of base J in the regulation of antigenic variation, we are characterizing the regulatory mechanism of J biosynthesis. We have recently proposed a model in which chromatin remodeling by a SWI2/SNF2-like protein (JBP2) regulates the developmental and de novo site-specific localization of J synthesis within bloodstream form trypanosome DNA. Consistent with this model, we now show that JBP2 (-/-) bloodstream form trypanosomes contain five-fold less base J and are unable to stimulate de novo J synthesis in newly generated telomeric arrays.

Eatwell Guide: modelling the dietary and cost implications of incorporating new sugar and fibre guidelines.

OBJECTIVES: To model food group consumption and price of diet associated with achieving UK dietary recommendations while deviating as little as possible from the current UK diet, in order to support the redevelopment of the UK food-based dietary guidelines (now called the Eatwell Guide). DESIGN: Optimisation modelling, minimising an objective function of the difference between population mean modelled and current consumption of 125 food groups, and constraints of nutrient and food-based recommendations. SETTING: The UK. POPULATION: Adults aged 19 years and above from the National Diet and Nutrition Survey 2008-2011. MAIN OUTCOME MEASURES: Proportion of diet consisting of major foods groups and price of the optimised diet. RESULTS: The optimised diet has an increase in consumption of 'potatoes, bread, rice, pasta and other starchy carbohydrates' (+69%) and 'fruit and vegetables' (+54%) and reductions in consumption of 'beans, pulses, fish, eggs, meat and other proteins' (-24%), 'dairy and alternatives' (-21%) and 'foods high in fat and sugar' (-53%). Results within food groups show considerable variety (eg, +90% for beans and pulses, -78% for red meat). The modelled diet would cost £5.99 (£5.93 to £6.05) per adult per day, very similar to the cost of the current diet: £6.02 (£5.96 to £6.08). The optimised diet would result in increased consumption of n-3 fatty acids and most micronutrients (including iron and folate), but decreased consumption of zinc and small decreases in consumption of calcium and riboflavin. CONCLUSIONS: To achieve the UK dietary recommendations would require large changes in the average diet of UK adults, including in food groups where current average consumption is well within the recommended range (eg, processed meat) or where there are no current recommendations (eg, dairy). These large changes in the diet will not lead to significant changes in the price of the diet.

Experimental evidence that ovary and oviducal gland extracts influence male agonistic behavior in squids.

Recent investigations of sensory and behavioral cues that initiate sexual selection processes in the squid Loligo pealeii have determined that egg capsules deposited on the substrate provide a strong visual and chemotactile stimulus to males, even in the absence of females (1, 2, 3). The visual stimulus of egg capsules attracts males to the eggs, and when the males touch the eggs, they encounter a chemical stimulus that leads to highly aggressive fighting behavior. We have recently demonstrated that egg capsule extracts implanted in artificial egg capsules elicit this aggressive behavior (4). In this communication, we present evidence that the salient chemical factor originates in the ovary and perhaps the oviducal gland of the female reproductive tract.