The economics of alcohol:a collection of essays

This thesis consists of three self-contained essays on the economics of alcohol demand. Chapter 2 examines the price elasticity of demand for alcohol across the drinking distribution, using household expenditure data to test whether heavy drinkers respond the same as light drinkers to price increases. Both conditional and unconditional quantile regression are used to compare results generated by the two different methods. The chapter finds that when price increases, heavier drinkers decrease consumption proportionately less than lighter drinkers whilst substituting more towards lower quality beverages. This is an important result since it shows that price-based policies may have little effect in reducing heavy consumption whilst creating large welfare losses for moderate drinkers. Chapter 3 uses several different methods including the Tobit and Double-Hurdle models to estimate the mean price elasticity of demand for alcohol. In doing so, it tests how the price elasticity estimates can differ depending on model choice, even when the same data is used. Household expenditure data contains a large number of households who do not purchase any alcohol, for three distinct reasons: price reasons, non-price reasons, and infrequent purchase. A double-hurdle model is developed which can accommodate all three types of non-purchase. The results suggest that, compared to the double-hurdle model, the frequently-used Tobit model produces larger absolute estimates of the price elasticity of demand for alcohol. The double-hurdle model is the preferred specification since it incorporates all reasons for zeros in alcohol expenditure. Chapter 4 explores changes in alcohol consumption across the lifecourse using a large number of waves of a cross-sectional survey, the General Household Survey, to create synthetic cohorts. Whilst the existing literature looks at how the mean consumption differs across birth cohorts, this chapter instead looks at different quantiles of the drinking distribution to examine whether the changes are consistent across all drinkers, including abstention. This is important because it shows how the alcohol consumption distribution has changed across time, age and birth cohort. It finds that generally, alcohol consumption decreases both as age increases and in older birth cohorts. Alcohol consumption by females has particularly changed; younger birth cohorts drinking much more than their parents’ cohorts did, yet younger birth cohorts are also more likely not to drink at all. Whilst these chapters can be considered stand-alone essays, they are also linked and show how different and cutting edge techniques, applied to the best available data, can be used to show new and interesting results which can aid policymakers and policy decisions

Insights into the structures adopted by titanocalix[6 and 8]arenes and their use in the ring opening polymerization of cyclic esters

Interaction of p-tert-butylcalix[6]areneH6, L1H6, with [TiCl4] afforded the complex [Ti2Cl3(MeCN)2(OH2)(L1H)][Ti2Cl3(MeCN)3(L1H)]∙4.5MeCN (1∙4.5MeCN), in which two pseudo octahedral titanium centres are bound to one calix[6]arene. A similar reaction but employing THF resulted in the THF ring-opened product [Ti4Cl2(μ3-O)2(NCMe)2(L)2(O(CH2)4Cl)2]∙4MeCN (2∙4MeCN), where LH4 = p-tert-butylcalix[4]areneH4. Interaction of L1H6 with TiF4 (3 equiv.) led, after work-up, to the complex [(TiF)2(μ -F)L1H]2∙6.5MeCN (3∙6.5MeCN). Treatment of p-tert-butylcalix[8]areneH8, L2H8, with [TiCl4] led to the isolation of the complex [(TiCl)2(TiClNCMe)2(μ3-O)2(L2)]∙1.5MeCN (4∙1.5MeCN). From a similar reaction, a co-crystallized complex [Ti4O2Cl4(MeCN)2(L2)][Ti3Cl6(MeCN)5(OH2)(L2H2)]·H2O∙11MeCN (5·H2O 11MeCN) was isolated. Extension of the L2H8 chemistry to [TiBr4] afforded, depending on the stoichiometry, the complexes [(TiBr)2(TiBrNCMe)2(μ3-O)2(L2)]∙6MeCN (6∙6MeCN) or [Ti(NCMe)2Br]2[Ti(O)Br2(NCMe)](L2)]∙7.5MeCN (7∙7.5MeCN), whilst use of [TiF4] afforded complexes containing Ca2+ and Na+, thought to originate from drying agents, namely [Ti8CaF20(OH2)Na2(MeCN)4(L2)2]∙14MeCN (8∙14MeCN), [Na(MeCN)2][Ti8CaF20NaO16(L2)2]∙7MeCN (9∙7MeCN) or [Na]6[Ti8F20Na(MeCN)2(L2)][Ti8F20Na(MeCN)0.5(L2)]∙15.5(C2H3N) (10∙15.5MeCN). In the case of TiI4, the ladder [(TiI)2(TiINCMe)2(μ3-O)2(L2)]∙7.25CH2Cl2 (11∙7.25CH2Cl2) was isolated. These complexes have been screened for their potential to act as catalysts in the ring opening polymerization (ROP) of ε-caprolactone (ε-CL), δ-valerolactone (δ-VL) and rac-lactide (r-LA), both in air and N2. For ε-CL and δ-VL, moderate activity at 130 oC over 24 h was observed for 1, 9 and 11; for r-LA, only 1 exhibited reasonable activity. In the case of the co-polymerization of ε-CL with δ-VL, the complexes 1 and 11 afforded reasonable conversions and low molecular weight polymers, whilst 4, 6, and 9 were less effective. None of the complexes proved to be active in the co-polymerization of ε-CL and r-LA under the conditions employed herein

Bank voles show more impulsivity in IntelliCage learning tasks than wood mice

Impulsivity is a personality trait of healthy individuals, but in extreme forms common in mental disorders. Previous behavioral testing of wild-caught bank voles and wood mice suggested impulsiveness in bank voles. Here, we compared behavioral performance of bank voles and wood mice in tests for response control in the IntelliCage. In the reaction time task, a test similar to the five-choice serial-reaction time task (5CSRTT), bank voles made more premature responses. Impulsivity in the reaction time task was associated with smaller medial habenular nucleus in bank voles. Additional tests revealed reduced behavioral flexibility in the self-paced flexibility task in bank voles, but equal spatial and reversal learning in the chaining/reversal task in both species. Expression of immediate early gene Arc after behavioral testing was low in medial prefrontal cortex, but high in hypothalamic supraoptic and paraventricular nucleus in bank voles. Wood mice showed the opposite pattern. Numbers of Arc-positive cells in the dorsal hippocampus were higher in bank voles than wood mice. Due to continuous behavioral testing (24/7), associations between behavioral performance and Arc were rare. Corticosterone measurements at the end of experiments suggested that IntelliCage testing did not elicit a stress response in these wild rodents. In summary, habenular size differences and altered activation of brain areas after testing might indicate differently balanced activations of cortico-limbic and cortico-hypothalamic circuits in bank voles compared to wood mice. Behavioral performance of bank voles suggest that these rodents could be a natural animal model for investigating impulsive and perseverative behaviors

Chronic social stress induces peripheral and central immune activation, blunted mesolimbic dopamine function, and reduced reward-directed behaviour in mice

Psychosocial stress is a major risk factor for depression, stress leads to peripheral and central immune activation, immune activation is associated with blunted dopamine (DA) neural function, DA function underlies reward interest, and reduced reward interest is a core symptom of depression. These states might be inter-independent in a complex causal pathway. Whilst animal-model evidence exists for some specific steps in the pathway, there is currently no animal model in which it has been demonstrated that social stress leads to each of these immune, neural and behavioural states. Such a model would provide important existential evidence for the complex pathway and would enable the study of causality and mediating mechanisms at specific steps in the pathway. Therefore, in the present mouse study we investigated for effects of 15-day resident-intruder chronic social stress (CSS) on each of these states. Relative to controls, CSS mice exhibited higher spleen levels of granulocytes, inflammatory monocytes and T helper 17 cells; plasma levels of inducible nitric oxide synthase; and liver expression of genes encoding kynurenine pathway enzymes. CSS led in the ventral tegmental area to higher levels of kynurenine and the microglia markers Iba1 and Cd11b and higher binding activity of DA D1 receptor; and in the nucleus accumbens (NAcc) to higher kynurenine, lower DA turnover and lower c-fos expression. Pharmacological challenge with DA reuptake inhibitor identified attenuation of DA stimulatory effects on locomotor activity and NAcc c-fos expression in CSS mice. In behavioural tests of operant responding for sucrose reward validated as sensitive assays for NAcc DA function, CSS mice exhibited less reward-directed behaviour. Therefore, this mouse study demonstrates that a chronic social stressor leads to changes in each of the immune, neural and behavioural states proposed to mediate between stress and disruption of DA-dependent reward processing. The model can now be applied to investigate causality and, if demonstrated, underlying mechanisms in specific steps of this immune-neural-behavioural pathway, and thereby to identify potential therapeutic targets

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.</p

Effectiveness of subnational implementation of minimum unit price for alcohol: policy appraisal modelling for local authorities in England

Aims: Evidence exists on the potential impact of national level minimum unit price (MUP) policies for alcohol. This study investigated the potential effectiveness of implementing MUP at regional and local levels compared with national implementation. Design: Evidence synthesis and computer modelling using the Sheffield Alcohol Policy Model (Local Authority version 4.0; SAPMLA). Setting: Results are produced for 23 Upper Tier Local Authorities (UTLAs) in North West England, 12 UTLAs in North East England, 15 UTLAs in Yorkshire and Humber, the nine English Government Office regions and England as a whole. Cases: Health Survey for England (HSE) data 2011–13 (n = 24 685). Measurements: Alcohol consumption, consumer spending, retailers’ revenues, hospitalizations, National Health Service costs, crimes and alcohol-attributable deaths and health inequalities. Findings: Implementing a local £0.50 MUP for alcohol in northern English regions is estimated to result in larger percentage reductions in harms than the national average. The reductions for England, North West, North East and Yorkshire and Humber regions, respectively, in annual alcohol-attributable deaths are 1024 (−10.4%), 205 (−11.4%), 121 (−17.4%) and 159 (−16.9%); for hospitalizations are 29 943 (−4.6%), 5956 (−5.5%), 3255 (−7.9%) and 4610 (−6.9%); and for crimes are 54 229 (−2.4%), 8528 (−2.5%), 4380 (−3.5%) and 8220 (−3.2%). Results vary among local authorities; for example, annual alcohol-attributable deaths estimated to change by between −8.0 and −24.8% throughout the 50 UTLAs examined. Conclusions: A minimum unit price local policy for alcohol is likely to be more effective in those regions, such as the three northern regions of England, which have higher levels of alcohol consumption and higher rates of alcohol harm than for the national average. In such regions, the minimum unit price policy would achieve larger reductions in alcohol consumption, alcohol-attributable mortality, hospitalization rates, NHS costs, crime rates and health inequalities

Association of Variants at 1q32 and STAT3 with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn's Disease

Ankylosing spondylitis (AS) is a common inflammatory arthritic condition. Overt inflammatory bowel disease (IBD) occurs in about 10% of AS patients, and in addition 70% of AS cases may have subclinical terminal ileitis. Spondyloarthritis is also common in IBD patients. We therefore tested Crohn's disease susceptibility genes for association with AS, aiming to identify pleiotropic genetic associations with both diseases. Genotyping was carried out using Sequenom and Applied Biosystems TaqMan and OpenArray technologies on 53 markers selected from 30 Crohn's disease associated genomic regions. We tested genotypes in a population of unrelated individual cases (n = 2,773) and controls (n = 2,215) of white European ancestry for association with AS. Statistical analysis was carried out using a Cochran-Armitage test for trend in PLINK. Strong association was detected at chr1q32 near KIF21B (rs11584383, P = 1.6×10−10, odds ratio (OR) = 0.74, 95% CI:0.68–0.82). Association with disease was also detected for 2 variants within STAT3 (rs6503695, P = 4.6×10−4. OR = 0.86 (95% CI:0.79–0.93); rs744166, P = 2.6×10−5, OR = 0.84 (95% CI:0.77–0.91)). Association was confirmed for IL23R (rs11465804, P = 1.2×10−5, OR = 0.65 (95% CI:0.54–0.79)), and further associations were detected for IL12B (rs10045431, P = 5.2×10−5, OR = 0.83 (95% CI:0.76–0.91)), CDKAL1 (rs6908425, P = 1.1×10−4, OR = 0.82 (95% CI:0.74–0.91)), LRRK2/MUC19 (rs11175593, P = 9.9×10−5, OR = 1.92 (95% CI: 1.38–2.67)), and chr13q14 (rs3764147, P = 5.9×10−4, OR = 1.19 (95% CI: 1.08–1.31)). Excluding cases with clinical IBD did not significantly affect these findings. This study identifies chr1q32 and STAT3 as ankylosing spondylitis susceptibility loci. It also further confirms association for IL23R and detects suggestive association with another 4 loci. STAT3 is a key signaling molecule within the Th17 lymphocyte differentiation pathway and further enhances the case for a major role of this T-lymphocyte subset in ankylosing spondylitis. Finally these findings suggest common aetiopathogenic pathways for AS and Crohn's disease and further highlight the involvement of common risk variants across multiple diseases

The Resilient Dairy Genome Project - a general overview of methods and objectives related to feed efficiency and methane emissions.

The Resilient Dairy Genome Project (RDGP) is an international large-scale applied research project that aims to generate genomic tools to breed more resilient dairy cows. In this context, improving feed efficiency and reducing greenhouse gases from dairy is a high priority. The inclusion of traits related to feed efficiency (e.g., dry matter intake [DMI]) or greenhouse gases (e.g., methane emissions [CH4]) relies on available genotypes as well as high quality phenotypes. Currently, 7 countries, i.e., Australia [AUS], Canada [CAN], Denmark [DNK], Germany [DEU], Spain [ESP], Switzerland [CHE], and United States of America [USA] contribute with genotypes and phenotypes including DMI and CH4. However, combining data is challenging due to differences in recording protocols, measurement technology, genotyping, and animal management across sources. In this study, we provide an overview of how the RDGP partners address these issues to advance international collaboration to generate genomic tools for resilient dairy. Specifically, we describe the current state of the RDGP database, data collection protocols in each country, and the strategies used for managing the shared data. As of February 2022, the database contains 1,289,593 DMI records from 12,687 cows and 17,403 CH4 records from 3,093 cows and continues to grow as countries upload new data over the coming years. No strong genomic differentiation between the populations was identified in this study, which may be beneficial for eventual across-country genomic predictions. Moreover, our results reinforce the need to account for the heterogeneity in the DMI and CH4 phenotypes in genomic analysis