Genetic analysis of maximum cigarette-use phenotypes

BACKGROUND: Using the Framingham Heart Study data set provided for Genetic Analysis Workshop 13, we defined the cigarette-use phenotype M for smokers to be the maximum number of cigarettes-per-day (MAXCIG) reported over the longitudinal course of the study. Adjustments were made for the significant covariates of gender and year of birth, and sib-pair based linkage analysis was performed. RESULTS: The primary analyses, in which individuals with MAXCIG = 0 were considered to have missing phenotype, resulted in modest linkage evidence, with LOD scores over 1 on chromosomes 5, 9, 13, 14, and 22. CONCLUSIONS: While the results reported here do not indicate definitive evidence for linkage to specific chromosomal regions, future studies may find it useful to include direct assessments of maximum and quantitative cigarette use. In defining and analyzing quantitative or "maximum use" phenotypes, the choice of how to handle individuals with MAXCIG = 0, or alternatively, individuals who are substance-naive, is a crucial one for genetic studies of nicotine and other substance use. In this study, the linkage results vary greatly depending on whether or not these "unexposed" individuals are included in the analyses

Genetic analysis of the maximum drinks phenotype

Using data provided by the Collaborative Study on the Genetics of Alcoholism we studied the genetics of a quantitative trait: the maximum number of drinks consumed in a 24-hour period. A two-stage method was used. First, linkage analysis was performed, followed by association analysis in regions where linkage was detected. Additionally, the extent of linkage disequilibrium among single-nucleotide polymorphisms (SNP) associated with the phenotype was assessed. Linkage to chromosomes 2 and 7 was detected, and follow-up association analysis found multiple trait-associated SNPs in the chromosome 7 linkage region. Chromosome 4, which has been implicated in previous studies of the maximum drinks phenotype, did not pass our threshold for linkage evidence in stage 1, but secondary analyses of this chromosome indicated modest evidence for both linkage and association. The evidence suggests that chromosome 7 may harbor an additional locus influencing the maximum drinks consumption phenotype

Columbia River Basin Water Law Institutions and Policies Survey: Report to the Western Water Policy Review Advisory Commission

Report to the Western Water Policy Review Advisory Commissio

Branch-and-lift algorithm for deterministic global optimization in nonlinear optimal control

This paper presents a branch-and-lift algorithm for solving optimal control problems with smooth nonlinear dynamics and potentially nonconvex objective and constraint functionals to guaranteed global optimality. This algorithm features a direct sequential method and builds upon a generic, spatial branch-and-bound algorithm. A new operation, called lifting, is introduced, which refines the control parameterization via a Gram-Schmidt orthogonalization process, while simultaneously eliminating control subregions that are either infeasible or that provably cannot contain any global optima. Conditions are given under which the image of the control parameterization error in the state space contracts exponentially as the parameterization order is increased, thereby making the lifting operation efficient. A computational technique based on ellipsoidal calculus is also developed that satisfies these conditions. The practical applicability of branch-and-lift is illustrated in a numerical example. © 2013 Springer Science+Business Media New York

The association between asymmetric information, hospital competition and quality of healthcare: evidence from Italy

We study the effect of competition on adverse hospital health outcomes in a context in which information about hospital quality is not publicly available. We use data on patients who were admitted to hospitals in the Lombardy region of Italy. Although risk-adjusted hospital rankings are estimated yearly in this region, such rankings are provided to hospital managers only and are not available to general practitioners or citizens. Hence, patients may choose the hospital where to be admitted on the basis of different criteria such as their geographical closeness to the hospital, local network information and referrals by general practitioners.We first estimate a model of patient hospital choices and include among the determinants a variable capturing social interaction, which represents a proxy for the quality of hospitals perceived by patients. Using patient-predicted choice probabilities, we then construct a set of competition indices and measure their effect on a composite index of mortality and readmission rates that represents, in our settings, hospital quality in terms of adverse health outcomes. Our results show that no association exists between such adverse events and hospital competition. Our finding may be the result of asymmetric information, as well as the difficulty of building good quality health indicators

Revisiting the 'Missing Middle' in English Sub-National Governance

In the light of the new Coalition Government’s proposed ‘rescaling’ of sub-national governance away from the regional level, it is an opportune time to re-consider the strength and weaknesses of the city or sub-regional approach to economic development and to search, once more, for the ‘missing middle’ in English Governance. In this context, the article initially assesses the case for city or sub regions as tiers of economic governance, before examining the lessons to be learnt from the experiences of the existing city regions in the North East of England. It argues that while contemporary plans to develop Local Enterprise Partnerships (LEPs) can be usefully considered within the context of the emerging city regional developments under the previous Labour Governments, a number of important challenges remain, particularly in relation to ensuring accountable structures of governance, a range of appropriate functions, adequate funding, and comprehensive coverage across a variety of sub-regional contexts. While the proposals of the new Government create the necessary ‘space’ to develop sub-regional bodies and offer genuine opportunities for both city and county LEPs, the scale of the sub-regional challenge should not be underestimated, particularly given the context of economic recession and major reductions in the public sector

Transfer of training in an academic leadership development program for program coordinators

The higher education sector has increasingly begun to pay more attention to academic leadership. This qualitative study explores how such an investment in a 20-week leadership development program influenced the behaviour of 10 academic staff in the role of program coordinator 6 to 12 months following participation in the program. Otherwise known as program directors or department chairs, academic staff in this role are responsible for coordinating and leading degree courses or programs. Leadership learning and changes in the behaviour of program coordinators was evident, particularly in regard to building influence, communicating more effectively and managing upwards. Improved confidence in their ability to perform the role was a lasting outcome and the use of peer learning and coaching was an important part of the success of the intervention. However, workload factors, succession planning and orientation were seen to be factors that impact on leadership development in this role. The findings suggest that participation in well designed academic leadership programs can result in a lasting transfer of training for program coordinators

Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with ‘pleasurable buzz’ during early experimentation with smoking

AimsTo extend the previously identified association between a single nucleotide polymorphism (SNP) in neuronal acetylcholine receptor subunit alpha-5 (CHRNA5) and nicotine dependence to current smoking and initial smoking-experience phenotypes.Design, setting, participantsCase–control association study with a community-based sample, comprising 363 Caucasians and 72 African Americans (203 cases, 232 controls).MeasurementsCases had smoked ≥ five cigarettes/day for ≥ 5 years and had smoked at their current rate for the past 6 months. Controls had smoked between one and 100 cigarettes in their life-time, but never regularly. Participants also rated, retrospectively, pleasurable and displeasurable sensations experienced when they first smoked. We tested for associations between smoking phenotypes and the top 25 SNPs tested for association with nicotine dependence in a previous study.FindingsA non-synonymous coding SNP in CHRNA5, rs16969968, was associated with case status [odds ratio (OR) = 1.5, P = 0.01] and, in Caucasians, with experiencing a pleasurable rush or buzz during the first cigarette (OR = 1.6, P = 0.01); these sensations were associated highly with current smoking (OR = 8.2, P = 0.0001).ConclusionsWe replicated the observation that the minor allele of rs16969968 affects smoking behavior, and extended these findings to sensitivity to smoking effects upon experimentation. While the ability to test genetic associations was limited by sample size, the polymorphism in the CHRNA5 subunit was shown to be associated significantly with enhanced pleasurable responses to initial cigarettes in regular smokers in an a priori test. The findings suggest that phenotypes related to subjective experiences upon smoking experimentation may mediate the development of nicotine dependence