Estimating Two-Stage Models for Genetic Influences on Alcohol, Tobacco or Drug Use Initiation and Dependence Vulnerability in Twin and Family Data

Genetic research on risk of alcohol, tobacco or drug dependence must make allowance for the partial overlap of risk-factors for initiation of use, and risk-factors for dependence or other outcomes in users. Except in the extreme cases where genetic and environmental risk-factors for initiation and dependence overlap completely or are uncorrelated, there is no consensus about how best to estimate the magnitude of genetic or environmental correlations between Initiation and Dependence in twin and family data. We explore by computer simulation the biases to estimates of genetic and environmental parameters caused by model misspecification when Initiation can only be defined as a binary variable. For plausible simulated parameter values, the two-stage genetic models that we consider yield estimates of genetic and environmental variances for Dependence that, although biased, are not very discrepant from the true values. However, estimates of genetic (or environmental) correlations between Initiation and Dependence may be seriously biased, and may differ markedly under different two-stage models. Such estimates may have little credibility unless external data favor selection of one particular model. These problems can be avoided if Initiation can be assessed as a multiple-category variable (e.g. never versus early-onset versus later onset user), with at least two categories measurable in users at risk for dependence. Under these conditions, under certain distributional assumptions., recovery of simulated genetic and environmental correlations becomes possible, Illustrative application of the model to Australian twin data on smoking confirmed substantial heritability of smoking persistence (42%) with minimal overlap with genetic influences on initiation.

Testing insect movement theory: empirical analysis of pest data routinely collected from agricultural crops

Observations of an insect's movement lead to theory on the insect's flight behaviour and the role of movement in the species' population dynamics. This theory leads to predictions of the way the population changes in time under different conditions. If a hypothesis on movement predicts a specific change in the population, then the hypothesis can be tested against observations of population change. Routine pest monitoring of agricultural crops provides a convenient source of data for studying movement into a region and among fields within a region. Examples of the use of statistical and computational methods for testing hypotheses with such data are presented. The types of questions that can be addressed with these methods and the limitations of pest monitoring data when used for this purpose are discussed. (C) 2002 Elsevier Science B.V. All rights reserved.

Whither our Art? Clinical Wisdom & Evidence-based Medicine

The relationship between evidence-based medicine (EBM) and clinical judgement is the subject of conceptual and practical dispute. For example, EBM and clinical guidelines are seen to increasingly dominate medical decision-making at the expense of other, human elements, and to threaten the art of medicine. Clinical wisdom always remains open to question. We want to know why particular beliefs are held, and the epistemological status of claims based in wisdom or experience. The paper critically appraises a number of claims and distinctions, and attempts to clarify the connections between EBM, clinical experience and judgement, and the objective and evaluative categories of medicine. I conclude that to demystify clinical wisdom is not to devalue it. EBM ought not be conceived as needing to be limited or balanced by clinical wisdom, since if its language is translatable into terms comprehensible and applicable to individuals, it helps constitute clinical wisdom. Failure to appreciate this constitutive relation will help perpetuate medical paternalism and delay the adoption of properly evidence-based practice, which would be both unethical and unwise.

Phase equilibrium data and liquidus for the system "MnO"-CaO-(Al2O3+SiO2) at Al2O3/SiO2 of 0.41

Phase-equilibrium data and the liquidus for the system. "MnO"-CaO-(Al2O3-SiO2) at a manganese-rich alloy saturation have been determined in the temperature range from 1423 to 1723 K. The results are presented in the form of a pseudoternary section "MnO"-CaO-(Al2O3 + SiO2) with an Al2O3/SiO2 weight ratio of 0.41. The following primary phases are present in the range of conditions investigated:, 3Al(2)O(3).2SiO(2); SiO2; MnO.Al2O3-2SiO(2); (Mn,Ca)O.SiO2; 2(Mn,Ca)O.SiO2; MnO.Al2O3; (Mn,Ca)O; alpha-2CaO.SiO2; alpha'-2CaO.SiO2; 2CaO.Al2O3.SiO2; CaO.SiO2, and CaO.Al2O3.2SiO(2). The presence of alumina in this system is shown to have a significant effect on the liquidus compared to the system "MnO"-CaO-SiO2, leading to, the stabilization of the anorthite and gehlenite phases.

Mineral chemistry, whole-rock compositions, and petrogenesis of leg 176 gabbros: Data and discussion

We report mineral chemistry, whole-rock major element compositions, and trace element analyses on Hole 735B samples drilled and selected during Leg 176. We discuss these data, together with Leg 176 shipboard data and Leg 118 sample data from the literature, in terms of primary igneous petrogenesis. Despite mineral compositional variation in a given sample, major constituent minerals in Hole 735B gabbroic rocks display good chemical equilibrium as shown by significant correlations among Mg# (= Mg/[Mg+Fe2+]) of olivine, clinopyroxene, and orthopyroxene and An (=Ca/[Ca+Na]) of plagioclase. This indicates that the mineral assemblages olivine + plagioclase in troctolite, plagioclase + clinopyroxene in gabbro, plagioclases + clinopyroxene + olivine in olivine gabbro, and plagioclase + clinopyroxene + olivine + orthopyroxene in gabbronorite, and so on, have all coprecipitated from their respective parental melts. Fe-Ti oxides (ilmenite and titanomagnetite), which are ubiquitous in most of these rocks, are not in chemical equilibrium with olivine, clinopyroxene, and plagioclase, but precipitated later at lower temperatures. Disseminated oxides in some samples may have precipitated from trapped Fe-Ti–rich melts. Oxides that concentrate along shear bands/zones may mark zones of melt coalescence/transport expelled from the cumulate sequence as a result of compaction or filter pressing. Bulk Hole 735B is of cumulate composition. The most primitive olivine, with Fo = 0.842, in Hole 735B suggests that the most primitive melt parental to Hole 735B lithologies must have Mg# ≤ 0.637, which is significantly less than Mg# = 0.714 of bulk Hole 735B.

Robust model-order reduction of complex biological processes

This paper addresses robust model-order reduction of a high dimensional nonlinear partial differential equation (PDE) model of a complex biological process. Based on a nonlinear, distributed parameter model of the same process which was validated against experimental data of an existing, pilot-scale BNR activated sludge plant, we developed a state-space model with 154 state variables in this work. A general algorithm for robustly reducing the nonlinear PDE model is presented and based on an investigation of five state-of-the-art model-order reduction techniques, we are able to reduce the original model to a model with only 30 states without incurring pronounced modelling errors. The Singular perturbation approximation balanced truncating technique is found to give the lowest modelling errors in low frequency ranges and hence is deemed most suitable for controller design and other real-time applications. (C) 2002 Elsevier Science Ltd. All rights reserved.

Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58 515 women with breast cancer and 95 067 women without the disease

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P