Subtypes of Illicit Drug Users: A Latent Class Analysis of Data From an Australian Twin Sample

This article applies methods of latent class analysis (LCA) to data on lifetime illicit drug use in order to determine whether qualitatively distinct classes of illicit drug users can be identified. Self-report data on lifetime illicit drug use (cannabis, stimulants, hallucinogens, sedatives, inhalants, cocaine, opioids and solvents) collected from a sample of 6265 Australian twins (average age 30 years) were analyzed using LCA. Rates of childhood sexual and physical abuse, lifetime alcohol and tobacco dependence, symptoms of illicit drug abuse/dependence and psychiatric comorbidity were compared across classes using multinomial logistic regression. LCA identified a 5-class model: Class 1 (68.5%) had low risks of the use of all drugs except cannabis; Class 2 (17.8%) had moderate risks of the use of all drugs; Class 3 (6.6%) had high rates of cocaine, other stimulant and hallucinogen use but lower risks for the use of sedatives or opioids. Conversely, Class 4 (3.0%) had relatively low risks of cocaine, other stimulant or hallucinogen use but high rates of sedative and opioid use. Finally, Class 5 (4.2%) had uniformly high probabilities for the use of all drugs. Rates of psychiatric comorbidity were highest in the polydrug class although the sedative/opioid class had elevated rates of depression/suicidal behaviors and exposure to childhood abuse. Aggregation of population-level data may obscure important subgroup differences in patterns of illicit drug use and psychiatric comorbidity. Further exploration of a 'self-medicating' subgroup is needed.

Latent class and genetic analysis does not support migraine with aura and migraine without aura as separate entities

Latent class and genetic analyses were used to identify subgroups of migraine sufferers in a community sample of 6,265 Australian twins (55% female) aged 25-36 who had completed an interview based on International Headache Society UHS) criteria. Consistent with prevalence rates from other population-based studies, 703 (20%) female and 250 (9%) male twins satisfied the IHS criteria for migraine without aura (MO), and of these, 432 (13%) female and 166 (6%) male twins satisfied the criteria for migraine with aura (MA) as indicated by visual symptoms. Latent class analysis (LCA) of IHS symptoms identified three major symptomatic classes, representing 1) a mild form of recurrent nonmigrainous headache, 2) a moderately severe form of migraine, typically without visual aura symptoms (although 40% of individuals in this class were positive for aura), and 3) a severe form of migraine typically with visual aura symptoms (although 24% of individuals were negative for aura). Using the LCA classification, many more individuals were considered affected to some degree than when using IHS criteria (35% vs. 13%). Furthermore, genetic model fitting indicated a greater genetic contribution to migraine using the LCA classification (heritability, h(2) =0.40; 95% CI, 0.29-0.46) compared with the IHS classification (h(2)=0.36; 95% CI, 0.22-0.42). Exploratory latent class modeling, fitting up to 10 classes, did not identify classes corresponding to either the IHS MO or MA classification. Our data indicate the existence of a continuum of severity, with MA more severe but not etiologically distinct from MO. In searching for predisposing genes, we should therefore expect to find some genes that may underlie all major recurrent headache subtypes, with modifying genetic or environmental factors that may lead to differential expression of the liability for migraine. (C) 2004 Wiley-Liss, Inc.

Genomewide significant linkage to migrainous Hheadache on chromosome 5q21

Familial typical migraine is a common, complex disorder that shows strong familial aggregation. Using latent-class analysis (LCA), we identified subgroups of people with migraine/severe headache in a community sample of 12,245 Australian twins (60% female), drawn from two cohorts of individuals aged 23-90 years who completed an interview based on International Headache Society criteria. We report results from genomewide linkage analyses involving 756 twin families containing a total of 790 independent sib pairs ( 130 affected concordant, 324 discordant, and 336 unaffected concordant for LCA-derived migraine). Quantitative-trait linkage analysis produced evidence of significant linkage on chromosome 5q21 and suggestive linkage on chromosomes 8, 10, and 13. In addition, we replicated previously reported typical-migraine susceptibility loci on chromosomes 6p12.2-p21.1 and 1q21-q23, the latter being within 3 cM of the rare autosomal dominant familial hemiplegic migraine gene (ATP1A2), a finding which potentially implicates ATP1A2 in familial typical migraine for the first time. Linkage analyses of individual migraine symptoms for our six most interesting chromosomes provide tantalizing hints of the phenotypic and genetic complexity of migraine. Specifically, the chromosome 1 locus is most associated with phonophobia; the chromosome 5 peak is predominantly associated with pulsating headache; the chromosome 6 locus is associated with activity-prohibiting headache and photophobia; the chromosome 8 locus is associated with nausea/vomiting and moderate/severe headache; the chromosome 10 peak is most associated with phonophobia and photophobia; and the chromosome 13 peak is completely due to association with photophobia. These results will prove to be invaluable in the design and analysis of future linkage and linkage disequilibrium studies of migraine.

Migraine With Aura and Migraine Without Aura Are Not Distinct Entities: Further Evidence From a Large Dutch Population Study

It is often debated whether migraine with aura (MA) and migraine without aura (MO) are etiologically distinct disorders. A previous study using latent class analysis (LCA) in Australian twins showed no evidence for separate subtypes of MO and MA. The aim of the present study was to replicate these results in a population of Dutch twins and their parents, siblings and partners (N = 10,144). Latent class analysis of International Headache Society (IHS)-based migraine symptoms resulted in the identification of 4 classes: a class of unaffected subjects (class 0), a mild form of nonmigrainous headache (class 1), a moderately severe type of migraine (class 2), typically without neurological symptoms or aura (8% reporting aura symptoms), and a severe type of migraine (class 3), typically with neurological symptoms, and aura symptoms in approximately half of the cases. Given the overlap of neurological symptoms and nonmutual exclusivity of aura symptoms, these results do not support the MO and MA subtypes as being etiologically distinct. The heritability in female twins of migraine based on LCA classification was estimated at .50 (95% confidence intervals [0CI} .27 -.59), similar to IHS-based migraine diagnosis (h(2) = .49, 95% Cl .19-.57). However, using a dichotomous classification (affected-unaffected) decreased heritability for the IHS-based classification (h(2) = .33, 95% Cl .00-.60), but not the LCA-based classification (h(2) = .51, 95% Cl. 23-.61). Importantly, use of the LCA-based classification increased the number of subjects classified as affected. The heritability of the screening question was similar to more detailed LCA and IHS classifications, suggesting that the screening procedure is an important determining factor in genetic studies of migraine.

Embracing ligands. Synthesis, characterisation and the correlation between 59Co NMR and ligand field parameters of Co(III) complexes with a new class of nitrogen-thioether multidentate ligand

The syntheses of the hexadentate ligands 2,2,10,10-tetra(methyleneamine)-4,8-dithiaundecane (PrN(4)S(2)amp), 2,2,11,11-tetra(methyleneamine)-4,9-dithiadodecane (BuN(4)S(2)amp), and 1,2-bis(4,4-methyleneamine)-2-thiapentyl)benzene (XyN(4)S(2)amp) are reported and the complexes [Co(RN(4)S(2)amp)](3+) (R = Pr, Bu, Xy) characterised by single crystal X-ray study. The low-temperature (11 K) absorption spectra have been measured in Nafion films. From the observed positions of both spin-allowed (1)A(1g) --> T-1(1g) and (1)A(1g) --> T-1(2g) and spin forbidden (1)A(1g) --> T-3(1g) and (1)A(1g) --> T-3(2g) bands, octahedral ligand-field parameters (10D(q), B and C) have been determined. DFT calculations suggest that significant interaction between the d-d and CT excitations occurs for the complexes. The calculations offer an explanation for the observed deviations from linearity of the relationship between Co-59 magnetogyric ratio and beta(DeltaE)(-1) (beta = the nephelauxetic ratio; DeltaE the energy of the (1)A(1g) --> T-1(1g) transition) for a series of amine and mixed amine/thioether donor complexes.

Accelerating precursory activity within a class of earthquake analogue automata

A statistical fractal automaton model is described which displays two modes of dynamical behaviour. The first mode, termed recurrent criticality, is characterised by quasi-periodic, characteristic events that are preceded by accelerating precursory activity. The second mode is more reminiscent of SOC automata in which large events are not preceded by an acceleration in activity. Extending upon previous studies of statistical fractal automata, a redistribution law is introduced which incorporates two model parameters: a dissipation factor and a stress transfer ratio. Results from a parameter space investigation indicate that a straight line through parameter space marks a transition from recurrent criticality to unpredictable dynamics. Recurrent criticality only occurs for models within one corner of the parameter space. The location of the transition displays a simple dependence upon the fractal correlation dimension of the cell strength distribution. Analysis of stress field evolution indicates that recurrent criticality occurs in models with significant long-range stress correlations. A constant rate of activity is associated with a decorrelated stress field.

Approximating persistence in a general class of population processes

We provide a general framework for estimating persistence in populations which may be affected by catastrophic events, and which are either unbounded or have very large ceilings. We model the population using a birth-death process modified to allow for downward jumps of arbitrary size. For such processes, it is typically necessary to truncate the process in order to make the evaluation of expected extinction times (and higher-order moments) computationally feasible. Hence, we give particular attention to the selection of a cut-off point at which to truncate the process, and we present a simple method for obtaining quantitative indicators of the suitability of a chosen cut-off. (c) 2005 Elsevier Inc. All rights reserved.

Subgeometric rates of convergence for a class of continuous-time Markov process

Let (Phi(t))(t is an element of R+) be a Harris ergodic continuous-time Markov process on a general state space, with invariant probability measure pi. We investigate the rates of convergence of the transition function P-t(x, (.)) to pi; specifically, we find conditions under which r(t) vertical bar vertical bar P-t (x, (.)) - pi vertical bar vertical bar -> 0 as t -> infinity, for suitable subgeometric rate functions r(t), where vertical bar vertical bar - vertical bar vertical bar denotes the usual total variation norm for a signed measure. We derive sufficient conditions for the convergence to hold, in terms of the existence of suitable points on which the first hitting time moments are bounded. In particular, for stochastically ordered Markov processes, explicit bounds on subgeometric rates of convergence are obtained. These results are illustrated in several examples.

Investigation of an acetate-fed denitrifying microbial community by stable isotope probing, full-cycle rRNA analysis, and fluorescent in situ hybridization-microautoradiography

The acetate-utilizing microbial consortium in a full-scale activated sludge process was investigated without prior enrichment using stable isotope probing (SIP). [C-13]acetate was used in SIP to label the DNA of the denitrifiers. The [C-13]DNA fraction that was extracted was subjected to a full-cycle rRNA analysis. The dominant 16S rRNA gene phylotypes in the C-13 library were closely related to the bacterial families Comamonadaceae and Rhodocyclaceae in the class Betaproteobacteria. Seven oligonucleotide probes for use in fluorescent in situ hybridization (FISH) were designed to specifically target these clones. Application of these probes to the sludge of a continuously fed denitrifying sequencing batch reactor (CFDSBR) operated for 16 days revealed that there was a significant positive correlation between the CFDSBR denitrification rate and the relative abundance of all probe-targeted bacteria in the CFDSBR community. FISH-microautoradiography demonstrated that the DEN581 and DEN124 probe-targeted cells that dominated the CFDSBR were capable of taking Up [C-14] acetate under anoxic conditions. Initially, DEN444 and DEN1454 probe-targeted bacteria also dominated the CFDSBR biomass, but eventually DEN581 and DEN124 probe-targeted bacteria were the dominant bacterial groups. All probe-targeted bacteria assessed in this study were denitrifiers capable of utilizing acetate as a source of carbon. The rapid increase in the number of organisms positively correlated with the immediate increase in denitrification rates observed by plant operators when acetate is used as an external source of carbon to enhance denitrification. We suggest that the impact of bacteria on activated sludge subjected to intermittent acetate supplementation should be assessed prior to the widespread use of acetate in the waste-water industry to enhance denitrification.

Dietary analysis of the herbivorous hemiramphid Hyporhamphus regularis ardelio: an isotopic approach

The stable isotope values for a range of size classes of Hyporhamphus regularis ardelio from Moreton Bay, south-east Australia were determined. There was a positive linear relationship between 613 C and standard length (L-s) (delta(13)C = 0.034 Ls - 16-23; r(2) = 0.78). delta(13)C ranged from -8.48 to - 17.29 parts per thousand with the smallest size class (50 mm Ls) being on average 1.04 parts per thousand enriched with respect to that of zooplankton (Temora turbinata) and 7.97 parts per thousand depleted compared to Zostera capricorni. delta(13)C was positively correlated with Ls (P 0.0 1) with delta(15) N, ranging from 9.18 to 11.00 parts per thousand. Fish of all size classes were on average 2.32 and 7.63 parts per thousand more enriched than zooplankton and seagrass, respectively. Carbon isotope data indicate that H. r. ardelio commence life as carnivores and change to a diet in which seagrass is the primary carbon source. The dependence on animal matter, however, is always present. Due to the low percentage of nitrogen in Z. capricorni (2.5%) compared to zooplankton (9.1%) it appears that nitrogen from zooplankton is necessary throughout their life history with the carbon requirements for these fish coming chiefly from Z. capricorni. (c) 2005 The Fisheries Society of the British Isles.

Reflective analysis: Techniques for facilitating reflection

This paper describes a number of techniques for facilitating reflective critical analysis as a means of eliciting in-depth reflections on practice. The authors have previously used similar techniques in the research context, to assist practitioners to identify and analyse the basis of their work with clients. The techniques presented in this paper have been adapted for use in social work education, including in class-based and field education contexts, and to professional supervision.

Leading coordinate analysis of reaction pathways in proton chain transfer: Application to a two-proton transfer model for the green fluorescent protein

The ‘leading coordinate’ approach to computing an approximate reaction pathway, with subsequent determination of the true minimum energy profile, is applied to a two-proton chain transfer model based on the chromophore and its surrounding moieties within the green fluorescent protein (GFP). Using an ab initio quantum chemical method, a number of different relaxed energy profiles are found for several plausible guesses at leading coordinates. The results obtained for different trial leading coordinates are rationalized through the calculation of a two-dimensional relaxed potential energy surface (PES) for the system. Analysis of the 2-D relaxed PES reveals that two of the trial pathways are entirely spurious, while two others contain useful information and can be used to furnish starting points for successful saddle-point searches. Implications for selection of trial leading coordinates in this class of proton chain transfer reactions are discussed, and a simple diagnostic function is proposed for revealing whether or not a relaxed pathway based on a trial leading coordinate is likely to furnish useful information.

Prediction of HLA-DQ3.2 beta ligands: evidence of multiple registers in class II binding peptides

Motivation: While processing of MHC class II antigens for presentation to helper T-cells is essential for normal immune response, it is also implicated in the pathogenesis of autoimmune disorders and hypersensitivity reactions. Sequence-based computational techniques for predicting HLA-DQ binding peptides have encountered limited success, with few prediction techniques developed using three-dimensional models. Methods: We describe a structure-based prediction model for modeling peptide-DQ3.2 beta complexes. We have developed a rapid and accurate protocol for docking candidate peptides into the DQ3.2 beta receptor and a scoring function to discriminate binders from the background. The scoring function was rigorously trained, tested and validated using experimentally verified DQ3.2 beta binding and non-binding peptides obtained from biochemical and functional studies. Results: Our model predicts DQ3.2 beta binding peptides with high accuracy [area under the receiver operating characteristic (ROC) curve A(ROC) > 0.90], compared with experimental data. We investigated the binding patterns of DQ3.2 beta peptides and illustrate that several registers exist within a candidate binding peptide. Further analysis reveals that peptides with multiple registers occur predominantly for high-affinity binders.

A class of self-stabilizing MCA learning algorithms

In this letter, we propose a class of self-stabilizing learning algorithms for minor component analysis (MCA), which includes a few well-known MCA learning algorithms. Self-stabilizing means that the sign of the weight vector length change is independent of the presented input vector. For these algorithms, rigorous global convergence proof is given and the convergence rate is also discussed. By combining the positive properties of these algorithms, a new learning algorithm is proposed which can improve the performance. Simulations are employed to confirm our theoretical results.