Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics

Context Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulatioin in BD. Objective: To use tract-based spatial statistics (TBSS) to examine VVM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Design: Cross-sectional, case-control, whole-brain DTI using TBSS. Setting: University research institute. Participants: Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type 1 (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Main Outcome Measures: Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Results: Subjects with BD vs controls had significantly greater FA (t > 3.0, P <=.05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P <=.05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P <.01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P <.01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. Conclusions: To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

A Comparison of Bayesian and Sampling Theory Inferences in a Probit Model

HE PROBIT MODEL IS A POPULAR DEVICE for explaining binary choice decisions in econometrics. It has been used to describe choices such as labor force participation, travel mode, home ownership, and type of education. These and many more examples can be found in papers by Amemiya (1981) and Maddala (1983). Given the contribution of economics towards explaining such choices, and given the nature of data that are collected, prior information on the relationship between a choice probability and several explanatory variables frequently exists. Bayesian inference is a convenient vehicle for including such prior information. Given the increasing popularity of Bayesian inference it is useful to ask whether inferences from a probit model are sensitive to a choice between Bayesian and sampling theory techniques. Of interest is the sensitivity of inference on coefficients, probabilities, and elasticities. We consider these issues in a model designed to explain choice between fixed and variable interest rate mortgages. Two Bayesian priors are employed: a uniform prior on the coefficients, designed to be noninformative for the coefficients, and an inequality restricted prior on the signs of the coefficients. We often know, a priori, whether increasing the value of a particular explanatory variable will have a positive or negative effect on a choice probability. This knowledge can be captured by using a prior probability density function (pdf) that is truncated to be positive or negative. Thus, three sets of results are compared:those from maximum likelihood (ML) estimation, those from Bayesian estimation with an unrestricted uniform prior on the coefficients, and those from Bayesian estimation with a uniform prior truncated to accommodate inequality restrictions on the coefficients.

Effects of sampling opportunities on preference for adults with severe disabilities

A variable that appears to affect preference development is the exposure to a variety of options. Providing opportunities for systematically sampling different options is one procedure that can facilitate the development of preference, which is indicated by the consistency of selections. The purpose of this study was to evaluate the effects of providing sampling opportunities on the preference development for two adults with severe disabilities. Opportunities for sampling a variety of drink items were presented, followed by choice opportunities for selections at the site where sampling occurred and at a non-sampling site (a grocery store). Results show that the participants developed a definite response consistency in selections at both sites. Implications for sampling practices are discussed.

Design of clinical pharmacology trials

1. There are a variety of methods that could be used to increase the efficiency of the design of experiments. However, it is only recently that such methods have been considered in the design of clinical pharmacology trials. 2. Two such methods, termed data-dependent (e.g. simulation) and data-independent (e.g. analytical evaluation of the information in a particular design), are becoming increasingly used as efficient methods for designing clinical trials. These two design methods have tended to be viewed as competitive, although a complementary role in design is proposed here. 3. The impetus for the use of these two methods has been the need for a more fully integrated approach to the drug development process that specifically allows for sequential development (i.e. where the results of early phase studies influence later-phase studies). 4. The present article briefly presents the background and theory that underpins both the data-dependent and -independent methods with the use of illustrative examples from the literature. In addition, the potential advantages and disadvantages of each method are discussed.

Recent trends in pay equity: Beyond the aggregate statistics

The earnings gap between men and women has remained comparatively stable at an aggregate level over the 1990s in Australia. From one perspective, this is a reminder of the considerable difficulty of addressing wage differentials once the most overt forms of wage discrimination have been removed, and of the limited impact of most policy initiatives. From another, it may be seen as evidence that dire predictions about the effects of decentralisation on the earnings gap have failed to materialise. In this paper, I use Australian Bureau of Statistics data to show that a number of different trends are evident underneath the relatively static picture shown by the aggregate statistics, particularly as wage dispersion has increased. The data suggest not only that the prospects for pay equity are far from benign, but also that in the current labour market the issue of gender pay inequality cannot be effectively addressed separately from wage inequality more generally.

Resolution of natural groups using iterative assignment tests: an example from two species of Australian native rats (Rattus)

Sympatric individuals of Rattus fuscipes and Rattus leucopus, two Australian native rats from the tropical wet forests of north Queensland, are difficult to distinguish morphologically and are often confused in the field. When we started a study on fine-scale movements of these species, using microsatellite markers, we found that the species as identified in the field did not form coherent genetic groups. In this study, we examined the potential of an iterative process of genetic assignment to separate specimens from distinct (e.g. species, populations) natural groups. Five loci with extensive overlap in allele distributions between species were used for the iterative process. Samples were randomly distributed into two starting groups of equal size and then subjected to the test. At each iteration, misassigned samples switched groups, and the output groups from a given round of assignment formed the input groups for the next round. All samples were assigned correctly on the 10th iteration, in which two genetic groups were clearly separated. Mitochondrial DNA sequences were obtained from samples from each genetic group identified by assignment, together with those of museum voucher specimens, to assess which species corresponded to which genetic group. The iterative procedure was also used to resolve groups within species, adequately separating the genetically identified R. leucopus from our two sampling sites. These results show that the iterative assignment process can correctly differentiate samples into their appropriate natural groups when diagnostic genetic markers are not available, which allowed us to resolve accurately the two R. leucopus and R. fuscipes species. Our approach provides an analytical tool that may be applicable to a broad variety of situations where genetic groups need to be resolved.

Low-density koala (Phascolarctos cinereus) populations in the mulgalands of south-west Queensland. I. Faecal pellet sampling protocol

Koala (Phascolarctos cinereus) populations in eastern Australia are threatened by land clearing for agricultural and urban development. At the same time, conservation efforts are hindered by a dearth of information about inland populations. Faecal deposits offer a source of information that is readily available and easily collected non-invasively. We detail a faecal pellet sampling protocol that was developed for use in a large rangeland biogeographic region. The method samples trees in belt transects, uses a thorough search at the tree base to quickly identify trees with koala pellets under them, then estimates the abundance of faecal pellets under those trees using 1-m(2) quadrats. There was a strong linear relationship between these estimates and a complete enumeration of pellet abundance under the same trees. We evaluated the accuracy of our method in detecting trees where pellets were present by means of a misclassification index that was weighed more heavily for missed trees that had high numbers of pellets under them. This showed acceptable accuracy in all landforms except riverine, where some trees with large numbers of pellets were missed. Here, accuracy in detecting pellet presence was improved by sampling with quadrats, rather than basal searches. Finally, we developed a method to reliably age pellets and demonstrate how this protocol could be used with the faecal-standing-crop method to derive a regional estimate of absolute koala abundance.