An integrative approach for studying the etiology of alcoholism and other addictions

Studies of alcoholism etiology often focus on genetic or psy-chosocial approaches, but not both. Greater understanding of the etiology of alcohol, tobacco and other addictions will come from integration of these research traditions. A research approach is outlined to test three models for the etiology of addictions — behavioral undercontrol, pharmacologic vulnerability, negative affect regulation — addressing key questions including (i) mediators of genetic effects, (ii) genotype-environment correlation effects, (iii) genotype x environment interaction effects, (iv) the developmental unfolding of genetic and environmental effects, (v) subtyping including identification of distinct trajectories of substance involvement, (vi) identification of individual genes that contribute to risk, and (vii) the consequences of excessive use. By using coordinated research designs, including prospective assessment of adolescent twins and their siblings and parents; of adult substance dependent and control twins and their MZ and DZ cotwins, the spouses of these pairs, and their adolescent offspring; and of regular families; by selecting for gene-mapping approaches sibships screened for extreme concordance or discordance on quantitative indices of substance use; and by using experimental (drug challenge) as well as survey approaches, a number of key questions concerning addiction etiology can be addressed. We discuss complementary strengths and weaknesses of different sampling strategies, as well as methods to implement such an integrated approach illustrated for the study of alcoholism etiology. A coordinated program of twin and family studies will allow a comprehensive dissection of the interplay of genetic and environmental risk-factors in the etiology of alcoholism and other addictions.

Patterns of community integration 2-5 years post-discharge from brain injury rehabilitation

Outcome after traumatic brain injury (TBI) is characterized by a high degree of variability which has often been difficult to capture in traditional outcome studies. The purpose of this study was to describe patterns of community integration 2-5 years after TBI. Participants were 208 patients admitted to a Brain Injury Rehabilitation Unit between 1991-1995 in Brisbane, Australia. The design comprised retrospective data collection and questionnaire follow-up by mail. Mean follow-up was 3.5 years. Demographic, injury severity and functional status variables were retrieved from hospital records. Community integration was assessed using the Community Integration Questionnaire (CIQ), and vocational status measured by a self administered questionnaire. Data was analysed using cluster analysis which divided the data into meaningful subsets. Based on the CIQ subscale scores of home, social and productive integration, a three cluster solution was selected, with groups labelled as working (n = 78), balanced (n = 46) and poorly integrated (n = 84). Although 38% of the sample returned to a high level of productive activity and 22% achieved a balanced lifestyle, overall community integration was poor for the remainder. This poorly integrated group had more severe injury characterized by longer periods of acute care and post-traumatic amnesia (PTA) and greater functional disability on discharge. These findings have implications for service delivery prior to and during the process of reintegration after brain injury.

Hemin reconstitutes proton extrusion in an H+-ATPase-negative mutant of Lactococcus lactis

H+-ATPase is considered essential for growth of Lactococcus lactis. However, media containing hemin restored the aerobic growth of an H+-ATPase-negative mutant, suggesting that hemin complements proton extrusion. We show that inverted membrane vesicles prepared from hemin-grown L. lactis cells are capable of coupling NADH oxidation to proton translocation.

Employee adjustment to an organizational merger: An intergroup perspective

Adopting an intergroup perspective, the research was designed to examine predictors of employee responses to an organizational merger Data were collected from 465 fleet staff employed in a newly merged airline company. As predicted from social identity theory, the negative effects of the merger were most marked for employees of the low-status premerger organization. Also, as predicted, the perception of permeable intergroup boundaries in the new organization was associated positively with identification with the new organization and both job-related and person-related outcomes among employees of the low-status premerger organization but negatively with person-related outcomes among employees of the high-status premerger organization. As predicted, there was some evidence that the main and interactive effects involving status, perceived permeability, and intergroup contact on employee adjustment were mediated through strength of identification with the new organization.

An evaluation approach for a new paradigm - health care integration

This paper explores an approach to the implementation and evaluation of integrated health service delivery. It identifies the key issues involved in integration evaluation, provides a framework for assessment and identifies areas for the development of new tools and measures. A proactive role for evaluators in responding to health service reform is advocated.

Specification, refinement and verification of concurrent systems - An integration of Object-Z and CSP

This paper presents a method of formally specifying, refining and verifying concurrent systems which uses the object-oriented state-based specification language Object-Z together with the process algebra CSP. Object-Z provides a convenient way of modelling complex data structures needed to define the component processes of such systems, and CSP enables the concise specification of process interactions. The basis of the integration is a semantics of Object-Z classes identical to that of CSP processes. This allows classes specified in Object-Z to he used directly within the CSP part of the specification. In addition to specification, we also discuss refinement and verification in this model. The common semantic basis enables a unified method of refinement to be used, based upon CSP refinement. To enable state-based techniques to be used fur the Object-Z components of a specification we develop state-based refinement relations which are sound and complete with respect to CSP refinement. In addition, a verification method for static and dynamic properties is presented. The method allows us to verify properties of the CSP system specification in terms of its component Object-Z classes by using the laws of the the CSP operators together with the logic for Object-Z.

(Book review) Neuropsychotherapy and Community Integration: Brain Illness, Emotions, and Behavior. T. Judd. 1999. New York: Kluwer Academic/Plenum Publishers

As individuals gain expertise in a chosen field they can begin to conceptualize how what they know can be applied more broadly, to new populations and situations, or to increase desirable outcomes. Judd's book does just this. It takes our current understanding of the etiology, course, and sequelae of brain injuries, combines this with established psychotherapy and rehabilitation techniques, and expands these into a cogent model of what Judd calls “neuropsychotherapy.” Simply put, neuropsychotherapy attempts to address the cognitive, emotional and behavioral changes in brain-injured persons, changes that may go undiagnosed, misdiagnosed, or untreated.

A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance

Recent studies have indicated a role for caveolin in regulating cholesterol-dependent signaling events. In the present study we have analyzed the role of caveolins in intracellular cholesterol cycling using a dominant negative caveolin mutant. The mutant caveolin protein, cav-3(DGV) specifically associates with the membrane surrounding large lipid droplets. These structures contain neutral lipids, and are accessed by caveolin 1-3 upon overexpression. Fluorescence, electron, and video microscopy observations are consistent with formation of the membrane-enclosed lipid rich structures by maturation of subdomains of the ER. The caveolin mutant causes the intracellular accumulation of free cholesterol (FC) in late endosomes, a decrease in surface cholesterol and a decrease in cholesterol efflux and synthesis. The amphiphile U18666A acts synergistically with cav(DGV) to increase intracellular accumulation of FC. Incubation of cells with oleic acid induces a significant accumulation of full-length caveolins in the enlarged lipid droplets. We conclude that caveolin can associate with the membrane surrounding lipid droplets and is a key component involved in intracellular cholesterol balance and lipid transport in fibroblasts.

Postoperative vaginal vault brachytherapy for node-negative Stage II (occult) endometrial carcinoma

Objective. The aim of this study is to look at the efficacy of extended surgical staging and postoperative vaginal vault brachytherapy in patients with Stage II (occult) endometrial carcinoma. Methods. Between January 1989 and December 1997, there were 30 patients with Stage II (occult) endometrial carcinoma who received postoperative vaginal vault brachytherapy as the only adjuvant treatment. The study group consisted of 15 of these patients who had extended surgical staging (including lymphadenectomy). Results. At a median follow-up of 36 months (range 17 to 113 months), there has been no recurrence. There were no major complications from surgery. Only 1 patient had mild rectal bleeding following vaginal vault brachytherapy and there were no grade 3 or 4 bowel toxicities. Conclusions. Extended surgical staging and postoperative vaginal vault brachytherapy for Stage II (occult) endometrial carcinoma is associated with minimal morbidity and excellent survival. (C) 2001 Academic Press.

Set-valued Markov chains and negative semitrajectories of discretized dynamical systems

Computer simulation of dynamical systems involves a phase space which is the finite set of machine arithmetic. Rounding state values of the continuous system to this grid yields a spatially discrete dynamical system, often with different dynamical behaviour. Discretization of an invertible smooth system gives a system with set-valued negative semitrajectories. As the grid is refined, asymptotic behaviour of the semitrajectories follows probabilistic laws which correspond to a set-valued Markov chain, whose transition probabilities can be explicitly calculated. The results are illustrated for two-dimensional dynamical systems obtained by discretization of fractional linear transformations of the unit disc in the complex plane.

The nexus of value chain integration and e-business applications on public sector agriculture R&D management

We examine the potential impact of interconnectivity of value chain partnerships through electronic means (e-business practices) on the management of Public Sector Agriculture R&D in Australia. We review the changing forms of managing research and development, the forces driving these changes, and R&D processes that are theoretically consistent with the move towards value chain involvement and the increase in active constituents in Public Sector Agriculture R&D. We then explore the potential of emerging e-business models to change the patterns of inter-connectivity, speed and omnipresence of partners in the value chain. Three e-business R&D management practices are identified that provide the prerequisite flexibility necessary to take advantage of opportunistic markets. These R&D business practices are: compressing R&D to reduce time to market, fostering co-development to enter a market at the last moment and building flexible products that allow adjustment at the last possible moment. Some fundamental reallocation of existing resources will be required to meet these markets. Implications of these e-business practices for R&D management are discussed.

Negative ion electrospray mass spectra of caerulein peptides: an aid to structural determination

MS/MS data derived from the [M-H](-) ions of desulfated caerulein peptides provide (i) sequencing information from a combination of alpha, beta and gamma backbone cleavages, and (ii) identification of specific amino acid side chains by side-chain cleavages [e.g. Ser (-CH2O), Thr (-CH3CHO) and Asp (-H2O)] (fragmentations having no counterparts in positive ion spectra). In addition, delta and/or gamma backbone cleavage ions from Asp residues identify the position of these residues in the peptide. In contrast, neither delta nor gamma cleavage ions are observed from either the Gln2 residue nor from Phe residues. Full structural information can be obtained from a consideration of the positive and negative ion MS/MS data in concert. Copyright (C) 2002 John Wiley Sons, Ltd.