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Selected Abstracts


HEPATITIS C AND ADDICTION: Retention rate and side effects in a prospective trial on hepatitis C treatment with pegylated interferon alpha-2a and ribavirin in opioid-dependent patients

ADDICTION BIOLOGY, Issue 2 2009
Nina Ebner
ABSTRACT Hepatitis C viral (HCV) infection is present in 30 to 98% of intravenous drug users. Intravenous substance abuse represents the main route of HCV transmission in industrialized countries. A multi-centre, randomized, controlled, prospective study assessed sustained virological response (SVR), adverse events such as depressive episodes and retention rate of HCV treatment in opioid-dependent patients. Stabilized, opioid-dependent patients with chronic HCV infection (genotype 2 or 3) received pegylated interferon alpha-2a in combination with ribavirin 800 mg/day (Group A) or 400 mg/day (Group B). Participants were randomized, blocked and stratified by genotype and viral load. A standardized psychiatric assessment, Beck Depression Inventory (BDI) and Van Zerssen's list of complaints were administered at each study visit. In 31 months, 300 opioid-dependent patients were screened; 190 (63.3%) were hepatitis C antibody positive. According to study protocol, out of 75 ,potential-to-treat' patients with genotype 2 or 3, 17 stable patients (22.6%) were included in the study. All participants completed the study. Significant haemoglobin decreases occurred in both Groups A (P = 0.001) and B (P = 0.011). All the patients had an end-of-treatment (week 24) HCV RNA negativity. Fifteen (88.2%) achieved SVR at week 48. Overall, 52.9% developed depressive symptoms during treatment. Because of the prompt initiation of antidepressant medication at first appearance of depressive symptoms, no severe depressive episodes occurred. Our data show a high retention rate and reliability, and good viral response for both treatments. Hepatitis C treatment in stable opioid-dependent patients was efficacious, suggesting that addiction clinics can offer antiviral therapy in combination with agonistic treatment as part of multi-disciplinary treatment. [source]


Questioning the impact of the ,graduatization' of the managerial labour force upon the management of human resources in the Scottish hotel industry

INTERNATIONAL JOURNAL OF CONSUMER STUDIES, Issue 4 2000
Arthur Ingram
Abstract This paper outlines the findings of a questionnaire survey returned by 125 Scottish hotels from a sample of 500 small and middle-sized enterprises. We asked questions on the level of impact that hospitality graduates have had upon human resource management practices within individual units. The research reports that, although the cumulative graduatization of the managerial workforce appears to be under way, the main route to a permanent management post still remains one of practical work experience, rather than the attainment of a hospitality-related degree. Although manpower planning is widely used by line managers for managing the conditions of local/external labour markets and operatives' jobs, there is less evidence of a systematic approach to the management of graduate careers/skills or of the management of internal job structures and labour market processes in order to improve the quality of customer service. Our work suggests a need for smaller hotels to strike a fresh balance between traditional operationally driven approaches to people management and strategic human resource management frameworks. [source]


Acceleration of nitric oxide autoxidation and nitrosation by membranes

IUBMB LIFE, Issue 4-5 2007
Matias N. Möller
Abstract The reaction between nitric oxide (,NO) and oxygen yields reactive species capable of oxidizing and nitrosating proteins, as well as deaminating DNA bases. Although this reaction is considered too slow to be biologically relevant, it has been shown that membranes, lipoproteins, mitochondria and possibly proteins can accelerate this reaction. This effect stems from the higher solubility of both ,NO and O2in the hydrophobic phase of these biological particles, leading to a concentration of both reagents and so a higher rate of reaction. It has been determined that this reaction occurs from 30 to 300 times more rapidly within the membrane, while even higher values have been suggested for proteins. The autoxidation of ,NO in membranes is not the main route for cellular ,NO consumption but an important consequence of this phenomenon is to focus the generation of significant amounts of oxidizing and nitrosating molecules (nitrogen dioxide and dinitrogen trioxide) in the small volume comprised by cellular membranes. Even so, these reactive species are diffusible and their ultimate fate will depend on the reactivity towards available substrates rather than on physical barriers. The acceleration of ,NO autoxidation by biological hydrophobic phases may thus be a general phenomenon that increases in importance in cases of ,NO overproduction. IUBMB Life, 59: 243-248, 2007 [source]


Assessment of anaerobic wastewater treatment failure using terminal restriction fragment length polymorphism analysis

JOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2005
C. Scully
Abstract Aims:, The suitability of genetic fingerprinting to study the microbiological basis of anaerobic bioreactor failure is investigated. Methods and Results:, Two laboratory-scale anaerobic expanded granular sludge bed bioreactors, R1 and R2, were used for the mesophilic (37°C) treatment of high-strength [10 g chemical oxygen demand (COD) l,1] synthetic industrial-like wastewater over a 100-day trial period. A successful start up was achieved by both bioreactors with COD removal over 90%. Both reactors were operated under identical parameters; however, increased organic loading during the trial induced a reduction in the COD removal of R1, while R2 maintained satisfactory performance (COD removal >90%) throughout the experiment. Specific methanogenic activity measurements of biomass from both reactors indicated that the main route of methane production was hydrogenotrophic methanogenesis. Terminal restriction fragment length polymorphism (TRFLP) analysis was applied to the characterization of microbial community dynamics within the system during the trial. The principal differences between the two consortia analysed included an increased abundance of Thiovulum - and Methanococcus -like organisms and uncultured Crenarchaeota in R1. Conclusions:, The results indicated that there was a microbiological basis for the deviation, in terms of operational performance, of R1 and R2. Significance and Impact of the Study:, High-throughput fingerprinting techniques, such as TRFLP, have been demonstrated as practically relevant for biomonitoring of anaerobic reactor communities. [source]


Preferential vulnerability of mesencephalic dopamine neurons to glutamate transporter dysfunction

JOURNAL OF NEUROCHEMISTRY, Issue 2 2008
Imane Nafia
Abstract Nigral depletion of the main brain antioxidant GSH is the earliest biochemical event involved in Parkinson's disease pathogenesis. Its causes are completely unknown but increasing number of evidence suggests that glutamate transporters [excitatory amino acid transporters (EAATs)] are the main route by which GSH precursors may enter the cell. In this study, we report that dopamine (DA) neurons, which express the excitatory amino acid carrier 1, are preferentially affected by EAAT dysfunction when compared with non-DA neurons. In rat embryonic mesencephalic cultures, l -trans-pyrrolidine-2,4-dicarboxylate, a substrate inhibitor of EAATs, is directly and preferentially toxic for DA neurons by decreasing the availability of GSH precursors and lowering their resistance threshold to glutamate excitotoxicity through NMDA-receptors. In adult rat, acute intranigral injection of l -trans-pyrrolidine-2,4-dicarboxylate induces a large regionally selective and dose-dependent loss of DA neurons and ,-synuclein aggregate formation. These data highlight for the first time the importance of excitatory amino acid carrier 1 function for the maintenance of antioxidant defense in DA neurons and suggest its dysfunction as a candidate mechanism for the selective death of DA neurons such as occurring in Parkinson's disease. [source]


,-cyclodextrin reduces bioavailability of orally administered [3H]benzo[a]pyrene in the rat

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2005
Goran Westerberg
Abstract The excretion and plasma kinetics of total radioactivity were studied following single oral administration of [3H]benzo[a]pyrene after multiple oral administration of ,-cyclodextrin at 0, 5, 50, or 500 mg/kg/day. The AUC and Cmax values in male and female rats following administration of [3H]benzo[a]pyrene in combination with 5 to 500 mg/kg ,-cyclodextrin were considerably lower than that in rats administered [3H]benzo[a]pyrene alone. At all dose levels of ,-cyclodextrin, the excretion of total radioactivity was almost entirely via feces, with <2% recovered in urine, demonstrating either that absorption of the orally administered dose was low or that, for any absorbed material, biliary excretion was the main route of excretion. However, following administration of vehicle, up to 5% of the administered radioactivity was recovered in the urine, suggesting that absorption may have been reduced by the presence of ,-cyclodextrin in the intestine. At all dose levels of ,-cyclodextrin, there was minimal retention of radioactivity in the carcase at the end of the collection period. ,-Cyclodextrin did not affect the apparent terminal half-life of radioactivity. Therefore, the reduced systemic exposure of rats to radioactivity in the presence of ,-cyclodextrin is likely related to a reduced oral bioavailability. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:114,119, 2005 [source]


Genetic structure of the European polecat (Mustela putorius) and its implication for conservation strategies

JOURNAL OF ZOOLOGY, Issue 1 2006
C. Pertoldi
Abstract During the last century, the European polecat Mustela putorius populations in most of Europe declined and survived in fragmented patches, because of habitat alterations and direct persecution. To assess the genetic consequences of the demographic decline and to describe the spatial pattern of genetic diversity, 250 polecats sampled at seven localities from five European countries , Poland, Denmark (southern Denmark and northern Denmark), Spain, Belgium (eastern and western) and the Netherlands , were screened by means of nine microsatellite loci. Genetic diversity estimated by mean expected heterozygosity (HE) and allelic richness (AR) were moderately high within populations [range: 0.50 (northern Denmark) ,HE,0.64 (Poland) and 1.33,AR,7.80] as compared with other carnivores and mustelids. Bottleneck tests suggested that polecat populations in southern Denmark and Poland have declined recently and populations from northern Denmark and the Netherlands have expanded recently, whereas the remaining populations did not show any sign of demographic change. Recent demographic changes could suggest that some of the populations are still not in equilibrium, which could partly explain the relatively high genetic variability observed in polecat populations despite the drastic decline in population size observed in several European countries. A significant heterozygote deficiency [FIS=0.19; 0.01,95% confidence interval (CI),0.32] suggests substructuring within the total European sample. Partitioning of the genetic variation among sampling locations (FST=0.14; 0.06,95% CI,0.23) and pairwise FST between localities (range: 0.01,FST,0.37) without any correlation with the geographic distances between localities were found, suggesting a recent divergence and a restriction of gene flow between populations and the action of genetic drift. An assignment test showed that the Polish and the northern Danish populations were the most unique, whereas the other populations were partially admixed. Factorial component analysis tests indicate a subdivision of the total sample into two distinct groups: one including the samples from Poland and the two Danish localities and the second group comprising the remaining localities investigated. The observed pattern of genetic differentiation is suggested to be due to two main routes of recolonization after the last glacial period. To compare the results obtained with microsatellite data, the most variable region of the mitochondrial DNA (d-loop) was sequenced and different phylogenetic reconstructions and genetic diversity analyses based on nucleotide (,) and haplotype diversity (h) measures within populations were performed using a subsample of populations. The lack of well-defined geographical structure, as well as the reduced level of mitochondrial DNA variability (,: 0.00274±0.00038; h: 0.876±0.028) that was found, has been previously reported in several studies on different carnivores and supports the hypothesis of post-glacial recolonization from southern or eastern refugees of Europe as suggested by the microsatellite data. Implications for conservation strategies of the polecat at the European level are discussed. [source]


ROUTES TO HIGHER-ORDER ACCURACY IN PARAMETRIC INFERENCE

AUSTRALIAN & NEW ZEALAND JOURNAL OF STATISTICS, Issue 2 2009
G. Alastair Young
Summary Developments in the theory of frequentist parametric inference in recent decades have been driven largely by the desire to achieve higher-order accuracy, in particular distributional approximations that improve on first-order asymptotic theory by one or two orders of magnitude. At the same time, much methodology is specifically designed to respect key principles of parametric inference, in particular conditionality principles. Two main routes to higher-order accuracy have emerged: analytic methods based on ,small-sample asymptotics', and simulation, or ,bootstrap', approaches. It is argued here that, of these, the simulation methodology provides a simple and effective approach, which nevertheless retains finer inferential components of theory. The paper seeks to track likely developments of parametric inference, in an era dominated by the emergence of methodological problems involving complex dependences and/or high-dimensional parameters that typically exceed available data sample sizes. [source]