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- Björnsson, Einar, 1958, et al.
(author)
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Long-term follow-up of patients with alcoholic liver disease after liver transplantation in Sweden: impact of structured management on recidivism
- 2005
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In: Scandinavian journal of gastroenterology. - 0036-5521. ; 40:2, s. 206-16
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Journal article (peer-reviewed)abstract
- OBJECTIVE: No systematic evaluation has been performed previously in the Scandinavian countries on patients transplanted for alcoholic liver disease (ALD). Data are limited on the impact of structured management of the alcohol problem on the risk of recidivism following transplantation in ALD. MATERIAL AND METHODS: A total of 103 ALD patients were compared with a control group of patients with non-alcoholic liver disease (NALD). The recidivism rates for ALD patients transplanted between 1988 and 1997 as well as after 1998 (institution of structured management) were compared. RESULTS: The median follow-up was 31 (6-60) months in the ALD group and 37 (12-63) months in the control group (NS). The overall survival rates at 1- and 5 years were, respectively, 81% and 69% for the ALD group and 87% and 83% for the non-alcoholic group. The proportion of patients with Child-Pugh C (75%) was higher in ALD patients than in NALD patients (44%) (p<0.01). Thirty-two (33%) ALD patients resumed taking some alcohol after transplantation; 17 patients (18%) were heavy drinkers. A multivariate analysis showed that: sex, age, marital and employment status, benzodiazepine use and a history of illicit drug abuse did not predict the risk of alcohol relapse post-Tx. Nineteen out of 40 (48%) patients transplanted before the start of structured management had resumed alcohol but 13 (22%) out of 58 after this intervention (p=0.002). CONCLUSIONS: ALD is a good indication for liver transplantation, with similar results in the ALD patients. Structured management of the alcohol problem before and after transplantation is important in minimizing the risk of recidivism.
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- C Stummann, Tina C, et al.
(author)
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Report and Recommendations of the Workshop of the European Centre for the Validation of Alternative Methods for Drug-Induced Cardiotoxicity
- 2009
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In: CARDIOVASCULAR TOXICOLOGY. - : Springer Science and Business Media LLC. - 1530-7905 .- 1559-0259. ; 9:3, s. 107-125
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Research review (other academic/artistic)abstract
- Cardiotoxicity is among the leading reasons for drug attrition and is therefore a core subject in non-clinical and clinical safety testing of new drugs. European Centre for the Validation of Alternative Methods held in March 2008 a workshop on "Alternative Methods for Drug-induced Cardiotoxicity" in order to promote acceptance of alternative methods reducing, refining or replacing the use of laboratory animals in this field. This review reports the outcome of the workshop. The participants identified the major clinical manifestations, which are sensitive to conventional drugs, to be arrhythmias, contractility toxicity, ischaemia toxicity, secondary cardiotoxicity and valve toxicity. They gave an overview of the current use of alternative tests in cardiac safety assessments. Moreover, they elaborated on new cardiotoxicological endpoints for which alternative tests can have an impact and provided recommendations on how to cover them.
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- Wallén-Mackenzie, Åsa, et al.
(author)
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Restricted cortical and amygdaloid removal of vesicular glutamate transporter 2 in preadolescent mice impacts dopaminergic activity and neuronal circuitry of higher brain function.
- 2009
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In: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401 .- 0270-6474. ; 29:7, s. 2238-51
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Journal article (peer-reviewed)abstract
- A major challenge in neuroscience is to resolve the connection between gene functionality, neuronal circuits, and behavior. Most, if not all, neuronal circuits of the adult brain contain a glutamatergic component, the nature of which has been difficult to assess because of the vast cellular abundance of glutamate. In this study, we wanted to determine the role of a restricted subpopulation of glutamatergic neurons within the forebrain, the Vglut2-expressing neurons, in neuronal circuitry of higher brain function. Vglut2 expression was selectively deleted in the cortex, hippocampus, and amygdala of preadolescent mice, which resulted in increased locomotor activity, altered social dominance and risk assessment, decreased sensorimotor gating, and impaired long-term spatial memory. Presynaptic VGLUT2-positive terminals were lost in the cortex, striatum, nucleus accumbens, and hippocampus, and a downstream effect on dopamine binding site availability in the striatum was evident. A connection between the induced late-onset, chronic reduction of glutamatergic neurotransmission and dopamine signaling within the circuitry was further substantiated by a partial attenuation of the deficits in sensorimotor gating by the dopamine-stabilizing antipsychotic drug aripiprazole and an increased sensitivity to amphetamine. Somewhat surprisingly, given the restricted expression of Vglut2 in regions responsible for higher brain function, our analyses show that VGLUT2-mediated neurotransmission is required for certain aspects of cognitive, emotional, and social behavior. The present study provides support for the existence of a neurocircuitry that connects changes in VGLUT2-mediated neurotransmission to alterations in the dopaminergic system with schizophrenia-like behavioral deficits as a major outcome.
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- Boone, Jan, et al.
(author)
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Optimal unemployment insurance with monitoring and sanctions
- 2007
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In: Economic Journal. - : Oxford University Press (OUP). - 0013-0133 .- 1468-0297. ; 117:518, s. 399-421
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Journal article (peer-reviewed)abstract
- This article analyses the design of optimal unemployment insurance in a search equilibrium framework where search effort among the unemployed is not perfectly observable. We examine to what extent the optimal policy involves monitoring of search effort and benefit sanctions if observed search is deemed insufficient. We find that introducing monitoring and sanctions represents a welfare improvement for reasonable estimates of monitoring costs; this conclusion holds both relative to a system featuring indefinite payments of benefits and a system with a time limit on unemployment benefit receipt.
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- Dhindaw, B. K., et al.
(author)
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Microstructure development and solute redistribution in aluminium alloys under low and moderate shear rates during rheo processing
- 2005
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In: Materials Science & Engineering. - : Elsevier BV. - 0921-5093 .- 1873-4936. ; 413, s. 156-164
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Journal article (peer-reviewed)abstract
- Microstructural features and microsegregational behaviour of solute are studied in shear or stir-cast aluminium alloys under low and moderate shear rates. Alloys studied are Al-6.2% Cu, Al-7.3% Si and Al-13.2% Mg. In all the cases, microstructures of the primary pre-quench solid for stir-cast samples show rosette or ellipsoidal morphologies. Volume fractions of pre-quenched solid phase show significantly higher values for stir-cast alloys as compared to calculated. Microsegregation studies by microprobe analysis along the grains of the samples solidified under different treatment conditions show that stir casting changes the segregation pattern significantly. Except for Al-13.2% Mg alloys lower values than those calculated by Scheil's microsegregation equation are observed for other systems. A model for microstructure evolution during stir casting is presented. The microsegregation patterns have been discussed in terms of interaction between the diffusing solute and the vacancies migrating from solid into liquid.
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