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One of the key features of addiction is the escalated drug intake. The neural mechanisms involved in the transition to addiction remain to be elucidated. Since abnormal neuronal activity within the subthalamic nucleus (STN) stands as potential general neuromarker common to impulse control spectrum deficits, as observed in obsessive–compulsive disorders, the present study recorded and manipulated STN neuronal activity during the initial transition to addiction (i.e., escalation) and post-abstinence relapse (i.e., re-escalation) in rats with extended drug access. We found that low-frequency (theta and beta bands) neuronal oscillations in the STN increase with escalation of cocaine intake and that either lesion or high-frequency stimulation prevents the escalation of cocaine intake. STN–HFS also reduces re-escalation after prolonged, but not short, protracted abstinence, suggesting that STN–HFS is an effective prevention for relapse when baseline rates of self-administration have been re-established. Thus, STN dysfunctions may represent an underlying mechanism for cocaine addiction and therefore a promising target for the treatment of addiction.

Drug addiction is driven, in part, by powerful and enduring memories of sensory cues associated with drug intake. As such, relapse to drug use during abstinence is frequently triggered by an encounter with drug-associated cues, including the drug itself. L-type Ca2+channels (LTCCs) are known to regulate different forms of synaptic plasticity, the major neural substrate for learning and memory, in various brain areas. Long-term potentiation (LTP) of NMDA receptor (NMDAR)-mediated glutamatergic transmission in the ventral tegmental area (VTA) may contribute to the increased motivational valence of drug-associated cues triggering relapse. In this study, using rat brain slices, we found that isradipine, a general LTCC antagonist used as antihypertensive medication, not only blocks the induction of NMDAR LTP but also promotes the reversal of previously induced LTP in the VTA. In behaving rats, isradipine injected into the VTA suppressed the acquisition of cocaine-paired contextual cue memory assessed using a conditioned place preference (CPP) paradigm. Furthermore, administration of isradipine or a CaV1.3 subtype-selective LTCC antagonist (systemic or intra-VTA) before a single extinction or reinstatement session, while having no immediate effect at the time of administration, abolished previously acquired cocaine and alcohol (ethanol) CPP on subsequent days. Notably, CPP thus extinguished cannot be reinstated by drug re-exposure, even after 2 weeks of withdrawal. These results suggest that LTCC blockade during exposure to drug-associated cues may cause unlearning of the increased valence of those cues, presumably via reversal of glutamatergic synaptic plasticity in the VTA.

A new miniaturised Light Scattering (LS) apparatus coupled with a capillary viscometer has been developed which analyses sequentially small size fractions of eluent (1 cm3). The apparatus can be used in an autonomous manner in order to obtain the weight-average molar mass (Mw), the z-average radius of gyration (Rg), the second virial coefficient (A2), the intrinsic viscosity ([ η] ) and the Huggins constant (k) by analysing a given polymer sample at different concentrations. The device can be coupled to a standard Size-Exclusion Chromatography chain in which the detector not only provides mean values, but also the evolution of [ η] , Mwand Rg. as a function of elution volume (Ve). Specific calibration curves (log (Mw) = f (Ve)) can be constructed for any sample, and then be used without the combined detector. In this way the molecular weight dependence of [ η] and Rgis readily obtained. Moreover, the special design of the detector allows simple collection of fractions. A number of problems which need to be solved in order to allow an efficient use of the detector are discussed. Results on polystyrene standards illustrate the good performance of the apparatus.

Ethylene/α-olefin copolymers having bimodal molar weight distribution are investigated in comparison with unimodal copolymers in order to understand the incidence of the molecular architecture on the stress cracking resistance. The preferred introduction of the co-units in the longest chains of bimodal copolymers is suggested to favour the occurrence of intercrystalline tie molecules during crystallisation. The more complex is the molecular architecture, the greater is the difficulty for crystallisation by regular chain folding. Intermolecular chemical heterogeneity resulting from preferred incorporation of the co-units in the long chains enhances the co-unit disturbing effect on crystallisation without reducing crystallinity. Intra-molecular heterogeneity of the co-unit distribution is also suggested to be an efficient means to generate tie molecules and random chain folding at the expense of regular chain folding. Isothermal crystallisation is used to probe the effect of molecular architecture on the crystallisation kinetics. It appeared that the correlations between kinetics, molecular architecture and molecular topology of unimodal copolymers no longer hold when considering bimodal copolymers. In contrast, the crystal surface free energy proved to be sensitive to topological changes resulting from molecular architecture modifications.

We point out the specificities of the separation process at work during liquid chromatography of polymers in a gradient of composition of the eluent. The main feature is that, after a transient regime, the concentration profile tends to move as a front, i.e., without diffusive spreading in time. This results in relatively sharp peaks and the uselessness of long columns. We propose a simple analytical model for this self-focusing process that allows us to anticipate optimal conditions of operation. This analysis is supported by experimental tests.

Data coming from the French national statistics on the cause of deaths are used to calculate the probabilities of death from pathologies. These probabilities are calculated according to age, sex, and place of residence of the patient to “personalize” the estimate. This individual prediction of the risk of death is proposed for pathologies for which the feasibility and the utility of prevention measures had been demonstrated. Relative risks of death according to the socioprofessional category, which are coming from the scientific literature, are used to adjust the probabilities of death as a function of the patient socioprofessional category. The aim of this work is to guide a scientist toward a prevention strategy according to the age and characteristics of patient. The use of computers by the scientists will make possible the diffusion of such tool of prediction to improve a personalized prevention.

Labeled IgG was evaluated versus labeled albumin for measurement of plasma volume, to see whether it would give a smaller initial dilution volume (indicating a smaller premixing extravascular loss of label) and a smaller difference between initial dilution volume and dilution volume at time 10 min (indicating a negligible extravascular loss in the first 10 min after mixing). IgG was found to have a lower transcapillary escape rate than albumin (P<0.01) in eight normal volunteers and in eight hypertensive subjects, hypertension being associated with an increased transcapillary escape of both proteins. Despite this, the dilution volumes obtained were indistinguishable and the need for a correction through a retropolation procedure was the same with both proteins. Albumin and IgG dilution volumes were highly correlated in 21 subjects (r=0.977) so that use of labeled IgG is a proper alternative to use of labeled albumin for plasma volume determination. However, since IgG brings no consistent advantage, labeled albumin remains the best available tracer for that purpose.

The number needed to treat is a meaningful way of expressing the benefit of an active treatment over a control. It can be used either for summarising the results of a therapeutic trial or for medical decision making about an individual patient, but its use at the bedside has been impeded by the need for time consuming calculations. A nomogram has therefore been devised that will greatly simplify the calculations. Since calculations are now easy, the number needed to treat can be used to access the value of several interventions, although it does have its limitations. In particular it should not be used when it is not known whether the relative risk reduction associated with an intervention is constant for all levels of risk, or for periods of time longer than that studied in the original trials.

After a brief description of the main domains of application of medical informatics, a typology of questions to be assessed, and of the involved actors, is presented. Dimensions of technology assessment include techniques, medical and health efficacy, economics, sociology, and law and ethics. Barriers to evaluation are analysed. They include barriers related to the domain complexity, human motivation and methodological barriers. Finally categories of solutions and research areas are suggested.

This article examines several criteria for the evaluation of software engineering environments (SEE) in medicine. The study is restricted to the evaluation of the SEE itself, not of its by-products which are the medical applications developed with the SEE. Basic principles for an evaluation methodology are presented. They consist in determining the evaluation objectives and judging a SEE according to criteria which are grouped into three broad categories–functional, generic and environmental. Each category reflects a particular domain of evaluation of the SEE. Methods of measurement and questions highlighting these specific areas are mentioned. Criteria are extracted from the list of objectives that follows the HELIOS European ALM project of the Commission of the European Communities. Special emphasis is drawn on the criteria for which the medical specificity and usefulness of a SEE can be approached. For this purpose a method of measurement of such appropriateness is proposed.

Alcohol consumption and glycosuria were found to be associated (p < 0.001) in a population of 6571 salaried employees who underwent a systematic examination. The prevalence of glycosuria was found to range from 1.3% among 2609 non-drinkers to 5% among 816 heavy drinkers (six glasses or more of alcoholic beverage daily). This association was still significant after adjustement for age, sex and body mass index. Similarly, a positive association was observed between fasting glycemia and alcoholic intake in a subgroup of 998 subjects when such a result was available (p < 0.05).

A total of 6,665 subjects (3,896 men and 2,769 women) employed by small and medium-sized companies in the Paris region were examined. Mean systolic blood pressure (SBP) was significantly higher in the lowest than in the highest occupational categories (p less than 0.001), even when results were adjusted for age (p less than 0.001) and body mass index (p less than 0.001). Diastolic blood pressure (DBP) differed among the occupational categories (p less than 0.001); the differences were still significant after adjustment for age but not for body mass index, suggesting that the latter might be partly responsible for the differences in DBP. Prevalence of hypertension was 14.7% and was negatively associated with a high occupational category (p less than 0.001). Multivariate analysis confirmed the influence of occupational category on SBP (p less than 0.001). Exposure to noise at work and assembly line work were associated with high SBP (p less than 0.01 for both). Of the subjects with detected hypertension, 65.6% were aware of their illness, and 35.3% were undergoing treatment. Both the percentage of treated patients and compliance with treatment were positively associated with occupational category (p less than 0.01 in both cases). Among women, SBP of treated hypertensives was higher in the lowest than in the highest occupational categories (p less than 0.05). It is suggested that the differences in blood pressure levels observed among occupational categories are partly due to working conditions, and that poor compliance with treatment among the low occupational categories enhances these differences.