A magnetic massive star has experienced a stellar merger.

Massive stars (those ≥8 solar masses at formation) have radiative envelopes that cannot sustain a dynamo, the mechanism that produces magnetic fields in lower-mass stars. Despite this, approximately 7% of massive stars have observed magnetic fields, the origin of which is debated. We used multi-epoch interferometric and spectroscopic observations to characterize HD 148937, a binary system of two massive stars. We found that only one star is magnetic and that it appears younger than its companion. The system properties and a surrounding bipolar nebula can be reproduced with a model in which two stars merged (in a previous triple system) to produce the magnetic massive star. Our results provide observational evidence that magnetic fields form in at least some massive stars through stellar mergers.

[Psychiatric care for asylum seekers in Geneva: a multidisciplinary approach for individualized care]. / Soins psychiatriques pour les requérants d'asile à geneve. Une approche multidisciplinaire pour préserver la singularité des soins.

Asylum seekers constitute a vulnerable population insofar as they are submitted to numerous stress factors which facilitate the emergence of mental disorders, such as low socio-economic status, forced separation from loved ones and exposure to violence. Asylum seekers who consult at our community psychiatry facility usually have short-term residence permits, live in collective housing and do not speak the local language. The most frequent diagnoses are depressive disorder (64.7%) and post-traumatic stress disorder (34.5%). Due to their specific clinical and social situation and to the involvement of several professionals in these situations, a specialized psychiatric intervention coordinated with the rest of the network seems necessary.

Liver kidney microsomal type 1 antibodies reduce the CYP2D6 activity in patients with chronic hepatitis C virus infection.

Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease the CYP2D6 activity in vitro and are present in a minority of patients with chronic hepatitis C infection. We investigated whether LKM-1 antibodies might reduce the CYP2D6 activity in vivo. All patients enrolled in the Swiss Hepatitis C Cohort Study and tested for LKM-1 antibodies were assessed (n = 1723): 10 eligible patients were matched with patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specific substrate using the dextromethorphan/dextrorphan metabolic ratio to classify patients into four activity phenotypes. All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with the CYP2D6 genotype in most LKM-negative patients, whereas only three LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was sixfold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, P = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies. In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies.

Correction of sickle cell disease in transgenic mouse models by gene therapy.

Sickle cell disease (SCD) is caused by a single point mutation in the human betaA globin gene that results in the formation of an abnormal hemoglobin [HbS (alpha2betaS2)]. We designed a betaA globin gene variant that prevents HbS polymerization and introduced it into a lentiviral vector we optimized for transfer to hematopoietic stem cells and gene expression in the adult red blood cell lineage. Long-term expression (up to 10 months) was achieved, without preselection, in all transplanted mice with erythroid-specific accumulation of the antisickling protein in up to 52% of total hemoglobin and 99% of circulating red blood cells. In two mouse SCD models, Berkeley and SAD, inhibition of red blood cell dehydration and sickling was achieved with correction of hematological parameters, splenomegaly, and prevention of the characteristic urine concentration defect.

[Current topics in pharmacokinetics and pharmacogenetics of antidepressant drugs]. / Actualités pharmacocinétiques et pharmacogénétiques des antidépresseurs.

For antidepressants as well as for other drugs, personalized prescription has become a major challenge, provided the large interindividual variability encountered both at the pharmacokinetic and the efficacy and tolerance levels. Better identification of the numerous relevant factors and quantification of their effects are prerequisites to progress in that direction. On the basis of recent literature, genetic factors are first reviewed, including polymorphisms of genes coding for drug-metabolizing enzymes, transporters and pharmacodynamic target molecules. Current recommendations with respect to therapeutic drug monitoring of antidepressants and use of pharmacogenetic testing are then summarized.

Productive and physiological responses of lactating dairy cows supplemented with phytogenic feed ingredients.

This experiment compared milk production, milk composition, and physiological responses in lactating dairy cows supplemented with or without a mixture of condensed tannins, encapsulated cinnamaldehyde, curcumin, capsaicin, and piperine. Thirty-six lactating, multiparous, pregnant ¾ Holstein × » Gir cows were maintained in a single drylot pen with ad libitum access to water and a total-mixed ration and were milked twice daily (d -7 to 84). On d 0, cows were ranked by days in milk (86 ± 3 d), milk yield (27.8 ± 1.0 kg), body weight (BW; 584 ± 10 kg), and body condition score (BCS; 3.04 ± 0.06) and assigned to receive (SUPP; n = 18) or not (CON; n = 18) 30 g/cow daily (as-fed basis) of Actifor Pro (Delacon Biotechnik GmbH; Steyregg, Austria). From d 0 to 84, SUPP cows individually received (as-fed basis) 15 g of Actifor Pro mixed with 85 g of finely ground corn through self-locking headgates before each milking of the day. Each CON cow concurrently received 85 g (as-fed basis) of finely ground corn through self-locking headgates. Throughout the experimental period (d -7 to 84), cows from both treatments were administered 500 mg of sometribove zinc at 14-d intervals and were monitored daily for morbidity, including clinical mastitis. Individual milk production was recorded daily, whereas milk samples were collected weekly for analysis of milk composition. Cow BW, BCS, and blood samples were also collected weekly. Cows receiving SUPP gained more BCS (P = 0.05) and had greater (P = 0.04) milk yield during the experiment compared with CON cows (0.22 vs. 0.07 of BCS, SEM = 0.05; 29.5 vs. 27.9 kg/d, SEM = 0.5). Milk composition did not differ (P ≥ 0.15) between SUPP and CON cows; hence, SUPP cows also had greater (P ≤ 0.02) production of fat-corrected and energy-corrected milk. Incidence of clinical mastitis did not differ (P ≥ 0.49) between SUPP and CON cows. No treatment differences were also detected (P ≥ 0.21) for serum concentrations of glucose and serum urea N. Mean serum haptoglobin concentration during the experiment was greater (P = 0.05) in CON vs. SUPP cows. Cows receiving SUPP had less (P ≤ 0.04) serum cortisol concentrations on d 21 and 42, and greater (P ≤ 0.05) serum concentrations of insulin-like growth factor-I on d 7, 35, and 63 compared with CON cows (treatment × day interactions; P ≤ 0.02). Collectively, supplementing phytogenic feed ingredients improved nutritional status and milk production of lactating ¾ Holstein × » Gir cows.

Frequency of dysphoria and mixed states.

BACKGROUND: Mixed states are a complex entity in the field of mood disorders. Dysphoria has been advocated as an important clinical dimension of mixed states. The objective of this work is to study the frequency of dysphoria within a population of patients with DSM-IV major depressive and/or manic episodes and to determine if it may help establish diagnostic criteria for subthreshold cases of depressive or manic mixed states. SAMPLING AND METHODS: A total of 165 patients were assessed using the Mini International Neuropsychiatric Interview complemented by a section defining dysphoria as a constellation of 3 among 4 symptoms (inner tension, irritability, aggressive behavior and hostility). RESULTS: When classifying patients according to the number of symptoms of the opposite polarity, changes in the frequency of dysphoria revealed a clear contrast between the 2 opposite manic and depressive poles and the full mixed state (DSM-IV definition). The frequency of dysphoria was 17.5% in pure depression, 22.7% in pure mania and 73.3% in full mixed state. Two threshold effects were identified: (1) the frequency of dysphoria increased from 17.5 to 61.1% (p = 0.002) when the number of manic symptoms in DSM-IV depressed patients increased from 0 to 1, and (2) dysphoria increased from 14.3 to 69.2% (p = 0.057) when the number of depressive symptoms increased from 2 to 3 in DSM-IV manic patients. CONCLUSION: Dysphoria is strongly but not necessarily associated with mixed states. When used as a clinical marker for mixed states, dysphoria confirms the modern delimitations of sub-threshold mixed states by specifying the required number of symptoms of the opposite polarity (which could be lower for depressive mixed states than for manic mixed states). The study has limitations related to the inclusion of patients who are not drug-free, to the definition of dysphoria and to the sample size.

Developmental delay in communication among toddlers and its relationship to caregiving behavior among violence-exposed, posttraumatically stressed mothers.

OBJECTIVES: This study aimed to understand if maternal interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) is associated with delayed language development among very young children ("toddlers"). METHODS: Data were collected from 61 mothers and toddlers (ages 12-42 months, mean age = 25.6 months SD = 8.70). Child expressive and receptive language development was assessed by the Ages and Stages Questionnaire (ASQ) communication subscale (ASQCS) that measures language acquisition. Observed maternal caregiving behavior was coded from videos of 10-min free-play interactions via the CARE-Index. Correlations, Mann-Whitney tests, and multiple linear regression were performed. RESULTS: There was no significant association between maternal IPV-PTSD severity and the ASQCS. Maternal IPV-PTSD severity was associated with continuous maternal behavior variables (i.e. sensitive and controlling behavior on the CARE-Index) across the entire sample and regardless of child gender. Maternal sensitivity was positively and significantly associated with the ASQCS. Controlling behavior was negatively and significantly associated with the ASQCS. CONCLUSIONS: Results are consistent with the literature that while maternal IPV-PTSD severity is not associated with child language delays, the quality of maternal interactive behavior is associated both with child language development and with maternal IPV-PTSD severity. Further study is needed to understand if the level of child language development contributes to intergenerational risk or resilience for relational violence and/or victimization.

Erythrocytes in sickle cell anemia are heterogeneous in their rheological and hemodynamic characteristics.

To understand the contribution to the pathophysiology of sickle cell anemia of the different erythrocyte density types present in the blood of these patients, we have studied the viscosimetric and hemodynamic characteristics of four major classes of hemoglobin SS erythrocytes. We have isolated reticulocytes, discocytes, dense discocytes, and irreversibly sickled cells (fractions I-IV) on Percoll-Renografin density gradients. Bulk viscosity was studied in a coneplate viscosimeter and the hemodynamic studies were performed on the isolated, artificially perfused mesoappendix vasculature of the rat (Baez preparation). Bulk viscosity measurements at shear rates of 230 S-1 demonstrate that when the cells are oxygenated, fraction I (reticulocyte rich) has a higher viscosity than expected from its low intracellular hemoglobin concentration. The rest of the fractions exhibit moderate increases in bulk viscosity pari-passu with the corresponding increases in density (mean corpuscular hemoglobin concentration). When deoxygenated, all cell fractions nearly doubled their bulk viscosity and the deoxy-oxy differences remained constant. The Baez preparation renders a different picture: oxygenated fractions behave as predicted by the viscosimetric data, but, when deoxygenated, cell fractions exhibit dramatically increased peripheral resistance and the deoxy-oxy difference are directly proportional to cell density, thus, the largest increases were observed for fractions III and IV. The differences between the rheological and the hemodynamic measurements are most probably due to the different sensitivity of the two methods to the extent of intracellular polymerization. These results also demonstrate that the hitherto unrecognized fraction III cells (very dense discocytes that change shape very little on deoxygenation) are as detrimental to the microcirculation as the irreversibly sickled cell-rich fraction IV. They may, however, induce obstruction by a different mechanism. As the extent to which these fractions are populated by erythrocytes varies considerably from patient to patient, the distribution function of cell densities in each sickle cell anemia patient might have consequences for the type of pathophysiological events occurring in their microcirculation.

Magnetic resonance evidence of hypoxia in a homozygous alpha-knockout of a transgenic mouse model for sickle cell disease.

All transgenic mouse models for sickle cell disease express residual levels of mouse globins which complicate the interpretation of experimental results. We now report on a mouse expressing high levels of human betaS and 100% human alpha-globin. These mice were created by breeding the alpha-knockout and the mouse beta(major)-deletion to homozygosity in mice expressing human alpha- and betaS-transgenes. These betaS-alpha-knockout mice have accelerated red cell destruction, altered hematological indices, ongoing organ damage, and pathology under ambient conditions which are comparable with those found in alphaH betaS-Ant[betaMDD] mice without introduction of additional mutations which convert betaS into a "super-betaS" such as the doubly mutated betaS-Antilles. This is of particular importance for testing strategies for gene therapy of sickle cell disease. Spin echo magnetic resonance imaging at room air and 100% oxygen demonstrated the presence of blood hypoxia (high levels of deoxygenated hemoglobin) in the liver and kidneys that was absent in control mice. We demonstrate here that transgenic mice can be useful to test new noninvasive diagnostic procedures, since the magnetic resonance imaging technique described here potentially can be applied to patients with sickle cell disease.

In vivo demonstration of red cell-endothelial interaction, sickling and altered microvascular response to oxygen in the sickle transgenic mouse.

Intravascular sickling, red cell-endothelium interaction, and altered microvascular responses have been suggested to contribute to the pathophysiology of human sickle cell disease, but have never been demonstrated under in vivo flow. To address this issue, we have examined a transgenic mouse line, alphaHbetaSbetaS-Antilles [betaMDD] which has a combined high (78%) expression of beta S and beta S-Antilles globins. In vivo microcirculatory studies using the cremaster muscle preparation showed adhesion of red cells, restricted to postcapillary venules, in transgenic mice but not in control mice. Electron microscopy revealed distinct contacts between the red cell membrane and the endothelium surface. Some red cells exhibiting sickling were regularly observed in the venular flow. Infusion of transgenic mouse red cells into the ex vivo mesocecum vasculature also showed adhesion of mouse red cells exclusively in venules. Under resting conditions (pO2, 15-20 mmHg), there were no differences in the cremaster microvascular diameters of control and transgenic mice; however, transgenic mice showed a drastic reduction in microvascular red cell velocities (Vrbc) with maximal Vrbc decrease (> 60%) occurring in venules, the sites of red cell adhesion and sickling. Local, transient hyperoxia (pO2, 150 mmHg) resulted in striking differences between control and transgenic mice. In controls, oxygen caused a 69% arteriolar constriction, accompanied by 75% reduction in Vrbc. In contrast, in transgenic mice, hyperoxia resulted in only 8% decrease in the arteriolar diameter and in 68% increase in VrBC; the latter is probably due to an improved flow behavior of red cells as a consequence of unsickling. In summary, the high expression of human sickle hemoglobin in the mouse results not only in intravascular sickling but also red cell-endothelium interaction. The altered microvascular response to oxygen could be secondary to blood rheological changes, although possible intrinsic differences in the endothelial cell/vascular smooth muscle function in the transgenic mouse may also contribute. These sickle transgenic mice could serve as a useful model to investigate vasoocclusive mechanisms, as well as to test potential therapies.

Some aspects of the pathophysiology of homozygous Hb CC erythrocytes.

We have studied erythrocytes from homozygous CC patients in vitro and in perfused rat mesoappendix vasculature to answer some long-standing questions. By examination of wet whole blood preparations, and by comparing the cell distribution on isopycnic continuous density gradients of whole blood samples from a splenectomized CC patient with those from three intact CC patients, we have demonstrated the presence of a distinct crystal-containing band of cells that is present in the former, but totally absent from the latter. We conclude that Hb CC cells containing crystals circulate in Hb CC individuals, but in intact patients they are effectively removed by the spleen. By use of 31P nuclear magnetic resonance and viscosity measurements on cells, we have demonstrated that intracellular aggregation of hemoglobin C occurs on deoxygenation even when no crystal formation is detectable by morphological methods. These two observations are in apparent contradiction with the absence of clinical microcirculatory impairment found in both intact and splenectomized CC patients. The contradiction was resolved by rheological studies on isolated rat mesoappendix preparations and erythrocyte diameter measurements that lead to the conclusion that the hemorheological properties of CC cells in the microcirculation are nearly normal because their increased viscosity is offset by their smaller diameter and size.

Impairment of the growth of Plasmodium falciparum in HbEE erythrocytes.

HbE is a beta-chain mutant frequently found among inhabitants of Southeast Asia and surrounding territories. We find that Plasmodium falciparum multiplies more slowly in erythrocytes from individuals homozygous for HbE than in cells from HbA individuals. In contrast, this parasite grows normally in erythrocytes heterozygous for HbE. This is the first direct evidence that suggests what has been suspected on the basis of circumstantial data, that HbE-containing erythrocytes might be advantageous to the carrier in regions with endemic malaria.

SC erythrocytes have an abnormally high intracellular hemoglobin concentration. Pathophysiological consequences.

We have examined 20 SC patients on Percoll-Stractan continuous density gradients and find that they have an elevated mean corpuscular hemoglobin concentration (MCHC). Reduction of the MCHC to normal values results in amelioration of four physiologically important blood abnormalities: decreased oxygen affinity, viscosity of deoxygenated erythrocyte suspensions, rate of sickling, and deoxygenation induced K+ efflux. These observations suggest that the rehydration of SC cells to normal values should be considered a potential approach in the therapeutic manipulation of this disease.

High levels of human gamma-globin gene expression in adult mice carrying a transgene of deletion-type hereditary persistence of fetal hemoglobin.

Persistent expression of the gamma-globin genes in adults with deletion types of hereditary persistence of fetal hemoglobin (HPFH) is thought to be mediated by enhancer-like effects of DNA sequences at the 3' breakpoints of the deletions. A transgenic mouse model of deletion-type HPFH was generated by using a DNA fragment containing both human gamma-globin genes and HPFH-2 breakpoint DNA sequences linked to the core sequences of the locus control region (LCR) of the human beta-globin gene cluster. Analysis of gamma-globin expression in six HPFH transgenic lines demonstrated persistence of gamma-globin mRNA and peptides in erythrocytes of adult HPFH transgenic mice. Analysis of the hemoglobin phenotype of adult HPFH transgenic animals by isoelectric focusing showed the presence of hybrid mouse alpha2-human gamma2 tetramers as well as human gamma4 homotetramers (hemoglobin Bart's). In contrast, correct developmental regulation of the gamma-globin genes with essentially absent gamma-globin gene expression in adult erythroid cells was observed in two control non-HPFH transgenic lines, consistent with autonomous silencing of normal human gamma-globin expression in adult transgenic mice. Interestingly, marked preferential overexpression of the LCR-distal (A)gamma-globin gene but not of the LCR-proximal (G)gamma-globin gene was observed at all developmental stages in erythroid cells of HPFH-2 transgenic mice. These findings were also associated with the formation of a DNase I-hypersensitive site in the HPFH-2 breakpoint DNA of transgenic murine erythroid cells, as occurs in normal human erythroid cells in vivo. These results indicate that breakpoint DNA sequences in deletion-type HPFH-2 can modify the developmentally regulated expression of the gamma-globin genes.

A stepwise drug treatment algorithm to obtain complete remission in depression: a Geneva study.

QUESTIONS UNDER STUDY/PRINCIPLES: We describe the proportion of severely depressed outpatients reaching complete remission at the different stages of a drug treatment algorithm. We compare several treatment options for SSRI (selective serotonin reuptake inhibitor) non-responders and test the feasibility of the algorithm in clinical conditions. METHODS: Patients with severe depressive disorders (ICD-10; MADRS > or = 25) admitted to an academic outpatient clinic were enrolled in this algorithm-guided sequential treatment protocol (starting with an SSRI and ending with a tricyclic, lithium, triodothyronine combination). The general principle of the algorithm was to boost the drug therapy in the event of non-response. RESULTS: 135 patients entered the study and 131 were eligible for analysis. From this group, 86 patients dropped out (65.6%), 40 reached complete remission (30.5%) and 5 patients did not reach remission at all (3.8%). In the 117 patients to whom a last observation carried forward approach was applied, the median improvement of the MADRS score was 48.0% (range -20.7%-100%), with 48.7% of patients considered responders, 23.1% partial responders and 28.2% non-responders. Median retention time was 8 weeks (range 2-34). CONCLUSIONS: This algorithm-guided antidepressant treatment was acceptable for clinicians and resulted in an elevated final response rate among study completers. However, the dropout rate was high, mainly due to treatment interruption or non-observance.

Structural basis of HIV-1 and HIV-2 protease inhibition by a monoclonal antibody.

BACKGROUND: Since the demonstration that the protease of the human immunodeficiency virus (HIV Pr) is essential in the viral life cycle, this enzyme has become one of the primary targets for antiviral drug design. The murine monoclonal antibody 1696 (mAb1696), produced by immunization with the HIV-1 protease, inhibits the catalytic activity of the enzyme of both the HIV-1 and HIV-2 isolates with inhibition constants in the low nanomolar range. The antibody cross-reacts with peptides that include the N terminus of the enzyme, a region that is highly conserved in sequence among different viral strains and that, furthermore, is crucial for homodimerization to the active enzymatic form. RESULTS: We report here the crystal structure at 2.7 A resolution of a recombinant single-chain Fv fragment of mAb1696 as a complex with a cross-reactive peptide of the HIV-1 protease. The antibody-antigen interactions observed in this complex provide a structural basis for understanding the origin of the broad reactivity of mAb-1696 for the HIV-1 and HIV-2 proteases and their respective N-terminal peptides. CONCLUSION: A possible mechanism of HIV-protease inhibition by mAb1696 is proposed that could help the design of inhibitors aimed at binding inactive monomeric species.

[Validation of the QFS measuring the frequency and satisfaction in social behaviours in psychiatric adult population]. / Validation du Questionnaire de fonctionnement social (QFS), un autoquestionnaire mesurant la fréquence et la satisfaction des comportements sociaux d'une population adulte psychiatrique.

INTRODUCTION: Although everyone working in routine mental health services recognizes the scientific and ethical importance to ensure that treatments being provided are of highest quality, there is a clear lack of consensus regarding what outcome domains to include, what measure of assessment to use and, moreover, who to question when assessing. LITERATURE FINDINGS: Since the fifties, social functioning is considered as an important dimension to take into account for treatment planning and outcome measuring. But for many years, symptoms scales have been considered as sufficient outcome measures and social functioning improvement expected on the basis of symptoms alleviation. As symptoms and social adjustment sometimes appear relatively independent, no accurate conclusion concerning the patient's social functioning can so be driven on the basis of his clinical symptoms. More attention has then been directed toward the development of instruments specifically intended to measure the extent and nature of social functioning impairments observed in most psychiatric syndromes. Many of these instruments are designed to be completed by caregivers or remain time consuming and difficult to use routinely. Presently, in clinical practice, there is a need to rely on simple and brief instruments considering patients'perspective about their social adjustment as a function of time. AIM OF THE STUDY: The aim of this study is to present a new instrument, the QFS, initially developed in order to assess social functioning in patients involved in group psychotherapy programs conducted in a specialist mental health setting, as well as its psychometric characteristics. METHODOLOGY: It was designed to be completed in less than 10 minutes and the questions are phrased in a simple and redundant way, in order to limit problems inherent to illiteracy or language comprehension. The QFS is a 16 items self-report instrument that assesses both the frequency of (8 items) and the satisfaction with (8 items) various social behaviours adopted during the 2 weeks period preceding the assessment. It yields three separate indexes of social functioning, defined a priori and labelled "frequency", "satisfaction" and "global". The higher the scores, the better the social functioning. The QFS was administered to 457 subjects, aged between 18 and 65, including 176 outpatients (99 with anxious or depressive disorders, 25 with personality disorders and 52 with psychotic disorders) and 281 healthy control subjects. RESULTS: No significant difference was found between patients and controls according to age or gender distribution. Acceptance rate was high (>95%). Moreover, the QFS was generally acceptable to the clinicians who used it. Internal consistency calculated for each index ranged from 0.65 to 0.83 (Cronbach alpha). Test-retest reliability, calculated within a 15 days time interval on a sample of 49 healthy controls, ranged from 0.69 to 0.71 (intraclass correlation coefficient). Discriminant validity was calculated on healthy controls and patients divided into sub-groups according to their diagnosis. It showed to be excellent, with significantly higher scores in control subjects than in psychiatric patients and significant differences across diagnostic categories (Kruskal-Wallis ANOVA with post-hoc tests, all p<0.05). The convergent validity of the QFS with other measures of social functioning was calculated, using the Social Adaptation Self-Evaluation Scale (SASS) and the Social Adjustment Scale Self-Report (SAS-SR). With the SASS, the convergent validity was higher among patients (Spearman rS 0.71 to 0.92, p<0.01) than controls (rS from 0.49 to 0.66, p<0.001). In healthy controls, correlation with the SAS-SR was moderate but statistically significant (rS from - 0.21 to - 0.44, p<0.05). When comparing QFS scores with self-rated symptoms severity, lower levels of social functioning were significantly associated with more severe symptoms according to the Brief Symptom Inventory (BSI: rS from - 0.38 to - 0.65, p<0.001). The QFS indexes demonstrated sensitivity to change (Wilcoxon: all p<0.05) on a sample of 27 out-patients suffering from anxious-depressive disorders questioned before and after 4 months of cognitive behavioural group therapy running on a weekly basis during 16 sessions of 2 hours each.The factorial validity of the QFS was measured through 3 separate factor analysis conducted using the data of 457 subjects. The first analysis considered only Frequency items; 7 out of 8 items had loadings above 0.5 on Factor 1 accounting for 30.7% (unrotaded) of the variance. The second analysis considered only Satisfaction items; all items had loadings above 0.6 on Factor 1 explaining 43.4% (unrotaded) of the variance. And finally, in the third factor analysis, all QFS items were included; 15 out of 16 items had loadings above 0.4 on Factor 1 accounting for 30% (unrotated) of the variance. Concerning the factorial validity of the instrument, these results suggest that all QFS items belong to the same underlying dimension. DISCUSSION: Finally, provisional norms for the QFS are provided for healthy controls, in order to characterise individual patients or patient subgroups. In conclusion, the need for assessment in clinical routine, in order to estimate different aspects of patients conditions as well as the quality of the treatment provided, has contributed to the development of a large variety of instruments measuring several domains. Concerning the level of social functioning, many instruments fail to meet chief criterion of feasibility, remaining often too complex or time onsuming. Moreover, only few of them are available in French. CONCLUSION: The QFS presented here is a brief, simple and easy to administer self-rating scale that displays satisfactory psychometric properties. It seems to be a valuable instrument for the monitoring of social functioning in psychiatric patients which, from a therapeutic point of view, may have a clear impact as it sets up expectation of change and allows both to reality test patients and therapists beliefs about the presence of progress or not and to identify if therapy is working on this specific outcome domain. Though, to date, the administration of the QFS to other populations and treatment modalities requires further investigation.

Purification and properties of the RNA polymerase of an extremely thermophilic bacterium: Thermus aquaticus T2.

The RNA polymerase of the extremely thermophilic bacterium Thermus aquaticus T 2 has been purified to homogeneity. The apparent molecular weights of the subunits of the enzyme are : 165 000, 130000, 92 000 and 44 000. The in vitro temperature optimum of enzyme activity is around 65 degrees C. The enzyme has a preference towards the homologous template and is strongly inhibited by KCI. Rifampicin inhibits the enzyme only to 50% even at very high concentrations. Heparin inhibits it completely, but only at higher molar excess than in the case of the Escherichia coli enzyme. The enzyme can form heparin-resistant complexes at elevated temperatures on the homologous template, but not on E. coli DNA.

Hydrophobic interactions of Escherichia coli ribosomes.

We have demonstrated the presence of hydrophobic sites on the surface of Escherichia coli ribosomes by means of hydrophobic chromatography on Octyl-Sepharose. Both 30-S and 50-S ribosomal subunits adsorb to Octyl-Sepharose at a low salt concentration, and can be eluted from it with a nonionic detergent without substantial changes in structure or activity. By testing a series of LiCl-derived ribosomal cores for their ability to adsorb to Octyl-Sepharose we have shown that the interaction of ribosomal particles with Octyl-Sepharose is dependent on the presence of certain ribosomal proteins; the core particles which lack these proteins do not bind to Octyl-Sepharose. The binding of a series of different ribosomal cores to nitrocellulose filters (Millipore) yielded the same pattern as was observed with Octyl-Sepharose, i.e. the more protein-depleted the particles, the less they were adsorbed. Thus, the adsorption of ribosomes to Millipore filters and to Octyl-Sepharose is presumably of the same hydrophobic nature.