Synergy of Turbulent Momentum Drive and Magnetic Braking.

In absence of external torque, plasma rotation in tokamaks results from a balance between collisional magnetic braking and turbulent drive. The outcome of this competition and cooperation is essential to determine the plasma flow. A reduced model, supported by gyrokinetic simulations, is first used to explain and quantify the competition only. The ripple amplitude above which magnetic drag overcomes turbulent viscosity is obtained. The synergetic impact of ripple on the turbulent toroidal Reynolds stress is explored. Simulations show that the main effect comes from an enhancement of the radial electric field shear by the ripple, which in turn impacts the residual stress.

Depressive relapse during lithium treatment associated with increased serum thyroid-stimulating hormone: results from two placebo-controlled bipolar I maintenance studies.

OBJECTIVE: To assess the relationship between depressive relapse and change in thyroid function in an exploratory post hoc analysis from a controlled maintenance evaluation of bipolar I disorder. METHOD: Mean thyroid-stimulating hormone (TSH) and outcome data were pooled from two 18-month, double-blind, placebo-controlled, maintenance studies of lamotrigine and lithium monotherapy. A post hoc analysis of 109 subjects (n = 55 lamotrigine, n = 32 lithium, n = 22 placebo) with serum TSH values at screening and either week 52 (+/-14 days) or study drop-out was conducted. RESULTS: Lithium-treated subjects who required an intervention for a depressive episode had a significantly higher adjusted mean TSH level (4.4 microIU/ml) compared with lithium-treated subjects who did not require intervention for a depressive episode (2.4 microIU/ml). CONCLUSION: Lithium-related changes in thyroid function are clinically relevant and should be carefully monitored in the maintenance phase of bipolar disorder to maximize mood stability and minimize the risk of subsyndromal or syndromal depressive relapse.

Quantitative analysis of HBV cccDNA from clinical specimens: correlation with clinical and virological response during antiviral therapy.

Attempts to investigate changes in various forms of intrahepatic hepatitis B virus (HBV) DNA during antiviral therapy have been hampered by limitations in technologies and scarcity of adequate tissue for analysis. We used a sensitive, specific assay to detect and quantitate covalently closed circular DNA (cccDNA) from total intrahepatic HBV DNA in clinical liver specimens. Total HBV DNA and cccDNA from 21 needle-biopsy specimens were quantified, with levels ranging from 0.1 to 9.8 copies/cell and 0.3 to 491.0 copies/cell, respectively. Then, we performed the same determinations on baseline and week-52 liver needle-biopsy specimens from eight patients enrolled in a clinical trial and evaluated the association between intrahepatic HBV DNA levels and serological and virological endpoints. In most patients, levels of intrahepatic HBV DNA, including cccDNA, decreased over the 52-week study, regardless of therapy or serological outcome. Higher ratios of cccDNA to total HBV DNA were detected at week 52 than at baseline indicating a shift in predominance of nonreplicating virus in posttreatment specimens. In patients who achieved treatment-related or spontaneous hepatitis B e antigen (HBeAg) responses, including those harbouring tyrosine-methionine-aspartate-aspartate-mutant HBV, levels of intrahepatic and serum HBV DNA suppression were greater than those in patients without HBeAg responses. In conclusion, this pilot study of intrahepatic HBV replicative forms in patients with chronic hepatitis B indicated that total intrahepatic and, specifically, cccDNA levels are not static but change as a reflection of serological and virological events.

Quantitation of hepatitis B viremia and emergence of YMDD variants in patients with chronic hepatitis B treated with lamivudine.

Hepatitis B viremia and emergence of hepatitis B virus (HBV) YMDD variants with reduced susceptibility to lamivudine were analyzed in patient sera from a phase II study of extended lamivudine therapy. Within 12 weeks, all patients exhibited a marked virologic response to lamivudine: >99% reduction (median 5 log decrease) in serum HBV DNA levels. Virus remained at >104 genomes/mL in 11 patients and decreased to <104 genomes/mL in the remaining 12 patients. In 10 patients, detectable YMDD variants emerged during the course of treatment. Six patients, including 3 with YMDD variants, experienced hepatitis B e antigen seroconversion while on lamivudine therapy or soon after its discontinuation. No patients with HBV DNA levels >104 genomes/mL seroconverted. Thus, patients who respond to lamivudine therapy with dramatic reductions in viral DNA level (to <104 genomes/mL) appear more likely to seroconvert than patients who do not achieve this level of HBV clearance.

Two sensitive PCR-based methods for detection of hepatitis B virus variants associated with reduced susceptibility to lamivudine.

Two novel assays, a restriction fragment length polymorphism (RFLP) assay and an assay based on the 5'-nuclease activity of Taq DNA polymerase, were developed for screening viral variants in lamivudine-treated patients' sera containing <1,000 copies of the hepatitis B virus (HBV) genome per ml. Both assays were designed to detect single-nucleotide changes within the HBV DNA polymerase gene that are associated with lamivudine resistance in vitro and have been used to screen a number of patients' sera for variant virus. Results obtained with these assays and standard sequencing technology were compared with regard to throughput, ability to detect individual virus species present at low concentrations, and ability to detect, distinguish, and quantitate wild-type (wt) and HBV tyrosine methionine(552) aspartate aspartate motif variants in mixed viral populations. Unlike DNA sequencing, both assays are amenable to high-throughput screening and were shown to be able to quantitatively detect variant virus in the presence of a background of wt virus. As with DNA sequencing, both new assays incorporate a PCR amplification step and are able to detect the relatively low amounts of virus found in lamivudine-treated patients' sera. However, these assays are far less labor intensive than the DNA-sequencing techniques presently in use. Overall, the RFLP assay was more sensitive than DNA sequencing in detecting and determining the ratios of wt to variant virus. Furthermore, the RFLP assay and 5'-nuclease assay were equally sensitive in the detection of mixed viral species, but the RFLP assay was superior to the 5'-nuclease assay in the quantitation of mixed viral species. These assays should prove useful for further understanding of virological response to therapy and disease progression.

The state of research on ego identity: A review and appraisal : Part I.

Considerable research on ego identity has appeared over the past 15 years, indicating the need for an overall review. Part I commences by considering the complexity of Erikson's concept and suggesting several different theoretical contexts in which it has been used. The validity of investigators' attempts to operationalize the concept "ego identity" is assumed to depend in part upon their interpretations of its meaning. The subsequent review of empirical literature is organized according to different procedures which have been used to measure ego identity. A first section summarizes and evaluates research utilizing Q-sort and self-report questionnaire measures, while a second considers the large number of investigations that have employed James Marcia's Identity Status Interview. The latter group of studies are ordered according to the type of dependent variable (e.g., cognitive, behavioral, personality, developmental) examined in relation to ego identity status (i.e., achievement, moratorium, foreclosure, diffusion). Part II of the review, to appear in the next issue of this journal, will recapitulate the identity status literature, present an overall evaluation of the identity status paradigm, and suggest a number of issues for future research.

The state of research on ego identity: A review and appraisal : Part II.

In the first part of this review (see Volume 7, Number 3 of this journal), a comprehensive survey of empirical research on ego identity was presented. Special emphasis was given to the large number of studies employing James Marcia's "identity status" paradigm. Research within this paradigm is recapitulated here by presenting empirical results which typify each of the four identity statuses (i.e., achievement, moratorium, foreclosure, and diffusion). A detailed evaluation of the identity status paradigm itself follows. Among the topics considered are (1) the construct and external validity of the approach as a whole, (2) the rationale and discriminant validity of the identity statuses, and (3) the reliability of the Identity Status Interview. Part II concludes by considering a number of problems for future research. Several persisting methodological and substantive issues within the identity status paradigm are noted. Finally, it is suggested that investigators turn their attention to the processes mediating identity formation. Contemporary psychoanalytic conceptions of adolescent development are viewed as providing one possible theoretical framework for investigating such processes.

Can we describe an individual's personality? agreement of stereotype versus individual attributes.

Group members described other members of their group (known for at least a year) by four different procedures (free-descriptive phrases, free-descriptive adjectives, an adjective checklist, and a rating scale) at weekly intervals. As expected, the agreement between pairs of observers, as measured by overlap of content, increased from the free to the structured tasks. However, observers, agreement by chance and on group stereotypes, assessed by counting overlap between their descriptions of two separate persons, also increased. When chance and stereotype-associated aggreement were subtracted from overall agreement, the remaining, "person-specific" agreement averaged about 5%. Agreement measured separately by a matching procedure averaged 14%. No significant increase in person-specific agreement was foud between the free-descriptive and standard tasks. The findings indicate that agreement on individuating features of a person is very low and is not appreciably improved by providing observers with standard descriptive tasks.

Further observations on the activation of lysosomal acid alpha-glucosidase by cortisone derivatives.

1. Cortisone acetate activates the acid alpha-glucosidase in rat liver slices and in isolated liver lysosomes. 2. The reaction is steroid specific and moreover does not occur with lysosomal acid phosphatase or beta-galactosidase. 3. After pretreatment of the lysosomes with cortisone, substrate (maltose) binding to the soluble lysosomal acid alpha-glucosidase is not affected, but the steroid does increase the V(max.) value. Membrane-bound enzyme is not activated by cortisone. 4. 4-[(14)C]Cortisone is preferentially bound to the lysosomal membrane and the possible involvement of this structure in the activation phenomenon is discussed.

Studies on type II glycogenosis. Effects of cortisone derivatives on acid -glucosidase.

Cortisone causes a marked increase in the activity of liver acid alpha-glucosidase 2h after injection into male Wistar rats. Studies on rat liver tissue slices, isolated lysosomes and cultured skin fibroblasts have demonstrated similar elevations of acid alpha-glucosidase activity after incubation with cortisone. Cortisone-treated human liver tissue, obtained by needle biopsy, also shows an increase in acid alpha-glucosidase activity. Neutral alpha-glucosidase activity was not stimulated by cortisone in vivo or in liver slices.

The structure and deposition of human-liver glycogens.

1. Glycogen was extracted from and the amount determined in human foetal livers ranging in age from 13(1/2) to 26 weeks. 2. The detailed structures of human foetal- and child-liver glycogens were examined and shown to be essentially the same. 3. The deposition of glycogen in different mammalian species is discussed.