Comparison of the frequency and enjoyability of pleasant events in cocaine abusers vs. non-abusers using a standardized behavioral inventory

AIMS: To examine whether cocaine abusers differ from non-abusers in their frequency and enjoyability of engaging in various "pleasant events", in order to approximate the density of positive reinforcement experienced in their natural environment. DESIGN: Comparisons of cocaine abusers to normative data and matched controls. SETTING: An outpatient substance abuse treatment center in Burlington, Vermont, USA. PARTICIPANTS: Subjects included 100 individuals enrolled in outpatient treatment for cocaine abuse or dependence and 50 community volunteers without histories of drug abuse or other major psychiatric illness and matched to cocaine-dependent patients on age, sex and SES. MEASUREMENTS: Diagnostic assessments were based upon clinical interviews using the DSM-III-R checklist. The primary focus of this study was the Pleasant Events Schedule (PES), a self-rated behavioral inventory of the frequency and enjoyability of engaging in "pleasant" activities. Cocaine use history, treatment outcome and other relevant variables were also assessed. FINDINGS: Cocaine abusers reliably reported lower frequency of non-social, introverted, passive outdoor and mood-related activities than controls. These differences remained after controlling for demographic and life-style differences between groups, with the exception of mood-related activities. Perceived enjoyability of the activities did not differ across groups. Intravenous cocaine use and prior treatment for cocaine abuse predicted particularly low frequency of pleasant activities. Greater frequency of non-social activities predicted better treatment outcome. CONCLUSIONS: Drug abuse is associated with low density of certain types of non-drug reinforcement. Systematic increases in these activities may improve treatment outcome.     

Solution structure of glutathione bound to human glutathione transferase P1-1: comparison of NMR measurements with the crystal structure

The conformation of the bound glutathione (GSH) in the active site of the human glutathione transferase P1-1 (EC 2.5.1.18) has been studied by transferred NOE measurements and compared with those obtained by X-ray diffraction data. Two-dimensional TRNOESY and TRROESY experiments have been performed under fast-exchange conditions. The family of GSH conformers, compatible with TRNOE distance constraints, shows a backbone structure very similar to the crystal model. Interesting differences have been found in the side chain regions. After restrained energy minimization of a representative NMR conformer in the active site, the sulfur atom is not found in hydrogen-bonding distance of the hydroxyl group of Tyr 7. This situation is similar to the one observed in an "atypical" crystal complex grown at low pH and low temperature. The NMR conformers display also a poorly defined structure of the glutamyl moiety, and the presence of an unexpected intermolecular NOE could indicate a different interaction of this substrate portion with the G-site. The NMR data seem to provide a snapshot of GSH in a precomplex where the GSH glutamyl end is bound in a different fashion. The existence of this precomplex is supported by pre-steady-state kinetic experiments [Caccuri, A. M., Lo Bello, M., Nuccetelli, M., Nicotra, M., Rossi, P., Antonini, G., Federici, G., and Ricci, G. (1998) Biochemistry 37, 3028-3034] and preliminary time-resolved fluorescence data.     

Speech perception performance in experienced cochlear-implant patients receiving the SPEAK processing strategy in the Nucleus Spectra-22 cochlear implant

Sixteen experienced cochlear implant patients with a wide range of speech-perception abilities received the SPEAK processing strategy in the Nucleus Spectra-22 cochlear implant. Speech perception was assessed in quiet and in noise with SPEAK and with the patients' previous strategies (for most, Multipeak) at the study onset, as well as after using SPEAK for 6 months. Comparisons were made within and across the two test sessions to elucidate possible learning effects. Patients were also asked to rate the strategies on seven speech recognition and sound quality scales. After 6 months' experience with SPEAK, patients showed significantly improved mean performance on a range of speech recognition measures in quiet and noise. When mean subjective ratings were compared over time there were no significant differences noted between strategies. However, many individuals rated the SPEAK strategy better for two or more of the seven subjective measures. Ratings for "appreciation of music" and "quality of my own voice" in particular were generally higher for SPEAK. Improvements were realized by patients with a wide range of speech perception abilities, including those with little or no open-set speech recognition.     

Homology and functional similarity of an hrp-linked pathogenicity locus, dspEF, of Erwinia amylovora and the avirulence locus avrE of Pseudomonas syringae pathovar tomato

The "disease-specific" (dsp) region next to the hrp gene cluster of Erwinia amylovora is required for pathogenicity but not for elicitation of the hypersensitive reaction. A 6.6-kb apparent operon, dspEF, was found responsible for this phenotype. The operon contains genes dspE and dspF and is positively regulated by hrpL. A BLAST search revealed similarity in the dspE gene to a partial sequence of the avrE locus of Pseudomonas syringae pathovar tomato. The entire avrE locus was sequenced. Homologs of dspE and dspF were found in juxtaposed operons and were designated avrE and avrF. Introduced on a plasmid, the dspEF locus rendered P. syringae pv. glycinea race 4 avirulent on soybean. An E. amylovora dspE mutant, however, elicited a hypersensitive reaction in soybean. The avrE locus in trans restored pathogenicity to dspE strains of E. amylovora, although restored strains were low in virulence. DspE and AvrE are large (198 kDa and 195 kDa) and hydrophilic. DspF and AvrF are small (16 kDa and 14 kDa) and acidic with predicted amphipathic alpha helices in their C termini; they resemble chaperones for virulence factors secreted by type III secretion systems of animal pathogens.     

Pinhole-array x-ray spectrometer for laser-fusion experiments

A pinhole-array x-ray spectrometer for laser-fusion experiments is demonstrated. An array of approximately 300 pinholes is placed in front of a flat-crystal spectrometer, yielding target images at photon energies ~10 eV apart (for photon energies of ~4 to 5 keV). For wideband radiation the images are two dimensional, whereas when a single spectral line is used, the field of view in the direction of dispersion is limited. However, single spectral line images can have a field of view sufficient for imaging the compressed target core. We show the image at the Ti-Kalpha-line fluorescence from a Ti-doped shell, which we show to be excited by continuum radiation from the compressed core. The Kalpha image delineates the cold, compressed shell at peak compression, which can otherwise be obtained only through backlighting. In addition, the array provides spectra of high spectral resolution because of the reduction in the effective source size.     

Psychosexual development of women with congenital adrenal hyperplasia

Women with congenital adrenal hyperplasia (CAH) (N = 31) and their unaffected sisters or female cousins (N = 15) participated in a study of psychosexual development. All participants were > or = 18 years of age (mean age, 25 years; range, 18-40). Comparisons were also made between the CAH women with the salt-wasting (SW) form of the disorder and those with simple virilization (SV). A psychosexual assessment protocol examined six variables: (1) sex assignment at birth (probands only); (2) recalled sex-typed behavior during childhood; (3) gender identity and gender role identification in adulthood; (4) relationship status; (5) sexual orientation in fantasy; and (6) sexual orientation in behavior. Salt-wasting status and sex assignment at birth were also ascertained for the CAH women who either refused to participate in the study (N = 10) or could not be traced (N = 13). Compared to the controls, the women with CAH recalled more cross-gender role behavior and less comfort with their sense of "femininity" during childhood. The two groups did not differ in degree of gender dysphoria in adulthood, although the probands showed more cross-gender role identification. Three of the nonparticipant probands were living, as adults, in the male social role (2 reared from birth as boys and 1 who changed from the female to the male social role during adolescence). The CAH women and the controls did not differ in relationship status (married/cohabiting vs. single). The CAH women had lower rates of exclusive heterosexual fantasy and fewer sexual experiences with men than the controls; however, the CAH women did not have more sexual experiences with women than the controls. Comparisons between the SW and SV revealed several differences: the SW were less likely to be assigned to the female sex at birth, recalled more cross-gender role behavior during childhood, were less likely to be married or cohabiting, and had lower rates of sexual experiences with men. The results were discussed in relation to the effects of prenatal androgens on psychosexual differentiation.     

An experimental micromechanics measurement technique for submicrometre domains

Orthogonal arrays of dots applied to surfaces can be used to directly measure microscopic strain fields. The spatial and strain resolution are both limited by the size of the dots placed on the surface. Two techniques using the beam of a scanning electron microscope (SEM) have been developed which make possible the placement of very fine dots with diameters of only 0.5 and 0.02 m, respectively, on the surface of the specimen, allowing local strain measurements on the scale of 0.2–10 m when specimens are loaded in the SEM. Measurements of strains fields around the tips of growing cracks in both polymers and polymeric composites are presented to illustrate the capabilities of the technique.     

Coping, drinking motives, goal attainment expectancies and family models in relation to alcohol use among college students

Associations between coping responses, drinking motivations, expectations of meeting social and academic goals, and family of origin problem drinking and measures of college students' quantity/frequency of alcohol use and social complications of alcohol use were investigated in a sample of 218 college students. Positive associations were found between "emotion-focused" forms of coping such as detachment and the criterion measures, whereas "problem-focused coping" was not significantly associated with quantity/frequency of alcohol use or drinking complications. Positive correlations were also found between drinking motives, goal attainment expectancies and family models measures and the criterion measures. Regression models constructed for alcohol quantity/frequency and drinking complications implicated the total number of drinking motives, family models of problem drinking and the coping strategy of self-blame as strongly related to criterion measures. Positive social drinking motives and coping by seeking social support were implicated as possible protective factors.     

Loss of heterozygosity in tuberous sclerosis hamartomas

We have previously described in tuberous sclerosis (TSC) hamartomas the phenomenon of loss of heterozygosity (LOH) for DNA markers in the region of both the TSC2 gene on chromosome 16p13.3 and the TSC1 gene on 9q34. We now describe the spectrum of LOH in 51 TSC hamartomas from 34 cases of TSC. DNA was extracted from leucocytes or normal paraffin embedded tissue, and from frozen paraffin embedded hamartoma tissue from the same patient. The samples were analysed for 11 markers spanning the TSC1 locus and nine markers spanning the TSC2 locus. Twenty-one of 51 hamartomas showed LOH (41%). There was significantly more LOH on 16p13.3, with 16 hamartomas showing LOH around TSC2, and five in the vicinity of TSC1. No hamartoma showed LOH for markers around both loci. All the areas of LOH on chromosome 9 were large, but the smallest region of overlap lay between the markers D9S149 and D9S114, providing independent evidence for the localisation of the TSC1 gene. These data show that LOH is a common finding in a wide range of hamartomas, affecting the same TSC locus in different lesions from the same patient but not affecting both loci. These data support the hypothesis that both the TSC genes act as tumour suppressors and that the manifestations of TSC in patients with germline TSC mutations rise from "second hit" somatic mutations inactivating the remaining normal copy of the TSC gene.