Search PubMed⌕ Search

Biomedical subjects

C Hughes

Publications and source records attributed to C Hughes.

At least 127 records · Page 7Linked to original sources

Assessing social integration in employment settings: current knowledge and future directions.

Based on a review of descriptive studies found in the employment literature from 1985 through 1995, we classified empirical measures that have been used to assess the social integration of employees with disabilities. In addition, we aggregated findings that described social interaction patterns in employment and summarized similarities and differences between the interactions of employees with and without disabilities. Ten categories of measures of social interaction were identified, and occurrence of social interaction was found to vary by environmental context and presence of disability. Findings were then compared to those of social skills interventions conducted in the workplace. Although aggregated findings revealed important information about social integration in work settings, critical gaps were found in current knowledge bases.

Adolescent↗

Trick or treat?: uneven understanding of mind and emotion and executive dysfunction in "hard-to-manage" preschoolers.

It is widely recognised that impaired social relations are characteristic of school-aged children with behavioural disorders, and predict a poor long-term outcome (Parker & Asher, 1987). However, little is known about the early antecedents of social impairment in behaviourally disturbed children. The aim of the present study was to explore three areas of potential dysfunction in younger children: theory of mind, emotion understanding, and executive function. Forty preschoolers, rated by their parents on the Strengths and Difficulties Questionnaire (Goodman, 1994) as "hard to manage" (H2M) were compared with a control group on a set of: (1) theory of mind tasks (including an emotion prediction task involving either a nice or a nasty surprise); (2) emotion understanding stories (that required affective perspective-taking skills as well as situational understanding); and (3) simple executive function tasks (adapted for preschoolers, and tapping inhibitory control, attentional set-shifting, and working memory). Small but significant group differences were found in all three cognitive domains. In particular, hard-to-manage preschoolers showed poor understanding of emotion and executive control, poor prediction or recall of a false belief, and better understanding of the belief-dependency of emotion in the context of a trick than a treat. Moreover, executive function was associated with performance on the theory of mind tasks for the hard-to-manage group alone, suggesting both direct and indirect links between executive dysfunction and disruptive behaviour.

Affect↗

A locus coding for putative non-ribosomal peptide/polyketide synthase functions is mutated in a swarming-defective Proteus mirabilis strain.

We describe a large bacterial locus that, unusually, encodes components typically required for both the non-ribosomal synthesis of peptides and also polyketide/fatty acid synthase function. Two tandem ABC transporter genes in this putative nrp (non-ribosomal peptide/polyketide) operon suggest that the principal product may be secreted. Immediately distal to the nrp operon is a gene, irpP, encoding a small peptide similar to the Bacillus ComX pheromone that in its mature, extracellular form increases expression of unlinked non-ribosomal peptide synthesis genes. Transcription of both the nrp operon and irpP was up-regulated in iron-limiting culture conditions, consistent with the presence of a putative Fur repressor-binding site 5' of irpP. The locus was isolated from Proteus mirabilis as the site of a TnphoA insertion causing impaired swarm cell differentiation and an aberrant swarming pattern. The mutation was in one of the transporter genes, but a comparable swarming defect resulted from interposon disruption of the putative nrp synthetase gene.

ATP-Binding Cassette Transporters↗

Controlled trial of pretest education approaches to enhance informed decision-making for BRCA1 gene testing.

BACKGROUND: In response to the isolation of the BRCA1 gene, a breast-ovarian cancer-susceptibility gene, biotechnology companies are already marketing genetic tests to health care providers and to the public. Initial studies indicate interest in BRCA1 testing in the general public and in populations at high risk. However, the optimal strategies for educating and counseling individuals have yet to be determined. PURPOSE: Our goal was to evaluate the impact of alternate strategies for pretest education and counseling on decision-making regarding BRCA1 testing among women at low to moderate risk who have a family history of breast and/or ovarian cancer. METHODS: A randomized trial design was used to evaluate the effects of education only (educational approach) and education plus counseling (counseling approach), as compared with a waiting-list (control) condition (n = 400 for all groups combined). The educational approach reviewed information about personal risk factors, inheritance of cancer susceptibility, the benefits, limitations, and risks of BRCA1 testing, and cancer screening and prevention options. The counseling approach included this information, as well as a personalized discussion of experiences with cancer in the family and the potential psychological and social impact of testing. Data on knowledge of inherited cancer and BRCA1 test characteristics, perceived risk, perceived benefits, limitations and risks of BRCA1 testing, and testing intentions were collected by use of structured telephone interviews at baseline and at 1-month follow-up. Provision of a blood sample for future testing served as a proxy measure of intention to be tested (in the education and counseling arms of the study). The effects of intervention group on study outcomes were evaluated by use of hierarchical linear regression modeling and logistic regression modeling (for the blood sample outcome). All P values are for two-sided tests. RESULTS: The educational and counseling approaches both led to significant increases in knowledge, relative to the control condition (P < .001 for both). The counseling approach, but not the educational approach, was superior to the control condition in producing significant increases in perceived limitations and risks of BRCA1 testing (P < .01) and decreases in perceived benefits (P < .05). However, neither approach produced changes in intentions to have BRCA1 testing. Prior to and following both education only and education plus counseling, approximately one half of the participants stated that they intended to be tested; after the session, 52% provided a blood sample. CONCLUSIONS: Standard educational approaches may be equally effective as expanded counseling approaches in enhancing knowledge. Since knowledge is a key aspect of medical decision-making, standard education may be adequate in situations where genetic testing must be streamlined. On the other hand, it has been argued that optimal decision-making requires not only knowledge, but also a reasoned evaluation of the positive and negative consequences of alternate decisions. Although the counseling approach is more likely to achieve this goal, it may not diminish interest in testing, even among women at low to moderate risk. Future research should focus on the merits of these alternate approaches for subgroups of individuals with different backgrounds who are being counseled in the variety of settings where BRCA1 testing is likely to be offered.

Adult↗

Social behaviour in pervasive developmental disorders: effects of informant, group and "theory-of-mind".

Theory of mind skills and a range of social behaviour in everyday life were assessed in a sample of 21 children with pervasive developmental disorders and 22 normally-developing preschoolers. Parents, teachers and therapists were interviewed using the Vineland Adaptive Behaviour Scales and a new supplementary scale, the "Echelle d'Adaptation Sociale pour Enfants" (EASE). Teachers and therapists were able to differentiate subtle forms of social problems in everyday life between subgroups of children diagnosed later to have either autism (n = 13) or PDDNOS (n = 8), according to DSM-III-R (1) criteria. This study offers a (small) cross-cultural replication of recent work suggesting that differences in the mentalising skills of children with autism are reflected in the everyday social behaviour of this group. A significant effect of informant was found for the PDD group, and this effect was particularly pronounced when children with autism were considered separately. The implications of informant differences are discussed.

Activities of Daily Living↗

Psychological distress in women seeking genetic counseling for breast-ovarian cancer risk: the contributions of personality and appraisal.

The purpose of the present study was two-fold: (a) to characterize the psychological status of women with a family history of breast or ovarian cancer who self-refer for genetic counseling and BRCA1 testing; and (b) to identify specific demographic, personality, and appraisal factors that contribute to cancer-specific distress and general distress in this group of women. Participants were 256 women ages 18 and older who had at least one first-degree relative (FDR) with breast and/or ovarian cancer. Participants were recruited through breast cancer clinics and obstetrics/gynecology departments at two medical centers by responding to program information described in a brochure. The results revealed moderate distress levels in this population. The results of a hierarchical regression of general distress indicated that women with higher levels of general distress were less likely to be married, less optimistic, and had heightened breast cancer risk perceptions accompanied by feelings of low perceptions of control over the development of breast cancer (R2 = .44, p = .0001). Women with higher levels of cancer-specific distress tended to be younger and non-White and had low perceptions of control over developing breast cancer (R2 = .15, p = .0002). These findings suggest that self-referred genetic counseling participants may be psychologically vulnerable and may benefit from interventions designed to decrease distress and the perceived absence of control over developing breast cancer.

Adaptation, Psychological↗

Executive function in parents of children with autism.

BACKGROUND: Previous studies have shown that individuals with autism show impaired performance on tests of executive function (Ozonoff et al. 1991, 1993; Hughes & Russell, 1993; Hughes et al. 1994). There is also strong evidence for genetic involvement in autism (see Rutter, 1991 for review). If executive dysfunction is a core impairment in autism, then similar impairments are hypothesized to exist in a subtler form among the parents of autistic children. METHODS: Forty parents of autistic children were compared with 40 parents of learning disabled children and 36 adults from unaffected families on three computerized tests of executive function. These tasks tapped attentional-shifting skills, visuospatial planning and working memory. Participants also received a computerized control test of spatial memory-span. In addition, the interviewer's initial impressions of family members were coded using a new 33-item questionnaire. RESULTS: A significant proportion of parents of autistic children (especially fathers) showed impaired executive function. By contrast, parents did as well as both comparison groups on a control test of spatial span, and on other 'non-executive' measures from the tasks, indicating that the autism group were as able and motivated as comparison groups. Interestingly, impairment of executive function was significantly correlated with the interviewer's pre-test impression of social abnormality among parents of autistic children. CONCLUSIONS: The hypothesis that a significant proportion of parents of autistic children show impaired executive function was supported. Parents showed good memory ability, but relatively poor planning skills and attentional flexibility. The extent to which this is an inherent trait in family members, rather than a reflection of the difficulties involved in caring for an autistic child, remains to be examined.

Adolescent↗

The influence of psychological distress on use of genetic testing for cancer risk.

The recent identification of BRCA1, a breast cancer susceptibility gene, offers an unprecedented opportunity for high-risk individuals to learn whether they are genetically predisposed to develop breast or ovarian cancer. This study examined the relationships between psychological distress and use of BRCA1 testing by 149 high-risk individuals from hereditary cancer families. After a baseline assessment of demographics, objective risk, cancer-specific distress, and global distress (depressive symptoms), study participants were offered the opportunity to receive genetic counseling and to learn whether they carry a mutation in the BRCA1 gene. Overall, 58% of study participants requested BRCA1 test results, and 42% declined to learn their genetic status. After controlling for demographic factors and risk status, cancer-specific distress was significantly and positively related to BRCA1 test use, whereas global distress was unrelated to test use.

Adult↗

A motile but non-swarming mutant of Proteus mirabilis lacks FlgN, a facilitator of flagella filament assembly.

A TnphoA mutant of Proteus mirabilis was isolated, which had lost the ability to swarm, yet was still motile. The transposon had inserted into flgN, a flagella gene encoding a 147-amino-acid protein of undefined function. Proteus flgN is arranged in an operon with the class III anti-sigma28 gene, flgM, flanked by the class II genes, flgA, flgBCD and flhBA, and a novel putative virulence-related gene. The flgN mutation caused a substantial reduction in cell surface-associated flagellin, particularly during differentiation to the normally hyperflagellated swarm cell. This was not due to an effect on flagella gene expression or a typical defect in the flagella export apparatus as there was no class III gene downregulation by FlgM feedback, or intracellular flagellin accumulation. Loss of FlgN nevertheless caused a severe reduction in the incorporation of pulse-labelled flagellin into the membrane/flagellum fraction of differentiating cells. Substantial amounts of both non-oligomeric flagellin and flagellin degradation products appeared in the extracellular medium, although the few mature filaments made by the mutant were no more sensitive to proteolysis than those of the wild type. FlgN appeared soluble and active in the cytosol. The data suggest that the function of FlgN is to facilitate the initiation of flagella filament assembly, a role that may be especially critical in attaining the much higher concentration of surface flagellin required for swarming. Proteus FlgN has leucine zipper-like motifs arranged on potential amphipathic helices, a feature conserved in cytosolic chaperones for the exported substrates of flagella-related type III virulence systems. While gel filtration of FlgN from the soluble cell fraction did not establish an interaction with flagellin, it indicated that FlgN may associate with an unknown component and/or form an oligomer.

Amino Acid Sequence↗

RfaH and the ops element, components of a novel system controlling bacterial transcription elongation.

The RfaH protein controls the transcription of a specialized group of Escherichia coli and Salmonella operons that direct the synthesis, assembly and export of the lipopolysaccharide core, exopolysaccharide, F conjugation pilus and haemolysin toxin. RfaH is a specific regulator of transcript elongation; its loss increases transcription polarity in these operons without affecting initiation from the operon promoters. The operons of the RfaH-dependent regulon contain a short conserved 5' sequence, the ops element, deletion of which increases operon polarity to an extent similar to that caused by loss of RfaH. The ops element is also present upstream of polysaccharide gene clusters of Shigella flexneri, Yersinia enterocolitica, Vibrio cholerae and Klebsiella pneumoniae and the RP4 fertility operon of Pseudomonas aeruginosa, suggesting that this is a widely spread control system. The mechanistic coupling of RfaH and the ops element has been demonstrated in vitro and in vivo, and we suggest that the ops element recruits RfaH and potentially other factors to the RNA polymerase complex, modifying the complex to increase its processivity and allowing transcription to proceed over long distances.

Bacterial Proteins↗

Possible nosocomial transmission of psittacosis.

OBJECTIVES: To investigate a cluster of seven pneumonia cases among persons exposed to a pet-shop worker hospitalized with psittacosis. DESIGN: Epidemiological study of the outbreak, sero-diagnostic evaluation of exposed persons with pneumonia; and retrospective review of the pneumonia cases. SETTING: 450-bed teaching community hospital. PARTICIPANTS: Employees of the nursing unit where the patient with psittacosis was hospitalized. RESULTS: The index case had laboratory and clinical evidence of psittacosis. Four of the seven exposed persons who developed pneumonia had serologic results that met criteria for a diagnosis of psittacosis, and three met criteria for Chlamydia pneumoniae infection, possibly reflecting cross-reactivity between the microimmunofluorescence assays for the two diseases. The epidemiological graph suggested a relationship between the index case and the cluster of pneumonias in exposed individuals. CONCLUSIONS: Psittacosis may have been transmitted person to person in a hospital setting.

Chlamydophila psittaci↗

A nonswarming mutant of Proteus mirabilis lacks the Lrp global transcriptional regulator.

Proteus swarming is the rapid cyclical population migration across surfaces by elongated cells that hyperexpress flagellar and virulence genes. The mini-Tn5 transposon mutant mns2 was isolated as a tight nonswarming mutant that did not elongate or upregulate flagellar and hemolysin genes. Individual cell motility was retained but was reduced. The transposon had inserted in the gene encoding the global transcriptional regulator Lrp (leucine-responsive regulatory protein), expression of which was upregulated in differentiating swarm cells. Swarming was restored to the lrp mutant by artificial overexpression of the flhDC flagellar regulatory master operon. Lrp may be a key component in generating or relaying signals that are required for flagellation and swarming, possibly acting through the flhDC operon.

Amino Acid Sequence↗

Negative feedback from a Proteus class II flagellum export defect to the flhDC master operon controlling cell division and flagellum assembly.

The Proteus mirabilis flagellum class I flhDC operon was isolated, and its transcript was shown to originate from a sigma70 promoter 244 bp 5' of flhD and 29 bp 3' of a putative cyclic AMP receptor protein-binding site. Expression of this regulatory master operon increased strongly as cells differentiated into elongated hyperflagellated swarm filaments, and cell populations artificially overexpressing flhDC migrated sooner and faster. A class II flhA transposon mutant was reduced in flagellum class III gene expression, as would be expected from the FlgM anti-sigma28 accumulation demonstrated in Salmonella typhimurium, but was unexpectedly also reduced in cell elongation. Here, we show that levels of flhDC transcript were ca. 10-fold lower in this flagellum export mutant, indicating that in cells defective in flagellum assembly, there is additional negative feedback via flhDC. In support of this view, artificial overexpression of flhDC in the flhA mutant restored elongation but not class III flagellum gene transcription.

Amino Acid Sequence↗

Functional analysis and treatment of social-communicative behavior of adolescents with developmental disabilities.

This investigation used functional analyses to identify the social variables that maintained the inappropriate social-communicative behaviors of 2 adolescent students with mental retardation. Analyses were performed in the students' classrooms with the assistance of peers and teachers. The results of these assessments were used to identify appropriate, functionally equivalent behaviors that the students were taught to self-monitor. Findings showed substantial decreases in inappropriate social responding and increases in the use of appropriate social skills.

Adolescent↗

Anger attacks and treatment nonadherence in a perinatal psychiatry clinic.

Anger attacks are common in depressive disorders. High levels of anger have been associated with treatment nonadherence in medical and psychiatric patients. In this study we examined the relationship between anger attacks and treatment nonadherence in a perinatal psychiatry clinic that treats pregnant and postpartum women. Treatment adherence was examined by chart review. Patients with anger attacks at initial assessment were more likely to drop out of treatment than were patients without anger attacks at initial assessment (11/34 vs. 2/21; one-tailed Fisher's exact test p < .05). Treatment nonadherence among pregnant and postpartum women with anger attacks may be an important problem because of its impact on treatment outcome and because anger in depressed mothers is frequently directed at their children.

Adult↗