The Development and Well-Being Assessment (DAWBA) is a novel package of questionnaires, interviews, and rating techniques designed to generate ICD-10 and DSM-IV psychiatric diagnoses on 5-16-year-olds. Nonclinical interviewers administer a structured interview to parents about psychiatric symptoms and resultant impact. When definite symptoms are identified by the structured questions, interviewers use open-ended questions and supplementary prompts to get parents to describe the problems in their own words. These descriptions are transcribed verbatim by the interviewers but are not rated by them. A similar interview is administered to 11-16-year-olds. Teachers complete a brief questionnaire covering the main conduct, emotional, and hyperactivity symptoms and any resultant impairment. The different sorts of information are brought together by a computer program that also predicts likely diagnoses. These computer-generated summary sheets and diagnoses form a convenient starting point for experienced clinical raters, who decide whether to accept or overturn the computer diagnosis (or lack of diagnosis) in the light of their review of all the data, including transcripts. In the present study, the DAWBA was administered to community (N = 491) and clinic (N = 39) samples. There was excellent discrimination between community and clinic samples in rates of diagnosed disorder. Within the community sample, subjects with and without diagnosed disorders differed markedly in external characteristics and prognosis. In the clinic sample, there was substantial agreement between DAWBA and case note diagnoses, though the DAWBA diagnosed more comorbid disorders. The use of screening questions and skip rules greatly reduced interview length by allowing many sections to be omitted with very little loss of positive information. Overall, the DAWBA successfully combined the cheapness and simplicity of respondent-based measures with the clinical persuasiveness of investigator-based diagnoses. The DAWBA has considerable potential as an epidemiological measure, and may prove to be of clinical value too.
Multiple myeloma(MM) is the second commonest haematological malignancy and remains incurable. Beyond tumour biology and genomic features driving disease resistance, host factors including impaired immunity and frailty also contribute to poor outcomes. Despite reports of immune dysfunction in this cancer, clear evidence for the contribution to clinical outcomes remains lacking.We show, for the first time, that high abundance of Treg and PD-1+CD4 effector cells in bone marrow of newly diagnosed patients are independent predictors of early relapse. This work supports growing literature on the importance of CD4 effector cells in MM, and confirms a role for the PD-1/PD-L1 axis to MM pathobiology.Our work identifies Tregs and PD-1+CD4 effectors as potential therapeutic targets, and opens up avenues for further mechanistic studies into early relapse. Pending confirmation in future patient cohorts, such immune parameters may refine existing risk models, facilitating patient stratification for therapeutic strategies targeting key CD4 populations.Research.
Antibiotic-resistant bacteria pose a serious threat to human health; hence the mechanisms that lead to their selection need to be investigated. One possible mechanism is that the silver and mercury in amalgam dental restorations may select for bacteria that contain heavy metal and antibiotic-resistance determinants, leading to the spread of these resistances, particularly if they are contained on the same mobile genetic element. The incidence of silver-resistant bacteria on teeth is investigated in this work. Two silver-resistant Enterobacter cloacae isolates were isolated from infected teeth containing dental restorations. Both isolates were also resistant to ampicillin, erythromycin, and clindamycin. The silE gene, which is encoded on the silver resistance operon, has been sequenced from both isolates. Results suggest that the silver resistance operon is encoded on plasmid DNA.
Genes encoding resistance to mercury and to antibiotics are often carried on the same mobile genetic element and so it is possible that mercury-containing dental materials may select for bacteria resistant to mercury and to antibiotics. The main aim of this study was to determine whether the prevalence of Hg-resistant oral bacteria was greater in children with mercury amalgam fillings than in those without. A secondary aim was to determine whether the Hg-resistant isolates were also antibiotic resistant. Bacteria in dental plaque and saliva from 41 children with amalgam fillings and 42 children without such fillings were screened for mercury resistance by cultivation on a HgCl(2)-containing medium. Surviving organisms were identified and their susceptibility to mercury and to several antibiotics was determined. Seventy-eight per cent and 74% of children in the amalgam group and amalgam-free group, respectively, harboured Hg-resistant bacteria; this difference was not statistically significant. Nor was there any significant difference between the groups in terms of the proportions of Hg-resistant bacteria in the oral microflora of the children. Of Hg-resistant bacteria, 88% and 92% from the amalgam group and the amalgam-free group, respectively, were streptococci; 41% and 33% were resistant to at least one antibiotic, most frequently tetracycline. The results of this study show that there was no significant difference between children with amalgam fillings and those without such fillings with regard to the prevalence, or the proportion, of Hg-resistant bacteria in their oral microflora. The study also found that Hg-resistant bacteria were common in children regardless of whether or not they had amalgam fillings and that many of these organisms were also resistant to antibiotics.
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