We have identified six children in three families with subtelomeric deletions of 6p25 and a recognizable phenotype consisting of ptosis, posterior embryotoxon, optic nerve abnormalities, mild glaucoma, Dandy-Walker malformation, hydrocephalus, atrial septal defect, patent ductus arteriosus, and mild mental retardation. There is considerable clinical overlap between these children and individuals with the Ritscher-Schinzel (or cranio-cerebello-cardiac (3C)) syndrome (OMIM #220210). Clinical features of 3C syndrome include craniofacial anomalies (macrocephaly, prominent forehead and occiput, foramina parietalia, hypertelorism, down-slanting palpebral fissures, ocular colobomas, depressed nasal bridge, narrow or cleft palate, and low-set ears), cerebellar malformations (variable manifestations of a Dandy-Walker malformation with moderate mental retardation), and cardiac defects (primarily septal defects). Since the original report, over 25 patients with 3C syndrome have been reported. Recessive inheritance has been postulated based on recurrence in siblings born to unaffected parents and parental consanguinity in two familial cases. Molecular and cytogenetic mapping of the 6p deletions in these three families with subtelomeric deletions of chromosome 6p have defined a 1.3 Mb minimally deleted critical region. To determine if 6p deletions are common in 3C syndrome, we analyzed seven unrelated individuals with 3C syndrome for deletions of this region. Three forkhead genes (FOXF1 and FOXQ1 from within the critical region, and FOXC1 proximal to this region) were evaluated as potential candidate disease genes for this disorder. No deletions or disease-causing mutations were identified.
Wei and Hemmings [2000: Nat Genet 25:376-377], using 80 British parent-offspring trios, identified a number of NOTCH4 variants and haplotypes that showed statistically significant evidence of association to schizophrenia. Specifically, the 10 repeat allele of a (CTG)(n) marker and the 8 repeat allele of a (TAA)(n) marker demonstrated excess transmission to affected individuals; SNP21 and haplotypes SNP2-(CTG)(n) and SNP12-SNP2-(CTG)(n) also showed significant associations. In an attempt to replicate these findings, we tested for linkage and association between the same five markers used by Wei and Hemmings in 166 families collected from a multi-center study conducted by the Department of Veterans Affairs (DVA) Cooperative Study Program (CSP). The families include 392 affected subjects (schizophrenia or schizoaffective disorder, depressed) and 216 affected sibling pairs. The families represent a mix of European Americans (n = 62, 37%), African Americans (n = 60, 36%), and racially mixed or other races (n = 44, 27%). We identified moderate evidence for linkage in the pooled race sample (LOD = 1.25) and found excess transmission of the 8 (P = 0.06) and 13 (P = 0.04) repeat alleles of the (TAA)(n) marker to African American schizophrenic subjects. The 8 and 13 repeat alleles were previously identified to be positively associated with schizophrenia by Wei and Hemmings [2000: Nat Genet 25:376-377] and Sklar et al. [2001: Nat Genet 28:126-128], respectively.
Previous studies have reported genetic linkage evidence for a schizophrenia gene on chromosome 15q. Here, chromosome 15 was examined by genetic linkage analysis using 166 schizophrenia families, each with two or more affected subjects. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Study Program, consisted of 392 sampled affected subjects and 216 affected sibling pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizo-affective disorder, depressed. Participating families had diverse ethnic backgrounds. The largest single group were northern European American families (n = 62, 37%), but a substantial proportion was African American kindreds (n = 60, 36%). The chromosome 15 markers tested were spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the region surrounding the alpha-7 nicotinic cholinergic receptor subunit gene (CHRNA7). These markers were genotyped and the data analyzed using semiparametric affecteds-only linkage analysis. In the European American families, there was a maximum Z-score of 1.65 between markers D15S165 and D15S1010. These markers are within 1 cM from CHRNA-7, the site previously implicated in schizophrenia. However, there was no evidence for linkage to this region in the African America kindreds.
This article presents a description and preliminary evidence on validity of self-report interview methods being used in a study of HIV-1 infection and AIDS among intravenous drug users (IVDUs). The study population includes 2,616 currently active IVDUs living in or near Baltimore City, Maryland (USA), many of them reporting no prior treatment for drug dependence, and many with no history of criminal arrest or incarceration. These IVDUs were recruited in 1988–89 by extensive community outreach efforts; most learned of the study by word-of-mouth. To study IV drug use and HIV-1 infection in relation to onset of AIDS, the subjects are being interviewed, examined, and tested at baseline (recruitment), and periodically thereafter. This report compares information from the self-report baseline interview with independently collected data on physical stigmata of drug injection, T-lymphocyte cell subsets, and HIV-1 serostatus. The evidence generally supports the validity of these self-report data on IV drug use, including data from a year-by-year history of sharing injection equipment, obtained by retrospection at baseline.
Background The unprecedented increase in critically ill patients due to the COVID-19 pandemic mandated rapid training in critical care for redeployed staff to work safely in intensive care units (ICU). Methods The COVID-19 ICU Remote-Learning Course (CIRLC) is a remote delivery course developed in response to the pandemic. This was a one-day course focused on the fundamentals of Intensive Care. The course used blended learning with recorded lectures and interactive tutorials delivered by shielding and frontline ICU trained professionals. The course was developed within one week and piloted at three NHS Trusts. It was then made publicly available free of charge to redeployed healthcare professionals across the UK and Ireland. An iterative cycle of improvement was used to update the course content weekly. A course confidence questionnaire with quantitative and qualitative questions was used to evaluate effectiveness. Data is reported as n (%), means (SD) and thematic analysis was used for the open questions. Results 1,269 candidates from 171 organisations completed the course, with 99 volunteer trainers. 96% of respondents rated the course as very or extremely useful. 86% rated the online platform as excellent. Overall confidence improved from 2.7/5 to 3.9/5. Qualitative data showed that the course was pitched at the appropriate level, accessible and built clinicians confidence to work in intensive care. Conclusion This model of educational delivery with a rapid iteration cycle was a pragmatic, effective solution to knowledge-based training under social distancing measures. Whilst full course evaluation was not possible, we believe that this work demonstrates practical guidance on educational response in a pandemic as well as highlighting the altruistic nature of the critical care community.
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