Comparison of prevalence of schizophrenia among residents of hostels for homeless people in 1966 and 1992.

OBJECTIVE--To determine whether the prevalence of schizophrenia among the homeless population of Edinburgh resident in hostels has changed between 1966 and 1992. DESIGN--Comparison of two cross sectional surveys. SETTINGS--Hostels for homeless people in Edinburgh. SUBJECTS--In 1966 a random sample of 98 residents of three common lodging houses. In 1992 a random sample of 198 residents of nine hostels. MAIN OUTCOME MEASURE--Prevalence of schizophrenia. RESULTS--The prevalence of schizophrenia in 1992 was 12/136 (9%) compared with 20/79 (25%) in 1966 (odds ratio 0.29; 95% confidence interval 0.13 to 0.62; P = 0.001). Adjustment for confounding by age, current hostel, and duration of unemployment by means of logistic regression produced an adjusted odds ratio of 0.22 (0.08 to 0.58). CONCLUSIONS--The prevalence of schizophrenia was lower in 1992 even after other changes in the population resident in hostels occurring between 1966 and 1992 were taken into account. The findings are not consistent with an increase in the prevalence of schizophrenia among homeless people despite a 66% reduction in adult psychiatric beds in the region during 1966-92.     

Distinctions betweenHordeum bulbosum andH. murinum s.l. in seed and herbarium collections

It is sometimes necessary to identify eitherH. bulbosum orH. murinum on the basis of the inflorescence or seeds alone. The majority of taxonomic keys use the presence of swollen basal culms for the former against the annual habit for the latter. Confusion is due to similarities in inflorescences and spikelet morphology. Lodicules which always persist and are present beside the fruit in a mature caryopsis, and other characters such as the awns of the lemmas of the lateral spikelets enable conclusive distinction.     

Immobilization of enzymes on activated carbon: selection and preparation of the carbon support.

Based upon its superior catalytic activity for H2O2 decomposition, a bituminous coal-based activated carbon was selected for investigations of pretreatment and enzyme immobilization methods. Pretreatments considered include acid washing, exposure to strong oxidizing agents, contact with concentrated peroxide solutions, nitration and amination, isothiocyanate derivatization, silanization, and stearic acid coating. Effects of these pretreatments on morphology and trace-metal content of the carbon pellets have been studied using scanning electron microscopy and dispersive analysis of x rays. Immobilization of glucoamylase by adsorption, glutaraldehyde crosslinking, and covalent attachment to carbon activated by water-soluble diimide or diazotization have been examined. These different enzyme-carbon catalysts have been characterized by their enzyme loading, enzyme activity, catalytic activity for H2O2 decomposition, or combinations of these measures of performance.     

Neutrophil transendothelial migration in vitro to Streptococcus pneumoniae is pneumolysin dependent

The recruitment of polymorphonuclear leukocytes (PMN) from the vascular space to the alveolar air space is an early event in host defense against pneumococcal pneumonia. Pneumolysin is a virulence factor for Streptococcus pneumoniae, but a specific role for pneumolysin in neutrophil-endothelial cell interactions has not been investigated. Using a Transwell system, we studied in vitro migration of PMNs across a monolayer of human pulmonary microvascular endothelial cells in response to wild-type S. pneumoniae (D39) and a pneumolysin-deficient mutant (plnA(-)) incubated on the abluminal surface of the monolayer. S. pneumoniae induction of PMN migration was dose dependent and elicited by > or =10(5) D39. Mutants lacking pneumolysin had dramatically reduced potency for eliciting PMN migration compared with the parent strain (5 x 10(6) plnA(-) elicits 18.6% PMN migration vs. 55.5% for 5 x 10(6) D39). The disparity between D39 and plnA(-) persisted in ethanol-fixed bacteria, consistent with the properties of pneumolysin. Neither conditioned medium from D39 nor purified pneumolysin elicited PMN migration to the same extent as the intact D39, suggesting that the role of pneumolysin in eliciting PMN migration requires a more complex interaction between the organism, the endothelium, and the PMN. Both D39 and plnA(-) adhered to, and translocated across, the endothelium in the abluminal to luminal direction and elicited similar levels of IL-8 production. Neither strain elicited upregulation of the endothelial adhesion molecules ICAM-1, VCAM-1, or E-selectin, and they did not cause translocation of NF-kappaB to the nucleus. These findings demonstrate a novel role for pneumolysin in pneumococcus-induced PMN recruitment across the pulmonary endothelium.     

A whole genome long-range haplotype (WGLRH) test for detecting imprints of positive selection in human populations

MOTIVATION: The identification of signatures of positive selection can provide important insights into recent evolutionary history in human populations. Current methods mostly rely on allele frequency determination or focus on one or a small number of candidate chromosomal regions per study. With the availability of large-scale genotype data, efficient approaches for an unbiased whole genome scan are becoming necessary. METHODS: We have developed a new method, the whole genome long-range haplotype test (WGLRH), which uses genome-wide distributions to test for recent positive selection. Adapted from the long-range haplotype (LRH) test, the WGLRH test uses patterns of linkage disequilibrium (LD) to identify regions with extremely low historic recombination. Common haplotypes with significantly longer than expected ranges of LD given their frequencies are identified as putative signatures of recent positive selection. In addition, we have also determined the ancestral alleles of SNPs by genotyping chimpanzee and gorilla DNA, and have identified SNPs where the non-ancestral alleles have risen to extremely high frequencies in human populations, termed 'flipped SNPs'. Combining the haplotype test and the flipped SNPs determination, the WGLRH test serves as an unbiased genome-wide screen for regions under putative selection, and is potentially applicable to the study of other human populations. RESULTS: Using WGLRH and high-density oligonucleotide arrays interrogating 116 204 SNPs, we rapidly identified putative regions of positive selection in three populations (Asian, Caucasian, African-American), and extended these observations to a fourth population, Yoruba, with data obtained from the International HapMap consortium. We mapped significant regions to annotated genes. While some regions overlap with genes previously suggested to be under positive selection, many of the genes have not been previously implicated in natural selection and offer intriguing possibilities for further study. AVAILABILITY: the programs for the WGLRH algorithm are freely available and can be downloaded at http://www.affymetrix.com/support/supplement/WGLRH_program.zip.     

Animal carcinogenicity studies: 1. Poor human predictivity

The regulation of human exposure to potentially carcinogenic chemicals constitutes society's most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency's (EPA's) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or animal data also assessed by the World Health Organisation's International Agency for Research on Cancer (IARC), human carcinogenicity classifications were compatible with EPA classifications only for those 17 having at least limited human data (p = 0.5896). For those 111 primarily reliant on animal data, the EPA was much more likely than the IARC to assign carcinogenicity classifications indicative of greater human risk (p < 0.0001). The IARC is a leading international authority on carcinogenicity assessments, and its significantly different human carcinogenicity classifications of identical chemicals indicate that: 1) in the absence of significant human data, the EPA is over-reliant on animal carcinogenicity data; 2) as a result, the EPA tends to over-predict carcinogenic risk; and 3) the true predictivity for human carcinogenicity of animal data is even poorer than is indicated by EPA figures alone. The EPA policy of erroneously assuming that tumours in animals are indicative of human carcinogenicity is implicated as a primary cause of these errors.