A study of the effects of exposure misclassification due to the time-window design in pharmacoepidemiologic studies

This paper presents a model for predicting blood lead levels in adults who are exposed to elevated environmental levels of lead. The model assumes a baseline blood lead level based on average blood lead levels for adults described in two recent U.S. studies. The baseline blood level in adults arises primarily from exposure to lead in diet. Media-specific ingestion and absorption parameters are assessed for the adult population, and a biokinetic slope factor that relates uptake of lead into the body to blood lead levels is estimated. These parameters are applied to predict blood lead levels for adults exposed to a hypothetical site with elevated lead levels in soil, dust and air. Blood lead levels ranging from approximately 3-57 micrograms/dl are predicted, depending on the exposure scenarios and assumptions.     

Contemplating the new DSM-V: Considerations from psychologists who work with school children.

The standard psychiatric classification system, the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text revision; DSM-IV-TR; American Psychiatric Association, 2000), is about to be updated. This is important because the DSM-IV-TR, a touchstone document for service providers across several disciplines, contains only some of the conditions reported in the vast developmental/learning, psychiatric, and health literature that are known to hamper school success. Practicing psychologists who work with school-age children and those who conduct educational research confront further limitations when using DSM-IV-TR or the commonly used special education scheme (the Individuals With Disabilities Education Act [IDEA], 2004). IDEA has limited heuristic potential because it was devised for educational administrative purposes, whereas the DSM-IV-TR is a medical nosological system with little concern for school issues. Neither system fully informs needed studies of epidemiology, natural history, and disorder-specific causes and treatments. This article provides a rationale for a set of proposed changes to the new DSM-V and explains how adopting these changes will benefit psychologists concerned with understanding and treating school-age children. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evolution and phylogenetic utility of the period gene in Lepidoptera

Evolution and phylogenetic utility of the period gene are explored through sequence analysis of a relatively conserved 909-bp fragment in 26 lepidopteran species. Taxa range from tribes to superfamilies, primarily within the putative clade Macrolepidotera plus near outgroups, and include both strongly established and problematic groupings. Their divergence dates probably range from the late Cretaceous through much of the Tertiary. Comparisons within the same set of closely related species show that amino acid substitutions in period occur 4.9 and 44 times as frequently as they do in two other nuclear genes--dopa decarboxylase and elongation factor-1 alpha, respectively. In contrast, rates of observed synonymous substitution are within 60% of each other for these three genes. Synonymous changes in period approach saturation by the family level, whereas nonsynonymous and amino acid divergences across the Macrolepidoptera are less than half the maximal values reported for this gene. Phylogenetic analyses of period strongly supported groupings at the family level and below. In contrast to previous analyses at this level with other nuclear genes, much of the information lies in nonsynonymous change. Relationships up to the superfamily level were recovered with decreasing effectiveness, and little, if any, signal was apparent regarding relationships among superfamilies. This could reflect rapid radiation of the superfamilies, however, rather than saturation in the period locus; thus, period, in combination with other genes, remains a plausible candidate for approaching the difficult problems of lepidopteran family and superfamily relationships.     

The making of the dominant MHC class I ligand SYFPEITHI

The proteasome contributes to the generation of most of the peptide ligands of MHC class I molecules. To compare the identity of the peptides generated by the proteasome with those finally presented by MHC class I molecules, we generated a monoclonal antibody recognizing the C-terminal part of the dominant H2-Kd ligand SYFPEITHI derived from the JAK1 tyrosine kinase. Immunoprecipitations of lysates from H2-Kd-expressing or non-expressing cells revealed that only in the presence of H2-Kd SYFPEITHI could be isolated. No longer potential precursor peptide containing SYFPEITHI could be detected. Surprisingly, a peptide lacking the first two amino acids, FPEITHI, was isolated independently of the presence of H2-Kd molecules. The detection of only SYFPEITHI and FPEITHI in cell lysates corresponded with the strong generation of these two peptides in in vitro digests of elongated SYFPEITHI-containing peptides with purified 20S proteasomes. Our results indicate that MHC ligands can be generated directly by the proteasome in vivo and that at least for SYFPEITHI the expression of the corresponding MHC molecule is critical for protection of the ligand in vivo.     

Comparison of the combined cortical thickness of the second metacarpal with Sharp's method for scoring hand microradiographs in rheumatoid arthritis

OBJECTIVE: To compare the correlation and specificity of the combined cortical thickness of the second metacarpal (CCT-MC) with Sharp's method (SM) for scoring joint erosions and joint space narrowing in rheumatoid arthritis (RA) and to compare the degree of interobserver agreement between the 2 methods. METHODS: Hand microradiographs of 22 women with RA, functional classes III and IV, were scored independently by 3 rheumatologists using the CCT-MC and the CCT of the middle phalanx and SM. RESULTS: (1) There was a highly significant correlation between the total SM score and the CCT-MC for the 3 observers (r = 0.61, p = 0.0026), but not between the CCT of the middle phalanx and SM (r = 0.15, p = 0.53). There was a lower degree of agreement between the observers for SM erosion scores compared to the CCT-MC (intraclass correlation 0.88 for the CCT-MC and 0.63 for the SM); (2) Both joint space narrowing and erosion scores correlated highly with the CCT-MC (r = -0.60, p = 0.004; and r = -0.51, p = 0.014, respectively); (3) CCT-MC measurements are more closely related to the inner (d) as opposed to the outer (D) diameter of the 2nd metacarpal; (4) The mean time to obtain the CCT-MC score was 3.43 min (SD = 1.38) versus 9.83 min (SD = 3.20) for SM (p = 0.0001); (5) the derivative, (D2-d2)/D2, was significantly correlated with SM (r = -0.72, p = 0.0002) and its erosion and joint space narrowing components (r = -0.63, p = 0.0019; and r = -0.71, p = 0.0002, respectively). CONCLUSION: The CCT-MC is a rapid, practical method with higher agreement among observers compared to SM and correlates highly with SM scores for joint damage in RA. CCT-MC appears to have a higher degree of specificity than other sites for CCT measurement. The CCT-MC is more closely related to the inner diameter than the outer diameter, which supports the notion that the principal site of accelerated bone loss due to RA in the hand occurs at the endosteal surface. The CCT-MC should be further assessed with respect to monitoring radiological progression in RA.     

A parallel, comparative study of intravenous iron versus intravenous ascorbic acid for erythropoietin-hyporesponsive anaemia in haemodialysis patients with iron overload

BACKGROUND: Functional iron deficiency may develop and cause erythropoietin resistance in haemodialysis patients with iron overload. Controversy remains as to whether intravenous iron medication can improve this hyporesponsiveness due to decreased iron availability, or whether iron therapy will aggravate haemosiderosis. Intravenous administration of ascorbic acid has been shown to effectively circumvent resistant anaemia associated with iron overload in a small preliminary study. To elucidate further the possible mechanisms of this resistance, a parallel, comparative study was conducted to compare the effects of intravenous iron and ascorbate therapies in iron-overloaded haemodialysis patients. METHODS: Fifty haemodialysis patients with serum ferritin of > 500 microg/l were randomly divided into two protocols. They were further stratified into controls (Control I, n = 11) and intravenous iron group (IVFE, n = 15) in protocol I; and into controls (Control II, n = 12) and intravenous ascorbic acid group (IVAA, n = 12) in protocol II. Controls had a haematocrit of > 30% and did not receive any adjuvant therapy. IVFE and IVAA patients were hyporesponsive to erythropoietin and functionally iron deficient. Ferric saccharate (100 mg dose) was administered intravenously postdialysis on five consecutive dialysis sessions in the first 2 weeks; and ascorbic acid (300 mg dose) thrice a week for 8 weeks. Red cell and iron metabolism indices were examined before and following therapy. RESULTS: Mean values of haematocrit and transferrin saturation were significantly lower, and erythropoietin dose was higher in IVFE and IVAA patients compared to controls. Intravenous iron therapy neither improved erythropoiesis nor reduced erythropoietin dose during 12 weeks. Iron metabolism indices significantly increased at 2 and 6 weeks, but decreased at 12 weeks returning to the baselines. In contrast, mean haematocrit significantly increased from 25.8+/-0.5 to 30.6+/-0.6% with a concomitant reduction of 20% in erythropoietin dose after 8 weeks of ascorbate therapy. Serum ferritin modestly fell but with no statistical significance. The enhanced erythropoiesis paralleled a rise in transferrin saturation from 27+/-3 to 48+/-6% and serum iron from 70+/-11 to 107+/-19 microg/dl (P<0.05). CONCLUSIONS: Short term intravenous iron therapy cannot resolve the issue of functional iron deficiency in haemodialysis patients with iron overload. Intravenous administration of ascorbic acid not only facilitates iron release from storage sites, but also increases iron utilization in the erythron. Our study draws attention to a potential adjuvant therapy, intravenous ascorbic acid, to treat erythropoietin-hyporesponsive anaemia in iron-overloaded patients.     

Internal jugular vein haemodialysis catheter-induced right atrium endocarditis--case report and review of the literature

OBJECTIVE: To determine the distribution and prevalence of sarcoptic mange in wombats, particularly the common wombat (Vombatus ursinus). DESIGN: Questionnaire survey in two parts. PROCEDURE: Questionnaires were distributed to biologists, rangers, animal carers and naturalists. Part 1 of the questionnaire aimed to determine the present distribution of sarcoptic mange in wombats (103 responses). Part 2 invited respondents to assess the prevalence of sarcoptic mange in wombats over a 3 month period (four responses). Information on wombats from 66 localities was received. Each locality represented an area of about 2500 km2. RESULTS: Mange was observed at 93% of localities surveyed and Sarcoptes scabiei was present in common wombats at 52% of localities. Sarcoptic mange was highly prevalent (22%) in two common wombat populations in Victoria. Anecdotal evidence suggested that mange epizootics are sporadic, cause significant morbidity and mortality and have a substantial effect on local abundance. The respondents did not report sarcoptic mange in either northern hairy-nosed wombats (Lasiorhinus krefftii) or southern hairy-nosed wombats (Lasiorhinus latifrons). CONCLUSIONS: Sarcoptic mange occurs in common wombat populations throughout the range of the common wombat including Tasmania and Flinders Island. While mange epizootics are sporadic, they have the potential to threaten the long-term survival of small, remnant populations.     

Molecular epidemiology of HIV-1 infection in the Philippines, 1985 to 1997: transmission of subtypes B and E and potential emergence of subtypes C and F

OBJECTIVES: to identify the risk factors for hepatitis B (HBV) and hepatitis C (HCV) virus infections in drug users attending two drug treatment centres in Northwest England, and to evaluate the effect of both needle exchange and hepatitis B vaccination on the prevalence of hepatitis B and hepatitis C infections. METHODS: a retrospective, cross-sectional study performed at the Regional Infectious Disease Unit and a Primary Care Centre for drug users in Liverpool. The study population included 773 drug users who had hepatitis serology performed between January 1992 and April 1996. Information on risk factors was obtained from clinical records; hepatitis serology data were obtained from the Liverpool Public Health Laboratory database. RESULTS: the overall seroprevalences of exposure markers for HBV (anti-HBc antibody) and HCV (anti-HCV antibody) were 48% and 67%, respectively. Duration of injecting drug use was the strongest predictor of HCV infection, with a crude odds ratio of 8.9 (95% confidence interval (CI): 4.5-17) for >10 compared to <3 years of injecting, and was also a strong predictor of HBV infection, with an adjusted odds ratio (controlled for the effects of HBV vaccination) of 5.7 (95% CI: 3.2-10) for >10 compared to <3 years' injecting. Vaccination against HBV was associated with greatly reduced HBV seroprevalence (crude odds ratio 0.11, 95% CI: 0.06-0.18). Overall, HCV was acquired earlier in the injecting career than HBV, but drug users who were not vaccinated against HBV acquired markers for HBV even more rapidly than for HCV. We found no independent protective effect for either anti-HBc or anti-HCV acquisition after the introduction of a needle-exchange scheme. CONCLUSIONS: hepatitis C is highly prevalent among Merseyside drug users and is likely to prove difficult to control because of rapid acquisition early in the injecting career. Vaccination against hepatitis B is the best means of protecting drug users from hepatitis B, and should be offered before injecting is commenced.     

Maximal growth occurs at a broad range of essential amino acids to total nitrogen ratios in kittens

Low concentrations of antibodies, specific to human respiratory syncytial virus (RSV) have been shown to enhance virus replication in human monocytic cell lines by several workers. In the present study, replication of bovine RSV in ovine peripheral blood monocytes was shown to be enhanced in the presence of low concentration of bovine RSV-specific antibodies. Antibodies had no enhancing effect on virus replication in secondary lamb testis cells or monocytic cell lines derived from peripheral blood monocytes. The possible effects of low titres of bovine RSV-specific antibodies on the development of clinical disease were examined by inoculating groups of lambs with a mixture of virus and antibodies and assessing the severity of clinical disease and by measuring venous oxygen (PO2) and carbon dioxide (PCO2) tensions, as hypoxia has been associated with respiratory diseases. Inoculation of bovine RSV and virus-specific antibody complexes to lambs did not enhance clinical disease and had no effect on the clinical chemistry, haematology and PO2 and PCO2 tensions. Groups of lambs inoculated with virus alone or virus-antibody complexes developed significant humoral and cellular immune responses. There was no significant difference in the cellular immune responses of lambs exposed to virus alone and lambs exposed to virus-antibody mixture, as measured by virus-specific lymphocyte transformation or by cytotoxicity assays but the period of virus shedding was longer in lambs inoculated with a mixture of virus and immune serum.     

Virtual Control Desks for Nuclear Power Plant Simulation: Improving Operator Training

Current nuclear power plant simulators employ interfaces that use multiple computer displays to represent a simplified control desk. To make the simulation more realistic and effective, a proposed approach replaces the displays with a virtual control desk that precisely mimics the original.