23 research outputs found

    Pharmaceuticals and the Developing World

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    The Effect of Sample Handling on Cross Sectional HIV Incidence Testing Results

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    To determine if mishandling prior to testing would make a sample from a chronically infected subject appear recently infected when tested by cross-sectional HIV incidence assays.Serum samples from 31 subjects with chronic HIV infection were tested. Samples were subjected to different handling conditions, including incubation at 4 °C, 25 °C and 37 °C, for 1, 3, 7 or 15 days prior to testing. Samples were also subjected to 1,3, 7 and 15 freeze-thaw cycles prior to testing. Samples were tested using the BED capture enzyme immuno assay (BED-CEIA), Vironostika-less sensitive (V-LS), and an avidity assay using the Genetic Systems HIV-1/HIV-2 plus O EIA (avidity assay).Compared to the sample that was not subjected to any mishandling conditions, for the BED-CEIA, V-LS and avidity assay, there was no significant change in test results for samples incubated at 4 °C or 25 °C prior to testing. No impact on test results occurred after 15 freeze-thaw cycles. A decrease in assay results was observed when samples were held for 3 days or longer at 37 °C prior to testing.Samples can be subjected up to 15 freeze-thaw cycles without affecting the results the BED-CEIA, Vironostika-LS, or avidity assays. Storing samples at 4 °C or 25 °C for up to fifteen days prior to testing had no impact on test results. However, storing samples at 37°C for three or more days did affect results obtained with these assays

    Quantitative and Molecular Genetic Analyses of Mutations Increasing Drosophila Life Span

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    Understanding the genetic and environmental factors that affect variation in life span and senescence is of major interest for human health and evolutionary biology. Multiple mechanisms affect longevity, many of which are conserved across species, but the genetic networks underlying each mechanism and cross-talk between networks are unknown. We report the results of a screen for mutations affecting Drosophila life span. One third of the 1,332 homozygous P–element insertion lines assessed had quantitative effects on life span; mutations reducing life span were twice as common as mutations increasing life span. We confirmed 58 mutations with increased longevity, only one of which is in a gene previously associated with life span. The effects of the mutations increasing life span were highly sex-specific, with a trend towards opposite effects in males and females. Mutations in the same gene were associated with both increased and decreased life span, depending on the location and orientation of the P–element insertion, and genetic background. We observed substantial—and sex-specific—epistasis among a sample of ten mutations with increased life span. All mutations increasing life span had at least one deleterious pleiotropic effect on stress resistance or general health, with different patterns of pleiotropy for males and females. Whole-genome transcript profiles of seven of the mutant lines and the wild type revealed 4,488 differentially expressed transcripts, 553 of which were common to four or more of the mutant lines, which include genes previously associated with life span and novel genes implicated by this study. Therefore longevity has a large mutational target size; genes affecting life span have variable allelic effects; alleles affecting life span exhibit antagonistic pleiotropy and form epistatic networks; and sex-specific mutational effects are ubiquitous. Comparison of transcript profiles of long-lived mutations and the control line reveals a transcriptional signature of increased life span

    Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

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    AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

    Novel Non-mecA-Containing Staphylococcal Chromosomal Cassette Composite Island Containing pbp4 and tagF Genes in a Commensal Staphylococcal Species: a Possible Reservoir for Antibiotic Resistance Islands in Staphylococcus aureus

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    Among methicillin-resistant Staphylococcus aureus isolates, a staphylococcal chromosomal cassette containing the mecA gene (SCCmec) is integrated into the chromosome at a unique site. SCCmec also contains unique ccrAB recombinase genes mediating its integration and excision from the genome and is flanked by characteristic left and right direct- and inverted-repeat sequences. A few non-mecA-containing SCC elements that have the other molecular features described above have recently been described. The origin of these cassettes is not clear. We have identified two new members of the SCC family integrated within orfX in Staphylococcus epidermidis strain ATCC 12228, neither of which carries mecA. One is a 57-kb element flanked by a unique 28-bp SCC direct repeat. It was called the SCC composite island (SCC-CI) because it carries a 19-kb SCC element (SCCpbp4) nested within it. SCCpbp4 contains pbp4 and tagF genes, as well as one pair of ccrAB genes (allotype 2) flanked by classical SCC-specific terminal repeats. External to SCCpbp4, SCC-CI contains a second pair of ccrAB genes (allotype 4), three IS431 elements, and genes mediating resistance to heavy metals. Genes mediating restriction-modification that may facilitate horizontal transfer are also present within SCC-CI, both within and outside SCCpbp4. Several novel arrangements of the SCC direct and inverted repeats were identified. Several long stretches of homology with other SCCs were found within and outside SCCpbp4. In view of the fact that SCC-CI was found in a commensal species, it may represent a reservoir for sequences involved in genetic shuffling between staphylococci and may contribute to the diversity found in SCC elements

    Chapter 8, Pertussis: 8 --1 Chapter 8: Pertussis

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    e in the 1940s, the average incidence of pertussis decreased from 150 per 100,000 persons between 1922 and 1940, to 0.5 per 100,000 in 1976. 2 However, since the 1980s, the incidence of reported pertussis cases has increased. The increase has been primarily among infants aged &lt; 4 months and among adolescents and adults. An increase in the number of reported deaths from pertussis among very young infants has paralleled the increase in the number of reported cases. 5 Reasons for the increases in pertussis are not completely clear; improvements in diagnosis and reporting of pertussis in adolescents and adults appear to be important factors contributing to the overall increase. Outbreaks are being recognized increasingly in high schools and middle schools. Sports teams have been the focus of infection in some Chapter 8, Pertussis: 8 --2 schools. 6 Infected school-aged children and adults may introduce pertussis into households where susceptible preschool-aged children are expose

    Antiviral Treatment among Pregnant Women with Chronic Hepatitis B

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    Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women received antiviral treatment (P < 0.01). Pregnant women were most commonly prescribed tenofovir (73.4%) and lamivudine (21.9%); nonpregnant women were most commonly prescribed tenofovir (50.2%) and entecavir (41.3%) (P < 0.01). Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3%) were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2%) started treatment during the third trimester and continued at least one month after delivery. Conclusion. Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection
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