First-trimester or second-trimester screening, or both, for Down's syndrome

BACKGROUND: It is uncertain how best to screen pregnant women for the presence of fetal Down's syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters.METHODS: Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement of alpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency).RESULTS: First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening.CONCLUSIONS: First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down's syndrome, with low false positive rates

Genetic analysis of the capsule polysaccharide (K antigen) and exopolysaccharide genes in pandemic Vibrio parahaemolyticus O3:K6

<p>Abstract</p> <p>Background</p> <p>Pandemic <it>Vibrio parahaemolyticus </it>has undergone rapid changes in both K- and O-antigens, making detection of outbreaks more difficult. In order to understand these rapid changes, the genetic regions encoding these antigens must be examined. In <it>Vibrio cholerae </it>and <it>Vibrio vulnificus</it>, both O-antigen and capsular polysaccharides are encoded in a single region on the large chromosome; a similar arrangement in pandemic <it>V. parahaemolyticus </it>would help explain the rapid serotype changes. However, previous reports on "capsule" genes are controversial. Therefore, we set out to clarify and characterize these regions in pandemic <it>V. parahaemolyticus </it>O3:K6 by gene deletion using a chitin based transformation strategy.</p> <p>Results</p> <p>We generated different deletion mutants of putative polysaccharide genes and examined the mutants by immuno-blots with O and K specific antisera. Our results showed that O- and K-antigen genes are separated in <it>V. parahaemolyticus </it>O3:K6; the region encoding both O-antigen and capsule biosynthesis in other vibrios, i.e. genes between <it>gmhD </it>and <it>rjg</it>, determines the K6-antigen but not the O3-antigen in <it>V. parahaemolyticus</it>. The previously identified "capsule genes" on the smaller chromosome were related to exopolysaccharide synthesis, not K-antigen.</p> <p>Conclusion</p> <p>Understanding of the genetic basis of O- and K-antigens is critical to understanding the rapid changes in these polysaccharides seen in pandemic <it>V. parahaemolyticus. </it>This report confirms the genetic location of K-antigen synthesis in <it>V. parahaemolyticus </it>O3:K6 allowing us to focus future studies of the evolution of serotypes to this region.</p

Quantifying Rates of Evolutionary Adaptation in Response to Ocean Acidification

The global acidification of the earth's oceans is predicted to impact biodiversity via physiological effects impacting growth, survival, reproduction, and immunology, leading to changes in species abundances and global distributions. However, the degree to which these changes will play out critically depends on the evolutionary rate at which populations will respond to natural selection imposed by ocean acidification, which remains largely unquantified. Here we measure the potential for an evolutionary response to ocean acidification in larval development rate in two coastal invertebrates using a full-factorial breeding design. We show that the sea urchin species Strongylocentrotus franciscanus has vastly greater levels of phenotypic and genetic variation for larval size in future CO2 conditions compared to the mussel species Mytilus trossulus. Using these measures we demonstrate that S. franciscanus may have faster evolutionary responses within 50 years of the onset of predicted year-2100 CO2 conditions despite having lower population turnover rates. Our comparisons suggest that information on genetic variation, phenotypic variation, and key demographic parameters, may lend valuable insight into relative evolutionary potentials across a large number of species

The capsule polysaccharide structure and biogenesis for non-O1 Vibrio cholerae NRT36S: genes are embedded in the LPS region

BACKGROUND: In V. cholerae, the biogenesis of capsule polysaccharide is poorly understood. The elucidation of capsule structure and biogenesis is critical to understanding the evolution of surface polysaccharide and the internal relationship between the capsule and LPS in this species. V. cholerae serogroup O31 NRT36S, a human pathogen that produces a heat-stable enterotoxin (NAG-ST), is encapsulated. Here, we report the covalent structure and studies of the biogenesis of the capsule in V. cholerae NRT36S. RESULTS: The structure of the capsular (CPS) polysaccharide was determined by high resolution NMR spectroscopy and shown to be a complex structure with four residues in the repeating subunit. The gene cluster of capsule biogenesis was identified by transposon mutagenesis combined with whole genome sequencing data (GenBank accession DQ915177). The capsule gene cluster shared the same genetic locus as that of the O-antigen of lipopolysaccharide (LPS) biogenesis gene cluster. Other than V. cholerae O139, this is the first V. cholerae CPS for which a structure has been fully elucidated and the genetic locus responsible for biosynthesis identified. CONCLUSION: The co-location of CPS and LPS biosynthesis genes was unexpected, and would provide a mechanism for simultaneous emergence of new O and K antigens in a single strain. This, in turn, may be a key element for V. cholerae to evolve new strains that can escape immunologic detection by host populations

Weather conditions and daily television use in the Netherlands, 1996–2005

This study examines the impact of daily atmospheric weather conditions on daily television use in the Netherlands for the period 1996–2005. The effects of the weather parameters are considered in the context of mood and mood management theory. It is proposed that inclement and uncomfortable weather conditions are associated with lower human mood, and that watching entertainment and avoiding informational programs may serve to repair such mood. We consequently hypothesize that people spend more time watching television if inclement and uncomfortable weather conditions (low temperatures, little sunshine, much precipitation, high wind velocity, less daylight) coincide with more airtime for entertainment programs, but that they view less if the same weather conditions coincide with more airtime devoted to information fare. We put this interaction thesis to a test using a time series analysis of daily television viewing data of the Dutch audience obtained from telemeters (T = 3,653), merged with meteorological weather station statistics and program broadcast figures, whilst controlling for a wide array of recurrent and one-time societal events. The results provide substantial support for the proposed interaction of program airtime and the weather parameters temperature and sunshine on aggregate television viewing time. Implications of the findings are discussed

Real-Time High Resolution 3D Imaging of the Lyme Disease Spirochete Adhering to and Escaping from the Vasculature of a Living Host

Pathogenic spirochetes are bacteria that cause a number of emerging and re-emerging diseases worldwide, including syphilis, leptospirosis, relapsing fever, and Lyme borreliosis. They navigate efficiently through dense extracellular matrix and cross the blood–brain barrier by unknown mechanisms. Due to their slender morphology, spirochetes are difficult to visualize by standard light microscopy, impeding studies of their behavior in situ. We engineered a fluorescent infectious strain of Borrelia burgdorferi, the Lyme disease pathogen, which expressed green fluorescent protein (GFP). Real-time 3D and 4D quantitative analysis of fluorescent spirochete dissemination from the microvasculature of living mice at high resolution revealed that dissemination was a multi-stage process that included transient tethering-type associations, short-term dragging interactions, and stationary adhesion. Stationary adhesions and extravasating spirochetes were most commonly observed at endothelial junctions, and translational motility of spirochetes appeared to play an integral role in transendothelial migration. To our knowledge, this is the first report of high resolution 3D and 4D visualization of dissemination of a bacterial pathogen in a living mammalian host, and provides the first direct insight into spirochete dissemination in vivo

First-Trimester or Second-Trimester Screening, or Both, for Down's Syndrome

BACKGROUND It is uncertain how best to screen pregnant women for the presence of fetal Down's syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters. METHODS Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement ofalpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency). RESULTS First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening. CONCLUSIONS First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection ofDown's syndrome, with low false positive rates

Impact of DOTS expansion on tuberculosis related outcomes and costs in Haiti

BACKGROUND: Implementation of the World Health Organization's DOTS strategy (Directly Observed Treatment Short-course therapy) can result in significant reduction in tuberculosis incidence. We estimated potential costs and benefits of DOTS expansion in Haiti from the government, and societal perspectives. METHODS: Using decision analysis incorporating multiple Markov processes (Markov modelling), we compared expected tuberculosis morbidity, mortality and costs in Haiti with DOTS expansion to reach all of the country, and achieve WHO benchmarks, or if the current situation did not change. Probabilities of tuberculosis related outcomes were derived from the published literature. Government health expenditures, patient and family costs were measured in direct surveys in Haiti and expressed in 2003 US$. RESULTS: Starting in 2003, DOTS expansion in Haiti is anticipated to cost$4.2 million and result in 63,080 fewer tuberculosis cases, 53,120 fewer tuberculosis deaths, and net societal savings of $131 million, over 20 years. Current government spending for tuberculosis is high, relative to the per capita income, and would be only slightly lower with DOTS. Societal savings would begin within 4 years, and would be substantial in all scenarios considered, including higher HIV seroprevalence or drug resistance, unchanged incidence following DOTS expansion, or doubling of initial and ongoing costs for DOTS expansion. CONCLUSION: A modest investment for DOTS expansion in Haiti would provide considerable humanitarian benefit by reducing tuberculosis-related morbidity, mortality and costs for patients and their families. These benefits, together with projected minimal Haitian government savings, argue strongly for donor support for DOTS expansion

Reducing the Activity and Secretion of Microbial Antioxidants Enhances the Immunogenicity of BCG

BACKGROUND:In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB). Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production. METHODOLOGY/PRINCIPAL FINDINGS:To determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli. CONCLUSIONS/SIGNIFICANCE:We conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG's ability to protect against pulmonary TB