The effect of systematic pediatric care on neonatal mortality and hospitalizations of infants born with oral clefts

<p>Abstract</p> <p>Background</p> <p>Cleft lip and/or palate (CL/P) increase mortality and morbidity risks for affected infants especially in less developed countries. This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P) in South America.</p> <p>Methods</p> <p>The intervention group included live-born infants with isolated or associated CL/P in 47 hospitals between 2003 and 2005. The control group included live-born infants with CL/P between 2001 and 2002 in the same hospitals. The intervention group received systematic pediatric care between the 7^thand 28^thday of life. The primary outcomes were mortality between the 7^thand 28^thday of life and hospitalization days in this period among survivors adjusted for relevant baseline covariates.</p> <p>Results</p> <p>There were no significant mortality differences between the intervention and control groups. However, surviving infants with associated CL/P in the intervention group had fewer hospitalization days by about six days compared to the associated control group.</p> <p>Conclusions</p> <p>Early systematic pediatric care may significantly reduce neonatal hospitalizations of infants with CL/P and additional birth defects in South America. Given the large healthcare and financial burden of CL/P on affected families and the relatively low cost of systematic pediatric care, improving access to such care may be a cost-effective public policy intervention.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00097149">NCT00097149</a></p

Quantitative Detection and Biological Propagation of Scrapie Seeding Activity In Vitro Facilitate Use of Prions as Model Pathogens for Disinfection

Prions are pathogens with an unusually high tolerance to inactivation and constitute a complex challenge to the re-processing of surgical instruments. On the other hand, however, they provide an informative paradigm which has been exploited successfully for the development of novel broad-range disinfectants simultaneously active also against bacteria, viruses and fungi. Here we report on the development of a methodological platform that further facilitates the use of scrapie prions as model pathogens for disinfection. We used specifically adapted serial protein misfolding cyclic amplification (PMCA) for the quantitative detection, on steel wires providing model carriers for decontamination, of 263K scrapie seeding activity converting normal protease-sensitive into abnormal protease-resistant prion protein. Reference steel wires carrying defined amounts of scrapie infectivity were used for assay calibration, while scrapie-contaminated test steel wires were subjected to fifteen different procedures for disinfection that yielded scrapie titre reductions of ≤101- to ≥105.5-fold. As confirmed by titration in hamsters the residual scrapie infectivity on test wires could be reliably deduced for all examined disinfection procedures, from our quantitative seeding activity assay. Furthermore, we found that scrapie seeding activity present in 263K hamster brain homogenate or multiplied by PMCA of scrapie-contaminated steel wires both triggered accumulation of protease-resistant prion protein and was further propagated in a novel cell assay for 263K scrapie prions, i.e., cerebral glial cell cultures from hamsters. The findings from our PMCA- and glial cell culture assays revealed scrapie seeding activity as a biochemically and biologically replicative principle in vitro, with the former being quantitatively linked to prion infectivity detected on steel wires in vivo. When combined, our in vitro assays provide an alternative to titrations of biological scrapie infectivity in animals that substantially facilitates the use of prions as potentially highly indicative test agents in the search for novel broad-range disinfectants

Detection of Prion Protein Particles in Blood Plasma of Scrapie Infected Sheep

Prion diseases are transmissible neurodegenerative diseases affecting humans and animals. The agent of the disease is the prion consisting mainly, if not solely, of a misfolded and aggregated isoform of the host-encoded prion protein (PrP). Transmission of prions can occur naturally but also accidentally, e.g. by blood transfusion, which has raised serious concerns about blood product safety and emphasized the need for a reliable diagnostic test. In this report we present a method based on surface-FIDA (fluorescence intensity distribution analysis), that exploits the high state of molecular aggregation of PrP as an unequivocal diagnostic marker of the disease, and show that it can detect infection in blood. To prepare PrP aggregates from blood plasma we introduced a detergent and lipase treatment to separate PrP from blood lipophilic components. Prion protein aggregates were subsequently precipitated by phosphotungstic acid, immobilized on a glass surface by covalently bound capture antibodies, and finally labeled with fluorescent antibody probes. Individual PrP aggregates were visualized by laser scanning microscopy where signal intensity was proportional to aggregate size. After signal processing to remove the background from low fluorescence particles, fluorescence intensities of all remaining PrP particles were summed. We detected PrP aggregates in plasma samples from six out of ten scrapie-positive sheep with no false positives from uninfected sheep. Applying simultaneous intensity and size discrimination, ten out of ten samples from scrapie sheep could be differentiated from uninfected sheep. The implications for ante mortem diagnosis of prion diseases are discussed

A Simple, Versatile and Sensitive Cell-Based Assay for Prions from Various Species

Detection and quantification of prion infectivity is a crucial step for various fundamental and applied aspects of prion research. Identification of cell lines highly sensitive to prion infection led to the development of cell-based titration procedures aiming at replacing animal bioassays, usually performed in mice or hamsters. However, most of these cell lines are only permissive to mouse-adapted prions strains and do not allow titration of prions from other species. In this study, we show that epithelial RK13, a cell line permissive to mouse and bank vole prion strains and to natural prion agents from sheep and cervids, enables a robust and sensitive detection of mouse and ovine-derived prions. Importantly, the cell culture work is strongly reduced as the RK13 cell assay procedure designed here does not require subcultivation of the inoculated cultures. We also show that prions effectively bind to culture plastic vessel and are quantitatively detected by the cell assay. The possibility to easily quantify a wider range of prions, including rodent experimental strains but also natural agents from sheep and cervids, should prompt the spread of cell assays for routine prion titration and lead to valuable information in fundamental and applied studies

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure

The Dijet Mass Spectrum and a Search for Quark Compositeness in bar{p}p Collisions at sqrt{s} = 1.8 TeV

Using the DZero detector at the 1.8 TeV pbarp Fermilab Tevatron collider, we have measured the inclusive dijet mass spectrum in the central pseudorapidity region |eta_jet| < 1.0 for dijet masses greater than 200 Gev/c^2. We have also measured the ratio of spectra sigma(|eta_jet| < 0.5)/sigma(0.5 < |eta_jet| < 1.0). The order alpha_s^3 QCD predictions are in good agreement with the data and we rule out models of quark compositeness with a contact interaction scale < 2.4 TeV at the 95% confidence level.Comment: 11 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let

Search for High Mass Photon Pairs in p-pbar --> gamma-gamma-jet-jet Events at sqrt(s)=1.8 TeV

A search has been carried out for events in the channel p-barp --> gamma gamma jet jet. Such a signature can characterize the production of a non-standard Higgs boson together with a W or Z boson. We refer to this non-standard Higgs, having standard model couplings to vector bosons but no coupling to fermions, as a "bosonic Higgs." With the requirement of two high transverse energy photons and two jets, the diphoton mass (m(gamma gamma)) distribution is consistent with expected background. A 90(95)% C.L. upper limit on the cross section as a function of mass is calculated, ranging from 0.60(0.80) pb for m(gamma gamma) = 65 GeV/c^2 to 0.26(0.34) pb for m(gamma gamma) = 150 GeV/c^2, corresponding to a 95% C.L. lower limit on the mass of a bosonic Higgs of 78.5 GeV/c^2.Comment: 9 pages, 3 figures. Replacement has new H->gamma gamma branching ratios and corresponding new mass limit

The socio-demographic patterning of sexual risk behaviour: a survey of young men in Finland and Estonia

<p>Abstract</p> <p>Background</p> <p>Sexually transmitted infections (STIs) among the youth are an increasing challenge for public health in Europe. This study provided estimates of men's (18–25 years) sexual risk behaviour and self-reported STIs and their socio-demographic patterning in Finland and Estonia; two countries that are geographically close, but have very different STI epidemics.</p> <p>Method</p> <p>Nationally representative cross-sectional population surveys with comparable survey questions were used. Data from self-administered questionnaires for 1765 men aged 18–25 years in Finland (85% of the age cohort was included in the sampling frame, 95% of the sample responded) and 748 in Estonia, with a response rate of 43% respectively, were analysed. Socio-demographic patterning of multiple partners, condom use and self-reported STIs are presented was studied using multiple logistic regression analysis.</p> <p>Results</p> <p>The main findings focus on associations found within each country. In Finland, higher age, low education and to a lesser extent relationship with a non-steady partner increased the likelihood of reporting multiple lifetime-partners, while in Estonia only higher age and low education revealed this effect. In relation to unprotected intercourse, in Finland, higher age, low education and relationship status with a steady partner increased the likelihood of reporting unprotected intercourse. In Estonia, the same was observed only for relationship status. In Finland the likelihood of self-reported STIs increased by older age and lower education and decreased by being with a non-steady partner, while in Estonia, a non-significant increase in self-reported STIs was observed only in the older age group.</p> <p>Conclusion</p> <p>A clear socio-demographic patterning for sexual behaviour and self-reported STIs was revealed in Finland, but a less consistent trend was seen in Estonia. The findings of this study suggest that prevention strategies should focus in Finland on less educated singles and in Estonia on young men generally.</p