Decision Making in Expanded Newborn Screening: The Case of Duchenne Muscular Dystrophy.

Background. Newborn screening (NBS) is a mandatory public health program aimed at the early identification of babies with conditions that will benefit from early diagnosis and treatment. With increasing technology, some programs have offered optional NBS for diseases for which there is limited treatment efficiency data. This dissertation used Duchenne muscular dystrophy (DMD) as an exemplar to address whether variation in the presentation and structural characteristics of NBS influence decision making. Methods. In 3 randomized survey experiments using Internet samples, I explored characteristics of test structure and presentation that may motivate utilization of DMD NBS. The primary outcome variable was intent to utilize DMD NBS with additional outcome variables of attitudes towards DMD NBS. Results. Providing a context of mandatory NBS (either bundled or unbundled) influenced DMD NBS intent and attitudes towards DMD NBS. When participants were not given this broader context in which to place a specific optional NBS, they were more hesitant to choose testing. Neither the mode of results release, nor the overall test purpose guiding the release, were significant predictors when parents lacked any specific reason to believe their child was at risk. However, an interaction of DMD NBS purpose and perceived vulnerability showed that personal purpose increased DMD NBS intent when perceived vulnerability existed, but DMD NBS intent was relatively consistent regardless of perceived vulnerability when the test’s main purpose was research. Conclusions. New parents are increasingly being faced with optional NBS decisions, yet there is no consistent policy regarding optional NBS communication, in terms of the information included and the way this information is presented. The results suggest that future optional NBS programs should be careful to present testing information in a way that explains how a single optional NBS test fits into overall mandatory NBS. Additionally, health professionals should attend to parents’ perceptions of their child’s vulnerability, which appears to be a broader construct than simply family history of a specific disease. Increasing attention to the influence of such structural factors and individual differences on optional NBS decision making will become more and more important as NBS programs are likely to continue expanding.PHDHealth Behavior & Health EducationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/98052/1/selillie_1.pd

The effects of globin on microarray-based gene expression analysis of mouse blood

Peer reviewe

Caries dental en niños con necesidades especiales de un colegio de bajos recursos en el Perú

Objetivos: Determinar la prevalencia de caries dental en los niños del centro de educación básica especial Helen Keller situado en el Callao, Perú durante el 2015. Material y Métodos: Estudio observacional, transversal sobre los datos de 30 niños del centro de educación básica especial Helen Keller. Información recogida por alumnos de la Facultad de Estomatología de la Universidad Peruana Cayetano Heredia (UPCH), en el centro educativo durante el año 2015. Se analizaron las características de los niños (edad, sexo, y diagnóstico sistémico). Para caries dental se utilizó el índice CPOD/ceod y el índice CPOS/ceos. Resultados: El 90% (n=27) de los escolares presentó caries dental. El retardo mental fue la condición más prevalente (43,3%, n=13). Se encontró un índice de CPOD de 2,9 (DE 3,8) y en dientes deciduos (ceod) de 6,0 (DE 4,0). Conclusiones: Existe una alta prevalencia de caries dental en los niños del centro de educación básica especial Helen Keller Callao, Perú en el año 2015

Influence of Genetic Polymorphisms on the Effect of High- and Standard-Dose Clopidogrel After Percutaneous Coronary Intervention The GIFT (Genotype Information and Functional Testing) Study

ObjectivesThis study sought to evaluate the influence of single nucleotide polymorphisms (SNPs) on the pharmacodynamic effect of high- or standard-dose clopidogrel after percutaneous coronary intervention (PCI).BackgroundThere is a lack of prospective, multicenter data regarding the effect of different genetic variants on clopidogrel pharmacodynamics over time in patients undergoing PCI.MethodsThe GRAVITAS (Gauging Responsiveness with A VerifyNow assay–Impact on Thrombosis And Safety) trial screened patients with platelet function testing after PCI and randomly assigned those with high on-treatment reactivity (OTR) to either high- or standard-dose clopidogrel; a cohort of patients without high OTR were also followed. DNA samples obtained from 1,028 patients were genotyped for 41 SNPs in 17 genes related to platelet reactivity. After adjusting for clinical characteristics, the associations between the SNPs and OTR using linear regression were evaluated.ResultsCYP2C19*2 was significantly associated with OTR at 12 to 24 h (R2 = 0.07, p = 2.2 × 10−15), 30 days (R2 = 0.10, p = 1.3 × 10−7), and 6 months after PCI (R2 = 0.07, p = 1.9 × 10−11), whereas PON1, ABCB1 3435 C→T, and other candidate SNPs were not. Carriers of 1 and 2 reduced-function CYP2C19 alleles were significantly more likely to display persistently high OTR at 30 days and 6 months, irrespective of treatment assignment. The portion of the risk of persistently high OTR at 30 days attributable to reduced-function CYP2C19 allele carriage was 5.2% in the patients randomly assigned to high-dose clopidogrel.ConclusionsCYP2C19, but not PON1 or ABCB1, is a significant determinant of the pharmacodynamic effects of clopidogrel, both early and late after PCI. In patients with high OTR identified by platelet function testing, the CYP2C19 genotype provides limited incremental information regarding the risk of persistently high reactivity with clopidogrel 150-mg maintenance dosing. (Genotype Information and Functional Testing Study [GIFT]; NCT00992420

Simplified Models for LHC New Physics Searches

This document proposes a collection of simplified models relevant to the design of new-physics searches at the LHC and the characterization of their results. Both ATLAS and CMS have already presented some results in terms of simplified models, and we encourage them to continue and expand this effort, which supplements both signature-based results and benchmark model interpretations. A simplified model is defined by an effective Lagrangian describing the interactions of a small number of new particles. Simplified models can equally well be described by a small number of masses and cross-sections. These parameters are directly related to collider physics observables, making simplified models a particularly effective framework for evaluating searches and a useful starting point for characterizing positive signals of new physics. This document serves as an official summary of the results from the "Topologies for Early LHC Searches" workshop, held at SLAC in September of 2010, the purpose of which was to develop a set of representative models that can be used to cover all relevant phase space in experimental searches. Particular emphasis is placed on searches relevant for the first ~50-500 pb-1 of data and those motivated by supersymmetric models. This note largely summarizes material posted at http://lhcnewphysics.org/, which includes simplified model definitions, Monte Carlo material, and supporting contacts within the theory community. We also comment on future developments that may be useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results from "Topologies for Early LHC Searches" workshop (SLAC, September 2010). Supplementary material can be found at http://lhcnewphysics.or

Genes controlling vaccine responses and disease resistance to respiratory viral pathogens in cattle

AbstractFarm animals remain at risk of endemic, exotic and newly emerging viruses. Vaccination is often promoted as the best possible solution, and yet for many pathogens, either there are no appropriate vaccines or those that are available are far from ideal. A complementary approach to disease control may be to identify genes and chromosomal regions that underlie genetic variation in disease resistance and response to vaccination. However, identification of the causal polymorphisms is not straightforward as it generally requires large numbers of animals with linked phenotypes and genotypes. Investigation of genes underlying complex traits such as resistance or response to viral pathogens requires several genetic approaches including candidate genes deduced from knowledge about the cellular pathways leading to protection or pathology, or unbiased whole genome scans using markers spread across the genome.Evidence for host genetic variation exists for a number of viral diseases in cattle including bovine respiratory disease and anecdotally, foot and mouth disease virus (FMDV). We immunised and vaccinated a cattle cross herd with a 40-mer peptide derived from FMDV and a vaccine against bovine respiratory syncytial virus (BRSV). Genetic variation has been quantified. A candidate gene approach has grouped high and low antibody and T cell responders by common motifs in the peptide binding pockets of the bovine major histocompatibility complex (BoLA) DRB3 gene. This suggests that vaccines with a minimal number of epitopes that are recognised by most cattle could be designed. Whole genome scans using microsatellite and single nucleotide polymorphism (SNP) markers has revealed many novel quantitative trait loci (QTL) and SNP markers controlling both humoral and cell-mediated immunity, some of which are in genes of known immunological relevance including the toll-like receptors (TLRs).The sequencing, assembly and annotation of livestock genomes and is continuing apace. In addition, provision of high-density SNP chips should make it possible to link phenotypes with genotypes in field populations without the need for structured populations or pedigree information. This will hopefully enable fine mapping of QTL and ultimate identification of the causal gene(s). The research could lead to selection of animals that are more resistant to disease and new ways to improve vaccine efficacy