998-61 Population Prevalence of Wolff-Parkinson-White Syndrome

Little is known about the epidemiology of Wolff-Parkinson-White (WPW) syndrome in the general population. Virtually all previous studies have been either case series from tertiary care centers or limited to young adult males screened for military training. To date, there are no detailed studies of the prevalence of WPW in the general population. To determine the prevalence of WPW in the general population, we used the Marshfield Epidemiologic Study Area (MESA), a population laboratory of 50,000 people residing in 12 contiguous zip codes in central Wisconsin. Prevalence was determined as of 7/1/91 among MESA residents who had a diagnosis of WPW between 1/1/79 and 6/30/91. Cases were identified by reviewing the medical records and electrocardiograms of: a) all 32 MESA residents with the WPW diagnosis identified by International Classification of Diseases, 9th Revision (ICD-9) Code 426.7 as a hospital discharge or outpatient clinic diagnosis, b) 600 patients with suspected supraventricular arrhythmias identified by three ICD 9 codes, and c) all patients who had an invasive electrophysiology study for overt WPW syndrome in our institution over the last 10 years.ResultsWe identified 25 prevalent cases of WPW resulting in an overall population prevalence of 5.1/10,000 (95% C.I., 3.1–7.1).Age specific-prevalence rates per 10,000 were: 0–19 years –2.0; 20–39 years –5.5; 40–59 years –9.6; > 60 years –4.8. There was no significant difference in males versus females. Al1 25 verified cases were identified from the 32 potential cases with ICD-9 Code 426.7, indicating that this code is 100% sensitive and has a 78% positive predictive value for WPW syndrome.Conclusions1) The prevalence of WPW in the general population is lower than that reported in selected populations and appears to be highest in those of late middle-age. 2) Based on the findings of our study, we estimate that there are approximately 130,000 individuals in the United States with electrocardiographic documentation of WPW

The Status of Masked Bobwhite Recovery in the United States and Mexico

The masked bobwhite (Colinus virginianus ridgwayi) is an endangered species currently numbering \u3c1500 individuals and restricted to 2 locales in southeastern Arizona and northcentral Sonora, Mexico. The subspecies\u27 endangered status is attributed to overgrazing of Sonora savanna grassland that began during the late 1880\u27s and continued well into the 20th century. This overgrazing resulted in the conversion of many native grass pastures to the exotic bufflegrass (Cenchrus ciliaris). The Arizona masked bobwhite population was extirpated around the turn of the century, and the Sonoran population was thought to have disappeared during the 1940\u27s until a small remnant population was discovered on a ranch near Benjamin Hill, Sonora , in 1964 . Masked bobwhite recovery efforts have a dynamic, long history of nearly six decades. Current masked bobwhite recovery efforts focus on reestablishing a self-sustaining population on the Buenos Aires National Wildlife Refuge (BANWR) in the United States, as well as 2 remnant wild populations located on privately owned ranches in northcentral Sonora

Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination

BACKGROUND: HIV-1 recombination between different subtypes has a major impact on the global epidemic. The generation of these intersubtype recombinants follows a defined set of events starting with dual infection of a host cell, heterodiploid virus production, strand transfers during reverse transcription, and then selection. In this study, recombination frequencies were measured in the C1-C4 regions of the envelope gene in the presence (using a multiple cycle infection system) and absence (in vitro reverse transcription and single cycle infection systems) of selection for replication-competent virus. Ugandan subtypes A and D HIV-1 env sequences (115-A, 120-A, 89-D, 122-D, 126-D) were employed in all three assay systems. These subtypes co-circulate in East Africa and frequently recombine in this human population. RESULTS: Increased sequence identity between viruses or RNA templates resulted in increased recombination frequencies, with the exception of the 115-A virus or RNA template. Analyses of the recombination breakpoints and mechanistic studies revealed that the presence of a recombination hotspot in the C3/V4 env region, unique to 115-A as donor RNA, could account for the higher recombination frequencies with the 115-A virus/template. Single-cycle infections supported proportionally less recombination than the in vitro reverse transcription assay but both systems still had significantly higher recombination frequencies than observed in the multiple-cycle virus replication system. In the multiple cycle assay, increased replicative fitness of one HIV-1 over the other in a dual infection dramatically decreased recombination frequencies. CONCLUSION: Sequence variation at specific sites between HIV-1 isolates can introduce unique recombination hotspots, which increase recombination frequencies and skew the general observation that decreased HIV-1 sequence identity reduces recombination rates. These findings also suggest that the majority of intra- or intersubtype A/D HIV-1 recombinants, generated with each round of infection, are not replication-competent and do not survive in the multiple-cycle system. Ability of one HIV-1 isolate to outgrow the other leads to reduced co-infections, heterozygous virus production, and recombination frequencies

Trans-lesion synthesis and RNaseH activity by reverse transcriptases on a true abasic RNA template

While much is known about abasic DNA, the biological impact of abasic RNA is largely unexplored. To test the mutagenic potential of this RNA lesion in the context of retroviruses, we synthesized a 31-mer oligoribonucleotide containing an abasic (rAS) site and used it as a template for studying DNA primer extension by HIV-1, avian myeloblastosis virus (AMV) and moloney murine leukemia virus (MMLV) reversed transcriptases (RT). We found that trans-lesion synthesis readily takes place with HIV-1 RT and to a lesser extent with AMV RT while MMLV RT aborts DNA synthesis. The preference of dNTP incorporation follows the order A∼G > C∼T and thus obeys to the ‘A-rule’. In the case of HIV-1 RT, we measured the kinetic data of dNTP incorporation and compared it to abasic DNA. We found that A-incorporation is only 2-fold slower relative to a matched (undamaged) RNA template while it is 7-fold slower in the case of DNA. Furthermore, there is less discrimination in incorporation between the four dNTPs in the case of abasic RNA compared to abasic DNA. These experiments clearly point to a higher promiscuity of lesion bypass on abasic RNA. Given their known higher chemical stability, such rAS sites can clearly contribute to (retro)viral evolution

Associations of NINJ2 sequence variants with incident ischemic stroke in the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) consortium

Background<p></p> Stroke, the leading neurologic cause of death and disability, has a substantial genetic component. We previously conducted a genome-wide association study (GWAS) in four prospective studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and demonstrated that sequence variants near the NINJ2 gene are associated with incident ischemic stroke. Here, we sought to fine-map functional variants in the region and evaluate the contribution of rare variants to ischemic stroke risk.<p></p> Methods and Results<p></p> We sequenced 196 kb around NINJ2 on chromosome 12p13 among 3,986 European ancestry participants, including 475 ischemic stroke cases, from the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, and Framingham Heart Study. Meta-analyses of single-variant tests for 425 common variants (minor allele frequency [MAF] ≥ 1%) confirmed the original GWAS results and identified an independent intronic variant, rs34166160 (MAF = 0.012), most significantly associated with incident ischemic stroke (HR = 1.80, p = 0.0003). Aggregating 278 putatively-functional variants with MAF≤ 1% using count statistics, we observed a nominally statistically significant association, with the burden of rare NINJ2 variants contributing to decreased ischemic stroke incidence (HR = 0.81; p = 0.026).<p></p> Conclusion<p></p> Common and rare variants in the NINJ2 region were nominally associated with incident ischemic stroke among a subset of CHARGE participants. Allelic heterogeneity at this locus, caused by multiple rare, low frequency, and common variants with disparate effects on risk, may explain the difficulties in replicating the original GWAS results. Additional studies that take into account the complex allelic architecture at this locus are needed to confirm these findings

Systems of education governance and cultures of justice in Ireland, Scotland and Pakistan

This chapter compares the issue of cultures of justice in the systems of education governance in three education systems: Ireland, Scotland and Pakistan. The focus for the comparison are the current policies which shape the regulation of education. These policies were reviewed to identify key issues relating to social justice and equality, decision-making and accountability. From the analysis of each system, three central issues were identified: firstly, the improvement of a state education system; secondly, the degree of decentralisation and centralisation in governance structures and thirdly, the expectations placed on school leaders. The chapter concludes by discussing the tensions between the drive for system improvement and opportunities for school leaders to build strategies to address issues of inequality in schools

Regression, developmental trajectory and associated problems in disorders in the autism spectrum: the SNAP study

We report rates of regression and associated findings in a population derived group of 255 children aged 9-14 years, participating in a prevalence study of autism spectrum disorders (ASD); 53 with narrowly defined autism, 105 with broader ASD and 97 with non-ASD neurodevelopmental problems, drawn from those with special educational needs within a population of 56,946 children. Language regression was reported in 30% with narrowly defined autism, 8% with broader ASD and less than 3% with developmental problems without ASD. A smaller group of children were identified who underwent a less clear setback. Regression was associated with higher rates of autistic symptoms and a deviation in developmental trajectory. Regression was not associated with epilepsy or gastrointestinal problems