Probabilistic Daily ILI Syndromic Surveillance with a Spatio-Temporal Bayesian Hierarchical Model

BACKGROUND: For daily syndromic surveillance to be effective, an efficient and sensible algorithm would be expected to detect aberrations in influenza illness, and alert public health workers prior to any impending epidemic. This detection or alert surely contains uncertainty, and thus should be evaluated with a proper probabilistic measure. However, traditional monitoring mechanisms simply provide a binary alert, failing to adequately address this uncertainty. METHODS AND FINDINGS: Based on the Bayesian posterior probability of influenza-like illness (ILI) visits, the intensity of outbreak can be directly assessed. The numbers of daily emergency room ILI visits at five community hospitals in Taipei City during 2006-2007 were collected and fitted with a Bayesian hierarchical model containing meteorological factors such as temperature and vapor pressure, spatial interaction with conditional autoregressive structure, weekend and holiday effects, seasonality factors, and previous ILI visits. The proposed algorithm recommends an alert for action if the posterior probability is larger than 70%. External data from January to February of 2008 were retained for validation. The decision rule detects successfully the peak in the validation period. When comparing the posterior probability evaluation with the modified Cusum method, results show that the proposed method is able to detect the signals 1-2 days prior to the rise of ILI visits. CONCLUSIONS: This Bayesian hierarchical model not only constitutes a dynamic surveillance system but also constructs a stochastic evaluation of the need to call for alert. The monitoring mechanism provides earlier detection as well as a complementary tool for current surveillance programs

Fatal Prion Disease in a Mouse Model of Genetic E200K Creutzfeldt-Jakob Disease

Genetic prion diseases are late onset fatal neurodegenerative disorders linked to pathogenic mutations in the prion protein-encoding gene, PRNP. The most prevalent of these is the substitution of Glutamate for Lysine at codon 200 (E200K), causing genetic Creutzfeldt-Jakob disease (gCJD) in several clusters, including Jews of Libyan origin. Investigating the pathogenesis of genetic CJD, as well as developing prophylactic treatments for young asymptomatic carriers of this and other PrP mutations, may well depend upon the availability of appropriate animal models in which long term treatments can be evaluated for efficacy and toxicity. Here we present the first effective mouse model for E200KCJD, which expresses chimeric mouse/human (TgMHu2M) E199KPrP on both a null and a wt PrP background, as is the case for heterozygous patients and carriers. Mice from both lines suffered from distinct neurological symptoms as early as 5–6 month of age and deteriorated to death several months thereafter. Histopathological examination of the brain and spinal cord revealed early gliosis and age-related intraneuronal deposition of disease-associated PrP similarly to human E200K gCJD. Concomitantly we detected aggregated, proteinase K resistant, truncated and oxidized PrP forms on immunoblots. Inoculation of brain extracts from TgMHu2ME199K mice readily induced, the first time for any mutant prion transgenic model, a distinct fatal prion disease in wt mice. We believe that these mice may serve as an ideal platform for the investigation of the pathogenesis of genetic prion disease and thus for the monitoring of anti-prion treatments

Prehospital Electronic Patient Care Report Systems: Early Experiences from Emergency Medical Services Agency Leaders

Background: As the United States embraces electronic health records (EHRs), improved emergency medical services (EMS) information systems are also a priority; however, little is known about the experiences of EMS agencies as they adopt and implement electronic patient care report (e-PCR) systems. We sought to characterize motivations for adoption of e-PCR systems, challenges associated with adoption and implementation, and emerging implementation strategies. Methods: We conducted a qualitative study using semi-structured in-depth interviews with EMS agency leaders. Participants were recruited through a web-based survey of National Association of EMS Physicians (NAEMSP) members, a didactic session at the 2010 NAEMSP Annual Meeting, and snowball sampling. Interviews lasted approximately 30 minutes, were recorded and professionally transcribed. Analysis was conducted by a five-person team, employing the constant comparative method to identify recurrent themes. Results: Twenty-three interviewees represented 20 EMS agencies from the United States and Canada; 14 EMS agencies were currently using e-PCR systems. The primary reason for adoption was the potential for e-PCR systems to support quality assurance efforts. Challenges to e-PCR system adoption included those common to any health information technology project, as well as challenges unique to the prehospital setting, including: fear of increased ambulance run times leading to decreased ambulance availability, difficulty integrating with existing hospital information systems, and unfunded mandates requiring adoption of e-PCR systems. Three recurring strategies emerged to improve e-PCR system adoption and implementation: 1) identify creative funding sources; 2) leverage regional health information organizations; and 3) build internal information technology capacity. Conclusion: EMS agencies are highly motivated to adopt e-PCR systems to support quality assurance efforts; however, adoption and implementation of e-PCR systems has been challenging for many. Emerging strategies from EMS agencies and others that have successfully implemented EHRs may be useful in expanding e-PCR system use and facilitating this transition for other EMS agencies

A population study on the association between leisure time physical activity and self-rated health among diabetics in Taiwan

<p>Abstract</p> <p>Background</p> <p>There is strong evidence for the beneficial effects of physical activity in diabetes. There has been little research demonstrating a dose-response relationship between physical activity and self-rated health in diabetics. The aim of this study was to explore the dose-response association between leisure time physical activity and self-rated health among diabetics in Taiwan.</p> <p>Methods</p> <p>Data came from the 2001 Taiwan National Health Interview Survey (NHIS). Inclusion criteria were a physician confirmed diagnosis of diabetes mellitus and age 18 years and above (n = 797). Self-rated health was assessed by the question "In general, would you say that your health is excellent, very good, good, fair, or poor?" Individuals with a self perceived health status of good, very good, or excellent were considered to have positive health status.</p> <p>Results</p> <p>In the full model, the odds ratio (OR) for positive health was 2.51(95% CI = 1.53-4.13), 1.62(95% CI = 0.93-2.84), and 1.35(95% CI = 0.77-2.37), for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals. Those with duration over 10 years (OR = 0.53, 95%CI = 0.30-0.94), heart disease (OR = 0.50, 95%CI = 0.30-0.85), and dyslipidemia (OR = 0.65, 95% CI = 0.43-0.98) were less likely to have positive health than their counterparts. After stratified participants by duration, those with a duration of diabetes < 6 years, the adjusted OR for positive health was 1.95(95% CI = 1.02-3.72), 1.22(95% CI = 0.59-2.52), and 1.19(95% CI = 0.58-2.41) for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals. In participants with a duration of diabetes ≥ 6 years, total energy expenditure showed a gradient effect on self-perceived positive health. The adjusted OR for positive health was 3.45(95% CI = 1.53-7.79), 2.77(95% CI = 1.11-6.92), and 1.90(95% CI = 0.73-4.94) for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals.</p> <p>Conclusions</p> <p>Our results highlight that regular leisure activity with an energy expenditure ≧ 500 kcal per week is associated with better self-rated health for those with longstanding diabetes.</p

Complete Chloroplast Genome Sequence of an Orchid Model Plant Candidate: Erycina pusilla Apply in Tropical Oncidium Breeding

Oncidium is an important ornamental plant but the study of its functional genomics is difficult. Erycina pusilla is a fast-growing Oncidiinae species. Several characteristics including low chromosome number, small genome size, short growth period, and its ability to complete its life cycle in vitro make E. pusilla a good model candidate and parent for hybridization for orchids. Although genetic information remains limited, systematic molecular analysis of its chloroplast genome might provide useful genetic information. By combining bacterial artificial chromosome (BAC) clones and next-generation sequencing (NGS), the chloroplast (cp) genome of E. pusilla was sequenced accurately, efficiently and economically. The cp genome of E. pusilla shares 89 and 84% similarity with Oncidium Gower Ramsey and Phalanopsis aphrodite, respectively. Comparing these 3 cp genomes, 5 regions have been identified as showing diversity. Using PCR analysis of 19 species belonging to the Epidendroideae subfamily, a conserved deletion was found in the rps15-trnN region of the Cymbidieae tribe. Because commercial Oncidium varieties in Taiwan are limited, identification of potential parents using molecular breeding method has become very important. To demonstrate the relationship between taxonomic position and hybrid compatibility of E. pusilla, 4 DNA regions of 36 tropically adapted Oncidiinae varieties have been analyzed. The results indicated that trnF-ndhJ and trnH-psbA were suitable for phylogenetic analysis. E. pusilla proved to be phylogenetically closer to Rodriguezia and Tolumnia than Oncidium, despite its similar floral appearance to Oncidium. These results indicate the hybrid compatibility of E. pusilla, its cp genome providing important information for Oncidium breeding

NMR Structure of the Human Prion Protein with the Pathological Q212P Mutation Reveals Unique Structural Features

Prion diseases are fatal neurodegenerative disorders caused by an aberrant accumulation of the misfolded cellular prion protein (PrPC) conformer, denoted as infectious scrapie isoform or PrPSc. In inherited human prion diseases, mutations in the open reading frame of the PrP gene (PRNP) are hypothesized to favor spontaneous generation of PrPSc in specific brain regions leading to neuronal cell degeneration and death. Here, we describe the NMR solution structure of the truncated recombinant human PrP from residue 90 to 231 carrying the Q212P mutation, which is believed to cause Gerstmann-Sträussler-Scheinker (GSS) syndrome, a familial prion disease. The secondary structure of the Q212P mutant consists of a flexible disordered tail (residues 90–124) and a globular domain (residues 125–231). The substitution of a glutamine by a proline at the position 212 introduces novel structural differences in comparison to the known wild-type PrP structures. The most remarkable differences involve the C-terminal end of the protein and the β2–α2 loop region. This structure might provide new insights into the early events of conformational transition of PrPC into PrPSc. Indeed, the spontaneous formation of prions in familial cases might be due to the disruptions of the hydrophobic core consisting of β2–α2 loop and α3 helix

Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c

Cortico-basal ganglia circuits are critical for speech and language and are implicated in autism spectrum disorder, in which language function can be severely affected. We demonstrate that in the mouse striatum, the gene Foxp2 negatively interacts with the synapse suppressor gene Mef2c. We present causal evidence that Mef2c inhibition by Foxp2 in neonatal mouse striatum controls synaptogenesis of corticostriatal inputs and vocalization in neonates. Mef2c suppresses corticostriatal synapse formation and striatal spinogenesis, but can itself be repressed by Foxp2 through direct DNA binding. Foxp2 deletion de-represses Mef2c, and both intrastriatal and global decrease of Mef2c rescue vocalization and striatal spinogenesis defects of Foxp2-deletion mutants. These findings suggest that Foxp2-Mef2C signaling is critical to corticostriatal circuit formation. If found in humans, such signaling defects could contribute to a range of neurologic and neuropsychiatric disorders.National Institutes of Health (U.S.) (Grant R37 HD028341)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Award R37 HD028341