Emergency Mosquito Control on a Selected Area in Eastern North Carolina After Hurricane Irene

Natural disasters such as hurricanes may contribute to mosquito abundance and, consequently, arbovirus transmission risk. In 2011, flooding from Hurricane Irene in eastern North Carolina (NC) resulted in increased mosquito populations that hindered recovery efforts. Budget shortfalls in NC have reduced the functionality of long-term mosquito surveillance and control programs; hence, many counties rely on the Federal Emergency Management Agency for post-disaster mosquito control. This pilot study examines mosquito abundance pre- and post-aerial insecticide spraying at eight study sites in Washington and Tyrrell Counties in rural eastern NC after Hurricane Irene. Percent change was calculated and compared for traps in areas that received aerial pesticide application and those that did not. Traps in spray zones show decreases in mosquito abundance when compared to control traps (treatment: −52.93%; control: 3.55%), although no significant differences (P = 0.286) were found in mosquito abundance between groups. Implications of reactive rather than proactive mosquito control responses are discussed

Circumventing antivector immunity: potential use of nonhuman adenoviral vectors

Adenoviruses are efficient gene delivery vectors based on their ability to transduce a wide variety of cell types and drive high-level transient transgene expression. While there have been advances in modifying human adenoviral (HAdV) vectors to increase their safety profile, there are still pitfalls that need to be further addressed. Preexisting humoral and cellular immunity against common HAdV serotypes limits the efficacy of gene transfer and duration of transgene expression. As an alternative, nonhuman AdV (NHAdV) vectors can circumvent neutralizing antibodies against HAdVs in immunized mice and monkeys and in human sera, suggesting that NHAdV vectors could circumvent preexisting humoral immunity against HAdVs in a clinical setting. Consequently, there has been an increased interest in developing NHAdV vectors for gene delivery in humans. In this review, we outline the recent advances and limitations of HAdV vectors for gene therapy and describe examples of NHAdV vectors focusing on their immunogenicity, tropism, and potential as effective gene therapy vehicles

Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10 -6 ). Rare variant and gene expression changes were assessed using a false discovery rate approach. AKR7A3 and HSD17B13 were associated with lipid changes in white subjects (q < 0.2). Mice fed fenofibrate displayed reductions in Hsd17b13 gene expression (q < 0.1). Associations of variants in SMAD3, IPO11, and HSD17B13, with gene expression changes in mice indicate that transforming growth factor-beta (TGF-β) and NRF2 signaling pathways may influence fenofibrate effects on dyslipidemia in patients with T2D

PPARA polymorphism influences the cardiovascular benefit of fenofibrate in type 2 diabetes: Findings from accord-lipid

The cardiovascular benefits of fibrates have been shown to be heterogeneous and to depend on the presence of atherogenic dyslipidemia. We investigated whether genetic variability in the PPARA gene, coding for the pharmacological target of fibrates (PPAR-a), could be used to improve the selection of patients with type 2 diabetes who may derive cardiovascular benefit from addition of this treatment to statins. We identified a common variant at the PPARA locus (rs6008845, C/T) displaying a study-wide significant influence on the effect of fenofibrate on major cardiovascular events (MACE) among 3,065 self-reported white subjects treated with simvastatin and randomized to fenofibrate or placebo in the ACCORD-Lipid trial. T/T homozygotes (36% of participants) experienced a 51% MACE reduction in response to fenofibrate (hazard ratio 0.49; 95% CI 0.34–0.72), whereas no benefit was observed for other genotypes (Pinteraction 5 3.7 3 1024). The rs6008845-by-fenofibrate interaction on MACE was replicated in African Americans from ACCORD (N 5 585, P 5 0.02) and in external cohorts (ACCORD-BP, ORIGIN, and TRIUMPH, total N 5 3059, P 5 0.005). Remarkably, rs6008845 T/T homozygotes experienced a cardiovascular benefit from fibrate even in the absence of atherogenic dyslipidemia. Among these individuals, but not among carriers of other genotypes, fenofibrate treatment was associated with lower circulating levels of CCL11—a proinflammatory and atherogenic chemokine also known as eotaxin (P for rs6008845-by-fenofibrate interaction 5 0.003). The GTEx data set revealed regulatory functions of rs6008845 on PPARA expression in many tissues. In summary, we have found a common PPARA regulatory variant that influences the cardiovascular effects of fenofibrate and that could be used to identify patients with type 2 diabetes who would derive benefit from fenofibrate treatment, in addition to those with atherogenic dyslipidemia

A History of Discrete Event Simulation Programming Languages

The history of simulation programming languages is organized as a progression in periods of similar developments. The five periods, spanning 1955-1986, are labeled: The Period of Search (1955-1960); The Advent (1961-1965); The Formative Period (1966-1970); The Expansional Period (1971-1978); and The Period of Consolidation and Regeneration (1979-1986). The focus is on recognizing the people and places that have made important contributions in addition to the nature of the contribution. A balance between comprehensive and in-depth treatment has been reached by providing more detailed description of those languages which have or have had major use. Over 30 languages are mentioned, and numerous variations are described in the major contributors. A concluding summary notes the concepts and techniques either originating with simulation programming languages or given significant visibility by them