Impact of six rounds of mass drug administration on brugian filariasis and soil-transmitted helminth infections in Eastern Indonesia

BACKGROUND: The lymphatic filarial parasite Brugia timori occurs only in eastern Indonesia where it causes high morbidity. The absence of an animal reservoir, the inefficient transmission by Anopheles mosquitoes and the high sensitivity to DEC/albendazole treatment make this species a prime candidate for elimination by mass drug administration (MDA). METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the effect of MDA using DEC and albendazole on B. timori and soil transmitted helminths (STH) in a cross-sectional study of a sentinel village on Alor Island annually over a period of 10 years. Pre-MDA the microfilaria (MF) prevalence was 26% and 80% of the residents had filaria-specific IgG4 antibodies. In 2010, 34 months after the 6(th) round of MDA, MF and antibody rates were only 0.17% and 6.4%, respectively. The MDA campaign had also a beneficial effect on STH. Baseline prevalence rates for Ascaris, hookworm and Trichuris were 34%, 28%, and 11%, respectively; these rates were reduced to 27%, 4%, and 2% one year after the 5(th) round of MDA. Unfortunately, STH rates rebounded 34 months after cessation of MDA and approached pre-MDA rates. However, the intensity of STH infection in 2009 was still reduced, and no heavy infections were detected. CONCLUSIONS/SIGNIFICANCE: MDA with DEC/albendazole has had a major impact on B. timori MF and IgG4 antibody rates, providing a proof of principle that elimination is feasible. We also documented the value of annual DEC/albendazole as a mass de-worming intervention and the importance of continuing some form of STH control after cessation of MDA for filariasis

Solution structure of the inner DysF domain of myoferlin and implications for limb girdle muscular dystrophy type 2b

Mutations in the protein dysferlin, a member of the ferlin family, lead to limb girdle muscular dystrophy type 2B and Myoshi myopathy. The ferlins are large proteins characterised by multiple C2 domains and a single C-terminal membrane-spanning helix. However, there is sequence conservation in some of the ferlin family in regions outside the C2 domains. In one annotation of the domain structure of these proteins, an unusual internal duplication event has been noted where a putative domain is inserted in between the N- and C-terminal parts of a homologous domain. This domain is known as the DysF domain. Here, we present the solution structure of the inner DysF domain of the dysferlin paralogue myoferlin, which has a unique fold held together by stacking of arginine and tryptophans, mutations that lead to clinical disease in dysferlin

Genetic Determinants of Cardiovascular Events among Women with Migraine: A Genome-Wide Association Study

Migraine is associated with an increased risk for cardiovascular disease (CVD). Both migraine and CVD are highly heritable. However, the genetic liability for CVD among migraineurs is unclear.We performed a genome-wide association study for incident CVD events during 12 years of follow-up among 5,122 migraineurs participating in the population-based Women's Genome Health Study. Migraine was self-reported and CVD events were confirmed after medical records review. We calculated odds ratios (OR) and 95% confidence intervals (CI) and considered a genome-wide p-value <5×10(-8) as significant.Among the 5,122 women with migraine 164 incident CVD events occurred during follow-up. No SNP was associated with major CVD, ischemic stroke, myocardial infarction, or CVD death at the genome-wide level; however, five SNPs showed association with p<5×10(-6). Among migraineurs with aura rs7698623 in MEPE (OR = 6.37; 95% CI 3.15-12.90; p = 2.7×10(-7)) and rs4975709 in IRX4 (OR = 5.06; 95% CI 2.66-9.62; p = 7.7×10(-7)) appeared to be associated with ischemic stroke, rs2143678 located close to MDF1 with major CVD (OR = 3.05; 95% CI 1.98-4.69; p = 4.3×10(-7)), and the intergenic rs1406961 with CVD death (OR = 12.33; 95% CI 4.62-32.87; p = 5.2×10(-7)). Further, rs1047964 in BACE1 appeared to be associated with CVD death among women with any migraine (OR = 4.67; 95% CI 2.53-8.62; p = 8.0×10(-7)).Our results provide some suggestion for an association of five SNPs with CVD events among women with migraine; none of the results was genome-wide significant. Four associations appeared among migraineurs with aura, two of those with ischemic stroke. Although our population is among the largest with migraine and incident CVD information, these results must be treated with caution, given the limited number of CVD events among women with migraine and the low minor allele frequencies for three of the SNPs. Our results await independent replication and should be considered hypothesis generating for future research

Canadian report card on health equity across the life-course:Analysis of time trends and cross-national comparisons with the United Kingdom

Addressing social determinants of health (SDoH) has been acknowledged as an essential objective for the promotion of both population health and health equity. Extant literature has identified seven potential areas of investment to address SDoH: investments in sexual and reproductive health and family planning, early learning and child care, education, universal health care, as well as investments to reduce child poverty, ensure sustainable economic development, and control health hazards. The aim of this paper is to produce a ‘report card’ on Canada’s success in reducing socioeconomic and health inequities pertaining to these seven policy domains, and to assess how Canadian trends compare to those in the United Kingdom (UK), a country with a similar health and welfare system. Summarising evidence from published studies and national statistics, we found that Canada’s best successes were in reducing socioeconomic inequalities in early learning and child care and reproductive health—specifically in improving equity in maternal employment and infant mortality. Comparative data suggest that Canada’s outcomes in the latter areas were like those in the UK. In contrast, Canada’s least promising equity outcomes were in relation to health hazard control (specifically, tobacco) and child poverty. Though Canada and the UK observed similar inequities in smoking, Canada’s slow upward trend in child poverty prevalence is distinct from the UK’s small but steady reduction of child poverty. This divergence from the UK’s trends indicates that alternative investment types and levels may be needed in Canada to achieve similar outcomes to those in the UK. Keywords: Canada, United Kingdom, Health equity, Health and social policy, Lifecourse epidemiology, Public healt

A finite element model of the EUROSID dummy

36th Stapp Car Crash Conference, SEATTLE, ETATS-UNIS, 01-/11/1992 - 01/11/1992In occupant safety simulations it is desirable to extend existing rigid body occupant models towards deformable Finite Element models. Thereby a wider range of occupant / structure interactions can be covered and a better accuracy can be achieved. This paper describes some aspects of the FE modelling of the EUROSID thorax for use in an explicit Finite Element code. First a single rib model is evaluated, then a full thorax is generated and inserted into a rigid body Dummy model. Experimental results from impactor tests serve as a basis for the validation of the model

Good Efficacy of Artemether-Lumefantrine for Uncomplicated Falciparum Malaria in Eastern Sumba, East Nusatenggara, Indonesia

Aim: to evaluate the safety and efficacy of a fixed combination of artemether-lumefantrine for likely use against failures of the artesunate-amodiaquine first line therapy. Methods: the study was an open label single arm uncontrolled trial. we evaluated the safety and efficacy of standard artemether-lumefantrine therapy in 59 subjects with uncomplicated malaria caused by Plasmodium falciparum on the island of Sumba in eastern Indonesia. No treatment failures occurred up to day 35. One subject had recurrent parasitemia on day 42 that showed a genotype consistent with recrudescence. The efficacy of this therapy was thus estimated to be 98.3% (95% confidence interval=95%-100%). Descriptive analysis was done using the SPSS 12 computer software. Results: two hundred and thirteen P. falciparum patients met the inclusion criteria for in vivo efficacy study, 79 were given artemether-lumefantrine and 134 were treated under another protocol with artesunate-amodiaquine or sulfadoxine-pyrimethamine. Among 79 eligible subjects, 59 successfully completed the 42-day test. As expected, the mean PCT was longer than the mean FCT, i.e. 1.34+-0.67 (95% CI 1.21–1.47) and 1.05+-0.05 (95% CI 0.95–1.15) days, respectively. On day 3 of treatment, both fever and asexual stage of P. falciparum disappeared in all subjects. Observation until Day 35 showed that all of the 59 subjects treated with artemether-lumefantrine were cured. Conclusion: the findings of this uncontrolled study suggest good safety and efficacy of artemether-lumefantrine for treatment of uncomplicated falciparum malaria on Sumba Island in the Lesser Sundas archipelago of eastern Indonesia

Advances in finite element modelling of the EUROSID-1 dummy

ESV 1994, 14th International Technical Conference on the Enhanced Safety of Vehicles, MUNICH, ALLEMAGNE, 23-/05/1994 - 26/05/199