Bayesian estimates of linkage disequilibrium

[Background] The maximum likelihood estimator of D' – a standard measure of linkage disequilibrium – is biased toward disequilibrium, and the bias is particularly evident in small samples and rare haplotypes. [Results] This paper proposes a Bayesian estimation of D' to address this problem. The reduction of the bias is achieved by using a prior distribution on the pair-wise associations between single nucleotide polymorphisms (SNP)s that increases the likelihood of equilibrium with increasing physical distances between pairs of SNPs. We show how to compute the Bayesian estimate using a stochastic estimation based on MCMC methods, and also propose a numerical approximation to the Bayesian estimates that can be used to estimate patterns of LD in large datasets of SNPs. [Conclusion] Our Bayesian estimator of D' corrects the bias toward disequilibrium that affects the maximum likelihood estimator. A consequence of this feature is a more objective view about the extent of linkage disequilibrium in the human genome, and a more realistic number of tagging SNPs to fully exploit the power of genome wide association studies.Research supported by NIH/NHLBI grant R21 HL080463-01, NIH/NIDDK 1R01DK069646-01A1 and the Spanish research program [projects TIN2004-06204-C03-02 and TIN2005-02516]

Metodología empleada por los entrenadores de hockey hierba-sala en España

The objective of this research has been to know the methodology used by grass-room hockey coaches throughout the national territory. A total of 172 coaches from all over Spain, (57 women, 33.10%  and 115 men, 66.90%), divided into 9 Autonomous Communities through a questionnaire were studied. The most relevant results showed that hockey coaches use both managerial and discovery teaching methods. Also, technical-tactical means are prioritized with respect to physical aspects, and the game is present in all sessions. The coaches consider, to a greater extent than the coaches, that the competition in these ages is adapted to the psychoevolutive characteristics of the players (p = 0.039). On the contrary, they are more in agreement with the fact of maintaining cordial relations with the parents of their players (p = 0.025).El objetivo de la presente investigación ha consistido en conocer la metodología empleada por los entrenadores de iniciación de hockey hierba-sala en todo el territorio nacional a través de un cuestionario. Participaron un total de 172 entrenadores de toda España (57 mujeres, 33.10% y 115 hombres, 66.90%), repartidos en 9 Comunidades Autónomas. Los resultados más relevantes mostraron que los entrenadores de hockey utilizan tanto métodos de enseñanza directivos, como de descubrimiento. Se priorizan los medios técnico-tácticos frente a los aspectos físicos, y el juego está presente en todas las sesiones. Las entrenadoras consideran, en mayor medida que los entrenadores, que la competición en estas edades está adaptada a las características psicoevolutivas de los jugadores y jugadoras (p=0.039). Por el contrario, ellos están más de acuerdo con el hecho de mantener relaciones cordiales con los padres de sus jugadores (p=0.025)

Limitations of selective deltamethrin application for triatomine control in central coastal Ecuador

<p>Abstract</p> <p>Background</p> <p>This year-long study evaluated the effectiveness of a strategy involving selective deltamethrin spraying and community education for control of Chagas disease vectors in domestic units located in rural communities of coastal Ecuador.</p> <p>Results</p> <p>Surveys for triatomines revealed peridomestic infestation with <it>Rhodnius ecuadoriensis </it>and <it>Panstrongylus howardi</it>, with infestation indices remaining high during the study (13%, 17%, and 10%, at initial, 6-month, and 12-month visits, respectively), which indicates a limitation of this strategy for triatomine population control. Infestation was found 6 and 12 months after spraying with deltamethrin. In addition, a large number of previously vector-free domestic units also were found infested at the 6- and 12-month surveys, which indicates new infestations by sylvatic triatomines. The predominance of young nymphs and adults suggests new infestation events, likely from sylvatic foci. In addition, infection with <it>Trypanosoma cruzi </it>was found in 65%, 21% and 29% at initial, 6-month and 12-month visits, respectively. All parasites isolated (n = 20) were identified as TcI.</p> <p>Conclusion</p> <p>New vector control strategies need to be devised and evaluated for reduction of <it>T. cruzi </it>transmission in this region.</p

Multivariable control of a grid-connected wind energy conversion system with power quality enhancement

This document is the Accepted Manuscript version of the following article: Kaddour Fouad, Houari Merabet Boulouiha, Ahmed Allali, Ali Taibi, and Mouloud Denai, ‘Multivariable control of a grid-connected wind energy conversion system with power quality enhancement’, Energy Systems, Vol. 9 (1): 25-57, February 2018. The final publication is available at Springer via: https://doi.org/10.1007/s12667-016-0223-7This paper proposes the design of a multivariable robust control strategy for a variable-speed WECS based on a SCIG. Optimal speed control of the SCIG is achieved by a conventional PI controller combined with a MPPT strategy. DTC-SVM technique based on a simple Clarke transformation is used to control the generator-side three-level converter in the variable speed WECS. The flow of real and reactive power between the inverter and the grid is controlled via the grid real and reactive currents and the DC link voltage using multivariable H∞ control. The overall WECS and control scheme are developed in Matlab/Simulink and the performance of the proposed control strategy is evaluated via a set of simulation scenarios replicating various operating conditions of the WECS such as variable wind speed and asymmetric single grid faults. The power quality of the WECS system under H∞ control control approach is assessed and the results show a significant improvement in the total harmonic distorsion as compared to that achieved with a classical PI control.Peer reviewedFinal Accepted Versio

AAV-mediated in vivo knockdown of luciferase using combinatorial RNAi and U1i

RNA interference (RNAi) has been successfully employed for specific inhibition of gene expression; however, safety and delivery of RNAi remain critical issues. We investigated the combinatorial use of RNAi and U1 interference (U1i). U1i is a gene-silencing technique that acts on the pre-mRNA by preventing polyadenylation. RNAi and U1i have distinct mechanisms of action in different cellular compartments and their combined effect allows usage of minimal doses, thereby avoiding toxicity while retaining high target inhibition. As a proof of concept, we investigated knockdown of the firefly luciferase reporter gene by combinatorial use of RNAi and U1i, and evaluated their inhibitory potential both in vitro and in vivo. Co-transfection of RNAi and U1i constructs showed additive reduction of luciferase expression up to 95% in vitro. We attained similar knockdown when RNAi and U1i constructs were hydrodynamically transfected into murine liver, demonstrating for the first time successful in vivo application of U1i. Moreover, we demonstrated long-term gene silencing by AAV-mediated transduction of murine muscle with RNAi/U1i constructs targeting firefly luciferase. In conclusion, these results provide a proof of principle for the combinatorial use of RNAi and U1i to enhance target gene knockdown in vivo

Reliability of a 1-week recall period for the Medical Outcomes Study Sleep Scale (MOS-SS) in patients with fibromyalgia

<p>Abstract</p> <p>Objective</p> <p>To evaluate the reliability of a one-week versus a four-week recall period of the Medical Outcomes Study Sleep Scale (MOS-SS) in patients with fibromyalgia (FM).</p> <p>Methods</p> <p>The MOS-SS was administered by mail to patients with a confirmed diagnosis of FM and a current pain rating of > 2 (0–10 point numerical rating scale) recruited through newspapers, support groups, and the Internet. Reliability of MOS-SS subscale domains was evaluated using test-retest methodology separated by a 1–3 day interval for the 4-week recall period and a 7-day interval for the 1-week recall period. Patient Impression of Change was evaluated for sleep, and for patients with no change, the intraclass correlation coefficient (ICC) and the Pearson correlation coefficient was calculated for MOS-SS subscales.</p> <p>Results</p> <p>Of 129 patients enrolled, 91.3% were female, mean age was 49.4 ± 11.0 years; self-rated FM severity was moderate-to-severe in 88.1% of patients. MOS-SS subscale scores were similar for both recall periods with little variation between test-retest. The 9-item Sleep Problems Index scores ranged from 57.2 ± 14.5 to 61.9 ± 15.8 across all assessments and demonstrated high reliability which was similar for the 1-week (ICC 0.81) and 4-week (ICC 0.89) recall periods. For the other MOS-SS subscales, the 1-week recall period also showed good reliability, which was consistent for the ICC and Pearson correlation coefficients.</p> <p>Conclusion</p> <p>A 1-week recall period is adequately reliable for use of the MOS-SS in studies evaluating sleep disturbance in patients with FM.</p

Microsatellites Reveal a High Population Structure in Triatoma infestans from Chuquisaca, Bolivia

Chagas disease is a protozoan infection caused by the parasite Trypanosoma cruzi. Chagas is prevalent throughout Central and South America, and it remains a chief concern in Bolivia. A movement that began in 1991 called the Southern Cone Initiative has been successful in reducing the incidence of Chagas disease in the Southern Cone countries of Argentina, Brazil, Chile, and Uruguay; but due to socio-economic and other factors, incidence remains high in Bolivia. The most important mode of transmission of T. cruzi to humans and other mammals is through feces of triatomine bugs. Thus, disease control and transmission prevention focus on elimination of triatomine vectors, and more specifically in Bolivia, it focuses on the elimination of Triatoma infestans. This study focuses on T. infestans in the Department of Chuquisaca, Bolivia. Ten highly variable microsatellite markers were used to analyze the population structure of insects collected in different towns. Statistical analyses show that T. infestans are highly structured, which means that they colonize on a small geographic scale. The results also suggest little active dispersal. These findings should be implemented during control efforts so that insecticide spraying focuses on geographic areas of colonization and re-colonization

A Field Trial of Alternative Targeted Screening Strategies for Chagas Disease in Arequipa, Peru

In the wake of emerging T. cruzi infection in children of periurban Arequipa, Peru, we conducted a prospective field trial to evaluate alternative targeted screening strategies for Chagas disease across the city. Using insect vector data that is routinely collected during Ministry of Health insecticide application campaigns in 3 periurban districts of Arequipa, we separated into 4 categories those households with 1) infected vectors; 2) high vector densities; 3) low vector densities; and 4) no vectors. Residents of all infected-vector households and a random sample of those in the other 3 categories were invited for serological screening for T. cruzi infection. Subsequently, all residents of households within a 15-meter radius of detected seropositive individuals were invited to be screened in a ring case-detection scheme. Of 923 participants, 21 (2.28%) were seropositive. There were no significant differences in prevalence across the 4 screening strategies, indicating that household entomologic factors alone could not predict the risk of infection. Indeed, the most predictive variable of infection was the number of years a person lived in a location with triatomine insects. Therefore, a simple residence history questionnaire may be a useful screening tool in large, diverse urban environments with emerging Chagas disease

Ska3 Ensures Timely Mitotic Progression by Interacting Directly With Microtubules and Ska1 Microtubule Binding Domain

The establishment of physical attachment between the kinetochore and dynamic spindle microtubules, which undergo cycles of polymerization and depolymerization generating straight and curved microtubule structures, is essential for accurate chromosome segregation. The Ndc80 and Ska complexes are the major microtubule-binding factors of the kinetochore responsible for maintaining chromosome-microtubule coupling during chromosome segregation. We previously showed that the Ska1 subunit of the Ska complex binds dynamic microtubules using multiple contact sites in a mode that allows conformation-independent binding. Here, we show that the Ska3 subunit is required to modulate the microtubule binding capability of the Ska complex (i) by directly interacting with tubulin monomers and (ii) indirectly by interacting with tubulin contacting regions of Ska1 suggesting an allosteric regulation. Perturbing either the Ska3-microtubule interaction or the Ska3-Ska1 interactions negatively influences microtubule binding by the Ska complex in vitro and affects the timely onset of anaphase in cells. Thus, Ska3 employs additional modulatory elements within the Ska complex to ensure robust kinetochore-microtubule attachments and timely progression of mitosis

Determination of Preferred pH for Root-knot Nematode Aggregation Using Pluronic F-127 Gel

Root-knot nematodes (Meloidogyne spp.) are obligate endoparasites of a wide range of plant species. The infective stage is attracted strongly to and enters host roots at the zone of elongation, but the compounds responsible for this attraction have not been identified. We developed a simple assay to investigate nematode response to chemical gradients that uses Pluronic F-127, a synthetic block copolymer that, as a 23% aqueous solution, forms a liquid at low temperature and a gel at room temperature. Test chemicals are put into a modified pipette tip, or ‘chemical dispenser,’ and dispensers are inserted into the gel in which nematodes have been dispersed. Meloidogyne hapla is attracted to pH gradients formed by acetic acid and several other Brønsted acids and aggregates between pH 4.5 and 5.4. While this pH range was attractive to all tested root-knot nematode strains and species, the level of aggregation depended on the species/strain assessed. For actively growing roots, the pH at the root surface is most acidic at the zone of elongation. This observation is consistent with the idea that low pH is an attractant for nematodes. Root-knot nematodes have been reported to be attracted to carbon dioxide, but our experiments suggest that the observed attraction may be due to acidification of solutions by dissolved CO2 rather than to CO2 itself. These results suggest that Pluronic F-127 gel will be broadly applicable for examining responses of a range of organisms to chemical gradients or to each other