Associations between SNPs in candidate immune-relevant genes and rubella antibody levels: a multigenic assessment

<p>Abstract</p> <p>Background</p> <p>The mechanisms of immune response are structured within a highly complex regulatory system. Genetic associations with variation in the immune response to rubella vaccine have typically been assessed one locus at a time. We simultaneously assessed the associations between 726 SNPs tagging 84 candidate immune response genes and rubella-specific antibody levels. Blood samples were obtained from 714 school-aged children who had received two doses of MMR vaccine. Associations between rubella-specific antibody levels and 726 candidate tagSNPs were assessed both one SNP at a time and in a variety of multigenic analyses.</p> <p>Results</p> <p>Single-SNP assessments identified 4 SNPs that appeared to be univariately associated with rubella antibody levels: rs2844482 (p = 0.0002) and rs2857708 (p = 0.001) in the 5'UTR of the LTA gene, rs7801617 in the 5'UTR of the IL6 gene (p = 0.0005), and rs4787947 in the 5'UTR of the IL4R gene (p = 0.002). While there was not significant evidence in favor of epistatic genetic associations among the candidate SNPs, multigenic analyses identified 29 SNPs significantly associated with rubella antibody levels when selected as a group (p = 0.017). This collection of SNPs included not only those that were significant univariately, but others that would not have been identified if only considered in isolation from the other SNPs.</p> <p>Conclusions</p> <p>For the first time, multigenic assessment of associations between candidate SNPs and rubella antibody levels identified a broad number of genetic associations that would not have been deemed important univariately. It is important to consider approaches like those applied here in order to better understand the full genetic complexity of response to vaccination.</p

Interaction of teachers with parentsin the solution of the problems of literary development preschool children

Статья посвящена проблеме взаимодействия педагогов и родителей как социальных партнеров детского сада в вопросах литературного развития детей дошкольного возраста. Обоснована необходимость литературного развития дошкольников в условиях сотрудничества семьи и детского сада. Обобщены теоретические аспекты проблемы литературного развития дошкольников: скорректировано определение данного понятия, перечислены задачи литературного развития, читательские и художественно-речевые умения, которые формируются у ребенка в процессе полноценного восприятия произведения и под его влиянием в регламентированной и свободной деятельности детей. Описан опыт педагогов филиала МБДОУ детский сад "Детство" - детского сада No. 40/228 г. Екатеринбурга по литературному развитию детей дошкольного возраста посредством внедрения разных форм взаимодействия участников образовательного процесса: мастер-класса "Сказка на песке", проектов "Чудо-дерево" и "Книжный календарь", конкурса лэпбуков "Сказка нашей семьи".The article is devoted to the problem of interaction between teachers and parents as social partners of the kindergarten in the literary development of preschool children. The necessity of literary development of preschoolers in the conditions of family and kindergarten cooperation is substantiated. The theoretical aspects of the problem of literary development of preschoolers are summarized: the definition of this concept is adjusted, the tasks of literary development, reading and artistic and speech skills that are formed in a child in the process of a full perception of a work and under its influence in a regulated and free activity of children are listed. The experience of teachers of kindergarten No. 40/228 in Yekaterinburg on the literary development of preschool children through the introduction of various forms of interaction between participants in the educational process: the master class “Tale in the Sand”, the projects “Miracle Tree” and “Book Calendar”, a competition for laptops is described “The Tale of Our Family”

STUDY OF THE EFFICIENCY AND SAFETY OF MYCOPHENOLATE MOFETIL THERAPY IN PATIENTSWITH SYSTEMIC SCLERODERMA

Interstitial lung disease (ILD) is one of the major causes of death in systemic scleroderma (SSD). Treatment of these patients remains difficult and controversial. Mycophenolate mofetil (MPM) has been in vitro shown to inhibit overproduction of type I collagen and hence may be effective against SSD. Objective: to study the efficiency and safety of MPM therapy in patients with SSD and clinically relevant ILD in an open-label prospective study. Subjects and methods. Ten patients with SSD (7 and 3 with its diffuse and limited forms, respectively) and ILD were given MPM in combination with glucocorticoids (mean daily dose was 10+4 mg). The mean MPM therapy duration was 11.4+1.3 months. The Rodnan total skin thickness score, flexion index, forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and European Scleroderma Study Group (EScSG) activity index were estimated and a 6-minute walk test (6MWT) was carried out before and after MPM therapy. Results. After therapy, the whole group showed a significant reduction in skin scores from 12.9+9.8 to 5.6+3.2 (p=0.036) and EScSG from 3.9+1.4 to 2.25+1.03 (p=0.015) and an increase in exercise tolerance from 446+155 to 535+78 m (p=0.03) as evidenced by 6MWT. The degree of flexion contractures decreased from 15+21 to 3.7+11.3 mm (p>0.05). FVC (77.8+18.7% versus 73.8+11.3%) and DLCO (45+14.4% versus 42+16.4%) were significantly unchanged. A 10% or more clinically significant fall was noted in FVC and DLCO in 3 and 1 patients, respectively. In the remaining patients, the lung functional test results remained stable. MPM tolerability was satisfactory. All the patients completed their course of treatment. Conclusion. Stabilization of lung function with higher exercise tolerance and significantly reduced skin density allow therapy with MPM in combination with low-dose glucocorticoids to be regarded as an effective and well-tolerated treatment in patients with ILD in the presence of SS

The LBNO long-baseline oscillation sensitivities with two conventional neutrino beams at different baselines

The proposed Long Baseline Neutrino Observatory (LBNO) initially consists of $\sim 20$ kton liquid double phase TPC complemented by a magnetised iron calorimeter, to be installed at the Pyh\"asalmi mine, at a distance of 2300 km from CERN. The conventional neutrino beam is produced by 400 GeV protons accelerated at the SPS accelerator delivering 700 kW of power. The long baseline provides a unique opportunity to study neutrino flavour oscillations over their 1st and 2nd oscillation maxima exploring the $L/E$ behaviour, and distinguishing effects arising from $\delta_{CP}$ and matter. In this paper we show how this comprehensive physics case can be further enhanced and complemented if a neutrino beam produced at the Protvino IHEP accelerator complex, at a distance of 1160 km, and with modest power of 450 kW is aimed towards the same far detectors. We show that the coupling of two independent sub-MW conventional neutrino and antineutrino beams at different baselines from CERN and Protvino will allow to measure CP violation in the leptonic sector at a confidence level of at least $3\sigma$ for 50\% of the true values of $\delta_{CP}$ with a 20 kton detector. With a far detector of 70 kton, the combination allows a $3\sigma$ sensitivity for 75\% of the true values of $\delta_{CP}$ after 10 years of running. Running two independent neutrino beams, each at a power below 1 MW, is more within today's state of the art than the long-term operation of a new single high-energy multi-MW facility, which has several technical challenges and will likely require a learning curve.Comment: 21 pages, 12 figure

Search for short baseline nu(e) disappearance with the T2K near detector

8 pages, 6 figures, submitted to PRD rapid communication8 pages, 6 figures, submitted to PRD rapid communicationWe thank the J-PARC staff for superb accelerator performance and the CERN NA61 collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC and CFI, Canada; Commissariat `a l’Energie Atomique and Centre National de la Recherche Scientifique–Institut National de Physique Nucle´aire et de Physique des Particules, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; Russian Science Foundation, RFBR and Ministry of Education and Science, Russia; MINECO and European Regional Development Fund, Spain; Swiss National Science Foundation and State Secretariat for Education, Research and Innovation, Switzerland; STFC, UK; and DOE, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK. In addition participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; DOE Early Career program, USA

Measurement of νˉμ\bar{\nu}_{\mu} and νμ\nu_{\mu} charged current inclusive cross sections and their ratio with the T2K off-axis near detector

We report a measurement of cross section $\sigma(\nu_{\mu}+{\rm nucleus}\rightarrow\mu^{-}+X)$ and the first measurements of the cross section $\sigma(\bar{\nu}_{\mu}+{\rm nucleus}\rightarrow\mu^{+}+X)$ and their ratio $R(\frac{\sigma(\bar \nu)}{\sigma(\nu)})$ at (anti-)neutrino energies below 1.5 GeV. We determine the single momentum bin cross section measurements, averaged over the T2K $\bar{\nu}/\nu$-flux, for the detector target material (mainly Carbon, Oxygen, Hydrogen and Copper) with phase space restricted laboratory frame kinematics of $\theta_{\mu}$500 MeV/c. The results are $\sigma(\bar{\nu})=\left( 0.900\pm0.029{\rm (stat.)}\pm0.088{\rm (syst.)}\right)\times10^{-39}$ and $\sigma(\nu)=\left( 2.41\ \pm0.022{\rm{(stat.)}}\pm0.231{\rm (syst.)}\ \right)\times10^{-39}$in units of cm$^{2}$/nucleon and$R\left(\frac{\sigma(\bar{\nu})}{\sigma(\nu)}\right)= 0.373\pm0.012{\rm (stat.)}\pm0.015{\rm (syst.)}$.Comment: 18 pages, 8 figure

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA

Measurement of the electron neutrino charged-current interaction rate on water with the T2K ND280 pi(0) detector

10 pages, 6 figures, Submitted to PRDhttp://journals.aps.org/prd/abstract/10.1103/PhysRevD.91.112010© 2015 American Physical Society11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PR