Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study

BACKGROUND: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. METHODS:We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families. Multivariable-adjusted residuals were computed using appropriate models (Cox proportional hazards, logistic, or linear regression) and the residuals from these models were used to test for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate [greater than or equal to]80%, minor allele frequency [greater than or equal to]10%, Hardy-Weinberg test p [greater than or equal to] 0.001).RESULTS:In family-based association test (FBAT) models, 8 SNPs in two regions approximately 500 kb apart on chromosome 1 (physical positions 73,091,610 and 73, 527,652) were associated with age at death (p-value < 10-5). The two sets of SNPs were in high linkage disequilibrium (minimum r2 = 0.58). The top 30 SNPs for generalized estimating equation (GEE) tests of association with age at death included rs10507486 (p = 0.0001) and rs4943794 (p = 0.0002), SNPs intronic to FOXO1A, a gene implicated in lifespan extension in animal models. FBAT models identified 7 SNPs and GEE models identified 9 SNPs associated with both age at death and morbidity-free survival at age 65 including rs2374983 near PON1. In the analysis of selected candidate genes, SNP associations (FBAT or GEE p-value < 0.01) were identified for age at death in or near the following genes: FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN. Top ranked SNP associations in the GEE model for age at natural menopause included rs6910534 (p = 0.00003) near FOXO3a and rs3751591 (p = 0.00006) in CYP19A1. Results of all longevity phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. CONCLUSION: Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging.

Optimisation of the food dairy coop supply chain

In the European Union under the Common Agricultural Policy (CAP) milk production was restricted by milk quotas since 1984. However, due to recent changes in the Common Agricultural Policy (CAP), milk quotas will be abolished by 2015. Therefore, the European dairy sector will soon face an opportunity, for the first time in a generation, to expand. Numerous studies have shown that milk production in Ireland will increase significantly post quotas (Laepple and Hennessy (2010), Donnellan and Hennessy (2007) and Lips and Reider (2005)). The research in this thesis explored milk transport and dairy product processing in the Irish dairy processing sector in the context of milk quota removal and expansion by 2020. In this study a national milk transport model was developed for the Irish dairy industry, the model was used to examine different efficiency factors in milk transport and to estimate milk transport costs post milk quota abolition. Secondly, the impact of different milk supply profiles on milk transport costs was investigated using the milk transport model. Current processing capacity in Ireland was compared against future supply, it was concluded that additional milk processing capacity would not be sufficient to process the additional milk. Thirdly, the milk transport model was used to identify the least cost locations (based on transport costs) to process the additional milk supply in 2020. Finally, an optimisation model was developed to identify the optimum configuration for the Irish dairy processing sector in 2020 taking cognisance of increasing transport costs and decreasing processing costs.

Practice-Level Variation in Outpatient Cardiac Care and Association With Outcomes.

BACKGROUND: Utilization of cardiac services varies across regions and hospitals, yet little is known regarding variation in the intensity of outpatient cardiac care across cardiology physician practices or the association with clinical endpoints, an area of potential importance to promote efficient care. METHODS AND RESULTS: We included 7 160 732 Medicare beneficiaries who received services from 5635 cardiology practices in 2012. Beneficiaries were assigned to practices providing the plurality of office visits, and practices were ranked and assigned to quartiles using the ratio of observed to predicted annual payments per beneficiary for common cardiac services (outpatient intensity index). The median (interquartile range) outpatient intensity index was 1.00 (0.81-1.24). Mean payments for beneficiaries attributed to practices in the highest (Q4) and lowest (Q1) quartile of outpatient intensity were: all cardiac payments (Q4 $1272 vs Q1 $581; ratio, 2.2); cardiac catheterization (Q4 $215 vs Q1 $64; ratio, 3.4); myocardial perfusion imaging (Q4 $253 vs Q1 $83; ratio, 3.0); and electrophysiology device procedures (Q4 $353 vs Q1 $142; ratio, 2.5). The adjusted odds ratios (95% CI) for 1 incremental quartile of outpatient intensity for each outcome was: cardiac surgical/procedural hospitalization (1.09 [1.09, 1.10]); cardiac medical hospitalization (1.00 [0.99, 1.00]); noncardiac hospitalization (0.99 [0.99, 0.99]); and death at 1 year (1.00 [0.99, 1.00]). CONCLUSION: Substantial variation in the intensity of outpatient care exists at the cardiology practice level, and higher intensity is not associated with reduced mortality or hospitalizations. Outpatient cardiac care is a potentially important target for efforts to improve efficiency in the Medicare population.

Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes.

Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.

Las igualdades producidas en el proceso de traducción algebraico: estudio de las igualdades correctas

En este trabajo se indican las tareas que debe realizar un usuario competente en el manejo del Método Cartesiano para poner un problema verbal en ecuaciones. Mediante el uso de una colección de 13 problemas de distintas subfamilias propuestos a 258 estudiantes de bachillerato, 15-18 años, se indaga la manera en que los estudiantes usan el Método cartesiano cuando producen igualdades correctas. Se concluye que los estudiantes producen una diversidad de igualdades correctas en las que manifiestan algunas preferencias y tendencias, encontrándose un invariante de conducta: todas las expresiones algebraicas que contienen las igualdades correctas provienen de una lectura algebraica del problema.

El diseño del laboratorio de física como herramienta para la resignificación de conceptos matemáticos

La presente ponencia resume el inicio de la construcción de un laboratorio de física y matemáticas en el programa de la Licenciatura en Matemáticas y Tecnologías de la Información, de la Universidad La Gran Colombia. Se presenta la experiencia en el diseño de la primera actividad y de los constructos teóricos y prácticos que se tuvieron en cuenta. Esta experiencia de aula está avalada dentro de la conformación de un semillero de investigación de la facultad, y muestra cómo a partir de un sistema masaresorte se pueden construir algunos conceptos fundamentales como el período de funciones, el comportamiento de las mismas y destacar la importancia del modelado de datos para su respectivo análisis y obtener así una aproximación por medio de la matemática.

Aircraft accident statistics and knowledge database: analyzing passenger behavior in aviation accidents

The Aircraft Accident Statistics and Knowledge (AASK) database is a repository of passenger accounts from survivable aviation accidents/incidents compiled from interview data collected by agencies such as the US NTSB. Its main purpose is to store observational and anecdotal data from the actual interviews of the occupants involved in aircraft accidents. The database has wide application to aviation safety analysis, being a source of factual data regarding the evacuation process. It also plays a significant role in the development of the airEXODUS aircraft evacuation model, where insight into how people actually behave during evacuation from survivable aircraft crashes is required. This paper describes the latest version of the database (Version 4.0) and includes some analysis of passenger behavior during actual accidents/incidents.

Effects of magnetic fields on crystal growth

The effects of a constant uniform magnetic field on dendritic solidification were investigated using a 2-dimensional enthalpy based numerical model. The interaction between thermoelectic currents and the magnetic field generates a Lorentz force that creates a flow. This flow causes a change in the morphology of the dendrite; secondary growth is promoted on one side of the dendrite arm and the tip velocity of the primary arm is increased.

A fast, streaming SIMD extensions 2, logistic squashing function

Schraudolph proposed an excellent exponential approximation providing increased performance particularly suited to the logistic squashing function used within many neural networking applications. This note applies Intel's streaming SIMD Extensions 2 (SSE2), where SIMD is single instruction multiple data, of the Pentum IV class processor to Schraudolph's technique, further increasing the performance of the logistic squashing function. It was found that the calculation of the new 32-bit SSE2 logistic squashing function described here was up to 38 times faster than the conventional exponential function and up to 16 times faster than a Schraudolph-style 32-bit method on an Intel Pentum D 3.6 GHz CPU.

Exploration of the student experience of e-learning: beginning to bridge the learning divide

Introduction This proposal aims, through debate within symposium to explore the student experience of e-learning. The team facilitating the discussion will draw upon their experience of an HEA funded pathfinder project, the main aim of which was to collect learner stories about their experience of using technology in their everyday learning activities at the University of Greenwich across a range of programmes, levels, locations and student groups. Method The project design responded to the growing body of student voice literature and then utilised and built upon the JISC-funded studies that focussed on understanding the learner perspectives on the role of technology in learning, namely: • the LEX study which investigated a broad spectrum of technology use by eliciting rich data about learners’ feelings, beliefs and intentions towards e-learning (Creanor et al, 2006); • the LXP studies which explored disciplinary differences in uses of technology by university students through a variety of methodologies (Conole et al, 2006). Results The symposium will be organised as a round table discussion that will be structured into three sections: • Designing an online survey tool, and the results of our survey. • Exploring student stories. • What can learned from the project and taking the findings back to enhance learning. To stimulate discussion each section will start by asking the participants to discuss and debate a particular question, this will be followed by an interactive presentation by the respective member of the project team who will share the findings of the project and invite contributions to the resulting discussion from personal perspectives. The questions are: • What is effective learning within a context of digital technology? • What are the myths and truths about the identity of today's learners? • What practical changes need to happen in order to see real change? Conclusion The final section of the symposium will invite contributions from the participants in order to collate the views and perspectives of all the participants in order to focus the discussion on the following: • The issues that have arisen as a result of the round table debates. • New speculative approaches to enhancing the student experience. • A controversial stand to the future of Higher Education teaching and learning and the role and integration of technology within that education. The symposium will provide an opportunity to explore the predictive value of Student Experience of E-Learning Laboratory (SEEL) project.

Student Experience of E-Learning (SEEL)

The Student Experience of E-Learning project (SEEL) was an institutional response to the university’s HEA/JISC Benchmarking exercise (Ryan and Kandler, 2007). The study had a social constructivist approach which recognised the importance of listening to the student voice (JISC 2007) within the University of Greenwich context, to interpret the student experience of e-learning. Nearly 1000 students responded to an online survey on their approaches to, and their use of, learning technology. The quantitative and qualitative questions used included identifying study patterns, using specific online tools, within the context of learning and beyond, and student’s attitudes towards using e-learning in their studies. Initially, individual responses to questions were analysed in depth, giving a general indication of the student experience. Further depth was applied through a filtering mechanism, beginning with a cross-slicing of individual student responses to produce cameos. Audio logs and individual interviews were drawn from these cameos. Analysis of the cameos is in progress but has already revealed some unexpected results. There was a mismatch between students’ expectations of the university’s use of technology and their experiences and awareness of its possible use in other contexts. Students recognised the importance of social interaction as a vehicle for learning (Vygotsky 1978, Bruner 2006) but expressed polarised views on the use of social networking sites such as Facebook for e-learning. Their experiences in commercial contexts led them to see the university VLE as unimaginative and the tutors’ use of it as lacking in vision. Whereas analysis of the individual questions provided a limited picture, the cameos gave a truer reflection of the students lived experiences and identified a gulf between the university’s provision and the students’ expectation of e-learning and their customary use of technology. However it is recognised that the very nature of an online survey necessarily excludes students who chose not to engage, either through lack of skills or through disillusionment and this would constitute a separate area for study.

La Web Semántica y los archivos de televisión: estado de la cuestión

Se analizan y describen las principales líneas de trabajo de la Web Semántica en el ámbito de los archivos de televisión. Para ello, se analiza y contextualiza la web semántica desde una perspectiva general para posteriormente analizar las principales iniciativas que trabajan con lo audiovisual: Proyecto MuNCH, Proyecto S5T, Semantic Television y VideoActive.

An Experimental and Predictive Evaluation of Unsteady Gas Flow through Automotive Catalyst Elements

The incorporation of one-dimensional simulation codes within engine modelling applications has proved to be a useful tool in evaluating unsteady gas flow through elements in the exhaust system. This paper reports on an experimental and theoretical investigation into the behaviour of unsteady gas flow through catalyst substrate elements. A one-dimensional (1-D) catalyst model has been incorporated into a 1-D simulation code to predict this behaviour.

Experimental data was acquired using a ‘single pulse’ test rig. Substrate samples were tested under ambient conditions in order to investigate a range of regimes experienced by the catalyst during operation. This allowed reflection and transmission characteristics to be quantified in relation to both geometric and physical properties of substrate elements. Correlation between measured and predicted results is demonstrably good and the model provides an effective analysis tool for evaluating unsteady gas flow through different catalytic converter designs.