Genetic Variation and Antioxidant Response Gene Expression in the Bronchial Airway Epithelium of Smokers at Risk for Lung Cancer

Prior microarray studies of smokers at high risk for lung cancer have demonstrated that heterogeneity in bronchial airway epithelial cell gene expression response to smoking can serve as an early diagnostic biomarker for lung cancer. As a first step in applying functional genomic analysis to population studies, we have examined the relationship between gene expression variation and genetic variation in a central molecular pathway (NRF2-mediated antioxidant response) associated with smoking exposure and lung cancer. We assessed global gene expression in histologically normal airway epithelial cells obtained at bronchoscopy from smokers who developed lung cancer (SC, n=20), smokers without lung cancer (SNC, n=24), and never smokers (NS, n=8). Functional enrichment analysis showed that the NRF2-mediated, antioxidant response element (ARE)-regulated genes, were significantly lower in SC, when compared with expression levels in SNC. Importantly, we found that the expression of MAFG (a binding partner of NRF2) was correlated with the expression of ARE genes, suggesting MAFG levels may limit target gene induction. Bioinformatically we identified single nucleotide polymorphisms (SNPs) in putative ARE genes and to test the impact of genetic variation, we genotyped these putative regulatory SNPs and other tag SNPs in selected NRF2 pathway genes. Sequencing MAFG locus, we identified 30 novel SNPs and two were associated with either gene expression or lung cancer status among smokers. This work demonstrates an analysis approach that integrates bioinformatics pathway and transcription factor binding site analysis with genotype, gene expression and disease status to identify SNPs that may be associated with individual differences in gene expression and/or cancer status in smokers. These polymorphisms might ultimately contribute to lung cancer risk via their effect on the airway gene expression response to tobacco-smoke exposure.Intramural Research Program of the National Institute of Environmental Health Sciences; National Institutes of Health (Z01 ES100475, U01ES016035, R01CA124640

e-Social Science and Evidence-Based Policy Assessment : Challenges and Solutions

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UCL Qualitative health research symposium 2017: collaboration in qualitative health research

In recent years, there have been increasing calls for collaboration between academia and the wider healthcare community in health research. This is largely driven by efforts to engage the public in the “co-production” of evidence-based healthcare and healthcare decision-making, as well as penetrate borders between disciplines. As a result, traditional "lone researcher" models of qualitative health research have shifted to include research teams which are increasingly made up of qualitative researchers alongside quantitative researchers, members of the public, health professionals, policy-makers and other stakeholders. In these ways, health research is assumed to be more relevant, ethically justifiable, and broadly applicable. However, such collaborations may be complex and may create challenges. To date, there has been limited critical consideration of these challenges and little is known about the assumptions and effectiveness of these collaborations. We organised a one-day symposium to explore themes related to engagement, co-production and collaborative meaning making in qualitative health research. The oral presentations and posters used examples of collaborative studies to critically explore the processes used to carry out research as a diverse team. The discussions throughout the day alluded to the need to understand the multiple forms and levels of patient and public involvement in research, and distinguish between patient representatives and members of the public. Collaborative research requires flexibility, and might lead the researcher to occupy “mediating” roles such as that of the “cultural broker” or “boundary spanner”. The symposium created a forum to critically reflect on current approaches to inform improved ways of collaborating and engaging with diverse stakeholders to meaningfully impact on health and healthcare delivery. We should continue to search for ways to unpack the concept of “collaboration” to identify the purpose of collaborative relationships, the required activities and the actors involved

It’s hard to reach the "hard-to-reach": the challenges of recruiting people who do not access preventative healthcare services into interview studies

In this article, we discuss the challenges faced in recruiting “hard-to-reach” groups for interview studies, specifically those who do not access preventative healthcare services. We do this by reflecting on the varying success of different recruitment methods we have used in two recent studies; one investigating ethnic disparities in human papillomavirus vaccination uptake and another exploring difference in cervical screening non-participation. Engaging new community groups to help with recruitment proved particularly difficult, as did recruiting online. Our most successful recruitment methods included recruiting through community groups with whom we had previously established relationships, recruiting through schools and re-contacting participants who previously completed a related survey. We conclude that successful recruitment is dependent on study awareness and engagement. We urge others to be transparent in reporting recruitment methods in order to benefit the qualitative research community and suggest that details are published as supplementary material alongside qualitative articles in future

Challenging Methods and Results Obtained from User-Generated Content in Barcelona’s Public Open Spaces

User-generated content (UGC) provides useful resources for academics, technicians and policymakers to obtain and analyse results in order to improve lives of individuals in urban settings. User-generated content comes from people who voluntarily contribute data, information, or media that then appears in a way which can be viewed by others; usually on the Web. However, to date little is known about how complex methodologies for getting results are subject to methodology-formation errors, personal data protection, and reliability of outcomes. Different researches have been approaching to inquire big data methods for a better understanding of social groups for planners and economic needs. In this chapter, through UGC from Tweets of users located in Barcelona, we present different research experiments. Data collection is based on the use of REST API; while analysis and representation of UGC follow different ways of processing and providing a plurality of information. The first objective is to study the results at a different geographical scale, Barcelona’s Metropolitan Area and at two Public Open Spaces (POS) in Barcelona, Enric Granados Street and the area around the Fòrum de les Cultures; during similar days in two periods of time - in January of 2015 and 2017. The second objective is intended to better understand how different types of POS’ Twitter-users draw urban patterns. The Origin-Destination patterns generated illustrate new social behaviours, addressed to multifunctional uses. This chapter aims to be influential in the use of UGC analysis for planning purposes and to increase quality of life

Desynchronization and Wave Pattern Formation in MPI-Parallel and Hybrid Memory-Bound Programs

Analytic, first-principles performance modeling of distributed-memory parallel codes is notoriously imprecise. Even for applications with extremely regular and homogeneous compute-communicate phases, simply adding communication time to computation time does often not yield a satisfactory prediction of parallel runtime due to deviations from the expected simple lockstep pattern caused by system noise, variations in communication time, and inherent load imbalance. In this paper, we highlight the specific cases of provoked and spontaneous desynchronization of memory-bound, bulk-synchronous pure MPI and hybrid MPI+OpenMP programs. Using simple microbenchmarks we observe that although desynchronization can introduce increased waiting time per process, it does not necessarily cause lower resource utilization but can lead to an increase in available bandwidth per core. In case of significant communication overhead, even natural noise can shove the system into a state of automatic overlap of communication and computation, improving the overall time to solution. The saturation point, i.e., the number of processes per memory domain required to achieve full memory bandwidth, is pivotal in the dynamics of this process and the emerging stable wave pattern. We also demonstrate how hybrid MPI-OpenMP programming can prevent desirable desynchronization by eliminating the bandwidth bottleneck among processes. A Chebyshev filter diagonalization application is used to demonstrate some of the observed effects in a realistic setting.Comment: 18 pages, 8 figure

Sunglass Filter Transmission and Its Operational Effect in Solar Protection for Civilian Pilots.

INTRODUCTION: The ocular effects of excess solar radiation exposure are well documented. Recent evidence suggests that ocular ultraviolet radiation (UVR) exposure to professional pilots may fall outside international guideline limits unless eye protection is used. Nonprescription sunglasses should be manufactured to meet either international or national standards. The mean increase in UVR and blue light hazards at altitude has been quantified and the aim of this research was to assess the effectiveness of typical pilot sunglasses in reducing UVR and blue light hazard exposure in flight. METHOD: A series of sunglass filter transmittance measurements were taken from personal sunglasses (N = 20) used by pilots together with a series of new sunglasses (N = 18). RESULTS: All nonprescription sunglasses measured conformed to international standards for UVR transmittance and offered sufficient UVR protection for pilots. There was no difference between right and left lenses or between new and used sunglasses. All sunglasses offered sufficient attenuation to counter the mean increase in blue light exposure that pilots experience at altitude, although used sunglasses with scratched lenses were marginally less effective. One pair of prescription sunglasses offered insufficient UVR attenuation for some flights, but would have met requirements of international and national standards for UV-A transmittance. This was likely due to insufficient UVR blocking properties of the lens material. CONCLUSIONS: Lenses manufactured to minimally comply with standards for UVR transmittance could result in excess UVR exposure to a pilot based on in-flight irradiance data; an additional requirement of less than 10% transmittance at 380 nm is recommended

Giga-Hertz quantized charge pumping in bottom gate defined InAs nanowire quantum dots

Semiconducting nanowires (NWs) are a versatile, highly tunable material platform at the heart of many new developments in nanoscale and quantum physics. Here, we demonstrate charge pumping, i.e., the controlled transport of individual electrons through an InAs NW quantum dot (QD) device at frequencies up to $1.3\,$GHz. The QD is induced electrostatically in the NW by a series of local bottom gates in a state of the art device geometry. A periodic modulation of a single gate is enough to obtain a dc current proportional to the frequency of the modulation. The dc bias, the modulation amplitude and the gate voltages on the local gates can be used to control the number of charges conveyed per cycle. Charge pumping in InAs NWs is relevant not only in metrology as a current standard, but also opens up the opportunity to investigate a variety of exotic states of matter, e.g. Majorana modes, by single electron spectroscopy and correlation experiments.Comment: 21 page