81 research outputs found

    Particle Physics from Almost Commutative Spacetimes

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    Our aim in this review article is to present the applications of Connes' noncommutative geometry to elementary particle physics. Whereas the existing literature is mostly focused on a mathematical audience, in this article we introduce the ideas and concepts from noncommutative geometry using physicists' terminology, gearing towards the predictions that can be derived from the noncommutative description. Focusing on a light package of noncommutative geometry (so-called 'almost commutative manifolds'), we shall introduce in steps: electrodynamics, the electroweak model, culminating in the full Standard Model. We hope that our approach helps in understanding the role noncommutative geometry could play in describing particle physics models, eventually unifying them with Einstein's (geometrical) theory of gravity.Comment: 104 pages, 5 figures, version 2 (minor changes and some additional references

    Estimating and comparing incidence and prevalence of chronic diseases by combining GP registry data: the role of uncertainty

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    Background: Estimates of disease incidence and prevalence are core indicators of public health. The manner in which these indicators stand out against each other provide guidance as to which diseases are most common and what health problems deserve priority. Our aim was to investigate how routinely collected data from different general practitioner registration networks (GPRNs) can be combined to estimate incidence and prevalence of chronic diseases and to explore the role of uncertainty when comparing diseases. Methods. Incidence and prevalence counts, specified by gender and age, of 18 chronic diseases from 5 GPRNs in the Netherlands from the year 2007 were used as input. Generalized linear mixed models were fitted with the GPRN identifier acting as random intercept, and age and gender as explanatory variables. Using predictions of the regression models we estimated the incidence and prevalence for 18 chronic diseases and calculated a stochastic ranking of diseases in terms of incidence and prevalence per 1,000. Results: Incidence was highest for coronary heart disease and prevalence was highest for diabetes if we looked at the point estimates. The between GPRN variance in general was higher for incidence than for prevalence. Since uncertainty intervals were wide for some diseases and overlapped, the ranking of diseases was subject to uncertainty. For incidence shifts in rank of up to twelve positions were observed. For prevalence, most diseases shifted maximally three or four places in rank. Conclusion: Estimates of incidence and prevalence can be obtained by combining data from GPRNs. Uncertainty in the estimates of absolute figures may lead to different rankings of diseases and, hence, should be taken into consideration when comparing disease incidences and prevalences

    A survey of spectral models of gravity coupled to matter

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    This is a survey of the historical development of the Spectral Standard Model and beyond, starting with the ground breaking paper of Alain Connes in 1988 where he observed that there is a link between Higgs fields and finite noncommutative spaces. We present the important contributions that helped in the search and identification of the noncommutative space that characterizes the fine structure of space-time. The nature and properties of the noncommutative space are arrived at by independent routes and show the uniqueness of the Spectral Standard Model at low energies and the Pati-Salam unification model at high energies.Comment: An appendix is added to include scalar potential analysis for a Pati-Salam model. 58 Page

    Intersecting single-cell transcriptomics and genome-wide association studies identifies crucial cell populations and candidate genes for atherosclerosis

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    Genome-wide association studies (GWASs) have discovered hundreds of common genetic variants for atherosclerotic disease and cardiovascular risk factors. The translation of susceptibility loci into biological mechanisms and targets for drug discovery remains challenging. Intersecting genetic and gene expression data has led to the identification of candidate genes. However, previously studied tissues are often non-diseased and heterogeneous in cell composition, hindering accurate candidate prioritization. Therefore, we analysed single-cell transcriptomics from atherosclerotic plaques for cell-type-specific expression to identify atherosclerosis-associated candidate gene-cell pairs.\nWe applied gene-based analyses using GWAS summary statistics from 46 atherosclerotic and cardiovascular disease, risk factors, and other traits. We then intersected these candidates with single-cell RNA sequencing (scRNA-seq) data to identify genes specific for individual cell (sub)populations in atherosclerotic plaques. The coronary artery disease (CAD) loci demonstrated a prominent signal in plaque smooth muscle cells (SMCs) (SKI, KANK2, and SORT1) P-adj. = 0.0012, and endothelial cells (ECs) (SLC44A1, ATP2B1) P-adj. = 0.0011. Finally, we used liver-derived scRNA-seq data and showed hepatocyte-specific enrichment of genes involved in serum lipid levels.\nWe discovered novel and known gene-cell pairs pointing to new biological mechanisms of atherosclerotic disease. We highlight that loci associated with CAD reveal prominent association levels in mainly plaque SMC and EC populations. We present an intuitive single-cell transcriptomics-driven workflow rooted in human large-scale genetic studies to identify putative candidate genes and affected cells associated with cardiovascular traits. Collectively, our workflow allows for the identification of cell-specific targets relevant for atherosclerosis and can be universally applied to other complex genetic diseases and traits.Biopharmaceutic

    Incidence and prevalence of dementia in linked administrative health data in Saskatchewan, Canada: a retrospective cohort study.

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    Determining the epidemiology of dementia among the population as a whole in specific jurisdictions - including the long-term care population-is essential to providing appropriate care. The objectives of this study were to use linked administrative databases in the province of Saskatchewan to determine the 12-month incidence and prevalence of dementia for the 2012/13 period (1) among individuals aged 45 and older in the province of Saskatchewan, (2) according to age group and sex, and (3) according to diagnosis code and other case definition criteria
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