Clinical practice: Coeliac disease

Coeliac disease (CD) is an immune-mediated systemic condition elicited by gluten and related prolamines in genetically predisposed individuals and characterised by gluten-induced symptoms and signs, specific antibodies, a specific human leukocyte antigen (HLA) type and enteropathy. The risk of coeliac disease is increased in first-degree relatives, certain syndromes including Down syndrome and autoimmune disorders. It is thought to occur in 1 in 100–200 individuals, but still only one in four cases is diagnosed. Small-bowel biopsy is no longer deemed necessary in a subgroup of patients, i.e. when all of the following are present: typical symptoms or signs, high titres of and transglutaminase antibodies, endomysial antibodies, and HLA-type DQ2 or DQ8. In all other cases, small-bowel biopsy remains mandatory for a correct diagnosis. Therapy consists of a strictly gluten-free diet. This should result in complete disappearance of symptoms and of serological markers. Adequate follow-up is considered essential. Conclusion: Although small-bowel biopsy may be omitted in a minority of patients, small-bowel biopsy is essential for a correct diagnosis of CD in all other cases. Diagnostic work-up should be completed before treatment with gluten-free diet instituted

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

q and p(m) dependence of the He-3(e,e ' d)p reaction

The cross section for the He-3(e, e'd)p reaction has been measured for a range of missing momentum p, at incident electron energies of 370 and 576 MeV and for values of the three-momentum transfer q of 412, 504, and 604 MeV/c. The longitudinal and transverse structure functions have been separated for q = 412 and 504 MeV/c. The data are compared to exact three-body Faddeev calculations and calculations based on a covariant, gauge-invariant diagrammatic expansion. In general, fair to good agreement is observed, but there are some differences between the data and the calculations, especially for the q dependence and for the transverse structure function W-T

The He-3(e, e ' d)p reaction in (q, omega)-constant kinematics

The cross section for the He-3(e, c' d)p reaction has been measured as a function of the missing momentum p(m) in (q, omega)-constant kinematics at beam energies of 370 and 576 MeV for values of the three-momentum transfer q of 412, 504 and 604 MeV/c. The L(+ TT), T and LT structure functions have been separated for q = 412 and 504 MeV/c. The data are compared to three-body Faddeev calculations, including meson-exchange currents (MEC), and to calculations based on a covariant diagrammatic expansion. The influence of final-state interactions and meson-exchange currents is discussed. The p(m)-dependence of the data is reasonably well described by all calculations. However, the most advanced Faddeev calculations, which employ the AV 18 nucleon-nucleon interaction and include MEC, overestimate the measured cross sections, especially the longitudinal part, and at the larger values of q. The diagrammatic approach gives a fair description of the cross section, but under(over)estimates the longitudinal (transverse) structure function. (C) 2002 Elsevier Science B.V. All rights reserved

Phased whole-genome genetic risk in a family quartet using a major allele reference sequence

Whole-genome sequencing harbors unprecedented potential for characterization of individual and family genetic variation. Here, we develop a novel synthetic human reference sequence that is ethnically concordant and use it for the analysis of genomes from a nuclear family with history of familial thrombophilia. We demonstrate that the use of the major allele reference sequence results in improved genotype accuracy for disease-associated variant loci. We infer recombination sites to the lowest median resolution demonstrated to date (< 1,000 base pairs). We use family inheritance state analysis to control sequencing error and inform family-wide haplotype phasing, allowing quantification of genome-wide compound heterozygosity. We develop a sequence-based methodology for Human Leukocyte Antigen typing that contributes to disease risk prediction. Finally, we advance methods for analysis of disease and pharmacogenomic risk across the coding and non-coding genome that incorporate phased variant data. We show these methods are capable of identifying multigenic risk for inherited thrombophilia and informing the appropriate pharmacological therapy. These ethnicity-specific, family-based approaches to interpretation of genetic variation are emblematic of the next generation of genetic risk assessment using whole-genome sequencing