A method for sensitivity analysis to assess the effects of measurement error in multiple exposure variables using external validation data

Measurement error in self-reported dietary intakes is known to bias the association between dietary intake and a health outcome of interest such as risk of a disease. The association can be distorted further by mismeasured confounders, leading to invalid results and conclusions. It is, however, difficult to adjust for the bias in the association when there is no internal validation data

International Lattice Data Grid

We propose the co-ordination of lattice QCD grid developments in different countries to allow transparent exchange of gauge configurations in future, should participants wish to do so. We describe briefly UKQCD's XML schema for labelling and cataloguing the data. A meeting to further develop these ideas will be held in Edinburgh on 19/20 December 2002, and will be available over AccessGrid.Comment: Lattice2002(plenary

Structure of 55Sc and development of the N=34 subshell closure

The low-lying structure of $^{55}$Sc has been investigated using in-beam $\gamma$-ray spectroscopy with the $^{9}$Be($^{56}$Ti,$^{55}$Sc+$\gamma$)$X$ one-proton removal and $^{9}$Be($^{55}$Sc,$^{55}$Sc+$\gamma$)$X$ inelastic-scattering reactions at the RIKEN Radioactive Isotope Beam Factory. Transitions with energies of 572(4), 695(5), 1539(10), 1730(20), 1854(27), 2091(19), 2452(26), and 3241(39) keV are reported, and a level scheme has been constructed using $\gamma\gamma$ coincidence relationships and $\gamma$-ray relative intensities. The results are compared to large-scale shell-model calculations in the $sd$-$pf$ model space, which account for positive-parity states from proton-hole cross-shell excitations, and to it ab initio shell-model calculations from the in-medium similarity renormalization group that includes three-nucleon forces explicitly. The results of proton-removal reaction theory with the eikonal model approach were adopted to aid identification of positive-parity states in the level scheme; experimental counterparts of theoretical $1/2^{+}_{1}$ and $3/2^{+}_{1}$ states are suggested from measured decay patterns. The energy of the first $3/2^{-}$ state, which is sensitive to the neutron shell gap at the Fermi surface, was determined. The result indicates a rapid weakening of the $N=34$ subshell closure in $pf$-shell nuclei at $Z>20$, even when only a single proton occupies the $\pi f_{7/2}$ orbital

Glassy Dynamics of Protein Folding

A coarse grained model of a random polypeptide chain, with only discrete torsional degrees of freedom and Hookean springs connecting pairs of hydrophobic residues is shown to display stretched exponential relaxation under Metropolis dynamics at low temperatures with the exponent $\beta\simeq 1/4$, in agreement with the best experimental results. The time dependent correlation functions for fluctuations about the native state, computed in the Gaussian approximation for real proteins, have also been found to have the same functional form. Our results indicate that the energy landscape exhibits universal features over a very large range of energies and is relatively independent of the specific dynamics.Comment: RevTeX, 4 pages, multicolumn, including 5 figures; larger computations performed, error bars improve

Structural evolution in the neutron-rich nuclei 106Zr and 108Zr

The low-lying states in 106Zr and 108Zr have been investigated by means of {\beta}-{\gamma} and isomer spectroscopy at the RI beam factory, respectively. A new isomer with a half-life of 620\pm150 ns has been identified in 108Zr. For the sequence of even-even Zr isotopes, the excitation energies of the first 2+ states reach a minimum at N = 64 and gradually increase as the neutron number increases up to N = 68, suggesting a deformed sub-shell closure at N = 64. The deformed ground state of 108Zr indicates that a spherical sub-shell gap predicted at N = 70 is not large enough to change the ground state of 108Zr to the spherical shape. The possibility of a tetrahedral shape isomer in 108Zr is also discussed.Comment: 10 pages, 3 figures, Accepted for publication in Phys. Rev. Let

Association studies of transforming growth factor-beta 1 and Alzheimer’s disease

Substantial laboratory evidence suggests Transforming Growth Factor-b1 (TGFB1) is linked to Alzheimer's Disease (AD) pathology. The purpose of the study was to estimate the genetic association of TGFB1 with AD while controlling for apolipoprotein E4 allele (APOE4) status, the only well-established genetic risk factor for AD. Two study populations were genotyped for the TGFB1À509 and þ869 single nucleotide polymorphisms (SNPs) that have been associated with TGFB1 levels. Constituting these populations were 203 families from the NIMH AD Genetic Initiative with at least two affected siblings and a normal sibling, and a population of 126 AfricanAmerican (AA) AD cases versus 93 age matched controls. Results from family-based analyses showed a significant association between the TGFB1 À509 SNP and AD for the entire set of 203 families (P ¼ 0.007), and a subset of these families without a homozygous APOE4 family member (P ¼ 0.026). Results from family-based analyses on the TGFB1 þ869 SNP were not significant in the 203 families. While associations for the main effects of the TGFB1 þ869 and À509 SNP with AD in the AA case-control study were also not significant, results did indicate that TGFB1 may function as an effect modifier of APOE4 risk. Specifically, the odds of AD associated with having at least one APOE4 allele increased in an additive fashion with one or two copies of the higher producer allele when stratified by TGFB1 À509 genotype and by TGFB1 þ869 genotype. Results support a role for TGFB1 in AD pathogenesis

Conformations of Proteins in Equilibrium

We introduce a simple theoretical approach for an equilibrium study of proteins with known native state structures. We test our approach with results on well-studied globular proteins, Chymotrypsin Inhibitor (2ci2), Barnase and the alpha spectrin SH3 domain and present evidence for a hierarchical onset of order on lowering the temperature with significant organization at the local level even at high temperatures. A further application to the folding process of HIV-1 protease shows that the model can be reliably used to identify key folding sites that are responsible for the development of drug resistance .Comment: 6 pages, 3 eps figure

Experiences of refugees and asylum seekers in general practice: a qualitative study

Background: There has been much debate regarding the refugee health situation in the UK. However most of the existing literature fails to take account of the opinions of refugees themselves. This study was established to determine the views of asylum seekers and refugees on their overall experiences in primary care and to suggest improvements to their care. Methods: Qualitative study of adult asylum seekers and refugees who had entered the UK in the last 10 years. The study was set in Barnet Refugee Walk in Service, London. 11 Semi structured interviews were conducted and analysed using framework analysis. Results: Access to GPs may be more difficult for failed asylum seekers and those without support from refugee agencies or family. There may be concerns amongst some in the refugee community regarding the access to and confidentiality of professional interpreters. Most participants stated their preference for GPs who offered advice rather than prescriptions. The stigma associated with refugee status in the UK may have led to some refugees altering their help seeking behaviour. Conclusion: The problem of poor access for those with inadequate support may be improved by better education and support for GPs in how to provide for refugees. Primary Care Trusts could also supply information to newly arrived refugees on how to access services. GPs should be aware that, in some situations, professional interpreters may not always be desired and that instead, it may be advisable to reach a consensus as to who should be used as an interpreter. A better doctor-patient experience resulting from improvements in access and communication may help to reduce the stigma associated with refugee status and lead to more appropriate help seeking behaviour. Given the small nature of our investigation, larger studies need to be conducted to confirm and to quantify these results

Protein structures and optimal folding emerging from a geometrical variational principle

Novel numerical techniques, validated by an analysis of barnase and chymotrypsin inhibitor, are used to elucidate the paramount role played by the geometry of the protein backbone in steering the folding to the correct native state. It is found that, irrespective of the sequence, the native state of a protein has exceedingly large number of conformations with a given amount of structural overlap compared to other compact artificial backbones; moreover the conformational entropies of unrelated proteins of the same length are nearly equal at any given stage of folding. These results are suggestive of an extremality principle underlying protein evolution, which, in turn, is shown to be associated with the emergence of secondary structures.Comment: Revtex, 5 pages, 5 postscript figure