Data quality in European primary care research databases. Report of a workshop held in London September 2013

Primary care research databases provide a significant resource for health services and epidemiological research. However since data are recorded primarily for clinical care their suitability for research may vary widely according to the research application or recording practices of individual general practitioners. A methodological approach for characterising data quality is required. We describe a one-day workshop entitled “Towards a common protocol for measuring and monitoring data quality in European primary care research databases”. Researchers, database experts and clinicians were invited to give their perspectives on data quality and to exchange ideas on what data quality metrics should be made available to researchers. We report the main outcomes of this workshop, including a summary of the presentations and discussions and suggested way forward

A pragmatic approach for measuring data quality in primary care databases

There is currently no widely recognised methodology for undertaking data quality assessment in electronic health records used for research. In an attempt to address this, we have developed a protocol for measuring and monitoring data quality in primary care research databases, whereby practice-based data quality measures are tailored to the intended use of the data. Our approach was informed by an in-depth investigation of aspects of data quality in the Clinical Practice Research Datalink Gold database and presentations of the results to data users. Although based on a primary care database, much of our proposed approach would be equally applicable to other health care databases

Parity of ranks for elliptic curves with a cyclic isogeny

Let E be an elliptic curve over a number field K which admits a cyclic p-isogeny with p odd and semistable at primes above p. We determine the root number and the parity of the p-Selmer rank for E/K, in particular confirming the parity conjecture for such curves. We prove the analogous results for p=2 under the additional assumption that E is not supersingular at primes above 2.Comment: Minor corrections; 17 pages, to appear in J. Number Theor

On the Birch-Swinnerton-Dyer quotients modulo squares

Let A be an abelian variety over a number field K. An identity between the L-functions L(A/K_i,s) for extensions K_i of K induces a conjectural relation between the Birch-Swinnerton-Dyer quotients. We prove these relations modulo finiteness of Sha, and give an analogous statement for Selmer groups. Based on this, we develop a method for determining the parity of various combinations of ranks of A over extensions of K. As one of the applications, we establish the parity conjecture for elliptic curves assuming finiteness of Sha[6^\infty] and some restrictions on the reduction at primes above 2 and 3: the parity of the Mordell-Weil rank of E/K agrees with the parity of the analytic rank, as determined by the root number. We also prove the p-parity conjecture for all elliptic curves over Q and all primes p: the parities of the p^\infty-Selmer rank and the analytic rank agree.Comment: 29 pages; minor changes; to appear in Annals of Mathematic

Quality of recording of diabetes in the UK: how does the GP’s method of coding clinical data affect incidence estimates? Cross-sectional study using the CPRD database

Objective: To assess the effect of coding quality on estimates of the incidence of diabetes in the UK between 1995 and 2014. Design: A cross-sectional analysis examining diabetes coding from 1995 to 2014 and how the choice of codes (diagnosis codes vs codes which suggest diagnosis) and quality of coding affect estimated incidence. Setting: Routine primary care data from 684 practices contributing to the UK Clinical Practice Research Datalink (data contributed from Vision (INPS) practices). Main outcome measure: Incidence rates of diabetes and how they are affected by (1) GP coding and (2) excluding ‘poor’ quality practices with at least 10% incident patients inaccurately coded between 2004 and 2014. Results: Incidence rates and accuracy of coding varied widely between practices and the trends differed according to selected category of code. If diagnosis codes were used, the incidence of type 2 increased sharply until 2004 (when the UK Quality Outcomes Framework was introduced), and then flattened off, until 2009, after which they decreased. If non-diagnosis codes were included, the numbers continued to increase until 2012. Although coding quality improved over time, 15% of the 666 practices that contributed data between 2004 and 2014 were labelled ‘poor’ quality. When these practices were dropped from the analyses, the downward trend in the incidence of type 2 after 2009 became less marked and incidence rates were higher. Conclusions: In contrast to some previous reports, diabetes incidence (based on diagnostic codes) appears not to have increased since 2004 in the UK. Choice of codes can make a significant difference to incidence estimates, as can quality of recording. Codes and data quality should be checked when assessing incidence rates using GP data

Modeling the pore structure of voltage-gated sodium channels in closed, open, and fast-inactivated conformation reveals details of site 1 toxin and local anesthetic binding

In this work molecular modeling was applied to generate homology models of the pore region of the Na v 1.2 and Na v 1.8 isoforms of human voltage-gated sodium channels. The models represent the channels in the resting, open, and fast-inactivated states. The transmembrane portions of the channels were based on the equivalent domains of the closed and open conformation potassium channels KcsA and MthK, respectively. The critical selectivity loops were modeled using a structural template identified by a novel 3D-search technique and subsequently merged with the transmembrane portions. The resulting draft models were used to study the differences of tetrodotoxin binding to the tetrodotoxin-sensitive Na v 1.2 (EC50: 0.012μM) and -insensitive Na v 1.8 (EC50: 60μM) isoforms, respectively. Furthermore, we investigated binding of the local anesthetic tetracaine to Na v 1.8 (EC50: 12.5μM) in resting, conducting, and fast-inactivated state. In accordance with experimental mutagenesis studies, computational docking of tetrodotoxin and tetracaine provided (1) a description of site 1 toxin and local anesthetic binding sites in voltage-gated sodium channels. (2) A rationale for site 1 toxin-sensitivity versus -insensitivity in atomic detail involving interactions of the Na v 1.2 residues F385-I and W943-II. (3) A working hypothesis of interactions between Na v 1.8 in different conformational states and the local anesthetic tetracaine. Figure Tetracaine in complex with Nav1.8 in fast-inactivated form. The ligand is represented in CPK and colored by atom type. Ribbons and amino acids are colored by domain: yellow = domain I, blue = domain II, green = domain III, red = domain IV, pink = inactivation gate. Main interaction partners are shown in CPK. a) Tetracaine bound to the inner vestibule. View along the membrane plane. b) Same view as in a but limited to main interaction partners only. The polar head group of tetracaine interacts with the DEKA-motif residues, its hydrophobic tail with the hydrophobic and mainly aromatic residues of S6-IV and the inactivation gat

Regulator constants and the parity conjecture

The p-parity conjecture for twists of elliptic curves relates multiplicities of Artin representations in p-infinity Selmer groups to root numbers. In this paper we prove this conjecture for a class of such twists. For example, if E/Q is semistable at 2 and 3, K/Q is abelian and K^\infty is its maximal pro-p extension, then the p-parity conjecture holds for twists of E by all orthogonal Artin representations of Gal(K^\infty/Q). We also give analogous results when K/Q is non-abelian, the base field is not Q and E is replaced by an abelian variety. The heart of the paper is a study of relations between permutation representations of finite groups, their "regulator constants", and compatibility between local root numbers and local Tamagawa numbers of abelian varieties in such relations.Comment: 50 pages; minor corrections; final version, to appear in Invent. Mat

Exile Vol. XVI No. 1

DRAMA God\u27s Pocket by Robert R. Bowie, Jr. 5-12 FICTION The Wagon by John Anderson 18-19 An Infinity of Mirrors by Keith McWalter 23-25 Commitment by John Whitt 28-29 It began not long ago... by Linda Notzelman 32-33 Jaundiced Evening by John Benes 35-39 POETRY Paralysis Outline by Lauren Shakely 13 A Woman Reads Camus by Lauren Shakely 14 don\u27t sell my rings by Lauren Shakely 14 Drift by John Whitt 17 Haiku by M. S. Wallace 19 To Begin W. K. Mayo 19 Dark is Right by Louise Tate 20 I am waiting by Louise Tate 21 My mother died as I shall die by Tim Cope 20 I never blamed you by Tim Cope 26 For Miss Didawick by Tim Cope 34 Separidian by Bill Whitmore 27 He walks on into by Whitney Carman 31 As Drowned Men Rise by Paul Bennett 34 The Tolling of the Bell by Keith McWalter 39 ARTWORK by Wandi Solez 4, 13, 16, 22, 36 by W. A. Hoffman 21, 30 by Stephen Sneeringer 27 by Christine Michael 19 Cover & Title Page Design: Keith McWalter Layouts: Keith McWalter Publicity- Special thanks to Gail Moore and Karen Baker Photographs courtesy the Sierra Club- From NOT MAN APART, Copyright 196

Differences in SMA-like polymer architecture dictate the conformational changes exhibited by the membrane protein rhodopsin encapsulated in lipid nano-particles

Membrane proteins are of fundamental importance to cellular processes and nano-encapsulation strategies that preserve their native lipid bilayer environment are particularly attractive for studying and exploiting these proteins. Poly(styrene-co-maleic acid) (SMA) and related polymers poly(styrene-co-(N-(3-N′,N′-dimethylaminopropyl)maleimide)) (SMI) and poly(diisobutylene-alt-maleic acid) (DIBMA) have revolutionised the study of membrane proteins by spontaneously solubilising membrane proteins direct from cell membranes within nanoscale discs of native bilayer called SMA lipid particles (SMALPs), SMILPs and DIBMALPs respectively. This systematic study shows for the first time, that conformational changes of the encapsulated protein are dictated by the solubilising polymer. The photoactivation pathway of rhodopsin (Rho), a G-protein-coupled receptor (GPCR), comprises structurally-defined intermediates with characteristic absorbance spectra that revealed conformational restrictions with styrene-containing SMA and SMI, so that photoactivation proceeded only as far as metarhodopsin-I, absorbing at 478 nm, in a SMALP or SMILP. In contrast, full attainment of metarhodopsin-II, absorbing at 382 nm, was observed in a DIBMALP. Consequently, different intermediate states of Rho could be generated readily by simply employing different SMA-like polymers. Dynamic light-scattering and analytical ultracentrifugation revealed differences in size and thermostability between SMALP, SMILP and DIBMALP. Moreover, encapsulated Rho exhibited different stability in a SMALP, SMILP or DIBMALP. Overall, we establish that SMA, SMI and DIBMA constitute a ‘toolkit’ of solubilising polymers, so that selection of the appropriate solubilising polymer provides a spectrum of useful attributes for studying membrane proteins

For the Progress of “Faustus and Helen”: Crane, Whitman, and the Metropolitan Progress Poem

This essay is meant to invigorate a critical discussion of the progress poem—a genre that, while prevalent in American literature, has been virtually ignored by critics and scholars. In lieu of tackling the genre in its entirety, a project too large for just one article, the author focuses the argument through the well-known alignment between Walt Whitman and Hart Crane on the subject of the modern city. It is through the progress poem genre that Crane and Whitman’s peculiar place in metropolitan poetics can best be understood, and it is through their poetry that scholars can begin to approach the broader issue of the progress poem’s place in American literature. Cet article vise à soulever un débat critique au sujet de la poésie du progrès, un genre courant dans la littérature étatsunienne, mais pratiquement ignoré par les critiques et les commentateurs. Plutôt que d’aborder le genre dans son entièreté – un projet qui déborde du cadre d’un article –, l’auteur resserre l’argumentation autour du parallèle bien connu entre Walt Whitman et Hart Crane concernant le traitement de la ville moderne. C’est la poésie du progrès en tant que genre qui permet le mieux de comprendre la place particulière qu’occupent ces deux auteurs dans la poésie métropolitaine, et c’est par leurs poèmes que les chercheurs peuvent aborder la question plus vaste de la place du poème sur le progrès dans la littérature étatsunienne