Can analyses of electronic patient records be independently and externally validated? The effect of statins on the mortality of patients with ischaemic heart disease: a cohort study with nested case-control analysis

Objective To conduct a fully independent and external validation of a research study based on one electronic health record database, using a different electronic database sampling the same population. Design Using the Clinical Practice Research Datalink (CPRD), we replicated a published investigation into the effects of statins in patients with ischaemic heart disease (IHD) by a different research team using QResearch. We replicated the original methods and analysed all-cause mortality using: (1) a cohort analysis and (2) a case-control analysis nested within the full cohort. Setting Electronic health record databases containing longitudinal patient consultation data from large numbers of general practices distributed throughout the UK. Participants CPRD data for 34 925 patients with IHD from 224 general practices, compared to previously published results from QResearch for 13 029 patients from 89 general practices. The study period was from January 1996 to December 2003. Results We successfully replicated the methods of the original study very closely. In a cohort analysis, risk of death was lower by 55% for patients on statins, compared with 53% for QResearch (adjusted HR 0.45, 95% CI 0.40 to 0.50; vs 0.47, 95% CI 0.41 to 0.53). In case-control analyses, patients on statins had a 31% lower odds of death, compared with 39% for QResearch (adjusted OR 0.69, 95% CI 0.63 to 0.75; vs OR 0.61, 95% CI 0.52 to 0.72). Results were also close for individual statins. Conclusions Database differences in population characteristics and in data definitions, recording, quality and completeness had a minimal impact on key statistical outputs. The results uphold the validity of research using CPRD and QResearch by providing independent evidence that both datasets produce very similar estimates of treatment effect, leading to the same clinical and policy decisions. Together with other non-independent replication studies, there is a nascent body of evidence for wider validity

Gamete compatibility and reproductive success in the North Atlantic right whale

162 leaves : illustrations (some coloured) ; 29 cmIncludes abstract and appendices.Includes bibliographical references.The goal of this project was to assess the influence that genetic characteristics at gamete compatibility genes have on the reduced reproductive rates in the endangered North Atlantic right whale. To do this candidate genes were identified that play a role in fertilization, and primers were developed for the amplification of the putative functional sites of these genes. Mother-father-calf triads were sequenced to test for non-random mating patterns and non-Mendelian inheritance patterns, which would be indicative of mate choice and/or biased fertilization based on the characteristics of these genes. Overall there was low variability across individuals, but a slight bias in mate choice for mates with similar genotypes within loci, but differing across loci. One locus also showed signs of biased fertilization patterns, with successful fertilizations resulting when offspring inherit the same allele from both parents

Withdrawing performance indicators: retrospective analysis of general practice performance under UK Quality and Outcomes Framework.

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.OBJECTIVES: To investigate the effect of withdrawing incentives on recorded quality of care, in the context of the UK Quality and Outcomes Framework pay for performance scheme. DESIGN: Retrospective longitudinal study. SETTING: Data for 644 general practices, from 2004/05 to 2011/12, extracted from the Clinical Practice Research Datalink. PARTICIPANTS: All patients registered with any of the practices over the study period-13,772,992 in total. INTERVENTION: Removal of financial incentives for aspects of care for patients with asthma, coronary heart disease, diabetes, stroke, and psychosis. MAIN OUTCOME MEASURES: Performance on eight clinical quality indicators withdrawn from a national incentive scheme: influenza immunisation (asthma) and lithium treatment monitoring (psychosis), removed in April 2006; blood pressure monitoring (coronary heart disease, diabetes, stroke), cholesterol concentration monitoring (coronary heart disease, diabetes), and blood glucose monitoring (diabetes), removed in April 2011. Multilevel mixed effects multiple linear regression models were used to quantify the effect of incentive withdrawal. RESULTS: Mean levels of performance were generally stable after the removal of the incentives, in both the short and long term. For the two indicators removed in April 2006, levels in 2011/12 were very close to 2005/06 levels, although a small but statistically significant drop was estimated for influenza immunisation. For five of the six indicators withdrawn from April 2011, no significant effect on performance was seen following removal and differences between predicted and observed scores were small. Performance on related outcome indicators retained in the scheme (such as blood pressure control) was generally unaffected. CONCLUSIONS: Following the removal of incentives, levels of performance across a range of clinical activities generally remained stable. This indicates that health benefits from incentive schemes can potentially be increased by periodically replacing existing indicators with new indicators relating to alternative aspects of care. However, all aspects of care investigated remained indirectly or partly incentivised in other indicators, and further work is needed to assess the generalisability of the findings when incentives are fully withdrawn.National Institute for Health Research (NIHR

rEHR: An R package for manipulating and analysing Electronic Health Record data

Research with structured Electronic Health Records (EHRs) is expanding as data becomes more accessible; analytic methods advance; and the scientific validity of such studies is increasingly accepted. However, data science methodology to enable the rapid searching/extraction, cleaning and analysis of these large, often complex, datasets is less well developed. In addition, commonly used software is inadequate, resulting in bottlenecks in research workflows and in obstacles to increased transparency and reproducibility of the research. Preparing a research-ready dataset from EHRs is a complex and time consuming task requiring substantial data science skills, even for simple designs. In addition, certain aspects of the workflow are computationally intensive, for example extraction of longitudinal data and matching controls to a large cohort, which may take days or even weeks to run using standard software. The rEHR package simplifies and accelerates the process of extracting ready-for-analysis datasets from EHR databases. It has a simple import function to a database backend that greatly accelerates data access times. A set of generic query functions allow users to extract data efficiently without needing detailed knowledge of SQL queries. Longitudinal data extractions can also be made in a single command, making use of parallel processing. The package also contains functions for cutting data by time-varying covariates, matching controls to cases, unit conversion and construction of clinical code lists. There are also functions to synthesise dummy EHR. The package has been tested with one for the largest primary care EHRs, the Clinical Practice Research Datalink (CPRD), but allows for a common interface to other EHRs. This simplified and accelerated work flow for EHR data extraction results in simpler, cleaner scripts that are more easily debugged, shared and reproduced

Ramifications of Optical Pumping on the Interpretation of Time-Resolved Photoemission Experiments on Graphene

In pump-probe time and angle-resolved photoemission spectroscopy (TR-ARPES) experiments the presence of the pump pulse adds a new level of complexity to the photoemission process in comparison to conventional ARPES. This is evidenced by pump-induced vacuum space-charge effects and surface photovoltages, as well as multiple pump excitations due to internal reflections in the sample-substrate system. These processes can severely affect a correct interpretation of the data by masking the out-of-equilibrium electron dynamics intrinsic to the sample. In this study, we show that such effects indeed influence TR-ARPES data of graphene on a silicon carbide (SiC) substrate. In particular, we find a time- and laser fluence-dependent spectral shift and broadening of the acquired spectra, and unambiguously show the presence of a double pump excitation. The dynamics of these effects is slower than the electron dynamics in the graphene sample, thereby permitting us to deconvolve the signals in the time domain. Our results demonstrate that complex pump-related processes should always be considered in the experimental setup and data analysis.Comment: 9 pages, 4 figure

Ultrafast Dynamics of Massive Dirac Fermions in Bilayer Graphene

Bilayer graphene is a highly promising material for electronic and optoelectronic applications since it is supporting massive Dirac fermions with a tuneable band gap. However, no consistent picture of the gap's effect on the optical and transport behavior has emerged so far, and it has been proposed that the insulating nature of the gap could be compromised by unavoidable structural defects, by topological in-gap states, or that the electronic structure could be altogether changed by many-body effects. Here we directly follow the excited carriers in bilayer graphene on a femtosecond time scale, using ultrafast time- and angle-resolved photoemission. We find a behavior consistent with a single-particle band gap. Compared to monolayer graphene, the existence of this band gap leads to an increased carrier lifetime in the minimum of the lowest conduction band. This is in sharp contrast to the second sub-state of the conduction band, in which the excited electrons decay through fast, phonon-assisted inter-band transitions.Comment: 5 pages, 4 figure

Asymmetric emission of high energy electrons in the two-dimensional hydrodynamic expansion of large xenon clusters irradiated by intense laser fields

Energy spectra and angular distributions have been measured of electrons that are emitted upon disassembly of $Xe_{150000}$ following irradiation by intense (10$^{15}-10^{16}$ W cm$^{-2}$) laser pulses whose durations are varied over the 100-2200 fs range. The cluster explosion dynamics occur in the hydrodynamic regime. Electron emission is found to be unexpectedly asymmetric and exhibits a resonance when the laser pulse duration is $\sim$1 ps. These results are rationalized by extending the hydrodynamic model to also take into account the force that the light field exerts on the polarization charge that is induced on surface of the cluster. We show that the magnitude of this electrostrictive force is comparable to those of Coulombic and the hydrodynamic forces, and it exhibits resonance behavior. Contrary to earlier understanding, we find that low-energy electrons are connected to the resonance in energy absorption by the cluster. The high-energy electrons seem to be produced by a mechanism that is not so strongly influenced by the resonance.Comment: 1 Revtex file, 8 figs. in eps forma

Characterization of doping levels in heteronuclear, gas-phase, van der Waals clusters and their energy absorption from an intense optical field

A simple mass spectrometric method has been developed to quantify dopant levels in heteronuclear clusters in the gas phase. The method is demonstrated with reference to quantification of the water content in supersonic beams of water-doped argon clusters. Such doped clusters have assumed much importance in the context of recently-reported doping-induced enhancement in the emission of energetic charged particles and photons upon their interaction with intense laser pulses. We have also measured the energy that a doped cluster absorbs from the optical field; we find that energy absorption increases with increasing level of doping. The oft-used linear model of energy absorption is found to be quantitatively inadequate.Comment: To appear in Chemical Physics Letter

Evolution of Ultracold, Neutral Plasmas

We present the first large-scale simulations of an ultracold, neutral plasma, produced by photoionization of laser-cooled xenon atoms, from creation to initial expansion, using classical molecular dynamics methods with open boundary conditions. We reproduce many of the experimental findings such as the trapping efficiency of electrons with increased ion number, a minimum electron temperature achieved on approach to the photoionization threshold, and recombination into Rydberg states of anomalously-low principal quantum number. In addition, many of these effects establish themselves very early in the plasma evolution ($\sim$ ns) before present experimental observations begin.Comment: 4 pages, 3 figures, submitted to PR

Possible observation of parametrically amplified coherent phasons in K0.3MoO3 using time-resolved extreme-ultraviolet ARPES

We use time- and angle-resolved photoemission spectroscopy (tr-ARPES) in the Extreme Ultraviolet (EUV) to measure the time- and momentum-dependent electronic structure of photo-excited K0.3MoO3. Prompt depletion of the Charge Density Wave (CDW) condensate launches coherent oscillations of the amplitude mode, observed as a 1.7-THz-frequency modulation of the bonding band position. In contrast, the anti-bonding band oscillates at about half this frequency. We attribute these oscillations to coherent excitation of phasons via parametric amplification of phase fluctuations.Comment: 4 figure