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

Tracking primary thermalization events in graphene with photoemission at extreme timescales

Direct and inverse Auger scattering are amongst the primary processes that mediate the thermalization of hot carriers in semiconductors. These two processes involve the annihilation or generation of an electron-hole pair by exchanging energy with a third carrier, which is either accelerated or decelerated. Inverse Auger scattering is generally suppressed, as the decelerated carriers must have excess energies higher than the band gap itself. In graphene, which is gapless, inverse Auger scattering is instead predicted to be dominant at the earliest time delays. Here, $<8$ femtosecond extreme-ultraviolet pulses are used to detect this imbalance, tracking both the number of excited electrons and their kinetic energy with time- and angle-resolved photoemission spectroscopy. Over a time window of approximately 25 fs after absorption of the pump pulse, we observe an increase in conduction band carrier density and a simultaneous decrease of the average carrier kinetic energy, revealing that relaxation is in fact dominated by inverse Auger scattering. Measurements of carrier scattering at extreme timescales by photoemission will serve as a guide to ultrafast control of electronic properties in solids for PetaHertz electronics.Comment: 16 pages, 8 figure

Revealing the role of electrons and phonons in the ultrafast recovery of charge density wave correlations in 1TT-TiSe2_2

Using time- and angle-resolved photoemission spectroscopy with selective near- and mid-infrared photon excitations, we investigate the femtosecond dynamics of the charge density wave (CDW) phase in 1$T$-TiSe$_2$, as well as the dynamics of CDW fluctuations at 240 K. In the CDW phase, we observe the coherent oscillation of the CDW amplitude mode. At 240 K, we single out an ultrafast component in the recovery of the CDW correlations, which we explain as the manifestation of electron-hole correlations. Our momentum-resolved study of femtosecond electron dynamics supports a mechanism for the CDW phase resulting from the cooperation between the interband Coulomb interaction, the mechanism of excitonic insulator phase formation, and electron-phonon coupling.Comment: 9 pages, 6 figure

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

Evidence of reduced surface electron-phonon scattering in the conduction band of Bi_{2}Se_{3} by non-equilibrium ARPES

The nature of the Dirac quasiparticles in topological insulators calls for a direct investigation of the electron-phonon scattering at the \emph{surface}. By comparing time-resolved ARPES measurements of the TI Bi_{2}Se_{3} with different probing depths we show that the relaxation dynamics of the electronic temperature of the conduction band is much slower at the surface than in the bulk. This observation suggests that surface phonons are less effective in cooling the electron gas in the conduction band.Comment: 5 pages, 3 figure

Enhanced electron-phonon coupling in graphene with periodically distorted lattice

Electron-phonon coupling directly determines the stability of cooperative order in solids, including superconductivity, charge and spin density waves. Therefore, the ability to enhance or reduce electron-phonon coupling by optical driving may open up new possibilities to steer materials' functionalities, potentially at high speeds. Here we explore the response of bilayer graphene to dynamical modulation of the lattice, achieved by driving optically-active in-plane bond stretching vibrations with femtosecond mid-infrared pulses. The driven state is studied by two different ultrafast spectroscopic techniques. Firstly, TeraHertz time-domain spectroscopy reveals that the Drude scattering rate decreases upon driving. Secondly, the relaxation rate of hot quasi-particles, as measured by time- and angle-resolved photoemission spectroscopy, increases. These two independent observations are quantitatively consistent with one another and can be explained by a transient three-fold enhancement of the electron-phonon coupling constant. The findings reported here provide useful perspective for related experiments, which reported the enhancement of superconductivity in alkali-doped fullerites when a similar phonon mode was driven.Comment: 12 pages, 4 figure

Momentum resolved spin dynamics of bulk and surface excited states in the topological insulator Bi2Se3\mathrm{Bi_{2}Se_{3}}

The prospective of optically inducing a spin polarized current for spintronic devices has generated a vast interest in the out-of-equilibrium electronic and spin structure of topological insulators (TIs). In this Letter we prove that only by measuring the spin intensity signal over several order of magnitude in spin, time and angle resolved photoemission spectroscopy (STAR-PES) experiments is it possible to comprehensively describe the optically excited electronic states in TIs materials. The experiments performed on $\mathrm{Bi_{2}Se_{3}}$ reveal the existence of a Surface-Resonance-State in the 2nd bulk band gap interpreted on the basis of fully relativistic ab-initio spin resolved photoemission calculations. Remarkably, the spin dependent relaxation of the hot carriers is well reproduced by a spin dynamics model considering two non-interacting electronic systems, derived from the excited surface and bulk states, with different electronic temperatures.Comment: 5 pages and 4 figure