143174 research outputs found
Sort by
Coherent two dimensional electronic-X-ray spectroscopy
No full textPreprint versionUltrafast pump-probe time resolved X-ray spectroscopy carries information on the valence-core dynamics of molecular systems. Here, a coherent two-dimensional nonlinear electronic-X-ray spectroscopy (2DEX) application is proposed in order to reveal the frequency-frequency correlations for the valence and the core transition excitations. 2DEX is in the class of extreme-cross peak correlation spectroscopy and is experimentally straightforward to measure as an adaptation of the conventional optical pump-X-ray probe technique by creating a phase-locked pulse pair of the ultrafast laser for the valence excitation. Theoretical evaluation of the coherences and populations for several applications of ultrafast valence-core spectroscopy experiments is shown. Using a response function approach, 2DEX four wave signals are calculated and evaluated with respect to frequency separation in the electronic and X-ray ranges as well as the lineshape characteristics. It is shown that stationary and oscillatory contributions to the rephasing, nonrephasing and absorptive signals can be resolved depending on pulse shaping and phase cycling, phase matching, X-ray spectrometer and material response parameters. Calculations are shown for examples that include the valence-core coherences for a vibrational monomer and for Frenkel and charge transfer (CT) electronic exciton states, which in the X-ray absorption near-edge structure (XANES) spectral region have the potential to resolve the population and coherence contributions in the atomic localised basis
A unified spin-harmonic framework for correlating pulsar timing, astrometric deflection, and shimmering gravitational wave observations
No full textWe present a unified spin-weighted harmonic framework that delivers analytic, diagonal expressions for the overlap (correlation) functions of three low frequency gravitational wave observables-pulsar timing redshifts, astrometric deflections, and time-dependent image distortions (``shimmering''). Writing each response in spin-s spherical harmonics and rotating to a basis in which the wave tensor has definite helicity, we obtain compact closed-form series for every auto- and cross-correlation, recovering the Hellings-Downs curve as the s = 0 limit and deriving its astrometric (s = 1) and shimmering ( ) analogues. The formalism naturally extends to non-standard scalar-breathing, longitudinal, and vector polarisation modes, clarifying when higher-spin observables are (and are not) sourced and providing a complete set of harmonic spectra ready for parameter estimation pipelines. These results supply the common theoretical language needed to combine upcoming pulsar timing, Gaia-class astrometric, and high resolution imaging data sets, enabling coherent, multi probe searches for stochastic gravitational wave backgrounds, tests of general relativity and its alternatives across the nano- to micro-hertz gravitational wave band
Optimising haemodynamics in cardiac critical care
No full textWhilst there has been much research into cardiac surgery and percutaneous coronary intervention there has been much less focus on other components of care that are important in optimising the haemodynamics of patients undergoing these interventions.
Successful overall management of a patient’s physiological state in these situations involves: (1) accurate monitoring of patients to recognise early signs that cardiac output is compromised, (2) interpreting this data accurately, so that (3) effective and timeous treatment can be implemented.
This thesis addresses these three domains by studying two interventions for patients in these critical cardiac states. The first is cardiac pacing after cardiac surgery. The second is the early identification and methods of treatment in cardiogenic shock.
I address this overall question by examining eight specific questions:
(1) Are haemodynamics and outcomes better when temporary pacing after cardiac surgery is performed using dual-chamber or atrio-biventricular devices?
(2) What effect does systematic optimisation of temporary pacing have upon arterial blood pressure and cardiac output after cardiac surgery?
(3) Can haemodynamic optimisation of temporary pacing be performed using central venous pressure in addition to arterial blood pressure readings?
(4) Can continuous haemodynamic parameters be more accurately measured by incorporating information from the central venous system into pulse-contour algorithms?
(5) If a patient’s haemodynamic state requires permanent pacemaker implantation after cardiac surgery, can one define an optimum time to wait before device implantation?
(6) Is it possible to create a fast and accurate scoring system to identify patients at high risk of haemodynamic compromise on admission with acute coronary syndromes?
(7) Having identified patients at high risk of haemodynamic compromise when presenting with acute coronary syndromes and multivessel disease, which patients should undergo complete revascularisation?
(8) In patients requiring further haemodynamic support with microaxial flow devices, is it possible to create an easily-implemented prognostication system?Open Acces
BMP9 knockout impairs pulmonary vessel muscularisation and confers aberrant tamoxifen sensitivity
No full textDeleterious mutations in the GDF2 gene, encoding BMP9, are causative of pulmonary arterial hypertension and hereditary haemorrhagic telangiectasia. Paradoxically, BMP9 germ-line knockout (Gdf2−/−; Bmp9 KO) and double Bmp9 KO/conditional Bmp10 cKO (dKO) mice exhibit an attenuated response to PAH-inducing stimuli. We asked whether this contradiction is due to the pathological, physiological, or genetic consequences of BMP9 knockout. In Bmp9 KO mice we observed reduced pulmonary vascular smooth muscle cell (SMC) coverage and using RNA-seq analysis of Bmp9 KO mouse lungs identified two novel genes, COLQ and ITGA6, which were differentially regulated in a human PAH RNA-seq dataset. In order to study BMP10 loss, postnatal tamoxifen treatment was required to induce Bmp10 cKO. As previously reported, in dKO mice we observed cardiomegaly and splenomegaly, as well as hyperplasia and hemosiderosis in the pulmonary vasculature. Surprisingly, tamoxifen treated Bmp9 KO control mice phenocopied these pathological changes in dKO mice and downregulated SMC marker gene transcription. Loss of BMP10 is not critical for severe tissue remodelling in the lung, heart, and spleen, rather Bmp9 KO mice appear sensitive to tamoxifen and BMP9 loss is the primary cause of mild vessel remodelling due to a basal reduction of smooth muscle cell coverage. This study suggests that interaction of the BMP pathway with tamoxifen needs to be carefully considered when studying Bmp9 KO mice and urges caution in the context of tamoxifen use when studying cardiovascular and pulmonary disease models
RAAC panels can suddenly collapse before any warning of corrosion-induced surface cracking
No full textHeterogeneity in responses to ribosome-targeting antibiotics mediated by bacterial RNA repair
No full textRNA repair is critical for cellular function. The Rtc system maintains RNA integrity within the translational machinery of bacteria. In E. coli, Rtc expression enables cells to rescue growth and survive treatment by conferring transient resistance to ribosome-targeting antibiotics, yet the mechanisms underpinning this resistance remain obscure. Here, we present a computational model of Rtc-regulated repair of translational RNAs. Integrating model predictions with experimental validations, we uncover notable cell-to-cell heterogeneity in rtc expression that impacts on translational capacity, indicating that rtc may induce a form of heteroresistance. We moreover identify Rtc targets that may reduce the translational capacity of cells and so potentiate antibiotic effects. Our findings elucidate a complex response underpinning resistance conferred by Rtc, offering alternate routes for addressing resistance in E. coli and other relevant pathogens
High density evaluation of the arrhythmogenic substrate in atrial fibrillation (HEAT-AF)
No full textBackground: Left atrial (LA) fibrosis is a key component of arrhythmogenic remodelling in atrial fibrillation (AF). LA low-voltage areas (LVAs) are considered surrogates for fibrosis and novel targets for ablation. However, there are no established criteria for identifying such potential pathogenic areas, particularly when utilising omnipolar mapping (OT).
Objective: To evaluate the correlation between OT and conventional bipolar voltage (BiV) in AF and regular rhythms.
Methods: Bipolar and OT mapping was performed in 17 patients undergoing de novo ablation for persistent AF. Mapping was performed in AF and coronary sinus pacing (CSP) at 600ms. BiV <0.5mV were defined as low voltage.
Results: LA voltage in AF correlated poorly with CSP using either BiV (r=0.15), or OT (r=0.16). OT yielded higher voltages than BiV in AF (0.62±0.24 vs. 0.49±0.18mV, p<0.050) and during CSP (1.85±0.78 vs. 1.60±0.80mV, p<0.050). LVA burden, as percentage of LA surface area, varied significantly depending on the atrial rhythm and mapping approach (AF bipolar: 65.0 ± 15.6%, AF OT: 56.2 ± 17.0%, CSP bipolar: 34.2±18.9%, CSP OT: 24.56±13.5%, p<0.050). BiV thresholds of 0.5mV during CSP and 0.3mV in AF corresponded to an OT voltage of 0.84mV and 0.40mV, respectively.
Conclusion: The mapping tool and atrial rhythm significantly influence LA voltage and LVA burden for both bipolar and OT mapping. Applying a universal bipolar or OT cut-off for low voltage in AF and sinus rhythm will not accurately reflect the arrhythmogenic substrate. OT yields higher voltage than corresponding bipolar measurements, thus adjustments in thresholds are required when using OT
Development of START-EDI guidelines for reporting equality, diversity and inclusion in research: a study protocol
No full textIntroduction: Acknowledging equality, diversity and inclusion (EDI) in research is not only a moral imperative but also an important step in avoiding bias and ensuring generalisability of results. This protocol describes the development of STAndards for ReporTing EDI (START-EDI) in research, which will provide a set of minimum standards to help researchers improve their consistency, completeness and transparency in EDI reporting. We anticipate that these guidelines will benefit authors, reviewers, editors, funding organisations, patients and the public and healthcare providers.
Methods and analysis: To create START-EDI reporting guidelines, the following five stages are proposed: (i) establish a diverse, multidisciplinary Steering Committee that will lead and coordinate guideline development; (ii) a systematic review to identify the essential principles and methodological approaches for EDI to generate preliminary checklist items; (iii) conduct an international Delphi process to reach a consensus on the checklist items; (iv) finalise the reporting guidelines and create a separate Explanation and Elaboration (E&E) document, and; (v) broad dissemination and implementation of START-EDI guidelines. We will work with patient and public involvement representatives and under-served groups in research throughout the project stages.
Ethics and dissemination: The study has received ethical approval from the Imperial College London Research Ethics Committee (study ID: 7592283). Informed consent and conflict of interest forms will be obtained from all participants in the Delphi process. The reporting guidelines will be published in open access peer-reviewed publications and presented in international conferences, and disseminated through community networks and forums.
Registration details: The project is pre-registered within the Open Science Framework (https://osf.io/8udbq/) and the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network
Trials special series - the collection, analysis and reporting of adverse events in randomised controlled trials
No full textBackground
While the design and analysis of randomised controlled trials has progressed rapidly in the last decade, the analysis of harm outcomes has seen minimal change [1,2,3]. Integral to assessing harm is what and how data is collected. Considerations of all these aspects vary across the different types of interventions e.g. pharmaceutical, surgical, behavioural etc. While there has been an increase in research to progress how data should be collected, synthesised and reported for harm outcomes, there is little evidence of progress in implementing these approaches and the analysis and reporting of harm outcomes remains rudimentary [3].
In this special series, Trials invited submissions that related to the collection, analysis and reporting of adverse events in clinical trials. To date twelve articles have been published in the series. In this editorial, we summarise each of these submissions and briefly discuss the implications on applied clinical trials and future methodological research