Realising the full potential of data-enabled trials in the UK: a call for action

Rationale: Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up. Approach: The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for ‘data-enabled clinical trials’. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation. Reflection:Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a ‘route map’ to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution. Discussion: EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial’s specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR’s funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale

High frequency diffraction of an electromagnetic plane wave by an imperfectly conducting rectangular cylinder

Copyright @ 2011 IEEEWe shall consider the the problem of determining the scattered far wave field produced when a plane E-polarized wave is incident on an imperfectly conducting rectangular cylinder. By using the the uniform asymptotic solution for the problem of the diffraction of a plane wave by a right-angled impedance wedge, in conjunction with Keller's method, the a high frequency far field solution to the problem is given

Stochastic Background Search Correlating ALLEGRO with LIGO Engineering Data

We describe the role of correlation measurements between the LIGO interferometer in Livingston, LA, and the ALLEGRO resonant bar detector in Baton Rouge, LA, in searches for a stochastic background of gravitational waves. Such measurements provide a valuable complement to correlations between interferometers at the two LIGO sites, since they are sensitive in a different, higher, frequency band. Additionally, the variable orientation of the ALLEGRO detector provides a means to distinguish gravitational wave correlations from correlated environmental noise. We describe the analysis underway to set a limit on the strength of a stochastic background at frequencies near 900 Hz using ALLEGRO data and data from LIGO's E7 Engineering Run.Comment: 8 pages, 2 encapsulated PostScript figures, uses IOP class files, submitted to the proceedings of the 7th Gravitational Wave Data Analysis Workshop (which will be published in Classical and Quantum Gravity

Thin-Skin Electromagnetic Fields Around Surface-Breaking Cracks in Metals

In situations where the electrical skin depth δ is small compared with a typical crack dimension l, substantial progress has been achieved in recent years in modeling surface electromagnetic fields and the perturbations that are produced in them by surface-breaking flaws [1,2,3]. The development of an unfolding theory at UCL for thin-skin surface fields was based on the approximation that the electric and magnetic field vectors E and H are essentially tangential to the surface of the material in the surface skin. It was motivated by the desire to measure fatigue cracks in ferrous materials used in large-scale steel structures such as offshore oil rigs [2], and the method to which it was applied was the a.c. field measurement technique. Auld et al [4,5] later adapted the unfolding approach in considering thin-skin field models for the eddy current method, and their major concern was with applications to non-ferrous materials used in airframe and aero-engine manufacture. For acfm work, the unfolding theory leads to a surface Laplacian field on both the metal surface and the crack face and information on the crack presence is deduced by measuring perturbations in the surface field. Auld’s model for eddy currents also has a plane Laplacian field on the crack face, but it is assumed that the crack produces no change in the field on the metal surface. Field lines in the unfolded plane for both models are shown schematically in Figure 1(b,c) for the case when the interrogating field is uniform and the crack is semi-circular. Auld’s model has been described as a Born type of approximation from an analogy with wave scattering theory which ignores the scattered field when calculating scattering cross-sections

Non-Linear Integral Equations for complex Affine Toda associated to simply laced Lie algebras

A set of coupled non-linear integral equations is derived for a class of models connected with the quantum group $U_q(\hat g)$ ($g$ simply laced Lie algebra), which are solvable using the Bethe Ansatz; these equations describe arbitrary excited states of a system with finite spatial length $L$. They generalize the Destri-De Vega equation for the Sine-Gordon/massive Thirring model to affine Toda field theory with imaginary coupling constant. As an application, the central charge and all the conformal weights of the UV conformal field theory are extracted in a straightforward manner. The quantum group truncation for $q$ at a root of unity is discussed in detail; in the UV limit we recover through this procedure the RCFTs with extended $W(g)$ conformal symmetry.Comment: 33 pages, TeX with lanlmac (revised: minor misprints corrected, some comments added, appendix slightly expanded revised 05/98: more misprints corrected, important refs added

Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences

Pleuropulmonary blastoma is a rare childhood malignancy of lung mesenchymal cells that can remain dormant as epithelial cysts or progress to high-grade sarcoma. Predisposing germline loss-of-function DICER1 variants have been described. We sought to uncover additional contributors through whole exome sequencing of 15 tumor/normal pairs, followed by targeted resequencing, miRNA analysis and immunohistochemical analysis of additional tumors. In addition to frequent biallelic loss of TP53 and mutations of NRAS or BRAF in some cases, each case had compound disruption of DICER1: a germline (12 cases) or somatic (3 cases) loss-of-function variant plus a somatic missense mutation in the RNase IIIb domain. 5p-Derived microRNA (miRNA) transcripts retained abnormal precursor miRNA loop sequences normally removed by DICER1. This work both defines a genetic interaction landscape with DICER1 mutation and provides evidence for alteration in miRNA transcripts as a consequence of DICER1 disruption in cancer