Modelled mortality benefits of multi-cancer early detection screening in England

Background: Screening programmes utilising blood-based multi-cancer early detection (MCED) tests, which can detect a shared cancer signal from any site in the body with a single, low false-positive rate, could reduce cancer burden through early diagnosis. Methods: A natural history (‘interception’) model of cancer was previously used to characterise potential benefits of MCED screening (based on published performance of an MCED test). We built upon this using a two-population survival model to account for an increased risk of death from cfDNA-detectable cancers relative to cfDNA-non-detectable cancers. We developed another model allowing some cancers to metastasise directly from stage I, bypassing intermediate tumour stages. We used incidence and survival-by-stage data from the National Cancer Registration and Analysis Service in England to estimate longer-term benefits to a cohort screened between ages 50–79 years. Results: Estimated late-stage and mortality reductions were robust to a range of assumptions. With the least favourable dwell (sojourn) time and cfDNA status hazard ratio assumptions, we estimated, among 100,000 screened individuals, 67 (17%) fewer cancer deaths per year corresponding to 2029 fewer deaths in those screened between ages 50–79 years. Conclusion: Realising the potential benefits of MCED tests could substantially reduce late-stage cancer diagnoses and mortality

Modelled mortality benefits of multi-cancer early detection screening in England

Background Screening programmes utilising blood-based multi-cancer early detection (MCED) tests, which can detect a shared cancer signal from any site in the body with a single, low false-positive rate, could reduce cancer burden through early diagnosis. Methods A natural history (‘interception’) model of cancer was previously used to characterise potential benefits of MCED screening (based on published performance of an MCED test). We built upon this using a two-population survival model to account for an increased risk of death from cfDNA-detectable cancers relative to cfDNA-non-detectable cancers. We developed another model allowing some cancers to metastasise directly from stage I, bypassing intermediate tumour stages. We used incidence and survival-by-stage data from the National Cancer Registration and Analysis Service in England to estimate longer-term benefits to a cohort screened between ages 50–79 years. Results Estimated late-stage and mortality reductions were robust to a range of assumptions. With the least favourable dwell (sojourn) time and cfDNA status hazard ratio assumptions, we estimated, among 100,000 screened individuals, 67 (17%) fewer cancer deaths per year corresponding to 2029 fewer deaths in those screened between ages 50–79 years. Conclusion Realising the potential benefits of MCED tests could substantially reduce late-stage cancer diagnoses and mortality

To dd, or not to dd: Recent developments and comparisons of regularization schemes

We give an introduction to several regularization schemes that deal with ultraviolet and infrared singularities appearing in higher-order computations in quantum field theories. Comparing the computation of simple quantities in the various schemes, we point out similarities and differences between them.Comment: 61 pages, 12 figures; version sent to EPJC, references update

Muon-electron scattering at NNLO

We present the first calculation of the complete set of NNLO QED corrections for muon-electron scattering. This includes leptonic, non-perturbative hadronic, and photonic contributions. All fermionic corrections as well as the photonic subset that only corrects the electron or the muon line are included with full mass dependence. The genuine four-point two-loop topologies are computed as an expansion in the small electron mass, taking into account both, logarithmically enhanced as well as constant mass effects using massification. A fast and stable implementation of the numerically delicate real-virtual contribution is achieved by combining OpenLoops with next-to-soft stabilisation. All matrix elements are implemented in the McMule framework, which allows for the fully-differential calculation of any infrared-safe observable. This calculation is to be viewed in the context of the MUonE experiment requiring a background prediction at the level of 10 ppm. Our results thus represent a major milestone towards this ambitious precision goal

Adjuvant chemotherapy for breast cancer in older women: an analysis of retrospective English cancer registration data

Aims Adjuvant chemotherapy is recommended as a treatment for women with high recurrence risk early breast cancer. Older women are less likely to receive chemotherapy than younger women. This study investigated the impact of chemotherapy on breast cancer-specific survival in women aged 70 + years using English registry data. Materials and methods Cancer registration data were obtained from two English regions from 2002 to 2012 (n = 29 728). The impact of patient-level characteristics on the probability of receiving adjuvant chemotherapy was explored using logistic regression. Survival modelling was undertaken to show the effect of chemotherapy and age/health status on breast cancer-specific survival. Missing data were handled using multiple imputation. Results In total, 11 735 surgically treated early breast cancer patients were identified. Use of adjuvant chemotherapy has increased over time. Younger age at diagnosis, increased nodal involvement, tumour size and grade, oestrogen receptor-negative or human epidermal growth factor receptor 2-positive disease were all associated with increased probability of receiving chemotherapy. Chemotherapy was associated with a significant reduction in the hazard of breast cancer-specific mortality in women with high risk cancer, after adjusting for patient-level characteristics (hazard ratio 0.74, 95% confidence interval 0.67–0.81). Discussion Chemotherapy is associated with an improved breast cancer-specific survival in older women with early breast cancer at high risk of recurrence . Lower rates of chemotherapy use in older women may, therefore, contribute to inferior cancer outcomes. Decisions on potential benefits for individual patients should be made on the basis of life expectancy, treatment tolerance and patient preference

Effecting a national implementation project through distributed leadership in the West Midlands: rising to the spread challenge

© 2021 The Authors. Published by BMJ. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://dx.doi.org/10.1136/bmjoq-2020-001227We describe the utility and impact of a distributed leadership model to implement a National Health Service (NHS) England Academic Health Sciences national quality improvement programme, in the West Midlands. This model was adopted to address the inherent difficulties of implementing change in practice in a large geographical region with a diverse population of health service personnel. We report on the inclusion of a senior trainee as part of the implementation team, supported by a multidisciplinary clinical consultant team, with equal agency in decision making, acting as mentors and activators in the background.Published versio

Climate-induced variability in South Atlantic wave direction over the past three millennia.

ABSTRACT: Through alteration of wave-generating atmospheric systems, global climate changes play a fundamental role in regional wave climate. However, long-term wave-climate cycles and their associated forcing mechanisms remain poorly constrained, in part due to a relative dearth of highly resolved archives. Here we use the morphology of former shorelines preserved in beach-foredune ridges (BFR) within a protected embayment to reconstruct changes in predominant wave directions in the Subtropical South Atlantic during the last ~3000 years. These analyses reveal multi-centennial cycles of oscillation in predominant wave direction in accordance with stronger (weaker) South Atlantic mid- to high-latitudes mean sea-level pressure gradient and zonal westerly winds, favouring wave generation zones in higher (lower) latitudes and consequent southerly (easterly) wave components. We identify the Southern Annular Mode as the primary climate driver responsible for these changes. Long-term variations in interhemispheric surface temperature anomalies coexist with oscillations in wave direction, which indicates the influence of temperature-driven atmospheric teleconnections on wave-generation cycles. These results provide a novel geomorphic proxy for paleoenvironmental reconstructions and present new insights into the role of global multi-decadal to multi-centennial climate variability in controlling coastal-ocean wave climate.A.P.S. and A.H.F.K. acknowledge the Brazilian Ministry of Environment for funding through the SMC-Brazil project. A.H.F.K. acknowledges the Rede Clima, INCT MarCOI “Oceanografia Integrada e Usos Multiplos da Plataforma Continental e Oceano Adjacente—Centro de Oceanografia Integrada (COI)”, CNPQ (PQ2- CNPQ 301963/2015-0, PQ1D CNPQ 301597/2018-9, CNPQ 441545/2017-3) and, CAPES Brazil-Finance Code 001 and Capes/PROEX 88881.146046/2017-01 for financial support. F.J.M. acknowledges the funding from the Spanish Ministry of Science and Innovation through the project PID2019-107053RB-I00. A.P.S. acknowledges the CESM1(CAM5) Last Millennium Ensemble Community Project and supercomputing resources provided by NSF/CISL/Yellowstone. C.J.H. acknowledges that this paper is Contribution 3957 of the Virginia Institute of Marine Science, William & Mary

The two-loop four-fermion scattering amplitude in QED

We present the analytic evaluation of the two-loop corrections to the amplitude for the scattering of four fermions in Quantum Electrodynamics, $f^- + f^+ + F^- + F^+ \to 0$, with $f$ and $F$ representing a massless and a massive lepton, respectively. Dimensional regularization is employed to evaluate the loop integrals. Ultraviolet divergences are removed by renormalizing the coupling constant in the ${\overline{\text{MS}}}$-scheme, and the lepton mass as well as the external fields in the on-shell scheme. The analytic result for the renormalized amplitude is expressed as Laurent series around $d=4$ space-time dimensions, and contains Generalized Polylogarithms with up to weight four. The structure of the residual infrared divergences of the virtual amplitude is in agreement with the prediction of the Soft Collinear Effective Theory. Our analytic results are an essential ingredient for the computation of the scattering cross section for massive fermion-pair production in massless fermion-pair annihilation, i.e. $f^- f^+ \to F^- F^+$, and crossing related processes such as the elastic scattering $f F \to f F$, with up to Next-to-Next to Leading Order accuracy.Comment: 5 pages, 2 figures, 1 table + supplemental materia

Two-Loop Four-Fermion Scattering Amplitude in QED

We present the first fully analytic evaluation of the transition amplitude for the scattering of a massless into a massive pair of fermions at the two-loop level in quantum electrodynamics. Our result is an essential ingredient for the determination of the electromagnetic coupling within scattering reactions, beyond the currently known accuracy, which has a crucial impact on the evaluation of the anomalous magnetic moment of the muon. It will allow, in particular, for a precise determination of the leading hadronic contribution to the (g−2)μ in the MUonE experiment at CERN, and therefore can be used to shed light on the current discrepancy between the standard model prediction and the experimental measurement for this important physical observable