External validation of a colorectal cancer model against screening trial long term follow-up data

Objectives: The ScHARR Bowel Cancer Screening Model has been used to make decisions about screening strategies in England. The objective of this study was to perform external validation of the ScHARR model against long-term follow-up data about colorectal cancer (CRC) incidence and mortality reductions due to screening, from the Nottingham Trial of guaiac Faecal Occult Blood Testing for CRC, and the UK Flexible Sigmoidoscopy Screening Trial. Methods: The ScHARR model was adapted prior to validation to reflect the setting of each trial in terms of population characteristics, details of screening and surveillance programmes, uptake of screening and further investigations and study follow-up. The impact of using current versus historical CRC incidence and mortality data in the validation was also examined by carrying out a series of analyses in which historical data from different years was included in the model. Results: The ScHARR model was able to predict CRC incidence and mortality rate/hazard ratios from both trials to well within the 95% confidence intervals in the observed data. Whilst it was less accurate in predicting absolute incidence and mortality rates, modelling historical incidence and mortality data enabled these predictions to be improved considerably. Conclusions: The ScHARR model is able to replicate the long-term relative benefit from screening observed in two large-scale UK based screening trials and can therefore be considered to be an appropriate tool to facilitate decision making around the English bowel cancer screening programme

A serpin with a finger in many PAI’s : PAI-1’s central function in thromboinflammation and cardiovascular disease

FUNDING NM and CW are funded by grants from the British Heart Foundation PG/15/82/31721 and PG/20/17/35050 and Friends of Anchor RS 2019 003 and Aberdeen Development Trust. GM, CW, and NM were also funded by NHS Grampian Endowment Fund COV19-004.Peer reviewedPublisher PD

Hydrogenic retention with high-Z plasma facing surfaces in Alcator C-Mod

The retention of deuterium (D) fuel in the Alcator C-Mod tokamak is studied using a new 'static' gas balance method. C-Mod solely employs high-Z molybdenum (Mo) and tungsten (W) for its plasma facing materials, with intermittent application of thin boron (B) films. The primarily Mo surfaces are found to retain large fractions, similar to 20-50%, of the D-2 gas fuelled per quiescent discharge, regardless of whether the Mo surfaces are cleaned of, or partially covered by, B films. Several experiments and calculations show that it is improbable that B retains significant fractions of the fuel. Rather, retention occurs in Mo and W surfaces through ion bombardment, implantation and diffusion to trap sites. Roughly 1% D of the incident ion fluence, Phi(D), to surfaces is retained, and with no indication of the retention rate decreasing after 25 s of integrated plasma exposure. The magnitude of retention is significantly larger than that extrapolated from the results of laboratory studies for either Mo or W. The high levels of D/Mo in the near surface, measured directly post-campaign (similar to 0.01) in tiles and inferred from gas balance, are consistent with trapping sites for fuel retention in the Mo being created, or expanded, by high D atom densities in the near surface which arise as a result of high incident ion fluxes. Differences between C-Mod and laboratory retention results may be due to such factors as the multiply ionized B ions incident on the surface directly creating traps, the condition of Mo (impurities, annealing) and the high-flux densities in the C-Mod divertor which are similar to ITER, but 10-100x those used in laboratory studies. Disruptions produce rapid heating of the surfaces, releasing trapped hydrogenic species into the vessel for recovery. The measurements of the large amount of gas released in disruptions are consistent with the analysis of tiles removed from the vessel post-campaign-the campaign-integrated retention is very low, of order 1000x less than that observed in a single, non-disruptive discharge

Optimising Bowel Cancer Screening Phase 1: Optimising the cost effectiveness of repeated FIT screening and screening strategies combining bowel scope and FIT screening

ScHARR has been commissioned by the UK National Screening Committee (NSC) to consider the costeffectiveness and endoscopy capacity requirements of a variety of different screening options incorporating faecal immunochemical testing (FIT) and bowel scope (BS) within the Bowel Cancer Screening Programme (BCSP). An existing cost-effectiveness model was used. The model was refined considerably, new data included and model validation was undertaken. All FIT thresholds between 20 and 180 µg/ml were modelled. Analyses were undertaken to determine which screening strategies involving repeated FIT screening and/or bowel scope are most cost-effective given endoscopy constraints. Note that the conclusions reached are based on optimising cost-effectiveness where effectiveness is measured in terms of QALYs gained. If the aim was to optimise QALY gains or CRC incidence/mortality reduction then conclusions would be different. The analysis without endoscopy constraints indicates that the most cost effective screening strategy is the one which delivers the most intensive screening. Regardless of capacity constraints the current screening strategies (gFOBT 2-yearly 60-74 with or without bowel scope age 55) are dominated by a FIT screening strategy (i.e. a FIT strategy exists which is more effective and less expensive). For repeated FIT screening it is recommended that the screening interval is kept to 2-yearly screening. However, increased benefits may be obtained by re-inviting non-attenders after a 1 year interval. The optimal starting age for a repeated FIT screening strategy is 50 or 51 hence it is suggested that the screening start age is reduced compared to what is currently used in the BCSP. The optimal upper screening age varies between 65 and 74, depending on the capacity constraint used. The optimal FIT threshold depends on the available capacity for screening referral colonoscopies. With 50,000 screening referral colonoscopies (current capacity) then we recommend a strategy of 2-yearly, age 51-65, FIT161 (8 screens). With 70,000 screening referral colonoscopies (current capacity) then we recommend a strategy of: 2-yearly, age 50-70, FIT153 (11 screens). If 90,000 screening referral colonoscopies is considered feasible to achieve in the future then we recommend a strategy of 2-yearly, age 50-74, FIT124 (13 screens). In terms of bowel scope screening the model found uncertainty in whether it is cost effective to replace one FIT screen with a one-off bowel scope at age 58/59. However, a repeated FIT screening strategy requiring 125k screening referral colonoscopies annually would be far more effective and cost effective than a one-off bowel scope at age 59. Such strategies could be considered to have equivalent ‘endoscopy capacity’ (assuming that 10 bowel scopes and 4 screening referral colonoscopies are equivalent ).Hence, if bowel scope capacity could be used for undertaking screening referral colonoscopies this would result in higher effectiveness and cost-effectiveness

Fourier transforming a trapped Bose-Einstein condensate by waiting a quarter of the trap period: simulation and applications

We investigate the property of isotropic harmonic traps to Fourier transform a weakly interacting Bose–Einstein condensate (BEC) every quarter of a trap period. We solve the Gross–Pitaevskii equation numerically to investigate the time evolution of interacting BECs in the context of the Fourier transform, and we suggest potential applications

Conceptual design study for heat exhaust management in the ARC fusion pilot plant

The ARC pilot plant conceptual design study has been extended beyond its initial scope [B. N. Sorbom et al., FED 100 (2015) 378] to explore options for managing ~525 MW of fusion power generated in a compact, high field (B_0 = 9.2 T) tokamak that is approximately the size of JET (R_0 = 3.3 m). Taking advantage of ARC's novel design - demountable high temperature superconductor toroidal field (TF) magnets, poloidal magnetic field coils located inside the TF, and vacuum vessel (VV) immersed in molten salt FLiBe blanket - this follow-on study has identified innovative and potentially robust power exhaust management solutions.Comment: Accepted by Fusion Engineering and Desig

The association between long-term conditions and uptake of population-based screening for colorectal cancer: results from two English cohort studies

Introduction: Uptake of screening for colorectal cancer (CRC) can reduce mortality, and population-based screening is offered in England. To date, there is little evidence on the association between having a long-term condition (LTC) and CRC screening uptake. The objective of this study was to examine the association between having an LTC and uptake of CRC screening in England with the guaiac fecal occult blood test, with a particular focus on common mental disorders. Methods: The study was a preregistered secondary analysis of two cohorts: first, a linked data set between the regional Yorkshire Health Study (YHS) and the National Health Service National Bowel Cancer Screening Program (BCSP, years 2006–2014); second, the national English Longitudinal Study of Ageing (ELSA, years 2014–2015). Individuals eligible for BCSP screening who participated in either the YHS (7,142) or ELSA Wave 7 (4,099) were included. Study registration: ClinicalTrials.gov, number NCT02503969. Results: In both the cohorts, diabetes was associated with lower uptake (YHS odds ratio [OR] for non-uptake 1.35, 95% CI 1.03–1.78; ELSA 1.33, 1.03–1.72) and osteoarthritis was associated with increased uptake (YHS 0.75, 0.57–0.99; ELSA 0.76, 0.62–0.93). After controlling for broader determinants of health, there was no evidence of significantly different uptake for individuals with common mental disorders. Conclusion: Two large independent cohorts provided evidence that uptake of CRC screening is lower among individuals with diabetes and higher among individuals with osteoarthritis. Further work should compare barriers and facilitators to screening among individuals with either of these conditions. This study also demonstrates the benefits of data linkage for improving clinical decision-making