The impact of eliminating age inequalities in stage at diagnosis on breast cancer survival for older women.

BACKGROUND: Older women with breast cancer have poorer relative survival outcomes, but whether achieving earlier stage at diagnosis would translate to substantial reductions in mortality is uncertain. METHODS: We analysed data on East of England women with breast cancer (2006-2010) aged 70+ years. We estimated survival for different stage-deprivation-age group strata using both the observed and a hypothetical stage distribution (assuming that all women aged 75+ years acquired the stage distribution of those aged 70-74 years). We subsequently estimated deaths that could be postponed beyond 5 years from diagnosis if women aged 75+ years had the hypothetical stage distribution. We projected findings to the English population using appropriate age and socioeconomic group weights. RESULTS: For a typically sized annual cohort in the East of England, 27 deaths in women with breast cancer aged 75+ years can be postponed within 5 years from diagnosis if their stage distribution matched that of the women aged 70-74 years (4.8% of all 566 deaths within 5 years post diagnosis in this population). Under assumptions, we estimate that the respective number for England would be 280 deaths (5.0% of all deaths within 5 years post diagnosis in this population). CONCLUSIONS: The findings support ongoing development of targeted campaigns aimed at encouraging prompt presentation in older women.This article is an independent research supported by different funding bodies, beyond the authors’ own employing organisations. MJR was partially funded by a Cancer Research UK Postdoctoral Fellowship (CRUK_A13275). GL is supported by a Postdoctoral Fellowship award by the National Institute for Health Research (NIHR PDF-2011-04-047) to end of 2014 and a Cancer Research UK Clinician Scientist Fellowship award (A18180) from 2015. We thank all staff at the National Cancer Registration Service, Public Health England, Eastern Office who helped collect and code data used in this study. We particularly acknowledge the help of Dr Clement H Brown and Dr Brian A Rous who were responsible for staging.This is the final published version. It first appeared at http://www.nature.com/bjc/journal/v112/n1s/full/bjc201551a.html#ack

Higher derivative type II string effective actions, automorphic forms and E11

By dimensionally reducing the ten-dimensional higher derivative type IIA string theory effective action we place constraints on the automorphic forms that appear in the effective action in lower dimensions. We propose a number of properties of such automorphic forms and consider the prospects that E11 can play a role in the formulation of the higher derivative string theory effective action.Comment: 34 page

Spacelike Singularities and Hidden Symmetries of Gravity

We review the intimate connection between (super-)gravity close to a spacelike singularity (the "BKL-limit") and the theory of Lorentzian Kac-Moody algebras. We show that in this limit the gravitational theory can be reformulated in terms of billiard motion in a region of hyperbolic space, revealing that the dynamics is completely determined by a (possibly infinite) sequence of reflections, which are elements of a Lorentzian Coxeter group. Such Coxeter groups are the Weyl groups of infinite-dimensional Kac-Moody algebras, suggesting that these algebras yield symmetries of gravitational theories. Our presentation is aimed to be a self-contained and comprehensive treatment of the subject, with all the relevant mathematical background material introduced and explained in detail. We also review attempts at making the infinite-dimensional symmetries manifest, through the construction of a geodesic sigma model based on a Lorentzian Kac-Moody algebra. An explicit example is provided for the case of the hyperbolic algebra E10, which is conjectured to be an underlying symmetry of M-theory. Illustrations of this conjecture are also discussed in the context of cosmological solutions to eleven-dimensional supergravity.Comment: 228 pages. Typos corrected. References added. Subject index added. Published versio

Strategic engagement and librarians

The future of the academic book is a strategic engagement issue for librarians. Books might not be stored in or purchased for university libraries; they might not even exist in a physical form. How will academic books be organised and accessed in the future, if they are not in libraries? How will librarians at universities engage academic researchers in strategic conversations about the future of their academic books? This chapter argues that conversations between librarians and academic book authors about the future are more important than ever. It puts the current challenges in context, using data from the Research Excellence Framework and the University of Nottingham library catalogue, identifying the strategic role of librarians in shaping the future of the academic book through strategic engagement

A preliminary study of the effect of closed incision management with negative pressure wound therapy over high-risk incisions

Background Certain postoperative wounds are recognised to be associated with more complications than others and may be termed high-risk. Wound healing can be particularly challenging following high-energy trauma where wound necrosis and infection rates are high. Surgical incision for joint arthrodesis can also be considered high-risk as it requires extensive and invasive surgery and postoperative distal limb swelling and wound dehiscence are common. Recent human literature has investigated the use of negative pressure wound therapy (NPWT) over high-risk closed surgical incisions and beneficial effects have been noted including decreased drainage, decreased dehiscence and decreased infection rates. In a randomised, controlled study twenty cases undergoing distal limb high-energy fracture stabilisation or arthrodesis were randomised to NPWT or control groups. All cases had a modified Robert-Jones dressing applied for 72 h postoperatively and NPWT was applied for 24 h in the NPWT group. Morphometric assessment of limb circumference was performed at six sites preoperatively, 24 and 72 h postoperatively. Wound discharge was assessed at 24 and 72 h. Postoperative analgesia protocol was standardised and a Glasgow Composite Measure Pain Score (GCPS) carried out at 24, 48 and 72 h. Complications were noted and differences between groups were assessed. Results Percentage change in limb circumference between preoperative and 24 and 72 h postoperative measurements was significantly less at all sites for the NPWT group with exception of the joint proximal to the surgical site and the centre of the operated bone at 72 h. Median discharge score was lower in the NPWT group than the control group at 24 h. No significant differences in GCPS or complication rates were noted. Conclusions Digital swelling and wound discharge were reduced when NPWT was employed for closed incision management. Larger studies are required to evaluate whether this will result in reduced discomfort and complication rates postoperatively

Eisenstein series for infinite-dimensional U-duality groups

We consider Eisenstein series appearing as coefficients of curvature corrections in the low-energy expansion of type II string theory four-graviton scattering amplitudes. We define these Eisenstein series over all groups in the E_n series of string duality groups, and in particular for the infinite-dimensional Kac-Moody groups E9, E10 and E11. We show that, remarkably, the so-called constant term of Kac-Moody-Eisenstein series contains only a finite number of terms for particular choices of a parameter appearing in the definition of the series. This resonates with the idea that the constant term of the Eisenstein series encodes perturbative string corrections in BPS-protected sectors allowing only a finite number of corrections. We underpin our findings with an extensive discussion of physical degeneration limits in D<3 space-time dimensions.Comment: 69 pages. v2: Added references and small additions, to be published in JHE

The impact of eliminating age inequalities in stage at diagnosis on breast cancer survival for older women

This is the final published version. Available from Springer Nature via the DOI in this record.BACKGROUND: Older women with breast cancer have poorer relative survival outcomes, but whether achieving earlier stage at diagnosis would translate to substantial reductions in mortality is uncertain.METHODS: We analysed data on East of England women with breast cancer (2006-2010) aged 70+ years. We estimated survival for different stage-deprivation-age group strata using both the observed and a hypothetical stage distribution (assuming that all women aged 75+ years acquired the stage distribution of those aged 70-74 years). We subsequently estimated deaths that could be postponed beyond 5 years from diagnosis if women aged 75+ years had the hypothetical stage distribution. We projected findings to the English population using appropriate age and socioeconomic group weights.RESULTS: For a typically sized annual cohort in the East of England, 27 deaths in women with breast cancer aged 75+ years can be postponed within 5 years from diagnosis if their stage distribution matched that of the women aged 70-74 years (4.8% of all 566 deaths within 5 years post diagnosis in this population). Under assumptions, we estimate that the respective number for England would be 280 deaths (5.0% of all deaths within 5 years post diagnosis in this population).CONCLUSIONS: The findings support ongoing development of targeted campaigns aimed at encouraging prompt presentation in older women.Cancer Research UKCancer Research UKNational Institute for Health Research (NIHR

Understanding the impact of socioeconomic differences in colorectal cancer survival: potential gain in life-years

Background Colorectal cancer prognosis varies substantially with socioeconomic status. We investigated differences in life expectancy between socioeconomic groups and estimated the potential gain in life-years if cancer-related survival differences could be eliminated. Methods This population-based study included 470,000 individuals diagnosed with colon and rectal cancers between 1998 and 2013 in England. Using flexible parametric survival models, we obtained a range of life expectancy measures by deprivation status. The number of life-years that could be gained if differences in cancer-related survival between the least and most deprived groups were removed was also estimated. Results We observed up to 10% points differences in 5-year relative survival between the least and most deprived. If these differences had been eliminated for colon and rectal cancers diagnosed in 2013 then almost 8231 and 7295 life-years would have been gained respectively. This results for instance in more than 1-year gain for each colon cancer male patient in the most deprived group on average. Cancer-related differences are more profound earlier on, as conditioning on 1-year survival the main reason for socioeconomic differences were factors other than cancer. Conclusion This study highlights the importance of policies to eliminate socioeconomic differences in cancer survival as in this way many life-years could be gained

Exploring diurnal variation using piecewise linear splines:an example using blood pressure

Background: There are many examples of physiological processes that follow a circadian cycle and researchers are interested in alternative methods to illustrate and quantify this diurnal variation. Circadian blood pressure (BP) deserves additional attention given uncertainty relating to the prognostic significance of BP variability in relation to cardiovascular disease. However, the majority of studies exploring variability in ambulatory blood pressure monitoring (ABPM) collapse the data into single readings ignoring the temporal nature of the data. Advanced statistical techniques are required to explore complete variation over 24 h. Methods: We use piecewise linear splines in a mixed-effects model with a constraint to ensure periodicity as a novel application for modelling daily blood pressure. Data from the Mitchelstown Study, a cross-sectional study of Irish adults aged 47–73 years (n = 2047) was utilized. A subsample (1207) underwent 24-h ABPM. We compared patterns between those with and without evidence of subclinical target organ damage (microalbuminuria). Results: We were able to quantify the steepest rise and fall in SBP, which occurred just after waking (2.23 mmHg/30 min) and immediately after falling asleep (−1.93 mmHg/30 min) respectively. The variation about an individual’s trajectory over 24 h was 12.3 mmHg (standard deviation). On average those with microalbuminuria were found to have significantly higher SBP (7.6 mmHg, 95% CI 5.0–10.1) after adjustment for age, sex and BMI. Including an interaction term between each linear spline and microalbuminuria did not improve model fit. Conclusion: We have introduced a practical method for the analysis of ABPM where we can determine the rate of increase or decrease for different periods of the day. This may be particularly useful in examining chronotherapy effects of antihypertensive medication. It offers new measures of short-term BP variability as we can quantify the variation about an individual’s trajectory but also allows examination of the variation in slopes between individuals (random-effects)

The impact of life tables adjusted for smoking on the socio-economic difference in net survival for laryngeal and lung cancer.

BACKGROUND: Net survival is a key measure in cancer control, but estimates for cancers that are strongly associated with smoking may be biased. General population life tables represent background mortality in net survival, but may not adequately reflect the higher mortality experienced by smokers. METHODS: Life tables adjusted for smoking were developed, and their impact on net survival and inequalities in net survival for laryngeal and lung cancers was examined. RESULTS: The 5-year net survival estimated with smoking-adjusted life tables was consistently higher than the survival estimated with unadjusted life tables: 7% higher for laryngeal cancer and 1.5% higher for lung cancer. The impact of using smoking-adjusted life tables was more pronounced in affluent patients; the deprivation gap in 5-year net survival for laryngeal cancer widened by 3%, from 11% to 14%. CONCLUSIONS: Using smoking-adjusted life tables to estimate net survival has only a small impact on the deprivation gap in survival, even when inequalities are substantial. Adjusting for the higher, smoking-related background mortality did increase the estimates of net survival for all deprivation groups, and may be more important when measuring the public health impact of differences or changes in survival, such as avoidable deaths or crude probabilities of death