Survival trends of cancer amongst the south Asian and non-south Asian population under 30 years of age in Yorkshire, UK.

Introduction: Several studies have shown differences in survival trends between ethnic groups across adults with cancer in the UK. It is unclear whether these differences exist exclusively in the older adult population or whether they begin to emerge in children and young adults. Methods: Subjects (n = 3534) diagnosed with cancer under 30 years of age in Yorkshire between 1990 and 2005 were analysed. Differences in survival rates for diagnostic subgroups were estimated by ethnic group (south Asian or not) using Kaplan–Meier estimation and Cox regression. Results: When compared to non-south Asians (all other ethnic groups excluding south Asians) a significant increased risk of death was seen for south Asians with leukaemia (hazard ratio (HR) = 1.75; 95% confidence interval (CI) = 1.11–2.76) and lymphoma (HR = 2.05; 95% CI = 1.09–3.87), whereas south Asians with solid tumours other than central nervous system tumours had a significantly reduced risk of death(HR = 0.50; 95% CI = 0.28–0.89). This was independent of socioeconomic deprivation. Conclusion: We found evidence of poorer survival outcomes for south Asians compared to non-south Asian children and young adults with leukaemia and lymphoma, but better outcomes for south Asian children and young adults with other solid tumours. This needs to be explained, and carefully addressed in the on-going development of cancer services

Socio-economic and ethnic disparities in childhood cancer survival, Yorkshire, UK

Background Establishing the existence of health inequalities remains a high research and policy agenda item in the United Kingdom. We describe ethnic and socio-economic differences in paediatric cancer survival, focusing specifically on the extent to which disparities have changed over a 20-year period. Methods Cancer registration data for 2674 children (0–14 years) in Yorkshire were analysed. Five-year survival estimates by ethnic group (south Asian/non-south Asian) and Townsend deprivation fifths (I–V) were compared over time (1997–2016) for leukaemia, lymphoma, central nervous system (CNS) and other solid tumours. Hazard ratios (HR: 95% CI) from adjusted Cox models quantified the joint effect of ethnicity and deprivation on mortality risk over time, framed through causal interpretation of the deprivation coefficient. Results Increasing deprivation was associated with significantly higher risk of death for children with leukaemia (1.11 (1.03–1.20)) and all cancers between 1997 and 2001. While we observed a trend towards reducing differences in survival over time in this group, a contrasting trend was observed for CNS tumours whereby sizeable variation in outcome remained for cases diagnosed until 2012. South Asian children with lymphoma had a 15% reduced chance of surviving at least 5 years compared to non-south Asian, across the study period. Discussion Even in the United Kingdom, with a universally accessible healthcare system, socio-economic and ethnic disparities in childhood cancer survival exist. Findings should inform where resources should be directed to provide all children with an equitable survival outcome following a cancer diagnosis

Maternal Undernutrition Significantly Impacts Ovarian Follicle Number and Increases Ovarian Oxidative Stress in Adult Rat Offspring

BACKGROUND: We have shown recently that maternal undernutrition (UN) advanced female pubertal onset in a manner that is dependent upon the timing of UN. The long-term consequence of this accelerated puberty on ovarian function is unknown. Recent findings suggest that oxidative stress may be one mechanism whereby early life events impact on later physiological functioning. Therefore, using an established rodent model of maternal UN at critical windows of development, we examined maternal UN-induced changes in offspring ovarian function and determined whether these changes were underpinned by ovarian oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: Our study is the first to show that maternal UN significantly reduced primordial and secondary follicle number in offspring in a manner that was dependent upon the timing of maternal UN. Specifically, a reduction in these early stage follicles was observed in offspring born to mothers undernourished throughout both pregnancy and lactation. Additionally, antral follicle number was reduced in offspring born to all mothers that were UN regardless of whether the period of UN was restricted to pregnancy or lactation or both. These reductions were associated with decreased mRNA levels of genes critical for follicle maturation and ovulation. Increased ovarian protein carbonyls were observed in offspring born to mothers UN during pregnancy and/or lactation and this was associated with peroxiredoxin 3 hyperoxidation and reduced mRNA levels; suggesting compromised antioxidant defence. This was not observed in offspring of mothers UN during lactation alone. CONCLUSIONS: We propose that maternal UN, particularly at a time-point that includes pregnancy, results in reduced offspring ovarian follicle numbers and mRNA levels of regulatory genes and may be mediated by increased ovarian oxidative stress coupled with a decreased ability to repair the resultant oxidative damage. Together these data are suggestive of maternal UN potentially contributing to premature ovarian ageing in offspring

On step width adaptation in simulated annealing for continuous parameter optimisation

Abstract. Simulated annealing is a general optimisation algorithm, based on hill-climbing. As in hill-climbing, new candidate solutions are selected from the ‘neighbourhood ’ of the current solution. For continuous parameter optimisation, it is practically impossible to choose direct neighbours, because of the vast number of points in the search space. In this case, it is necessary to choose new candidate solutions from a wider neighbourhood, i.e. from some distance of the current solution, for performance reasons. The right choice of this distance is often crucial for the success of the algorithm, especially in real-world application where the number of fitness evaluations is limited. This paper explains how in such a case the use of a variable radius of this neighbourhood, refereed to as maximum step width, can increase the over-all performance of simulated annealing. A real-world example demonstrates the increased performance of the modified algorithm.