Alternative models for measuring temporal trends in incidence and mortality rates

The average percent change (APC) is often used to measure temporal trends. Under the assumption of linearity on the logarithmic scale, the APC is estimated by using a generalized linear model. A serious limitation of least-squares type estimators is their sensitivity to outliers. The goal of this study is two-fold: firstly, we propose a robust and easy-to-compute measure of the temporal trend based on the median of the rates (median percent change - MPC), rather than their mean; secondly, we investigate the performance of several models for estimating the rate of change when some of the most common model assumptions are violated. We provide some general guidance on the practices of the estimation of temporal trends when using different models under different circumstances. Also, we analyzed an English cancer registration dataset to illustrate the proposed method. The MPC provides a robust alternative to APC. We believe that, as a good practice, both APC and MPC should be presented when sensitivity issues arise. The modelling of data subsets, in any case, should reflect the peculiarity of the process from where the dataset has originated

Survival from cancer in teenagers and young adults in England, 1979–2003

Cancer is the leading cause of disease-related death in teenagers and young adults aged 13–24 years (TYAs) in England. We have analysed national 5-year relative survival among more than 30 000 incident cancer cases in TYAs. For cancer overall, 5-year survival improved from 63% in 1979–84 to 74% during 1996–2001 (P<0.001). However, there were no sustained improvements in survival over time among high-grade brain tumours and bone and soft tissue sarcomas. Survival patterns varied by age group (13–16, 17–20, 21–24 years), sex and diagnosis. Survival from leukaemia and brain tumours was better in the youngest age group but in the oldest from germ-cell tumours (GCTs). For lymphomas, bone and soft tissue sarcomas, melanoma and carcinomas, survival was not significantly associated with age. Females had a better survival than males except for GCTs. Most groups showed no association between survival and socioeconomic deprivation, but for leukaemias, head and neck carcinoma and colorectal carcinoma, survival was significantly poorer with increasing deprivation. These results will aid the development of national specialised service provision for this age group and identify areas of clinical need that present the greatest challenges

Rates of inclusion of teenagers and young adults in England into National Cancer Research Network clinical trials: Report from the National Cancer Research Institute (NCRI) Teenage and Young Adult Clinical Studies Development Group

Poor inclusion rates into clinical trials for teenagers and young adults (TYA; aged 13–24 years) have been assumed but not systematically investigated in England. We analysed accrual rates (AR) from 1 April 2005 up to 31 March 2007 to National Cancer Research Network (NCRN) Phase III trials for the commonest tumour types occurring in TYA and children: leukaemia, lymphoma, brain and central nervous system, bone sarcomas and male germ cell tumours. AR for 2005–2007 were 43.2% for patients aged 10–14 years, 25.2% for patients aged 15–19 years, and 13.1% for patients aged 20–24 years in the tumour types analysed. Compared with accrual from 1 April 2005 to 31 March 2006, AR between 1 April 2006 and 31 March 2007 increased for those aged 10–14 and 15–19 years, but fell for those aged 20–24 years. AR varied considerably among cancer types. Despite four trials being available, patients over 16 years with central nervous system tumours were not recruited. Rates of participation in clinical trials in England from 2005 to 2007 were much lower for TYA older than 15 years compared with children and younger teenagers. The variations in open trials, trial age eligibility criteria and extent of trial activation in treatment centres in part explain this observation. Other possible influences, such as difficulties associated with the consent of TYA require further evaluation. Closer dialogue between those involved in planning and running trials for children and for adults is necessary to improve trial availability and recruitment. Further research is required to identify trends in trial availability and accrual for those tumours constituting the remaining 26% of TYA cancers

Increasing incidence of childhood tumours of the central nervous system in Denmark, 1980–1996

The registered incidence rate of childhood central nervous system (CNS) tumours has increased in several countries. It is uncertain whether these increases are biologically real or owing to improved diagnostic methods. We explored the medical records of 626 CNS tumours diagnosed in Danish children between 1980 and 1996. Population-based registers were used to extract data on mortality and background population. Temporal patterns were analysed by regression techniques. Most tumours were verified by computed tomography (78%) or magnetic resonance imaging (14%). Overall, the incidence rate increased by 2.9% per year (95% confidence interval (CI): 1.3;4.5) and the mortality rate increased by 1.4% per year (95% CI: −0.4;3.3). Among children aged 0–4 years, the survival rate after diagnosis remained almost unchanged, whereas among children aged 5–14 years, the 10-year survival rate improved from 59 to 74%. These data suggest that the incidence rate of CNS tumours among Danish children has truly increased, although alternative explanations cannot be excluded

Long Time to Diagnosis of Medulloblastoma in Children Is Not Associated with Decreased Survival or with Worse Neurological Outcome

International audienceBACKGROUND: The long time to diagnosis of medulloblastoma, one of the most frequent brain tumors in children, is the source of painful remorse and sometimes lawsuits. We analyzed its consequences for tumor stage, survival, and sequelae. PATIENTS AND METHODS: This retrospective population-based cohort study included all cases of pediatric medulloblastoma from a region of France between 1990 and 2005. We collected the demographic, clinical, and tumor data and analyzed the relations between the interval from symptom onset until diagnosis, initial disease stage, survival, and neuropsychological and neurological outcome. RESULTS: The median interval from symptom onset until diagnosis for the 166 cases was 65 days (interquartile range 31-121, range 3-457). A long interval (defined as longer than the median) was associated with a lower frequency of metastasis in the univariate and multivariate analyses and with a larger tumor volume, desmoplastic histology, and longer survival in the univariate analysis, but not after adjustment for confounding factors. The time to diagnosis was significantly associated with IQ score among survivors. No significant relation was found between the time to diagnosis and neurological disability. In the 62 patients with metastases, a long prediagnosis interval was associated with a higher T stage, infiltration of the fourth ventricle floor, and incomplete surgical resection; it nonetheless did not influence survival significantly in this subgroup. CONCLUSIONS: We found complex and often inverse relations between time to diagnosis of medulloblastoma in children and initial severity factors, survival, and neuropsychological and neurological outcome. This interval appears due more to the nature of the tumor and its progression than to parental or medical factors. These conclusions should be taken into account in the information provided to parents and in expert assessments produced for malpractice claims

Root Herbivore Effects on Aboveground Multitrophic Interactions: Patterns, Processes and Mechanisms

In terrestrial food webs, the study of multitrophic interactions traditionally has focused on organisms that share a common domain, mainly above ground. In the last two decades, it has become clear that to further understand multitrophic interactions, the barrier between the belowground and aboveground domains has to be crossed. Belowground organisms that are intimately associated with the roots of terrestrial plants can influence the levels of primary and secondary chemistry and biomass of aboveground plant parts. These changes, in turn, influence the growth, development, and survival of aboveground insect herbivores. The discovery that soil organisms, which are usually out of sight and out of mind, can affect plant-herbivore interactions aboveground raised the question if and how higher trophic level organisms, such as carnivores, could be influenced. At present, the study of above-belowground interactions is evolving from interactions between organisms directly associated with the plant roots and shoots (e.g., root feeders - plant - foliar herbivores) to interactions involving members of higher trophic levels (e.g., parasitoids), as well as non-herbivorous organisms (e.g., decomposers, symbiotic plant mutualists, and pollinators). This multitrophic approach linking above- and belowground food webs aims at addressing interactions between plants, herbivores, and carnivores in a more realistic community setting. The ultimate goal is to understand the ecology and evolution of species in communities and, ultimately how community interactions contribute to the functioning of terrestrial ecosystems. Here, we summarize studies on the effects of root feeders on aboveground insect herbivores and parasitoids and discuss if there are common trends. We discuss the mechanisms that have been reported to mediate these effects, from changes in concentrations of plant nutritional quality and secondary chemistry to defense signaling. Finally, we discuss how the traditional framework of fixed paired combinations of root- and shoot-related organisms feeding on a common plant can be transformed into a more dynamic and realistic framework that incorporates community variation in species, densities, space and time, in order to gain further insight in this exciting and rapidly developing field

Black hole spin: theory and observation

In the standard paradigm, astrophysical black holes can be described solely by their mass and angular momentum - commonly referred to as `spin' - resulting from the process of their birth and subsequent growth via accretion. Whilst the mass has a standard Newtonian interpretation, the spin does not, with the effect of non-zero spin leaving an indelible imprint on the space-time closest to the black hole. As a consequence of relativistic frame-dragging, particle orbits are affected both in terms of stability and precession, which impacts on the emission characteristics of accreting black holes both stellar mass in black hole binaries (BHBs) and supermassive in active galactic nuclei (AGN). Over the last 30 years, techniques have been developed that take into account these changes to estimate the spin which can then be used to understand the birth and growth of black holes and potentially the powering of powerful jets. In this chapter we provide a broad overview of both the theoretical effects of spin, the means by which it can be estimated and the results of ongoing campaigns.Comment: 55 pages, 5 figures. Published in: "Astrophysics of Black Holes - From fundamental aspects to latest developments", Ed. Cosimo Bambi, Springer: Astrophysics and Space Science Library. Additional corrections mad

Population mixing for leukaemia, lymphoma and CNS tumours in teenagers and young adults in England, 1996-2005

Background: Little aetiological epidemiological research has been undertaken for major cancers occurring in teenagers and young adults (TYA). Population mixing, as a possible proxy for infectious exposure, has been well researched for childhood malignancies. We aimed to investigate effects of population mixing in this older age group using an English national cancer dataset.Methods: Cases of leukaemia, lymphoma and central nervous system (CNS) tumours amongst 15-24 year olds in England (diagnosed 1996-2005) were included in the study. Data were obtained by ward of diagnosis and linked to 1991 census variables including population mixing (Shannon index); data on person-weighted population density and deprivation (Townsend score) were also used and considered as explanatory variables. Associations between TYA cancer incidence and census variables were investigated using negative binomial regression, and results presented as incidence rate ratios (IRR) with 95% confidence intervals (CI).Results: A total of 6251 cases of leukaemia (21%), lymphoma (49%) and CNS tumours (30%) were analysed. Higher levels of population mixing were associated with a significant decrease in the incidence of CNS tumours (IRR = 0.83, 95% CI = 0.75-0.91), accounted for by astrocytomas and 'other CNS tumours'; however, there was no association with leukaemia or lymphoma. Incidence of CNS tumours and lymphoma was 3% lower in more deprived areas (IRR = 0.97, 95% CI = 0.96-0.99 and IRR = 0.97, 95% CI =0.96-0.98 respectively). Population density was not associated with the incidence of leukaemia, lymphoma or CNS tumours.Conclusions: Our results suggest a possible role for environmental risk factors with population correlates in the aetiology of CNS tumours amongst TYAs. Unlike studies of childhood cancer, associations between population mixing and the incidence of leukaemia and lymphoma were not observed