Global surveillance of cancer survival 1995–2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control.

METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights.

FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease.

INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems.

Do persistent organic pollutants interact with the stress response? Individual compounds, and their mixtures, interaction with the glucocorticoid receptor

Persistent organic pollutants (POPs) are toxic substances, highly resistant to environmental degradation, which can bio-accumulate and have long-range atmospheric transport potential (UNEP 2001). The majority of studies on endocrine disruption have focused on interferences on the sexual steroid hormones and so have overlooked disruption to glucocorticoid hormones. Here the endocrine disrupting potential of individual POPs and their mixtures has been investigated in vitro to identify any disruption to glucocorticoid nuclear receptor transcriptional activity. POP mixtures were screened for glucocorticoid receptor (GR) translocation using a GR redistribution assay (RA) on a CellInsight(TM) NXT High Content Screening (HCS) platform. A mammalian reporter gene assay (RGA) was then used to assess the individual POPs, and their mixtures, for effects on glucocorticoid nuclear receptor transactivation. POP mixtures did not induce GR translocation in the GR RA or produce an agonist response in the GR RGA. However, in the antagonist test, in the presence of cortisol, an individual POP, p,p'-dichlorodiphenyldichloroethylene (DDE), was found to decrease glucocorticoid nuclear receptor transcriptional activity to 72.5% (in comparison to the positive cortisol control). Enhanced nuclear transcriptional activity, in the presence of cortisol, was evident for the two lowest concentrations of perfluorodecanoic acid (PFOS) potassium salt (0.0147mg/ml and 0.0294mg/ml), the two highest concentrations of perfluorodecanoic acid (PFDA) (0.0025mg/ml and 0.005mg/ml) and the highest concentration of 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) (0.0000858mg/ml). It is important to gain a better understanding of how POPs can interact with GRs as the disruption of glucocorticoid action is thought to contribute to complex diseases.

Individual factors and perceived community characteristics in relation to mental health and mental well-being

Background
It has been argued that though correlated with mental health, mental well-being is a distinct entity. Despite the wealth of literature on mental health, less is known about mental well-being. Mental health is something experienced by individuals, whereas mental well-being can be assessed at the population level. Accordingly it is important to differentiate the individual and population level factors (environmental and social) that could be associated with mental health and well-being, and as people living in deprived areas have a higher prevalence of poor mental health, these relationships should be compared across different levels of neighbourhood deprivation.

Methods
A cross-sectional representative random sample of 1,209 adults from 62 Super Output Areas (SOAs) in Belfast, Northern Ireland (Feb 2010 – Jan 2011) were recruited in the PARC Study. Interview-administered questionnaires recorded data on socio-demographic characteristics, health-related behaviours, individual social capital, self-rated health, mental health (SF-8) and mental well-being (WEMWBS). Multi-variable linear regression analyses, with inclusion of clustering by SOAs, were used to explore the associations between individual and perceived community characteristics and mental health and mental well-being, and to investigate how these associations differed by the level of neighbourhood deprivation.

Results
Thirty-eight and 30 % of variability in the measures of mental well-being and mental health, respectively, could be explained by individual factors and the perceived community characteristics. In the total sample and stratified by neighbourhood deprivation, age, marital status and self-rated health were associated with both mental health and well-being, with the ‘social connections’ and local area satisfaction elements of social capital also emerging as explanatory variables. An increase of +1 in EQ-5D-3 L was associated with +1SD of the population mean in both mental health and well-being. Similarly, a change from ‘very dissatisfied’ to ‘very satisfied’ for local area satisfaction would result in +8.75 for mental well-being, but only in the more affluent of areas.

Conclusions
Self-rated health was associated with both mental health and mental well-being. Of the individual social capital explanatory variables, ‘social connections’ was more important for mental well-being. Although similarities in the explanatory variables of mental health and mental well-being exist, socio-ecological interventions designed to improve them may not have equivalent impacts in rich and poor neighbourhoods.

Laterality as an indicator of emotional stress in ewes and lambs during a separation test

We assessed motor laterality in sheep to explore species-specific brain hemi-field dominance and how this could be affected by genetic or developmental factors. Further, we investigated whether directionality and strength of laterality could be linked to emotional stress in ewes and their lambs during partial separation. Forty-three ewes and their singleton lambs were scored on the (left/right) direction of turn in a y-maze to rejoin a conspecific (laterality test). Further, their behavioural response (i.e. time spent near the fence, vocalisations, and activity level) during forced separation by an open-mesh fence was assessed (separation test). Individual laterality was recorded for 44.2 % ewes (significant right bias) and 81.4 % lambs (equally biased to the left and the right). There was no significant association in side bias between dams and offspring. The Chi-squared test revealed a significant population bias for both groups (p < 0.05). Evolutionary adaptive strategies or stimuli-related visual laterality may provide explanation for this decision-making process. Absolute strength of laterality (irrespective of side) was high (Kolmogorov–Smirnov test, dams: D = 0.2; p < 0.001; lambs: D = 0.36, p < 0.0001). The Wilcoxon test showed that lateralised lambs and dams spent significantly more time near each other during separation than non-lateralised animals (p < 0.05), and that lateralised dams were also more active than non-lateralised ones. Arguably, the lateralised animals showed a greater attraction to their pair because they were more disturbed and thus required greater reassurance. The data show that measures of laterality offer a potential novel non-invasive indicator of separation stress.

A novel method of microsatellite genotyping-by-sequencing using individual combinatorial barcoding

This study examines the potential of next-generation sequencing based ‘genotyping-by-sequencing’ (GBS) of microsatellite loci for rapid and cost-effective genotyping in large-scale population genetic studies. The recovery of individual genotypes from large sequence pools was achieved by PCR-incorporated combinatorial barcoding using universal primers. Three experimental conditions were employed to explore the possibility of using this approach with existing and novel multiplex marker panels and weighted amplicon mixture. The GBS approach was validated against microsatellite data generated by capillary electrophoresis. GBS allows access to the underlying nucleotide sequences that can reveal homoplasy, even in large datasets and facilitates cross laboratory transfer. GBS of microsatellites, using individual combinatorial barcoding, is potentially faster and cheaper than current microsatellite approaches and offers better and more data.

Validating the use of intrinsic markers in body feathers to identify inter‑individual differences in non‑breeding areas of northern fulmars

Many wildlife studies use chemical analyses to explore spatio-temporal variation in diet, migratory patterns and contaminant exposure. Intrinsic markers are particularly valuable for studying non-breeding marine predators, when direct methods of investigation are rarely feasible. However, any inferences regarding foraging ecology are dependent upon the time scale over which tissues such as feathers are formed. In this study, we validate the use of body feathers for studying non-breeding foraging patterns in a pelagic seabird, the northern fulmar. Analysis of carcasses of successfully breeding adult fulmars indicated that body feathers moulted between September and March, whereas analyses of carcasses and activity patterns suggested that wing feather and tail feather moult occurred during more restricted periods (September to October and September to January, respectively). By randomly sampling relevant body feathers, average values for individual birds were shown to be consistent. We also integrated chemical analyses of body feather with geolocation tracking data to demonstrate that analyses of δ13C and δ15N values successfully assigned 88 % of birds to one of two broad wintering regions used by breeding adult fulmars from a Scottish study colony. These data provide strong support for the use of body feathers as a tool for exploring non-breeding foraging patterns and diet in wide-ranging, pelagic seabirds.

Efficient Key Generation by Exploiting Randomness from Channel Responses of Individual OFDM Subcarriers

Key generation from the randomness of wireless channels is a promising technique to establish a secret cryptographic key securely between legitimate users. This paper proposes a new approach to extract keys efficiently from channel responses of individual orthogonal frequency-division multiplexing (OFDM) subcarriers. The efficiency is achieved by (i) fully exploiting randomness from time and frequency domains and (ii) improving the cross-correlation of the channel measurements. Through the theoretical modelling of the time and frequency autocorrelation relationship of the OFDM subcarrier's channel responses, we can obtain the optimal probing rate and use multiple uncorrelated subcarriers as random sources. We also study the effects of non-simultaneous measurements and noise on the cross-correlation of the channel measurements. We find the cross-correlation is mainly impacted by noise effects in a slow fading channel and use a low pass filter (LPF) to reduce the key disagreement rate and extend the system's working signal-to-noise ratio range. The system is evaluated in terms of randomness, key generation rate, and key disagreement rate, verifying that it is feasible to extract randomness from both time and frequency domains of the OFDM subcarrier's channel responses.

Verification of Key Generation from Individual OFDM Subcarrier's Channel Response

This paper presents a key generation system derived from the channel response of individual subcarrier in orthogonal frequency-division multiplexing (OFDM) systems. Practical aspects of the security were investigated by implementing our key generation scheme on a wireless open-access research platform (WARP), which enables us to obtain channel estimation of individual OFDM subcarriers, a feature not currently available in most commercial wireless interface cards. Channel response of individual OFDM subcarrier is usually a wide sense stationary random process, which allows us to find the optimal probing period and maximize the key generation rate. The implementation requires cross layer design as it involves interaction between physical and MAC layer. We have experimentally verified the feasibility and principles of key generation, and also evaluated the performance of our system in terms of randomness, key generation rate and key disagreement rate, which proves that OFDM subcarrier's channel responses are valid for key generation.

Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium

BACKGROUND: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality.

METHODS: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.

RESULTS: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.

CONCLUSIONS: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.

Physical activity in deprived communities in London: examining individual and neighbourhood-level factors

Introduction: The objectives of this study were to examine relationships between neighbourhood-level and individual-level characteristics and physical activity in deprived London neighbourhoods. Methods: In 40 of the most deprived neighbourhoods in London (ranked in top 11% in London by Index of Multiple Deprivation) a cross-sectional survey (n = 4107 adults aged > = 16 years), neighbourhood audit tool, GIS measures and routine data measured neighbourhood and individual-level characteristics. The binary outcome was meeting the minimum recommended (CMO, UK) 5×30 mins moderate physical activity per week. Multilevel modelling was used to examine associations between physical activity and individual and neighbourhood-level characteristics. Results: Respondents living more than 300 m away from accessible greenspace had lower odds of achieving recommended physical activity levels than those who lived within 300 m; from 301–600 m (OR = 0.7; 95% CI 0.5–0.9) and from 601–900 m (OR = 0.6; 95% CI 0.4–0.8). There was substantial residual between-neighbourhood variance in physical activity (median odds ratio = 1.7). Other objectively measured neighbourhood-level characteristics were not associated with physical activity levels. Conclusions Distance to nearest greenspace is associated with meeting recommended physical activity levels in deprived London neighbourhoods. Despite residual variance in physical activity levels between neighbourhoods, we found little evidence for the influence of other measured neighbourhood-level characteristics.

Brain responses to audiovisual speech mismatch in infants are associated with individual differences in looking behaviour

Research on audiovisual speech integration has reported high levels of individual variability, especially among young infants. In the present study we tested the hypothesis that this variability results from individual differences in the maturation of audiovisual speech processing during infancy. A developmental shift in selective attention to audiovisual speech has been demonstrated between 6 and 9 months with an increase in the time spent looking to articulating mouths as compared to eyes (Lewkowicz & Hansen-Tift. (2012) Proc. Natl Acad. Sci. USA, 109, 1431–1436; Tomalski et al. (2012) Eur. J. Dev. Psychol., 1–14). In the present study we tested whether these changes in behavioural maturational level are associated with differences in brain responses to audiovisual speech across this age range. We measured high-density event-related potentials (ERPs) in response to videos of audiovisually matching and mismatched syllables /ba/ and /ga/, and subsequently examined visual scanning of the same stimuli with eye-tracking. There were no clear age-specific changes in ERPs, but the amplitude of audiovisual mismatch response (AVMMR) to the combination of visual /ba/ and auditory /ga/ was strongly negatively associated with looking time to the mouth in the same condition. These results have significant implications for our understanding of individual differences in neural signatures of audiovisual speech processing in infants, suggesting that they are not strictly related to chronological age but instead associated with the maturation of looking behaviour, and develop at individual rates in the second half of the first year of life.