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.

Locations of peculiar supernovae as a diagnostic of their origins

We put constraints on the properties of the progenitors of peculiar calcium-rich transients using the distribution of locations within their host galaxies. We confirm that this class of transients do not follow the galaxy stellar mass profile and are more likely to be found in remote locations of their apparent hosts. We test the hypothesis that these transients are from low-metallicity progenitors by comparing their spatial distributions with the predictions of self-consistent cosmological simulations that include star formation and chemical enrichment. We find that while metal-poor stars and our transient sample show a consistent preference for large offsets, metallicity alone cannot explain the extreme cases. Invoking a lower age limit on the progenitor helps to improve the match, indicating these events may result from a very old metal-poor population. We also investigate the radial distribution of globular cluster systems, and show that they too are consistent with the class of calcium-rich transients. Because photometric upper limits exist for globular clusters for some members of the class, a production mechanism related to the dense environment of globular clusters is not favoured for the calcium-rich events. However, the methods developed in this paper may be used in the future to constrain the effects of low metallicity on radially distant core-collapse events or help establish a correlation with globular clusters for other classes of peculiar explosions.

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.

Observation of the inhomogeneous spatial distribution of MeV ions accelerated by the hydrodynamic ambipolar expansion of clusters

An inhomogeneous spatial distribution of laser accelerated carbon/oxygen ions produced via the hydrodynamic ambipolar expansion of CO₂ clusters has been measured by using CR-39 detectors. An inhomogeneous etch pits spatial distribution has appeared on the etched CR-39 detector installed on the laser propagation direction, while homogeneous ones are appeared on those installed at 45°and 90°from the laser propagation direction. From the range of ions in CR-39 obtained by using the multi-step etching technique, the averaged energies of carbon/oxygen ions for all directions are determined as 0.78 ± 0.09 MeV/n. The number of ions in the laser propagation direction is about 1.5 times larger than those in other directions. The inhomogeneous etch pits spatial distribution in the laser propagation direction could originate from an ion beam collimation and modulation by the effect of electromagnetic structures created in the laser plasma.

TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma

Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. In a cross-sectional study of asthmatics of varying severity (n = 51), endobronchial tissue gene expression analysis revealed three major patient clusters: TH2-high, TH17-high, and TH2/17-low. TH2-high and TH17-high patterns were mutually exclusive in individual patient samples, and their gene signatures were inversely correlated and differentially regulated by interleukin-13 (IL-13) and IL-17A. To understand this dichotomous pattern of T helper 2 (TH2) and TH17 signatures, we investigated the potential of type 2 cytokine suppression in promoting TH17 responses in a preclinical model of allergen-induced asthma. Neutralization of IL-4 and/or IL-13 resulted in increased TH17 cells and neutrophilic inflammation in the lung. However, neutralization of IL-13 and IL-17 protected mice from eosinophilia, mucus hyperplasia, and airway hyperreactivity and abolished the neutrophilic inflammation, suggesting that combination therapies targeting both pathways may maximize therapeutic efficacy across a patient population comprising both TH2 and TH17 endotypes.

Change in psychological distress in longer-term oesophageal cancer carers: are clusters of illness perception change a useful determinant?

Objective: This study provides a longitudinal assessment of distress in longer-term oesophageal cancer carers, while examining illness perception schema as a possible determinant of change in distress over time.
Methods: Oesophageal cancer carers (n=171), 48-months post-diagnosis, were assessed at baseline and 12-months later with the Illness Perception Questionnaire-Revised, Cancer Coping Questionnaire, Hospital Anxiety and Depression Scale and Concerns About Recurrence Scale.
Results: Findings report deterioration from normal to probable anxiety in 35.7% of carers and probable depression in 28.7% carers over time. Fear of recurrence remained stable. Changes in control, consequence and cause beliefs were identified as key determinants of a change in psychological morbidity.
Conclusions: Illness beliefs appear to be valuable targets for psychological intervention to improve wellbeing among carers of people with oesophageal cancer.

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.

Theorizing temporary spatial clusters and institutional boundary-work in industrial markets

To better understand the nature of temporary spatial clusters (TSC’s) in industrial marketing settings, this conceptual paper first provides a theoretical synthesis of spatial understanding from the industrial marketing (IM) and economic geography (EG) fields, focusing particularly on Doreen Massey’s work on relational space. This leads to a conceptual schema for organizing the IM literature in terms of spatiality, and which also helps clarify the ontological nature of TSCs. We then move to introduce the notion of institutional boundary-work, drawing on the work of Thomas Gieryn, and Andrea Brighenti’s examination of territorology, to conceptualize the activities of market actors engaged in the ongoing social accomplishment of TSCs. Such activities, we suggest, involve these actors ‘marching’ boundaries to assume network influence and maintain market order in IM settings. In summary, therefore, our paper addresses two fundamental questions: i) How do we conceptualize the form of TSCs in IM settings? And, ii) what function(s) are TSCs performing (and how is this being undertaken) in IM? The paper closes by providing methodological guidance for how a research agenda on TSCs within IM activity might be developed, followed by a summary of the managerial implications that emerge from our theorizations.