Comparing survival from cancer using population-based cancer registry data - methods and applications

Over the past decade, population-based cancer registry data have been used increasingly worldwide to evaluate and improve the quality of cancer care. The utility of the conclusions from such studies relies heavily on the data quality and the methods used to analyse the data. Interpretation of comparative survival from such data, examining either temporal trends or geographical differences, is generally not easy. The observed differences could be due to methodological and statistical approaches or to real effects. For example, geographical differences in cancer survival could be due to a number of real factors, including access to primary health care, the availability of diagnostic and treatment facilities and the treatment actually given, or to artefact, such as lead-time bias, stage migration, sampling error or measurement error. Likewise, a temporal increase in survival could be the result of earlier diagnosis and improved treatment of cancer; it could also be due to artefact after the introduction of screening programs (adding lead time), changes in the definition of cancer, stage migration or several of these factors, producing both real and artefactual trends. In this thesis, I report methods that I modified and applied, some technical issues in the use of such data, and an analysis of data from the State of New South Wales (NSW), Australia, illustrating their use in evaluating and potentially improving the quality of cancer care, showing how data quality might affect the conclusions of such analyses. This thesis describes studies of comparative survival based on population-based cancer registry data, with three published papers and one accepted manuscript (subject to minor revision). In the first paper, I describe a modified method for estimating spatial variation in cancer survival using empirical Bayes methods (which was published in Cancer Causes and Control 2004). I demonstrate in this paper that the empirical Bayes method is preferable to standard approaches and show how it can be used to identify cancer types where a focus on reducing area differentials in survival might lead to important gains in survival. In the second paper (published in the European Journal of Cancer 2005), I apply this method to a more complete analysis of spatial variation in survival from colorectal cancer in NSW and show that estimates of spatial variation in colorectal cancer can help to identify subgroups of patients for whom better application of treatment guidelines could improve outcome. I also show how estimates of the numbers of lives that could be extended might assist in setting priorities for treatment improvement. In the third paper, I examine time trends in survival from 28 cancers in NSW between 1980 and 1996 (published in the International Journal of Cancer 2006) and conclude that for many cancers, falls in excess deaths in NSW from 1980 to 1996 are unlikely to be attributable to earlier diagnosis or stage migration; thus, advances in cancer treatment have probably contributed to them. In the accepted manuscript, I described an extension of the work reported in the second paper, investigating the accuracy of staging information recorded in the registry database and assessing the impact of error in its measurement on estimates of spatial variation in survival from colorectal cancer. The results indicate that misclassified registry stage can have an important impact on estimates of spatial variation in stage-specific survival from colorectal cancer. Thus, if cancer registry data are to be used effectively in evaluating and improving cancer care, the quality of stage data might have to be improved. Taken together, the four papers show that creative, informed use of population-based cancer registry data, with appropriate statistical methods and acknowledgement of the limitations of the data, can be a valuable tool for evaluating and possibly improving cancer care. Use of these findings to stimulate evaluation of the quality of cancer care should enhance the value of the investment in cancer registries. They should also stimulate improvement in the quality of cancer registry data, particularly that on stage at diagnosis. The methods developed in this thesis may also be used to improve estimation of geographical variation in other count-based health measures when the available data are sparse

Temperature Dependence of the Effective Bag Constant and the Radius of a Nucleon in the Global Color Symmetry Model of QCD

We study the temperature dependence of the effective bag constant, the mass, and the radius of a nucleon in the formalism of the simple global color symmetry model in the Dyson-Schwinger equation approach of QCD with a Gaussian-type effective gluon propagator. We obtain that, as the temperature is lower than a critical value, the effective bag constant and the mass decrease and the radius increases with the temperature increasing. As the critical temperature is reached, the effective bag constant and the mass vanish and the radius tends to infinity. At the same time, the chiral quark condensate disappears. These phenomena indicate that the deconfinement and the chiral symmetry restoration phase transitions can take place at high temperature. The dependence of the critical temperature on the interaction strength parameter in the effective gluon propagator of the approach is given.Comment: 10 pages, 9 figure

Dyson-Schwinger Equations with a Parameterized Metric

We construct and solve the Dyson-Schwinger equation (DSE) of quark propagator with a parameterized metric, which connects the Euclidean metric with the Minkowskian one. We show, in some models, the Minkowskian vacuum is different from the Euclidean vacuum. The usual analytic continuation of Green function does not make sense in these cases. While with the algorithm we proposed and the quark-gluon vertex ansatz which preserves the Ward-Takahashi identity, the vacuum keeps being unchanged in the evolution of the metric. In this case, analytic continuation becomes meaningful and can be fully carried out.Comment: 10 pages, 7 figures. To appear in Physical Review

Phase diagram and critical endpoint for strongly-interacting quarks

We introduce a method based on the chiral susceptibility, which enables one to draw a phase diagram in the chemical-potential/temperature plane for strongly-interacting quarks whose interactions are described by any reasonable gap equation, even if the diagrammatic content of the quark-gluon vertex is unknown. We locate a critical endpoint (CEP) at (\mu^E,T^E) ~ (1.0,0.9)T_c, where T_c is the critical temperature for chiral symmetry restoration at \mu=0; and find that a domain of phase coexistence opens at the CEP whose area increases as a confinement length-scale grows.Comment: 4 pages, 3 figure

Quark spectral density and a strongly-coupled QGP

The maximum entropy method is used to compute the dressed-quark spectral density from the self-consistent numerical solution of a rainbow truncation of QCD's gap equation at temperatures above that for which chiral symmetry is restored. In addition to the normal and plasmino modes, the spectral function also exhibits an essentially nonperturbative zero mode for temperatures extending to 1.4-1.8-times the critical temperature, T_c. In the neighbourhood of T_c, this long-wavelength mode contains the bulk of the spectral strength and so long as this mode persists, the system may fairly be described as a strongly-coupled state of matter.Comment: 4 pages, 2 figure

Zero mode in a strongly coupled quark gluon plasma

In connection with massless two-flavour QCD, we analyse the chiral symmetry restoring phase transition using three distinct gluon-quark vertices and two different assumptions about the long-range part of the quark-quark interaction. In each case, we solve the gap equation, locate the transition temperature T_c, and use the maximum entropy method to extract the dressed-quark spectral function at T>T_c. Our best estimate for the chiral transition temperature is T_c=(147 +/- 8)MeV; and the deconfinement transition is coincident. For temperatures markedly above T_c, we find a spectral density that is consistent with those produced using a hard thermal loop expansion, exhibiting both a normal and plasmino mode. On a domain T\in[T_c,T_s], with T_s approximately 1.5T_c, however, with each of the six kernels we considered, the spectral function contains a significant additional feature. Namely, it displays a third peak, associated with a zero mode, which is essentially nonperturbative in origin and dominates the spectral function at T=T_c. We suggest that the existence of this mode is a signal for the formation of a strongly-coupled quark-gluon plasma and that this strongly-interacting state of matter is likely a distinctive feature of the QCD phase transition.Comment: 11 pages, 5 figures, 1 tabl

Practical corollaries of transverse Ward-Green-Takahashi identities

The gauge principle is fundamental in formulating the Standard Model. Fermion--gauge-boson couplings are the inescapable consequence and the primary determining factor for observable phenomena. Vertices describing such couplings are simple in perturbation theory and yet the existence of strong-interaction bound-states guarantees that many phenomena within the Model are nonperturbative. It is therefore crucial to understand how dynamics dresses the vertices and thereby fundamentally alters the appearance of fermion--gauge-boson interactions. We consider the coupling of a dressed-fermion to an Abelian gauge boson, and describe a unified treatment and solution of the familiar longitudinal Ward-Green-Takahashi identity and its less well known transverse counterparts. Novel consequences for the dressed-fermion--gauge-boson vertex are exposed.Comment: 5 pages, 1 figur

Simultaneous profiling of transcriptome and DNA methylome from a single cell.

BackgroundSingle-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear.ResultsHere, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression.ConclusionsOur method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation

Phase diagram and thermal properties of strong-interaction matter

We introduce a novel procedure for computing the (mu,T)-dependent pressure in continuum QCD; and therefrom obtain a complex phase diagram and predictions for thermal properties of the system, providing the in-medium behaviour of the trace anomaly, speed of sound, latent heat and heat capacity.Comment: 6 pages, 4 figures. Minor amendments in the version accepted for publicatio