Changes over time in socioeconomic inequalities in breast and rectal cancer survival in England and Wales during a 32-year period (1973-2004): the potential role of health care.

BACKGROUND: Socioeconomic inequalities in cancer survival are well documented but they vary for different cancers and over time. Reasons for these differences are poorly understood. PATIENTS AND METHODS: For England and Wales, we examined trends in socioeconomic survival inequalities for breast cancer in women and rectal cancer in men during the 32-year period 1973-2004. We used a theoretical framework based on Victora's 'inverse equity' law, under which survival inequalities could change with the advent of successive new treatments, of varying effectiveness, which are disseminated with different speed among patients of different socioeconomic groups. We estimated 5-year relative survival for patients of different deprivation quintiles and examined trends in survival inequalities in light of major treatment innovations. RESULTS: Inequalities in breast cancer survival (921,611 cases) narrowed steadily during the study (from -10% to -6%). In contrast, inequalities in rectal cancer survival (187,104 cases) widened overall (form -5% to -11%) with fluctuating periods of narrowing inequality. CONCLUSIONS: Trends in socioeconomic differences in tumour or patient factors are unlikely explanations of observed changes over time in survival inequalities. The sequential introduction into clinical practice of new treatments of progressively smaller incremental benefit may partly explain the reduction in inequality in breast cancer survival

Exact, E=0, Solutions for General Power-Law Potentials. I. Classical Orbits

For zero energy, $E=0$, we derive exact, classical solutions for {\em all} power-law potentials, $V(r)=-\gamma/r^\nu$, with $\gamma>0$ and $-\infty <\nu<\infty$. When the angular momentum is non-zero, these solutions lead to the orbits $\r(t)= [\cos \mu (\th(t)-\th_0(t))]^{1/\mu}$, for all $\mu \equiv \nu/2-1 \ne 0$. When $\nu>2$, the orbits are bound and go through the origin. This leads to discrete discontinuities in the functional dependence of $\th(t)$ and $\th_0(t)$, as functions of $t$, as the orbits pass through the origin. We describe a procedure to connect different analytic solutions for successive orbits at the origin. We calculate the periods and precessions of these bound orbits, and graph a number of specific examples. Also, we explain why they all must violate the virial theorem. The unbound orbits are also discussed in detail. This includes the unusual orbits which have finite travel times to infinity and also the special $\nu = 2$ case.Comment: LaTeX, 27 pages with 12 figures available from the authors or can be generated from Mathematica instructions at end of the fil

Tapasin gene polymorphism in systemic onset juvenile rheumatoid arthritis: a family-based case-control study

Juvenile rheumatoid arthritis (JRA) comprises a group of chronic systemic inflammatory disorders that primarily affect joints and can cause long-term disability. JRA is likely to be a complex genetic trait, or a series of such traits, with both genetic and environmental factors contributing to the risk for developing the disease and to its progression. The HLA region on the short arm of chromosome 6 has been intensively evaluated for genetic contributors to JRA, and multiple associations, and more recently linkage, has been detected. Other genes involved in innate and acquired immunity also map to near the HLA cluster on 6p, and it is possible that variation within these genes also confers risk for developing JRA. We examined the TPSN gene, which encodes tapasin, an endoplasmic reticulum chaperone that is involved in antigen processing, to elucidate its involvement, if any, in JRA. We employed both a case-control approach and the transmission disequilibrium test, and found linkage and association between the TPSN allele (Arg260) and the systemic onset subtype of JRA. Two independent JRA cohorts were used, one recruited from the Rheumatology Clinic at Cincinnati Children's Hospital Medical Center (82 simplex families) and one collected by the British Paediatric Rheumatology Group in London, England (74 simplex families). The transmission disequilibrium test for these cohorts combined was statistically significant (chi(2) = 4.2, one degree of freedom; P = 0.04). Linkage disequilibrium testing between the HLA alleles that are known to be associated with systemic onset JRA did not reveal linkage disequilibrium with the Arg260 allele, either in the Cincinnati systemic onset JRA cohort or in 113 Caucasian healthy individuals. These results suggest that there is a weak association between systemic onset JRA and the TPSN polymorphism, possibly due to linkage disequilibrium with an as yet unknown susceptibility allele in the centromeric part of chromosome 6

A Learning 2.0 Programme: raising library staff awareness of Web 2.0 at Imperial College London

Published versio

Distinct human stem cell populations in small and large intestine

The intestine is composed of an epithelial layer containing rapidly proliferating cells that mature into two regions, the small and the large intestine. Although previous studies have identified stem cells as the cell-of-origin for intestinal epithelial cells, no studies have directly compared stem cells derived from these anatomically distinct regions. Here, we examine intrinsic differences between primary epithelial cells isolated from human fetal small and large intestine, after in vitro expansion, using the Wnt agonist R-spondin 2.We utilized flow cytometry, fluorescence-activated cell sorting, gene expression analysis and a three-dimensional in vitro differentiation assay to characterize their stemcell properties. We identified stem cell markers that separate subpopulations of colony-forming cells in the small and large intestine and revealed important differences in differentiation, proliferation and disease pathways using gene expression analysis. Single cells from small and large intestine cultures formed organoids that reflect the distinct cellular hierarchy found in vivo and respond differently to identical exogenous cues. Our characterization identified numerous differences between small and large intestine epithelial stem cells suggesting possible connections to intestinal disease

Distribution of macroinvertebrate communities across surface and groundwater habitats in response to hydrological variability

Macroinvertebrate communities are strongly influenced by hydrological variability in surface waters. However, the response of these communities in corresponding groundwater-dependent habitats is not well understood. This study characterised the macroinvertebrate fauna and physicochemical characteristics of a chalk aquifer and its rivers in southern England. Over one year, samples were collected from five paired benthic-hyporheic sites located in perennial or temporary rivers, and a further seven phreatic sites in the surrounding aquifer. The study was preceded by a period of below average rainfall, providing an opportunity to assess the response of macro-invertebrate communities to unseasonal declines in river discharge and groundwater levels. Benthic, hyporheic and phreatic habitats each supported a distinct macroinvertebrate community, with the hyporheic habitat support- ing both epigean taxa and stygofauna. As discharge declined, the composition of these communities changed. In particular, the abundance of the epigean amphipod Gammarus pulex was higher in hyporheic than benthic habitats during periods of low river discharge, suggesting potential refuge-seeking behaviour. Similarly, fluctuations in the abundance and distribution of two stygofauna, Crangonyx subterraneus and Niphargus fontanus, coincided with marked changes in groundwater levels, suggesting that the contraction of available habitat and changes in connectivity also influenced the phreatic community. The variable distribution of macroinvertebrates between these habitats, especially in response to hydrological variability, suggests a dynamic connection between the river and its aquifer. This connection is an important consideration for the assessment and conservation management of both surface and groundwater communities and may help underpin integrated, catchment-based management, especially in river systems with temporary reaches

Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye.

Accumulation of protein- and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD). The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.5-20 μm in diameter), hollow, hydroxyapatite (HAP) spherules in Bruch's membrane in human eyes. These spherules are distinct in form, placement, and staining from the well-known calcification of the elastin layer of the aging Bruch's membrane. Secondary ion mass spectrometry (SIMS) imaging confirmed the presence of calcium phosphate in the spherules and identified cholesterol enrichment in their core. Using HAP-selective fluorescent dyes, we show that all types of sub-RPE deposits in the macula, as well as in the periphery, contain numerous HAP spherules. Immunohistochemical labeling for proteins characteristic of sub-RPE deposits, such as complement factor H, vitronectin, and amyloid beta, revealed that HAP spherules were coated with these proteins. HAP spherules were also found outside the sub-RPE deposits, ready to bind proteins at the RPE/choroid interface. Based on these results, we propose a novel mechanism for the growth, and possibly even the formation, of sub-RPE deposits, namely, that the deposit growth and formation begin with the deposition of insoluble HAP shells around naturally occurring, cholesterol-containing extracellular lipid droplets at the RPE/choroid interface; proteins and lipids then attach to these shells, initiating or supporting the growth of sub-RPE deposits