A survey of statistics in three UK general practice journal

Background Many medical specialities have reviewed the statistical content of their journals. To our knowledge this has not been done in general practice. Given the main role of a general practitioner as a diagnostician we thought it would be of interest to see whether the statistical methods reported reflect the diagnostic process. Methods Hand search of three UK journals of general practice namely the British Medical Journal (general practice section), British Journal of General Practice and Family Practice over a one-year period (1 January to 31 December 2000). Results A wide variety of statistical techniques were used. The most common methods included t-tests and Chi-squared tests. There were few articles reporting likelihood ratios and other useful diagnostic methods. There was evidence that the journals with the more thorough statistical review process reported a more complex and wider variety of statistical techniques. Conclusions The BMJ had a wider range and greater diversity of statistical methods than the other two journals. However, in all three journals there was a dearth of papers reflecting the diagnostic process. Across all three journals there were relatively few papers describing randomised controlled trials thus recognising the difficulty of implementing this design in general practice

Wait times for breast cancer care

Measurement of care time intervals is complex, being influenced by many factors. The definition of the care interval monitored can also bias the detection of changes in waits. The implications of using different care interval definitions to report wait times and identify delays in care provision were examined using a retrospective chart review of 637 women with surgically treated breast cancer who were referred to a cancer centre between September 1999 and 2000 or September 2003 and 2004. Overall waits between detection and adjuvant treatment increased by 12 days over the two periods, but their exact location and cause(s) could not be determined at such a low-resolution interval. At higher resolutions of care intervals, reporting the comprehensive sequence of care events, the prolongation was mainly associated with delayed access to surgery (4 days) and delivery of adjuvant chemotherapy (4 days). The latter went unnoticed when waits were reported at intermediate (referral to adjuvant treatment) and low (detection to adjuvant treatment) resolutions. Disease stage and type of first adjuvant treatment consistently and significantly influenced the length of waits. Comprehensive monitoring of the entire care path is essential to effectively prioritize interventions, assess their outcomes and optimise access to cancer care

Delocalized single-photon Dicke states and the Leggett- Garg inequality in solid state systems

We show how to realize a single-photon Dicke state in a large one-dimensional array of two- level systems, and discuss how to test its quantum properties. Realization of single-photon Dicke states relies on the cooperative nature of the interaction between a field reservoir and an array of two-level-emitters. The resulting dynamics of the delocalized state can display Rabi-like oscillations when the number of two-level emitters exceeds several hundred. In this case the large array of emitters is essentially behaving like a mirror-less cavity. We outline how this might be realized using a multiple-quantum-well structure and discuss how the quantum nature of these oscillations could be tested with the Leggett-Garg inequality and its extensions.Comment: 29 pages, 5 figures, journal pape

The Size Distribution of Void Filaments in a LCDM Cosmology

The size distribution of mini-filaments in voids has been derived from the Millennium Run halo catalogs at redshifts z=0,0.5,1 and 2. It is assumed that the primordial tidal field originated the presence of filamentary substructures in voids and that the void filaments have evolved only little, keeping the initial memory of the primordial tidal field. Applying the filament-finding algorithm based on the minimal spanning tree (MST) technique to the Millennium voids, we identify the mini-filaments running through voids and measure their sizes at each redshift. Then, we calculate the comoving number density of void filaments as a function of their sizes in the logarithmic interval and determine an analytic fitting function for it. It is found that the size distribution of void mini-filaments in the logarithmic interval has an almost universal shape, insensitive to the redshift: In the short-size section it is well approximated as a power-law, while in the long-size section it decreases exponentially. We expect that the universal size distribution of void filaments may provide a useful cosmological probe without resorting to the rms density fluctuations.Comment: MNRAS in press, revised version, two different definitions of void size considered, chi^2 tests of the universality included, more discussions on the universality of the void size distribution adde

Evolutionary Dynamics of Co-Segregating Gene Clusters Associated with Complex Diseases

BACKGROUND: The distribution of human disease-associated mutations is not random across the human genome. Despite the fact that natural selection continually removes disease-associated mutations, an enrichment of these variants can be observed in regions of low recombination. There are a number of mechanisms by which such a clustering could occur, including genetic perturbations or demographic effects within different populations. Recent genome-wide association studies (GWAS) suggest that single nucleotide polymorphisms (SNPs) associated with complex disease traits are not randomly distributed throughout the genome, but tend to cluster in regions of low recombination. PRINCIPAL FINDINGS: Here we investigated whether deleterious mutations have accumulated in regions of low recombination due to the impact of recent positive selection and genetic hitchhiking. Using publicly available data on common complex diseases and population demography, we observed an enrichment of hitchhiked disease associations in conserved gene clusters subject to selection pressure. Evolutionary analysis revealed that these conserved gene clusters arose by multiple concerted rearrangements events across the vertebrate lineage. We observed distinct clustering of disease-associated SNPs in evolutionary rearranged regions of low recombination and high gene density, which harbor genes involved in immunity, that is, the interleukin cluster on 5q31 or RhoA on 3p21. CONCLUSIONS: Our results suggest that multiple lineage specific rearrangements led to a physical clustering of functionally related and linked genes exhibiting an enrichment of susceptibility loci for complex traits. This implies that besides recent evolutionary adaptations other evolutionary dynamics have played a role in the formation of linked gene clusters associated with complex disease traits

Impacts of organic and conventional crop management on diversity and activity of free-living nitrogen fixing bacteria and total bacteria are subsidiary to temporal effects

A three year field study (2007-2009) of the diversity and numbers of the total and metabolically active free-living diazotophic bacteria and total bacterial communities in organic and conventionally managed agricultural soil was conducted at the Nafferton Factorial Systems Comparison (NFSC) study, in northeast England. The result demonstrated that there was no consistent effect of either organic or conventional soil management across the three years on the diversity or quantity of either diazotrophic or total bacterial communities. However, ordination analyses carried out on data from each individual year showed that factors associated with the different fertility management measures including availability of nitrogen species, organic carbon and pH, did exert significant effects on the structure of both diazotrophic and total bacterial communities. It appeared that the dominant drivers of qualitative and quantitative changes in both communities were annual and seasonal effects. Moreover, regression analyses showed activity of both communities was significantly affected by soil temperature and climatic conditions. The diazotrophic community showed no significant change in diversity across the three years, however, the total bacterial community significantly increased in diversity year on year. Diversity was always greatest during March for both diazotrophic and total bacterial communities. Quantitative analyses using qPCR of each community indicated that metabolically active diazotrophs were highest in year 1 but the population significantly declined in year 2 before recovering somewhat in the final year. The total bacterial population in contrast increased significantly each year. Seasonal effects were less consistent in this quantitative study

Voids in a Λ\LambdaCDM Universe

We study the formation and evolution of voids in the dark matter distribution using various simulations of the popular $\Lambda$ Cold Dark Matter cosmogony. We identify voids by requiring them to be regions of space with a mean overdensity of -0.8 or less. Each of the simulations contains thousands of voids. The distribution of void sizes in the different simulations shows good agreement. Voids very clearly correspond to minima in the smoothed initial density field. We find a universal void mass profile of the form $\rho(<r)/\rho(r_{\rm eff}) \propto \exp[(r/r_{\rm eff})^\alpha]$ where $r_{\rm eff}$ is the effective radius of a void and $\alpha\sim 2$. The mass function of haloes in voids is steeper than that of haloes that populate denser regions. The abundances of void haloes seem to evolve somewhat more strongly between redshifts $\sim 1$ and 0 than the global abundances of haloes. (abridged)Comment: 12 pages, 16 figures, submitted to MNRAS; 13 pages, 17 figures, revised version, accepted for publicatio

?2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH

Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of ?2-microglobulin (?2m), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of anionic lipid bilayers in vitro. However, the effect of lipid composition and the chemical environment in which ?2m-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of ?2m monomers and fibrils with lipid bilayers. Using dye release, tryptophan fluorescence quenching and fluorescence confocal microscopy assays we investigate the effect of anionic lipid composition and pH on the susceptibility of liposomes to fibril-induced membrane damage. We show that ?2m fibril-induced membrane disruption is modulated by anionic lipid composition and is enhanced by acidic pH. Most strikingly, the greatest degree of membrane disruption is observed for liposomes containing bis(monoacylglycero)phosphate (BMP) at acidic pH, conditions likely to reflect those encountered in the endocytic pathway. The results suggest that the interaction between ?2m fibrils and membranes of endosomal origin may play a role in the molecular mechanism of ?2m amyloid-associated osteoarticular tissue destruction in DRA