Investigation of spatial clustering from individually matched case-control studies

The paper demonstrates how existing theory to assess spatial clustering based on second-moment properties of a labelled point process can be adapted to matched case-control studies. The null hypothesis that cases are a random sample from the superposition of cases and controls is replaced by the hypothesis that each case is a random sample from the set consisting of itself and its k matched controls. We compare the proposed test with other tests of spatial clustering, and describe an application to data on childhood diabetes in Yorkshire, England.     

A geostatistical framework for combining spatially referenced disease prevalence data from multiple diagnostics

Multiple diagnostic tests are often used due to limited resources or because they provide complementary information on the epidemiology of a disease under investigation. Existing statistical methods to combine prevalence data from multiple diagnostics ignore the potential overdispersion induced by the spatial correlations in the data. To address this issue, we develop a geostatistical framework that allows for joint modelling of data from multiple diagnostics by considering two main classes of inferential problems: (a) to predict prevalence for a gold-standard diagnostic using low-cost and potentially biased alternative tests; (b) to carry out joint prediction of prevalence from multiple tests. We apply the proposed framework to two case studies: mapping Loa loa prevalence in Central and West Africa, using miscroscopy, and a questionnaire-based test called RAPLOA; mapping Plasmodium falciparum malaria prevalence in the highlands of Western Kenya using polymerase chain reaction and a rapid diagnostic test. We also develop a Monte Carlo procedure based on the variogram in order to identify parsimonious geostatistical models that are compatible with the data. Our study highlights (a) the importance of accounting for diagnostic-specific residual spatial variation and (b) the benefits accrued from joint geostatistical modelling so as to deliver more reliable and precise inferences on disease prevalence.     

Protist predation can favour cooperation within bacterial species

Here, we studied how protist predation affects cooperation in the opportunistic pathogen bacterium Pseudomonas aeruginosa, which uses quorum sensing (QS) cell-to-cell signalling to regulate the production of public goods. By competing wild-type bacteria with QS mutants (cheats), we show that a functioning QS system confers an elevated resistance to predation. Surprisingly, cheats were unable to exploit this resistance in the presence of cooperators, which suggests that resistance does not appear to result from activation of QS-regulated public goods. Instead, elevated resistance of wild-type bacteria was related to the ability to form more predation-resistant biofilms. This could be explained by the expression of QS-regulated resistance traits in densely populated biofilms and floating cell aggregations, or alternatively, by a pleiotropic cost of cheating where less resistant cheats are selectively removed from biofilms. These results show that trophic interactions among species can maintain cooperation within species, and have further implications for P. aeruginosa virulence in environmental reservoirs by potentially enriching the cooperative and highly infective strains with functional QS system.     

Validation of mark‐recapture population estimates for invasive common carp,Cyprinus carpio,in Lake Crescent,Tasmania

A mark‐recapture study based on the Petersen method was implemented in 1998 to estimate the abundance of the invasive common carp, Cyprinus carpio L., in Lake Crescent, Tasmania. Multiple gear types were employed to minimise capture bias, with multiple capture and recapture events providing an opportunity to compute and compare Petersen and Schnabel estimates. A single Petersen estimate on recapture data and two Schnabel estimates – one each on mark (forward‐Schnabel estimate) and recapture (reverse‐Schnabel estimate) data – were conducted. An independent long‐term double tag study facilitated estimation of the annual natural mortality. Subsequent fish‐down of the population suggests that, in all likelihood, the carp have been eradicated from the lake, providing an unprecedented opportunity to verify the forward population estimates carried out in 1998. Results suggest that all three estimates were close to the true population size, with the reverse‐Schnabel estimate being the most accurate and within 1% of the true population in this relatively large lake (～2365 ha). Greater accuracy of the reverse‐Schnabel approach can be attributed to either minimised fish behavioural (i.e. gear susceptibility or avoidance) or computational bias associated with the forward‐Schnabel and Petersen approaches, respectively. While the original estimates served as a guide in eradication of carp from the lake, the ultimate validation provides a reliable framework for abundance estimation of this invasive fish in relatively large water bodies elsewhere.     

Social evolution theory for microorganisms

Microorganisms communicate and cooperate to perform a wide range of multicellular behaviours, such as dispersal, nutrient acquisition, biofilm formation and quorum sensing. Microbiologists are rapidly gaining a greater understanding of the molecular mechanisms involved in these behaviours, and the underlying genetic regulation. Such behaviours are also interesting from the perspective of social evolution - why do microorganisms engage in these behaviours given that cooperative individuals can be exploited by selfish cheaters, who gain the benefit of cooperation without paying their share of the cost? There is great potential for interdisciplinary research in this fledgling field of sociomicrobiology, but a limiting factor is the lack of effective communication of social evolution theory to microbiologists. Here, we provide a conceptual overview of the different mechanisms through which cooperative behaviours can be stabilized, emphasizing the aspects most relevant to microorganisms, the novel problems that microorganisms pose and the new insights that can be gained from applying evolutionary theory to microorganisms.     

N;-3 and n;-6 polyunsaturated fatty acids induce cytostasis in human urothelial cells independent of p53 gene function

The role of long-chain polyunsaturated fatty acids (PUFA) in the etiopathology and treatment of cancer is poorly understood. We have studied the effects of n;-3 and n;-6 PUFA on the proliferation and survival of normal human uroepithelial (NHU) cells, cells with disabled p53 function after stable transfection with the human papillomavirus 16 (HPV16) E6 gene (HU-E6), and p53-disabled cells that had passed through crisis and acquired karyotypic abnormalities (HU-E6P). The n;-3 and n;-6 PUFA had distinct reversible antiproliferative and irreversible cytostatic effects according to concentration and exposure time. The reversible antiproliferative effect was partly due to the production of lipoxygenase metabolites. NHU and HU-E6 cells were equally sensitive to n;-3 and n;-6 PUFA, but HU-E6P cells were more resistant to both the antiproliferative and cytostatic effects. Cytostatic concentrations of n;-3 and n;-6 PUFA did not induce apoptosis, but caused permanent growth arrest ("interphase" or "reproductive" cell death) and mRNA levels for genes involved in cell cycle control (p21, p16, p27, cdk1, cdk2, and cdk4) were not altered. Neither n;-3 nor n;-6 PUFA promoted acquisition of karyotypic abnormalities in HU-E6 cells, suggesting that n;-3 and n;-6 PUFA do not cause genotoxic damage.In conclusion, our studies show that the antiproliferative and cytostatic effects of n;-3 and n;-6 PUFA are not dependent on p53 function and, further, that transformation results in a loss of sensitivity to n;-3 and n;-6 PUFA-mediated growth inhibition.     

Pyrosequencing™

Nucleotide sequencing is an established method for gaining information relating to partial gene, whole gene, or whole genome sequence. Here we describe some of the background leading to the advent of modern nucleotide sequencing and how it has led to the development of Pyrosequencing™, a relatively new method for real-time nucleotide sequencing. In particular, we describe how this method can be used for typing bacterial pathogens.