Clustering of equine grass sickness cases in the United Kingdom: a study considering the effect of position-dependent reporting on the space-time K-function

Equine grass sickness (EGS) is a largely fatal, pasture-associated dysautonomia. Although the aetiology of this disease is unknown, there is increasing evidence that Clostridium botulinum type C plays an important role in this condition. The disease is widespread in the United Kingdom, with the highest incidence believed to occur in Scotland. EGS also shows strong seasonal variation (most cases are reported between April and July). Data from histologically confirmed cases of EGS from England and Wales in 1999 and 2000 were collected from UK veterinary diagnostic centres. The data did not represent a complete census of cases, and the proportion of all cases reported to the centres would have varied in space and, independently, in time. We consider the variable reporting of this condition and the appropriateness of the space–time K-function when exploring the spatial-temporal properties of a ‘thinned’ point process. We conclude that such position-dependent under-reporting of EGS does not invalidate the Monte Carlo test for space–time interaction, and find strong evidence for space–time clustering of EGS cases (P<0.001). This may be attributed to contagious or other spatially and temporally localized processes such as local climate and/or pasture management practices

The fitness of pseudomonas aeruginosa quorum sensing signal cheats is influenced by the diffusivity of the environment

Experiments examining the social dynamics of bacterial quorum sensing (QS) have focused on mutants which do not respond to signals and the role of QS-regulated exoproducts as public goods. The potential for QS signal molecules to themselves be social public goods has received much less attention. Here, we analyze how signal-deficient (lasI) mutants of the opportunistic pathogen Pseudomonas aeruginosa interact with wild-type cells in an environment where QS is required for growth. We show that when growth requires a “private” intracellular metabolic mechanism activated by the presence of QS signal, lasI mutants act as social cheats and outcompete signal-producing wild-type bacteria in mixed cultures, because they can exploit the signals produced by wild-type cells. However, reducing the ability of signal molecules to diffuse through the growth medium results in signal molecules becoming less accessible to mutants, leading to reduced cheating. Our results indicate that QS signal molecules can be considered social public goods in a way that has been previously described for other exoproducts but that spatial structuring of populations reduces exploitation by noncooperative signal cheats

Inhibition of double-strand break non-homologous end-joining by cisplatin adducts in human cell extracts

The effect of cis-diaminedichloroplatinum(II) (cisplatin) DNA damage on the repair of double-strand breaks by non-homologous end-joining (NHEJ) was determined using cell-free extracts. NHEJ was dramatically decreased when plasmid DNA was damaged to contain multiple types of DNA adducts, along the molecule and at the termini, by incubation of DNA with cisplatin; this was a cisplatin concentration-dependent effect. We investigated the effect a single GTG cisplatination site starting 10 bp from the DNA termini would have when surrounded by the regions of AT-rich DNA which were devoid of the major adduct target sequences. Cisplatination of a substrate containing short terminal 13–15 bp AT-rich sequences reduced NHEJ to a greater extent than that of a substrate with longer (31–33 bp) AT-rich sequences. However, cisplatination at the single GTG site within the AT sequence had no significant effect on NHEJ, owing to the influence of additional minor monoadduct and dinucleotide adduct sites within the AT-rich region and owing to the influence of cisplatination at sites upstream of the AT-rich regions. We then studied the effect on NHEJ of one cis-[Pt(NH(3))(2){d(GpTpG)-N7(1),-N7(3)} [abbreviated as 1,3-d(GpTpG)] cisplatin adduct in the entire DNA molecule, which is more reflective of the situation in vivo during concurrent chemoradiation. The presence of a single 1,3-d(GpTpG) cisplatin adduct 10 bases from each of the two DNA ends to be joined resulted in a small (30%) but significant decrease in NHEJ efficiency. This process, which was DNA-dependent protein kinase and Ku dependent, may in part explain the radiosensitizing effect of cisplatin administered during concurrent chemoradiation

Deep three-dimensional solid-state qubit arrays with long-lived spin coherence

Nitrogen-vacancy centers (NVCs) in diamond show promise for quantum computing, communication, and sensing. However, the best current method for entangling two NVCs requires that each one is in a separate cryostat, which is not scalable. We show that single NVCs can be laser written 6–15-µm deep inside of a diamond with spin coherence times that are an order of magnitude longer than previous laser-written NVCs and at least as long as naturally occurring NVCs. This depth is suitable for integration with solid immersion lenses or optical cavities and we present depth-dependent T2 measurements. 200 000 of these NVCs would fit into one diamond

Disease prevention versus data privacy : using landcover maps to inform spatial epidemic models

The availability of epidemiological data in the early stages of an outbreak of an infectious disease is vital for modelers to make accurate predictions regarding the likely spread of disease and preferred intervention strategies. However, in some countries, the necessary demographic data are only available at an aggregate scale. We investigated the ability of models of livestock infectious diseases to predict epidemic spread and obtain optimal control policies in the event of imperfect, aggregated data. Taking a geographic information approach, we used land cover data to predict UK farm locations and investigated the influence of using these synthetic location data sets upon epidemiological predictions in the event of an outbreak of foot-and-mouth disease. When broadly classified land cover data were used to create synthetic farm locations, model predictions deviated significantly from those simulated on true data. However, when more resolved subclass land use data were used, moderate to highly accurate predictions of epidemic size, duration and optimal vaccination and ring culling strategies were obtained. This suggests that a geographic information approach may be useful where individual farm-level data are not available, to allow predictive analyses to be carried out regarding the likely spread of disease. This method can also be used for contingency planning in collaboration with policy makers to determine preferred control strategies in the event of a future outbreak of infectious disease in livestock

How many cows do I need? Sample size calculations for testing co-infection using existing study data

Background There is little empirical research on the co-infection of Fasciola hepatica and Escherichia coli O157 in cattle. E. coli is controlled in the gut by a Type 1 immune response, whereas F. hepatica is known to suppress these immune responses and induce an anti-inflammatory environment in the host. We evaluate the statistical feasibility of re-testing isolates from a planned UK Food Standards Agency study on E. coli prevalence for F. hepatica presence, in order to establish whether there is an association. Methods We simulate synthetic datasets representing the proposed FSA sampling strategy. Sample sizes within farms and F. hepatica infections are simulated using Beta-Binomial distributions. E. coli infections are simulated using a logistic random-intercepts model under an alternative hypothesis that the odds ratio of E. coli presence is double when F. hepatica is present, with farm- and isolate-level prevalence rates constrained to current estimates. Statistical power is calculated by fitting models to each of the simulated datasets assuming a type I error rate of 5%. Owing to the E. coli status being known in advance of the F. hepatica test, we restrict the sampling strategy to only test farms with >0% an

Families of covariance functions for bivariate random fields on spheres

This paper proposes a new class of covariance functions for bivariate random fields on spheres, having the same properties as the bivariate Matérn model proposed in Euclidean spaces. The new class depends on the geodesic distance on a sphere; it allows for indexing differentiability (in the mean square sense) and fractal dimensions of the components of any bivariate Gaussian random field having such covariance structure. We find parameter conditions ensuring positive definiteness. We discuss other possible models and illustrate our findings through a simulation study, where we explore the performance of maximum likelihood estimation method for the parameters of the new covariance function. A data illustration then follows, through a bivariate data set of temperatures and precipitations, observed over a large portion of the Earth, provided by the National Oceanic and Atmospheric Administration Earth System Research Laboratory

Cholera outbreak in districts around Lake Chilwa, Malawi: Lessons learned

BackgroundCholera is endemic in Malawi with seasonal outbreaks during the wet season. People living around Lake Chilwa rely on the lake for their water supply. From May 2009 to May 2010, a cholera outbreak occurred in fishing communities around Lake Chilwa. This paper describes the outbreak response and lessons learned for prevention and management of future outbreaks.MethodsStarting in January 2010, M&#233;decins Sans Fronti&#232;res (MSF) helped District Health Management Teams (DHMTs) to distribute educational materials, water disinfectant and hygiene supplies, and oral rehydration solution (ORS) in fishing communities. MSF also supported case management by mentoring health workers and providing equipment and supplies.ResultsA total of 1,171 cholera cases and 21 deaths were reported in the districts around the lake, with cases also being reported on the Mozambican side of the lake. The attack rate was highest among people living on or around the lake, particularly among fishermen. Samples of lake water had high turbidity conducive to the propagation of Vibrio cholerae.ConclusionA number of practical measures could be taken to prevent future outbreaks and to manage outbreaks more effectively. These measures should address surveillance, environmental management, outbreak preparedness, and case management

CD4 testing at clinics to assess eligibility for Antiretroviral therapy

BackgroundIn 2011, the Ministry of Health raised the CD4 threshold for antiretroviral therapy (ART) eligibility from &lt;250 cells/&#956;l and &lt;350 cells/&#956;l, but at the same time only 8.8% of facilities in Malawi with HIV services provided CD4 testing. We conducted a record review at 10 rural clinics in Thyolo District to assess the impact of introducing CD4 testing on identifying patients eligible for ART.Methods:We abstracted CD4 counts of all ART-na&#239;ve, HIV-infected patients with WHO clinical stages 1 and 2 and an initial CD4 test between May 2008 and June 2009. At four clinics, we also abstracted CD4 counts of patients not initially eligible for ART who were retested before April 2010.ResultsOf 1,113 patients tested, the initial CD4 was &#8220;&#8804;250 cells/&#956;l&#8221; and &#8220;&#8804;350 cells/&#956;l&#8221; in 534 (48.0%). Of 203 patients with follow-up results, the most recent CD4 was &#8804;250 cells/&#956;l in 34 (24.5%), and &#8804;350 cells/&#956;l in 64 (46.0%).ConclusionsCD4 testing in rural clinics is feasible and identifies many patients eligible for ART who would not be identified without CD4 testing. CD4 testing needs to be scaled-up to identify patients eligible for ART. ART services need to be scaled-up concurrently to meet the resulting increased demand

Impact of Type 2 diabetes prevention programmes based on risk identification and lifestyle intervention intensity strategies: a cost-effectiveness analysis

Aim To develop a cost-effectiveness model to compare Type 2 diabetes prevention programmes that target different at-risk population subgroups through lifestyle interventions of varying intensity. Methods An individual patient simulation model simulated the development of diabetes in a representative sample of adults without diabetes from the UK population. The model incorporates trajectories for HbA1c, 2-h glucose, fasting plasma glucose, BMI, systolic blood pressure, total cholesterol and HDL cholesterol. In the model, patients can be diagnosed with diabetes, cardiovascular disease, microvascular complications of diabetes, cancer, osteoarthritis and depression, or can die. The model collects costs and utilities over a lifetime horizon. The perspective is the UK National Health Service and Personal Social Services. We used the model to evaluate the population-wide impact of targeting a lifestyle intervention of varying intensity to six population subgroups defined as at high risk for diabetes. Results The intervention produces 0.0020 to 0.0026 incremental quality-adjusted life-years and saves £15 to £23 per person in the general population, depending on the subgroup targeted. Cost-effectiveness increases with intervention intensity. The most cost-effective options were to target South-Asian people and those with HbA1c levels > 42 mmol/mol (6%). Conclusion The model indicates that diabetes prevention interventions are likely to be cost-saving. The criteria for selecting at-risk individuals differentially has an impact on diabetes and cardiovascular disease outcomes, and on the timing of costs and benefits. The model is not currently able to account for potential differential uptake or efficacy between subgroups. These findings have implications for deciding who should be targeted for diabetes prevention interventions.NIH