Extending backcalculation to analyse BSE data.

We review the origins of backcalculation (or back projection) methods developed for the analysis of AIDS (acquired immunodeficiency syndrome) incidence data. These techniques have been used extensively for >15 years to deconvolute clinical case incidence, given knowledge of the incubation period distribution, to obtain estimates of past HIV (human immunodeficiency virus) infection incidence and short-term predictions of future AIDS incidence. Adaptations required for the analysis of bovine spongiform encephalopathy (BSE) incidence included: stratification of BSE incidence by age as well as birth cohort; allowance for incomplete survival between infection and the onset of clinical signs of disease; and decomposition of the age- and time-related infection incidence into a time-dependent feed risk component and an age-dependent exposure/susceptibility function. The most recent methodological developments focus on the incorporation of data from clinically unaffected cattle screened using recently developed tests for preclinical BSE infection. Backcalculation-based predictions of future BSE incidence obtained since 1996 are examined. Finally, future directions of epidemiological analysis of BSE epidemics are discussed taking into account ongoing developments in the science of BSE and possible changes in BSE-related policies

Benthic algae control sediment-water column fluxes of organic and inorganic nitrogen compounds in a temperate lagoon

Coastal lagoons are a common land-margin feature worldwide and function as an important filter for nutrients entering from the watershed. The shallow nature of lagoons leads to dominance by benthic autotrophs, which can regulate benthic-pelagic coupling. Here we demonstrate that both microalgae and macroalgae are important in controlling dissolved inorganic as well as organic nitrogen (DIN and DON) fluxes between the sediments and the water column. Fluxes of nitrogen (NH4+, NO3-, DON, urea, and dissolved free and combined amino acids [DFAA, DCAA]) and O-2 were measured from October 1998 through August 1999 in sediment cores collected from Hog Island Bay, Virginia. Cores were collected from four sites representing the range of environmental conditions across this shallow lagoon: muddy, high-nutrient and sandy, low-nutrient sites that were both dominated by benthic microalgae, and a mid-lagoon site with fine sands covered by dense macroalgal mats. Sediment-water column DON fluxes were highly variable and comparable in magnitude to DIN fluxes; fluxes of individual compounds (urea, DFAA, DCAA) often proceeded simultaneously in different directions. Where sediment metabolism was net autotrophic because of microalgal activity, TDN (total dissolved nitrogen) fluxes, mostly comprised of DIN, urea, and DFAA, were directed into the sediments. Heterotrophic sediments, including those underlying macroalgal mats, were a net source of TDN, mostly as DIN. Macroalgae intercepted sediment-water column fluxes of DIN, urea, and DFAA, which accounted for 27-75% of calculated N demand. DON uptake was important in satisfying macroalgal N demand seasonally and where DIN concentrations were low. Up to 22% of total N uptake was released to the water column as DCAA. Overall, macroalgae assimilated, transformed, and rereleased to the water column both organic and inorganic N on short (minutes-hours) and long (months) time scales. Microalgae and macroalgae clearly regulate benthic-pelagic coupling and thereby influence transformations and retention of N moving across the land-sea interface

Microbial mediation of \u27reactive\u27 nitrogen transformations in a temperate lagoon

Coastal lagoons positioned along the land margin may play an important role in removing or transforming \u27reactive\u27 nitrogen during its transport from land to the ocean. Hog Island Bay is a shallow, coastal lagoon located on the ocean-side of the Delmarva Peninsula in Virginia (USA). External nitrogen inputs are derived primarily from agriculturally enriched groundwater, and these support, in part, the high production of benthic macroalgae and microalgae as the dominant primary producers. This study focuses on processes in the water column (phytoplankton and bacterial) and in the sediments (microalgal and bacterial) responsible for transformations of dissolved inorganic and organic nitrogen (N). Sediment-water exchanges of dissolved inorganic and organic N were measured as well as sediment gross and net mineralization of organic N. Net changes in dissolved inorganic nitrogen concentrations were greater in the water-column incubations than in the incubations including sediment and water. In the water column, metabolism resulted in net uptake of NH4+ during all seasons and in net uptake of NO3- during most seasons. In the sediments, gross mineralization, which ranged from 0.9 to 6.5 mmol N m(-2) d(-1), resulted in short turnover times (\u3c 1 d) for the sediment NH4+ pool; however, sediment-water fluxes of both NH4+ and NO3- were either negligible or directed into the sediments. The NH4+ produced by gross mineralization was rapidly consumed in the dark. Biological processes potentially responsible for removal of sediment NH4+ and NO3- include coupled nitrification-denitrification, dark uptake by benthic microalgae, and immobilization by heterotrophic bacteria. In the absence of dark uptake of NH4+ by benthic microalgae, potential nitrification calculated as the difference between gross mineralization and NH4+ fluxes, would range from 1.5 to 6.4 mmol N m(-2) d(-1), similar to rates observed in a range of other systems. Similarly, potential denitrification rates estimated as the difference between calculated nitrification rates and measured NO3- fluxes would vary from 1.88 to 5.16 mol N m(-2) d(-1) and fall within the range of rates reported for similar systems. However, since calculated benthic microalgal N demand (2.51 to 16.11 mmol N m(-2) d(-1)) exceeded NH4+ release by gross mineralization at all sites and during all seasons, this suggests that dark benthic microalgal uptake was likely to be an important sink for mineralized N. Finally, sediment bacterial N immobilization may also be important given the relatively high C/N of sediment organic matter. These estimates of the potential consumptive processes for mineralized sediment N indicate that the lagoon is likely to retard and or remove \u27reactive\u27 N during its transport to the coastal ocean

An atypical presentation of a common infection.

Case Report: A six-year-old girl presented with a one year history of painless, non-purulent conjunctivitis of her left eye which had been treated on two occasions with topical antibiotics with no effect

Validity of interpretation: A user validity perspective beyond the test score

This paper introduces the concept of user validity and provides a new perspective on the validity of interpretations from tests. Test interpretation is based on outputs such as test scores, profiles, reports, spreadsheets of multiple candidates' scores, etc. The user validity perspective focuses on the interpretations a test user makes given the purpose of the test and the information provided in the test output. This innovative perspective focuses on how user validity can be extended to content, criterion, and to some extent construct-related validity. It provides a basis for researching the validity of interpretations and an improved understanding of the appropriateness of different approaches to score interpretation, as well as how to design test outputs and assessments that are pragmatic and optimal

Methods for estimating the case fatality ratio for a novel, emerging infectious disease.

During the course of an epidemic of a potentially fatal disease, it is important that the case fatality ratio be well estimated. The authors propose a novel method for doing so based on the Kaplan-Meier survival procedure, jointly considering two outcomes (death and recovery), and evaluate its performance by using data from the 2003 epidemic of severe acute respiratory syndrome in Hong Kong, People's Republic of China. They compare this estimate obtained at various points in the epidemic with the case fatality ratio eventually observed; with two commonly quoted, naïve estimates derived from cumulative incidence and mortality statistics at single time points; and with estimates in which a parametric mixture model is used. They demonstrate the importance of patient characteristics regarding outcome by analyzing subgroups defined by age at admission to the hospital

Optimising spatial accessibility to inform rationalisation of specialist health services

BACKGROUND: In an era of budget constraints for healthcare services, strategies for provision of services that improve quality whilst saving costs are highly valued. A proposed means to achieve this is consolidation of services into fewer specialist centres, but this may lead to reduced spatial accessibility. We describe a methodology which includes implementing a combinatorial optimisation algorithm to derive combinations of services which optimise spatial accessibility in the context of service rationalisation, and demonstrate its use through the exemplar of tuberculosis clinics in London. METHODS: Our methodology involves (1) identifying the spatial distribution of the patient population using the service; (2) calculating patient travel times to each service location, and (3) using a combinatorial optimisation algorithm to identify subsets of locations that minimise overall travel time. We estimated travel times for tuberculosis patients notified in London between 2010 and 2013 to each of 29 clinics in the city. Travel time estimates were derived from the Transport for London Journey Planner service. We identified the subset of clinics that would provide the shortest overall travel time for each possible number of clinic subsets (1-28). RESULTS: Based on the 29 existing clinic locations, mean estimated travel time to clinics used by 12,061 tuberculosis patients in London was 33 min; and mean time to their nearest clinics was 28 min. Using optimum combinations of clinic locations, and assuming that patients attended their nearest clinics, a mean travel time of less than 45 min could be achieved with three clinics; of 34 min with ten clinics, and of less than 30 min with 18 clinics. CONCLUSIONS: We have developed a methodological approach to optimise spatial accessibility which can be used to inform rationalisation of health services. In urban conurbations, this may enable service reorganisation which increases quality and efficiency without substantially affecting spatial accessibility. This approach could be used to inform planning of service reorganisations, but may not be generalisable to rural areas or smaller urban centres

Multiple large clusters of tuberculosis in London: a cross-sectional analysis of molecular and spatial data

Large outbreaks of tuberculosis (TB) represent a particular threat to disease control because they reflect multiple instances of active transmission. The extent to which long chains of transmission contribute to high TB incidence in London is unknown. We aimed to estimate the contribution of large clusters to the burden of TB in London and identify risk factors. We identified TB patients resident in London notified between 2010 and 2014, and used 24-locus mycobacterial interspersed repetitive units-variable number tandem repeat strain typing data to classify cases according to molecular cluster size. We used spatial scan statistics to test for spatial clustering and analysed risk factors through multinomial logistic regression. TB isolates from 7458 patients were included in the analysis. There were 20 large molecular clusters (with n>20 cases), comprising 795 (11%) of all cases; 18 (90%) large clusters exhibited significant spatial clustering. Cases in large clusters were more likely to be UK born (adjusted odds ratio 2.93, 95% CI 2.28-3.77), of black-Caribbean ethnicity (adjusted odds ratio 3.64, 95% CI 2.23-5.94) and have multiple social risk factors (adjusted odds ratio 3.75, 95% CI 1.96-7.16). Large clusters of cases contribute substantially to the burden of TB in London. Targeting interventions such as screening in deprived areas and social risk groups, including those of black ethnicities and born in the UK, should be a priority for reducing transmission