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International audience; BackgroundAn oral vaccine is a potential tool to tackle the reservoir of Mycobacterium bovis in European badgers (Meles meles), which contributes to tuberculosis of cattle in the British Isles. Inferences about vaccine protection against experimental challenge with M. bovis depend on the measurement of tuberculosis. Assessment of tuberculosis in larger species, such as badgers, is typically based on the tuberculous lesions visible at post-mortem examination and histopathology. We have developed a robust scoring system for tuberculous lesions by combining several parallel measures, which we call the “disease burden score” (DBS).MethodsAlternative scoring systems were compared within a regression analysis applied to observations from a total of 168 badgers from eight studies, including 107 badgers subjected to vaccination treatment and 61 non-vaccinated controls. The analysis included incidental observations that were recorded from each badger as potential covariate factors explaining some of the variation among animals sourced from the wild.ResultsDBS was found to be the most accurate and reliable of the scoring systems compared. By taking account of significant covariates affecting disease, application of the DBS reduced residual variance by 22.9%. A previously used measure, based on assessment of visible lesions, was suboptimal due to non-uniform variance that increased with expected value, although square root transformation addressed this issue. The covariate model fitted to DBS included sex (males had higher DBS), weight (negatively associated with DBS) and immunological evidence of prior exposure to Mycobacterium avium (positively associated with DBS).ConclusionsWe identified improved measures of tuberculous disease derived from data already collected. We also demonstrated that the proper scaling of measurements of disease in such models is necessary and can be determined empirically. The covariates which were most strongly associated with the severity of disease are important in experimental studies involving outbred animals with variable background.

Two techniques to set the tension of retropubic midurethral slings provide similar rates of cure but different rates of obstruction, bladder overactivity, and mesh erosion., OBJECTIVE: To evaluate whether the use of a Mayo Scissor as a suburethral spacer compared with a Babcock clamp holding a loop of tape under the urethra results in different rates of abnormal bladder outcomes 12 months after retropubic midurethral sling surgery. METHODS: The MUST (Mid-Urethral Sling Tensioning) trial was a block-randomized, double-blind, multicenter clinical trial that allocated women to have their retropubic midurethral slings tensioned by Scissor or Babcock technique. The primary outcome (abnormal bladder) was a composite of persistent stress urinary incontinence (SUI), overactive bladder, and urinary retention. Secondary outcomes included outcomes of the composite, postoperative catheterization, incontinence-related questionnaires, repeat incontinence treatment, and uroflowmetry. Sample size of 159 in each arm (N=318) was planned for a superiority trial, hypothesizing a 10% difference in primary outcome. RESULTS: From September 2015 to December 2017, 506 women were screened and 318 were randomized. Baseline characteristics were similar in each arm. At 12 months, 253 (79.6%) women provided information on primary outcome: 40 of 128 (31.3%) patients with midurethral slings tensioned by Scissor experienced abnormal bladder, compared with 23 of 125 (18.4%) of those with midurethral slings tensioned by Babcock (P=.018, relative difference 12.9%). Secondary analyses favored Babcock for median duration of catheterization and the proportions of women experiencing urinary retention requiring sling lysis. Uroflowmetry parameters suggest the Scissor technique is more restrictive. Rates of mesh erosion were lower for the Scissor arm. No differences occurred in proportions of women experiencing patient reported persistent SUI after surgery. CONCLUSION: Abnormal bladder outcomes were 12.9% less frequent for women with midurethral slings tensioned by Babcock. Both techniques provided a comparable patient reported cure for SUI at 12 months. Women with midurethral slings tensioned by Scissors experienced more intervention for obstruction, whereas those with midurethral slings tensioned by Babcock experienced higher rates of mesh erosion. This information about how the postoperative courses differ allows surgeons to better counsel patients preoperatively or tailor their choice of technique. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02480231. FUNDING SOURCE: Boston Scientific.

summary Stolon growth and branching in Glechoma hederacea L. was analyzed, using a plastochron index based on the number of ramets on each stolon and internode growth. New methods, employing this index, were used to detect fluctuations in the rate of stolon extension, and to analyse the development of secondary stolons. The plastochron index had a strong linear correlation with time, with a new primary ramet appearing every 3.5 d. The overall stolon extension rate fluctuated between 1.9 and 2.9 cm d−1 through each plastochron cycle. The age at which each node produced secondary stolons was related to its position on the plant, but the initial rates of secondary stolon development differed little between nodes. Rate of development of secondary stolons was strongly correlated with the time at which they started to grow. Thus, later developing secondary stolons grew more slowly than those developing earlier from nodes in equivalent positions.

Mycobacterium bovis Bacillus Calmette&ndash, Gu&eacute, rin (M. bovis BCG) was generated over a century ago for protection against Mycobacterium tuberculosis (Mtb) and is one the oldest vaccines still in use. The BCG vaccine is currently produced using a pellicle growth method, which is a complex and lengthy process that has been challenging to standardise. Fermentation for BCG vaccine production would reduce the complexity associated with pellicle growth and increase batch to batch reproducibility. This more standardised growth lends itself to quantification of the total number of bacilli in the BCG vaccine by alternative approaches, such as flow cytometry, which can also provide information about the metabolic status of the bacterial population. The aim of the work reported here was to determine which batch fermentation conditions and storage conditions give the most favourable outcomes in terms of the yield and stability of live M. bovis BCG Danish bacilli. We compared different media and assessed growth over time in culture, using total viable counts, total bacterial counts, and turbidity throughout culture. We applied fluorescent viability dyes and flow cytometry to measure real-time within-culture viability. Culture samples were stored in different cryoprotectants at different temperatures to assess the effect of these combined conditions on bacterial titres. Roisin&rsquo, s minimal medium and Middlebrook 7H9 medium gave comparable, high titres in fermenters. Flow cytometry proved to be a useful tool for enumeration of total bacterial counts and in the assessment of within-culture cell viability and cell death. Of the cryoprotectants evaluated, 5% (v/v) DMSO showed the most significant positive effect on survival and reduced the negative effects of low temperature storage on M. bovis BCG Danish viability. In conclusion, we have shown a reproducible, more standardised approach for the production, evaluation, and storage of high titre, viable, BCG vaccine.

Bovine tuberculosis (TB) in Great Britain adversely affects animal health and welfare and is a cause of considerable economic loss. The situation is exacerbated by European badgers (Meles meles) acting as a wildlife source of recurrent Mycobacterium bovis infection to cattle. Vaccination of badgers against TB is a possible means to reduce and control bovine TB. The delivery of vaccine in oral bait holds the best prospect for vaccinating badgers over a wide geographical area. There are practical limitations over the volume and concentration of Bacillus of Calmette and Gu&eacute, rin (BCG) that can be prepared for inclusion in bait. The production of BCG in a bioreactor may overcome these issues. We evaluated the efficacy of oral, bioreactor-grown BCG against experimental TB in badgers. We demonstrated repeatable protection through the direct administration of at least 2.0 &times, 108 colony forming units of BCG to the oral cavity, whereas vaccination via voluntary consumption of bait containing the same preparation of BCG did not result in demonstrable protection at the group-level, although a minority of badgers consuming bait showed immunological responses and protection after challenge equivalent to badgers receiving oral vaccine by direct administration. The need to deliver oral BCG in the context of a palatable and environmentally robust bait appears to introduce such variation in BCG delivery to sites of immune induction in the badger as to render experimental studies variable and inconsistent.

In order to develop improved vaccinations against tuberculosis, it is essential to understand the effect of vaccination on the immune response, and to overcome the mechanisms by which mycobacteria regulate this immune response. In this study, we examine the effect of intradermal vaccination with Mycobacterium bovis bacille Calmette-Guerin on macrophage phenotype following intranasal challenge with virulent Mycobacterium bovis. Preserved lung tissues used in the present study were obtained from a previous vaccination trial in BALB/c mice. Vaccinated mice showed less extensive pulmonary lesions along with a significant decrease in bacterial lung burden when compared to control mice. Immunohistochemical markers of classically activated macrophages (iNOS) and alternatively activated macrophages (Arg1, FIZZ1) were applied to lung sections. Vaccination led to a statistically significant decrease in the number of Arg1+ macrophages. The presence of macrophages that expressed Arginase 1 in pulmonary lesions was much smaller than the presence of macrophages expressing iNOS. The low presence of Arg1+ macrophages induced by vaccination may be caused by Th1 polarization and may reduce alternative activation of macrophages, with an overall more effective intracellular killing of bacteria.

Background Bovine tuberculosis (bTB) is a zoonotic disease of cattle caused by Mycobacterium bovis, widespread in England and Wales. It has high incidence towards the South West of England and Wales, with much lower incidence to the East and North. A stochastic simulation model was developed to simulate M. bovis transmission among cattle, transfer by cattle movements and transmission from environmental reservoirs (often wildlife and especially badgers). It distinguishes five surveillance streams, including herd tests, pre-movement testing and slaughter surveillance. The model thereby simulates interventions in bTB surveillance and control, and generates outputs directly comparable to detailed disease records. An anonymized version of the executable model with its input data has been released. The model was fitted to cattle bTB records for 2008–2010 in a cross-sectional comparison, and its projection was compared with records from 2010 to 2016 for validation. Results The fitted model explained over 99% of the variation among numbers of breakdowns in four defined regions and surveillance streams in 2010. It classified 7800 (95% confidence interval c. 5500 – 14,000) holdings within high incidence regions as exposed to infectious environmental reservoirs, out of over 31,000 cattle holdings identified as potentially exposed to such sources. The model was consistent with previous estimates of low M. bovis transmission rate among cattle, but cattle to cattle transmission was clearly required to generate the number of cattle cases observed. When projected to 2016, the model as fitted to 2010 continued to match the distribution of bTB among counties, although it was notable that the actual distribution of bTB in 2010 was itself a close match for its distribution in 2016. Conclusions The close model fit demonstrated that cattle movements could generate breakdowns as observed in low incidence regions, if persistent environmental reservoirs such as wildlife maintained infection levels in the high incidence regions. The model suggests that environmental reservoirs may be a challenge for control, because, although many holdings are exposed to infection from wildlife or the environment, they are a minority of holdings. Large impacts on disease in wildlife will be required to avoid each individual transmission event to cattle. Electronic supplementary material The online version of this article (10.1186/s12917-018-1595-9) contains supplementary material, which is available to authorized users.

To compare anatomical and patient-reported outcomes at 12 months postoperatively for women who had anterior compartment pelvic organ prolapse (POP) surgery using a repair augmented with porcine small intestine submucosa mesh (Mesh Group) compared with those who had a native tissue repair (No Mesh Group).This was a randomized controlled trial with 12 months follow-up. The surgical procedure was identical in both groups except for the placement of intervening mesh. The primary outcome was anatomical "cure" (Ba of -1 or less on Pelvic Organ Prolapse Quantification [POP-Q]). Secondary outcomes included POP-Q stage, patient-reported outcomes, and patient satisfaction. The study was powered to detect a 40% difference at 80% power (α=0.05).Fifty-seven women were randomized (28 to Mesh Group, 29 to No Mesh Group). Forty-five (79%) underwent concomitant surgery. At the 12-month follow-up, 56% (15/27) in the Mesh Group and 61% (17/28) in the No Mesh Group were considered cured (relative risk 0.90, 95% confidence interval 0.52-1.54). There were no significant differences between groups in recurrent or persistent prolapse (7% in each group) nor in patient-reported outcomes at 12 months. Pelvic girdle pain occurred in 4 of 27 in the Mesh Group and 3 of 28 in the No Mesh Group.No significant differences were observed in anatomical or patient-reported outcomes outcome parameters at 12 months after correction of symptomatic anterior POP by mesh or no mesh repair. In our study, porcine small intestine submucosa mesh did not confer additional benefit over a native tissue repair.ClinicalTrials.gov, www.clinicaltrials.gov, NCT0095544. LEVEL OF EVEDIENCE: I.

When analyzing the geographical variations of disease risk, one common problem is data sparseness. In such a setting, we investigate the possibility of using Bayesian shared spatial component models to strengthen inference and correct for any spatially structured sources of bias, when distinct data sources on one or more related diseases are available. Specifically, we apply our models to analyze the spatial variation of risk of two forms of scrapie infection affecting sheep in Wales (UK) using three surveillance sources on each disease. We first model each disease separately from the combined data sources and then extend our approach to jointly analyze diseases and data sources. We assess the predictive performances of several nested joint models through pseudo cross-validatory predictive model checks.

We describe the application of Bayesian hierarchical models (BHM) to the analysis of risk of sheep scrapie using data from multiple surveillance sources. More specifically, we analysed data from the test results of three surveillance sources on classical and atypical scrapie in Wales for the period 2002-2006. For each form of scrapie, a BHM was fitted to assess the occurrence of spatial patterns of risk shared by the multiple surveillance sources and the association between covariates and disease. We defined a shared-component model whereby the two types of data sources: exhaustive lists (e.g. reports of clinical cases) and sample-based data sources (e.g. abattoir survey) shared a common spatial pattern of risks at parish level. This shared component was adjusted by a risk-gradient parameter that moderated the individual contribution of the datasets. For both forms of scrapie, the risk-gradient was not significantly different indicating that the sensitivity of the two types of dataset was similar for the two diseases. The spatial patterns of the combinations of data sources appeared similar within disease. However, our results suggest that classical and atypical scrapie differ in their spatial patterns and disease determinants. The joint approach permitted inference from all the available evidence and resulted in robust and less biased estimates of risk, particularly for atypical scrapie where the number of observations was very limited.

Rectangular grids are frequently used in spatial simulations, often with nearest neighbour interactions, but each cell has diagonal as well as orthogonal nearest neighbours. Here, a simple, abstract model of weed spread demonstrates that the relative strength of diagonal and orthogonal interactions affects simulation outcomes, by determining the threshold conditions required for spread from isolated and aggregated colonized cells. The relative strength of diagonal and orthogonal interactions implicitly represents the range of interaction processes. The von Neumann neighbourhood, which has no diagonal interactions, represents processes with zero or negligible range, such as contact processes; increasing the relative strength of diagonal interactions represents processes with increasing range, such as seed dispersal. Diagonal interactions are only likely to equal orthogonal interactions for processes with ranges that allow significant interactions beyond the nearest neighbours of a cell. Thus, the Moore neighbourhood of diagonal and orthogonal nearest neighbours with equal weight may be considered an inaccurate approximation to a larger neighbourhood. Accurate diagonal and orthogonal nearest neighbour interactions can be calculated by a method proposed by Buffon in the 18th century. This method is also useful for calculating the impacts of rescaling a grid on intercellular interactions. If the area represented by each cell in the grid is increased, diagonal interactions should be reduced more than orthogonal interactions. In a rectangular grid, setting diagonal interactions to half the strength of orthogonal interactions can achieve a good match to an equivalent simulation in a hexagonal grid in some cases, but not always.

Summary • Plants spread vegetatively at rates that depend on both their own and their neighbours’ traits. We tested hypotheses that such rates also interact with defoliation intensity and differ between sites. • Well-established monoculture patches (20 × 20 cm) of five grass species were arranged in plots so that every species patch had all the remaining species as neighbours. Sites were in central Scotland, UK, and at a drier location in eastern Scotland. Plots were cut at 3 cm (‘short’) or 6 cm (‘tall’), either uniformly or in a chessboard pattern. • Invasiveness and resistance to invasion followed the transitive hierarchy, Agrostis capillaris > Festuca rubra > Lolium perenne = Holcus lanatus > Poa trivialis , except that P. trivialis strongly invaded H. lanatus at the damper, more fertile site. ‘Tall’ patches spread and intermixed most, independent of species. The effects of cutting neighbouring patches depended on both invading and invaded species’ traits. • Thus, defoliation altered the relationships between species, as did differences between sites, influencing both the speed and direction of species replacement.

The dwarf shrub heather Calluna vulgaris is an important component of the UK landscape, with value for amenity, nature conservation and animal production. A model, called "HeathMod", is described, which investigates the impact of grazing on upland heather. It combines an empirical model of production with a simple process-based model of grazing impacts. Validation from short-term studies in the literature indicated that the model predicts grazing impacts well, although more studies of grazing impacts are required to confirm the model's accuracy. Analysis of the model allowed derivation of a simple general formula for predicting sustainable levels of grazing, given knowledge of local site productivity. Predicted levels of sustainable grazing were lower than previous estimates, mainly because the model predicts the long-term impacts of sustained grazing. Application of the model is most appropriate in areas where heather is in mixed-age stands, because there is inadequate information available to model interactions between grazing and degeneration in even-aged stands of heather. (C) 2002 Elsevier Science Ltd. All rights reserved.

A new spatial simulation model of vegetation dynamics, called ‘VegeTate’, was applied to relationships between expansion of bracken (Pteridium aquilinum(L.) Kuhn) patches and grazing. VegeTate simulates multispecies dynamics within each cell of its grid, including localized apparent competition mediated by grazing and trampling. It can be parameterized to simulate various plant communities and species, includes seasonality and uses a hexagonal grid. Dynamics of individual bracken patches in grassland, and of heathland initially containing sparse grass and bracken were simulated. Mixtures of grass and bracken formed mosaics, in which locally high grass densities were associated with low standing mass and high grazing intensity, whereas high bracken densities were associated with high standing mass and low grazing intensity. Control of bracken by grazing depended on the impact of trampling. In simulations, small bracken patches occupying one or a few cells could be controlled by grazing, but not the expansion of large patches. In a sensitivity analysis, this phenomenon was reproduced after substantial changes in parameter values and environmental conditions, suggesting that it should be observable in the field. Interaction between patch size and grazing impact strongly influenced the spatial dynamics of simulated vegetation. The size of bracken patches became bimodal, so that most of the area of bracken was within a few large patches. Both spatial and temporal vegetation dynamics became non-linear. These results are consistent with observations that some bracken patches contain several genets and some genets occupy several patches. The hexagonal grid and trampling were important factors in the simulation results.

A new sigmoid growth equation is presented for curve-fitting, analysis and simulation of growth curves. Like the logistic growth equation, it increases monotonically, with both upper and lower asymptotes. Like the Richards growth equation, it can have its maximum slope at any value between its minimum and maximum. The new sigmoid equation is unique because it always tends towards exponential growth at small sizes or low densities, unlike the Richards equation, which only has this characteristic in part of its range. The new sigmoid equation is therefore uniquely suitable for circumstances in which growth at small sizes or low densities is expected to be approximately exponential, and the maximum slope of the growth curve can be at any value. Eleven widely different sigmoid curves were constructed with an exponential form at low values, using an independent algorithm. Sets of 100 variations of sequences of 20 points along each curve were created by adding random errors. In general, the new sigmoid equation fitted the sequences of points as closely as the original curves that they were generated from. The new sigmoid equation always gave closer fits and more accurate estimates of the characteristics of the 11 original sigmoid curves than the Richards equation. The Richards equation could not estimate the maximum intrinsic rate of increase (relative growth rate) of several of the curves. Both equations tended to estimate that points of inflexion were closer to half the maximum size than was actually the case; the Richards equation underestimated asymmetry by more than the new sigmoid equation. When the two equations were compared by fitting to the example dataset that was used in the original presentation of the Richards growth equation, both equations gave good fits. The Richards equation is sometimes suitable for growth processes that may or may not be close to exponential during initial growth. The new sigmoid is more suitable when initial growth is believed to be generally close to exponential, when estimates of maximum relative growth rate are required, or for generic growth simulations.

The youngest parts of clonal plants benefit from substantial physiological support from older parts, but the extent to which this physiological dependence persists through time is poorly understood. The development of autonomy among connected subunits was therefore analysed in the clonal species Glechoma hederacea. The stolons of a series of clonal fragments with differing numbers of primary ramets were severed at a fixed point relative to the four oldest primary ramets. The subsequent growth of both parts of the severed fragments was compared with that of a series of intact fragments.

OBJECTIVE : This study aimed to determine the midterm efficacy of porcine small intestine submucosa for paravaginal repairs of anterior vaginal prolapse. METHODS : One hundred five women underwent repairs between 2003 and 2006 and met our inclusion criteria. Women were invited to return for a pelvic examination and to fill out validated questionnaires. Objective failure was defined as anterior prolapse recurrence at or beyond the hymen. RESULTS : Fifty-nine women (56%) were available for follow-up. Median age of patients was 60 years (range, 26-80 years) and 83% had a parity of 2 or more. Ninety-seven percent of patients had a preoperative prolapse stage of 2 or more. Follow-up ranged from 1 to 5 years (median, 27.5 months; interquartile range, 14.5). The most common postoperative complication was transient voiding dysfunction (23.7%). Objective cure rate was 68.8%. A positive change in bladder, vaginal, and bowel symptoms (a little better, much better, or very much better) was reported by 69.5%, 59.3%, and 25.5% of women, respectively. Thirty-one women (52.5%) were sexually active at postoperative follow-up. Only 4 women (6.8%) were not sexually active because of pelvic symptoms. Dyspareunia was reported by 8.3% of the 48 women who returned for a clinic follow-up. Twenty-four women (40.7%) were not sexually active postoperatively, for reasons unrelated to their surgeries. CONCLUSIONS : Vaginal paravaginal repair using porcine xenograft is a safe procedure whose long-term efficacy needs further evaluation through prospective trials.

The number of cattle herds placed under movement restrictions in Great Britain (GB) due to the suspected presence of bovine tuberculosis (bTB) has progressively increased over the past 25 years despite an intensive and costly test-and-slaughter control program. Around 38% of herds that clear movement restrictions experience a recurrent incident (breakdown) within 24 months, suggesting that infection may be persisting within herds. Reactivity to tuberculin, the basis of diagnostic testing, is dependent on the time from infection. Thus, testing efficiency varies between outbreaks, depending on weight of transmission and cannot be directly estimated. In this paper, we use Approximate Bayesian Computation (ABC) to parameterize two within-herd transmission models within a rigorous inferential framework. Previous within-herd models of bTB have relied on ad-hoc methods of parameterization and used a single model structure (SORI) where animals are assumed to become detectable by testing before they become infectious. We study such a conventional within-herd model of bTB and an alternative model, motivated by recent animal challenge studies, where there is no period of epidemiological latency before animals become infectious (SOR). Under both models we estimate that cattle-to-cattle transmission rates are non-linearly density dependent. The basic reproductive ratio for our conventional within-herd model, estimated for scenarios with no statutory controls, increases from 1.5 (0.26–4.9; 95% CI) in a herd of 30 cattle up to 4.9 (0.99–14.0) in a herd of 400. Under this model we estimate that 50% (33–67) of recurrent breakdowns in Britain can be attributed to infection missed by tuberculin testing. However this figure falls to 24% (11–42) of recurrent breakdowns under our alternative model. Under both models the estimated extrinsic force of infection increases with the burden of missed infection. Hence, improved herd-level testing is unlikely to reduce recurrence unless this extrinsic infectious pressure is simultaneously addressed., Author Summary Epidemic models are commonly used to assess the impact of alternative management strategies. The efficacy of controls is typically assumed from “expert opinion” rather than estimated from data. Managed endemic diseases such as bovine tuberculosis offer the potential to estimate the efficiency of control directly from epidemiological data. Our methodology constitutes a shift in the level of statistical rigor applied to “policy” models and offers insights into the epidemiology of Bovine tuberculosis in Great Britain. bTB continues to persist and spread relentlessly in Britain, despite extensive testing and control programs. Cattle farmers question the efficacy of cattle controls, blaming the badger wildlife reservoir. Contrary to much public perception, we demonstrate the importance of cattle-to-cattle transmission, especially in larger herds. We estimate that in the worst case scenario up to 21% of herds may be harboring infection after they clear restrictions. However, we also estimate that there is a high rate of re-introduction of infection into herds, particularly in high incidence areas. Eliminating the hidden burden of infection alone is unlikely to be sufficient to prevent recurrent breakdowns. Rather, the high rate of external infection, both through cattle movements and environmental sources, must be addressed if recurrence is to be reduced.

Background This paper explores the spatial distribution of sampling within the active surveillance of sheep scrapie in Great Britain. We investigated the geographic distribution of the birth holdings of sheep sampled for scrapie during 2002 – 2005, including samples taken in abattoir surveys (c. 83,100) and from sheep that died in the field ("fallen stock", c. 14,600). We mapped the birth holdings by county and calculated the sampling rate, defined as the proportion of the holdings in each county sampled by the surveys. The Moran index was used to estimate the global spatial autocorrelation across Great Britain. The contributions of each county to the global Moran index were analysed by a local indicator of spatial autocorrelation (LISA). Results The sampling rate differed among counties in both surveys, which affected the distribution of detected cases of scrapie. Within each survey, the county sampling rates in different years were positively correlated during 2002–2005, with the abattoir survey being more strongly autocorrelated through time than the fallen stock survey. In the abattoir survey, spatial indices indicated that sampling rates in neighbouring counties tended to be similar, with few significant contrasts. Sampling rates were strongly correlated with sheep density, being highest in Wales, Southwest England and Northern England. This relationship with sheep density accounted for over 80% of the variation in sampling rate among counties. In the fallen stock survey, sampling rates in neighbouring counties tended to be different, with more statistically significant contrasts. The fallen stock survey also included a larger proportion of holdings providing many samples. Conclusion Sampling will continue to be uneven unless action is taken to make it more uniform, if more uniform sampling becomes a target. Alternatively, analyses of scrapie occurrence in these datasets can take account of the distribution of sampling. Combining the surveys only partially reduces uneven sampling. Adjusting the distribution of sampling between abattoirs to reduce the bias in favour of regions with high sheep densities could probably achieve more even sampling. However, any adjustment of sampling should take account of the current understanding of the distribution of scrapie cases, which will be improved by further analysis of this dataset.

Following the bovine spongiform encephalopathy (BSE) crisis, the European Union has introduced policies for eradicating transmissible spongiform encephalopathies (TSEs), including scrapie, from large ruminants. However, recent European Union surveillance has identified a novel prion disease, ‘atypical’ scrapie, substantially different from classical scrapie. It is unknown whether atypical scrapie is naturally transmissible or zoonotic, like BSE. Furthermore, cases have occurred in scrapie-resistant genotypes that are targets for selection in legislated selective breeding programmes. Here, the first epidemiological study of British cases of atypical scrapie is described, focusing on the demographics and trading patterns of farms and using databases of recorded livestock movements. Triplet comparisons found that farms with atypical scrapie stock more sheep than those of the general, non-affected population. They also move larger numbers of animals than control farms, but similar numbers to farms reporting classical scrapie. Whilst there is weak evidence of association through sheep trading of farms reporting classical scrapie, atypical scrapie shows no such evidence, being well-distributed across regions of Great Britain and through the sheep-trading network. Thus, although cases are few in number so far, our study suggests that, should natural transmission of atypical scrapie be occurring at all, it is doing so slowly.

Movement records are often used to identify animal sample provenance by retracing the movements of individuals. Here we present an alternative method, which uses the same identity tags and movement records as are used to retrace movements, but ignores individual movement paths. The first step uses a simple query to identify the most likely birth holding for every identity tag included in a database recording departures from agricultural holdings. The second step rejects a proportion of the birth holding locations to leave a list of birth holding locations that are relatively reliable. The method was used to trace the birth locations of sheep sampled for scrapie in abattoirs, or on farm as fallen stock. Over 82% of the sheep sampled in the fallen stock survey died at the holding of birth. This lack of movement may be an important constraint on scrapie transmission. These static sheep provided relatively reliable birth locations, which were used to define criteria for selecting reliable traces. The criteria rejected 16.8% of fallen stock traces and 11.9% of abattoir survey traces. Two tests provided estimates that selection reduced error in fallen stock traces from 11.3% to 3.2%, and in abattoir survey traces from 8.1% to 1.8%. This method generated 14,591 accepted traces of fallen stock from samples taken during 2002–2005 and 83,136 accepted traces from abattoir samples. The absence or ambiguity of flock tag records at the time of slaughter prevented the tracing of 16–24% of abattoir samples during 2002–2004, although flock tag records improved in 2005. The use of internal scoring to generate and evaluate results from the database query, and the confirmation of results by comparison with other database fields, are analogous to methods used in web search engines. Such methods may have wide application in tracing samples and in adding value to biological datasets.

BACKGROUND Before introducing the transobturator tape into our practice we undertook 52 transobturator tape procedures. The transobturator tape procedures were undertaken with an "outside-in" approach, using nonwoven polypropylene mesh with average pore size of 50 mum. CASES Five cases of vaginal erosions have been identified, 1 complicated by a groin abscess. All cases required further procedures to trim (n = 3), resect (n = 1) or remove (n = 1) the tape. One woman had a tension-free vaginal tape procedure. To date, 3 women remain incontinent. CONCLUSION Possible reasons for the complications include 1) surgical inexperience (unlikely, given that we have undertaken more than 2000 tension-free vaginal tape procedures without similar complication rates); 2) inherent susceptibility of the "hammock" position of the transobturator tape; or 3) the nonwoven polypropylene tape with mesh size of 50 microm itself may predispose to erosion or abscess.

In a spatially explicit simulation model of vegetation dynamics (‘VegeTate’), I labelled the initial mass of Pteridium aquilinum in each of 225 cells as a single, unique genet or clone. The physical environment was homogeneous and all genets shared the same phenotype. The aim was to discover whether and how the success of each genet was affected by its initial position relative to other genets and a competing grass species. In a scenario in which grazing generated a grass-bracken mosaic with complex spatial dynamics, the amount of growth of each genet ranged widely, from frequent extinction to mass increase by over 300 times. The main factor in the impact of position on genet growth was shown to be a benefit from the initial presence or proximity of a large mass of P. aquilinum. This was because a high density of P. aquilinum reduced local grazing intensity, allowing plant mass to accumulate and shifting the balance of competition in favour of P. aquilinum. Thus variations between cells in initial mass of P. aquilinum were greatly amplified. The implications of this amplification of initial differences between sites for population genetics are briefly discussed. Qualitative features of the spatial distribution of genets at the end of simulations matched reported observations on patchily distributed field populations of P. aquilinum. These features included dominance of a large population by a small minority of genets, widespread mixtures of a dominant genet and one or more subordinate genets, and the presence of patches of P. aquilinum formed both by agglomeration from neighbouring foci and by spread of dominant genets. Under less intense grazing, which allowed little or no development of vegetation mosaics, genet growth varied relatively little and initial variations in relative mass between genets were little changed. Based on this study, I hypothesize that any processes that generate non-linear spatial dynamics will also generate complex genet dynamics.

Livestock movements in Great Britain are well recorded, have been extensively analysed with respect to their role in disease spread, and have been used in real time to advise governments on the control of infectious diseases. Typically, livestock holdings are treated as distinct entities that must observe movement standstills upon receipt of livestock, and must report livestock movements. However, there are currently two dispensations that can exempt holdings from either observing standstills or reporting movements, namely the Sole Occupancy Authority (SOA) and Cattle Tracing System (CTS) Links, respectively. In this report we have used a combination of data analyses and computational modelling to investigate the usage and potential impact of such linked holdings on the size of a Foot-and-Mouth Disease (FMD) epidemic. Our analyses show that although SOAs are abundant, their dynamics appear relatively stagnant. The number of CTS Links is also abundant, and increasing rapidly. Although most linked holdings are only involved in a single CTS Link, some holdings are involved in numerous links that can be amalgamated to form "CTS Chains" which can be both large and geographically dispersed. Our model predicts that under a worst case scenario of "one infected - all infected", SOAs do pose a risk of increasing the size (in terms of number of infected holdings) of a FMD epidemic, but this increase is mainly due to intra-SOA infection spread events. Furthermore, although SOAs do increase the geographic spread of an epidemic, this increase is predominantly local. Whereas, CTS Chains pose a risk of increasing both the size and the geographical spread of the disease substantially, under a worse case scenario. Our results highlight the need for further investigations into whether CTS Chains are transmission chains, and also investigations into intra-SOA movements and livestock distributions due to the lack of current data.

Resistance against pesticides is a widespread and increasing problem. The control of pesticide dose and the mixing of pesticides have been proposed as methods to reduce the rate at which pesticide resistance develops. A mathematical model is developed to analyse the relationship between pesticide dose and the rate of development of pesticide resistance. The model is applicable to pesticides generally, including fungicides, herbicides and insecticides. The model measures dose in terms of its impact on a specific, sensitive pest phenotype. This measure depends both on the amount of pesticide applied and the application regime. The model separates the impact of a pesticide into a part that differs between pest phenotypes with different levels of resistance and a part that is similar for all phenotypes. Cases in which pesticide resistance can be delayed by reducing pesticide impact are defined algebraically. For these cases a simple relationship is presented between the rate at which pesticide resistance builds up, the variance of resistance in the pest population and the size of the part of the pesticide impact that differs between pest phenotypes. If pesticide resistance can be delayed by reducing pesticide impact, the part of the impact of a pesticide that does not differ between pest phenotypes determines whether it is suitable for use in mixtures. If it is positive (i.e. causes a reduction in pest growth), the pesticide is suitable for use in mixtures. Mixing only reduces the build-up of pesticide resistance by reducing the required doses of the pesticides that are mixed. Although the development of resistance against two different pesticides is delayed when resistance against one is negatively correlated with resistance against the other, mixing them is not necessarily preferable to using them in rotation. The decision whether to mix the two pesticides should still be based on their individual suitabilities for mixing, as defined above.

1 To allow assessment of the ability of plants to exploit heterogeneous habitats, the growth of the stoloniferous herb Glechoma hederacea was compared in three artificial soil environments. In the control treatment named 'uniform', potting compost was evenly mixed with sand; the treatment named 'patchy' contained the same quantity of potting compost, but half was concentrated in a central resource-rich circle in each box. In the treatment named 'low', compost was distributed homogeneously as in the first treatment, but the total quantity of potting compost was halved. 2 The biomass of G. hederacea produced in the patchy treatment was over two and a half times that produced in the uniform treatment, and over ten times that produced in the low treatment. In addition, more leaves were produced in the patchy treatment than in the other two treatments. Almost twice as many stolons reached the perimeters of the boxes. in the patchy treatment as in the uniform treatment. However, the biomass of the portions of the clones that had no basipetal connections via stolons into the central circle did not differ between treatments. 3 There was little evidence that above-ground biomass or ramets were concentrated inside the central circle of the patchy treatment relative to the other two treatments. 4 In contrast, 80% of the root biomass of plants in the patchy treatment was concentrated within the resource-rich central circle. Contrary to the situation in plants grown in homogeneous conditions, root:shoot ratio was highest where soil-derived resources were locally most abundant. Inside the central circle, ramets developed roots earlier in the patchy treatment than in the uniform treatment; outside the central circle, ramets developed roots later in the patchy treatment than in the uniform treatment. 5 In a supplementary experiment the length of young root systems increased exponentially from whatever time their growth was initiated. Thus, local delay or advancement of the initiation of root growth, in response to variations in soil characteristics, could have generated the observed concentration of root biomass inside the central circle of the patchy treatment. 6 G. hederacea can exploit environmental heterogeneity through local functional specialization of plant parts. In many habitats, species that have this ability may outcompete those adapted solely to resource-poor conditions.

The ability of clonal plants to respond morphologically to environmental conditions may be an important factor in their ability to survie environmental change. Interpretation of changes in morphology that appear to be responses to changing conditions must be based on an understanding of plant development. The morphology and architecture of G. hederacea result from the processes of internode elongation, leaf expansion, petiole extension and secondary development. To increase our understanding of plant development, we recorded these processes relative to an index of plant size, the plastochron index, which was based on the number of new primary ramets and internode elongation. Internodes completed their elongation very early relative to other parts of each ramet (...)