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Biomedical subjects

S W Martin

Publications and source records attributed to S W Martin.

At least 19 recordsLinked to original sources

The use of randomization tests to assess the degree of similarity in PFGE patterns of E. coli O157 isolates from known outbreaks and statistical space-time clusters.

Using isolates from reported cases of Escherichia coli O157 from Alberta, Canada in 2002, we applied randomization tests to determine if cases associated with an outbreak or statistical space-time cluster had more similar pulsed-field gel electrophoresis patterns, based on Dice coefficients, than expected by chance alone. Within each outbreak and space-time cluster, we assessed the mean, median, 25th percentile, 75th percentile, standard deviation, coefficient of variation, and interquartile range of the Dice coefficients of each pairwise comparison among the isolates. To assess the statistical significance of measures of location (e.g. mean) and variation (e.g. standard deviation) we created randomization distributions using all isolates or only isolates from sporadic cases. We determined that randomization tests are an appropriate tool for evaluating the similarity among isolates from cases that have been linked epidemiologically or statistically. We found little difference between using all cases or only sporadic cases when creating our randomization distributions.

Disease Outbreaks↗

Genotype and subtype analyses of Cryptosporidium isolates from dairy calves and humans in Ontario.

To assess the importance of dairy cattle as a source of human Cryptosporidium infections in Ontario, Canada, 44 Cryptosporidium isolates from neonatal dairy calves and 11 from sporadic human cases of cryptosporidiosis in the province were genotyped by PCR-RFLP analyses of the Cryptosporidium oocyst wall protein (COWP) and 18S rRNA genes. Isolates were also subtyped by sequence analysis of the 60-kDa glycoprotein (GP60) gene. All bovine isolates successfully subtyped belonged to Cryptosporidium parvum subtype family (allele) IIa. Seven subtypes of this family were identified among the bovine isolates. Four human isolates were Cryptosporidium hominis, of alleles Ia, Id, and Ie. Of the remaining seven human specimens, four were C. parvum allele IIa, two were C. parvum of an undetermined subtype, and one was identified as Cryptosporidium cervine genotype. Three of the C. parvum isolates from humans were the same subtypes as isolates from the calves. These findings suggest that cattle and other ruminants may be a source of sporadic human infections in Ontario. This is the first published description of Cryptosporidium genotypes and subtypes in Ontario, and is the second published report of human infection with Cryptosporidium cervine genotype.

Animals↗

Quantifying badger exposure and the risk of bovine tuberculosis for cattle herds in county Kilkenny, Ireland.

The objectives of the study were to quantify the levels of badger exposure for cattle and to test the hypothesis that increased badger exposure does not increase the risk of bovine tuberculosis (BTB) in a herd. Information that became available from the targeted removal of badgers over the study period, and from a badger-removal project in county Kilkenny, during 1996-1999 was used. The specific location of cattle within each farm, and the length of time that cattle spent in each farm field during the grazing season, and in the barnyard during winter, was used to build an exposure coefficient to quantify the amount of badger exposure that cattle encountered either on pasture or in the barn. The study design was a matched case-control study in which the control herds were selected using incidence density sampling. During the 4-year study period, 543 badgers were removed and of these 96 badgers were classified as tuberculosis positive; 96 BTB herd breakdowns occurred. There was a significant association between case herds and having a higher badger sett exposure coefficient during 1996-1998. No significant association between case herds and having a higher exposure coefficient based on the number of badgers, or the number of tuberculous badgers, during September 1997-December 1999 was found.

Animals↗

Phosphorylation sites on calcium channel alpha1 and beta subunits regulate ERK-dependent modulation of neuronal N-type calcium channels.

Voltage-dependent calcium channels (VDCCs) in sensory neurones are tonically up-regulated via Ras/extracellular signal regulated kinase (ERK) signalling. The presence of putative ERK consensus sites within the intracellular loop linking domains I and II of neuronal N-type (Ca(v)2.2) calcium channels and all four neuronal calcium channel beta subunits (Ca(v)beta), suggests that Ca(v)2.2 and/or Ca(v)betas may be ERK-phosphorylated. Here we report that GST-Ca(v)2.2 I-II loop, and to a lesser extent Ca(v)beta1b-His(6), are substrates for ERK1/2 phosphorylation. Serine to alanine mutation of Ser-409 and/or Ser-447 on GST-Ca(v)2.2 I-II loop significantly reduced phosphorylation. Loss of Ser-447 reduced phosphorylation to a greater extent than mutation of Ser-409. Patch-clamp recordings from wild-type Ca(v)2.2,beta1b,alpha2delta1 versus mutant Ca(v)2.2(S447A) or Ca(v)2.2(S409A) channels revealed that mutation of either site significantly reduced current inhibition by UO126, a MEK (ERK kinase)-specific inhibitor that down-regulates ERK activity. However, no additive effect was observed by mutating both residues together, suggesting some functional redundancy between these sites. Mutation of both Ser-161 and Ser-348 on Ca(v)beta1b did not significantly reduce phosphorylation but did reduce UO126-induced current inhibition. Crucially, co-expression of Ca(v)2.2(S447A) with Ca(v)beta1b(S161,348A) had an additive effect, abolishing the action of UO126 on channel current, an effect not seen when Ca(v)beta1b(S161,348A) was co-expressed with Ca(v)2.2(S409A). Thus, Ser-447 on Ca(v)2.2 and Ser-161 and Ser-348 of Ca(v)beta1b appear to be both necessary and sufficient for ERK-dependent modulation of these channels. Together, our data strongly suggest that modulation of neuronal N-type VDCCs by ERK involves phosphorylation of Ca(v)2.2alpha1 and to a lesser extent possibly also Ca(v)beta subunits.

Amino Acid Sequence↗

The use of outbreak information in the interpretation of clustering of reported cases of Escherichia coli O157 in space and time in Alberta, Canada, 2000-2002.

We obtained a list of all reported cases of Escherichia coli O157 in Alberta during the 2000-2002 period, and using scan statistics we identified yearly temporal and spatial clusters of reported cases of E. coli O157 during the summer and in southern Alberta. However, the location of the spatial cluster in the south was variable among years. The impact of using both outbreak and sporadic data or only sporadic data on the identification of spatial and temporal clusters was small when analysing individual years, but the difference between spatial clusters was pronounced when scanning the entire study period. We also identified space-time clusters that incorporated known outbreaks, and clusters that were suggestive of undetected outbreaks that we attempted to validate with molecular data. Our results suggest that scan statistics, based on a space-time permutation model, may have a role in outbreak investigation and surveillance programmes by identifying previously undetected outbreaks.

Alberta↗

On the use of zero-inflated and hurdle models for modeling vaccine adverse event count data.

We compared several modeling strategies for vaccine adverse event count data in which the data are characterized by excess zeroes and heteroskedasticity. Count data are routinely modeled using Poisson and Negative Binomial (NB) regression but zero-inflated and hurdle models may be advantageous in this setting. Here we compared the fit of the Poisson, Negative Binomial (NB), zero-inflated Poisson (ZIP), zero-inflated Negative Binomial (ZINB), Poisson Hurdle (PH), and Negative Binomial Hurdle (NBH) models. In general, for public health studies, we may conceptualize zero-inflated models as allowing zeroes to arise from at-risk and not-at-risk populations. In contrast, hurdle models may be conceptualized as having zeroes only from an at-risk population. Our results illustrate, for our data, that the ZINB and NBH models are preferred but these models are indistinguishable with respect to fit. Choosing between the zero-inflated and hurdle modeling framework, assuming Poisson and NB models are inadequate because of excess zeroes, should generally be based on the study design and purpose. If the study's purpose is inference then modeling framework should be considered. For example, if the study design leads to count endpoints with both structural and sample zeroes then generally the zero-inflated modeling framework is more appropriate, while in contrast, if the endpoint of interest, by design, only exhibits sample zeroes (e.g., at-risk participants) then the hurdle model framework is generally preferred. Conversely, if the study's primary purpose it is to develop a prediction model then both the zero-inflated and hurdle modeling frameworks should be adequate.

Adolescent↗

A model of contagious bovine pleuropneumonia transmission dynamics in East Africa.

The dynamics of contagious bovine pleuropneumonia (CBPP) transmission vary widely between livestock production systems. This paper describes the development of a homogeneous, stochastic, compartmental model for CBPP transmission in pastoral herds of East Africa. The model was built using parameter estimates based on data published in the literature and on observations of livestock owners obtained through participatory research. The basic reproduction number for CBPP in southern Sudan was estimated to range from 3.2 to 4.6. The homogeneous model indicates that the critical community size for the persistence of CBPP falls within the typical herd sizes for pastoral communities in East Africa suggesting that individual isolated herds are capable of maintaining infection indefinitely. Vaccination alone with currently available vaccines was unlikely to eradicate the disease.

Africa, Eastern↗

A heterogeneous population model for contagious bovine pleuropneumonia transmission and control in pastoral communities of East Africa.

Pastoral cattle live in highly structured communities characterized by complex contact patterns. The present paper describes a spatially heterogeneous model for the transmission of contagious bovine pleuropneumonia (CBPP) developed specifically for pastoral communities of East Africa. The model is validated against serological data on the prevalence of CBPP infection in several communities of southern Sudan and against livestock owner information on community structure, livestock contact and cattle exchange. The model is used to assess the impact of alternative control strategies including mass and elective vaccination programmes, potential treatment regimes and the combination of vaccination and treatment in a single unified strategy. The results indicate that the eradication of CBPP using mass vaccination with currently available vaccines is unlikely to succeed. On the other hand, elective control programmes based on herd level vaccination, treatment of clinical cases or a combination of both vaccination and treatment enabled individual livestock owners to capture a large benefit in terms of reduced animal-level prevalence and mortality experience. The most promising intervention scenario was a programme which combined the vaccination of healthy animals with treatment of clinical cases.

Africa, Eastern↗

Spatial relationship between Mycobacterium bovis strains in cattle and badgers in four areas in Ireland.

We investigated whether strains (restriction fragment length polymorphism, RFLP-types) of Mycobacterium bovis isolated from badgers and from cattle clustered among and within four areas in Ireland. The spatial scan test and nearest-neighbor analysis were used as the spatial cluster-detection techniques. In addition, for each of the major strains, associations between the distance to badger setts and the "centroid" of the cattle farm were assessed in a logistic model. Overall, between September 1997 and May 2000, 316 and 287 M. bovis samples, from badgers and cattle, respectively, were strain-typed. The distribution of strains in badgers, and separately in cattle, differed among areas. Within each of the four large areas, badgers and cattle tended to have similar strains; this is consistent with the sharing of M. bovis strains within an area. In more detailed within-area analyses, some spatial clusters of M. bovis strains were detected, separately, in both cattle and badgers. Almost half of the infected badger setts with a specific strain were located outside of the "detected" clusters. There was no association between the number of infected badgers with a specific M. bovis strain within 2 or 5 km distances to cattle herds, and the risk of the same strain in cattle. We speculate about the dynamic nature of badger movements, as an explanation for the absence of more clusters of most of the strains of M. bovis isolated from badgers, and its impact on trying to study transmission of M. bovis between cattle and badger.

Animals↗

Breakdown severity during a bovine tuberculosis episode as a predictor of future herd breakdowns in Ireland.

A retrospective cohort study of Irish cattle herds investigated whether the severity of a herd's bovine tuberculosis (BTB) breakdown was a predictor of the hazard of a future BTB breakdown in that herd. Data on 10,926 herds not having had BTB in 1995 (the "non-exposed" group) were obtained using a 10% random sample from all herds without BTB in 1995. Data on 6757 herds that had a new BTB breakdown in 1995 (the "exposed" group) were obtained and categorized into five increasing exposure-severity classes based on the total number of standard reactors (to the single intra-dermal comparative cervical tuberculin test) detected during the breakdown. Exposed herds were deemed to be free of BTB after they passed a 6-month check test; non-exposed herds were deemed free as of the date of the first negative herd-test in 1995. In the 5 years after 1995, 18% of the non-exposed herds had a BTB breakdown, whereas 31% of the exposed herds had a subsequent breakdown. Relative to the hazard for non-exposed herds, the hazard for the first future singleton standard reactor breakdown, was 1.6-times higher for exposed herds with only 1 standard reactor in 1995, and 1.8-times higher for those exposed herds with 4-8 standard reactors during the 1995 episode. When the outcome for future breakdowns was 2 or more standard reactors, the hazard ratios ranged from 1.6 for exposed herds with only 1 standard reactor in 1995 up to 2.9 in exposed herds with 8 or more standard reactors during the 1995 episode. The latter hazard ratio varied over time, decreasing to 1.7 after 3 years of risk. The hazard of a future BTB breakdown increased directly with number of cattle in the herd, a positive history of previous BTB in the herd, and the local herd prevalence of BTB. The presence of confirmed BTB lesions in reactor cattle was not predictive of the future breakdown hazard when the effects of other factors were controlled.

Animals↗

Determinants of the geographical distribution of endemic giardiasis in Ontario, Canada: a spatial modelling approach.

Giardiasis surveillance data as well as drinking water, socioeconomic and land-use data were used in spatial regression models to investigate determinants of the geographic distribution of endemic giardiasis in southern Ontario. Higher giardiasis rates were observed in areas using surface water [rate ratio (RR) 2.36, 95 % CI 1.38-4.05] and in rural areas (RR 1.79, 95 % CI 1.32-2.37). Lower rates were observed in areas using filtered water (RR 0.55, 95 % CI 0.42-0.94) and in those with high median income (RR 0.62, 95 % CI 0.42-0.92). Chlorination of drinking water, cattle density and intensity of manure application on farmland were not significant determinants. The study shows that waterborne transmission plays an important role in giardiasis distribution in southern Ontario and that well-collected routine surveillance data could be useful for investigation of disease determinants and identification of high-risk communities. This information is useful in guiding decisions on control strategies.

Animals↗

Serotonin-induced potentiation of cholinergic responses to electrical field stimulation in normal and neurogenic overactive human detrusor muscle.

OBJECTIVE: To compare the serotonin (5-HT)4-receptor-mediated effects of 5-HT on the potentiation of cholinergic responses to electrical-field stimulation (EFS) in isolated strips of detrusor muscle from patients with normal or neurogenic overactive bladders. MATERIAL AND METHODS: Strips of detrusor muscle were field-stimulated (10 Hz, 0.01 ms duration, 60 V for 5 s) at 100-s intervals until consistent responses were obtained. In the presence of methiothepin, ketanserin and ondansetron (all 1 mumol/L) to block 5-HT1, 5-HT2 and 5-HT3 receptors, respectively, the cumulative administration of 5-HT or the selective 5-HT4 agonist cisapride, produced concentration-dependent enhancement of responses to EFS in both types of tissue. RESULTS: The maximum potentiation induced by 5-HT in neurogenic overactive detrusor muscle was reduced (P < 0.05) by about half compared to normal detrusor muscle, but EC50 values obtained in normal and overactive tissue were not significantly different. Cisapride was less potent than 5-HT and acted as a partial agonist relative to 5-HT. The selective 5-HT4 receptor antagonist RS-100235 was a potent antagonist of the 5-HT-induced potentiation of responses to EFS. At 3 nmol/L RS-100235 antagonized the effects of 5-HT in both groups of tissues without affecting the maximum responses. The affinity estimates (apparent pKB values of 9.2-9.5) for this antagonist were similar in normal and overactive detrusor muscle. CONCLUSIONS: These results indicate that 5-HT4 receptor-mediated potentiation of field-stimulated responses is lower in the neurogenic overactive detrusor muscle than in normal tissue. 5-HT4 receptor antagonist affinity is unchanged in the neurogenic overactive bladder.

Adult↗

Bovine tuberculosis in badgers in four areas in Ireland: does tuberculosis cluster?

We described the distribution of badger populations in four different areas in the Republic of Ireland. The data came from periodic targeted badger-removal and subsequent post-mortem examinations conducted between 1989 and September 1997, and from a formal badger-removal project in the same areas from 1997 through 1999. Records were complete for 2292 badgers regarding the date of capture, tuberculosis status, geographical area and specific sett from where the badgers were snared. Of 3187 setts, 2290 had no badgers recorded against them (i.e. were inactive). The badger-level prevalence of tuberculosis differed among areas (range 13-29%). Badger populations were highly clustered by sett, and this result was similar over the four study areas. The median number of badgers per active sett was 2. Tuberculous badgers also clustered within a sett. The third quartile of tuberculous badgers was 1 per active sett. The prevalence of tuberculous badgers within a sett was not related to the total number of badgers. There was little evidence of spatial clustering with only one local cluster of tuberculous setts in each of three areas, and none in the fourth area. After adjusting for the number of badgers per sett, only one area had spatial clusters identified.

Animals↗

Lack of associations between air emissions from sour-gas processing plants and beef cow-calf herd health and productivity in Alberta, Canada.

This paper describes a large-scale investigation into the effects of licensed air emissions from sour-gas processing plants on the health and productivity of beef cow-calf herds in the province of Alberta, Canada. In conjunction with a geographical information system, two atmospheric-dispersion models were used to assess historical exposures at 5726 beef cow-calf farm-sites from 1987 to 1990. We did secondary analyses of health, productivity, and management data, from a government-extension survey previously administered to beef cow-calf producers across the province. Statistical models (adjusted for potential confounding and clustering within herd and over time) were used to determine associations with estimates of sour-gas emission exposure. All analyses were conducted at the herd-level. There were no significant (P>0.05) detrimental associations of exposure and the annual herd risk for culling, calf-crop delivered, calf-crop season profile, stillbirth and twinning, calfhood mortality, or calf-crop weaned.

Air Pollutants↗

Air emissions from sour-gas processing plants and dairy-cattle reproduction in Alberta, Canada.

The dispersion of air pollutants from all 231 licensed sour-gas processing plants in Alberta, Canada, was modeled on a monthly basis over a 10-year period (1985-1994). Exposure estimates for sulfur dioxide (SO(2)-used as a surrogate for exposure to combusted emissions) then were assigned to 1382 provincial dairy farms using a geographical-information system. Individual average and peak exposure for periods prior to each of 15 months of age and conception (four exposure-averaging periods for each of two dispersion models) were estimated for 163,988 primiparous female dairy-cattle between 1986 and 1994. Monthly or annual average farm-site exposure estimates likewise were assigned to associated herd-level data sets for the biologically relevant period of interest for each of three additional reproductive outcomes: monthly herd-average calving interval, stillbirth risk, and twinning risk. In one of the main-effects models, the maximum (i.e., peak) monthly sour-gas exposure experienced by individual-animals from birth to conception was associated with an increased time to first-calving in the very-highest exposure category (hazard ratio=0.86, 95% CI=0.80, 0.92). This equates to a decreased hazard (lambda) of calving (in each month subsequent to 22 months of age) for the highest-exposure animals (lambda=0.170) versus the zero-exposure animals (lambda=0.198) in a model with referent values for agro-ecological region and season of birth. The dose-response was not consistent across the full range of exposure categories. There was significant (P=0.003) interaction of emissions with agro-ecological region. After accounting for the interaction, a more-consistent dose-response was evident for some (but not all) agro-ecological regions. This suggests that any effect of emissions on dairy-heifer reproduction is subject to modification by features of soil type, vegetative cover, and/or climate. The increase in monthly herd-average calving interval on farms exposed to the very-highest levels of emissions appeared quite small and of limited practical importance within the range of expected exposures. There was no association between exposure and the risk for twinning. Herds exposed to higher emissions exhibited a slight decrease in risk for stillbirth.

Aging↗

Irish soil and land-use classifications as predictors of numbers of badgers and badger setts.

This study investigated possible associations between soil types, land use and badger numbers in an area of the Irish Midlands where badger removal had been conducted during 1989-1994. For this purpose, the area was divided into approximately 2500 geo-referenced square grids of 0.5 degrees km per side. For the outcomes (setts per grid, badgers per grid and tuberculous badgers per grid), Poisson models of land use, of soil type, and a combination of these two were developed. Influential grids were removed and the models adjusted for over-dispersion in the badger outcomes. Mineral-based soils, dry and very-dry peat soils supported increased numbers of setts and badgers. High-quality pasture was the major land use (pastures often are found on mineral-based soils) and supported increased numbers of setts, badgers, and tuberculous badgers. "Natural" areas also supported more setts and broad-leaf forested areas were associated with increased tuberculous badger numbers. Discontinuous urban areas tended to decrease sett numbers per grid. Hedgerow length was not an important predictor given the information on soil type and land use. Spatial correlations existed for badger setts in 1 degrees km grids, for badger numbers in 1.5 degrees km grids, and for tuberculous badgers in 2 degrees km grids. The latter two grids have approximately the same area as the territory size used by a social group of badgers. There were no spatial correlations at the smallest (0.5 km) grid size.

Agriculture↗

Time to first calving and calving interval in bovine virus diarrhoea virus (BVDV) sero-converted dairy herds in Norway.

Dairy herds in Møre and Romsdal County, Norway (regarded as initially free from the bovine virus diarrhoea virus (BVDV) infection) were studied retrospectively from 1992 to 1996. The herd reproductive performance (time to first calving, calving interval, and number of breeding services) was investigated for a potential effect of BVDV sero-conversion. The herd culling pattern--possibly affecting the above measurements--was included for investigation. Two different statistical models were used: the generalised estimating equation (GEE) method and multilevel modelling using Gibbs sampling. Though slightly different estimates resulted, both models agreed on an effect of BVDV in the second year after sero-conversion on the herd average time to first calving by--on an average-- 14-16 days. In subsets of case herds testing positive for BVDV antibodies among young stock, the impact on time to first calving tended to be more pronounced by an additional increase of 18 days. No effect on the number of breeding services for heifers or cows was observed (indicating a need to search for other determinants than reduced conception risk). There appeared to be no effect of BVDV on the herd average calving interval. There was a tendency for a higher risk for reporting animals lost/died in sero-converted herds, which we believe might be related to the occurrence of mucosal disease.

Abortion, Veterinary↗