Spatial-temporal clustering of companion animal enteric syndrome: detection and investigation through the use of electronic medical records from participating private practices

SUMMARY There is interest in the potential of companion animal surveillance to provide data to improve pet health and to provide early warning of environmental hazards to people. We implemented a companion animal surveillance system in Calgary, Alberta and the surrounding communities. Informatics technologies automatically extracted electronic medical records from participating veterinary practices and identified cases of enteric syndrome in the warehoused records. The data were analysed using time-series analyses and a retrospective space-time permutation scan statistic. We identified a seasonal pattern of reports of occurrences of enteric syndromes in companion animals and four statistically significant clusters of enteric syndrome cases. The cases within each cluster were examined and information about the animals involved (species, age, sex), their vaccination history, possible exposure or risk behaviour history, information about disease severity, and the aetiological diagnosis was collected. We then assessed whether the cases within the cluster were unusual and if they represented an animal or public health threat. There was often insufficient information recorded in the medical record to characterize the clusters by aetiology or exposures. Space-time analysis of companion animal enteric syndrome cases found evidence of clustering. Collection of more epidemiologically relevant data would enhance the utility of practice-based companion animal surveillance.

Experimental infection of the pig with Mycobacterium ulcerans: a novel model for studying the pathogenesis of Buruli ulcer disease.

BACKGROUND Buruli ulcer (BU) is a slowly progressing, necrotising disease of the skin caused by infection with Mycobacterium ulcerans. Non-ulcerative manifestations are nodules, plaques and oedema, which may progress to ulceration of large parts of the skin. Histopathologically, BU is characterized by coagulative necrosis, fat cell ghosts, epidermal hyperplasia, clusters of extracellular acid fast bacilli (AFB) in the subcutaneous tissue and lack of major inflammatory infiltration. The mode of transmission of BU is not clear and there is only limited information on the early pathogenesis of the disease available. METHODOLOGY/PRINCIPAL FINDINGS For evaluating the potential of the pig as experimental infection model for BU, we infected pigs subcutaneously with different doses of M. ulcerans. The infected skin sites were excised 2.5 or 6.5 weeks after infection and processed for histopathological analysis. With doses of 2 × 10(7) and 2 × 10(6) colony forming units (CFU) we observed the development of nodular lesions that subsequently progressed to ulcerative or plaque-like lesions. At lower inoculation doses signs of infection found after 2.5 weeks had spontaneously resolved at 6.5 weeks. The observed macroscopic and histopathological changes closely resembled those found in M. ulcerans disease in humans. CONCLUSION/SIGNIFICANCE Our results demonstrate that the pig can be infected with M. ulcerans. Productive infection leads to the development of lesions that closely resemble human BU lesions. The pig infection model therefore has great potential for studying the early pathogenesis of BU and for the development of new therapeutic and prophylactic interventions.

Molecular and pathogenetic aspects of tumor budding in colorectal cancer.

In recent years, tumor budding in colorectal cancer has gained much attention as an indicator of lymph node metastasis, distant metastatic disease, local recurrence, worse overall and disease-free survival, and as an independent prognostic factor. Tumor buds, defined as the presence of single tumor cells or small clusters of up to five tumor cells at the peritumoral invasive front (peritumoral buds) or within the main tumor body (intratumoral buds), are thought to represent the morphological correlate of cancer cells having undergone epithelial-mesenchymal transition (EMT), an important mechanism for the progression of epithelial cancers. In contrast to their undisputed prognostic power and potential to influence clinical management, our current understanding of the biological background of tumor buds is less established. Most studies examining tumor buds have attempted to recapitulate findings of mechanistic EMT studies using immunohistochemical markers. The aim of this review is to provide a comprehensive summary of studies examining protein expression profiles of tumor buds and to illustrate the molecular pathways and crosstalk involved in their formation and maintenance.

Interpretation of fluid inclusions in quartz deformed by weak ductile shearing: reconstruction of differential stress magnitudes and pre-deformation fluid properties

A well developed theoretical framework is available in which paleofluid properties, such as chemical composition and density, can be reconstructed from fluid inclusions in minerals that have undergone no ductile deformation. The present study extends this framework to encompass fluid inclusions hosted by quartz that has undergone weak ductile deformation following fluid entrapment. Recent experiments have shown that such deformation causes inclusions to become dismembered into clusters of irregularly shaped relict inclusions surrounded by planar arrays of tiny, new-formed (neonate) inclusions. Comparison of the experimental samples with a naturally sheared quartz vein from Grimsel Pass, Aar Massif, Central Alps, Switzerland, reveals striking similarities. This strong concordance justifies applying the experimentally derived rules of fluid inclusion behaviour to nature. Thus, planar arrays of dismembered inclusions defining cleavage planes in quartz may be taken as diagnostic of small amounts of intracrystalline strain. Deformed inclusions preserve their pre-deformation concentration ratios of gases to electrolytes, but their H2O contents typically have changed. Morphologically intact inclusions, in contrast, preserve the pre-deformation composition and density of their originally trapped fluid. The orientation of the maximum principal compressive stress (σ1σ1) at the time of shear deformation can be derived from the pole to the cleavage plane within which the dismembered inclusions are aligned. Finally, the density of neonate inclusions is commensurate with the pressure value of σ1σ1 at the temperature and time of deformation. This last rule offers a means to estimate magnitudes of shear stresses from fluid inclusion studies. Application of this new paleopiezometer approach to the Grimsel vein yields a differential stress (σ1–σ3σ1–σ3) of ∼300 MPa∼300 MPa at View the MathML source390±30°C during late Miocene NNW–SSE orogenic shortening and regional uplift of the Aar Massif. This differential stress resulted in strain-hardening of the quartz at very low total strain (<5%<5%) while nearby shear zones were accommodating significant displacements. Further implementation of these experimentally derived rules should provide new insight into processes of fluid–rock interaction in the ductile regime within the Earth's crust.

Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial.

BACKGROUND A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV) is a promising Ebola vaccine candidate. We report the results of an interim analysis of a trial of rVSV-ZEBOV in Guinea, west Africa. METHODS For this open-label, cluster-randomised ring vaccination trial, suspected cases of Ebola virus disease in Basse-Guinée (Guinea, west Africa) were independently ascertained by Ebola response teams as part of a national surveillance system. After laboratory confirmation of a new case, clusters of all contacts and contacts of contacts were defined and randomly allocated 1:1 to immediate vaccination or delayed (21 days later) vaccination with rVSV-ZEBOV (one dose of 2 × 10(7) plaque-forming units, administered intramuscularly in the deltoid muscle). Adults (age ≥18 years) who were not pregnant or breastfeeding were eligible for vaccination. Block randomisation was used, with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 vs >20 individuals). The study is open label and masking of participants and field teams to the time of vaccination is not possible, but Ebola response teams and laboratory workers were unaware of allocation to immediate or delayed vaccination. Taking into account the incubation period of the virus of about 10 days, the prespecified primary outcome was laboratory-confirmed Ebola virus disease with onset of symptoms at least 10 days after randomisation. The primary analysis was per protocol and compared the incidence of Ebola virus disease in eligible and vaccinated individuals in immediate vaccination clusters with the incidence in eligible individuals in delayed vaccination clusters. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. FINDINGS Between April 1, 2015, and July 20, 2015, 90 clusters, with a total population of 7651 people were included in the planned interim analysis. 48 of these clusters (4123 people) were randomly assigned to immediate vaccination with rVSV-ZEBOV, and 42 clusters (3528 people) were randomly assigned to delayed vaccination with rVSV-ZEBOV. In the immediate vaccination group, there were no cases of Ebola virus disease with symptom onset at least 10 days after randomisation, whereas in the delayed vaccination group there were 16 cases of Ebola virus disease from seven clusters, showing a vaccine efficacy of 100% (95% CI 74·7-100·0; p=0·0036). No new cases of Ebola virus disease were diagnosed in vaccinees from the immediate or delayed groups from 6 days post-vaccination. At the cluster level, with the inclusion of all eligible adults, vaccine effectiveness was 75·1% (95% CI -7·1 to 94·2; p=0·1791), and 76·3% (95% CI -15·5 to 95·1; p=0·3351) with the inclusion of everyone (eligible or not eligible for vaccination). 43 serious adverse events were reported; one serious adverse event was judged to be causally related to vaccination (a febrile episode in a vaccinated participant, which resolved without sequelae). Assessment of serious adverse events is ongoing. INTERPRETATION The results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus disease outbreak via a ring vaccination strategy. FUNDING WHO, with support from the Wellcome Trust (UK); Médecins Sans Frontières; the Norwegian Ministry of Foreign Affairs through the Research Council of Norway; and the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre, and Department of Foreign Affairs, Trade and Development.

Prefrontal Thinning Affects Functional Connectivity and Regional Homogeneity of the Anterior Cingulate Cortex in Depression

Major depressive disorder (MDD) is associated with structural and functional alterations in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Enhanced ACC activity at rest (measured using various imaging methodologies) is found in treatment-responsive patients and is hypothesized to bolster treatment response by fostering adaptive rumination. However, whether structural changes influence functional coupling between fronto-cingulate regions and ACC regional homogeneity (ReHo) and whether these functional changes are related to levels of adaptive rumination and treatment response is still unclear. Cortical thickness and ReHo maps were calculated in 21 unmedicated depressed patients and 35 healthy controls. Regions with reduced cortical thickness defined the seeds for the subsequent functional connectivity (FC) analyses. Patients completed the Response Style Questionnaire, which provided a measure of adaptive rumination associated with better response to psychotherapy. Compared with controls, depressed patients showed thinning of the right anterior PFC, increased prefrontal connectivity with the supragenual ACC (suACC), and higher ReHo in the suACC. The suACC clusters of increased ReHo and FC spatially overlapped. In depressed patients, suACC ReHo scores positively correlated with PFC thickness and with FC strength. Moreover, stronger fronto-cingulate connectivity was related to higher levels of adaptive rumination. Greater suACC ReHo and connectivity with the right anterior PFC seem to foster adaptive forms of self-referential processing associated with better response to psychotherapy, whereas prefrontal thinning impairs the ability of depressed patients to engage the suACC during a major depressive episode. Bolstering the function of the suACC may represent a potential target for treatment.

Resilience as a correlate of acute stress disorder symptoms in patients with acute myocardial infarction

OBJECTIVES Myocardial infarction (MI) may be experienced as a traumatic event causing acute stress disorder (ASD). This mental disorder has an impact on the daily life of patients and is associated with the development of post-traumatic stress disorder. Trait resilience has been shown to be a protective factor for post-traumatic stress disorder, but its association with ASD in patients with MI is elusive and was examined in this study. METHODS We investigated 71 consecutive patients with acute MI within 48 h of having stable haemodynamic conditions established and for 3 months thereafter. All patients completed the Acute Stress Disorder Scale and the Resilience Scale to self-rate the severity of ASD symptoms and trait resilience, respectively. RESULTS Hierarchical regression analysis showed that greater resilience was associated with lower symptoms of ASD independent of covariates (b=-0.22, p<0.05). Post hoc analysis revealed resilience level to be inversely associated with the ASD symptom clusters of re-experiencing (b=-0.05, p<0.05) and arousal (b=-0.09, p<0.05), but not with dissociation and avoidance. CONCLUSIONS The findings suggest that patients with acute MI with higher trait resilience experience relatively fewer symptoms of ASD during MI. Resilience was particularly associated with re-experiencing and arousal symptoms. Our findings contribute to a better understanding of resilience as a potentially important correlate of ASD in the context of traumatic situations such as acute MI. These results emphasise the importance of identifying patients with low resilience in medical settings and to offer them adequate support.

What to Expect in the Intake Interview? Impression Management Tactics of Psychotherapy Patients

The therapeutic alliance consists of a mutual dependency between patient and therapist. Whereas earlier studies have focused on the therapists' behavioral influence, the present study examined patients' impression management tactics. The motivation to manage the impressions one has on others is particularly strong during first contact. Patients' behavioral influence was thus examined in the intake interview. Twelve possible impression management tactics were defined on the basis of theoretical conceptions of the therapeutic alliance and discussions with practicing psychotherapists. After a comprehensive training, judges rated 60 videotaped interviews. Interjudge agreement was fair to good. Influence attempts could be observed in roughly 30% of all patients' utterances. The most frequent tactics were Supplication, Provoking a response from the therapist, and Self-promotion. Patients could be grouped into three different clusters of tactic employers: Negative self-presenters, positive self-presenters, and response provokers. Male and female patients did not differ with respect to the total amount of tactics used and to the choice of specific tactics. However, when the therapist was female, male patients used significantly more tactics overall and significantly more often the tactic Negative reports about third persons. Being sensitive to patients' behavioral influence can help therapists to better understand their interactional goals and to better tailor the therapeutic alliance.

Investigating the potential of reported cattle mortality data in Switzerland for syndromic surveillance

Systems for the identification and registration of cattle have gradually been receiving attention for use in syndromic surveillance, a relatively recent approach for the early detection of infectious disease outbreaks. Real or near real-time monitoring of deaths or stillbirths reported to these systems offer an opportunity to detect temporal or spatial clusters of increased mortality that could be caused by an infectious disease epidemic. In Switzerland, such data are recorded in the "Tierverkehrsdatenbank" (TVD). To investigate the potential of the Swiss TVD for syndromic surveillance, 3 years of data (2009-2011) were assessed in terms of data quality, including timeliness of reporting and completeness of geographic data. Two time-series consisting of reported on-farm deaths and stillbirths were retrospectively analysed to define and quantify the temporal patterns that result from non-health related factors. Geographic data were almost always present in the TVD data; often at different spatial scales. On-farm deaths were reported to the database by farmers in a timely fashion; stillbirths were less timely. Timeliness and geographic coverage are two important features of disease surveillance systems, highlighting the suitability of the TVD for use in a syndromic surveillance system. Both time series exhibited different temporal patterns that were associated with non-health related factors. To avoid false positive signals, these patterns need to be removed from the data or accounted for in some way before applying aberration detection algorithms in real-time. Evaluating mortality data reported to systems for the identification and registration of cattle is of value for comparing national data systems and as a first step towards a European-wide early detection system for emerging and re-emerging cattle diseases.

Reproductive Biology of the Deep-Sea Polychaete Gorgoniapolynoe Caeciliae (Polynoidae), a Commensal Species Associated with Octocorals

Some aspects of the reproductive biology of the polychaete Gorgoniapolynoe caeciliae have been described for the first time. Gorgoniapolynoe caeciliae is a deep-sea commensal species associated with Candidella imbricala, all octocoral that populates the New England Seamount chain. Gorgoniapolynoe caeciliae is a dioccious species with an equal sex ratio and fertile segments throughout most of the adult body. The gonads of both sexes are associated with genital blood vessels emerging from the posterior surface of most intersegmental septa. In the female, oogenesis is intraovarian with oocytes being retained within the ovary until vitellogenesis is completed. The largest female examined contained over 3000 eggs with a maximum diameter of 80-90 mu m. In the male, the testes are repeated in numerous segments and consist of small clusters of spermatogonia, spermatocytes and early spermatids associated with the walls of the genital blood vessels. Early spermatids are shed into the coelom where they complete differentiation into mature ect-aquasperm with a spherical head (4 mu m), a small cap-like acrosome, and a short mid-piece with four mitochondria. Indirect evidence suggests that this species is an annual breeder that releases its gametes into seawater and produces a planktotrophic larva following fertilization. The reproductive biology of G. caeciliae is consistent with that of most other polynoids including many shallow water species suggesting that phylogenetic history strongly shapes its biology.

Bayesian models for the analysis of genetic structure when populations are correlated

Motivation: Population allele frequencies are correlated when populations have a shared history or when they exchange genes. Unfortunately, most models for allele frequency and inference about population structure ignore this correlation. Recent analytical results show that among populations, correlations can be very high, which could affect estimates of population genetic structure. In this study, we propose a mixture beta model to characterize the allele frequency distribution among populations. This formulation incorporates the correlation among populations as well as extending the model to data with different clusters of populations. Results: Using simulated data, we show that in general, the mixture model provides a good approximation of the among-population allele frequency distribution and a good estimate of correlation among populations. Results from fitting the mixture model to a dataset of genotypes at 377 autosomal microsatellite loci from human populations indicate high correlation among populations, which may not be appropriate to neglect. Traditional measures of population structure tend to over-estimate the amount of genetic differentiation when correlation is neglected. Inference is performed in a Bayesian framework.

Use of pulsed-field gel electrophoresis in surveillance of Salmonella in Houston, Texas

Background. Pulsed-field gel electrophoresis (PFGE) is a laboratory technique in which Salmonella DNA banding patterns are used as molecular fingerprints for epidemiologic study for "PFGE clusters". State and national health departments (CDC) use PFGE to detect clusters of related cases and to discover common sources of bacteria in outbreaks. ^ Objectives. Using Houston Department of Health and Human Services (HDHHS) data, the study sought: (1) to describe the epidemiology of Salmonella in Houston, with PFGE subtype as a variable; and (2) to determine whether PFGE patterns and clusters detected in Houston were local appearances of PFGE patterns or clusters that occurred statewide. ^ Methods. During the years 2002 to 2005, the HDHHS collected and analyzed data from routine surveillance of Salmonella. We implemented a protocol, between May 1, 2007 and December 31, 2007, in which PFGE patterns from local cases were sent via e-mail to the Texas Department of State Health Services, to verify whether the local PFGE patterns were also part of statewide clusters. PFGE was performed from 106 patients providing a sample from which Salmonella was isolated in that time period. Local PFGE clusters were investigated, with the enhanced picture obtained by linking local PFGE patterns to PFGE patterns at the state and national level. ^ Results. We found that, during the years 2002 to 2005, there were 66 PFGE clusters, ranging in size from 2 to 22 patients within each cluster. Between different serotypes, there were marked differences in the sizes of PFGE clusters. A common source or risk factor was found in fewer than 5 of the 66 PFGE clusters. With the revised protocol, we found that 19 of 66 local PFGE patterns were indistinguishable from PFGE patterns at Texas DSHS. During the eight months, we identified ten local PFGE clusters with a total of 42 patients. The PFGE pattern for eight of the ten clusters matched the PFGE patterns for cases reported to Texas DSHS from other geographic areas. Five of the ten PFGE patterns matched PFGE patterns for clusters under investigation at PulseNet at the national level. HDHHS epidemiologists identified a mode of transmission in two of the ten local clusters and a common risk factor in a third local cluster. ^ Conclusion. In the extended-study protocol, Houston PFGE patterns were linked to patterns seen at the state and national level. The investigation of PFGE clusters was more efficacious in detecting a common transmission when local data were linked to state and national data. ^

AN ANALYSIS OF THE GENERAL WELL-BEING OF BLACKS AND WHITES

The importance of race as a factor in mental health status has been a topic of controversy. This study reviews the history of research in this area and examines racial variances in the relationship between selected socio-demographic variables and general well-being. The study also examines the appropriateness of an additive versus an interactive statistical model for this investigation.^ The sample consists of 6,913 persons who completed the General Well-Being Schedules as administered in the detailed component of the first National Health and Nutrition Examination Survey (NHANES I) conducted by the National Center for Health Statistics between April, 1971 and October, 1975. The sampling design is a multistage, probability sample of clusters of persons in area based segments. Of the 6,913 persons, 873 are Black.^ Unlike other recent community based mental health studies, this study revealed significant differences between the general well-being of Blacks and Whites. Blacks continued to exhibit significantly lower levels of well-being even after adjustments were made for income, education, marital status, sex, age and place of residence. Statistical interaction was found between race and sex with Black females reporting lower levels of well-being than either Black or White males or their White female counterparts.^ The study includes a detailed review of the NHANES I sample design. It is shown that selected aspects of the design make it difficult to render appropriate national comparisons of Black-White differences. As a result conclusions pertaining to these differences based on NHANES I may be of questionable validity. ^

Kawasaki syndrome: Cluster analysis of incident cases presenting to a pediatric tertiary care hospital in Texas from January 1, 2005 to December 31, 2009

Background: Despite almost 40 years of research into the etiology of Kawasaki Syndrome (KS), there is little research published on spatial and temporal clustering of KS cases. Previous analysis has found significant spatial and temporal clustering of cases, therefore cluster analyses were performed to substantiate these findings and provide insight into incident KS cases discharged from a pediatric tertiary care hospital. Identifying clusters from a single institution would allow for prospective analysis of risk factors and potential exposures for further insight into KS etiology. ^ Methods: A retrospective study was carried out to examine the epidemiology and distribution of patients presenting to Texas Children’s Hospital in Houston, Texas, with a diagnosis of Acute Febrile Mucocutaneous Lymph Node Syndrome (MCLS) upon discharge from January 1, 2005 to December 31, 2009. Spatial, temporal, and space-time cluster analyses were performed using the Bernoulli model with case and control event data. ^ Results: 397 of 102,761 total patients admitted to Texas Children’s Hospital had a principal or secondary diagnosis of Acute Febrile MCLS upon over the 5 year period. Demographic data for KS cases remained consistent with known disease epidemiology. Spatial, temporal, and space-time analyses of clustering using the Bernoulli model demonstrated no statistically significant clusters. ^ Discussion: Despite previous findings of spatial-temporal clustering of KS cases, there were no significant clusters of KS cases discharged from a single institution. This implicates the need for an expanded approach to conducting spatial-temporal cluster analysis and KS surveillance given the limitations of evaluating data from a single institution.^

Correlation of tuberculosis and human immunodeficiency virus in Harris County, Texas from 2009 through 2010 using Geographic Information Systems

A population based ecological study was conducted to identify areas with a high number of TB and HIV new diagnoses in Harris County, Texas from 2009 through 2010 by applying Geographic Information Systems to determine whether distinguished spatial patterns exist at the census tract level through the use of exploratory mapping. As of 2010, Texas has the fourth highest occurrence of new diagnoses of HIV/AIDS and TB.[31] The Texas Department of State Health Services (DSHS) has identified HIV infected persons as a high risk population for TB in Harris County.[29] In order to explore this relationship further, GIS was utilized to identify spatial trends. ^ The specific aims were to map TB and HIV new diagnoses rates and spatially identify hotspots and high value clusters at the census tract level. The potential association between HIV and TB was analyzed using spatial autocorrelation and linear regression analysis. The spatial statistics used were ArcGIS 9.3 Hotspot Analysis and Cluster and Outlier Analysis. Spatial autocorrelation was determined through Global Moran's I and linear regression analysis. ^ Hotspots and clusters of TB and HIV are located within the same spatial areas of Harris County. The areas with high value clusters and hotspots for each infection are located within the central downtown area of the city of Houston. There is an additional hotspot area of TB located directly north of I-10 and a hotspot area of HIV northeast of Interstate 610. ^ The Moran's I Index of 0.17 (Z score = 3.6 standard deviations, p-value = 0.01) suggests that TB is statistically clustered with a less than 1% chance that this pattern is due to random chance. However, there were a high number of features with no neighbors which may invalidate the statistical properties of the test. Linear regression analysis indicated that HIV new diagnoses rates (β=−0.006, SE=0.147, p=0.970) and census tracts (β=0.000, SE=0.000, p=0.866) were not significant predictors of TB new diagnoses rates. ^ Mapping products indicate that census tracts with overlapping hotspots and high value clusters of TB and HIV should be a targeted focus for prevention efforts, most particularly within central Harris County. While the statistical association was not confirmed, evidence suggests that there is a relationship between HIV and TB within this two year period.^