The ontology of craniofacial development and malformation for translational craniofacial research.

We introduce the Ontology of Craniofacial Development and Malformation (OCDM) as a mechanism for representing knowledge about craniofacial development and malformation, and for using that knowledge to facilitate integrating craniofacial data obtained via multiple techniques from multiple labs and at multiple levels of granularity. The OCDM is a project of the NIDCR-sponsored FaceBase Consortium, whose goal is to promote and enable research into the genetic and epigenetic causes of specific craniofacial abnormalities through the provision of publicly accessible, integrated craniofacial data. However, the OCDM should be usable for integrating any web-accessible craniofacial data, not just those data available through FaceBase. The OCDM is based on the Foundational Model of Anatomy (FMA), our comprehensive ontology of canonical human adult anatomy, and includes modules to represent adult and developmental craniofacial anatomy in both human and mouse, mappings between homologous structures in human and mouse, and associated malformations. We describe these modules, as well as prototype uses of the OCDM for integrating craniofacial data. By using the terms from the OCDM to annotate data, and by combining queries over the ontology with those over annotated data, it becomes possible to create "intelligent" queries that can, for example, find gene expression data obtained from mouse structures that are precursors to homologous human structures involved in malformations such as cleft lip. We suggest that the OCDM can be useful not only for integrating craniofacial data, but also for expressing new knowledge gained from analyzing the integrated data.

Spatial-symbolic Query Engine in Anatomy.

OBJECTIVES: Currently, the primary means for answering anatomical questions such as 'what vital organs would potentially be impacted by a bullet wound to the abdomen?' is to look them up in textbooks or to browse online sources. In this work we describe a semantic web service and spatial query processor that permits a user to graphically pose such questions as joined queries over separately defined spatial and symbolic knowledge sources. METHODS: Spatial relations (e.g. anterior) were defined by two anatomy experts, and based on a 3-D volume of labeled images of the thorax, all the labeled anatomical structures were queried to retrieve the target structures for every query structure and every spatial relation. A web user interface and a web service were designed to relate existing symbolic information from the Foundational Model of Anatomy ontology (FMA) with spatial information provided by the spatial query processor, and to permit users to select anatomical structures and define queries. RESULTS: We evaluated the accuracy of results returned by the queries, and since there is no independent gold standard, we used two anatomy experts' opinions as the gold standard for comparison. We asked the same experts to define the gold standard and to define the spatial relations. The F-measure for the overall evaluation is 0.90 for rater 1 and 0.56 for rater 2. The percentage of observed agreement is 99% and Cohen's kappa coefficient reaches 0.51. The main source of disagreement relates to issues with the labels used in the dataset, and not with the tool itself. CONCLUSIONS: In its current state the system can be used as an end-user application but it is likely to be of most use as a framework for building end-user applications such as displaying the results as a 3-D anatomical scene. The system promises potential practical utility for obtaining and navigating spatial and symbolic data.

The epidemiology of scrapie.

This review provides an update on the epidemiology of scrapie. The authors provide historical and recent information regarding the determination of geographical distribution, pathogenesis, transmission, genetic influence and the dynamics of scrapie within a flock. Also described are the risk factors associated with the disease and its spread within and between flocks. The current science may assist in providing a foundation on which prevention and control programmes may be based. Some examples of current national scrapie programmes are summarised.

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: background, evolution, and current concerns.

The epidemic of bovine spongiform encephalopathy (BSE) in the United Kingdom, which began in 1986 and has affected nearly 200,000 cattle, is waning to a conclusion, but leaves in its wake an outbreak of human Creutzfeldt-Jakob disease, most probably resulting from the consumption of beef products contaminated by central nervous system tissue. Although averaging only 10-15 cases a year since its first appearance in 1994, its future magnitude and geographic distribution (in countries that have imported infected British cattle or cattle products, or have endogenous BSE) cannot yet be predicted. The possibility that large numbers of apparently healthy persons might be incubating the disease raises concerns about iatrogenic transmissions through instrumentation (surgery and medical diagnostic procedures) and blood and organ donations. Government agencies in many countries continue to implement new measures to minimize this risk.

Bovine spongiform encephalopathy: an overview.

Bovine spongiform encephalopathy (BSE), widely known as "mad cow disease," is a chronic, degenerative disease affecting the central nervous system of cattle. Worldwide, there have been more than 180,000 cases since the disease was first diagnosed in 1986 in Great Britain. Bovine spongiform encephalopathy has had a substantial impact on the livestock industry in the United Kingdom. The disease has also been confirmed in native-born cattle in Belgium, Denmark, France, Ireland, Luxembourg, Liechtenstein, The Netherlands, Northern Ireland, Portugal, and Switzerland. However, over 95% of all BSE cases have occurred in the United Kingdom. Bovine spongiform encephalopathy is not known to exist in the United States.

Epidemiologic analysis of reported scrapie in sheep in the United States: 1,117 cases (1947-1992)

OBJECTIVE: To determine epidemiologic features associated with reported cases of scrapie in sheep in the United States. DESIGN: Retrospective study. SAMPLE POPULATION: Records for scrapie-positive sheep flocks and sheep with clinical signs consistent with scrapie reported to the USDA from 1947 through 1992. PROCEDURE: Records from the USDA's scrapie control and eradication program were abstracted, entered into a computer database, and statistically analyzed. RESULTS: 1,117 sheep from 657 flocks located in 39 states were scrapie positive during the study period. Seasonal or spatial trends were not evident. Mean yearly proportion of scrapie-positive flocks increased slightly from 1965 through 1992. One hundred sixty-eight rams and 949 ewes were reported to be scrapie positive during the study period, which was slightly more rams than expected if the disease was equally likely to affect rams and ewes. Suffolks (972/1,117; 87%) and Hampshires (68/1,117; 6%) were most commonly affected. CLINICAL IMPLICATIONS: The prevalence of scrapie in sheep in the United States is unknown. Bias in this study may have resulted from inconsistencies in available information, misclassification of sheep with clinically suspicious signs of scrapie, and changes in the national scrapie control and eradication program that likely affected willingness of owners and veterinarians to report potentially infected sheep.

Sourcing pharmaceutical, biological and medical components from livestock in the United States.

The practice of using livestock as a source of pharmaceutical, biological and medicinal components is growing. Livestock donors may be kept in research-type settings where the majority of variables are controlled. Livestock or livestock by-products may originate from known farms where there is some input into management, or products may be obtained from random-source livestock at slaughter. In the case of random-source animals, little or no information may be available about the health status of the individual animal or the farm of origin.

Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie.

Natural scrapie has been viewed both as a recessive trait and as a contagious disease modulated by a host locus. To address this conundrum, we determined the structure of the sheep prion protein (PrP) gene, which contains three exons and extends over 20 kb of DNA. In the United States 86.4% of scrapie cases occur in Suffolk sheep, and within this breed 49 +/- 6% (+/- S.D., n = 69) of healthy animals carry one or more PrP alleles encoding Arg (R)-171. Four scrapie-affected sheep were homozygous for wild-type PrP open reading frames encoding the alternative Gln (Q)-171 allele. Analysis of additional cases revealed that all were Q/Q-171 homozygotes (n = 31), yielding a probability of 0.000004 that PrP genotype is unrelated to susceptibility. These data imply that homozygosity for Q-171 codons is necessary but not sufficient for the development of natural scrapie, echo reports of recessive manifestation, and parallel over-representation of PRNP codon 129 homozygotes in Creutzfeldt-Jakob disease of humans. Whereas progress has been substantial regarding experimental scrapie in rodents, the occurrence and spread of disease in flocks of sheep has remained enigmatic. Appreciation of the relationship between codon 171 genotype and susceptibility may help define the molecular basis of natural scrapie.

Scrapie.

A detailed review is presented of the history, geographical distribution, cause, epidemiology, clinical features, pathogenesis, pathology, diagnosis, prevention, control and economic effects of scrapie in sheep. Brief mention is made of the disease in goats and moufflon. The nature of the agent causing scrapie, the genetic control of the incubation period in sheep and the natural transmission of scrapie in sheep and goats are discussed. National efforts to control scrapie in various countries are outlined.

Outbreak of Pontiac fever due to Legionella anisa.

An outbreak of Pontiac fever occurred among 34 of 56 people attending conferences at a hotel in Santa Clara County, California, in 1988. Two groups had an acute febrile upper respiratory illness, with a mean attack rate of 82% and a mean incubation period of 56 hours. Symptoms resolved spontaneously within 5 days. Legionella anisa, which had not previously been associated with outbreaks of Pontiac fever or legionnaires' disease, was isolated from a decorative fountain in the hotel lobby. In addition, 5 of 8 pairs of serum samples from cases showed a more than fourfold rise in antibody titre to the L anisa recovered from the fountain. 42% of hotel employees had titres greater than or equal to 256 against L anisa, whereas none of 48 serum samples from matched controls had titres greater than or equal to 128. The findings raise concern about water treatment protocols for extent of disease that might be caused by exposure to aerosols containing L anisa and other Legionella species.