Gas chromatography-mass spectrometry method for rapid identification and differentiation of Burkholderia pseudomallei and Burkholderia mallei from each other, Burkholderia thailandensis and several members of the Burkholderia cepacia complex.

AIMS: To develop a simple gas chromatography-mass spectrometry (GC-MS) method for the detection and differentiation of Burkholderia pseudomallei and Burkholderia mallei from each other, Burkholderia thailandensis and several members of the Burkholderia cepacia complex. METHODS AND RESULTS: Biomarkers were generated by one-step thermochemolysis (TCM) and analysed using a GC-MS system. Fragments of poly-3-hydroxybutyrate-co-hydroxyvalerate [poly(3HBA-co-3HVA)] produced by TCM were useful biomarkers. Several cellular fatty acid methyl esters were important in differentiating the various Burkholderia species. A statistical discrimination algorithm was constructed using a combination of biomarkers. The identities of four B. pseudomallei strains, four B. mallei strains and one strain of each near neighbour were confirmed in a statistically designed test using the algorithm. The detection limit for this method was found to be approximately 4000 cells. CONCLUSIONS: The method is fast, accurate and easy to use. The algorithm is robust against different growth conditions (medium and temperature). SIGNIFICANCE AND IMPACT OF THE STUDY: This assay may prove beneficial in a clinical diagnostic setting, where the rapid identification of B. pseudomallei is essential to effective treatment. This method could also be easily employed after a biological attack to confirm the presence of either B. pseudomallei or B. mallei.

Frequency distribution of Echinococcus granulosus hydatid cysts in sheep populations in the Xinjiang Uygur Autonomous Region, China.

Age-prevalence and age-intensity data of Echinococcus granulosus hydatid cysts in sheep populations were collected in an abattoir in the Xinjiang Uygur Autonomous Region, People's Republic of China. The frequency distribution of the larval cysts per sheep was empirically described by the negative binomial model, with parameter k being 0.5273. A mathematical model for the life cycle of E. granulosus was applied to the collected data and the results show that the infection pressure on sheep was 0.4362 (female) or 0.4119 (male) infections per year, the mean number of cysts increased linearly by 0.8824 (female) or 0.9971 (male) cysts every year and acquired immunity was too low to depress this rate of increase. According to certain definitions of steady states for taeniid populations, it was concluded that at least in some parts of Xinjiang, the life cycle of E. granulosus was and may still be in an endemic steady state. Consequently, the regular dog-dosing program would readily drive the infection from an endemic state towards extinction.

Frequency distribution of Echinococcus granulosus in dog populations in the Xinjiang Uygur Autonomous Region, China.

Age-prevalence and age-intensity data of Echinococcus granulosus in dog populations were collected in four counties in the Xinjiang Uygur Autonomous Region, People's Republic of China. The frequency distribution of the parasite per dog was adequately described by the negative binomial model, with parameter k being 0.0571. The mathematical model of the life cycle of E. granulosus constructed by Roberts et al. (1986--Parasitology, Vol. 92, pages 621-641) was used to estimate the epidemiologic parameters of E. granulosus in Xinjiang. This model showed that the prevailing infection pressure on dogs was 0.4560 infectious insults year-1 and the mean length of an infection was 1.4975 years. The effect of acquired immunity on the prevalence of E. granulosus in dogs was considered to be insignificant.

Rectangularization of the survival curve: implications of an ill-posed question.

There has been considerable interest in the question of whether the human survival curve is becoming more rectangular as life expectancy in developed countries increases. However, despite the intuitive appeal of the rectangularization concept it has not been translated into a formally stated hypothesis about the shape of the human survival curve. This article examines how the hypothesis of rectangularization can be formally stated and the implications of that formalization for research on health and functional changes at later ages.

Cystic echinococcosis in the Xinjiang/Uygur Autonomous Region, People's Republic of China. II. Comparison of three levels of a local preventive and control program.

A project to compare different levels of a hydatid disease control program was instigated and evaluated in 16 randomly selected villages in the Xinjiang/Uygur Autonomous Region, PRC (China). Factors tested included the effect of: 1) the role of a village hydatid disease control officer, 2) the use of praziquantel-medicated "bait" tablets for treatment of Echinococcus granulosus tapeworms in dogs, and 3) the use of educational materials for children and adults. Evaluation of contrasting treatment levels was done by determining infection rates of E. granulosus in about 25 dogs examined from each of the 16 villages before and after the trial period, and by use of pre- and post-treatment questionnaires distributed to 40 randomly selected households in each village. Optimum results were obtained in those villages which received medicated tablets and support visits from a control officer on a monthly basis (so-called "moderate intervention level").

Cystic echinococcosis in the Xinjiang/Uygur Autonomous Region, People's Republic of China. I. Demographic and epidemiologic data.

Demographic and epidemiologic data on those factors potentially related to the prevalence and transmission of hydatid disease caused by Echinococcus granulosus were collected in 1987 from each household in 85 villages in the two communities of Yuanhucun and Ershilidian within Hutubi County in the Xinjiang/Uygur Autonomous Region, PRC, with additional questionnaire data collected from approximately 40 households randomly selected from each of 16 villages within those communities. Yuanhucun and Ershilidian represent a combined area of 522.7 square km, and have 4,853 households with 25,684 inhabitants. Of those households, 69.9% are of the Han ethnic group, 22.1% Hui, 5.3% Uygur, and 2.7% Kazak. The total number of animals censused included 4,169 dogs, 41,369 sheep, 3,673 goats, 2,639 cattle, 5,400 pigs, 1,472 horses, and 59 donkeys. Levels of infection of the causative organism of cystic hydatid disease in various hosts were: dogs harboring Echinococcus granulosus tapeworms - 63 (16.2%) positive of 390 examined in 16 villages; domestic animals with hydatid cysts - 1,593 (88.6%) sheep of 1,797 examined, 69 (56.1%) of 123 goats, and 47 (94.0%) of 50 cattle; and 15 surgeries in inhabitants from 85 villages during the last 16 months prior to completion of the survey (annual case rate of 43.8/100,000). Questionnaire data collected from inhabitants in 16 villages showed that about 82% of the families owned at least one dog and 78% owned sheep. Of those families with sheep, most (84%) killed sheep for meat at least periodically, 76% had seen hydatid cysts in liver or lungs of butchered animals, and 77% routinely gave raw offal to their dog.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlling risk in capitation payment. Multivariate definitions of risk groups.

There are a number of different reimbursement strategies proposed for health maintenance organization (HMO) style health care providers. Each of those strategies is designed to leave the provider at risk to provide incentives for him to increase the efficiency of his organization. Many such systems do not include as underwriting factors the medical status of the patient. Failure to include adjustment for the patient's medical status can: 1) leave the provider at risk due to real variation in the mix of the medical needs of the enrolled population (i.e., in areas with a sicker than average patient population, HMOs can fail by simply providing appropriate levels of care) and 2) provide incentives for selective enrollment and disenrollment based on the beneficiaries' medical status to see if such financial loss can be avoided. The authors analyzed two capitation reimbursement scenarios with adjustments for medical status to see if such adverse effects could be avoided while maintaining incentives for efficiency.

Toxicology of 85Kr: effects of whole-body immersion exposure on newborn rats.

Newborn rats exposed to 85Kr exhibited acute radiation effects, e.g. epilation, skin scaling and abnormal development of the extremities, at beta immersion doses in excess of 1000 rad to the skin surface. The incidence of skin tumors, principally basal-cell carcinomas, was increased at all dose levels over the range from 1000 to 4750 rad. The effective skin-surface dose to induce basal-cell carcinoma in the newborn Wistar rat is apparently less than 1000 rad, the lowest dose employed in this study. No lung tumors attributable to 85Kr exposure were observed in these rats.

Toxicology of 85Kr: chronic exposure studies.

Male and female Wistar rats were exposed chronically to graded doses of 85Kr to determine long-term biological effects of simulated environmental exposure. Rats were exposed in 4 groups, including room air-exposed controls and 3 groups exposed to 85Kr concentrations equivalent to 10(2), 10(3) and 10(4) times the maximum permissible concentration (MPC) for the general population (3 X 10(-7) microCi/ml). Exposures continued 24 hr/day, 7 days/week for 808 days, until only approximately 10% of the original 400 rats were alive. No effect of 85Kr exposure was observed on weight gain or tumor incidence, including leukemias. The results support the adequacy of established 85Kr exposure limits for the general population in light of the absence of evidence of build-up in tissues after chronic exposure and the lack of exposure-related biological effects in rats after near-lifespan exposure to concentrations equivalent to 10,000 times the MPC.

A comparison of test statistics for assessing the effects of concomitant variables in survival analysis.

In data analysis involving the proportional-hazards regression model due to Cox (1972, Journal of the Royal Statistical Society, Series B 34, 187-220), the test criteria commonly used for assessing the partial contribution to survival of subsets of concomitant variables are the classical likelihood ratio (LR) and Wald statistics. This paper presents an investigation of three other test criteria with potentially major computational advantages over the classical tests, especially for stepwise variable selection in moderate to large data sets. The alternative criteria considered are Rao's efficient score statistic and two other score statistics. Under the Cox model, the performance of these tests is examined empirically and compared with the performance of the LR and Wald statistics. Rao's test performs comparably to the LR test in all the cases considered. The performance of the other criteria is competitive in many cases. The use of these statistics is illustrated in a study of coronary artery disease.

On the stochastic modeling of tracer kinetics.

Virtually all of the mathematical models in current use to describe tracer kinetics are deterministic (non-stochastic). However, in this paper we suggest that the "real world" of tracer kinetics is stochastic, and we formulate a unified one-compartment model structure that incorporates multiple sources of stochasticity. The stochastic models are presented with various combinations of a probabilistic transfer mechanism, a random rate coefficient, and a random initial condition, and the mean value functions and covariances are derived for these models with both time-independent and time-varying rate coefficients. The covariances have unique forms that are helpful in model identification and many of the means are non-exponential functions. Outstanding among the conclusions are 1) a proof that a deterministic model is not always equivalent in an average sense to its stochastic counterpart; 2) the existence of many rich, practical, and realistic alternatives to the exponential decay function; and 3) the notion that models are identifiable from their covariance structure.

A stochastic compartment model of stomach cancer with correlated waiting time distributions.

The incidence and growth rate of stomach cancer in the US population is modelled, for each sex, as a partially observed, discrete state stochastic process. Explicit evaluation of the transition rates between the states of the model is made possible by identifying them as specific functions of the time spent within each state. The functions used in the model were selected from the medical and epidemiological literature. With the model it was found possible to obtain fits to the age distribution of deaths due to stomach cancer for white males in 1975 and for selected age ranges for white females. These results suggested that the natural history of stomach cancer is different for females above and below age 65.

A linear models application of competing risks to multiple causes of death.

An analysis is performed to ascertain the joint incidence of two causes of death, acute myocardial infarct and stroke, for the deaths of residents of Massachusetts and North Carolina in 1969. To assay their association an explicit biological model of the nature of the relation is posited. It is shown that, under this model, Chiang's (1968) theory of competing risks may be extended to the case in which an individual's death may have multiple causes. Furthermore, techniques are developed which allow us to model the survival parameters derived under the model by categorical data procedures of the type introduced by Grizzle, Starmer and Koch (1969). The study shows that there is a greater incidence of the joint occurrence of stroke and myocardial infarct on death certificates in North Carolina than in Massachusetts, a pattern consistent with the generally higher stroke mortality in North Carolina. Furthermore, the incidence of the joint occurrence of the two diseases shows a clear age "gradient" increasing through the age range of the analysis. Males and females show somewhat different patterns of age variation in that state-by-age interaction terms are more prominent in the model fitted for females than for males.

Compartment model approach to the estimation of tumor incidence and growth: investigation of a model of cancer latency.

Consideration is made of the problems involved in determining the effects of a chronic disease process, such as stomach cancer, on the observed mortality of the U.S. population. Specifically, since the time of initiation of tumor growth is unknown and the tumor becomes clinically manifest only after reaching considerable size, the early rate and pattern of tumor growth is unobserved. As a possible solution to the analysis of such problems, it is proposed to use stochastic compartment modelling techniques which deal with the problems of estimating the transition probabilities of a partially observed stochastic process. Implementation of the stochastic compartment techniques in this case depends on the selection of certain mathematical expressions from theories of carcinogenesis, epidemiologic studies and animal studies which allow the calculation of transition probabilities to unobserved states by making them explicit functions of time or age. Though the selection of the specific functions might be subject to debate, the general strategy of explicitly selecting such functions, and thereby exposing them for review in terms of biologic reasonableness and consistency with the data, seems to be a valid and useful methodology. Furthermore, various ways of viewing the model results (say from its internal behavior, e.g., from implied distributions of waiting times in various disease states) yield different insights into the various factors in carcinogenesis. The model, with parameters representing tumor incidence, time to tumor death given onset, genetic susceptibility to tumor growth and the effects of competing forces of mortality, is fitted to data on deaths due to stomach cancer for male U.S. residents age 25 and over in 1969. Two basic forms of the model, one with a waiting time distribution for occupants of the latent state and another with a single latency time, achieved excellent fits to the data. Examination of parameter estimates and compartment waiting time distributions are consistent with theoretical expectations and intuition. It is concluded that such strategies, involving the integration of clinical, experimental and vital statistics data into a comprehensive model of population carcinogenesis, are potentially powerful tools for investigation of the temporal dimensions of disease development in a human population.

The cost of auditing outpatient records.

When patient records are to be auditied in a program designed to assess the quality of medical care rendered, careful consideration must be given to the cost of the system implemented. Structured data collection and a defined treatment plan are advantageous in facilitating the use of nonphysicians for the majority of the audit. A system using checklists to ensure adequate recording of subjective and objective data and a defined treatment plan for a common symptom complex were implemented by physicians and physician's assistants with a patient load averaging more than 1,000 patient contacts per week in a general medical clinic at Duke University Medical Center. Audit was subsequently accomplished at a cost of 96 cents per record. To reduce this cost, more efficient methods of selecting records for audit should be developed.

An application of the clumped binomial model to the analysis of clustered attribute data.

This paper is concerned with the statistical analysis of situations where the experimental units are clusters of subjects, each of whom is classified with respect to the presence of a particular (binary response) attribute. For this purpose, the clumped binomial probability model is used to define an underlying mean rate parameter in terms of which the effects of certain treatments as well as cluster size itself can be investigated. The resulting methodology involves a synthesis of certain maximum likelihood and weighted least squares procedures; it is illustrated for a three-dimensional contingency table pertaining to numbers of deaths in litters of baby mice.