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Applications of a quadratic variance model for counting data.

A quadratic variance model expressed as a function of sample mean is used to describe counting variance for a mechanical system that exhibits extra-Poisson variance. The nonlinear term describes the extra-Poisson variance, and the linear terms describe the intrinsic and propagated Poisson variance. The quadratic variance model also is applied to repetitive bioassay data, where the nonlinear term describes the well-known phenomenon of biological variance, which is a special case of extra-Poisson variance. The model was found to be suitable for the bioassay data as well. Detection limits for extra-Poisson variance are discussed, as well as the estimation of net signal detection limits, intake, and committed effective dose equivalent using the quadratic variance model.

Biological Assay↗

Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: application of a three-dimensional, stereologic counting method.

Neuropsychologic testing in schizophrenic patients has underscored the prominence of dysfunction in cognitive processes associated with the dorsolateral prefrontal cortex. Quantitative cytometric analysis of area 46 was undertaken in brains from schizophrenic patients to determine whether there are morphologic changes underlying these cognitive deficits. Postmortem brain specimens from 9 schizophrenic patients, 10 normal subjects, and 8 Huntington's diseased patients were fixed in formalin and celloidin embedded. A direct, three-dimensional counting method was used to determine cell density and cortical thickness in Nissl-stained sections of area 46. Overall neuronal density was 21% greater in brains from schizophrenic patients in comparison to normal controls. Significant elevations in neuronal density were observed in layers II, III, IV, and VI. The cortical ribbon was slightly (8%) but not significantly thinner. However, layer II exhibited disproportionate thinning compared with all other layers. In brains from Huntington's diseased patients, increases in neuronal (35%) and glial (61%) density with substantial cortical thinning (30%) were observed. The neuropathology of area 46 in schizophrenia is similar in direction and magnitude to that previously described in area 9 (Selemon et al. [1995] Arch. Gen. Psychiatry 52:805-818), except for the abnormalities in layer II, which are specific to area 46. In contrast to Huntington's disease, in which cortical atrophy and gliosis are present, no evidence for cortical cell loss was uncovered in the schizophrenic cohort. The observed elevation in neuronal density suggests that a reduction in interneuronal neuropil may constitute the anatomical substrate for prefrontal cortical dysfunction in schizophrenia.

Adult↗

Reduction of absolute lymphocyte count in children with recurrent medulloblastoma.

The complete blood cell (CBC) count with differential cell counts of 36 children with medulloblastoma showed a substantial reduction of the absolute lymphocyte count at recurrence. The preoperative value of the CBC count with differential cell counts failed to predict the survival of patients with medulloblastoma. A prospective study with serial measurement of the CBC count with differential cell counts will be needed to determine sensitivity and specificity of the CBC count with differential cell counts to clinical application for early detection of recurrence of medulloblastoma.

Adolescent↗

Modeling markers of disease progression by a hidden Markov process: application to characterizing CD4 cell decline.

Multistate models have been increasingly used to model natural history of many diseases as well as to characterize the follow-up of patients under varied clinical protocols. This modeling allows describing disease evolution, estimating the transition rates, and evaluating the therapy effects on progression. In many cases, the staging is defined on the basis of a discretization of the values of continuous markers (CD4 cell count for HIV application) that are subject to great variability due mainly to short time-scale noise (intraindividual variability) and measurement errors. This led us to formulate a Bayesian hierarchical model where, at a first level, a disease process (Markov model on the true states, which are unobserved) is introduced and, at a second level, the measurement process making the link between the true states and the observed marker values is modeled. This hierarchical formulation allows joint estimation of the parameters of both processes. Estimation of the quantities of interest is performed via stochastic algorithms of the family of Markov chain Monte Carlo methods. The flexibility of this approach is illustrated by analyzing the CD4 data on HIV patients of the Concorde clinical trial.

Algorithms↗

Current status of whole-body counting as a means to detect and quantify previous exposures to radioactive materials. Whole-body Counting Working Group.

This report discusses the principles, techniques, and application of whole-body counting with respect to previous radiation exposure. Whole-body counting facilities are located nationwide and have a wide range of capabilities. A listing of these facilities is provided in Appendix A. However, only a few facilities are truly state-of-the-art and have the sophisticated capabilities required to attempt detection of low-level activity in vivo. Measurements made many years after exposure can be extremely difficult to interpret. The precision and accuracy of resulting dose estimates are functions of such factors as the assumptions made concerning intake, time since intake, radionuclide metabolism, and level of intake. The indiscriminate application of metabolic models to current body contents or minimum detectable amounts of radionuclides with relatively short effective half-lives (such as 137Cs) can lead to absurd results when used as a basis for calculating intakes 25 and 40 y ago. Skull counting for 90Sr-90Y and 239,240Pu can set upper limits on possible uptakes and radiation doses, but in the case of 239,240Pu, the limits are rather high. In both cases, the accuracy of the limits depends on the metabolic models used in the calculations. These models (ICRP 1979) were developed to set safety standards for the intakes of radionuclides by workers and are not intended to be used to back-calculate uptakes and radiation doses from measurements made long after the uptake. There are, therefore, large uncertainties in any conclusions derived from these calculations. The experience gained over the years with whole- and partial-body counting has consistently shown that they are of little use in determining body contents of radionuclides resulting from exposure to weapons debris decades earlier. The development of new detectors such as an array of lithium-drifted silicon devices offers some hope of lowering the minimum detectable amount (MDA) for Pu and Am, but such detectors are still several years from routine application and do not represent current state-of-the-art. Furthermore, it is doubtful that such improvements will be sufficient to meet the need of assessing radiation exposures that occurred decades earlier.

Accidents↗

The applicability of simple blood and bone marrow variables in prediction of acute leukaemia in patients with acquired bi- or pancytopenia.

A retrospective study of 44 patients presenting with acquired bi- or pancytopenia (B/PC) and no evidence of any causal disorder was carried out. 12 patients developed acute non-lymphoblastic leukaemia after 2-51 months. Compared to the nonleukaemic subjects the preleukaemic patients at the onset of B/PC had significantly higher counts of myeloblasts and other myelopoietic cells in the bone marrow, more cellular marrows due to more dense cellularities of all compartments, higher blood granulocyte and monocyte counts, more pronounced anisocytosis, and in some cases a small number of circulating myeloblasts. A stepwise multiple logistic regression analysis identified 3 combinations of variables displaying significant simultaneous association with subsequent leukaemic transformation. Among these the combination of marrow myeloblast percentage and blood granulocyte count might be applicable to early prospective identification of patients with preleukaemic B/PC.

Acute Disease↗

Calibration of the Computer Science and Applications, Inc. accelerometer.

PURPOSE: We established accelerometer count ranges for the Computer Science and Applications, Inc. (CSA) activity monitor corresponding to commonly employed MET categories. METHODS: Data were obtained from 50 adults (25 males, 25 females) during treadmill exercise at three different speeds (4.8, 6.4, and 9.7 km x h(-1)). RESULTS: Activity counts and steady-state oxygen consumption were highly correlated (r = 0.88), and count ranges corresponding to light, moderate, hard, and very hard intensity levels were < or = 1951, 1952-5724, 5725-9498, > or = 9499 cnts x min(-1), respectively. A model to predict energy expenditure from activity counts and body mass was developed using data from a random sample of 35 subjects (r2 = 0.82, SEE = 1.40 kcal x min(-1)). Cross validation with data from the remaining 15 subjects revealed no significant differences between actual and predicted energy expenditure at any treadmill speed (SEE = 0.50-1.40 kcal x min(-1)). CONCLUSIONS: These data provide a template on which patterns of activity can be classified into intensity levels using the CSA accelerometer.

Adult↗

Defibrotide in extracorporeal circulation on healthy rabbits.

Defibrotide, a partially depolymerized DNA fraction obtained from mammalian lung, was found to have significant antithrombotic and fibrinolytic activities. On the basis of this evidence defibrotide could be of clinical value during hemoperfusive treatment. The present study was designed to evaluate the biological tolerance of this technique in a model of extracorporeal circulation, using an original Silastic apparatus, with defibrotide (0.83 mg/kg-1/min-1 after a 50 mg/kg-1 bolus injection) and heparin (0.66 IU/kg-1/min-1 after a 400 IU/kg-1 bolus injection) in ten rabbits (Group 1) and heparin only in ten others (Group 2, control group). In this study defibrotide produced a significantly lower pressure inside the circuit compared to the control group and gave a protective effect against those pathological changes which appeared during extracorporeal circulation and that may be considered omens of a state of shock. However the use of defibrotide in addition to heparin seemed to have a poor effect on platelet and leukocyte count alterations during application of this technique.

Animals↗

Evaluating ultra-low volume ground applications of malathion against Aedes aegypti using landing counts in Puerto Rico, 1980-84.

Landing counts made in a residential area in San Juan, Puerto Rico during the 5-year period, 1980-84 indicated that malathion ULV applied by LECO Fog Generators was not effective against Aedes aegypti. Of 25 applications only 6 resulted in a decrease on the first day after treatment and only one remained much less than the pretreatment count on the second and third days after treatment. Daily, the number of mosquitoes landing for a 5-minute period at each of 2 stations was recorded. An ideal year created by averaging the monthly data suggested that the seasonal variation of mosquitoes was inverse to that of reported dengue incidence.

Aedes↗

Use of a microplate scintillation counter as a radioactivity detector for miniaturized separation techniques in drug metabolism.

In miniaturized separation techniques, such as capillary electrophoresis (CE) or capillary liquid chromatography (LC), conventional on-line radioactivity detection of labeled compounds is restricted, because of insufficient sensitivity. It will be shown that a microplate scintillation counter for 96-well plates (TopCount) can be used as a sensitive and easy-to-handle radioactivity detector for capillary LC and CE. The attractive combination of capillary LC, eluent fractionation, and subsequent off-line counting is described. The new method is applied for rapid and sensitive separation and detection of 3H-labeled parent drug and its metabolites at levels between 25 and 700 cpm in rat urine. The advantages of capillary LC coupled to the TopCount, and combined with LC-MS data, can be of benefit in many analytical areas, including the characterization of metabolites at low concentration within complex biological fluids. With the same setup, the fractionation with subsequent off-line counting is equally applicable to CE. This is demonstrated with electrophoretically separated 14C-labeled impurities, nicely resolved from a negatively charged main compound, at low levels.

Animals↗

Application and evaluation of male-specific bacteriophage as a process integrity or faecal contamination indicator in a pork slaughterhouse environment.

A male-specific bacteriophage plaque assay was evaluated as a faecal contamination or process integrity indicator for aspects of the pork slaughter process. Over 400 samples were tested including: sponge swabs from animal hauling trailer floors and dressed carcass surfaces; faecal material; water from slaughter sites; and water from each stage of wastewater treatment. Bacteriophage were observed in wastewater, trailers, slaughter process water and swine faeces. No bacteriophage were observed on dressed carcasses. Numbers of phage plaque-forming units per gram or millilitre showed greater variation and were usually lower than standard indicators, including total coliform or Escherichia coli counts. Among the applications studied, male-specific bacteriophage appear to be best suited for process control verification for wastewater treatment.

Abattoirs↗

Control of fleas on naturally infested dogs and cats and in private residences with topical spot applications of fipronil or imidacloprid.

Thirty-four flea-infested dogs and cats residing in 20 homes in Tampa, FL were randomly placed into 1 of 2 treatment groups during the summer of 1997. Pets were treated topically with either 10.0%w/v imidacloprid or 10%w/v fipronil spot-on on day 0, then once for every 28-30 days for 90 days. Flea populations were assessed in the environment using an intermittent-light trap, while pet flea burdens were assessed using visual area counts. A single application of imidacloprid was 95.3 and 97.4% effective in reducing flea populations on pets at 7 and 28 days, respectively. A single application of fipronil was 97.5 and 97.0% effective in reducing flea populations on pets at the same time points. Following 3 monthly applications of either imidacloprid or fipronil, flea burdens on pets were reduced by 99.5 and 96.5%, respectively. In addition, flea numbers in the in-home environment were reduced by 99. 0 and 98.6% in homes, where pets were treated with imidacloprid or fipronil, respectively.

Administration, Topical↗

[Demonstration of tumor inhibiting properties of a strongly immunostimulating low-molecular weight substance. Comparative studies with ifosfamide on the immuno-labile DS carcinosarcoma. Stimulation of the autoimmune activity for approx. 20 days by BA 1, a N-(2-cyanoethylene)-urea. Novel prophylactic possibilities].

A report is given on the recent discovery of outstanding immunological properties in BA 1 [N-(2-cyanoethylene)-urea] having a (low) molecular mass M = 111.104. Experiments in 214 DS carcinosarcoma bearing Wistar rats have shown that BA 1, at a dosage of only about 12 percent LD50 (150 mg kg) and negligible lethality (1.7 percent), results in a recovery rate of 40 percent without hyperglycemia and, in one test, of 80 percent with hyperglycemia. Under otherwise unchanged conditions the reference substance ifosfamide (IF) -- a further development of cyclophosphamide -- applied without hyperglycemia in its most efficient dosage of 47 percent LD50 (150 mg kg) brought about a recovery rate of 25 percent at a lethality of 18 percent. (Contrary to BA 1, 250-min hyperglycemia caused no further improvement of the recovery rate.) However this comparison is characterized by the fact that both substances exhibit two quite different (complementary) mechanisms of action. Leucocyte counts made after application of the said cancerostatics and dosages have shown a pronounced stimulation with BA 1 and with ifosfamide, the known suppression in the post-therapeutic interval usually found with standard cancerostatics. In combination with the cited plaque test for BA 1, blood pictures then allow conclusions on the immunity status. Since IF can be taken as one of the most efficient cancerostatics--there is no other chemotherapeutic known up to now that has a more significant effect on the DS carcinosarcoma in rats -- these findings are of special importance. Finally, the total amount of leucocytes and lymphocytes as well as their time behaviour was determined from the blood picture of tumour-free rats after i.v. application of BA 1. The thus obtained numerical values clearly show that further research work on the prophylactic use of this substance seems to be necessary and very promising.

Animals↗