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A probabilistic model of bathing beach safety.

An improved mathematical model for bathing beach safety is proposed. It is derived by joining the probability of infection from a given dose (Poisson distribution and the probability of acquiring such a dose (lognormal distribution). Even in the absence of better clinical and epidemiological data, the model permits an assessment of relative risk from certain hazards and the design of more meaningful bacteriological standards for individual beaches.

Bacteria↗

Monitoring of hospital emergency room visits as a method for detecting health effects of environmental exposures.

We excepted from the logs of the adult and children's emergency room at Soroka Hospital Medical Center the number and types of services requested by day for the year 1980. Both total visits and visits for respiratory conditions were examined in order to test whether rain, heat, or pollutants led to increased requests for emergency room care. The total visits for adults were 72,375, of which 1,727 (2.4%) were for selected respiratory conditions. The total visits for children were 19,232, and respiratory conditions were 3,980 (20.7%). There is marked seasonal excess for respiratory visits for children in winter, and a lesser excess for adult respiratory conditions. Non-respiratory conditions and overall visits are higher in summer months. Fewer visits occur on Saturday and on Friday, with the maximum on Sunday. Otitis and bronchitis among children show little day-of-week trends. "High event" days for admissions are determined by fitting a Poisson distribution to the numbers of admissions by day for various respiratory complaints, and we then examine the concordance between these high event days and days with rain, high pollution or temperature. Adult respiratory conditions were more likely to occur on days with high total particulates (TSP) and "respirable" particulates (RSP). When the mean values of RSP and TSP for high asthma and shortness of breath days were compared with a random day for the same month, significant differences were found for RSP for adults, but not for TSP. Natural dust is the more likely cause of this association. Emergency room monitoring should be useful in locations with high levels of man-made pollutants.

Adult↗

An optimal linear filter for the reduction of noise superimposed to the EEG signal.

In the present paper a procedure for the reduction of super-imposed noise on EEG tracings is described, which makes use of linear digital filtering and identification methods. In particular, an optimal filter (a Kalman filter) has been developed which is intended to capture the disturbances of the electromyographic noise on the basis of an a priori modelling which considers a series of impulses with a temporal occurrence according to a Poisson distribution as a noise generating mechanism. The experimental results refer to the EEG tracings recorded from 20 patients in normal resting conditions: the procedure consists of a preprocessing phase (which uses also a low-pass FIR digital filter), followed by the implementation of the identification and the Kalman filter. The performance of the filters is satisfactory also from the clinical standpoint, obtaining a marked reduction of noise without distorting the useful information contained in the signal. Furthermore, when using the introduced method, the EEG signal generating mechanism is accordingly parametrized as AR/ARMA models, thus obtaining an extremely sensitive feature extraction with interesting and not yet completely studied pathophysiological meanings. The above procedure may find a general application in the field of noise reduction and the better enhancement of information contained in the wide set of biological signals.

Computers↗

Stability of pBR322-derived plasmids.

The stability of pBR322-derived plasmids was studied during growth of their Escherichia coli host in the absence of antibiotics. Plasmid pBR322, as well as its delta rom and delta bla derivatives, were lost from their host within 60 generations, but a number of delta tet derivatives were quite stable under the same conditions. An evaluation of the data indicated that primary plasmid loss due to random partitioning corresponds to the generation of a plasmid-free cell about every 10(4) divisions (probability P0; = "intrinsic" instability). Secondary loss of plasmid-carrying cells resulted from a growth advantage of the plasmid-free cells when bacteria die, perhaps due to unrepaired lethal damage in the DNA, under conditions of stationary incubation (= "apparent" instability). This cell death also occurred in the absence of plasmids but was accelerated by the presence of extra plasmid DNA in the cell and further accelerated by a functional tet gene. This was the reason for the differential apparent stabilities of delta bla and delta tet plasmids. There was no indication that an accumulation of plasmid multimers contributed to the plasmid instability, as has been suggested in the literature. The value of P0 = 10(-4) is 14 orders of magnitude greater than expected under the assumption of a random (Poisson) distribution of plasmid copy numbers in a population of cells.

Chromosome Deletion↗

Statistical limits for detecting change in the cumulative sum derivative of the peristimulus time histogram.

The peristimulus time histogram (psth) provides a means of correlating the discharges of neurones with other events. The cumulative sum (cusum) derived from the psth facilitates the detection of small changes in the psth that may be obscured by random fluctuations in counts. The cusum integrates differences from the mean control level of counts in the psth. Any signal in the data that is related to the stimulus appears as a slope in the cusum. Psth's constructed from the rhythmic discharges of single neurones are shown to contain periodical fluctuations in counts that arise from refractoriness. This periodicity results in a cusum which deviates less from the horizontal line than predicted from a Poisson distribution of points. The more regular the spike train, i.e., the lower the coefficient of variation of the distribution of interspike intervals, the flatter is the cusum. The theory of stochastic point processes is used to derive an algorithm for calculating the best approximation of variance of the cusum. Significance limits set at 3 standard deviations of the cusum are shown to provide a good fit to cusums for unit discharges over a wide range of coefficients of variation (0.09-0.60).

Action Potentials↗

A cytogenetic approach for detecting the selective toxicity of drugs in avian embryonic B and T lymphocytes.

The developing immune system of late stage embryos and neonates may be particularly susceptible to the toxicity of drugs and environmental contaminants due to high rates of cell proliferation and ongoing processes of differentiation. We have developed a cytogenetic assay to study the mechanisms of the selective targeting of cyclophosphamide (CP) to B lymphocytes compared to T lymphocytes in chicken embryos at days 18-19 of incubation. 5-Bromo-2'-deoxyuridine (BrdU; 3 mg/200 microliters PBS; two doses; 3-h interval) was pipetted onto the inner shell membrane in order to label DNA of replicating lymphoid cells. CP (1.25-40 mg/kg) was injected 1 h after the initial BrdU dose, and the embryos were exposed to colcemid (10 micrograms/100 microliters H2O) at hour 17. Three hours later, the bursa and thymus were removed, and the lymphocytes were swollen in hypotonic solution, fixed, and processed through a fluorescence-plus-Giemsa technique to differentiate sister chromatids. Based on reductions in mitotic indices, B cells were approximately 213 times more susceptible than T cells to the cytotoxicity of CP. Because the mitotic indices of B and T cells were comparable (21.3 +/- 3.7%, vs. 25.5 +/- 6.9%), the differential toxicity cannot be ascribed to greater numbers of B cells being in mitosis. CP induced a dose-related increase in the sister-chromatid exchange frequency in B cells of up to 10.4-fold above controls, representing one of the most sensitive vertebrate systems for detecting the genotoxicity of CP. The average generation time was slowed from 9.8 +/- 0.3 h in control B cells to 19.4 +/- 0.9 h in embryos exposed to 10 mg CP/kg. Furthermore, an analysis of control SCE data from 56 embryos indicated that there was a significant overdispersion of B cells exhibiting relatively high SCE frequencies compared to a Poisson distribution. Our data indicate that the chicken embryo in the late developmental stage is a good model for detecting the presence and selective toxicity of drugs and environmental toxins in differentiating B and T lymphocytes in vivo.

Animals↗

Site-directed mutagenesis in single cells: transitions produced by DNA carrying a single O6-alkylguanine residue.

Using a single burst assay based on a Poisson Distribution, I have determined the mutant virus frequency in single spheroplasts transfected with phi X174 form I' DNA carrying an O6-methyl-, ethyl-, n-propyl- or n-butylguanine residue at position 2401 of the minus strand. One set of experiments was performed with spheroplasts derived from Escherichia coli AB1157, which has normal DNA-repair systems. Of the cells examined after transfection with DNA carrying a methylguanine moiety, 30% produced mutant virus and 12% contained only mutants; with ethylguanine, 55% of the cells had mutants and 41% produced only mutants; with butylguanine, 6% of the cells had mutants and 3% contained only mutants; with propylguanine no mutants were detected in the 33 cells examined. In similar experiments carried out with spheroplasts defective in excision repair (E. coli AB1157 uvrA6) the percentage of cells producing mutant phage after transfection with DNA carrying an O6-butylguanine residue increased from 6 to 21%, and the percentage of cells producing only mutants increased from 3 to 8%; with DNA carrying an O6-methylguanine moiety, the percentage of cells producing mutants decreased from 30 to 6% and the percentage of cells producing only mutants fell from 12% to 0. In order for an individual uvrA cell to produce exclusively mutant phage from a single O6-alkylguanine residue some form of selection must occur during replication because one strand of the transfecting DNA is wild-type, and excision repair, which could lead to a homoduplex with the transition in both strands, is defective in these cells. This selection must also occur in cells with normal DNA repair. The first event in the selection process is critical; if replication of the alkyl-DNA occurs first and if a mutation is produced, then there is a significant probability that the cell will produce only mutant virus regardless of whether or not repair occurs in subsequent events, but the frequency one observes is influenced strongly by the status of the repair systems in the cell.

Bacteriophage phi X 174↗

Organization of the tonically active pathways through the superior cervical ganglion of the rabbit.

Responses of the neurons of the rabbit superior cervical ganglion to stimulation of the fascicles of preganglionic nerve fibres dissected from the cervical sympathetic trunk, and tonic activity of these neurons were recorded with intracellular electrodes in vitro and in vivo, respectively. It was found that on average 8.5 +/- 1.2 preganglionic fibres converge on each ganglion cell. In each preparation a single input spike could be evoked in a ganglion cell by stimulation of only one of all tested fascicles. The interspike intervals for single and multiple preganglionic inputs in tonic activity of ganglion neurons displayed Gaussian and Poisson distributions, respectively. The frequencies of spikes showing a Gaussian distribution correspond in most cases to pulse and respiratory frequencies. These data suggest that (1) single input is formed by a single preganglionic fibre which evokes EPSP of an amplitude high enough to trigger a postsynaptic spike, and that (2) regular activity of the ganglion neuron triggered by single input is probably due to a regular afferent drive. A cross-correlation analysis between the intracellular tonic activity and the tonic activity simultaneously recorded from the postganglionic nerve was made. The results of the analysis were compared with those obtained when intracellular spikes were evoked by stimulation of one particular neuron. From this comparison it has been concluded that about 100 ganglion cells, on the average, discharge synchronously within the 20-ms range during their tonic activity.

Animals↗

Significance of lymphocytic sister chromatid exchange frequencies in ovarian cancer patients.

Very few studies report the analysis of sister chromatid exchanges in ovarian cancer patients. We tested the null hypothesis that SCE frequency increases with the advancing stages of ovarian cancer and follows a Poisson distribution. As controls we examined age- and sex-matched healthy volunteers who had no such past history. An increased average SCE frequency was observed in ovarian cancer patients (6.34 +/- 0.09) vis-à-vis controls (4.47 +/- 0.12). Further, the data also suggested a stage-wise increase in the SCE frequency.

Adult↗

Quantal analysis of potentiating action of phorbol ester on synaptic transmission in the hippocampus.

The mechanism of the potentiating action of phorbol diacetate on synaptic transmission in the hippocampus was studied by the quantal analysis technique. Thin transverse sections were prepared from guinea pig hippocampus and intracellular potentials were recorded from CA3 neurons. Unitary excitatory postsynaptic potentials (EPSPs) were induced in the impaled neurons by brief glutamate pulses administered to granule cells. The amplitude of the unitary EPSPs fluctuated according to Poisson distribution. From the mean and variance of the amplitude of the unitary EPSPs, the mean quantal content (m) and the mean quantal amplitude (q) were calculated. Before phorbol diacetate administration, the values of m and q were 9.7 +/- 1.4 and 1.1 +/- 0.28 mV (mean +/- S.D.), respectively. Potentiation of synaptic transmission by phorbol diacetate was accompanied by increases in the value of m. The value of q remained unchanged in most neurons and decreased in some. These results indicate that the phorbol ester causes an increase in release of neurotransmitter and thereby potentiates synaptic transmission.

Animals↗

The relative risk in a cohort study with Poisson cases.

This paper deals with making statistical inference about the relative risk (or risk ratio) in a cohort (or prospective) study with dichotomous exposure when the number of cases is a Poisson distributed variable. The exact procedure for testing the null hypothesis for the relative risk and the exact computation of its confidence interval for a single 2 X 2 table is presented. Maximum likelihood methods and the homogeneity test are presented for the common risk ratio when data is stratified in several 2 X 2 tables. These methods are based upon a sufficient statistic and therefore are considered proper statistical alternatives to the more descriptive epidemiological measures such as (in)directly standardized mortality (morbidity) ratios. All computations can be done on a programmable pocket calculator. With the HP-41 CV more than 70 strata can be distinguished.

Adolescent↗

Prevention of nosocomial aspergillosis.

Unfiltered outside air averages 1-15 pathogenic Aspergillus sp. colony forming units (cfu) m-3 although short-term fluctuations are substantial. Seasonal variation reflects increased spore prevalence during periods of greater availability of non-viable matter. In hospital, airborne spores reflect incomplete filtration, infiltration of outside air and shedding of adherent spores from introduced objects. In highly protected hospital areas supplied with air filtered at high efficiency, where aspergillus cfus may be as low as 0.01 cfu m-3, infiltration and shedding contribute a high fraction of ambient spores. Nosocomial aspergillosis occurs in linear proportion to the mean ambient hospital airborne spore content. An analysis presuming a steady-state dynamic equilibrium is imperfect because repeated sampling produces occasional high counts which violate a Poisson distribution. 'Mini-bursts' arise from disturbance of settled spores in dust, shedding spores from clothes or other subtle sources. These sources are best mitigated by increasing the air change rate. It is most important to protect bone marrow transplant patients, leukaemia and lymphoma patients undergoing intensive, potentially curative therapy. The optimal protective environments include high filtration efficiency, point-of-use filters, protection against infiltration and filter bypass, elimination of in-hospital sources, and high air change rates.

Air Microbiology↗

Incidence of neuronal dye-coupling in neocortical slices depends on the plane of section.

The fluorescent dye Lucifer Yellow CH was intracellularly injected into neurons in slices of guinea-pig visual neocortex which had been prepared by sectioning either in a plane normal to the pial surface (radial slices) or in a plane parallel to the pial surface (tangential slices). In radial slices 44.3% of the injections resulted in dye-coupling and the number of cells coupled to the impaled neuron per injection followed a Poisson distribution. In contrast dye-coupling was not observed in tangential slices. Incidence of dye-coupling in slices that had been sectioned in both the radial and tangential planes was the same as in intact radial slices, indicating that slicing in the radial plane induced the formation of pathways for dye movement between neurons. The results suggest that formation and/or strengthening of direct intercellular junctions between neocortical neurons may occur as a specific neuronal response to partial dendrotomy.

Animals↗

The hybrid spheroid clonogenic assay for the intrinsic radio- and chemo-sensitivities of human tumors.

The Hybrid Spheroid assay is based on packaging tumor cells into agglomerates of non-proliferating, but metabolically active, HeLa cells. These agglomerates provide an in vivo-like environment for entrapped test cells. Clonogenicity is determined by varying the number of test cells per hybrid spheroid so that some, but not all, spheroids give rise to macrocolonies. From the fraction of noncolony forming spheroids and the Poisson distribution, the average number of clonogens per spheroid can be calculated. The clonogenicity and radiation survival curves of cells derived from human tumors (of the maxilla, tongue, larynx, mouth floor, lung, breast, ovary, and colon) were so determined. Plating efficiency was increased in these normally poorly plating tumor cells, thus enabling survival measurements which are not practical using conventional methods. The Hybrid Spheroid assay has also been applied to determine the chemosensitivity of colon cancer cells.

Cell Aggregation↗

A rapid, quantitative assay for titration of bovine virus diarrhoea-mucosal disease virus.

An end point dilution microtitration assay is described that can be used for the titration of both cytopathic and non-cytopathic isolates of bovine virus diarrhoea-mucosal disease virus. Indirect immunofluorescence is used to detect infected MDBK cells in the wells of Terasaki plates. The virus titre is derived from the number of uninfected wells, using the Poisson distribution. The assay is simple, fast and economical. Titres of cytopathic virus determined by the microtitration assay and standard plaque assay are equivalent.

Animals↗

Wiener and Volterra analyses applied to the auditory system.

The application of a particular branch of non-linear system analysis, the functional series expansion or integral method, to the auditory system is reviewed. Both the Volterra and Wiener approach are discussed and an extension of the Wiener method from its traditional white-noise stimulus approach to that of Poisson distributed clicks is presented. This type of analysis has been applied to compound and single-unit responses from the auditory nerve, cochlear nucleus, auditory midbrain and medial geniculate body. Most studies have estimated only first-order Wiener kernels but in recent years second-order Wiener and Volterra kernels have been estimated, particularly with reference to dynamic non-linearities. A particular form of second-order analysis, the Spectro Temporal Receptive Field, offers an alternative to first-order cross-correlation when phase-lock is absent. The correlation method has revealed that neural synchronization is less affected by intensity changes and damage to the hair cells than is neural firing rate. Although the presence of the static cochlear non-linearity could be demonstrated on the basis of the intensity dependence of the first-order Wiener kernel, the identification of the exact form of the nonlinearity of the peripheral auditory system on basis of higher-order Wiener kernels has so far been inconclusive. However, successes of the method can be found in the description of the dynamic non-linearities and non-linear neural interactions.

Acoustic Stimulation↗

Application of the maximum likelihood principle to separate exponential terms in T2 relaxation of nuclear magnetic resonance.

The method of maximum likelihood has been implemented for the estimation of multiple exponential components of T2 decay curves in spin echo NMR measurements on biologic tissues. Each Each component contributes an exponential term described by two parameters (initial amplitude and T2) to the T2 decay curve. The maximum likelihood method estimates the parameters and their standard errors for all terms simultaneously, avoiding the subjectivity inherent in methods such as graphical peeling. In the model used, it was assumed that water protons are compartmentalized and that the measured spin echo signals from the protons undergoing relaxation obey the Poisson distribution. A system of non-linear equations was derived and solved iteratively for the values of the exponential parameters which maximize the likelihood of obtaining the observed data under these assumptions. The approach was implemented for bi- and tri-exponential models on a MicroVAX II computer (Digital Equipment Corporation, Maynard, MA). Simulations of bi- and tri-exponential data, with and without system noise, were analyzed to assess the accuracy and reproducibility of the method. A subset of the simulations was repeated with non-linear least squares techniques and was compared to the results obtained with maximum likelihood. Rabbit muscle and gerbil brain samples were measured and analyzed with the maximum likelihood method. The simulations showed that within specific limits on relative sizes and relaxation rates of components, these parameters can be estimated with errors less than 5%. The comparison to non-linear least squares analysis showed that the maximum likelihood method is generally superior in estimating the parameters in difficult cases. The results from tissue measurements demonstrate that the method is effective even in cases where graphical peeling would clearly not yield reliable results.

Algorithms↗

The importance of temporal structure in analyzing schizophrenic behavior: some theoretical and diagnostic implications.

THEME, a new method for analyzing the temporal structure of responding on a two-choice task, is described. This method reveals the time relationships (temporal patterns) between all response events, even those not occurring in direct sequence. It selects those temporal patterns that are significantly different (p < 0.0001) from the patterns found in a random Poisson distribution of the same events. The method was applied to data from Lyon et al. (1986) in which n = 17 outpatient schizophrenics were compared with n = 17 age-, sex-, and education-matched normal control subjects. Results revealed that responding of schizophrenic outpatients, in comparison to control subjects, had a larger number of significant temporal patterns, more different types of patterns, and more branching (connectivity) of patterns at a higher level. The latter indicates a higher degree of internal structure. These results are not predicted by standard (DSM-III-R) diagnostic procedures, but are in agreement with studies of two-choice behavior in schizophrenia based on the Lyon-Robbins (1975) theory of behavioral change, which has possible relationship to dopamine/acetylcholine imbalance in the brain. Diagnostic procedures in schizophrenia might benefit from tests oriented toward these findings, which are also consistent with Bleuler's original descriptions of schizophrenic symptomatology.

Adult↗