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Measurement of fractional lipid synthesis using deuterated water (2H2O) and mass isotopomer analysis.

Fractional biosynthesis of palmitate, stearate, and cholesterol was determined with deuterated water (2H2O) using mass isotopomer analysis in Hep G2 and MCA sarcoma cells in culture. The method employed differs from previous ones in that the number of deuterium atoms from 2H2O incorporated into newly synthesized molecules was determined and not assumed. After correction for background natural abundances, the isotopomer distribution due to deuterium incorporation in fatty acids and cholesterol was shown to follow a simple binomial distribution depending on the deuterium enrichment in water (p) and the maximum number of deuterium atoms incorporated per molecule (N). Under a wide range of 2H2O enrichments, N could be determined to be 17 for palmitate, 20 for stearate, and 20 for cholesterol by regression analysis or from a series of consecutive mass isotopomer ratios. The fraction derived from de novo synthesis was given by the ratio of the observed to the theoretical deuterium enrichment, which is the product (N x p). The new synthesized fraction of palmitate and stearate by Hep G2 cells for the length of the experiment was found to be 77 and 65%, respectively. These values were confirmed by experiments with [U-13C]glucose as the precursor. In MCA sarcoma cells grown in lipid-poor medium, the average values for fractional synthesis of palmitate, stearate, and cholesterol were 70, 35, and 70%, respectively. This approach should be generally applicable to the simultaneous determined of fractional synthesis of a number of compounds with either deuterium or 13C tracers. Its application is only limited by the accuracy of mass spectrometric analysis.

Animals↗

Generalized linear modelling for parasitologists.

Typically, the distribution of macroparasites over their host population is highly aggregated and empirically best described by the negative binomial distribution. For parasitologists, this poses a statistical provlem, which is often tackled by log-transforming the parasite data prior to analysis by parametric tests. Here, Ken Wilson and Bryan Grenfell show that this method is particularly prone to type I errors, and highlight a much more powerful and flexible alternative: generalized linear modelling.

Journal Article↗

Epidemiology and control of ascariasis in Korea.

In view of the epidemiology and control strategy, ascariasis was reviewed with special reference to the data obtained for the past years in Korea. The range of length and prepatent period of A. lumbricoides to become fertile were 12.5-13.5 cm and 1.8-2.1 months for females, and 10.5-11.5 cm and 2.1-2.5 months for males, respectively. In the female worm burden 1 per case, the egglaying capacity steadily increased from 12.6 cm of their length up to 25.0 cm and then decreased significantly after their growth to 27.5 cm. Analysed the egg discharging pattern, it was turned out that the cases with six or more worms have no probability to be false negative or unfertilized ova passer, and 52% of all false negatives were found infected only with male(s). The sex ratio was in the range of 0.74-0.82 (male/female). Basic reproductive rate was calculated in the range of 1.16-2.11 in rural areas, but it was approaching nearly to the 'break point' in some areas. It was observed that the 'U-rate' was increased from 19.4% (1973) to 61.1% (1989) for the past seventeen years. According to the survey in 6 rural areas, the average worm burden was 2.2 per population and 4.5 per infected. The frequency distribution pattern of A. lumbricoides per person in a rural community was well fitted to the negative binomial distribution. Seasonal fluctuation was shown in two, smaller and larger, peaks. The annual prevalence in student group was initially 55.4% in 1969, but decreased to 0.3% in 1989, and it is evident that the decrease has been greatly owing to the national control project. It was proved that the efficacy of a quarter dose of pyrantel pamoate used in long term control programme was almost equal to that of conventional dose (10 mg/kg). The comparatie efficacy of various interval mass chemotherapy schemes was evaluated through 2 year observations, and it was confirmed that at least biannual mass chemotherapy is necessitated to expect gradual lowering of reinfection. In the case of blanket treatments with 2-month interval in a village, all of inhabitants have been free from reinfection for the period of 28 months after the initial treatment. It was fully recognized that without specific legislation and organization supported by the government, the national mass control programme has almost no chance of success, especially in developing countries.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Expression of Mdh1 locus alleles in apozygotic progenies of sugar beet (Beta vulgaris L.)].

Expression of Mdh1 alleles has been studied in 60 apozygotic (agamospermic) sugar beet progenies. Seed progenies were obtained by uniparental (pollen less) mode of seed reproduction: selfing of pollen-sterile plants isolated with paper bags. The apozygotic seed progenies demonstrate a disomic gamete autosegregation, i.e., the ratio between genotypes in the progenies correspond to the gamete segregation in a duplex heterozygote of an autotetraploid. It was shown that the ratio between the Mdh1 phenotypes in apozygotic progenies is strongly affected by spontaneous inactivation of one of the alleles. In most progenies, the excess of FF phenotypes and the deficit of SS phenotypes were observed. In our opinion, such deviations in genotype and phenotype frequencies result from conversion of the active Mdh1-S into the inactive Mdh1-S0 allele (epigenetic gene inactivation). The spontaneous inactivation of one allele results in extremely variable frequencies of heterozygous Mdh1-F/Mdh1-S genotypes and phenotypes in the apozygotic seed progenies. The empirical distribution of the frequencies of heterozygous genotypes in the apozygotic seed progenies is given by a negative binomial distribution describing the expected time of occurrence of random events.

Alleles↗

[Form of branching of pulmonary air pathways in the canine lung].

The degree of regularity in bronchial dichotomy has been studied in 5 corrosive preparations of the dog bronchial tree by the method of E. R. Weibel. It has been demonstrated that a high degree of regularity is specific for the dog lungs that makes 0.82 +/- 0.12 regarding small and large diameters. Approximation in distribution of bronchi having the diameter of 3--3.5 mm in 1--9 generations by means of binomial distribution gives a good result. The greatest bronchial rate with the diameter mentioned above has been registered in 5--7 generations. Theoretical data are presented to demonstrate the necessity in regularity of bronchial branching in order to maintain an optimal gaseous exchange in lungs.

Animals↗

In vivo study of the biosynthesis of long-chain fatty acids using deuterated water.

To determine the contributions of preexisting fatty acid, de novo synthesis, and chain elongation in long-chain fatty acid (LCFA) synthesis, the synthesis of LCFAs, palmitate (16:0), stearate (18:0), arachidate (20:0), behenate (22:0), and lignocerate (24:0), in the epidermis, liver, and spinal cord was determined using deuterated water and mass isotopomer distribution analysis in hairless mice and Sprague-Dawley rats. Animals were given 4% deuterated water for 5 days or 8 wk in their drinking water. Blood was withdrawn at the end of these times for the determination of deuterium enrichment, and the animals were killed to isolate the various tissues for lipid extraction for the determination of the mass isotopomer distributions. The mass isotopomer distributions in LCFA were incompatible with synthesis from a single pool of primer. The synthesis of palmitate, stearate, arachidate, behenate, and lignocerate followed the expected biochemical pathways for the synthesis of LCFAs. On average, three deuterium atoms were incorporated for every addition of an acetyl unit. The isotopomer distribution resulting from chain elongation and de novo synthesis can be described by the linear combination of two binomial distributions. The proportions of preexisting, chain elongation, and de novo-synthesized fatty acids as a percentage of the total fatty acids were determined using multiple linear regression analysis. Fractional synthesis was found to vary, depending on the tissue type and the fatty acid, from 47 to 87%. A substantial fraction (24-40%) of the newly synthesized molecules was derived from chain elongation of unlabeled (recycled) palmitate.

Animals↗

[Spontaneous level of sister chromosome exchanges and their distribution in human cells].

Blood of practically healthy donors of both sexes (27 females and 23 males) was cultured under the standard conditions during 96 hours. Bromodeoxyuridine (BUdR) was added at the final concentration of 10 mkg/ml 28 hours before harvesting. The slides were stained with acridine orange and Giemsa for differential staining of chromatids. In each culture sister chromatid exchanges (SCE) were analysed in 50 cells, and the part of cells undergoing the first, second and third mitoses at the time of harvesting, was calculated. According to the mean number of SCE per cell, the distribution of individuals was consistent with the normal law, the mean being 6.525 and standard deviation--0.956. A significant heterogeneity in the speed of cell cycle of cultures was observed. The coefficient of variation for the part of cells undergoing the first mitosis was 50%, for the cells in the second mitosis--15%, and for the cells in the third mitosis--154%. Correlation analysis showed a positive dependence of the mean level of SCF upon the age of a donor and upon the part of cells in the second mitosis in this individual. No reliable correlation of the SCE level with the donor's sex was observed. The distribution of cells, obtained from the culture of one individual, was best approximated by beta-distribution, and the distribution of cells obtained from the cultures of different individuals--by gamma-distribution. In both there was obtained a satisfactory approximation by Pearson's distribution of the 1 type, and significant deviations were found from the normal, Poison's and the negative binomial distribution. The conditions were found of similarity of empirical distribution of SCE in cells to the normal one. For that, it is not the value of SCE for a separate cell that should be used as a unit of measurement, but the mean from the values of frequencies for 5-10 cells. Hence, it was shown that for the evaluation of the mean frequency of SCE with the precision of 1 exchange in separate individuals it is necessary to analyse 40 cells, and to observe the 15% increase of spontaneous SCE level under the action of deleterious factors--8 individuals are enough to analyse.

Adolescent↗

[Studies of the numerical distribution of microfilariae in foci of lymphatic filariasis (author's transl)].

The frequency distribution of Wuchereria bancrofti microfilariae counts in capillary blood, at a community level, is shown to differ significantly from the log-normal distribution, commonly used (and recommended by WHO). A much better fit is obtained with a truncated negative-binomial distribution, the k exponent of which is estimated to 0.3. This value does not seem to be affected by the endemic level, by microfilaricide mass-treatments or by the blood sample volume. This result has immediate practical interests: 1) it facilitates a posteriori comparisons between surveys in which different volumes of blood were examined; 2) at a given density it allows calculation the change in sensitivity (detection rate) as a function of a change in the volume of blood examined, thus allowing better a priori planning of surveys. The paper provides the formulae required to calculate k, or, given k, to calculate the expected numbers in the various density classes. It also provides nomograms (fig. 4a & b) giving estimates of the true mean M and of the detection rate TD, given any one of the three following observations, made on observed positives: the median Dmf. 50, the mean m, or the percentage Pl having only 1 mf. The effect of changing the volume of blood on the rate of detection can then be read easily from the nomogram. These results, likely to apply to other important parasitic diseases, should instigate more elaborated statistical research in this direction.

Animals↗

A brief history of numbers and statistics with cytometric applications.

A brief history of numbers and statistics traces the development of numbers from prehistory to completion of our current system of numeration with the introduction of the decimal fraction by Viete, Stevin, Burgi, and Galileo at the turn of the 16th century. This was followed by the development of what we now know as probability theory by Pascal, Fermat, and Huygens in the mid-17th century which arose in connection with questions in gambling with dice and can be regarded as the origin of statistics. The three main probability distributions on which statistics depend were introduced and/or formalized between the mid-17th and early 19th centuries: the binomial distribution by Pascal; the normal distribution by de Moivre, Gauss, and Laplace, and the Poisson distribution by Poisson. The formal discipline of statistics commenced with the works of Pearson, Yule, and Gosset at the turn of the 19th century when the first statistical tests were introduced. Elementary descriptions of the statistical tests most likely to be used in conjunction with cytometric data are given and it is shown how these can be applied to the analysis of difficult immunofluorescence distributions when there is overlap between the labeled and unlabeled cell populations.

Cell Count↗

Performance of number-between g-type statistical control charts for monitoring adverse events.

Alternate Shewhart-type statistical control charts, called "g" and "h" charts, have been developed for monitoring the number of cases between hospital-acquired infections and other adverse events, such as heart surgery complications, catheter-related infections, surgical site infections, contaminated needle sticks, medication errors, and other care-induced concerns. This article investigates the statistical properties of these new charts and illustrates several design considerations that significantly can improve their operating characteristics and sensitivity, including the use of within-limit rules, a new in-control rule, redefined Bernoulli trials, and probability-based limits. These new charts are based on inverse sampling from geometric and negative binomial distributions, are simple for practitioners to use, and in some cases exhibit significantly greater detection power over conventional binomial-based approaches, particularly for infrequent events and low "defect" rates.

Cross Infection↗

Characterization of structural reorganization in rice piles.

Diagnostics applied to a rice-pile cellular automaton reveal different mechanisms producing power-law behaviors of statistical attributes of grains which are germane to self organised critical phenomena. The probability distributions for these quantities can be derived from two distinct random walk models that account for correlated clustered behavior through incorporating fluctuations in the number of steps in the walk. The first model describes the distribution for a spatial quantity, the resultant flight length of grains. This has a power-law tail caused by grains moving through a discrete, power-law distributed number of random steps of finite length. Developing this model into a random walk obtains distributions for the resultant flight length with characteristics similar to Lévy distributions. The second random walk model is devised to explain a temporal quantity, the distribution of "trapping" or "residence" times of grains at single locations in the pile. Diagnostics reveal that the trapping time can be constructed as a sum of "subtrapping times," which are described by a Lévy distribution where the number of terms in the sum is a discrete random variable accurately described by a negative binomial distribution. The infinitely divisible, two-parameter, limit distribution for the resultant of such a random walk is discussed, and describes a dual-scale power-law behavior if the number fluctuations are strongly clustered. The form for the distribution of transit times of grains results as a corollary.

Journal Article↗

Spatial distribution patterns of malaria vectors and sample size determination in spatially heterogeneous environments: a case study in the west Kenyan highland.

The current study examined temporal and spatial distribution patterns of anopheline malaria vectors in a highland site and determined the number of houses to be sampled to achieve the targeted precision level. Adult mosquito sampling was conducted seasonally in May and August 2002 in a 3 by 3-km2 area, and in November 2002 and February 2003 in an expanded 4 by 4-km2 area in Kakamega District, western Kenya. Anopheles gambiae Giles was the predominant malaria vector species, constituting 84.6% of the specimens, whereas Anopheles funestus Giles constituted 15.4% of the vector populations. An. gambiae abundance increased by six- to eight-fold in the long rainy season over the dry seasons, but An. funestus abundance peaked 3 mo after the long rainy season. For both species, the coefficient of variation was larger than 1, suggesting that the distribution of mosquito adults was aggregated. Mosquito clustering occurred in houses <400 m from a valley bottom. The negative binomial distribution was accepted in one sample period (August 2002) for An. gambiae and in two sampling periods (May and August 2002) for An. funestus. Taylor's power law analyses indicated that An. gambiae distribution was more aggregated in the wet seasons than in the dry seasons, whereas the degree of aggregation of An. funestus was similar in all four seasons. The minimum number of houses required to estimate anopheline female abundance within the commonly acceptable precision level (0.2) should be 17 houses per km2 for An. gambiae and 42 houses per km2 for An. funestus. The potential factors causing aggregated anopheline mosquito distribution are discussed.

Animals↗

Cryptosporidium monitoring system at a water treatment plant, based on waterborne risk assessment.

The water volume required for daily monitoring of Cryptosporidium (which can statistically ensure an annual risk of infection below 10(-4)), was assessed by evaluating the applicability of the Poisson lognormal (PLN) distribution in microbial risk assessment. PLN showed as good a fit to the observed data as to the negative binomial distribution. From the estimated PLN distributions for the source and finished water, the efficacy of the oocyst removal by the conventional water treatment process was estimated to follow log-normal distribution (median = 3.16 log10, 95% CI = 4.27-2.05 log10). The 365 consecutive negative results of daily monitoring for 180 L of finished water were found to be statistically equivalent to the annual risk of infection below 10(-4). This research also suggested the possibility of applying a qualitative detection method, such as CC-PCR, as a routine monitoring method for the quantitative risk management.

Animals↗

[The ratio between the level of the number of sheep botflies and the host immune response].

The dependence of indices of the larvae number and their biomass upon characteristics of the immune response in ELISA at organism and population levels of the Oestris ovis parasitic system is discussed. It was determined, that the majority of larvae distribution excerptions in the host population and the distribution of specific antibodies level indices in the serum blood of animals correspond to the model of the negative binomial distribution. The straight dependence of the parasitic larvae number on the specific antibodies level in the serum blood of host at the organism level of the parasitic system was not determined. The high correlative dependences of the mean number indices and of the distribution of larvae upon the mean value of extinction in the immunity enzyme reaction and upon the mean level of specific antibodies in the serum blood of the host population at the population level were determined. The control of the sheep bot fly larvae number is possible by the determination of the mean specific antibodies level in host population in ELISA.

Animals↗

Some properties of the transmitter release mechanism at the rat ganglionic synapse during potassium stimulation.

In the present investigation a study has been made using intracellular recordings in the rat superior cervical ganglion of the mode of transmitter release induced by raised external potassium ion concentration (40 mM), after acetylcholine synthesis has been blocked by hemicholinium-3. It is shown that the progressive decline in the rate of acetylcholine output from the ganglion is related to a decrease in the number of quanta being released. Furthermore, under these conditions there is no evidence for a reduction in the size of the transmitter quantum. The statistical foundations of the quantal release process at the rat ganglionic synapse have been investigated by comparing the distribution of the number of miniature EPSPs during successive constant time intervals in the tracings with the corresponding Poisson and binomial predictions. Analyses have shown that the probability for a quantum to be released is so small as to produce a binomial distribution of responses indistinquishable fro- the corresponding Poisson distribution, both at the beginning of the potassium-induced quantum discharge and when transmitter release level is low after exhaustion of acetylcholine tissue content.

Acetylcholine↗

Abundance-prevalence relationship of gill congeneric ectoparasites: testing the core satellite hypothesis and ecological specialisation.

We investigated the abundance-prevalence relationships in monogeneans belonging to the genus Dactylogyrus. A total of 182 dactylogyrid populations representing nine species were collected from the gills of roach ( Rutilus rutilus). Local abundance was found to be strongly positively correlated with prevalence. Two hypotheses were tested to explain this relationship: (1) the core-satellite hypothesis, and (2) the ecological specialisation hypothesis. Abundance was log-normally distributed, and the relationship between mean abundance and variance of abundance followed Taylor's power law prediction. Prevalence showed a negative binomial distribution, which does not confirm the core-satellite hypothesis. The positive relationship between abundance and prevalence was found for both specialists and generalists. However, generalists were found to be more widely distributed among hosts and had higher abundances than specialists, which supports the ecological specialisation hypothesis.

Animals↗

On the quantal hypothesis of neurotransmitter release: an explanation for the calcium dependence of the binomial parameters.

Results for quantal neurotransmitter release can be explained by assuming a binomial distribution with a population of N elements each with a probability p to release a quantum in a given trial. The binomial parameter N was unexpectedly observed to depend on external calcium concentration and (to a lesser extent) on the frequency of stimulation. This observation is explained here by the hypothesis that the release population is not homogeneous. It is shown that the same hypothesis can also account for other experimental findings. A possible cause for this inhomogeneity is suggested.

Calcium↗

Distribution of different fibre types in human skeletal muscles: a method for the detection of neurogenic disorders.

Human skeletal muscles are composed of two distinguishable types of fibres, which in healthy muscles appear to be randomly arranged. Large groups of one fibre type are commonly regarded as evidence of a neuropathological process affecting the peripheral nerves or the nerve cells in the spinal cord. An objective method that detects non-random arrangements as a sign of a neurogenic disorder, particularly in its early stages, could improve diagnosis. The randomness, or otherwise, of the fibre type arrangement is here considered in terms of the numbers of fibres surrounded entirely by others of the same type (enclosed fibres). The distribution of the number of enclosed fibres is studied for a free-sampling model using Monte Carlo methods. The negative binomial distribution is shown to fit closely, where the parameters can be expressed in terms of the number of fibres and the fibre type proportion in a sample area. This result permits the calculation of significance levels for a sample area and the combination of information in several sample areas. Finally, the method is applied to whole cross-sections of 24 male human autopsied muscles.

Humans↗