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Estimation of numbers of malaria clones in blood samples.

Methods are derived for estimating the mean number of clones of the haploid malaria parasite Plasmodium falciparum from samples of blood of infected hosts which have been tested for the presence of alleles at marker loci. For example, at a locus with three alleles the sample might contain only A1, or A1 and A2, or A1, A2 and A3, with multiple allele classes being more common at high infection rates. Assuming either a Poisson or negative binomial distribution of numbers of infections per host, formulae are derived for the frequency of different classes of blood samples, and maximum likelihood methods are used to estimate the mean number of clones and allele frequencies. Two data sets, each on two loci, are analysed. One data set was from the same locality in Tanzania from which oocysts of the parasite in mosquito vectors were tested for clonality (i.e. diploid unions of gametes from the same clone) using genetic markers. Good agreement was obtained between the observed clonality in oocysts and that expected from the number of infections per host (mean approximately three).

Alleles↗

Open-state substructure of single chloride channels from Torpedo electroplax.

Chloride channels from Torpedo californica electroplax were inserted into planar phospholipid membranes, and single-channel currents were studied at high time-resolution. The open channel fluctuates rapidly between three substates, with conductances of 18.5, 9.4 and 0 pS in 150 mM Cl-. Under various ionic conditions the three substates are always equally spaced in conductance; at various voltages leading to different probabilities of observing the three substates, the substate frequencies are always binomially distributed. The conclusion emerges that the conducting of unit of Cl- channel is composed of two identical Cl- diffusion pathways, each with a voltage-dependent gate.

Animals↗

Antibunched photons emitted by a quantum point contact out of equilibrium.

Motivated by the experimental search for "GHz nonclassical light," we identify the conditions under which current fluctuations in a narrow constriction generate sub-Poissonian radiation. Antibunched electrons generically produce bunched photons, because the same photon mode can be populated by electrons decaying independently from a range of initial energies. Photon antibunching becomes possible at frequencies close to the applied voltage V x e/variant Planck's over 2pi, when the initial energy range of a decaying electron is restricted. The condition for photon antibunching in a narrow frequency interval below eV/variant Planck's over 2pi reads [SigmanTn(1-Tn)]2<2Sigman[Tn(1-Tn)]2, with Tn an eigenvalue of the transmission matrix. This condition is satisfied in a quantum point contact, where only a single Tn differs from 0 or 1. The photon statistics is then a superposition of binomial distributions.

Journal Article↗

Plant NAD(H)-Glutamate Dehydrogenase Consists of Two Subunit Polypeptides and Their Participation in the Seven Isoenzymes Occurs in an Ordered Ratio.

The structure and function of NAD(H)-glutamate dehydrogenase in plants was studied by using grapevine (Vitis vinifera L. cv Sultanina) callus grown under different nitrogen sources. The enzyme consists of two subunit-polypeptides, alpha and beta, with similar antigenic properties but with different molecular mass and charge. The two polypeptides have molecular masses of 43.0 and 42.5 kilodaltons, respectively. The holoenzyme is hexameric and is resolved into seven isoenzymes by native gel electrophoresis. Two-dimensional native/SDS-PAGE revealed that the 1 and 7 isoenzymes are homohexamers and the isoenzymes 2 through 6 are hybrids of the two polypeptides following an ordered ratio. The total quantity of alpha- and beta-polypeptides and the isoenzymic pattern was altered by the exogenous nitrogen source. The sample derived from callus grown on nitrate or glutamic acid contained a slightly greater amount of beta-polypeptide and of the more cathodal isoenzymes, whereas alpha-polypeptide and the more anodal isoenzymes predominated in callus grown in the presence of either ammonium or glutamine. The anabolic reaction was correlated with the alpha- and the catabolic reaction with the beta-polypeptide; this could suggest that each isoenzyme exhibits anabolic and catabolic function of different magnitude. The isoenzymic patterns did not obey the expected binomial distribution proportions.

Journal Article↗

A method of analyzing nonstationary ionic channel current fluctuations in the presence of an additive measurement noise.

A method of estimating the parameters of nonstationary ionic channel current fluctuations (NST-ICF's) in the presence of an additive measurement noise is proposed. The case is considered in which the sample records of NST-ICT's corrupted by the measurement noise are available for estimation, where the experiment can be repeated many times to calculate the statistics of noisy NST-ICF's. The conventional second-order regression model expressed in terms of the mean and variance of noisy NST-ICF's is derived theoretically, assuming that NST-ICF's are binomially distributed. Since the coefficients of the regression model are explicitly related to not only the parameters of NST-ICF's but also the measurement noise component, the parameters of NST-ICF's that are of interest can be estimated without interference from the additive measurement noise by identifying the regression coefficients. Furthermore, the accuracy of the parameter estimates is theoretically evaluated using the error-covariance matrix of the regression coefficients. The validity and effectiveness of the proposed method are demonstrated in a Monte Carlo simulation in which a fundamental kinetic scheme of Na+ channels is treated as a specific example.

Ion Channels↗

Modeling virus inactivation on salad crops using microbial count data.

Microbial counts of the persistent Bacteroides fragilis bacteriophage B40-8 from a virus decay experiment conducted under glasshouse conditions were used to model the decay of viruses on wastewater-irrigated lettuce and carrot crops. The modeling approach applied gave specific consideration to the discrete nature of microbial count data. The experimental counts were best fit by a negative binomial distribution indicating highly dispersed distribution of viruses on lettuce and carrot crops following irrigation with wastewater. In addition, there was evidence for biphasic inactivation of viruses, signifying the presence of a persistent subpopulation of viruses that decayed slowly, resulting in virus accumulation on the crop surface over subsequent irrigations. Maximum likelihood estimates of initial and persistent subpopulation inactivation rates were 2.48 day(-1) and 0.51 day(-1) for lettuces and 0.84 day(-1) and 0.046 day(-1) for carrots. Maximum likelihood estimates of the persistent virus subpopulation size were 0.12% and 2% for lettuce and carrots, respectively.

Agriculture↗

Estimation and testing with overdispersed proportions using the beta-logistic regression model of Heckman and Willis.

Methods are presented for modeling dose-related effects in proportion data when extra-binomial variability is a concern. Motivation is taken from experiments in developmental toxicology, where similarity among conceptuses within a litter leads to intralitter correlations and to overdispersion in the observed proportions. Appeal is made to the well-known beta-binomial distribution to represent the overdispersion. From this, an exponential function of the linear predictor is used to model the dose-response relationship. The specification was introduced previously for econometric applications by Heckman and Willis; it induces a form of logistic regression for the mean response, together with a reciprocal biexponential model for the intralitter correlation. Large-sample, likelihood-based methods for estimating and testing the joint proportion-correlation response are studied. A developmental toxicity data set illustrates the methods.

Animals↗

Immune-mediated regulation of chronic intestinal nematode infection.

Gastrointestinal nematode infection is extremely prevalent worldwide in humans and animals. Infection levels vary between individuals in infected populations and exhibit a negative binomial distribution, and some individuals appear to be predisposed to certain infection levels. Moreover, infection tends to be chronic, despite evidence for the acquisition of some degree of acquired immunity. The host is subject to constant and repeated antigenic challenge, and individuals vary in the response they make. While a considerable amount of information is emerging on the immunoregulatory mechanisms operating during acute nematode infection from a variety of laboratory model systems, relatively little work has been carried out on the immune mechanisms underlying chronic infection. This review details some of the work that has addressed this important facet of gut nematode infection, highlighting studies from model systems that give insight into the induction of nonprotective immunity, while at the same time avoiding the induction of host-damaging pathology.

Animals↗

A parametric model for detecting hormetic effects in developmental toxicity studies.

Hormetic effects have been observed at low exposure levels based on the dose-response pattern of data from developmental toxicity studies. This indicates that there might actually be a reduced risk of exhibiting toxic effects at low exposure levels. Hormesis implies the existence of a threshold dose level and there are dose-response models that include parameters that account for the threshold. We propose a function that introduces a parameter to account for hormesis. This function is a subset of the set of all functions that could represent a hormetic dose-response relationship at low exposure levels to toxic agents. We characterize the overall dose-response relationship with a piecewise function that consists of a hormetic u-shape curve at low dose levels and a logistic curve at high dose levels. We apply our model to a data set from an experiment conducted at the National Toxicology Program (NTP). We also use the beta-binomial distribution to model the litter response data. It can be seen by observing the structure of these data that current experimental designs for developmental studies employ a limited number of dose groups. These designs may not be satisfactory when the goal is to illustrate the existence of hormesis. In particular, increasing the number of low-level doses improves the power for detecting hormetic effects. Therefore, we also provide the results of simulations that were done to characterize the power of current designs in detecting hormesis and to demonstrate how this power can be improved upon by altering these designs with the addition of only a few low exposure levels.

Animals↗

Prevalence of Theileria in the tick Hyalomma detritum detritum in the Doukkala region, Morocco.

The overall prevalence of Theileria species, mainly, if not exclusively, T.annulata, in 901 Hyalomma detritum detritum collected from cattle in the Doukkala region of Morocco over a period of 2 years was 21.5%. The quantity of infection (number of sporoblasts per infected tick) followed the negative binomial distribution with between one and 250 sporoblasts per infected tick. Infected ticks were found in eight of fourteen areas examined whilst T.annulata was present in all fourteen. There were significant differences in both the prevalence and the quantity of infection between ticks collected from different farms, and between nymphs collected in the autumn from these farms, and moulted in the laboratory, and adults collected in the following summer. The prevalence, but not the quantity, of infection was higher in female than in male ticks. No correlations were established between infection of engorged nymphs and the breed, sex and Theileria piroplasm parasitaemia of the host animal. However, calves infected a greater proportion of nymphs than adult cattle and the heavier the infestation of nymphs on an animal, up to a plateau, the higher the prevalence of infection in those nymphs. There were no differences in infection between ticks moulted at 24 degrees C and 37 degrees C, after the engorged nymphs had been stored at 18 degrees C to simulate over-wintering.

Animals↗

Chirality in the umbilical cord.

OBJECT: To determine the chiral varieties of the vascular helix of the umbilical cord and find their normal proportions. DESIGN: Differences between the sexes were tested by a chi 2 test and the hypothesis that left-handed types occur in 50% of cases was tested using the binomial distribution. SETTING: United Arab Emirates. SUBJECT: Gulf Arab singletons from consecutive normal births, 100 male and 100 female. RESULTS: Left-handed helices predominate at 76.5%; right-handed contribute 15.5%; mixed forms, where both chiralities co-exist, were found in 6.5%; indeterminable chirality due to poor helix formation, or varices, reached 1.5%. A significant sex difference could not be established. Chiral generation, on genetic and mechanical-rotational hypotheses, is discussed. CONCLUSION: The chirality of the cord is easily determined and is the sole distinguishing feature of the cord. Chirality should be entered in the birth record and in pathological descriptions for whatever value it may have in relation to fetal, or postnatal, characteristics and morbidity.

Female↗

The impact of maternal age on clinical pregnancy and spontaneous abortion in women undergoing in vitro fertilization and gamete intra-fallopian transfer.

The age at which women should be advised against proceeding with initial or further infertility treatment is one of the many unresolved questions in this area of women's health and was the subject of investigation in this study. One of the major difficulties in determining the impact of maternal age on outcomes is the practice of researchers (publishing in journals) and infertility practitioners (reporting to national registers) of coding age as a categorical rather than a continuous variable. In this study, groups of younger (< 30 years) and older (> 35 years) women undergoing assisted reproduction treatments were compared with regards to clinical pregnancy and spontaneous abortion rates following in vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT). Response to different ovarian stimulation protocols was also assessed for the 2 groups. The significance of the relationship between maternal age, clinical pregnancy rates, spontaneous abortion rates and the type of treatment and stimulation protocol employed, was tested using a series of binomial distributions. The results indicated that maternal age adversely affects both clinical pregnancy rates and rates of spontaneous abortion, when summed across treatments and stimulation protocols. However, while the age/outcome relationship held for IVF, the GIFT by age relationship was not significant. Stimulation protocols using clomiphene citrate (CC) or gonadotrophin agonists (GnRHa) may impact negatively on older women.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗

Mathematical modeling of reproductive and developmental toxic effects for quantitative risk assessment.

A new mathematical dose-response model for reproductive and developmental risk assessment is proposed. The model includes the possibility of an exposure threshold as well as a litter-size effect. Correlation of responses of offspring from the same litter is taken into account through the use of the beta-binomial distribution. Confidence limits for low-dose extrapolation are based on the asymptotic distribution of the likelihood ratio. An empirical comparison of the proposed procedure to that of Rai and Van Ryzin demonstrates the improvement that can be achieved with the new procedure.

Animals↗

Statistical inference in a stochastic epidemic SEIR model with control intervention: Ebola as a case study.

A stochastic discrete-time susceptible-exposed-infectious-recovered (SEIR) model for infectious diseases is developed with the aim of estimating parameters from daily incidence and mortality time series for an outbreak of Ebola in the Democratic Republic of Congo in 1995. The incidence time series exhibit many low integers as well as zero counts requiring an intrinsically stochastic modeling approach. In order to capture the stochastic nature of the transitions between the compartmental populations in such a model we specify appropriate conditional binomial distributions. In addition, a relatively simple temporally varying transmission rate function is introduced that allows for the effect of control interventions. We develop Markov chain Monte Carlo methods for inference that are used to explore the posterior distribution of the parameters. The algorithm is further extended to integrate numerically over state variables of the model, which are unobserved. This provides a realistic stochastic model that can be used by epidemiologists to study the dynamics of the disease and the effect of control interventions.

Algorithms↗

Polyp miss rate determined by tandem colonoscopy: a systematic review.

BACKGROUND AND AIMS: Colonoscopy is the best available method to detect and remove colonic polyps and therefore serves as the gold standard for less invasive tests such as virtual colonoscopy. Although gastroenterologists agree that colonoscopy is not infallible, there is no clarity on the numbers and rates of missed polyps. The purpose of this systematic review was to obtain summary estimates of the polyp miss rate as determined by tandem colonoscopy. METHODS: An extensive search was performed within PUBMED, EMBASE, and the Cochrane Library databases to identify studies in which patients had undergone two same-day colonoscopies with polypectomy. Random effects models based on the binomial distribution were used to calculate pooled estimates of miss rates. RESULTS: Six studies with a total of 465 patients could be included. The pooled miss rate for polyps of any size was 22% (95% CI: 19-26%; 370/1,650 polyps). Adenoma miss rate by size was, respectively, 2.1% (95% CI: 0.3-7.3%; 2/96 adenomas > or =10 mm), 13% (95% CI: 8.0-18%; 16/124 adenomas 5-10 mm), and 26% (95% CI: 27-35%; 151/587 adenomas 1-5 mm). Three studies reported data on nonadenomatous polyps: zero of eight nonadenomatous polyps > or =10 mm were missed (0%; 95% CI: 0-36.9%) and 83 of 384 nonadenomatous polyps <10 mm were missed (22%; 95% CI: 18-26%). CONCLUSIONS: Colonoscopy rarely misses polyps > or =10 mm, but the miss rate increases significantly in smaller sized polyps. The available evidence is based on a small number of studies with heterogeneous study designs and inclusion criteria.

Colonic Polyps↗

Efficacy of diltiazem for coronary artery spasm.

The introduction of calcium entry blockers which caused marked vascular smooth muscle relaxation with minimal effects on myocardial contractility have provided a new approach to the patient with angina due to coronary artery spasm. Multiple, double-blinded, randomized studies of diltiazem versus placebo have demonstrated that this agent results in reduction in angina frequency and nitroglycerin consumption by 30% to 70% with a demonstrated dose response. A long-term, open label follow-up study of 18 patients who participated in a 44-week prospective, double-blind crossover trial of 240 mg of diltiazem versus placebo for prophylaxis of angina in patients with coronary artery spasm demonstrated a 75% decrease in angina attacks during the first five months of the study and an 80% decrease compared to the placebo period during the second six months. Both the short- and long-term studies have demonstrated very few adverse side effects, less than 7%. A recent long-term study of 43 patients who took diltiazem regularly and were followed in the Coronary Artery Spasm Clinic at Stanford University Medical Center for a mean of 19.6 months (range 6 to 28.5 months) was analyzed for cardiovascular events in the 19.6 months prior to therapy and the 19.6 months after the initiation of therapy. Cardiovascular events on diltiazem, including sudden cardiac death, myocardial infarction, and hospitalization to rule out myocardial infarction utilizing a binomial distribution showed over a 90% reduction compared to the pre-diltiazem period. Adverse effects were reported in six patients who reported minimal to mild pedal oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Theoretical aspects of detection of bacteraemia as a function of the volume of blood cultured.

UNLABELLED: Clinically significant bacteraemia in adults is characterized by low numbers of circulating bacteria. Assuming a Poisson or a binomial distribution we have calculated the probability of detecting bacteria as a function of the concentration in blood, estimated the concentration of bacteria in blood from a given test result, and calculated the blood volume required to detect bacterial growth with a probability of 95% at a given mean number of colony-forming units (cfu) per sample unit. These theoretical assumptions have been used on an empirical population of patients with proven bacteraemia. RESULTS: 18% of Staphylococcus aureus bacteraemias and 29% of Escherichia coli bacteraemias have circulating bacteria with an estimated spread of less than 0.04 cfu/ml. With a 95% probability of detection of a bacteraemia, a concentration in blood corresponding to 3 cfu/sampling unit is necessary. In our empirical material, where 30 ml was cultured, the probability of detection of E. coli bacteraemias would have decreased by 11% if 20 ml had been cultured, and 27% if only 10 ml had been cultured. The corresponding figures for S. aureus were 6% and 15%, respectively. For low grade E. coli bacteraemias (< 0.04 cfu/ml) the decrease would have been 33% and 67%, respectively.

Bacteremia↗

Cellular origin, antigen reactivity, and VH segment structure of IgM mAbs from AIDS lymphomas.

In the present studies we analyzed the Ag specificity, VH gene structure, and cellular origin of three IgM mAb-producing cell lines established in vitro from bioptic specimens of three AIDS patients with BL. We found that (i) both HBL-2 and HBL-3 IgM mAbs were cold agglutinins highly specific for the i blood group determinant, a self Ag the expression of which is dominant in the early stages of life, and both mAbs used somatically point-mutated VH 4-21 segments; (ii) HBL-1 IgM mAb, the Ag-specificity of which has not been determined, used a putatively mutated member of the VHIII family; and (iii) both HBL-1 and HBL-2, but not HBL-3, cells expressed CD5 mRNA, suggesting a B-1 cell origin. The utilization of VH4-21 by the HBL-2 and HBL-3 cold agglutinins is consistent with the usage of this gene segment by all the reported pathogenic except the naturally occurring cold agglutinins. This restricted VH gene usage may reflect an inherent affinity of the germline VH4-21 gene product for the i/I carbohydrate structure, and, perhaps, an overrepresentation of VH4-21 in the human early and late B-cell repertoire. Consistent with both an early and late developmental expression of the VH4-21 gene is the B-1 and B-2 cellular origin of the two VH4-21+ cold agglutinins reported here. Thus, the two cold agglutinin autoantibodies possibly emerged at different stages of the natural history of the B-cell repertoires of these patients and might display a different temporal relationship, as discussed below, to the time of emergence of the respective tumoral cells. The somatically mutated status of the HBL-2 and HBL-3 mAb VH segments was suggested by the monomorphism of the human VH4-21 gene, the extension of the nucleotide differences to the, in general, highly conserved JH segment; and it was formally proved in HBL-3 mAb. Positive selection by Ag of the R mutations in the HBL-2 and HBL-3 mAb VH segments was suggested by the differential R:S mutation ratios in the CDRs and FRs (HBL-2 mAb, 5.0 and 1.1, respectively; HBL-3 mAb, 2.2 and 0.3, respectively) but not substantiated by appropriate statistical analysis according to the binomial distribution model.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗