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PubMed1989

A surveillance system based on a short memory scheme.

A surveillance system is proposed to detect an increase in the mean of a Poisson distribution of cases of a disease. This system, called short memory (SM), is based on conditional binomial tests which are performed sequentially at fixed time intervals. The probability of rejection at each test defines the run length distribution which has a geometric tail. A standard SM scheme outperforms other SM schemes. The CUSUM outperforms the SM schemes when the baseline mean is specified correctly. This type of misspecification does not affect the SM scheme.

Data Interpretation, Statistical↗
PubMed2004

Sexual orientation, health risk factors, and physical functioning in the Nurses' Health Study II.

OBJECTIVES: To examine associations between sexual orientation and breast cancer risk factors, cardiovascular disease (CVD) risk factors, mental health status, and health-related functioning. METHODS: We compared participants in the Nurses' Health Study II (NHSII) reporting a lesbian or bisexual orientation with those reporting a heterosexual orientation, with heterosexuals serving as the reference group for all comparisons. Prevalence of health behaviors and conditions was adjusted for differences in the distribution of age, ancestry, and region of residence by standardizing to the distribution of the overall cohort. Multivariate prevalence ratios were calculated to compare lesbians and bisexuals with heterosexuals using binomial regression with the log link function. Means of health conditions were measured using continuous scales standardized to the distribution of the overall cohort. Differences in means comparing lesbians and bisexuals with heterosexuals were tested by multivariate linear regression. All comparisons were adjusted for age, ancestry, and region of residence. RESULTS: Based on information from 90,823 women aged 32-51 in 1995, those reporting a sexual orientation of lesbian (n = 694) had a higher prevalence of risk factors for breast cancer, including nulliparity and high daily alcohol intake, compared with heterosexual women. Lesbians also had a higher prevalence of several risk factors for CVD, including higher body mass index (BMI) and elevated prevalence of current smoking. Lesbians were more likely to report depression and the use of antidepressants. Key results for health risk factors were similar for lesbians and bisexual women (n = 317). CONCLUSIONS: Lesbian and bisexual women were found to have a higher prevalence of several important risk factors for breast cancer, CVD, and poor mental health and functioning outcomes. Most of these risk factors are modifiable, and appropriate interventions could play an important role in improving the health status of lesbian and bisexual women.

Adult↗
PubMed1998

Binomial cokriging for estimating and mapping the risk of childhood cancer.

The incidences of human diseases vary from place to place, and this is also likely to be so for the risk of people developing many of them. We have analysed the spatial distribution of childhood cancer in the West Midland Health Authority Region of England from 1980 to 1984. This is a rare disease which is considered to be noncontagious. The observed frequencies of the disease in the electoral wards have been converted to proportions that estimate the risk of a child's developing it. The spatial autocorrelation of the risk, expressed in the variogram, was determined in a novel way from the proportions within electoral wards by treating them as binomial variables dependent on the risk and the numbers of children in the wards. The observed variogram was modelled by Whittle's elementary two-dimensional correlation. Covariances of the proportion and cross covariances between the proportion and the risk were derived, and from the latter and the proportions the risk was estimated in two ways by a form of cokriging: ordinary and conditional unbiased cokriging. The variogram of the risk shows strong autocorrelation, and the kriged estimates, when mapped, have a distribution that is far from even. There are patches where the estimated risk is large, especially in the rural south west and the suburban north east; and there are other patches, notably the more densely populated areas, where it is small.

Adolescent↗
PubMed1993

A Monte Carlo investigation of the robustness of the Wald, likelihood Ratio, and Median tests with specified symmetric and asymmetric marginal distributions.

The effect of nonnormality on the Type I (tau) error when comparing two independent binomial proportions (P) or the nonparametric alternatives, the Median (Me), Wald (W), and Likelihood Ratio (LR), has not been investigated. If these selected tests are overly conservative the implied loss of power would moderate their practical use. The purpose of the present study was to investigate the impact of nonnormality on small to moderate sample sizes on the estimated tau for alpha = 0.10, 0.05, and 0.01 for the P, Me, W, and LR tests. Samples were generated from nine long-tailed symmetric and asymmetric distributions using a multiplicative congruential generator. For each marginal distribution and for a variety of sample sizes, the proportion of samples for which the test statistic exceeded the 10, 5, and 1 percentage points was tabulated. For data that mimic a symmetric distribution, the median test uniformly yields an empirical alpha considerably less than tau, while the likelihood ratio test consistently overestimates tau for small samples (n < or = 15) over all symmetric distributions and empirical alpha levels. For asymmetric distributions, the median test again yields an empirical alpha significantly less than tau. Similar underestimates of tau were found for the chi-square (2 df), chi-square (4 df) log normal, and gamma (2, 1) distributions. The likelihood ratio test consistently overestimates tau for small samples (n < or = 15) over all asymmetric distributions and empirical alpha levels. The independent proportions test produces an empirical alpha closest to tau for n = 10 for all asymmetric distributions.(ABSTRACT TRUNCATED AT 250 WORDS)

Data Interpretation, Statistical↗
PubMed2002

Statistical inference for familial disease clusters.

In many epidemiologic studies, the first indication of an environmental or genetic contribution to the disease is the way in which the diseased cases cluster within the same family units. The concept of clustering is contrasted with incidence. We assume that all individuals are exchangeable except for their disease status. This assumption is used to provide an exact test of the initial hypothesis of no familial link with the disease, conditional on the number of diseased cases and the distribution of the sizes of the various family units. New parametric generalizations of binomial sampling models are described to provide measures of the effect size of the disease clustering. We consider models and an example that takes covariates into account. Ascertainment bias is described and the appropriate sampling distribution is demonstrated. Four numerical examples with real data illustrate these methods.

Adult↗
PubMedDate not supplied

Familial aggregation of Trypanosoma brucei gambiense trypanosomiasis in a very high incidence community in Zaire.

Familial aggregation of Trypanosoma brucei gambiense human African trypanosomiasis (HAT) was investigated in 3 adjacent villages of central Zaire where 318/1431 inhabitants had previously suffered from HAT. Neither spatial nor familial aggregation was detected when analysing the distribution of cases in the whole community using Poisson, negative binomial and pairwise odds ratio models. However, clustering of cases was observed when specific familial relationships were examined. The risk of HAT for a child was significantly increased if the mother had also had HAT, but it was not influenced by a past history of HAT in the father. Sisters and brothers of cases of HAT had a higher risk of HAT than siblings of individuals who had never had HAT, but no such association was documented for half-sisters and half-brothers. Among married couples, a past history of HAT in one spouse had no impact on the other spouse's risk of HAT. Indirect arguments suggested that familial clustering was a consequence of shared exposure, either sequential or simultaneous, rather than of genetic susceptibility. The existence of familial clustering should be kept in mind when implementing passive or active case-finding activities.

Adolescent↗
PubMed2005

The evolving national birth prevalence of Down syndrome in Taiwan. A study on the impact of second-trimester maternal serum screening.

OBJECTIVES: The aim of the present study was to determine whether the liberal use of second-trimester maternal serum screening in Taiwan started in 1994 had a measurable impact on birth prevalence of infants with Down syndrome (DS) in the past decade. METHODS: We based our study on the databases of 'National Birth Defect Registration and Notification System', 'Amniocentesis in Pregnant Women', and 'Demographic Fact Book' in Taiwan. Collected data included total registered birth number, the registered number of stillbirths, the registered numbers of live births and of DS stillbirths affected with DS, amniocentesis rates each year in pregnant women aged 35 or more, and the age distribution of pregnant women in Taiwan. The live birth rate of and total birth rate of fetuses affected with DS, and the rates of live birth and stillbirth to total birth with DS, were analyzed year by year, in order to understand the change of birth rate of infants affected with DS between 1993 and 2001. Those with isolated cleft palate (ICP) were also analyzed as internal control variable. Confidence interval of live birth rate of infants with DS under Poisson distribution was calculated. Chi-square test for trend in binomial proportions was performed to see if there is an increasing (or decreasing) trend in the proportion of incidence of fetuses affected with DS. The difference was statistically significant if a p value was <0.05. RESULTS: A total of 1 331 616 deliveries were collected during the study period, including 840 cases of DS confirmed by karyotyping study. A marked decrease in the live birth rates of case with DS occurred in 1994-95, from 0.63 per 1000 births to 0.23 per 1000 births. There was a crossover from more live births with DS to more stillbirths with DS during 1994 to 1996 after the implementation of second-trimester maternal serum screening for DS in 1994. In 1993, 76.9% of births diagnosed with DS were born alive, compared to 32.5% in 2001 (p < 0.001). CONCLUSIONS: The policy of prenatal diagnosis program including amniocentesis for pregnant women aged 35 or more and the liberal application of maternal serum screening for DS in younger women was responsible for the marked decrease in the live births affected with DS in Taiwan from 1993 to 2001.

Age Distribution↗
PubMed2003

[Structures and spatial distribution patterns of dominant populations in Sycopsis sinensis community in Houhe Nature Reserve].

Based on the investigation data of 2 quadrats (1,600 m2 and 2,400 m2) in Houhe Nature Reserve, tree size class method was applied to analyze the structures of the dominant populations, and t-test of v/m ratio, mean crowing index, negative binomial parameter, patchiness index and Morisita index were applied to analyze the spatial distribution patterns of two dominant populations. The clumping degrees were also evaluated according to their size classes in different quadrats. The results showed that Sycopsis sinensis population was a declining population, dominated by IV trees and difficult to regenerate. In the population, the individual percentage of IV trees accounted for 79.4% in Q1 and 87.4% in Q2, and those of I trees and II trees were few. However, the population of Cyclobalanopsis axyodon was an growing one, and the individual percentages declined with the increasing size classes. The spatial distribution patterns of the two dominant populations distributed in clumps, but the clumping degrees existed diversity. With the increase of the size classes, the clumping degree of the population of Sycopsis sinensis intensified from random to clumping distribution, while that of the population of Cyclobalanopsis axyodon weakened from clumping to random distribution.

Conservation of Natural Resources↗
PubMed1993

Voltage-dependent block by internal Ca2+ ions of inwardly rectifying K+ channels in guinea-pig ventricular cells.

1. The block of the inwardly rectifying K+ channel by intracellular Ca2+ was studied in guinea-pig ventricular cells. 2. Single-channel currents through the inwardly rectifying K+ channel were recorded in the inside-out configuration at 150 mM external and internal K+. Internal Ca2+, at a concentration of 0.4-10 microM, induced subconductance levels with one-third and two-thirds of the unitary amplitude in the outward currents without affecting the inward currents. 3. Occupancy at each sublevel was estimated from the amplitude histogram which showed four equally spaced peaks in the presence of internal Ca2+. At different degrees of blockade, the distribution of the current levels showed a reasonable agreement with the binomial theorem. 4. The outward mean open-channel currents were measured at different Ca2+ concentrations and voltages. The current-voltage relation rectified inwardly in the presence of internal Ca2+ in a concentration-dependent manner. 5. The outward mean open-channel currents were normalized to unitary amplitudes in the absence of Ca2+. The normalized current-Ca2+ concentration curve was fitted by saturation kinetics with a Hill coefficient of 1 at each voltage. The voltage dependence of the dissociation constants gives the value for the fractional electrical distance of the Ca2+ binding site of 0.7. 6. The dwell times in each substrate were distributed exponentially. On the assumption that the inwardly rectifying K+ channel of cardiac cells is composed of three identical conducting subunits and each subunit is blocked by Ca2+ independently, the blocking (mu) and unblocking (lambda) rates were calculated. The value of mu increased with higher Ca2+ concentrations or larger depolarizations, while lambda was independent of Ca2+ and decreased with larger depolarization. 7. It is thus concluded that internal Ca2+ produces a voltage-dependent block of the channel to cause inward rectification although the blocking effect is less potent than that of Mg2+. The substate behaviour seen with internal Ca2+ supports the triple-barrelled structure of the cardiac inwardly rectifying K+ channel.

Animals↗
PubMed2004

Bayesian modeling of animal- and herd-level prevalences.

We reviewed Bayesian approaches for animal-level and herd-level prevalence estimation based on cross-sectional sampling designs and demonstrated fitting of these models using the WinBUGS software. We considered estimation of infection prevalence based on use of a single diagnostic test applied to a single herd with binomial and hypergeometric sampling. We then considered multiple herds under binomial sampling with the primary goal of estimating the prevalence distribution and the proportion of infected herds. A new model is presented that can be used to estimate the herd-level prevalence in a region, including the posterior probability that all herds are non-infected. Using this model, inferences for the distribution of prevalences, mean prevalence in the region, and predicted prevalence of herds in the region (including the predicted probability of zero prevalence) are also available. In the models presented, both animal- and herd-level prevalences are modeled as mixture distributions to allow for zero infection prevalences. (If mixture models for the prevalences were not used, prevalence estimates might be artificially inflated, especially in herds and regions with low or zero prevalence.) Finally, we considered estimation of animal-level prevalence based on pooled samples.

Animals↗
PubMed2004

Crossover of weighted mean fragment mass scaling in two-dimensional brittle fragmentation.

We performed vertical and horizontal sandwich two-dimensional brittle fragmentation experiments. The weighted mean fragment mass was scaled using the multiplicity mu. The scaling exponent crossed over at log(10) mu(c) approximately equal to -1.4 . In the small mu (<< mu(c) ) regime, the binomial multiplicative (BM) model was suitable and the fragment mass distribution obeyed log-normal form. However, in the large mu (>> mu(c) ) regime, in which a clear power-law cumulative fragment mass distribution was observed, it was impossible to describe the scaling exponent using the BM model. We also found that the scaling exponent of the cumulative fragment mass distribution depended on the manner of impact (loading conditions): it was 0.5 in the vertical sandwich experiment and approximately 1.0 in the horizontal sandwich experiment.

Journal Article↗
PubMed1989

Triple-barrel structure of inwardly rectifying K+ channels revealed by Cs+ and Rb+ block in guinea-pig heart cells.

1. The hypothesis that the inwardly rectifying K+ channel consists of a triple-barrel structure was investigated. Inward currents were recorded under the blocking effects of external Cs+ or Rb+ in the cell-attached configuration of the patch-clamp technique using single ventricular cells enzymatically isolated from guinea-pig hearts. 2. Cs+ (10-100 microM) or Rb+ (20-100 microM) added to the 150 mM-K+ pipette solution induced rapid open-blocked transitions in the inward open-channel currents. In about 20% of experiments the inward current showed two intermediate current levels equally spaced between the unit amplitude and the zero-conductance level. The current fluctuated between these four levels. In the remaining experiments no obvious sublevels were observed except spontaneous ones, whose amplitudes were not always equal to one-third or two-thirds of the unit amplitude. 3. In experiments showing sublevels, the probability that the open-channel current stayed at each level was measured at various concentrations of blockers and membrane potentials. In both Cs+ and Rb+ block, the distribution of the current levels showed reasonable agreement with the binomial theorem. This finding suggests that the inwardly rectifying K+ channel is composed of three equally conductive subunits and each subunit is independently blocked by Cs+ or Rb+. 4. The dwell-time histogram in each substate was well fitted with a single-exponential function. On the assumption of the binomial model, the blocking (mu) and unblocking (lambda) rate for Cs+ and Rb+ were calculated. The value of mu was linearly proportional to the concentration of the blocking ion at a given membrane potential and increased with hyperpolarization (e-fold increase with a change of -43.5 mV in the Cs+ block). lambda was almost independent of the concentration of the blocking ion and less dependent on the membrane potential than mu. 5. The open and blocked times were calculated in experiments showing no clear sublevels. The mean open time was almost equal to the mean dwell time at the full open level in experiments showing sublevels under the same conditions. On the other hand, the mean blocked time was about two or three times longer than the mean dwell time at the zero-conductance level measured in experiments with sublevels. These results may suggest that the instant one of the three subunits is plugged by blocking ions, the remaining two subunits are closed by unknown mechanisms. 6. Our results support the hypothesis that the cardiac inwardly rectifying K+ channel is composed of three equally conductive subunits.

Animals↗
PubMed1983

A note on life tables and nonlinear death processes.

This note is viewing survival data of a natural cohort as being generated by a possibly nonlinear, nonhomogeneous death process. It proves that the usual conditional distributions of the number of survivors at a certain age are binomial if and only if the death process is linear. Thus the customary statistical methods for the analysis of life table data are, strictly speaking, invalid whenever the underlying death process is nonlinear. For example, if a contagious disease is the cause of some or all of the deaths, the deaths will not be independent and the death process, not linear. One should then base the statistical analysis on a model for the spread of the disease rather than the routine binomial model.

Age Factors↗
PubMed1989

Foveal cone thresholds.

The method of constant stimuli was used to estimate the psychometric functions for detection of one or two flashes when two light pulses were presented. The test stimulus consisted of two simultaneous 0.5 msec, 1' pulses separated by 17'. Observers reported seeing 0, 1 or 2 flashes. A computer-controlled direct-view apparatus allowed sampling of slightly different foveal locations on each trial. The data were analyzed assuming a binomial probability for sampling of L and M cones and Poisson distributed quantal fluctuation. Under these assumptions, the measurements imply that detection requires a minimum of 5-7 quanta absorbed per cone, and that the effective number of cones illuminated by the 1', 0.5 msec pulse is two. The estimated L/M cone ratio was 1.6 for one observer and 4.0 for the other; each observer's ratio was in general agreement with the value estimated independently by heterochromatic flicker photometry.

Adult↗
PubMed2005

Effects of aggregation and sample size on composite faecal egg counts in sheep.

Composite faecal egg counts (FEC) are increasingly used to support strategic anthelmintic treatment decisions in grazing livestock. However, their accuracy as estimators of group mean FEC is affected by the number of individual samples included, how thoroughly they are mixed, and the underlying degree of parasite aggregation between individual hosts. This paper uses a Negative Binomial model for parasite aggregation, and a Poisson model for egg distribution within faecal suspensions, in order to optimise composite FEC protocol for commercial sheep flocks. Our results suggest that faecal egg density in a well-mixed composite sample from 10 sheep (3g of faeces from each), estimated by examination of four independently filled McMaster chambers, is likely to provide an adequate estimate of group mean FEC in the majority of situations. However, extra care is needed in groups of sheep for which high levels of FEC aggregation might be expected. The implications of statistical error in FEC estimates depend on how they are used. The simulation-based approach presented here is a powerful tool for investigating the risks of error in FEC-driven treatment decisions in different situations, as well as for the statistical analysis of parasitological data in general.

Animals↗
PubMed1998

Human extracellular proteins display a different pattern of local sequence similarity with the four classes of human T-cell receptor V-regions than foreign proteins and human intracellular proteins: a preliminary report.

A pool of 110 randomly selected/generated amino acids sequences was used to perform specific local sequence similarity alignment analysis with the pool of 279 reported sequences of human T-cell receptor (TCR) V-regions. The 110 analyzed sequences were divided, according to their origin and nature, into six protein groups, as: human intracellular (hi), extracellular/transmembrane (he) and extracellular adhesive matrix (ha) proteins, 'average' human proteins (hum), proteins of non-human origin (nhum) and randomly generated quasi-protein sequences (r). These sequences were decomposed into all their overlapping 11-mer segments, generating a total of 56,836 derived peptides (at least 8000 per group). Each derived peptide was aligned with the 279 human TCR V-regions and assigned to the category (alpha-like, beta-like, gamma-like or delta-like) corresponding to the class (V alpha, Vbeta, Vgamma or Vdelta) of the V-region encompassing the most similar segment, as determined by the performed similarity-search. The six protein groups were found to differ significantly in their distribution of derived peptides among the four categories. According to the binomial tests results, human proteins from the extracellular compartment (he, ha) comprise a higher proportion of delta-like segments (P = 2.3 x 10(-2) and P < 10(-8), respectively) than the 'average' human proteins (hum). In addition, and in accordance with this finding, proteins that are normally not found in that topological compartment comprise a lower proportion of delta-like peptides (P = 1.4 x 10(-5) and P < 10(-8) for groups nhum and hi, respectively) than the 'average' human proteins (hum). In contrast, these proteins comprise a higher proportion of gamma-like segments (P = 8.3 x 10(-3), P = 1.4 x 10(-3) and P = 1.7 x 10(-4), for groups r, nhum and hi, respectively) than the 'average' human proteins (hum). These findings indicate significant differences between proteins encountered in the extracellular compartment--that are normally immunologically tolerated--and those the presence of which is usually non-tolerated. The results suggest that the discrimination and the reaction of the human immune network to proteins found in the extracellular compartment correlate with the proteins' pattern of preferential local sequence similarity with the Vgamma and Vdelta classes of human TCR V-regions, implying a specific and an important role of gammadelta-cells in the maintenance of the immune homeostasis. Whether this implication represents a rule associated with self-tolerance, will be investigated by future analyses.

Amino Acid Sequence↗
PubMed1994

Quantal analysis of excitatory postsynaptic currents at the hippocampal mossy fiber-CA3 pyramidal cell synapse.

Unitary excitatory postsynaptic current (EPSC) amplitude histograms obtained from synapses between mossy fibers (MF) and CA3 pyramidal cells in hippocampus were analyzed with the aim of deriving the mean peak current of quantal events, its coefficient of variation CVq, the number of release sites NS, and the release probability PR. Unitary EPSC histograms with multiple peaks were fitted satisfactorily under the assumption that quantal events have a slightly skewed amplitude distribution and that the release mechanism is described by models with either binomial (standard), nonuniform, or nonstationary statistics. The average peak current of the quantal event derived from these fits reflected the opening of between 15 and 65 glutamate receptor (GluR) channels of the AMPAR subtype. The variability in the amplitude of quantal events is characterized by a CVq of 25% to 30%. The best fits to multiple peak EPSC histograms are obtained if it is assumed that the number of release sites contained within a single MF-bouton is between 8 and 21, a value comparable to the published number of morphologically measured presynpatic active zones and postsynaptic densities (PSDs) of individual MF-CA3 synapses. This suggests that at the MF-CA3 synapse each presynaptic zone and its associated PSD act as independent units, contributing one quantal event to unitary EPSCs. Simulations of unitary EPSC distributions, based on measurements of PSD size could, however, indicate that the interpretation of multipeak EPSC amplitude distributions at MF-CA3 synapses in terms of fluctuating release probabilities might be an over-simplification, and that postsynaptic factors may contribute significantly to fluctuations of unitary EPSC amplitudes.

Animals↗