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Contrasting patterns in the small-scale heterogeneity of human helminth infections in urban and rural environments in Brazil.

Marked heterogeneity exists in the patterns of parasitic infection between individuals, households and communities. Analysis of parasite distributions within populations is complicated by the fact that parasite distributions are highly aggregated and few studies have explicitly incorporated this distribution when investigating small-scale spatial heterogeneities. This study aimed to quantify the small-scale (within- and between-household) heterogeneity of helminth infection in an area of Minas Gerais State, Brazil, with rural and urban sectors. Parasitological data from a cross-sectional survey of 1,249 individuals aged 0-86 years from 242 households were analysed. Within-household clustering of infection was assessed using random effect logistic regression models and between-household spatial heterogeneity was assessed using a Bayesian negative binomial spatial model. The overall prevalence of hookworm (Necator americanus) was 66.9%, the prevalence of Schistosoma mansoni was 44.9% and the prevalence of Ascaris lumbricoides was 48.8%. Statistical analysis indicated significant (within) household and (between household) spatial clustering of hookworm in both rural and urban areas and of S. mansoni in rural areas. There was no evidence of either household or spatial clustering of S. mansoni in urban areas. The spatial correlation of S. mansoni was estimated to reduce by half over a distance of 700 m in the rural area. Rural hookworm had a much smaller half-distance (28 m) and urban hookworm showed an even smaller half-distance (12 m). We suggest that such species-specific differences in patterns of infection by environment are primarily due to variation in exposure and parasite life cycle, although host genetic factors cannot be ruled out.

Adolescent↗

Place of death: analysis of cancer deaths in part of North West England.

BACKGROUND: Relatively little work of a detailed geographical nature has been undertaken on the distribution of place of death. In particular, given evidence that most cancer patients would prefer to die at home there is a need to examine the extent to which this preference is met differentially from place to place. METHODS: Using data on cancer deaths for a single Health Authority in North West England we conducted both small area and individual analyses of place of death, using binomial and binary logistic regression models, respectively. RESULTS: Results from the small area analysis show that in more deprived areas cancer patients are more likely to die in hospital or hospice, and less likely to die at home, but that the effect disappears for home and hospice deaths once other factors are controlled for. At the individual level, the probability of death at home decreases among those living in deprived areas, whereas the probability of death in hospital increases as area deprivation increases. Age, gender, type of cancer, and proximity to hospital or hospice all have some effect on the probability of dying in a particular setting. CONCLUSION: There is significant place-to-place variation in place of death among cancer patients in part of North West England. However, studies of place of death among cancer patients need to consider the full range of settings and, if examining the impact of deprivation or social class, need to adjust for other factors, including proximity to different settings.

Death↗

Mechanism of nanoparticle formation in self-assembled colloidal templates: population balance model and Monte Carlo simulation.

Modeling the nanoparticle formation mechanism in water-in-oil microemulsion, a self-assembled colloidal template, has been addressed in this paper by two formalisms: the deterministic population balance equation (PBE) model and stochastic Monte Carlo (MC) simulation. These are based on time-scale analysis of elementary events consisting of reactant mass transport, solid solubilization, reaction, coalescence-exchange of drops, and finally nucleation and growth of nanoparticles. For the first time in such a PBE model, realistic binomial redistribution of molecules in the daughter drops (after coalescence-exchange of two drops) has been explicitly implemented. This has resulted in a very general model, applicable to processes with arbitrary relative rates of coalescence-exchange and nucleation. Both the deterministic and stochastic routes could account for the inherent randomness in the elementary events and successfully explained temporal evolution of mean and variance of nanoparticle size distribution. This has been illustrated by comparison with different yet broadly similar experiments, operating either under coalescence (lime carbonation to make CaCO(3) nanoparticles) or nucleation (hydride hydrolysis to make Ca(OH)(2) nanoparticles) dominant regimes. Our calculations are robust in being able to predict for very diverse process operation times: up to 26 min and 5 h for carbonation and hydrolysis experiments, respectively. Model predictions show that an increase in the external reactant addition rate to microemulsion solution is beneficial under certain general conditions, increasing the nanoparticle production rate significantly without any undesirable and perceptible change in particle size.

Journal Article↗

Allelic variation in gene expression identified through computational analysis of the dbEST database.

Differential expression between the two alleles of an individual and between people with different genotypes has been commonly observed. Quantitative differences in gene expression between people may provide the genetic basis for the phenotypic difference between individuals and may be the primary cause of complex diseases. In this paper, we developed a computational method to identify genes that displayed allelic variation in gene expression in human EST libraries. To model allele-specific gene expression, we first identified EST libraries in which both A and B alleles were expressed and then identified allelic variation in gene expression based on the EST counts for each allele using a binomial test. Among 1107 SNPs that had a sufficient number of ESTs for the analysis, 524 (47%) displayed allelic variation in at least one cDNA library. We verified experimentally the allelic variation in gene expression for 6 of these SNPs. The frequency of allelic variation observed in EST libraries was similar to the previous studies using the SNP chip and primer extension method. We found that genes that displayed allelic variation were distributed throughout the human genome and were enriched in certain chromosome regions. The SNPs and genes identified in this study will provide a rich source for evaluating the effects of those SNPs and associated haplotypes in human health and diseases.

Alleles↗

Temporal Trends and Spatial Variation in Preterm Prelabour Rupture of Membranes: A Population-Based Study.

OBJECTIVE: To describe the temporal trends in Preterm prelabour rupture of membranes (PPROM) in metropolitan France and the geographical distribution at the administrative division level. DESIGN: Exploratory population-based study using administrative data of the French National Health Data System. SETTING: Metropolitan France, 2015 to 2023. POPULATION: Pregnancy with a diagnosis of PROM before 37 SA. METHODS: Annual crude incidence of PPROM was calculated by dividing the number of pregnancies with PPROM diagnosis by the number of live births recorded during the same period. Annual trend was estimated by a binomial negative mixed model. Smoothed standardised incidence ratios were estimated based on a BYM2 model, which accounts for spatial variability between departments. MAIN OUTCOME: PPROM cases, defined as pregnancies with first hospitalizations with a diagnosis of PROM before 37 weeks. RESULTS: Over the study period, we included 150 615 PPROM cases representing 16 735 (±596) per year. Incidence of PPROM cases showed an ascending trend over time (incidence rate ratio 1.023 per year; 95% CI: 1.017-1.030) with an annual crude incidence ranging from 2.2% in 2015 to 2.7% in 2023. A decrease in the incidence was observed in 2020 relative to other years (incidence rate ratio 0.903, 95% CI: 0.887-0.920). A map of smoothed SIRs of PPROM cases at the French administrative division level revealed geographical inequalities. CONCLUSIONS: This first population-based study describing PPROM cases in metropolitan France paves the way for further studies to explore environmental hypotheses. Identifying temporal and geographical disparities in PPROM incidence is relevant to public health policy and practice as such disparities argue for the development of targeted prevention strategies in high-risk areas.

French national health data system↗

Modeling young driver motor vehicle crashes: data with extra zeros.

Much of the data collected on motor vehicle crashes is count data. The standard Poisson regression approach used to model this type of data does not take into account the fact there are few crash events and hence, many observed zeros. In this paper, we applied the zero-inflated Poisson (ZIP) model (which adjusts for the many observed zeros) and the negative binomial (NB) model to analyze young driver motor vehicle crashes. The results of the ZIP regression model are comparable to those from fitting a NB regression model for general over-dispersion. The findings highlight that driver confidence/adventurousness and the frequency of driving prior to licensing are significant predictors of crash outcome in the first 12 months of driving. We encourage researchers, when analyzing motor vehicle crash data, to consider the empirical frequency distribution first and to apply the ZIP and NB models in the presence of extra zeros due, for example, to under-reporting.

Accidents, Traffic↗

Four-year surveillance of major Gram-negative pathogens in a Saudi tertiary hospital: clinical distribution, comorbidity profiles, and antimicrobial resistance.

PURPOSE: To describe four-year diagnostic-distribution, burden, and antimicrobial-resistances of major Enterobacterales and Pseudomonas aeruginosa in a tertiary-care surveillance framework. PATIENTS AND METHODS: We retrospectively studied first non-duplicate-isolate per/patient/organism between 2022-2025 at a Saudi tertiary-care. Diagnostics used automated-platforms with GeneXpert-Carba-R employed parallel to cultures. Susceptibility interpretations used CLSI-breakpoints relevant to test-year. Annual-trends were assessed with grouped-binomial logistic-regression, and Benjamini-Hochberg false-discovery-rate correction was applied within prespecified analysis. RESULTS: Among 1,857 isolates, Klebsiella pneumoniae was most frequent (36.2%), followed by P.&#xa0;aeruginosa (33.4%), Escherichia coli (17.9%), and Enterobacter cloacae (12.3%). Mean patient age was 64.8&#x2009;years, 51.3% isolates were from intensive-care, 37.4% from urine, and 80.8% records had comorbidity. K.&#xa0;pneumoniae showed overall ESBL (76.6%), CRE (59.9%), MDR (69.3%), panel-defined XDR (64.7%), and panel-defined PDR (15.2%) frequencies. Enterobacterales ESBL-positivity increased (58.1% to 76.8%;q&#x2009;<0.001), whereas meropenem non-susceptibility decreased (52.6% to 33.2%;q&#x2009;<0.001). In P.&#xa0;aeruginosa, ceftazidime non-susceptibility increased (55.2% to 78.6%;q&#x2009;<0.001), meropenem decreased (46.8% to 32.9%;q&#x2009;=&#x2009;0.031), and tobramycin increased (22.2% to 45.7%;q&#x2009;=&#x2009;0.030). Crude-comorbidity differences remained insignificant after false-discovery-rate correction. CONCLUSION: We show a persistent species-specific Gram-negative resistance burden, led by K.&#xa0;pneumoniae and accompanied by substantial P.&#xa0;aeruginosa non-susceptibility. This supports organism-specific detections, antibiograms and continued multicenter-surveillance linked to antimicrobial exposure, genomic-data, and patient outcomes.

ESBL↗

The spatial distribution of fixed mutations within genes coding for proteins.

We have examined the extensive amino acid sequence data now available for five protein families - the alpha crystallin A chain, myoglobin, alpha and beta hemoglobin, and the cytochromes c - with the goal of estimating the true spatial distribution of base substitutions within genes that code for proteins. In every case the commonly used Poisson density failed to even approximate the experimental pattern of base substitution. For the 87 species of beta hemoglobin examined, for example, the probability that the observed results were from a Poisson process was the minuscule 10(-44). Analogous results were obtained for the other functional families. All the data were reasonably, but not perfectly, described by the negative binomial density. In particular, most of the data were described by one of the very simple limiting forms of this density, the geometric density. The implications of this for evolutionary inference are discussed. It is evident that most estimates of total base substitutions between genes are badly in need of revision.

Amino Acid Sequence↗

Distribution of macrovascular disease in scleroderma.

OBJECTIVE: Macrovascular disease in scleroderma has recently been described in two comparative studies. The aim of this study was to map its anatomical distribution. METHODS: In a retrospective cohort study of 20 scleroderma patients, the results of Doppler studies of arteries in the limbs, neck, and abdomen were compared with those from 20 cohort negative patients. The latter were matched for age, sex, and the presence/absence of hypertension, hyperlipidaemia, smoking, and diabetes status. Arteries were compared quantitatively using a body surface area adjusted measurement of intraluminal diameter, and qualitatively using descriptive characteristics of the arterial walls. The latter were binomially categorised under three non-exclusive headings--thickening, stenosis, and calcification. RESULTS: The ulnar arteries in scleroderma patients were significantly narrower than those of the negative cohort. The arterial walls were also characterised by smooth thickening along their entire length. The characteristics of the other arteries, including those of the lower limbs, were not significantly different from those of the negative cohort. CONCLUSION: The ulnar artery seems to be specifically targeted in patients with scleroderma. Assessment of the ulnar artery should be considered in these patients by means of a modified Allen's test or Doppler sonography especially in the presence of digital gangrene.

Aged↗

Transformation of binomial input by the postsynaptic membrane at a central synapse.

Although a binomial model gives an adequate description of the release properties of central afferent synapses, slight differences between experimental and predicted probability density functions are observed, with an excess number of responses recorded around the means. These discrepancies can be quantified by comparing experimental and theoretical entropies, which could relate to information transfer at these junctions. A model, based on the experimentally supported assumption that the postsynaptic membrane functions as a nonlinear processor, minimizes the differences between the distributions of the recorded and predicted potentials. According to this model, the nonlinearity is due to a localized interaction between the effects of simultaneously activated adjacent synapses.

Animals↗

The quantal nature of transmission and spontaneous potentials at the Torpedo electromotor junction.

Miniature and stimulus evoked electroplaque potentials (mEpPs and EpPs) were recorded in Torpedo electrocytes intracellularly and extracellularly. The quantal release parameters of EpPs and the time course of quantal EpCs were estimated in normal and low Ca2+-high Mg2+ solutions. Amplitude-frequency distribution of mEpPs showed Gaussian or uneven character with an average mean value of 0.3 +/- 0.08 mV (S.D.). The mean coefficient of variation of mEpPs was 26.8 +/- 7.2% (n = 6). Tetrodotoxin reversibly blocked the stimulus evoked EpP but hardly influenced the amplitude-frequency histogram of spontaneous EpPs in 10(-8)-10(-6) M concentration. The quantum content of stimulus evoked EpPs varied between 100-400 in normal solution which decreased in low Ca2+-high Mg2+ solution and the quantal release conformed to binomial statistics and allowed determination of the parameters p and n. Frequency of the spontaneous discharges varied highly from electrocyte to electrocyte but an analysis of the time intervals showed randomness for the events. The decay phase of quantal current composed of non-exponential and exponential sections which was characteristic with 0.75 +/- 0.16 msec (mean, S.D., at 20 degrees C) time constant of exponential decay. Although, two types of mEpCs could be differentiated having significantly slower and faster time courses. Neostigmine prolonged the time constant of decay of mEpCs in dose-dependent manner with a factor of 2 in 10(-6) M and of 4 in 10(-5) M concentrations (at about 20 degrees C).

Animals↗

Exact 95% confidence intervals for differences in binomial proportions.

A method is described that allows exact 95% confidence intervals to be computed for differences in binomial proportions. The method itself is not iterative, but it uses the iteratively computed 95% confidence intervals for the individual binomial proportions. The method converges with the usual normal approximation method, as denominators become large. It correlates very closely with the Yates-corrected chi-square test. The method works regardless of the definition of success or failure in the proportions and regardless of the order of the proportions.

Algorithms↗

Clinical and genetic investigations of idiopathic epilepsy in the Bernese mountain dog.

A study was conducted to investigate the clinical aspects and to define the mode of inheritance of idiopathic epilepsy in the Bernese mountain dog. Pedigree analyses were carried out on an open, non-preselected population of 4005 dogs. Five different subpopulations with 50 epileptic dogs from 13 generations were included. Almost all epileptic patients showed generalised seizures of the grand-mal type with a well-defined prodromal and postictal phase. The majority (62 per cent) of the epileptic dogs had had their first seizures at between one and three years of age and it was found that the age at first seizure was significantly (P < 0.05) lower in dogs from affected parental animals than in dogs from healthy parental animals. A clear predisposition for males was also noted. Additionally, there was no correlation between inbreeding coefficient and age at first seizure or incidence rate of seizures. The increased occurrence of the disease in different subpopulations and different families of the same sires or dams showed that there was a genetic basis for the condition in the Bernese mountain dog. Furthermore, the results of the pedigree analyses and binomial test support the hypothesis that idiopathic epilepsy has a polygenic, recessive mode of inheritance in the breed. Additional objective test-mating programmes would however be necessary to define the exact mode of inheritance.

Animals↗

Estimating treatment efficacy over time: a logistic regression model for binary longitudinal outcomes.

This paper presents a case study in longitudinal data analysis where the goal is to estimate the efficacy of a new drug for treatment of a severe chronic constipation. Data consist of long sequences of binary outcomes (relief/no relief) on each of a large number of patients randomized to treatment (low and high dose) or placebo. Data characteristics indicate: (1) the treatment effects vary non-linearly with time; (2) there is substantial heterogeneity across subjects in their responses to treatment; and (3) there is a high proportion of subjects who never experience any relief (the non-responders). To overcome these challenges, we develop a hierarchical model for binary longitudinal data with a mixture distribution on the probability of response to account for the high frequency of non-responders. While the model is specified conditionally on subject-specific latent variables, we also draw inferences on key population-average parameters for the assessment of the treatments' efficacy in a population. In addition we employ a model-checking method to compare the goodness-of-fit for our model against simpler modelling approaches for aggregated counts, such as the zero-inflated Poisson and zero-inflated negative binomial models. We estimate subject-specific and population-average rate ratios of relief for the treatment with respect to the placebo as functions of time (RR(t)), and compare them with the rate ratios estimated from the models for aggregated counts. We find that: (1) the treatment is effective with respect to the placebo with higher efficacy at the beginning of the study; (2) the estimated rate ratios from the models for aggregated counts appear to be similar to the average across time of the population-average rate ratios estimated under our model; and (3) model-checking suggests that the hierarchical and zero-inflated negative binomial model fit the data best. If we are mainly interested to establish the overall efficacy (or safety) of a new drug, it is appropriate to aggregate the longitudinal data over time and analyse the count data by use of standard statistical methods. However, the models for aggregated counts cannot capture time trend of treatment such as the initial treatment benefit or the development of tolerance during the early stage of the treatment which may be important information to physicians to predict the treatment effects for their patients.

Biometry↗

Applications of the expectation-maximization algorithm to quantal analysis of postsynaptic potentials.

The expectation-maximization (EM) algorithm is a robust method for maximum likelihood estimation of the parameters of an incompletely sampled distribution. It has been used to resolve the trial-to-trial amplitude fluctuations of postsynaptic potentials, when these are recorded in the presence of noise. Its use has however been limited by the need for different recursion equations for each set of conditions defined by the signal and noise processes. These equations are derived for the following conditions which arise in studies of synaptic transmission: non-gaussian noise process; quantal fluctuation; quantal variability. In addition, a constraint can be incorporated to accommodate simple and compound binomial models of transmitter release. Some advantages of these methods are illustrated by Monte Carlo simulations.

Algorithms↗

Within-plant distribution of twospotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), on ivy geranium: development of a presence-absence sampling plan.

The twospotted spider mite, Tetranychus urticae Koch, is an important pest of ivy geranium and other ornamental plants. As a part of our long-term goal to develop an integrated crop management program for ivy geraniums, the focus of this study was to produce a reliable sampling method for T. urticae on this bedding plant. Within-plant mite distribution data from a greenhouse experiment were used to identify the young-fully-opened leaf as the sampling unit. We found that 53% of the mites on a plant are on the young-fully-opened leaves. On average 22, 37, and 41% of the leaves belonged to the young, young-fully-opened, and old leaf categories, respectively. We then developed a presence-absence sampling method for T. urticae in ivy geranium using generic Taylor's coefficients for this pest. We found the optimal binomial sample sizes for estimating populations of T. urticae at densities of between 0 and 3 mites/leaf to be quite large; therefore, we recommend the use of numerical sampling within this range of T. urticae densities. We also suggest that population estimates of T. urticae on ivy geranium be done based on mite density/unit area of greenhouse space, both for conventional greenhouse pest management, and for determining how many phytoseid predators to release when using biological control.

Animals↗

Evaluating risk factors associated with severe hypoglycaemia in epidemiology studies-what method should we use?

AIMS: To determine the most appropriate regression models to use when assessing risk factors for severe hypoglycaemia and to investigate the impact of model misspecification and its clinical implications. METHODS: A total of 1229 children with Type 1 diabetes (mean age 11.7 years sd 4.1), of which 605 (49.2%) were males, were studied. Prospective assessment of severe hypoglycaemia (an event leading to loss of consciousness or seizure) was made over the 9-year period, 1992-2001. Patients were seen every 3 months and episodes of hypoglycaemia along with clinical data were recorded. Over 70% of children never experienced a severe hypoglycaemic event. Data were analysed using the Poisson regression, negative binomial, zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) models. The over-dispersion and likelihood ratio statistics were calculated and the analytical methods compared. RESULTS: The Poisson regression model did not fit the data well. The negative binomial and the zero inflated Poisson and negative binomial models fitted the data better than Poisson. CONCLUSIONS: The commonly used Poisson regression models to analyse hypoglycaemia epidemiology may lead to biased parameter estimates and incorrect determination of risk factors for hypoglycaemia. We recommend the use of the negative binomial or zero inflated models to examine any risk factors associated with severe hypoglycaemia. Careful consideration must be given to the interpretation of hypoglycaemia surveys and their analysis.

Age Factors↗

Assessing screening tests: extensions of McNemar's test.

We address the problem of comparing a new screening test to a currently available screening test in the absence of a gold standard. When both tests are given to each participant in a clinical trial, the usual analytical approach is to apply McNemar's test for equality of the off-diagonal probabilities, with rejection of the null hypothesis implying that the tests differ. For assessing equivalence, however, we consider a compound null hypothesis that the new test gives either fewer or more positive results than the standard. If both parts of this hypothesis are rejected, we assert equivalence in the rate of positive responses. We propose an extension of McNemar's test for this situation. A companion step is to construct a confidence interval for the ratio of the marginal probabilities and assert equivalence if the interval is sufficiently small. It is also important that the tests agree a large proportion of the time. This can be verified with a complementary two-tailed binomial test. Another situation arises when there is a gold standard for disease diagnosis, and we wish to compare the sensitivity and specificity of two screening tests. We show that a 2 degrees-of-freedom chi-square test based on two McNemar-like tables is an appropriate test.

Chi-Square Distribution↗