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PubMed1999

Laterality of hand, foot, eye, and ear in twins.

Information on handedness, footedness, eyedness, and earedness was collected from 33 monozygotic (MZ) twin pairs and 67 dizygotic (DZ) twin pairs. The incidence of nonright-sidedness in the twins is not higher than that reported in the literature for singletons. Similar results are found for the other lateralities. The results of assessing handedness with preference tests do not differ from those carried out with performance tests. There are no differences in incidence of nonright-sidedness between MZ and DZ twins. The concordance of lateralities is similar in MZ and DZ twins. The proportions of Right-Right, Right-Nonright, and Nonright-Nonright pairs in both groups of twins show a binomial distribution. The present results do not confirm a genetic hypothesis of determination of sidedness in humans and are comparable with the results obtained by other twin studies.

Journal Article↗

PubMed2000

A method for detecting current temporal clusters of toxic events through data monitoring by poison control centers.

BACKGROUND: Poison control centers have become a widely recognized source of data for chemical and other environmental exposures. Concurrently, increased emphasis on early identification of temporal clustering of toxic exposures has stimulated development of sensitive statistical methods to detect clusters at the time of occurrence. METHOD: This paper discusses the scan test which has been applied to retrospective data to detect carbon monoxide poisoning clusters. We propose a more sensitive method, based on the binomial distribution to detect current clusters of only 1 or more days duration during the ongoing data collection and monitoring process. RESULTS: Applied to daily carbon monoxide poisoning incidence data on which the scan test has been applied, the new test for current clustering evidently has much more power. For retrospective identification of previous clusters lasting more than 1 day, the scan test is recommended. However, for previous daily clusters, a third method is recommended. CONCLUSION: Certain toxic events such as carbon monoxide poisoning occasionally occur in daily clusters, or in clusters lasting a few days. Timely detection of clusters requires application of early intervention strategies fostered by sensitive statistical methods of detection, as presented here.

Carbon Monoxide Poisoning↗

PubMed1998

Robustness and power of the maximum-likelihood-binomial and maximum-likelihood-score methods, in multipoint linkage analysis of affected-sibship data.

The maximum-likelihood-binomial (MLB) method, based on the binomial distribution of parental marker alleles among affected offspring, recently was shown to provide promising results by two-point linkage analysis of affected-sibship data. In this article, we extend the MLB method to multipoint linkage analysis, using the general framework of hidden Markov models. Furthermore, we perform a large simulation study to investigate the robustness and power of the MLB method, compared with those of the maximum-likelihood-score (MLS) method as implemented in MAPMAKER/SIBS, in the multipoint analysis of different affected-sibship samples. Analyses of multiple-affected sibships by means of the MLS were conducted by consideration of all possible sib pairs, with (weighted MLS [MLSw]) or without (unweighted MLS [MLSu]) application of a classic weighting procedure. In simulations under the null hypothesis, the MLB provided very consistent type I errors regardless of the type of family sample (sib pairs or multiple-affected sibships), as did the MLS for samples with sib pairs only. When samples included multiple-affected sibships, the MLSu led to inflation of low type I errors, whereas the MLSw yielded very conservative tests. Power comparisons showed that the MLB generally was more powerful than the MLS, except in recessive models with allele frequencies <.3. Missing parental marker data did not strongly influence type I error and power results in these multipoint analyses. The MLB approach, which in a natural way accounts for multiple-affected sibships and which provides a simple likelihood-ratio test for linkage, is an interesting alternative for multipoint analysis of sibships.

Computer Simulation↗

PubMed2000

What's the score?

If you have calculated a confidence interval for an infection rate and found the interval extending into meaningless negative numbers, chances are the error is due to use of approximation formulae. Many of us unknowingly were taught to use the Wald approximation, which does not always approximate the exact binomial distribution accurately. Poor approximation can occur in infection surveillance at both small and large sample sizes.

Cross Infection↗

PubMed1996

Analysis of infection control surveillance data in a long-term-care facility: use of threshold testing.

OBJECTIVE: To describe long-term trends in nosocomial infection rates and the threshold testing method for evaluating nosocomial surveillance data in a long-term-care facility (LTCF). DESIGN: Descriptive epidemiology of prospectively collected infection control surveillance data and application of threshold testing for detecting possible outbreaks. Threshold testing uses the binomial distribution to calculate probabilities of infection frequency at selected endemic levels (mean number of infections per month) and compares these probabilities to observed infection frequency. SETTING: One hundred twenty-bed LTCF located within a public, university-affiliated hospital. PATIENTS AND METHODS: The study period was 1987 through 1994. Yearly endemic levels of specific types of infection were calculated and threshold levels were determined using a previously published method. In this study, a probability of P = .01 was chosen to determine the threshold at a specific endemic level; if the observed number of infections in a month reached or exceeded the threshold level, the likelihood that this occurred by chance alone was 1% or less. INTERVENTIONS: None. RESULTS: The overall mean nosocomial infection rate ranged from three to five episodes per 1,000 resident care days per year; mean yearly rates from 1990 onward were higher and more stable than those from 1987 to 1989. The most common infections identified were lower respiratory tract, skin and soft tissue, urinary tract, and conjunctivitis. For each of these infections, threshold levels were calculated periodically, using only the monthly frequency of infection. Despite variations in the yearly mean endemic level of various infections, threshold levels were stable except for skin and soft-tissue infection. CONCLUSIONS: Threshold testing for analysis of infection control surveillance data in the LTCF setting is straightforward and does not require knowledge of statistics, special computer software, or calculation of rates; given the stable population in the typical LTCF, threshold testing can be based on variations in the monthly count of infections and provides an objective evaluation of surveillance data and a method to identify when outbreaks may be occurring.

Analysis of Variance↗

PubMed1996

An outbreak of viral gastroenteritis in a nursing home: importance of excluding ill employees.

BACKGROUND: In May 1994, 43 persons in a nursing home were reported with gastroenteritis. An outbreak investigation was conducted to determine risk factors for gastroenteritis among residents and staff. METHODS: Data were analyzed using contingency tables; relative risks (RR) and statistical significance were determined with Fisher's Exact Test. The chi-squared statistic to perform a goodness of fit test for the binomial distribution was used to determine whether cases occurred randomly and independently of each other. Stools were tested for bacterial enteric pathogens, ova, and parasites and were examined by electron microscopy, Southern hybridization, and reverse transcription-polymerase chain reaction. Paired sera were collected to detect fourfold rises in antibody titer by enzyme immunoassay against Norwalk viruses. RESULTS: Of 121 residents, 62 (51%) had gastroenteritis, as did 64 (47%) of the 136 staff. The index case was a nurse who became ill at work and continued to work, while symptomatic, for another 2 days. Only residents who had received medications from this nurse between May 17 and May 20 became ill on the first day of the outbreak (13 of 35 versus 0 of 5). Nurses and nurse aides were more likely than employees without direct resident contact to be cases (46 of 68 versus 18 of 58; RR, 2.18; P < .001). Bacterial stool cultures and parasite examinations were negative. Results of electron microscopy, polymerase chain reaction with Southern hybridization, and enzyme immunoassay indicated the causative agent was a small, round, structured virus similar to the Snow Mountain Agent. CONCLUSION: To minimize outbreaks in nursing homes, we recommend that ill staff be excluded from work until symptoms resolve.

Adult↗

PubMed2004

Effect on tumour control of time interval between surgery and postoperative radiotherapy: an empirical approach using Monte Carlo simulation.

In this work, a procedure, based on Monte Carlo techniques, to analyse the effect on the tumour control probability of the time interval between surgery and postoperative radiotherapy is presented. The approach includes the tumour growth as well as the survival of tumour cells undergoing fractionated radiotherapy. Both processes are described in terms of the binomial distribution. We have considered two different growth models, exponential and Gompertz, the parameters of which have been fixed to reproduce the clinical outcome corresponding to a retrospective study for patients with head and neck squamous cell carcinomas. In the cases analysed, we have not found significant differences between the results obtained for both growth models. The mean doubling times found for residual clonogens after surgery are less than 40 days. The rate of decrease in local control is around 0.09% per day of delay between surgery and radiotherapy and the corresponding time factor is about 0.11 Gy per day.

Algorithms↗

PubMed2004

Infectious titer assay for adeno-associated virus vectors with sensitivity sufficient to detect single infectious events.

A highly sensitive assay for determination of infectious titers of recombinant adeno-associated virus (AAV) by limiting dilution analysis is described. This assay is capable of detecting single infectious events and can therefore provide an absolute rather than relative measure of infectivity. The assay utilizes a HeLa-derived AAV2 Rep/Cap-expressing cell line, D7-4, grown in 96-well plates and infected with replicate 10-fold serial dilutions of AAV2 vectors in the presence of adenovirus type 5. Forty-eight hours after infection, vector genome replication is determined by quantitative PCR (Q-PCR). A linear relationship between vector genome input and replicated copy number (slope = 2670 copies per vector genome) was determined, enabling detection of one infectious event per well by Q-PCR. The observed binomial distribution of the end-point data confirmed that single infectious events could be detected, and allowed calculation of infectious titers by the Kärber method. Analysis of an AAV2 reference vector, AAV-hFIX16, in 21 independent determinations gave an average ratio of AAV vector genomes (VG) to infectious units (IU) of 8.3 +/- 4.2 VG/IU, a value close to the theoretical limit. No significant differences in vector particle-to-infectious unit ratios were observed between vectors purified by column chromatography (9.3 +/- 5.0 VG/IU, n = 7) and cesium chloride gradient ultracentrifugation (6.4 +/- 3.2 VG/IU, n = 7).

Cell Line, Tumor↗

PubMed2001

ADAPTSITE: detecting natural selection at single amino acid sites.

UNLABELLED: ADAPTSITE is a program package for detecting natural selection at single amino acid sites, using a multiple alignment of protein-coding sequences for a given phylogenetic tree. The program infers ancestral codons at all interior nodes, and computes the total numbers of synonymous (c(S)) and nonsynonymous (c(N)) substitutions as well as the average numbers of synonymous (s(S)) and nonsynonymous (s(N)) sites for each codon site. The probabilities of occurrence of synonymous and nonsynonymous substitutions are approximated by s(S) / (s(S) + s(N)) and s(N) / (s(S) + s(N)), respectively. The null hypothesis of selective neutrality is tested for each codon site, assuming a binomial distribution for the probability of obtaining c(S) and c(N). AVAILABILITY: ADAPTSITE is available free of charge at the World-Wide Web sites http://mep.bio.psu.edu/adaptivevol.html and http://www.cib.nig.ac.jp/dda/yossuzuk/welcome.html. The package includes the source code written in C, binary files for UNIX operating systems, manual, and example files.

Algorithms↗

PubMed2026

Striping artifact removal in VisiumHD data through nuclear counts modeling.

MOTIVATION: 10x Genomics VisiumHD enables spatial transcriptomics at 2 µm × 2 µm resolution but exhibits slide-specific, non-periodic striping artifacts due to lane-width variability. These multiplicative row/column effects distort bin total counts and can bias downstream analyses. The state-of-the-art destriping approach is the normalization procedure used as a preprocessing step in bin2cell; it applies sequential high-quantile row- then column-wise normalization, which is asymmetric and can introduce edge effects/macro-stripes and distortions of large-scale total-count structure. RESULTS: We propose a statistical destriping approach that leverages nuclei segmentation from the co-registered H&E image. Assuming transcript abundance is constant within each nucleus, we model bin counts with a negative binomial distribution whose mean is a product of a nucleus-specific concentration and row- and column-specific stripe-factors reflecting lane-width variation. We fit all parameters in a generalized linear modeling framework with cross-validated regularization on stripe-factors and iterative dispersion estimation, and use the fitted parameters to correct the observed counts into a destriped image. On synthetic data with known ground truth, our method improves stripe-factor estimation accuracy and reduces error in corrected counts relative to bin2cell and bin2cell-derived baselines. Across four public VisiumHD slides, it consistently lowers striping intensity while substantially better preserving biological signal present in the large-scale global count structure and avoiding the artifacts introduced by other methods. AVAILABILITY AND IMPLEMENTATION: All source code and links to publicly available data used for this study are available at https://github.com/paolamalsot/destriping-GLM.

Artifacts↗

PubMed1998

Modelling the human olfactory stimulus-response function.

Two models, derived from the equations of Michaelis-Menten and Hill, were adapted to olfaction. Their ability to model human olfactory stimulus-response relationships was compared with that of the classical laws of Fechner and Stevens. First, these four models were systematically compared on data available in the literature concerning 20 pure odorous compounds. At the lower concentrations of the odorous compound, the model of Stevens was found to be as good as the model of Hill. However, when the concentration range was extended further and included the concentration at half the maximum intensity, the model of Hill was found to be better. Second, the four models were tested on different parts of a true stimulus-response sigmoid curve with 5% noise added. The comparison confirmed the results obtained when experimental data were used. Third, the hypothesis that the psychophysical response is the sum of sigmoidal responses generated at the more peripheral parts of the olfactory system was examined, assuming a binomial distribution of receptor affinities. Within a very large range of variation in their characteristics, the sums of several sigmoids are indeed correctly modelled by Hill equations with exponents reflecting the distribution of receptor affinities.

Humans↗

PubMed1988

Quantification of arrhythmias using scoring systems: an examination of seven scores in an in vivo model of regional myocardial ischaemia.

Arrhythmia scores have been used in recent years to facilitate the analysis of arrhythmias, particularly in relation to regional myocardial ischaemia. The recent Lambeth Conventions recommended caution in the use of arrhythmia scores since their use may be misleading. In the present study seven scoring systems were examined in an attempt to validate the use of arrhythmia scores. A strong positive correlation was present between all seven scores. Furthermore, the scores all correlated with the incidences of ventricular fibrillation, ventricular tachycardia, and ventricular premature beats in early myocardial ischaemia. All seven scores successfully detected statistically significant reductions in the incidence of ventricular fibrillation resulting from the administration of two drugs. Some of the scores occasionally showed statistically significant reductions when effects on the raw arrhythmia data were not statistically significant. In this respect, parametric statistical analysis of arrhythmia scores may be a more sensitive method of quantifying arrhythmias than non-parametric analysis of binomially distributed raw data such as the incidence of ventricular fibrillation (in accordance with the power of such tests) indicating that the scores have precision. However, none of the scores incorrectly showed a statistically significant reduction when the raw data expressed a statistically significant or non-significant increase, indicating that the scores have accuracy. In conclusion, it is possible to design many arrhythmia scores that show changes in arrhythmia severity when more conventional analyses show only non-statistically significant trends. When used in conjunction with raw arrhythmia data, comprehensive drug dose ranges, and appropriate parametric statistical tests, arrhythmia scores facilitate the quantification of arrhythmias. It is recommended that arrhythmia scores should be used only for quantifying group data and model building and not for prognostic purposes in individuals.

Animals↗

PubMed2002

Female sex selection using clomiphene citrate and albumin separation of human sperm.

BACKGROUND: This study was undertaken to assess whether the use of clomiphene citrate in conjunction with albumin-separated sperm would alter the sex ratio (expressed as the proportion of males) towards females and, if so, whether this skewing was due solely to the induction of ovulation. METHODS: The sex ratios of 184 single and 42 twin births at five assisted reproduction biology clinics were determined. The normal approximation to the binomial distribution was used to determine significant differences between these sex ratios and the established sex ratios for single, twin and combined (single and twin) non- and ovulation-induced births. RESULTS: The non-ovulation-induced sex ratios for singletons (51.4%) and twins (50.2%) were greater than the treatment singleton (27.7%; P < 0.001) and twin (33.3%; P < 0.01) sex ratios respectively. Correspondingly, the non-induced sex ratio for combined births (51.4%) was greater than the treatment sex ratio (28.8%; P < 0.001). The previously established induced singleton and twin sex ratios (48.1%) were lower than the non-induced sex ratio (51.4%), but higher than the treatment singleton (27.7%; P < 0.001) or twin (33.3%; P < 0.03) sex ratios. The ovulation-induced combined ratio (48.1%) was less than the non-induced combined (51.4%) sex ratio, although greater than the treatment combined sex ratio (28.8%; P < 0.001). CONCLUSION: Clomiphene citrate in conjunction with albumin-separated sperm decreased the sex ratio; a reduction that was not exclusively due to induction of ovulation.

Cell Separation↗

PubMed1994

Chlamydia pneumoniae IgG antibody prevalence in south-western and eastern Finland in 1982 and 1987.

Chlamydia pneumonia IgG antibody prevalence was examined in a representative sample (2342 subjects) of the population aged 25-59 years in south-western and eastern Finland in 1982 and 1987. Microimmunofluorescence was used to measure IgG antibodies. Prevalence of C. pneumoniae was modelled using the GLIM statistical package assuming that the prevalence had a binomial distribution. The prevalence was assumed to be a function of the year, subjects' gender, age and place of residence. The effect of the year on the prevalence was significant in both regions (P < 0.05 in the south-west and P < 0.001 in the east). In each year the prevalence was higher in the south-west than in the east and it increased between 1982 and 1987 from 55% to 63% in the south-west and from 41% to 59% in the east. The prevalence increased with age, but the age-related antibody pattern was different between sexes. The highest prevalence was found in men aged 49-59 years. The different increase in prevalence with age in the south-western and the eastern parts of the country indicates that the outbreaks of infection were not related. The endemic level of C. pneumoniae infection in the south-west is consistently higher than in the east, or there was an outbreak of C. pneumoniae infection in both the years we examined. Thus it is more likely that the high prevalence in south-western Finland was connected more with the epidemics reported elsewhere in Scandinavia in the same years than with the occurrence of C. pneumoniae infection in eastern Finland.

Adult↗

PubMed1996

Influence of gender on susceptibility to multiple sclerosis and age of onset in concordant sibships.

BACKGROUND: Research has produced conflicting findings about whether there is an excess of like-sexed pairs among concordant multiple sclerosis (MS) sibships. Although a positive correlation in onset age among sibling pairs overall has been reported, no data have been published describing age at onset correlations for like-sexed versus unlike-sexed pairs. The purpose of this study was to provide additional information on both issues. METHODS: Patients with an MS sibling were sought through the files of the University of Alberta MS clinic (Edmonton, Canada). The clinic neurologist either reviewed clinical/autopsy material or assessed relatives of index cases prior to accepting the relative as having MS. Pairs of siblings (excluding twins) were divided into (1) male-male pairs, (2) female-female pairs, and (3) female-male pairs. RESULTS: A total of 62 concordant sibling pairs were identified. There were 33 like-sexed pairs (6 male-male/27 female-female) and 29 unlike-sexed pairs. The observed number of like-sexed pairs was not significantly different from the expected frequency using 2 x 2 chi2 analysis, where expected values represent the binomial distribution predicted from the frequency of each sex as determined by total number of males and females. The age at onset intraclass correlation coefficient was -0.09 for sibling pairs overall, -0.22 for like-sexed pairs and +0.02 for unlike-sexed pairs. CONCLUSIONS: This study does not provide evidence for an association between disease susceptibility and gender in siblings concordant for MS; nor does it suggest that genetics plays a role in onset age.

Age of Onset↗

PubMed1997

Familial aggregation of oesophageal cancer in a high incidence area in China.

BACKGROUND: The high incidence of oesophageal cancer in northern China is attributed predominantly to environmental factors. The role of genetic factors has not been extensively studied. METHODS: Our aim was to study familial aggregation of oesophageal cancer in pedigrees from a defined population base in a high incidence area in China and to quantify the risk associated with different first degree relatives using different analytical approaches. Detailed data on family members of three successive generations and the occurrence of oesophageal and other cancers in family members were collected from a population-based series of 244 oesophageal cancer cases which occurred between 1987 and mid-1992 in Huixian County, Henan. RESULTS: Compared to expected rates, the standardized mortality ratio (SMR) of oesophageal cancer among first degree relatives of oesophageal cancer patients was 2.4 (2.2 in male and 2.7 in female relatives). The corresponding SMR for first and second degree relatives were 1.6 and 2.2. The null hypothesis of 'no familial aggregation' was rejected using Tarone's one-sided score test for binomial distributions indicating some evidence for clustering within families. To account for variance due to between-pairs correlation and family and/or individual specific variables, we fitted a series of regression models using a Generalized Estimation Equations (GEE) approach. The pairwise odds ratios were 2.3 for parent-parent, 1.9 for sib-parent and 1.1 for sib-sib, adjusted for sex, age and sex of index case. DISCUSSION: The existence of familial aggregation of oesophageal cancer in the study population was confirmed using different analyses and a two- to threefold increased risk was found for first degree relatives. The clear association of disease between parent and sib provides some indication of a genetic component. The pairwise association between parents but not between sibs suggests that environmental factors have a stronger action after childhood.

Aged↗

PubMed1999

Lot sampling plans in the measure of quality of care indicators.

OBJECTIVE: Application of the lot sampling technique to measure indicators of quality of care on screening activities directed toward women: detection of risk factor for cardiovascular diseases, screening for breast cancer and for cervical cancer. DESIGN: The sampling plan adopted involved, in each centre, a sample size of 15 and a maximum of four non-compliers that the random sample would tolerate. The binomial distribution was used. This 15-4 sampling plan sets the probability of concluding that an indicator is performing well for a lot or population that has an 80% compliance level at 0.84, keeping the alpha error or provider's risk at 0.16, while those for a population that has a 50% compliance is set at only 0.059, keeping the beta error or consumer's risk at 0.059. SETTING: Ten primary care centres of the Catalan Health Institute. PATIENTS: Random sample of all women aged 40-65 years enrolled in each centre. RESULTS: For indicators of risk factors for cardiovascular disease detection, six out of 10 centres performed well for hypertension and obesity, and five out of 10 centres performed well for hypercholesterolaemia. However, no centre was acceptable either in cervical cancer or breast cancer screening. DISCUSSION: Rather than seeking to obtain precise estimates, this technique aims to facilitate the decision-making process regarding the quality levels of the indicators examined. Despite some limitations, the technique is a good test for detecting gross departures from stated compliance thresholds. It has several advantages for application in health services: (i) the use of small sample sizes; (ii) the fact that it can detect deficiencies in small areas; and (iii) the simplicity of applying this technique by relying on ready-made tables.

Adult↗

PubMed2003

Sequential sampling and biorational chemistries for management of lepidopteran pests of vegetable amaranth in the Caribbean.

Although vegetable amaranth, Amaranthus viridis L. and A. dubius Mart. ex Thell., production and economic importance is increasing in diversified peri-urban farms in Jamaica, lepidopteran herbivory is common even during weekly pyrethroid applications. We developed and validated a sampling plan, and investigated insecticides with new modes of action, for a complex of five species (Pyralidae: Spoladea recurvalis (F.), Herpetogramma bipunctalis (F.), Noctuidae: Spodoptera exigua (Hubner), S. frugiperda (J. E. Smith), and S. eridania Stoll). Significant within-plant variation occurred with H. bipunctalis, and a six-leaf sample unit including leaves from the inner and outer whorl was selected to sample all species. Larval counts best fit a negative binomial distribution. We developed a sequential sampling plan using a threshold of one larva per sample unit and the fitted distribution with a k(c) of 0.645. When compared with a fixed plan of 25 plants, sequential sampling recommended the same management decision on 87.5%, additional samples on 9.4%, and gave inaccurate recommendations on 3.1% of 32 farms, while reducing sample size by 46%. Insecticide frequency was reduced 33-60% when management decisions were based on sampled data compared with grower-standards, with no effect on crop damage. Damage remained high or variable (10-46%) with pyrethroid applications. Lepidopteran control was dramatically improved with ecdysone agonists (tebufenozide) or microbial metabolites (spinosyns and emamectin benzoate). This work facilitates resistance management efforts concurrent with the introduction of newer modes of action for lepidopteran control in leafy vegetable production in the Caribbean.

Amaranthus↗