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PubMed2000

Hitchhiking under positive Darwinian selection.

Positive selection can be inferred from its effect on linked neutral variation. In the restrictive case when there is no recombination, all linked variation is removed. If recombination is present but rare, both deterministic and stochastic models of positive selection show that linked variation hitchhikes to either low or high frequencies. While the frequency distribution of variation can be influenced by a number of evolutionary processes, an excess of derived variants at high frequency is a unique pattern produced by hitchhiking (derived refers to the nonancestral state as determined from an outgroup). We adopt a statistic, H, to measure an excess of high compared to intermediate frequency variants. Only a few high-frequency variants are needed to detect hitchhiking since not many are expected under neutrality. This is of particular utility in regions of low recombination where there is not much variation and in regions of normal or high recombination, where the hitchhiking effect can be limited to a small (<1 kb) region. Application of the H test to published surveys of Drosophila variation reveals an excess of high frequency variants that are likely to have been influenced by positive selection.

Animals↗
PubMed1986

[Sonographically detectable changes in placental structures in pregnancy. 4. Statistical comparison of the frequency distribution of placental stages 0-3 in newborn infants in a pregnancy of 37-42 weeks duration].

Among women with a duration of pregnancy between 37 and 42 gestational weeks procentual frequency, confidence intervals of O. Bunke, pounts of separability and areas of unsharpners were analysed. 1412 sonographical examinations were done in 645 pregnant women. Stage 0 was found statistically significant more frequent with error of probability alpha = 0.05 until the 30. week of pregnancy, stage 1 between the 21. and 36. week of pregnancy, stage 2 between the 33. and 36. gestational week and stage 3 in 37. and 38. week. Transformation (areas of unsharpness) from stage 0 to stage 1 occurs between the 24. and 32. gestational week, from stage 1 to stage 2 between the 31. and 34. week, from stage 2 to stage 3 between the 36. and 42. gestational week.

Birth Weight↗
PubMed2003

Boltzmann-type distribution of side-chain conformation in proteins.

We analyze packing imperfections in globular proteins as reflected in deviations of torsion angles from the equilibrium values for the isolated side chains. The distribution of conformations of methionine and lysine residues in a database of high-resolution structures is compared with energies of model compounds calculated with high-level quantum-mechanics. The distribution of the C-C and C-S torsion angles (chi(3)) correlates well with the Boltzmann factor of the torsion energy, exp(-betaE) of the model compounds C(2)H(5)-C(2)H(5) and C(2)H(5)-S-CH(3). An exponential relation was again found between the relative occurrence of g+, g- and t conformations for C(alpha)-C(beta) bonds in long side chains and the energy differences of rotamers of alpha-amino n-butyric acid, when dependence on backbone conformation was taken into account. The distribution of all 27 rotamers of methionine was correlated with the energy differences between the model's rotamers, corrected for clashes with nearby residues, the correlation being good for a set with backbone in the beta-conformation, but less clear for backbone alpha-conformation. In all correlations, the value of the coefficient beta corresponds to a temperature of circa 300 K. These results can be interpreted with a model that considers the structure of a folded protein as resulting from packing imperfectly complementary parts, with a requirement of an overall low energy. Compromises are required to optimize the fit of nonbonded contacts with surrounding groups, and side chains assume conformations away from the energy minimum. An exponential distribution is a most probable distribution, and this can be established easily under conditions other than thermal equilibrium.

Butanes↗
PubMed1993

Multi method approach to the assessment of data quality in the Finnish Medical Birth Registry.

OBJECTIVE: To assess comprehensively the validity of the data in the Finnish Medical Birth Registry (MBR) by the combined use of several controls and internal analysis of the data. DESIGN: The MBR data were individually linked to a medical record sample (n = 775) and to all perinatal death certificates in 1987. The data were also compared with annual hospital statistics. The distributions of birth weights and gestational ages were examined. SUBJECTS: All stillborn and liveborn babies registered in the MBR in 1987 (n = 59,370). SETTING: The nationwide MBR data were compared with medical records from one third of the Finnish hospitals, with statistics for all hospitals, and with nationwide cause of death registry data. MEASUREMENTS AND MAIN RESULTS: With regard to most variables, the data quality was good or satisfactory (agreement with medical records 95% or more). Allowing for minor deviations in variables with continuous scales improved the agreement rates further. Explanations could be deduced for items with poor agreement values. For most variables, the amount of missing data was less than 1%. With the exception of caesarean sections, medical procedures were registered in only 30 to 72% of the cases, and the proportion varied strongly between the hospitals. Common diagnoses (32 to 86%) and primary causes of death (59 to 78%) were also poorly recorded. CONCLUSIONS: Combined use of several control materials and internal analyses was successful in investigating the whole data content. The data in the MBR were generally valid but diagnoses and most data on medical procedures were not of sufficiently good quality.

Birth Certificates↗
PubMed2003

Multimodal particle size distributions emitted from HFA-134a solution pressurized metered-dose inhalers.

The purpose of this research was to investigate the measurement and in vitro delivery implications of multimodal distributions, occurring near or in the respirable range, emitted from pressurized metered-dose inhalers (pMDIs). Particle size distributions of solution pMDIs containing hydrofluoroalkane-134a (HFA-134a) and ethanol were evaluated using 2 complementary particle-sizing methods: laser diffraction (LD) and cascade impaction (CI). Solution pMDIs were formulated from mixtures of HFA-134a (50%-97.5% wt/wt) and ethanol. A range of propellant concentrations was selected for a range of vapor pressures. The fluorescent probe, Rhodamine B, was included for chemical analysis. The complementary nature of LD and CI allowed identification of 2 dominant particle size modes at 1 and 10 micro m or greater. Increasing propellant concentrations resulted in increases in the proportion of the size distributions at the 1- micro m mode and also reduced the particle size of the larger droplet population. Despite significant spatial differences and time scales of measurement between the particle-sizing techniques, the fine particle fractions obtained from LD and CI were practically identical. This was consistent with LD experiments, which showed that particle sizes did not decrease with increasing measurement distance, and may be explained by the absence of significant evaporation/disintegration of larger droplets. The fine particle fractions (FPFs) emitted from HFA-134a/ethanol solution pMDI can be predicted on the basis of formulation parameters and is independent of measurement technique. These results highlight the importance of presenting particle size distribution data from complementary particle size techniques.

Aerosols↗
PubMed2003

[Cholecystectomy in the elderly: early results of open versus laparoscopic approach].

UNLABELLED: The rise of elderly population is due to the improvement of life expectancy. The biliary lithiasis is the most common condition requiring intra-abdominal surgery. Half of these patients sustain associated diseases and frequently develops acute and complicated forms of cholelithiasis. Therefore, cholecystectomy is indicated for patients with chronic symptomatic disease. During a long period open cholecystectomy has been practiced, with low complications and mortality rates. Videolaparoscopy has been recently proposed as an option in these cases, however, few studies compared its advantages over open cholecystectomy for elderly patients. OBJECTIVE: To access the early results of the surgical treatment for cholelithiasis in the elderly submitted to an open or laparoscopic cholecystectomy. METHODS: retrospective study with 246 patients > 65 years old, who underwent elective cholecystectomy through a subcostal incision (group I) or laparoscopic approach (group II). We employed Student's t test and Spearman's correlation for statistical analysis, considering p < 0,05 as significant. RESULTS: A hundred and twenty patients were arranged in group I and 126 in group II. Associated diseases were present in 155 cases (63). There were no differences between the groups regarding both the distribution of comorbid conditions. Conversion was evaluated in 10 patients (8.3%). The mean operative time was 133 minutes in group I and 112 minutes in group II (p=0.001). The mean hospital stay in group I was 3,3 days and in group II was 3.2 days p=0.698. Thirteen patients in each group developed complications: group I (10.8%) and group II (10.3%) p=0,896. There was no statistis significance in complication rate related to gender, age, associated diseases and ASA when the both groups were compared. There were two deaths, both in group II, although the mortality rate was not statiscally significant between the groups (p=0.158). CONCLUSION: Both open and laparoscopic cholecystectomy can be practiced in the elderly with low and similar rate of complications.

Age Distribution↗
PubMed1985

A prospective study of body fat distribution and weight loss.

Previous studies have suggested an association between adipose tissue cellularity and body fat distribution, and between adipose tissue cellularity and ability to lose weight. To determine whether there was an association between body fat distribution and ability to lose weight, we prospectively studied 187 severely obese women. The women were all 50 percent or more above ideal body weight, with personal physician documentation of no known major illnesses. Weights were recorded at the beginning and end of a 3-week hospitalization and every 3 months following hospitalization, for up to 2 years. The ratio of waist girth to hip girth (WHR) was used as an index of body fat distribution. A statistical analysis which adjusted for age and weight on admission did not find any association between WHR and weight loss during hospitalization, or at any time up to 2 years after hospital discharge. We conclude that the WHR index of body fat distribution is not a useful prognostic indicator of weight change for severely obese women with refractory obesity.

Adipose Tissue↗
PubMed1993

A task-based statistical model of a worker's exposure distribution: Part II--Application to sampling strategy.

A task-based statistical model of a worker's exposure distribution for an airborne chemical toxicant is applied to estimating the long-term average exposure level, mu. The precision in estimation is represented by the variance of the sample estimator, denoted by Var[mu]. A traditional sampling strategy consists of integratively measuring the 8-hr time-weighted average exposure level on randomly selected workdays, and computing the sample mean; this strategy is termed "simple one-stage cluster sampling," where each 8-hr workday is a cluster of thirty-two 15-min periods. Three alternative strategies involving measurements of 15-min TWAs are examined: simple random sampling of 15-min periods, and stratified random sampling of 15-min periods with proportional allocation by task, and with optimum allocation by task. All four survey designs provide unbiased estimates of mu. However, for a fixed cost, the stratified sampling designs may provide a lower Var[mu] than simple one-stage cluster sampling for less work time monitored.

Air Pollutants, Occupational↗
PubMed2004

An accident waiting to happen: a spatial approach to proactive pedestrian planning.

There are about 75,000 pedestrian crashes in the United States each year. Approximately 5000 of these crashes are fatal, accounting for 12% of all roadway deaths. On college campuses, pedestrian exposure and crash-risk can be quite high. Therefore, we analyzed pedestrian crashes on the campus of the University of North Carolina at Chapel Hill (UNC) as a test case for our spatially-oriented prototype tool that combines perceived-risk (survey) data with police-reported crash data to obtain a more complete picture of pedestrian crash-risk. We use spatial analysis techniques combined with regression models to understand factors associated with risk. The spatial analysis is based on comparing two distributions, i.e. the locations of perceived-risk with police-reported crash locations. The differences between the two distributions are statistically significant, implying that certain locations on campus are perceived as dangerous, though pedestrian crashes have not yet occurred there, and there are actual locations of police-reported crashes that are not perceived to be dangerous by pedestrians or drivers. Furthermore, we estimate negative binomial regression models to combine pedestrian and automobile exposure with roadway characteristics and spatial/land use information. The models show that high exposure, incomplete sidewalks and high crosswalk density are associated with greater observed and perceived pedestrian crash-risk. Additionally, we found that people perceive a lower risk near university libraries, stadiums, and academic buildings, despite the occurrence of crashes.

Accidents, Traffic↗
PubMed2004

The effect of Monte Carlo statistical uncertainties on the evaluation of dose distributions in radiation treatment planning.

This paper discusses the effect of statistical uncertainties present in Monte Carlo (MC) calculated dose distributions on the evaluation of a 'cost function' that expresses the suitability of a treatment plan for the intended treatment. The mathematical derivations given are valid for any 'well-behaved' cost function. The validity of the general expressions is demonstrated using numerical examples. It is shown that random dose uncertainties lead to statistical and systematic uncertainties on the cost function. The balance between the two types of uncertainty and the desired accuracy on the cost function presents a clear criterion for the maximum acceptable MC dose uncertainties. It is demonstrated that it is possible to remove the systematic cost function uncertainty. Finally, it is shown that when the dose distribution is close to a true optimum, MC calculations of the cost function converge to the true result as one over the number of particles simulated, i.e. much faster than the individual dose uncertainties.

Humans↗
PubMed1999

Epidemiological approach to quality assessment in echocardiographic diagnosis.

OBJECTIVES: This study sought to determine whether statistical analysis of a computerized clinical diagnostic database can be used as a tool for quality assessment by determining the contribution of reader bias to variance in diagnostic output. BACKGROUND: In industry, measurement of product uniformity is a key component of quality assessment. In echocardiography, quality assessment has focused on review of small numbers of cases, or prospective determination of reader variability in selected and relatively small subsets. However, diagnostic biases in clinical practice might be discerned utilizing large computerized databases to determine interreader differences in diagnostic prevalence and, with use of appropriate statistical methods, to determine the association of reader selection with diagnostic prevalence independently of other covariates. METHODS: We analyzed 6,026 echocardiograms in a computerized database, read by one of three level 3 (American Society of Echocardiography) readers, for differences in frequency among four coded echocardiographic diagnoses: mitral valve prolapse, valvular vegetations, left ventricular (LV) thrombus, and LV regional wall-motion abnormality. RESULTS: Significant differences (up to fourfold) were found between readers, which persisted after statistical adjustment for those population characteristics, which differed slightly between readers. The low population prevalence of these conditions would have made it unlikely that these interreader differences could be detected by nonstatistical methods. Additionally, chamber dimensions differed between readers and were not normally distributed. CONCLUSIONS: Statistically based quality assessment analysis of computerized clinical databases facilitates ongoing monitoring of interreader bias despite low diagnostic prevalence, and targets opportunities for subsequent quality improvement.

Diagnostic Errors↗
PubMed2005

PAGE: parametric analysis of gene set enrichment.

BACKGROUND: Gene set enrichment analysis (GSEA) is a microarray data analysis method that uses predefined gene sets and ranks of genes to identify significant biological changes in microarray data sets. GSEA is especially useful when gene expression changes in a given microarray data set is minimal or moderate. RESULTS: We developed a modified gene set enrichment analysis method based on a parametric statistical analysis model. Compared with GSEA, the parametric analysis of gene set enrichment (PAGE) detected a larger number of significantly altered gene sets and their p-values were lower than the corresponding p-values calculated by GSEA. Because PAGE uses normal distribution for statistical inference, it requires less computation than GSEA, which needs repeated computation of the permutated data set. PAGE was able to detect significantly changed gene sets from microarray data irrespective of different Affymetrix probe level analysis methods or different microarray platforms. Comparison of two aged muscle microarray data sets at gene set level using PAGE revealed common biological themes better than comparison at individual gene level. CONCLUSION: PAGE was statistically more sensitive and required much less computational effort than GSEA, it could identify significantly changed biological themes from microarray data irrespective of analysis methods or microarray platforms, and it was useful in comparison of multiple microarray data sets. We offer PAGE as a useful microarray analysis method.

Computational Biology↗
PubMed2002

Use of cumulative distribution functions to characterize mass spectra of intact proteins.

The MH+ ions of matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) spectra for a series of closely related but otherwise indistinguishable proteins were analyzed for singularity using a distribution free statistic, the Kolmogorov-Smirnov non-parametric statistic, K-S. The approach allows spectra which might otherwise be taken as identical, to be distinguished. Such analysis of the spectra may lead to a greater understanding of the chemistry of the proteins under investigation. The analysis requires only standard instrumentation. A standard data analysis protocol was developed and applied to generate a normalized cumulative distribution function (NCDF) for each spectrum. Differences in the NCDF for two different spectra were calculated and the maximum difference, deltamax compared to critical values of K-S. Values of deltamax exceeding the critical value of K-S are taken as the basis for rejecting the statistical null-hypothesis and assigning statistical significance to the differences in the two spectra. We have shown that this approach allows spectra of 1:1 mixtures of closely related recombinant proteins to be distinguished from either protein alone, and that mixtures of a 45 kDa protein and a labeled version of that protein can be distinguished from the pure material and from one another at the level of about 25%. In addition, we are able to use this approach to characterize the extent to which a synthetic glyococonjugation reaction has proceeded under circumstances of differing reaction times.

Animals↗
PubMed1970

Statistical theories of success.

The Pareto and the log-normal distributions are commonly used to describe the statistical distribution of success. A detailed comparison of these distributions is made with Lotka's extensive observations on success as measured by rate of publication. These distributions are found to adequately describe the observed distribution only for low and moderate success. Contrariwise, the flat factor analysis of performance recently developed by the author in these Proceedings (59, 1078 (1968)) is shown to give an excellent agreement over the whole range of success. Lotka's data allows a determination of the number of environmental factors.The Pareto distribution does give an excellent agreement with the tail of the success distribution where success is defined as income. An interpretation of this distribution is here presented based upon the expected behavior of entrepreneurs.

Journal Article↗