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PubMed1992

Infant mortality and crisis in Mexico.

Data derived from the Encuesta Nacional de Fecundidad y Salud (ENFES) confirm that overall levels of infant mortality in Mexico have been steadily declining. However, a more specific analysis furnishes evidence that this decline has occurred at varying rates within different social groups, reflecting an increase in social inequalities. The analytical strategy used in this article leads to three basic conclusions: (1) the impact of the economic crisis on infant mortality is reflected not in a reversal of the declining trend but an increase in social inequalities; (2) certain variables universally accepted as determinants of infant mortality, such as mother's education, seem nonsignificant for some social sectors; and (3) certain biodemographic characteristics assumed to have a uniform mortality-related behavior vary among sectors, suggesting that even these constants are determined by social factors.

Educational Status↗
PubMed2000

Microtubules switch occasionally into unfavorable configurations during elongation.

Tubulin assembles to form a range of structures that differ by their protofilament and monomer helix-start numbers. The microtubule lattice is believed to accommodate these different configurations by skewing the protofilaments so that the lateral interactions between tubulin subunits are maintained. Here, we present the characterization of 14 types of microtubules, including six novel ones, through an extensive analysis of microtubules assembled in vitro from pure tubulin. Although the six new types represented only 1 % of the total length of the population examined ( approximately 17 mm), they define the limits of microtubule structure and assembly. Protofilament skewing is restricted to within +/-2 degrees. Outside this range, the restoring force induced by the skewed protofilaments is compensated by a longitudinal shift (less than +/-0.2 nm) between adjacent protofilaments. Configurations with theoretical protofilament skew angles larger than +/-4 degrees or that necessitate larger modifications of the microtubule surface lattice were not observed. Analysis of the microtubule types distribution reveals that it is sharply peaked around the less skewed conformations. These results indicate that both the flexibility of the protofilaments and the strength of their lateral interactions restrict the range of structures assembled. They also demonstrate that growing microtubules can occasionally switch into energetically unfavorable configurations, a behavior that may account for the stochastic nature of catastrophes.

Animals↗
PubMed2006

Spatially uniform sampling in 4-D EPR spectral-spatial imaging.

Four-dimensional EPR imaging involves a computationally intensive inversion of the sampled Radon transform. Conventionally, N-dimensional reconstructions have been carried out with N-1 stages of 2-D backprojection to exploit a dimension-dependent reduction in execution time. The huge data size of 4-D EPR imaging demands the use of a 3-stage reconstruction each consisting of 2-D backprojections. This gives three orders of magnitude reduction in computation relative to a single stage 4-D filtered backprojection. The multi-stage reconstruction, however, requires a uniform angular sampling that yields an inefficient distribution of gradient directions. We introduce a solution that involves acquisition of projections uniformly distributed in solid angle and reconstructs in three 2-D stages with the spatial uniform solid angle data set converted to uniform linear angular projections using 2-D interpolation. Images were taken from the two sampling schemes to compare the spatial resolution and the line width resolution. The degradation in the image quality due to the additional interpolation was small, and we achieved approximately 30% reduction in data acquisition time.

Algorithms↗
PubMed2005

Are there predictors for the outcome of a PGE1 treatment in peripheral arterial disease with critical limb ischaemia?

BACKGROUND: In a multivariate retrospective analysis was conducted to examine whether and to what extent PGE1 is therapeutically effective and whether there are predictors of response. PATIENTS AND METHODS: The examination included 767 patients (448 women, 319 men) of a mean age of 71.2 years and with peripheral arterial disease (PAD) having existed for 44.7 months on the average. They suffered from critical limb ischaemia (Fontaine's stages III/IV) and showed average tcpO2 values at the instep of 2 mmHg (0 to 15) and average systolic malleolar artery pressures of 18 mmHg (0 to 35 mmHg). Between 1989 and 2001, the patients had received treatments in hospital with i.v. PGE1 doses (2x20 microg or 1x60 microg/day) for an average of 34.2 days (mean of responder- and non-responder group). Patients were called responders when pain had markedly decreased or disappeared, necroses had been reduced or healed completely, and vascular reconstruction, PTA or amputations were not necessary. RESULTS: The clinical analysis showed 82.4% of the patients to be responders and 17.6% to be non-responders. It was demonstrated that the outcome of the therapy was not dependent on the supine or sitting tcpO2, the malleolar artery pressure, the patient's age or sex, the duration of PAD, the number or kind of concomitant diseases, the patient's general condition, the localization and number of vascular occlusions, the kind of prior therapy, or the number of previous amputations, although differences in some of the parameters, while clinically irrelevant, were found to be statistically significant. They are not predictors of the outcome of a PGE, therapy. CONCLUSIONS: Even in extremely bad haemodynamic situations at the beginning of a therapy (malleolar artery pressures from 0 to 35 mmHg, tcpO2 0 to 15 mmHg, multilevel occlusive disease, multiple previous operations and concomitant diseases), PGE, therapies of more than 20 days - on the average 35.6 days (mean of responder group) - duration allow clinically relevant positive results to be achieved.

Age Distribution↗
PubMed2005

Application of the compound probability density function for characterization of breast masses in ultrasound B scans.

The compound probability density function (pdf) is investigated for the ability of its parameters to classify masses in ultrasonic B scan breast images. Results of 198 images (29 malignant and 70 benign cases and two images per case) are reported and compared to the classification performance reported by us earlier in this journal. A new parameter, the speckle factor, calculated from the parameters of the compound pdf was explored to separate benign and malignant masses. The receiver operating characteristic curve for the parameter resulted in an A(z) value of 0.852. This parameter was combined with one of the parameters from our previous work, namely the ratio of the K distribution parameter at the site and away from the site. This combined parameter resulted in an A(z) value of 0.955. In conclusion, the parameters of the K distribution and the compound pdf may be useful in the classification of breast masses. These parameters can be calculated in an automated fashion. It should be possible to combine the results of the ultrasonic image analysis with those of traditional mammography, thereby increasing the accuracy of breast cancer diagnosis.

Algorithms↗
PubMed2005

Maximum likelihood estimation of haplotype effects and haplotype-environment interactions in association studies.

The associations between haplotypes and disease phenotypes offer valuable clues about the genetic determinants of complex diseases. It is highly challenging to make statistical inferences about these associations because of the unknown gametic phase in genotype data. We describe a general likelihood-based approach to inferring haplotype-disease associations in studies of unrelated individuals. We consider all possible phenotypes (including disease indicator, quantitative trait, and potentially censored age at onset of disease) and all commonly used study designs (including cross-sectional, case-control, cohort, nested case-control, and case-cohort). The effects of haplotypes on phenotype are characterized by appropriate regression models, which allow various genetic mechanisms and gene-environment interactions. We present the likelihood functions for all study designs and disease phenotypes under Hardy-Weinberg disequilibrium. The corresponding maximum likelihood estimators are approximately unbiased, normally distributed, and statistically efficient. We provide simple and efficient numerical algorithms to calculate the maximum likelihood estimators and their variances, and implement these algorithms in a freely available computer program. Extensive simulation studies demonstrate that the proposed methods perform well in realistic situations. An application to the Carolina Breast Cancer Study reveals significant haplotype effects and haplotype-smoking interactions in the development of breast cancer.

Algorithms↗
PubMed2006

Surnames in Western Europe: a comparison of the subcontinental populations through isonymy.

We studied the isonymic structure of Western Europe using the distributions of 26.2 million surnames in 8 countries, 125 regions and 2094 towns of the Subcontinent. We found that, for the whole of Western Europe, Nei's distance was correlated with geographic distance (r=0.610+/-0.009). It was observed that at long geographic distances the isonymyc distance stays below linearity and tends to become asymptotic, and this was attributed to long distance migration. A dendrogram of the125 regions was built and the clusters identified by the dendrogram are almost exactly coincident with the nations of the Subcontinent. Random inbreeding calculated from isonymy, F(ST), was highest in Spanish regions, and lowest in France. The geographical distribution of alpha in 2094 towns, high in the Center and East of the Subcontinent and lower in Spain, is compatible with the settlement of subsequent waves of migrants moving from the West and from the South toward the centre of the Continent. The present surname structure of Western Europe is strictly linked to local languages.

Consanguinity↗
PubMed2000

Management of data used in clinical trials which is unevenly distributed at baseline.

In this study, 63 healthy adult males were selected for participation in a clinical trial. After initial screening to determine their suitability for participation in the trial, an appointment was scheduled for a professional prophylaxis to derive baseline data and to instruct volunteers in the use of a standard oral hygiene regimen for the trial. Volunteers were then randomly assigned to test and control groups. Follow-up appointments were scheduled two and four weeks thereafter for collection of data. The presence of dental plaque and calculus was assessed at each appointment. Data was to be analysed by using a Student's 't'-test for paired data, but significant differences in the plaque scores were found between the test and control groups at baseline. As a result, the data could not be analysed in this way to obtain a meaningful result. An initial scatter plot of the data revealed six subjects whose plaque scores varied considerably from the group. The aim of this analysis was to evaluate how two different approaches to statistical analysis of data in which significant differences between test and control groups at baseline might affect the inferences drawn from the data. Reasons for significant differences in baseline data in randomly selected groups of volunteers were considered, as well as methods of avoiding this situation. Suggestions on the management of situations in which databases significantly differ include the elimination of 'outliers' and the use of techniques like the Standard Normal Deviate (SND). The data for this study were analysed using these techniques. Although no statistical differences were identified between the two methods of analysis, numerical differences were evident which altered with the type of analysis used. It was concluded that techniques for transformation of the data, like those used in this study, made no difference to the results of subsequent statistical analysis by comparison with the original data set. The influence of sample selection and analysis of data on the results of clinical trials are discussed. The difficulties in interpretation of the results of statistical analyses were highlighted. The influence of imbalances in the data set on the interpretation of the results of statistical analysis was shown to be minimal in this clinical trial.

Adult↗
PubMed2004

Dynamic response of Permian brachiopod communities to long-term environmental change.

The fossil record preserves numerous natural experiments that can shed light on the response of ecological communities to environmental change. However, directly observing the community dynamics of extinct organisms is not possible. As an alternative, neutral ecological models suggest that species abundance distributions reflect dynamical processes like migration, competition, recruitment, and extinction. Live-dead comparisons suggest that such distributions can be faithfully preserved in the rock record. Here we use a maximum-likelihood approach to show that brachiopod (lamp shell) abundance distributions from four temporally distinct ecological landscapes from the Glass Mountains, Texas (of the Permian period), exhibit significant differences. Further, all four are better fitted by zero-sum multinomial distributions, characteristic of Hubbell's neutral model, than by log-normal distributions, as predicted by the traditional ecological null hypothesis. Using the neutral model as a guide, we suggest that sea level fluctuations spanning about 10 Myr altered the degrees of isolation and exchange among local communities within these ecological landscapes. Neither these long-term environmental changes nor higher-frequency sea level fluctuations resulted in wholesale extinction or major innovation within evolutionary lineages.

Animals↗
PubMedDate not supplied

[Is running associated with premature degenerative arthritis of the hip? A systematic review].

AIM: The study was performed to investigated correlations between running and degenerative arthritis of the hip, according to the principles of evidence-based medicine. METHOD: The database Medline, the Cochrane Library, the centre for Evidence Based Medicine in Oxford and the sports science database Spolit, Spofor and Spowis were scanned systematically for the keywords "arthritis, osteoarthritis, degenerative, hip, sports, running, jogging, walking". RESULTS: 10 retrospective case control studies and 3 prospective studies were included for further analysis. The clinical examinations reported in the prospective studies did not reveal a significant difference between runners and non-runners. In one study a slightly increased risk for signs of arthritis at the X-ray was found in runners below 50 years with a very high mileage. No increased risk for degenerative arthritis was reported in most of the retrospective studies. A few authors of retrospective studies reported a slightly to moderately increased risk. The pooled estimate of the included studies showed a slightly increased risk for degenerative arthritis in runners (pooled OR 1.24 95 % CI 0.87-1.85). However, the increased risk did not reach a level of statistical significance. The graphic analysis of the data with the technique of the funnel plot gives an OR of 1.04. CONCLUSION: There is no evidence that running is associated with an increased risk for degenerative arthritis of the hip. There is no evidence for a different risk in men and women.

Case-Control Studies↗
PubMed2003

Common CYP21 gene mutations in Czech patients and statistical analysis of worldwide mutation distribution.

CYP21 gene molecular analysis was performed to determine the mutational analysis of 87 unrelated Czech patients with different forms of steroid 21-hydroxylase deficiency. Eight of the most common point mutations (intron 2 splice, P30L, 8 bp deletion in exon 3, I172N, V281L, Q318X, R356W, P453S) were analyzed using Amplification-created restriction site method. Cluster in exon 6 mutation was analyzed using allele-specific oligonucleotide hybridisation. Deletions and conversions were screened by modification of an sequence specific oligonucleotides hybridisation. The most frequent mutation in Czech patients was intron 2 splice mutation (45.4%). The comparison of mutation frequencies was made among Czech and European population (high frequency of intron 2 splice, 8bp deletion, P30L, P453S and low frequency of deletions/conversions in Czech population) and among Czech and different regions worldwide (low frequency of deletions/large gene conversions, V281L, R356W, high frequency of intron2, 8bp deletion, P30L and P453S in Czech population). We compared common mutation frequencies of different regions worldwide (North and South America, Asia, North Africa, Europe). Significant differencies in selected regions were determined by ANOVA statistical analysis (One-sample t-test, confidence interval) at value of p<0.05.

Adolescent↗
PubMed1998

Characterization of submicron systems via optical methods.

As a means of addressing the issues of drug delivery, submicron colloidal systems have become increasingly used as pharmaceutical formulations. Accurately characterizing physical properties of the constituent particulates present in these systems is an indispensable activity. However, measuring descriptors such as particle size distribution and surface potential presents an experimental challenge. This paper describes the physical basis for a number of optically based techniques that are useful in this task. In addition, the caveats and benefits of these methods are discussed and reference is made to their use in the examination of various multiphase systems such as liposomes, nanoparticles, and emulsions.

Chemical Phenomena↗
PubMed1997

On the degree of solute mixing in liver models of drug elimination.

One of the fundamental differences between various liver models regards the underlying assumptions on the intrahepatic mixing process. A model-independent method for the evaluation of the departure from the perfectly mixed system is proposed which is based on an application of the relative entropy concept to hepatic transit time distributions of intravascular markers. This approach provides a measure of the distance between two probability distributions. Available data measured in isolated perfused livers indicate that sinusoidal solute mixing is nearly optimal. The suggestion of maximum mixedness in the liver may explain the discrepancy between the apparent validity of the venous equilibrium model and the physiological irrelevance of the underlying well-stirred assumption. In terms of the dispersion model the results are in accordance with the model equation obtained for mixed boundary conditions.

Entropy↗
PubMed2001

Does the manic/mixed episode distinction in bipolar disorder patients run true over time?

OBJECTIVE: The authors sought to determine whether the manic/mixed episode distinction in patients with bipolar disorder runs true over time. METHOD: Over an 11-year period, the observed distribution of manic and mixed episodes (N=1,224) for patients with three or more entries in the management information system of a community mental health center (N=241) was compared to the expected distribution determined by averaging 1,000 randomly generated simulations. RESULTS: Episodes were consistent (all manic or all mixed) in significantly more patients than would be expected by chance. CONCLUSIONS: These data suggest a pattern of diagnostic stability over time for manic and mixed episodes in patients with bipolar disorder. Careful prospective studies of this issue are needed.

Bipolar Disorder↗
PubMed2006

[Oral health of institutionalized elderly in the eastern zone of São Paulo, Brazil, 1999].

The objective was to verify oral health conditions in institutionalized elderly people in the city of São Paulo, Brazil, through epidemiological analysis. The sample consisted of 293 subjects and was stratified according to age (65-74 years and over 75) and gender. Epidemiological analysis was conducted according to WHO criteria to determine prevalence of oral disease. Chi-square and Mann-Whitney tests were used to check differences between strata. Of the subjects evaluated, 64.8% were women and 65.2% were over 75 years old. DMFT was 30.8 with tooth loss of 96.3%, and this percentage was statistically greater for women (97.0%); 94.7% showed calculus as a major degree of periodontal condition, and only 1.8% presented healthy periodontal conditions and 33.3% presented loss of attachment ranging from 6 to 8 mm. Some 48.1% used total upper and 22.5% total lower prostheses. Edentulism was 68.3%. The data indicate unsatisfactory clinical conditions, as shown by the high CPO-D index and high percentage of edentulism.

Age Distribution↗
PubMed2006

Stochastic kinetics description of a simple transcription model.

We study a stochastic model of transcription kinetics in order to characterize the distributions of transcriptional delay and of elongation rates. Transcriptional delay is the time which elapses between the binding of RNA polymerase to a promoter sequence and its dissociation from the DNA template strand with consequent release of the transcript. Transcription elongation is the process by which the RNA polymerase slides along the template strand. The model considers a DNA template strand with one promoter site and n nucleotide sites, and five types of reaction processes, which we think are key ones in transcription. The chemical master equation is a set of ordinary differential equations in 3(n) variables, where n is the number of bases in the template. This model is too huge to be handled if n is large. We manage to get a reduced Markov model which has only 2n independent variables and can well approximate the original dynamics. We obtain a number of analytical and numerical results for this model, including delay and transcript elongation rate distributions. Recent studies of single-RNA polymerase transcription by using optical-trapping techniques raise an issue of whether the elongation rates measured in a population are heterogeneous or not. Our model implies that in the cases studied, different RNA polymerase molecules move at different characteristic rates along the template strand. We also discuss the implications of this work for the mathematical modeling of genetic regulatory circuits.

Algorithms↗