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Beat-to-beat stroke volume estimation from aortic pressure waveform in conscious rats: comparison of models.

Several methods for estimating stroke volume (SV) were tested in conscious, freely moving rats in which ascending aortic pressure and cardiac flow were simultaneously (beat-to-beat) recorded. We compared two pulse-contour models to two new statistical models including eight parameters extracted from the pressure waveform in a multiple linear regression. Global as well as individual statistical models gave higher correlation coefficients between estimated and measured SV (model 1, r = 0.97; model 2, r = 0.96) than pulse-contour models (model 1, r = 0.83; model 2, r = 0.91). The latter models as well as statistical model 1 used the pulsatile systolic area and thus could be applied to only 47 +/- 17% of the cardiac beats. In contrast, statistical model 2 used the pressure-increase characteristics and was therefore established for all of the cardiac beats. The global statistical model 2 applied to data sets independent of those used to establish the model gave reliable SV estimates: r = 0.54 +/- 0.07, a small bias between -8% to +10%, and a mean precision of 7%. This work demonstrated the limits of pulse-contour models to estimate SV in conscious, unrestrained rats. A multivariate statistical model using eight parameters easily extracted from the aortic waveform could be applied to all cardiac beats with good precision.

Animals↗

Structural diversity of bacterial communities in a heavy metal mineralized granite outcrop.

This laboratory study of a variably mineralized and hydrothermally altered granite outcrop investigated the influences of rock-surface chemistry and heavy metal content on resident bacterial populations. Results indicated that elevated heavy metal concentrations had a profound impact on bacterial community structure, with strong relationships found between certain ribotypes and particular chemical/heavy metal elements. Automated ribosomal intergenic sequence analysis (ARISA) was used to assess the nature and extent of bacterial diversity, and this was combined with chemical analysis and multivariate statistics to identify the main geochemical factors influencing bacterial community structure. A randomization test revealed significant changes in bacterial structure between samples, while canonical correspondence analysis (CCA) related each individual ARISA profile to linear combinations of the chemical variables (mineralogy, major element and heavy metal concentrations) revealing the geochemical factors that correlated with changes in the ARISA data. anova was performed to further explore interactions between individual ribotypes and chemical/heavy metal composition, and revealed that a high proportion of ribotypes correlated significantly with heavy metals.

Bacteria↗

Race independently predicts prostate specific antigen testing frequency following a prostate carcinoma diagnosis.

BACKGROUND: The goals of the current study were to describe patterns of prostate specific antigen (PSA) surveillance for prostate carcinoma progression in a community-based cohort of patients and to identify independent clinical and sociodemographic factors that predict the frequency of surveillance. METHODS: Patients diagnosed with localized prostate carcinoma from October 1, 1991 to December 31, 1992 in New Haven and Hartford, Connecticut, were identified. Data were collected through standardized outpatient medical record review. Multivariate statistical methods were used to determine the factors that independently predicted the frequency of surveillance. RESULTS: Six hundred fifty-eight men with localized prostate carcinoma were included in the cohort. Forty-five percent of all patients were tested at least once annually, and 69% were tested at least once every 2 years. Multivariate models indicated that African American men were half as likely as Caucasian men to receive annual testing (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.24-0.97). Men diagnosed at age 70 years or older were 38% less likely to have annual testing than men diagnosed between the ages of 65 and 69 (OR, 0.62; 95% CI, 0.41-0.94). A higher Gleason score and PSA at presentation also were associated independently with higher rates of annual PSA surveillance. CONCLUSIONS: Postdiagnosis PSA surveillance is common, although not universal. African American men were at significantly greater risk for receiving less frequent testing compared with Caucasian men. This disparity in access to care may explain, in part, previously observed racial differences in survival in prostate carcinoma. Further research is needed to identify the reasons for the racial disparity in PSA surveillance and to design interventions to lessen these differences.

Adult↗

Computational methods to rationalize experimental strategies in biocatalysis.

Computational methods are more and more widely applied in biocatalysis to gain rational guidelines, to orient experimental planning and, ultimately, to avoid expensive and time-consuming experiments. In this respect, molecular modelling, multivariate statistical analysis and chemometrics in general are useful computational tools, although they follow completely different investigative approaches.

Biotechnology↗

Favorable and unfavorable morphological prognostic factors in peripheral adenocarcinoma of the lung 3 cm or less in diameter.

Many small adenocarcinomas can be detected as a result of recent advances in diagnostic radiology. Since the histological and biological heterogeneity of adenocarcinoma often makes it difficult to predict the outcome of operated patients, clarifying the morphological prognostic factors of the tumor is indispensable to the selection of appropriate treatment. We examined 200 cases of adenocarcinoma of the lung 3 cm or less in diameter (T1). Tumor size, tumor cell characteristics, growth pattern, characteristics of fibrosis, vessel and stromal invasion, and metastasis were evaluated to define favorable and unfavorable morphological prognostic factors by univariate and multivariate statistical analysis. There were no deaths in the 66 cases with more than a 75% of lepidic growth component defined as a region of tumor cells growing along alveolar walls and without stromal invasion, central focus of fibrosis 5 mm or less in maximum diameter, or no elastic fiber framework destruction by tumor cells. Multivariate analysis to investigate unfavorable factors revealed that vascular invasion (P<0.001) and a greater than 25% papillary growth component (P=0.043) were the most significant determinants of an unfavorable outcome. The favorable and unfavorable factors demonstrated in this study will be of great value in selecting the treatment of patients with small peripheral adenocarcinoma of the lung.

Adenocarcinoma↗

Case finding for patients at risk of readmission to hospital: development of algorithm to identify high risk patients.

OBJECTIVE: To develop a method of identifying patients at high risk of readmission to hospital in the next 12 months for practical use by primary care trusts and general practices in the NHS in England. DATA SOURCES: Data from hospital episode statistics showing all admissions in NHS trusts in England over five years, 1999-2000 to 2003-4; data from the 2001 census for England. Population All residents in England admitted to hospital in the previous four years with a subset of "reference" conditions for which improved management may help to prevent future admissions. DESIGN: Multivariate statistical analysis of routinely collected data to develop an algorithm to predict patients at highest risk of readmission in the next 12 months. The algorithm was developed by using a 10% sample of hospital episode statistics data for all of England for the period indicated. The coefficients for 21 most powerful (and statistically significant) variables were then applied against a second 10% test sample to validate the findings of the algorithm from the first sample. RESULTS: The key factors predicting subsequent admission included age, sex, ethnicity, number of previous admissions, and clinical condition. The algorithm produces a risk score (from 0 to 100) for each patient admitted with a reference condition. At a risk score threshold of 50, the algorithm identified 54.3% of patients admitted with a reference condition who would have an admission in the next 12 months; 34.7% of patients were "flagged" incorrectly (they would not have a subsequent admission). At risk score threshold levels of 70 and 80, the rate of incorrectly "flagged" patients dropped to 22.6% and 15.7%, but the algorithm found a lower percentage of patients who would be readmitted. The algorithm is made freely available to primary care trusts via a website. CONCLUSIONS: A method of predicting individual patients at highest risk of readmission to hospital in the next 12 months has been developed, which has a reasonable level of sensitivity and specificity. Using various assumptions a "business case" has been modelled to demonstrate to primary care trusts and practices the potential costs and impact of an intervention using the algorithm to reduce hospital admissions.

Aged↗

Revision total knee arthroplasty: 1990 through 2002. A review of the Finnish arthroplasty registry.

BACKGROUND: National and regional arthroplasty registries have been used to study the results of primary total knee arthroplasties. The purpose of this paper was to present the results of revision total knee replacements and describe predictors of survival of those replacements, with repeat revision as the end point. METHODS: The nationwide Finnish Arthroplasty Registry included 2637 revision total knee arthroplasties from 1990 through 2002. Survivorship of the revision total knee arthroplasties was analyzed, with repeat revision as the end point. The survivorship analyses comprised evaluations of the proportional hazards assumption followed by calculations of univariate and multivariate statistics and model diagnostics as appropriate. RESULTS: The survival rate following the revision total knee arthroplasties was 95% (95% confidence interval, 94% to 96%) at two years (1874 knees), 89% (95% confidence interval, 88% to 90%) at five years (944 knees), and 79% (95% confidence interval, 78% to 81%) at ten years (141 knees). Multivariate regression analysis showed the most significant predictors of prosthetic survival to be the age of the patient and the life in service of the primary total knee replacement (that is, the time between the primary total knee replacement and the revision). Survivorship was also significantly predicted by the year of the first revision total knee arthroplasty and the reason for the revision. CONCLUSIONS: An age greater than seventy years, revision five years or more after the primary arthroplasty, and absence of patellar subluxation are positive indicators of survival of a revision total knee replacement. We believe that normal aging as well as the deconditioning effect of disease (osteoarthritis and rheumatoid arthritis) and its treatment (primary total knee replacement) may lead to a reduced activity level, which, together with a presumed reluctance to operate on elderly patients, protects against repeat revisions. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

Adolescent↗

The clinical and prognostic relevance of grading in intracranial ependymomas.

The clinical relevance of grading in ependymomas is almost always regarded as controversial. According to the classification of brain tumours revised by the World Health Organization (WHO) in 1993, brain tumours of ependymal origin are differentiated as subependymomas Grade I, ependymomas Grade II, and anaplastic (malignant) ependymomas Grade III. The purpose of the present retrospective study of 126 patients with intracranial ependymomas was to assess the clinical and prognostic significance of the topical classification and grading system by a uni- and multivariate statistical analysis. 87 Grade II ependymomas were predominantly located in the midline and in the fourth ventricle, whereas 39 anaplastic ependymomas Grade III were most often found in the cerebral hemispheres. Excluding the localization-linked operative mortality, progression-free survival (PFS) was significantly dependent on the histological grading. Median PFS time was 7.5 years in Grade II, but only 1.5 years in Grade III ependymomas. Stratifying for the two time intervals 1951-1970 and 1971-1990, and excluding the operative mortality, a multivariate Cox' model analysis of the covariates age, localization, grading, extent of surgery, and radiation therapy revealed that only the histological grading and radiation therapy had a significant impact on PFS. Thus, the WHO grading system has a statistically significant relevance for the long-term prognosis of intracranial ependymomas. However, the therapeutic management including radical tumour resection and additional local irradiation should be independent of the grading.

Adolescent↗

Wilms' tumor: prognostic factors for patients without metastases at diagnosis: results of the National Wilms' Tumor Study.

Multivariate statistical analyses are used to evaluate a wide range of factors in predicting relapse and survival for 429 children enrolled in the National Wilms' Tumor Study. Anaplastic or sarcomatous histology, specimen weight over 250 grams, positive regional lymph nodes, treatment with only a single drug and age over two years are the most important predictors of relapse. The first three factors also predict mortality. Laterality, capsular penetration, intrarenal vascular invasion, direct regional extension and operative spillage have lesser effects which do not contribute significantly to the multivariate prediction equations, while sex, race and the presence of a tumor thrombus in the renal vein have essentially no effect. Treatment with combination chemotherapy is confirmed to be efficacious regardless of what prognostic factors are operating. A statistical model allows prediction of relapse and death for each of 24 patient subgroups, with the estimates of percentage relapsed ranging from 3% to 100%.

Child↗

Similarity pattern analysis in mutational distributions.

The validity and applicability of the statistical procedure - similarity pattern analysis (SPAN) - to the study of mutational distributions (MDs) was demonstrated with two sets of data. The first was mutational spectra (MS) for 697 GC to AT transitions produced with eight alkylating agents (AAs) in the lacI gene of Escherichia coli. The second was a recently summarized data on the distributions of 11562 spontaneous, radiation- and chemical-induced forward mutations in the ad-3 region of heterokaryon 12 of Neurospora crassa. They were analyzed as large two-way contingency tables (CTs) where two kinds of profiles were compared: site (or genotypic class) profiles and origin (or mutagen) profiles. To measure similarity (homogeneity) between any pair of profiles, the relevant sufficient statistics, Kastenbaum-Hirotsu squared distance (KHi(2)), was used. Collapsing the similar profiles into distinct internally homogeneous clusters named 'collapsets' revealed their similarity pattern. To facilitate the procedure, the computer program, COLLAPSE, was elaborated. The results of SPAN for the lacI spectra were found comparable with the results of their previous analysis with two multivariate statistical methods, the factor and cluster analyses. In the ad-3 data set, five collapsets were revealed among origin profiles (OPs): (I) ENU = 4NQO = 4HAQO = FANFT = SQ18506; (II) AF-2 = EI = MMS = DEP; (III) ETO = UV; (IV) AHA = PROCARB; and (V) He ions = protons. Moreover, the previous observation that MDs are dose-dependent was confirmed for X-ray-induced MDs. Profiles induced with the low doses of X-rays are similar to that induced with 85Sr, and profiles induced with the medium X-ray doses to those induced with protons and He ions. Evaluated similarities appear to be rather reasonable: mutagens with similar mode of action induce similar MDs. Similarity pattern revealed among genotypic class profiles (GCPs) seems to be also interpretable. When supplemented with descriptive cluster analysis, SPAN appears to be a fruitful methodology in MS analysis.

Chromosome Mapping↗

Correlation between multielement stable isotope ratio and geographical origin in Peretta cows' milk cheese.

The aim of this study was to characterize the isotopic composition and protect "Peretta" cows' milk cheese, a typical product of Sardinia, against other cheeses of the same appearance sold under the same name, but made of raw materials from northern Europe. The study was concerned with 3 types of cheese: those produced in local dairies from milk from free-grazing or pasture-grazing cows in Sardinia (local dairy product), cheeses made on an industrial scale from milk produced by intensive farming in Sardinia (factory cheese), and cheeses made with raw materials imported from other countries (imported product). To distinguish the Sardinian cheeses from the imported product, the stable isotope ratios 13C/12C, 15N/14N, D/H, 34S/32S, and (18)O/(16)O were used. Determination of the isotopic data delta13C, delta15N, delta2H, and delta34S was performed in the casein fraction, whereas delta(18)O and delta13C were determined in the glycerol fraction. Measurements were performed by isotope ratio mass spectrometry. A comparison between mean values of the isotope ratios by statistical analysis (ANOVA and Tukey's test) showed that the greatest difference between the 3 types of cheese (local dairy, factory, and imported products) was in the 13C/12C, 34S/32S, and (18)O/(16)O isotope ratios. In the other parameters, either no differences (delta15N) or minimal differences (delta2H) were found. Evaluation of the data by multivariate statistical analysis (principal component analysis and hierarchical cluster analysis) revealed that the isotope characteristics of the factory products were similar to those of the cheeses produced from imported raw materials, whereas a difference was found between the local dairy-produced cheeses and the products in the other 2 categories.

Analysis of Variance↗

Prognostic factors related to survival and complication-free times in airmen medically certified after coronary surgery.

This study was designed to identify prognostic factors for survival and complication-free times among airmen who had regained their medical certificate after coronary bypass surgery. Airmen who had petitioned the Federal Aviation Administration for a special issuance of medical certification to fly because they have had coronary bypass surgery were identified and followed retrospectively from 1970 to the end of 1980. There were 261 airmen in the study population. Demographic, medical, and prognostic information were collected on each airmen before and after surgery. Univariate and multivariate statistical methods were used in analysing the data. From the univariate analysis, presurgery diastolic blood pressure and coffee history, and postsurgery coffee history were identified as being related to complication-free time. Diagnosis for surgery, smoking history, and development of complications were identified as being related to survival after coronary bypass surgery. From the multivariate analysis, four prognostic factors: postsurgery serum cholesterol, number of grafts, postsurgery serum triglyceride, and postsurgery alcohol history were identified for complication-free time. It was concluded that using pre- and post-surgery information can help determine the long term survivors and those who will stay complication-free 11 years after coronary bypass surgery.

Aerospace Medicine↗

Differential diagnosis of borderline and invasive serous cystadenocarcinomas of the ovary by computerized interactive morphometric analysis of nuclear features.

Whether borderline serous tumors of the ovary can be differentiated from invasive serous cystadenocarcinomas by morphometric analysis of nuclear features of the neoplastic epithelium was examined. Multiple descriptors extracted from nuclear tracings and intranuclear gray-level analysis of argyrophilic nucleolar organizer regions were evaluated in 11 borderline and 18 invasive tumors using computerized interactive morphometric analysis. These descriptors included: nuclear area and perimeter; number, area, and perimeter of argyrophilic nucleolar organizer regions; standard deviations of these findings; and a size distribution of nuclear areas in discrete classes. Multivariate statistical analysis showed the internal consistency of the two groups in terms of physical descriptors and the discriminating value of the parameters of nuclear size and pleomorphism (independently of nucleolar organizer region parameters). The results indicated that interactive morphometric analysis of nuclear features, combined with appropriate statistical methods, could be used to distinguish between these tumors.

Cell Nucleus↗

A preprocessing method for improving data mining techniques. Application to a large medical diabetes database.

The Knowledge Discovery in Databases (KDD) methodology seems to be attractive on the analyze of large clinical databases. In the KDD process, the preprocessing step (data cleaning and handling of missing values) is paramount since it conditions the quality of the results obtained by data mining procedures and represents about 80% of the whole project time. The aims of the present study were to analyze this step and provide tools to handle inconsistent data and missing values. We have broken down the process into 3 main stages: data cleaning--explanatory study of missing values--choice of the procedure used for handling missing values. The data cleaning stage was based on a system of logical rules to correct mistakes and on cluster analysis to discard the poorly filled files. The missing-data mechanism was analyzed by means of multivariate statistical procedures. Two methods to deal with missing values were compared: imputation by the most common value (mode) and imputation using decision trees. This study was performed on a large medical diabetes database (23,601 patients) including numerous missing values. A system of logical rules allowed to correct mistakes on essential parameters (for example, the type of diabetes). Cluster analysis allowed to identify 10% of poorly filled files. After multivariate analysis, the missing-data mechanism could be considered as random. For variables with low number of missing values (< 10%) and categories (< 4), imputation using decision trees provided better results than imputation by mode.

Data Interpretation, Statistical↗

Can contrast-enhanced MR imaging predict survival in breast cancer?

PURPOSE: To investigate the value of pre-operative contrast-enhanced MR imaging (CE-MRI) in predicting the disease-free and overall survival in breast cancer. MATERIAL AND METHODS: The study population consisted of 50 consecutive patients with histopathologically verified primary breast cancer who pre-operatively underwent CE-MRI examination between 1992 and 1993. A three-time point MR examination was performed where the enhancement rates (C1 and C2), signal enhancement ratio (SER=C1/C2) and washout (W=C1-C2) were calculated. The relation of these MR parameters to disease-free and overall survival was investigated. The median follow-up for surviving patients was 95 months. Univariate and multivariate statistical analyses were performed to evaluate the impact of different factors on prediction of survival. RESULTS: Of the MR parameters examined at univariate analysis, increased C1 (p=0.029), W (p=0.0081) and SER values (p=0.0081) were significantly associated with shorter disease-free survival, and only C1 (p=0.016) was related significantly to overall survival. Multivariate analysis for disease-free survival showed that the SER (p=0.014) and tumor size (p=0.001) were significant and independent predictors. Age (p=0.003), lymph node status (p=0.014), tumor size (p=0.039) and proliferating cell nuclear antigen index (p=0.053) remained independently associated with overall survival at multivariate analysis. C1 was not confirmed as an independent predictor of overall survival. CONCLUSION: Our findings support the presumption that CE-MRI is useful in predicting the disease-free survival in patients with breast cancer.

Breast Neoplasms↗

Growth in extremely low birth weight infants up to three years.

OBJECTIVE: To evaluate postnatal growth of extremely low birth weight infants (ELBW, <1,000 g) until 36 months of corrected age (CA), and to relate growth outcome to anthropometric parameters at birth, sex, fetal growth status (small or appropriate for gestational age--SGA/AGA), period of admission and major perinatal events. STUDY DESIGN/METHOD: Weight (Wt), height (Ht) and head circumference (HC) were assessed in 159 ELBW infants. Data were standardized with Z-scores following Usher and McLean and Sempe growth curves. Uni- and multivariate statistical analysis were performed. RESULTS: The mean birth weight was 851.2+/-116.5 g. Z-scores decreased from birth to term, at a deeper rate for AGA than for SGA infants (p<0.005 for Ht, Wt, and HC). Between term and 36 months, growth was better in SGA compared with AGA infants (p=0.003 for Ht). Multivariate analysis showed that anthropometric parameters at birth were positive determinants for Wt, Ht and HC at term, and also for Wt and Ht at 36 months CA (Z-scores). Oxygen therapy after 36 weeks of post-conceptional age was a negative determinant influencing growth at 36 months CA (Z-scores). CONCLUSIONS: Significant catch-up growth took place between birth and 36 months, which was greater for SGA than for AGA infants. Anthropometric parameters at birth and oxygen therapy at 36 weeks post-conceptional age are the main predictive factors for growth at 36 months CA.

Birth Weight↗

Venous coronary artery bypass surgery. A 15-year follow-up study.

BACKGROUND: Although the long-term results of isolated venous coronary artery bypass surgery are well known, there are few multivariate statistical data on such patient groups. METHODS AND RESULTS: We report on 428 consecutive patients, 383 men and 45 women with a mean age of 52.6 years, who underwent isolated venous aortocoronary bypass graft surgery with or without left ventricular aneurysm surgery between April 1, 1976, and April 1, 1977, and whom we followed prospectively. A multivariate analysis using the Cox regression model was performed to establish the determinants of long-term outcome. The hospital mortality and myocardial infarction rates were 3% and 6.3%, respectively. Complete revascularization was obtained in 77.6%. Follow-up was 99.8% complete and averaged 13.4 years (range, 1.5 months to 16.6 years). Actuarial survival after 5, 10, and 15 years is 94.2%, 82.4%, and 63%, respectively. The cumulative probability of event-free survival for cardiac death, acute myocardial infarction, reintervention, and angina pectoris at 5, 10, and 15 years, respectively, are 97.8%, 90.1%, 74.4%; 98.5%, 89.0%, 77.4%; 97.0%, 83.0%, 62.1%; and 77.8%, 52.1%, 26.8%. Left ventricular function and the number of vessels diseased are the independent preprocedural predictors of cardiac survival. Obesity and hypertriglyceridemia are preprocedural predictors of late myocardial infarction. Preoperative validity (Canadian Cardiovascular Society) and the number of diseased vessels are the predictors of recurrent angina. CONCLUSIONS: We conclude that the long-term results of isolated venous bypass graft surgery are dependent not only on well-known preprocedural factors such as number of vessels diseased, left ventricular function, and age but also on obesity and hypertriglyceridemia.

Actuarial Analysis↗

Statistical analysis of heterogeneous pharmacokinetic data from the literature.

To obtain the reliable pharmacokinetic quantities necessary for the adjustment of individual drug dosages, the pharmacokinetic data in the literature must be analysed by various appropriate statistical methods. Generally, pharmacokinetic quantities have been calculated from small sample sizes and published in different ways (the coefficient of variation of an estimated pharmacokinetic quantity is often higher than 40 percent). In the present study data were therefore structured and clustered according to the important influence variables. The important influence variables were obtained by known multivariate statistical methods. To obtain optimal estimators (uniformly minimum variance unbiased estimators) for the quantities inside the clusters, goodness of fit tests must be performed. Skewed distributions and samples with heterogeneous variances must be subjected to transformation procedures to obtain normally distributed values with homogeneous variances. The population-derived estimate of the a priori knowledge of pharmacokinetic quantities can be obtained by a statistical algorithm proposed in this paper. Information on the quantities half-life, total body clearance and volume of distribution of vancomycin were extracted from over 200 publications. These data were analysed with the proposed statistical algorithm, yielding population-based estimates for half-life, clearance and volume of vancomycin, taking into consideration the detected influence variables--renal function and the age of the patient. Important dependencies between different variables are discussed.

Age Factors↗