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PubMedDate not supplied

A statistical overview on univariate calibration, inverse regression, and detection limits: Application to gas chromatography/mass spectrometry technique.

The paper summarizes critically the current approaches for the calculation of the limits of detection and quantification. In the context of the description of the method based on the calibration line, the arguments concerning the underlying experimental design, the choice of the appropriate model in the univariate regression, the effects of the dispersion characteristics of the data are deeply discussed. The effects of the scedasticity of the experimental data are taken into account in the obtainment of the calibration curve and in its utilization. To gain transparency, adaptability, and tutorial effectiveness the explicit formulas relevant to the use of straight line and quadratic models are reported. An application of the described procedures to GC-MS data is reported as an illustrative example.

Algorithms↗
PubMedDate not supplied

A six-hour extrapolated sampling strategy for monitoring mycophenolic acid in renal transplant patients in the Indian subcontinent.

BACKGROUND: Therapeutic drug monitoring for mycophenolic acid (MPA) is increasingly being advocated. The present therapeutic range relates to the 12-hour area under the serum concentration time profile (AUC).However, this is a cumbersome, tedious, cost restricting procedure. Is it possible to reduce this sampling period? AIM: To compare the AUC from a reduced sampling strategy with the full 12-hour profile for MPA. SETTINGS AND DESIGN: Clinical Pharmacology Unit of a tertiary care hospital in South India. Retrospective, paired data. MATERIALS AND METHODS: Thirty-four 12-hour profiles from post-renal transplant patients on Cellcept were evaluated. Profiles were grouped according to steroid and immunosuppressant co-medication and the time after transplant. MPA was estimated by high performance liquid chromatography with UV detection. From the 12-hour profiles the AUC up to only six hours was calculated by the trapezoidal rule and a correction factor applied. These two AUCs were then compared. STATISTICAL ANALYSIS: Linear regression, intra-class correlations (ICC) and a two-tailed paired t-test were applied to the data. RESULTS: Comparing the 12-hour AUC with the paired 6-hour extrapolated AUC, the ICC and linear regression(r2) were very good for all three groups. No statistical difference was found by a two-tailed paired t-test. No bias was seen with a Bland Altman plot or by calculation. CONCLUSION: For patients on Cellcept with prednisolone +/- cyclosporine the 6-hour corrected is an accurate measure of the full 12-hour AUC.

Adolescent↗
PubMed1996

On the relations between single cell activity in the motor cortex and the direction and magnitude of three-dimensional static isometric force.

We examined the relations between the steady-state frequency of discharge of cells in the arm area of the motor cortex of the monkey and the direction and magnitude of the three-dimensional static force exerted by the arm on an isometric manipulandum. Data were analyzed from two monkeys (n = 188 cells) using stepwise multiple linear regression. In 154 of 188 (81.9%) cells the regression model was statistically significant (P < 0.05). In 121 of 154 (78.6%) cells the direction but not the magnitude of force had a statistically significant effect on cell activity; in 11 of 154 (7.1%) cells only the magnitude effect was significant; and in 22 of 154 (14.3%) cells both the direction and magnitude effects were significant. The same analysis was used to assess the effect of the direction and magnitude of force on the electromyographic activity of 9 muscles of the arm and shoulder girdle. The regression model was statistically significant. For all the muscles studied in 4 of 9 (44.4%) muscles only the direction effect was significant whereas in the remaining 5 of 9 (55.6%) muscles both the direction and the magnitude were significant. No muscle studied showed a significant effect of force magnitude alone. These differences in the frequency of occurrence of directional and magnitude effects between cells and muscles were statistically significant (P < 0.005, chi 2 test). These findings underscore the fundamental importance of the direction of force in space for both motor cortical cells and proximal muscles and underline the differential relations of the cells and muscles to the direction and magnitude of force. These results indicate that the specification of the magnitude of three-dimensional force is embedded within the directional signal; this combined direction+magnitude effect was 3.9 times more prevalent in the muscles than in the cells studied. In contrast, the pure directional effect was 1.8 times more prevalent in the cells than in the muscles studied. This suggests that the direction of force can be controlled independently of its magnitude and that this direction signal is especially prominent in the motor cortex.

Animals↗
PubMed2000

Familial associations of lipid profiles: a generalized estimating equations approach.

Elevated plasma levels of apolipoproteins A1 (apoA1) and B (apoB) are important protective factors and risk factors, respectively, for atherosclerosis and coronary heart disease. It is well known that both apoA1 and apoB reveal strong familial aggregation. Our goal was to investigate whether exogenous variables influence these associations. We used marginal regression models for the mean and association structure (generalized estimating equations 2; GEE2) to analyse data from 1435 family members within 469 families of different sizes included in the Donolo-Tel Aviv Three-Generation Offspring Study. The usual robust variance matrix was approximated by extensions of jack-knife estimators of variance to GEE2 models. Estimation of standard errors in models with quite complex correlation structures was possible using this approach. All analyses were easily carried out using a menu-driven stand-alone software tool for marginal regression modelling. We demonstrate that a variety of hypotheses can be tested using Wald statistics by modelling regression matrices for the association structure. We show that correlation for apoB between parent-offspring pairs increased with decreasing age difference and that pairs with individuals of the same gender had more similar apoA1 levels than individuals of different gender. Associations between different relative pairs did not all agree with those expected from differences in kinship coefficients. The analysis using GEE2 models revealed structures that would not have been detected by other models and should therefore be used in addition to traditional approaches of analysing family data. GEE2 should be considered a standard method for the investigation of familial aggregation.

Apolipoproteins A↗
PubMed2007

The adverse effects of race, insurance status, and low income on the rate of amputation in patients presenting with lower extremity ischemia.

OBJECTIVES: A consequence of delay in the diagnosis of peripheral vascular disease limb loss. This study was undertaken to determine the correlation of low socioeconomic status and race on the severity of ischemic presentation and the subsequent amputation rate. METHODS: Data from the Nationwide Inpatient Sample (NIS) from 1998 to 2002 on patients from urban hospitals with the diagnosis of lower extremity ischemia were evaluated. The population was divided into two groups: the amputation group (AMP) and lower extremity revascularization group (LER). Comorbidities, age, gender, race, ischemic gangrene at presentation, insurance status (no/noncommercial or commercial), and income status at admission were determined. These variables were compared using multivariate logistic regression analyses of the data for risk adjustment. RESULTS: Of 691,833 patients presenting with lower extremity ischemia, 363,193 underwent revascularization (66.3%) or amputation (33.7%). Univariate analysis correlated a statistically significant (P < .0001) higher rate of amputation and multivariate analysis associated significantly higher odds of amputation with the following variables: nonwhites (1.91, 95% confidence interval [CI], 1.65, 2.20), low-income bracket (1.41, 95% CI, 1.18, 1.60), and Medicare & Medicaid (1.81, 95% CI, 1.66, 1.97). Adjusting for other variables of statistical significance, multivariate regression analysis showed a statistically significant risk for amputation based on the nonteaching status of the institution (odds ratio [OR], 1.17, 95% CI, 1.08, 1.30). CONCLUSIONS: Primary amputation was performed with a higher frequency on patients with lower extremity ischemia who were nonwhite, low income, and without commercial insurance. The observed advanced ischemia among these economically disadvantaged patients suggests a delayed diagnosis of peripheral vascular disease, probably due to lack of access to adequate primary care or vascular surgery providers, or both. Better education of the general population and primary care providers to the symptoms and consequences of PVD may reduce the amputation rate in this group.

Aged↗
PubMed1988

A clinical evaluation of the accuracy of the Nellcor N-100 and Ohmeda 3700 pulse oximeters.

Two pulse oximeters, the Nellcor N-100 and the Ohmeda 3700, were compared with arterial blood values and with each other in a clinical evaluation of performance. Three hundred twenty-nine simultaneously sampled blood/oximeter data pairs from use of both makes of pulse oximeters on each of 152 test subjects were included in the comparison analysis for each oximeter. Among the patients, disease type and severity and hospital location varied widely. Basic descriptive statistics and linear regression analysis were employed to facilitate comparison. Both oximeters displayed a statistically significant but clinically insignificant bias when compared with arterial blood oxyhemoglobin: -0.31 (P = 0.023) and 0.59 (P = 0.001) for the Ohmeda 3700 pulse oximeter and the Nellcor N-100 pulse oximeter, respectively. Relative to arterial blood oxyhemoglobin, the 95% tolerance intervals were +4.84 to -5.45 (10.3) for the Ohmeda 3700 and +6.94 to -5.76 (12.7) for the Nellcor N-100. Regressed against [oxyhemoglobin + carboxyhemoglobin + methemoglobin] as x, the Nellcor N-100 read y = 0.85(x) + 12.5, r = 0.83, P less than 0.0001, and the Ohmeda 3700 read y = 1.02(x) - 5.3, r = 0.86, P less than 0.0001.

Female↗
PubMed2006

Some statistical issues related to multiple linear regression modeling of beach bacteria concentrations.

As a fast and effective technique, the multiple linear regression (MLR) method has been widely used in modeling and prediction of beach bacteria concentrations. Among previous works on this subject, however, several issues were insufficiently or inconsistently addressed. Those issues include the value and use of interaction terms, the serial correlation, the criteria for model selection, and model assessment. The present work shows that serial correlations, as often present in sequentially observed data records, deserve full attention from the modeler. The testing and adjustment for the time-series effect should be implemented in a statistically rigorous framework. The R(2) and Cp-statistic as joint criteria are recommended for the model selection process, while using the t-statistics associated with the full model is erroneous. During model selection, using interaction terms can often help to decrease the bias in reduced models, although the resulting improvement in the numerical performance may be limited. For the assessment of the model predictive capacity, which is different from testing the goodness of fit, a comprehensive set of statistics are advocated to allow for an objective evaluation of different models. Results obtained from the data at Huntington Beach, OH, show that erroneous conclusions could be drawn if only the model R(2) and the count of type I and type II errors are considered. In this sense, several previous works deserve further investigation.

Bathing Beaches↗
PubMed2005

A note on age-related biomarkers.

Forty-eight randomly selected age-related human biological functions were analyzed in order to establish whether or not their (linear) regressions were modified by age-related standard errors. Possible reasons for this are advanced. Statistically significant multiple regressions were obtained in 25%, and 21% of the functions yielded statistically significant changes in the correlations between data and age when partial correlation coefficients were calculated. The conclusion is that age-related data need to be subjected to the above tests in order to minimize confounding factors.

Age Factors↗
PubMed1992

Can experienced clinicians predict the outcome of lupus nephritis?

The ability of four experienced clinicians to predict short-term outcome (serum creatinine level at 1 year) and long-term outcome (renal insufficiency) was evaluated in 87 patients with lupus nephritis. The correlational agreement and the accuracy of their predictions were contrasted with the actual outcomes observed and with statistically generated prognostic regression models. In contrast to previously published data, all four clinicians predicted both short-term outcomes (P < 0.001) and long-term outcomes (P < 0.02) well. The clinicians' predictions approximated that of a statistically generated computer model for both agreement and accuracy for renal function at 1 year. The four clinicians identified nearly identical clinical variables as important in determining prognosis. Provision of biopsy data to the clinicians improved short-term and long-term prediction slightly. The value of the statistical models was 'validated' by demonstrating that three of the four clinical variables identified by the models, but not by the clinicians, could enhance clinical prediction (P < 0.05). In addition, the extent of tubulo-interstitial involvement on biopsy, a predictor that has recently received increased attention, could improve the long-term clinical predictions of all four clinicians (P < 0.05).

Adolescent↗
PubMed2004

Identification of dynamic leaching kinetics of stabilized, water-soluble wastes.

A one-dimensional diffusion model based on Fick's second law with a non-zero surface concentration at the solid-solution interface was developed to calculate effective calcium and sulfate diffusion coefficients of composites placed in saltwater. A regression method was used to identify the leaching kinetics. The regression method decomposes the stabilized PG leaching processes into diffusion, surface wash-off, and immediate and long-term precipitation. The immediate surface precipitation of both calcium and sulfate ions occurred only in three of the PG composite combinations. The effective diffusion coefficients of calcium (2.58-4.68 x 10(-13) m2 s(-1)) and sulfate (2.77-5.02 x 10(-13) m2 s(-1)) obtained from the regression method are similar to those obtained from methods of cumulative flux and daily flux associated with the simple diffusion model, provided that the leaching processes do not deviate significantly from that of the diffusion. The ratio (1.13) of effective sulfate to calcium diffusion coefficients obtained using the regression analysis is statistically consistent with the theoretical value (1.31), which further justifies the regression method. The research also implies that the leaching processes of calcium and sulfate ions stop after a certain period of time (300-900 d for calcium and 80-170 d for sulfate) and that the precipitations of calcium and sulfate affect the leaching processes. The regression method can be used to identify the leaching mechanisms and to predict the long-term stability of the stabilized wastes.

Calcium↗
PubMed1996

Necropsy study of the association between sudden cardiac death, cardiac isoenzymes and contraction band necrosis.

AIMS: To assess whether a quantitative analysis of myocardial contraction bands could aid the postmortem identification of early myocardial infarction, especially if used in conjunction with cardiac isoenzyme activities. METHODS: Sixty four coroner's necropsies were grouped by gross and histological findings into 26 cases of definite non-cardiac death, 12 cases of definite myocardial infarction and 26 cases in which there was occlusive coronary artery atheroma, but no demonstrable evidence of infarction. Using multiple sections of left ventricular myocardium stained with Heidenhain's iron haematoxylin, the number of myocardial cells containing contraction bands per unit area was quantified. The results were analysed statistically using logistic regression, and were then compared and combined with results from the statistical analysis of postmortem cardiac isoenzymes that had recently been undertaken on the same cases. RESULTS: The number of cells containing contraction bands per unit area was higher in cases of definite myocardial infarction compared with those of non-cardiac deaths. In addition, cases of occlusive coronary artery atheroma only could be identified, indicating the presence of early myocardial infarction. The accuracy of this identification could be improved by combining these results with the results from the statistical analysis of postmortem cardiac isoenzymes. CONCLUSION: The quantitative assessment of myocardial contraction band necrosis can provide useful additional information in cases of sudden death, where myocardial infarction is suspected but not identified on routine histological staining. The value of the information obtained is increased when used in conjunction with the postmortem measurement of cardiac isoenzyme activities.

Coronary Artery Disease↗
PubMed2003

Different regional organisational models and the quality of health care: the case of coronary artery bypass graft surgery.

OBJECTIVES: The Italian regions of Emilia-Romagna and Lombardy within the Italian National Health Service provide an opportunity to see if two different approaches to the organisation of care--one more hierarchical and planned, the other more competitive and market-like--influence its quality through examining the relationship between the number of coronary artery bypass grafts (CABGs) and the rate of in-hospital mortality using administrative data for the period 1996-1998. METHODS: Descriptive statistics and logistic regression models were used. RESULTS: The volume-outcome relation was statistically significant in both regions (odds ratio 0.71, P < 0.0001). Although CABG performance in Emilia-Romagna was slightly poorer than in Lombardy (OR 1.22, P < 0.05), the potential advantage in terms of the reduced risk of death for patients treated at high-volume versus low-volume hospitals was significantly greater. In Emilia-Romagna, the average performance advantage of high-volume units was more substantial in the case of private accredited hospitals than public hospitals (OR = 0.50, P < 0.0001 versus OR = 0.64, P < 0.0001). In Lombardy, the performance advantage of concentrating CABG procedures was greater in private research hospitals (OR = 0.67, P < 0.0001), whereas results were not statistically significant for the other types of hospital, indicating a good level of performance in both public and private hospitals even at low volumes. This also partially explained the lower mortality rate observed in that region. CONCLUSIONS: The degree of hierarchical regionalisation versus market-like arrangements characterising the two systems produced contrasting effects in terms of the quality of CABG surgery. Lombardy's more competitive environment appeared to achieve better performance in terms of a slightly lower probability of adverse outcomes, in a system with no formal assessment of population need and very high per capita revascularisation rates. To improve performance in the more hierarchical system adopted in Emilia-Romagna would require considerable effort to increase CABG surgery in low-volume cardiac units, and to sharpen performance incentives.

Aged↗
PubMed1987

[Factors causing absenteeism due to diseases of the circulatory system: a model analysis].

The rate of absenteeism due to the circulatory system diseases--one of the major causes of work disablement--has largely risen recently. Those diseases constitute a serious health problem within the sickness absenteeism of workers over 40. The presented analysis refers to the impact of the so called non-health-related variables and certain variables indirectly affecting workers' health upon the absenteeism caused by the circulatory system diseases (expressed by the number of absenteeism days annually and average duration of absenteeism case). As investigating tools, multidimensional methods of statistical analysis (multiple regression model) have been used to select the factors bearing a statistically significant effect upon the sickness absenteeism caused by circulatory diseases. The developed models are related to absenteeism of men and women aged 39, over 40 and totally. The results of the analysis demonstrated that both absenteeism of men and women was largely affected by occupational and work-environment-related factors (exposure, worker's affiliation to some working group, piece-work payments). The absenteeism of men over 40 was significantly affected by age, whereas the absenteeism of women was affected by such variables as family "size", and traveling to work. Furthermore, absenteeism caused by circulatory diseases is accounted for by the variables directly determining the health condition, such as health self-estimation and absenteeism rate caused by those diseases prior to the investigation.

Absenteeism↗
PubMed2006

Association between adolescent idiopathic scoliosis prevalence and age at menarche in different geographic latitudes.

BACKGROUND: Age at menarche is considered a reliable prognostic factor for idiopathic scoliosis and varies in different geographic latitudes. Adolescent idiopathic scoliosis prevalence has also been reported to be different in various latitudes and demonstrates higher values in northern countries. A study on epidemiological reports from the literature was conducted to investigate a possible association between prevalence of adolescent idiopathic scoliosis and age at menarche among normal girls in various geographic latitudes. An attempt is also made to implicate a possible role of melatonin in the above association. MATERIAL-METHODS: 20 peer-reviewed published papers reporting adolescent idiopathic scoliosis prevalence and 33 peer-reviewed papers reporting age at menarche in normal girls from most geographic areas of the northern hemisphere were retrieved from the literature. The geographic latitude of each centre where a particular study was originated was documented. The statistical analysis included regression of the adolescent idiopathic scoliosis prevalence and age at menarche by latitude. RESULTS: The regression of prevalence of adolescent idiopathic scoliosis and age at menarche by latitude is statistically significant (p < 0.001) and are following a parallel declining course of their regression curves, especially in latitudes northern than 25 degrees. CONCLUSION: Late age at menarche is parallel with higher prevalence of adolescent idiopathic scoliosis. Pubarche appears later in girls that live in northern latitudes and thus prolongs the period of spine vulnerability while other pre-existing or aetiological factors are contributing to the development of adolescent idiopathic scoliosis. A possible role of geography in the pathogenesis of idiopathic scoliosis is discussed, as it appears that latitude which differentiates the sunlight influences melatonin secretion and modifies age at menarche, which is associated to the prevalence of idiopathic scoliosis.

Journal Article↗
PubMed2003

Integration of association statistics over genomic regions using Bayesian adaptive regression splines.

In the search for genetic determinants of complex disease, two approaches to association analysis are most often employed, testing single loci or testing a small group of loci jointly via haplotypes for their relationship to disease status. It is still debatable which of these approaches is more favourable, and under what conditions. The former has the advantage of simplicity but suffers severely when alleles at the tested loci are not in linkage disequilibrium (LD) with liability alleles; the latter should capture more of the signal encoded in LD, but is far from simple. The complexity of haplotype analysis could be especially troublesome for association scans over large genomic regions, which, in fact, is becoming the standard design. For these reasons, the authors have been evaluating statistical methods that bridge the gap between single-locus and haplotype-based tests. In this article, they present one such method, which uses non-parametric regression techniques embodied by Bayesian adaptive regression splines (BARS). For a set of markers falling within a common genomic region and a corresponding set of single-locus association statistics, the BARS procedure integrates these results into a single test by examining the class of smooth curves consistent with the data. The non-parametric BARS procedure generally finds no signal when no liability allele exists in the tested region (ie it achieves the specified size of the test) and it is sensitive enough to pick up signals when a liability allele is present. The BARS procedure provides a robust and potentially powerful alternative to classical tests of association, diminishes the multiple testing problem inherent in those tests and can be applied to a wide range of data types, including genotype frequencies estimated from pooled samples.

Algorithms↗
PubMed1992

Case-mix groups for VA hospital-based home care.

The purpose of this study is to group hospital-based home care (HBHC) patients homogeneously by their characteristics with respect to cost of care to develop alternative case mix methods for management and reimbursement (allocation) purposes. Six Veterans Affairs (VA) HBHC programs in Fiscal Year (FY) 1986 that maximized patient, program, and regional variation were selected, all of which agreed to participate. All HBHC patients active in each program on October 1, 1987, in addition to all new admissions through September 30, 1988 (FY88), comprised the sample of 874 unique patients. Statistical methods include the use of classification and regression trees (CART software: Statistical Software; Lafayette, CA), analysis of variance, and multiple linear regression techniques. The resulting algorithm is a three-factor model that explains 20% of the cost variance (R2 = 20%, with a cross validation R2 of 12%). Similar classifications such as the RUG-II, which is utilized for VA nursing home and intermediate care, the VA outpatient resource allocation model, and the RUG-HHC, utilized in some states for reimbursing home health care in the private sector, explained less of the cost variance and, therefore, are less adequate for VA home care resource allocation.

Aftercare↗
PubMed2004

Exploring QSAR with E-state index: selectivity requirements for COX-2 versus COX-1 binding of terphenyl methyl sulfones and sulfonamides.

An attempt has been made to explore selectivity requirements for cyclooxygenase-2 (COX-2) versus cyclooxygenase-1 (COX-1) binding of terphenyl methyl sulfones and sulfonamides using electrotopological state (E-state) index and suitable indicator parameters. Multiple linear regression analyses produced statistically acceptable equations: the best relation based on 'all-possible-subsets regression' for COX-1 binding (n=18) showed predicted variance and explained variance of 0.675 and 0.777, respectively, while in case of the best equation for COX-2 binding (n=38), these values rose to 0.842 and 0.874, respectively. For the selectivity relation (n=17), predicted variance and explained variance values were 0.601 and 0.687, respectively. Based on the results of the analyses, three important sites have been suggested: sites A (methylsulfonyl or aminosulfonyl moiety), B (central phenyl ring), and C (terminal phenyl ring containing different substituents). All three sites are important for COX-2 binding while sites B and C are important for COX-1 binding. For COX-2 selectivity, only site C plays an important role. The study shows the utility of E-state index in developing statistically acceptable model having direct physicochemical significance.

Binding Sites↗
PubMed2004

The role of apolipoprotein E gene polymorphisms in primary open-angle glaucoma.

OBJECTIVE: To test the hypothesis that genetic polymorphisms of the apolipoprotein E (APOE) gene are associated with primary open-angle glaucoma (POAG), based on the association between neurodegenerative diseases and the APOE genotype. METHODS: Genomic DNA was examined from an unrelated cohort of 137 POAG patients and 75 control subjects from the ophthalmology department of the Royal Victoria Infirmary. The APOE allele frequency (epsilon2, epsilon3, and epsilon4 alleles) was studied by polymerase chain reaction amplification of the related locus (19q13.2), enzymatic digestion of the products, gel electrophoresis, and imaging under UV illumination. For statistical analysis, we used a logistic regression model that included intraocular pressure as a continuous variable to study the possible correlation between POAG and APOE allele frequency. RESULTS: Logistic regression analysis showed no statistically significant association between the frequency of the APOE allele and POAG for the population studied, irrespective of the IOP (epsilon2 odds ratio, 0.82; 95% confidence interval, 0.12-5.79 [P =.84]; epsilon3 odds ratio, 0.39; 95% confidence interval, 0.10-1.49 [P =.17]; and epsilon4 odds ratio, 3.84; 95% confidence interval, 0.80-18.49 [P =.09]). CONCLUSION: In our cohort, the APOE genotype does not constitute a risk factor for developing POAG, even in patients with normal-tension glaucoma.Clinical Relevance Apolipoprotein E polymorphisms do not appear to be contributory to POAG.

Aged↗