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A test of a path model of biocultural transmission of fertility.

A model adapted to a general linear model of phenotypic transmission (two components: (1) genetic additive, (2) cultural [age at marriage]) has been used to analyse the familial correlations of fertility (number of children) born before the demographic transition at Arthez d'Asson (Béarn, 1744-1889). The model is rejected: chi 2 = 55.7 with 6d.f. In the ancient demographical regime, reproduction and nuptiality of a couple were not influenced by their parents but by their generation.

Culture↗

Monte Carlo EM for missing covariates in parametric regression models.

We propose a method for estimating parameters for general parametric regression models with an arbitrary number of missing covariates. We allow any pattern of missing data and assume that the missing data mechanism is ignorable throughout. When the missing covariates are categorical, a useful technique for obtaining parameter estimates is the EM algorithm by the method of weights proposed in Ibrahim (1990, Journal of the American Statistical Association 85, 765-769). We extend this method to continuous or mixed categorical and continuous covariates, and for arbitrary parametric regression models, by adapting a Monte Carlo version of the EM algorithm as discussed by Wei and Tanner (1990, Journal of the American Statistical Association 85, 699-704). In addition, we discuss the Gibbs sampler for sampling from the conditional distribution of the missing covariates given the observed data and show that the appropriate complete conditionals are log-concave. The log-concavity property of the conditional distributions will facilitate a straightforward implementation of the Gibbs sampler via the adaptive rejection algorithm of Gilks and Wild (1992, Applied Statistics 41, 337-348). We assume the model for the response given the covariates is an arbitrary parametric regression model, such as a generalized linear model, a parametric survival model, or a nonlinear model. We model the marginal distribution of the covariates as a product of one-dimensional conditional distributions. This allows us a great deal of flexibility in modeling the distribution of the covariates and reduces the number of nuisance parameters that are introduced in the E-step. We present examples involving both simulated and real data.

Algorithms↗

A comparison of several regression models for analysing cost of CABG surgery.

Investigators in clinical research are often interested in determining the association between patient characteristics and cost of medical or surgical treatment. However, there is no uniformly agreed upon regression model with which to analyse cost data. The objective of the current study was to compare the performance of linear regression, linear regression with log-transformed cost, generalized linear models with Poisson, negative binomial and gamma distributions, median regression, and proportional hazards models for analysing costs in a cohort of patients undergoing CABG surgery. The study was performed on data comprising 1959 patients who underwent CABG surgery in Calgary, Alberta, between June 1994 and March 1998. Ten of 21 patient characteristics were significantly associated with cost of surgery in all seven models. Eight variables were not significantly associated with cost of surgery in all seven models. Using mean squared prediction error as a loss function, proportional hazards regression and the three generalized linear models were best able to predict cost in independent validation data. Using mean absolute error, linear regression with log-transformed cost, proportional hazards regression, and median regression to predict median cost, were best able to predict cost in independent validation data. Since the models demonstrated good consistency in identifying factors associated with increased cost of CABG surgery, any of the seven models can be used for identifying factors associated with increased cost of surgery. However, the magnitude of, and the interpretation of, the coefficients vary across models. Researchers are encouraged to consider a variety of candidate models, including those better known in the econometrics literature, rather than begin data analysis with one regression model selected a priori. The final choice of regression model should be made after a careful assessment of how best to assess predictive ability and should be tailored to the particular data in question.

Aged↗

Does percent reduction in seizure frequency correlate with plasma concentration of anticonvulsant drugs? Experience with four anticonvulsant drugs.

OBJECTIVE: To investigate the relationship between the percentage reduction in seizure frequency in patients with epilepsy and plasma concentrations after oral administration of 4 anticonvulsant drugs. METHODS: Patients with a minimum of 25% reduction in their seizure frequency from their baseline value were declared responders. The percentage reduction in seizure frequency was plotted against plasma concentrations with use of pharmacodynamic models (linear, log-linear, Emax, and sigmoidal Emax models). In addition to pharmacodynamic models, a logistic regression model was also fitted to the concentration-response data, with a value of 1 for responders and 0 for nonresponders. RESULTS: The concentration-effect relationship could not be adequately described either by the pharmacodynamic models or by the logistic regression analysis. CONCLUSIONS: Based on the results obtained from both pharmacodynamic models and logistic regression analysis the percentage reduction in seizure frequency may not be a true surrogate marker for anticonvulsant drugs to establish a pharmacodynamic relationship with plasma concentrations.

Anticonvulsants↗

A screening procedure for identifying acid-sensitive lakes from catchment characteristics.

Monitoring of Wilderness lakes for potential acidification requires information on lake sensitivity to acidification. Catchment properties can be used to estimate the acid neutralizing capacity (ANC) of lakes. Conceptual and general linear models were developed to predict the ANC of lakes in high-elevation (> or = 2170 m) Wilderness Areas in California's Sierra Nevada mountains. Catchment-to-lake area ratio, lake perimeter-to-area ratio, bedrock lithology, vegetation cover, and lake headwater location are significant variables explaining ANC. The general linear models were validated against independently collected water chemistry data and were used as part of a first stage screen to identify Wilderness lakes with low ANC. Expanded monitoring of atmospheric deposition is essential for improving the predictability of lake ANC.

Acid Rain↗

Kappa-like indices of observer agreement viewed from a latent class perspective.

It is common practice to assess consistency of diagnostic ratings in terms of 'agreement beyond chance'. To explore the interpretation of such a term we consider relevant statistical techniques such as Cohen's kappa and log-linear models for agreement on nominal ratings. We relate these approaches to a special latent class concept that decomposes observed ratings into a class of systematically consistent and a class of fortuitous ratings. This decomposition provides a common framework in which the specific premises of Cohen's kappa and of log-linear models can be identified and put into perspective. As a result it is shown that Cohen's kappa may be an inadequate and biased index of chance-corrected agreement in studies of intra-observer as well as inter-observer consistency. We suggest a more critical use and interpretation of measures gauging observer reliability by the amount of agreement beyond chance.

Adult↗

A model for evaluating droperidol's effect on the median QTc interval.

UNLABELLED: Controversy surrounds the use of the antiemetic droperidol, because of the Food and Drug Administration-imposed "black box" warning alleging that even small doses of the drug can lead to serious (even fatal) arrhythmias when it is used for antiemetic prophylaxis during the perioperative period. We used mathematical modeling of electrocardiographic QT interval data published in a peer-reviewed manuscript to evaluate the relationship between the dose of droperidol (0.1-0.25 mg/kg i.v.) and QT(c) prolongation. In comparing the calculated QT(c) values based on the logarithm model (27-63 ms), the linear model (27-67 ms) and the square-root model (36-57 ms) to the actual measured QT(c) values (37-59 ms), the square-root model provided the best simulation of the experimental findings. Other models that we evaluated included the polynomial model and various exponent models (e.g., quartic-root model, cubic-root model, square model, and cubic model). The estimated median prolongation of the median QT(c) interval produced by droperidol 0.625-1.25 mg i.v. would vary from 9 +/- 3 to 18 +/- 3 ms. Therefore, this regression analysis suggests that small "antiemetic" doses of droperidol (< or =1.25 mg) would be unlikely to produce proarrhythmogenic effects in the perioperative period. IMPLICATIONS: Using a square-root curve fit model to evaluate the relationship between the dose of droperidol and QT(c) prolongation, small-dose droperidol (0.625-1.25 mg i.v.) would be expected to produce <30-ms prolongation of the QT(c) interval. Therefore, small "antiemetic" doses of droperidol would not be expected to produce proarrhythmogenic effects when used for prophylaxis in surgical patients.

Algorithms↗

Time-related decay of the benefits of biofeedback therapy.

Although immediate results are good to excellent in great majority of patients who undergo biofeedback treatment (BFT) for chronic constipation and fecal incontinence, they tend to loose the benefit over a period of time. The purpose of this study was to evaluate the long-term sustainability of results after successful biofeedback treatment. Two groups of patients who successfully completed BFT at our institution from 1995 to 1997 were created based on the date of completion. The first had a mean follow-up of 35 months and the second group was followed for an average of 12 months. Both groups were questioned as to the presence of constipation and incontinence. The questioning was focused depending on the patient's diagnosis. This information was then compared with the initial BFT results. Overall, all patients were satisfied by the initial BFT results. All patients initially had an excellent or good response to BFT. However, after a mean of 35 months, in the first group, 19 of 22 patients had a near complete regression back to their pre-biofeedback status. In the 14 patients in the second group with mean follow-up of 12 months, 11 had a significant decay in benefits. Only time was a significant factor in the decay of BFT benefits. In conclusion, BFT is highly effective in the treatment of selected patients with complex defecation disorders. Although there is a high initial success rate, there is a clear loss of the immediate benefits over time. Other factors such as dietary habits, pelvic floor exercises, manometry, invasive EMG, and rectal sensation did not correlate with long-term outcomes. The comparison between the two groups reveals a linear model describing the time decay of the benefits of BFT. Based on the linear model, patients may need reevaluation after one year and may benefit from additional BFT.

Adult↗

Fetal head moulding: finite element analysis of a fetal skull subjected to uterine pressures during the first stage of labour.

Fetal head moulding is a phenomenon which may contribute to satisfactory progress during delivery as it allows the fetal head to accommodate to the geometry of the passage. In contrast, excessive head moulding may result in cranial birth injuries and thus affect the infant shortly or even long after birth. One group of researchers in the past investigated the biomechanics of fetal head moulding from an engineering point of view and limited themselves to a static, linear model of the parietal bones. In this paper, we present a non-linear model of the deformation of a complete fetal skull, when subjected to pressures exerted by the cervix, during the first stage of labour. The design of the model involves four main steps: shape recovery of the fetal skull, the generation of a valid and compatible mesh for finite element analysis (FEA), the specification of a physical model and the analysis of deformation. Results of the analysis show good agreement with those obtained from clinical experiments on the quantitative assessment of fetal head moulding. The model also displays shapes after moulding which have been reported in previous studies and which are generally known in the obstetric and paediatric communities.

Biomechanical Phenomena↗

Estimation of expiratory time constants via fuzzy clustering.

OBJECTIVE: In mechanically ventilated patients the expiratory time constant provides information about respiratory mechanics. In the present study a new method, fuzzy clustering, is proposed to determine expiratory time constants. Fuzzy clustering differs from other methods since it neither interferes with expiration nor presumes any functional relationship between the variables analysed. Furthermore, time constant behaviour during expiration can be assessed, instead of an average time constant. The time constants obtained with fuzzy clustering are compared to time constants conventionally calculated from the same expirations. METHODS: 20 mechanically ventilated patients, including 10 patients with COPD, were studied. The data of flow, volume and pressure were sampled. From these data, four local linear models were detected by fuzzy clustering. The time constants (tau) of the local linear models (clusters) were calculated by a least-squares technique. Time constant behaviour was analysed. Time constants obtained with fuzzy clustering were compared to time constants calculated from flow-volume curves using a conventional method. RESULTS: Fuzzy clustering revealed two patterns of expiratory time constant behaviour. In the patients with COPD an initial low time constant was found (mean tau1: 0.33 s, SD 0.21) followed by higher time constants; mean tau2: 2.00 s (SD 0.91s), mean tau3: 3.45 s (SD 1.44) and mean tau4: 5.47 s (SD 2.93). In the other patients only minor changes in time constants were found; mean tau1: 0.74 s (SD 0.30), mean tau2: 0.90 s (SD 0.23), mean tau3: 1.04 s (SD 0.42) and mean tau4: 1.74 s (SD 0.78). Both the pattern of expiratory time constants, as well as the time constants calculated from the separate clusters, were significantly different between the patients with and without COPD. Time constants obtained with fuzzy clustering for cluster 2, 3 and 4 correlated well with time constants obtained from the flow-volume curves. CONCLUSIONS: In mechanically ventilated patients, expiratory time constant behaviour can be accurately assessed by fuzzy clustering. A good correlation was found between time constants obtained with fuzzy clustering and time constants obtained by conventional analysis. On the basis of the time constants obtained with fuzzy clustering, a clear distinction was made between patients with and without

Adult↗

Relationship of heart rate variability to parasympathetic effect.

BACKGROUND: Baroreflex-mediated parasympathetic stimulation has variable effects on heart rate variability (HRV). We postulated that a quadratic function would describe the relationship between HRV and parasympathetic effect better than a linear function. METHODS AND RESULTS: Twenty-nine normal volunteers (15 women; mean age 39+/-12 years) were studied after beta-adrenergic blockade with intravenous propranolol. Five-minute ECG recordings were made during graded infusions of phenylephrine and nitroprusside to achieve baroreflex-mediated increases and decreases in parasympathetic effect, respectively. Time- and frequency-domain measures of HRV were calculated from the R-R interval tachograms. The R-R interval and the vagal-sympathetic effect (VSE=R-R interval/intrinsic R-R interval) were used as indices of parasympathetic effect. The data were fit to both quadratic and linear models. In each case, the quadratic model (with a negative coefficient for the squared term) was superior to the linear model. There was some evidence that age influenced the responsiveness of the HRV parameters with changing parasympathetic effect, although the regression analysis was significant only in the models for MSSD (P<0.03) and pNN50 (P<0.001). CONCLUSIONS: The relationship between HRV and parasympathetic effect is best described by a function in which there is an ascending limb where HRV increases as parasympathetic effect increases until it reaches a plateau level; HRV then decreases as parasympathetic effect increases. Because there is marked interindividual variation in this relationship, differences in HRV between individuals may reflect differences in this relationship and/or differences in autonomic effects.

Adrenergic beta-Antagonists↗

Analytical considerations in the use of capture-recapture to estimate prevalence: case studies of the estimation of opiate use in the metropolitan area of Barcelona, Spain.

Capture-recapture, an indirect method widely used to estimate undetected populations, has been criticized because it causes problems due to a lack of compliance with several important assumptions and model selection strategies. This paper expands on the problems encountered when applying this methodology to drug abuse estimations, specifically the prevalence of opiate use in the metropolitan area of Barcelona, Spain, in 1993. Three samples of opiate users (from hospital emergency rooms, treatment centers, and prisons) were available in the area studied; an additional sample (mortality data) was analyzed for the city of Barcelona. Log-linear models that provided a good fit were considered, to which further model selection strategies were applied. A total of 3,207 unique individuals aged 15-44 years were identified in the three samples from the greater Barcelona area; the mortality sample from the city of Barcelona contained an additional 83 individuals. Heterogeneity was observed in different age, sex, and residence area subgroups. Population estimates differed widely according to the log-linear model chosen. Minimum Akaike's information criterion model and saturated model estimates were used to produce population prevalence rates. The main problems the authors encountered in this study were related to population definition, source heterogeneity, and assessment of an adequate model, a problem associated with sample size.

Adolescent↗

Effectiveness of four manual toothbrushes in a cohort of patients undergoing fixed orthodontic treatment in an academic training hospital.

A single-blind, cross-over study design was used to evaluate the effectiveness of four different manual toothbrushes and to determine whether patient toothbrush preference is directly related to plaque control in patients with fixed orthodontic appliances. The brushes evaluated were Orthodontic Oral-B, Oral-B Advantage 30, Colgate Precision and Aquafresh. Forty-six subjects, aged 11 to 27, undergoing fixed orthodontic treatment were screened and recruited with parental consent. Subjects were randomly allocated into four groups. All subjects had their teeth scaled and polished at week 0. Baseline recordings of PI and GI were done four weeks later and the first toothbrush was given. After using the toothbrush for a period of 2 weeks the PI and GI were again recorded and teeth were again scaled and polished. A period of four weeks elapsed before new baseline recordings were done and the sequence followed as described for the first toothbrush. This was done until all subjects had used all four toothbrushes. At the end of the clinical trial, each subject was asked which toothbrushes they preferred. PI and GI values were relatively low at baseline as well as after the use of the toothbrushes. General linear model procedure showed no statistical difference between the Mean Plaque Index (MPI) before and after use of each toothbrush as well as the Difference in Mean Plaque Index (DMPI). There was a slight difference in the Difference in Mean Gingival Index (DMGI) between the Colgate Precision and Aquafresh toothbrush. For all the other comparisons general linear model procedure showed no difference between the Mean Gingival Index before and after use of each brush. There was no correlation between the toothbrush preferred by the patient and oral cleanliness as measured by DMPI and DMGI.

Adolescent↗

Piecewise hypersphere modeling by particle swarm optimization in QSAR studies of bioactivities of chemical compounds.

As the structural diversity in a quantitative structure-activity relationship (QSAR) model increases, constructing a good model becomes increasingly difficult, and simply performing variable selection might not be sufficient to improve the model quality to make it practically usable. To combat this difficulty, an approach based on piecewise hypersphere modeling by particle swarm optimization (PHMPSO) is developed in this paper. It treats the linear models describing the sought-for subsets as hyperspheres which have different radii in the data space. According to the attribute of each hypersphere, all compounds in the training set are allocated to hyperspheres to construct submodels, and particle swarm optimization (PSO) is applied to search the optimal hyperspheres for finding satisfactory piecewise linear models. A new objective function is formulated to determine the appropriate piecewise models. The performance is assessed using three QSAR data sets. Experimental results have shown the good performance of this technique in improving the QSAR modeling.

Angiotensin II↗

Wigner-Ville analysis and classification of electrocardiograms during thrombolysis.

Non-stationary analysis of electrocardiograms (ECGs) using Wigner-Ville distribution is presented. Analysis was performed on subjects with acute myocardial infarction who had undergone thrombolysis, in Holter recordings of lead V1. The distinction between successfully and non-successfully thrombolysed patients was evaluated, based on time-frequency features of the Wigner-Ville transformed ECGs at the sixth hour after lysis. Characteristic parameters were extracted from time-frequency areas, and linear discriminant analysis was performed on these parameters, leading to a prediction index to distinguish the two classes. Thirteen features were found statistically significant by t-test and were used for the classification with linear modelling. Out of these features, four corresponded to frequencies lower than 25 Hz and higher than 50 Hz for, roughly, the QRS complex, five features corresponded to all the frequency bands of, roughly, the ST area, and the last four features corresponded to the T-wave. The feature-vector used in linear modelling was iteratively generated, and the iterative prediction found all 18 features significant. The iterative method resulted in better classification than that of the standard statistical procedure (3.8% error against 18.1% with the classic method). The evolution of the prediction index with time for the first 12 h was different for the successfully and non-successfully thrombolysed groups. Specifically, in the successful thrombolysis group, oscillations and variation with time were more obvious, indicating a possible difference in the dynamics of the cardiac system.

Electrocardiography, Ambulatory↗

From profession-based leadership to service line management in the Veterans Health Administration: impact on mental health care.

OBJECTIVES: To investigate the impact of implementing service line organization on the delivery of mental health services. METHODS: Survey data on the implementation of service lines and facility-level administrative data on the delivery of mental health services at 139 Department of Veterans Affairs medical centers (VAMCs), over a 6-year period, were used to examine the relationship between service line implementation and subsequent performance in 4 areas: 1) continuity of care (COC), 2) readmission after inpatient discharge, 3) emphasis on community-based mental health care (as contrasted with inpatient care), and 4) maintenance of proportionate funding for mental health care. Models were analyzed using hierarchical linear modeling techniques to control for potential autocorrelation. RESULTS: Of 6 COC measures, 1 strongly improved in all years following service line implementation, and 3 of the 5 other measures demonstrated improvement in the first year. One of 2 readmission measures showed a decline in the first year after service line implementation. Service line implementation was associated with only 1 indicator of increased emphasis on community-based mental health care (and only in the first year), whereas 3 of the 4 other measures suggested a decline in such emphasis. Lastly, although there were increases in per capita mental health expenditures 3 or more years after service line implementation, 2 related measures indicated that service line implementation was associated with a decline in mental health expenditures relative to nonmental health services. CONCLUSION: Service line implementation was associated with significant, although predominantly short-term, improvement in patient level variables such as continuity of care and hospital readmission, but less so with regard to institutional measures addressing emphasis on outpatient care and maintaining proportionate funding of mental health services.

Community Mental Health Services↗

[Quantification of the probability of milk contamination by Listeria monocytogenes during manufacture of hard cheese].

BACKGROUND: The present work is concerned with the probability of contamination by Listeria monocytogenes in the artisanal manufacture of Swiss Emmental hard cheese made from raw milk. The simulation model follows the evolution of the contaminant flora from raw milk at the farm to milk mixing, storage at the cheese factory and to the cheese manufacturing process. METHODS: The simulations are based on models of predictive microbiology, namely the exponential growth model of bacteria including the lag-time, a cardinal growth model and a Log-linear model of thermal deactivation of bacteria. RESULTS: The results of the actual simulation indicate that the contamination of milk at the farm is a rare event (P=0.0036), but the mixing of milk at the cheese factory leads to a higher probability of contamination of cheese milk (P=0.07). Elevated bacterial concentrations are mainly due to cases of mastitis involving Listeria monocytogenes. The decline in bacterial counts during cheese manufacture depends on the curing temperature (52-54 degrees C) and varies between 1.5 and 3.2 Log cfu/ml. Freshly manufactured Emmental-cheese made from contaminated raw milk is expected to have only 4.6 cfu of heat injured Listeria monocytogenes /kg cheese mass in the press. CONCLUSION: Depending on listeria evolution, from the press to the product consumption, consumer exposure has been evaluated and might result in 1 to 10 Listeria monocytogenes per portion of cheese. The bacterial presence could be due to recontamination during packaging, distribution and cheese preparation by the consumer. Based on the presented data and estimations, it is concluded that the consumption of traditionally/artisanal manufactured Swiss Emmental hard cheese presents an extremely low, but existent risk, especially for people with a deficient or diminished immune system.

Animals↗

Incorporation of docosahexaenoic acid into nerve membrane phospholipids: bridging the gap between animals and cultured cells.

BACKGROUND: Functional maturation of nervous tissues depends on membrane accretion of docosahexaenoic acid (DHA). Animal studies have shown that incorporation of dietary DHA into membrane phospholipids is dose dependent. The molecular effects of DHA are commonly studied in cultured cells, but questions remain about the physiologic connection between animal and cell models. OBJECTIVE: We developed a linear model for comparing the responses of rat nervous tissues to dietary DHA with the responses of human cell lines to DHA in medium. DESIGN: Rats were rendered chronically deficient in n-3 fatty acids by being reared on a peanut oil diet. DHA status was replenished in the F2 generation by using increasing supplements of a microalgal oil. Human retinoblastoma and neuroblastoma cells were dosed with unesterified DHA. DHA accumulation into phospholipids was defined by the plateau of the dose-response curve (DHA(max)) and by the supplement required to produce one-half the DHA(max) (DHA(50)). RESULTS: The DHA(max) values for 4 brain regions and 2 neuroblastoma lines were similar, and the value for the retinoblastoma line was similar to the retinal value. Expressing the DHA input as micro mol/10 g diet and as micro mol/L medium resulted in similar values for the ratio of DHA(max) to DHA(50) in the 4 brain regions and the 3 cell lines. The DHA(max)-DHA(50) ratios in the ethanolamine phosphoglyceride and phosphatidylcholine fractions in retinal phospholipids were 6 and 10 times, respectively, those in the brain and cultured cells. CONCLUSIONS: The dose-dependent responses of cells and the brain to DHA supplements can be compared by using DHA(max)-DHA(50) ratios. We propose a counting frame that allows the comparison of the dose responses of the brain and cells to exogenous DHA.

Animals↗