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PubMed2000

How many data sources are needed to determine diabetes prevalence by capture-recapture?

BACKGROUND: Capture-recapture (CR) methods are increasingly used to estimate the size of human populations, including those with diabetes. Few studies have examined the demographic details needed to match patients on the lists used in these techniques, or to determine the optimum number of lists. METHODS: Six lists of known diabetic patients attending different medical settings during the study year were obtained. The effects on total enumeration after aggregation of these lists were examined using increasing numbers of demographic data items as patient identifiers. The CR estimates of prevalence were obtained using 15 different combinations of two lists. Estimates were obtained after log-linear modelling for interdependence between different combinations of three and four lists, and after combining the six available lists into three logical lists. RESULTS: For matching patients, adding date of birth to first name and family name as matching criteria increased the total of identified patients from 2500 to 2585 (3% increase), corresponding to a period prevalence of 1.5% (95% CI : 1.41-1.52). Addition of further identifiers, such as partial postcode, only increased the estimate by a further 15 patients (0.5%), and more detailed matching with full postcode introduced uncertainty. The use of two-list CR yielded widely varying estimates of the total diabetic population from 1379 (95% CI : 435-2273) to 9554 (95% CI : 7291-10 983). Log-linear modelling using different combinations of three and four lists produced estimates of 5074 (95% CI : 4417-5947) and 5578 (95% CI : 4918-7081), respectively, after compensating for statistical interdependence between the lists used. The appropriate condensation of six available lists into three lists for modelling yielded estimates of 5492 (95% CI : 4870-6285), corresponding to a CR-adjusted period prevalence of 3.1% (95% CI : 3.03-3.19%). CONCLUSIONS: In a Western population, the only demographic data required for matching patients on lists used for CR methods are first name, family name and date of birth, if unique identifiers such as social security numbers are not available. Two lists alone do not produce reliable data, and at least three lists are needed to allow for modelling for 'dependence' between datasets. The use of more than three lists does not substantially alter the absolute value or confidence of enumeration, and multiple lists (if available) should be condensed into three lists for use in CR calculations.

Databases, Factual↗

PubMed1991

Objective outcome criteria in trials of anti-parkinsonian therapy in the elderly: sensitivity, specificity and reliability of measures of brady- and hypo-kinesia.

1. We compare the sensitivity and specificity of chosen outcome criteria in a placebo-controlled, randomised cross-over study of the efficacy of maintenance therapy with the levodopa/carbidopa combination (Sinemet Plus) alone. Patients were characterised by having idiopathic Parkinsonism with no overt fluctuations in control in relation to individual doses of medication. 2. The effect of omission of a morning dose of maintenance therapy on simple timed tests of mobility and manual dexterity, and on distance/time parameters of gait was studied in fourteen patients (aged 64 to 88 years). Measurements made 2, 4 and 6 h after morning active and placebo treatments were standardised by taking the pre-treatment measurement on that day as baseline. 3. In a linear model, which allowed for the structure of the study, neither the total time taken by each patient to get up from a chair, walk an individually set distance, turn, return to and sit in the chair, nor the rate of progress at fastening the same set of buttons, was sensitive to the treatment effect. 4. Three of the gait parameters, free walking speed, mean stride length and mean double support time, were sensitive to the treatment effect. Correction for the speed of each walk, caused some reduction in the sensitivity of stride length to treatment effect, but that of double support time remained. Speed, and double support time or stride length, appeared to be complementary in defining the treatment effect. 5. The linear modelling revealed the complexity of the treatment effect. Although active treatment, by comparison with placebo, increased free walking speed (P = 0.019), the more levodopa found in the plasma following treatment, (P = 0.0005) and the greater the increment in the concentration of its peripheral metabolite, 3-O-methyldopa (P = 0.006), the less the beneficial effect. This model may reflect reduced uptake into the brain and/or an adverse effect of parent drug or a metabolite. 6. The specificity of free walking speed for the treatment effect was good, as was that of mean stride length, after it had been corrected for speed of each walk, and of mean double support time, after correction for speed and incorporation of the change in lying blood pressure accompanying treatment into the model. 7. The measurements of gait parameters were ranked according to reliability.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

PubMed2003

PET evidence of neuroplasticity in adult auditory cortex of postlingual deafness.

UNLABELLED: Controversy regarding functional reorganization in the adult brain remains. To investigate whether neuroplasticity is present in adults with postlingual deafness, we examined the pattern of cerebral glucose metabolism on (18)F-FDG brain PET images of postlingually deaf patients by comparing the auditory cortical activation pattern with those of age- and sex-matched healthy control subjects. We also correlated the cerebral glucose metabolism in deaf patients with the duration of deafness using statistical parametric mapping. METHODS: In the resting state (eye closed, ears unoccluded in a dark and quiet environment), (18)F-FDG brain PET scans were performed on 9 postlingually deaf patients and 9 age- and sex-matched healthy volunteers. Significant increases and decreases of regional cerebral metabolism in the patient group were estimated by comparing their PET images with those of the healthy volunteers using t statistics at every voxel. To reveal regions in which metabolism was significantly correlated with the duration of deafness, the general linear model with the duration of deafness as a covariate was tested at each voxel. RESULTS: When we compared (18)F-FDG brain PET images of postlingually deaf patients with those of age- and sex-matched healthy control subjects by performing a t test at every voxel, the glucose metabolism of deaf patients was significantly (P < 0.001) lower than that of the control subjects in both anterior cingulate gyri (Brodmann area 24 [BA24]) and superior temporal cortices (BA41, BA42) and in the right parahippocampal gyrus. No area showed a significant increase of metabolism in deaf patients with the same threshold. When we correlated glucose metabolism of deaf patients with the duration of deafness after total deprivation of hearing capability using a general linear model with the duration of deafness as a covariate at every voxel, metabolism in both anterior cingulate gyri (BA24) and superior temporal cortices (BA41, BA42) showed a significant (P < 0.005) positive correlation with the duration of deafness. CONCLUSION: This study suggests that plasticity is present in adult brains of postlingually deaf patients. In the mature brain, auditory deprivation decreased neuronal activity transiently in primary auditory and auditory-related cortices, and, over time, functional reorganization likely takes place in the auditory cortex. Plasticity was prominent in superior temporal and anterior cingulate gyri in the sensory-deprived mature brain and militated against postimplantation improvement in patients with cochlear implants.

Adult↗

PubMed1987

Inbreeding and prereproductive mortality in the Old Order Amish. III. Direct and indirect effects of inbreeding.

Direct and indirect (mediated by biologic factors) effects of inbreeding on prereproductive mortality (death before age 20 years) were investigated in a case-control study conducted in the Lancaster County, Pennsylvania, Old Order Amish. A total of 211 cases of prereproductive death between 1969 and 1980 and 213 live controls were compared for differences in inbreeding coefficients, congenital malformations, birth weight, gestational age, birth complications, and other demographic factors, obtained by linking cases and controls to vital records and the Amish genealogic registry dating back to the 1700s. Inbreeding coefficients (F) for cases and controls were computed using the path method of tracing common ancestors in the multigenerational pedigrees. Close inbreeding (F greater than or equal to 1/64) was a significant risk factor for prereproductive mortality; odds ratio = 1.55. Using the log-linear model, the effect of close inbreeding on mortality was found to be mediated by three indirect casual mechanisms: Regardless of case-control status, inbreeding was significantly related to congenital malformations (recorded at birth), intrauterine growth retardation (birth weight less than 10th percentile for gestational age), and the occurrence of other deaths in the sibship. In turn, each of these factors was independently related to mortality regardless of inbreeding. No significant direct effect of inbreeding remained after adjustment for these factors. There were no effects of inbreeding on prematurity (less than 37 weeks), or birth complications. This study suggests that inbreeding increases the risk of prereproductive mortality by increasing the risk of intrauterine growth retardation and congenital malformations but not prematurity. The log-linear model provides a useful approach to the analysis of direct and indirect risk factors using biologic mechanisms.

Congenital Abnormalities↗

PubMed1990

Spectral analysis of heart rate variability during constant and pseudorandom exercise.

The purpose of this study was to investigate the limitation for applying a linear model to the cardiorespiratory control system. Four subjects performed the two types of exercise bouts, constant (CONST) and pseudorandom (PRBS) exercise, on an electrically braked cycle ergometer at three different work rates. The target work rate of CONST were set to 80, 100, 120% of the individual anaerobic threshold (AT). In PRBS, the work rates were varied between +/- 10% of the individual AT around the respective target work rates of CONST. Although the spectral density of beat-to-beat heart rate fluctuations showed the conventional patterns for most cases, there was no obvious difference between CONST and PRBS. These results indicated that the variation of +/- 10% of AT did not affect the heart rate variation as the output response, suggesting a dilemma inevitable to apply a linear model based on the transfer function.

Adult↗

PubMedDate not supplied

Segmented regression with errors in predictors: semi-parametric and parametric methods.

We consider the estimation of parameters in a particular segmented generalized linear model with additive measurement error in predictors, with a focus on linear and logistic regression. In epidemiologic studies segmented regression models often occur as threshold models, where it is assumed that the exposure has no influence on the response up to a possibly unknown threshold. Furthermore, in occupational and environmental studies the exposure typically cannot be measured exactly. Ignoring this measurement error leads to asymptotically biased estimators of the threshold. It is shown that this asymptotic bias is different from that observed for estimating standard generalized linear model parameters in the presence of measurement error, being both larger and in different directions than expected. In most cases considered the threshold is asymptotically underestimated. Two standard general methods for correcting for this bias are considered; regression calibration and simulation extrapolation (simex). In ordinary logistic and linear regression these procedures behave similarly, but in the threshold segmented regression model they operate quite differently. The regression calibration estimator usually has more bias but less variance than the simex estimator. Regression calibration and simex are typically thought of as functional methods, also known as semi-parametric methods, because they make no assumptions about the distribution of the unobservable covariate X. The contrasting structural, parametric maximum likelihood estimate assumes a parametric distributional form for X. In ordinary linear regression there is typically little difference between structural and functional methods. One of the major, surprising findings of our study is that in threshold regression, the functional and structural methods differ substantially in their performance. In one of our simulations, approximately consistent functional estimates can be as much as 25 times more variable than the maximum likelihood estimate for a properly specified parametric model. Structural (parametric) modelling ought not be a neglected tool in measurement error models. An example involving dust concentration and bronchitis in a mechanical engineering plant in Munich is used to illustrate the results.

Bias↗

PubMed2004

Dose-response relationships within the parotid gland after radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: To determine the salivary function, after parotid-sparing radiotherapy (RT), of different regions within the parotid gland and to evaluate dose-function relationships within the parotid glands and between patients. PATIENTS AND METHODS: Sixteen head and neck cancer patients, irradiated between September 1999 and November 2000 using a conformal parotid-sparing technique, were included in this study. Before RT and 7 months after RT (range 6-10 months), a salivary gland scintigraphy was performed in all patients combined with a single photon emission computed tomography (SPECT). The salivary excretion fraction (SEF) was measured, after stimulation, in 8-12 transverse 5mm SPECT slices of each parotid. Loss of salivary excretion fraction (dSEF %) of these slices was calculated as the proportion of SEF after RT as compared to SEF before RT. Since the planning CT-scan and the SPECT-scintigraphy were performed in the same treatment position, the dose to a transverse slice within the parotid gland could be matched to the loss of salivary excretion fraction of that respective slice. A non-linear model was fitted to the dose-loss of function data and the dose resulting in 50% loss of salivary excretion fraction (D50) was calculated. RESULTS: Before RT, all but one patient presented with normal salivary excretion fractions (SEF) of both parotid glands. Within the same parotid gland, the SEF's of the different slices were almost equal. Seven months after RT, the reduction in SEF was statistically significant (P-value<0.0001). A significant difference in loss of salivary excretion fraction (dSEF) was also observed between both parotid glands (P<0.0001) as a result of the parotid-sparing technique. When plotting the dSEF of a slice versus the dose given to that slice, doses as low as 10-15 Gy could result in a serious loss of function (dSEF>50%). After fitting a non-linear model to these plots, the mean dose resulting in 50% loss of salivary excretion fraction (D50) 7 months after RT was 22.5 Gy. A large inter-patient variability was found in D50. CONCLUSIONS: Salivary SPECT is a useful tool for the evaluation of the salivary function of different slices within the parotid gland. Before irradiation, the different slices within one parotid gland act as functional sub-units contributing equally to the function of the entire gland. Seven months after an average dose of 22.5 Gy (D50) the functional sub-unit has lost 50% of its excretion fraction. The high inter-patient variability in D50 and the observation that low doses (10-15 Gy) can induce serious loss of function should prompt us in the clinic to reduce the dose to the parotids even lower than the threshold of 22.5 Gy.

Adult↗

PubMed1985

Use of the average antibody-antigen bond concept and probability theory to simplify modeling of linear and circular antibody-antigen complex formation.

We illustrate use of a simple approach to describe the equilibrium interactions of mixtures of monoclonal antibodies and antigens. This procedure is based on elementary concepts in probability theory and is readily suited to describing interactions of antibodies and antigens which form circular as well as linear complexes. The method is also suited to describing the inhibitory effects of antibodies which compete for overlapping epitopes and an example is provided to show how the procedure can be used to describe the interactions of antibodies which inhibit circular complex formation. We also outline simple strategies for preparing computer programs to simulate binding of antigens to defined antibody mixtures. The methods described should facilitate design of immunoassay procedures based on the use of defined mixtures of monoclonal antibodies.

Antibodies, Monoclonal↗

PubMed1993

Physician prescribing decisions: the effects of situational involvement and task complexity on information acquisition and decision making.

This research utilized conjoint analysis and an analysis of information acquisition to examine the effects of situational involvement and task complexity on physician's decision-making process. The predictive accuracy of the linear model in predicting drug choice across situations was also assessed. A contingency model for the selection of decision strategies was used as a framework in the study. A sample of forty-eight physicians was asked to indicate their preferences and choices for hypothetical anti-infective drugs. Situational involvement was manipulated by telling physicians in the experimental group via the written scenario to assume that his/her decision would be reviewed and evaluated by peers and (s)he would be asked to justify drug choice. Task complexity was manipulated by varying the number of drug alternatives in a choice set. Results of the study indicated that physicians shifted from using compensatory to noncompensatory decision-making processes when task complexity increased. The effect of situational involvement on the decision-making process was not supported. However, physicians in the two groups were found to differ in choice outcomes and the attention given to specific drug attribute information. Finally, the linear model was found to be robust in predicting drug choice across contexts.

Adult↗

PubMed2007

Fundus microperimetry patterns of fixation in type 2 diabetic patients with diffuse macular edema.

BACKGROUND: Recently developed fundus microperimetry (MP-1; Nidek Technologies, Srl. Vigonza PD, Italy) was used to evaluate fixation patterns and retinal sensitivity in patients who had clinically significant macular edema with a diffuse pattern and type 2 diabetes mellitus. METHODS: In a prospective, observational case series study, 84 consecutive patients with type 2 diabetes (84 eyes) who had clinically significant macular edema with a diffuse pattern were studied by means of MP-1. Main outcome measures were fixation stability and position and mean retinal sensitivities within the central 2 degrees and 8 degrees areas. Logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) was evaluated by means of an Early Treatment of Diabetic Retinopathy Study chart. Foveal thickness was measured by Stratus optical coherence tomography (OCT; Carl Zeiss Meditec, Inc., Dublin, CA). Age, duration of diabetes, hemoglobin A1c (HbA1c) levels, duration of symptoms, history of panretinal photocoagulation, vitreomacular adhesion, and cystoid macular changes were documented. Patients were grouped according to both position of fixation (central or eccentric) and stability of fixation (stable or unstable). Statistical analyses included independent samples t-test, binomial test, Bonferroni correction for multiple comparisons, and generalized linear model univariate analysis. RESULTS: Of 84 eyes, 44 (52.4%) had central fixation, and 40 (47.6%) had eccentric fixation. Of 84 eyes, 34 (40.5%) had stable fixation, and 50 (59.5%) had unstable fixation. In the whole sample, mean central 2 degrees retinal sensitivity +/- SD was 6.26 +/- 3.19 dB (range, 0-14.80 dB), and mean central 8 degrees retinal sensitivity +/- SD was 7.62 +/- 2.55 (range, 3.85-14.90 dB); logMAR BCVA ranged from 0.1 to 1.3 (mean +/- SD, 0.6 +/- 0.29). Mean OCT foveal thickness +/- SD was 300.77 +/- 66.93 m (range, 220-525 m). Both comparisons between groups (stable vs. unstable and central vs. eccentric) showed statistically significant differences in mean logMAR BCVA, mean central 2 degrees and 8 degrees retinal sensitivities, and mean OCT foveal thickness. Duration of symptoms was significantly longer and HbA1c levels were higher in the groups with deterioration of stability or centrality of fixation. The prevalence of cystoid macular changes was significantly higher in the groups with eccentric or unstable fixation (P < 0.001). Generalized linear model statistical analysis showed that logMAR BCVA was significantly associated with stability of fixation (P = 0.020), mean central 8 degrees retinal sensitivity (P < 0.001), and mean OCT foveal thickness (P < 0.001). The interaction between stability of fixation and mean OCT foveal thickness showed a statistically significant association with logMAR BCVA (P = 0.003). Some eyes with eccentric fixation presented with stable fixation, especially in the presence of long-lasting symptoms, and had better visual acuity than eyes with central, but unstable fixation. CONCLUSION: Visual acuity, central retinal sensitivity, foveal thickness, duration of symptoms, HbA1c levels, and presence of cystoid macular changes were strongly associated with fixation impairment in type 2 diabetic patients who had clinically significant macular edema with a diffuse pattern. Stability of fixation and foveal thickness play a major role in conditioning BCVA.

Aged↗

PubMed2001

Pharmacokinetics and tissue distribution of halofuginone (NSC 713205) in CD2F1 mice and Fischer 344 rats.

PURPOSE: Halofuginone (HF) inhibits synthesis of collagen type I and matrix metalloproteinase-2 and is being considered for clinical evaluation as an antineoplastic agent. Pharmacokinetic studies were performed in rodents to define the plasma pharmacokinetics, tissue distribution, and urinary excretion of HF after i.v. delivery and the bioavailability of HF after i.p. and oral delivery. MATERIALS AND METHODS: Studies were performed in CD2F1 mice and Fischer 344 rats. In preliminary toxicity studies in mice single HF i.v. bolus doses between 1.0 and 5.0 mg/kg were used. Pharmacokinetic studies were conducted in mice after administration of 1.5 mg/kg HF. In preliminary toxicity studies in male rats HF i.v. bolus doses between 0.75 and 4.5 mg/kg were used. In pharmacokinetic studies in rats an HF dose of 3.0 mg/kg was used. Compartmental and non-compartmental analyses were applied to the plasma concentration versus time data. Plasma, red blood cells, various organs, and urine were collected for analysis. RESULTS: HF doses > or = 1.5 mg/kg proved excessively toxic to mice. In mice, i.v. bolus delivery of 1.5 mg/kg HF produced "peak" plasma HF concentrations between 313 and 386 ng/ml, and an AUC of 19,874 ng/ml min, which corresponded to a total body clearance (CLtb) of 75 ml/min per kg. Plasma HF concentration versus time data were best fit by a two-compartment open linear model. The bioavailability of HF after i.p. and oral delivery to mice was 100% and 0%, respectively. After i.v. bolus delivery to mice, HF distributed rapidly to all tissues, except brain. HF persisted in lung, liver, kidney, spleen, and skeletal muscle longer than in plasma. In the oral study, HF was undetectable in plasma and red blood cells, but was easily detectable in kidney, liver, and lung, and persisted in those tissues for 48 h. Urinary excretion of HF accounted for 7-11% of the administered dose within the first 72 h after i.v. dosing and 15-16% and 16% of the administered dose within 24 and 48 h, respectively, after oral dosing. There were no observed metabolites of HF in mouse plasma or tissues. In rats, i.v. bolus delivery of 3.0 mg/kg produced a "peak" plasma HF concentration of 348 ng/ml, and an AUC of 43,946 ng/ml min, which corresponded to a CLtb of 68 ml/min per kg. Plasma HF concentration versus time data were best fit by a two-compartment open linear model. After i.v. bolus delivery to rats, HF distributed rapidly to all tissues, with low concentrations detectable in brain and testes. HF was detectable in some tissues for up to 48 h. HF could be detected in rat plasma after a 3 mg/kg oral dose. Peak HF concentration (34 ng/ml) occurred at 90 min, but HF concentrations were less than the lower limit of quantitation (LLQ) by 420 min. Urinary excretion of HF accounted for 8-11% of the administered dose within the first 48 h after i.v. dosing. No HF metabolites were detected in plasma, tissue, or urine. CONCLUSIONS: HF was rapidly and widely distributed to rodent tissues and was not converted to detectable metabolites. In mice, HF was 100% bioavailable when given i.p. but could not be detected in plasma after oral administration, suggesting limited oral bioavailability. However, substantial concentrations were present in liver, kidney, and lungs. HF was present in rat plasma after an oral dose, but the time course and low concentrations achieved precluded reliable estimation of bioavailability. These data may assist in designing and interpreting additional preclinical and clinical studies of HF.

Animals↗

PubMed2007

Analyzing the effect of wind on flight: pitfalls and solutions.

How flying organisms alter their air speed in response to wind is important in theories of flight energetics. Numerous studies have investigated the relationship between air and wind as a function of ground speed and air speed. This study shows that this approach can lead to erroneous results, due to spurious correlations. An alternative way to analyze air speed is proposed that overcomes the problems of one-dimensional linear models. The new model is non-linear and has two explanatory variables. Using two synthetic data sets with known properties and a data set with real observations of migratory bird tracks and wind observations, we illustrate the weaknesses of the conventional analysis as well as the strengths of the newly proposed model. This leads to the conclusion that for many studies a reanalysis of the effect of wind on air speed is desirable.

Animals↗

PubMed1996

Dose-response relationship for rat liver DNA damage caused by 1,2-dimethylhydrazine.

An experimental approach was taken to the question of dose-response curves for chemical carcinogenesis, using DNA damage as a biomarker. Female rats were give 13 different doses of 1,2-dimethylhydrazine (from 1.4 to 135,000 micrograms/kg) and the subsequent hepatic DNA damage was determined by the alkaline elution technique. DMH doses below 450 micrograms/kg did not significantly damage DNA; all DMH doses of 1000 micrograms/kg or higher damaged rat hepatic DNA (P < 0.05). In this study the x values (dose) ranged over five orders of magnitude and the y values (DNA damage) ranged 30-fold. Ten different regression models (linear, quadratic, cubic, power, and six nonlinear transition models) were compared in their ability to fit the experimental data. With respect to log transformed dose, the six nonlinear transition equations fit the data considerably better than the four power type of equations. A sigmoid model fit to the log transformed dose of 1,2-dimethylhydrazine had an r2 of 0.9979, a degree of freedom adjusted r2 of 0.9969, a F-statistic of 1,457, and a fit standard error of 0.50. With respect to untransformed dose, only three equations (sigmoid, cascade and gaussian cumulative) could creditably fit the DMH data. The experimental results are interpreted with respect to hormesis, use of log transformed dose, sigmoid dose-response models, thresholds of biological response and cancer risk assessment.

1,2-Dimethylhydrazine↗

PubMed1989

Contribution of the otoliths to the calculation of linear displacement.

1. The present work is a quantitative study of the eye movements induced by linear translation when the subject is instructed to stabilize his gaze on a memorized earth-fixed target. These experiments may allow a better understanding of the central processing of otolithic signals. 2. Human subjects were submitted to either sinusoidal or step-like horizontal linear displacements along the interaural (Y)-axis in darkness, seated in a cart moving along a linear track. Each subject's head was fixed by a helmet secured to the cart. They were asked to keep their eyes on an earth-fixed memorized target at 63 cm from them on the X-axis. 3. During sinusoidal motion, a combination of low smooth compensatory eye movements and of compensatory saccades allowed the subjects to track the memorized target. The linear model of the responses of five subjects (seven sessions) exhibited a near-ideal slope of 1.14 (range 0.84-1.58). Two subjects did not compensate properly for their displacement. The mean "vestibular-saccadic" (VS) gain (ratio of overall eye movement peak-peak amplitude versus head displacement amplitude) was 1.52 +/- 0.80 (SD), showing an overestimation of head displacement. 4. The otolith-ocular reflex (OOR) mean gain values (ratio of slow phase cumulated peak-peak amplitude versus head displacement amplitude) were about 0.13 degrees/cm. This value is 5 times higher than what has been reported in the literature, probably due to the fact that the target was at a short distance. 5. The number of saccades occurring during sinusoidal stimulations varied according to the different subjects. They were obviously compensatory saccades and not quick phases. They indicate that although the gain of the OOR was small, the brain has computed the adequate desired eye position. 6. During steplike head displacements in darkness, although the OOR gain was also small, seven of the eight subjects could stabilize their gaze with a mean VS gain of 1.01 +/- 0.70. The linear model for the pooled responses of these subjects exhibited a slope of 0.82. 7. When subjects were instructed not to move their eyes during the translation, three of the five examined could still correctly reproduce the head movement amplitude with saccades, even as late as 50 s after motion had stopped. This indicates that head displacement was stored with the adequate metrics and could be used to drive the saccadic system. 8. Bilabyrinthectomized patients could not perform any adequate gaze stabilization. This shows that the observed performance was of vestibular origin.

Adult↗

PubMed1991

Effects of breed, age of donor and dosage of follicle stimulating hormone on the superovulatory response of beef cows.

Data were obtained on 1039 recoveries of embryos from beef cows of four breeds at two locations, in clinic and on farm. General linear models procedures were utilized to determine the effects of breed, location, age of donor, dosage of follicle stimulating hormone (FSH) and the interaction of age and FSH on the following dependent variables: 1) the mean number of ova (unfertilized oocytes and embryos) recovered; 2) the mean number and percentage of embryos (fertilized; live and dead) recovered; and 3) the mean number and percentage of transferable embryos recovered. The interaction of age of donor and dosage of FSH with breed and location prevented the pooling of data over breed and location. The mean number of ova recovered was affected by age of the donor (Charolais-in clinic), or the interaction between age of donor and dosage of FSH (Polled Hereford-in clinic and -on farm and Simmental -on farm). The mean number of embryos was affected by age of donor (Polled Hereford-in clinic), dosage of FSH (Simmental-in clinic) or their interaction (Angus-on farm). The mean number of transferable embryos was affected by age of donor (Polled Hereford-in clinic and -on farm, Simmental-in clinic and Angus-on farm). General linear models procedures were utilized to determine the effects of the embryo (stage of development and quality) and the recipient (synchrony with the donor) on the rate of pregnancy. Rate of pregnancy varied with embryo quality score and synchrony of the recipient and the embryo. In conclusion, the superovulatory response was found to be highly breed-specific, and most of the variability in embryos produced was attributed to the number of ova recovered. However, the number of ova, embryos and transferable embryos recovered was further influenced by age of the donor, dosage of FSH or their interaction.

Journal Article↗

PubMed1980

Compartment- and model-independent linear plateau principle of drugs during a constant-rate absorption or intravenous infusion.

A simple general equation is derived to show the linear plateau principle under various conditions during or after a constant or changing rate of absorption or intravenous infusion. The time required to cause a certain fraction (ft) of the total shift or change between the two steady-state plasma concentrations is equal to the time required for the cumulative (from time zero) plasma area, AUC 0 leads to t, to reach the same fracton of AUC 0 leads to infinity assumed to be obtained after an instantaneous intravenous dosing. The role of the terminal biological half-life and the importance of the early distribution phase and its exponential half-life or lives in the plateau principle are discussed. Clinical implications and applications to multiple dosage regimens are also discussed.

Humans↗

PubMed1994

Statistical analysis of proliferative index data in clinical trials.

Measurements of proliferative activity in colonic epithelial cells are being used as surrogate endpoints in clinical trials for colon cancer prevention. Proliferative index data exemplify an important type of clinical trial endpoint. The outcome variable is a proportion in which the denominator is an ancillary statistic and in which measurement error and technician judgement are important sources of variability. The paper proposes a statistical model for a repeated measures clinical trial with this type of endpoint, in the context of proliferative activity data. The model is a two-stage random effects linear model in the log scale. In addition to fixed effects covariates, it explicitly incorporates two major sources of variability: the number of epithelial cells counted and the reader effect. Although the resulting likelihood is complicated, one can fit an approximate likelihood with minimal loss of efficiency using standard packages. We apply the model to a pilot randomized clinical trial.

Cell Division↗

PubMed1993

Nonlinear processes in visual pattern discrimination.

Visual performance on many simple pattern discrimination tasks can be accurately predicted by quasi-linear models composed of oriented linear filters followed by simple contrast nonlinearities. However, many complex discrimination tasks require highly nonlinear processes for their explanation. Evidence is provided for two nonlinear processes in pattern discrimination: (i) one process involves a sequence of filtering, rectification, and subsequent filtering to extract texture boundaries; (ii) the second process results from contrast gain-control processes. It is suggested that quasi-linear processes and nonlinear texture-boundary processes, each with an appropriate contrast gain control, may operate in parallel to provide the basis for all higher-level visual analyses.

Discrimination, Psychological↗