Non-invasive estimation of the diastolic elastic and viscoelastic properties of the left ventricle

The present study applies a non-invasive method to the quantitative evaluation of left ventricular stiffness in normal subjects and in patients with ischaemic heart disease (IHD). We have studied 20 patients with IHD and 25 healthy subjects. The third heart sound (S3) was detectable in all patients. We have correlated the energy spectrum of S3, divided into 15 Hz bands, with a series of echocardiographic parameters. The existence of a significant correlation between the spectrum energy and the diameter and thickness of the left ventricle at the moment of S3 allowed us to explore the possibility of interpreting the origin of S3 based on a mathematical model. Our hypothesis has been that, once the left ventricle starts vibrating, it behaves as a simple physical model composed of a mass and an elastic element. To this purely elastic model one can add a factor accounting for viscosity, with a damping effect, to obtain a more complex viscoelastic model. The stiffness coefficient 'k' was computed in both models from the peak frequency of S3 and the left ventricular mass at the moment of S3. Furthermore, in the viscoelastic model, the damping element 'c' was also computed. Both parameters--k and c--were significantly increased in the group with IHD compared with the control group. Although a simplification of the vibrating system, these models make it possible to obtain non-invasively information on the characteristics of the left ventricle through the combined use of echocardiography and spectral analysis of S3.     

Methods for analysis of a food frequency questionnaire

Fifty-five students and staff at Robert Gordon's Institute of Technology completed a food frequency questionnaire and then weighed their food for one week. Several methods of calculating nutrient intakes from the questionnaire are compared to results from the weighed inventory. Intakes of energy and several nutrients calculated using estimated typical portion weights were less than those derived from the weighed inventory. Food groups contributing to the apparent under-estimation have been identified. A further method of calculation involved derivation of a factor for each food group such that the frequency estimated from the questionnaire multiplied by the factor equalled the average weight of the foods in that group that had been eaten. Using these factors instead of the typical portion weights resulted in closer agreement to the weighed inventory method, but the difference ranged from positive for some groups to negative for others. Use of separate factors for each group of subjects reduced the range of differences to the weighed inventory method.     

Novel ROC-type method for testing the efficiency of multivariate statistical methods in fMRI.

The receiver operating characteristic (ROC) method is a useful and popular tool for testing the efficiency of various diagnostic tests applicable to functional MRI (fMRI) data. Typically, the diagnostic tests are applied on simulated and pseudo-human fMRI data, and the area under the ROC curve is used as a measure of the efficiency of the diagnostic test. The effectiveness of such a method depends on how well the simulated data approximate the real data. For multivariate statistical methods, however, this technique is usually inadequate, as the spatial dependence among voxels is ignored for simulated data. In this work a modified ROC method using real fMRI data with a broader scope is proposed. This method can be applied to most fMRI postprocessing techniques, including multivariate analyses such as canonical correlation analysis (CCA). Also, the relationship of the modified ROC method with the conventional ROC method is discussed in detail.     

Efficacy of Lung Cancer Screening; Comparison of Results from a Case-Control Study and a Survival Analysis

A case-control study to evaluate the efficacy of lung cancer screening conducted by us showed that lung cancer screening may reduce the mortality of the disease up to 28%. Assuming this efficacy is unbiased, and that the screening rate is 51.6%, which was observed in the control group in the above study, the number of lung cancer deaths prevented by screening in the study period was calculated to be 47 for males and females combined. In the same study population, screen-detected lung cancer patients (N = 207) in the same study period were followed and the 7-year survival rate (46.9%) was compared to the 5-year survival rate (11.3%) obtained by the Osaka Cancer Registry, in which screen-detected lung cancer patients were only 1.8%. The number of lung cancer deaths prevented by screening, estimated by the difference in the above two survival rates, was 74 (95% confidence interval; 55–93). The number of lung cancer deaths prevented by screening estimated from the case-control study was significantly lower than that estimated from the survival analysis. This indicates that the efficacy of lung cancer screening estimated by the case-control study was within the range that could be explained by the actual long-term survivors among the screen-detected patients in the study population.     

Specific statistical considerations relevantto the design and analysis of gingivitis trials demonstrating

Simulation studies were conducted to address specific statistical issues which arise in the design and analysis of gingivitis studies whose principal aim is the demonstration of superiority or equivalence of one product to another. The effects of measurement scale, using differences or ratios of group means, particular statistical test produces and specific rules demonstrating superiority or equivalence were investigated. An alternative concept to equivalence—denoted “least as good”—was also defined and evaluated. For a wide class of possible distributions of gingivitis scores, characterized by specific gamma distributions, the student-t test applied to means of subject GI gingivitis scores proved to be the most powerful of the test produces considered, having statistical properties quite similar to the randomization or permutation test procedure. Transformations of subject GI mean gingivitis scores did not produce an advantage in demonstrating either superiority or equivalence, and in some cases made it more difficult. Little difference was observed in test results when using the difference in group means as compared with using the ratio of group means for demonstrating either equivalence or superiority. The clinically significant rule produced the lowest false-positive rates for products slightly better than the active control, and similar false-positive and -negative rates as the statistically significant rule for products clearly superior to the active control. Demonstration of product equivalence will require more subjects per group than demonstrating product superiority, the size of this difference being a function of the definition of superiority that is accepted. Showing that the 90% confidence interval for 100*R is completely contained within the [90%, 110%] interval is the preferred method of demonstrating equivalence today, although much more research needs to be done to improve methods for demonstrating product equivalence. The “least as good” alternative to “equivalence” makes it easier to demonstrate “equivalence” for products slightly better than the active control product, but both experience great difficulty in demonstrating equivalence for lest products not quite as good as the active control.     

Sequences in the proximal 5′ flanking region of the rat neuron-specific enolase (NSE) gene are sufficient for cell type-specific reporter gene expression

We investigated the regulation of the rat neuron-specific enolase gene using a transient transfection approach. Recent transgenic mouse studies have shown that a 1.8-kb segment of the ratNSE gene 5′ flanking region, including the first (noncoding) exon but not the first intron, is able to drive expression of a reporter gene in parallel with endogenousNSE. These data suggest thatcis-acting elements responsible for the spatial and temporal pattern ofNSE gene expression are located within the proximal 1.8 kb of the 5′ flanking sequence. To further investigate this region, we joined the 1.8-kb regulatory cassette to thecat reporter gene and generated a number of constructs in which the flanking sequence was progressively deleted from the 5′ end. These constructs were tested by transient transfection into neuronal and nonneuronal cells, followed by an assay for CAT activity. We found that as little as 255 bp of 5′ flanking sequence was able to confer cell type-specificity on the reporter gene. Further truncation to 120 bp of 5′ sequence resulted in a sharp downregulation of reporter activity in PC12 cells but a significant rise in both Neuro-2A neuroblastoma cells and nonneuronal Ltk- cells, indicating thatcis-acting elements controlling the regulation ofNSE in Ltk-, Neuro-2A, and PC12 cells may lie within the 135 bp region covered by this deletion. This region contains an AP-2 site and an element similar in sequence and position to a motif identified in the proximal promoter region of the neuron-specific peripherin gene. Reduction to 95 bp of 5′ sequence resulted in a slight downregulation of CAT activity in all cell lines tested, and further truncation to 65 bp of 5′ sequence caused a universal reduction to background levels of CAT activity, concomitant with the disruption of the basalNSE promoter. Our results show that the 5′ flanking region of theNSE gene is capable of conferring cell type-specificity on a heterologous gene in transfected cells and that elements responsible for this are located within the proximal 255 bp.     

Home, training and work: mobility of British doctors

This study examines the locations of family homes, medical schools and places of specialist training, and work of doctors qualifying from UK medical schools in 5 calendar years between 1974 and 1993. The contribution of each UK region to the medical workforce relative to its population is assessed and trends over time are examined. The relationship between place of family home and medical school attended is examined for 14,108 doctors. Career appointment location and its relationship to medical school and family home loc‐ation are examined for over 4000 doctors. For the qualifiers of 1983, an additional analysis incorporating place of training is included. Large differences were found in the percentage of medical students from local family homes attending each regional medical school. In some cases differences reflected local populations but other cases had no obvious cause. Over all cohorts studied, 38% of respondents attended a medical school in the region of their family home (32% of 1993 qualifiers), 42% held a career post in the same region as their medical school, and 38% held a career post in the same region as their family home. Among the qualifiers of 1983, 65% had a career post in the same region as their postgraduate training, 34% also attended medical school in the same region, and 19% also came from family homes in the same region. More women than men took up a career post in the same region as their postgraduate training. The relationships to family home and medical school did not differ by gender. Consultants appeared slightly less likely than GPs to have stayed within a region, but this difference was not statistically significant.     

A method for calculating the mean absorption time of drugs undergoing reversible and first-pass metabolism

A method has been derived for calculating the mean absorption time of an oral drug and its interconversion metabolite which is generated from the drug systemically and presystemically. The method evolves from the convolution integral and requires plasma AUC and AUMC values after separate intravenous administration of the drug and its interconversion metabolite and oral administration of the drug. It can also be used to calculate the mean input time of a drug undergoing reversible metabolism and administered by any other extravascular route. Results of a simulation study using both errorless and errant data indicate that, when the absorption rate constant of a drug or its interconversion metabolite is not much larger than the apparent elimination rate constant, the proposed method performs satisfactorily. However, when the absorption rate constant of a drug or its interconversion metabolite is much larger than the apparent elimination rate constant, the proposed method appears to be inaccurate.     

Measurement of upper extremity orientation by video stereometry system

In the attempt to gain a broader understanding of the causal relationships behind work-related symptoms of pain in the human shoulder, monitoring of arm position is crucial. Different methods have been used with varying accuracy. A video-based stereometry system, using infra-red light and reflecting markers for motion analysis, has been introduced for measurements in the fields of ergonomics, biomechanics and sports medicine. The purpose of this study is to investigate the sources of error in using this system for posture registration of the upper limb. Measurements are performed on a calibration fixture, on a mechanical model of the upper limb and on a subject with an exoskeleton. Particular, attention is given to inconsistencies and relative errors due to the finite geometrical precision with which the markers are positioned in the calibration fixture and on the studied objects, the limited capability to align the objects relative to the coordinate system of the calibration fixture and the errors connected to angular measurements using protractors etc. It is concluded that the system makes a valuable addition to existing instruments for non-contact posture measurement, and produces position data with an adequate accuracy in normal handling.