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Lateralization in stroke syndromes as a factor in ambulation.

Lateralization should not be ignored in any rehabilitation program for patients with stroke syndromes. Despite the known differences resulting from the localization in the dominant versus the nondominant hemisphere (spatial perception, speech, etc.), practical application of this knowledge in gait training is sparse. The authors looked into different stages of ambulation and the time sequence between these stages and the onset of disease. Standing and walking in parallel bars and outside, as well as elevation activities were given numerical values in an effort to assess abilities quantitatively. The assessment of each patient was recorded graphically (stage of gait against time) and then the different graphs were summated in order to form a common right hemiparetic versus left hemiparetic curve. This study of 236 out of 298 patients (129 left hemiparetics and 107 right ones) showed the following: (1) The right hemiparetics progressed more rapidly in all stages of ambulation, statistically significant figures being obtained for the first two stages; (2) a greater percentage of right versus left hemiparetics reached the assigned levels of ambulation: and (3) 89% out of the 236 patients included in our study were able to ambulate in parallel bars, 81% outside the bars and 38.5% were proficient in stair climbing. Out of the original total number of patients (298), 64% were able able to ambulate outside the bars.

Adolescent

A laser densitometer for selective spot analysis on dot blots and two-dimensional gel autoradiograms.

We describe an inexpensive densitometer, employing a small HeNe laser and an IBM-compatible personal computer that performs accurate measurements of selected spots on two-dimensional gel autoradiograms or chromatograms with an accuracy and a sensitivity equal or superior to those of many commercial instruments. Our open-table design allows the operator to visually monitor the scanning process in room lighting, and provides great flexibility in both the size and the nature of items to be scanned. The instrument has two moving parts (a prism and a small motor). A commercially available software package (ASYST) acquires digital data, graphs the data on the TV monitor, converts the data to optical density or to radioactive incorporation (cpm), subtracts background, integrates peak areas, and stores data on disk. The total time for these operations is 20-30 s per spot. The instrument has a dynamic range of 0.25 to 3.0 OD units and can measure a 10,000-fold range of 14C or 35S isotope concentrations on autoradiograms. The complete device can be assembled with a hobbyist's knowledge of electronics, moderate programming abilities (no machine language required), and a cost of less than $3000, not including the IBM PC.

Costs and Cost Analysis

Mathematical model of oxygen transport: a teaching aid for normal physiology adaptable to extracorporeal oxygenation circuits.

The ultimate aim of most intensive care therapies is to improve tissue oxygen delivery; consequently, a detailed knowledge of this area of physiology is important to a wide range of Critical Care Staff. We describe a simple mathematical model of oxygen transport that was initially written as a training aid for extracorporeal oxygenation training. The model has subsequently proved useful for explaining the determinants of oxygen transport to a broader audience. It is based on simple linear equations and is easily displayed with a standard computer spreadsheet. Apart from its teaching value, the model can also generate a graph of oxygen saturation vs. inspired oxygen fraction for different degrees of pulmonary shunt. This provides a noninvasive method for determining the magnitude of pulmonary venous admixture and may also prove to have some clinical value.

Biological Transport, Active

Mathematical assessment of the spatial distribution of Langerhans cells in guinea pig epidermis.

Two mathematical indexes, Hopkins-Skellam index (HSI) and Morisita index (MI), were applied to assess the distribution of ATPase-stained epidermal Langerhans cells (ELC) in the guinea pig skin. To our knowledge, this is the first report in which the degree of regularity has been expressed numerically by computation based on theoretical equations. The regularity of ELC in the normal skin was confirmed by the value of HSI (P < 0.0001). In the topical steroid applied skin, the number of ELC decreased significantly but the value of HSI was similar to that of the normal skin; while in the ultraviolet B (UVB) exposed skin, both number of ELC and regularity of ELC distribution decreased significantly. The graph of MI for the UVB exposed skin clearly showed that the distribution of ELC had local clumps. The two indexes, HSI and MI have been quite useful for determining the regularity of ELC. These indexes may have a wide application to other cells.

Animals

Biological applications of the SAS system: an overview.

The SAS system provides biologists with a flexible, easy to use software package for data analysis. Through a combination of data management tools, a wide variety of pre-programmed procedures for sorting, graphing, and statistical analysis and a sophisticated programming language, SAS software can perform all analytical needs for most problems. The recent availability of SAS software on mainframes other than IBM, and more recently on the microcomputer, means that most scientists can have access to the software. In this review we discuss the structure of the SAS language and demonstrate its power in the analysis of biological problems. Although to a lesser extent now than originally, the SAS system is statistically oriented and a working knowledge of statistics is recommended before using its statistical capabilities. However, all biologists will find its data management and summarization capabilities very useful.

Biology

Clinical trials in surgery.

Scientific knowledge is reliable because it has been built on accurate measurements. Clinical knowledge is not. The science of biometry was started in 1835 by the Belgian astronomer Adolphe Quetelet. In the last fifty years a precise set of rules have been invented for this science. The method is suitable for a wide range of problems in clinical medicine and as the result of its application in recent years a firm foundation has been laid upon which scientific clinical knowledge can be built. Surge-ns, particularly, have been slow to apply biometrical methods to their clinical problems; but a start has now been made. The outcome of a particular type of treatment is determined by a complex set of inter-acting factors. The basis of the appropriate biometrical method is the elimination of all bias in favour of one of the rival techniques being compared. If this precaution is taken the observed results of the trial can be fitted onto Quetelet's distribution graph, and the probability of the observed difference in the results being due to chance, and nothing else, can be measured mathematically. The accuracy of this measurement deteriorates the greater are the number of the patients who can not be found and examined at the end of the trial. To make this point two trials conducted by the author are used. In the trial designed to discover if postoperative deep vein thrombosis and pulmonary embolism could be prevented by electrically stimulating the patients legs during the operation there was no difficulty. All the patients were examined at the end of the trial, because it ended before any of the patients left the hospital. The trial to discover if the primary treatment of varicose veins ought to be by Fegan's sclerotherapy or by operation was the exact opposite. At the end of the first year of the two year trial 15% of the patients could not be traced. The results in these patients, therefore, was unknown. Because of this, elaborate mathematical calculations had to be made to try and reach a reliable conclusion to the trial. The loss of patients before the end of the trial is a very serious practical difficulty which besets all long-term clinical trials.

Clinical Trials as Topic

A hybrid system for diagnosing multiple disorders.

This paper investigates the advantages of introducing feedback between the processes of automated medical diagnosis and automated diagnostic-knowledge acquisition. Experimental results show that a diagnostic system with such feedback is capable of an efficiency/accuracy trade-off when applied to the problem of diagnosing multiple disorders. A primary feature of this work is a new mechanism, called the "diagnostic-unit" representation, for remembering results of previous diagnoses. The diagnostic-unit representation is explicitly tailored to capture the most likely relationships between disorders and clusters of findings. Unlike typical bipartite "If-Then" representations, the diagnostic-unit representation uses a general graph representation to efficiently represent complex causal relationships between disorders and clusters of findings. In addition to the basic diagnostic-unit concept, this paper presents experience-based strategies for incrementally deriving and updating diagnostic units and the various relationships between them. Techniques for selecting diagnostic units relevant to a given problem and then combining them to generate solutions are also described.

Artificial Intelligence

The biomechanics of the long jump.

The preceding review has been based on over 200 publications in Czech, English, French, German, Japanese, Polish, and Russian. Even a cursory perusal of these materials is sufficient to show that much has been done to try and obtain a scientific understanding of long jump techniques. It is clear, too, that still more remains to be done. Much of the work to date has been focused on just a few aspects of long jump technique. Other important aspects have received relatively little attention. The latter include the accuracy of the approach, the techniques used during the final strides of the approach, the role of elastic energy in the takeoff, the initiation and control of the jumper's angular momentum, and the techniques used in the landing. Future research efforts might well be directed towards resolving major issues concerning these aspects of long jump technique. The methods used to gather data in the studies reviewed have been rather unimaginative. Two-dimensional cinematography has been used in the vast majority of the studies and force platforms in a few. Other data-gathering procedures like three-dimensional cinematography, electromyography and accelerometry have rarely, if ever, been used. In only one or two studies was anything remotely approaching experimental or technological innovation in evidence. The methods used to analyze data have also been very limited. With the notable exception of a study by Ballreich, few papers have involved anything more sophisticated than means, standard deviations, correlation coefficients and an occasional multiple regression equation. Given these facts, it is hard to avoid the conclusion that our knowledge of long jump techniques might be greatly improved if the full range of available and appropriate procedures were turned to the purpose. Finally, no review of the literature on long jump techniques would be complete without reference to the level of scholarship displayed in the works under consideration. With only a few exceptions, the level shown in the scientific papers reviewed here left much to be desired. Time and again, variables were not defined, crucial measurement techniques were not described and major results were not presented or discussed. In addition, much of the data presented in tables and graphs were patently in error. In light of all this, it is clear that unless the level of scholarship improves, future progress in this area of sports biomechanics is likely to be very slow.

Biomechanical Phenomena

Systematic method of development in liquid chromatography applied to the determination of antiepileptic drugs.

The object of a liquid-chromatographic analysis is to separate, identify, and quantitate the constituents of interest in a sample mixture within an acceptable analysis time. This will be achieved by a systematic analysis development rather than by a trial-and-error approach. Such a systematic procedure requires a knowledge of the chromatographic parameters governing resolution and analysis time and their relative influences on resolution and its experimental implication. Furthermore, basic information about the mechanisms of the modes of liquid chromatography (adsorption, partition, ion exchange, and steric exclusion) and about the types of sample which can be preferentially analyzed by them is necessary. This information leads to a rational selection of the separation system that promises the best chance of success. In the subsequent experimental work, the analyst systematically measures and calculates resolution and analysis time as functions of selectivity, capacity, and efficiency of the phase system under selected chromatographic conditions. The essential chromatograms, tables, and graphs resulting from this systematic method of development are documented so that it is possible to replicate the analysis procedure in the laboratories involved. The result is a set of chromatographic conditions capable of achieving an optimum compromise between resolution and analysis time. The procedure is applied to routine therapeutic drug monitoring of antiepileptic drugs in patient serum.

Anticonvulsants

Isotachophoretic separation of organic acids in biological fluids.

The operating conditions for the isotachophoretic separation of organic acids were evaluated. At pH values ranging from 2.90 to 4.25 both relative step heights and molar flow-rates were determined experimentally for 26 anions. Comparing the observed values with simulated data, highly significant (p = 0.0001) correlation coefficients of 0.993 and 0.920, respectively, were found at pH 3.50. Whereas the concentration of the leading electrolyte did not affect the relative step heights, it increased the molar flow-rates significantly. The same applied to the detection current. The time of analysis was observed to be a function of the concentration of the leading electrolyte. However, the time elapsed between injection of the analyte and its detection depended solely on the volume and not on the amount of analyte injected. In isotachophoresis, incomplete separation of two compounds is indicated by the occurrence of a mixed zone which can hardly be distinguished from a pure zone. Thus, knowledge of the separation capacity is a prime prerequisite in optimizing the system for the analysis of biological fluids. The separability of nine equimolar pairs of anions was determined at pH values ranging from 2.90 to 4.25. Although two ionogenic constituents would separate only when their migration rates in the mixed state were different, no clear correlation was observed between separation capacity and difference in relative mobility. Separability, however, was found to increase with increasing concentration of the leading electrolyte. While the separation capacity was not influenced by the electric current, it was significantly affected by the volume injected. In subsequent analyses of serum, cerebrospinal fluid, seminal plasma and prostatic fluid, a variety of organic acids could be detected. Calibration graphs for the detected anions revealed a detection limit of 1 nmol and linearity over their biological concentration ranges. Further, the isotachophoretic results correlated well with high-performance liquid chromatographic and enzymatic analyses of citric acid and lactic acid in human seminal plasma and cerebrospinal fluid, respectively.

Acids

Adding meaning to a design copy task through representational stimuli.

Occupational therapists frequently use their knowledge of occupation to add meaning and purpose to therapeutic tasks. This study investigated the effects of an attempt to add meaning to a particular occupational situation--a design copy task. Added meaning was given to the design copy task through the use of stimulus figures that were representational of familiar objects--an arrow, a house, and a face. The control condition consisted of three nonrepresentational figures composed of the same geometric shapes, in the same locations on the paper as the representational figures, but combined differently. The order of presentation was controlled for. The study used 30 elderly subjects (22 women and 8 men) from six nursing homes. The accuracy of the drawings was measured by a blind rater using graph overlays and predetermined rules of scoring. A two-way analysis of variance with one repeated measure (Order X Type of Figure) indicated significant differences at the .01 level between the representational and nonrepresentational figures. This study demonstrates how added meaning can enhance performance on a visuomotor task in a vulnerable population.

Aged

Affiliations among steroid receptors as revealed by multivariate analysis of steroid binding data.

To illustrate the informative value of descriptive multivariate analysis in biochemical screening, we have analyzed several data matrices relating to the binding of steroids to the estrogen, progestin, androgen, glucocorticoid and mineralocorticoid receptors in different organs and species. We first compared dendrograms of steroid hormone receptors, that were obtained by an automatic hierarchical classification analysis of the binding data, to published phylogenetic trees of nuclear receptors based on amino-acid sequence analysis. The former classification describes the affiliations among the receptors as given by the binding specificity of a population of 187 steroids in a traditional cytosol binding assay (an indirect comparison of ligand binding sites); the latter describes the affiliations among the receptors as given by a comparison of selected primary sequences involved in ligand-dependent regulation of transactivation and dimerization. A similar hierarchical classification was also performed on the binding data of 62 steroids to myometrium cytosol from different species in order to show to what extent the progesterone-binding proteins in these species are affiliated. Hierarchical clustering methods classify each type of variable (receptor or steroid) independently. In order to be able to correlate both types of variable (receptors and steroids) on single-display graphs, it is necessary to resort to correspondence factorial analysis (CFA). CFA ranks the information content within the experimental system, highlighting major correlations and disclosing secondary correlations by eliminating redundant information and background noise. This multivariate method, applied to the analysis of published data, illustrated the particular specificity of estrogen binding in human vagina and raised the question of the nature of the binding protein in this tissue. Our examples are based on small data tables that can and have been analyzed de visu. However, it is certain that such descriptive multivariate techniques are indispensable for the analysis of large data banks not only to define structure-activity relationships but to estimate the degrees of affiliation among the biological variables being measured. Knowledge of such affiliations will help to organize available information in a context where the complexity of the biological systems under study is becoming increasingly apparent.

Animals

Can nutrition information increase sales of healthful vended snacks?

Snack selections from unrefrigerated vending machines were studied in relation to increasing availability of nutrient-dense snack options and providing nutrient information at four selected vending sites on a large university campus. Only four of 133 different snacks available for unrefrigerated vending met the criterion for nutrient-dense snacks. When snack proportion was changed to increase availability of nutrient-dense snacks, sales dropped. When nutrition information in bar graph form was posted on the machines, sales increased but not back to the original level. Although snack sales increased after graphic nutrition information was posted, sales were primarily for the least nutrient-dense, perhaps because few well-liked, nutrient-dense snacks were available for unrefrigerated vending. Schools concerned about providing a selection of vended snacks in agreement with the U.S. Dietary Guidelines might be advised to maintain refrigerated vending or to pursue a "healthy snack" machine concept.

Adolescent

Cyclosporine challenge in the decision of combined kidney-pancreas versus solitary pancreas transplantation.

Combined kidney-pancreas transplantation has become the treatment of choice for many patients with end-stage diabetic nephropathy. Pancreas transplantation (PTx) alone is an option for type I diabetic patients without end-stage diabetic nephropathy. Knowledge of factors contributing to or predicting the rate of renal deterioration (including the effect of CsA on the patient's renal function before transplantation) is necessary to determine candidacy for either kidney-pancreas transplantation or PTx alone. To address this issue, we selected 12 pre-uremic patients with creatinine clearances (CrCl) above 40 ml/min and less than 100 ml/min to participate in a 6-week oral CsA challenge test. Serum chemistries, including serum creatinine (SCr) and CsA level, were measured weekly. Urinary protein and CrCl were measured at 0, 2, 4, and 6 weeks. Glomerular filtration rate (GFR) (by 125I-sodium iothalamate clearance) was measured at 0, 3, and 6 weeks. All patients initially received oral CsA at 10 mg/kg/day in 2 divided doses. Doses were adjusted to maintain a 12-hr trough level of 500-1000 ng/ml using a whole blood polyclonal TDX assay. Data are presented as mean +/- SEM and as box-plot graphs. One patient was a CsA challenge test failure because SCr exceeded 3.0 mg/dl despite a reduction in CsA dose and level. Therefore, this patient was not a candidate for PTx alone and was excluded from further analysis. Among the 11 nonfailures, the mean CsA level at 6 weeks was 640 +/- 76 ng/ml. SCr increased from 1.2 +/- 0.1 mg/dl to 1.6 +/- 0.1 mg/dl (33% increase) (P = 0.0001). CrCl decreased from 82 +/- 9 ml/min to 63 +/- 8 ml/min (24% decrease) (P = 0.03). GFR decreased from 95 +/- 15 ml/min to 70 +/- 10 ml/min (26% decrease) (P = 0.009). CrCl and GFR did not differ from one another at 0 and 6 weeks (r = 0.77 and 0.98; P = 0.3 and 0.7, respectively). Urinary protein decreased from 1.0 +/- 0.3 g/day to 0.7 +/- 0.3 g/day at both 4 and 6 weeks (P = 0.03 and 0.06, respectively). Three of the 11 patients have not yet received transplants. Eight patients subsequently received PTx alone and were followed prospectively. Two allografts were lost early to rejection. Six were followed from 5 to 19 months after PTx alone. Serum creatinine and CrCL measurements during the CsA challenge test predicted post-PTx levels: SCr 1.6 +/- 0.1 vs. 1.7 +/- 0.3 mg/dl, P = 0.48, and CrCl 68 +/- 10 vs. 53 +/- 3 ml/min, P = 0.17, respectively.

Adult

Expert system support using Bayesian belief networks in the diagnosis of fine needle aspiration biopsy specimens of the breast.

AIM: To develop an expert system model for the diagnosis of fine needle aspiration cytology (FNAC) of the breast. METHODS: Knowledge and uncertainty were represented in the form of a Bayesian belief network which permitted the combination of diagnostic evidence in a cumulative manner and provided a final probability for the possible diagnostic outcomes. The network comprised 10 cytological features (evidence nodes), each independently linked to the diagnosis (decision node) by a conditional probability matrix. The system was designed to be interactive in that the cytopathologist entered evidence into the network in the form of likelihood ratios for the outcomes at each evidence node. RESULTS: The efficiency of the network was tested on a series of 40 breast FNAC specimens. The highest diagnostic probability provided by the network agreed with the cytopathologists' diagnosis in 100% of cases for the assessment of discrete, benign, and malignant aspirates. Atypical probably benign cases were given probabilities in favour of a benign diagnosis. Suspicious cases tended to have similar probabilities for both diagnostic outcomes and so, correctly, could not be assigned as benign or malignant. A closer examination of cumulative belief graphs for the diagnostic sequence of each case provided insight into the diagnostic process, and quantitative data which improved the identification of suspicious cases. CONCLUSION: The further development of such a system will have three important roles in breast cytodiagnosis: (1) to aid the cytologist in making a more consistent and objective diagnosis; (2) to provide a teaching tool on breast cytological diagnosis for the non-expert; and (3) it is the first stage in the development of a system capable of automated diagnosis through the use of expert system machine vision.

Bayes Theorem

The prenatal development of the normal human skeleton: a combined ultrasonographic and post-mortem radiographic study.

Post-mortem radiography of fetuses with skeletal dysplasia is essential for diagnostic classification. Interpretation of the radiographs should be based on the knowledge of morphology and dimensions of the normal skeleton in all stages of development. A retrospective post-mortem radiographic study is presented with measurements of the lengths of the long bones and thoracic and lumbar spine. The study included 69 fetuses and neonates with a normal skeleton, whose gestational age ranged from 13-42 weeks and who died perinatally or lived for less than one week. The measurements of the long bones were plotted on growth curves obtained from a prospective longitudinal ultrasonographic investigation of another group of 63 normal fetuses from 12-40 weeks of gestation. Thoracic and lumbar spine measurements by ultrasonography were not available. The radiographic data of thoracic and lumbar spine were, therefore, compared to radiographic studies from the literature. No disagreement with these studies was found. It can be concluded that measurements of bones from standardized post-mortem radiographs in cases of questionable gestational age or defects of bone development can be compared with ultrasonographic measurements. To illustrate the usefulness of the graphs, 13 fetuses with various types of skeletal dysplasia were evaluated retrospectively.

Bone Diseases, Developmental

Learning directed acyclic graphs for ligands and receptors based on spatially resolved transcriptomic data of ovarian cancer.

To unravel the mechanism of immune activation and suppression within tumors, a critical step is to identify transcriptional signals governing cell-cell communication between tumor and immune/stromal cells in the tumor microenvironment. Central to this communication are interactions between secreted ligands and cell-surface receptors, creating a highly connected signaling network among cells. Recent advancements in in situ-omics profiling, particularly spatial transcriptomic (ST) technology, provide unique opportunities to directly characterize ligand-receptor signaling networks that power cell-cell communication. In this paper, we propose a novel statistical method, LRnetST, to characterize the ligand-receptor interaction networks between adjacent tumor and immune/stroma cells based on ST data. LRnetST utilizes a directed acyclic graph model with a novel approach to handle the zero-inflated distributions of ST data. It also leverages existing ligand-receptor regulation databases as prior information, and employs a bootstrap aggregation strategy to achieve robust network estimation. Application of LRnetST to ST data of high-grade serous ovarian tumor samples revealed both common and distinct ligand-receptor regulations across different tumors. Some of these interactions were validated through both a MERFISH dataset and a CosMx SMI dataset of independent ovarian tumor samples. These results cast light on biological processes relating to the communication between tumor and immune/stromal cells in ovarian tumors. An open-source R package of LRnetST is available on GitHub at https://github.com/jie108/LRnetST.

Humans

[The effect of synchronization on estrus and pregnancy in sheep and on levels of thyroxine, triiodothyronine, 17 beta-estradiol, progesterone and cholesterol].

Knowledge of pathogenesis of sexual dysfunctions at altered thyroid activity is limited by the knowledge of multiple and ubiquitous action of its hormones throughout the organism. One of the possibilities of modulatory influence of thyroid hormones on sexual functions can be realized through the participation of thyroxine and triiodothyronine in the synthesis and metabolism of primary substrate of steroid synthesis--cholesterol. The presented work is aimed at the study of simultaneous dynamic changes of concentrations of thyroxine (T4), triiodothyronine (T3), 17 beta-estradiol (E2), progesterone (P4) and cholesterol (Chol) during synchronization of the rutting period and gravidity at parallel correlative evaluation of mutual relations of the followed parameters in ten Merino sheep in the seasonal period. Synchronization was achieved by chlorsuperlutin (Agelin--vaginal swabs, Spofa; 20 mg of chlorsuperlutin/swab) and PMSG (500 I. U./animal). Blood was sampled by means of a jugular vein puncture at the time of swab insertion (-13th day) and after three (-10th day) and seven (-7th day) following days, at the removal of swabs and application of PMSG (-3rd day), on the day of insemination (zero day), on the 7th, 14th and 17th day and in the middle of the 2nd, 3rd, 4th and 5th month of gravidity. In the phase of oestrus synchronization a significant increase of E2 concentrations on days -7 and -3 of the experiment (0.47 +/- 0.079 and 0.542 +/- 0.177 nmol.l-1 of serum, P less than 0.001; P less than 0.001) was observed compared to the E2 values on day -13 (0.084 +/- 0.036 nmol.l-1 of serum). Parallel to these observations, marked intermittent changes of T4 (Tab. I, Graph 1) were recorded with the lowest values of this parameter observed on days -10 (41.75 +/- 20.23, P less than 0.05) and -3 (50.22 +/- 18.77, P less than 0.05) and the highest on day -7 (96.77 +/- 17.51 nmol.l-1, P less than 0.01) and day zero (85.40 +/- 19.59 nmol.l-1 of serum, P less than 0.05) in comparison with the -13th day (67.22 +/- 18.29 nmol.l-1 of serum). Concentrations of P4 (Tab. I, Graph 4) declined to the lowest values on day zero observation (0.09 +/- 0.08 nmol.l-1 of serum, P less than 0.05 vs 3.40 +/- 3.61 nmol.l-1 on day -13). No significant changes of concentrations of T3 (Tab. I, Graph 2) and Chol (Tab. I, Graph 5) were observed during oestrus synchronization. During gravidity, concentrations of E2 (Tab. I Graph 3) showed an increasing trend compared to the -13th day.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals