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PubMed1998

Detecting measurement confounding in epidemiological research: construct validity in scaling risk behaviours: based on a population sample in Minnesota, USA.

STUDY OBJECTIVE: The purpose of this study was to construct and validate a behavioral risk index scale to determine if the scaled variable could be used to study possible latent dimensions of risk behaviour. DESIGN: Data from the Minnesota Behavioral Risk Factor Surveillance System (BRFSS) were used to construct and validate a behavioral risk index using item response theory methods. PARTICIPANTS: A representative sample of 3303 Minnesota adults 18 years of age and older. RESULTS: Massive evidence was found against the construct validity of the index scale as a measure of risk behaviour. Seven commonly studied risk behaviours could not be scaled into a valid construct of health behaviour for either men or women. Tests of scalability, homogeneity, and item independence were rejected. In addition, item bias was found for all of the items in relation to important exogenous variables, especially age and education. CONCLUSIONS: The risk behaviours do not represent sufficiently similar types of phenomena to form an additive scale of health related risk taking. Not only do the practices fall on different, undefined dimensions of behavior, subgroup differences in risk taking would be hidden by data reductions summing the behavioral practices into additive scales. The findings indicate that the behaviors have quite distinct meanings that should be studied separately.

Adolescent↗
PubMed2000

Genetic screens for factors involved in the notum bristle loss of interspecific hybrids between Drosophila melanogaster and D. simulans.

Interspecific cross is a powerful means to uncover hidden within- and between-species variation in populations. One example is a bristle loss phenotype of hybrids between Drosophila melanogaster and D. simulans, although both the pure species have exactly the same pattern of bristle formation on the notum. There exists a large amount of genetic variability in the simulans populations with respect to the number of missing bristles in hybrids, and the variation is largely attributable to simulans X chromosomes. Using nine molecular markers, I screened the simulans X chromosome for genetic factors that were responsible for the differences between a pair of simulans lines with high (H) and low (L) missing bristle numbers. Together with duplication-rescue experiments, a single major quantitative locus was mapped to a 13F-14F region. Importantly, this region accounted for most of the differences between H and L lines in three other independent pairs, suggesting segregation of H and L alleles at the single locus in different populations. Moreover, a deficiency screening uncovered several regions with factors that potentially cause the hybrid bristle loss due to epistatic interactions with the other factors.

Animals↗
PubMed2005

Residents' end-of-life decision making with adult hospitalized patients: a review of the literature.

PURPOSE: The authors performed a structured literature review to understand residents' experiences with end-of-life (EOL) decision making with adult hospitalized patients, specifically regarding decisions to withhold or withdraw advanced life-support measures. METHOD: An Ovid-based strategy was used to search Medline, ERIC, PsychINFO, and CINHAL databases for articles published between 1966 and February 2005, combining the domains of "resuscitation orders," "decision making," and "internship and residency." All quantitative and qualitative studies examining residents' EOL decision making with adult hospitalized patients were included. The authors developed and applied a scoring system for relevance and quality, performed data abstraction and quality assessment independently and in duplicate, then met to collate findings and identify factors in residents' EOL decision making. RESULTS: The searches yielded 884 articles, of which 26 were included. Variable methodologies precluded meta-analysis. In these studies, residents felt unprepared to handle patient EOL decision making, although exposure to EOL discussions helped them gain confidence. Residents' attitudes, skills, and knowledge were key determinants of whether EOL decisions were addressed. Many misinterpreted the terms "DNR" and "futility." Residents' understanding of the patient EOL decision-making process could be extremely variable, and their do-not-resuscitate discussions suboptimal. Residents' lived practice experience of the patient EOL decision-making process was often at odds with what they were taught in formal curricula. CONCLUSIONS: Educational strategies aimed at changing residents' knowledge, skills and attitude should address the hidden curriculum for the patient EOL decision-making process that is part of the experienced culture of every day practice. Future studies of this experienced culture would inform specific educational interventions.

Adult↗
PubMed1994

Visual field analysis using artificial neural networks.

There have been several reports on the application of artificial neural networks (ANNs) to visual field classification. While these have demonstrated that neural networks can be used with good results they have not explored the effects that the training set can have upon network performance nor emphasized the unique value of ANNs in visual field analysis. This paper considers the problem of differentiating normal and glaucomatous visual fields and explores different training set characteristics using field data collected from a Henson CFS2000 perimeter. Training set properties including size, balance between normals and glaucomas, extent of field loss and the spatial location of glaucomatous defects are explored. A multilayer network with 132 input nodes, 20 hidden layer nodes and 2 output nodes in trained using an error backpropagation algorithm. Both sensitivity and specificity are measured during testing. The results demonstrate that large random sets are better than small random sets since sensitivity improves with size and specificity is not adversely affected. The variability in performance also reduces as training set size increases. In addition, sets that are biased towards glaucoma examples are more sensitive and less specific, while sets biased with normal examples are more specific and less sensitive than balanced sets. Thus large training sets with class balance are generally desirable for good sensitivities and specificities. The actual glaucoma examples contained in the set are also important. A training set deficient in examples has no detrimental effect on sensitivity or specificity. The spatial distribution of defects is also crucial. Spatially biased sets are unable to recognize defects that occur in locations where no previous defect has been presented while more balanced sets lead to better performance. In conclusion the 'ideal' training set should contain many examples of early defects that represent the full range of locations where these defects may occur.

Algorithms↗
PubMed1999

Prediction of tacrolimus blood levels by using the neural network with genetic algorithm in liver transplantation patients.

The neural network (NN) is a technique using an artificial intelligent concept in predicting outcomes by using various input variables. Tacrolimus pharmacokinetics has wide inter- and intra-subject variability and it is often difficult to predict its blood concentrations by dose alone. The objectives of this study are to select the clinically significant variables and to predict the blood concentration of tacrolimus in liver transplant patients by NN combined with genetic algorithm (GA). A total of thirty-two adult liver transplant patients from the University of Iowa Hospitals and Clinics were selected and the patients' data were retrospectively collected. These patient were randomly assigned into two groups: either the training group (n = 10), or testing group (n = 22). A back propagation (BP) NN was developed which contained two hidden layers. A dynamic BP NN based on the time series concept was trained by using the current and previous data sets to predict the trough levels of tacrolimus. The mean of the NN prediction for tacrolimus blood levels was not significantly different from the observed value by a paired t-test comparison (12.05+/-2.67 ng/ml vs. 12.14+/-2.64 ng/ml, p = 0.80). The average difference of the testing sets between the observed and predicted levels was 1.74 ng/ml with a range from 0.08 to 5.26 ng/ml which is clinically acceptable range. Thirty-seven out of 44 data sets (84%) in the testing group were within 3.0 ng/ml of the observed values. This study demonstrated that tacrolimus blood concentrations are precisely predictable in liver transplant patients using patients variables by NN.

Adult↗
PubMed2005

Prediction of vascular tissue engineering results with artificial neural networks.

Tissue engineers are often confused on finding the most successful strategy for specific patient. In this study, we used artificial neural networks to predict the outcomes of different vascular tissue engineering strategies, thus providing advisory information for experimental designers. Over 30 variables were used as features of the tissue engineering strategies. Different architectures of artificial neural networks with back propagation algorithm were tested to obtain the best model configuration for the prediction of the tissue engineering strategies. In the computational experiments, the artificial neural networks with one and two hidden layers could, respectively, detect unsuccessful strategies with the highest predictive accuracy of 91.45 and 94.24%. In conclusion, artificial intelligence has great potential in tissue engineering decision support. It can provide accurate advisory information for tissue engineers, thus reducing failures and improving therapeutic effects.

Animals↗
PubMed1998

A characterization of performance by men and women in a virtual Morris water task: a large and reliable sex difference.

In many mammalian species, it is known that males and females differ in place learning ability. The performance by men and women is commonly reported to also differ, despite a large amount of variability and ambiguity in measuring spatial abilities. In the non-human literature, the gold standard for measuring place learning ability in mammals is the Morris water task. This task requires subjects to use the spatial arrangement of cues outside of a circular pool to swim to a hidden goal platform located in a fixed location. We used a computerized version of the Morris water task to assess whether this task will generalize into the human domain and to examine whether sex differences exist in this domain of topographical learning and memory. Across three separate experiments, varying in attempts to maximize spatial performance, we consistently found males navigate to the hidden platform better than females across a variety of measures. The effect sizes of these differences are some of the largest ever reported and are robust and replicable across experiments. These results are the first to demonstrate the effectiveness and utility of the virtual Morris water task for humans and show a robust sex difference in virtual place learning.

Adult↗
PubMed2001

No overall relationship between average daily weight gain and the serological response to Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae in eight chronically infected Danish swine herds.

The association between the average daily weight gain (from approximately 4 to 20 weeks of age) and the serological responses to respiratory infections was examined in a longitudinal study including 825 pigs from eight chronically infected herds. Pigs were bled every 4th week (starting from approximately 4 weeks of age), and sera were analyzed for antibodies to Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae serotypes 2, 5-7 and 12.Mixed analysis of covariance analyzed the relationship between the average daily weight gain and a categorical variable defining seroconversion as none, early or late as compared to the median time (estimated across herds) of seroconversion for the particular pathogen. The variables "gender", "weight at an approximate age of 4 weeks" and "time" (defining the exact length of the follow-up period), were included as explanatory variables, and "litter" and "herd" were included as explanatory random variables. The individual pig was the unit of concern. The variable defining time at seroconversion was not significantly associated with the average daily weight gain, when evaluating models across all eight herds. The apparent lack of effect could be because most pigs included in the study were subclinically infected, or because a temporary negative influence of the infections is hidden due to an increased growth in the period following infection. In conclusion, at least in these eight herds, seroresponses to M. hyopneumoniae and A. pleuropneumoniae could not be used to predict the effect of the pathogens on the daily weight gain.

Actinobacillus Infections↗
PubMed1999

Positional statistical significance in sequence alignment.

Beginning with the concept of near-optimal sequence alignments, we can assign a probability that each element in one sequence is paired in an alignment with each element in another sequence. This involves a sum over the set of all possible pairwise alignments. The method employs a designed hidden Markov model (HMM) and the rigorous forward and forward-backward algorithms of Rabiner. The approach can use any standard sequence-element-to-element probabilistic similarity measures and affine gap penalty functions. This allows the positional alignment statistical significance to be obtained as a function of such variables. A measure of the probabilistic relationship between any single sequence and a set of sequences can be directly obtained. In addition, the employed HMM with the Viterbi algorithm provides a simple link to the standard dynamic programming optimal alignment algorithms.

Adenylate Kinase↗
PubMed2004

Selectivity control in the separation of aromatic amino acid enantiomers with sulphated beta-cyclodextrin.

Control of selectivity in the enantiomeric separation of three aromatic amino acids (phenylalanine, tyrosine and tryptophan) is demonstrated by electrokinetic capillary chromatography utilising temperature variations coupled with the use of sulphated-beta-cyclodextrin (s-beta-CD) as a pseudostationary phase. The concentration of s-beta-CD and temperature were used as experimental variables to control the observed selectivity. A double-coated capillary was used and proved very robust with reproducibility of migration times being <2.0% R.S.D. between runs and <2.6% on using a new capillary. The system was modelled successfully using an artificial neural network (ANN) comprising one input layer, two hidden layers and one output layer. The model accurately described the observed separations with a correlation coefficient of 0.999 being observed between predicted and observed migration times. Selectivity optimisation was achieved using the normalised resolution product and minimum resolution criteria, with both providing optima at different experimental conditions. The selectivity changes observed also allowed the estimation of electrolyte temperatures within the capillary at high operating currents (>100 microA). Using a 50 microm i.d. capillary and an electrolyte comprising 20 mM phosphate and 15 mM s-beta-CD, a temperature of 52 degrees C was calculated within the capillary at an applied voltage of +30 kV.

Amino Acids, Aromatic↗
PubMed2003

Hippocampal map realignment and spatial learning.

The spatial selectivity of hippocampal neurons suggests that they contribute to an internal representation of current location. The activity of hippocampal pyramidal cells was recorded while adult (10-13 months old) and aged (24-28 months old) rats performed a task in which two spatial reference frames were put in conflict. Rats attempted to find an unmarked goal whose position was fixed relative to only one of the two reference frames. The ability of a rat's hippocampus to adjust to the conflicting information and use the 'correct' position estimate (hippocampal map 'realignment') was correlated with the rat's ability to find the hidden goal. In addition, aged rats were impaired relative to adult rats in both goal-finding accuracy and map realignment. Thus, changes in the effectiveness with which the hippocampal spatial representation is updated on the basis of external cues may contribute to both within-age-group spatial learning variability and age-related spatial learning deficits.

Adaptation, Physiological↗
PubMed1997

Products of partial digestion with Hae III. Part 1. Characterization, casework experience and confirmation of the theory of three-, four- and five-banded RFLP pattern origins using partial digestion.

The sizes of Hae III partial digestion products at D1S7, D2S44, D4S139, D5S110, D10S28, and D17S26 were evaluated in experimentally generated partial digestions of liquid blood DNA. The partial digestion products were highly predictable, suggesting a very high level of sequence conservation in regions flanking variable number tandem repeat (VNTR) blocks. Partial digestion bands associated with three-or-more-banded patterns were also characterized. Partial digestion of three-banded patterns can be used to determine whether the extra bands arise due to internal Hae III sites in the VNTR block and to identify hidden three-banded patterns. Partial digestion products from forensic casework also conformed to size expectations. Presumed partial digestion bands from 27 forensic samples were compared to the experimentally generated data. The causes of partial digestion are examined and recommendations for interpreting forensic DNA evidence exhibiting partial digestion products are given.

Blood Stains↗
PubMed2002

On the emergence of rules in neural networks.

A simple associationist neural network learns to factor abstract rules (i.e., grammars) from sequences of arbitrary input symbols by inventing abstract representations that accommodate unseen symbol sets as well as unseen but similar grammars. The neural network is shown to have the ability to transfer grammatical knowledge to both new symbol vocabularies and new grammars. Analysis of the state-space shows that the network learns generalized abstract structures of the input and is not simply memorizing the input strings. These representations are context sensitive, hierarchical, and based on the state variable of the finite-state machines that the neural network has learned. Generalization to new symbol sets or grammars arises from the spatial nature of the internal representations used by the network, allowing new symbol sets to be encoded close to symbol sets that have already been learned in the hidden unit space of the network. The results are counter to the arguments that learning algorithms based on weight adaptation after each exemplar presentation (such as the long term potentiation found in the mammalian nervous system) cannot in principle extract symbolic knowledge from positive examples as prescribed by prevailing human linguistic theory and evolutionary psychology.

Algorithms↗
PubMed1999

Maternal passive smoking during pregnancy and foetal developmental toxicity. Part 2: histological changes.

1. Evidence has been accumulating on the growth suppressing effects of maternal passive smoking on foetus. Reviewing all literature released during the last two decades and screening for all possible variables such as previous smoking history, maternal age and weight gain, parity and length of gestation, placental weight, and diet, we found no reason to doubt the role of passive smoking during pregnancy in the induction of growth retardation. However, no literature indicates whether these birthweight deficits might hint at other possible hidden abnormalities in tissues. To verify this question, we performed an experiment on rats. 2. We have already reported that pups born to rats with previous exposure to cigarette's sidestream smoke during pregnancy showed a significant and dose-dependent growth retardation. Those pregnant rats were exposed each in a 150 dm3 glass chamber to diluted sidestream smoke of either 1, 2, 3 or 4 commercial blond filter brand cigarettes during either first, second or third week of pregnancy. We have selected a part of each group of pups at random and examined for possible histological changes of lung, liver, stomach, kidney and intestinal tissues. 3. Compared to controls, lung tissues of newborns of smoke exposed mothers showed an enhanced incidence of apoptosis, mesenchymal changes, and hyperplasia of bronchial muscles. Pronounced abnormal changes in haematopoiesis and proliferation of bile duct cells were the most variations from norm observed in liver tissues of exposed pups. Immature glomeruli of kidney, epithelhypoplasia of stomach, and hypoplasia of intestinal villi were common among newborns of exposed mothers than among controls. 4. These results indicate that passive smoking upon pregnancy causes abnormal morphological changes in internal tissues of newborns. At present, we can draw no conclusion as to whether these histological changes will result in functional malformations or possibly late effects, although they should be expected.

Animals↗
PubMed2002

Comparison of four artificial neural network software programs used to predict the in vitro dissolution of controlled-release tablets.

The purpose of this study was to evaluate four commercially available artificial neural network (ANN) software programs: NeuroShell2 v3.0, BrainMaker v3.7, CAD/Chem v5.0, and NeuralWorks Professional II/Plus for prediction of in vitro dissolution-time profiles of controlled-release tablets containing a model sympathomimetic drug. Seven independent formulation variables and three other tablet variables (moisture content of granules, granule particle size, and tablet hardness), for 22 tablet formulations, were used as the ANN model input. In vitro dissolution time-profiles at 10 different sampling times were used as the output. The models' optimum architectures were determined for each ANN software by varying the number of hidden layers and number of nodes in hidden layer(s). The ANN developed from the four software programs were validated by predicting the in vitro dissolution time-profiles of each of the 19 formulations, which were excluded from the training process. Although the same data set was used, the optimum ANN architectures generated from the four software programs were different. Using the four optimum ANN models, the plots of predicted vs. observed percentage of drug dissolved gave slopes ranging from 0.95 to 1.01 and r2 values ranging from 0.95 to 0.99 for all 190 dissolution data points for the 19 training formulations. The difference factors (f1) and similarity factors (f2) between the ANN predicted and the observed in vitro dissolution profiles were also used to compare the predictions for the four software programs. It was concluded that the four programs provided reasonable predictions of in vitro dissolution profiles for the data set employed in this study, with NeuralShell2 showing the best overall prediction.

Delayed-Action Preparations↗
PubMed2002

Immunoassay to quantify the major peach allergen Pru p 3 in foodstuffs. Differential allergen release and stability under physiological conditions.

Pru p 3 is a lipid transfer protein (LTP) that has been identified as the major peach (Prunus persica) allergen. However, little is known about the amount present in both raw and processed foodstuffs. Moreover, the in vivo release upon consumption of peach-containing foods remains unclear. We have developed a sensitive monoclonal antibody-based ELISA for Pru p 3. The method has been applied to measure the allergen levels in foodstuffs and the allergen release under different physiological conditions. A significant variability in all raw peaches and peach-containing foods tested has been detected. The allergen was extracted more efficiently at a low pH, and it was highly resistant to pepsin. This ELISA will be very useful in controlling the allergen concentration in diagnostics, in evaluating threshold levels in provocation tests, and in detecting hidden allergens in processed foods and cosmetics.

Allergens↗
PubMed1993

Phenylketonuria: variable phenotypic outcomes of the R261Q mutation and maternal PKU in the offspring of a healthy homozygote.

Phenylketonuria (PKU) and benign hyperphenylalaninaemia (HPA) result from a variety of mutations in the gene for the hepatic enzyme phenylalanine hydroxylase. PKU has been found in the Israeli population in two variants, classical and atypical. The two are clinically indistinguishable and require treatment with low phenylalanine diet to prevent mental retardation, but show differences in serum phenylalanine levels and in tolerance to this amino acid. Maternal PKU is a syndrome of congenital anomalies and mental retardation that appears in offspring of PKU mothers as a result of fetal exposure to the high phenylalanine level in the maternal blood. We studied a family in which two children with severe, classical PKU and their unaffected brother showed mild signs of maternal PKU. Their mother had no clinical signs of PKU, but the phenylalanine concentration in her serum reached a level that usually characterises PKU patients. This woman represents a rare phenotype, benign atypical PKU. Such 'hidden' PKU in women may lead to maternal PKU in the offspring, similar to overt PKU. Special attention should therefore be paid to women having children with any of the clinical hallmarks of maternal PKU, and to children born to women known to have benign HPA. The mother was also found to be homozygous for a missense mutation at the phenylalanine hydroxylase locus, R261Q, which does not abolish enzymatic activity completely. In two other families, homozygosity for this mutation resulted in atypical PKU in four children. This observation suggests that mutations that do not completely destroy phenylalanine hydroxylase activity may exhibit variable phenotypic expression which is unpredictable. Compound heterozygosity for R261Q and other mutations led in other patients either to classical PKU or to mild benign HPA.

Adult↗
PubMed1998

Limited conscious monitoring of motor performance in normal subjects.

Normal subjects traced sagittal lines on a graphic tablet using a stylus held in their right hand. The hand was hidden by a mirror in which they saw the lines projected from a computer screen. In normal trials, the line seen in the mirror exactly corresponded to the traced line. In perturbed trials, a bias was introduced by the computer, so that the line appeared to deviate in one direction (right or left) by a variable angle (2, 5, 7 or 10 degrees). Subjects consistently displaced their hand in the opposite direction for producing a visually sagittal line. After each trial, they were asked in which direction they thought their hand had moved. In perturbed trials, they grossly underestimated the hand deviation. In addition, a post-hoc analysis revealed that one group of subjects misperceived the direction of their hand movement in the direction opposite to the perturbation (Group 1, including 9 Ss), whereas the other group gave responses in the correct direction (Group 2, including 4 Ss). In a second session using the same experimental paradigm, a motor response was asked for: subjects had to indicate the perceived direction of their hand during each trial by drawing a line with their eyes closed. Again, responses indicated a poor conscious monitoring of motor performance. These results suggest that normal subjects are not aware of signals generated by their own movements.

Adult↗