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PubMed1997

Cerebellar contribution to spatial event processing: right/left discrimination abilities in rats.

Recently, we demonstrated the involvement of cerebellar circuits in the procedural components of spatial information processing by testing hemicerebellectomized (HCbed) rats in classical spatial paradigms, such as the Morris Water Maze and the water T-maze. Since procedural components are strongly present in these tests, an impairment also in processing more abstract spatial information, linked to 'where an object is' rather than to 'how to find it', could be hidden by the severe procedural deficits. On this basis, we investigated the influence of cerebellar lesions on spatial abilities strictly reducing procedural variables by employing an active avoidance task, first without and then with a request for right/left discrimination. In the two-way active avoidance task without spatial requests, controls and cerebellar operated rats developed active avoidance responses which were not statistically different, demonstrating that this kind of associative learning is not significantly affected by hemicerebellectomy (HCb). A second experimental group of cerebellar lesioned rats was tested in a modified version of this basic paradigm in which a right/left discrimination request was added. This group displayed severe deficits, which even in the last testing sessions prevented them from performing comparably to the control animals. Reversal of the rewarded choice, even if it affected the performances of both controls and operated rats in the first inversion trials, elicited the lowest number of correct responses in HCbed rats throughout the entire spatial reversal learning, suggesting a severe deficit in the ability to change an initially learned behaviour. These results demonstrate that, beside having a marked impairment in facing procedural components of spatial processing, cerebellar lesioned rats are severely defective also in right/left discrimination tasks, suggesting a role of cerebellar networks also in the discriminative spatial information processing.

Analysis of Variance↗
PubMed1995

Epidemiology and the Italian national health service.

The Italian national health services is under criticism. Although recent legislative changes are intended to introduce managed competition, there is no clear epidemiological view of the health care needs and priorities. Several inconsistencies and inequalities (particularly between the northern and the southern regions) are obvious, both in the health status of the population and in the provision of health care. Problems that should be addressed by future governments are: the uneven distribution of medical technology; the persistence of large inequalities, documented by outcomes such as rheumatic fever, between northern and southern regions; the large variability in clinical practices; the lack of an explicit policy as far as the diffusion of advanced technology is concerned; the ensuing "hidden" rationing; and the peculiar relationship between public and private health structures. Both the current ideological shift towards a market economy for health care and the traditional lack of epidemiological input in health care planning could threaten a rational approach to these problems.

Breast Neoplasms↗
PubMed1977

[Basic patterns in the formation of sluggish schizophrenia according to epidemiologic findings].

The study is based on clinico-epidemiological data concerning sluggish schizophrenia revealed in 214 patients. Conclusions of the formation of a slowly progressive process are made by a retrospective clinical analysis of the disease from the initial period, to the ordinal transition of syndromes, up to the moment of the interview. The unification of the assessment of the present state was accomplished with the aid of a glossary of syndromes. Despite the clinical variants of sluggish schizophrenia the author established some general regularities in the development of the disease with 3 stages. In such forms of the process during the 2nd stage the clinical variability disappears and is substituted by monomorphity. The negative symptoms appear early during the first stage but during decades they may remain hidden by vividly expressed pseudoneurotic and psychopath-like syndromes.

Humans↗
PubMed2006

Object boundaries influence toddlers' performance in a search task.

Previous research has shown that young children have difficulty searching for a hidden object whose location depends on the position of a partly visible physical barrier. Across four experiments, we tested whether children's search errors are affected by two variables that influence adults' object-directed attention: object boundaries and proximity relations. Toddlers searched for a car that rolled down a ramp behind an occluding panel and stopped on contact with a barrier. The car's location on each trial depended on the placement of the barrier behind one of two doors in the panel. In Experiment 1, when a part of the car (a pompom on an antenna) was visible at the same distance from the object as the barrier wall in past research, search performance was above chance but below ceiling. In Experiments 2 and 3, when the visible part was close to the hidden body of the car and could be seen through one of two windows in the doors of the occluding panel, performance was near ceiling. In Experiment 4, when only the barrier was visible through one of the same windows, performance was at chance. Toddlers' search for a hidden object therefore is affected by the proximity of a visible part of the object, though not by the proximity of a separate visible landmark. These findings suggest a parallel between the object representations of young children and those of adults, whose attention is directed to objects and spreads in a gradient-like fashion within an object.

Attention↗
PubMed1983

The analysis of hidden electrophoretic variation: interspecific electrophoretic differentiation and amino acid divergence.

In a study of 25 human variants and 23 "evolutionary alleles" of hemoglobin we show that intraspecific and interspecific patterns of electrophoretic variability are not comparable. Significant deviation from the predicted electrophoretic differentiation between evolutionary alleles is normally found only when amino acid sequence divergence exceeds 10%. When two sequences had diverged at less than 30 out of 287 amino acid residues sites, only 7% of comparisons showed significant deviations from the expected difference of electrophoretic mobility, while significant deviation was shown by 57% of comparisons involving 30-40 residue differences, by 79% in the case of 51-60 differences and by all of the comparisons involving more than 60 differences. In contrast, human variants, which differ by only one or two amino acid residues (less than 1% difference), had significant deviations in 58% of comparisons. Those mutations that appear as fixed differences in the evolutionary material probably represent only a subset of the mutations which can appear within the species. The results suggest that statistical comparisons such as genetic distance may not measure the same process within a species as between species. This is due not to inherent problems with the statistic, but rather to inherent differences in the nature of molecular changes that are detectable by electrophoresis at different stages of population divergence.

Amino Acid Sequence↗
PubMed2006

The "hidden" semantic category dissociation in mild-moderate Alzheimer's disease patients.

In patients manifesting mild-moderate Alzheimer's disease (AD), lexical semantic tasks are known to be influenced by several variables which should be adequately taken into account when studying semantic category dissociations. The following study provides indexes of three new variables (imageability (I), percentage of name agreement (pNA) and number of target alternatives (nTA)) and investigates their role in naming in a group of people with AD and in matched older adults controls. Forty young healthy participants rated I, pNA and nTA of 155 stimuli (including living and non-living items) from and sets. Forty-eight people with mild-moderate AD and 40 older adults were given the two naming tests and their naming ratings were analysed with a two-way ANOVA (two groupsxtwo categories) to assess category specificity and the effect of interaction. The influence of relevant concomitant variables in naming was measured using a multiple regression analysis. Semi-partial correlations were carried out to assess the independent contribution of each variable to naming. We found that living items were more imageable and had fewer lexical alternatives and higher name agreement than non-living items. We also found that controls significantly named better than AD patients (F=37.551, p<.001), whilst the two-way ANOVA showed no significant effect of category (F=.649, p=.423). Notably category effect emerged when assessing its independent contribution performing a semi-partial correlation (beta=-.278, p<.001) which kept the effect of relevant concomitant variables under control. Our results confirm that category dissociation does emerge in mild-moderate AD patients when the effect of relevant concomitant variables is adequately taken into account. The hypothesis that the highly correlated properties of items from biological categories may play a protective effect on living things, making them less prone to impairment in the early stages of AD, is discussed.

Age Factors↗
PubMed1988

Connectionist networks learn to transmit chaos.

Evidence presented in the preceding paper indicates that the activity of some neurons during the generation of coordinated motor patterns may be attributable to chaos. Because even "simple" biological systems are difficult to control, we have used connectionist networks in order to inquire into the question of whether a chaotic signal originating in one part of the nervous system can be learned and transmitted by another. We have examined a number of different architectures, and report here the findings for a simple network consisting of one input unit, four hidden units, and one output unit. During training sessions, the input of the circuit was given analog values of either the 3.60 or 3.95 logistic equation, or of one variable of the three-variable Rössler attractor. The backpropagated error in the learning algorithm was a function of the difference between the input value and the output at each iteration. Iterations involving small changes in analog value resulted in good similarity between the input and output signals, but little learning occurred because of the small error propagated back to the synapses. With larger differences in the analog values (and larger feedback error) at each iteration, we found that networks learned to transmit different chaotic attractors. Once the network learned one input, it could transmit another without changing the synapses. Increasing the number of hidden units increased the rate of learning.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Simulation↗
PubMed2004

The importance of 'memory' in statistical models for animal feeding behaviour.

We investigate models for animal feeding behaviour, with the aim of improving understanding of how animals organise their behaviour in the short term. We consider three classes of model: hidden Markov, latent Gaussian and semi-Markov. Each can predict the typical 'clustered' feeding behaviour that is generally observed, however they differ in the extent to which 'memory' of previous behaviour is allowed to affect future behaviour. The hidden Markov model has 'lack of memory', the current behavioural state being dependent on the previous state only. The latent Gaussian model assumes feeding/non-feeding periods to occur by the thresholding of an underlying continuous variable, thereby incorporating some 'short-term memory'. The semi-Markov model, by taking into account the duration of time spent in the previous state, can be said to incorporate 'longer-term memory'. We fit each of these models to a dataset of cow feeding behaviour. We find the semi-Markov model (longer-term memory) to have the best fit to the data and the hidden Markov model (lack of memory) the worst. We argue that in view of effects of satiety on short-term feeding behaviour of animal species in general, biologically suitable models should allow 'memory' to play a role. We conclude that our findings are equally relevant for the analysis of other types of short-term behaviour that are governed by satiety-like principles.

Animals↗
PubMed1996

Multiple neural network response variability as a predictor of neural network accuracy for chromosome recognition.

Human chromosome classification requires all chromosome appearing in a microphotograph of a dividing human cell to be classified within the known normal or abnormal 24 chromosome types. In recent years, research has focused on the use of neural networks for classification of normal chromosomes. Experimental work in this area led us to question whether learning variability, resulting when multiple neural networks are trained to solve the same problem, could be used as a predictor of classification performance. The Copenhagen chromosome data bank, consisting of 30-component feature vectors from 8106 chromosomes isolated from 180 cells, was divided into a training and a test subsets. Back propagation neural networks with 30 input nodes, 1 to 100 nodes in the hidden layer, and 24 output nodes were trained with the same learning parameters. After training, each neural network was tested. The neural network yielding the best classification was labeled as the optimal neural network. An error variability score was calculated for each test chromosome. This score was a function of all (100) neural network outputs obtained for that chromosome. The error variability scores ranged from 0.16 to 1.31 with a mean value of 0.41 and a SD of 0.12. There was significant difference (p < 0.0001) between the variability scores from chromosomes classified correctly (mean = 0.4, SD = 0.1, n = 3804) and incorrectly (mean = 0.62, SD = 0.19, n = 241) by the optimal neural network. When the variability score was used as a threshold to decide whether or not to accept the output of the optimal neural network, a peak classification rate of 98.93% was observed for chromosomes with an error variability score < 0.35. Results indicate that the error variability of multiple neural network responses can be used as a confidence indicator for a optimal neural network.

Humans↗
PubMed2001

A full-length and potentially active LINE element is integrated polymorphically within the IGL locus in a genomically unstable region of chromosome 22.

Leukemic cells of a patient diagnosed with chronic myeloid leukemia (CML) showed a complex BCR-ABL1 rearrangement hidden within a normal appearing karyotype. Previous molecular studies had established that the 3' BCR had recombined at a novel site within the variable region of the immunoglobulin lambda locus ( IGL). A segment of DNA mapping very close to the site of the IGL/3' BCR recombination recognized a previously undescribed insertion polymorphism. A combination of molecular hybridization studies and long-range polymerase chain reaction was used to isolate a 6-kb full-length long interspersed nuclear element (LINE or L1), here designated L1(IGL), which occupies 19% of alleles in the general population. Although unclonable, DNA sequence analysis by a primer walking approach established that L1(IGL) has features characteristic of an actively retrotransposing element. The L1(IGL) element has a 5' untranslated region, two open reading frames (ORF-1 and ORF-2), a 3' untranslated region and terminates in a poly-A tail. We compared the DNA sequence and the predicted amino acid sequence of L1(IGL) with a consensus sequence compiled from seven reported active L1 elements. This analysis indicated that L1(IGL) has high potential for involvement in as yet undetermined somatically and constitutionally acquired disease, not only through recombination mechanisms, but also through retrotransposition events. This full-length L1 element maps close within the IGLlocus to L1.2, one of only nine active L1 elements that have been reported so far. L1(IGL) and L1.2 map within a wider and well-recognized region of genomic instability on chromosome 22.

Base Sequence↗
PubMed2002

Inferences from whole-genome sequences of bacterial pathogens.

Genomic sequencing of bacterial pathogens has recently moved from the study of distantly related organisms to within-species comparisons of multiple strains. Strains often differ in their ability to cause disease, and comparative genomics is uncovering novel virulence determinants, hidden aspects of pathogenesis, and new targets for vaccine development. DNA microarrays and other gene-survey techniques are being used to quantify variability in gene content within bacterial populations, and to reveal the strain-specific basis for diversity and severity of pathology.

Bacteria↗
PubMed1997

Adaptive sampling in behavioral surveys.

Studies of populations such as drug users encounter difficulties because the members of the populations are rare, hidden, or hard to reach. Conventionally designed large-scale surveys detect relatively few members of the populations so that estimates of population characteristics have high uncertainty. Ethnographic studies, on the other hand, reach suitable numbers of individuals only through the use of link-tracing, chain referral, or snowball sampling procedures that often leave the investigators unable to make inferences from their sample to the hidden population as a whole. In adaptive sampling, the procedure for selecting people or other units to be in the sample depends on variables of interest observed during the survey, so the design adapts to the population as encountered. For example, when self-reported drug use is found among members of the sample, sampling effort may be increased in nearby areas. Types of adaptive sampling designs include ordinary sequential sampling, adaptive allocation in stratified sampling, adaptive cluster sampling, and optimal model-based designs. Graph sampling refers to situations with nodes (for example, people) connected by edges (such as social links or geographic proximity). An initial sample of nodes or edges is selected and edges are subsequently followed to bring other nodes into the sample. Graph sampling designs include network sampling, snowball sampling, link-tracing, chain referral, and adaptive cluster sampling. A graph sampling design is adaptive if the decision to include linked nodes depends on variables of interest observed on nodes already in the sample. Adjustment methods for nonsampling errors such as imperfect detection of drug users in the sample apply to adaptive as well as conventional designs.

Behavior↗
PubMed1990

On the hidden physical dimensions of the allometric equation.

The aim of the present study was to submit Huxley's allometric equation (Y = aMb) to a dimensional analysis; in this equation Y is any biological variable, a is the mass-coefficient, M represents body mass, and b the mass-exponent. The dimensions of each of its components is thoroughly analyzed by means of the MLT-system of physics, as is the dimensionality of the whole equation. The relationship between the dimensional analysis and the postulates of some theories of biological similarity is discussed. In conclusion, parameter a of the allometric equation is always dimensionless, while the physical dimensions of the dependent variable Y can be defined by means of the power function Mb.

Biometry↗
PubMedDate not supplied

[Application of artificial neural networks for risk stratification of hospital mortality].

OBJECTIVE: To compare the ability of an artificial neural network (ANN) to predict hospital mortality with that of the Acute Physiology and Chronic Health Evaluation II (APACHE II) system and multiple logistic regression (LR). A secondary objective was to compare the allocation of individual probability among the models. METHOD: The variables required for calculating the APACHE II were prospectively collected. A total of 1146 patients were divided (randomly 70% and 30%) into the Development (800) and the Validation (346) sets. With the same variables an LR model and an ANN were carried out (a 3-layer perceptron trained by algorithm backpropagation with bootstrap resampling and with 9 nodes in the hidden layer) in the Development set. The models developed were contrasted with the Validation set and their discrimination properties were evaluated using the area under the ROC curve (AUC [95% CI]) and calibration with the Hosmer-Lemeshow C (HLC) test. Differences between the probabilities were evaluated using the Bland-Altman test. RESULTS: The Validation set showed an APACHE II with an AUC = 0.79 (0.75-0.84) and HLC = 11 (p = 0.329); LR model AUC = 0.81 (0.76-0.85) and HLC = 29 (p = 0.0001) and an ANN AUC = 0.82 (0.77-0.86) and HLC = 10 (p = 0.404). The patients with the most important differences in the allocation of probability between LR and ANN (8% of the total) were neurological. The worst results were found in trauma patients with an AUC of not greater than 0.75 in all the models. In respiratory patients, the ANN achieved the best AUC = 0.87 (0.78-0.91). CONCLUSIONS: The ANN was able to stratify hospital mortality risk by using the APACHE II system variables. The ANN tended to achieve better results than LR, since, in order to work, it does not require lineal restrictions or independent variables. Allocation of individual probability differed in each model.

Female↗
PubMed2002

Preparation of name and address data for record linkage using hidden Markov models.

BACKGROUND: Record linkage refers to the process of joining records that relate to the same entity or event in one or more data collections. In the absence of a shared, unique key, record linkage involves the comparison of ensembles of partially-identifying, non-unique data items between pairs of records. Data items with variable formats, such as names and addresses, need to be transformed and normalised in order to validly carry out these comparisons. Traditionally, deterministic rule-based data processing systems have been used to carry out this pre-processing, which is commonly referred to as "standardisation". This paper describes an alternative approach to standardisation, using a combination of lexicon-based tokenisation and probabilistic hidden Markov models (HMMs). METHODS: HMMs were trained to standardise typical Australian name and address data drawn from a range of health data collections. The accuracy of the results was compared to that produced by rule-based systems. RESULTS: Training of HMMs was found to be quick and did not require any specialised skills. For addresses, HMMs produced equal or better standardisation accuracy than a widely-used rule-based system. However, accuracy was worse when used with simpler name data. Possible reasons for this poorer performance are discussed. CONCLUSION: Lexicon-based tokenisation and HMMs provide a viable and effort-effective alternative to rule-based systems for pre-processing more complex variably formatted data such as addresses. Further work is required to improve the performance of this approach with simpler data such as names. Software which implements the methods described in this paper is freely available under an open source license for other researchers to use and improve.

Data Collection↗
PubMed1998

Sequence, structural, functional, and phylogenetic analyses of three glycosidase families.

Glycosidases, which cleave the glycosidic bond between a carbohydrate and another moiety, have been classified into over 63 families. Here, a variety of computational techniques have been employed to examine three families important in normal and abnormal pathology with the aim of developing a framework for future homology modeling, experimental and other studies. Family 1 includes bacterial and archaeal enzymes as well as lactase phlorizin-hydrolase and klotho, glycosidases implicated in disaccharide intolerance II and aging respectively. A statistical model, a hidden Markov model (HMM), for the family 1 glycosidase domain was trained and used as the basis for comparative examination of the conserved and variable sequence and structural features as well as the phylogenetic relationships between family members. Although the structures of four family 1 glycosidases have been determined, this is the first comparative examination of all these enzymes. Aspects that are unique to specific members or subfamilies (substrate binding loops) as well those common to all members (a beta/alpha)8 barrel fold) have been defined. Active site residues in some domains in klotho and lactase-phlorizin hydrolases differ from other members and in one instance may bind but not cleave substrate. The four invariant and most highly conserved residues are not residues implicated in catalysis and/or substrate binding. Of these, a histidine may be involved in transition state stabilization. Glucosylceramidase (family 30) and galactosylceramidase (family 59) are mutated in the lysosomal storage disorders Gaucher disease and Krabbe disease, respectively. HMM-based analysis, structure prediction studies and examination of disease mutations reveal a glycosidase domain common to these two families that also occurs in some bacterial glycosidases. Similarities in the reactions catalyzed by families 30 and 59 are reflected in the presence of a structurally and functionally related (beta/alpha)8 barrel fold related to that in family 1.

Amino Acid Sequence↗
PubMed1990

Complex translocations, simple variant translocations and Ph-negative cases in chronic myelogenous leukaemia.

A proportion of cases of chronic myelogenous leukaemia (CML) has been described either (1) with a variant translocation, or (2) without the apparent involvement of both 9q34 and 22q11 (Ph-negative CML). All variant translocations have been further demonstrated to be complex implicating 9q34,22q11, plus another breakpoint on a variable chromosome. Complex translocations may be due to two successive events. Some of the breakpoints on the variable chromosome appear to be recurrent, and these remain to be studied for prognostic significance. Ph-negative CML comprises (1) cases of submicroscopic (hidden) insertion of 9q34-ABL within 22q11-BCR, and (2) cases without BCR-ABL rearrangement. We propose this last category to be called "CML-like disease", not to be confused anymore with true CML, and consequently to be studied as a separate entity.

Chromosomes, Human, Pair 22↗
PubMed2001

Mathematical elegance with biochemical realism: the covarion model of molecular evolution.

There is an apparent paradox in our understanding of molecular evolution. Current biochemically based models predict that evolutionary trees should not be recoverable for divergences beyond a few hundred million years. In practice, however, trees often appear to be recovered from much older times. Mathematical models, such as those assuming that sites evolve at different rates [including a Gamma distribution of rates across sites (RAS)] may in theory allow the recovery of some ancient divergences. However, such models require that each site maintain its characteristic rate over the whole evolutionary period. This assumption, however, contradicts the knowledge that tertiary structures diverge with time, invalidating the rate-constancy assumption of purely mathematical models. We report here that a hidden Markov version of the covarion model can meet both biochemical and statistical requirements for the analysis of sequence data. The model was proposed on biochemical grounds and can be implemented with only two additional parameters. The two hidden parts of this model are the proportion of sites free to vary (covarions) and the rate of interchange between fixed sites and these variable sites. Simulation results are consistent with this approach, providing a better framework for understanding anciently diverged sequences than the standard RAS models. However, a Gamma distribution of rates may approximate a covarion model and may possibly be justified on these grounds. The accurate reconstruction of older divergences from sequence data is still a major problem, and molecular evolution still requires mathematical models that also have a sound biochemical basis.

Evolution, Molecular↗