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PubMed1973

Stimulus control and auditory discrimination learning sets in the bottlenose dolphin.

The learning efficiency of an Atlantic bottlenose dolphin was evaluated using auditory discrimination learning-set tasks. Efficiency, as measured by the probability of a correct response on Trial 2 of a new discrete-trial, two-choice auditory discrimination problem, reached levels comparable to those attained by advanced species of nonhuman primates. Runs of errorless problems in some cases rivaled those reported for individual rhesus monkeys in visual discrimination learning-set tasks. This level of stimulus control of responses to new auditory discriminanda was attained through (a) the development of a sequential within-trial method for presentation of a pair of auditory discriminanda; (b) the extensive use of fading methods to train initial discriminations, followed by the fadeout of the use of fading; (c) the development of listening behavior through control of the animal's responses during projection of the auditory discriminanda; and (d) the use of highly discriminable auditory stimuli, by applying results of a parametric evaluation of discriminability of selected acoustic variables. Learning efficiency was tested using a cueing method on Trial 1 of each new discrimination, to allow the animal to identify the positive stimulus before its response. Efficiency was also tested with the more common blind baiting method, in which the Trial 1 response was reinforced on only a random half of the problems. Efficiency was high for both methods. The overall results were generally in keeping with exceptations of learning capacity based on the large size and high degree of cortical complexity of the brain of the bottlenose dolphin.

Journal Article↗
PubMed1978

[Effects of bilateral amygdalectomy on levers pressing for food reward in the rabbit (author's transl)].

Effects for continuous reinforcement (CRF) learning and differential reinforcement of low rate (DRL) learning for food in the rabbit by bilateral amygdalectomy were examined with the Skinner box. There was no changes in general behaviour and no impediment of CRF learning. But the completion of DRL learning was delayed by amygdalectomy. In the stage of completion of DRL learning there was no difference of total number of the reinforcement and the lever pressing between the control group and amygdalectmized group. But there was the impediment of DRL learning by the analysis of frequency distribution of inter-response time and of transition probability matrix in the amygdalectimized group. We thought that this impediment of DRL learning was due to the impediment of selection of decision of lever pressing action. The memory of the preamygdalectomy was maintained well after amygdalectomy.

Amygdala↗
PubMed1997

Treatment of agitation in dementia.

Agitation occurs commonly in patients with dementia. Before symptomatic pharmacotherapy is undertaken, it is imperative to perform a sequence of evaluations and interventions to establish whether simpler and safer, nonpharmacologic approaches will be beneficial. When psychotropic medications are used they should be used judiciously, in the lowest effective doses and for the shortest period of time necessary. Ineffective medications should be stopped, and even effective medications should be empirically tapered in most patients to learn whether treatment is still necessary. Antipsychotics probably show the greatest benefit for agitation associated with psychotic features; they have less demonstrated efficacy for agitation not associated with psychotic features. The side effects of typical agents are legion; data are pending regarding atypical agents. The available evidence regarding nonneuroleptic medications ranges from case reports to well-designed, double-blind, placebo-controlled, randomized, parallel group studies. Literature exists describing the use of anticonvulsants, anxiolytics, serotonergic antidepressants, and other agents to manage agitation. Carbamazepine and divalproex sodium (valproate) have demonstrated efficacy in uncontrolled studies, whereas the use of carbamazepine has produced negative results in one small controlled study and positive results in two larger controlled studies. Buspirone has shown benefit in some open trials. Encouraging early findings have been reported for trazodone, including from one controlled trial. Varying results have been obtained using selective serotonin reuptake inhibitors, but with consistently encouraging anecdotes. In the aggregate, the evidence suggests but does not prove that alternatives to traditional antipsychotics exist. Again, none of these agents has yet been approved for this purpose by the FDA. As more studies become available we will have a better idea about which classes of agents are most efficacious. It is likely that there may be a role for "rational" polypharmacy in the management of this distressing complication of dementia. However, no studies that we know of address combination therapy, so the clinician must contemplate this option on a case-by-case basis. Clinical trials data are pending from studies with divalproex sodium, carbamazepine, haloperidol versus trazodone versus placebo, risperidone, olanzapine, quetiapine, donepezil, xanomeline, tacrine, buspirone, and sertraline, at the very least. These data will undoubtedly have a major impact on how we care for our patients and lead to revisions of current practice guidelines.

Aged↗
PubMed2005

Signal-dependent wavelets for electromyogram classification.

In the study, an efficient method to perform supervised classification of surface electromyogram (EMG) signals is proposed. The method is based on the choice of a relevant representation space and its optimisation with respect to a training set. As EMG signals are the summation of compact-support waveforms (the motor unit action potentials), a natural tool for their representation is the discrete dyadic wavelet transform. The feature space was thus built from the marginals of a discrete wavelet decomposition. The mother wavelet was designed to minimise the probability of classification error estimated on the learning set (supervised classification). As a representative example, the method was applied to simulate surface EMG signals generated by motor units with different degrees of short-term synchronisation. The proposed approach was able to distinguish surface EMG signals with degrees of synchronisation that differed by 10%, with a misclassification rate of 8%. The performance of a spectral-based classification (error rate approximately 33%) and of the classification with Daubechies wavelet (21%) was significantly poorer than with the proposed wavelet optimisation. The method can be used for a number of different application fields of surface EMG classification, as the feature space is adapted to the characteristics of the signal that discriminate between classes.

Action Potentials↗
PubMed1995

Clinical research in ancient Babylon: methodologic insights from the book of Daniel.

Around 600 BC, Daniel of Judah conducted what is widely regarded as the earliest recorded clinical trial. His trial compared the health effects of a vegetarian diet with those of a royal Babylonian diet over a 10-day period. The strengths of his study include the use of a contemporaneous control group, use of an independent assessor of outcome, and striking brevity in the published report. Weaknesses include probable selection bias, ascertainment bias, and confounding by divine intervention. Although Daniel probably never achieved tenure, he did get "learning and skill in all letters and wisdom ... and understanding in all visions and dreams" (well before Freud). Despite the trial's dramatic findings, over 4 centuries elapsed before publication of Daniel's results. Daniel apparently perished, then published.

Bible↗
PubMed2006

Probabilistic inference in human semantic memory.

The idea of viewing human cognition as a rational solution to computational problems posed by the environment has influenced several recent theories of human memory. The first rational models of memory demonstrated that human memory seems to be remarkably well adapted to environmental statistics but made only minimal assumptions about the form of the environmental information represented in memory. Recently, several probabilistic methods for representing the latent semantic structure of language have been developed, drawing on research in computer science, statistics and computational linguistics. These methods provide a means of extending rational models of memory retrieval to linguistic stimuli, and a way to explore the influence of the statistics of language on human memory.

Association Learning↗
PubMed1989

Development of rotorod performance in normal and congenitally hypothyroid mutant mice.

Balancing behavior on a rotating cylinder was measured in genetically hypothyroid (hyt/hyt) mutant mice and their phenotypically normal littermates (hyt/+) at 10 different ages between Day 12 and Day 55. Normal mice showed competent balancing behavior in this task by 23 days of age, but mutant hypothyroid mice were incapable of balancing throughout the period of testing. Similar results were found with animals initially tested as adults, indicating that the developmental effects are probably not attributable to different rates of learning. These results are discussed in terms of documented central nervous system abnormalities in animals deprived of thyroid hormone early in life.

Aging↗
PubMed1998

Teaching critical thinking for transfer across domains. Dispositions, skills, structure training, and metacognitive monitoring.

Advances in technology and changes in necessary workplace skills have made the ability to think critically more important than ever before, yet there is ample evidence that many adults consistently engage in flawed thinking. Numerous studies have shown that critical thinking, defined as the deliberate use of skills and strategies that increase the probability of a desirable outcome, can be learned in ways that promote transfer to novel contexts. A 4-part empirically based model is proposed to guide teaching and learning for critical thinking: (a) a dispositional component to prepare learners for effortful cognitive work, (b) instruction in the skills of critical thinking, (c) training in the structural aspects of problems and arguments to promote transcontextual transfer of critical-thinking skills, and (d) a metacognitive component that includes checking for accuracy and monitoring progress toward the goal.

Adult↗
PubMed2000

Self-regulation and depletion of limited resources: does self-control resemble a muscle?

The authors review evidence that self-control may consume a limited resource. Exerting self-control may consume self-control strength, reducing the amount of strength available for subsequent self-control efforts. Coping with stress, regulating negative affect, and resisting temptations require self-control, and after such self-control efforts, subsequent attempts at self-control are more likely to fail. Continuous self-control efforts, such as vigilance, also degrade over time. These decrements in self-control are probably not due to negative moods or learned helplessness produced by the initial self-control attempt. These decrements appear to be specific to behaviors that involve self-control; behaviors that do not require self-control neither consume nor require self-control strength. It is concluded that the executive component of the self--in particular, inhibition--relies on a limited, consumable resource.

Attention↗
PubMed2000

Optimal amnesic probabilistic automata or how to learn and classify proteins in linear time and space.

Statistical modeling of sequences is a central paradigm of machine learning that finds multiple uses in computational molecular biology and many other domains. The probabilistic automata typically built in these contexts are subtended by uniform, fixed-memory Markov models. In practice, such automata tend to be unnecessarily bulky and computationally imposing both during their synthesis and use. Recently, D. Ron, Y. Singer, and N. Tishby built much more compact, tree-shaped variants of probabilistic automata under the assumption of an underlying Markov process of variable memory length. These variants, called Probabilistic Suffix Trees (PSTs) were subsequently adapted by G. Bejerano and G. Yona and applied successfully to learning and prediction of protein families. The process of learning the automaton from a given training set S of sequences requires theta(Ln2) worst-case time, where n is the total length of the sequences in S and L is the length of a longest substring of S to be considered for a candidate state in the automaton. Once the automaton is built, predicting the likelihood of a query sequence of m characters may cost time theta(m2) in the worst case. The main contribution of this paper is to introduce automata equivalent to PSTs but having the following properties: Learning the automaton, for any L, takes O (n) time. Prediction of a string of m symbols by the automaton takes O (m) time. Along the way, the paper presents an evolving learning scheme and addresses notions of empirical probability and related efficient computation, which is a by-product possibly of more general interest.

Algorithms↗
PubMed2004

Optimizing exact genetic linkage computations.

Genetic linkage analysis is a challenging application which requires Bayesian networks consisting of thousands of vertices. Consequently, computing the probability of data, which is needed for learning linkage parameters, using exact computation procedures calls for an extremely efficient implementation that carefully optimizes the order of conditioning and summation operations. In this paper, we present the use of stochastic greedy algorithms for optimizing this order. Our algorithm has been incorporated into the newest version of SUPERLINK, which is a fast genetic linkage program for exact likelihood computations in general pedigrees. We demonstrate an order of magnitude improvement in run times of likelihood computations using our new optimization algorithm and hence enlarge the class of problems that can be handled effectively by exact computations.

Algorithms↗
PubMed1993

Dyslexia and visual perception: is there a relation?

Opinions differ concerning the relation between dyslexia and visual perception. In this pilot study we addressed this question by analyzing the results of visual perceptual testing on 19 elementary grade subjects diagnosed as having dyseidesia, one type of dyslexia that manifests as problems with sight-word recognition. The subjects, who have different degrees of severity of dyseidesia, were compared with 11 subjects tested as nondyslexic, but with reading problems. The Dyslexia Determination Test (DDT) and the Test of Visual Perceptual Skills (TVPS) were given to all subjects. Both multivariate analysis of variance (MANOVA) and univariate one-way analysis of variance (ANOVA) to test for differences in performance among four test groups (ranging from nondyslexic to increasing levels of severity of dyseidesia) showed no trends of either statistical or clinical importance. An individual with reading problems may be nondyslexic but have poor visual perceptual skills, or may be dyslexic with good visual perceptual skills. These results are consistent with the contention that reading problems caused by dyseidesia (as defined by the DDT) and those caused by visual perceptual deficiencies (as defined by the TVPS) are different. Although dyseidetic dyslexia results in characteristic coding patterns producing specific reading problems, it is probable that visual perceptual deficiencies contribute to learning problems that include general reading problems. Each condition would, therefore, require different forms of therapy. Limitations of this study and recommendations for future research are discussed.

Adolescent↗
PubMed2005

Model-based segmentation of medical imagery by matching distributions.

The segmentation of deformable objects from three-dimensional (3-D) images is an important and challenging problem, especially in the context of medical imagery. We present a new segmentation algorithm based on matching probability distributions of photometric variables that incorporates learned shape and appearance models for the objects of interest. The main innovation over similar approaches is that there is no need to compute a pixelwise correspondence between the model and the image. This allows for a fast, principled algorithm. We present promising results on difficult imagery for 3-D computed tomography images of the male pelvis for the purpose of image-guided radiotherapy of the prostate.

Algorithms↗
PubMed1985

Comparison of abilities of preterm and maturely born children at 5 years of age.

This study investigated whether the development of 5 year old preterm born children was appropriate for age and equivalent to or different from their peers who were full term at birth. At the adjusted age of 5 years, the development of 106 children born 5 or more weeks before term was compared with the development of 103 children who were born at term. This latter group of children were matched to the preterm group in sex, year of birth, birthplace, race and residential location. No cerebral palsy children were included in either subject group. The results indicated a significant difference between the two groups. Factors distinguishing the preterm children from their full term peers included small involuntary hand movements, less competent gross motor ability, poorer verbal performance and more variability in behaviour, postural response and balance. A higher than average incidence of minor motor, speech, behaviour and learning problems in early school years is probable.

Child Behavior↗
PubMed2006

A novel scoring schema for peptide identification by searching protein sequence databases using tandem mass spectrometry data.

BACKGROUND: Tandem mass spectrometry (MS/MS) is a powerful tool for protein identification. Although great efforts have been made in scoring the correlation between tandem mass spectra and an amino acid sequence database, improvements could be made in three aspects, including characterization ofpeaks in spectra, adoption of effective scoring functions and access to thereliability of matching between peptides and spectra. RESULTS: A novel scoring function is presented, along with criteria to estimate the performance confidence of the function. Through learning the typesof product ions and the probability of generating them, a hypothetic spectrum was generated for each candidate peptide. Then relative entropy was introduced to measure the similarity between the hypothetic and the observed spectra. Based on the extreme value distribution (EVD) theory, a threshold was chosen to distinguish a true peptide assignment from a random one. Tests on a public MS/MS dataset demonstrated that this method performs better than the well-known SEQUEST. CONCLUSION: A reliable identification of proteins from the spectra promises a more efficient application of tandem mass spectrometry to proteomes with high complexity.

Algorithms↗
PubMed2003

Diagnosis and treatment of dysthymia in children and adolescents.

Dysthymic disorder is a chronic depressive condition occurring in 0.6-4.6% of children and 1.6-8.0% of adolescents. Although symptoms are less severe than those observed in major depression, childhood-onset dysthymic disorder is characterised by a persistent and long-term depressed or irritable mood (mean episode duration 3-4 years), a worse outcome than major depression and, frequently, comorbid disorders (in around 50% of patients). Long-lasting depressive symptoms seem responsible for long-term disabling consequences on social skill learning, psychosocial functioning and consequent professional life, probably contributing to a higher risk of relapse or development of major depression. Consistently, the first episode of major depression occurs 2-3 years after the onset of dysthymic disorder, suggesting that the latter is one of the gateways to recurrent mood disorders. The primary aims of treatment for dysthymic disorder should be to resolve depressive symptoms, reduce the risk of developing other mood disorders over time and strengthen psychosocial functioning, especially in children and adolescents, in order to prevent the potentially serious sequelae of this disorder. As children with dysthymia often have multiple problems, interventions should involve multiple levels and measures: individual psychotherapy, family therapy/education and pharmacological treatment. Psychotherapeutic techniques, such as cognitive-behaviour therapy and interpersonal therapy, have been found to be efficacious interventions in treating children and adolescents with mild to moderate depression in studies including patients with either dysthmia or double depression. SSRIs are the first-line drug treatment for children and adolescents because of their safety, adverse effect profile and ease of use (the safety of paroxetine is currently under investigation). Several nonblind studies have shown the efficacy and good tolerability of SSRIs in children and adolescents with dysthymic disorder, but further research is needed to confirm their efficacy and that of newer antidepressants in the treatment of this disorder. Regardless of whether psychotherapeutic or medical treatments are planned, according to clinical experience, psychoeducational interventions and psychosocial support should be provided to parents and other caregivers during the acute treatment phase to help manage the child's irritable mood and foster a therapeutic alliance and better compliance with treatment. Unfortunately, no studies have focused on continuation treatment of paediatric dysthymic disorder. Given the chronicity, recurrence, psychosocial consequences and peculiar response pattern to treatment of dysthymic disorder, establishing effective 'acute' and 'continuation' interventions in this group of patients should be a priority in mental health management.

Adolescent↗
PubMed2004

Measuring hot flashes: summary of a National Institutes of Health workshop.

The etiology and mechanism of hot flashes remain incompletely understood. Future studies of hormonal and neurologic systems may provide promising leads to improve our understanding of the basic phenomenon and perhaps also shed light on the placebo effect. However, this is likely a complex undertaking. Critical to this effort is the ability to reliably identify when a hot flash has occurred. The leading objective measure in use today--sternal skin conductance monitoring--has some limitations in ambulatory settings. However, a more severe limitation is the inability of sternal skin conductance to provide any information on duration, intensity, and interference with activities. Ultimately, researchers desire a convenient and cost-effective sensor for monitoring hot flashes without cumbersome electrodes that might become compromised if a subject experiences extensive sweating or takes a shower and one that can capture data continuously for relatively long periods of observation. However, researchers also need well-characterized methods for collecting self-reported data. If the primary concern is helping women with hot flashes find relief, then subjective measures collected through diaries or interviews cannot be dismissed. Given the importance of this information, it would make sense to undertake methodologic research to ensure that the best possible systems are used to collect valid and reliable information. The factors that we want to measure with respect to hot flashes are likely to change over time as more is learned about the underlying phenomenon. This will probably be an evolutionary process, one involving decisions about what biological factors will be most useful for the task at hand, what technologies might be available or easily adaptable, which measures should be bundled together to maximize the precision of data collected with the available technology, and the analysis of the data to generate new hypotheses and perhaps the need for new measurement tools. Investigators face several challenges when considering the design of studies of hot flashes. Substantial placebo effects and small sample sizes have produced studies with equivocal findings. The placebo effect, while remarkable in its dimensions in some studies of hot flash interventions, is not understood. Distinguishing placebo effects from the natural dissipation of symptoms over time would be extremely helpful. Similarly, the ability to induce a placebo effect to reduce the discomfort and annoyance associated with hot flashes might be helpful. The use of neuroimaging technology offers potential for greater understanding of the placebo effect. The group concluded that better measures of hot flashes require improved knowledge in several areas: The physical processes underlying hot flashes, which will identify additional factors to measure and the factors that influence the perception and reporting of hot flashes. Improved sternal skin conductance systems, with additional tools to be developed when other factors of hot flashes are identified. The performance characteristics of questionnaires and diaries to collect self-reported data on hot flash frequency. Improved and validated instruments for collecting data on intensity and interference with daily activities. The mechanism(s) of action of placebo, which may also help distinguish natural attrition of symptoms from placebo effect. Animal models to elucidate triggers and mechanisms of hot flashes and to screen potential treatments. Investigators interested in studying hot flashes face complex issues. The incomplete understanding of the basic physiology underlying hot flashes clearly calls for further work in this area. Some mechanistic studies cannot be conducted with human subjects; thus, animal models are needed. Animal models could be particularly helpful for understanding the neurobiology of hot flashes and perhaps placebo effects. Bringing scientists together from different fields would appear to be a promising approach to moving this area forward. Scientific advances are being made increasingly at the interfaces of traditional disciplines, and approaches to science are becoming more integrative. Finding appropriate collaborators from other disciplines is not necessarily easy, and meeting a collaborator from another discipline is only the first step in building a multidisciplinary research team. Effective teams begin with compelling reasons for their existence, but further incentives must be developed to ensure full realization of their potential. The success of team science depends on individuals who are comfortable with boundary-crossing activities. Working as part of a team that is seeking solutions to complex problems requires a willingness to work in an interdisciplinary environment, to collaborate with different types of organizations, and to recognize the importance of a variety of roles in the project. It is likely that a multidisciplinary approach to hot flash research would be helpful given the number of physiologic, clinical, and behavioral factors involved. For example, psychologists and sociologists could contribute to identifying factors that may influence the placebo effect, such as pill color; developing and validating questionnaire items and diary formats; ascertaining the effect of mode of data collection on the quality of the resulting data; and determining the best ways to provide information to subjects. However, if they were part of a multidisciplinary team that included basic scientists, clinicians, and bioengineers, different questions might be asked, and better tools might be developed to collect both subjective and objective data on hot flashes. The increasing emphasis on collaborative science is also embraced at the NIH level. Since May 2002, the NIH has been engaged in a series of activities collectively known as the "NIH Roadmap," whose goal, in keeping with the NIH mission of uncovering new knowledge about the prevention, detection, diagnosis, and treatment of disease and disability, is to accelerate both the pace of discovery in these key areas and the translation of therapies from bench to bedside. The timing of this workshop to assess measures of hot flashes appears auspicious for several reasons. First, the issue of refining and validating self-reported measures of symptoms through the use of biomarkers and multidisciplinary research teams is consonant with an NIH Roadmap initiative. Second, the new National Institute for Biomedical Imaging and Bioengineering at the NIH offers impetus for linking biomedical, social, and behavioral scientists with bioengineers to assess and improve existing technology or develop new technologies to collect data on physiological markers specific to hot flashes. Third, people are already purchasing and using CAM modalities or are resuming hormone therapy for relief of hot flashes, and they and their clinicians are eager for and deserve more information on the safety and efficacy of these remedies.

Animals↗
PubMed1999

Apoptosis induced by granzyme B-glycosaminoglycan complexes: implications for granule-mediated apoptosis in vivo.

Lymphocyte granule-mediated apoptosis occurs by perforin-mediated intracellular delivery of granule-associated serine proteases (granzymes). A granule-associated proteoglycan, namely serglycin, that contains chondroitin 4-sulfate (CS) glycosaminoglycans is present in the granules of cytotoxic cells. Serglycin acts as scaffold for packaging the positively charged granzymes and probably chaperones the proteases secreted extracellularly. To learn how the interaction of granzyme B (GrB) with serglycin might influence the apoptotic potential of this proteases, we have evaluated a model system where desalted CS is combined with isolated human granzyme. CS-GrB complexes were very stable, remaining undissociated in salt concentrations upwards to 500 mM (pH 7.4). On the basis of a capture enzyme immunoassay that accurately detects GrB, equivalent amounts of active free and CS-GrB, delivered by perforin or adenovirus, efficiently induced apoptosis in Jurkat cells and produced a similar time-dependent increase in caspase-3-like activity. CS-GrB processed isolated caspases-3 and -7 less efficiently than free granzyme. However, when added to cytosolic extracts, rates of processing were nearly equivalent for the two forms, suggesting cationic GrB may nonspecifically bind cytosolic proteins, leading to reduce proteolytic activity. Finally, GrB was found to be exocytosed from lymphocyte-activated killer cells as a neutral, high macromolecular weight complex, which possessed apoptotic activity. Collectively, the results indicate that neutral, high m.w. GrB has the capacity to induce cell death and will be useful to study the mechanism of cytotoxic cell-mediated apoptosis in vitro.

Apoptosis↗