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PubMed2006

Supervisory control of mobile sensor networks: math formulation, simulation, and implementation.

This paper uses a novel discrete-event controller (DEC) for the coordination of cooperating heterogeneous wireless sensor networks (WSNs) containing both unattended ground sensors (UGSs) and mobile sensor robots. The DEC sequences the most suitable tasks for each agent and assigns sensor resources according to the current perception of the environment. A matrix formulation makes this DEC particularly useful for WSN, where missions change and sensor agents may be added or may fail. WSN have peculiarities that complicate their supervisory control. Therefore, this paper introduces several new tools for DEC design and operation, including methods for generating the required supervisory matrices based on mission planning, methods for modifying the matrices in the event of failed nodes, or nodes entering the network, and a novel dynamic priority assignment weighting approach for selecting the most appropriate and useful sensors for a given mission task. The resulting DEC represents a complete dynamical description of the WSN system, which allows a fast programming of deployable WSN, a computer simulation analysis, and an efficient implementation. The DEC is actually implemented on an experimental wireless-sensor-network prototyping system. Both simulation and experimental results are presented to show the effectiveness and versatility of the developed control architecture.

Algorithms↗

PubMed2006

Levodopa-induced alterations in speech rate in advanced Parkinson's disease.

The effect of speech rate on overall intelligibility in Parkinson's Disease (PD) is still a matter of debate. A comparison of the results of previous studies on speech rate in PD is hampered by methodological differences. In this study, we evaluated the effects of levodopa on speech rate and on its variability in a standardized reading task. Twenty-five patients were studied before and after levodopa administration while reading a standardized text. In accordance with previous studies, no significant improvement of speech rate was found. Rather an increased variability of speech rate in the on-medication state could be demonstrated. It is possible that this increased variability may be the consequence of respiratory deficits due to levodopa-induced dyskinesia or an increase of dysfluencies. However, the effects of defective auditory feedback and disturbed executive function cannot be ruled out.

Antiparkinson Agents↗

PubMed1994

Vestibular dysfunction in a child with embryonic exposure to accutane.

Children with a history of embryonic exposure to Accutane (isotretinoin) are at great risk for major physical malformations, brain malformations, and decreased intelligence. A case is presented of a 4-year 7-month-old black male with a history of embryonic exposure to Accutane who was born with embryopathy that includes bilateral major ear deformities. The child has a significant bilateral conductive hearing loss, and, in addition, a left sided sensorineural loss. Vestibular function testing revealed evidence of peripheral and central vestibular dysfunction. A course of diphenhydramine hydrochloride and Donnatal (phenobarbital, hyoscyamine sulfate, atropine sulfate, and scopolamine hydrobromide) significantly alleviated the symptoms of vestibular dysfunction. Otologic management of these children should include clinical documentation of the external deformities, evaluation of cochlear function, and early auditory habilitation. Vestibular function should also be evaluated in all children with a history of embryonic exposure to isotretinoin.

Child, Preschool↗

PubMed1976

Prospective evaluation of treatment of Hemophilus influenzae meningitis.

Fifty children with Hemophilus influenzae meningitis have been enrolled in a prospective study. Patients were randomly assigned chloramphenicol or ampicillin treatment; there were no significant differences between groups in other respects. Countercurrent immunoelectrophoresis proved to be a valuable tool for rapid diagnosis of the causative agent even in pretreated patients. Increasing quantities of capsular polyribosephosphate antigen detected in the initial cerebrospinal fluid correlated significantly (r=0.62419; p less than 0.01) with early and late sequelae of meningitis. None of the patients died. Severe and persistent neurologic or intellectual deficits were noted in four (8%) of the children, and an additional 14 (28%) had IQ scores between 70 and 90. The presence of bactericidal antibody in serum was not protective. Anti-PRP antibody generally was not present in acute serum specimens and irrespective of the quantity of antigenic stimulus provided by the disease was nondetectable in 21 of 24 children less than 17 months of age following recovery.

Adolescent↗

PubMed1978

Interactions of liposomes with mammalian cells.

In this review we have attempted to highlight each of the major areas of interest in liposome-cell interactions: the purely physical chemical, the cell biological, and the medical. Liposomes can be generated in a number of ways and are classified as small unilamellar, large unilamellar, and multilamellar vesicles. Although liposomes are easy to prepare, it is important to consider the effects of impurities, and also the possible changes in liposome properties with time (particularly at or below the phase transition temperature). Intelligent application of liposomes to cell biological and clinical problems requires an understanding of their mechanisms of interaction with cells. The mechanisms thus far delineated, largely by studies in vitro, are fusion, endocytosis, lipid transfer, and stable adsorption. In practice, demonstrating the occurrence of a given mechanism in an actual system is difficult because these are not mutually exclusive. Cell type, conditions of incubation, and liposome properties (charge, fluidity, size) are important in determining mechanism and appear to organize the literature effectively. However, this may be an oversimplification resulting from the sketchiness of current information. Liposomes have been used in cell biology to alter the phospholipid and cholesterol composition of cells, to bypass the membrane permeability barrier to normally impermeant solutes, and to promote cell-cell fusion. Perhaps the most fruitful of these applications has been the alteration of cholesterol, which can result in changes in cell permeability and morphology. On the other hand, delivery into cells of liposome-entrapped, water-soluble materials has not yet proved an effective tool in cell biology; delivery, and consequent physiological changes, have been demonstrated, but generally to answer questions about liposome-cell interactions, not to answer questions about the cells. Much of the current interest in liposomes derives from their potential applications in vivo. Liposomes are envisioned as pharmacological capsules for delivery of therapeutic agents in treatment of such conditions as diabetes, enzyme deficiencies, heavy metal poisoning, and neoplasms. Although much of the literature to date has been concerned with the end applications, it seems clear that a more systematic approach to the pharmacokinetics of liposomes will be necessary. In particular, such aspects as their leakage rates and their ability to cross cell and anatomical barriers require further study. Targeting of liposomes to particular cells or tissues will be essential for many applications. Finally, it must be remembered that all of these in vivo applications of liposomes are future tense; as with other technologies, passage from demonstration of the phenomenon to practical application is likely to be arduous.

Adsorption↗

PubMed1997

Anti-retroviral therapy and cognitive function.

BACKGROUND: The effect of anti-retroviral medications on the cognitive functions important in flying has not been determined. HYPOTHESIS: Anti-retroviral medications have no effect on the cognitive performance of individuals at the CDC 4C2 (symptomatic HIV disease with no illness indicative of full-blown AIDS) stage of infection. METHODS: A two-group study using a cross-sectional design was used. The participants in each group represented a sample of convenience obtained from a larger, naturalistic study. Each group consisted of 10 HIV+ males at the CDC 4C2 stage of infection. The two groups were found to be comparable on age, education, pre-morbid intelligence, and ethnicity. All members of the anti-retroviral medication group had been receiving medications for at least 3 mo. Those in the control group (no anti-retroviral medication) had received no anti-retroviral medications for at least 6 mo. Cognitive functioning was assessed using a computerized information processing battery that included test similar to those under consideration for inclusion in military pilot selection batteries and a neuropsychological battery. As part of the larger study, the participants were carefully and repetitively screened on factors known to affect performance on neuropsychological instruments. RESULTS: The groups showed little difference in cognitive functioning. CONCLUSION: Although more research is needed, anti-retroviral medication does not impair, and may improve, the cognitive processes of individuals with symptomatic HIV infection who do not have AIDS.

Adult↗

PubMed2006

Bioinformatics for cancer management in the post-genome era.

Human cancer is caused by multiple factors, such as genetic predisposition, chronic persistent inflammation, environmental factors, life style, and aging. Dysregulated proliferation, dysregulated adhesion, resistance to apoptosis, resistance to senescence, and resistance to anti-cancer drugs are features of cancer cells. Accumulation of multiple epigenetic changes and genetic alterations of cancer-associated genes during multi-stage carcinogenesis results in more malignant phenotypes. Post-genome science is characterized by omics data related to genome, transcriptome, proteome, metabolome, interactome, and epigenome as well as by high-throughput technology, such as whole-genome tiling oligonucleotide array, array CGH with 32,433 overlapping BAC clones, transcriptome microarray, mass spectrometry, tissue-based expression array, and cell-based transfection array. Benchtop oncology supplies Desktop oncology with large amounts of omics data produced by high-throughput technology. Desktop oncology establishes knowledge on cancer-related biomarkers, such as predisposition markers, diagnostic markers, prognostic markers, and therapeutic markers, by using bioinformatics and human intelligence of experts for data mining and text mining. Bedside oncology applies the knowledge established by Desktop oncology to determine therapeutics for cancer patients. Antibody drugs (Trastuzumab/Herceptin, Cetuximab/Erbitux, Bevacizumab/Avastin, et cetera), small molecule inhibitors for tyrosine kinases (Gefitinib/Iressa, Erlotinib/Tarceva, Imatinib/Gleevec, et cetera), conventional cytotoxic drugs, and anti-hormonal drugs are used for cancer chemotherapy. Biomarker monitoring contributes to therapeutic optional choice and drug dosage determination for cancer patients. Knowledge on biomarkers is feedforwarded from desktop to bedside in the translational research, and then biomarker monitoring is feedbacked from bedside to desktop in the reverse translational research. Desktop oncology is indispensable for cancer research in the post-genome era. Combination of genetic screening for cancer predisposition in the general population and precise selection of therapeutic options during cancer management could contribute to the realization of personalized prevention and to dramatically improve the prognosis of cancer patients in the future.

Antineoplastic Agents↗

PubMed1999

The application of a computerized measurement of the content analysis of natural language to the assessment of the effects of psychoactive drugs.

This article aims to answer the question whether developing technology is now capable of measuring objectively and accurately the effects of psychoactive pharmacological agents by means of computerized assessments of psychological states and traits through the analysis of content and form of people's speech. At the present time, psychopharmacological researchers involved in clinical trials rely on DSM-IV criteria and standardized self-report measures and observer rating scales to assess psychoactive drug effects. Attention is drawn to the potentially unrecognized measurement errors and relatively low interrater reliability by these methods--for example, all raters are not free of observer bias and every subject administered a drug is not equally and accurately well-informed about the self. The computerized content analysis methods tend to avoid these biases and measurement errors. A review is provided describing the Gottschalk-Gleser method of measuring psychobiological dimensions from the form and content of short (usually five-minute) speech samples of verbal behavior, generally elicited by standardized and purposely ambiguous instructions to talk about any interesting or dramatic personal life experiences. Norms have been obtained by this method of speech elicitation, adjusted for age, sex and educational level. Sections are provided covering cross-cultural and language validation research on the Gottschalk-Gleser content analysis method, the influence of medical or psychiatric illness as well as psychoactive drugs on verbal content analysis-derived scores, and the research carried out for more than 20 years computerizing this content analysis procedure through the development of artificial intelligence software enabling these measurements to be done from typescripts of speech samples on computer diskettes. A brief review deals with the general applications of this method of measurement to basic and clinical psychiatry, psychosomatic medicine, neuropsychology, the diagnostic process in a psychiatry outpatient clinic, children's mental health problems, dream research, and assessment of mental processes during PET scanning of the brain. This is followed by a review of the applications of this method of content analysis of speech to neuropsychopharmacological testing of antianxiety, antidepressive, antipsychotic, and other psychoactive drugs, as well as to pharmacokinetic variables and clinical response. This method is now in the process of being used in clinical trials in psychopharmacology and is recommended for more extensive use in this research area.

Artificial Intelligence↗

PubMed2006

The dynamic neural field approach to cognitive robotics.

This tutorial presents an architecture for autonomous robots to generate behavior in joint action tasks. To efficiently interact with another agent in solving a mutual task, a robot should be endowed with cognitive skills such as memory, decision making, action understanding and prediction. The proposed architecture is strongly inspired by our current understanding of the processing principles and the neuronal circuitry underlying these functionalities in the primate brain. As a mathematical framework, we use a coupled system of dynamic neural fields, each representing the basic functionality of neuronal populations in different brain areas. It implements goal-directed behavior in joint action as a continuous process that builds on the interpretation of observed movements in terms of the partner's action goal. We validate the architecture in two experimental paradigms: (1) a joint search task; (2) a reproduction of an observed or inferred end state of a grasping-placing sequence. We also review some of the mathematical results about dynamic neural fields that are important for the implementation work.

Animals↗

PubMed1994

Superiority of antagonic-stress composition versus nicergoline in gerontopsychiatry.

Nicergoline (NE)--a cerebral vasodilator with nicotinic acid esterified in its molecule--and Antagonic-Stress (AS) composition--a neurometabolic nootropic, also containing nicotinic acid but with fast and prolonged release--were evaluated in senile dementia of Alzheimer's type (SDAT), mild to moderate intensity (DSM-IV Options Book, 1991 and ICD-10, 1990 criteria). A double-blind, randomized, comparative, and parallel clinical trial was performed on 62 old people divided into 2 groups and exclusively treated with NE or AS. Psychogeriatric evaluations (Sandoz Clinical Assessment-Geriatric scale, Self-Assessment Scale-Geriatric and their subscales) and psychometric tests (digit symbol of WAIS, Wechsler Memory Scale, and Wechsler Adult Intelligence Scale-WAIS) were made before and after 3 months of treatment. Prolonged and large dose treatments with NE and AS significantly decreased the psychogeriatric scores, diminished the deterioration index, and improved cognitive performances (ANOVA). Therapeutical effects of AS were significantly higher than those of NE (ANCOVA). The better actions of AS in senile dementia and for improving cognitive function and behavior are discussed in connection with its multiple neurometabolic composition, the synergism of components, the antiischemic action of its antioxidants, its anti-free radical complementary action (deceleration of the aging rate, brain and erythrocyte lipofuscinolysis, complex antioxidative and scavenger formula), the multivitamin and multimineral supplementation and, finally, with the superiority of multitherapy vs. monotherapy.

Aged↗

PubMed2006

A functional magnetic resonance imaging study of the long-term influences of early indomethacin exposure on language processing in the brains of prematurely born children.

BACKGROUND: Previous studies have demonstrated that indomethacin lowers the incidence and decreases the severity of intraventricular hemorrhage, as well as improves the cognitive outcome, in prematurely born male infants. OBJECTIVE: The purpose of this work was to use functional magnetic resonance imaging to test the hypothesis that neonatal indomethacin treatment would differentially affect brain activation across genders in school-aged, prematurely born children during performance of a language task. METHODS: Forty-seven prematurely born children (600-1250-g birth weight) and 24 matched term control subjects were evaluated using a functional magnetic resonance imaging passive language task and neurodevelopmental assessments that included the Wechsler Intelligence Scale for Children-III and the Peabody Picture Vocabulary Test-Revised. Neural activity was assessed during both phonologic and semantic processing in the functional magnetic resonance imaging protocol. RESULTS: Neurodevelopmental assessments demonstrated significant differences in full-scale, verbal, and performance intelligence quotient, as well as Peabody Picture Vocabulary Test scores, between the preterm and term control subjects. Rates of perinatal complications did not differ significantly across preterm treatment groups, but male preterm subjects randomly assigned to saline tended to have lower Peabody Picture Vocabulary Test-Revised scores than did all of the other preterm groups. During phonological processing, a significant treatment-by-gender effect was demonstrated in 3 brain regions: the left inferior parietal lobule, the left inferior frontal gyrus (Broca's area), and the right dorsolateral prefrontal cortex. CONCLUSIONS: These data demonstrate a differential effect of indomethacin administration early in postnatal life on the subsequent development of neural systems that subserve language functioning in these male and female preterm infants.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1996

Synthesis of an anaesthetic agent administration system using fuzzy inductive reasoning.

Control of the depth of anaesthesia is a difficult undertaking. Progress has been made during recent years by use of different methodologies and monitoring systems that suggest the safe amount of an anaesthetic drug, considering the condition of an individual patient. Despite these improvements, anaesthetists still rely heavily on personal experience when suggesting the anaesthetic dosage during surgical operations. The purposes of this paper are twofold. One is a description of the design of an anaesthetic agent control system using a qualitative modelling and simulation methodology called Fuzzy Inductive Reasoning (FIR). A comparison with a system developed for the same application using a neural network approach is also presented. The second purpose is a discussion of the problem of separating system-generic from patient-specific behaviour in the context of inductive modeling using the FIR methodology. In order to be useful, the model generated by FIR should reflect upon system-generic behavioural characteristics exclusively, while suppressing patient-specific behavioural patterns. A technique based on combining knowledge obtained from different patients is designed that makes it possible to derive a single model characterizing a specific class of similar patients undergoing similar operations, preserving the common characteristics of all these patients while filtering out the specific behavioural patterns of any one of the individual patients from whom the data were obtained.

Anesthetics↗

PubMed2004

Neuropsychological dysfunction in antipsychotic-naive first-episode unipolar psychotic depression.

OBJECTIVE: The profile of neuropsychological impairment associated with unipolar psychotic depression remains unclear. The authors used a neuropsychological test battery to characterize the neuropsychiatric profile of patients with unipolar psychotic depression, relative to that of patients with nonpsychotic unipolar depression, patients with schizophrenia, and healthy comparison subjects. METHOD: Study subjects included antipsychotic-naive patients with a first episode of psychotic unipolar depression (N=20), antipsychotic-naive and unmedicated patients with nonpsychotic unipolar depression (N=14), antipsychotic-naive patients with first-episode schizophrenia (N=86), and healthy volunteers (N=81). Groups were matched on age, sex, race, education, parental socioeconomic status, and estimated premorbid intelligence. Psychotic patients were followed clinically for 2 years to confirm diagnosis. All participants completed a standard neuropsychological battery, including tests of general intelligence, executive function, attention, verbal memory, motor skills, and visual-spatial perception. RESULTS: Patients with psychotic depression had a pattern of neuropsychological dysfunction that was similar to but less severe than that of patients with schizophrenia. In contrast, patients with nonpsychotic unipolar depression had a neuropsychological profile that was similar to that of healthy individuals but that included mild dysfunction on tests of attention. Neuropsychological test performance was generally independent of acute clinical symptoms, but some pairwise group differences were attenuated by covariation for symptom severity. CONCLUSIONS: The similar neuropsychological profiles for schizophrenia and psychotic depression suggest that these psychotic disorders may have common pathophysiological features. The dramatic differences in performance between the patients with psychotic depression and those with nonpsychotic depression point to a marked distinction in neurocognitive function associated with the expression of psychosis in depressed patients.

Adult↗

PubMedDate not supplied

[Fetal alcohol syndrome: neurobehavioral effects of prenatal alcohol exposure].

Alcohol has been established as a teratogenic agent that in prenatal exposure can cause a variety of adverse pregnancy outcomes depending on dose, timing, and conditions of exposure. Although alcohol, like many other teratogenes, can cause alterations in morphology, growth, and neurobehavioral outcomes, this report focuses primarily on the latter effects. As with other teratogens causing neurobehavioral aberrations, the neurobehavioral effects of prenatal alcohol are produced at lower exposure levels than the morphologic or growth effects, and except in extreme cases, they are more devastating to the offspring. Neurobehavioral effects are difficult to measure, however, because their manifestations change with the age of the offspring, and because, at the current state of art, their measurement involves outcomes that can be exacerbated or ameliorated by postnatal experience. This report describes results of the studies on the long-term developmental and behavioral consequences of prenatal alcohol exposure.

Adolescent↗

PubMed2004

Liposome-based nanocapsules.

Here we present three different types of mechanically stable nanometer-sized hollow capsules. The common point of the currently developed systems in our laboratory is that they are liposome based. Biomolecules can be used to functionalize lipid vesicles to create a new type of intelligent material. For example, insertion of membrane channels into the capsule wall can modify the permeability. Covalent binding of antibodies allows targeting of the capsule to specific sites. Liposomes loaded with enzymes may provide an optimal environment for them with respect to the maximal turnover and may stabilize the enzyme. However, the main drawback of liposomes is their instability in biological media as well as their sensitivity to many external parameters such as temperature or osmotic pressure. To increase their stability we follow different strategies: 1) polymerize a two-dimensional network in the hydrophobic core of the membrane; 2) coat the liposome with a polyelectrolyte shell; or 3) add surface active polymers to form mixed vesicular structures.

Capsules↗

PubMedDate not supplied

Data representation for subsequent image interpretation.

Radiological scans acquired using either the X-ray CT or the NMR imaging techniques provide a wealth of information about tissue behaviour under that imaging modality and contrast agent. To reason about the image in an interpretation stage the scans have to be converted from a pixel by pixel representation to a symbolic form. The technique used by us to generate such a description is region-based segmentation. Each region refers to a pixel or group of pixels having a common attribute. This work has provided a quantitative measure for the partial evaluation of the segmentation which can be applied independent of attribute or combination of attributes. From our initial studies of the behaviour of CT scans a precept for segmentation was developed. The segmentation employs a one-to-one map as an adaptive mechanism. The segmentation criterion at each point in the image therefore depends on the value at the corresponding point in the map. Any process can be used to generate this map, and so easily utilizes new operators as they are developed.

Artificial Intelligence↗

PubMed2002

HIV and chemokines: implications for therapy and vaccine.

The unexpected encounter between the fields of chemokines and HIV has opened new perspectives for understanding the mechanisms of AIDS pathogenesis, as well as for the development of effective therapies and vaccines. An increasing body of evidence supports the concept that the level of CCR5-binding chemokines (i.e., RANTES, MIP-1alpha and MIP-1beta) measured in vivo or ex vivo can provide an accurate correlate of natural or vaccine-induced protection from primate immunodeficiency viruses. In addition, by virtue of their unique immunomodulatory activities, chemokines may represent a new class of "intelligent" vaccine adjuvants, capable of finely tuning both humoral and cellular immune responses by recruiting specific cell types at the site of immunization. Chemokines that bind the major HIV coreceptors (i.e., CCR5 and CXCR4) are potent natural inhibitors of HIV, although a potential limitation to their therapeutic use is the risk of inducing inflammatory side-effects or of interfering with the physiology of the homeostatic chemokine system. However, recent data indicate that the ability of chemokines to block HIV infection can be uncoupled from their signaling activity. Thus, both modified chemokines and small derivative molecules maintaining the HIV-inhibitory function, but devoid of receptor-activating capability, have been generated. Moreover, for the CC chemokine RANTES, the structural determinants of receptor recognition and antiviral function have been elucidated. Altogether, these findings provide a theoretical foundation for the rational design of safe and effective HIV-coreceptor inhibitors.

AIDS Vaccines↗

PubMedDate not supplied

[Present and future therapeutic strategies in rheumatoid arthritis].

The triad of inflammation, immunoproliferation and synovial hyperplasia is recognized in the pathogenesis of rheumatoid arthritis, however, the sequence of events remains as highly controversial as ever. The "RA pyramid" was established on the assumption that inflammation is at the top with the destructive processes as sequelae. The moderate successes achieved by conservative therapy with regard to long-term outcome cast doubt on this hypothesis. Inhibitors of prostaglandin synthesis have not been and are not disease modifying. Do substances which influence the endothelial adhesion molecules or leucocyte adhesion receptors (leumedines) promise to be more successful? Do the empirically developed disease modifying antirheumatic drugs (Gold parenteral, MTX) have to be administered earlier? Unfortunately, there is a need for a differential diagnosis which is prognostically valid with regard to the dynamics and aggressiveness of rheumatoid arthritis. Moreover, a pharmacological basis for optimally founded combination strategies is also lacking. Presently, the emphasis of research is directed at the regulation of dysfunctional immune systems. Immunosuppressives (cyclosporin A), cytokine antagonists, receptor antagonists and soluble cytokine receptors (IL-1, IL-6, TNF-alpha), antibodies against lymphocyte subgroups (CD4, CD7) or against cytokines and their receptors are part of the arsenal for the medium term. Too little is still known about the role of protective cytokines (TGF-beta, IL-4, gamma-INF). Currently, however, it is prognosticated that these targeted therapies will only succeed in RA subgroups or only in intelligent combinations. More attractive alternative are strategic therapy modalities which intervene very early in the pathological process, such as the modulation of antigen presentation (MHC blocking peptides, T-cell receptor antagonists, T-cell vaccination) or the induction of tolerance against autoantigens through the oral administration of antigens (collagen II, HSP's, OM-8980). If the center of the pathological process, however, is found in the synovial proliferation of tumor-like cell clusters, then there are only a few years at the beginning of the disease when there is a real chance to impede destruction. In this case, aggressive induction therapy can be the only key to success. In the future, specifically active cytostatics (inhibitors of angiogenesis) will have to be developed and clinical trials conducted on adjuvant therapies with substances which strengthen bone and cartilage, making them more resistant to aggressive cell clusters (bisphosphonates, calcitonins, metalloproteinase- or collagenase-inhibitors).

Adjuvants, Immunologic↗