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PubMed1994

Comparison of community and institutional prescription of antiepileptic drugs for individuals with learning disabilities.

The use of antiepileptic agents for individuals with learning disabilities (mental handicap) resident both within National Health Service facilities and the community was surveyed in the UK. There was no difference in rates of polypharmacy, but there were significant differences in choice of antiepileptic agent. In particular, individuals resident in the community were more likely to be in receipt of phenytoin, primidone and phenobarbitone, which are particularly recognized as producing adverse effects on cognition and behaviour.

Adult↗
PubMed2004

Tracking the trajectories of evolution.

This article proposes a method of visualizing and measuring evolution in artificial life simulations. The evolving population of agents is treated as a dynamical system. The proposed method is inspired by the notion of trajectory. The article provides examples of tracking of trajectories of evolutionary systems in the spaces of genotypes, strategies, and some global characteristics. Visualization similar to a bifurcation diagram is used to represent results of a series of simulations.

Artificial Intelligence↗
PubMed2005

Obesity Drug Development Summit. 21-22 July, 2005, Arlington, VA, USA.

The Center for Business Intelligence (CBI) presented this 2-day conference as part of its business of discovery series. The meeting, which targeted senior level industry personnel, highlighted the latest developments in the search for effective and safe obesity drugs. The adverse health consequences and growing prevalence of obesity make this condition a major worldwide public health concern. Consistent with the multi-faceted nature of the body weight regulatory system, the presentations featured a variety of approaches aimed at different neuroendocrine and peripheral tissue targets. Clinical as well as basic data on agents in various stages of development were presented. These included rimonabant, an inhibitor of the endocannabinoid system, which has undergone extensive phase III clinical testing, and two selective 5-HT(2C) agonists, ATH-88651 (Athersys Inc) and APD-356 (Arena Pharmaceuticals Inc), which are in earlier stage development. Synthetic analogs of the gut and islet peptide hormones, PYY3-36 and amylin, which are in early-stage development as anorexigenic agents, were also discussed. More basic research-oriented presentations featured the potential therapeutic utility of melanocortin 4 receptor agonists and the inhibition of the gastric peptide ghrelin and the enzymes diacylglycerol acyltransferase 1 and 11beta-hydroxysteroid dehydrogenase 1. Another presentation addressed the problem of leptin resistance. A novel technology that measures extracellular flux rates and its application in screening obesity agents that target thermogenesis was also discussed.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2026

Precision Medicine in Transfusion-Dependent and Non-Transfusion-Dependent β-Thalassemia: Toward Personalized Diagnosis and Therapy.

β-thalassemia comprises a clinically heterogeneous group of disorders in which anemia severity, transfusion exposure, iron loading, and organ complications vary widely among individuals. This structured narrative review summarizes practical applications of precision medicine in transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT), with explicit attention to which strategies apply to each clinical category. Literature indexed in PubMed and Scopus from 2000 to 2025 was reviewed using terms related to thalassemia, precision medicine, magnetic resonance imaging (MRI), chelation tailoring, next-generation sequencing (NGS), fetal hemoglobin (HbF) modifiers, luspatercept, mitapivat, hepcidin, gene therapy, gene editing, and artificial intelligence (AI). Evidence was synthesized descriptively because interventions, outcomes, and populations were heterogeneous, and no pooled meta-analysis was performed. In TDT, precision care is centered on individualized transfusion planning, extended red-cell antigen matching, MRI-guided cardiac and hepatic iron monitoring, organ-directed chelation intensification, and selection of disease-modifying or curative approaches. In NTDT, precision care emphasizes accurate phenotype classification, MRI liver iron concentration, because serum ferritin may underestimate iron burden, selective chelation, surveillance for NTDT-specific complications, and individualized use of agents that improve anemia. Personalized chelation should include deferiprone, either alone or in combination, when cardiac iron is increased. Comprehensive molecular diagnosis should include HBB together with HBA1 and HBA2 assessment, while secondary and tertiary modifiers help explain phenotypic variability and complication risk. Hepcidin and growth differentiation factor 15 (GDF-15) are discussed as investigational biomarkers; transferrin saturation is not recommended for routine iron-overload assessment in thalassemia. AI currently has its strongest role in screening and diagnosis, whereas risk-stratification models remain exploratory. Equitable implementation requires standardized TDT/NTDT pathways, regional MRI and genomics access, longitudinal registries, and multidisciplinary interpretation.

Humans↗
PubMed2006

Comparison of potential adjustment variables representing primary intellectual level in epidemiological studies on neurotoxicity.

BACKGROUND: Primary intellectual abilities (PIA) are a confounder in epidemiological studies on neurotoxicity. A good measure of this confounder should be independent of age as PIA is an intrinsic ability. Furthermore, as PIA is related to health endpoints, any measure of PIA should reveal this association. This study is aimed at comparing vocabulary test, diploma and age at end of schooling properties as measures of PIA in a non-exposed population of workers. METHODS: The design was a cross-sectional study of 413 non-exposed workers (203 women and 210 men) selected from a health check-up center. The effect of age on the vocabulary score was assessed using an analysis of covariance adjusted for diploma. Relationships between neuropsychological performances and vocabulary score, diploma and end of schooling age were, respectively, assessed using multiple linear regressions adjusted for age and gender. RESULTS: Vocabulary score increased significantly with age, both for men and women. The increase was 0.14 word per year for women, and 0.18 word per year for men. The explained variance of the models evaluating the relationships between age at end of schooling, diploma, vocabulary test, and neuropsychological performances was quite similar for the three measures of PIA. CONCLUSIONS: Vocabulary score was found to be age-related, even after adjustment for diploma. No difference was found between these three variables in terms of their relationship to neuropsychological endpoints. Moreover, the literature shows that vocabulary test performances are influenced by exposure to neurotoxic agents. These results suggest that vocabulary score could be of interest for participants of similar ages and similar diplomas. Otherwise, the other two variables would be better PIA measures in neurotoxicology studies.

Adult↗
PubMed1993

Two approaches to the facilitation of grammar in children with language impairment: an experimental evaluation.

Two approaches to grammar facilitation in preschool-age children with language impairment were evaluated. One approach was administered by a speech-language pathologist and the other was presented by the subjects' parents, who were trained by the speech-language pathologist. Both treatment packages ran for 4 1/2 months and made use of focused stimulation procedures and a cyclical goal-attack strategy. Subjects were 30 children between the ages of 3:8 and 5:10 (years:months) who had marked delays in grammatical development. Children who served in a delayed-treatment control group averaged no gains over their no-treatment period. In contrast, large treatment effects were observed for both treatment groups on three of four measures of grammatical expression. However, closer inspection of the data revealed that the effects for the clinician treatment were more consistent across treatment administrations than were those for the parent treatment. Although the specific contributions of the focused stimulation procedures and the cyclical goal attack strategy were not evaluated, the results support the viability of these components as parts of larger treatment packages. The results also support the participation of parents as primary intervention agents in grammar facilitation programs. When parents take such a large role in the intervention process, however, it is imperative that the children's progress be monitored carefully and that program adjustments be made whenever gains are smaller than expected.

Child↗
PubMedDate not supplied

Issues in developmental neurotoxicology: interpretation and implications of the data.

The potential for environmental contaminants to produce neurological, cognitive, or other behaviour deficits as a result of developmental exposure has received increasing attention. The focus has shifted from description of frank neurotoxicity observed in a relatively few individuals to more subtle impairment in a much greater number of children. With this shift has come the recognition that subtle deficits such as a small decrease in IQ can have important societal impact when large numbers of children are affected. For example, the result of a 1 microgram/dL decrease in blood lead concentration in children in the United States with blood lead concentrations between 10 and 20 micrograms/dL would translate into a savings of 5-7.5 billion U.S. dollars a year in increased earning power alone. In addition, behavioural problems such as increased aggression and poor social adjustment identified early in childhood may escalate to serious antisocial behaviour such as delinquency as the child approaches puberty. Exposure to neurotoxic agents during development or over a significant portion of the lifespan may also result in acceleration of age-related neurodegenerative diseases. Such changes in the functional abilities of a significant proportion of a population have potentially serious consequences for society as well as for affected individuals.

Brain↗
PubMed2005

Neurodevelopmental toxicology.

The fields of neurotoxicology and developmental toxicology are exploding in research and interest. Much of the data currently known are from epidemiologic human studies or studies of animal models. Each of these modes is difficult to translate to individual clinical encounters. It is often difficult to state with certainty which of the numerous chemical or physical agents in our environment are neurotoxic. Basic scientists will help with advances in molecular biology and toxicology. Improved clinical understanding of these issues may help patients to understand the medical issues; allay feelings of anxiety, guilt, or fear; and avoid unnecessary testing. For exposures that manifest as threshold phenomena, such as lead, the risk to society is even greater than to an individual. Individual risk may be less of a concern than the population's risk because small elevations in the average BLL can cause profound shifts in the normative curve of intelligence, increasing the burden on our institutions and bankrupting the brain trust. Good scholarship and interpersonal judgement are vital when counseling patients on the potential consequences of chemical exposures and are no less important when making policy. The challenge for the clinician reading the research is to remain aware of the limitations and biases of our science.

Adult↗
PubMed1996

Twenty years of epidemiology in fertility regulation.

This paper summarizes findings from epidemiological research in fertility regulation which have helped in formulating policies nationally and internationally, without pretending to be all-encompassing; rather, it should help in demonstrating the usefulness and importance of epidemiological research and in discussing outstanding issues of public health relevance.

Cardiovascular Diseases↗
PubMedDate not supplied

Acidifying enemas (lactitol and lactose) vs. nonacidifying enemas (tap water) to treat acute portal-systemic encephalopathy: a double-blind, randomized clinical trial.

A double-blind, controlled trial to study the efficacy of acidifying enemas of lactitol, a new galactoside-sorbitol disaccharide, and lactose vs. nonacidifying tap-water enemas was performed in 45 episodes of acute portal-systemic encephalopathy. At the time of randomization, all patients had encephalopathy of at least Grade 2+ severity, delay in the performance of number connection tests and hyperammonemia. A sequential analysis was performed which revealed after the inclusion of the first 20 patients, a significant failure of the nonacidifying enemas as compared to the lactitol enemas (p less than 0.004). The tap-water enema group was, therefore, suspended but the rest of the study continued after rerandomization for lactose and lactitol groups. A favorable response to treatment was obtained in 19 (86%) of the patients receiving lactitol enemas and in 14 (78%) of those receiving lactose enemas. A similar significant improvement in portal-systemic encephalopathy parameters and index was observed after both treatments. Both types of acidifying enemas induced a significant pH decrease in stool (p less than 0.05). These data suggest that acidifying agents like lactose and lactitol are effective and superior to tap-water enemas for the treatment of acute nitrogenous portal-systemic encephalopathy.

Ammonia↗
PubMed2004

Evolvable social agents for bacterial systems modeling.

We present two approaches to the individual-based modeling (IbM) of bacterial ecologies and evolution using computational tools. The IbM approach is introduced, and its important complementary role to biosystems modeling is discussed. A fine-grained model of bacterial evolution is then presented that is based on networks of interactivity between computational objects representing genes and proteins. This is followed by a coarser grained agent-based model, which is designed to explore the evolvability of adaptive behavioral strategies in artificial bacteria represented by learning classifier systems. The structure and implementation of the two proposed individual-based bacterial models are discussed, and some results from simulation experiments are presented, illustrating their adaptive properties.

Adaptation, Physiological↗
PubMed1978

Chronic neurotic encopresis as a paradigm of a multifactorial psychiatric disorder.

Chronic neurotic encopresis (CNE), a childhood psychiatric disorder characterized by inappropriate fecal soiling, necessitated the formation of the following specific etiological factors: a) a neurologically immature developmental musculature, an organic condition which may complicate toilet training; b) premature or harsh toilet training; c) a family constellation in which the father is frequently absent and the mother erratic, emotionally inappropriate, and distant; d) the child's formation of a noncommunicative, passive, dependent personality. All of these factors are helpful in explaining the occurrence of CNE, which is thus seen as the result of a synergistic interaction among them. The complexity of etiological agents dictates a multifactorial rather than unicausal model of mental illness. Future research and tactics of psychotherapeutic intervention should focus on the interplay among these factors rather than attempting to single out one primary predisposing factor.

Central Nervous System↗
PubMed2003

Information, knowledge and the future of machines.

This wide-ranging survey considers the future of machines in terms of information, complexity and the growth of knowledge shared amongst agents. Mechanical and human agents are compared and contrasted, and it is argued that, for the foreseeable future, their roles will be complementary. The future development of machines is examined in terms of unions of human and machine agency evolving as part of economic activity. Limits to, and threats posed by, the continuing evolution of such a society of agency are considered.

Artificial Intelligence↗
PubMed1998

A multi-agent softbot to retrieve medical information on Internet.

World-Wide Web is a media where information is unstructured, distributed, multimedia and multilingual. Many tools have been developed to help users search for information: subject hierarchies, general search engines, browsers and search assistants. Although helpful, they show serious limitations, mainly in terms of precision, multilingual indexing and distribution. The M.A.R.V.I.N. project (Multi Agent Retrieval Vagabond on Information Networks) proposes solutions with a distribution of the indexing task in agents specialized in a given domain. M.A.R.V.I.N. has been successfully applied to the medical domain. The medical index and its associated search engine MedHunt (Medical Hunter) demonstrate the interest of such an approach with currently 50,000 indexed medical sites and more than 100,000 accesses each month.

Abstracting and Indexing↗
PubMed2003

Modelling the world in real time: how robots engineer information.

Programming robots and other autonomous systems to interact with the world in real time is bringing into sharp focus general questions about representation, inference and understanding. These artificial agents use digital computation to interpret the data gleaned from sensors and produce decisions and actions to guide their future behaviour. In a physical system, however, finite computational resources unavoidably impose the need to approximate and make selective use of the information available to reach prompt deductions. Recent research has led to widespread adoption of the methodology of Bayesian inference, which provides the absolute framework to understand this process fully via modelling as informed, fully acknowledged approximation. The performance of modern systems has improved greatly on the heuristic methods of the early days of artificial intelligence. We discuss the general problem of real-time inference and computation, and draw on examples from recent research in computer vision and robotics: specifically visual tracking and simultaneous localization and mapping.

Artificial Intelligence↗
PubMed2000

[Efficacy of methylprednisolone pulse and mild hypothermia therapies in patients with acute encephalopathy].

Five patients with acute encephalopathy underwent methylprednisolone pulse (mPSL-P), hypothermia and their combination therapies (3 cases, 1 case and 1 case, respectively), with excellent outcome. Two cases with severe brain edema survived. One had severe brain damage as a sequelae. The remaining one recovered well after the combination therapy with mPSL-p and mild hypothermia, despite complete obstruction of the fourth ventricle on the first CT scan; the sequelae, hemiplegia and intelligent disturbance, was only mild. Four patients who received mPSL-P therapy within 6 hours after the onset of CNS symptoms recovered well though one was left with epilepsy. These results indicate that mPSL-P and/or hypothermia therapy will be chosen as the treatment of acute encephalopathy.

Acute Disease↗
PubMed2002

Optimum methamphetamine profiling with sample preparation by solid-phase microextraction.

Solid-phase microextraction (SPME) is a relatively new technique in which a small, polymer-coated fiber is employed to extract volatile and semivolatile organic compounds from the sealed headspace above a questioned sample. SPME, coupled with gas chromatography/mass spectrometry (GC/MS), was used to characterize impurities in illicit methamphetamine samples. Trace impurities present in a specimen were tentatively identified using mass-spectral databases and included 1,2-dimethyl-3-phenyl-aziridine (indicating synthesis via a halogenated ephedrine intermediate), ethyl vanillin (a flavoring compound), and caffeine (a stimulant used as cutting agent). The types and numbers of organic compounds sampled by SPME were compared with those collected by various solvent extraction protocols. In addition to unambiguously confirming the presence of methamphetamine, SPME-GC/MS analyses detected approximately 30 more organic analytes than were found by GC/MS following the ethyl acetate extraction method adopted by the United Nations International Drug Control Programme. SPME-GC/MS is a superior method for generating material "fingerprint" profiles in methamphetamine samples. The detection and characterization of increased points of comparison in drug samples provide more detailed chemical signatures for both intelligence and operational information.

Journal Article↗