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Neurocognitive functioning in children with mild and moderate asthma in the childhood asthma management program. The Childhood Asthma Management Program (CAMP) Research Group.

BACKGROUND: The Childhood Asthma Management Program (CAMP) is a multicenter double-blind, randomized, placebo-controlled, clinical trial of two anti-inflammatory agents and placebo in children with mild and moderate asthma. OBJECTIVE: The interrelationship between asthma severity and neurocognitive functioning among 1041 children (age range, 5-12 years) enrolled in the CAMP trial was examined. METHODS: Asthma severity was established at baseline with a clinical history of asthma symptomatology and measures of lung function (spirometry and methacholine challenge). Diary cards were used in a screening to record nighttime awakenings and doctor contacts caused by asthma symptoms, symptom severity, and number of puffs from a rescue inhaler. All children received a comprehensive neurocognitive assessment at the end of the 28-day screening period (before randomization), including measures of intelligence, attention, memory, and academic achievement. RESULTS: Significant differences were found between children with mild and moderate asthma on lung function and symptom outcome variables (log(e)FEV(1)PC(20), DeltaFEV(1) percent predicted, change in peak flow percent predicted, nighttime awakenings caused by asthma, average symptom severity score, and average daily number of puffs from a rescue inhaler) but not on neurocognitive variables. Multiple regression analyses revealed that asthma outcomes could not be predicted by neurocognitive variables despite controlling for socioeconomic status. The prevalence of neurocognitive dysfunction, as indicated by the use of psychostimulant medication, was found to be consistent with that found in the existing literature. CONCLUSION: Mild and moderate asthma symptoms are not related to neurocognitive functioning in the children enrolled in CAMP. Mean performance on neurocognitive variables was found to be similar to that of national normative data.

Asthma↗

The use of consequential reasoning in cancer chemotherapy.

Knowledge-based decision support systems traditionally rely on condition-action rule structures, an adequate representation for simple decisions. In complex domains an important part of decision-making includes analysis of the consequences of a decision. Consequential reasoning is particularly important in medicine as potential risk and/or benefit can be included. In this paper, a knowledge structure and inference engine is described that permits the representation and analysis of consequential reasoning in a computer-assisted decision support system. The use of consequential reasoning is then illustrated in an application designed to assist in cancer chemotherapy decisions. The result is a method that is sensitive to individual patient reactions to chemotherapy agents, permitting an individualized approach to therapy. Individualized drug therapy is becoming increasingly feasible due to advances made in the field of genomics. The system is structured so that new information can be incorporated easily. Although the application shown here is to chemotherapy, the general methodology can be used in any area in which the consequences should significantly influence the decision.

Artificial Intelligence↗

Neonatal 192 IgG-saporin lesion of forebrain cholinergic neurons: focus on the life span?

The cholinergic immunotoxin 192 IgG-saporin can be used to effect selective, substantial and permanent lesions of basal forebrain neurons in the neonatal rat. Human neurodevelopmental disorders such as Rett and Down syndromes are characterized by early cholinergic dysfunction and cognitive impairment. Hence, the study of the neonatal 192 IgG-saporin lesioned rat should illuminate the role of cholinergic dysfunction in these human disorders. To date, we and others have failed to observe notable effects of this neonatal lesion on learning and memory, even when combined with a severe lesion of noradrenergic forebrain innervation. As well, attention seems not to be affected. However, complex problem solving (intelligence?) is compromised by the cholinergic lesion. There also appears to be reduced cortical dendritic branching indicative of synapse loss but further research is needed to characterize this. Even if the synapse loss due to neonatal cholinergic lesion is modest and thus insufficient to cause a significant neurodevelopmental dysfunction, its consequences may be devastating during old age.

Acetylcholine↗

Comparison of cognitive performances during a placebo period and an atypical antipsychotic treatment period in schizophrenia: critical examination of confounds.

Although previous studies report cognitive improvement following atypical antipsychotic administration in schizophrenia (SC), few placebo-controlled within-subject studies with examination of confounds (symptom reduction, cooperation, learning, and outliers) have been reported. The present study examines the effects of atypicals and confounds upon cognition in SC. The hypothesis tested was that relative to placebo, atypicals as a general class of medication would elicit cognitive improvement in SC. In all, 19 patients with SC (15 males) completed the double-blind, counterbalanced, randomized within-subject study of the effects of atypical antipsychotics (risperidone, clozapine, olanzapine, or quetiapine) vs placebo administration upon cognitive performance in the domains of executive function, attention, memory, language, visual perception, and general intellect. Significant cognitive improvement during atypical antipsychotic administration relative to placebo withdrawal occurred in most cognitive domains with robust improvements in intelligence (p=0.001), memory (p=0.0009), and fluency (p <0.002) even after outliers and unmotivated performances were excluded. These findings suggest that relative to placebo withdrawal, atypicals improve cognitive performance in SC. However, this finding may not be specific to atypicals, since analogous studies of typicals have not been performed.

Adult↗

[Clinical study on effects of zhiling decoction in treating senile vascular dementia].

OBJECTIVE: To observe clinical effects of Zhiling Decoction (ZLD) in treating senile vascular dementia. METHODS: Seventy-eight patients were randomly divided into treated group and control group. In treated group which was treated with ZLD, a self-formulated proved recipe. In control group, which was administered with Naofukang ([symbol: see text]). RESULTS: ZLD could decrease the level of serum cholesterol, serum triglyceride and plasma LPO significantly; increase the level of high density lipoprotein (HDL) and SOD in red blood cells; dilate cerebral vessels, increase cerebral blood flow. As for P300, an index to reflect intelligence, the latency of P3 was shorter and the amplitude was raised, the brain electrical activity monitoring (BEAM) was improved remarkably, the revised Nagayakawa dementia scale scoring (NDS) of patients promoted, clinical symptom was improved significantly. Total effective rate in clinical practice reached 87%. CONCLUSION: ZLD had good effects on senile vascular dementia indeed.

Aged↗

Towards cooperative patient management through organizational and medical ontologies.

Within knowledge and data engineering a new research paradigm is emerging based on the Multi-Agent System (MAS) architectural framework, allowing human and software agents to interoperate and thus cooperate within common application areas. In such a framework, knowledgeable agents of heterogeneous nature, that possess diverse but at least partially compatible or inter-translatable conceptual views, or ontologies, modeling both their own expertise and the external environment, make somehow available their information resources or problem-solving abilities for cooperative processes addressing the construction of a new agent or the achievement of some common goal through a correlated execution of tasks. In this paper, we restrict our analysis to the case of an organization of cognitive agents, illustrated with examples from a prototypical healthcare MAS, that is, a so-called Distributed Healthcare Information System (D-HIS). The prototype makes use of an ontological library written in the standard language Ontolingua. An ongoing application of the methodology to the main problem of Clinical Practice Guidelines (GLs) computer-based dissemination and enforcement is described.

Artificial Intelligence↗

Safety evaluation concepts.

The approach to safety evaluation is strongly influenced by the standard of safety to which one aspires. Practical considerations demand that realistic limits be set to the attainable assurances of freedom from anticipated hazard under actual conditions of use of a product. The fact is that, in the interests of consumer health, more can be expected from a flexible, intelligent, and experienced approach to safety evaluation than from efforts at conformity with a set of rigidly standardized requirements that are theoretically all-encompassing. Establishment of safety demands a wide background of information about the properties and likely uses of the product; above all, knowledge of the chemical composition of the product and its impurities, degradation products, and metabolites is essential. Lack of such information is a frequent source of errors in safety evaluation. Based on a secure foundation of this sort, a program of investigations may be designed, aimed at establishing the basic biological properties of the material. Determination of the metabolic dynamics of the principal chemical agent or agents makes possible the emergence of a clear picture of the behavior of the compound(s) in the body and paves the way for more specialized studies of long term toxicity, carcinogenicity, effects on reproduction and teratogenesis, and investigations of multitest mutagenic potential. Emphasis is laid on the problems of interpretation of results in terms of hazard to man and on the crucial contribution that experience of human exposure can make toward assuring safety-in-use. Decisions on acceptable risk are the joint responsibility of many individuals but an essential element in reaching such decisions is contributed by the depth of understanding and broad experiences of the toxicologist.

Accident Prevention↗

Multinuclide evaluation of hepatic mass lesions.

Radionuclide imaging with labeled colloids is widely used to evaluate and localize primary and metastatic tumors of the liver. The method is fairly sensitive, but the nonspecificity of focal defects remains a significant limitation. Lesions such as cysts and abscesses appear as space occupying areas that are indistinguishable from neoplastic masses. Utilizing a variety of radiopharmaceuticals, one may obtain additional information concerning such lesions. Hepatic blood flow scintiphotography is performed with the Anger camera following the intravenous injection of a high activity, small volume bolus of 99m-Tc pertechnetate. Vascular lesions such as hepatomas or hemangiomas will show increased activity in the lesion which should easily differentiate them from avascular processes such as abscesses, cirrhotic pseudomasses and most metastatic lesions, all of which remain "cold" on these flow studies. If one does not posses a camera, useful blood pool rectilinear scans of these lesions may be obtained with 131-I or 99m-Tc human serum albumin or ionic 113m-In. Additional information concerning the metabolic activity of focal defects on the colloid study is obtained using 75-Se-selenomethionine or 67-Ga. The former is an indicator of active protein metabolism while the latter attaches to lysozymes of metabolically active cells. With either agent, hepatomas show avid uptake, metastatic lesions show variable uptake, and cysts or chronic pseudotumors of cirrhosis show poor uptake. The two agents differ in abscess detection where 75-Se-selenomethionine uptake is poor while 67-Ga concentration generally is intense. 131-I-Rose Bengal occasionally may prove useful in demonstrating impression by an atypically positioned gallbladder or focal dilatation of the biliary tract as a cause of a defect on the colloid scan. Ultrasound examination may complement the radionuclide studies. It is useful for corroborating the presence of lesions and for evaluating their consistency (cystic vs. solid). The information obtained from this multinuclide approach has made scintigraphy examination of the livermore specific. After the completion of this non-invasive series of studies, one generally may venture an intelligent opinion concerning the etiology of the space occupying disease.

Aneurysm↗

Collateral sensitivity-harnessing microbial vulnerabilities as a solution to antimicrobial resistance.

Bacteria exhibit an evolutionary trade-off through their development of collateral sensitivity (CS) which allows them to resist one antibiotic while becoming more vulnerable to another. This vulnerability offers a compelling therapeutic opportunity by selecting against resistant isolates. Laboratory evolution studies, genome sequencing, deep mutagenesis and use of artificial intelligence and machine learning can design the bespoke strategy against multi-drug-resistant bacteria. This review discusses about recent studies that are rationally designed to harness this evolutionary trade-off for the development of alternative antimicrobial strategies. The translational barriers to the clinical implementation of CS are addressed and evidence-based design principles for optimization of CS-guided therapy are discussed.

Bacteria↗

Influences on cognitive heterogeneity in schizophrenia.

A study was conducted of diagnostic reliability, clinical, demographic, iatrogenic, and neurological comorbidity influences on heterogeneity in cognitive function among schizophrenic patients. Comparisons were made between a previously described (Goldstein, 1990) retrospective sample of clinically diagnosed schizophrenic patients and a new sample based on a prospective study of patients meeting strict DSM-III-R diagnostic criteria for schizophrenia. A cluster analysis of a brief battery of cognitive tests suggested a four cluster solution in both samples. The cluster pattern was found to be similar in both samples, indicating that diagnostic unreliability is unlikely to be strongly associated with heterogeneity. Age, general intelligence, and education were found to have significant influences on cluster membership, with length of illness and hospitalization having less robust influences. It was concluded that heterogeneity has a relatively mild relationship with the various influences studied, but a great deal of the diversity in level and pattern of cognitive function found among schizophrenic patients is likely to be a function of heterogeneity within the disorder itself.

Adult↗

Community-acquired pneumonia in the emergency department: a practical approach to diagnosis and management.

Pneumonia is one of the most common conditions for which patients seek emergency care. It is a challenging infection in that the spectrum of illness ranges from the nontoxic patient appropriate for outpatient antibiotics to the critically ill patient requiring intensive care hospitalization. Current data and diagnostic technology provide the emergency physician with the tools for an appropriately rapid evaluation and consideration of the differential diagnosis. Key critical thinking and application of published findings allow for intelligent empirical antibiotic treatment and risk stratification for the best disposition. Although antibiotic-resistant organisms increasingly are being identified, patients continue to benefit from early institution of standard ED treatment. Coverage for atypical organisms improves patient response and outcome. Finally, identification and treatment of the complications of pneumonia and accompanying sepsis must be considered by the ED physician when evaluating critically ill patients.

Aged↗

Modeling all dialogue system participants to generate empathetic responses.

A dialogue system between an expert system and its users is described which combines two recent hypotheses. First, that the dialogue system should explicitly model both the person directly interacting with the dialogue system (the agent) and the person reasoned about by the expert system (the patient) in order to communicate meaningfully with both people. Second, that a dialogue system can model the domain-related beliefs, preferences and concerns of both its users and generate responses empathetic to both. This dialogue system is called SERUM, standing for 'System for Empathetic Responses with User Models.' SERUM generates natural-language responses about attribute values of domain objects, via three transformations. First, the system converts properties of the agent and patient, and domain knowledge, into a pragmatic objective like empathy. Second, SERUM converts the pragmatic objectives into surface structure cues like object emphasis and level of technicality. Finally, SERUM converts the surface structure cues to realize text that is natural, appropriately technical and emotionally empathetic. SERUM is demonstrated in describing tests and treatments for lung disease in AIDS patients, a sensitive domain where empathetic responses may be needed.

Algorithms↗

Clinical observations in children after prenatal benzodiazepine exposure.

Eight children excessively exposed to benzodiazepines (BZD) in utero are described. Five of the 8 mothers admitted regular use of BZD and in 3 mothers, stored serum from early pregnancy could be analysed and found positive for BZD and its metabolite. All the children had similar dysmorphic features, in addition, 1 child had aplasia of one kidney and 2 had cleft palate. At follow-up 2 children had become microcephalic. 2 were severely mentally retarded, 5 had a mild mental retardation and only 1 was of normal intelligence. In a case-control study, 4 neonatal diagnoses of congenital malformations, in our experience characteristic of fetal BZD exposure, were chosen as inclusion criteria. In 8 of 18 cases, blood samples from early pregnancy were positive for BZD as compared to 2 of 60 control samples. An association between BZD-positive serum tests and the particular diagnoses could be demonstrated (p = 0.00006).

Abnormalities, Drug-Induced↗

[Antiparasite therapy].

The lack of any parasite vaccine makes prevention against parasitic diseases to be based, as in the past, in ecological measures such as the environmental health and vector control to interrupt the biological cycle; on the other hand, it is also based in anti-parasite drugs. Once the disease has been acquired it is just possible to take medication. Studies on the way of action allow to understand more about the physiology of the parasite and, on the other hand, to understand better the physiology of the parasite allows to design new more effective drugs. However, the vast majority of these new drugs have been obtained thanks to intelligent and selective screening of generic molecules more than from the result of the knowledge of the biochemistry of the parasite. Despite all this, it is well known the mechanisms of action of many antiparasite drugs which have led us, when possible, to the discussion about possible targets to give an idea of how the rational approximation to design new medicaments is done.

Antiparasitic Agents↗

A three year follow up of preterm infants after moderately early treatment with dexamethasone.

OBJECTIVE: To assess the effect of moderately early postnatal dexamethasone treatment on growth and neurodevelopmental outcome in preterm infants. METHODS: Thirty preterm infants enrolled in a randomised clinical trial to investigate the effectiveness of moderately early dexamethasone administration in the treatment of chronic lung disease were routinely followed up. Fifteen babies received a total dose of 4.75 mg/kg over 14 days from the 10th day of life, and 15 babies were untreated. Five infants in each group received open label steroids to facilitate extubation later in their clinical course. Growth and neurodevelopmental outcome are reported. RESULTS: The mean body weight, height, and head circumference as well as the number of babies with anthropometric measurements within normal range were similar in treated and untreated babies. There was no significant difference between treated and control groups with respect to incidence of cerebral palsy, major neurosensory impairment, mean intelligence quotient scores, and behavioural abnormalities. CONCLUSIONS: Postnatal dexamethasone treatment with the schedule used in this study did not impair growth and neurodevelopmental outcome in preterm infants. Data from larger trials have raised major concern that postnatal steroid treatment may increase neurodevelopmental impairment. The full extent of the risk will only be known when more trials have reported follow up data.

Administration, Topical↗

Prediction of primate splice junction gene sequences with a cooperative knowledge acquisition system.

We propose a cooperative conceptual modelling environment in which two agents interact: the machine and the human expert. The former is able to extract knowledge from data using a symbolic-numeric machine learning system, and the latter is able to control the learning process by accepting and validating the machine results, or by criticizing those results or the explanation that the system produces on them. The improvement of the conceptual modelling relies on the cooperation between the two agents. Results obtained with our method on prediction of primate splice junctions sites in genetic sequences are far better than those reported in the literature with other symbolic machine learning systems, and are as better as those obtained with some artificial neural networks methods reported at present. But in opposite to neural networks which lack of argumentation, our system provides the user a plausible explanation of its prediction.

Algorithms↗

Synthetic ground truth for validation of brain tumor MRI segmentation.

Validation and method of comparison for segmentation of magnetic resonance images (MRI) presenting pathology is a challenging task due to the lack of reliable ground truth. We propose a new method for generating synthetic multi-modal 3D brain MRI with tumor and edema, along with the ground truth. Tumor mass effect is modeled using a biomechanical model, while tumor and edema infiltration is modeled as a reaction-diffusion process that is guided by a modified diffusion tensor MRI. We propose the use of warping and geodesic interpolation on the diffusion tensors to simulate the displacement and the destruction of the white matter fibers. We also model the process where the contrast agent tends to accumulate in cortical csf regions and active tumor regions to obtain contrast enhanced T1w MR image that appear realistic. The result is simulated multi-modal MRI with ground truth available as sets of probability maps. The system will be able to generate large sets of simulation images with tumors of varying size, shape and location, and will additionally generate infiltrated and deformed healthy tissue probabilities.

Algorithms↗

Miniature language system acquisition by children with different learning proficiencies.

Sixteen children, aged 7:8 to 9:10, learned two miniature languages while playing a communication game. Both languages expressed Action (Agent, Patient) meanings and incorporated a Patient suffix. They differed in word order: VSO (Language I) versus SOV (Language II). Children found the SOV language easier; they also made more suffix errors and fewer word order errors in this language. The results suggest that the perceptual salience of an utterance-final particle may hinder grammatical analysis, at least if capacity limits and perseverative learning strategies intervene.

Attention↗