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PubMed2002

Predicting nearest agent distances in artificial worlds.

In a number of multi-agent artificial life studies where agents interact over limited distances, the emergence and/or evolution of a specific behavior may depend critically upon interagent distances. Little theoretical analysis has been done previously concerning how to predict such distances. In this paper, we derive a probabilistic method that, for an agent at an arbitrary location in a two-dimensional cellular world, predicts the expected distance to a nearest other agent. Our method works for many world topologies, and we apply it to determine the expected distance for six commonly used ones. Further, the method is readily adapted to handle special restrictions. Over a wide variety of agent densities we show that the theoretically predicted distances are largely in agreement with the distances measured in computational experiments with randomly placed agents. We then utilize our prediction method to interpret recent observations that an imprecise threshold in the density of agents exists for the evolution of communication. We thus illustrate that, despite its conceptual simplicity, our method can aid the analysis and even the design of complex artificial environments populated by agents that have the potential to interact with one another.

Artificial Intelligence↗
PubMed2005

Olanzapine-induced weight gain and disturbances of lipid and glucose metabolism.

Among the atypical antipsychotics, clozapine and olanzapine are known to cause significant weight gain. Along with quetiapine, they may impair glucose metabolism and increase the risk for type 2 diabetes. They are also associated with a rise in triglyceride levels and an increased risk for coronary artery disease. Clinicians should take these risks seriously in prescribing these antipsychotics and employ intelligent safeguards if and when they use them.

Antipsychotic Agents↗
PubMed1995

Decision support systems from the standpoint of knowledge representation.

Relationships between decision-support systems and knowledge representation are examined from three different points of view: the characteristics of medical decisions that might influence the selection of appropriate knowledge representations,--the extent to which different knowledge representations can support efficient medical decisions and,--the validation of knowledge hypotheses through the practice of decision support systems. A three-level model of knowledge representation is proposed that includes a contextual, a conceptual and a computational level. Taking into consideration the context that leads to the selection of a given representation raises the issue of multiexpertise and multirepresentation modeling. Implementation of decision support systems as sets of cooperative agents and integration in the health information systems are considered.

Artificial Intelligence↗
PubMed1988

CASE, the computer-automated structure evaluation system, as an alternative to extensive animal testing.

CASE, an artificial intelligence system with demonstrated ability to predict biological activity based on structural considerations, correctly predicts animal carcinogenicity. It can, therefore, play a pivotal role in classifying chemicals as carcinogens and prioritizing them for further testing. Additionally, CASE shows promise in the design of pharmacologically active agents by reducing the number of drugs that need to be synthesized and tested. For both of these applications, CASE provides a mechanism to conserve animal and other testing resources.

Animal Testing Alternatives↗
PubMed1982

Bipolar illness in adolescents with major depression: clinical, genetic, and psychopharmacologic predictors in a three- to four-year prospective follow-up investigation.

Sixty adolescents, aged 13 to 16 years, hospitalized for major depression were studied prospectively, for three to four years to determine the utility of clinical, genetic, and pharmacologic response variables in predicting a bipolar course of illness. Bipolar outcome was observed in 20% of the cohort. Statistical analyses showed that bipolarity was predicted by (1) a depressive symptom cluster comprising rapid symptom onset, psychomotor retardation, and mood-congruent psychotic features; (2) a "loading" of affective disorder in the family pedigree, a family history of bipolar illness, and the presence of illness in three successive generations of the pedigree; and (3) pharmacologically induced hypomania. All predictors were shown to have high specificity for bipolar outcome, whereas pharmacologic hypomania and symptom cluster permitted the highest confidence of prediction, 100% and 80%, respectively. Even in juvenile depression, careful attention to clinical and biologic variables may aid in the predictive differentiation of meaningful diagnostic subtypes.

Adolescent↗
PubMed2004

Correlates of treatment-related decision-making capacity among middle-aged and older patients with schizophrenia.

BACKGROUND: Antipsychotic medications constitute the backbone of treatment for schizophrenia. Current guidelines require clinicians to obtain patients' informed consent for treatment, but few empirical studies of the capacity of patients with schizophrenia for meaningful consent in this context exist. This issue may be particularly relevant for middle-aged and older patients, as the cognitive changes associated with normal aging may have an adverse impact on decision-making processes. We examined the range, stability, and correlates of treatment-related decisional capacity in this patient population. METHODS: Participants included 59 middle-aged and older patients with schizophrenia or schizoaffective disorder and 38 normal comparison subjects. Baseline measures included the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), psychopathology rating scales, and the Mattis Dementia Rating Scale. Patients also completed a neuropsychological test battery. The MacCAT-T was readministered to patients at a 1-month follow-up. RESULTS: Relative to the comparison subjects, the patients had worse understanding of disclosed material; however, a wide range of performance was observed among patients. Variability in MacCAT-T performance was not predicted by demographic characteristics; there were no significant correlations between psychopathology ratings and MacCAT-T scores. Cognitive test scores were often significant correlates of capacity, particularly in terms of understanding and reasoning. The MacCAT-T scores were stable during the 1-month follow-up. CONCLUSIONS: Overall, middle-aged and older outpatients with schizophrenia had worse understanding of disclosed information than did normal comparison subjects, but such group comparisons obscure remarkable heterogeneity among patients. Differences in capacity appeared more related to cognitive functions than to severity of psychopathology. Such information about barriers to capacity may help in developing more effective methods of providing informed consent.

Aged↗
PubMed1984

The Genain Quadruplets: psychological studies.

A series of behavioral studies is reported on the Genain Quadruplets. These monozygous women, all of whom have suffered or are suffering from schizophrenia, were studied previously at the National Institute of Mental Health (1955-1958) and were the subject of an extensive report by Rosenthal (1963). Although the Genains are genetically identical, the expression of the schizophrenic disorder is unequal among the quads, and this circumstance has led to speculation about the relative contributions of nature and nurture (or diathesis and stress in Rosenthal's terminology) in the development of this disease. Two goals were pursued in this investigation: one concerned a comparison of the status of the Genains in 1981 as compared with 1958; the other concerned whether data from the armamentarium of newer behavioral and neurobiological techniques invented and employed since 1958 might shed some light on the unequal expression of schizophrenia among the quadruplets. We conclude that the Genains are functioning about as well as they ever have in their adult lives, and scores on attentional tests show improvement as compared to 1958 measures. This is probably attributable to the medication (primarily neuroleptics) and other supportive treatments they have received over the years. With respect to the varying degrees of illness seen in the Genains, scrutiny of the biochemical, physiological, neuroradiological, immunogenetic, and behavioral test data leads to speculation that certain unique biochemical findings interacting with differing types and amounts of cerebral pathology constitute a major cause of the variable expression of the schizophrenic diathesis.

Antipsychotic Agents↗
PubMed2001

Less adrenergic response to mental task during verapamil compared to amlodipine treatment in hypertensive subjects.

We compared the effects of amlodipine and verapamil slow release on autonomic responses to a 5-min mental arithmetic test (MST) in patients with mild to moderate hypertension. Twenty subjects received 8 weeks of verapamil slow release 240 mg or amlodipine 10 mg in a double-blind crossover design, both after 4 weeks' placebo. Heart rate (HR) and blood pressure (BP) were continuously monitored. Venous plasma catecholamines were analysed by a radioenzymatic assay. Baroreflex sensitivity (BRS) was estimated with the transfer function technique. Calculations of the area under the curve (AUC) were used to estimate average HR, BP and catecholamine concentrations. The reactivity to MST was estimated as percent change from the basal AUC. A paired t-test was performed. Data are means +/-SEM. Compared to verapamil, amlodipine increased average noradrenaline (NA) concentrations (245 +/- 23 vs 191 +/- 17 pg/l, respectively, p = 0.005), NA reactivity (14.0 +/- 5.5% vs -2.9 +/- 3.3, p = 0.004), average HR (65 +/- 2 vs 61 +/- 2 beats/min, p < 0.001) and HR reactivity (2.5 +/- 1.0 vs 0.1 +/- 0.9%, p = 0.056). BP did not differ significantly. BRS correlated with average and baseline HR on both medications (r = -0.53 and -0.63, p < or = 0.03). We conclude that adrenergic responses to MST are blunted on treatment with verapamil compared to amlodipine in hypertensive patients.

Adrenergic Agents↗
PubMed1997

Blood pressure and performance on the Mini-Mental State Examination in the very old. Cross-sectional and longitudinal data from the Kungsholmen Project.

The authors examined the association of blood pressure with cognitive function as assessed by the Mini-Mental State Examination (MMSE) in a community-based Swedish cohort of 1,736 people aged 75-101 years. Age, sex, education, antihypertensive medication use, heart disease, and stroke were considered as covariates. Multiple linear regression analysis indicated that both systolic and diastolic blood pressure, measured in 1987-1989, were positively and significantly related to baseline MMSE score; baseline systolic pressure was also positively and significantly related to follow-up MMSE score, measured after an average period of 40.5 months among subjects who were not taking antihypertensive medication at baseline. Furthermore, in the nontreated group, multiple logistic regression showed that individuals with a baseline systolic pressure less than 130 mmHg had an odds ratio of 1.88 (p = 0.05) for follow-up cognitive impairment (MMSE score < 24) compared with those whose systolic pressure was 130-159 mmHg. An increased but not statistically significant risk of cognitive impairment was associated with high blood pressure (systolic pressure > or = 180 mmHg or diastolic pressure > or = 95 mmHg) only in persons taking antihypertensive medication at baseline. Subjects with systolic pressure of 160-179 mmHg tended to be at lower risk of cognitive impairment. These results may support the view that a certain blood pressure level, particularly a systolic pressure of at least 130 mmHg, is important to the maintenance of cognitive functioning in the very old. They also suggest that severe hypertension that is not well controlled (systolic pressure > or = 180 mmHg or diastolic pressure > or = 95 mmHg) is still a threat to cognitive function in this age group. However, the use of blood pressure measurements made at a single visit and the relatively short follow-up period should be considered when interpreting these results.

Aged↗
PubMed1995

No neurological improvement after liver transplantation for Wilson's disease.

Orthotopic liver transplantation (OLT) represents the sole etiological treatment for Wilson's disease (WD), but its efficacy in resolving the neurological symptoms is still a matter of debate. We present the case of a young male affected with WD with hepatic and neurological involvement, who underwent OLT for subacute liver failure. Clinical, neuropsychological and neuroradiological assessment were performed before and after OLT. OLT had no effect on neurological symptoms, suggesting that the basal ganglia damage may be irreversible. Nineteen months after OLT, the patient went on to develop new permanent extrapyramidal symptoms. We postulate a sequela of an early post-operative central pontine and extrapontine myelinolysis.

Adult↗
PubMed1998

Early and late effects of breast-feeding: does breast-feeding really matter?

Breast-feeding protects the newborn against infectious diseases in developing as well as in industrialized countries. Protection is conferred against gastrointestinal and respiratory tract diseases as well as against otitis media. This protection provided by specific (antibody dependent) and broad, nonspecific protective factors in human milk (proteins, glycoproteins, and lipids) is associated with lower global morbidity and mortality of breast-fed infants as compared with formula-fed infants. While protection against diseases that develop later in life, such as insulin-dependent diabetes mellitus, inflammatory bowel disease, and childhood cancer, has been reported, well-planned prospective studies are essential in order to confirm these observations. Similar studies are essential in order to ascertain the small but consistently reported higher cognitive ability of breast-fed infants.

Anti-Infective Agents↗
PubMed1998

Die Vision einer pragmatischen klinischen Forschung oder das Ende der Diskussion über < > und < >

The Concept of Pragmatic Clinical Research or the End of Discussion about 'Placebo' and 'Specific Effects&rsquoThe reorientation of clinical research towards the questions of treatment benefit (beyond the question of treatment efficacy) and of how much clinical trials represent actual practice (external validity) is the timely path to clinical research questions of real interest and importance. Postmodern 'anything goes' makes it possible to also consider thus far looked down on placebo effects as valuable, however, it requires the precise documentation of the external validity of such effects. Not disease as such, but the disease context, not therapy as such, but the therapy context, not the patient as such, but the patient context, not a test as such, but the test situation have become the important focuses of clinical research. In respect to test results current medicine has to recognize its illiterate mystification of allegedly 'objective' and 'hard' data. The patient context can determine whether an 'efficacious' therapy is beneficial or harmful, and thus, it is the proper definition of the patient context which makes medicine scientific, no matter how 'objective' or 'subjective' the effect of therapy is. The consideration of the therapy context leads to the important distinction between efficacy and effectiveness (or benefit), and it becomes intelligible that the randomised controlled trial in its traditional design as the placebo-controlled double-blind trial is limited to the evaluation of an agent theory. The evaluation of treatment effectiveness requires more pragmatic trials which study treatment operations and not isolated components and which may even compare entire treatment strategies. Pragmatic clinical trials, in future, will not only allow the study of 'pathogenesis blockers'., but also the study of 'salutogenetic' interventions working with the formation of the host. The focus of attention and research in the new school of evidencebased medicine with clinical epidemiology as its basic science (if not superficially understood as mere literature medicine) has long ago been identified as illness as the product of host, disease and environment. The dispute about 'placebo' and 'specific effects', in the meantime, has become obsolete.

Journal Article↗
PubMed1988

Effect of long-term administration of buflomedil on regional cerebral blood flow in chronic cerebral infarction.

The influence of long-term oral administration of buflomedil on regional cerebral blood flow was investigated in 10 patients with chronic cerebral infarction and mild to moderate mental deterioration. Patients were given 150 mg buflomedil three times daily for a period of eight weeks. Regional cerebral blood flow (rCBF) was measured in patients before they began buflomedil treatment and during the last week of treatment. The interval of the rCBF measurements in the control subjects (n = 12) ranged from seven to forty-eight days. Mental function in the patients studied was evaluated by use of Hasegawa's simple intelligence scale for the aged and Zung's self-rating depression scale, before and during the last week of buflomedil treatment. The results showed a mean increase in rCBF of 10.5% +/- 12.1% in the patient group. The control group demonstrated virtually no change in rCBF measurements. Improvements in the mental function scores of the buflomedil-treated group were noted, and 5 of the 10 patients reported improvement in subjective symptoms.

Cerebral Infarction↗
PubMed1998

Effects of radiation and chemotherapy on cognitive function in patients with high-grade glioma.

PURPOSE: The effect of radiotherapy on the long-term cognitive performance of patients treated for intracranial neoplasm is a major concern to clinicians and patients, particularly as long-term survival or cure is possible for a small minority of patients. To assess the effects of cranial radiotherapy and chemotherapy on the cognitive performance of high-grade glioma patients, we analyzed cognitive performance data collected in a series of prospective clinical trials. METHODS: We studied 701 high-grade brain tumor patients entered onto two consecutive North Central Cancer Treatment Group (NCCTG) randomized treatment trials designed to compare radiotherapy and carmustine (BCNU) versus radiotherapy and 1-(2-chloroethyl)-3(2,6 dioxo-l-piperidyl)-1-nitrosource a (PCNU) (first trial) and radiotherapy and BCNU and interferon alfa (IFN) versus radiotherapy and BCNU (second trial). Folstein Mini-Mental Status Exam (MMSE) score and Eastern Cooperative Oncology Group (ECOG) performance score (PS) recorded at baseline and 6, 12, 18, and 24 months were analyzed to assess cognitive and physical function over time. Patients who did not demonstrate tumor progression within 60 days of the assessment time were considered nonprogressors at that evaluation. A loss of greater than 3 points on the MMSE was considered significant deterioration. RESULTS: The number of patients who experienced a greater than 3-point decrease in MMSE from baseline was 13 of 119 nonprogressors (10.9%; 95% confidence interval [CI], 6.3% to 18.9%) at 6 months, three of 54 nonprogressors (5.5%; 95% CI, 0.5% to 12.8%) at 12 months, three of 30 nonprogressors (10%; 95% CI, 2.1% to 26.5%) at 18 months, and four of 22 nonprogressors (18.2%; 95% CI, 5.2% to 40.3%) at 24 months. The CIs at all times overlapped, which indicates no statistically significant increase in the percentage of patients who experienced a significant decrease in their MMSE score. Patients who demonstrated a significant decrease in their MMSE score were significantly older than those who did not (P = .0017) at 6 months and remained so throughout follow-up; moreover, they had a significantly shorter time to progression and death. ECOG PS was strongly negatively correlated with MMSE score throughout the study, and MMSE score at all time intervals was correlated with baseline PS. CONCLUSION: In this population of glioma patients who received radiotherapy, there is no clear trend to cognitive worsening. Factors such as older age, poorer PS, and subclinical tumor progression may be more significant factors in those patients who did demonstrate a significant cognitive decline.

Adolescent↗
PubMed1985

Neuropsychological sequelae of childhood cancer in long-term survivors.

In order to assess the effects of various cancer treatments on neuropsychological functioning, 74 long-term survivors of childhood cancer were examined. A comprehensive battery of tests was administered to two CNS treatment groups (irradiated and nonirradiated leukemia and lymphoma patients) and a control group (solid tumor and Hodgkin disease patients receiving no CNS treatment). The CNS-irradiated group obtained lower scores than the other two groups, with significant differences in visual-motor and fine motor skills, spatial memory, and arithmetic achievement resulting in significant differences in IQ scores (VIQ, PIQ, FSIQ). The results are discussed in relation to: (1) the effects of CNS irradiation on cognitive development; (2) the specificity of these effects; and (3) the relationship of age at diagnosis to treatment effects. It is concluded that although there is a general lowering of scores after CNS irradiation, the effect is most pronounced for nonlanguage skills. Age at diagnosis was less important than the type of treatment, with CNS irradiation reducing performance regardless of when cancer was diagnosed. There were indications that children with any type of cancer diagnosed before age 5 years are more likely to have some cognitive difficulties.

Age Factors↗
PubMed1985

[CO2 laser in treating head and neck cancer].

CO2 laser is especially useful in treating cancer of tube- and cavity-organs. For carcinomas of the tongue, we have employed three types of laser usage. Carcinomas confined within the mucosa are treated by laser alone. For carcinomas invading the muscle to some extent, we make a mass reduction surgery by means of laser which is followed by (chemo)radiotherapy. Carcinomas with extensive muscular invasion are first treated with induction chemotherapy. If the chemotherapy is effective, we add laser surgery for the purpose of mass reduction and chemoradiotherapy follows. 26 patients were treated and none has developed local recurrence. For glottic carcinomas, we have applied laser in two ways: laser surgery alone and laser combined with (chemo)radiotherapy. We have treated 58 patients with glottic carcinoma. 14 developed local recurrence. Of these 14, 13 were successfully treated but the other died because he refused to have further treatment.

Antineoplastic Agents↗