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PubMed2006

Genetic stability and territorial structure facilitate the evolution of tag-mediated altruism.

Evolutionary theorists have long been interested in the conditions that permit the evolution of altruistic cooperation. Recent work has demonstrated that altruistic donation can evolve in surprisingly simple models, in which agents base their decisions to donate solely on the similarity of evolved "tags" relative to evolved tag-difference tolerances. There is disagreement, however, about the conditions under which tag-mediated altruism will in fact evolve. Here we vary two critical parameters in a standard model of tag-mediated altruism-genetic stability and territorial structure-and show that altruism evolves in a wide range of conditions. We demonstrate the evolution of significant levels of altruism even when the immediate costs to donors equal the benefits to recipients. We describe the mechanism that permits the emergence of altruism in the model as a form of kin selection that is facilitated by interactions between altruism, genetic drift, and fecundity.

Altruism↗

PubMed2006

Advances in the treatment for haematological malignancies.

Despite the progress made in the last decade in the treatment of haematological malignancies, most of the patients still have a dismal prognosis. However, the improved knowledge of tumour biology opened the possibility to develop new 'intelligent' therapeutic strategies, the so-named targeted therapies. These approaches aim to selectively kill cancer cells by basing this selectivity on both the expression of a specific molecule on their surface or the activation of particular molecular pathways secondary to malignant transformation. In this article, the authors review the main targeted therapies available in haematology, such as monoclonal antibodies, tyrosine kinase, farnesyltransferase, as well as proteasome inhibitors, antiangiogenesis compounds and antisense oligonuceotides. Finally, the authors focus on the application of imatinib mesylate in chronic myeloid leukaemia as the paradigm of molecular treatment. Although these novel therapies are beginning to fulfil their promise, continued research efforts are needed to determine the optimal role of these strategies in haemato-oncology.

Antineoplastic Agents↗

PubMed2004

Behavioral and neuroendocrine changes during mental stress and repeated treatment with antidepressants in healthy men.

Excessive stress loadings in daily life are believed to play a role in the development of affective disorders. Our recent finding of enhanced neuroendocrine activation during stress of hypoglycemia after repeated antidepressant treatment in healthy men supports the hypothesis that the clinical effects of antidepressant treatment may be partly due to the adjustment of the stress response, which was reported to be blunted in depressive patients. The present double-blind placebo-controlled study investigated the effects of 6 days of treatment with the antidepressants citalopram or tianeptine on neuroendocrine activation during mental stress. Blood pressure, heart rate, and salivary cortisol values were measured. The stress procedure, lasting 17 min, consisted of a short intelligence test followed by the Stroop word-color interference test. Citalopram treatment was associated with a significant enhancement of stress-related increase in systolic and diastolic blood pressure. No differences were observed in the heart rates and salivary cortisol. Comparisons based on cluster analysis revealed that subjects with poor performance in the Stroop test displayed a significantly lower rise of systolic and diastolic blood pressure values after the stress procedure and lower prestress cortisol levels in saliva when compared to the good performing subjects. Our findings show that antidepressant treatment can enhance the neuroendocrine response also during mental stress, and suggest that mental performance during stress is related to the pattern of cardiovascular and adrenocortical activation.

Adult↗

PubMed2006

Neurocognitive effects of treatment for childhood cancer.

We review research on the neuropsychological effects that central nervous system (CNS) cancer treatments have on the cognitive abilities of children and adolescents. The authors focus on the two most common malignancies of childhood: leukemias and brain tumors. The literature review is structured so as to separate out earlier studies, generally those published prior to 1995, as opposed to manuscripts that have been published within the past decade. This is an important distinction for both leukemia and brain tumors. Earlier studies were ground breaking in that they began to map out what could be expected in terms of intelligence and academic problems in survivors of pediatric malignancies. Survivorship in this population has and continues to markedly increase and this is largely due to changes in treatment protocols. Research on neurocognitive effects of disease and treatment in pediatric oncology has become increasingly sophisticated, and this literature review not only reflects this trend, but highlights the growing collaboration between neuropsychology, cognitive neuroscience, and neuro-imaging. Thus, our goal was to provide a historical foundation, lead the reader towards the progression of research methodology up to the current state of the art, and perhaps most importantly, discuss future directions. These directions are especially relevant to the concepts of remediation and treatment of cognitive problems, and this is emphasized at the conclusion of the review.

Antineoplastic Agents↗

PubMed2005

The effects of temporal modification of second speech signals on stuttering inhibition at two speech rates in adults.

The recovery of 'gestural' speech information via the engagement of mirror neurons has been suggested to be the key agent in stuttering inhibition during the presentation of exogenous second speech signals. Based on this hypothesis, we expect the amount of stuttering inhibition to depend on the ease of recovery of exogenous speech gestures. To examine this possibility, linguistically non-congruent second speech signals were temporally compressed and expanded in two experiments. In Experiment 1, 12 participants who stutter read passages aloud at normal and fast speech rates while listening to second speech signals that were 0, 40, 80% compressed, and 40 and 80% expanded. Except for the 80% compressed speech signal, all other stimuli induced significant stuttering inhibition relative to the control condition. The 80% compressed speech signal was the first exogenously presented speech signal that failed to significantly reduce stuttering frequency by 60--70% that has been the case in our research over the years. It was hypothesized that at a compression ratio of 80%, exogenous speech signals generated too many gestures per unit time to allow for adequate gestural recovery via mirror neurons. However, considering that 80% compressed signal was also highly unintelligible, a second experiment was conducted to further examine whether the effects of temporal compression on stuttering inhibition are mediated by speech intelligibility. In Experiment 2, 10 participants who stutter read passages at a normal rate while listening to linguistically non-congruent second speech signals that were compressed by 0, 20, 40, 60, and 80%. Results revealed that 0 and 20% compressed speech signals induced approximately 52% stuttering inhibition. In contrast, compression ratios of 40% and beyond induced only 27% stuttering inhibition although 40 and 60% compressed signals were perceptually intelligible. Our findings suggest that recovery of gestural information is affected by temporal compression before intelligibility starts to decrease.

Adult↗

PubMed2000

Selective and intelligent use of antibiotics in endodontics.

Antibiotics have been used extensively for the management of odontogenic infections since their discovery early this century. Although they have been invaluable in the management of acute and severe infections, many members of the dental and medical professions have unfortunately used these drugs inappropriately for the management of dental pain when "local" dental treatment would have sufficed. This, and the general over-use of antibiotics in other situations such as for growth enhancement in animals for human consumption, is leading to the widespread development of strains of bacteria that are resistant to antibiotics--hence, their effectiveness is being reduced at a rapid rate. The dental profession has a responsibility to patients and to the community as a whole to restrict the use of antibiotics to those situations that actually require them. This philosophy should also be extended to other professions who may be called upon to manage dental pain at times.

Agrochemicals↗

PubMed2004

A new Q-learning algorithm based on the metropolis criterion.

The balance between exploration and exploitation is one of the key problems of action selection in Q-learning. Pure exploitation causes the agent to reach the locally optimal policies quickly, whereas excessive exploration degrades the performance of the Q-learning algorithm even if it may accelerate the learning process and allow avoiding the locally optimal policies. In this paper, finding the optimum policy in Q-learning is described as search for the optimum solution in combinatorial optimization. The Metropolis criterion of simulated annealing algorithm is introduced in order to balance exploration and exploitation of Q-learning, and the modified Q-learning algorithm based on this criterion, SA-Q-learning, is presented. Experiments show that SA-Q-learning converges more quickly than Q-learning or Boltzmann exploration, and that the search does not suffer of performance degradation due to excessive exploration.

Algorithms↗

PubMed1989

Small intestinal physiology and pathophysiology.

The small intestine, like the rest of the gastrointestinal tract, is an intelligent organ. It generates a wide variety of motor patterns to meet motility requirements in different situations. Its basic motor function after a meal is to mix the chyme with exocrine and intestinal secretions, agitate its contents to uniformly and evenly expose them to the mucosal surface, and to propel them distally at a rate that allows optimal absorption of food components, and reabsorption of bile. Most of these functions are performed by individual phasic contractions. In humans, the phasic contractions are largely disorganized in time and space. These contractions may cause mixing and agitation of luminal contents with slow distal propulsion. Occasionally, an individual contraction of large amplitude and long duration migrates over several centimeters and may rapidly propel the contents over this distance. In general, the spatial and temporal relationships of individual phasic contractions become less organized distally, resulting in a slower propulsion rate in the distal small intestine than in the proximal small intestine. The migrating clustered contractions generated after a meal may also be propulsive, but because of their unpredictable and irregular occurrence, their precise role in postprandial propulsion is incompletely understood. Rapidly migrating contractions may occur when the electrical control activity is obliterated by pharmacologic agents or during parasitic infections. Their effects on motility are not known yet. Between meals, when digestion is complete, the small intestine generates migrating motor complexes that help keep the small intestine clean by dislodging debris from the villi and dumping them into the colon. This may prevent decay of these materials in the small intestine and limit their contribution to bacterial overgrowth. Giant migrating contractions may perform a similar function in the distal small intestine as well as return any refluxed fecal material back to the colon. However, the major role of giant migrating contractions may be, in pathologic states, associated with abdominal cramping and diarrhea. Giant migrating contractions are associated with mass movements. Vomiting is preceded by a retrograde giant contraction. This contraction rapidly empties the contents of the proximal half of small intestine into the stomach in preparation for vomitus expulsion by contraction of abdominal and diaphragmatic muscles. The three basic mechanisms of control of spatial and temporal patterns of contractions are myogenic, neural, and chemical.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2001

CDC's strategic plan for bioterrorism preparedness and response.

The Department of Health and Human Services (DHHS) has played a critical lead role over the past two years in fostering activities associated with the medical and public health response to bioterrorism. Based on a charge from Secretary Donna Shalala in 1998, the Centers for Disease Control and Prevention (CDC) is leading public health efforts to strengthen the nation's capacity to detect and respond to a bioterrorist event. As a result of our efforts, federal, state, and local communities are improving their public health capacities to respond to these types of emergencies. For many of us in public health, developing plans and capacities to respond to acts of bioterrorism is an extension of our long-standing roles and responsibilities. These are stated in the CDC Mission Statement: to promote health and quality of life by preventing and controlling disease, injury, and disability, and the Bioterrorism Mission: to lead the public health effort in enhancing readiness to detect and respond to bioterrorism. CDC's infectious diseases control efforts are summarized below: --Initially formed to address malaria control in 1946; --Established the epidemic Intelligence Service in 1951; --Participated in global smallpox eradication and other immunization programs; --Estimated 800-1,000 + field investigations/year since late 1990s; --New diseases: Legionnaire's Disease, toxic shock syndrome, Lyme disease, HIV, hantavirus pulmonary syndrome, West Nile, etc. -- Today: focus on emerging infections and bioterrorism. Over the past 50 years, CDC has seen a decline in the incidence of some infectious diseases and an increase in some, whereas others continue to present on a more unpredictable basis (i.e., hantavirus). Outbreak identification, investigation, and control have been an integral part of what we do for more than 50 years. We estimate that 800 to 1,000 field investigations have occurred every year since the late 1990s. Today, however, we have a new focus on emerging infectious diseases and bioterrorism.

Anti-Infective Agents↗

PubMed1979

Assessment of clinical status of schizophrenic patients by the WAIS comprehension subtest.

A previous study indicated that the Comprehension subtest of the Wechsler Adult Intelligence Scale (WAIS) might be a sensitive instrument for evaluating mental status in schizophrenic patients. To test this hypothesis, 3 groups of subjects were given the WAIS Comprehension subtest repeatedly at brief intervals. The results indicate that for a given individual (normal control or stable chronic schizophrenic), scores do not increase even with 4 consecutive weeks of testing. In contrast, a group of schizophrenic patients tested shortly after readmission and again after being established on neuroleptic medication showed a marked improvement in scores which, somewhat surprisingly, were not correlated with changes in global ratings of disordered thinking by the treating psychiatrist. This standardized test may offer a convenient objective technique for quantifying some aspects of thinking in schizophrenic patients.

Adolescent↗

PubMed1998

[Targeting of anticancer drug using intelligent polymers].

To fabricate the drug targeting system, it is very effective to combine passive targeting with intelligent polymeric system such as temperature-responsive polymers. We have been studying the passive targeting of anticancer drug bonded with or physically trapped in polymeric micelle derived from poly (ethylene oxide) (PEO) and poly (aspartic acid) block copolymer. On the other hand, Poly(N-isopropylacrylamide) (PIPAAm) is known to be a thermo-responsive polymer which has lower critical solution temperature (LCST, 32 degrees C). PIPAAm shows the reversible phase transition above and below LCST. Attempts to apply thermo-responsive drug carriers were made to enhance the site-specificity of polymeric micelle. Namely, novel type of polymeric micelle were prepared from block copolymers comprising N-isopropylacrylamide (IPAAm)-hydrophobic polymers. This temperature responsive micelles were expected to induce selective accumulation controlled by temperature modulation.

Acrylic Resins↗

PubMed1991

Reversal of neuromuscular blockade.

Intelligent, safe use of muscle relaxants dictates that the clinician monitor neuromuscular function in all patients to determine each patient's sensitivity to relaxants. Restoration of muscle strength is a function of pharmacological antagonism of residual NMB, spontaneous recovery as the concentration of relaxant declines at the neuromuscular junction, or both. In addition to recovery of "normal function" by clinical and monitoring criteria, some margin of safety of neuromuscular function must be restored. As new relaxants with very short half-lives become available, it is likely that steady states of relaxation will increasingly be maintained with continuous infusions. In this setting, the rapid rate of spontaneous recovery of both clinical neuromuscular function and an adequate margin of safety may vastly reduce the need for pharmacological antagonism.

Anesthesia Recovery Period↗

PubMedDate not supplied

Blood pressure and cognitive function in an African-American and a Caucasian-American sample: the Maine-Syracuse Study.

OBJECTIVE: The primary purpose of this study was to examine associations between indices of blood pressure (BP) and cognitive function for African-American participants in the Maine-Syracuse Longitudinal Study (MSLS). Corresponding data for the Caucasian-American MSLS participants were included to provide a basis for comparison. Interactions of age with BP indices were also assessed in relation to cognitive function. METHODS: Data were drawn from the baseline MSLS questionnaires, medical interviews and examinations, Wechsler Adult Intelligence Scale subtests, and measurements of BP for 1563 participants, of whom 147 were African American. Multiple linear regression analyses were employed to examine the relationship between several BP predictors and cognitive outcomes with statistical adjustment for demographic, psychosocial, and cardiovascular risk factors. RESULTS: Significant inverse associations between BP indices and cognitive performance were obtained for both racial cohorts but were generally of higher magnitude for the African-American cohort. Interactions of BP with age were not obtained for any of the cognitive test scores. CONCLUSIONS: Elevations in BP are associated with poorer cognitive function for African-American and Caucasian-American cohorts. These associations are similar for younger and older participants.

Adolescent↗

PubMed2006

An agent- and ontology-based system for integrating public gene, protein, and disease databases.

In this paper, we describe OntoFusion, a database integration system. This system has been designed to provide unified access to multiple, heterogeneous biological and medical data sources that are publicly available over Internet. Many of these databases do not offer a direct connection, and inquiries must be made via Web forms, returning results as HTML pages. A special module in the OntoFusion system is needed to integrate these public 'Web-based' databases. Domain ontologies are used to do this and provide database mapping and unification. We have used the system to integrate seven significant and widely used public biomedical databases: OMIM, PubMed, Enzyme, Prosite and Prosite documentation, PDB, SNP, and InterPro. A case study is detailed in depth, showing system performance. We analyze the system's architecture and methods and discuss its use as a tool for biomedical researchers.

Animals↗

PubMed2002

Macromolecules containing bipyridine and terpyridine metal complexes: towards metallosupramolecular polymers.

The ability of a broad range of N-heterocycles to act as very effective and stable complexation agents for several transition metal ions, such as cobalt(II), copper(II), nickel(II), and ruthenium(II), has long been known in analytical chemistry. This behavior was later utilized in supramolecular chemistry for the construction of highly sophisticated architectures, such as helicates, racks, and grids. The discovery of macromolecules by Staudinger in 1922 opened up avenues towards sophisticated materials with properties hitherto completely unknown. In the last few decades, the combination of macromolecular and supramolecular chemistry has been attempted by developing metal-complexing and metal-containing polymers for a wide variety of applications that range from filtration to catalysis. The stability of the polymer-metal complex is a fundamental requirement for such applications. In this respect, the use of bi- and terpyridines as chelating ligands is highly promising, since these molecules are known to form highly stable complexes with interesting physical properties with transition-metal ions. A large number of different structures have been designed for many different applications, but polymers based on the application of coordinative forces have been prepared in a few cases only. Furthermore, the synthetic procedures applied frequently resulted in low yields. During the last few years, strong efforts have been made in the direction of self-assembling and supramolecular polymers as novel materials with "intelligent" and tunable properties. In this review, an overview of this active area at the interface of supramolecular and macromolecular chemistry is given.

Journal Article↗

PubMed1989

Effects of antihypertensive therapy on blood pressure control, cognition, and reactivity. A placebo-controlled comparison of prazosin, propranolol, and hydrochlorothiazide.

A randomized, placebo-controlled trial was conducted to compare the effects of treatment with prazosin, propranolol, or hydrochlorothiazide on the following variables: blood pressure, cognitive and psychomotor skills, cardiovascular reactivity to natural and laboratory challenges, and serum lipid and lipoprotein levels. Side effects were recorded and patients evaluated how they felt during their treatment. Sixty-nine men, 35 percent black, aged 25 to 55 (mean 51.3) years, with diastolic blood pressures between 90 and 104 mm Hg (mean, 93.3 mm Hg), completed the study. There were no differences between active treatment groups in the proportion of patients with controlled blood pressure during the maintenance phase of the study. In the cognitive and psychomotor tests, the hydrochlorothiazide group showed significantly less improvement from baseline than the other treatment groups on the block design subscale of the Wechsler Adult Intelligence Scale-Revised, and there was a trend for the propranolol group to have less improvement from baseline than the other groups on the digit span subscale. There were no other significant pretreatment to post-treatment changes in the other cognitive or psychomotor tests, the Russell Revision of the Wechsler Memory Scale, or a number of computerized reaction-time and signal-detection tasks. In the reactivity testing, there was a significantly lower increase in heart rate in the prazosin group compared with placebo during the second laboratory challenge of the Stroop Color Interference Test. Post-treatment declines in ambulatory blood pressure were seen in all of the drug treatment groups in average and maximal diastolic and systolic blood pressures. Both propranolol and hydrochlorothiazide treatment resulted in low-density lipoprotein cholesterol levels that were higher than baseline and the hydrochlorothiazide treatment had significantly increased total cholesterol levels. In contrast, the prazosin-treated group experienced no adverse changes in these parameters. Overall, the propranolol group had significantly more moderate and severe side effects than did the other three groups. Considering the pattern of blood pressure control, cognitive and psychomotor effects, changes in lipid levels, and magnitude of side effects, prazosin seems to have the most advantageous profile in this study of the three anti-hypertensive agents evaluated.

Antihypertensive Agents↗

PubMed1995

Improving the balance between treatment and diagnosis: a role for radioimmunodetection.

Despite major advances in diagnostic testing, including the introduction and widespread availability of high-resolution computed tomography (CT) and magnetic resonance imaging, inadequate diagnostic information still interferes with proper management of many patients with cancers. This is particularly true for recurrent colorectal cancer, for example. In the course of this symposium, significant advances have been reported which are likely to improve management of this clinical situation. 111In, oncoscint for colorectal and ovarian cancer imaging, has been approved for single use only, and is a product licensed by the Food and Drug Administration. It has been shown to be significantly more effective than CT for detecting the presence of disease that is confined to the abdomen outside the liver. This agent is very useful in a limited role. A larger opportunity awaits other preparations reported at this conference, especially 99mTc-labeled Immu-4 carcinoembryonic antigen, which is significantly better than CT for determining resectability of recurrent cancer (T. Behr et al., Cancer Res. 55 (Suppl.): 5777S-5785S, 1995). The 99mTc-labeled compound preparations offer the advantages of low immunogenicity, excellent imaging energies of 99mTc, and "same-day" imaging. Even the most effective cancer treatment such as surgical resection, if applied to a patient who basically does not need it, can be a needless expense and a trauma to the patient. To date, our emphasis in oncology research has been heavily weighted toward developing new therapies. The success of radioimmunodetection is one indication of why it is time for a paradigm shift, during which we can move toward a more balanced program that emphasizes both diagnosis and therapy. To achieve this we must urge research institutions such as the National Cancer Institute and American Cancer Society to make major investments in the diagnostic aspects of cancer care. With the knowledge base that we have now, we can make improvements in patient care by emphasizing development of improved diagnostic methods and support for cost-effectiveness studies for developed methods, in order that currently available treatments can be more intelligently applied.

Humans↗

PubMed2002

Neuropsychological performance in medicated vs. unmedicated patients with obsessive-compulsive disorder.

To date, there have been no formal investigations of neuropsychological performance in patients with obsessive-compulsive disorder (OCD) taking psychotropic medications. The purpose of this study was to determine whether medicated and unmedicated patients with OCD demonstrate differences in neuropsychological functioning. Fifty-two patients with a primary DSM-IV diagnosis of OCD participated in the study; 28 were taking serotonin reuptake inhibitors (SRIs), and 24 were treatment-naïve (n=8) or had finished a washout period prior to their inclusion in other studies (n=16). The groups were well matched with regard to demographic and clinical variables, including symptom severity. Each group was administered a comprehensive neuropsychological battery to assess general intelligence, attention, verbal and non-verbal working memory, declarative and procedural learning, visuo-constructive skills, and executive functions. SRI-medicated did not differ from SRI-free patients on any neuropsychological measure. Benzodiazepines seemed to improve the patients' functioning on a semantic verbal fluency test. In addition, there were significant interactions between SRIs and benzodiazepines on the perseverative errors of the Wisconsin Card Sorting Test and on reaction times. SRI-medicated patients with OCD are able to perform on cognitive functioning tests at a comparable level with that of SRI-free patients, and these results have positive implications for OCD patients who respond to SRIs. The interactions between SRIs and benzodiazepines and their effect on cognition in OCD are likely to be complex and deserve further study.

Adult↗