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PubMed1986

Prostatitis. A continuing enigma.

After all is said and done, prostatitis is still a syndrome often difficult to interpret and with an unclear etiology and pathogenesis in many patients. However, if approached intelligently by an interested, knowledgeable, and honest physician, prostatitis in its different variations can be diagnosed correctly and the adequate treatment adjusted accordingly wherever possible. When no specific treatment is available, reassurance and general supportive measures will often alleviate the condition remarkably.

Anti-Bacterial Agents↗

PubMed1999

Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents.

PURPOSE: Antiepileptic drugs (AEDs) are potential teratogenic agents. The purpose of this study was to examine the long-term effects of intrauterine AED exposure on neurologic and psychological functioning. METHODS: Of a prospective study, "Epilepsy, pregnancy, and child development," children could be retraced at school age and adolescence. Sixty-seven were born to mothers with epilepsy [no drugs during pregnancy (n = 13), monotherapy (n = 31), polytherapy (n = 23)]; 49 were nonafflicted control children. Assessments included an intelligence test (Wechsler), a neurologic examination (Touwen), and an EEG. Data analyses were performed, controlling for parental social status, type of maternal drug therapy and drug dosage, type of epilepsy, frequency of seizures during pregnancy, the original subgroups, and specific drug effects. RESULTS: Type of maternal epilepsy and type and kind of AED therapy, but not maternal seizures during pregnancy correlated with an increase in abnormal EEG patterns. Minor neurologic dysfunction was diagnosed, with increased frequency from the control to the risk/no drug or monotherapy to the polytherapy group. The compromised intelligence score of the polytherapy group was primarily due to those children who had been exposed to primidone (PRM). Level of IQ was negatively associated with PRM dosage. CONCLUSIONS: Maternal epilepsy and AED therapy during pregnancy appear to have long-term effects on the offspring well into adolescence, as evinced in EEG patterns, minor neurologic dysfunction, and intellectual performance. Severity of effects increased from control group to epilepsy/no-drug group to monotherapy group and was most marked in the polytherapy group. These group differences are assumed to reflect differential neural vulnerability to social and family factors.

Adolescent↗

PubMed1998

Adjuvants and delivery issues related to immunization: a survey of the recent patent literature.

Vaccines have provided generations of individuals with protection against a number of devastating childhood diseases and, in the case of smallpox, have eradicated the disease. Arguably, this preventive approach to health care may have saved more lives than all other therapeutic approaches combined. Being commonly composed of killed-whole or live-attenuated organisms, successful vaccines have been capable of not only presenting crucial epitopes required for protective immunity but also components which stimulate the immune system provide a response of sufficient intensity to provide sustained protection. It is unlikely, however, that these same vaccines would be approved in today's regulatory climate where manufacturers must validate a highly reproducible manufacturing process and demonstrate the exact composition of the final product through stringent quality control (Gupta, 1997). Therefore, companies involved in the identification of new vaccines and their production appear to be moving away from the ill-defined and poorly-controlled immunogens of the past. Instead, they have started employing recombinant biotechnology to produce large quantities of specific antigens with the hope that these antigens will provide protective immunity. Antigen identification can take years of investigation. This process could be speeded up, however, by understanding the mechanisms which pathogens such as viruses and bacteria use to infect the host, their replication cycle and the steps they frequently take to evade the host immune system. Such a rational approach to immunogen design results in what has been termed an "intelligent" vaccine (Plough, 1998). "Intelligent" vaccines will likely be completely composed of artificial or synthetically derived products using recombinant and cell culture technologies and hopefully will allow manufacturers to develop products with the desired efficacy and safety profiles required by regulatory authorities. But unlike the complex and ill-defined immunogens of the past, these specific antigens are frequently poorly antigenic by themselves when compared to whole organisms. Co-delivery with a variety of agents, known as adjuvants, has been shown to increase the antigenicity of these poorly antigenic immunogens. In this editorial, I review the recent patent literature as it pertains to targeting of specific antigens and the role played by various classes of adjuvants to enable or enhance such targeted deliveries.

Adjuvants, Immunologic↗

PubMed2004

A parameter control method in reinforcement learning to rapidly follow unexpected environmental changes.

In order to rapidly follow unexpected environmental changes, we propose a parameter control method in reinforcement learning that changes each of learning parameters in appropriate directions. We determine each appropriate direction on the basis of relationships between behaviors and neuromodulators by considering an emergency as a key word. Computer experiments show that the agents using our proposed method could rapidly respond to unexpected environmental changes, not depending on either two reinforcement learning algorithms (Q-learning and actor-critic (AC) architecture) or two learning problems (discontinuous and continuous state-action problems).

Adaptation, Physiological↗

PubMed1983

The management of acute thermal injuries to the upper extremity.

In summary, although thermal injuries of the upper extremity can produce permanent functional compromise, intelligent management of burns of the hands and fingers can produce fully functional and cosmetically acceptable hands. When the dorsal aspects of the hands alone are injured by thermal insult, the immediate excision of the burned tissue and replacement by split-thickness skin grafts will produce functional and esthetically satisfying results. Should immediate excision and grafting be contraindicated because of massive burns of the body, management by application of topical antibacterial agents and dressings is possible. With this treatment, carefully supervised exercises are mandatory. Revisions of hypertrophic and contracted scars can be done at a later date. The stiff and painful hand is not the direct consequence of thermally destroyed skin, but is due instead to the metabolic and biologic complications of unhealed burn wounds. It follows, therefore, that the burn illness should preferably be terminated by prompt excision of the eschar and wound closure by the application of split-thickness skin grafts.

Adult↗

PubMed2005

Release kinetics from bio-polymeric nanoparticles encapsulating protein synthesis inhibitor- cycloheximide, for possible therapeutic applications.

Cycloheximide, a protein synthesis inhibitor, was encapsulated in cross-linked gelatin nanoparticles (Type B, Bovine skin, 75 Bloom) of 168 nm diameter with 26% entrapment efficiency. In-vitro release kinetics of the drug from the nanoparticles was done in phosphate buffer saline (PBS) at pH 7.4 and pH 5.8. The release kinetics showed a bi-phasic curve. Interestingly, the release of drug is approx 90% in acidic pH as compared to 50% release in neutral pH. The particle size was determined by Dynamic Light Scattering (DLS) technique, and size distribution spectra at different pH were observed to vary inversely with increase in pH. These drug loaded nanoparticles were found to be stable in whole blood showing negligible haemolysis. Cytotoxicity in HBL-100 and MCF-7, breast cancer cell lines was done in a 24-72 hrs assay, showing increased anti-tumour activity over a period of time indicating slow release. Dose dependent cytotoxicity was observed after 24 hours upto 72 hours of incubation of nanoparticles while the drug per se (<4 microg) showed 93% toxicity within 24 hours. Phase contrast microscopy of nanoparticle-cell interaction, clearly indicated aggregation along the lipid cell-membrane. Electron Microscopy (TEM, SEM) studies revealed its size and spherical shape. The stability of the particle, the slow and controlled release of drug from the gelatin nanoparticles indicate that it is a good candidate to deliver bio-pharmaceuticals. These behave as "intelligent" carriers for drug delivery, and can be exploited to empty their drug load in acidic medium. The paper focuses on the release kinetics of the gelatin nanoparticles that can be successfully exploited to treat solid tumors.

Antineoplastic Agents↗

PubMed1991

Diagnostic applications of DNA probes.

This review has described several of the most common molecular biologic techniques that are, or will be, employed in the diagnostic laboratory. The potential advantages of these DNA probe assays in the diagnosis of infectious diseases include: rapid detection and identification of infectious agents; the ability to screen selected specimens using batteries of probes; and the detection of nonviable or difficult-to-culture organisms. The potential disadvantages of DNA probe assays include: the use of isotopic detection methods for optimum sensitivity; limited diagnostic sensitivity of current assays; slow turna-round time for some assay formats; expense of current reagents; limited availability of many probes; lack of technical expertise in most diagnostic laboratories; and the requirement for antimicrobial susceptibility testing (requires culture). Given the above advantages and disadvantages, there are several key issues that must be considered before adopting DNA probe technology in the diagnostic laboratory; the cost of performing routine culture and identification versus the cost of screening with probes--both the number and type of specimens and the time savings that may be realized by eliminating routine cultures; the prevalence of the infectious agent--even the best DNA probe assay may not be useful or practical in a low-prevalence situation; the need for additional equipment and space; and the interpretation of false-positive and false-negative results--additional research is needed in this area. However, laboratories must consider these issues when using a test other than the current gold standard (i.e., culture). DNA probe technology is with us and expanding rapidly. The intelligent application of this new technology will require communication between laboratorians and clinicians and careful consideration of the many advantages and disadvantages discussed above.

Blotting, Southern↗

PubMed1981

Genetics society of Canada award of excellence lecture. The genetics of common familial disorders--major genes or multifactorial?

The common familial disorders were, until recently, neglected by geneticists because their familial distributions did not neatly fit the Mendelian mold, and no specific genes could be identified. The multifactorial-threshold model made the familial characteristics of these disorders more intelligible. Although it originally postulated a polygenic genetic component the model can also accommodate one or more major genes with low penetrance. The resulting upsurge of interest has led to (1) the development of increasingly sophisticated mathematical models from which to calculate recurrence risks for specific family situations and (2) the identification of specific predisposing genes in a number of such disorders. One of the corollaries of the model is that any pharmacological agent at therapeutic doses is likely to be teratogenic to at least some embryos, so that regulation should be in terms of "acceptably low" levels of teratogenicity rather than "safety".

Abnormalities, Drug-Induced↗

PubMed2002

Complexity of environment and parsimony of decision rules in insect societies.

This paper shows how colonies of social insects process information and solve problems in a complex environment, while keeping some parsimony at the level of the individuals' decision rules. Two studies on ant foraging reveal the diversity of adaptive colony-level patterns that can be generated through self-organization, based on the same individual-level recruitment rules. Regarding prey scavenging, the "ability to retrieve the prey" rule accounts for changes in foraging patterns, with increasing prey size, that show all stages intermediate between an individual and a mass exploitation of food resources. Regarding liquid food foraging, the "ability to ingest a desired volume" rule enables a colony to adjust the number of tending ants to the honeydew production of aphids. In both cases, decision rules are based on intelligent criteria that intrinsically integrate information on multiple variables that are relevant to the ants. Furthermore, the environment can contribute directly to the emergence of collective patterns, independently of any individual behavioral changes. Each environmental factor, including abiotic ones, that alters the dynamics of information transfer in group-living animals should be reconsidered not simply as a constraint but also as a part of the decision-making process and as a agent that shapes the collective pattern.

Animal Communication↗

PubMed2000

A cooperative framework for segmentation of MRI brain scans.

Automatic segmentation of MRI brain scans is a complex task for two main reasons: the large variability of the human brain anatomy, which limits the use of general knowledge and, inherent to MRI acquisition, the artifacts present in the images that are difficult to process. To tackle these difficulties, we propose to mix, in a cooperative framework, several types of information and knowledge provided and used by complementary individual systems: presently, a multi-agent system, a deformable model and an edge detector. The outcome is a cooperative segmentation performed by a set of region and edge agents constrained automatically and dynamically by both, the specific gray levels in the considered image, statistical models of the brain structures and general knowledge about MRI brain scans. Interactions between the individual systems follow three modes of cooperation: integrative, augmentative and confrontational cooperation, combined during the three steps of the segmentation process namely, the specialization of the seeded-region-growing agents, the fusion of heterogeneous information and the retroaction over slices. The described cooperative framework allows the dynamic adaptation of the segmentation process to the own characteristics of each MRI brain scan. Its evaluation using realistic brain phantoms is reported.

Artificial Intelligence↗

PubMed1997

Changing delivery methods for obstructive lung diseases.

There are three types of modalities for production of aerosolized medications, but numerous specific devices using these techniques are available. The recognition that children and adults need to use optimal methods to derive maximum therapeutic benefit with minimal side effects has resulted in recent developments such as spacers for pressurized metered-dose inhalers and breath-actuated dry powder inhalers and nebulizers. These methods provide finer aerosols that can be readily inhaled and deposited in the lung with improved efficiency. Delivery systems designed specifically for particular formulations have generally been well studied, but there is a paucity of information from manufactures characterizing the drug aerosols available from their devices. Clinicians are guided by data from drug trials, but must also be furnished with details of the delivery systems to allow them to compare devices and make intelligent choices for their patients. The material presented in this review provides an evaluation of some of the systems currently available for treating asthma and other lung diseases as well as a discussion of devices planned for the future.

Administration, Inhalation↗

PubMed2005

Statistical analysis of network traffic for adaptive faults detection.

This paper addresses the problem of normal operation baselining for automatic detection of network anomalies. A model of network traffic is presented in which studied variables are viewed as sampled from a finite mixture model. Based on the stochastic approximation of the maximum likelihood function, we propose baselining network normal operation, using the asymptotic distribution of the difference between successive estimates of model parameters. The baseline random variable is shown to be stationary, with mean zero under normal operation. Anomalous events are shown to induce an abrupt jump in the mean. Detection is formulated as an online change point problem, where the task is to process the baseline random variable realizations, sequentially, and raise alarms as soon as anomalies occur. An analytical expression of false alarm rate allows us to choose the design threshold, automatically. Extensive experimental results on a real network showed that our monitoring agent is able to detect unusual changes in the characteristics of network traffic, adapt to diurnal traffic patterns, while maintaining a low alarm rate. Despite large fluctuations in network traffic, this work proves that tailoring traffic modeling to specific goals can be efficiently achieved.

Algorithms↗

PubMed2005

Self-organizing network services with evolutionary adaptation.

This paper proposes a novel framework for developing adaptive and scalable network services. In the proposed framework, a network service is implemented as a group of autonomous agents that interact in the network environment. Agents in the proposed framework are autonomous and capable of simple behaviors (e.g., replication, migration, and death). In this paper, an evolutionary adaptation mechanism is designed using genetic algorithms (GAs) for agents to evolve their behaviors and improve their fitness values (e.g., response time to a service request) to the environment. The proposed framework is evaluated through simulations, and the simulation results demonstrate the ability of autonomous agents to adapt to the network environment. The proposed framework may be suitable for disseminating network services in dynamic and large-scale networks where a large number of data and services need to be replicated, moved, and deleted in a decentralized manner.

Algorithms↗

PubMedDate not supplied

Modelling epidemiology of leprosy.

A simulation model for leprosy transmission and control has been developed with specific objectives. Several sensitivity experiments have been carried out by altering the various inputs based on empirical data combined with intelligent guessing. The outputs generated through these exercises were on the expected lines. While incremental exercises would improve the model, it can be used even at the existing stage as a tool for programme managers.

Forecasting↗

PubMedDate not supplied

A society of goal-oriented agents for the analysis of living cells.

This paper presents a new model for the segmentation and analysis of living cells. A multi-agent model has been developed for this application. It is based on a generic agent model, which is composed of different behaviors: perception, interaction and reproduction. The agent is further specialized to accomplish a specific goal. Different goals are defined from the different components of the cell images. The specialization specifies the parameters of the behaviors for the achievement of the agent's goal. From these goal-oriented agents, a society is defined, and it evolves dynamically as the agents are created and deleted. An internal manager is integrated in the agent to control the behavior's execution. It makes use of an event-driven scheme to manage the behavior priorities. The present design is mainly oriented toward image segmentation, however, it includes some features on tracking and motion analysis.

Animals↗

PubMed1998

Growth and development four years after treatment for the Trichuris dysentery syndrome.

A follow-up study is reported of 18 children 4 y after treatment for the Trichuris dysentery syndrome (TDS) and matched control children. The TDS children were initially severely stunted and had extremely low developmental levels. They showed catch-up in height of 1.9 z-scores even though they remained in very poor environments. Their intelligence quotients, school achievement and cognitive function remained significantly lower than those of the controls. Controlling for their earlier developmental levels, the TDS children showed a small improvement in mental development relative to the controls.

Antinematodal Agents↗

PubMedDate not supplied

Accurate visible speech synthesis based on concatenating variable length motion capture data.

We present a novel approach to synthesizing accurate visible speech based on searching and concatenating optimal variable-length units in a large corpus of motion capture data. Based on a set of visual prototypes selected on a source face and a corresponding set designated for a target face, we propose a machine learning technique to automatically map the facial motions observed on the source face to the target face. In order to model the long distance coarticulation effects in visible speech, a large-scale corpus that covers the most common syllables in English was collected, annotated and analyzed. For any input text, a search algorithm to locate the optimal sequences of concatenated units for synthesis is desrcribed. A new algorithm to adapt lip motions from a generic 3D face model to a specific 3D face model is also proposed. A complete, end-to-end visible speech animation system is implemented based on the approach. This system is currently used in more than 60 kindergarten through third grade classrooms to teach students to read using a lifelike conversational animated agent. To evaluate the quality of the visible speech produced by the animation system, both subjective evaluation and objective evaluation are conducted. The evaluation results show that the proposed approach is accurate and powerful for visible speech synthesis.

Algorithms↗

PubMed2004

A multi-agent system architecture for geographic information gathering.

World Wide Web (WWW) is a vast repository of information, including a great deal of geographic information. But the location and retrieval of geographic information will require a significant amount of time and effort. In addition, different users usually have different views and interests in the same information. To resolve such problems, this paper first proposed a model of geographic information gathering based on multi-Agent (MA) architecture. Then based on this model, we construct a prototype system with GML (Geography Markup Language). This system consists of three tiers-Client, Web Server and Data Resource. Finally, we expatiate on the process of Web Server.

Algorithms↗