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PubMed2006

The Independent LifeStyle Assistant: lessons learned.

The Independent LifeStyle Assistant (I.L.S.A.) is an agent-based monitoring and support system to help elderly people live longer in their homes by reducing caregiver burden. I.L.S.A. is a multiagent system that incorporates a unified sensing model, situation assessments, response planning, real-time responses, and machine learning. This paper describes the six-month study of the system we fielded in elders' homes and the major lessons we learned during development.

Activities of Daily Living↗

PubMed1994

Therapeutic dilemma of disseminated CNS germinoma and the potential of increased platinum-based chemotherapy delivery with osmotic blood-brain barrier disruption.

In contrast to disseminated extraneural germinoma, systemic chemotherapy in disseminated central nervous system germinoma often results in only transient responses. After surgery, cytoreduction was accomplished with systemic multiagent platinum-based chemotherapy in 4 consecutive patients known to have a poor prognosis, due to central nervous system germinoma at more than one anatomic site. When tumor enhancement resolved (i.e., blood-brain barrier integrity was restored), intensive consolidation therapy with carboplatin and etoposide was given in association with mannitol-induced osmotic blood-brain barrier disruption. Complete responses occurred in all 4 patients and currently 3 are tumor-free without radiotherapy 24-40 months from diagnosis, suggesting the importance of increased drug delivery for an extended period.

Adolescent↗

PubMed2005

Toward a systems- and control-oriented agent framework.

This paper develops a systems- and control-oriented intelligent agent framework called the hybrid intelligent control agent (HICA), as well as its composition into specific kinds of multiagent systems. HICA is essentially developed around a hybrid control system core so that knowledge-based planning and coordination can be integrated with verified hybrid control primitives to achieve the coordinated control of multiple multimode dynamical systems. The scheme is applied to the control of teams of unmanned air and ground vehicles engaged in a pursuit-evasion war game. Results are demonstrated in simulation.

Algorithms↗

PubMed2004

Coordinated problem solving through resource sharing in a distributed environment.

An important feature in a distributed problem solving system is that the resources of different nodes can be shared through cooperation. In this paper, the generalized partial global planning (GPGP) approach used for multiagent systems is extended by providing a coordination mechanism for resource sharing across nodes. In our framework, multiple conflicting criteria (or objectives) like quality, cost, and duration may be associated with an input task. Preference ratings expressed subjectively may be assigned to each of the criteria. Task assignment in this system, which is a multiobjective decision making problem, is important for the satisfaction of the criteria. It has to be done with imprecise information since the system is dynamic and preference ratings are specified subjectively. A technique for task assignment using the fuzzy set approach is also presented in this paper. Simulation studies for the coordination mechanism and the task assignment have been performed to demonstrate their effectiveness.

Letter↗

PubMed2004

Cooperative action of coherent groups in broadly heterogeneous populations of interacting chemical oscillators.

We present laboratory experiments on the effects of global coupling in a population of electrochemical oscillators with a multimodal frequency distribution. The experiments show that complex collective signals are generated by this system through spontaneous emergence and joint operation of coherently acting groups representing hierarchically organized resonant clusters. Numerical simulations support these experimental findings. Our results suggest that some forms of internal self-organization, characteristic for complex multiagent systems, are already possible in simple chemical systems.

Animals↗

PubMed1990

Delayed central nervous system (CNS) radiation in childhood CNS acute lymphoblastic leukemia. Results of a pilot trial.

With the introduction of effective prophylactic central nervous system (CNS) therapy in childhood acute lymphoblastic leukemia (ALL), the incidence of CNS relapse has been significantly reduced. Nonetheless, there is a continuing need for effective CNS therapy for the 5% to 10% of children who escape prophylaxis and in whom active CNS disease develops. In July 1985, a pilot study was initiated whereby the consolidative CNS treatment, given in the form of craniospinal axis radiation, was delayed and administered after delivery of a prolonged course of intensive systemic and CNS chemotherapy. Ten leukemic patients with CNS relapse were treated according to this pilot study. One patient did not respond to pre-CNS consolidative therapy and died at 2 months with progressive disease. The remaining nine patients have completed the craniospinal axis radiation. Five patients are off all therapy and remain in remission at a median time of 38 months (range, 31 to 46 months). Two patients are near completion of therapy and are disease-free at 22 and 24 months. Testicular relapse occurred in two patients at 14 and 29 months. CNS chemotherapy, as used in this trial, appears to have allowed for a delay in the administration of the consolidative craniospinal radiation without negatively affecting the CNS remission rate or duration. In turn, this delay has allowed for the uncompromised delivery of intensive multiagent systemic chemotherapy, as well as the separation of those patients destined to early systemic relapse from those who will achieve a sustained complete remission. In both cases, a reduction in the need for multiple courses of potentially toxic CNS therapy as a result of CNS reseeding after radiation is anticipated.

Adolescent↗

PubMed1976

Acute and late effects on normal tissues following combined chemo- and radiotherapy for childhood rhabdomyosarcoma and Ewing's sarcoma.

Twenty-three patients with rhabdomyosarcoma and 15 patients with Ewing's sarcoma, treated with radiation therapy to the local site and systemic multiagent chemotherapy are described. Acute reactions from combination chemotherapy and radiation therapy were noted in both groups of patients. These reactions often appeared after low doses of irradiation, required unplanned interruptions of treatments, and in some patients, led to discontinuation of radiation therapy. The chronic effects on normal tissues in both groups of patients have been severe in several cases.

Antineoplastic Agents↗

PubMed2003

Mycophenolate mofetil for the treatment of scleritis.

PURPOSE: To evaluate the usefulness of mycophenolate mofetil (MMF) (CellCept, Roche, Nutley, NJ), an antimetabolite immunosuppressant with a selective antiproliferative effect on T and B lymphocytes, for the treatment of scleritis. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Eight patients with scleritis treated with MMF in a tertiary referral center. METHODS: Review of the clinical records of patients evaluated at the National Eye Institute and prescribed MMF for the treatment of scleritis. MAIN OUTCOME MEASURES: Control of scleral inflammation, the ability to taper prednisone or other immunosuppressive medications, and adverse events were recorded for each patient. Mycophenolate mofetil was determined to be an effective steroid-sparing agent if the daily prednisone dosage could be reduced by 50% or more and was determined to be an effective adjunctive immunosuppressive agent if the scleral inflammation was controlled in patients with active scleritis. RESULTS: Four patients with diffuse anterior scleritis, two with necrotizing scleritis with inflammation, one with nodular anterior scleritis, and one with nodular anterior and posterior scleritis, were identified. Mycophenolate mofetil administration was initiated as a steroid-sparing agent in 4 patients with controlled scleritis and as an additional immunosuppressive agent in 4 patients with active scleritis receiving concomitant treatment with prednisone and cyclosporine or methotrexate. In 3 of the 4 patients started on MMF as a steroid-sparing agent, the scleritis remained controlled while the prednisone dosage was tapered by more than 50%. One of the patients started on MMF as a steroid-sparing agent had recurrent scleritis, and each of the patients with active scleritis continued to have persistent scleral inflammation requiring additional immunosuppressive therapy. Adverse effects recorded in 4 of the 8 patients included a rash, gastrointestinal symptoms, paresthesias, and laboratory evidence of hepatotoxicity and renal toxicity. CONCLUSIONS: Although MMF maybe be useful as a steroid-sparing agent, it was not effective as an adjunctive immunosuppressive agent in patients with active scleritis in our small, tertiary referral series. The adverse effects encountered with the use of MMF in this study cannot be attributed conclusively to MMF and are more likely complications of the multiagent systemic immunosuppressive therapy required for the treatment of recalcitrant scleritis.

Adult↗

PubMed2005

ESHAP for primary cutaneous T-cell lymphomas: efficacy and tolerance in 11 patients.

Systemic multiagent hemotherapy has been used to treat aggressive forms of primary cutaneous T-cell lymphomas (CTCL) with controversial results. Our objective was to retrospectively assess efficacy and toxicity of ESHAP (etoposide, cisplatin, high-dose aracytine, methylprednisolone) in patients with advanced CTCL. A total of 11 patients with aggressive primary CTCL, treated with the ESHAP protocol between 1995 and 2002, were studied. Two patients achieved complete remissions lasting 30+ and 6+ months, seven had partial remissions of short duration, one had stable disease and one experienced disease progression. ESHAP was poorly tolerated because of prolonged myelosuppression (91%) and infectious complications (82%). Our results suggest that ESHAP has a poor risk/benefit ratio in advanced CTCL because of the low number of complete remissions, the short duration of partial remissions and its high-grade toxicity.

Adult↗

PubMed2000

Chemo-resistant choriocarcinoma cured by pulmonary lobectomy and craniotomy.

This is a case report of a 31 year-old female with choriocarcinomatous metastasis in brain and lung. Her serum beta-HCG level rose six times following normalization during 61 months of diverse multiagent systemic chemotherapy. Pulmonary lobectomy was done in March 1997 (57 months after initial diagnosis) due to persistent pulmonary nodule and poor response to chemotherapy. Histologic examination disclosed metastatic choriocarcinoma. However, her serum beta-HCG level did not normalize. Meanwhile, repeated measurement of beta-HCG concentration in cerebrospinal fluid was normal and imaging studies did not indicate evidence of metastasis. Sixty-one months after initial diagnosis fulminant intracerebral hemorrhage made emergency craniotomy mandatory. Histologic examination revealed metastatic choriocarcinoma. Serum beta-HCG levels returned to normal immediately after craniotomy and she reached complete remission after whole brain irradiation in January 2000. She is free of disease 91 months from initial diagnosis. The role of surgery in the treatment of patients with metastatic choriocarcinoma has been diminished by the responsiveness to chemotherapy. However, local resection of metastases still seems to play a significant role in controlling complications of gestational trophoblastic neoplasia and even in curing the disease in a small subset of patients.

Journal Article↗

PubMed2002

Software agents and the route to the information economy.

Humans are on the verge of losing their status as the sole economic species on the planet. In private laboratories and in the Internet laboratory, researchers and developers are creating a variety of autonomous economically motivated software agents endowed with algorithms for maximizing profit or utility. Many economic software agents will function as miniature businesses, purchasing information inputs from other agents, combining and refining them into information goods and services, and selling them to humans or other agents. Their mutual interactions will form the information economy: a complex economic web of information goods and services that will adapt to the ever-changing needs of people and agents. The information economy will be the largest multiagent system ever conceived and an integral part of the world's economy. I discuss a possible route toward this vision, beginning with present-day Internet trends suggesting that agents will charge one another for information goods and services. Then, to establish that agents can be competent price setters, I describe some laboratory experiments pitting software bidding agents against human bidders. The agents' superior performance suggests they will be used on a broad scale, which in turn suggests that interactions among agents will become frequent and significant. How will this affect macroscopic economic behavior? I describe some interesting phenomena that my colleagues and I have observed in simulations of large populations of automated buyers and sellers, such as price war cycles. I conclude by discussing fundamental scientific challenges that remain to be addressed as we journey toward the information economy.

Journal Article↗

PubMed1992

Prophylactic cranial irradiation: advantages and disadvantages.

Anaplastic small cell carcinoma of the lung is a disease that responds to multiagent systemic therapy. Unfortunately, a high incidence of central nervous system (CNS) relapse has been observed by many investigators. Cranial irradiation has been successfully used in acute lymphoblastic leukemia to reduce CNS relapse and improve survival. A similar application of prophylactic cranial irradiation in patients undergoing therapy for small cell anaplastic carcinoma of the lung has been noted to decrease CNS relapse from approximately 25% to approximately 5%. However, CNS toxicity has been noted to occur with CNS prophylaxis. We can reduce the incidence of CNS toxicity by using modern treatment schedules and avoiding the use of doxorubicin with irradiation. Prophylactic cranial irradiation delivered to those patients who obtain a complete remission in response to induction chemotherapy can reduce the incidence of CNS relapse and can usually be delivered with minimal CNS toxicity. Unfortunately, long-term disease control with systemic agents is poor. Until more effective systemic agents are developed, the role of prophylactic cranial irradiation is one of palliation rather than improving survival.

Brain↗

PubMed1982

Microangiopathic hemolytic anemia with metastatic adenocarcinoma: response to chemotherapy.

Microangiopathic hemolytic anemia developed in two patients with metastatic malignancy, one with primary carcinoma of the colon and the other with ovarian carcinoma. There was no evidence of consumptive coagulopathy except severe thrombocytolysis in one patient. Both patients improved remarkably after chemotherapy. The colonic carcinoma responded to 5-fluorouracil delivered into the hepatic artery, and the ovarian tumor to multiagent systemic therapy.

Adenocarcinoma↗

PubMed1996

Chemotherapeutic treatment of malignant chordoma in children.

PURPOSE: We describe the effect of multiagent chemotherapy for malignant chordoma. Previous reports of other patients with malignant chordoma treated with chemotherapy as well as other therapeutic interventions are reviewed. PATIENTS AND METHODS: We describe a 19-month-old girl with unresectable cervical chordoma metastatic to the lungs at diagnosis treated with multiagent systemic chemotherapy. CNS disease was diagnosed after one course of therapy, and intrathecal chemotherapy was then administered. CONCLUSIONS: Ifosfamide and doxorubicin were efficacious in a patient with advanced metastatic disease, producing significant disease regression. The addition of intrathecal or intraventricular therapy with hydrocortisone, ARA-C, and methotrexate was effective in controlling CNS disease due to chordoma. There was no apparent benefit from the use of actinomycin-D, cyclophosphamide and vincristine nor the combination of cisplatin and 5-fluorouracil or high-dose methotrexate.

Adult↗

PubMed2004

Memory and self-induced shocks in an evolutionary population competing for limited resources.

We present a detailed discussion of the role played by memory, and the nature of self-induced shocks, in an evolutionary population competing for limited resources. Our study builds on a previously introduced multiagent system [Phys. Rev. Lett. 82, 3360 (1999)] which has attracted significant attention in the literature. This system exhibits self-segregation of the population based on the "gene" value p (where 0< or =p< or =1 ), transitions to "frozen" populations as a function of the global resource level, and self-induced large changes which spontaneously arise as the dynamical system evolves. We find that the large, macroscopic self-induced shocks that arise are controlled by microscopic changes within extreme subgroups of the population (i.e., subgroups with "gene" values p approximately 0 and p approximately 1).

Adaptation, Physiological↗

PubMed2006

Combining rate-adaptive cardiac pacing algorithms via multiagent negotiation.

Simulating and controlling physiological phenomena are notoriously complex tasks to tackle and require accurate models of the phenomena of interest. Currently, most physiological processes are described by a set of partial models capturing specific aspects of the phenomena, and usually their composition does not produce effective comprehensive models. A current open issue is thus the development of techniques able to effectively describe a phenomenon starting from partial models. This is particularly relevant for heart rate regulation modeling where a large number of heterogeneous partial models exists. In this paper we make the original proposal of adopting a multiagent paradigm, called anthropic agency, to provide a powerful and flexible tool for combining partial models of heart rate regulation for adaptive cardiac pacing applications. The partial models are embedded in autonomous computational entities, called agents, that cooperatively negotiate in order to smooth their conflicts on the values of the variables forming the global model the multiagent system provides. We experimentally evaluate our approach and we analyze its properties.

Adaptation, Physiological↗

PubMed1996

Gestational trophoblastic disease metastatic to the brain.

PURPOSE: To evaluate clinical characteristics, treatment technique, and results in patients with gestational trophoblastic disease metastatic to the brain. MATERIALS AND METHODS: From 1962 to 1994, 26 (4.1%) of 631 patients who underwent treatment for trophoblastic disease had or developed evidence of brain metastases (patients were aged 14-43 years). All patients received multiagent systemic chemotherapy and whole-brain irradiation. Total doses of radiation were 2,386-4,000 cGy (200-300 cGy per fraction). No patient received intrathecal chemotherapy. Patients were divided into three groups: group A, symptomatic brain metastases at presentation; group B, asymptomatic or minimally symptomatic brain disease at presentation; and group C, development of brain metastases during systemic chemotherapy. RESULTS: The overall 5-year actuarial survival rate was 51%. Multivariate analysis findings indicated that age, preceding pregnancy event, human chorionic gonadotropin level, World Health Organization score, performance of craniotomy, and number of brain metastases did not influence survival. The difference in the 5-year overall survival rates between groups A (39%) and B (100%) was significant (P = .03). CONCLUSION: Gestational trophoblastic disease metastatic to the brain is curable with systemic chemotherapy and whole-brain irradiation. The authors suggest treatment with steroids, chemotherapy (etoposide, high-dose methotrexate [1 g/m2], dactinomycin, cyclophosphamide, and vincristine sulfate), and concurrent whole-brain irradiation (3,000 cGy in 200-cGy fractions).

Adolescent↗

PubMed2006

Combination chemotherapy and radiation of human squamous cell carcinoma of the head and neck augments CTL-mediated lysis.

PURPOSE: The combination of systemic multiagent chemotherapy (5-fluorouracil + cisplatin) and tumor irradiation is standard of care for head and neck squamous cell carcinoma (HNSCC). Furthermore, it has been shown that sublethal doses of radiation or chemotherapeutic drugs in diverse cancer types may alter the phenotype or biology of neoplastic cells, making them more susceptible to CTL-mediated cytotoxicity. However, little is known about the potential synergistic effect of drug plus radiation on CTL killing. Here, we examined whether the combination of two chemotherapeutics and ionizing radiation enhanced CTL-mediated destruction of HNSCC more so than either modality separately, as well as the basis for the enhanced tumor cell lysis. EXPERIMENTAL DESIGN: Several HNSCC cell lines with distinct biological features were treated with sublethal doses of cisplatin and 5-fluorouracil for 24 hours and with 10-Gy irradiation. Seventy-two hours postirradiation, tumor cells were exposed to an antigen-specific CD8+ CTL directed against carcinoembryonic antigen or MUC-1. RESULTS: In three of three tumor cell lines tested, enhanced CTL activity was observed when the two modalities (chemotherapy and radiation) were combined as compared with target cells exposed to either modality separately. CTL-mediated lysis was MHC restricted and antigen specific and occurred almost entirely via the perforin pathway. Moreover, the combination treatment regimen led to a 50% reduction in Bcl-2 expression whereas single modality treatment had little bearing on the expression of this antiapoptotic gene. CONCLUSIONS: Overall, these results reveal that (a) CTL killing can be enhanced by combining multiagent chemotherapy and radiation and (b) combination treatment enhanced or sensitized HNSCC to the perforin pathway, perhaps by down-regulating Bcl-2 expression. These studies thus form the rational basis for clinical trials of immunotherapy concomitant with the current standard of care of HNSCC.

Antigens, Neoplasm↗