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Results for “multimodal modeling”

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PubMed1988

Studies on the growth of mast cells in rats. Changes in granule size between 1 and 6 months.

Mast cells from rats aged 1 month, 3 months and 5 to 7 months were compared with respect to cell size and secretory granule size and number. With increasing age there was an increase in mean total cell volume accounted for almost entirely by an increase in mean total granule volume/cell even though there was no apparent increase in the number of granules. An increase in histamine content closely paralleled the increase in total granule volume. In each age group, the distribution of equivalent volumes of granule profiles exhibited periodic multimodality consistent with a Poisson distribution of granule volume. We have interpreted these observations in terms of a model in which total granule volume/cell increases through the production of unit granules of uniform size; the increasing size of individual granules we attribute to the fusion of unit granules with each other and with larger granules.

Aging↗

PubMed2006

Kinetic prediction of functional group distributions in thermosensitive microgels.

A kinetic model accounting for the copolymerization of up to four comonomers is applied to predict both chain and radial functional group distributions in carboxylic-acid-functionalized poly(N-isopropylacrylamide) (NIPAM)-based microgels. The model can accurately predict the experimentally observed radial distributions of functional monomers in microgels prepared using a variety of different carboxylic-acid-functionalized monomers with significantly different hydrophobicities, copolymerization kinetics, and reactivities, without requiring the use of adjustable parameters. Multimodal distributions can both be predicted and experimentally generated by copolymerizing two -COOH-containing monomers with widely different reactivities. Chain distributions and monomer block formation can also be probed using the kinetic model, allowing for qualitative predictions of the potentiometric titration behavior of the microgels. The kinetic model reported herein therefore provides the first available analytical method for semiquantitatively predicting and controlling functional group distributions in bulk-polymerized microgel systems.

Journal Article↗

PubMedDate not supplied

Optical coherence tomography speckle reduction by a partially spatially coherent source.

Speckle in optical coherence tomography (OCT) images originates in the high spatial coherence of incident light that enables interference of light backscattered from spatially heterogenous tissue specimens. We report results of a numerical simulation and an experiment to test speckle reduction using a partially spatially coherent source. A Gaussian-Schell model for a partially spatially coherent source is used in the OCT simulation. For the experiment, such a source was generated by a spatially coherent boardband light source and a multimode fiber. The advantage of using a multimode fiber in combination with a broadband source is the large number of photons per coherence volume. To illustrate speckle reduction with a partially spatially coherent source, we record low-coherence interferograms of a scattering surface using single-mode and multimode source fibers. Interferograms recorded using a single-mode source fiber are indicative of those observed using conventional OCT. Speckle in OCT images recorded using a multimode source fiber is substantially reduced.

Algorithms↗

PubMed2006

Association between pathologic response in metastatic lymph nodes after preoperative chemoradiotherapy and risk of distant metastases in rectal cancer: An analysis of outcomes in a randomized trial.

PURPOSE: To compare 5 x 5 Gy preoperative radiotherapy with immediate surgery vs. preoperative chemoradiotherapy (50.4 Gy, 5-fluorouracil, leucovorin) with delayed surgery in a randomized trial for cT3-T4 low-lying rectal cancer. Despite the downstaging effect of chemoradiotherapy, similar long-term outcomes were observed in both groups. METHODS: The Cox model was used to evaluate the prognostic value of ypTN ("yp" denotes that pathologic classification was performed after initial multimodality therapy) categories and the surgical margin status in 291 patients. RESULTS: Disease-free survival (DFS) (hazard ratio [HR] 1.05, 95% confidence interval [CI], 0.73-1.51), distant metastases (HR, 1.17; 95% CI, 0.77-1.78), and local control (HR, 1.45; 95% CI, 0.74-2.84) were similar in both arms. The ypN status was the only independent prognostic factor for DFS (p < 0.001). An interaction (p = 0.016) between N stage and the assigned treatment was demonstrated. For ypN-negative patients, DFS was similar in both arms (HR, 0.83, 95% CI, 0.47-1.48); however, for ypN-positive patients, DFS was worse in the chemoradiotherapy arm (HR, 1.73; 95% CI, 1.07-2.77). The 4-year (median follow-up) DFS rate in N-positive patients was 51% in the 5 x 5-Gy arm vs. 25% in the chemoradiotherapy arm. The corresponding 4-year rates for the incidence of local recurrence and distant metastases were 14% vs. 27% (HR, 1.95; 95% CI, 0.78-4.86) and 38% vs. 68% (HR, 2.05; 95% CI, 1.21-3.48). CONCLUSION: N-positive disease after chemoradiotherapy indicates radiochemoresistance. N-positive disease after 5 x 5 Gy RT includes both radiosensitive and radioresistant tumors, because the interval between radiotherapy and surgery was too short for radiosensitive cancer to undergo necrosis. Thus, the greater risk of distant metastases recorded in the chemoradiotherapy arm suggests that radiochemoresistance of nodal metastases from rectal cancer is associated with a high potential for developing distant metastases.

Adult↗

PubMed2001

First-order statistics of human stabilogram.

We investigated the statistical properties of the centre of pressure (COP) vector during quiet standing, as measured on a force platform. To derive a statistical model for the data, the COP vector, locally averaged COP, and deviations from the average COP were analysed. Whereas indefinite multimodal distributions for the components of the COP were observed, the density functions of deviation from the averaged COP had reproducible properties. The anterior-posterior and mediolateral components of the deviations had in common that they were correlated variables with a non-circular statistic. The main axes of the equiprobability density curves were rotated with respect to the natural anterior-posterior and mediolateral directions. By means of more detailed statistical analysis of the data, two distinct populations of subjects were identified. In some cases we have found Gaussian distributions of the components of deviation from the average COP. In most cases the statistics was non-Gaussian. The average contrast, a new dimensionless characteristic quantity, independent of platform calibration, was introduced as a useful indicator of non-Gaussian effects in the postural control system.

Humans↗

PubMed2006

All-fiber multimode-interference-based refractometer sensor: proposal and design.

A novel all-fiber refractometer sensor is proposed, which is based on multimode interference in the multimode fiber core section sandwiched between two single-mode fibers. A wide-angle beam propagation method in the cylindrical coordinate is employed as the modeling tool for simulation and design of the proposed refractometer sensor. The design for a refractometer is presented that shows that the refractometer would have an estimated resolution of 5.4 x 10(-5) for refractive indices from 1.33 to 1.45 and of 3.3 x 10(-5) for refractive indices from 1.38 to 1.45 through the choice of an appropriate length of the multimode fiber core section.

Journal Article↗

PubMed2006

An object simulation model for modeling hypothetical disease epidemics - EpiFlex.

BACKGROUND: EpiFlex is a flexible, easy to use computer model for a single computer, intended to be operated by one user who need not be an expert. Its purpose is to study in-silico the epidemic behavior of a wide variety of diseases, both known and theoretical, by simulating their spread at the level of individuals contracting and infecting others. To understand the system fully, this paper must be read together in conjunction with study of the software and its results. EpiFlex is evaluated using results from modeling influenza A epidemics and comparing them with a variety of field data sources and other types of modeling. EpiFlex is an object-oriented Monte Carlo system, allocating entities to correspond to individuals, disease vectors, diseases, and the locations that hosts may inhabit. EpiFlex defines eight different contact types available for a disease. Contacts occur inside locations within the model. Populations are composed of demographic groups, each of which has a cycle of movement between locations. Within locations, superspreading is defined by skewing of contact distributions. RESULTS: EpiFlex indicates three phenomena of interest for public health: (1) R0 is variable, and the smaller the population, the larger the infected fraction within that population will be; (2) significant compression/synchronization between cities by a factor of roughly 2 occurs between the early incubation phase of a multi-city epidemic and the major manifestation phase; (3) if better true morbidity data were available, more asymptomatic hosts would be seen to spread disease than we currently believe is the case for influenza. These results suggest that field research to study such phenomena, while expensive, should be worthwhile. CONCLUSION: Since EpiFlex shows all stages of disease progression, detailed insight into the progress of epidemics is possible. EpiFlex shows the characteristic multimodality and apparently random variation characteristic of real world data, but does so as an emergent property of a carefully constructed model of disease dynamics and is not simply a stochastic system. EpiFlex can provide a better understanding of infectious diseases and strategies for response.

Computer Simulation↗

PubMed2002

Intervention research, theoretical mechanisms, and causal processes related to externalizing behavior patterns.

Intervention research with children and adolescents has suffered from a dearth of relevant theoretical grounding and from the lack of a reciprocal "feedback" mechanism by which clinical trials can inform relevant theorizing and conceptualization. There are hopeful signs, however, of increasing confluence between clinical efforts and theoretical models. Indeed, the key issue I discuss is how intervention studies can yield information about developmental and clinical theory as well as mechanisms related to psychopathology. Specific research examples in the field, particularly those emanating from the Multimodal Treatment Study of Children with attention deficit/hyperactivity disorder (MTA study), reveal that probes of moderator and mediator variables can clearly enhance our knowledge of relevant processes and mechanisms. In fact, recent MTA findings have relevance for models of genetic and epigenetic influence on symptomatology related to attentional deficits and hyperactivity. It would be overzealous, however, to make premature claims regarding etiologic variables from intervention research, as treatment studies typically address variables that are causally far "downstream" from primary causal factors and most clinical trials have statistical power that is barely sufficient for main outcome questions, much less mediational linkages. Overall, the field has severely underutilized experimental intervention research to subserve the dual ends of improving the lives of youth and advancing theoretical conceptualization regarding development and psychopathology.

Adolescent↗

PubMed2004

Experimental human pain models: a review of standardised methods for preclinical testing of analgesics.

Treatment of pain is one of the major challenges in clinical medicine. However, it is often difficult to evaluate the effect of a treatment, as the many symptoms of the underlying diseases often confound this assessment. Furthermore, as the pain mechanisms in many diseases are poorly understood, the limited successful trial and error approach is most often used in the selection of analgesics. Hence, there is a need for new methods in the characterization and treatment of pain. Human experimental pain models offer the possibility to explore the pain system under controlled settings. The models can also be used to screen the analgesic profiles of drugs targeted to treat pain. This review gives a brief introduction to the methods used to evoke and assess pain in the skin, muscle and viscera. New methods using multimodal stimulation and activation of central pain mechanisms can to a higher degree mimic the clinical situation, and such methods are recommended in the future screening of analgesics. Examples of the use of experimental pain models in the testing of analgesics are given. With these models the therapeutic spectrum may be defined from a differentiated knowledge on the effect of drugs on the pain system. Such information may be used in the future guidelines for trials and clinical use of analgesics.

Analgesics↗

PubMedDate not supplied

Heart, body, and soul: impact of church-based smoking cessation interventions on readiness to quit.

BACKGROUND: Given the relatively low spontaneous quit rates and poor treatment outcomes among African American smokers, this study was designed to evaluate the effects of a multimodal culturally relevant intervention for smoking behavior change compared with a self-help strategy among urban African Americans in Baltimore churches. METHOD: This randomized controlled trial in urban African American churches used the stages of change model to compare the effectiveness of two interventions in moving smokers along a continuum toward smoking cessation. Twenty-two churches were randomly assigned to either an intensive culturally specific intervention or a minimal self-help intervention. Smokers were interviewed at baseline church health fairs and at a 1-year follow-up. Self-reported quitters at follow-up were evaluated using saliva cotinine and exhaled carbon monoxide levels (CO). Stages of change were measured by applying a standardized stages of change instrument to individual interview response sequences. Analysis compared the two intervention groups at 1-year follow-up with baseline stages. Outcomes included quit rates and positive progress along the stages of change. RESULTS: Multiple logistic regression results, controlling for intrachurch correlation and demographic and baseline smoking characteristics, showed that the multimodal cultural intervention group was more likely to make positive progress along the stages of change continuum, compared with self-help intervention group (OR = 1.68; P = 0.04). Church denomination and intervention status interacted in the multivariate model; Baptists in the intensive intervention were three times (OR = 3.23; P = 0.010) more likely to make progress than all the other denomination groups. CONCLUSION: The multimodal culturally relevant intervention was more likely than a self-help intervention to positively influence smoking behavior. This is the first community-based intervention study to report progress along the stages of change as a process-oriented measure of success. It is notable that a spiritually based model focusing on environmental sanctions was more likely than a standard church disseminated self-help intervention to positively influence smoking behavior in an urban African American population.

Adult↗

PubMed2000

Molecular markers predictive of response and prognosis in the patient with advanced squamous cell carcinoma of the head and neck: evolution of a model beyond TNM staging.

Advanced head and neck cancer is a disease with poor prognosis. TNM staging is an inadequate prognostic indicator of individual response to evolving multimodal therapies. New markers have been studied in progressively more refined analyses. Even though their role in predicting response and prognosis of head and neck cancer is still under evolution, it is becoming clear that individual markers are inadequate in constructing a prognostically meaningful tumor profile for each patient. Rather the combined study of a number of well-characterized markers acting in unrelated cellular pathways may be much more successful in defining prognostic patient categories of greater utility than traditional TNM staging. Special attention should also be paid to the expression pattern and location of tumor markers within the biopsy specimen as these parameters also appear to influence prognostic significance.

Biomarkers, Tumor↗

PubMed2002

From view cells and place cells to cognitive map learning: processing stages of the hippocampal system.

The goal of this paper is to propose a model of the hippocampal system that reconciles the presence of neurons that look like "place cells" with the implication of the hippocampus (Hs) in other cognitive tasks (e.g., complex conditioning acquisition and memory tasks). In the proposed model, "place cells" or "view cells" are learned in the perirhinal and entorhinal cortex. The role of the Hs is not fundamentally dedicated to navigation or map building, the Hs is used to learn, store, and predict transitions between multimodal states. This transition prediction mechanism could be important for novelty detection but, above all, it is crucial to merge planning and sensory-motor functions in a single and coherent system. A neural architecture embedding this model has been successfully tested on an autonomous robot, during navigation and planning in an open environment.

Animals↗

PubMed2007

Three-dimensional investigation and scoring of extracellular matrix remodeling during lung fibrosis using multiphoton microscopy.

The organization of collagen during fibrotic processes is poorly characterized because of the lack of appropriate methodologies. Here we show that multimodal multiphoton microscopy provides novel insights into lung fibrosis. We characterize normal and fibrotic pulmonary tissue in the bleomycin model, and show that second-harmonic generation by fibrillar collagen reveals the micrometer-scale three-dimensional spatial distribution of the fibrosis. We find that combined two-photon excited fluorescence and second-harmonic imaging of unstained lung tissue allows separating the inflammatory and fibrotic steps in this pathology, underlining characteristic features of fibroblastic foci in human Idiopathic Pulmonary Fibrosis samples. Finally, we propose phenomenological scores of lung fibrosis and we show that they unambiguously sort out control and treated mice, with a better sensitivity and reproducibility in the subpleural region. These results should be readily generalized to other organs, as an accurate method to assess extracellular matrix remodeling during fibrosis.

Animals↗

PubMed2006

LONI visualization environment.

Over the past decade, the use of informatics to solve complex neuroscientific problems has increased dramatically. Many of these research endeavors involve examining large amounts of imaging, behavioral, genetic, neurobiological, and neuropsychiatric data. Superimposing, processing, visualizing, or interpreting such a complex cohort of datasets frequently becomes a challenge. We developed a new software environment that allows investigators to integrate multimodal imaging data, hierarchical brain ontology systems, on-line genetic and phylogenic databases, and 3D virtual data reconstruction models. The Laboratory of Neuro Imaging visualization environment (LONI Viz) consists of the following components: a sectional viewer for imaging data, an interactive 3D display for surface and volume rendering of imaging data, a brain ontology viewer, and an external database query system. The synchronization of all components according to stereotaxic coordinates, region name, hierarchical ontology, and genetic labels is achieved via a comprehensive BrainMapper functionality, which directly maps between position, structure name, database, and functional connectivity information. This environment is freely available, portable, and extensible, and may prove very useful for neurobiologists, neurogenetisists, brain mappers, and for other clinical, pedagogical, and research endeavors.

Brain Mapping↗

PubMed2002

Neuroprotection and neurodegenerative disease.

This paper will focus on commonalities in the aetiology and pathology in five areas of neurological disease with illustrative examples of therapy. Possibilities of multimodal and neuroprotective therapies in human disease, employing currently available drugs and showing evidence of neuroprotective potential in animal models, are discussed. By definition, neuroprotection is an effect that may result in salvage, recovery or regeneration of the nervous system, its cells, structure and function. It is thought that there are many neurochemical modulators of nervous system damage. In epilepsy, excessive glutamate-mediated neurotransmission, impaired voltage sensitive sodium and calcium channel functioning, impaired GABA-mediated inhibition and alterations in acid base balance, when set in motion, may trigger a cascade of events leading to neuronal damage and cell death. Acute and chronic nervous system damage in response to an insult may lead to acute or delayed neuronal death, apoptotic cell death, neuronal degeneration, injury and loss, and gliosis. Cell death in the CNS following injury can occur in the manner of apoptosis, necrosis or hybrid forms. In general, NMDA receptor and non-NMDA receptor mediated excitotoxic injury results in neurodegeneration along an apoptosis-necrosis continuum. The effects of neuronal injury depend on factors including the degree of brain maturity or site of the lesion. There is some evidence supporting the hypothesis that neuroprotection may be a practical and achievable target using drugs already available, at present employed only for limited indications. Using these drugs early in the disease, may save decades of development of new drugs, which would require evaluation in animal studies, and human clinical trials. New drugs would also need to be shown to be safe and acceptable, physiologically not detrimental to humans and free from idiosyncratic adverse effects.

Alzheimer Disease↗

PubMed1999

Concertina effect and facial aging: nonlinear aspects of youthfulness and skeletal remodeling, and why, perhaps, infants have jowls.

The effect of aging on the orbitomaxillary region is evaluated in the present study. The observation was made that infants look like aged individuals in terms of the midface soft-tissue contours of the midface. Because preliminary work has shown that the facial skeleton remodels throughout life, this observation led to the hypothesis that infants and older individuals appear similar because they have comparable skeletal dimensions, specifically in the orbitomaxillary region. The design is a retrospective analysis of three-dimensional computed tomographic scan data. Three groups of male subjects were studied: infant, ages 1 to 12 months (n = 5); youthful, ages 15 to 24 years (n = 13); and old, ages 53 to 76 years (n = 12). Orbital and zygomaticomaxillary vertical dimensions were measured in both medial and lateral planes between fixed anatomical landmarks. Results were compared by using analysis of variance, Student-Newman-Keuls, and Student's t tests. The findings show that skeletal remodeling is such that the ratio of the maxillary height to orbital height is greatest during youth; during infancy and old age, there is a short maxilla relative to a larger orbit. This finding is significant in the medial plane from orbital rim to pyriform aperture (p < 0.05). Furthermore, there is an actual decrease in vertical maxillary height in this medial plane (p < 0.01) from youth until old age, which occurs secondary to normal skeletal remodeling in the dentate individual. The combined effect of downward expansion of the orbital shelf and the upward migration of the pyriform effectively decreases the space available to support the overlying soft tissues of the midface. An accordion-like or "concertina" effect may lead to compression or restriction of the facial soft tissues over a relatively deficient bony platform. These results highlight the importance of skeletal remodeling in determining the soft-tissue contours of the aging face. The process of skeletal remodeling may also allow for a tentative definition of facial youthfulness. Infants are born with a short maxilla relative to a large orbit, and the maxillary wall is angled posteriorly. This ratio and angle change from infancy until youth, when there is a balance between the bony skeletal support and the overlying soft-tissue envelope, i.e., the skin, facial muscles, and adipose tissue. It is when skeletal remodeling continues past this point that a disharmony occurs. Because the ratio of maxilla/orbit, and the angle of the maxillary wall, in the older person reverts toward that of an infant, the attainment of youth occurs partly in a nonlinear or multimodal manner. This work is part of an emerging concept of facial aging, which we would term an integrated model of facial aging. This model allows facial aging to be viewed as a biological "system," in which there are primary and secondary factors that interact in the process of facial aging. Additional research such as this continues to suggest the importance of bony remodeling in facial aging.

Adolescent↗

PubMed2003

Comparisons of three alternative breast modalities in a common phantom imaging experiment.

Four model-based imaging systems are currently being developed for breast cancer detection at Dartmouth College. A potential advantage of multimodality imaging is the prospect of combining information collected from each system to provide a more complete diagnostic tool that covers the full range of the patient and pathology spectra. In this paper it is shown through common phantom experiments on three of these imaging systems that it was possible to correlate different types of image information to potentially improve the reliability of tumor detection. Imaging experiments were conducted with common phantoms which mimic both dielectric and optical properties of the human breast. Cross modality comparison was investigated through a statistical study based on the repeated data sets of reconstructed parameters for each modality. The system standard error between all methods was generally less than 10% and the correlation coefficient across modalities ranged from 0.68 to 0.91. Future work includes the minimization of bias (artifacts) on the periphery of electrical impedance spectroscopy images to improve cross modality correlation and implementation of the multimodality diagnosis for breast cancer detection.

Breast Neoplasms↗

PubMed1994

Developmental formulation and psychotherapy of borderline adolescents.

Treatment of the borderline adolescent requires a highly sophisticated, multimodal treatment formulation that is based on a developmental, psychodynamic formulation of the patient and family system. The therapeutic model chosen must fit the case as well as possible, but, of necessity, may change as the patient grows and develops. It is of utmost importance to understand the patient's process of growth and development and the utilization of each particular model of psychotherapy chosen. Therapeutic techniques should derive from the model(s) of treatment and should constantly be analyzed during the course of psychotherapy with these very difficult patients. The case example illustrates the treatment of a borderline personality patient who, in Goldstein and Jones's model, initially was in Group IV, the withdrawn and socially isolated group, but as therapy developed, fell into Group II in her defiance, disrespectful stance toward her mother, belligerance, and antagonism both in the family and in therapy. She progressively was able to relinquish her defensive stance of denial, projection, and splitting, and became more aware of her affect. As she progressed in therapy, her mood shifted from states of anger to states of depression and self-consciousness and her treatment was facilitated by use of pharmacotherapeutic agents and a very close-knit outpatient team. It is important to emphasize the value of a close-knit working outpatient team in the psychotherapy.

Adolescent↗