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Ensembling local learners through multimodal perturbation.

Ensemble learning algorithms train multiple component learners and then combine their predictions. In order to generate a strong ensemble, the component learners should be with high accuracy as well as high diversity. A popularly used scheme in generating accurate but diverse component learners is to perturb the training data with resampling methods, such as the bootstrap sampling used in bagging. However, such a scheme is not very effective on local learners such as nearest-neighbor classifiers because a slight change in training data can hardly result in local learners with big differences. In this paper, a new ensemble algorithm named Filtered Attribute Subspace based Bagging with Injected Randomness (FASBIR) is proposed for building ensembles of local learners, which utilizes multimodal perturbation to help generate accurate but diverse component learners. In detail, FASBIR employs the perturbation on the training data with bootstrap sampling, the perturbation on the input attributes with attribute filtering and attribute subspace selection, and the perturbation on the learning parameters with randomly configured distance metrics. A large empirical study shows that FASBIR is effective in building ensembles of nearest-neighbor classifiers, whose performance is better than that of many other ensemble algorithms.

Algorithms↗

ProFeel: low cost visual-haptic perceptualization of protein structure-structure alignments.

We describe ProFeel, an application for exploring molecular data from protein structure-structure alignments using a force-feedback joystick. Protein structure analysis is a useful application for multimodal information perceptualization because researchers in this area typically use several independent measures in assessment. A system that allows the user to simultaneously evaluate different criteria would therefore be quite useful. Four variables are assigned three different haptic effects each to allow the user to discern twelve separate data values. The haptic representation is coupled with a traditional molecular graphics visual display.

Computer Graphics↗

Survival of patients with localized high-grade soft tissue sarcoma with multimodality therapy. A matched control study.

Ten of 16 consecutive patients (63%) with Stages III-IVA soft tissue sarcoma presenting between 1975 and 1978 and treated with surgery, radiotherapy and adjuvant chemotherapy have remained disease-free with a median follow-up of three years (range, 28-68 months). Survival at three years was 86%. However, in the American Joint Committee (AJC) soft tissue sarcoma staging system published in 1977, Grade 3 soft tissue sarcomas were associated with a three-year survival of 35% and almost 90% of the patients destined to fail did so within three years of diagnosis (8). To determine if the observed improvement in survival resulted merely from lesions with favorable prognostic determinants at diagnosis, study patients were matched for stage, histologic type and location of the primary lesion with controls generated from these 1215 carefully reviewed sarcoma patients collected from the data base of the Task Force on Soft Tissue Sarcomas of the AJC. Only control cases whose histology had been reviewed and who had been treated with surgery (with or without radiotherapy) were included in the analysis. Cases survived significantly longer than controls at three years (p less than 0.001) and, in fact, disease-free survival of cases (63%) was superior to overall survival of controls (27%) (p less than 0.01). Our data support the conclusion that patients with high-grade soft tissue sarcoma treated by an experienced multimodality team have a three-year disease-free survival of approximately 63%. The impact of each component of multimodality therapy cannot be determined, and improved survival may result, in addition, from improved diagnostic and staging techniques currently available.

Adult↗

Automatic coregistration, segmentation and classification for multimodal cytopathology.

The paper describes the key component of the Multimodal Cell Analysis approach, a novel cytologic evaluation method for early cancer detection. The approach is based on a repeated staining of a cell smear. The correlation of features and data extracted from different stainings, and related to relocated individual cells, will yield a dramatic increase of diagnostic reliability. The necessary fully automatic preprocessing steps are presented: coregistration of multimodal images, segmentation, and classification of cell nuclei. Both efficiency and robustness of all steps reached at the current stage of research, are high regarding medical image material, and strongly support clinical application.

Autoanalysis↗

19. Correlation between FDG PET data and EEG dipole modeling.

Purpose: FDG-PET images and EEG dipole modelling were used to localization of interictal epileptogenic foci. A multimodality approach with the analysis of FDG-PET images, EEG dipoles and anatomical images (MRI) were applied to patients with drug-resistant epilepsy.Methods: Source location was determined using Brain Electromagnetic Source Analysis (BESA) program. The dipole location provided by BESA was then transformed into PET co-ordinates using the patient's MRI previously registered with the PET image. As a difference with other methods, no external markers are necessary.Results: The study group includes ten drug-resistant epileptic patients. FDG hypometabolism was found in all patients. Abnormalities in glucose uptake were always ipsilateral to the EEG dipole. However, quantitative analysis of FDG-PET within hypometabolic areas showed no significant correlation between decrease glucose uptake and location of EEG-dipole source. The comparison of the results using both methods shows that the dipole location matches the FDG-PET hypometabolic area for all the patients. Combining the spatial localization on FDG-PET with the temporal accuracy of EEG dipole source aids in the exact localization of the epileptogenic focus.Conclusion: As a conclusion, the results show that projection of EEG dipole data onto FDG-PET may play a key role in the indication of surgery for the treatment of drug-resistant epileptic patients, provided it is simple and easy to perform.

Journal Article↗

Evidence for training-induced crossmodal reorganization of cortical functions in trumpet players.

The aim of this study was to compare multimodal information processing in the somatosensory and auditory cortices and related multimodal areas in musicians (trumpet players) and non-musicians. Magnetoencephalographic activity (MEG) was recorded in response to five stimulus conditions from 10 professional trumpet players and nine musically untrained control subjects. Somatosensory and auditory stimuli were presented alone or in combination. Our data suggest that musicians, in general, process multisensory stimuli differently to the control group. When stimulating the lip in professional trumpet players, a multimodal interaction (expressed as difference between the multimodal response and the sum of unimodal responses) in the corresponding somatosensory cortex showed a positive peak at 33 ms, which was not found in the control group. Conversely, the control group shows a significant interaction of opposite polarity around 60-80 ms. We suggest that training-induced reorganization in musicians leads to a qualitatively different way to process multisensory information. It favors an early stage of cortical processing, which is modified by the connections between multimodal and auditory neurons from thalamus to primary somatosensory area.

Acoustic Stimulation↗

Characterization of the combined cellular survival effects of benzoquinone-ansamycins and ionizing radiation.

PURPOSE: Benzoquinone-ansamycins were the first compounds characterized with the ability to inhibit the function of heat shock protein 90 and its related family members. We investigated the composite effect of ionizing radiation and of these novel substances on the survival of malignant cells. METHODS: PC-3M prostate carcinoma cells were treated in vitro with increasing radiation doses in the presence or absence of Hsp90-active and Hsp90-inactive benzoquinone-ansamycins. Cytotoxicity was determined by the crystal violet dissolution assay. RESULTS: Twenty-four hour treatment with increasing geldanamycin doses (10 nM-1 microM) reduced cellular survival by 1.5 logs for all drug dose levels. Concomitant irradiation with a single fraction of 3 Gy reduced cellular survival by 2 logs, independently of drug dose. The treatment with 100 nM geldanamycin for 24 h combined with ionizing radiation (1-5 Gy) during the first hour of drug exposure reduced cellular survival by 1.5-2 logs depending on radiation-energy dose level, while no changes in cell survival were detectable with equimolar geldampicin, a benzoquinone-ansamycin known not to inhibit Hsp90. CONCLUSIONS: The inhibition of Hsp90 and the concomitant exposure to ionizing radiation decrease cellular survival of malignant cells. These data contribute to laying the foundation for the translational use of Hsp90 inhibitors in the multimodal therapy of cancer.

Animals↗

1H NMR spin-spin relaxation and imaging in porous systems: an application to the morphological study of white portland cement during hydration in the presence of organics.

Proton nuclear magnetic resonance (NMR) spin-spin relaxation and imaging have been applied to investigate white Portland cement pastes during hydration in the absence and in the presence of organic solvents. The main organic solvent investigated was methanol, alone or together with the organic waste 2-chloroaniline (2-CA), an aromatic amine representative of an important class of highly toxic compounds. For all the analysed samples, prepared with a solvent-to-cement ratio of 0.4, the decay of the echo magnetization has been fitted by adopting a model that combines an exponential component with a gaussian one. The calculated independent relaxation parameters have been discussed in terms of morphological and dynamical changes that occur during the cement hardening process and pore formation. Three kinds of water molecules: "solid-like" (chemically and physically bound), "liquid-like" (porous trapped) and "free" water, endowed with anisotropic, near isotropic and isotropic motion, respectively, were identified. Spin-echo images collected on the same samples during the hydration kinetics, allowed the changes of water and solvents spatial distribution in the porous network to be monitored, showing percolation phenomena and confirming the multimodal open channels structure of the hardened cement system. Both T(2) relaxation and imaging data indicated that a pronounced delay occurs in the cement hardening when organics are present.

Construction Materials↗

[Robotics in neurosurgery: current status and future prospects].

Neurosurgery is in essence a field of application development for robots, based on multimodal image guidance. Specific motorized tools have already been developed and routinely applied in stereotaxy to position a probe holder or in conventional neurosurgery to hold a microscope oriented towards a given target. The potentialities of these approaches have triggered industrial developments which are now commercially available. These systems use databases, primarily coming from multimodal numerical images from X-ray radiology to magnetic resonance imaging. These spatially encoded data are transferred through digital networks to workstations where images can be processed and surgical procedures are pre-planned, then transferred to the robotic systems to which they are connected. We have been using a stereotaxic robot since 1989 and a microscope robot since 1995 in various surgical routine procedures. The future of these applications rely mainly on the technical progress in informatics, about image recognition to adapt the pre-planning to the actual surgical situation, to correct brain shifts (for instance), about image fusion, integrated knowledge such as brain atlases, as well as virtual reality. The future developments, covering surgical procedure, research and teaching, are sure to be far beyond our wildest expectations.

Forecasting↗

Signaling inhibition with radiation in colorectal cancer: clinical trials.

Ras has been shown to increase radiation resistance. Thus, upstream and downstream pathways from Ras could be targets for manipulation of radiosensitivity. Epidermal growth factor receptor (EGFR) expression and Akt phosphorylation are also associated with the response to radiation. A retrospective study evaluating EGFR and Akt in patients treated with multimodality therapy found a significant association between P-Akt and treatment failure. Moreover, these data are strengthened by in vitro studies showing that inhibition of EGFR, Ras, PI3K, and Akt radiosensitized cancer cell lines. We have previously shown that PI3K is a mediator of Ras-induced radiation resistance. We now suggest that EGFR, which is upstream of PI3K, may also mediate resistance through a common pathway. In addition to EGFR and Ras, PTEN can also regulate the PI3K pathway. Identifying a common signal for EGFR, Ras, or PTEN that results in radiation resistance may uncover targets for developing molecular-based radiosensitization protocols for tumors resistant to radiation and thus improve local control.

Alkyl and Aryl Transferases↗

The eigenspace separation transform for neural-network classifiers.

This paper presents a linear transform that compresses data in a manner designed to improve the performance of a neural network used as a binary classifier. The classifier is intended to accommodate data distributions that may be non-normal, may have equal class means, may be multimodal, and have unknown a priori probabilities for the two classes. The transform, which is called the eigenspace separation transform, allows the reduction of the size of a neural network while enhancing its generalization accuracy as a binary classifier.

Journal Article↗

The RAS signal transduction pathway and its role in radiation sensitivity.

RAS has been shown to increase radiation resistance. Upstream and downstream pathways from RAS could thus be targets for manipulation of radiosensitivity. EGFR expression and AKT phosphorylation are also associated with the response to radiation. A retrospective study evaluating EGFR and AKT in patients treated with multimodality therapy found a significant association between P-AKT and treatment failure. Moreover, these data are strengthened by in vitro studies showing that inhibition of EGFR, RAS, PI3K, and AKT radiosensitized cancer cell lines. We have previously shown that PI3K is a mediator of RAS-induced radiation resistance. We now suggest that EGFR, which is upstream of PI3K, may also mediate resistance through a common pathway. In addition to EGFR and RAS, PTEN can also regulate the PI3K pathway. Identifying a common signal for EGFR, RAS, or PTEN that results in radiation resistance may uncover targets for developing molecular-based radiosensitization protocols for tumors resistant to radiation and thus improve local control.

Animals↗

[Results of drug therapy with cisplatin and 5-fluorouracil in squamous cell carcinoma of the head and neck region].

30 patients with advanced squamous cell carcinoma of the head and neck received initial chemotherapy with Cisplatin (100 mg/m2 i.v. day 1) and 5-Fluorouracil (1000 mg/m2 as 24-hour-infusion day 2-6). 1 patient reached complete remission, 16 patients presented a partial remission, 11 patients showed little response and 2 patients had progressive disease. Following chemotherapy, 29 patients were referred to surgery and/or irradiation. 16 patients received radical surgery. The surgical specimen of 5 patients had no histological evidence of cancer. Objective and subjective side effects of chemotherapy were serious and some patients refused further treatment or were rejected. The results were compared with the data from the literature. The considerably better results from Decker and Weaver et al. were partially explained by an overestimation of remission quality by clinical evaluation and by more therapy courses. At this time, there is no evidence of any benefit from chemotherapy, because there is no data on relapse free survival and over all survival. The position of chemotherapy in the multimodality treatment programme of head and neck cancer still needs to be discussed further.

Adult↗

Chemotherapy in brain metastases.

The use OF chemotherapy to treat patients with brain metastases has been viewed historically with skepticism. To date, a survival benefit has not been demonstrated with the use of systemic chemotherapy in patients with brain metastases. However, the introduction of novel agents and delivery techniques warrants a reexamination of the role of systemic chemotherapy in the management of brain metastases. Temozolomide has shown encouraging results in patients with nonsmall cell lung cancer, and implanted carmustine wafers have demonstrated excellent local tumor control rates. This review discusses clinical data from the past decade with emphasis on trial design, tumor histology, available agents, and multimodality strategies. In addition, delivery techniques that circumvent the blood-brain barrier are reviewed. Although chemotherapy is usually used as a salvage therapy, it may be considered for use in selected patients with newly diagnosed brain metastases. To better evaluate chemotherapy in brain metastases, future trials should evaluate novel agents in the preirradiation setting. Enhanced regional delivery methods warrant further investigation, and Phase III trials of current regimens stratified by histology and by prognostic factors will establish the role of specific chemotherapy regimens in the treatment of patients with brain metastases.

Antineoplastic Agents↗

SPECT in the year 2000: basic principles.

OBJECTIVE: SPECT has become a routine procedure in most nuclear medicine departments. SPECT provides significant technical challenges for the nuclear medicine technologist, as compared with planar imaging, in the areas of SPECT acquisition, image reconstruction, and data processing. Many new advances in SPECT methodology are becoming available, such as iterative reconstruction, multimodality fusion, and advanced gated cardiac SPECT. SPECT imaging is demanding and requires careful attention to proper acquisition protocols, whether circular or noncircular orbits, and postprocessing is becoming more complex with the addition of iterative reconstruction and attenuation correction algorithms, among others. Understanding the principles of SPECT is essential not only to produce the highest quality scans but also to identify image artifacts. After reading this article, the nuclear medicine technologist should be able to: (a) describe the historical development and benefits of SPECT imaging; (b) state the impact of image matrix size, number of projections, and arc of rotation on final SPECT image quality; (c) discuss the trade-offs between image noise content and spatial and contrast resolution in SPECT reconstruction; (d) discuss SPECT filters and their impact on image quality; (e) explain the differences between filtered backprojection and iterative reconstruction; and (f) describe the impact of attenuation and scatter in SPECT imaging and the advantages and pitfalls of attenuation correction methods.

Humans↗

[Clinical and neurophysiological characteristics of motor cortical responsiveness during prolonged cranial osteoplasty].

The data of global and stimulation poly-EMG were used to estimate the outcomes of multimodality treatment of sequelae of brain injury and stroke, which was based on the vasoactive effects of prolonged cranial osteoplasty. Thirteen patients (7 males and 6 females) aged 19 to 64 (mean 42 +/- 4) years who had signs of left- (n = 2) and right-sided (n = 11) spastic hemiparesis. Global and stimulation poly-EMG, which involved recording and analysis of resting and total EMG under the maximum voluntary tension, M-waves H-reflexes, transcranially evoked potentials. The muscles of the shoulder, forearm, hand, femur, leg, and foot were studied. The surgical procedure developed at the Russian Research Center "VTO" for stimulation of cerebral blood flow in combination with conventional conservative treatments (physiotherapy, therapeutical exercises, and adequate drug therapy) was shown to increase the transmission coefficient of an efferent signal in the motor cortex-spinal motor neurons-muscle system, which is clinically accompanied by improved coordination of simple and complex movements realized with the participation of the muscles of both the paretic and contralateral extremity. The ambiguous effects of the vasoactive factors of prolonged osteoplasty on the functions of unequally modal pathologically changed cerebral motor structures were noted. The findings may be considered as evidence for the low traumatic ability of the VTO's techniques for replacing posttraumatic defects of skull vault bones.

Adult↗

[Clinico-psychological analysis of the complaints of patients with neurotic and neurosis-like conditions (based on material from a general-somatic hospital)].

To study the patient's insight into the disease, the authors have reviewed the results of the follow-up of 366 patients with such somatic illnesses as coronary heart disease, essential hypertension, gastric and duodenal ulcers, chronic non-specific colitis, bronchial asthma, and chronic pneumonia. Four types of complaints have been identified, including (1) concrete-sensitive; (2) affective; (3) conceptualizing; and (4) evaluative-esthetising. These complaints were established to depend on the development of the psychological defense mechanisms. The data obtained are necessary not only for solving the questions of the differential diagnosis and multimodality therapy but also complying with the principles of medical deontology in the work of the physician of a general somatic hospital, encountering borderline psychopathologic disturbances.

Adult↗

Induction chemotherapy for advanced head and neck cancer: modification of response to chemotherapy by antiemetics.

Forty Stage IV head and neck cancer patients were entered on a multimodality trial of induction chemotherapy (cisplatin + infusional 5-fluorouracil), surgery, and radiation. During chemotherapy, the patients of Group A (the first 19 patients) were medicated with metoclopramide. The patients of Group B (the next 21 patients) were medicated with droperidol. The groups were comparable. The response rate (complete + partial) was 32% for Group A and 52% for Group B (p = 0.16). Primary site (p = 0.08) and surgical margin (p = 0.005) clearance of tumor were better in Group B. Nodal disease responded poorly to chemotherapy in both groups. Tumor necrosis (p = 0.006) and granulation tissue (p = 0.07) were reduced in surgical specimens after chemotherapy in Group B. The drugs were well tolerated with reversible toxicity; nausea/vomiting (p = 0.01) and weight loss (p = 0.07) after chemotherapy, were increased in Group B. The 2-year survival was 26% for Group A and 62% for Group B (p = 0.027). The median survival was 15 months for Group A and 33 months for Group B (p = 0.05). Progression-free survival improved in Group B (p greater than 0.17). These improvements in response and survival did not appear to reflect changes in surgical or radiotherapy management, but may have reflected an uninhibited effect of cisplatin in Group B. It is theorized that the metabisulfite formulated with metoclopramide altered the pharmacokinetics or pharmacodynamics of cisplatin. This resulted in the poor response to chemotherapy and poor survival in Group A. An analysis of a randomized trial comparing metoclopramide (formulated with metabisulfite) versus a control antiemetic can confirm the data presented in this pilot study. Overall, our patients survived as well as others in comparable multimodality studies in Europe and the United States.

Adult↗