Spray, Embracing Multimodality

We present Spray, a localization system that compensates for low accuracy of individual localization measurements by combining measurements from multiple localization modalities

Multiple solutions to the likelihood equations in the Behrens-Fisher problem

The Behrens-Fisher problem concerns testing the equality of the means of two normal populations with possibly different variances. The null hypothesis in this problem induces a statistical model for which the likelihood function may have more than one local maximum. We show that such multimodality contradicts the null hypothesis in the sense that if this hypothesis is true then the probability of multimodality converges to zero when both sample sizes tend to infinity. Additional results include a finite-sample bound on the probability of multimodality under the null and asymptotics for the probability of multimodality under the alternative

Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells

Colorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. © 2013 Song et al

Individualized Multilayer Tensor Learning with An Application in Imaging Analysis

This work is motivated by multimodality breast cancer imaging data, which is quite challenging in that the signals of discrete tumor-associated microvesicles (TMVs) are randomly distributed with heterogeneous patterns. This imposes a significant challenge for conventional imaging regression and dimension reduction models assuming a homogeneous feature structure. We develop an innovative multilayer tensor learning method to incorporate heterogeneity to a higher-order tensor decomposition and predict disease status effectively through utilizing subject-wise imaging features and multimodality information. Specifically, we construct a multilayer decomposition which leverages an individualized imaging layer in addition to a modality-specific tensor structure. One major advantage of our approach is that we are able to efficiently capture the heterogeneous spatial features of signals that are not characterized by a population structure as well as integrating multimodality information simultaneously. To achieve scalable computing, we develop a new bi-level block improvement algorithm. In theory, we investigate both the algorithm convergence property, tensor signal recovery error bound and asymptotic consistency for prediction model estimation. We also apply the proposed method for simulated and human breast cancer imaging data. Numerical results demonstrate that the proposed method outperforms other existing competing methods

Experiments and a model for pilot dynamics with visual and motion inputs

Multimodality pilot model for visual and motion feedbacks derived from simulator progra

Multimodality imaging in vivo for preclinical assessment of tumor-targeted doxorubicin nanoparticles.

This study presents a new multimodal imaging approach that includes high-frequency ultrasound, fluorescence intensity, confocal, and spectral imaging to improve the preclinical evaluation of new therapeutics in vivo. Here we use this approach to assess in vivo the therapeutic efficacy of the novel chemotherapy construct, HerDox during and after treatment. HerDox is comprised of doxorubicin non-covalently assembled in a viral-like particle targeted to HER2+ tumor cells, causing tumor cell death at over 10-fold lower dose compared to the untargeted drug, while sparing the heart. Whereas our initial proof-of-principle studies on HerDox used tumor growth/shrinkage rates as a measure of therapeutic efficacy, here we show that multimodal imaging deployed during and after treatment can supplement traditional modes of tumor monitoring to further characterize the particle in tissues of treated mice. Specifically, we show here that tumor cell apoptosis elicited by HerDox can be monitored in vivo during treatment using high frequency ultrasound imaging, while in situ confocal imaging of excised tumors shows that HerDox indeed penetrated tumor tissue and can be detected at the subcellular level, including in the nucleus, via Dox fluorescence. In addition, ratiometric spectral imaging of the same tumor tissue enables quantitative discrimination of HerDox fluorescence from autofluorescence in situ. In contrast to standard approaches of preclinical assessment, this new method provides multiple/complementary information that may shorten the time required for initial evaluation of in vivo efficacy, thus potentially reducing the time and cost for translating new drug molecules into the clinic

Intraoperative Neurophysiological Monitoring for Endoscopic Endonasal Approaches to the Skull Base: A Technical Guide.

Intraoperative neurophysiological monitoring during endoscopic, endonasal approaches to the skull base is both feasible and safe. Numerous reports have recently emerged from the literature evaluating the efficacy of different neuromonitoring tests during endonasal procedures, making them relatively well-studied. The authors report on a comprehensive, multimodality approach to monitoring the functional integrity of at risk nervous system structures, including the cerebral cortex, brainstem, cranial nerves, corticospinal tract, corticobulbar tract, and the thalamocortical somatosensory system during endonasal surgery of the skull base. The modalities employed include electroencephalography, somatosensory evoked potentials, free-running and electrically triggered electromyography, transcranial electric motor evoked potentials, and auditory evoked potentials. Methodological considerations as well as benefits and limitations are discussed. The authors argue that, while individual modalities have their limitations, multimodality neuromonitoring provides a real-time, comprehensive assessment of nervous system function and allows for safer, more aggressive management of skull base tumors via the endonasal route

Multimodality Treatment for Early-Stage Hepatocellular Carcinoma: A Bridging Therapy for Liver Transplantation

Purpose: To evaluate the efficiency of a multimodality approach consisting of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) as bridging therapy for patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT) and to evaluate the histopathological response in explant specimens. Materials and Methods: Between April 2001 and November 2011, 36 patients with 50 HCC nodules (1.4-5.0 cm, median 2.8 cm) on the waiting list for liver transplantation were treated by TACE and RFA. The drop-out rate during the follow-up period was recorded. The local efficacy was evaluated by histopathological examination of the explanted livers. Results: During a median follow-up time of 29 (4.0-95.3) months the cumulative drop-out rate for the patients on the waiting list was 0, 2.8, 5.5, 11.0, 13.9 and 16.7% at 3, 6, 12, 24, 36 and 48 months, respectively. 16 patients (with 26 HCC lesions) out of 36(44.4%) were transplanted by the end of study with a median waiting list time of 13.7 (2.5-37.8) months. The histopathological examination of the explanted specimens revealed a complete necrosis in 20 of 26 HCCs (76.9%), whereas 6 (23.1%) nodules showed viable residual tumor tissue. All transplanted patients are alive at a median time of 29.9 months. Imaging correlation showed 100% specificity and 66.7% sensitivity for the depiction of residual or recurrent tumor. Conclusion: We conclude that TACE.combined with RFA could provide an effective treatment to decrease the drop-out rate from the OLT waiting list for HCC patients. Furthermore, this combination therapy results in high rates of complete tumor necrosis as evaluated in the histopathological analysis of the explanted livers. Further randomized trials are needed to demonstrate if there is a benefit in comparison with a single-treatment approach. copyright (C) 2012 S. Karger AG, Base