221 research outputs found
Emerging Pharmacotherapy for Relapsed or Refractory Hodgkin’s Lymphoma: Focus on Brentuximab Vedotin
Hodgkins’ lymphoma (HL) which has relapsed post or is refractory to autologous bone marrow transplant presents an ongoing treatment challenge. Development of monoclonal antibodies (mAb) for the treatment of HL has aimed to replicate the success of mAb therapy in the treatment on Non Hodgkins Lymphoma. The identification of CD30 as a potential target for treatment has led to the development of a new antibody-drug conjugate, brentuximab vedotin (SGN-35), which conjugates monomethyl auristatin E to an anti-CD30 antibody to deliver targeted toxicity to the malignant Reed Sternberg cells of HL. This review describes CD30 as an antibody target, and focuses on the antibody-drug conjugate brentuximab vedotin, including current knowledge of the mechanism of action, preclinical, clinical and pharmacokinetic data available for Brentuximab Vedotin
Particle Acceleration in Pulsar Wind Nebulae: PIC modelling
We discuss the role of particle-in-cell (PIC) simulations in unveiling the
origin of the emitting particles in PWNe. After describing the basics of the
PIC technique, we summarize its implications for the quiescent and the flaring
emission of the Crab Nebula, as a prototype of PWNe. A consensus seems to be
emerging that, in addition to the standard scenario of particle acceleration
via the Fermi process at the termination shock of the pulsar wind, magnetic
reconnection in the wind, at the termination shock and in the Nebula plays a
major role in powering the multi-wavelength signatures of PWNe.Comment: 32 pages, 16 figures, to appear in the book "Modelling Nebulae"
edited by D. Torres for Springer, based on the invited contributions to the
workshop held in Sant Cugat (Barcelona), June 14-17, 201
Iterative algorithms for total variation-like reconstructions in seismic tomography
A qualitative comparison of total variation like penalties (total variation,
Huber variant of total variation, total generalized variation, ...) is made in
the context of global seismic tomography. Both penalized and constrained
formulations of seismic recovery problems are treated. A number of simple
iterative recovery algorithms applicable to these problems are described. The
convergence speed of these algorithms is compared numerically in this setting.
For the constrained formulation a new algorithm is proposed and its convergence
is proven.Comment: 28 pages, 8 figures. Corrected sign errors in formula (25
Recent Advances in Understanding Particle Acceleration Processes in Solar Flares
We review basic theoretical concepts in particle acceleration, with
particular emphasis on processes likely to occur in regions of magnetic
reconnection. Several new developments are discussed, including detailed
studies of reconnection in three-dimensional magnetic field configurations
(e.g., current sheets, collapsing traps, separatrix regions) and stochastic
acceleration in a turbulent environment. Fluid, test-particle, and
particle-in-cell approaches are used and results compared. While these studies
show considerable promise in accounting for the various observational
manifestations of solar flares, they are limited by a number of factors, mostly
relating to available computational power. Not the least of these issues is the
need to explicitly incorporate the electrodynamic feedback of the accelerated
particles themselves on the environment in which they are accelerated. A brief
prognosis for future advancement is offered.Comment: This is a chapter in a monograph on the physics of solar flares,
inspired by RHESSI observations. The individual articles are to appear in
Space Science Reviews (2011
Dinâmica do uso e cobertura da terra no sudeste de Roraima utilizando técnicas de detecção de mudanças
Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)/Magnetic Resonance Imaging (MRI) for Staging of Muscle-invasive Bladder Cancer (MIBC)
Introduction: Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [18F] Fluorodeoxyglucose positron emission tomography (FDG-PET)/magnetic resonance imaging (MRI) is a novel imaging modality incorporating functional imaging with improved soft tissue characterization. This pilot study evaluated the use of preoperative FDG-PET/MRI for staging of MIBC. Patients and Methods: Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of radiologists reviewed FDG-PET/MRI scans to determine: (1) presence of primary bladder tumor; and (2) lymph node involvement and distant metastases. FDG-PET/MRI was compared with cystectomy pathology and computed tomography (CT). Results: Eighteen patients were included in the final analysis, most (72.2%) of whom received neoadjuvant chemotherapy. Final pathology revealed 10 (56%) patients with muscle invasion and only 3 (17%) patients with lymph node involvement. Clustered analysis of FDG-PET/MRI radiology team reads revealed a sensitivity of 0.80 and a specificity of 0.56 for detection of the primary tumor with a sensitivity of 0 and a specificity of 1.00 for detection of lymph node involvement when compared with cystectomy pathology. CT imaging demonstrated similar rates in evaluation of the primary tumor (sensitivity, 0.91; specificity, 0.43) and lymph node involvement (sensitivity, 0; specificity, 0.93) when compared with pathology. Conclusions: This pilot single-institution experience of FDG-PET/MRI for preoperative staging of MIBC performed similar to CT for the detection of the primary tumor; however, the determination of lymph node status was limited by few patients with true pathologic lymph node involvement. Further studies are needed to evaluate the potential role for FDG-PET/MRI in the staging of MIBC. © 2020 Elsevier Inc.In this pilot study, preoperative staging with [18F] fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging in muscle-invasive bladder cancer detected the primary bladder tumor; however, the determination of lymph node status was limited by few patients with pathologic lymph node involvement. Additional studies are needed to evaluate the potential role for [18F] fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging in the staging of bladder cancer
Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites
Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited Îł-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels
MAIT cells are imprinted by the microbiota in early life and promote tissue repair
How early-life colonization and subsequent exposure to the microbiota affect long-term tissue immunity remains poorly understood. Here, we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens. In adults, cutaneous MAIT cells are a dominant population of interleukin-17A (IL-17A)-producing lymphocytes, which display a distinct transcriptional signature and can subsequently respond to skin commensals in an IL-1-, IL-18-, and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells, which sequentially controls both tissue-imprinting and subsequent responses to injury
Systematic compositional changes and their influence on lattice and optoelectronic properties of Cu2ZnSnSe4 kesterite solar cells
The transient analysis of a conducting crack in magneto-electro-elastic half-space under anti-plane mechanical and in-plane electric and magnetic impacts
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