368 research outputs found
Correlation of High-Resolution X-Ray Micro-Computed Tomography with Bioluminescence Imaging of Multiple Myeloma Growth in a Xenograft Mouse Model
Multiple myeloma (MM) is an incurable B-cell neoplasia in which progressive skeletal lesions are a characteristic feature. Earlier we established an animal model for human MM in the immune-deficient RAG2-/-γc-/- mouse, in which the growth of luciferase-transduced MM cells was visualized using noninvasive bioluminescence imaging (BLI). This model appeared well suited to study disease progression and response to therapy by identifying the location of various foci of MM tumor growth scattered throughout the skeleton and at subsequent time points the quantitative assessment of the tumor load by using BLI. We report here on the corresponding high-resolution X-ray micro-computed tomographic (micro-CT) analysis to study skeletal defects in the mice with full-blown MM. Several anatomical derangements were observed, including abnormalities in geometry and morphology, asymmetrical bone structures, decreased overall density in the remaining bone, loss of trabecular bone mass, destruction of the inner microarchitecture, as well as cortical perforations. Using the combination of BLI, micro-CT imaging, and immune-histopathological techniques, we found a high correlation between the micro-CT-identified lesions, exact tumor location, and infiltration leading to structural lesions and local bone deformation. This confirms that this animal model strongly resembles human MM and has the potential for studying the biology of MM growth and for preclinical testing of novel therapies for MM and for repair of MM-induced bone lesions
Electronic structure and optical properties of lightweight metal hydrides
We study the electronic structures and dielectric functions of the simple
hydrides LiH, NaH, MgH2 and AlH3, and the complex hydrides Li3AlH6, Na3AlH6,
LiAlH4, NaAlH4 and Mg(AlH4)2, using first principles density functional theory
and GW calculations. All these compounds are large gap insulators with GW
single particle band gaps varying from 3.5 eV in AlH3 to 6.5 eV in the MAlH4
compounds. The valence bands are dominated by the hydrogen atoms, whereas the
conduction bands have mixed contributions from the hydrogens and the metal
cations. The electronic structure of the aluminium compounds is determined
mainly by aluminium hydride complexes and their mutual interactions. Despite
considerable differences between the band structures and the band gaps of the
various compounds, their optical responses are qualitatively similar. In most
of the spectra the optical absorption rises sharply above 6 eV and has a strong
peak around 8 eV. The quantitative differences in the optical spectra are
interpreted in terms of the structure and the electronic structure of the
compounds.Comment: 13 pages, 10 figure
Verkenning high tech diermanagement in de varkens en pluimveehouderij
This report describes the results of interviews in the Dutch pig and poultry sector. The potential role of Precision Livestock Farming and realtime animal observations to support daily management were discussed
Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma
Daratumumab, a human CD38 immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day orally on days 1-21 of each cycle) and dexamethasone (40 mg/week). Part 2 (dose expansion) evaluated daratumumab at the recommended phase 2 dose (RP2D) plus lenalidomide/dexamethasone. Safety, efficacy, pharmacokinetics, immunogenicity, and accelerated daratumumab infusions were studied. In part 1 (13 patients), no dose-limiting toxicities were observed, and 16 mg/kg was selected as the R2PD. In part 2 (32 patients), median time since diagnosis was 3.2 years, with a median of 2 prior therapies (range, 1-3 prior therapies), including proteasome inhibitors (91%), alkylating agents (91%), autologous stem cell transplantation (78%), thalidomide (44%), and lenalidomide (34%); 22% of patients were refractory to the last line of therapy. Grade 3 to 4 adverse events (≥5%) included neutropenia, thrombocytopenia, and anemia. In part 2, infusion-related reactions (IRRs) occurred in 18 patients (56%); most were grade ≤2 (grade 3, 6.3%). IRRs predominantly occurred during first infusions and were more common during accelerated infusions. In part 2 (median follow-up of 15.6 months), overall response rate was 81%, with 8 stringent complete responses (25%), 3 complete responses (9%), and 9 very good partial responses (28%). Eighteen-month progression-free and overall survival rates were 72% (95% confidence interval, 51.7-85.0) and 90% (95% confidence interval, 73.1-96.8), respectively. Daratumumab plus lenalidomide/dexamethasone resulted in rapid, deep, durable responses. The combination was well tolerated and consistent with the safety profiles observed with lenalidomide/dexamethasone or daratumumab monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01615029
Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study.
IMPORTANCE: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown.
OBJECTIVE: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period.
INTERVENTIONS: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy.
MAIN OUTCOMES AND MEASURES: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens.
RESULTS: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure.
CONCLUSIONS AND RELEVANCE: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment
HIRAX:A Probe of Dark Energy and Radio Transients
The Hydrogen Intensity and Real-time Analysis eXperiment (HIRAX) is a new
400-800MHz radio interferometer under development for deployment in South
Africa. HIRAX will comprise 1024 six meter parabolic dishes on a compact grid
and will map most of the southern sky over the course of four years. HIRAX has
two primary science goals: to constrain Dark Energy and measure structure at
high redshift, and to study radio transients and pulsars. HIRAX will observe
unresolved sources of neutral hydrogen via their redshifted 21-cm emission line
(`hydrogen intensity mapping'). The resulting maps of large-scale structure at
redshifts 0.8-2.5 will be used to measure Baryon Acoustic Oscillations (BAO).
HIRAX will improve upon current BAO measurements from galaxy surveys by
observing a larger cosmological volume (larger in both survey area and redshift
range) and by measuring BAO at higher redshift when the expansion of the
universe transitioned to Dark Energy domination. HIRAX will complement CHIME, a
hydrogen intensity mapping experiment in the Northern Hemisphere, by completing
the sky coverage in the same redshift range. HIRAX's location in the Southern
Hemisphere also allows a variety of cross-correlation measurements with
large-scale structure surveys at many wavelengths. Daily maps of a few thousand
square degrees of the Southern Hemisphere, encompassing much of the Milky Way
galaxy, will also open new opportunities for discovering and monitoring radio
transients. The HIRAX correlator will have the ability to rapidly and
eXperimentciently detect transient events. This new data will shed light on the
poorly understood nature of fast radio bursts (FRBs), enable pulsar monitoring
to enhance long-wavelength gravitational wave searches, and provide a rich data
set for new radio transient phenomena searches. This paper discusses the HIRAX
instrument, science goals, and current status.Comment: 11 pages, 5 figure
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