88 research outputs found
Operational Radiology Recovery in Academic Radiology Departments After the COVID-19 Pandemic: Moving Toward Normalcy
This article presents a current snapshot in time, describing how radiology departments around the country are planning recovery from the baseline of the coronavirus disease 2019 pandemic, with a focus on different domains of recovery such as managing appointment availability, patient safety and workflow changes, and operational data and analytics. An e-mail survey was sent through the Society of Chairs of Academic Radiology Departments list server to 114 academic radiology departments. On the basis of data reported by the 38 survey respondents, best practices and shared experience are described for three key areas: (1) planning for recovery, (2) creating a new normal, and (3) measuring and forecasting. Radiology practices should be aware of the common approaches and preparations academic radiology departments have taken to reopening imaging in the post-coronavirus disease 2019 world. This should all be done when maintaining a safe and patient-centric environment and preparing to minimize the impact of future outbreaks or pandemics
64Cu-MM-302 Positron Emission Tomography Quantifies Variability of Enhanced Permeability and Retention of Nanoparticles in Relation to Treatment Response in Patients with Metastatic Breast Cancer
Purpose: Therapeutic nanoparticles are designed to deliver their drug payloads through enhanced permeability and retention (EPR) in solid tumors. The extent of EPR and its variability in human tumors is highly debated and has been proposed as an explanation for variable responses to therapeutic nanoparticles in clinical studies.
Experimental Design: We assessed the EPR effect in patients using a 64Cu-labeled nanoparticle, 64Cu-MM-302 (64Cu-labeled HER2-targeted PEGylated liposomal doxorubicin), and imaging by PET/CT. Nineteen patients with HER2-positive metastatic breast cancer underwent 2 to 3 PET/CT scans postadministration of 64Cu-MM-302 as part of a clinical trial of MM-302 plus trastuzumab with and without cyclophosphamide (NCT01304797).
Results: Significant background uptake of 64Cu-MM-302 was observed in liver and spleen. Tumor accumulation of 64Cu-MM-302 at 24 to 48 hours varied 35-fold (0.52–18.5 %ID/kg), including deposition in bone and brain lesions, and was independent of systemic plasma exposure. Computational analysis quantified rates of deposition and washout, indicating peak liposome deposition at 24 to 48 hours. Patients were classified on the basis of 64Cu-MM-302 lesion deposition using a cut-off point that is comparable with a response threshold in preclinical studies. In a retrospective exploratory analysis of patient outcomes relating to drug levels in tumor lesions, high 64Cu-MM-302 deposition was associated with more favorable treatment outcomes (HR = 0.42).
Conclusions: These findings provide important evidence and quantification of the EPR effect in human metastatic tumors and support imaging nanoparticle deposition in tumors as a potential means to identify patients well suited for treatment with therapeutic nanoparticles
Saúde Bucal na Ação Programática da Criança: indicadores e metas de um Serviço de Atenção Primária à Saúde
Dark Matter and Fundamental Physics with the Cherenkov Telescope Array
The Cherenkov Telescope Array (CTA) is a project for a next-generation
observatory for very high energy (GeV-TeV) ground-based gamma-ray astronomy,
currently in its design phase, and foreseen to be operative a few years from
now. Several tens of telescopes of 2-3 different sizes, distributed over a
large area, will allow for a sensitivity about a factor 10 better than current
instruments such as H.E.S.S, MAGIC and VERITAS, an energy coverage from a few
tens of GeV to several tens of TeV, and a field of view of up to 10 deg. In the
following study, we investigate the prospects for CTA to study several science
questions that influence our current knowledge of fundamental physics. Based on
conservative assumptions for the performance of the different CTA telescope
configurations, we employ a Monte Carlo based approach to evaluate the
prospects for detection. First, we discuss CTA prospects for cold dark matter
searches, following different observational strategies: in dwarf satellite
galaxies of the Milky Way, in the region close to the Galactic Centre, and in
clusters of galaxies. The possible search for spatial signatures, facilitated
by the larger field of view of CTA, is also discussed. Next we consider
searches for axion-like particles which, besides being possible candidates for
dark matter may also explain the unexpectedly low absorption by extragalactic
background light of gamma rays from very distant blazars. Simulated
light-curves of flaring sources are also used to determine the sensitivity to
violations of Lorentz Invariance by detection of the possible delay between the
arrival times of photons at different energies. Finally, we mention searches
for other exotic physics with CTA.Comment: (31 pages, Accepted for publication in Astroparticle Physics
Targeted Sequencing in Chromosome 17q Linkage Region Identifies Familial Glioma Candidates in the Gliogene Consortium
Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (,0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned
Capillary Regeneration in Scleroderma: Stem Cell Therapy Reverses Phenotype?
BACKGROUND. Scleroderma is an autoimmune disease with a characteristic vascular pathology. The vasculopathy associated with scleroderma is one of the major contributors to the clinical manifestations of the disease. METHODOLOGY/PRINCIPAL FINDINGS. We used immunohistochemical and mRNA in situ hybridization techniques to characterize this vasculopathy and showed with morphometry that scleroderma has true capillary rarefaction. We compared skin biopsies from 23 scleroderma patients and 24 normal controls and 7 scleroderma patients who had undergone high dose immunosuppressive therapy followed by autologous hematopoietic cell transplant. Along with the loss of capillaries there was a dramatic change in endothelial phenotype in the residual vessels. The molecules defining this phenotype are: vascular endothelial cadherin, a supposedly universal endothelial marker required for tube formation (lost in the scleroderma tissue), antiangiogenic interferon α (overexpressed in the scleroderma dermis) and RGS5, a signaling molecule whose expression coincides with the end of branching morphogenesis during development and tumor angiogenesis (also overexpressed in scleroderma skin. Following high dose immunosuppressive therapy, patients experienced clinical improvement and 5 of the 7 patients with scleroderma had increased capillary counts. It was also observed in the same 5 patients, that the interferon α and vascular endothelial cadherin had returned to normal as other clinical signs in the skin regressed, and in all 7 patients, RGS5 had returned to normal. CONCLUSION/SIGNIFICANCE. These data provide the first objective evidence for loss of vessels in scleroderma and show that this phenomenon is reversible. Coordinate changes in expression of three molecules already implicated in angiogenesis or anti-angiogenesis suggest that control of expression of these three molecules may be the underlying mechanism for at least the vascular component of this disease. Since rarefaction has been little studied, these data may have implications for other diseases characterized by loss of capillaries including hypertension, congestive heart failure and scar formation.Scleroderma Research Foundatio
Human epithelial cells trigger dendritic cell–mediated allergic inflammation by producing TSLP
The INTERPHONE study: design, epidemiological methods, and description of the study population
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