388 research outputs found

    Speciation and separation of fission product rhodium

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    The rhodium speciation in nitric acid has been identified, primarily by the use of 103Rh Nuclear Magnetic Resonance Spectroscopy. The results have indicated that the rhodium species in stored high level waste (HLW) will range from the hexaaquo ion, {Rh(H20)6}3+-to complexes of the general formula {Rh(H20)6-n(NO2)nl(3-n)+, depending on the nitrite ion concentration. The solvent extraction of these complexes by dinonylnaphthalene sulphonic acid and various organo-phosphine sulphides has been investigated, and an integrated scheme for recovering rhodium from HLW is proposed

    Identification of Germline Variants in Tumor Genomic Sequencing Analysis

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    This Correspondence relates to the article by Li et al (Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and the College of American Pathologists. J Mol Diagn 2017, 19:4–23)

    Prolonged intermediate syndrome pue to prganophosphate poisoning

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    Organophosphate poisoning can present as acute cholinergic syndrome, Intermediate syndrome and delayed neuropathy. Intermediate syndrome secondary to organophosphate poisoning is a serious health problem leading to increased morbidity and mortality. The incidence of problem varies and range from 8%-84% of organophosphate poisoning cases. The factors account for this difference is nature of organophosphate compound, severity of poisoning and inadequate Oxime therapy. The recognition of this syndrome is important as organophosphate poisoning is common in our country. We presented this case of organophosphate poisoning leading to prolonged intermediate syndrome. The muscle weakness associated with this syndrome generally resolves in 5-18 days but in our case this lasted for 23 days. After a prolonged Intensive Care Unit (ICU) stay patient was discharged home with no residual symptoms. The case highlights anticipation and recognition of this problem after cholinergic crisis is over

    A Mathematical Model of COVID-19 Transmission

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    Disease transmission is studied through disciplines like epidemiology, applied mathematics, and statistics. Mathematical simulation models for transmission have implications in solving public and personal health challenges. The SIR model uses a compartmental approach including dynamic and nonlinear behavior of transmission through three factors: susceptible, infected, and removed (recovered and deceased) individuals. Using the Lambert W Function, we propose a framework to study solutions of the SIR model. This demonstrates the applications of COVID-19 transmission data to model the spread of a real-world disease. Different models of disease including the SIR, SIRmp and SEIRρqr model are compared with respect to their ability to predict disease spread. Physical distancing impacts and personal protection equipment use are discussed with relevance to the COVID-19 spread

    Androgen receptors in areas of the spinal cord and brainstem: A study in adult male cats

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    Sex hormones, including androgens and estrogens, play an important role in autonomic, reproductive and sexual behavior. The areas that are important in these behaviors lie within the spinal cord and brainstem. Relevant dysfunctional behavior in patients with altered androgen availability or androgen receptor sensitivity might be explained by the distribution of androgens and their receptors in the central nervous system. We hypothesize that autonomic dysfunction is correlated with the androgen sensitivity of spinal cord and brainstem areas responsible for autonomic functions. In this study, androgen receptor immunoreactive (AR-IR) nuclei in the spinal cord and brainstem were studied using the androgen receptor antibody PG21 in four uncastrated young adult male cats. A dense distribution of AR-IR nuclei was detected in the superior layers of the dorsal horn, including lamina I. Intensely stained nuclei, but less densely distributed, were found in lamina X and preganglionic sympathetic and parasympathetic cells of the intermediolateral cell column. Areas in the caudal brainstem showing a high density of AR-IR nuclei included the area postrema, the dorsal motor vagus nucleus and the retrotrapezoid nucleus. More cranially, the central linear nucleus in the pons contained a dense distribution of AR-IR nuclei. The mesencephalic periaqueductal gray (PAG) showed a dense distribution of AR-IR nuclei apart from the

    Deposition and Characterization of Indium Selenide Thin Films for Opto-electronic Devices

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    Amongst all the III-VI semiconductors, ones that crystallize with a layered structure have gained special interest due to its significant usage in photovoltaic devices. III-VI layered semiconductor such as InSe has low density of dangling bonds on its surface therefore it is considered as vital material for the fabrication of opto-electronic devices like photo sensor, solar cell etc. In present work, InSe thin films were fabricated through a simple and facile drop-casting method, where the thin films were drop-casted between two silver paste electrodes on a glass substrate. The structural, surface morphological, compositional, electrical and optical properties of the prepared films were obsrved by XRD, SEM, EDAX, high precision digital multi-meter and UV-visible spectroscopy, respectively. XRD analysis of the prepared film shows the existence of nano-crystalline nature with monoclinic crystal structure of InSe. SEM images show good continuity of InSe film. InSe thin films are n-type with bandgap of 1.8 eV and their electrical conductivity is in the order of 10 – 10 S/cm that makes them appropriate for using as an absorber layer in the solar cell

    Exceptional chemotherapy response in metastatic colorectal cancer associated with hyper-indel-hypermutated cancer genome and comutation of POLD1 and MLH1

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    Purpose A 73-year-old woman with metastatic colon cancer experienced a complete response to chemotherapy with dose-intensified irinotecan that has been durable for 5 years.Wesequenced her tumor and germ line DNA and looked for similar patterns in publicly available genomic data from patients with colorectal cancer. Patients and Methods Tumor DNA was obtained from a biopsy before therapy, and germ line DNA was obtained from blood. Tumor and germline DNA were sequenced using a commercial panel with approximately 250 genes. Whole-genome amplification and exome sequencing were performed for POLE and POLD1. A POLD1 mutation was confirmed by Sanger sequencing. The somatic mutation and clinical annotation data files from the colon (n = 461) and rectal (n = 171) adenocarcinoma data sets were downloaded from The Cancer Genome Atlas data portal and analyzed for patterns of mutations and clinical outcomes in patients withPOLE- and/orPOLD1- mutated tumors. Results The pattern of alterations included APC biallelic inactivation and microsatellite instability high (MSI-H) phenotype, with somatic inactivation of MLH1 and hypermutation (estimated mutation rate > 200 per megabase). The extremely high mutation rate led us to investigate additional mechanisms for hypermutation, including loss of function of POLE. POLE was unaltered, but a related gene not typically associated with somatic mutation in colon cancer, POLD1, had a somatic mutation c.2171G > A[p.Gly724Glu]. Additionally, we noted that the high mutation rate was largely composed of dinucleotide deletions. A similar pattern of hypermutation (dinucleotide deletions, POLD1 mutations, MSI-H) was found in tumors from The Cancer Genome Atlas. Conclusion POLD1 mutation with associated MSI-H and hyper-indel-hypermutated cancer genome characterizes a previously unrecognized variant of colon cancer that was found in this patient with an exceptional response to chemotherapy

    Comprehensive molecular characterization of urachal adenocarcinoma reveals commonalities with colorectal cancer, including a hypermutable phenotype

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    Purpose Urachal adenocarcinoma is a rare type of primary bladder adenocarcinoma that comprises less than 1% of all bladder cancers. The low incidence of urachal adenocarcinomas does not allow for an evidence-based approach to therapy. Transcriptome profiling of urachal adenocarcinomas has not been previously reported.Wehypothesized that an in-depth molecular understanding of urachal adenocarcinoma would uncover rational therapeutic strategies. Patients and Methods We performed targeted exon sequencing and global transcriptome profiling of 12 urachal tumors to generate a comprehensive molecular portrait of urachal adenocarcinoma. A single patient with an MSH6 mutation was treated with the anti-programmed death-ligand 1 antibody, atezolizumab. Results Urachal adenocarcinoma closely resembles colorectal cancer at the level of RNA expression, which extends previous observations that urachal tumors harbor genomic alterations that are found in colorectal adenocarcinoma. A subset of tumors was found to have alterations in genes that are associated with microsatellite instability (MSH2 and MSH6) and hypermutation (POLE).Apatient with anMSH6mutation was treated withimmunecheckpoint blockade, which resulted in stable disease. Conclusion Because clinical trials are next to impossible for patients with rare tumors, precision oncology may be an important adjunct for treatment decisions. Our findings demonstrate that urachal adenocarcinomas molecularly resemble colorectal adenocarcinomas at the level ofRNA expression, are the first report, to our knowledge, of MSH2andMSH6mutations in this disease, and support the consideration of immune checkpoint blockade as a rational therapeutic treatment of this exceedingly rare tumor

    Enhancing Next-Generation Sequencing-Guided Cancer Care Through Cognitive Computing

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    Background: Using next-generation sequencing (NGS) to guide cancer therapy has created challenges in analyzing and reporting large volumes of genomic data to patients and caregivers. Specifically, providing current, accurate information on newly approved therapies and open clinical trials requires considerable manual curation performed mainly by human “molecular tumor boards” (MTBs). The purpose of this study was to determine the utility of cognitive computing as performed by Watson for Genomics (WfG) compared with a human MTB. Materials and Methods: One thousand eighteen patient cases that previously underwent targeted exon sequencing at the University of North Carolina (UNC) and subsequent analysis by the UNCseq informatics pipeline and the UNC MTB between November 7, 2011, and May 12, 2015, were analyzed with WfG, a cognitive computing technology for genomic analysis. Results: Using a WfG-curated actionable gene list, we identified additional genomic events of potential significance (not discovered by traditional MTB curation) in 323 (32%) patients. The majority of these additional genomic events were considered actionable based upon their ability to qualify patients for biomarker-selected clinical trials. Indeed, the opening of a relevant clinical trial within 1 month prior to WfG analysis provided the rationale for identification of a new actionable event in nearly a quarter of the 323 patients. This automated analysis took <3 minutes per case. Conclusion: These results demonstrate that the interpretation and actionability of somatic NGS results are evolving too rapidly to rely solely on human curation. Molecular tumor boards empowered by cognitive computing could potentially improve patient care by providing a rapid, comprehensive approach for data analysis and consideration of up-to-date availability of clinical trials. Implications for Practice: The results of this study demonstrate that the interpretation and actionability of somatic next-generation sequencing results are evolving too rapidly to rely solely on human curation. Molecular tumor boards empowered by cognitive computing can significantly improve patient care by providing a fast, cost-effective, and comprehensive approach for data analysis in the delivery of precision medicine. Patients and physicians who are considering enrollment in clinical trials may benefit from the support of such tools applied to genomic data

    Identification of clonal hematopoiesis mutations in solid tumor patients undergoing unpaired next-generation sequencing assays

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    Purpose: In this era of precision-based medicine, for optimal patient care, results reported from commercial next-generation sequencing (NGS) assays should adequately reflect the burden of somatic mutations in the tumor being sequenced. Here, we sought to determine the prevalence of clonal hematopoiesis leading to possible misattribution of tumor mutation calls on unpaired Foundation Medicine NGS assays. Experimental Design: This was a retrospective cohort study of individuals undergoing NGS of solid tumors from two large cancer centers. We identified and quantified mutations in genes known to be frequently altered in clonal hematopoiesis (DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2, SF3B1, CBL, JAK2) that were returned to physicians on clinical Foundation Medicine reports. For a subset of patients, we explored the frequency of true clonal hematopoiesis by comparing mutations on Foundation Medicine reports with matched blood sequencing. Results: Mutations in genes that are frequently altered in clonal hematopoiesis were identified in 65% (1,139/1,757) of patients undergoing NGS. When excluding TP53, which is often mutated in solid tumors, these events were still seen in 35% (619/1,757) of patients. Utilizing paired blood specimens, we were able to confirm that 8% (18/226) of mutations reported in these genes were true clonal hematopoiesis events. The majority of DNMT3A mutations (64%, 7/11) and minority of TP53 mutations (4%, 2/50) were clonal hematopoiesis. Conclusions: Clonal hematopoiesis mutations are commonly reported on unpaired NGS testing. It is important to recognize clonal hematopoiesis as a possible cause of misattribution of mutation origin when applying NGS findings to a patient's care
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