164 research outputs found

    Experience With Radical Resection in The Management of Proximal Bile Duct Cancer

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    Multiple surgical and nonsurgical approaches have been advocated for the treatment of proximal bile duct cancer. However, survival appears longest when a resection can be performed. Fifteen patients treated at a university center were managed with an aggressive surgical approach. Resection of the tumor was performed in 13 of 15 patients (87%). Of the patients undergoing resection, major hepatic resection was performed in 8 (62%), while excision of vessels with reconstruction was performed in 5 (38%). Eleven of the 13 resected patients (85%) were discharged from the hospital. Clinical symptoms of recurrent disease occurred between 3 and 36 months after surgery in 7 patients, 6 of whom have died. Three other patients are alive at 5, 21, and 36 months without clinical evidence of recurrence. There was no correlation between the completeness of resection and the duration of disease-free survival

    Early respiratory viral infections in infants with cystic fibrosis

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    This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Background Viral infections contribute to morbidity in cystic fibrosis (CF), but the impact of respiratory viruses on the development of airway disease is poorly understood. Methods Infants with CF identified by newborn screening were enrolled prior to 4 months of age to participate in a prospective observational study at 4 centers. Clinical data were collected at clinic visits and weekly phone calls. Multiplex PCR assays were performed on nasopharyngeal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and a subset underwent pulmonary function testing. We present findings through 8.5 months of life. Results Seventy infants were enrolled, mean age 3.1 ± 0.8 months. Rhinovirus was the most prevalent virus (66%), followed by parainfluenza (19%), and coronavirus (16%). Participants had a median of 1.5 viral positive swabs (range 0–10). Past viral infection was associated with elevated neutrophil concentrations and bacterial isolates in BAL fluid, including recovery of classic CF bacterial pathogens. When antibiotics were prescribed for respiratory-related indications, viruses were identified in 52% of those instances. Conclusions Early viral infections were associated with greater neutrophilic inflammation and bacterial pathogens. Early viral infections appear to contribute to initiation of lower airway inflammation in infants with CF. Antibiotics were commonly prescribed in the setting of a viral infection. Future investigations examining longitudinal relationships between viral infections, airway microbiome, and antibiotic use will allow us to elucidate the interplay between these factors in young children with CF

    Whither Magnetic Hyperthermia? A Tentative Roadmap

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    The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.This work was supported by the NoCanTher project, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 685795. The authors acknowledge support from the COST Association through the COST actions "RADIOMAG" (TD1402) and "MyWAVE" (CA17115). D.O., A.S.-O. and I.R.-R. acknowledge financial support from the Community of Madrid under Contracts No. PEJD-2017-PRE/IND-3663 and PEJ-2018-AI/IND-11069, from the Spanish Ministry of Science through the Ramon y Cajal grant RYC2018-025253-I and Research Networks RED2018-102626-T, as well as the Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, MAT2017-88148R and the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686). M.B. and N.T.K.T. would like to thank EPSRC for funding (grant EP/K038656/1 and EP/M015157/1) and AOARD (FA2386-171-4042) award. This work was additionally supported by the EMPIR program co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation program, grant no. 16NRM04 "MagNaStand". The work was further supported by the DFG grant CRC "Matrix in Vision" (SFB 1340/1 2018, no 372486779, project A02)

    Mechanisms of inorganic carbon-14 attenuation in contaminated groundwater: Effect of solution pH on isotopic exchange and carbonate precipitation reactions

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    Radioactive 14C is a significant contaminant associated with nuclear fuels and wastes that is potentially highly mobile in the environment as dissolved inorganic carbonate species. This study investigated the mechanisms by which dissolved inorganic 14C is retained in surface and groundwater environments via precipitation and isotopic exchange reactions. Precipitation of calcite in the presence and absence of nucleation sites is considered along with isotopic exchange with both atmospheric CO2 and solid carbonates. Precipitation occurs at calcite supersaturation values of SICAL > 1.5 in the absence of nucleation sites and SICAL > 0–0.5 in the presence of nucleation sites, suggesting that precipitation of 14C-bearing carbonates is much more likely in subsurface environments where nucleation sites are abundant. The maximum 14C removal in solid isotopic exchange experiments occurred after approximately 2 weeks equilibration. In these experiments the amount of 14C removed from solution was proportional to the amount of calcite surface area present, and removal from solution was equivalent to rapid equalisation of the isotope ratio in an 8–10 Å active surface layer. Although the reactivity of natural carbonates may be lower than the calcite samples used in this study, these results suggest isotopic exchange with solids will be an important 14C retardation mechanism in subsurface environments containing only modest TIC concentrations. These results suggest that if inorganic 14C is released into sub-surface environments, both precipitation and solid phase isotopic exchange can result in non-conservative 14C-DIC transport and 14C contamination may persist in groundwater for decades following accidental releases. In contrast, in experiments open to atmosphere with pH values below 9.3, complete loss of dissolved inorganic 14C was very rapid and occurred with timescales of 10's of hours. 14C loss was due to a rapid exchange of dissolved 14C species with 12CO2 (g) and the kinetics of 14C removal increased as pH values were lowered (i.e. atmospheric isotopic exchange was first order with respect to the concentration of carbonic acid present). Thus these results suggest that release of inorganic 14C to surface waters with pH values <9.3 would result in rapid exchange with 12CO2 (g) and 14C would not persist in the aqueous environment, whereas 14C-DIC released to saturated subsurface environments may persist close to the release site for decades due to precipitation and solid phase exchange reactions preventing/retarding transport with the groundwater

    Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

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    The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

    Epistatic interactions associated with fatty acid concentrations of beef from angus sired beef cattle

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    Consumers are becoming increasingly conscientious about the nutritional value of their food. Consumption of some fatty acids has been associated with human health traits such as blood pressure and cardiovascular disease. Therefore, it is important to investigate genetic variation in content of fatty acids present in meat. Previously publications reported regions of the cattle genome that are additively associated with variation in fatty acid content. This study evaluated epistatic interactions, which could account for additional genetic variation in fatty acid content. Epistatic interactions for 44 fatty acid traits in a population of Angus beef cattle were evaluated with EpiSNPmpi. False discovery rate (FDR) was controlled at 5 % and was limited to well-represented genotypic combinations. Epistatic interactions were detected for 37 triacylglyceride (TAG), 36 phospholipid (PL) fatty acid traits, and three weight traits. A total of 6,181, 7,168, and 0 significant epistatic interactions (FDR < 0.05, 50-animals per genotype combination) were associated with Triacylglyceride fatty acids, Phospholipid fatty acids, and weight traits respectively and most were additive-by-additive interactions. A large number of interactions occurred in potential regions of regulatory control along the chromosomes where genes related to fatty acid metabolism reside. Many fatty acids were associated with epistatic interactions. Despite a large number of significant interactions, there are a limited number of genomic locations that harbored these interactions. While larger population sizes are needed to accurately validate and quantify these epistatic interactions, the current findings point towards additional genetic variance that can be accounted for within these fatty acid traits.https://doi.org/10.1186/s12864-016-3235-

    Vanadium: a re-emerging environmental hazard

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    Vanadium (V) is a contaminant which has been long confined to the annals of regulatory history. This follows the reduction of its historical primary source (fossil fuel emissions) since the 1970s (e.g., by 80% in the UK). However, V is quickly becoming an important strategic resource which promises its return to environmental prominence because of changing industrial practices and emerging waste streams. We discuss below (i) what makes V a re-emerging environmental and human health hazard of global interest, (ii) the knowledge gaps that currently restrict prediction of environmental effect and mitigation, and (iii) opportunities for the community to address these gaps toward reducing the risk of an impending environmental hazard

    Pax6 Expression Is Sufficient to Induce a Neurogenic Fate in Glial Progenitors of the Neonatal Subventricular Zone

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    The forebrain subventricular zone (SVZ) of neonatal mammals contains a large, heterogeneous population of migratory and proliferating precursors of interneurons and glia. These cell types are produced in large numbers in the immediate postnatal period, the glioblasts populating the hemispheres with astrocytes and oligodendrocytes, the neuroblasts migrating to the olfactory bulb to become interneurons. How cell fate decisions are determined or stabilized in this mixed population is not clear, although previous studies indicate the importance of two transcription factors, Pax6 in neurons and Olig2 in glia, and suggest there may be reciprocal repression between these genes.In examining the SVZ of neonatal mouse and rat brain, we find that the very large majority of SVZ cells express either Pax6 or Olig2, but few express both. We have used in vivo retro- and lenti-virus injections into the neonatal SVZ and in vitro gene transfer to demonstrate that pax6 over-expression is sufficient to down-regulate olig2 and to promote a neuronal lineage development and migration pattern in olig2-expressing cells. Furthermore, we provide evidence that Pax6 binds to the olig2 promoter and that an HEB sequence in the promoter is required for the Pax6 repression of olig2 transcription. Lastly, we constructed a lentivirus to target olig2-expressing cells in the SVZ to trace their fates, and found that the very large majority developed into glia.We provide evidence for a direct repression of olig2 by Pax6. Since SVZ cells can display developmental plasticity in vitro, the cross-repression promotes a stabilization of cell fates. This repression may be critical in a germinal zone in which immature cells are highly migratory and are not organized into an epithelium
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