70 research outputs found

    Comparison of IgG diffusion and extracellular matrix composition in rhabdomyosarcomas grown in mice versus in vitro as spheroids reveals the role of host stromal cells

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    The tumour extracellular matrix acts as a barrier to the delivery of therapeutic agents. To test the hypothesis that extracellular matrix composition governs the penetration rate of macromolecules in tumour tissue, we measured the diffusion coefficient of nonspecific IgG in three rhabdomyosarcoma subclones growing as multicellular spheroids in vitro or as subcutaneous tumours in dorsal windows in vivo. In subcutaneous tumours, the diffusion coefficient decreased with increasing content of collagen and sulphated glycosaminoglycans. When grown as multicellular spheroids, no differences in either extracellular matrix composition or diffusion coefficient were found. Comparison of in vitro vs in vivo results suggests an over-riding role of host stromal cells in extracellular matrix production subjected to modulation by tumour cells. Penetration of therapeutic macromolecules through tumour extracellular matrix might thus be largely determined by the host organ. Hence, caution must be exercised in extrapolating drug penetrability from spheroids and multilayer cellular sandwiches consisting of only tumour cells to tumours in vivo

    The three-prong method: a novel assessment of residual stress in laser powder bed fusion

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    <p><b>Boxplots of quantitative parameters</b> included <b>a)</b> ratio of N-acetylaspartate and N-acetylaspartylglutamate (NAA) to creatine and phosphocreatine (Cr) both for chemical shift imaging (CSI) and single voxel (SV) measurements, <b>b)</b> ratio of choline containing compounds (Cho) to Cr both for CSI and SV, <b>c)</b> myelin water fraction (MWF), <b>d)</b> magnetization transfer ratio (MTR), <b>e)</b> quantitative susceptibility mapping (QSM), and <b>f)</b> R2*. Parameters were measured in frontal white matter (WM) and two parameters within the cortico-spinal tract (CST): at the level of the posterior limb of internal capsule (PLIC) and at the level of the centrum semiovale (CS), see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0167274#pone.0167274.g001" target="_blank">Fig 1</a>.</p

    Development and evaluation of a novel fast broad-range PCR and sequencing assay (FBR-PCR/S) using dual priming oligonucleotides targeting the ITS/LSU gene regions for rapid diagnosis of invasive fungal diseases: multi-year experience in a large Canadian healthcare zone

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    Abstract Background This study evaluated the performance of a novel fast broad range PCR and sequencing (FBR-PCR/S) assay for the improved diagnosis of invasive fungal disease (IFD) in high-risk patients in a large Canadian healthcare region. Methods A total of 114 clinical specimens (CS) including bronchoalveolar lavages (BALs) were prospectively tested from 107 patients over a 2-year period. Contrived BALs (n = 33) inoculated with known fungi pathogens were also tested to increase diversity. Patient characteristics, fungal stain and culture results were collected from the laboratory information system. Dual-priming oligonucleotide (DPO) primers targeted to the internal transcribed spacer (ITS) (~ 350 bp) and large subunit (LSU) (~ 550 bp) gene regions were used to perform FBR-PCR/S assays on extracted BALs/CS. The performance of the molecular test was evaluated against standard microbiological methods and clinical review for the presence of IFD. Results The 107 patients were predominantly male (67, 62.6%) with a mean age of 59 years (range = 0–85 years): 74 (69.2%) patients had at least one underlying comorbidity: 19 (34.5%) had confirmed and 12 (21.8%) had probable IFD. Culture recovered 66 fungal isolates from 55 BALs/CS with Candida spp. and Aspergillus spp. being most common. For BALs, the molecular assay vs. standard methods had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and efficiency of 88.5% vs.100%, 100% vs. 61.1%, 100% vs. 88.5%, 61.1% vs. 100%, and 90.2% for both. For other CS, the molecular assay had similar performance to standard methods with sensitivity, specificity, PPV, NPV and efficiency of 66.7%, 87.0%, 66.7%, 87.0% and 81.3% for both methods. Both methods also performed similarly, regardless of whether CS stain/microscopy showed yeast/fungal elements. FBR-PCR/S assays results were reported in ~ 8 h compared to fungal cultures that took between 4 and 6 weeks. Conclusions Rapid molecular testing compared to standard methods have equivalent diagnostic efficiency but improves clinical utility by reporting a rapid species-level identification the same dayshift (~ 8 h)

    Long term motor function after neonatal stroke: Lesion localization above all.

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    International audienceMotor outcome is variable following neonatal arterial ischemic stroke (NAIS). We analyzed the relationship between lesion characteristics on brain MRI and motor function in children who had suffered from NAIS. Thirty eight full term born children with unilateral NAIS were investigated at the age of seven. 3D T1- and 3D FLAIR-weighted MR images were acquired on a 3T MRI scanner. Lesion characteristics were compared between patients with and without cerebral palsy (CP) using the following approaches: lesion localization either using a category-based analysis, lesion mapping as well as voxel-based lesion-symptom mapping (VLSM). Using diffusion-weighted imaging the microstructure of the cortico-spinal tract (CST) was related to the status of CP by measuring DTI parameters. Whereas children with lesions sparing the primary motor system did not develop CP, CP was always present when extensive lesions damaged at least two brain structures involving the motor system. The VLSM approach provided a statistical map that confirmed the cortical lesions in the primary motor system and revealed that CP was highly correlated with lesions in close proximity to the CST. In children with CP, diffusion parameters indicated microstructural changes in the CST at the level of internal capsule and the centrum semiovale. White matter damage of the CST in centrum semiovale was a highly reproducible marker of CP. This is the first description of the implication of this latter region in motor impairment after NAIS. In conclusion, CP in childhood was closely linked to the location of the infarct in the motor system.© 2015 Wiley Periodicals, Inc

    The MEGAPIE 1 MW target in support to ADS development: status of R&D and design

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    International audienceThe MEGAPIE project is aimed at designing, building and operating a liquid metal spallation neutron target as a key experiment on the road to an experimental accelerator driven system and to improve the neutron flux at the PSI spallation source. The design of the target system has been completed. The target configuration and the operating conditions have been defined and the expected performance assessed. A preliminary safety analysis has been performed considering normal, off-normal and accident conditions and a corresponding report has been submitted to the authorities for licensing. The experience gained up to now shows that MEGAPIE may well be the first liquid metal target to be irradiated under high power beam conditions

    Does Contralesional Hand Function After Neonatal Stroke Only Depend on Lesion Characteristics?

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    International audienceBACKGROUND AND PURPOSE:In children having suffered from neonatal arterial ischemic stroke, the relationship between contralesional hand performance and structural changes in brain areas remote from the infarct site was examined.METHODS:Using voxel-based morphometry, we correlated contralesional gross manual dexterity assessed by the box and block test and whole-brain gray and white-matter volume changes on high-resolution magnetic resonance imaging in 37 7-year-old post-neonatal arterial ischemic stroke children. We also compared the volume of the identified structures with magnetic resonance imaging data of 10 typically developing age-matched children.RESULTS:Areas showing the highest positive correlation with the box and block test scores were ipsilesional mediodorsal thalamus, contralesional cerebellar lobule VIIa Crus I, and ipsilesional corticospinal tract at the level of superior corona radiata, the posterior limb of the internal capsule, and the cerebral peduncle and the ipsilesional body of corpus callosum. When compared with typically developing age-matched children, post-neonatal arterial ischemic stroke children with severe contralesional hand motor deficit exhibited significant volume reductions in these structures (except the cerebellum), whereas no differences were found with those with good manual dexterity. No negative correlation was found between box and block test scores and brain areas.CONCLUSIONS:Contralesional hand performance after neonatal arterial ischemic stroke is correlated with atrophy in brain areas directly or functionally connected but anatomically remote from the infarct. Our study suggests a role of the cerebellar lobule VIIa Crus I and mediodorsal thalamus in manual dexterity.CLINICAL TRIAL REGISTRATION:URL: https://clinicaltrials.gov. Unique identifier: NCT02511249.© 2016 American Heart Association, Inc
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