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| 2. |
- Benton, S., et al.
(författare)
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Impact of Next-generation Sequencing on Interobserver Agreement and Diagnosis of Spitzoid Neoplasms
- 2021
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Ingår i: American Journal of Surgical Pathology. - : Ovid Technologies (Wolters Kluwer Health). - 0147-5185 .- 1532-0979. ; 45:12, s. 1597-1605
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Tidskriftsartikel (refereegranskat)abstract
- Atypical Spitzoid melanocytic tumors are diagnostically challenging. Many studies have suggested various genomic markers to improve classification and prognostication. We aimed to assess whether next-generation sequencing studies using the Tempus xO assay assessing mutations in 1711 cancer-related genes and performing whole transcriptome mRNA sequencing for structural alterations could improve diagnostic agreement and accuracy in assessing neoplasms with Spitzoid histologic features. Twenty expert pathologists were asked to review 70 consultation level cases with Spitzoid features, once with limited clinical information and again with additional genomic information. There was an improvement in overall agreement with additional genomic information. Most significantly, there was increase in agreement of the diagnosis of conventional melanoma from moderate (kappa=0.470, SE=0.0105) to substantial (kappa=0.645, SE=0.0143) as measured by an average Cohen kappa. Clinical follow-up was available in all 70 cases which substantiated that the improved agreement was clinically significant. Among 3 patients with distant metastatic disease, there was a highly significant increase in diagnostic recognition of the cases as conventional melanoma with genomics (P<0.005). In one case, none of 20 pathologists recognized a tumor with BRAF and TERT promoter mutations associated with fatal outcome as a conventional melanoma when only limited clinical information was provided, whereas 60% of pathologists correctly diagnosed this case when genomic information was also available. There was also a significant improvement in agreement of which lesions should be classified in the Spitz category/WHO Pathway from an average Cohen kappa of 0.360 (SE=0.00921) to 0.607 (SE=0.0232) with genomics.
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| 3. |
- Cung, T. -T., et al.
(författare)
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Cyclosporine before PCI in Patients with Acute Myocardial Infarction
- 2015
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 373:11, s. 1021-1031
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval, 0.78 to 1.39; P = 0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.)
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| 4. |
- Emri, M., et al.
(författare)
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Software development framework supporting multimodal tomographic imaging
- 2007
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Ingår i: 2006 IEEE Nuclear Science Symposium Conference Record. - : IEEE. - 1424405610 - 9781424405619 ; , s. 1857-1859
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Konferensbidrag (refereegranskat)abstract
- Engineers specialized in multimodal tomography regularly face a wide scale of programming tasks requiring an integrated software system to ensure cost efficiency. Accordingly, a software development framework has been worked out comprising libraries for cluster-based data acquisition, image reconstruction, management of data files and complex multimodal volumetric visualization. This framework enabled us to develop complex software for our miniPET project [1]. This software contains a graphical application integrating data acquisition, cluster monitoring, event sorting, image reconstruction, interactive image processing tools for advanced multimodal visualization. It also contains utilities to solve these tasks without graphical user interface. The components of our acquisition program can run on embedded Linux systems making new ways to develop any other types of data acquisition software that uses embedded Linux systems. A versatile development framework is developed containing specific libraries and special file formats that support multimodal tomography. This framework was successfully used to elaborate our complex miniPET software.
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| 5. |
- Mitra, Aditee, et al.
(författare)
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The role of mixotrophic protists in the biological carbon pump
- 2014
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 11, s. 995-1005
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Tidskriftsartikel (refereegranskat)abstract
- The traditional view of the planktonic foodweb describes consumption of inorganic nutrientsby photo-autotrophic phytoplankton, which in turn supports zooplankton and ultimately higher trophic levels. Pathways centred on bacteria provide mechanisms for nutrient recycling. This structure lies at the foundation of most models used to explore biogeochemical cycling, functioning of the biological pump, and the impact of climate change on these processes. We suggest an alternative paradigm, which sees the bulk of the base of this foodweb supported by protist plankton (phytoplankton and microzooplankton) communities that are mixotrophic – combining phototrophy and phagotrophy within a single cell. The photoautotrophic eukaryotic plankton and their heterotrophic microzooplankton grazers dominate only within immature environments (e.g., spring bloom in temperate systems). With their flexible nutrition, mixotrophic protists dominate in more mature systems (e.g., temperate summer, established eutrophic systems and oligotrophic systems); the more stable water columns suggested under climate change may also be expected to favour these mixotrophs. We explore how such a predominantlymixotrophic structure affects microbial trophic dynamics and the biological pump. The mixotroph dominated structure differs fundamentally in its flow of energy and nutrients, with a shortened and potentially more efficient chain from nutrient regeneration to primary production. Furthermore, mixotrophy enables a direct conduit for the support of primary production from bacterial production. We show how the exclusion of an explicit mixotrophic component in studies of the pelagic microbial communities leads to a failure to capture the true dynamics of the carbon flow. In order to prevent a misinterpretation of the full implications of climate change upon biogeochemical cyclingand the functioning of the biological pump, we recommend inclusion of multi-nutrient mixotroph models within ecosystem studies.
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| 6. |
- Varriale, Simona, et al.
(författare)
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Evolution of the feruloyl esterase MtFae1a from Myceliophthora thermophila towards improved catalysts for antioxidants synthesis
- 2018
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Ingår i: Applied Microbiology and Biotechnology. - : Springer. - 0175-7598 .- 1432-0614. ; 102:12, s. 5185-5196
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Tidskriftsartikel (refereegranskat)abstract
- The chemical syntheses currently employed for industrial purposes, including in the manufacture of cosmetics, present limitations such as unwanted side reactions and the need for harsh chemical reaction conditions. In order to overcome these drawbacks, novel enzymes are developed to catalyze the targeted bioconversions. In the present study, a methodology for the construction and the automated screening of evolved variants library of a Type B feruloyl esterase from Myceliophthora thermophila (MtFae1a) was developed and applied to generation of 30,000 mutants and their screening for selecting the variants with higher activity than the wild-type enzyme. The library was generated by error-prone PCR of mtfae1a cDNA and expressed in Saccharomyces cerevisiae. Screening for extracellular enzymatic activity towards 4-nitrocatechol-1-yl ferulate, a new substrate developed ad hoc for high-throughput assays of feruloyl esterases, led to the selection of 30 improved enzyme variants. The best four variants and the wild-type MtFae1a were investigated in docking experiments with hydroxycinnamic acid esters using a model of 3D structure of MtFae1a. These variants were also used as biocatalysts in transesterification reactions leading to different target products in detergentless microemulsions and showed enhanced synthetic activities, although the screening strategy had been based on improved hydrolytic activity.
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| 9. |
- Hegyesi, G., et al.
(författare)
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Ethernet based distributed data acquisition system for a small animal PET
- 2006
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Ingår i: IEEE Transactions on Nuclear Science. - 0018-9499 .- 1558-1578. ; 53:4, s. 2112-2117
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Tidskriftsartikel (refereegranskat)abstract
- We report on the design of a small animal PET scanner being developed at our institutes. The existing setup is the first version of the miniPET machine consisting of four detector modules. Each detector module consists of an 8 x 8 LSO scintillator crystal block, a position sensitive photomultiplier, a digitizer including a digital signal processing board and an Ethernet interface board. There is no hardware coincidence detection implemented in the system and coincidence is determined based on a time stamp attached to every event by a digital CFD algorithm. The algorithm is implemented in the digital signal processing board and generates a time stamp with a coincidence resolution of less than 2 us. The data acquisition system is based on Ethernet network and is highly scalable in size and performance.
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| 10. |
- Imrek, J., et al.
(författare)
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Internals and evaluation of the miniPET-II detector module
- 2007
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Ingår i: 2007 IEEE Nuclear Science Symposium Conference Record. - 1424409233 - 9781424409235 ; , s. 2930-2932
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Konferensbidrag (refereegranskat)abstract
- We report on the architecture of the System-on-Module (SoM) developed by our group for miniPET-II, the second version of our small animal PET scanner. The paper describes the hardware and software implementation details of the SoM we realized inside the miniPET-II detector module, the embedded Linux operation system, and the the initial results of bandwidth test measurements on the assembled SoM. Detailed description is given on the interfacing of the updated miniPET IP Core to the SoM, on the efficient data transfer method that implements device-to-device DMA transfer, and on the usage of User Datagram Protocol (UDP/IP) for high speed data transfer.
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