40 research outputs found

    Diagnosing pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 in daily practice

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    Background: In multiple endocrine neoplasia type 1 (MEN1), pancreatic neuroendocrine tumors (PanNETs) have a high prevalence and represent the main cause of death. This study aimed to assess the diagnostic accuracy of the currently used conventional pancreatic imaging techniques and the added value of fine needle aspirations (FNAs). Methods: Patients who had at least one imaging study were included from the population-based MEN1 database of the DutchMEN Study Group from 1990 to 2017. Magnetic resonance imaging (MRI), computed tomography (CT), endoscopic ultrasonography (EUS), FNA, and surgical resection specimens were obtained. The first MRI, CT, or EUS was considered as the index test. For a comparison of the diagnostic accuracy of MRI versus CT, patients with their index test taken between 2010 and 2017 were included. The reference standard consisted of surgical histopathology or radiological follow-up. ResultsA total of 413 patients (92.8% of the database) underwent 3,477 imaging studies. The number of imaging studies per patient increased, and a preference for MRI was observed in the last decade. Overall diagnostic accuracy was good with a positive (PPV) and negative predictive value (NPV) of 88.9% (95% confidence interval, 76.0-95.6) and 92.8% (89.4-95.1), respectively, for PanNET in the pancreatic head and 92.0% (85.3-96.0) and 85.3% (80.5-89.1), respectively, in the body/tail. For MRI, PPV and NPV for pancreatic head tumors were 100% (76.1-100) and 87.1% (76.3-93.6) and for CT, 60.0% (22.9-88.4) and 70.4% (51.3-84.3), respectively. For body/tail tumors, PPV and NPV were 91.3% (72.0-98.8) and 87.0% (75.3-93.9), respectively, for MRI and 100% (74.9-100) and 77.8% (54.3-91.5), respectively, for CT. Pathology confirmed a PanNET in 106 out of 110 (96.4%) resection specimens. FNA was performed on 34 lesions in 33 patients and was considered PanNET in 24 [all confirmed PanNET by histology (10) or follow-up (14)], normal/cyst/unrepresentative in 6 (all confirmed PanNET by follow-up), and adenocarcinoma in 4 (2 confirmed and 2 PanNET). Three patients, all older than 60 years, had a final diagnosis of pancreatic adenocarcinoma. Conclusion: As the accuracy for diagnosing MEN1-related PanNET of MRI was higher than that of CT, MRI should be the preferred (non-invasive) imaging modality for PanNET screening/surveillance. The high diagnostic accuracy of pancreatic imaging and the sporadic occurrence of pancreatic adenocarcinoma question the need for routine (EUS-guided) FNA

    Variable loss of functional activities of androgen receptor mutants in patients with androgen insensitivity syndrome

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    Androgen receptor (AR) mutations in androgen insensitivity syndrome (AIS) are associated with a variety of clinical phenotypes. The aim of the present study was to compare the molecular properties and potential pathogenic nature of 8 novel and 3 recurrent AR variants with a broad variety of functional assays. Eleven AR variants (p.Cys177Gly, p.Arg609Met, p.Asp691del, p.Leu701Phe, p.Leu723Phe, p.Ser741Tyr, p.Ala766Ser, p.Arg775Leu, p.Phe814Cys, p.Lys913X, p.Ile915Thr) were analyzed for hormone binding, transcriptional activation, cofactor binding, translocation to the nucleus, nuclear dynamics, and structural conformation. Ligand-binding domain variants with low to intermediate transcriptional activation displayed aberrant Kd values for hormone binding and decreased nuclear translocation. Transcriptional activation data, FxxFF-like peptide binding and DNA binding correlated well for all variants, except for p.Arg609Met, p.Leu723Phe and p.Arg775Leu, which displayed a relatively higher peptide binding activity. Variants p.Cys177Gly, p.Asp691del, p.Ala766Ser, p.Phe814Cys, and p.Ile915Thr had intermediate or wild type values in all assays and showed a predominantly nuclear localization in living cells. All transcriptionally inactive variants (p.Arg609Met, p.Leu701Phe, p.Ser741Tyr, p.Arg775Leu, p.Lys913X) were unable to bind to DNA and were associated with complete AIS. Three variants (p.Asp691del, p.Arg775Leu, p.Ile915Thr) still displayed significant functional activities in in vitro assays, although the clinical phenotype was associated with complete AIS. The data show that molecular phenotyping based on 5 different functional assays matched in most (70%) but not all cases. Copyrigh

    Geographical variation in abdominal colour pattern in Criorhina pachymera (Egger, 1858) (Diptera: Syrphidae)

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    The bee-mimicking hoverfly species Criorhina pachymera shows pronounced geographical variation in abdominal colour pattern. Based on 218 records from 22 European countries, we describe six abdomen forms divided over two main groups. Group A in western, northern and central parts of Europe contains abdomen forms A1–A3 with slender pollinose bands on the third and fourth tergite. Group B in south-eastern Europe contains forms B1–B3 with broad pollinose bands. These groups are separated by the Alps and the Carpathians, such as the separation of the original distributions of the two main postglacial recolonization lineages of honey bees in Europe. As these honey bee groups differ by the width of the pollinose bands on the third to fifth tergite, Batesian mimicry can explain the group distribution of C. pachymera with slender or broad pollinose bands. The different forms of C. pachymera in both groups are categorised by the extent of orange colouration on the second and third tergite. The darkest form A1, has a widespread distribution in Europe. Intermediate bright forms A2 and A3 occur predominantly in a belt along the southern margin of the group A distribution and in Sweden. Dark form B1 and intermediate bright form B2 occur on the Balkan peninsula and in neighbouring regions. The brightest form B3, is found in Italy, Switzerland (Ticino) and Greece. There is an average increase in the extent of orange colouration on the second and third tergite with decreasing geographical latitude, making temperature a likely additional cause for the described abdominal colour variation

    [Püha Katariina müstiline abielu]

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    http://tartu.ester.ee/record=b2439976~S1*es

    Demagnetization fault detection in axial flux PM machines by using sensing coils and an analytical model

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    In this paper, a method is proposed to detect asymmetrical demagnetization defects in single-stator double-rotor axial flux permanent magnet synchronous machines (AFPMSMs). Sensing coils back-EMF data and an analytical model are combined to solve an electromagnetic inverse problem. The method is validated with numerical and experimental data
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