Mediamusic (E-Journal)
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    Epithelioid hemangioma of bone harboring FOS and FOSB gene rearrangements:A clinicopathologic and molecular study

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    The diagnosis of epithelioid hemangioma (EH) remains challenging due to its rarity, worrisome histologic features, and locally aggressive clinical and radiographic presentation. Especially in the bone, EH can be misdiagnosed as a malignant vascular neoplasm due its lytic, often destructive or multifocal growth, as well as atypical morphology. The discovery of recurrent FOS and FOSB gene fusions in the pathogenesis of most EH has strengthened its stand-alone classification, distinct from other malignant epithelioid vascular lesions, such as epithelioid hemangioendothelioma or angiosarcoma. In this study we investigate a group of molecularly confirmed skeletal EH by the presence of FOS or FOSB gene rearrangements to better define its clinical and pathologic characteristics within a homogenous molecular subset. The cohort included 38 patients (25 males, 13 females), with a mean age at diagnosis of 38 years (range, 4-75). Regional, multifocal presentation was noted in 10 cases. Only six cases were correctly recognized as EH by the referring institutions, while most were misdiagnosed as other vascular tumors. Of the 17 patients with follow-up data available, five patients (29%) developed local recurrence after marginal en bloc excision (n = 3) or curettage (n = 2). Local recurrence-free survival rates were 84% at 3 years and 38% at 5 years. No metastasis or disease-related death was identified. Imaging studies exhibited no specific features, showing cortical bone destruction and soft-tissue extension in 14 (38%) cases. FOS gene rearrangements were detected in 28 (74%) of cases, while FOSB rearrangements in 10 (26%) cases. Our results highlight the significant challenges encountered in establishing a correct diagnosis exclusive of the molecular testing, mainly due to its overlap to other malignant epithelioid vascular tumors. Skeletal EH emerges as a genetically defined locally aggressive vascular neoplasm, with a high rate of local recurrence, but lacking the propensity for distant spread.</p

    Attaining full professor:Women's and men's experiences in medical education

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    INTRODUCTION: The underrepresentation of women among senior faculty in medical education is a longstanding problem. The purpose of this international qualitative investigation was to explore women and men's experiences of attaining full professorship and to investigate why women remain underrepresented among the senior faculty ranks.METHODS: Conducted within a social constructionist orientation, our qualitative study employed narrative analysis. Two female and two male participants working in medical education were recruited from five nations: Australia, Canada, Netherlands, United Kingdom, and United States. All participants held an MD and/or PhD. During telephone interviews, participants narrated the story of their careers. The five faculty members on the research team were also interviewed. Their narratives were included in analysis, rendering their experiences equal to those of the participants.RESULTS: 24 full professors working in medical education were interviewed (n=15 female, n=9 male). While some aspects were present across all narratives (i.e., personal events, career milestones, and facilitating/impeding factors), participants' experience of those aspects differed by gender. Men did not narrate fatherhood as a role navigated professionally, but women narrated motherhood as intimately connected to their professional roles. Both men and women narrated career success in terms of hard work and overcoming obstacles; however, male participants described promotion as inevitable, whereas women narrated promotion as a tenuous navigation of social structures towards uncertain outcomes. Female and male participants encountered facilitators and inhibitors throughout their careers but described acting on those experiences differently within the cultural contexts they faced.DISCUSSION: Our data suggest that female and male participants had different experiences of the work involved in achieving full professor status. Understanding these gendered experiences and their impact on career progression is an important advancement for better understanding what leads to the underrepresentation of women among senior faculty in medical education.</p

    Urinary excretion of epidermal growth factor and rapid loss of kidney function

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    BACKGROUND: Lower urinary excretion of the kidney tubule-specific biomarker epidermal growth factor (uEGF) is associated with increased risk of renal function [glomerular filtration rate (GFR)] loss in diabetes and in patients with established chronic kidney disease (CKD). We investigated whether uEGF is associated with rapid GFR decline or incident CKD in the general population.METHODS: Subjects without CKD or diabetes were recruited from the general population in Tromso, Norway [Renal Iohexol Clearance Survey (RENIS); N = 1249] and Groningen, the Netherlands [Prevention of REnal and Vascular END-stage disease (PREVEND); N = 4534], with a median follow-up of 5.6 and 7.4 years, respectively. GFR was measured by iohexol clearance in the RENIS and estimated using the CKD Epidemiology Collaboration creatinine-cystatin C equation in the PREVEND study. Rapid GFR decline was defined as an annual GFR loss &gt;3.0 mL/min/1.73 m2 and in sensitivity analyses as subjects with the 10% steepest GFR slope within each cohort.RESULTS: Lower baseline uEGF excretion was associated with rapid GFR loss in both cohorts {RENIS, odds ratio [OR] per 1 μg/mmol lower uEGF 1.42 [95% confidence interval (CI) 1.06-1.91], P = 0.02; PREVEND, OR 1.29 [95% CI 1.10-1.53], P &lt; 0.01}, adjusted for baseline GFR, albumin:creatinine ratio and conventional CKD risk factors. Similar results were obtained using the outcome of the 10% steepest GFR slope in each cohort. Lower uEGF levels were associated with incident CKD in the combined analysis of both cohorts.CONCLUSIONS: Lower uEGF levels are associated with increased risk of rapid GFR loss and incident CKD in the general population. This finding, together with previous findings in CKD and high-risk populations, supports that uEGF may serve as a broadly applicable biomarker representing the tubular component of the current glomerulus-centric clinical risk assessment system.</p

    The Citrullinated and MMP-degraded Vimentin Biomarker (VICM) Predicts Early Response to Anti-TNF alpha Treatment in Crohn's Disease

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    Background: In Crohn's disease (CD), 10% to 40% of patients do not respond to anti-tumor necrosis factor- (TNF) treatment. Currently, there are no biomarkers with adequate sensitivity to separate responders from nonresponders at an early stage. Aim: The aim of this study was to investigated whether early changes in the VICM (citrullinated and matrix metalloproteinase-degraded vimentin) biomarker were associated with response to anti-TNF treatment in patients with CD. Methods: Serum VICM levels were measured by ELISA in 2 independent cohorts of CD patients (n=42) treated with anti-TNF (infliximab or adalimumab). Response was determined by achieving clinical remission (Harvey Bradshaw Index&lt;5). Results: Compared with baseline, VICM serum levels were reduced by anti-TNF in the infliximab cohort (week 6 and 14) and in the adalimumab cohort (week 8). VICM was lower in the responders compared with the nonresponders [infliximab: Week 6, P&lt;0.05; area under the curve (AUC)=0.90; adalimumab: Week 1, P&lt;0.01 (AUC=0.91), and week 8, P&lt;0.05 (AUC=0.86)], and were able to predict response to treatment after 1 week of treatment with an odds ratio of 42.5. Conclusions: The VICM biomarker was time dependently reduced in CD patients responding to anti-TNF treatment. We suggest that VICM may be used as a marker for monitoring early response to anti-TNF in patients with CD.</p

    Archaeological features and absolute dating of historical road tracks in the North-western European Sand Belt. An interdisciplinary case study of a late medieval and early modern trade route at the Hoge Veluwe National Park (Central Netherlands)

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    It is very difficult to obtain absolute historical datings of road features found at archaeological excavations. Nevertheless, various physical dating methods are developed for this purpose, including Optical Stimulated Luminescence (OSL). After a small-scale archaeological campaign, samples from a medieval trading route in the Veluwe area (Central Netherlands) on sandy soils have been dated with OSL, in order to compare these with archaeological and historical data of the same route. The absolute datings of four wheel tracks of this so-called Harderwijkerweg appeared to correspond largely with the archaeological interpretations and historical sources (datings between the 13th and 17th centuries). The soil profiles also revealed new insights on the diachronical development of the excavated tracks. It was concluded that the combination of archaeological excavation, OSL dating and historical archive research could be a reliable method for the dating and contextualization of historical roads on Pleistocene sandy soils

    Low body weight and involuntary weight loss are associated with Raynaud's phenomenon in both men and women

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    Objectives: Low body weight is an easily assessable cause of Raynaud’s phenomenon (RP), and is frequently overlooked by clinicians. We aim to investigate the association of low body weight (body mass index &lt; 18.5 kg/m2), involuntary weight loss, and nutritional restrictions with the presence of RP. Method: Participants from the Lifelines Cohort completed a validated self-administered connective tissue disease questionnaire. Subjects who reported cold-sensitive fingers and biphasic or triphasic colour changes were considered to suffer from RP. Patient characteristics, anthropometric measurements, and nutritional habits were collected. Statistical analyses was stratified for gender. Results: Altogether, 93 935 participants completed the questionnaire. The prevalence of RP was 4.2% [95% confidence interval (CI) 4.1–4.4%], and was three-fold higher in women than in men (5.7% vs 2.1%, p &lt; 0.001). Subjects with RP had a significantly lower daily caloric intake than those without RP. Multivariate analysis, correcting for creatinine level, daily caloric intake, and other known aetiological factors associated with RP, revealed that low body weight [men: odds ratio (OR) 5.55 (95% CI 2.82–10.93); women: 3.14 (2.40–4.10)] and involuntary weight loss [men: OR 1.32 (1.17–1.48); women: 1.31 (1.20–1.44)] were significantly associated with the presence of RP. Low-fat diet was also associated with RP in women [OR 1.27 (1.15–1.44)]. Conclusion: Low body weight and prior involuntary weight loss are associated with an increased risk of RP in both men and women. This study emphasizes that low body weight and weight loss are easily overlooked risk factors for RP, and should be assessed and monitored in subjects with RP.</p

    Patterns of ectoparasite infection in wild-caught and laboratory-bred cichlid fish, and their hybrids, implicate extrinsic rather than intrinsic causes of species differences in infection

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    Parasite-mediated selection may initiate or enhance differentiation between host populations that are exposed to different parasite infections. Variation in infection among populations may result from differences in host ecology (thereby exposure to certain parasites) and/or intrinsic immunological traits. Species of cichlid fish, even when recently diverged, often differ in parasite infection, but the contributions of intrinsic and extrinsic causes are unknown. Here, we compare infection patterns between two closely related host species from Lake Victoria (genusPundamilia), using wild-caught and first-generation laboratory-reared fish, as well as laboratory-reared hybrids. Three of the commonest ectoparasite species observed in the wild were also present in the laboratory populations. However, the infection differences between the host species as observed in the wild were not maintained in laboratory conditions. In addition, hybrids did not differ in infection from either parental species. These findings suggest that the observed species differences in infection in the wild might be mainly driven by ecology-related effects (i.e. differential exposure), rather than by intrinsic species differences in immunological traits. Thus, while there is scope for parasite-mediated selection inPundamiliain the wild, it has apparently not yet generated divergent evolutionary responses and may not enhance assortative mating among closely related species.</p

    Every Word is a Name:Autonymy and Quotation in Augustine

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    Augustine famously claims every word is a name. Some readers take Augustine to thereby maintain a purely referentialist semantic account according to which every word is a referential expression whose meaning is its extension. Other readers think that Augustine is no referentialist and is merely claiming that every word has some meaning. In this paper, I clarify Augustine’s arguments to the effect that every word is a name and argue that ‘every word is a name’ amounts to the claim that for any word, there exist tokens of that word which are autonymous nouns. Augustine takes this to be the result of universal lexical ambiguity or equivocity (that is, the fact that every word has more than one literal meaning) and I clarify how Augustine’s account of metalinguistic discourse, which is one of the most detailed to have survived from antiquity, differs from some ancient and modern theories

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