714 research outputs found

    Die Welt der Huzulen in Ethnografie und Literatur

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    Die Huzulen sind ein Gebirgsvolk im Karpatengebiet der Westukraine. Ihre Lebenswelt zeichnet sich durch vielfĂ€ltige Traditionen, farbenfrohe Trachten und archaisches Brauchtum aus. Im 19. Jahrhundert wurde das Gebiet von Ethnografen bereist, die ihre Beobachtungen aufzeichneten. In den 1930er Jahren verfasste der polnische Schriftsteller StanisƂaw Vincenz seinen epischen Zyklus Na wysokiej poƂoninie, einer gelungenen Synthese von Ethnografie, Folklore und Fiktion. Der erste Band dieser Trilogie, Prawda starowieku, wurde in der vorliegenden Arbeit ethnografischen Texten der 2. HĂ€lfte des 19. Jahrhunderts von Izydor Kopernicki, Leopold Waigiel, Sofron Witwicki und Julian Celewicz gegenĂŒbergestellt. Themen aus den Bereichen Religion, Brauchtum, Architektur, Kleidung und Landwirtschaft, die von Ethnografen und dem Autor behandelt wurden, wurden dabei auf Übereinstimmungen und Unterschiede in der Darstellungsweise untersucht

    Starting to fill the gaps of the Selinus geophysical map

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    We analyze ground-penetrating radar (GPR) data which was recorded in the tight confined spaces of an overgrown sand dune. The topography of the dune has the same scale as the penetration depth. We developed a 3D topographic migration algorithm and enable the generation and interpretation of layer parallel depth slices

    An efficient procedure for protein extraction from formalin-fixed, paraffin-embedded tissues for reverse phase protein arrays

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    INTRODUCTION: Protein extraction from formalin-fixed paraffin-embedded (FFPE) tissues is challenging due to extensive molecular crosslinking that occurs upon formalin fixation. Reverse-phase protein array (RPPA) is a high-throughput technology, which can detect changes in protein levels and protein functionality in numerous tissue and cell sources. It has been used to evaluate protein expression mainly in frozen preparations or FFPE-based studies of limited scope. Reproducibility and reliability of the technique in FFPE samples has not yet been demonstrated extensively. We developed and optimized an efficient and reproducible procedure for extraction of proteins from FFPE cells and xenografts, and then applied the method to FFPE patient tissues and evaluated its performance on RPPA. RESULTS: Fresh frozen and FFPE preparations from cell lines, xenografts and breast cancer and renal tissues were included in the study. Serial FFPE cell or xenograft sections were deparaffinized and extracted by six different protein extraction protocols. The yield and level of protein degradation were evaluated by SDS-PAGE and Western Blots. The most efficient protocol was used to prepare protein lysates from breast cancer and renal tissues, which were subsequently subjected to RPPA. Reproducibility was evaluated and Spearman correlation was calculated between matching fresh frozen and FFPE samples. The most effective approach from six protein extraction protocols tested enabled efficient extraction of immunoreactive protein from cell line, breast cancer and renal tissue sample sets. 85% of the total of 169 markers tested on RPPA demonstrated significant correlation between FFPE and frozen preparations (p < 0.05) in at least one cell or tissue type, with only 23 markers common in all three sample sets. In addition, FFPE preparations yielded biologically meaningful observations related to pathway signaling status in cell lines, and classification of renal tissues. CONCLUSIONS: With optimized protein extraction methods, FFPE tissues can be a valuable source in generating reproducible and biologically relevant proteomic profiles using RPPA, with specific marker performance varying according to tissue type

    Patient-reported Experience of Diagnosis, Management, and Burden of Renal Cell Carcinomas : Results from a Global Patient Survey in 43 Countries

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    Funding/Support and role of the sponsor: This project was funded by equal unrestricted grants from Bristol-Myers Squibb, Ipsen Pharma, Novartis, and Pfizer according to the IKCC code of conduct governing corporate funding (ikcc.org). The sponsors were not involved in the design or analysis of the survey or approval of the final manuscript.Peer reviewedPublisher PD

    Exposure-response modeling of cabozantinib in patients with renal cell carcinoma : Implications for patient care

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    Cabozantinib is an oral tyrosine kinase inhibitor (TKI) approved for the treatment of patients with advanced renal cell carcinoma (RCC) at a dose of 60 mg/day. As with other TKIs, cabozantinib is associated with high interpatient variability in drug clearance and exposure that can significantly impact safety and tolerability across a patient population. To optimize cabozantinib exposure (maintaining efficacy and tolerability) for the individual, patients may require treatment interruption with dose reduction (40 mg/day and then 20 mg/day). In the pivotal Phase 3 METEOR trial, cabozantinib significantly improved overall survival, progression-free survival and the objective response rate compared with everolimus in patients with advanced RCC who had received previous treatment with a VEGFR TKI. Dose reductions were common for patients receiving cabozantinib (60%) but effective as only 9% discontinued treatment due to adverse events (AEs). In this review, we discuss pharmacometric analyses that evaluated the impact of cabozantinib dose on efficacy and safety outcomes during the METEOR study. Exposure-response models demonstrate that the risk of experiencing adverse events and dose reduction is increased in patients with low cabozantinib clearance versus typical clearance and decreased in patients with high clearance. Dose reduction of cabozantinib to manage AEs is predicted to have minimal impact on efficacy as AEs are more likely to occur in patients with low clearance and higher exposure to cabozantinib. These analyses further support a dose modification strategy to optimize cabozantinib exposure for individual patients

    Understanding the Impact of Belzutifan on Treatment Strategies for Patients with VHL

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    Belzutifan was recently approved for the management of Von Hippel–Lindau disease (VHL). Given the morbidity of recurrent treatment, systemic therapy to reduce or eliminate the need for surgery has been long-awaited. Herein, we sought to gain insight about future utilization by surveying VHL  experts in the United States. A survey developed by members of the VHL Alliance (VHLA) Clinical Advisory Council was distributed to kidney cancer providers at VHLA and National Comprehensive Cancer Network (NCCN) centers. Surveys were administered on a secure web-based platform. A total of 60 respondents from 29 institutions participated. Urologists (50%) and medical oncologists (43%) represented the majority of participants. The majority (98%) of respondents anticipated that belzutifan’s approval would signifi-cantly change the current treatment landscape. Most reported that therapy should be continuous (76%). There was a difference in willingness to prescribe belzutifan by specialty (38% of urologists vs 91% of medical oncologists (P = 0.02). In individuals with renal tumors &lt;3 cm, 36% would still recommend surveillance, while 36% would initiate belzutifan to prevent growth. In those with multifocal renal lesions and growth of a solitary tumor on belzutifan, 50% would proceed with only treatment of that site. In conclusion, VHL kidney cancer specialists anticipate a paradigm shift with the approval of belzutifan. Provider roles may change with movement away from surgical management. Opinions on treatment indications, such as when to initiate therapy and how to best salvage, vary widely and collaborative efforts among experts may assist in the development of clinical guidelines

    The safety and efficacy of sunitinib before planned nephrectomy in metastatic clear cell renal cancer

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    Background: The safety and efficacy of upfront sunitinib, before nephrectomy in metastatic clear cell renal cancer (mCRC), has not been prospectively evaluated
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