| 1. |
- van Akkooi, Alexander C. J., et al.
(author)
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Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC)
- 2022
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In: ANNALS OF SURGICAL ONCOLOGY. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 29:6, s. 3694-3708
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Journal article (peer-reviewed)abstract
- Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.
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| 2. |
- Benton, S., et al.
(author)
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Impact of Next-generation Sequencing on Interobserver Agreement and Diagnosis of Spitzoid Neoplasms
- 2021
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In: American Journal of Surgical Pathology. - : Ovid Technologies (Wolters Kluwer Health). - 0147-5185 .- 1532-0979. ; 45:12, s. 1597-1605
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Journal article (peer-reviewed)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. |
- Lemme, Max C., 1970-, et al.
(author)
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Complementary metal oxide semiconductor integration of epitaxial Gd(2)O(3)
- 2009
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In: Journal of Vacuum Science & Technology B. - : American Vacuum Society. - 1071-1023 .- 1520-8567. ; 27:1, s. 258-261
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Journal article (peer-reviewed)abstract
- In this paper, epitaxial gadolinium oxide (Gd(2)O(3)) is reviewed as a potential high-K gate dielectric, both "as deposited" by molecular beam epitaxy as well as after integration into complementary metal oxide semiconductor (CMOS) processes. The material shows promising intrinsic properties, meeting critical ITRS targets for leakage current densities even at subnanometer equivalent oxide thicknesses. These epitaxial oxides can be integrated into a CMOS platform by a "gentle" replacement gate process. While high temperature processing potentially degrades the material, a route toward thermally stable epitaxial Gd(2)O(3) gate dielectrics is explored by carefully controlling the annealing conditions.
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| 4. |
- McDonnell, J.J., et al.
(author)
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How old is streamwater? : Open questions in catchment transit time conceptualization, modelling and analysis
- 2010
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In: Hydrological Processes. - : John Wiley & Sons. - 0885-6087 .- 1099-1085. ; 24:12, s. 1745-1754
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Journal article (peer-reviewed)abstract
- The time water spends travelling subsurface through a catchment to the stream network (i.e. the catchment water transit time) fundamentally describes the storage, flow pathway heterogeneity and sources of water in a catchment. The distribution of transit times reflects how catchments retain and release water and solutes that in turn set biogeochemical conditions and affect contamination release or persistence. Thus, quan- tifying the transit time distribution provides an important constraint on biogeochemical processes and catchment sensitivity to anthropogenic inputs, contamination and land-use change. Although the assumptions and limitations of past and present transit time modelling approaches have been recently reviewed (McGuire and McDonnell, 2006), there remain many fundamental research challenges for understanding how transit time can be used to quantify catchment flow processes and aid in the development and testing of rainfall–runoff models. In this Commen- tary study, we summarize what we think are the open research questions in transit time research. These thoughts come from a 3-day workshop in January 2009 at the International Atomic Energy Agency in Vienna. We attempt to lay out a roadmap for this work for the hydrological commu- nity over the next 10 years. We do this by first defining what we mean (qualitatively and quantitatively) by transit time and then organize our vision around needs in transit time theory, needs in field studies of tran- sit time and needs in rainfall – runoff modelling. Our goal in presenting this material is to encourage widespread use of transit time information in process studies to provide new insights to catchment function and to inform the structural development and testing of hydrologic models.
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