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1. Management of Melanoma Brain Metastases in the Era of Targeted Therapy

Author

Daniela Gonsalves Shapiro and Wolfram E. Samlowski

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Disseminated metastatic disease, including brain metastases, is commonly encountered in malignant melanoma. The classical treatment approach for melanoma brain metastases has been neurosurgical resection followed by whole brain radiotherapy. Traditionally, if lesions were either too numerous or surgical intervention would cause substantial neurologic deficits, patients were either treated with whole brain radiotherapy or referred to hospice and supportive care. Chemotherapy has not proven effective in treating brain metastases. Improvements in surgery, radiosurgery, and new drug discoveries have provided a wider range of treatment options. Additionally, recently discovered mutations in the melanoma genome have led to the development of “targeted therapy.” These vastly improved options are resulting in novel treatment paradigms for approaching melanoma brain metastases in patients with and without systemic metastatic disease. It is therefore likely that improved survival can currently be achieved in at least a subset of melanoma patients with brain metastases.

Published
2011
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3. High frequency of brain metastases after adjuvant therapy for high‐risk melanoma

Author

Samlowski, Wolfram E, Moon, James, Witter, Merle, Atkins, Michael B, Kirkwood, John M, Othus, Megan, Ribas, Antoni, Sondak, Vernon K, and Flaherty, Lawrence E

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Clinical Trials and Supportive Activities, Clinical Research, Cancer, Neurosciences, Prevention, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Antineoplastic Combined Chemotherapy Protocols, Brain Neoplasms, Cisplatin, Dacarbazine, Disease Progression, Disease-Free Survival, Female, Follow-Up Studies, Humans, Interferon alpha-2, Interferon-alpha, Lymph Nodes, Lymphatic Metastasis, Male, Melanoma, Neoplasm Staging, Recombinant Proteins, Retrospective Studies, Skin Neoplasms, Skin Ulcer, Survival Rate, Vinblastine, Biochemotherapy, brain metastases, interferon, lymph node metastases, melanoma, ulceration, Biochemistry and Cell Biology, Oncology and carcinogenesis
Abstract

The incidence of CNS progression in patients with high-risk regional melanoma (stages IIIAN2a-IIIC) is not well characterized. Data from the S0008 trial provided an opportunity to examine the role of CNS progression in treatment failure and survival. All patients were surgically staged. Following wide excision and full regional lymphadenectomy, patients were randomized to receive adjuvant biochemotherapy (BCT) or high-dose interferon alfa-2B (HDI). CNS progression was retrospectively identified from data forms. Survival was measured from date of CNS progression. A total of 402 eligible patients were included in the analysis (BCT: 199, HDI: 203). Median follow-up (if alive) was over 7 years (range: 1 month to 11 years). The site of initial progression was identifiable in 80% of relapsing patients. CNS progression was a component of systemic melanoma relapse in 59/402 patients (15% overall). In 34/402 patients (9%) CNS progression represented the initial site of treatment failure. CNS progression was a component of initial progression in 27% of all patients whose melanoma relapsed (59/221). The risk of CNS progression was highest within 3 years of randomization. The difference in CNS progression rates between treatment arms was not significant (BCT = 25, HDI = 34, P = 0.24). Lymph node macrometastases strongly associated with CNS progression (P = 0.001), while ulceration and head and neck primaries were not significant predictors. This retrospective analysis of the S0008 trial identified a high brain metastasis rate (15%) in regionally advanced melanoma patients. Further studies are needed to establish whether screening plus earlier treatment would improve survival following CNS progression.

Published
2017

4. Plant-derived products as antibiotic enhancers and antibiotic-resistance modifying agents

Author

Miron, A., Aelenei, P., Trifan, A., Rimbu, C.M., Horhogea, C.E., Luca, S.V., Neagu, A.N., Wolfram, E., Aprotosoaie, A.C., Miron, A., Aelenei, P., Trifan, A., Rimbu, C.M., Horhogea, C.E., Luca, S.V., Neagu, A.N., Wolfram, E., and Aprotosoaie, A.C.

Abstract

Combination of conventional antibiotics with natural products represents a promising strategy in overcoming antibiotic resistance. The aim of this work was to assess the interactions between plant-derived products and several antibiotics in order to identify potential synergistic antibacterial combinations. Both extracts and pure phytochemicals were included in this study. The effects of the combinations were evaluated against Gram-positive including methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria. Our studies on essential oils showed that coriander essential oil and its major constituent, linalool, acted synergistically with several antibiotics (oxacillin, gentamicin, tetracycline, ciprofloxacin) against both Gram-positive and Gram-negative bacteria with coriander essential oil reversing tetracycline resistance of Staphylococcus epidermitis [2]. Despite its moderate antibacterial activity, white mulberry leaf ethanolic extract was found to reverse oxacillin resistance of MRSA and to act synergistically with gentamicin against MRSA. Additionally, the extract showed synergy with gentamicin and tetracycline against Staphylococcus epidermitis [3]. Two of its constituents, namely morusin and kuwanon G, also reversed oxacillin resistance of MRSA and acted synergistically with gentamicin, tetracycline and ciprofloxacin against MRSA. Morusin also reversed tetracycline resistance of Staphylococcus epidermitis. Both morusin and kuwanon G increased the permeability of the bacterial membrane as shown by fluorescence and differential interference contrast microscopy. Conclusion: Plant-derived products are promising candidates for the development of novel treatment strategies in bacterial infections.

Published
2024

6. Quantum spin chains with frustration due to Dzyaloshinskii-Moriya interactions

Author

Hälg, Manuel, Lorenz, Wolfram E. A., Povarov, Kirill Yu., Månsson, Martin, Skourski, Yurii, and Zheludev, Andrey

Subjects
Condensed Matter - Strongly Correlated Electrons
Abstract

The properties of two quantum spin chain materials, K$_2$CuSO$_4$Cl$_2$ and K$_2$CuSO$_4$Br$_2$, are studied by a variety of experimental techniques, including bulk measurements, neutron spectroscopy and ESR. The hierarchy of relevant terms in the magnetic Hamiltonian is established. It is shown that these two compounds feature substantial Dzyaloshinskii-Moriya (DM) interactions that are uniform within each chain, but antiparallel in adjacent chains. The result is a peculiar type of frustration of inter-chain interactions, which leads to an unusual field-temperature phase diagram.

Published
2014
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7. A phase I, open-label study of trebananib combined with sorafenib or sunitinib in patients with advanced renal cell carcinoma.

Author

Hong, David S, Gordon, Michael S, Samlowski, Wolfram E, Kurzrock, Razelle, Tannir, Nizar, Friedland, David, Mendelson, David S, Vogelzang, Nicholas J, Rasmussen, Erik, Wu, Benjamin M, Bass, Michael B, Zhong, Zhandong D, Friberg, Gregory, and Appleman, Leonard J

Subjects
Humans, Carcinoma, Renal Cell, Kidney Neoplasms, Phenylurea Compounds, Niacinamide, Pyrroles, Indoles, Angiogenic Proteins, Recombinant Fusion Proteins, Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, Adult, Aged, Middle Aged, Female, Male, Biomarkers, Tumor, Sorafenib, Sunitinib, Angiogenesis, Angiopoietins, Targeted therapies, Tie2 receptor, Vascular growth factor receptor, Cancer, Clinical Research, Clinical Trials and Supportive Activities, Kidney Disease, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis
Abstract

BackgroundTrebananib, an investigational peptibody, binds to angiopoietin 1 and 2, thereby blocking their interaction with Tie2.Patients and methodsThis open-label phase I study examined trebananib 3 mg/kg or 10 mg/kg intravenous (I.V.) once weekly plus sorafenib 400 mg twice per day or sunitinib 50 mg once per day in advanced RCC. Primary end points were adverse event incidence and pharmacokinetics.ResultsThirty-seven patients were enrolled. During trebananib plus sorafenib administration (n = 17), the most common treatment-related adverse events (TRAEs) included rash (n = 12; 71%), diarrhea (n = 12; 71%), hypertension (n = 11; 65%), and fatigue (n = 11; 65%); grade ≥ 3 TRAEs (n = 7; 41%); and 2 patients (12%) had peripheral edema. During trebananib plus sunitinib administration (n = 19), the most common TRAEs included diarrhea (n = 14; 74%), fatigue (n = 13; 68%), hypertension (n = 11; 58%), and decreased appetite (n = 11; 58%); grade ≥ 3 TRAEs (n = 13; 68%); and 8 (42%) patients had peripheral edema. Trebananib did not appear to alter the pharmacokinetics of sorafenib or sunitinib. No patient developed anti-trebananib antibodies. Objective response rates were 29% (trebananib plus sorafenib) and 53% (trebananib plus sunitinib).ConclusionThe toxicities of trebananib 3 mg/kg or 10 mg/kg I.V. plus sorafenib or sunitinib in RCC were similar to those of sorafenib or sunitinib monotherapy, with peripheral edema being likely specific to the combinations. Antitumor activity was observed.

Published
2014

9. Beyond the First Offer: Decoding Negotiation Openings and their Impact on Economic and Subjective Outcomes

Author

Wolfram E. Lipp, Remigiusz Smolinski, and Peter Kesting

Subjects
Arts and Humanities (miscellaneous), Management of Technology and Innovation, Strategy and Management, General Social Sciences, General Decision Sciences
Abstract

First offers play a significant role in negotiations as they anchor negotiators’ perceptions and influence negotiation outcomes in favor of the first-offer proposer. However, negotiation is a joint decision-making process in which a first offer is typically succeeded by a counteroffer. The impact of a counteroffer has not yet been systematically researched. We propose that a counteroffer influences negotiation outcomes like a first offer. In addition, we conceptualize the “anchor zone” as the distance between the first offer and the counteroffer. We theorize that the anchor zone influences negotiation outcomes because it captures additional information compared to a single offer. To test our hypotheses, we conducted two studies: Study 1 was a vignette study (n = 190) in which participants reacted to a counteroffer that they received based on their first offer as part of a simulated negotiation. Study 2 was an online experiment (n = 212) in which participants negotiated by exchanging offers with no further communication. Our analysis suggests that the counteroffer is a significant predictor of economic outcomes. Thus, it works like a first offer, but with a lower impact. In addition, the anchor zone predicted how far the final agreement was from the first offer. Furthermore, we found that the third offer, the average concessions, and the number of offers mediated the effects of the counteroffer and anchor zone on economic outcomes. Finally, we discovered that a more aggressive counteroffer reduced the subjective value of both negotiators.

Published
2023

12. Saver-net uv-total solar irradiance monitoring network in Argentina

Author

Orte, Facundo, Wolfram, E., Luccini, Eduardo, D'Elia, R., Lusi, Anabela, Pallotta, J., Nollas, Fernando, Carmona, Facundo, Papandrea, Sebastián, Cabezas, Marcelo D., Carbajal Benítez, Gerardo, and Mizuno, Akira

Subjects
INDICE UV, Atmospheric Science, RED DE MONITOREO DE IRRADIANCIA, Saver-Net, RADIACION SOLAR
Abstract

Fil: Orte, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Unidad de Investigación y Desarrollo Estratégicos para la Defensa. Centro de Investigaciones en Láseres y Aplicaciones; Argentina Fil: Wolfram, E. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Wolfram, E. Servicio Meteorológico Nacional; Argentina Fil: Wolfram, E. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; Argentina Fil: Luccini, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina Fil: Luccini, Eduardo. Ponti cia Universidad Católica Argentina. Facultad de Química e Ingeniería del Rosario; Argentina Fil: D'Elia, R. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Lusi, Anabela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Orte, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Lusi, Anabela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Unidad de Investigación y Desarrollo Estratégicos para la Defensa. Centro de Investigaciones en Láseres y Aplicaciones; Argentina Fil: Pallotta, J. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Unidad de Investigación y Desarrollo Estratégicos para la Defensa. Centro de Investigaciones en Láseres y Aplicaciones; Argentina Fil: Nollas, Fernando. Servicio Meteorológico Nacional; Argentina Fil: Carmona, Facundo. Universidad Nacional del Centro de la Provincia de Buenos Aires. Instituto de Hidrología de Llanuras; Argentina Fil: Carmona, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Papandrea, Sebastián. Servicio Meteorológico Nacional; Argentina Fil: Cabezas, Marcelo D. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Unidad de Investigación y Desarrollo Estratégicos para la Defensa. Centro de Investigaciones en Láseres y Aplicaciones; Argentina Fil: Carbajal Benítez, Gerardo. Servicio Meteorológico Nacional; Argentina Fil: Mizuno, Akira. Universidad de Nagoya. Instituto de Investigación Ambiental Espacio-Tierra; Japón Resumen: El monitoreo simultáneo de la radiación solar localizada en diferentes rangos espectrales de banda ancha tiene varias ventajas importantes sobre el monitoreo aislado, tanto para la investigación básica como aplicada. Su integración en una red bajo protocolos estandarizados tiene a su vez valiosos beneficios, incluida la posibilidad de caracterizar geográficamente los niveles de radiación solar en grandes regiones. Recientemente, se ha desplegado en Argentina una red integrada de monitoreo de irradiancia solar UV-Total en 8 estaciones con nuevos instrumentos, sitios de medición y protocolos en el marco del proyecto Saver-Net (Japón, Argentina y Chile) llevado a cabo durante el período 2013- 2018. La red es administrada por el Servicio Meteorológico Nacional (SMN) de Argentina y el Instituto de Investigaciones Científicas y Técnicas para la Defensa (CITEDEF- UNIDEF). En este trabajo se describe la estructura y capacidad de la red y varios logros iniciales de la red argentina de monitoreo de irradiancia solar UV-Total con el objetivo de dar a conocer a la comunidad científica y poner a disposición estas bases de datos para su amplio uso en la investigación básica y aplicada. Además, se presenta la caracterización de los sitios donde se encuentra cada nodo de monitoreo de la red. Se observan valores extremos por encima de 1000 Wm−2 para la irradiancia solar Total, 60 Wm−2 para la irradiancia solar UVA e índices UV por encima de 9, aún en los sitios ubicados de la red Saver-Net ubicados más al sur, con su consecuente significancia en aplicaciones prácticas como la generación de energía solar e implicancias en la salud de las personas como el riesgo de contracción de eritema. Abstract: Simultaneous localized solar radiation monitoring in different broadband spectral ranges has several important advantages over isolated measurements for both basic and applied research. Its integration into a network under standardized protocols has, in turn, worthy benefits including the possibility to characterize geographically the solar radiation levels in large regions. Recently, an integrated UV-Total solar irradiance monitoring network has been deployed in Argentina in 8 stations with new instruments, measurement sites, and protocols into the frame of the Saver-Net project (Japan, Argentina, and Chile) carried out during the period 2013-2018. The network is managed by the Argentine Servicio Meteorol´ogico Nacional (SMN) and Instituto de Investigaciones Cient´ıficas y T´ecnicas para la Defensa (CITEDEFUNIDEF). In this paper, the structure, capability and several initial achievements of the Argentine UV-Total solar irradiance monitoring network are described with the aim to make these databases available to the scientific community for their broad use in basic and applied research. In addition, the irradiance characterization at each monitoring node of the network is presented. Extreme values over 1000 Wm−2 of Total solar irradiance, 60 Wm−2 of UVA solar irradiance and UV Index of 9 are registered even in the southernmost stations, with their consequent signification for the practical applications of the solar energy and health implications such as the risk to cause erythema.

Published
2022
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13. Renal Cell Cancer

Author

Wong, Bryan Y., Samlowski, Wolfram E., Shergill, I. S., editor, Arya, Manit, editor, Grange, Philippe R., editor, and Mundy, A.R., editor

Published
2010
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14. Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2

Author

Stenehjem, David D., Toole, Michael, Merriman, Joseph, Parikh, Kinjal, Daignault, Stephanie, Scarlett, Sarah, Esper, Peg, Skinner, Katherine, Udager, Aaron, Tantravahi, Srinivas Kiran, Gill, David, Straubhar, Alli M., Agarwal, Archana M., Grossmann, Kenneth F., Samlowski, Wolfram E., Redman, Bruce, Agarwal, Neeraj, and Alva, Ajjai

Published
2016
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20. Toward a Process Model of First Offers and Anchoring in Negotiations.

Author

Lipp, Wolfram E., Smolinski, Remigiusz, and Kesting, Peter

Subjects
NEGOTIATION, EVIDENCE gaps, ANCHORING effect, PERIODICAL articles
Abstract

There is a wide consensus that first offers have a significant impact on negotiation outcomes by causing an anchoring effect. Many aspects of first offers have been analyzed, including factors that lead to making the first offer and characteristics that strengthen the impact of first offers. However, a holistic view of the process of first offers in negotiations remains missing, and significant research gaps must be filled to fully understand the mechanisms of first offers. Furthermore, while extant research contains anecdotal advice for negotiators, no holistic overview of research findings has been presented to date. This study conducted a structured review of 119 journal articles published since 1967, contributing to the field in four main ways: (a) proposing a definition of first offers, (b) integrating previous findings into a process model of first offers in negotiation, (c) summarizing the results to date in a structured literature review, and (d) identifying crucial research gaps that must be addressed. Future research should conduct systematic investigations of the influence of first offers on negotiation outcomes, employing a "negotiation lens" to emphasize the dyadic and interactive character of negotiations. [ABSTRACT FROM AUTHOR]

Published
2023

21. Changes in the surface irradiance during the total solar eclipse 2020 in Valcheta, Argentina.

Author

Orte, P. F., Lajús, E. Fernández, Di Sisto, R. P., Wolfram, E. A., Lusi, A. R., Nicora, M. G., D'Elia, R. L., Verstraeten, F., Papandrea, S., and Carmona, F.

Subjects
TOTAL solar eclipses, SOLAR eclipses, ECLIPSES, WEATHER, SOLAR surface, SOLAR spectra
Abstract

On December 14, 2020, southern South America experienced a total solar eclipse close to the solar noon. The path of totality, about 90 km wide, extended over the continental region from the Chilean west coast to the Argentine east coast, passing through the provinces of Neuquén, Rio Negro and the extreme south of Buenos Aires. In order to study the effects on the atmosphere produced by the total eclipse, the Servicio Meteoroléogico Nacional Argentino (SMN) and Instituto de Investigaciones Cientéficas y Técnicas para la Defensa (CITEDEF) carried out a surface radiometric monitoring campaign in Valcheta (40.69°S; 66.15°W), Réo Negro, Argentina. In this work, we explore the global surface solar irradiance on a horizontal plane (GHI) with the main objective of quantifying the changes in this parameter for cloudy and clear sky atmospheric conditions, combining ground-based measurements and modeling. A solar limb-darkening function was successfully implemented in the calculation of the irradiance at the top of the atmosphere (TOA) during the eclipse. We estimated a significant GHI attenuation of 41 % between the first (C1) and last (C4) contacts of eclipse compared to similar atmospheric conditions without the total eclipse, which represent a daily reduction of 12 %. In terms of irradiation, a reduction of 3360.1 KJ/m2 3 was calculated. [ABSTRACT FROM AUTHOR]

Published
2023
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24. Hedgehog Inhibitor Induction with Addition of Concurrent Superficial Radiotherapy in Patients with Locally Advanced Basal Cell Carcinoma: A Case Series

Author

Joshua P. Weissman, Raul Meoz, and Wolfram E Samlowski

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Skin Neoplasms, medicine.medical_treatment, Vismodegib, Sonidegib, chemistry.chemical_compound, Internal medicine, medicine, Humans, Basal cell carcinoma, Hedgehog Proteins, Hedgehog, Retrospective Studies, business.industry, medicine.disease, Hedgehog signaling pathway, Radiation therapy, chemistry, Carcinoma, Basal Cell, Toxicity, medicine.symptom, Neoplasm Recurrence, Local, business, Muscle cramp, medicine.drug
Abstract

Background Locally advanced basal cell cancer is a rare and challenging clinical problem. Historically, these patients were treated with aggressive surgery or radiotherapy. Most sporadic basal cell carcinomas have somatic mutations in the hedgehog pathway. Oral hedgehog inhibitors induce rapid and often complete clinical responses in locally advanced basal cell tumors. Unfortunately, these responses are usually transient. We hypothesized that treatment failure represents persistence of drug resistant cells that could be eradicated by addition of localized radiotherapy. Materials and Methods We performed a retrospective review of our patients with locally advanced basal cell cancer treated with sonidegib or vismodegib induction therapy who were treated with added superficial radiotherapy at the time of maximal response. Results Twelve patients met inclusion criteria. All patients achieved a complete response following hedgehog inhibitor therapy with addition of radiotherapy. Progression-free survival at 40 months was 89%, with a median follow-up of 40 months. Relapses occurred in only 2 of 12 patients (16.6%). Nine patients experienced grade I–II toxicity from hedgehog inhibitor induction therapy (taste changes [3], weight loss [3], muscle cramps [3]). Eight patients experienced mild radiotherapy-induced skin toxicity during concurrent therapy. No patients had to discontinue treatment. Conclusion Induction therapy with hedgehog inhibitors followed by addition of concurrent radiation therapy resulted in an extremely high clinical response rate with relatively minor and reversible toxicity. This gave a high rate of progression-free survival and a low disease-specific progression rate. Further prospective evaluation of this treatment approach is needed to confirm the apparent clinical activity. Implications for Practice Locally advanced basal cell cancers are challenging to treat. Previously, aggressive surgical resection or radiotherapy represented the best treatment options. Most basal cell cancers have somatic mutations in the hedgehog pathway. Oral inhibitors of this pathway produce rapid but transient clinical responses. This study reports 12 patients treated with hedgehog inhibitor induction therapy to near-maximal response. Addition of concurrent involved field radiotherapy resulted in a very high complete response rate with minimal toxicity. There was prolonged progression-free survival in 90% of patients. This study identified a novel treatment approach for patients with advanced basal cell carcinoma.

Published
2021

26. Lalinet status - Station expansion and lidar ratio systematic measurements

Author

Universidad EAFIT. Departamento de Ciencias Básicas, Óptica Aplicada, Landulfo E., Lopes F., Moreira G.A., Da Silva J., Ristori P., Quel E., Otero L., Pallota J.V., Herrera M., Salvador J., Bali J.L., Wolfram E., Etala P., Barbero A., Forno R., Sanchez M.F., Barbosa H., Gouveia D., Santos A.V., Hoelzemann J., Fernandez J.H., Guedes A., Silva A., Barja B., Zamorano F., Legue R.P., Bastidas A., Zabala M.V., Velez J., Nisperuza D., Montilla E., Arredondo R.E., Marrero J.C.A., Vega A.R., Alados-Arboledas L., Guerrero-Rascado J.L., Sugimoto N., Yoshitaka J., Universidad EAFIT. Departamento de Ciencias Básicas, Óptica Aplicada, Landulfo E., Lopes F., Moreira G.A., Da Silva J., Ristori P., Quel E., Otero L., Pallota J.V., Herrera M., Salvador J., Bali J.L., Wolfram E., Etala P., Barbero A., Forno R., Sanchez M.F., Barbosa H., Gouveia D., Santos A.V., Hoelzemann J., Fernandez J.H., Guedes A., Silva A., Barja B., Zamorano F., Legue R.P., Bastidas A., Zabala M.V., Velez J., Nisperuza D., Montilla E., Arredondo R.E., Marrero J.C.A., Vega A.R., Alados-Arboledas L., Guerrero-Rascado J.L., Sugimoto N., and Yoshitaka J.

Abstract

LALINET is expanding regionally to guarantee spatial coverage over South and Central Americas. One of the network goals is to obtain a set of regional representative aerosol optical properties such as particle backscatter, extinction and lidar ratio. Given the North-South extension and influence of distinct airmass circulation patterns it is paramount to distinguish these optical parameters in order to gain better perfomance in radiation transfer models. A set of lidar ratio data is presented. © The Authors, published by EDP Sciences, 2018.

Published
2021

27. Expertinnen und Experten uneinig: Nach welchen Kriterien soll der Windenergieausbau in Deutschland räumlich verteilt werden? Experts disagree: Which criteria should guide the spatial allocation of wind power deployment in Germany?

Author

Lehmann, Paul, Ammermann, K., Gawel, Erik, Geiger, C., Hauck, J., Heilmann, J., Meier, J.-N., Ponitka, J., Schicketanz, S., Stemmer, B., Tafarte, P., Thrän, Daniela, Wolfram, E., Lehmann, Paul, Ammermann, K., Gawel, Erik, Geiger, C., Hauck, J., Heilmann, J., Meier, J.-N., Ponitka, J., Schicketanz, S., Stemmer, B., Tafarte, P., Thrän, Daniela, and Wolfram, E.

Abstract

Der Ausbau der Windenergie an Land verursacht räumliche Zielkonflikte, etwa zwischen der Minimierung von Stromsystemkosten, dem Anwohnerund Naturschutz oder der interregionalen Gerechtigkeit. Wo in Deutschland in welchem Umfang zukünftig Windräder installiert werden sollten, um die Energiewendeziele zu erreichen, hängt daher maßgeblich davon ab, wie diese Kriterien gewichtet werden. Die vorliegende Studie verdeutlicht mithilfe eines Planspiels, dass es unter Expertinnen und Experten keine allgemein akzeptierte Rangfolge von Kriterien für die räumliche Verteilung des Windenergieausbaus an Land gibt. Die Ergebnisse des Planspiels zeigen zudem, dass alle Expertinnen und Experten Gerechtigkeit bei der interregionalen Verteilung des Windenergieausbaus als wichtig erachten. Es bestehen jedoch unterschiedliche Vorstellungen darüber, wie genau interregionale Gerechtigkeit zu verstehen ist. Die Studienergebnisse unterstreichen einmal mehr die Wichtigkeit transparenter und partizipativer Verfahren für Standortentscheidungen bei der Windenergie an Land. The deployment of onshore wind energy involves spatial trade-offs, e. g. between the minimisation of energy system costs, the mitigation ofimpacts on humans and biodiversity, and interregional equity concerns. The weighting of these criteria is decisive to determine where wind turbines should be installed in the future to attain Germany's energy transition targets. The results of a simulation game played with experts illustrate that there is no unanimously agreed ranking of criteria to guide the spatial allocation of onshore wind energy. Experts agreed that interregional equity concerns should matter for the spatial allocation of wind turbines. However, they also revealed quite different understandings of what constitutes a spatially equitable interregional allocation. These results underpin once more the importance of transparent and participatory decision-making for onshore wind turbine siting decisions.

Published
2021

30. 220 Real-world outcomes of patients with resected stage IIIA melanoma treated with adjuvant nivolumab

Author

Wolfram E. Samlowski, Robert Nicholas, Anthony Salvatore, Jonathan Rajkumar, Tayla Poretta, Esmond D. Nwokeji, Andriy Moshyk, and Brian Stwalley

Subjects
Oncology, medicine.medical_specialty, Performance status, business.industry, Melanoma, Sentinel lymph node, Ipilimumab, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, lcsh:RC254-282, Internal medicine, Cutaneous melanoma, Adjuvant therapy, Medicine, Nivolumab, business, Cancer staging, medicine.drug
Abstract

Background Nivolumab is approved in the US and EU for the adjuvant treatment of resected stage III-IV melanoma based on results from the CheckMate-238 clinical trial.1,2 However, the trial did not enroll any patients with Stage IIIA disease per the American Joint Committee on Cancer (AJCC) 7th edition criteria and included a limited number of patients with stage IIIA disease per the AJCC 8th edition.3,4,5Recognizing the need for real-world data to assess outcomes of patients with resected stage IIIA melanoma treated with adjuvant nivolumab, a non-interventional study was conducted to investigate treatment patterns and outcomes among patients receiving adjuvant nivolumab within the US community practice setting. Methods A retrospective analysis of the US Oncology Network’s iKnowMed medical data was conducted to examine patients with resected stage IIIA melanoma treated with adjuvant nivolumab between 01-Jan-2018 and 31-Dec-2019 with a follow-up period through 31-Mar-2020. Patients were followed for up to 27 months after their sentinel lymph node biopsy. Baseline demographic/clinical characteristics and treatment patterns were examined descriptively. Duration of treatment (DOT) and overall survival were analyzed using the Kaplan-Meier method. Results A total of 58 patients with stage IIIA melanoma treated with adjuvant nivolumab were identified. Median age was 57.8 years (range 21.5–93.5), 62.1% were male, and 75.9% were Caucasian. Among patients with a documented Eastern Cooperative Oncology Group (ECOG) performance status (51.7%), all had an ECOG score of 0 or 1. Median follow-up time was 12.6 months (range 0.3–25.1). Median DOT was 10.6 months (range 6.8–12.0). Overall survival rates at 12 and 24 months were 97.7% (95% CI 84.6–99.7) and 92.2% (95% CI 69.6–98.2), respectively. Conclusions This real-world analysis of patients with stage IIIA melanoma treated with adjuvant nivolumab showed that a large proportion of patients were alive at the end of the study period, suggesting these patients have a favorable prognosis. Further investigation and follow-up is warranted to assess clinically relevant outcomes among patients with resected stage IIIA melanoma. Ethics Approval The study was approved by US Oncology Inc’s Institutional Review Board, approval number 20-020E-2020-0224-01. References Weber J, Mandala M, Del Vecchio M, et al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. NEJM 2017;377:1824–35. Weber J, Mandala M, Del Vecchio M, et al. Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: A randomized, double-blind, phase 3 trial (CheckMate 238). Ann Oncol 2017;28(5):632–33. Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009;27(36):6199–6206. Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 2017;67(6):472–492. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Cutaneous Melanoma Version 3.2020 - May 18, 2020. 2020.

Published
2020
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31. Comparison of OMI-DOAS total ozone column with ground-based measurements in Argentina

Author

Orte, P. F., Luccini, E., Wolfram, E., Nollas, F., Pallotta, J., D'Elia, R., Carbajal, G., Mbatha, N., Hlongwane, N., Orte, P. F., Luccini, E., Wolfram, E., Nollas, F., Pallotta, J., D'Elia, R., Carbajal, G., Mbatha, N., and Hlongwane, N.

Abstract

[EN] Total ozone column (TOC) measurements through the Ozone Monitoring Instrument (OMI/NASA EOSAura) are compared with ground-based observations made using Dobson and SAOZ instruments for the period 2004–2019 and 2008–02/2020, respectively. The OMI data were inverted using the Differential Optical Absorption Spectroscopy algorithm (overpass OMI-DOAS). The four ground-based sites used for the analysis are located in subpolar and subtropical latitudes spanning from 34°S to 54°S in the Southern Hemisphere, in the Argentine cities of Buenos Aires (34.58°S, 58.36°W; 25 m a.s.l.), Comodoro Rivadavia (45.86°S, 67.50°W; 46 m a.s.l.), Río Gallegos (51.60°S, 69.30°W; 72 m a.s.l.) and Ushuaia (54.80°S, 68.30°W; 14 m a.s.l.). The linear regression analyzes showed correlation values greater than 0.90 for all sites. The OMI measurements revealed an overestimation of less than 4 % with respect to the Dobson instruments, while the comparison with the SAOZ instrument presented a very low underestimation of less than 1 %., [ES] En este trabajo se comparan mediciones de columna total de ozono (CTO) del Ozone Monitoring Instrument (OMI/NASA EOS-Aura), con observaciones terrestres de instrumentos Dobson y SAOZ para el periodo 2004–2019 y 2008–02/2020, respectivamente. Los datos del OMI analizados fueron los invertidos mediante el algoritmo Differential Optical Absorption Spectroscopy (overpass OMI-DOAS). Las 4 estaciones terrestres están ubicadas en latitudes subpolares y subtropicales del Hemisferio Sur, en las ciudades argentinas de Buenos Aires (34,58°S, 58,36°O; 25 m s.n.m.), Comodoro Rivadavia (45,86°S, 67,50°O; 46 m s.n.m.), Río Gallegos (51,60°S, 69,30°O; 72 m s.n.m.) y Ushuaia (54,80°S, 68,30°O; 14 m s.n.m.) cubriendo un rango latitudinal desde los 34°S hasta los 54°S. Los análisis de regresión lineal presentan valores de correlación superior a 0,90. Las mediciones OMI– DOAS muestran una sobrestimación menor al 4 % respecto de los instrumentos Dobson, mientras que la comparación respecto al instrumento SAOZ presenta una muy baja subestimación, menor al 1 %.

Published
2020

32. Cystoseira barbata C. Agardh from Romanian Black Sea coast : phlorotannins profile, in vitro antioxidant and antiproliferative potential

Author

Trifan, A, Luca, SV, Wolfram, E, Vasincu, A, Opitz, EWS, Aprotosoaie, AC, Miron, A, Jitareanu, A, Neophytou, C, Constantinou, IA, Trifan, A, Luca, SV, Wolfram, E, Vasincu, A, Opitz, EWS, Aprotosoaie, AC, Miron, A, Jitareanu, A, Neophytou, C, and Constantinou, IA

Abstract

The Romanian Black Sea has abundant seaweed resources, but little effort has been done to screen their biological potential. The aim of the present study was to assess the in vitro antioxidant and antiproliferative activities of Cystoseira barbata Sargassaceae a brown alga inhbiting the costal line of Romanian Black Sea. 70% acetone, methanol and water were used for the extraction of the algal material. The antioxidant activity of C. barbata extracts was assessed by DPPH and ABTS radicals scavenging assays, reducing power and 15-lipoxygenase inhibition assays. Cytotoxic activity of the extracts was determined by MTT viability assay using three adenocarcinoma cell lines (mammary MCF-7, alveolar A549 and colorectal HT-29). The effect of the extracts in cell cycle distribution was evaluated using flow cytometry (FACS) [1],[2]. 70% acetone extract exhibited the highest antioxidant activities in all assays, with IC50 values comparable or higher than those of known antioxidants. The antitumor tests showed that 70% acetone extract had the most potent antiproliferative effects. MCF-7 was the most sensitive of all cell lines examined. FACS analysis revealed that the 70% acetone extract induced a significant increase in the subG1 fraction in MCF-7 and A549 cells, indicative of apoptosis induction. From these findings, the 70% acetone extract was investigated by HPLC-DAD-QTOF-ESI-MS/MS [3]; phlorotannins with molecular weights ranging from 375 to 870 Da were tentatively identified on the basis of their characteristic MS/MS fragmentation pattern. In conclusion, Cystoseira barbata represents an important source of bioactive compounds, with potential use in food and pharmaceutical industries.

Published
2020

38. A nonpeptidyl mimic of superoxide dismutase, M40403, inhibits dose-limiting hypotension associated with interleukin-2 and increases its antitumor effects

Author

Samlowski, Wolfram E, Petersen, Ryan, Cuzzocrea, Salvatore, Macarthur, Heather, Burton, Damali, McGregor, John R, and Salvemini, Daniela

Abstract

Interleukin-2 (IL-2) is used to treat metastatic renal cell carcinoma and malignant melanoma, but its use is limited by the severe hypotension it produces. We have shown here that M40403, a superoxide dismutase (SOD) mimetic, blocked IL-2-induced hypotension and allowed the dose of IL-2 to be increased in mice. The reversal of IL-2-mediated hypotension was associated with an increase in plasma catecholamines. In addition, M40403 increased lymphokine-activated killer (LAK) cell cytotoxicity in vitro and in vivo, through inhibition of macrophage superoxide production. Treatment of methylcholanthrene-induced (Meth A) ascites tumors with IL-2 and [greater than or equal to]3 mg per kg body weight M40403 induced 50% complete remissions lasting for more than 200 d, which was longer than those of untreated mice (15-d median survival) or mice treated with IL-2 alone (22-d median). Growth of subcutaneous implants of RENCA renal carcinoma was also inhibited by the combination of IL-2 and M40403. These results established that M40403 prevented IL-2 from causing dose-limiting hypotension, while enhancing its anticancer activity., Author(s): Wolfram E Samlowski [1]; Ryan Petersen [1]; Salvatore Cuzzocrea [2]; Heather Macarthur [3]; Damali Burton [1]; John R McGregor [1]; Daniela Salvemini (corresponding author) [4] IL-2, a cytokine synthesized [...]

Published
2003
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43. Ultrafast dynamics of cyclohexene and cyclohexene-d10 excited at 200 nm

Author

Fuss, Werner, Schmid, Wolfram E., and Trushin, Sergei A.

Subjects
Collisional excitation -- Research, Photochemical research -- Analysis, Chemistry
Abstract

Research into the femtosecond dynamics of cyclohexene and its fully deuterated isotopomer following excitation at 200 nm in the gas phase at room temperature is presented. The fragmentation pattern indicated that butadiene is not formed until at least 500 ps, with the retro-Diels-Alder reaction therefore only arising later.

Published
2001

49. High frequency of brain metastases after adjuvant therapy for high‐risk melanoma

Author

Wolfram E. Samlowski, Antoni Ribas, Lawrence E. Flaherty, Vernon K. Sondak, John M. Kirkwood, Megan Othus, Michael B. Atkins, Merle Witter, and James C. Moon

Subjects
Oncology, Male, Cancer Research, Skin Neoplasms, medicine.medical_treatment, 0302 clinical medicine, brain metastases, Antineoplastic Combined Chemotherapy Protocols, 030212 general & internal medicine, Cancer, Original Research, Brain Neoplasms, Melanoma, interferon, Recombinant Proteins, 3. Good health, Dacarbazine, Survival Rate, 6.1 Pharmaceuticals, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Disease Progression, Female, medicine.drug, lymph node metastases, medicine.medical_specialty, Clinical Trials and Supportive Activities, Oncology and Carcinogenesis, Alpha interferon, Interferon alpha-2, Vinblastine, Disease-Free Survival, 03 medical and health sciences, Rare Diseases, Clinical Research, Internal medicine, Biochemotherapy, Skin Ulcer, medicine, Adjuvant therapy, melanoma, Humans, Radiology, Nuclear Medicine and imaging, Survival rate, Neoplasm Staging, Retrospective Studies, business.industry, Prevention, Neurosciences, Evaluation of treatments and therapeutic interventions, Clinical Cancer Research, Interferon-alpha, Retrospective cohort study, medicine.disease, Surgery, ulceration, Lymphadenectomy, Biochemistry and Cell Biology, Lymph Nodes, Cisplatin, business, Brain metastasis, Follow-Up Studies
Abstract

The incidence of CNS progression in patients with high-risk regional melanoma (stages IIIAN2a-IIIC) is not well characterized. Data from the S0008 trial provided an opportunity to examine the role of CNS progression in treatment failure and survival. All patients were surgically staged. Following wide excision and full regional lymphadenectomy, patients were randomized to receive adjuvant biochemotherapy (BCT) or high-dose interferon alfa-2B (HDI). CNS progression was retrospectively identified from data forms. Survival was measured from date of CNS progression. A total of 402 eligible patients were included in the analysis (BCT: 199, HDI: 203). Median follow-up (if alive) was over 7years (range: 1month to 11years). The site of initial progression was identifiable in 80% of relapsing patients. CNS progression was a component of systemic melanoma relapse in 59/402 patients (15% overall). In 34/402 patients (9%) CNS progression represented the initial site of treatment failure. CNS progression was a component of initial progression in 27% of all patients whose melanoma relapsed (59/221). The risk of CNS progression was highest within 3years of randomization. The difference in CNS progression rates between treatment arms was not significant (BCT=25, HDI=34, P=0.24). Lymph node macrometastases strongly associated with CNS progression (P=0.001), while ulceration and head and neck primaries were not significant predictors. This retrospective analysis of the S0008 trial identified a high brain metastasis rate (15%) in regionally advanced melanoma patients. Further studies are needed to establish whether screening plus earlier treatment would improve survival following CNS progression.

Published
2017

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