329 research outputs found

    What is New in Melanoma Genetics and Treatment?

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    New therapies for advanced melanoma have led to major advances, which, for the first time, showed improved survival for patients with this very challenging neoplasm. These new treatments are based on gene-targeted therapies or stimulation of immune responses. However, these treatments are not without challenges in terms of resistance and toxicity. Physicians should be aware of these side effects as prompt treatment may save lives. Melanoma genetics is also unravelling new genetic risk factors involving telomere genes as well as new gene pathways at the somatic level which may soon become therapeutic targets. It is also shedding new light onto the pathology of this tumour with links to neural diseases and longevity

    "Too many goddamn echoes": historicizing the Iraq War in Don DeLillo's Point Omega

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    This piece provides a detailed engagement with Don DeLillo's depiction of the 2003 Iraq war in his latest novel, Point Omega. Framed through both formal aesthetic signposting of the interrelations between modernist and postmodernist practice and also through explicit thematic comparison between the conflicts, I trace DeLillo's treatment of Iraq in Point Omega back to his earlier writing on the Cold War in Underworld and focus upon the ways in which this comparative historical metaphor can be read with particular emphasis upon its implications for the nation state

    Sea-level rise: from global perspectives to local services

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    Coastal areas are highly diverse, ecologically rich, regions of key socio-economic activity, and are particularly sensitive to sea-level change. Over most of the 20th century, global mean sea level has risen mainly due to warming and subsequent expansion of the upper ocean layers as well as the melting of glaciers and ice caps. Over the last three decades, increased mass loss of the Greenland and Antarctic ice sheets has also started to contribute significantly to contemporary sea-level rise. The future mass loss of the two ice sheets, which combined represent a sea-level rise potential of ∌65 m, constitutes the main source of uncertainty in long-term (centennial to millennial) sea-level rise projections. Improved knowledge of the magnitude and rate of future sea-level change is therefore of utmost importance. Moreover, sea level does not change uniformly across the globe and can differ greatly at both regional and local scales. The most appropriate and feasible sea level mitigation and adaptation measures in coastal regions strongly depend on local land use and associated risk aversion. Here, we advocate that addressing the problem of future sea-level rise and its impacts requires (i) bringing together a transdisciplinary scientific community, from climate and cryospheric scientists to coastal impact specialists, and (ii) interacting closely and iteratively with users and local stakeholders to co-design and co-build coastal climate services, including addressing the high-end risks

    Eradication of peste des petits ruminants virus and the wildlife-livestock interface

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    Growing evidence suggests that multiple wildlife species can be infected with peste des petits ruminants virus (PPRV), with important consequences for the potential maintenance of PPRV in communities of susceptible hosts, and the threat that PPRV may pose to the conservation of wildlife populations and resilience of ecosystems. Significant knowledge gaps in the epidemiology of PPRV across the ruminant community (wildlife and domestic), and the understanding of infection in wildlife and other atypical host species groups (e.g., camelidae, suidae, and bovinae) hinder our ability to apply necessary integrated disease control and management interventions at the wildlife-livestock interface. Similarly, knowledge gaps limit the inclusion of wildlife in the FAO/OIE Global Strategy for the Control and Eradication of PPR, and the framework of activities in the PPR Global Eradication Programme that lays the foundation for eradicating PPR through national and regional efforts. This article reports on the first international meeting on, “Controlling PPR at the livestock-wildlife interface,” held in Rome, Italy, March 27–29, 2019. A large group representing national and international institutions discussed recent advances in our understanding of PPRV in wildlife, identified knowledge gaps and research priorities, and formulated recommendations. The need for a better understanding of PPRV epidemiology at the wildlife-livestock interface to support the integration of wildlife into PPR eradication efforts was highlighted by meeting participants along with the reminder that PPR eradication and wildlife conservation need not be viewed as competing priorities, but instead constitute two requisites of healthy socio-ecological systems

    Tristetraprolin regulates interleukin‐6, which is correlated with tumor progression in patients with head and neck squamous cell carcinoma

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    BACKGROUND: Tumor‐derived cytokines play a significant role in the progression of head and neck squamous cell carcinoma (HNSCC). Targeting proteins, such as tristetraprolin (TTP), that regulate multiple inflammatory cytokines may inhibit the progression of HNSCC. However, TTP's role in cancer is poorly understood. The goal of the current study was to determine whether TTP regulates inflammatory cytokines in patients with HNSCC. METHODS: TTP messenger RNA (mRNA) and protein expression were determined by quantitative real‐time–polymerase chain reaction (Q‐RT‐PCR) and Western blot analysis, respectively. mRNA stability and cytokine secretion were evaluated by quantitative RT‐PCR and enzyme‐linked immunoadsorbent assay, respectively, after overexpression or knockdown of TTP in HNSCC. HNSCC tissue microarrays were immunostained for interleukin‐6 (IL‐6) and TTP. RESULTS: TTP expression in HNSCC cell lines was found to be inversely correlated with the secretion of IL‐6, vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE 2 ) . Knockdown of TTP increased mRNA stability and the secretion of cytokines. Conversely, overexpression of TTP in HNSCC cells led to decreased secretion of IL‐6, VEGF, and PGE 2 . Immunohistochemical staining of tissue microarrays for IL‐6 demonstrated that staining intensity is prognostic for poor disease‐specific survival ( P = .023), tumor recurrence and development of second primary tumors ( P = .014), and poor overall survival ( P = .019). CONCLUSIONS: The results of the current study demonstrated that down‐regulation of TTP in HNSCC enhances mRNA stability and promotes secretion of IL‐6, VEGF, and PGE 2 . Furthermore, high IL‐6 secretion in HNSCC tissue is a biomarker for poor prognosis. In as much as enhanced cytokine secretion is associated with poor prognosis, TTP may be a therapeutic target to reduce multiple cytokines concurrently in patients with HNSCC. Cancer 2011. © 2011 American Cancer Society. Tristetraprolin (TTP), a protein that decreases the stability of messenger RNA (mRNA) of cytokines and proinflammatory factors, is reduced in patients with head and neck squamous cell carcinoma with a corresponding increase in interleukin‐6 (IL‐6), vascular endothelial growth factor, and cyclooxygenase‐2 secretion. One of these tumor‐derived cytokines, IL‐6, is prognostic for poor disease‐specific survival, tumor recurrence, second primary lesions, and poor overall survival.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86915/1/25859_ftp.pd

    The evolving field of Dermato-oncology and the role of dermatologists: Position Paper of the EADO, EADV and Task Forces, EDF, IDS, EBDV-UEMS and EORTC Cutaneous Lymphoma Task Force.

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    BACKGROUND The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. OBJECTIVE Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology. DISCUSSION Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients. CONCLUSION Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology

    Sea-level rise: From global perspectives to local services

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    Coastal areas are highly diverse, ecologically rich, regions of key socio-economic activity, and are particularly sensitive to sea-level change. Over most of the 20th century, global mean sea level has risen mainly due to warming and subsequent expansion of the upper ocean layers as well as the melting of glaciers and ice caps. Over the last three decades, increased mass loss of the Greenland and Antarctic ice sheets has also started to contribute significantly to contemporary sea-level rise. The future mass loss of the two ice sheets, which combined represent a sea-level rise potential of ∌65 m, constitutes the main source of uncertainty in long-term (centennial to millennial) sea-level rise projections. Improved knowledge of the magnitude and rate of future sea-level change is therefore of utmost importance. Moreover, sea level does not change uniformly across the globe and can differ greatly at both regional and local scales. The most appropriate and feasible sea level mitigation and adaptation measures in coastal regions strongly depend on local land use and associated risk aversion. Here, we advocate that addressing the problem of future sea-level rise and its impacts requires (i) bringing together a transdisciplinary scientific community, from climate and cryospheric scientists to coastal impact specialists, and (ii) interacting closely and iteratively with users and local stakeholders to co-design and co-build coastal climate services, including addressing the high-end risks
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