Future perspectives in melanoma research: meeting report from the "Melanoma Bridge";: Napoli, December 3rd-6th 2014.

The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma

Recycled oceanic crust observed in plagioclase within the source of Mauna Loa Lavas

The hypothesis that mantle plumes contain recycled oceanic crust is now widely accepted. Some specific source components of the Hawaiian plume have been inferred to represent recycled oceanic basalts, pelagic sediments or oceanic gabbros. Bulk lava compositions, however, retain the specific trace- element fingerprint of the original crustal component in only a highly attenuated form. Here we report the discovery of exotic, strontium-enriched melt inclusions in Mauna Loa olivines. Their complete trace-element patterns strongly resemble those of layered gabbros found in ophiolites, which are characterized by cumulus plagioclase with very high strontium abundances. The major-element compositions of these melts indicate that their composition cannot be the result of the assimilation of present-day oceanic crust through which the melts have travelled. Instead, the gabbro has been transformed into a (high-pressure) eclogite by subduction and recycling, and this eclogite has then been incorporated into the Hawaiian mantle plume. The trace-element signature of the original plagioclase is present only as a 'ghost' signature, which permits specific identification of the recycled rock type. The 'ghost plagioclase' trace-element signature demonstrates that the former gabbro can retain much of its original chemical identity through the convective cycle without completely mixing with other portions of the former oceanic crust

Ovarian Tumor Characterization and Classification Using Ultrasound-A New Online Paradigm

Among gynecological malignancies, ovarian cancer is the most frequent cause of death. Image mining algorithms have been predominantly used to give the physicians a more objective, fast, and accurate second opinion on the initial diagnosis made from medical images. The objective of this work is to develop an adjunct computer-aided diagnostic technique that uses 3D ultrasound images of the ovary to accurately characterize and classify benign and malignant ovarian tumors. In this algorithm, we first extract features based on the textural changes and higher-order spectra information. The significant features are then selected and used to train and evaluate the decision tree (DT) classifier. The proposed technique was validated using 1,000 benign and 1,000 malignant images, obtained from ten patients with benign and ten with malignant disease, respectively. On evaluating the classifier with tenfold stratified cross validation, the DT classifier presented a high accuracy of 97 %, sensitivity of 94.3 %, and specificity of 99.7 %. This high accuracy was achieved because of the use of the novel combination of the four features which adequately quantify the subtle changes and the nonlinearities in the pixel intensity variations. The rules output by the DT classifier are comprehensible to the end-user and, hence, allow the physicians to more confidently accept the results. The preliminary results show that the features are discriminative enough to yield good accuracy. Moreover, the proposed technique is completely automated, accurate, and can be easily written as a software application for use in any compute

The impact of information security threat awareness on privacy-protective behaviors

In this study, we examine how to motivate computer users to protect themselves from potential security and privacy threats. We draw on the Information Processing framework which posits that threat mitigation commonly occurs before full cognitive threat assessment and we conduct an empirical study to evaluate the effects of an exposure to general information security threats on the strength of passwords and the disclosure of personal information. Through an online experiment, we compare immediate computer user reactions to potential non-individually specific security and privacy threats in an extra-organizational context. We find evidence consistent with automatic security and privacy protective actions in response to these threats. Computer users exposed to news stories about corporate security breaches limit the disclosure of sensitive personal information and choose stronger passwords. The study complements the existing behavior modification research in information security by providing the theoretical and empirical foundation for the exploration of automatic security and privacy threat mitigation strategies across different contexts