Targeting Stress-Response Pathways and Therapeutic Resistance in Head and Neck Cancer

Head and neck cancer is the sixth leading cancer worldwide; head and neck squamous cell carcinoma (HNSCC) accounts for more than 90% of incident cases. In the US, cases of HNSCC associated with human papillomavirus (HPV) have been growing in proportion amongst a younger demographic with superior outcomes to the same treatments, relative to cases associated with tobacco. Yet failures to improve the long-term prognosis of advanced HNSCC over the last three decades persist in part due to intrinsic and acquired mechanisms of resistance. Deregulation of the pathways to respond to stress, such as apoptosis and autophagy, often contributes to drug resistance and tumor progression. Here we review the stress-response pathways in drug response and resistance in HNSCC to explore strategies to overcome these resistance mechanisms. We focus on the mechanisms of resistance to current standard cares, such as chemotherapy (i.e., cisplatin), radiation, and cetuximab. Then, we discuss the strategies to overcome these resistances, including novel combinations and immunotherapy

A systematic review to identify areas of enhancements of pandemic simulation models for operational use at provincial and local levels

<p>Abstract</p> <p>Background</p> <p>In recent years, computer simulation models have supported development of pandemic influenza preparedness policies. However, U.S. policymakers have raised several <it>concerns </it>about the practical use of these models. In this review paper, we examine the extent to which the current literature already addresses these <it>concerns </it>and identify means of enhancing the current models for higher operational use.</p> <p>Methods</p> <p>We surveyed PubMed and other sources for published research literature on simulation models for influenza pandemic preparedness. We identified 23 models published between 1990 and 2010 that consider single-region (e.g., country, province, city) outbreaks and multi-pronged mitigation strategies. We developed a plan for examination of the literature based on the concerns raised by the policymakers.</p> <p>Results</p> <p>While examining the concerns about the adequacy and validity of data, we found that though the epidemiological data supporting the models appears to be adequate, it should be validated through as many updates as possible during an outbreak. Demographical data must improve its interfaces for access, retrieval, and translation into model parameters. Regarding the concern about credibility and validity of modeling assumptions, we found that the models often simplify reality to reduce computational burden. Such simplifications may be permissible if they do not interfere with the performance assessment of the mitigation strategies. We also agreed with the concern that social behavior is inadequately represented in pandemic influenza models. Our review showed that the models consider only a few social-behavioral aspects including contact rates, withdrawal from work or school due to symptoms appearance or to care for sick relatives, and compliance to social distancing, vaccination, and antiviral prophylaxis. The concern about the degree of accessibility of the models is palpable, since we found three models that are currently accessible by the public while other models are seeking public accessibility. Policymakers would prefer models scalable to any population size that can be downloadable and operable in personal computers. But scaling models to larger populations would often require computational needs that cannot be handled with personal computers and laptops. As a limitation, we state that some existing models could not be included in our review due to their limited available documentation discussing the choice of relevant parameter values.</p> <p>Conclusions</p> <p>To adequately address the concerns of the policymakers, we need continuing model enhancements in critical areas including: updating of epidemiological data during a pandemic, smooth handling of large demographical databases, incorporation of a broader spectrum of social-behavioral aspects, updating information for contact patterns, adaptation of recent methodologies for collecting human mobility data, and improvement of computational efficiency and accessibility.</p

Search for light bosons in decays of the 125 GeV Higgs boson in proton-proton collisions at root s=8 TeV

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Search for new physics with dijet angular distributions in proton-proton collisions at root S = 13 TeV

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Cross section measurement of t-channel single top quark production in pp collisions at root s=13 TeV

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Search for dijet resonances in proton-proton collisions at root s=13 TeV and constraints on dark matter and other models

Correction: DOI:10.1016/j.physletb.2017.09.029Peer reviewe

Measurement of vector boson scattering and constraints on anomalous quartic couplings from events with four leptons and two jets in proton-proton collisions at root s=13 TeV

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Characterisation of irradiated thin silicon sensors for the CMS phase II pixel upgrade

The high luminosity upgrade of the Large Hadron Collider, foreseen for 2026, necessitates the replacement of the CMS experiment's silicon tracker. The innermost layer of the new pixel detector will be exposed to severe radiation, corresponding to a 1 MeV neutron equivalent fluence of up to Phi(eq) = 2x10(16) cm(-2), and an ionising dose of approximate to 5 MGy after an integrated luminosity of 3000 fb(-1). Thin, planar silicon sensors are good candidates for this application, since the degradation of the signal produced by traversing particles is less severe than for thicker devices. In this paper, the results obtained from the characterisation of 100 and 200 mu m thick p-bulk pad diodes and strip sensors irradiated up to fluences of Phi(eq) = 1.3 x 10(16) cm(-2) are shown.Peer reviewe

Search for single production of vector-like quarks decaying into a b quark and a W boson in proton-proton collisions at root s=13 TeV

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