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Novel algorithmic approach predicts tumor mutation load and correlates with immunotherapy clinical outcomes using a defined gene mutation set

BACKGROUND: While clinical outcomes following immunotherapy have shown an association with tumor mutation load using whole exome sequencing (WES), its clinical applicability is currently limited by cost and bioinformatics requirements. METHODS: We developed a method to accurately derive the predicted total mutation load (PTML) within individual tumors from a small set of genes that can be used in clinical next generation sequencing (NGS) panels. PTML was derived from the actual total mutation load (ATML) of 575 distinct melanoma and lung cancer samples and validated using independent melanoma (n = 312) and lung cancer (n = 217) cohorts. The correlation of PTML status with clinical outcome, following distinct immunotherapies, was assessed using the Kaplan–Meier method. RESULTS: PTML (derived from 170 genes) was highly correlated with ATML in cutaneous melanoma and lung adenocarcinoma validation cohorts (R(2) = 0.73 and R(2) = 0.82, respectively). PTML was strongly associated with clinical outcome to ipilimumab (anti-CTLA-4, three cohorts) and adoptive T-cell therapy (1 cohort) clinical outcome in melanoma. Clinical benefit from pembrolizumab (anti-PD-1) in lung cancer was also shown to significantly correlate with PTML status (log rank P value < 0.05 in all cohorts). CONCLUSIONS: The approach of using small NGS gene panels, already applied to guide employment of targeted therapies, may have utility in the personalized use of immunotherapy in cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-016-0705-4) contains supplementary material, which is available to authorized users

Judging Social Welfare Policy with the Solving of the Bargaining Problem

Current analysis addresses an apparently critical issue of wealth circulation in the society. We try to play a game with the welfare- related burden of taxation. Thus, the Negotiator No.1 stands up for citizens legal and moral rights to social services. The Negotiator No.2 proceeds from the needs of citizens for the provision of public goods. Quite the opposite, the Player, hereinafter called No.3, gives the private consumption a preference over social services and public goods, i.e., the citizens-taxpayers try to reduce their income taxes to be deposited in the tax pool – a common account of negotiators No.1 and No.2. In fact, the voters-citizens in the role of Player No.3, try to fulfil their expectations about taxes by a threat to acknowledge or to reject the bargaining agreement, e.g. a welfare committee must approve a motion against high taxes by unanimous vote. The government assesses and controls the wealth circulation by poverty line parameter. We provide an evidence for claim that 50% median income is an ideal choice of poverty line within the scope of given terms and conditions.: bargaining, decision, public goods, taxation, voting

A Survey on Personalized Recommendation Techniques

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Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab

Natalizumab is a monoclonal antibody that binds CD49d. Although it is one of the most effective treatments for Relapsing-Remitting Multiple Sclerosis (RRMS), a dosing regimen has not been optimized for safety and efficacy in individual patients. We aimed to identify biomarkers to monitor Natalizumab treatment and to establish a personalized dose utilizing an ongoing longitudinal study in 29 RRMS patients under Natalizumab with standard interval dose (SD) of 300 mg/4 wks or extended interval dose (EID) of 300 mg/6 wks. Blood samples were analyzed by flow cytometry to determine CD49d saturation and expression in several T and B lymphocytes subpopulations. Each patient was analyzed at two different timepoints separated by 3 Natalizumab administrations. Natalizumab and sVCAM-1 levels in serum were also analyzed using ELISA. To determine the reproducibility of various markers, two different timepoints were compared and no significant differences were observed for CD49d expression nor for saturation; SD patients had higher saturation levels (~80%) than EID patients (~60%). A positive correlation exists between CD49d saturation and Natalizumab serum levels. CD49d expression and saturation are stable parameters that could be used as biomarkers in the immunomonitoring of Natalizumab treatment. Moreover, Natalizumab and sVCAM-1 serum levels could be used to optimize an individual's dosing schedule

If you build it will they come? Services will make the difference in a portal

ManuscriptAbstract: Identifying and adding services to a library portal will add to its long term success in a market that pits libraries against commercial vendors like Google and Amazon.com. The current focus on portals has been on selecting collections and developing the basic functionality of the website. We look at the added features needed in order to make this a product that is attractive to today's researcher