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- Ocio, E. M., et al.
(författare)
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New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG)
- 2014
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 28:3, s. 525-542
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Forskningsöversikt (refereegranskat)abstract
- Treatment in medical oncology is gradually shifting from the use of nonspecific chemotherapeutic agents toward an era of novel targeted therapy in which drugs and their combinations target specific aspects of the biology of tumor cells. Multiple myeloma (MM) has become one of the best examples in this regard, reflected in the identification of new pathogenic mechanisms, together with the development of novel drugs that are being explored from the preclinical setting to the early phases of clinical development. We review the biological rationale for the use of the most important new agents for treating MM and summarize their clinical activity in an increasingly busy field. First, we discuss data from already approved and active agents (including second- and third-generation proteasome inhibitors (PIs), immunomodulatory agents and alkylators). Next, we focus on agents with novel mechanisms of action, such as monoclonal antibodies (MoAbs), cell cycle-specific drugs, deacetylase inhibitors, agents acting on the unfolded protein response, signaling transduction pathway inhibitors and kinase inhibitors. Among this plethora of new agents or mechanisms, some are specially promising: anti-CD38 MoAb, such as daratumumab, are the first antibodies with clinical activity as single agents in MM. Moreover, the kinesin spindle protein inhibitor Arry-520 is effective in monotherapy as well as in combination with dexamethasone in heavily pretreated patients. Immunotherapy against MM is also being explored, and probably the most attractive example of this approach is the combination of the anti-CS1 MoAb elotuzumab with lenalidomide and dexamethasone, which has produced exciting results in the relapsed/refractory setting.
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- Lange, David, et al.
(författare)
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An application of the PEER performance based earthquake engineering framework to structures in fire
- 2014
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Ingår i: Engineering structures. - : Elsevier BV. - 0141-0296 .- 1873-7323. ; 66:May, s. 100-115
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Tidskriftsartikel (refereegranskat)abstract
- The Pacific Earthquake Engineering Research (PEER) Center's Performance Based Earthquake Engineering (PBEE) framework is well documented. The framework is a linear methodology which is based upon obtaining in turn output from each of the following analyses: hazard analysis; structural analysis; loss analysis, and finally decision making based on variables of interest, such as downtime or cost to repair. The strength of the framework is in its linearity, its clear flexibility and in the consideration of uncertainty at every stage of the analysis. The framework has potential applications to other forms of extreme loading; however in order for this to be achieved the 'mapping' of the framework to the analysis of structures for other loading situations must be successful.This paper illustrates one such 'mapping' of the framework for Performance Based Fire Engineering (PBFE) of structures. Using a combination of simple analytical techniques and codified methods as well as random sampling techniques to develop a range of response records, the PEER framework is followed to illustrate its application to structural fire engineering. The end result is a successful application of the earthquake framework to fire which highlights both the assumptions which are inherent in the performance based design framework as well as subjects of future research which will allow more confidence in the design of structures for fire using performance based techniques.This article describes the PEER framework applied to structural earthquake design then follows the framework from start to completion applying suitable alternative tools to perform each stage of the analysis for structures in fire.
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