323,342 research outputs found
Lights and Shadows in Immuno-Oncology Drug Development.
No full textThe rapidly evolving landscape of immuno-oncology (IO) is redefining the treatment of a number of cancer types. IO treatments are becoming increasingly complex, with different types of drugs emerging beyond checkpoint inhibitors. However, many of the new drugs either do not progress from phase I-II clinical trials or even fail in late-phase trials. We have identified at least five areas in the development of promising IO treatments that should be redefined for more efficient designs and accelerated approvals. Here we review those critical aspects of IO drug development that could be optimized for more successful outcome rates in all cancer types. It is important to focus our efforts on the mechanisms of action, types of response and adverse events of these novel agents. The use of appropriate clinical trial designs with robust biomarkers of response and surrogate endpoints will undoubtedly facilitate the development and subsequent approval of these drugs. Further research is also needed to establish biomarker-driven strategies to select which patients may benefit from immunotherapy and identify potential mechanisms of resistance
Three essays in financial econometrics: fractional cointegration, nonlinearities and asynchronicities
No full textThis thesis develops theoretical tools for the stylised facts of multivariate volatility processes and stock returns in financial markets. The first essay of this thesis contributes to the literature of fractionally cointegrated processes. Threshold adjustment is allowed in the error correction of bivariate fractionally cointegrated systems. Hypothesis testing for the presence of threshold and simulation evidence are provided to support the need of threshold specification in the adjustment dynamics of fractionally cointegrated processes. Empirical application considers the cointegrating relation and adjustment dynamics of S&P500 option implied volatility index spot and futures. Empirical finding shows that investors tend to hedge against volatility by using volatility-tracking products during market turbulence. The next two essays investigate some econometric issues that arise from the use of asynchronous data on modelling the joint dynamics of stock returns. The return correlation is inaccurate if asynchronicity is not taken into consideration. As a result, portfolio risk management can be highly distorted. Aiming to develop an accurate estimation on the return correlation dynamics, several econometric techniques are introduced to tackle this asynchronicity problem that allow financial practitioners to adequately adjust the asynchronous stock return series. This research also attempts to analyse asynchronicity problem as a measurement error problem, parameter estimates from the conventional vector autoregressive models are inconsistent if the vector of multivariate stock returns contains asynchronous returns. A good proxy of measurement error can effectively correct the asynchronous return vector and hence yield consistent parameter estimates
MoDA Podcast Season 3, Episode 2, The empire at home
No full textAna Baeza Ruiz talks to Deborah Sugg Ryan and Sarah Cheang about how the British Empire shaped our everyday experiences of home
Emerging concepts about prenatal genesis, aberrant metabolism and treatment paradigms in polycystic ovary syndrome
No full textThe interactive nature of the 8th Annual Meeting of the Androgen Excess and PCOS Society Annual Meeting in Munich, Germany (AEPCOS 2010) and subsequent exchanges between speakers led to emerging concepts in PCOS regarding its genesis, metabolic dysfunction, and clinical treatment of inflammation, metabolic dysfunction, anovulation and hirsutism. Transition of care in congenital adrenal hyperplasia from pediatric to adult providers emerged as a potential model for care transition involving PCOS adolescents.Selma F. Witchel, Sergio E. Recabarren, Frank González, Evanthia Diamanti-Kandarakis, Kai I. Cheang, Antoni J. Duleba, Richard S. Legro, Roy Homburg, Renato Pasquali, Rogerio A. Lobo, Christos C. Zouboulis, Fahrettin Kelestimur, Franca Fruzzetti, Walter Futterweit, Robert J. Norman, David H. Abbot
Diffusive author(s), cohesive author: Analysis of S/N (1994)
No full textThis study indicates the ways in which various aspects of the author(s) are brought forth in Dumb type’s performance art, the S/N production. Previous research has suggested a non-hierarchical organization of Dumb type and the absence of a “privileged author” in Dumb type’s collaborative work, S/N. However, the results that I have investigated from member’s interviews on the creative process of S/N along with my analysis of the recorded images of S/N, indicate a different aspect of the author(s). First, S/N was created through, so to speak, the collective ideas of the members of Dumb type. Further, S/N has at least nine quotations from previous performances, installations, and printed writings, besides the work-in-progress technique. Explicating one of the “author functions” as given by Michel Foucault, each text has plural subjects of the author. However, it has been revealed from members’ interviews that Teiji Furuhashi had a decision-making role in selecting the members’ ideas within the performance. Since then, S/N has had plural subjects of creation; however, Furuhashi is one of the subjects of creation along with the “privileged author.” S/N has plural authors (diffusive authors) yet at the same time, it has a “privileged author,” Teiji Furuhashi (cohesive author)
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Suppression of long-term facilitation by Rab3-effector protein interaction
No full textLong-term facilitation (LTF) in Aplysia is achieved by the modulation of presynaptic release. However, the underlying mechanism that might be related with the regulation of synaptic vesicle release remains unknown. Since Rab3, a neuronal GTP-binding protein, is known to be a key regulator of synaptic vesicle fusion, we investigated the involvement of Rab3 in LTF. To address this issue, we examined the effect of overexpression of wild type Aplysia Rab3 (apRab3) and its mutant forms on LTF. Overexpression of either apRab3 Q80L, a constitutively active apRab3 mutant, or wild type apRab3 completely inhibited LTF. This inhibitory role of apRab3 appears to be mediated by an interaction with an effector molecule(s), possibly Rim. Expression of apRab3 Q80L, V54E double mutant, which do not bind effector molecules such as Rim or Rabphilin, had no effect on LTF Furthermore, expression of apRab3 Q80L, F18L, D19E triple mutant, which has reduced binding activity with Rim but normally binds with Rabphilin, enhanced evoked basal synaptic release, and the increase in synaptic strength occluded LTF. In conclusion, our data suggest that apRab3 may act as a negative clamp of LTF through the interaction with effector protein(s), possibly Rim. (c) 2005 Elsevier B.V. All rights reserved
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Author's address:
No full textCan archives of audiovisual TV interviews be used to make authors more visible to students, and thereby reduce the learning gap between native and non-native language speakers in college classes? We examined students in a college course who learned about one scholar's ideas through watching an audiovisual TV interview (i.e., visible author format) and about another scholar's ideas through reading a formal text description (i.e., invisible author format). For the invisible author, native language speakers scored significantly higher than the non-native language speakers on a corresponding exam question (i.e., a cognitive measure), generated more words on the exam question (i.e., a motivational measure), and mentioned the author's name more often in answering the exam question (i.e., an affective measure). For the visible author, the groups did not differ on any of these measures. These findings provide evidence for the idea that making the author visible through audiovisual TV interviews can eliminate the learning gap between native and non-native language speakers. 3 Universities around the world serve students who are non-native speakers of th
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