115 research outputs found

    Gene expression profile predicts response to the combination of tosedostat and low-dose cytarabine in elderly AML

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    Tosedostat is an orally administered metalloenzyme inhibitor with antiproliferative and antiangiogenic activity against hematological and solid human cancers. Clinical activity has been demonstrated in relapsed acutemyeloid leukemia (AML). Thirty-three elderly patients with AML (median age, 75 years) received 120mgtosedostat orally once daily combinedwith subcutaneous low-dose cytarabine (20 mg twice per day for 10 days, up to 8 cycles), until disease progression. Inductionmortality was 12%. According to an intention-to-treat analysis, the complete remission (CR) rate was 48.5%, and thus the primary end point of the study was reached (expected CR, 25%). The partial remission rate was 6.1%,with an overall response rate of 54.5%. Furthermore, 4 of 33 patients had stable disease (median: 286 days). Themedian progression-free survival and overall survival (OS)were 203 days and 222 days, respectively. Responding patients had a longer median OS than nonresponding patients (P=.001). Amicroarray analysis performed in 29 of 33 patients identified 188 genes associated with clinical response (CR vs no CR). Three of them (CD93, GORASP1, CXCL16) were validated by quantitative polymerase chain reaction, which correctly classified 83% of the patients. Specifically, CR achievement was efficiently predicted by the gene expression patterns, with an overall accuracy exceeding 90%. Finally, a negative predictive value of 100% was validated in an independent series, thus representing the first molecular predictor for clinical response to a specific combination drug treatment for AML

    "We're worth what we are paid": Unravelling the 'paradox of the contented female worker'

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    Pay satisfaction research has suggested that women are more satisfied with their pay than men, even though, in general, women earn less. This paper argues that this body of research has misconceptualised this phenomenon as an issue of women only. It also argues that previous explanations for this gender pay paradox have not adequately explained these patterns of satisfaction. A social constructionist approach to pay satisfaction is proposed which situates satisfaction within the context of structural inequality. This draws upon the scholarly work of feminist scholars and the conceptual ideas of Pierre Bourdieu. This theoretical approach is explored with data from qualitative interviews with support staff at universities in the United Kingdom. This evidence suggests that their pay satisfaction is influenced by beliefs about the ‘value’ of different occupations

    Privaros: A Framework for Privacy-Compliant Delivery Drones

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    We present Privaros, a framework to enforce privacy policies on drones. Privaros is designed for commercial delivery drones, such as the ones that will likely be used by Amazon Prime Air. Such drones visit a number of host airspaces, each of which may have different privacy requirements. Privaros provides an information flow control framework to enforce the policies of these hosts on the guest delivery drones. The mechanisms in Privaros are built on top of ROS, a middleware popular in many drone platforms. This paper presents the design and implementation of these mechanisms, describes how policies are specified, and shows that Privaros's policy specification can be integrated with India's Digital Sky portal. Our evaluation shows that a drone running Privaros can robustly enforce various privacy policies specified by hosts, and that its core mechanisms only marginally increase communication latency and power consumption

    The hOCT1 and ABCB1 polymorphisms do not influence the pharmacodynamics of nilotinib in chronic myeloid leukemia

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    First-line nilotinib in chronic myeloid leukemia is more effective than imatinib to achieve early and deep molecular responses, despite poor tolerability or failure observed in one-third of patients. The toxicity and efficacy of tyrosine kinase inhibitors might depend on the activity of transmembrane transporters. However, the impact of transporters genes polymorphisms in nilotinib setting is still debated. We investigated the possible correlation between single nucleotide polymorphisms of hOCT1 (rs683369 [c.480C > G]) and ABCB1 (rs1128503 [c.1236C > T], rs2032582 [c.2677G > T/A], rs1045642 [c.3435C > T]) and nilotinib efficacy and toxicity in a cohort of 78 patients affected by chronic myeloid leukemia in the context of current clinical practice. The early molecular response was achieved by 81% of patients while 64% of them attained deep molecular response (median time, 26 months). The 36-month event-free survival was 86%, whereas 58% of patients experienced toxicities. Interestingly, hOCT1 and ABCB1 polymorphisms alone or in combination did not influence event-free survival or the adverse events rate. Therefore, in contrast to data obtained in patients treated with imatinib, hOCT1 and ABCB1 polymorphisms do not impact on nilotinib efficacy or toxicity. This could be relevant in the choice of the first-line therapy: patients with polymorphisms that negatively condition imatinib efficacy might thus receive nilotinib as first-line therapy

    Ethnic entrepreneurs and online home-based businesses: an exploratory study

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    This exploratory, qualitative study considers how online home-based businesses offer opportunities for ethnic entrepreneurs to ‘break out’ of traditional highly competitive and low margin sectors. Previous studies have found a positive association between ethnic minorities’ high levels of entrepreneurship and home computer use in ethnic groups. Despite these associations, previous studies have overlooked the particular opportunities offered by home-based online businesses to ethnic entrepreneurs. The study adopts mixed embeddedness as a theoretical lens to guide interviews with 22 ethnic entrepreneurs who have started online home-based businesses in the UK. We find online home-based businesses offer ethnic entrepreneurs novel opportunities to draw on their ethnic advantages and address the constraints they face. The unique affordances of this type of business allow entrepreneurs to develop the necessary IT skills by self-learning and experimentation and to sub-contract more difficult or time consuming aspects to others. The findings also show that, consistent with the theory of mixed embeddedness, whilst the entrepreneurs are influenced by social, economic and institutional forces, online businesses allow them to exert their own agency and provide opportunities to uniquely shape these forces

    The Pleasures and Pains of Self-Employment: A Panel Data Analysis of Satisfaction with Life, Work, and Leisure

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    We investigate how a transition from paid employment to self-employment in the labor market influences life satisfaction. Furthermore, we consider the dynamics of work and leisure satisfaction because the balance between work and leisure is an important element of life satisfaction. Fixed-effects regressions using German Socio-Economic Panel data (1984-2012) reveal that switching to self-employment benefits life and work satisfaction. The effects on life satisfaction are weak and temporary, but they are pronounced and relatively persistent for work satisfaction. However, the gain in work satisfaction is outweighed by a decrease in leisure satisfaction, thus placing work-life balance under severe pressure
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