45 research outputs found
Midkine mediates intercellular crosstalk between drug-resistant and drug sensitive neuroblastoma cells in vitro and in vivo
Resistance to cytotoxic agents has long been known to be a major limitation in the treatment of human cancers. Although many mechanisms of drug resistance have been identified, chemotherapies targeting known mechanisms have failed to lead to effective reversal of drug resistance, suggesting that alternative mechanisms remain undiscovered. Previous work identified midkine (MK) as a novel putative survival molecule responsible for cytoprotective signaling between drug-resistant and drug-sensitive neuroblastoma, osteosarcoma and breast carcinoma cells in vitro. In the present study, we provide further in vitro and in vivo studies supporting the role of MK in neuroblastoma cytoprotection. MK overexpressing wild type neuroblastoma cells exhibit a cytoprotective effect on wild type cells when grown in a co-culture system, similar to that seen with doxorubicin resistant cells. siRNA knockdown of MK expression in doxorubicin resistant neuroblastoma and osteosarcoma cells ameliorates this protective effect. Overexpression of MK in wild type neuroblastoma cells leads to acquired drug resistance to doxorubicin and to the related drug etoposide. Mouse studies injecting various ratios of doxorubicin resistant or MK transfected cells with GFP transfected wild type cells confirm this cytoprotective effect in vivo. These findings provide additional evidence for the existence of intercellular cytoprotective signals mediated by MK which contribute to chemotherapy resistance in neuroblastoma
Factor structure and construct validity of the Adult Social Care Outcomes Toolkit for Carers (ASCOT-Carer)
Background: The ASCOT-Carer is a self-report instrument designed to measure social care-related quality of life (SCRQoL). This article presents the psychometric testing and validation of the ASCOT-Carer four response-level interview (INT4) in a sample of unpaid carers of adults who receive publicly-funded social care services in England.
Methods: Unpaid carers were identified through a survey of users of publicly-funded social care services in England. 387 carers completed a face-to-face or telephone interview. Data on variables hypothesised to be related to SCRQoL (for example, characteristics of the carer, cared-for person and care situation) and measures of carer experience, strain, health-related quality of life and overall QoL were collected. Relationships between these variables and overall SCRQoL score were evaluated through correlation, ANOVA and regression analysis to test the construct validity of the scale. Internal reliability was assessed using Cronbach’s alpha and feasibility by the number of missing responses.
Results: The construct validity was supported by statistically significant relationships between SCRQoL and scores on instruments of related constructs, as well as with characteristics of the carer and care recipient in univariate and multivariate analyses. A Cronbach’s alpha of 0.87 (7 items) indicates that the internal reliability of the instrument is satisfactory and a low number of missing responses (<1%) indicates a high level of acceptance.
Conclusions: The results provide evidence to support the construct validity, factor structure, internal reliability and feasibility of the ASCOT-Carer INT4 as an instrument for measuring social care-related quality of life of unpaid carers who care for adults with a variety of long-term conditions, disability or problems related to old age
Performance Scores in General Practice: A Comparison between the Clinical versus Medication-Based Approach to Identify Target Populations
CONTEXT: From one country to another, the pay-for-performance mechanisms differ on one significant point: the identification of target populations, that is, populations which serve as a basis for calculating the indicators. The aim of this study was to compare clinical versus medication-based identification of populations of patients with diabetes and hypertension over the age of 50 (for men) or 60 (for women), and any consequences this may have on the calculation of P4P indicators. METHODS: A comparative, retrospective, observational study was carried out with clinical and prescription data from a panel of general practitioners (GPs), the Observatory of General Medicine (OMG) for the year 2007. Two indicators regarding the prescription for statins and aspirin in these populations were calculated. RESULTS: We analyzed data from 21.690 patients collected by 61 GPs via electronic medical files. Following the clinical-based approach, 2.278 patients were diabetic, 8,271 had hypertension and 1.539 had both against respectively 1.730, 8.511 and 1.304 following the medication-based approach (% agreement = 96%, kappa = 0.69). The main reasons for these differences were: forgetting to code the morbidities in the clinical approach, not taking into account the population of patients who were given life style and diet rules only or taking into account patients for whom morbidities other than hypertension could justify the use of antihypertensive drugs in the medication-based approach. The mean (confidence interval) per doctor was 33.7% (31.5-35.9) for statin indicator and 38.4% (35.4-41.4) for aspirin indicator when the target populations were identified on the basis of clinical criteria whereas they were 37.9% (36.3-39.4) and 43.8% (41.4-46.3) on the basis of treatment criteria. CONCLUSION: The two approaches yield very "similar" scores but these scores cover different realities and offer food for thought on the possible usage of these indicators in the framework of P4P programmes
Do migrant remittances promote human capital formation? Evidence from 89 developing countries
The few published empirical studies on the effect of migrant remittances on educational attainments are roughly based on cross-sectional microdata from household surveys. This paper applies the generalised method of moments (GMM) estimator on aggregate level data from 1970 to 2010 in five-year intervals to examine the impact of migrant remittances on human capital formation in 89 developing countries. The estimation results show that, on average, an increase in migrant remittance inflows by 1% is associated with a 2% rise in years of schooling at both the secondary and tertiary levels. This suggests that migrant remittances have the potential to relax liquidity constraints and generate spillover effects that facilitate more schooling opportunities in remittance-receiving countries
In Search of a Trade Mark: Search Practices and Bureaucratic Poetics
Trade marks have been understood as quintessential ‘bureaucratic properties’. This article suggests that the making of trade marks has been historically influenced by bureaucratic practices of search and classification, which in turn were affected by the possibilities and limits of spatial organisation and technological means of access and storage. It shows how the organisation of access and retrieval did not only condition the possibility of conceiving new trade marks, but also served to delineate their intangible proprietary boundaries. Thereby they framed the very meaning of a trade mark. By advancing a historical analysis that is sensitive to shifts, both in actual materiality and in the administrative routines of trade mark law, the article highlights the legal form of trade mark as inherently social and materially shaped. We propose a historical understanding of trade mark law that regards legal practice and bureaucratic routines as being co-constitutive of the very legal object itself
The Effect of Gastrostomy Placement on Gastric Function in Children: a Prospective Cohort Study
A conceptual view of internationalization strategies under dual institutional pressures for legitimacy and conformity
Internacionalizar as operações requer que as empresas multinacionais (EMNs) desenvolvam estratégias capazes de lidar, simultaneamente, com as pressões institucionais externas, para a legitimidade, e as pressões institucionais internas, para a conformidade. Neste artigo conceitual e baseado na literatura de teoria institucional em negócios internacionais, desenvolve-se um conjunto de proposições teóricas sobre quais as estratégias de entrada nos mercados externos seguidas pelas EMNs face aos ambientes institucionais. Com foco predominante no ambiente institucional externo e nas diferenças de desenvolvimento institucional, também aborda a relevância de considerar o ambiente interno. As estratégias de entrada tendem a ser baseadas em modos de baixo envolvimento e em parcerias, como joint ventures, para entrar em países institucionalmente imaturos ou institucionalmente mais distantes. As aquisições e as parcerias podem ser usadas se as pressões institucionais forem menores. Conclui-se com uma discussão geral e o apontamento de questões para pesquisas futuras.info:eu-repo/semantics/publishedVersio