Standardization of diagnostic biomarker concentrations in urine; the hematuria caveat

Sensitive and specific urinary biomarkers can improve patient outcomes in many diseases through informing early diagnosis. Unfortunately, to date, the accuracy and translation of diagnostic urinary biomarkers into clinical practice has been disappointing. We believe this may be due to inappropriate standardization of diagnostic urinary biomarkers. Our objective was therefore to characterize the effects of standardizing urinary levels of IL-6, IL-8, and VEGF using the commonly applied standards namely urinary creatinine, osmolarity and protein. First, we report results based on the biomarker levels measured in 120 hematuric patients, 80 with pathologically confirmed bladder cancer, 27 with confounding pathologies and 13 in whom no underlying cause for their hematuria was identified, designated “no diagnosis”. Protein levels were related to final diagnostic categories (p = 0.022, ANOVA). Osmolarity (mean = 529 mOsm; median = 528 mOsm) was normally distributed, while creatinine (mean = 10163 µmol/l, median = 9350 µmol/l) and protein (0.3297, 0.1155 mg/ml) distributions were not. When we compared AUROCs for IL-6, IL-8 and VEGF levels, we found that protein standardized levels consistently resulted in the lowest AUROCs. The latter suggests that protein standardization attenuates the “true” differences in biomarker levels across controls and bladder cancer samples. Second, in 72 hematuric patients; 48 bladder cancer and 24 controls, in whom urine samples had been collected on recruitment and at follow-up (median = 11 (1 to 20 months)), we demonstrate that protein levels were approximately 24% lower at follow-up (Bland Altman plots). There was an association between differences in individual biomarkers and differences in protein levels over time, particularly in control patients.

Systematic Engineering of Uniform, Highly Efficient, Targeted and Shielded Viral-Mimetic Nanoparticles

In the past decades, numerous types of nanomedicines have been developed for the efficient and safe delivery of nucleic acid-based drugs for cancer therapy. Given that the destination sites for nucleic acid-based drugs are inside cancer cells, delivery systems need to be both targeted and shielded in order to overcome the extracellular and intracellular barriers. One of the major obstacles that has hindered the translation of nanotechnology-based gene-delivery systems into the clinic has been the complexity of the design and assembly processes, resulting in non-uniform nanocarriers with unpredictable surface properties and efficiencies. Consequently, no product has reached the clinic yet. In order to address this shortcoming, a multifunctional targeted biopolymer is genetically engineered in one step, eliminating the need for multiple chemical conjugations. Then, by systematic modulation of the ratios of the targeted recombinant vector to PEGylated peptides of different sizes, a library of targeted-shielded viral-mimetic nanoparticles (VMNs) with diverse surface properties are assembled. Through the use of physicochemical and biological assays, targeted-shielded VMNs with remarkably high transfection efficiencies (>95%) are screened. In addition, the batch-to-batch variability of the assembled targeted-shielded VMNs in terms of uniformity and efficiency is examined and, in both cases, the coefficient of variation is calculated to be below 20%, indicating a highly reproducible and uniform system. These results provide design parameters for engineering uniform, targeted-shielded VMNs with very high cell transfection rates that exhibit the important characteristics for in vivo translation. These design parameters and principles could be used to tailor-make and assemble targeted-shielded VMNs that could deliver any nucleic acid payload to any mammalian cell type.

Physicians' and Nurses' Perceived Usefulness and Acceptability of a Family Information Booklet about Comfort Care in Advanced Dementia

Background: Families of patients with advanced dementia need to be informed about the course of the dementia and comfort care. Conditional for health care providers educating families is their knowledge and comfort in family education. Methods: Perceived usefulness and acceptability of a Canadian family booklet explaining possible complications and comfort care in dementia was assessed by physicians and nurses caring for dementia patients in 14 nursing homes in Lombardy, Italy and 21 in the Netherlands. The practitioners received a questionnaire and translated versions adapted to local practice where needed. In 10 of 21 Dutch homes, physicians evaluated only the original Canadian version in English. A 15-item scale assessed the booklet's acceptability, for example, to inform families, or for educational purposes. Perceived usefulness referred to proportion of families of dementia patients for whom the booklet would be useful. A total of 168 evaluations were available for multivariable regression analyses. Results: The practitioners anticipated that the booklet would be useful for most families. Evaluation of the Dutch translation of the booklet was similar to the English version. Country (Netherlands) and profession (nurses) were independently associated with better acceptability. Usefulness was perceived as better by Italian respondents and nurses, but only in analyses unadjusted for the higher educational needs of these respondents. Conclusion: Overall, the concept of written information on comfort care was appreciated by practitioners of European countries differing in attitudes toward end-of-life care. A booklet may help practitioners, and in particular nurses, in providing comfort care for dementia patients and their families. © Copyright 2011, Mary Ann Liebert, Inc. 2011.

Efficient Drug Delivery and Induction of Apoptosis in Colorectal Tumors Using a Death Receptor 5-Targeted Nanomedicine

Death Receptor 5 (DR5) is a pro-apoptotic cell-surface receptor that is a potential therapeutic target in cancer. Despite the potency of DR5-targeting agents in preclinical models, the translation of these effects into the clinic remains disappointing. Herein, we report an alternative approach to exploiting DR5 tumor expression using antibody-targeted, chemotherapy-loaded nanoparticles. We describe the development of an optimized polymer-based nanotherapeutic incorporating both a functionalized polyethylene glycol (PEG) layer and targeting antibodies to limit premature phagocytic clearance whilst enabling targeting of DR5-expressing tumor cells. Using the HCT116 colorectal cancer model, we show that following binding to DR5, the nanoparticles activate caspase 8, enhancing the anti-tumor activity of the camptothecin payload both in vitro and in vivo. Importantly, the combination of nanoparticle-induced DR5 clustering with camptothecin delivery overcomes resistance to DR5-induced apoptosis caused by loss of BAX or overexpression of anti-apoptotic FLIP. This novel approach may improve the clinical activity of DR5-targeted therapeutics while increasing tumor-specific delivery of systemically toxic chemotherapeutics.Molecular Therapy (2014); doi:10.1038/mt.2014.137.

A Pilot Study of Reciprocal Peer Tutoring in Irish Medium Schools

A pilot study to investigate the effects of mathematics peer tutoring in Irish medium primary schools was undertaken. Five schools and 90 students took part in the pilot. Materials and resources that had previously been shown to work in English medium Scottish schools were translated into Irish by CCEA. Irish medium teachers attended three professional development days. Teachers implemented the peer tutoring techniques during mathematics lessons during a period of 16 weeks. Changes in attainment were measures with an Irish translation of the Scottish Survey of Achievement Mathematics Test. Results were positive. Student attainment was significantly raised during the 16-week implementation period by over one standard deviation. This equated to one-year’s worth of mathematics development during this time period. Results must be treated with caution. No control group was used in the pilot study. However, results are very promising and indicate that reciprocal role peer tutoring may be a useful pedagogy in Irish medium education. Further work would be required to establish this definitively.

Foreign Policy as Ethics: Toward a Re-Evaluation of Values

This article notes that while ethics is increasingly talked of in foreign policy, it remains a blind-spot for FPA. It argues that this must be rectified through a critical approach which conceptualises foreign policy as ethics. The first section examines how even constructivist approaches, which are highly attuned to the intersubjective sphere, still generally avoid dealing with morality. The second section looks at the possibilities and limits of one piece of constructivist theorizing that explores the translation of morality into foreign policy via ‘norms’. This demonstrates the problems that a constructivist account, with its tendency toward explanatory description without evaluation, will always face. The final section argues, through an examination of EU foreign policy (from 1999-2004) and its innovative use of ‘hospitality’, that FPA must critically reassess the value of the norms and principles by which foreign policy operates in order to suggest potentially more ethical modes of encounter.

Simulation of economic benefits achieved by water quality improvement for recreational and professional users, within the SPICOSSA SSA (SPICOSSA System Approach) 11 - Guadiana estuary ecosystem sic

Dissertação de Mestrado, Gestão da Água e da Costa, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2010

A corpus-based translation study on english-persian verb phrase ellipsis

Dissertação de mest., Natural Language Processing & Human Language Technology, Faculdade de Ciências Humanas e Sociais, Univ. do Algarve, 2011

Da transcrição à legendagem em busca da perda mínima de conteúdo

Como projeto final do Mestrado em Tradução e Interpretação Especializadas foi proposta a legendagem de um excerto de uma apresentação oral, em ambiente de debate, de um discurso do ator Stephen Fry. Inseriu-se o trabalho no âmbito do mestrado e no seguimento da licenciatura na mesma área, possibilitando o exercício de três das principais áreas do curso: transcrição, tradução e legendagem, por esta ordem. Procurou-se inovar no sentido de aproximar a transcrição à legendagem, com a menor supressão possível de texto e consequentemente da mensagem, enquanto se cumpriram na íntegra as normas e sugestões dos autores-chave da área. Como elementos técnicos do trabalho estão inseridos no corpo do texto a transcrição, a tradução e a legendagem, pois estes são os objetos práticos do trabalho e o grande desafio proposto foi o seguinte: manter a fidelidade entre estes três modos de transferência – obedecer a todo o procedimento distinto a que estes modos obrigam, mas mantendo entre eles uma similaridade que os torne praticamente iguais, no sentido de transmissão da mensagem. Apresentaram-se também uma breve história da tradução audiovisual, os diferentes tipos da mesma, uma abordagem à realidade da área em Portugal, uma contextualização do excerto e do seu conteúdo e a vertente técnica na sua globalidade.

Intersubjectivity and poetic translation

O artigo está disponível em livre acesso no link da versão do editor

Pronoun-dropping or zero anaphora in translation from german into portuguese

In this article I will analyse anaphoric references in German texts and their transaltion into Portuguese. I will take as main corpus Heinrich Böll's novel Haus ohne Hüter and its translation into Portuguese by Jorge Rosa with the title Casa Indefesa. I will concentrate on the use of personal pronouns and possessives in references to both people and objects in source text and target text and I will present patterns of symmetries and asymmetries. I will claim that asymmetries in the translation of such anaphoric references can be accounted for mainly by differences in the pronominal systems and verbal systems of both languages and by differences in the way each language marks theme/topic continuity/discontinuity in discourse. Issues related to style and the translation of anaphors will also be addressed. I will finally raise some questions related to ambiguous references which can not be solved within the scope of syntax or semantics, thus requiring pragmatic interpretation based on cultural knowledge/world knowledge.

Tradução e legendagem do documentário Fárria

Trabalho de Projeto Apresentado ao Instituto de Contabilidade e Administração do Porto para a obtenção do grau de Mestre em Tradução e Interpretação Especializadas, sob orientação da Mestre Graça Chorão e coorientação da Mestre Paula Almeida

O Arquivo Audiovisual da SIC: a reutilização dos conteúdos da estação na produção diária de notícias

Relatório de estágio apresentado à Escola Superior de Comunicação Social como parte dos requisitos para obtenção de grau de mestre em Audiovisual e Multimédia.

Sous-titrage de documentaire sur la capoeira

Trabalho de Projeto Apresentado ao Instituto de Contabilidade e Administração do Porto para a obtenção do grau de Mestre em Tradução e Interpretação Especializadas, sob orientação da professora Doutora Isabelle Tulekian Lopes e do professor Doutor Manuel Moreira da Silva

Directed integration of new insulated lentiviral vectors to heterochromatin towards safer gene transfer to stem cells

The need for better gene transfer systems towards improved risk=benefit balance for patients remains a major challenge in the clinical translation of gene therapy (GT). We have investigated the improvement of integrating vectors safety in combining (i) new short synthetic genetic insulator elements (GIE) and (ii) directing genetic integration to heterochromatin. We have designed SIN-insulated retrovectors with two candidate GIEs and could identify a specific combination of insulator 2 repeats which translates into best functional activity, high titers and boundary effect in both gammaretro (p20) and lentivectors (DCaro4) (see Duros et al, abstract ibid). Since GIEs are believed to shield the transgenic cassette from inhibitory effects and silencing, DCaro4 has been further tested with chimeric HIV-1 derived integrases which comprise C-ter chromodomains targeting heterochromatin through either histone H3 (ML6chimera) or methylatedCpGislands (ML10). With DCaro4 only and both chimeras, a homogeneous expression is evidenced in over 20% of the cells which is sustained over time. With control lentivectors, less than 2% of cells express GFP as compared to background using a control double-mutant in both catalytic and ledgf binding-sites; in addition, a two-times increase of expression can be induced with histone deacetylase inhibitors. Our approach could significantly reduce integration into open chromatin sensitive sites in stem cells at the time of transduction, a feature which might significantly decrease subsequent genotoxicity, according to X-SCIDs patients data.Work performed with the support of EC-DG research within the FP6-Network of Excellence, CLINIGENE: LSHB-CT-2006-018933