The utility of animal models in developing immunosuppressive agents

The immune system comprises an integrated network of cellular interactions. Some responses are predictable, while others are more stochastic. While in vitro the outcome of stimulating a single type of cell may be stereotyped and reproducible, in vivo this is often not the case. This phenomenon often merits the use of animal models in predicting the impact of immunosuppressant drugs. A heavy burden of responsibility lies on the shoulders of the investigator when using animal models to study immunosuppressive agents. The principles of the three R׳s: refine (less suffering,), reduce (lower animal numbers) and replace (alternative in vitro assays) must be applied, as described elsewhere in this issue. Well designed animal model experiments have allowed us to develop all the immunosuppressive agents currently available for treating autoimmune disease and transplant recipients. In this review, we examine the common animal models used in developing immunosuppressive agents, focusing on drugs used in transplant surgery. Autoimmune diseases, such as multiple sclerosis, are covered elsewhere in this issue. We look at the utility and limitations of small and large animal models in measuring potency and toxicity of immunosuppressive therapies.

Safety of Spectacles for Children's Vision: A Cluster-Randomized Controlled Trial.

Purpose: To study safety of children’s glasses in rural China, where fear that glasses harm vision is an important barrier for families and policy-makers. Design: Exploratory analysis from a cluster-randomized, investigator-masked, controlled trial.Methods: Among primary schools (n=252) in western China, children were randomized by school to one of three interventions: free glasses provided in class, vouchers for free glasses at a local facility or glasses prescriptions only (Control group). The main outcome of this analysis is uncorrected visual acuity after 8 months, adjusted for baseline acuity.Results: Among 19,934 children randomly selected for screening, 5852 myopic (spherical equivalent refractive error <= -0.5 D) eyes of 3001 children (14.7%, mean age 10.5 years) had VA <= 6/12 without glasses correctable to > 6/12 with glasses, and were eligible. Among these, 1903 (32.5%), 1798 (30.7%), and 2151 (36.8%) were randomized to Control, Voucher and Free Glasses respectively. Intention-to-treat analyses were performed on all 1831 (96.2%), 1699 (94.5%), and 2007 (93.3%) eyes of children with follow-up in Control, Voucher and Free Glasses groups. Final visual acuity for eyes of children in the treatment groups (Free Glasses and Voucher) was significantly better than for Control children, adjusting only for baseline visual acuity (difference of 0.023 logMAR units [0.23 vision chart lines, 95% CI: 0.03, 0.43]) or for other baseline factors as well (0.025 logMAR units [0.25 lines, 95% CI 0.04, 0.45]). Conclusion: We found no evidence that spectacles promote decline in uncorrected vision with aging among children.

Navigating the Borderlands: Brian McGilloway as Contemporary Cartographer of the Liminal in the Ulster Landscape

Set in the borderlands between Letterkenny and Derry-Londonderry, a landscape scarred by geological fold, river and cartographer’s pen, the Ulster crime novelist Brian McGilloway chronicles the hopes and fears of a contemporary society unable to escape a complicated history, redolent and entwined with the voices of its ‘ghosts of its past.’ Through his choice of chief protagonist, An Garda Síochána officer Benedict Devlin, McGilloway turns detective to critically investigate the both the seemingly straightforward and the unseen dwelling in the rural Ulster landscape. Following in the footsteps of Nordic and Tartan Noir in making commentary on current societ,y McGilloway recognises the importance of the past in trying to reach an understanding of the present. His critique however goes beyond criminal behaviour motivated primarily by politics or religion, allowing a deeper and more meaningful diagnosis of the ‘state of the nation’. Place, name and event become especially important in contextualising the liminality of McGilloway’s real rural border settings. In doing so, McGilloway continues in the rich tradition of Ulster poet such as Heaney, MacNiece, Muldoon and Hewitt in trying to rationalise the man-made amidst the elemental in the land of both the ‘Planter & The Gael.’ History, language, tradition and the sacral are all instruments of investigation in helping McGilloway present a revealing pathology and atlas of our times to his readers. Turning literary investigator, the author contends that there is much to learn from this physiography, not just for the borderlands region, but for the wider countryside and society beyond. Keywords Cultural Atlas, Crime Fiction, Place, Poetry, Rural.

An interview with Manuel Salto-Tellez on diagnostic pathology: the future is morphomolecular

Professor Manuel Salto-Tellez of Queen’s University, Belfast, Northern Ireland is an expert histopathologist and molecular diagnostician. Professor Salto-Tellez is a lead investigator at the Northern Ireland Molecular Pathology Laboratory and also serves as a member of the Editorial Advisory Board for Expert Review of Molecular Diagnostics. In this interview, he proposes directions for the future of molecular pathology and molecular diagnostics, integrating all aspects of pathology toward a common goal.

Effect of providing free glasses on children's educational outcomes in China: cluster randomized controlled trial

Objective: To assess the effect of provision of free glasses on academic performance in rural Chinese children with myopia. Design: Cluster randomized, investigator masked, controlled trial.Setting 252 primary schools in two prefectures in western China, 2012-13. Participants: 3177 of 19 934 children in fourth and fifth grades (mean age 10.5 years) with visual acuity <6/12 in either eye without glasses correctable to >6/12 with glasses. 3052 (96.0%) completed the study.Interventions Children were randomized by school (84 schools per arm) to one of three interventions at the beginning of the school year: prescription for glasses only (control group), vouchers for free glasses at a local facility, or free glasses provided in class. Main outcome measures: Spectacle wear at endline examination and end of year score on a specially designed mathematics test, adjusted for baseline score and expressed in standard deviations. Results: Among 3177 eligible children, 1036 (32.6%) were randomized to control, 988 (31.1%) to vouchers, and 1153 (36.3%) to free glasses in class. All eligible children would benefit from glasses, but only 15% wore them at baseline. At closeout glasses wear was 41% (observed) and 68% (self reported) in the free glasses group, and 26% (observed) and 37% (self reported) in the controls. Effect on test score was 0.11 SD (95% confidence interval 0.01 to 0.21) when the free glasses group was compared with the control group. The adjusted effect of providing free glasses (0.10, 0.002 to 0.19) was greater than parental education (0.03, −0.04 to 0.09) or family wealth (0.01, −0.06 to 0.08). This difference between groups was significant, but was smaller than the prespecified 0.20 SD difference that the study was powered to detect. Conclusions: The provision of free glasses to Chinese children with myopia improves children’s performance on mathematics testing to a statistically significant degree, despite imperfect compliance, although the observed difference between groups was smaller than the study was originally designed to detect. Myopia is common and rarely corrected in this setting. Trial Registration: Current Controlled Trials ISRCTN03252665.

Surgical strategies for coexisting glaucoma and cataract: an evidence-based update.

OBJECTIVE:

To assess short- and long-term control of intraocular pressure (IOP) with different surgical treatment strategies for coexisting cataract and glaucoma.

DESIGN:

Systematic literature review and analysis.

METHOD:

We performed a search of the published literature to identify all eligible articles pertaining to the surgical management of coexisting cataract and glaucoma in adults. One investigator abstracted the content of each article onto a custom-designed form. A second investigator corroborated the findings. The evidence supporting different approaches was graded by consensus as good, fair, weak, or insufficient.

MAIN OUTCOME MEASURES:

Short-term (24 hours or fewer) and long-term (more than 24 hours) IOP control.

RESULTS:

The evidence was good that long-term IOP is lowered more by combined glaucoma and cataract operations than by cataract operations alone. On average, the IOP was 3 to 4 mmHg lower in the combined groups with fewer medications required. The evidence was weak that extracapsular cataract extraction (ECCE) alone results in short-term increase in IOP and was insufficient to determine the short-term impact of phacoemulsification cataract extraction (PECE) on IOP in glaucoma patients. The evidence was weak that short-term IOP control was better with ECCE or PECE combined with an incisional glaucoma procedure compared with ECCE or PECE alone. The evidence was also weak (but consistent) that long-term IOP is lowered by 2 to 4 mmHg after ECCE or PECE. Finally, there was weak evidence that combined PECE and trabeculectomy produces slightly worse long-term IOP control than trabeculectomy alone, and there was fair evidence that the same is true for ECCE combined with trabeculectomy.

CONCLUSIONS:

There is strong evidence for better long-term control of IOP with combined glaucoma and cataract operations compared with cataract surgery alone. For other issues regarding surgical treatment strategies for cataract and glaucoma, the available evidence is limited or conflicting.

Concepções e práticas CTS dos professores de uma escola inovadora

Numa sociedade cada vez mais permeada pelo desenvolvimento científicotecnológico emerge o reconhecimento da importância da Educação em Ciência, Tecnologia e Sociedade (CTS). Neste sentido, investigações estão a ser produzidas sobre a relação existente entre as concepções dos professores sobre CTS e suas práticas de ensino, mas os resultados são controversos. Assim, o presente estudo procurou contribuir para compreensão da relação entre as concepções sobre CTS e as práticas didáctico-pedagógicas desenvolvidas por professores de uma escola portuguesa considerada inovadora. Através de um estudo de caso, de natureza qualitativa, a investigação envolveu dois professores que trabalham com alunos do 3º ao 6º ano de escolaridade e utilizou diversas técnicas e instrumentos de recolha de dados. As concepções sobre CTS foram levantadas com a aplicação do questionário VOSTS “Views on Science-Technology-Society” (versão portuguesa adaptada por Canavarro, 2000). As práticas didáctico-pedagógicas dos professores caracterizaram-se com o apoio do “Instrumento de Caracterização das Práticas Pedagógico-Didácticas CTS” (Vieira, 2003) e do registo das observações das aulas dos professores através do Diário do Investigador e de áudio-gravações. O processo de análise dos dados aponta para concepções ingénuas sobre CTS dos professores, onde a Ciência e a Tecnologia foi vista como, por exemplo, “domínios interligados que nem sempre repercutem na sociedade”. Relativamente às práticas didáctico-pedagógicas, evidencia-se um ensino que valoriza o conhecimento e, embora inserido num contexto sócio-construtivista de Escola, este não contempla explicitamente uma orientação CTS. Sobre a relação entre as concepções sobre CTS dos professores e suas práticas didáctico-pedagógicas implementadas no ensino de Ciências, os resultados obtidos não permitem estabelecer conclusivamente uma relação ou a ausência dela. Contudo, os resultados trazem contributos, ainda que modestos, para a compreensão desta questão e salientam a complexidade da problemática abordada. Quanto ao contexto escolar inovador em que se realizou a investigação, os resultados apontam algumas divergências entre a proposta teórica do projecto pedagógico e as práticas implementadas em sala de aula. Portanto, uma proposta pedagógica que apresenta potenciais para um ensino com orientação CTS não se consolida se os professores não forem preparados para explorar este potencial. Salienta-se, assim, a necessidade de formação inicial e continuada de professores no Ensino das Ciências com Orientação CTS. ABSTRACT: In one society more and more promoted by scientific and technological development emerges the recognition of the importance of the Science, Society, and Technology (STS) in our Education. In these sense, investigations are being follow up about the existing relation between the conceptions of the teachers about STS and their practices in education, but the results are controversial. Thus, the present study it looked forward to contribute for the knowledge of relations between the conceptions of STS and their didacticpedagogical issues developed by teachers of one portuguese school considered innovative. Through a study of a case, of qualitative nature, an investigation involving two teachers which work with students of the third and sixth year of scholarship and using a broad of diverse techniques and instruments of data acquire. Conceptions about STS where taken in account with the use a questionnaire VOSTS " Views on Science-Technology-Society " (Portuguese version adapted by Canavarro, 2000). The didactic-pedagogical practices used by teachers are characterized by the support of " Instruments of characterization of didacticpedagogical practices STS" (Vieira, 2003) and of the registry of class observations by the teachers through the Investigator Diary as well as audio recordings. The process of analysis of data acquire leads to ingénues conceptions about the STS of the teachers, where Science and Technology was seen as, for example, "inter ligated domains which not always have repercussions in society". Relatively to didactic-pedagogical issues, it is proven that one education that embraces knowledge but insert in a context of socialconstructiveness of School will not contemplate an explicit orientation towards STS. About relation between the conceptions related to STS used by the teachers and their didactic-pedagogical issues implemented in education of Science, the results do not allow to establish a conclusive connection them or the lack of it. However, the results bring modest contributes for the comprehension of these question and they point out the complexity of the topic taken in account. To sum up, in relation to the innovative school context in which the investigation was taken the results lead to some divergences between the theoretical proposal of the pedagogic project and the practices implemented in the school class. So, one pedagogical proposal, which shows potential positive issues for one education STS oriented, does not get consolidated if the teachers are not prepared to explore this issue. It is lined out, the necessity of initial formation and trough life by the teachers in Education of Sciences with orientation to STS.

Emerging Technologies

This book, written when Walker was Visiting Professor at the Technical University Munich in 2011, describes his research on the effects of digital technology on architectural design and construction, and on the development of ‘digital craft’. The primary example given is The Swarm, a digitally designed and manufactured pavilion, produced with students while Walker was at TU Munich. It now stands outside the Bayerischen Architektenkammer (Bavarian Chamber of Architects) in Munich. Through such research-by-design, Walker asks larger questions: what can designers craft without a master craftsman’s skills, and how can craft skills be recovered through digital fabrication? Another example in the book is the Swoosh Pavilion, one of two public-space-scale architectural pavilion prototypes Walker developed between 2008 and 2009 at the Architectural Association (AA), using applied digital modelling and CNC techniques to investigate methods of teaching and testing digital processes through making. Swoosh (2008) and a second AA pavilion, Driftwood (2009), were discussed by Walker and Martin Self, his co-investigator, in ‘Fractal, bad hair, Swoosh and Driftwood pavilions of Intermediate Unit 2, 2006–2009’, published in the AD reader, Manufacturing the Bespoke (2012), which includes essays by well-known critics and designers such as Mathias Kohler and Michael Stacey. Both AA pavilions were sponsored by FinnForest Merk, Arup, HOK and Building Design Magazine, and were seen by large international audiences in Bedford Square, London during the 2008–9 ‘AA Projects Review’ shows. The book Making Pavilions (Walker and Self, AA Agenda No. 9, Architectural Association Press, 2011) also discusses their work over seven years of teaching at the Architectural Association. At the same time, Walker collaborated on a series of Serpentine pavilions, commissioned annually by the Serpentine Gallery, London, co-designing these experimental structures with internationally renowned architects Daniel Libeskind, Oscar Niemeyer, Toyo Ito and Alvaro Siza.

Representações de professores de educação especial acerca do sucesso educativo de alunos com necessidades educativas especiais

Dissertação de mest., Psicologia da Educação, Especialidade: Necessidades Educativas Especiais, Universidade do Algarve, 2006

O erro como caminho para aprendizagem das operações com números naturais : um estudo com alunos do 2º ano de escolaridade

Tese de mestrado, Educação (Didática da Matemática), Universidade de Lisboa, Instituto de Educação, 2012

The role and performance of Herodotus as Narrator of the Histories

Thesis (Ph. D.)--University of Washington, 1987

Uma avaliação do processo de constituição e desenvolvimento de um observatório num agrupamento de escolas

Dissertação de mestrado, Ciências da Educação (Avaliação em Educação), Universidade de Lisboa, Instituto de Educação, 2014

Rethinking the capsid proteins of enveloped viruses: multifunctionality from genome packaging to genome transfection

© 2015 FEBS

New insights into host-parasite ubiquitin proteome dynamics in P. falciparum infected red blood cells using a TUBEs-MS approach

Malaria, caused by Plasmodium falciparum (P. falciparum), ranks as one of the most baleful infectious diseases worldwide. New antimalarial treatments are needed to face existing or emerging drug resistant strains. Protein degradation appears to play a significant role during the asexual intraerythrocytic developmental cycle (IDC) of P. falciparum. Inhibition of the ubiquitin proteasome system (UPS), a major intracellular proteolytic pathway, effectively reduces infection and parasite replication. P. falciparum and erythrocyte UPS coexist during IDC but the nature of their relationship is largely unknown. We used an approach based on Tandem Ubiquitin-Binding Entities (TUBEs) and 1D gel electrophoresis followed by mass spectrometry to identify major components of the TUBEs-associated ubiquitin proteome of both host and parasite during ring, trophozoite and schizont stages. Ring-exported protein (REX1), a P. falciparum protein located in Maurer's clefts and important for parasite nutrient import, was found to reach a maximum level of ubiquitylation in trophozoites stage. The Homo sapiens (H. sapiens) TUBEs associated ubiquitin proteome decreased during the infection, whereas the equivalent P. falciparum TUBEs-associated ubiquitin proteome counterpart increased. Major cellular processes such as DNA repair, replication, stress response, vesicular transport and catabolic events appear to be regulated by ubiquitylation along the IDC P. falciparum infection.

New insights into functional regulation in MS-based drug profiling

We present a novel data analysis strategy which combined with subcellular fractionation and liquid chromatography-mass spectrometry (LC-MS) based proteomics provides a simple and effective workflow for global drug profiling. Five subcellular fractions were obtained by differential centrifugation followed by high resolution LC-MS and complete functional regulation analysis. The methodology combines functional regulation and enrichment analysis into a single visual summary. The workflow enables improved insight into perturbations caused by drugs. We provide a statistical argument to demonstrate that even crude subcellular fractions leads to improved functional characterization. We demonstrate this data analysis strategy on data obtained in a MS-based global drug profiling study. However, this strategy can also be performed on other types of large scale biological data.