Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson's disease

Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson's disease.

A refined LEED analysis of water on Ru{0001}: an experimental test of the partial dissociation model

Despite a number of earlier studies which seemed to confirm molecular adsorption of water on close-packed surfaces of late transition metals, new controversy has arisen over a recent theoretical work by Feibelman, according to which partial dissociation occurs on the Ru{0001} surface leading to a mixed (H2O + OH + H) superstructure. Here, we present a refined LEED-IV analysis of the (root3 x root3)R30degrees-D2O-Ru{0001} structure, testing explicitly this new model by Feibelman. Our results favour the model proposed earlier by Held and Menzel assuming intact water molecules with almost coplanar oxygen atoms and out-of-plane hydrogen atoms atop the slightly higher oxygen atoms. The partially dissociated model with an almost identical arrangement of oxygen atoms can, however, not unambiguously be excluded, especially when the single hydrogen atoms are not present in the surface unit cell. In contrast to the earlier LEED-IV analysis, we can, however, clearly exclude a buckled geometry of oxygen atoms.

Using Patient Health Questionnaire-9 item parameters of a common metric resulted in similar depression scores compared to independent item response theory model reestimation

Objectives: To investigate the validity of a common depression metric in independent samples. Study Design and Setting: We applied a common metrics approach based on item-response theory for measuring depression to four German-speaking samples that completed the Patient Health Questionnaire (PHQ-9). We compared the PHQ item parameters reported for this common metric to reestimated item parameters that derived from fitting a generalized partial credit model solely to the PHQ-9 items. We calibrated the new model on the same scale as the common metric using two approaches (estimation with shifted prior and StockingeLord linking). By fitting a mixed-effects model and using BlandeAltman plots, we investigated the agreement between latent depression scores resulting from the different estimation models. Results: We found different item parameters across samples and estimation methods. Although differences in latent depression scores between different estimation methods were statistically significant, these were clinically irrelevant. Conclusion: Our findings provide evidence that it is possible to estimate latent depression scores by using the item parameters from a common metric instead of reestimating and linking a model. The use of common metric parameters is simple, for example, using a Web application (http://www.common-metrics.org) and offers a long-term perspective to improve the comparability of patient-reported outcome measures.

X-ray your data with Rasch

By using the Rasch model, much detailed diagnostic information is available to developers of survey and assessment instruments and to the researchers who use them. We outline an approach to the analysis of data obtained from the administration of survey instruments that can enable researchers to recognise and diagnose difficulties with those instruments and then to suggest remedial actions that can improve the measurement properties of the scales included in questionnaires. We illustrate the approach using examples drawn from recent research and demonstrate how the approach can be used to generate figures that make the results of Rasch analyses accessible to non-specialists.

Modelización de una prueba de afecto hacia la matemática con la teoría de respuesta al ítem

Resumen: Se aplicó el Modelo de Crédito Parcial (MCP) de la Teoría de Respuesta al Ítem (TRI) al análisis de ítems de una escala que mide Afecto hacia la Matemática. Esta variable describe el interés de los estudiantes de Psicología por involucrarse en actividades vinculadas a la matemática y los sentimientos asociados al uso de sus conceptos. La prueba consta de 8 ítems con formato de respuesta Likert de 6 opciones. Participaron 1875 estudiantes de Psicología de la Universidad de Buenos Aires (Argentina) de los cuales un 82% fueron mujeres. El análisis de la consistencia interna brindó un índice altamente satisfactorio (Alfa = .91). Se verificó la condición de unidimensionalidad requerida por el modelo mediante un análisis factorial exploratorio. Todos los análisis basados sobre la TRI se realizaron con el programa Winsteps. La estimación de los parámetros del modelo se efectuó por Máxima Verosimilitud Conjunta. El ajuste del MCP fue satisfactorio para todos los ítems. La Función de Información del Test fue elevada en un rango amplio de niveles del rasgo latente. Un ítem presentó una inversión en dos parámetros de umbral. Como consecuencia, 1 de las 6 categorías del ítem no fue máximamente probable en ningún intervalo de la escala del rasgo latente. Se analizan las implicancias de este hallazgo en la evaluación de la calidad psicométrica del ítem. Los resultados de este estudio permitieron profundizar el análisis del constructo y aportaron evidencias de validez basadas en las estructura interna de la escala

Construction d'une échelle décrivant les niveaux de compétence de collaboration, à partir d'indicateurs validés par des enseignants cliniciens en médecine

La collaboration est une compétence essentielle que les futurs médecins doivent développer. La détermination des niveaux de compétence est cruciale dans la planification de cet apprentissage. Les échelles descriptives suscitent un intérêt croissant, car elles décrivent en termes qualitatifs les performances attendues. Nous inspirant de la méthodologie mixte de Blais, Laurier, & Rousseau (2009), nous avons construit en cinq étapes une échelle de niveau de compétence de collaboration: 1) formulation d’une liste d’indicateurs situés à quatre niveaux de la formation médicale (préclinique, externat, résidence junior et sénior) par les chercheurs (n= 3) et un groupe d’éducateurs (n=7), leaders pédagogiques possédant une expertise pour la compétence de collaboration; 2) sondage en ligne comprenant quatre questionnaires portant sur les niveaux de 118 indicateurs, auprès d’enseignants cliniciens représentant les différentes spécialités (n=277); 3) analyse, avec le modèle partial credit de Rasch, des réponses aux questionnaires appariés par calibration concurrente; 4) détermination des niveaux des indicateurs par les éducateurs et les chercheurs; et 5) rédaction de l’échelle à partir des indicateurs de chaque niveau. L’analyse itérative des réponses montre une adéquation au modèle de Rasch et répartit les indicateurs sur l’échelle linéaire aux quatre niveaux. Les éducateurs déterminent le niveau des 111 indicateurs retenus en tenant compte des résultats du sondage et de la cohérence avec le curriculum. L’échelle comporte un paragraphe descriptif par niveau, selon trois capacités : 1) participer au fonctionnement d’une équipe; 2) prévenir et gérer les conflits; et 3) planifier, coordonner et dispenser les soins en équipe. Cette échelle rend explicites les comportements collaboratifs attendus à la fin de chaque niveau et est utile à la planification de l’apprentissage et de l’évaluation de cette compétence. La discordance entre les niveaux choisis par les éducateurs et ceux issus de l’analyse des réponses des enseignants cliniciens est principalement due au faible choix de réponse du niveau préclinique par les enseignants et aux problèmes d’adéquation pour les indicateurs décrivant la gestion des conflits. Cette recherche marque une avan- cée dans la compréhension de la compétence de collaboration et démontre l’efficacité de la méthodologie de Blais (2009) dans un contexte de compétence transversale, en sciences de la santé. Cette méthodologie pourrait aider à approfondir les trajectoires de développement d’autres compétences.

Reason for hope : primary students' mathematics learning environment

This paper reports the results of a student survey of perceptions of classroom learning environment conducted as part of a major investigation into effective pedagogical practices in mathematics and science. All primary school project participants were surveyed, The 36 Likert-type items were subjected to a Partial Credit Model analysis, and response categories subjected to statistical requirements. The results are presented graphically, their meanings examined, and the implications of the findings for both researchers and practitioners are discussed.

Entrenamiento de la visualización espacial mediante ejercicios informatizados de dibujo técnico

Neste trabalho descreve-se a construção, a aplicação e os resultados obtidos numa bateria de exercícios informatizados para treinamento da visualização espacial de estudantes de Engenharia. A bateria contém quatro exercícios baseados em tarefas muito comuns do ensino fundamental de desenho técnico. Cada exercício é composto por 18 itens com quatro opções de respostas das quais apenas uma é correta. Após responder a cada item o aluno recebe um feed-back imediato, com a demonstração da precisão da sua resposta. O formato de resposta dos exercícios denomina-se Responder até acertar, uma vez que se a resposta é incorreta, o aluno recebe a informação da pontuação obtida. Para avaliar a influencia do treinamento na visualização espacial foram administrados testes dessa aptidão no começo e no final do curso de desenho técnico. As figuras dos exercícios e os testes foram construídas com AutoCad e a programação foi realizada com Revolution Studio 2. Utilizaram-se vários modelos para obter as medidas: Partial Credit Model (Masters, 1982) e Rasch Model (Rasch, 1960). Observou-se que os alunos apresentaram uma melhora moderada em visualização espacial.

Using Rasch modeling to re-evaluate three scales related to physical activity: Enjoyment, perceived benefits and perceived barriers

Studies suggest that enjoyment, perceived benefits and perceived barriers may be important mediators of physical activity. However, the psychometric properties of these scales have not been assessed using Rasch modeling. The purpose of this study was to use Rasch modeling to evaluate the properties of three scales commonly used in physical activity studies: the Physical Activity Enjoyment Scale, the Benefits of Physical Activity Scale and the Barriers to Physical Activity Scale. The scales were administered to 378 healthy adults, aged 25–75 years (50% women, 62% Whites), at the baseline assessment for a lifestyle physical activity intervention trial. The ConQuest software was used to assess model fit, item difficulty, item functioning and standard error of measurement. For all scales, the partial credit model fit the data. Item content of one scale did not adequately cover all respondents. Response options of each scale were not targeting respondents appropriately, and standard error of measurement varied across the total score continuum of each scale. These findings indicate that each scale's effectiveness at detecting differences among individuals may be limited unless changes in scale content and response format are made.

Estimation of the Proportion of Underachieving Students in Compulsory Secondary Education in Spain: An Application of the Rasch Model

There are very few studies in Spain that treat underachievement rigorously, and those that do are typically related to gifted students. The present study examined the proportion of underachieving students using the Rasch measurement model. A sample of 643 first-year high school students (mean age = 12.09; SD = 0.47) from 8 schools in the province of Alicante (Spain) completed the Battery of Differential and General Skills (Badyg), and these students' General Points Average (GPAs) were recovered by teachers. Dichotomous and Partial credit Rasch models were performed. After adjusting the measurement instruments, the individual underachievement index provided a total sample of 181 underachieving students, or 28.14% of the total sample across the ability levels. This study confirms that the Rasch measurement model can accurately estimate the construct validity of both the intelligence test and the academic grades for the calculation of underachieving students. Furthermore, the present study constitutes a pioneer framework for the estimation of the prevalence of underachievement in Spain.

Designing Of Partial Similarity Models And Evaluation Method In Polymer Flooding Experiment

Based on the scaling criteria of polymer flooding reservoir obtained in our previous work in which the gravity and capillary forces, compressibility, non-Newtonian behavior, absorption, dispersion, and diffusion are considered, eight partial similarity models are designed. A new numerical approach of sensitivity analysis is suggested to quantify the dominance degree of relaxed dimensionless parameters for partial similarity model. The sensitivity factor quantifying the dominance degree of relaxed dimensionless parameter is defined. By solving the dimensionless governing equations including all dimensionless parameters, the sensitivity factor of each relaxed dimensionless parameter is calculated for each partial similarity model; thus, the dominance degree of the relaxed one is quantitatively determined. Based on the sensitivity analysis, the effect coefficient of partial similarity model is defined as the summation of product of sensitivity factor of relaxed dimensionless parameter and its relative relaxation quantity. The effect coefficient is used as a criterion to evaluate each partial similarity model. Then the partial similarity model with the smallest effect coefficient can be singled out to approximate to the prototype. Results show that the precision of partial similarity model is not only determined by the number of satisfied dimensionless parameters but also the relative relaxation quantity of the relaxed ones.

Model selection for prognostic time-to-event gene signature discovery with applications in early breast cancer data

Model selection between competing models is a key consideration in the discovery of prognostic multigene signatures. The use of appropriate statistical performance measures as well as verification of biological significance of the signatures is imperative to maximise the chance of external validation of the generated signatures. Current approaches in time-to-event studies often use only a single measure of performance in model selection, such as logrank test p-values, or dichotomise the follow-up times at some phase of the study to facilitate signature discovery. In this study we improve the prognostic signature discovery process through the application of the multivariate partial Cox model combined with the concordance index, hazard ratio of predictions, independence from available clinical covariates and biological enrichment as measures of signature performance. The proposed framework was applied to discover prognostic multigene signatures from early breast cancer data. The partial Cox model combined with the multiple performance measures were used in both guiding the selection of the optimal panel of prognostic genes and prediction of risk within cross validation without dichotomising the follow-up times at any stage. The signatures were successfully externally cross validated in independent breast cancer datasets, yielding a hazard ratio of 2.55 [1.44, 4.51] for the top ranking signature.

The Ultraviolet-Bright, Slowly Declining Transient PS1-11af as a Partial Tidal Disruption Event

We present the Pan-STARRS1 discovery of the long-lived and blue transient PS1-11af, which was also detected by Galaxy Evolution Explorer with coordinated observations in the near-ultraviolet (NUV) band. PS1-11af is associated with the nucleus of an early type galaxy at redshift z = 0.4046 that exhibits no evidence for star formation or active galactic nucleus activity. Four epochs of spectroscopy reveal a pair of transient broad absorption features in the UV on otherwise featureless spectra. Despite the superficial similarity of these features to P-Cygni absorptions of supernovae (SNe), we conclude that PS1-11af is not consistent with the properties of known types of SNe. Blackbody fits to the spectral energy distribution are inconsistent with the cooling, expanding ejecta of a SN, and the velocities of the absorption features are too high to represent material in homologous expansion near a SN photosphere. However, the constant blue colors and slow evolution of the luminosity are similar to previous optically selected tidal disruption events (TDEs). The shape of the optical light curve is consistent with models for TDEs, but the minimum accreted mass necessary to power the observed luminosity is only 0.002 M, which points to a partial disruption model. A full disruption model predicts higher bolometric luminosities, which would require most of the radiation to be emitted in a separate component at high energies where we lack observations. In addition, the observed temperature is lower than that predicted by pure accretion disk models for TDEs and requires reprocessing to a constant, lower temperature. Three deep non-detections in the radio with the Very Large Array over the first two years after the event set strict limits on the production of any relativistic outflow comparable to Swift J1644+57, even if off-axis.

What Makes Science Hard for Newcomers?

Part I What makes science hard for newcomers? 1) The background (briefly) of my research - (why the math anxiety model doesn’t fit) 2) The Tier analysis (a visual) – message: there are many types of science learners in your class than simply younger versions of yourself 3) Three approaches (bio, chem, physics) but only one Nature 4) The (different) vocabularies of the three Sciences 5) How mathematics is variously used in Science Part II Rules and rules-driven assignments- lQ vs OQ1) How to incorporate creativity into assignments and tests? 2) Tests- borrowing “thought questions" from other fields (If Columbus hadn't discovered the new World, when and under whose law would it have been discovered?) 3) Grading practices (partial credit, post-exam credit for finding and explaining nontrivial errors 4) Icing on the cake – applications, examples of science/engineering from Tuesdays NY Times Part III Making Change at the Departmental Level 1) Taking control of at least some portion of the curriculum 2) Varying style of presentation 3) Taking control of at least some portion of the exams 4) GRADING pros and cons of grading on a curve 5) Updating labs and lab reporting.

Risk sharing with Multilateral Financial Institutions in infrastructure and energy project financing : effect on capital relief for commercial banks

(Matsukawa and Habeck, 2007) analyse the main instruments for risk mitigation in infrastructure financing with Multilateral Financial Institutions (MFIs). Their review coincided with the global financial crisis of 2007-08, and is highly relevant in current times considering the sovereign debt crisis, the lack of available capital and the increases in bank regulation in Western economies. The current macroeconomic environment has seen a slowdown in the level of finance for infrastructure projects, as they pose a higher credit risk given their requirements for long term investments. The rationale for this work is to look for innovative solutions that are focused on the credit risk mitigation of infrastructure and energy projects whilst optimizing the economic capital allocation for commercial banks. This objective is achieved through risk-sharing with MFIs and looking for capital relief in project finance transactions. This research finds out the answer to the main question: "What is the impact of risk-sharing with MFIs on project finance transactions to increase their efficiency and viability?", and is developed from the perspective of a commercial bank assessing the economic capital used and analysing the relevant variables for it: Probability of Default, Loss Given Default and Recovery Rates, (Altman, 2010). An overview of project finance for the infrastructure and energy sectors in terms of the volume of transactions worldwide is outlined, along with a summary of risk-sharing financing with MFIs. A review of the current regulatory framework beneath risk-sharing in structured finance with MFIs is also analysed. From here, the impact of risk-sharing and the diversification effect in infrastructure and energy projects is assessed, from the perspective of economic capital allocation for a commercial bank. CreditMetrics (J. P. Morgan, 1997) is applied over an existing well diversified portfolio of project finance infrastructure and energy investments, working with the main risk capital measures: economic capital, RAROC, and EVA. The conclusions of this research show that economic capital allocation on a portfolio of project finance along with risk-sharing with MFIs have a huge impact on capital relief whilst increasing performance profitability for commercial banks. There is an outstanding diversification effect due to the portfolio, which is combined with risk mitigation and an improvement in recovery rates through Partial Credit Guarantees issued by MFIs. A stress test scenario analysis is applied to the current assumptions and credit risk model, considering a downgrade in the rating for the commercial bank (lender) and an increase of default in emerging countries, presenting a direct impact on economic capital, through an increase in expected loss and a decrease in performance profitability. Getting capital relief through risk-sharing makes it more viable for commercial banks to finance infrastructure and energy projects, with the beneficial effect of a direct impact of these investments on GDP growth and employment. The main contribution of this work is to promote a strategic economic capital allocation in infrastructure and energy financing through innovative risk-sharing with MFIs and economic pricing to create economic value added for banks, and to allow the financing of more infrastructure and energy projects. This work suggests several topics for further research in relation to issues analysed. (Matsukawa and Habeck, 2007) analizan los principales instrumentos de mitigación de riesgos en las Instituciones Financieras Multilaterales (IFMs) para la financiación de infraestructuras. Su presentación coincidió con el inicio de la crisis financiera en Agosto de 2007, y sus consecuencias persisten en la actualidad, destacando la deuda soberana en economías desarrolladas y los problemas capitalización de los bancos. Este entorno macroeconómico ha ralentizado la financiación de proyectos de infraestructuras. El actual trabajo de investigación tiene su motivación en la búsqueda de soluciones para la financiación de proyectos de infraestructuras y de energía, mitigando los riesgos inherentes, con el objeto de reducir el consumo de capital económico en los bancos financiadores. Este objetivo se alcanza compartiendo el riesgo de la financiación con IFMs, a través de estructuras de risk-sharing. La investigación responde la pregunta: "Cuál es el impacto de risk-sharing con IFMs, en la financiación de proyectos para aumentar su eficiencia y viabilidad?". El trabajo se desarrolla desde el enfoque de un banco comercial, estimando el consumo de capital económico en la financiación de proyectos y analizando las principales variables del riesgo de crédito, Probability of Default, Loss Given Default and Recovery Rates, (Altman, 2010). La investigación presenta las cifras globales de Project Finance en los sectores de infraestructuras y de energía, y analiza el marco regulatorio internacional en relación al consumo de capital económico en la financiación de proyectos en los que participan IFMs. A continuación, el trabajo modeliza una cartera real, bien diversificada, de Project Finance de infraestructuras y de energía, aplicando la metodología CreditMet- rics (J. P. Morgan, 1997). Su objeto es estimar el consumo de capital económico y la rentabilidad de la cartera de proyectos a través del RAROC y EVA. La modelización permite estimar el efecto diversificación y la liberación de capital económico consecuencia del risk-sharing. Los resultados muestran el enorme impacto del efecto diversificación de la cartera, así como de las garantías parciales de las IFMs que mitigan riesgos, mejoran el recovery rate de los proyectos y reducen el consumo de capital económico para el banco comercial, mientras aumentan la rentabilidad, RAROC, y crean valor económico, EVA. En escenarios económicos de inestabilidad, empeoramiento del rating de los bancos, aumentos de default en los proyectos y de correlación en las carteras, hay un impacto directo en el capital económico y en la pérdida de rentabilidad. La liberación de capital económico, como se plantea en la presente investigación, permitirá financiar más proyectos de infraestructuras y de energía, lo que repercutirá en un mayor crecimiento económico y creación de empleo. La principal contribución de este trabajo es promover la gestión activa del capital económico en la financiación de infraestructuras y de proyectos energéticos, a través de estructuras innovadoras de risk-sharing con IFMs y de creación de valor económico en los bancos comerciales, lo que mejoraría su eficiencia y capitalización. La aportación metodológica del trabajo se convierte por su originalidad en una contribución, que sugiere y facilita nuevas líneas de investigación académica en las principales variables del riesgo de crédito que afectan al capital económico en la financiación de proyectos.