Hypothesis testing in an errors-in-variables model with heteroscedastic measurement errors

In many epidemiological studies it is common to resort to regression models relating incidence of a disease and its risk factors. The main goal of this paper is to consider inference on such models with error-prone observations and variances of the measurement errors changing across observations. We suppose that the observations follow a bivariate normal distribution and the measurement errors are normally distributed. Aggregate data allow the estimation of the error variances. Maximum likelihood estimates are computed numerically via the EM algorithm. Consistent estimation of the asymptotic variance of the maximum likelihood estimators is also discussed. Test statistics are proposed for testing hypotheses of interest. Further, we implement a simple graphical device that enables an assessment of the model`s goodness of fit. Results of simulations concerning the properties of the test statistics are reported. The approach is illustrated with data from the WHO MONICA Project on cardiovascular disease. Copyright (C) 2008 John Wiley & Sons, Ltd.

Beta-binomial/Poisson regression models for repeated bivariate counts

We analyze data obtained from a study designed to evaluate training effects on the performance of certain motor activities of Parkinson`s disease patients. Maximum likelihood methods were used to fit beta-binomial/Poisson regression models tailored to evaluate the effects of training on the numbers of attempted and successful specified manual movements in 1 min periods, controlling for disease stage and use of the preferred hand. We extend models previously considered by other authors in univariate settings to account for the repeated measures nature of the data. The results suggest that the expected number of attempts and successes increase with training, except for patients with advanced stages of the disease using the non-preferred hand. Copyright (c) 2008 John Wiley & Sons, Ltd.

Gene expression profiling reveals molecular marker candidates of laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma is very common in head and neck cancer, with high mortality rates and poor prognosis. In this study, we compared expression profiles of clinical samples from 13 larynx tumors and 10 non-neoplastic larynx tissues using a custom-built cDNA microarray containing 331 probes for 284 genes previously identified by informatics analysis of EST databases as markers of head and neck tumors. Thirty-five genes showed statistically significant differences (SNR >= 11.01, p <= 0.001) in the expression between tumor and non-tumor larynx tissue samples. Functional annotation indicated that these genes are involved in cellular processes relevant to the cancer phenotype, such as apoptosis, cell cycle, DNA repair, proteolysis, protease inhibition, signal transduction and transcriptional regulation. Six of the identified transcripts map to intronic regions of protein-coding genes and may comprise non-annotated exons or as yet uncharacterized long ncRNAs with a regulatory role in the gene expression program of larynx tissue. The differential expression of 10 of these genes (ADCY6, AES, AL2SCR3, CRR9, CSTB, DUSP1, MAP3K5, PLAT, UBL1 and ZNF706) was independently confirmed by quantitative real-time RT-PCR. Among these, the CSTB gene product has cysteine protease inhibitor activity that has been associated with an antimetastatic function. Interestingly, CSTB showed a low expression in the tumor samples analyzed (p<0.0001). The set of genes identified here contribute to a better understanding of the molecular basis of larynx cancer, and provide candidate markers for improving diagnosis, prognosis and treatment of this carcinoma.

MPO Inhibitors Selected by Virtual Screening

The hemeprotein myeloperoxidase (MPO) participates in innate immune defense through its ability to generate potent microbicidal oxidants. However, these oxidants are also key mediators of the tissue damage associated with many inflammatory diseases. Thus, there is considerable interest in developing therapeutically useful MPO inhibitors. Here, we used structure-based drug design (SBDD) and ligand-based drug design (LBDD) to select for potentially new and selective MPO inhibitors. A pharmacophore model was developed based on the crystal structure of human MPO in complex with salicylhydroxamic acid (SHA), a known inhibitor of the enzyme. The pharmacophore model was used to screen the ZINC database for potential ligands, which were further filtered on the basis of their physical-chemical properties and docking score. The filtered compounds were visually inspected, and nine were purchased for experimental studies. Surprisingly, almost all of the selected compounds belonged to the aromatic hydrazide class, which had been previously described as MPO inhibitors. The compounds selected by virtual screening were shown to inhibit the chlorinating activity of MPO; the top four compounds displayed IC(50) values ranging from 1.0 to 2.8 mM. MPO inactivation by the most effective compound was shown to be irreversible. Overall, our results show that SBDD and LBDD may be useful for the rational development of new MPO inhibitors.

Integration of Ligand- and Target-Based Virtual Screening for the Discovery of Cruzain Inhibitors

A myriad of methods are available for virtual screening of small organic compound databases. In this study we have successfully applied a quantitative model of consensus measurements, using a combination of 3D similarity searches (ROCS and EON), Hologram Quantitative Structure Activity Relationships (HQSAR) and docking (FRED, FlexX, Glide and AutoDock Vina), to retrieve cruzain inhibitors from collected databases. All methods were assessed individually and then combined in a Ligand-Based Virtual Screening (LBVS) and Target-Based Virtual Screening (TBVS) consensus scoring, using Receiving Operating Characteristic (ROC) curves to evaluate their performance. Three consensus strategies were used: scaled-rank-by-number, rank-by-rank and rank-by-vote, with the most thriving the scaled-rank-by-number strategy, considering that the stiff ROC curve appeared to be satisfactory in every way to indicate a higher enrichment power at early retrieval of active compounds from the database. The ligand-based method provided access to a robust and predictive HQSAR model that was developed to show superior discrimination between active and inactive compounds, which was also better than ROCS and EON procedures. Overall, the integration of fast computational techniques based on ligand and target structures resulted in a more efficient retrieval of cruzain inhibitors with desired pharmacological profiles that may be useful to advance the discovery of new trypanocidal agents.

IT support for administrative planning of clinical practice.

The administration of clinical practice placements for nursing students is a highly complex and information driven task. This demonstration is intended to give insight into the web based system KliPP (a Swedish acronym for Clinical Practice Planning) and to discuss the possibilities for further development and use.

Validity and responsiveness of at-home touch-screen assessments in advanced Parkinson's disease

The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales. In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS respectively. The trends of the test scores were similar to the trends of clinical rating scores but dropout rate was high. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.

Design and use of mobile technology in distance language education : Matching learning practices with technologies-in-practice

This thesis focuses on the adaptation of formal education to people’s technology- use patterns, theirtechnology-in-practice, where the ubiquitous use of mobile technologies is central. The research question is: How can language learning practices occuring in informal learning environments be effectively integrated with formal education through the use of mobile technology? The study investigates the technical, pedagogical, social and cultural challenges involved in a design science approach. The thesis consists of four studies. The first study systematises MALL (mobile-assisted language learning) research. The second investigates Swedish and Chinese students’ attitudes towards the use of mobile technology in education. The third examines students’ use of technology in an online language course, with a specific focus on their learning practices in informal learning contexts and their understanding of how this use guides their learning. Based on the findings, a specifically designed MALL application was built and used in two courses. Study four analyses the app use in terms of students’ perceived level of self-regulation and structuration. The studies show that technology itself plays a very important role in reshaping peoples’ attitudes and that new learning methods are coconstructed in a sociotechnical system. Technology’s influence on student practices is equally strong across borders. Students’ established technologies-in-practice guide the ways they approach learning. Hence, designing effective online distance education involves three interrelated elements: technology, information, and social arrangements. This thesis contributes to mobile learning research by offering empirically and theoretically grounded insights that shift the focus from technology design to design of information systems.

Aspectos do projeto e implementação de ambientes multiparadigmas de programação

O desenvolvimento de software complexo de grande porte é muitas vezes dificultado pela carência de ferramentas adequadas para a clara expressão das idéias dos programadores em todos os aspectos técnicos do projeto. Isto é particularmente verdadeiro quando se lida com o poder de expressão de linguagens de programação. Como os grandes programas se compõem usualmente de segmentos com características técnicas diversificadas, parece natural disponibilizar ferramentas específicas para os programadores, de forma que uma boa expressividade seja obtida no código correspondente. As técnicas multiparadigma e multilinguagem são discutidas como formas alternativas de satisfazer essas necessidades, e a implementação de um ambiente de desenvolvimento multilinguagem (multiparadigma) é proposta e discutida em seus aspectos diversos. O artigo finaliza com uma bibliografia significativa sobre o tema, orientando os leitores interessados tanto nos aspectos de projeto como nos de caráter filosófico da técnica proposta.

Recursos da tecnologia da informatica no ensino / aprendizagem : a visao dos professores das escolas estaduais de ensino medio de Porto Alegre

Frente às transformações advindas do impacto das tecnologias na sociedade e nas organizações, bem como as novas habilidades e competências a serem adquiridas pelos profissionais no disputado mercado de trabalho atual, faz-se relevante atualizar os processos de ensino/aprendizagem, de forma a qualificar a formação profissional do egresso de ensino médio. O presente estudo tem por objetivo analisar a visão dos professores sobre as implicações da introdução dos recursos de informática nas organizações estaduais de ensino médio de Porto Alegre. Sua investigação tem como dimensão predominante uma abordagem quantitativa, de caráter exploratório sobre as percepções dos professores. Uma segunda dimensão - contextual - identifica as principais políticas educacionais para a área de informática no ensino médio. A dimensão do professor tem, por sua vez, duas subdimensões: o papel do professor frente ao processo de ensino-aprendizagem e suas percepções quanto à introdução dos recursos da tecnologia da informática no ensino médio. A base empírica desta dimensão adveio de dez escolas, selecionadas através de amostragem por cotas, tendo como instrumento de coleta de dados um questionário. Na dimensão contextual, foram realizadas pesquisa documental e entrevistas junto aos ór gãos oficiais responsáveis pelas políticas de informática educacional e direções de escolas e professores. Os resultados mostram que os professores do ensino médio das escolas estaduais de Porto Alegre concordam e percebem como prioritária a introdução dos recursos da tecnologia da informática nas escolas e que, para usufruir adequadamente destes recursos, os docentes devem assumir uma nova postura frente aos métodos de ensino-aprendizagem. Esta postura vem permitir e incentivar que o discente seja o sujeito do processo de construção do seu conhecimento. Esta pesquisa também identificou diretrizes para a formação de professores subsidiando, assim, políticas públicas para a área de educação no Estado.