A measure of stability as a criterion for the verification and analysis of simulation models

The aim of this study is to define a new statistic, PVL, based on the relative distance between the likelihood associated with the simulation replications and the likelihood of the conceptual model. Our results coming from several simulation experiments of a clinical trial show that the PVL statistic range can be a good measure of stability to establish when a computational model verifies the underlying conceptual model. PVL improves also the analysis of simulation replications because only one statistic is associated with all the simulation replications. As well it presents several verification scenarios, obtained by altering the simulation model, that show the usefulness of PVL. Further simulation experiments suggest that a 0 to 20 % range may define adequate limits for the verification problem, if considered from the viewpoint of an equivalence test.

Classification models for neurocognitive impairment in HIV infection based on demographic and clinical variables

Objective: We used demographic and clinical data to design practical classification models for prediction of neurocognitive impairment (NCI) in people with HIV infection. Methods: The study population comprised 331 HIV-infected patients with available demographic, clinical, and neurocognitive data collected using a comprehensive battery of neuropsychological tests. Classification and regression trees (CART) were developed to btain detailed and reliable models to predict NCI. Following a practical clinical approach, NCI was considered the main variable for study outcomes, and analyses were performed separately in treatment-naïve and treatment-experienced patients. Results: The study sample comprised 52 treatment-naïve and 279 experienced patients. In the first group, the variables identified as better predictors of NCI were CD4 cell count and age (correct classification [CC]: 79.6%, 3 final nodes). In treatment-experienced patients, the variables most closely related to NCI were years of education, nadir CD4 cell count, central nervous system penetration-effectiveness score, age, employment status, and confounding comorbidities (CC: 82.1%, 7 final nodes). In patients with an undetectable viral load and no comorbidities, we obtained a fairly accurate model in which the main variables were nadir CD4 cell count, current CD4 cell count, time on current treatment, and past highest viral load (CC: 88%, 6 final nodes). Conclusion: Practical classification models to predict NCI in HIV infection can be obtained using demographic and clinical variables. An approach based on CART analyses may facilitate screening for HIV-associated neurocognitive disorders and complement clinical information about risk and protective factors for NCI in HIV-infected patients.

Probabilistic graphical models to deal with age estimation of living persons

Due to the rise of criminal, civil and administrative judicial situations involving people lacking valid identity documents, age estimation of living persons has become an important operational procedure for numerous forensic and medicolegal services worldwide. The chronological age of a given person is generally estimated from the observed degree of maturity of some selected physical attributes by means of statistical methods. However, their application in the forensic framework suffers from some conceptual and practical drawbacks, as recently claimed in the specialised literature. The aim of this paper is therefore to offer an alternative solution for overcoming these limits, by reiterating the utility of a probabilistic Bayesian approach for age estimation. This approach allows one to deal in a transparent way with the uncertainty surrounding the age estimation process and to produce all the relevant information in the form of posterior probability distribution about the chronological age of the person under investigation. Furthermore, this probability distribution can also be used for evaluating in a coherent way the possibility that the examined individual is younger or older than a given legal age threshold having a particular legal interest. The main novelty introduced by this work is the development of a probabilistic graphical model, i.e. a Bayesian network, for dealing with the problem at hand. The use of this kind of probabilistic tool can significantly facilitate the application of the proposed methodology: examples are presented based on data related to the ossification status of the medial clavicular epiphysis. The reliability and the advantages of this probabilistic tool are presented and discussed.

Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary CNS in vitro models.

The present study was performed in an attempt to develop an in vitro integrated testing strategy (ITS) to evaluate drug-induced neurotoxicity. A number of endpoints were analyzed using two complementary brain cell culture models and an in vitro blood-brain barrier (BBB) model after single and repeated exposure treatments with selected drugs that covered the major biological, pharmacological and neuro-toxicological responses. Furthermore, four drugs (diazepam, cyclosporine A, chlorpromazine and amiodarone) were tested more in depth as representatives of different classes of neurotoxicants, inducing toxicity through different pathways of toxicity. The developed in vitro BBB model allowed detection of toxic effects at the level of BBB and evaluation of drug transport through the barrier for predicting free brain concentrations of the studied drugs. The measurement of neuronal electrical activity was found to be a sensitive tool to predict the neuroactivity and neurotoxicity of drugs after acute exposure. The histotypic 3D re-aggregating brain cell cultures, containing all brain cell types, were found to be well suited for OMICs analyses after both acute and long term treatment. The obtained data suggest that an in vitro ITS based on the information obtained from BBB studies and combined with metabolomics, proteomics and neuronal electrical activity measurements performed in stable in vitro neuronal cell culture systems, has high potential to improve current in vitro drug-induced neurotoxicity evaluation.

Courts and Courtly Cultures in Early Modern Italy and Europe: Models and Languages

This volume deals with the forms of propaganda and self-representation, through words and images, during the rise of the 'civiltà delle corti' and through processes typical of the time, such as confrontation, adaptation, competition and rivalry. This period, which marked the passage of Italian and European culture from the Middle Ages to the Renaissance, is fundamental in the development of Modern Europe, and it lasted up to the XVIII century and beyond. At the heart of many matters debated here lies the relationship between culture and politics. The formation of a 'Lombard identity', central to the Sinergia project which was the frame of the whole research and its conferences, is closely linked to this broad general context. It places the so called 'questione milanese' - above the traditional hierarchies 'Toscana oriented' - at the centre of many questions regarding Northern Italy as a whole, starting from the dissolution of the Medieval communes, through to the rise of the signorie, from the end of the XIII century and the beginning of the XIV century up to the early XVI century.

Reciprocal Effects on Neurocognitive and Metabolic Phenotypes in Mouse Models of 16p11.2 Deletion and Duplication Syndromes.

The 16p11.2 600 kb BP4-BP5 deletion and duplication syndromes have been associated with developmental delay; autism spectrum disorders; and reciprocal effects on the body mass index, head circumference and brain volumes. Here, we explored these relationships using novel engineered mouse models carrying a deletion (Del/+) or a duplication (Dup/+) of the Sult1a1-Spn region homologous to the human 16p11.2 BP4-BP5 locus. On a C57BL/6N inbred genetic background, Del/+ mice exhibited reduced weight and impaired adipogenesis, hyperactivity, repetitive behaviors, and recognition memory deficits. In contrast, Dup/+ mice showed largely opposite phenotypes. On a F1 C57BL/6N × C3B hybrid genetic background, we also observed alterations in social interaction in the Del/+ and the Dup/+ animals, with other robust phenotypes affecting recognition memory and weight. To explore the dosage effect of the 16p11.2 genes on metabolism, Del/+ and Dup/+ models were challenged with high fat and high sugar diet, which revealed opposite energy imbalance. Transcriptomic analysis revealed that the majority of the genes located in the Sult1a1-Spn region were sensitive to dosage with a major effect on several pathways associated with neurocognitive and metabolic phenotypes. Whereas the behavioral consequence of the 16p11 region genetic dosage was similar in mice and humans with activity and memory alterations, the metabolic defects were opposite: adult Del/+ mice are lean in comparison to the human obese phenotype and the Dup/+ mice are overweight in comparison to the human underweight phenotype. Together, these data indicate that the dosage imbalance at the 16p11.2 locus perturbs the expression of modifiers outside the CNV that can modulate the penetrance, expressivity and direction of effects in both humans and mice.

Student Journalism 2.0 : Testing Models for Participatory Learning in the Digital Age

Many educators and educational institutions have yet to integrate web-based practices into their classrooms and curricula. As a result, it can be difficult to prototype and evaluate approaches to transforming classrooms from static endpoints to dynamic, content-creating nodes in the online information ecosystem. But many scholastic journalism programs have already embraced the capabilities of the Internet for virtual collaboration, dissemination, and reader participation. Because of this, scholastic journalism can act as a test-bed for integrating web-based sharing and collaboration practices into classrooms. Student Journalism 2.0 was a research project to integrate open copyright licenses into two scholastic journalism programs, to document outcomes, and to identify recommendations and remaining challenges for similar integrations. Video and audio recordings of two participating high school journalism programs informed the research. In describing the steps of our integration process, we note some important legal, technical, and social challenges. Legal worries such as uncertainty over copyright ownership could lead districts and administrators to disallow open licensing of student work. Publication platforms among journalism classrooms are far from standardized, making any integration of new technologies and practices difficult to achieve at scale. And teachers and students face challenges re-conceptualizing the role their class work can play online.

Tests of International Asset Pricing Models in Scandinavian Stock Markets

This thesis examines whether global, local and exchange risks are priced in Scandinavian countries’ equity markets by using conditional international asset pricing models. The employed international asset pricing models are the world capital asset pricing model, the international asset pricing model augmented with the currency risk, and the partially segmented model augmented with the currency risk. Moreover, this research traces estimated equity risk premiums for the Scandinavian countries. The empirical part of the study is performed using generalized method of moments approach. Monthly observations from February 1994 to June 2007 are used. Investors’ conditional expectations are modeled using several instrumental variables. In order to keep system parsimonious the prices of risk are assumed to be constant whereas expected returns and conditional covariances vary over time. The empirical findings of this thesis suggest that the prices of global and local market risk are priced in the Scandinavian countries. This indicates that the Scandinavian countries are mildly segmented from the global markets. Furthermore, the results show that the exchange risk is priced in the Danish and Swedish stock markets when the partially segmented model is augmented with the currency risk factor.