The Equiprobability Bias from a Mathematical and Psychological Perspective

The equiprobability bias (EB) is a tendency to believe that every process in which randomness is involved corresponds to a fair distribution, with equal probabilities for any possible outcome. The EB is known to affect both children and adults, and to increase with probability education. Because it results in probability errors resistant to pedagogical interventions, it has been described as a deep misconception about randomness: the erroneous belief that randomness implies uniformity. In the present paper, we show that the EB is actually not the result of a conceptual error about the definition of randomness. On the contrary, the mathematical theory of randomness does imply uniformity. However, the EB is still a bias, because people tend to assume uniformity even in the case of events that are not random. The pervasiveness of the EB reveals a paradox: The combination of random processes is not necessarily random. The link between the EB and this paradox is discussed, and suggestions are made regarding educational design to overcome difficulties encountered by students as a consequence of the EB.

Dose-response relationship in phase 1 clinical trials: a European Drug Development Network (EDDN) Collaboration Study

Introduction: Because a dose–response relationship is characteristic of conventional chemotherapy, this concept is widely used for the development of novel cytotoxic (CTX) drugs. However, the need to reach the MTD to obtain optimal benefit with molecularly targeted agents (MTA) is controversial. In this study, we evaluated the relationship between dose and efficacy in a large cohort of phase I patients with solid tumors.

Experimental Design: We collected data on 1,182 consecutive patients treated in phase I trials in 14 European institutions in 2005–2007. Inclusion criteria were: (i) patients treated within completed single-agent studies in which a maximum-administered dose was defined and (ii) RECIST/survival data available.

Results: Seventy-two percent of patients were included in trials with MTA (N = 854) and 28% in trials with CTX (N = 328). The objective response (OR) rate was 3% and disease control at 6 months was 11%. OR for CTX was associated with higher doses (median 92% of MTD); this was not the case for MTA, where patients achieving OR received a median of 50% of MTD. For trials with MTA, patients treated at intermediate doses (40%–80%) had better survival compared with those receiving low or high doses (P = 0.038). On the contrary, there was a direct association between higher dose and better OS for CTX agents (P = 0.003).

Conclusion: Although these results support the development of novel CTX based on MTD, we found no direct relationship between higher doses and response with MTA in unselected patients. However, the longest OS was seen in patients treated with MTA at intermediate doses (40%–80% of MTD)

A role for whey acidic protein four-disulfide-core 12 (WFDC12) in the regulation of the inflammatory response in the lung

Introduction: Secretory leucocyte protease inhibitor and elafin are members of the whey acidic protein (WAP), or WAP four disulfide-core (WFDC), family of proteins and have multiple contributions to innate defence including inhibition of neutrophil serine proteases and inhibition of the inflammatory response to lipopolysaccharide (LPS). This study aimed to explore potential activities of WFDC12, a previously uncharacterised WFDC protein expressed in the lung. Methods: Recombinant expression and purification of WFDC12 were optimised in Escherichia coli. Antiprotease, antibacterial and immunomodulatory activities of recombinant WFDC12 were evaluated and levels of endogenous WFDC12 protein were characterised by immunostaining and ELISA. Results: Recombinant WFDC12 inhibited cathepsin G, but not elastase or proteinase-3 activity. Monocytic cells pretreated with recombinant WFDC12 before LPS stimulation produced significantly lower levels of the pro-inflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared with cells stimulated with LPS alone. Recombinant WFDC12 became conjugated to fibronectin in a transglutaminase-mediated reaction and retained antiprotease activity. In vivo WFDC12 expression was confirmed by immunostaining of human lung tissue sections. WFDC12 levels in human bronchoalveolar lavage fluid from healthy and lung-injured patients were quantitatively compared, showing WFDC12 to be elevated in both patients with acute respiratory distress syndrome and healthy subjects treated with LPS, relative to healthy controls. Conclusions: Together, these results suggest a role for this lesser known WFDC protein in the regulation of lung inflammation.

In vitro and in vivo methodologies for studying the Sigma 54-dependent transcription.

Here we describe approaches and methods to assaying in vitro the major variant bacterial sigma factor, Sigma 54 (σ54), in a purified system. We include the complete transcription system, binding interactions between σ54 and its activators, as well as the self-assembly and the critical ATPase activity of the cognate activators which serve to remodel the closed promoter complexes. We also present in vivo methodologies that are used to study the impact of physiological processes, metabolic states, global signalling networks, and cellular architecture on the control of σ54-dependent gene expression.

A new look towards BAC-based array CGH through a comprehensive comparison with oligo-based array CGH

BACKGROUND: Currently, two main technologies are used for screening of DNA copy number; the BAC (Bacterial Artificial Chromosome) and the recently developed oligonucleotide-based CGH (Chromosomal Comparative Genomic Hybridization) arrays which are capable of detecting small genomic regions with amplification or deletion. The correlation as well as the discriminative power of these platforms has never been compared statistically on a significant set of human patient samples.

RESULTS: In this paper, we present an exhaustive comparison between the two CGH platforms, undertaken at two independent sites using the same batch of DNA from 19 advanced prostate cancers. The comparison was performed directly on the raw data and a significant correlation was found between the two platforms. The correlation was greatly improved when the data were averaged over large chromosomic regions using a segmentation algorithm. In addition, this analysis has enabled the development of a statistical model to discriminate BAC outliers that might indicate microevents. These microevents were validated by the oligo platform results.

CONCLUSION: This article presents a genome-wide statistical validation of the oligo array platform on a large set of patient samples and demonstrates statistically its superiority over the BAC platform for the Identification of chromosomic events. Taking advantage of a large set of human samples treated by the two technologies, a statistical model has been developed to show that the BAC platform could also detect microevents.

High-dose therapy and autologous stem cell transplantation in first relapse for diffuse large B cell lymphoma in the rituximab era:an analysis based on data from the European Blood and Marrow Transplantation Registry

Autologous stem cell transplantation (ASCT) consolidation remains the treatment of choice for patients with relapsed diffuse large B cell lymphoma. The impact of rituximab combined with chemotherapy in either first- or second-line therapy on the ultimate results of ASCT remains to be determined, however. This study was designed to evaluate the benefit of ASCT in patients achieving a second complete remission after salvage chemotherapy by retrospectively comparing the disease-free survival (DFS) after ASCT for each patient with the duration of the first complete remission (CR1). Between 1990 and 2005, a total of 470 patients who had undergone ASCT and reported to the European Blood and Bone Transplantation Registry with Medical Essential Data Form B information were evaluated. Of these 470 patients, 351 (74%) had not received rituximab before ASCT, and 119 (25%) had received rituximab before ASCT. The median duration of CR1 was 11 months. The median time from diagnosis to ASCT was 24 months. The BEAM protocol was the most frequently used conditioning regimen (67%). After ASCT, the 5-year overall survival was 63% (95% confidence interval, 58%-67%) and 5-year DFS was 48% (95% confidence interval, 43%-53%) for the entire patient population. Statistical analysis showed a significant increase in DFS after ASCT compared with duration of CR1 (median, 51 months versus 11 months; P < .001). This difference was also highly significant for patients with previous exposure to rituximab (median, 10 months versus not reached; P < .001) and for patients who had experienced relapse before 1 year (median, 6 months versus 47 months; P < .001). Our data indicate that ASCT can significantly increase DFS compared with the duration of CR1 in relapsed diffuse large B cell lymphoma and can alter the disease course even in patients with high-risk disease previously treated with rituximab.

Les techniques du dinandier: formes et fonction des outils lithiques spécifiques à la déformation plastique des métaux

In recent years, the proliferation of discoveries has enabled studies of stone tools used in metal working to develop. The increasing number of tools, made mostly from Neolithic polished axes, reveals a typological and functional diversity that remained largely unsuspected. This diversity is an opportunity to understand the tools and address the technical issues relating to the plastic deformation of metals. The operations that are represented here demonstrate the techniques used by coppersmiths with specialised tools.

Estrategias pedagógicas basadas en el diseño universal para el aprendizaje: una aproximación desde la comunicación educativa

Libro que presenta estrategias pedagógicas para la educación inclusiva en las diferentes etapas educativas como preescolar, básica, media y universitaria.

ORBS and the limits of static slicing

Observation-based slicing is a recently-introduced, language-independent, slicing technique based on the dependencies observable from program behaviour. Due to the wellknown limits of dynamic analysis, we may only compute an under-approximation of the true observation-based slice. However, because the observation-based slice captures all possible dependence that can be observed, even such approximations can yield insight into the limitations of static slicing. For example, a static slice, S that is strictly smaller than the corresponding observation based slice is guaranteed to be unsafe. We present the results of three sets of experiments on 12 different programs, including benchmarks and larger programs, which investigate the relationship between static and observation-based slicing. We show that, in extreme cases, observation-based slices can find the true static minimal slice, where static techniques cannot. For more typical cases, our results illustrate the potential for observation-based slicing to highlight unsafe static slices. Finally, we report on the sensitivity of observation-based slicing to test quality.

Les effets du travail en équipe dans l'apprentissage par projets sur la motivation des étudiantes et des étudiants en formation des ingénieurs

Les représentants des secteurs industriels et les milieux professionnels en Amérique du Nord reprochaient aux universités de former des ingénieurs avec peu d'expérience pratique en résolution de problèmes et en conception. Quelques programmes de génie ont alors mis en place le travail en équipe dans l'apprentissage par projets. Beaucoup d'écrits font valoir les bénéfices de l'apprentissage par projets sur la motivation des étudiants. Or, ces bénéfices commencent à peine à faire l'objet de recherches visant à produire des données probantes à ce sujet.Les travaux sur la motivation en contexte d'apprentissage et les modèles théoriques développés sont issus d'environnements d'apprentissage marqués par l'enseignement magistral. Le modèle de la valeur attendue de la tâche (Eccles et Wigfield, 1995; Neuville, 2004) et le modèle du système-groupe (St-Arnaud, 2008) ont été retenus pour mesurer les effets du travail en équipe dans l'apprentissage par projets sur la motivation. La recherche visait aussi à approfondir et à nuancer la compréhension de la motivation des étudiants universitaires apprenant en contexte innovant.Les sujets constituent une cohorte (n=100) travaillant sur des projets d'intégration au cours des trois sessions initiales du programme de génie mécanique d'une université canadienne. L'analyse de régression multiple révèle que les construits de la motivation expliquent un tiers de la variance de l'engagement académique dans la réalisation du projet d'intégration.Les perceptions de l'"expectancy", de la valeur intrinsèque et utilitaire sont les déterminants principaux de l'engagement des étudiants. L'analyse de variance multivariée à mesures répétées indique que la motivation des étudiants pour le travail sur les projets d'intégration a augmenté au cours des trois sessions initiales du parcours de formation. Finalement, malgré l'absence d'interaction significative entre les variables de motivation et de l'équipe, les réponses des sujets indiquent une amélioration du travail en équipe au terme des trois sessions.

Inovação tecnológica nas PME e dinâmica regional em Portugal

Tese de dout., Economia (Economia da Informação), Faculdade de Economia, Univ. do Algarve, 2004

L’harmonie vocalique turque : entre théories et pratique

Dans ce travail, je propose que l’harmonie vocalique turque n’est plus un phénomène phonologique synchroniquement productif en cette langue. Ce qui est jugé harmonique n’est en fait que les traces d’un système harmonique ancien, traces qui se sont morphologisées. La démonstration est faite 1) en critiquant la littérature existante et en montrant les paradoxes auxquels elle mène et 2) en regardant du côté des travaux sur l’acquisition du langage, la perception du langage et le transfert linguistique. Il est montré que la seule raison de postuler l’harmonie vocalique turque tient à nos présupposés sur ce qu’est la morphologie d’une langue. Certains modèles phonologiques ne prenant pas en compte ces présupposés sont ensuite étudiés. Une formalisation utilisant le modèle morphologique Whole Word Morphology est finalement proposée.

How to increase brand value expanding the category and brand presence to the main meal occasion for Sumol- Compal

Having registered negative retail value growth of 4% in Portugal in 2014, the juice category is set to decline further by 5,5% until 2019. Manufacturers of juices and nectars are therefore increasingly looking for new categories in order to balance this negative forecast in their home territory. One apparent growth opportunity for Compal, the leading producer of juices and nectars, is to expand its commercial reach to new occasions of consumption. This report carefully analyzes the opportunities related to an expansion to the main meal occasion and introduces a complete marketing and communications plan for a possible new main meal juice, Compal à Mesa. The product concept represents a rather premium positioning for the main meal occasion, including new flavor mixes that are targeted at different occasions of meals. The justification of the introduced concept includes a discussion of the primary and secondary research that was performed

Mdx myotubes have normal excitability but show reduced contraction-relaxation dynamics.

The pathogenesis of Duchenne muscular dystrophy (DMD), characterised by lack of the cytoskeletal protein dystrophin, is not completely understood. An early event in the degenerative process of DMD muscle could be a rise in cytosolic calcium concentration. In order to investigate whether this leads to alterations of contractile behaviour, we studied the excitability and contractile properties of cultured myotubes from control (C57BL/10) and mdx mice, an animal model for DMD. The myotubes were stimulated electrically and their motion was recorded photometrically. No significant differences were found between control and mdx myotubes with respect to the following parameters: chronaxy and rheobase (0.33 +/- 0.03 ms and 23 +/- 4 V vs. 0.39 +/- 0.07 ms and 22 +/- 2 V for C57 and mdx myotubes, respectively), tetanisation frequency (a similar distribution pattern was found between 5 and 30 Hz), fatigue during tetanus (found in 35% of both types of myotubes) and post-tetanic contracture. In contrast, contraction and relaxation times were longer (P < 0.005) in mdx (36 +/- 2 and 142 +/- 13 ms, respectively) than in control myotubes (26 +/- 1 and 85 +/- 9 ms, respectively). Together with our earlier findings, these results suggest a decreased capacity for calcium removal in mdx cells leading, in particular, to alterations of muscle relaxation.

Glutathione deficit during development induces anomalies in the rat anterior cingulate GABAergic neurons: Relevance to schizophrenia.

A series of studies in schizophrenic patients report a decrease of glutathione (GSH) in prefrontal cortex (PFC) and cerebrospinal fluid, a decrease in mRNA levels for two GSH synthesizing enzymes and a deficit in parvalbumin (PV) expression in a subclass of GABA neurons in PFC. GSH is an important redox regulator, and its deficit could be responsible for cortical anomalies, particularly in regions rich in dopamine innervation. We tested in an animal model if redox imbalance (GSH deficit and excess extracellular dopamine) during postnatal development would affect PV-expressing neurons. Three populations of interneurons immunolabeled for calcium-binding proteins were analyzed quantitatively in 16-day-old rat brain sections. Treated rats showed specific reduction in parvalbumin immunoreactivity in the anterior cingulate cortex, but not for calbindin and calretinin. These results provide experimental evidence for the critical role of redox regulation in cortical development and validate this animal model used in schizophrenia research.