Avoiding deontic explosion by contextually restricting aggregation

In this paper, we present an adaptive logic for deontic conflicts, called P2.1(r), that is based on Goble's logic SDLaPe-a bimodal extension of Goble's logic P that invalidates aggregation for all prima facie obligations. The logic P2.1(r) has several advantages with respect to SDLaPe. For consistent sets of obligations it yields the same results as Standard Deontic Logic and for inconsistent sets of obligations, it validates aggregation "as much as possible". It thus leads to a richer consequence set than SDLaPe. The logic P2.1(r) avoids Goble's criticisms against other non-adjunctive systems of deontic logic. Moreover, it can handle all the 'toy examples' from the literature as well as more complex ones

Using Comparative Preference Statements in Hypervolume-Based Interactive Multiobjective Optimization

International audienceThe objective functions in multiobjective optimization problems are often non-linear, noisy, or not available in a closed form and evolutionary multiobjective optimization (EMO) algorithms have been shown to be well applicable in this case. Here, our objective is to facilitate interactive decision making by saving function evaluations outside the "interesting" regions of the search space within a hypervolume-based EMO algorithm. We focus on a basic model where the Decision Maker (DM) is always asked to pick the most desirable solution among a set. In addition to the scenario where this solution is chosen directly, we present the alternative to specify preferences via a set of so-called comparative preference statements. Examples on standard test problems show the working principles, the competitiveness, and the drawbacks of the proposed algorithm in comparison with the recent iTDEA algorithm

R&D Proposal Development of Micro-Pattern Gas Detector Technologies

Development of advanced gas-avalanche detector technologies and associated electronic-readout systems for applications in basic and applied researc

The Norm Implementation Problem in Normative Multi-Agent Systems

Abstract. The norm implementation problem consists in how to see to it that the agents in a system comply with the norms specified for that system by the system designer. It is part of the more general problem of how to synthesize or create norms for multi-agent systems, by, for example, highlighting the choice between regimentation and enforcement, or the punishment associated with a norm violation. In this paper we discuss how various ways to implement norms in a multi-agent system can be distinguished in a formal game-theoretic framework. In particular, we show how different types of norm implementation can all be uniformly specified and verified as types of transformations of extensive games. We introduce the notion of retarded preconditions to implement norms, and we illustrate the framework and the various ways to implement norms in the blocks world environment

Ottawa 2020 consensus statements for programmatic assessment 2: Implementation and practice

INTRODUCTION: Programmatic assessment is a longitudinal, developmental approach that fosters and harnesses the learning function of assessment. Yet the implementation, a critical step to translate theory into practice, can be challenging. As part of the Ottawa 2020 consensus statement on programmatic assessment, we sought to provide descriptions of the implementation of the 12 principles of programmatic assessment and to gain insight into enablers and barriers across different institutions and contexts. METHODS: After the 2020 Ottawa conference, we surveyed 15 Health Profession Education programmes from six different countries about the implementation of the 12 principles of programmatic assessment. Survey responses were analysed using a deductive thematic analysis. RESULTS AND DISCUSSION: A wide range of implementations were reported although the principles remained, for the most part, faithful to the original enunciation and rationale. Enablers included strong leadership support, ongoing faculty development, providing students with clear expectations about assessment, simultaneous curriculum renewal and organisational commitment to change. Most barriers were related to the need for a paradigm shift in the culture of assessment. Descriptions of implementations in relation to the theoretical principles, across multiple educational contexts, coupled with explanations of enablers and barriers, provided new insights and a clearer understanding of the strategic and operational considerations in the implementation of programmatic assessment. Future research is needed to further explore how contextual and cultural factors affect implementation

Down-titration of biologics for the treatment of rheumatoid arthritis: A systematic literature review

Biologic therapies have improved the management of rheumatoid arthritis (RA) and the treat-to-target approach has resulted in many patients achieving remission. In the current treatment landscape, clinicians have begun considering dose reduction/tapering for their patients. Rheumatology guidelines in Asia, Europe, and the United States include down-titration of biologics but admit that the level of evidence is moderate. We conducted a systematic literature review to assess the published studies that evaluate down-titration of biologics in RA. The published literature was searched for studies that down-titrated the following biologics: abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Eligible studies included randomized controlled trials (RCTs), non-RCTs, observational, and pharmacoeconomic studies. The outcomes of interest were (1) efficacy and health-related quality of life, (2) disease flares, and (3) impact on cost. Eleven full-text publications were identified; only three were RCTs. Study results suggest that dosing down may be an option in many patients who have achieved remission or low disease activity. However, some patients are likely to experience a disease flare. Across the studies, the definition of disease flare and the down-titration criteria were inconsistent, making it difficult to conclude which patients may be appropriate and when to attempt down-titration. Studies have evaluated the practice of dosing down biologic therapy in patients with RA; however, a relatively small number of RCTs have been published. Although down-titration may be an option for some patients in LDA or remission, additional RCTs are needed to provide guidance on this practice

Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer

BACKGROUND: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. METHODS: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. RESULTS: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. CONCLUSIONS: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.British Journal of Cancer advance online publication, 22 December 2016; doi:10.1038/bjc.2016.402 www.bjcancer.com

Susceptibility to COPD:Differential Proteomic Profiling after Acute Smoking

Cigarette smoking is the main risk factor for COPD (Chronic Obstructive Pulmonary Disease), yet only a subset of smokers develops COPD. Family members of patients with severe early-onset COPD have an increased risk to develop COPD and are therefore defined as "susceptible individuals". Here we perform unbiased analyses of proteomic profiles to assess how "susceptible individuals" differ from age-matched "non-susceptible individuals" in response to cigarette smoking. Epithelial lining fluid (ELF) was collected at baseline and 24 hours after smoking 3 cigarettes in young individuals susceptible or non-susceptible to develop COPD and older subjects with established COPD. Controls at baseline were older healthy smoking and non-smoking individuals. Five samples per group were pooled and analysed by stable isotope labelling (iTRAQ) in duplicate. Six proteins were selected and validated by ELISA or immunohistochemistry. After smoking, 23 proteins increased or decreased in young susceptible individuals, 7 in young non-susceptible individuals, and 13 in COPD in the first experiment; 23 proteins increased or decreased in young susceptible individuals, 32 in young non-susceptible individuals, and 11 in COPD in the second experiment. SerpinB3 and Uteroglobin decreased after acute smoke exposure in young non-susceptible individuals exclusively, whereas Peroxiredoxin I, S100A9, S100A8, ALDH3A1 (Aldehyde dehydrogenase 3A1) decreased both in young susceptible and non-susceptible individuals, changes being significantly different between groups for Uteroglobin with iTRAQ and for Serpin B3 with iTRAQ and ELISA measures. Peroxiredoxin I, SerpinB3 and ALDH3A1 increased in COPD patients after smoking. We conclude that smoking induces a differential protein response in ELF of susceptible and non-susceptible young individuals, which differs from patients with established COPD. This is the first study applying unbiased proteomic profiling to unravel the underlying mechanisms that induce COPD. Our data suggest that SerpinB3 and Uteroglobin could be interesting proteins in understanding the processes leading to COPD