Decoding semantics across fMRI sessions with different stimulus modalities:a practical MVPA study

Both embodied and symbolic accounts of conceptual organization would predict partial sharing and partial differentiation between the neural activations seen for concepts activated via different stimulus modalities. But cross-participant and cross-session variability in BOLD activity patterns makes analyses of such patterns with MVPA methods challenging. Here, we examine the effect of cross-modal and individual variation on the machine learning analysis of fMRI data recorded during a word property generation task. We present the same set of living and non-living concepts (land-mammals, or work tools) to a cohort of Japanese participants in two sessions: the first using auditory presentation of spoken words; the second using visual presentation of words written in Japanese characters. Classification accuracies confirmed that these semantic categories could be detected in single trials, with within-session predictive accuracies of 80-90%. However cross-session prediction (learning from auditory-task data to classify data from the written-word-task, or vice versa) suffered from a performance penalty, achieving 65-75% (still individually significant at p « 0.05). We carried out several follow-on analyses to investigate the reason for this shortfall, concluding that distributional differences in neither time nor space alone could account for it. Rather, combined spatio-temporal patterns of activity need to be identified for successful cross-session learning, and this suggests that feature selection strategies could be modified to take advantage of this.

Prevention of retinal capillary basement membrane thickening in diabetic dogs by a non-steroidal anti-inflammatory drug

AIMS/HYPOTHESIS: To investigate the effect of treatment with the non-steroidal anti-inflammatory drug Sulindac on the early vascular pathology of diabetic retinopathy in the dog, and it's effect on recognised biochemical indices of hyperglycaemia-related pathophysiology. METHODS: Experimental diabetes (streptozotocin/alloxan) was induced in 22 male beagle dogs and 12 of the animals were assigned at random to receive oral Sulindac (10 mg/kg daily). Age- and sex-matched control animals were maintained as non-diabetic controls. After 4 years, several morphological parameters were quantified in the retinal microvasculature of each animal group using an established stereological method. Also, the following diabetes-associated biochemical parameters were analysed: accumulation of advanced glycation end products (AGEs), red blood cell polyol levels and antioxidant status. RESULTS: Diabetes increased red blood cell sorbitol levels when compared to non-diabetic controls (p<or =0.05), however, there was no difference in sorbitol levels between the untreated and the treated diabetic animals. No significant differences were found in red blood cell myoinositol levels between the three groups of animals. Pentosidine and other AGEs were increased two- to three-fold in the diabetic animals (p<or =0.001) although treatment with Sulindac did not affect their accumulation in diabetic skin collagen or alter diabetes-induced rises in plasma malondialdehyde. Retinal capillary basement membrane volume was significantly increased in the untreated diabetic dogs compared to non-diabetic controls or Sulindac-treated diabetic animals (p<or =0.0001). CONCLUSION/INTERPRETATION: This study has confirmed the beneficial effect of a non-steroidal anti-inflammatory drug on the early vascular pathology of diabetic retinopathy. However the treatment benefit was not dependent on inhibition of polyol pathway activity, advanced glycation, or oxidative stress.

Model selection approaches for non-linear system identification: a review

The identification of non-linear systems using only observed finite datasets has become a mature research area over the last two decades. A class of linear-in-the-parameter models with universal approximation capabilities have been intensively studied and widely used due to the availability of many linear-learning algorithms and their inherent convergence conditions. This article presents a systematic overview of basic research on model selection approaches for linear-in-the-parameter models. One of the fundamental problems in non-linear system identification is to find the minimal model with the best model generalisation performance from observational data only. The important concepts in achieving good model generalisation used in various non-linear system-identification algorithms are first reviewed, including Bayesian parameter regularisation and models selective criteria based on the cross validation and experimental design. A significant advance in machine learning has been the development of the support vector machine as a means for identifying kernel models based on the structural risk minimisation principle. The developments on the convex optimisation-based model construction algorithms including the support vector regression algorithms are outlined. Input selection algorithms and on-line system identification algorithms are also included in this review. Finally, some industrial applications of non-linear models are discussed.

Metabolic effects of sub-chronic ablation of the incretin receptors by daily administration of (Pro(3))GIP and exendin(9-39)amide in obese diabetic (ob/ob) mice

Effects of chemical ablation of the GIP and GLP-1 receptors on metabolic aspects of obesity-diabetes were investigated using the stable receptor antagonists (Pro(3))GIP and exendin(9-39)amide. Ob/ob mice received a daily i.p. injection of saline vehicle, (Pro(3))GIP, exendin(9-39)amide or a combination of both peptides over a 14-day period. Non-fasting plasma glucose levels were significantly (p <0.05) lower in (Pro(3))GIP-treated mice compared to control mice after just 9 days of treatment. (Pro(3))GIP-treated mice also displayed significantly lower plasma glucose concentrations in response to feeding and intraperitoneal administration of either glucose or insulin (p <0.05 to p <0.001). The (Pro(3))GIP-treated group also exhibited significantly (p <0.05) reduced pancreatic insulin content. Acute administration of exendin(9-39) amide immediately prior to re-feeding completely annulled the beneficial effects of sub-chronic (Pro(3))GIP treatment, but non-fasting concentrations of active GLP-1 were unchanged. Combined sub-chronic administration of (Pro(3)GIP) with exendin(9-39)amide revealed no beneficial effects. Similarly, daily administration of exendin(9-39)amide alone had no significant effects on any of the metabolic parameters measured. These studies highlight an important role for GIP in obesity-related forms of diabetes, suggesting the possible involvement of GLP-1 in the beneficial actions of GIP receptor antagonism.

Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

Non-steroidal anti-inflammatory drug use and brain tumour risk:a case-control study within the Clinical Practice Research Datalink

Purpose: The aetiology of primary brain tumours is largely unknown; the role of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin use and glioma risk has been inconclusive, but few population-based studies with reliable prescribing data have been conducted, and the association with meningioma risk has yet to be assessed. Methods: The UK Clinical Practice Research Datalink was used to assess the association between aspirin and non-aspirin NSAID use and primary brain tumour risk using a nested case-control study design. Conditional logistic regression analysis was performed on 5,052 brain tumour patients aged 16 years and over, diagnosed between 1987 and 2009 and 42,678 controls matched on year of birth, gender and general practice, adjusting for history of allergy and hormone replacement therapy use in the glioma and meningioma models, respectively.

Results: In conditional logistic regression analysis, excluding drug use in the year preceding the index date, there was no association with non-aspirin NSAID use (OR 0.96, 95 % CI 0.81-1.13) or glioma risk comparing the highest category of daily defined dose to non-users; however, non-aspirin NSAID use was positively associated with meningioma risk (OR 1.35, 95 % CI 1.06-1.71). No association was seen with high- or low-dose aspirin use irrespective of histology.

Conclusions: This large nested case-control study finds no association between aspirin or non-aspirin NSAID use and risk of glioma but a slight increased risk with non-aspirin NSAIDs and meningioma. © 2013 Springer Science+Business Media Dordrecht.

Cases, Materials and Text on National, Supranational and International Non-Discrimination Law

This casebook, the result of the collaborative efforts of a panel of experts from various EU Member States, is the latest in the Ius Commune Casebook series developed at the Universities of Maastricht and Leuven. The book provides a comprehensive and skilfully designed resource for students, practitioners, researchers, public officials, NGOs, consumer organisations and the judiciary. In common with earlier books in the series, this casebook presents cases and other materials (legislative materials, international and European materials, excerpts from books or articles). As non-discrimination law is a comparatively new subject, the chapters search for and develop the concepts of discrimination law on the basis of a wide variety of young and often still emerging case law and legislation. The result is a comprehensive textbook with materials from a wide variety of EU Member States. The book is entirely in English (i.e. materials are translated where not available in English). At the end of each chapter a comparative overview ties the material together, with emphasis, where appropriate, on existing or emerging general principles in the legal systems within Europe.
The book illustrates the distinct relationship between international, European and national legislation in the field of non-discrimination law. It covers the grounds of discrimination addressed in the Racial Equality and Employment Equality Directives, as well as non-discrimination law relating to gender. In so doing, it covers the law of a large number of EU Member States, alongside some international comparisons.
The Ius Commune Casebook on Non-Discrimination Law
- provides practitioners with ready access to primary and secondary legal material needed to assist them in crafting test case strategies.
- provides the judiciary with the tools needed to respond sensitively to such cases.
- provides material for teaching non-discrimination law to law and other students.
- provides a basis for ongoing research on non-discrimination law.
- provides an up-to-date overview of the implementation of the Directives and of the state of the law.
This Casebook is the result of a project which has been supported by a grant from the European Commission's Anti-Discrimination Programme.

Experimental linear-optics simulation of multipartite non-locality in the ground state of a quantum Ising ring

Critical phenomena involve structural changes in the correlations of its constituents. Such changes can be reproduced and characterized in quantum simulators able to tackle medium-to-large-size systems. We demonstrate these concepts by engineering the ground state of a three-spin Ising ring by using a pair of entangled photons. The effect of a simulated magnetic field, leading to a critical modification of the correlations within the ring, is analysed by studying two- and three-spin entanglement. In particular, we connect the violation of a multipartite Bell inequality with the amount of tripartite entanglement in our ring.

European Union Non-Discrimination Law: Comparative Perspectives on Multidimensional Equality Law

EU equality law is multidimensional in being based on different rationales and concepts. Consequently, the concept of discrimination has become fragmented, with different instruments envisaging different scopes of protection. This raises questions as to the ability of EU law to address the situation of persons excluded on a number of grounds. This edited collection addresses the increasing complexity of European Equality Law from jurisprudential, sociological and political science perspectives. Internationally renowned researchers from Scandinavian, Continental and Central European countries and Britain analyse consequences of multiplying discrimination grounds within EU equality law, considering its multidimensionality and intersectionality. The contributors to the volume theorise the move from formal to substantive equality law and its interrelation to new forms of governance, demonstrating the specific combination of non-discrimination law with welfare state models which reveal the global implications of the European Union. The book will be of interest to academics and policy makers all over the world, in particular to those researching and studying law, political sciences and sociology with an interest in human rights, non discrimination law, contract and employment law or European studies.

The evaluative nature of the folk concepts of weakness and strength of will

This article examines the evaluative nature of the folk concepts of weakness and strength of will and hypothesizes that their evaluative nature is strongly connected to the folk concepts of blame and credit. We probed how people apply the concepts of weakness and strength of will to prototypical and non-prototypical scenarios. While regarding prototypical scenarios the great majority applied these concepts according to the predictions following from traditional philosophical analyses, when presented with non-prototypical scenarios, people were divided. Some, against traditional analyses, did not apply these concepts, which we explain in terms of a clash of evaluations involving different sorts of blame and credit. Others applied them according to traditional analyses, which we explain in terms of a disposition to be reflective and clearly set apart the different sorts of blame and credit involved. Still others applied them in an inverse way, seemingly bypassing the traditional components resolution and best judgment, which we explain in terms of a reinterpretation of the scenarios driven by an assumption that everyone knows deep inside that the best thing to do is to act morally. This division notwithstanding, we claim that our results are largely supportive of traditional analyses (qua analyses of folk concepts).

When innovation fails: An institutional perspective of the (non)adoption of boundary spanning IT innovation

We combine the concepts of legitimacy, institutional (mis)alignments, strategic responses and organizing visions to develop a conceptual framework to analyse the adoption of innovations that span organisational fields. We apply the framework to examine a telehealth innovation connecting a public sector hospital-based eye clinic with private sector optometry practices. We find that while compromise strategies were successful in encouraging adoption within each field, the innovation ultimately failed as fields developed different organising visions which could not be reconciled. The findings suggest that institutional misalignments within and between fields interact to amplify their overall effect on the adoption of hybrid innovations.

Validation of non‑stationary precipitation series for site‑specific impact assessment: comparison of two statistical downscaling techniques

Statistical downscaling (SD) methods have become a popular, low-cost and accessible means of bridging the gap between the coarse spatial resolution at which climate models output climate scenarios and the finer spatial scale at which impact modellers require these scenarios, with various different SD techniques used for a wide range of applications across the world. This paper compares the Generator for Point Climate Change (GPCC) model and the Statistical DownScaling Model (SDSM)—two contrasting SD methods—in terms of their ability to generate precipitation series under non-stationary conditions across ten contrasting global climates. The mean, maximum and a selection of distribution statistics as well as the cumulative frequencies of dry and wet spells for four different temporal resolutions were compared between the models and the observed series for a validation period. Results indicate that both methods can generate daily precipitation series that generally closely mirror observed series for a wide range of non-stationary climates. However, GPCC tends to overestimate higher precipitation amounts, whilst SDSM tends to underestimate these. This infers that GPCC is more likely to overestimate the effects of precipitation on a given impact sector, whilst SDSM is likely to underestimate the effects. GPCC performs better than SDSM in reproducing wet and dry day frequency, which is a key advantage for many impact sectors. Overall, the mixed performance of the two methods illustrates the importance of users performing a thorough validation in order to determine the influence of simulated precipitation on their chosen impact sector.

Measuring non-use value of environmental goods using the contingent valuation method:problems of information and cognition and the application of cognitive questionnaire design methods

Much interest now focuses on the use of the contingent valuation method (CVM) to assess non-use value of environmental goods. The paper reviews recent literature and highlights particular problems of information provision and respondent knowledge, comprehension and cognition. These must be dealt with by economists in designing CVM surveys for eliciting non-use values. Cognitive questionnaire design methods are presented which invoke concepts from psychology and tools from cognitive survey design (focus groups and verbal reports) to reduce a complex environmnetal good into a meaningful commodity that can be valued by respondents in a contingent market. This process is illustrated with examples from the authors' own research valuing alternative afforestation programmes. -Authors

Public Value as Performance: Politicians’ and Managers’ Perspectives on the Importance of Budgetary, Accruals and Non-Financial Information

Purpose
The study contributes to the literature on public value and performance examining politicians’ and managers’ perspectives by investigating the importance they attach to the different facets of performance information (i.e. budgetary, accrual based- and non-financial information (NFI)).

Design/methodology/approach
We survey politicians and managers in all Italian municipalities of at least 80,000 inhabitants.

Findings
Overall, NFI is more appreciated than financial information (FI). Moreover, budgetary accounting is preferred to accrual accounting. Politicians’ and managers’ preferences are generally aligned.

Research limitations/implications
NFI as a measure of public value is not alternative, but rather complementary, to FI. The latter remains a fundamental element of public sector accounting due to its role in resource allocation and control.

Practical implications
The preference for NFI over FI and of budgetary over accruals accounting suggests that the current predominant emphasis on (accrual-based) financial reporting might be misplaced.

Originality/value
Public value and performance are multi-faceted concepts. They can be captured by different types of information and evaluated according to different criteria, which will also depend on the category of stakeholders or users who assesses public performance. So far, most literature has considered the financial and non-financial facets of performance as virtually separate. Similarly, in the practice, financial management tends to be decoupled from non-financial performance management. However, this research shows that only by considering their joint interactions we can achieve an accurate representation of what public value really is.