Fear assessment in pigs exposed to a novel object test

The experiment aimed to study approach and locomotive behaviour as indicators of fear in a novel object test carried out in pigs. Thirty post-weaning (30 kg) and 30 finishing (90 kg) pigs were exposed to visual, auditory and olfactory novel stimuli during 2 different experiments. The facilities consisted of a test pen in which a trough was located. The trough contained chopped apples. Once the animals were trained to enter the test pen individually they were subjected to 3 different fear stimuli. These stimuli were applied in the test pen and next to the trough. The variables studied were feeding behaviour, approach behaviour (the distance and position of the animal with respect to the trough) and locomotive behaviour (general activity, reluctance to move, turning back and retreat attempts). Two groups were studied: saline and midazolam treated group. Twenty minutes before the start of the sessions, 15 post-weaning and finishing pigs received an intramuscular injection of 0.20 and 0.15 mg/kg, respectively, midazolam (Dormicum1). The saline pigs (15 animals per group) were injected with saline. The administration of midazolam increased the feeding behaviour and approaching behaviour, and reduced the locomotive behaviour. In front of the visual and olfactory stimuli post-weaning pigs showed a higher general activity than finishing pigs, but the contrary was found when the auditory stimulus was applied. The olfactory stimulus was more related to the turning back behaviour, whereas the visual stimulus was more related to retreat attempts. Although it could be concluded that reluctant to move was the most common response to the different fear stimuli applied in our study regardless of the age of animals, the combination of reluctant to move and turning back would be a good criterion to assess fear in domestic pigs. The use of midazolam as anxiolytic for studies of fear in commercial conditions in pigs is recommended.

Confirmatory factor analysis of an inventory of perception of insecurity and fear of crime

This paper focuses on the study of the factorial structure of an inventory to estimate the subjective perception of insecurity and fear of crime. Made from the review of the literature on the subject and the results obtained in previous works, this factor structure shows that this attitude towards insecurity and fear of crime is identified through a number of latent factors which are schematically summarized in (a) personal safety, (b) the perception of personal and social control, (c) the presence of threatening people or situations, (d) the processes of identity and space appropriation, (e) satisfaction with the environment, and (f) the environmental and the use of space. Such factors are relevant dimensions to analyze the phenomenon. Method: A sample of 571 participants in a neighborhood of Barcelona was evaluated with the proposed inventory, which yielded data from the distributions of all the items provided. The administration was conducted by researchers specially trained for it and the results were analyzed by using standard procedures in the confirmatory factor analysis (CFA) from the hypothesized theoretical structure. The analysis was performed by decatypes according to the different response scales prepared in the inventory and their ordinal nature, and by estimating the polychoric correlation coefficients. The results show an acceptable fit of the proposed model, an appropriate behavior of the residuals and statistically significant estimates of the factor loadings. This would indicate the goodness of the proposed factor structure.

On dictatorship, economic development and stability

This paper aims to account for varying economic performances and political stability under dictatorship. We argue that economic welfare and social order are the contemporary relevant factors of political regimes' stability. Societies with low natural level of social order tend to tolerate predatory behavior from dictators in exchange of a provision of civil peace. The fear of anarchy may explain why populations are locked in the worst dictatorships. In contrast, in societies enjoying a relative natural civil peace, dictatorship is less likely to be predatory because low economic welfare may destabilize it.

How tight should one's hands be tied? Fear of floating and credibility of exchange rate regimes

This paper analyzes the linkages between the credibility of a target zone regime, the volatility of the exchange rate, and the width of the band where the exchange rate is allowed to fluctuate. These three concepts should be related since the band width induces a trade-off between credibility and volatility. Narrower bands should give less scope for the exchange rate to fluctuate but may make agents perceive a larger probability of realignment which by itself should increase the volatility of the exchange rate. We build a model where this trade-off is made explicit. The model is used to understand the reduction in volatility experienced by most EMS countries after their target zones were widened on August 1993. As a natural extension, the model also rationalizes the existence of non-official, implicit target zones (or fear of floating), suggested by some authors.

Dissolution of Dynamic Electronic Institutions, a first approach: Relevant factors and causes

In the context of the digital business ecosystems, small organizations cooperate between them in order to achieve common goals or offer new services for expanding their markets. There are different approaches for these cooperation models such as virtual enterprises, virtual organizations or dynamic electronic institutions which in their lifecycle have in common a dissolution phase. However this phase has not been studied deeply in the current literature and it lacks formalization. In this paper a first approach for achieving and managing the dissolution phase is proposed, as well as a CBR process in order to support it in a multi-agent system

Development and validation of AMANDA, a new algorithm for selecting highly relevant regions in Molecular Interaction Fields

Descriptors based on Molecular Interaction Fields (MIF) are highly suitable for drug discovery, but their size (thousands of variables) often limits their application in practice. Here we describe a simple and fast computational method that extracts from a MIF a handful of highly informative points (hot spots) which summarize the most relevant information. The method was specifically developed for drug discovery, is fast, and does not require human supervision, being suitable for its application on very large series of compounds. The quality of the results has been tested by running the method on the ligand structure of a large number of ligand-receptor complexes and then comparing the position of the selected hot spots with actual atoms of the receptor. As an additional test, the hot spots obtained with the novel method were used to obtain GRIND-like molecular descriptors which were compared with the original GRIND. In both cases the results show that the novel method is highly suitable for describing ligand-receptor interactions and compares favorably with other state-of-the-art methods.

What can spike train distances tell us about the neural code?

Time scale parametric spike train distances like the Victor and the van Rossum distancesare often applied to study the neural code based on neural stimuli discrimination.Different neural coding hypotheses, such as rate or coincidence coding,can be assessed by combining a time scale parametric spike train distance with aclassifier in order to obtain the optimal discrimination performance. The time scalefor which the responses to different stimuli are distinguished best is assumed to bethe discriminative precision of the neural code. The relevance of temporal codingis evaluated by comparing the optimal discrimination performance with the oneachieved when assuming a rate code.We here characterize the measures quantifying the discrimination performance,the discriminative precision, and the relevance of temporal coding. Furthermore,we evaluate the information these quantities provide about the neural code. Weshow that the discriminative precision is too unspecific to be interpreted in termsof the time scales relevant for encoding. Accordingly, the time scale parametricnature of the distances is mainly an advantage because it allows maximizing thediscrimination performance across a whole set of measures with different sensitivitiesdetermined by the time scale parameter, but not due to the possibility toexamine the temporal properties of the neural code.

The social value of health programs: Is age a relevant factor?

In cost-effectiveness analysis (CEA) it is usually assumed that a QALY is of equal value to everybody, irrespective of the patient's age. However, it is possible that society assigns different social values to a QALY according to who gets it. In this paper we discuss the possibility of weighting health benefits for age in CEA. We also examinethe possibility that age-related preferences depend on the size of the health gain. An experiment was performedto test these hypotheses. The results assessing suggest that the patient's age is a relevant factor when assessing health gains.

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD'

New insights into cellular prion protein (PrPc) functions: the 'ying and yang' of a relevant protein.

The conversion of cellular prion protein (PrPc), a GPI-anchored protein, into a protease-K-resistant and infective form (generally termed PrPsc) is mainly responsible for Transmissible Spongiform Encephalopathies (TSEs), characterized by neuronal degeneration and progressive loss of basic brain functions. Although PrPc is expressed by a wide range of tissues throughout the body, the complete repertoire of its functions has not been fully determined. Recent studies have confirmed its participation in basic physiological processes such as cell proliferation and the regulation of cellular homeostasis. Other studies indicate that PrPc interacts with several molecules to activate signaling cascades with a high number of cellular effects. To determine PrPc functions, transgenic mouse models have been generated in the last decade. In particular, mice lacking specific domains of the PrPc protein have revealed the contribution of these domains to neurodegenerative processes. A dual role of PrPc has been shown, since most authors report protective roles for this protein while others describe pro-apoptotic functions. In this review, we summarize new findings on PrPc functions, especially those related to neural degeneration and cell signaling.

Concentrative nucleoside transporter 1 (hCNT1) promotes phenotypic changes relevant to tumor biology in a translocation independent manner

Nucleoside transporters (NTs) mediate the uptake of nucleosides and nucleobases across the plasma membrane, mostly for salvage purposes. The canonical NTs belong to two gene families, SLC29 and SLC28. The former encode equilibrative nucleoside transporter proteins (ENTs), which mediate the facilitative diffusion of natural nucleosides with broad selectivity, whereas the latter encode concentrative nucleoside transporters (CNTs), which are sodium-coupled and show high affinity for substrates with variable selectivity. These proteins are expressed in most cell types, exhibiting apparent functional redundancy. This might indicate that CNTs play specific roles in the physiology of the cell beyond nucleoside salvage. Here, we addressed this possibility using adenoviral vectors to restore tumor cell expression of hCNT1 or a polymorphic variant (hCNT1S546P) lacking nucleoside translocation ability. We found that hCNT1 restoration in pancreatic cancer cells significantly altered cell-cycle progression and phosphorylation status of key signal-transducing kinases, promoted poly-(ADP ribose) polymerase hyperactivation and cell death, and reduced tumor growth and cell migration. Importantly, the translocation-defective transporter triggered these same effects on cell physiology. These data predict a novel and totally unexpected biological role for the nucleoside transporter protein hCNT1 that appears to be independent of its role as mediator of nucleoside uptake by cells, thereby suggesting a transceptor function. Cell Death & Disease Anastasis Stephanou Receiving Editor Cell Death & Disease 19th Apr 2013 Dr Perez-Torras Av/ Diagonal 643. Edif. Prevosti, Pl -1 Barcelona 08028 Spain RE: Manuscript CDDIS-13-0136R, 'CDDIS-13-0136R' Dear Dr Perez-Torras, It is a pleasure to inform you that your manuscript has been evaluated at the editorial level and has now been officially accepted for publication in Cell Death & Disease, pending you meet the following editorial requirements: 1) the list of the abbreviations is missing please include Could you send us the revised text as word file via e-mail and we will proceed and transfer the paper onto our typesetters. Please download, print, sign, and return the Licence to Publish Form using the link below. This must be returned via FAX to ++ 39 06 7259 6977 before your manuscript can be published:

Defining ecologically relevant water quality targets for lakes in Europe

1. The implementation of the Water Framework Directive requires EU member states to establish and harmonize ecological status class boundaries for biological quality elements. In this paper, we describe an approach for defining ecological class boundaries that delineates shifts in lake ecosystem functioning and, therefore, provides ecologically meaningful targets for water policy in Europe. 2. We collected an extensive data set of 810 lake-years from nine Central European countries, and we used phytoplankton chlorophyll a, a metric widely used to measure the impact of eutrophication in lakes. Our approach establishes chlorophyll a target values in relation to three significant ecological effects of eutrophication: the decline of aquatic macrophytes, the dominance of potentially harmful cyanobacteria and the major functional switch from a clear water to a turbid state. 3. Ranges of threshold chlorophyll a concentrations are given for the two most common lake types in lowland Central Europe: for moderately deep lakes (mean depth 3–15 m), the greatest ecological shifts occur in the range 10–12 lg L 1 chlorophyll a, and for shallow lakes (<3 m mean depth), in the range 21–23 lg L 1 chlorophyll a. 4. Synthesis and applications. Our study provides class boundaries for determining the ecological status of lakes, which have robust ecological consequences for lake functioning and which, therefore, provide strong and objective targets for sustainable water management in Europe. The results have been endorsed by all participant member states and adopted in the European Commission legislation, marking the first attempt in international water policy to move from physico-chemical quality standards to harmonized ecologically based quality targets.

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD'

Selecting the most relevant variables for anaerobic digestion imbalances : Two case studies

In this study, a wrapper approach was applied to objectively select the most important variables related to two different anaerobic digestion imbalances, acidogenic states and foaming. This feature selection method, implemented in artificial neural networks (ANN), was performed using input and output data from a fully instrumented pilot plant (1 m 3 upflow fixed bed digester). Results for acidogenic states showed that pH, volatile fatty acids, and inflow rate were the most relevant variables. Results for foaming showed that inflow rate and total organic carbon were among the relevant variables, both of which were related to the feed loading of the digester. Because there is not a complete agreement on the causes of foaming, these results highlight the role of digester feeding patterns in the development of foaming

New insights into cellular prion protein (PrPc) functions: the 'ying and yang' of a relevant protein.

The conversion of cellular prion protein (PrPc), a GPI-anchored protein, into a protease-K-resistant and infective form (generally termed PrPsc) is mainly responsible for Transmissible Spongiform Encephalopathies (TSEs), characterized by neuronal degeneration and progressive loss of basic brain functions. Although PrPc is expressed by a wide range of tissues throughout the body, the complete repertoire of its functions has not been fully determined. Recent studies have confirmed its participation in basic physiological processes such as cell proliferation and the regulation of cellular homeostasis. Other studies indicate that PrPc interacts with several molecules to activate signaling cascades with a high number of cellular effects. To determine PrPc functions, transgenic mouse models have been generated in the last decade. In particular, mice lacking specific domains of the PrPc protein have revealed the contribution of these domains to neurodegenerative processes. A dual role of PrPc has been shown, since most authors report protective roles for this protein while others describe pro-apoptotic functions. In this review, we summarize new findings on PrPc functions, especially those related to neural degeneration and cell signaling.