Tragic Error and Agent Responsibility

The characters of tragedy are in some sense responsible for their errors. However, given their ignorance of the consequences of their actions, it seems that they ought not be held responsible by others for what they have done. This is a paradox. The way to resolve the paradox is to distinguish two kinds of agent responsibility: accountability and culpability. Being accountable is primarily a private affair, whereas being culpable entails the possibility of just punishment

Longitudinal white matter changes associated with cognitive training

Improvements in behavior are known to be accompanied by both structural and functional changes in the brain. However, whether those changes lead to more general improvements, beyond the behavior being trained, remains a contentious issue. We investigated whether training on one of two cognitive tasks would lead to either near transfer (that is, improvements on a quantifiably similar task) or far transfer (that is, improvements on a quantifiably different task), and furthermore, if such changes did occur, what the underlying neural mechanisms might be. Healthy adults (n = 16, 15 females) trained on either a verbal inhibitory control task or a visuospatial working memory task for 4 weeks, over the course of which they received five diffusion tensor imaging scans. Two additional tasks served as measures of near and far transfer. Behaviorally, participants improved on the task that they trained on, but did not improve on cognitively similar tests (near transfer), nor cognitively dissimilar tests (far transfer). Extensive changes to white matter microstructure were observed, with verbal inhibitory control training leading to changes in a left-lateralized network of frontotemporal and occipitofrontal tracts, and visuospatial working memory training leading to changes in right-lateralized frontoparietal tracts. Very little overlap was observed in changes between the two training groups. On the basis of these results, we suggest that near and far transfer were not observed because the changes in white matter tracts associated with training on each task are almost entirely nonoverlapping with, and therefore afford no advantages for, the untrained tasks

Evidence of a high incidence of subclinically affected calves in a herd of cattle with fatal cases of Bovine Neonatal Pancytopenia (BNP).

BACKGROUND: Bovine Neonatal Pancytopenia (BNP) is a disease of calves characterised by bone marrow trilineage hypoplasia, mediated by ingestion of alloantibodies in colostrum. Suspected subclinical forms of BNP have been reported, suggesting that observed clinical cases may not represent the full extent of the disease. However to date there are no objective data available on the incidence of subclinical disease or its temporal distribution. This study aimed to 1) ascertain whether subclinical BNP occurs and, if so, to determine the incidence on an affected farm and 2) determine whether there is evidence of temporal clustering of BNP cases on this farm. To achieve these aims, haematological screening of calves born on the farm during one calving season was carried out, utilising blood samples collected at defined ages. These data were then analysed in comparison to data from both known BNP-free control animals and histopathologically confirmed BNP cases. An ordinal logistic regression model was used to create a composite haematology score to predict the probabilities of calves being normal, based on their haematology measurements at 10–14 days old. RESULTS: This study revealed that 15% (21 of 139) of the clinically normal calves on this farm had profoundly abnormal haematology (<5% chance of being normal) and could be defined as affected by subclinical BNP. Together with clinical BNP cases, this gave the study farm a BNP incidence of 18%. Calves with BNP were found to be distributed throughout the calving period, with no clustering, and no significant differences in the date of birth of cases or subclinical cases were found compared to the rest of the calves. This study did not find any evidence of increased mortality or increased time from birth to sale in subclinical BNP calves but, as the study only involved a single farm and adverse effects may be determined by other inter-current diseases it remains possible that subclinical BNP has a detrimental impact on the health and productivity of calves under certain circumstances. CONCLUSIONS: Subclinical BNP was found to occur at a high incidence in a herd of cattle with fatal cases of BNP

Effects of selective serotonin reuptake inhibitor treatment on plasma oxytocin and cortisol in major depressive disorder

Background: Oxytocin is known for its capacity to facilitate social bonding, reduce anxiety and for its actions on the stress hypothalamopituitary adrenal (HPA) axis. Since oxytocin can physiologically suppress activity of the HPA axis, clinical applications of this neuropeptide have been proposed in conditions where the function of the HPA axis is dysregulated. One such condition is major depressive disorder (MDD). Dysregulation of the HPA system is the most prominent endocrine change seen with MDD, and normalizing the HPA axis is one of the major targets of recent treatments. The potential clinical application of oxytocin in MDD requires improved understanding of its relationship to the symptoms and underlying pathophysiology of MDD. Previous research has investigated potential correlations between oxytocin and symptoms of MDD, including a link between oxytocin and treatment related symptom reduction. The outcomes of studies investigating whether antidepressive treatment (pharmacological and non-pharmacological) influences oxytocin concentrations in MDD, have produced conflicting outcomes. These outcomes suggest the need for an investigation of the influence of a single treatment class on oxytocin concentrations, to determine whether there is a relationship between oxytocin, the HPA axis (e.g., oxytocin and cortisol) and MDD. Our objective was to measure oxytocin and cortisol in patients with MDD before and following treatment with selective serotonin reuptake inhibitors, SSRI. Method: We sampled blood from arterial plasma. Patients with MDD were studied at the same time twice; pre- and post- 12 weeks treatment, in an unblinded sequential design (clinicaltrials.govNCT00168493). Results: Results did not reveal differences in oxytocin or cortisol concentrations before relative to following SSRI treatment, and there were no significant relationships between oxytocin and cortisol, or these two physiological variables and psychological symptom scores, before or after treatment. Conclusions: These outcomes demonstrate that symptoms of MDD were reduced following effective treatment with an SSRI, and further, stress physiology was unlikely to be a key factor in this outcome. Further research is required to discriminate potential differences in underlying stress physiology for individuals with MDD who respond to antidepressant treatment, relative to those who experience treatment resistance.Charlotte Keating, Tye Dawood, David A Barton, Gavin W Lambert and Alan J Tilbroo

Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills

Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall (total N = 2196), verbal (total N = 2206) and non-verbal cognitive scores (total N = 3300). The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that variation in cord blood DNA methylation at single CpG sites is associated with cognitive skills and further studies are needed to confirm the association at DUSP22.Peer reviewe

Atlantic Leatherback Migratory Paths and Temporary Residence Areas

BACKGROUND: Sea turtles are long-distance migrants with considerable behavioural plasticity in terms of migratory patterns, habitat use and foraging sites within and among populations. However, for the most widely migrating turtle, the leatherback turtle Dermochelys coriacea, studies combining data from individuals of different populations are uncommon. Such studies are however critical to better understand intra- and inter-population variability and take it into account in the implementation of conservation strategies of this critically endangered species. Here, we investigated the movements and diving behaviour of 16 Atlantic leatherback turtles from three different nesting sites and one foraging site during their post-breeding migration to assess the potential determinants of intra- and inter-population variability in migratory patterns. METHODOLOGY/PRINCIPAL FINDINGS: Using satellite-derived behavioural and oceanographic data, we show that turtles used Temporary Residence Areas (TRAs) distributed all around the Atlantic Ocean: 9 in the neritic domain and 13 in the oceanic domain. These TRAs did not share a common oceanographic determinant but on the contrary were associated with mesoscale surface oceanographic features of different types (i.e., altimetric features and/or surface chlorophyll a concentration). Conversely, turtles exhibited relatively similar horizontal and vertical behaviours when in TRAs (i.e., slow swimming velocity/sinuous path/shallow dives) suggesting foraging activity in these productive regions. Migratory paths and TRAs distribution showed interesting similarities with the trajectories of passive satellite-tracked drifters, suggesting that the general dispersion pattern of adults from the nesting sites may reflect the extent of passive dispersion initially experienced by hatchlings. CONCLUSIONS/SIGNIFICANCE: Intra- and inter-population behavioural variability may therefore be linked with initial hatchling drift scenarios and be highly influenced by environmental conditions. This high degree of behavioural plasticity in Atlantic leatherback turtles makes species-targeted conservation strategies challenging and stresses the need for a larger dataset (>100 individuals) for providing general recommendations in terms of conservation