Prelimbic cortex maintains attention to category-relevant information and flexibly updates category representations

Category learning groups stimuli according to similarity or function. This involves finding and attending to stimulus features that reliably inform category membership. Although many of the neural mechanisms underlying categorization remain elusive, models of human category learning posit that prefrontal cortex plays a substantial role. Here, we investigated the role of the prelimbic cortex (PL) in rat visual category learning by administering excitotoxic lesions before category training and then evaluating the effects of the lesions with computational modeling. Using a touchscreen apparatus, rats (female and male) learned to categorize distributions of category stimuli that varied along two continuous dimensions. For some rats, categorizing the stimuli encouraged selective attention towards a single stimulus dimension (i.e., 1D tasks). For other rats, categorizing the stimuli required divided attention towards both stimulus dimensions (i.e., 2D tasks). Testing sessions then examined generalization to novel exemplars. PL lesions impaired learning and generalization for the 1D tasks, but not the 2D tasks. Then, a neural network was fit to the behavioral data to examine how the lesions affected categorization. The results suggest that the PL facilitates category learning by maintaining attention to category-relevant information and updating category representations

Eyeblink conditioning in the infant rat: an animal model of learning in developmental neurotoxicology.

Classical conditioning of the eyeblink reflex is a relatively simple procedure for studying associative learning that was first developed for use with human subjects more than half a century ago. The use of this procedure in laboratory animals by psychologists and neuroscientists over the past 30 years has produced a powerful animal model for studying the behavioral and biological mechanisms of learning. As a result, eyeblink conditioning is beginning to be pursued as a very promising model for predicting and understanding human learning and memory disorders. Among the many advantages of this procedure are (a) the fact that it can be carried out in the same manner in both humans and laboratory animals; (b) the many ways in which it permits one to characterize changes in learning at the behavioral level; (c) the readiness with which hypotheses regarding the neurological basis of behavioral disorders can be formulated and tested; (d) the fact that it can be used in the same way across the life-span; and (e) its ability to distinguish, from normative groups, populations suffering from neurological conditions associated with impaired learning and memory, including those produced by exposure to neurotoxicants. In this article, we argue that these properties of eyeblink conditioning make it an excellent model system for studying early impairments of learning and memory in developmental neurotoxicology. We also review progress that has been made in our laboratory in developing a rodent model of infant eyeblink conditioning for this purpose

Selective attention in rat visual category learning

A prominent theory of category learning, COVIS, posits that new categories are learned with either a declarative or procedural system, depending on the task. The declarative system uses the prefrontal cortex (PFC) to learn rule-based (RB) category tasks in which there is one relevant sensory dimension that can be used to establish a rule for solving the task, whereas the procedural system uses corticostriatal circuits for information integration (II) tasks in which there are multiple relevant dimensions, precluding use of explicit rules. Previous studies have found faster learning of RB versus II tasks in humans and monkeys but not in pigeons. The absence of a learning rate difference in pigeons has been attributed to their lacking a PFC. A major gap in this comparative analysis, however, is the lack of data from a nonprimate mammalian species, such as rats, that have a PFC but a less differentiated PFC than primates. Here, we investigated RB and II category learning in rats. Similar to pigeons, RB and II tasks were learned at the same rate. After reaching a learning criterion, wider distributions of stimuli were presented to examine generalization. A second experiment found equivalent RB and II learning with wider category distributions. Computational modeling revealed that rats extract and selectively attend to category-relevant information but do not consistently use rules to solve the RB task. These findings suggest rats are on a continuum of PFC function between birds and primates, with selective attention but limited ability to utilize rules relative to primates

Metadynamics simulations of calcite crystallization on self-assembled monolayers

We show that recent developments in the application of metadynamics methods to direct simulations of crystallization make it possible to predict the orientation of crystals grown on self-assembled monolayers. In contrast to previous studies, the method allows for dynamic treatment of the organic component and the inclusion of explicit surface water without the need for computationally intensive interfacial energy calculations or prior knowledge of the interfacial structure. The method is applied to calcite crystallization on carboxylate terminated alkanethiols arrayed on Au (111). We demonstrate that a dynamic treatment of the monolayer is sufficient to reproduce the experimental results without the need to impose epitaxial constraints on the system. We also observe an odd-even effect in the variation of selectivity with organic chain length, reproducing experimentally observed orientations in both cases. Analysis of the ordering process in our simulations suggests a cycle of mutual control in which both the organic and mineral components induce complementary local order across the interface, leading to the formation of a critical crystalline region. The influence of pH, together with some factors that might affect the range of applicability of our method, is discussed

Selective attention in rat visual category learning

A prominent theory of category learning, COVIS, posits that new categories are learned with either a declarative or procedural system, depending on the task. The declarative system uses the prefrontal cortex (PFC) to learn rule-based (RB) category tasks in which there is one relevant sensory dimension that can be used to establish a rule for solving the task, whereas the procedural system uses corticostriatal circuits for information integration (II) tasks in which there are multiple relevant dimensions, precluding use of explicit rules. Previous studies have found faster learning of RB versus II tasks in humans and monkeys but not in pigeons. The absence of a learning rate difference in pigeons has been attributed to their lacking a PFC. A major gap in this comparative analysis, however, is the lack of data from a nonprimate mammalian species, such as rats, that have a PFC but a less differentiated PFC than primates. Here, we investigated RB and II category learning in rats. Similar to pigeons, RB and II tasks were learned at the same rate. After reaching a learning criterion, wider distributions of stimuli were presented to examine generalization. A second experiment found equivalent RB and II learning with wider category distributions. Computational modeling revealed that rats extract and selectively attend to category-relevant information but do not consistently use rules to solve the RB task. These findings suggest rats are on a continuum of PFC function between birds and primates, with selective attention but limited ability to utilize rules relative to primates

UK experience of liver transplantation for erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is characterised by excess production of free protoporphyrin from the bone marrow, most commonly due to deficiency of the enzyme ferrochelatase. Excess protoporphyrin gives rise to the cutaneous photosensitivity characteristic of the disease, and in a minority of patients leads to end-stage liver disease necessitating liver transplantation (LT). There is limited information regarding the timing, impact and long-term outcome of LT in such patients, thus we aimed to identify the indications and outcomes of all transplants performed for EPP in the UK using data from the UK Transplant Registry. Between 1987 and 2009, five patients underwent LT for EPP liver disease. Median follow-up was 60 months, and there were two deaths at 44 and 95 months from causes unrelated to liver disease. The remaining recipients are alive at 22.4 years, 61 months and 55 months after transplant. A high rate of postoperative biliary stricturing requiring multiple biliary interventions was observed. Recurrent EPP-liver disease occurred in 4/5 (80%) of patients but graft failure has not been observed. Given the role of biliary obstruction in inducing EPP-mediated liver damage, we suggest that consideration should be given for construction of a Roux loop at the time of transplant. Thus we demonstrate that although EPP liver transplant recipients have a good long-term survival, comparable to patients undergoing LT for other indications, biliary complications and disease recurrence are almost universal, and bone marrow transplantation should be considered where possible

A comparison of the effectiveness of cognitive behavioural interventions based on delivery features for elevated symptoms of depression in adolescents: A systematic review

This is the final version. Available on open access from Wiley via the DOI in this record. Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.Background Depression is a public health problem and common amongst adolescents. Cognitive behavioural therapy (CBT) is widely used to treat adolescent depression but existing research does not provide clear conclusions regarding the relative effectiveness of different delivery modalities. Objectives The primary aim is to estimate the relative efficacy of different modes of CBT delivery compared with each other and control conditions for reducing depressive symptoms in adolescents. The secondary aim is to compare the different modes of delivery with regard to intervention completion/attrition (a proxy for intervention acceptability). Search Methods The Cochrane Depression, Anxiety and Neurosis Clinical Trials Register was searched in April 2020. MEDLINE, PsycInfo, EMBASE, four other electronic databases, the CENTRAL trial registry, Google Scholar and Google were searched in November 2020, together with reference checking, citation searching and hand-searching of two databases. Selection Criteria Randomised controlled trials (RCTs) of CBT interventions (irrespective of delivery mode) to reduce symptoms of depression in young people aged 10–19 years with clinically relevant symptoms or diagnosis of depression were included. Data Collection and Analysis Screening and data extraction were completed by two authors independently, with discrepancies addressed by a third author. CBT interventions were categorised as follows: group CBT, individual CBT, remote CBT, guided self-help, and unguided self-help. Effect on depressive symptom score was estimated across validated self-report measures using Hedges' g standardised mean difference. Acceptability was estimated based on loss to follow-up as an odds ratio. Treatment rankings were developed using the surface under the cumulative ranking curve (SUCRA). Pairwise meta-analyses were conducted using random effects models where there were two or more head-to-head trials. Network analyses were conducted using random effects models. Main Results Sixty-eight studies were included in the review. The mean age of participants ranged from 10 to 19.5 years, and on average 60% of participants were female. The majority of studies were conducted in schools (28) or universities (6); other settings included primary care, clinical settings and the home. The number of CBT sessions ranged from 1 to 16, the frequency of delivery from once every 2 weeks to twice a week and the duration of each session from 20 min to 2 h. The risk of bias was low across all domains for 23 studies, 24 studies had some concerns and the remaining 21 were assessed to be at high risk of bias. Sixty-two RCTs (representing 6435 participants) were included in the pairwise and network meta-analyses for post-intervention depressive symptom score at post-intervention. All pre-specified treatment and control categories were represented by at least one RCT. Although most CBT approaches, except remote CBT, demonstrated superiority over no intervention, no approaches performed clearly better than or equivalent to another. The highest and lowest ranking interventions were guided self-help (SUCRA 83%) and unguided self-help (SUCRA 51%), respectively (very low certainty in treatment ranking). Nineteen RCTs (3260 participants) were included in the pairwise and network meta-analyses for 6 to 12 month follow-up depressive symptom score. Neither guided self-help nor remote CBT were evaluated in the RCTs for this time point. Effects were generally attenuated for 6- to 12-month outcomes compared to posttest. No interventions demonstrated superiority to no intervention, although unguided self-help and group CBT both demonstrated superiority compared to TAU. No CBT approach demonstrated clear superiority over another. The highest and lowest ranking approaches were unguided self-help and individual CBT, respectively. Sixty-two RCTs (7347 participants) were included in the pairwise and network meta-analyses for intervention acceptability. All pre-specified treatment and control categories were represented by at least one RCT. Although point estimates tended to favour no intervention, no active treatments were clearly inferior. No CBT approach demonstrated clear superiority over another. The highest and lowest ranking active interventions were individual CBT and group CBT respectively. Pairwise meta-analytic findings were similar to those of the network meta-analysis for all analyses. There may be age-based subgroup effects on post-intervention depressive symptoms. Using the no intervention control group as the reference, the magnitudes of effects appear to be larger for the oldest age categories compared to the other subgroups for each given comparison. However, they were generally less precise and formal testing only indicated a significant difference for group CBT. Findings were robust to pre-specified sensitivity analyses separating out the type of placebo and excluding cluster-RCTs, as well as an additional analysis excluding studies where we had imputed standard deviations. Authors' Conclusions At posttreatment, all active treatments (group CBT, individual CBT, guided self-help, and unguided self-help) except for remote CBT were more effective than no treatment. Guided self-help was the most highly ranked intervention but only evaluated in trials with the oldest adolescents (16–19 years). Moreover, the studies of guided self-help vary in the type and amount of therapist support provided and longer-term results are needed to determine whether effects persist. The magnitude of effects was generally attenuated for 6- to 12-month outcomes. Although unguided self-help was the lowest-ranked active intervention at post-intervention, it was the highest ranked at follow-up. This suggests the need for further research into whether interventions with self-directed elements enable young people to maintain effects by continuing or revisiting the intervention independently, and whether therapist support would improve long-term outcomes. There was no clear evidence that any active treatments were more acceptable to participants than any others. The relative effectiveness of intervention delivery modes must be taken into account in the context of the needs and preferences of individual young people, particularly as the differences between effect sizes were relatively small. Further research into the type and amount of therapist support that is most acceptable to young people and most cost-effective would be particularly useful.Jacobs FoundationNational Institute for Health and Care Research (NIHR

Electronic structure and volume effect on thermoelectric transport in p-type Bi and Sb tellurides

Thermoelectric transport properties (Seebeck coefficient, S, and electrical conductivity, sigma) of p-type Bi and Sb tellurides are investigated using a first-principles all-electron density-functional approach. We demonstrate that the carrier concentration, band gap, and lattice constants have an important influence on the temperature behavior of S and that the volume expansion by 5.5% in Sb(2)Te(3) results in an increase in S by 33 mu V/K at 300 K. We argue that in addition to the electronic structure characteristics, the volume also affects the value of S and hence should be considered as an origin of the experimental observations that S can be enhanced by doping Sb(2)Te(3) with Bi (which has a larger ionic size) in Sb sites or by the deposition of thick Bi(2)Te(3) layers alternating with thinner Sb(2)Te(3) layers in a superlattice, Bi(2)Te(3)/Sb(2)Te(3). We show that the optimal carrier concentration for the best power factor of Bi(2)Te(3) and Sb(2)Te(3) is approximately 10(19) cm(-3).open114343sciescopu

Using Scenarios to Validate Requirements through the use of Eye-Tracking in Prototyping

Research has shown that eliciting and capturing the correct behavior of systems reduces the number of defects that a system contains. A requirements engineer will model the functions of the system to gain a comprehensive understanding of the system in question. Engineers must verify the model for correctness by either having another engineer review it or build a prototype and validate with a stakeholder. However, research has shown that this form of verification can be ineffective because looking at an existing model can be suggestive and stump the development of new ideas. This paper provides an automated technique that can be used as an unbiased review of use case scenarios. Using the prototype and a scenario, a stakeholder can be guided through the use case scenario demonstrating where they expect to find the next step while their eye movements are tracked. Analysis of the eye tracking data can be used to identify missing requirements such as interaction steps that should have alternative sequences or determining problems with the flow of actions