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Impulsivity is a multidimensional heritable phenotype that broadly refers to the tendency to act prematurely and is associated with multiple forms of psychopathology, including substance use disorders. We performed genome-wide association studies (GWAS) of eight impulsive personality traits from the Barratt Impulsiveness Scale and the short UPPS-P Impulsive Personality Scale (N = 123,509-133,517 23andMe research participants of European ancestry), and a measure of Drug Experimentation (N = 130,684). Because these GWAS implicated the gene CADM2, we next performed single-SNP phenome-wide studies (PheWAS) of several of the implicated variants in CADM2 in a multi-ancestral 23andMe cohort (N = 3,229,317, European; N = 579,623, Latin American; N = 199,663, African American). Finally, we produced Cadm2 mutant mice and used them to perform a Mouse-PheWAS ("MouseWAS") by testing them with a battery of relevant behavioral tasks. In humans, impulsive personality traits showed modest chip-heritability (~6-11%), and moderate genetic correlations (rg = 0.20-0.50) with other personality traits, and various psychiatric and medical traits. We identified significant associations proximal to genes such as TCF4 and PTPRF, and also identified nominal associations proximal to DRD2 and CRHR1. PheWAS for CADM2 variants identified associations with 378 traits in European participants, and 47 traits in Latin American participants, replicating associations with risky behaviors, cognition and BMI, and revealing novel associations including allergies, anxiety, irritable bowel syndrome, and migraine. Our MouseWAS recapitulated some of the associations found in humans, including impulsivity, cognition, and BMI. Our results further delineate the role of CADM2 in impulsivity and numerous other psychiatric and somatic traits across ancestries and species.

Technology has been playing an increasingly important role in teaching and learning because of its capacity to increase students' motivation and provide them with opportunities to explore and acquire new knowledge and skills. However, little is known regarding the effectiveness of using the digital interactive case-based instruction (CBI) approach to support teaching and learning. Hence, this study investigated the effectiveness of digital interactive CBI in supporting learning of behaviourism among 234 preservice teachers. The results indicated that digital interactive CBI was a useful tool for enhancing learning. Preservice teachers not only found the activity engaging, but also believed that it was helpful in deepening their understanding towards operant conditioning and improving their abilities to analyse and solve real-world problems. The detailed findings will provide helpful insights to teacher educators who are considering implementing CBI in teacher education programmes.

Enrichment in rodents affects brain structure, improves behavioral performance, and is neuroprotective. Similarly, in humans, according to the cognitive reserve concept, enriched experience is functionally protective against neuropathology. Despite this parallel, the ability to translate rodent studies to human clinical situations is limited. This limitation is likely due to the simple cognitive processes probed in rodent studies and the inability to control, with existing methods, the degree of rodent engagement with enrichment material. We overcome these two difficulties with behavioral tasks that probe, in a fine-grained manner, aspects of higher-order cognition associated with deterioration with aging and dementia, and a new enrichment protocol, the 'Obstacle Course' (OC), which enables controlled enrichment delivery, respectively. Together, these two advancements will enable better specification (and comparisons) of the nature of impairments in animal models of complex mental disorders and the potential for remediation from various types of intervention (e.g., enrichment, drugs). We found that two months of OC enrichment produced substantial and sustained enhancements in categorization memory, perceptual object invariance, and cross-modal sensory integration in mice. We also tested mice on behavioral tasks previously shown to benefit from traditional enrichment: spontaneous object recognition, object location memory, and pairwise visual discrimination. OC enrichment improved performance relative to standard housing on all six tasks and was in most cases superior to conventional home-cage enrichment and exercise track groups.

Abstract Impulsivity is a multidimensional heritable phenotype that broadly refers to the tendency to act prematurely and is associated with multiple forms of psychopathology, including substance use disorders. We performed genome-wide association studies (GWAS) of eight impulsive personality traits from the Barratt Impulsiveness Scale and the short UPPS-P Impulsive Personality Scale (N = 123,509–133,517 23andMe research participants of European ancestry), and a measure of Drug Experimentation (N = 130,684). Because these GWAS implicated the gene CADM2, we next performed single-SNP phenome-wide studies (PheWAS) of several of the implicated variants in CADM2 in a multi-ancestral 23andMe cohort (N = 3,229,317, European; N = 579,623, Latin American; N = 199,663, African American). Finally, we produced Cadm2 mutant mice and used them to perform a Mouse-PheWAS (“MouseWAS”) by testing them with a battery of relevant behavioral tasks. In humans, impulsive personality traits showed modest chip-heritability (~6–11%), and moderate genetic correlations (r g = 0.20–0.50) with other personality traits, and various psychiatric and medical traits. We identified significant associations proximal to genes such as TCF4 and PTPRF, and also identified nominal associations proximal to DRD2 and CRHR1. PheWAS for CADM2 variants identified associations with 378 traits in European participants, and 47 traits in Latin American participants, replicating associations with risky behaviors, cognition and BMI, and revealing novel associations including allergies, anxiety, irritable bowel syndrome, and migraine. Our MouseWAS recapitulated some of the associations found in humans, including impulsivity, cognition, and BMI. Our results further delineate the role of CADM2 in impulsivity and numerous other psychiatric and somatic traits across ancestries and species.

Histone acetylation, catalyzed by e, has emerged as a promising therapeutic strategy in Alzheimer's disease (AD). By longitudinally characterizing spatial memory at 3, 6, and 9 mo of age, we show that acute activation and inhibition of the histone acetyltransferase PCAF remediated memory impairments in 3xTG-AD mice in an age-related bidirectional manner. At 3 and 6 mo of age, PCAF activation ameliorated memory deficits. At 9 mo of age, PCAF activation had no effect on spatial memory, whereas PCAF inhibition improved memory deficits in females. This work reveals a complex potential therapeutic role for PCAF in AD, initially benefitting memory but becoming detrimental as the disease progresses.

Enrichment in rodents affects brain structure, improves behavioral performance, and is neuroprotective. Similarly, in humans, according to the cognitive reserve concept, enriched experience is functionally protective against neuropathology. Despite this parallel, the ability to translate rodent studies to human clinical situations is limited. This limitation is likely due to the simple cognitive processes probed in rodent studies and the inability to control, with existing methods, the degree of rodent engagement with enrichment material. We overcome these two difficulties with behavioral tasks that probe, in a fine-grained manner, aspects of higher-order cognition associated with deterioration with aging and dementia, and a new enrichment protocol, the 'Obstacle Course' (OC), which enables controlled enrichment delivery, respectively. Together, these two advancements will enable better specification (and comparisons) of the nature of impairments in animal models of complex mental disorders and the potential for remediation from various types of intervention (e.g., enrichment, drugs). We found that two months of OC enrichment produced substantial and sustained enhancements in categorization memory, perceptual object invariance, and cross-modal sensory integration in mice. We also tested mice on behavioral tasks previously shown to benefit from traditional enrichment: spontaneous object recognition, object location memory, and pairwise visual discrimination. OC enrichment improved performance relative to standard housing on all six tasks and was in most cases superior to conventional home-cage enrichment and exercise track groups.

The structurally-unique histone variant, mH2A1, influences learning and memory in mice to a greater extent than a similar variant, mH2A2.

Contribution: This paper furthers understanding of how to use studio culture to develop instruction that supports learners' epistemic development in the context of an engineering senior design course, with a focus on student development of epistemic frames. Background: Current capstone engineering design courses do not integrate the educational theories and practice of cognitive apprenticeship combined with studio culture. Combined, these can be useful constructs for developing instruction that encourages creativity and innovation in a situated, student-centered, and activity-focused environment. Prior research and evidence-based instructional methods from other non-engineering contexts were used to create an instructional environment that engenders epistemic change. Research Questions: How do instructional design methods based on studio culture impact the cognitive and epistemic development of engineering students in a Senior Design course? Methods: This exploratory case study examines the effects of instructional design methods based on studio culture to change an Engineering Senior Design course from lecture-based to activity-based instruction in a collaborative environment. The case study emerges from a design-based research intervention, and uses mixed methods data collection from multiple sources, including video interviews, classroom footage, and written debrief reflections. Data analysis applied an integrated thematic approach. Implications were developed through an emergent coding process. Findings: Cognitive apprenticeship methods used in a studio culture-based classroom provide learning experiences that benefit epistemic and cognitive growth for engineering students in a Senior Design course.

To test the hypothesis that drugs of abuse and their conditioned stimuli (CSs) enhance memory consolidation, the effects of post-training exposure to cocaine and nicotine were compared to the effects of post-training exposure to contextual stimuli that were paired with the effects of these drugs. Using the object recognition (OR) task, it was first demonstrated that both 10 and 20 mg/kg cocaine, and 0.2 and 0.4 mg/kg nicotine, enhanced recognition memory when administered immediately after, but not 6 h after the sample phase. To establish the drug CSs, rats were confined for 2 h in a chamber (the CS+) after injections of 20 mg/kg cocaine, or 0.4 mg/kg nicotine, and in another chamber (the CS-) after injections of vehicle. This was repeated over 10 d (5 drug/CS+ and 5 vehicle/CS- pairings in total). At the end of this conditioning period, when tested in a drug-free state, rats displayed conditioned hyperactivity in the CS+ relative to the CS-. More important, immediate, but not delayed, post-sample exposure to the cocaine CS+, or nicotine CS+, enhanced OR memory. Therefore, this study reports for the first time that contextual stimuli paired with cocaine and nicotine, like the drugs themselves, have the ability to enhance memory consolidation.

Acetylation of histone proteins by histone acetyltransferases (HATs), and the resultant change in gene expression, is a well-established mechanism necessary for long-term memory (LTM) consolidation, which is not required for short-term memory (STM). However, we previously demonstrated that the HAT p300/CBP-associated factor (PCAF) also influences hippocampus (HPC)-dependent STM in male rats. In addition to their epigenetic activity, HATs acetylate nonhistone proteins involved in nongenomic cellular processes, such as estrogen receptors (ERs). Given that ERs have rapid, nongenomic effects on HPC-dependent STM, we investigated the potential interaction between ERs and PCAF for STM mediated by the dorsal hippocampus (dHPC). Using a series of pharmacological agents administered directly into the dHPC, we reveal a functional interaction between PCAF and ERα in the facilitation of short-term object-in-place memory in male but not female rats. This interaction was specific to ERα, while ERβ agonism did not enhance STM. It was further specific to dHPC STM, as the effect was not present in the dHPC for LTM or in the perirhinal cortex. Further, while STM required local (i.e., dHPC) estrogen synthesis, the facilitatory interaction effect appeared independent of estrogens. Finally, western blot analyses demonstrated that PCAF activation in the dHPC rapidly (5 min) activated downstream estrogen-related cell signaling kinases (c-Jun N-terminal kinase and extracellular signal-related kinase). Collectively, these findings indicate that PCAF, which is typically implicated in LTM through epigenetic processes, also influences STM in the dHPC, possibly via nongenomic ER activity. Critically, this novel PCAF–ER interaction might exist as a male-specific mechanism supporting STM. [ABSTRACT FROM AUTHOR]

To control and optimize the power of the SPARC tokamak, we require information on the total radiated power of the plasma and its 2D and 3D spatial distribution. The SPARC bolometry diagnostic is being designed and built to measure the radiated power for controlling power balance, investigating the dissipation capabilities of various divertor concepts, and measuring the efficacy of the disruption thermal load mitigation. Proven resistive bolometer sensor technology will be used, with 248 lines of sight integrated into pinhole cameras in 20 different locations. This diversity of views will allow the bolometers to view the core, divertor, and particularly X-points of the plasma with high resolution. 14 of these camera locations are dedicated to 2D equilibrium radiated power, while the remaining six locations are designed to measure 3D radiated energy during disruptions. The bolometer sensor holders, pinhole camera boxes, and cabling have been designed to survive the high neutron flux (but low fluence) and up to 400 °C temperatures seen during operation and vacuum bake. The resistive bolometer sensors use Au absorbers with an Al heat conduction layer and C anti-reflective layer. These sensor chips are wire-bonded to an AlN circuit board, both of which are held inside a custom AlN and stainless steel bolometer holder. Design and optimization of the pinhole camera lines of sight are performed using Cherab. This work details the current state of the design of the SPARC bolometry diagnostic and its interfaces, as well as ongoing work to validate the design. [ABSTRACT FROM AUTHOR]

In recent years, a dramatic increase in the study of infrastructure has occurred in the social sciences and humanities, following upon foundational work in the physical sciences, architecture, planning, information science, and engineering. This article, authored by a multidisciplinary group of scholars, probes the generative potential of infrastructure at this historical juncture. Accounting for the conceptual and material capacities of infrastructure, the article argues for the importance of paradox in understanding infrastructure. Thematically the article is organized around three key points that speak to the study of infrastructure: ruin, retrofit, and risk. The first paradox of infrastructure, ruin, suggests that even as infrastructure is generative, it degenerates. A second paradox is found in retrofit, an apparent ontological oxymoron that attempts to bridge temporality from the present to the future and yet ultimately reveals that infrastructural solidity, in material and symbolic terms, is more apparent than actual. Finally, a third paradox of infrastructure, risk, demonstrates that while a key purpose of infrastructure is to mitigate risk, it also involves new risks as it comes to fruition. The article concludes with a series of suggestions and provocations to view the study of infrastructure in more contingent and paradoxical forms.

Kipling P Sharpe, 1 Richard Berkowitz, 2 William A Tyndall, 3 David Boyer, 4 Stewart W McCallum, 5 Randall J Mack, 5 Wei Du 6 1OrthoArizona, Gilbert, AZ, USA; 2Phoenix Clinical Research, Tamarac, FL, USA; 3University Orthopedics Center, Altoona, PA, USA; 4Shoals Clinical Research Associates, LLC, Florence, SC, USA; 5Baudax Bio, Inc., Malvern, PA, USA; 6Clinical Statistics Consulting, Blue Bell, PA, USACorrespondence: Randall J MackBaudax Bio, Inc., 490 Lapp Road, Malvern, PA 19355, USATel +1 484 395 2470Fax +1 484 395 2471Email rmack@baudaxbio.comObjective: A Phase 3 randomized multicenter, double-blind, placebo-controlled trial (NCT02720692) compared once-daily intravenous (IV) meloxicam 30 mg to placebo, when added to the standard of care pain management regimens, in adults with moderate-to-severe pain following major elective surgery and concluded that meloxicam IV had a safety profile similar to placebo and reduced opioid consumption.Methods: In this post hoc subgroup analysis of orthopedic surgery subjects, 379 subjects received meloxicam IV 30 mg or IV-administered placebo every 24 hrs for ≤ 7 doses. Safety was assessed via AEs, laboratory tests, vital signs, and ECG, with an emphasis on specific AEs, including injection site reactions, bleeding, cardiovascular, hepatic, renal, thrombotic, and wound healing events. Daily opioid consumption was assessed during treatment.Results: Among meloxicam IV-treated subjects, 64.7% experienced ≥ 1 AE versus 68.8% of placebo-treated subjects. Investigators assessed most AEs to be mild or moderate in intensity and unrelated to treatment. Total opioid consumption (36.8 mg versus 50.3 mg IV morphine equivalent dose; P=0.0081) and opioid consumption during time points 0‒24, 24‒48, 0‒48, and 0‒72 hrs were statistically significantly lower in the meloxicam IV group.Conclusion: Meloxicam IV demonstrated no significant differences in the number and frequency of AEs versus placebo in subjects following orthopedic surgery. Opioid consumption was reduced in the meloxicam IV group versus placebo.Trial registration: ClinicalTrials.gov (Identifier: NCT02720692).Keywords: meloxicam IV, NSAID, orthopedic surgery, postoperative pain, safety