Scn8a Antisense Oligonucleotide Is Protective in Mouse Models of SCN8A Encephalopathy and Dravet Syndrome

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154348/1/ana25676.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154348/2/ana25676_am.pd

Recognition memory, self-other source memory, and theory-of-mind in children with autism spectrum disorder.

This study investigated semantic and episodic memory in autism spectrum disorder (ASD), using a task which assessed recognition and self-other source memory. Children with ASD showed undiminished recognition memory but significantly diminished source memory, relative to age- and verbal ability-matched comparison children. Both children with and without ASD showed an “enactment effect”, demonstrating significantly better recognition and source memory for self-performed actions than other-person-performed actions. Within the comparison group, theory-of-mind (ToM) task performance was significantly correlated with source memory, specifically for other-person-performed actions (after statistically controlling for verbal ability). Within the ASD group, ToM task performance was not significantly correlated with source memory (after controlling for verbal ability). Possible explanations for these relations between source memory and ToM are considered

Tropical Pacific observing system

This paper reviews the design of the Tropical Pacific Observing System (TPOS) and its governance and takes a forward look at prospective change. The initial findings of the TPOS 2020 Project embrace new strategic approaches and technologies in a user-driven design and the variable focus of the Framework for Ocean Observing. User requirements arise from climate prediction and research, climate change and the climate record, and coupled modeling and data assimilation more generally. Requirements include focus on the upper ocean and air-sea interactions, sampling of diurnal variations, finer spatial scales and emerging demands related to biogeochemistry and ecosystems. One aim is to sample a diversity of climatic regimes in addition to the equatorial zone. The status and outlook for meeting the requirements of the design are discussed. This is accomplished through integrated and complementary capabilities of networks, including satellites, moorings, profiling floats and autonomous vehicles. Emerging technologies and methods are also discussed. The outlook highlights a few new foci of the design: biogeochemistry and ecosystems, low-latitude western boundary currents and the eastern Pacific. Low latitude western boundary currents are conduits of tropical-subtropical interactions, supplying waters of mid to high latitude origin to the western equatorial Pacific and into the Indonesian Throughflow. They are an essential part of the recharge/discharge of equatorial warm water volume at interannual timescales and play crucial roles in climate variability on regional and global scales. The tropical eastern Pacific, where extreme El Niño events develop, requires tailored approaches owing to the complex of processes at work there involving coastal upwelling, and equatorial cold tongue dynamics, the oxygen minimum zone and the seasonal double Intertropical Convergence Zone. A pilot program building on existing networks is envisaged, complemented by a process study of the East Pacific ITCZ/warm pool/cold tongue/stratus coupled system. The sustainability of TPOS depends on effective and strong collaborative partnerships and governance arrangements. Revisiting regional mechanisms and engaging new partners in the context of a planned and systematic design will ensure a multi-purpose, multi-faceted integrated approach that is sustainable and responsive to changing needs

Delayed self-recognition in children with autism spectrum disorder.

This study aimed to investigate temporally extended self-awareness (awareness of one’s place in and continued existence through time) in autism spectrum disorder (ASD), using the delayed self-recognition (DSR) paradigm (Povinelli et al., Child Development 67:1540–1554, 1996). Relative to age and verbal ability matched comparison children, children with ASD showed unattenuated performance on the DSR task, despite showing significant impairments in theory-of-mind task performance, and a reduced propensity to use personal pronouns to refer to themselves. The results may indicate intact temporally extended self-awareness in ASD. However, it may be that the DSR task is not an unambiguous measure of temporally extended self-awareness and it can be passed through strategies which do not require the possession of a temporally extended self-concept

Why alternative teenagers self-harm: exploring the link between non-suicidal self-injury, attempted suicide and adolescent identity

Background: The term ‘self-harm’ encompasses both attempted suicide and non-suicidal self-injury (NSSI). Specific adolescent subpopulations such as ethnic or sexual minorities, and more controversially, those who identify as ‘Alternative’ (Goth, Emo) have been proposed as being more likely to self-harm, while other groups such as ‘Jocks’ are linked with protective coping behaviours (for example exercise). NSSI has autonomic (it reduces negative emotions) and social (it communicates distress or facilitates group ‘bonding’) functions. This study explores the links between such aspects of self-harm, primarily NSSI, and youth subculture.<p></p> Methods: An anonymous survey was carried out of 452 15 year old German school students. Measures included: identification with different youth cultures, i.e. Alternative (Goth, Emo, Punk), Nerd (academic) or Jock (athletic); social background, e.g. socioeconomic status; and experience of victimisation. Self-harm (suicide and NSSI) was assessed using Self-harm Behavior Questionnaire and the Functional Assessment of Self-Mutilation (FASM).<p></p> Results: An “Alternative” identity was directly (r ≈ 0.3) and a “Jock” identity inversely (r ≈ -0.1) correlated with self-harm. “Alternative” teenagers self-injured more frequently (NSSI 45.5% vs. 18.8%), repeatedly self-injured, and were 4–8 times more likely to attempt suicide (even after adjusting for social background) than their non-Alternative peers. They were also more likely to self-injure for autonomic, communicative and social reasons than other adolescents.<p></p> Conclusions: About half of ‘Alternative’ adolescents’ self-injure, primarily to regulate emotions and communicate distress. However, a minority self-injure to reinforce their group identity, i.e. ‘To feel more a part of a group’

The Tides They are A-Changin\u27: A Comprehensive Review of Past and Future Nonastronomical Changes in Tides, Their Driving Mechanisms, and Future Implications

Scientists and engineers have observed for some time that tidal amplitudes at many locations are shifting considerably due to nonastronomical factors. Here we review comprehensively these important changes in tidal properties, many of which remain poorly understood. Over long geological time scales, tectonic processes drive variations in basin size, depth, and shape and hence the resonant properties of ocean basins. On shorter geological time scales, changes in oceanic tidal properties are dominated by variations in water depth. A growing number of studies have identified widespread, sometimes regionally coherent, positive, and negative trends in tidal constituents and levels during the 19th, 20th, and early 21st centuries. Determining the causes is challenging because a tide measured at a coastal gauge integrates the effects of local, regional, and oceanic changes. Here, we highlight six main factors that can cause changes in measured tidal statistics on local scales and a further eight possible regional/global driving mechanisms. Since only a few studies have combined observations and models, or modeled at a temporal/spatial resolution capable of resolving both ultralocal and large-scale global changes, the individual contributions from local and regional mechanisms remain uncertain. Nonetheless, modeling studies project that sea level rise and climate change will continue to alter tides over the next several centuries, with regionally coherent modes of change caused by alterations to coastal morphology and ice sheet extent. Hence, a better understanding of the causes and consequences of tidal variations is needed to help assess the implications for coastal defense, risk assessment, and ecological change

The Tides They Are A-Changin': A Comprehensive Review of Past and Future Nonastronomical Changes in Tides, Their Driving Mechanisms, and Future Implications:A comprehensive review of past and future non‐astronomical changes in tides, their driving mechanisms and future implications

Scientists and engineers have observed for some time that tidal amplitudes at many locations are shifting considerably due to non-astronomical factors. Here we review comprehensively these important changes in tidal properties, many of which remain poorly understood. Over long geological time-scales, tectonic processes drive variations in basin size, depth, and shape, and hence the resonant properties of ocean basins. On shorter geological time-scales, changes in oceanic tidal properties are dominated by variations in water depth. A growing number of studies have identified widespread, sometimes regionally-coherent, positive and negative trends in tidal constituents and levels during the 19th, 20th and early 21st centuries. Determining the causes is challenging because a tide measured at a coastal gauge integrates the effects of local, regional, and oceanic changes. Here, we highlight six main factors that can cause changes in measured tidal statistics on local scales, and a further eight possible regional/global driving mechanisms. Since only a few studies have combined observations and models, or modelled at a temporal/spatial resolution capable of resolving both ultra-local and large-scale global changes, the individual contributions from local and regional mechanisms remain uncertain. Nonetheless, modelling studies project that sea-level rise and climate change will continue to alter tides over the next several centuries, with regionally coherent modes of change caused by alterations to coastal morphology and ice sheet extent. Hence, a better understanding of the causes and consequences of tidal variations is needed to help assess the implications for coastal defense, risk assessment, and ecological change

Self-management for osteoarthritis of the knee: Does mode of delivery influence outcome?

Background Self-management has become increasingly popular in the management of chronic diseases. There are many different self-management models. Meta analyses of arthritis self-management have concluded that it is difficult to recommend any one program in preference to another due to inconsistencies in the study designs used to evaluate different programs. The Stanford Arthritis Self-Management Program (ASMP), most commonly delivered by trained lay leaders, is a generic program widely used for people with rheumatological disorders. We have developed a more specific program expressly for people with osteoarthritis of the knee (OAKP). It includes information designed to be delivered by health professionals and results in improvements in pain, function and quality of life. Aim: To determine whether, for people with osteoarthritis (OA) of the knee, the OAKP implemented in a primary health care setting can achieve and maintain clinically meaningful improvements in more participants than ASMP delivered in the same environment. Methods/Design The effectiveness of the programs will be compared in a single-blind randomized study. Participants: 146 participants with established OA knee will be recruited. Volunteers with coexistent inflammatory joint disease or serious co-morbidities will be excluded. Interventions: Participants will be randomised into either OAKP or ASMP groups and followed for 6 months. Measurements: Assessments will be immediately before and after the intervention and at 6 months. Primary outcome measures will be WOMAC and SF-36 questionnaires and a VAS for pain. Secondary outcomes will include balance, tested using a timed single leg balance test and a timed step test and self-efficacy. Data will be analysed using repeated measures ANOVA. Discussion With an aging population the health care costs for people with arthritis are ever increasing. Although cost analysis is beyond the scope of this study, it is reasonable to expect that costs will be greater when health professionals deliver self-management programs as opposed to lay leaders. Consequently it is critical to examine the relative effectiveness of the primary care management strategies available for OA

Judgment of Learning Accuracy in High-functioning Adolescents and Adults with Autism Spectrum Disorder

This study explored whether adults and adolescents with autism spectrum disorder (ASD) demonstrate difficulties making metacognitive judgments, specifically judgments of learning. Across two experiments, the study examined whether individuals with ASD could accurately judge whether they had learnt a piece of information (in this case word pairs). In Experiment 1, adults with ASD demonstrated typical accuracy on a standard ‘cue-alone’ judgment of learning (JOL) task, compared to age- and IQmatched neurotypical adults. Additionally, in Experiment 2, adolescents with ASD demonstrated typical accuracy on both a standard ‘cue-alone’ JOL task, and a ‘cue-target’ JOL task. These results suggest that JOL accuracy is unimpaired in ASD. These results have important implications for both theories of metacognition in ASD and educational practise

The adjuvant GLA-SE promotes human Tfh cell expansion and emergence of public TCRβ clonotypes

The generation of protective humoral immunity after vaccination relies on the productive interaction between antigen-specific B cells and T follicular helper (Tfh) cells. Despite the central role of Tfh cells in vaccine responses, there is currently no validated way to enhance their differentiation in humans. From paired human lymph node and blood samples, we identify a population of circulating Tfh cells that are transcriptionally and clonally similar to germinal center Tfh cells. In a clinical trial of vaccine formulations, circulating Tfh cells were expanded in Tanzanian volunteers when an experimental malaria vaccine was adjuvanted in GLA-SE but not when formulated in Alum. The GLA-SE–formulated peptide was associated with an increase in the extrafollicular antibody response, long-lived antibody production, and the emergence of public TCRβ clonotypes in circulating Tfh cells. We demonstrate that altering vaccine adjuvants is a rational approach for enhancing Tfh cells in humans, thereby supporting the long-lived humoral immunity that is required for effective vaccines.</jats:p