A comprehensive approach to modeling maternal immune activation in rodents

Prenatal brain development is a highly orchestrated process, making it a very vulnerable window to perturbations. Maternal stress and subsequent inflammation during pregnancy leads to a state referred to as, maternal immune activation (MIA). If persistent, MIA can pose as a significant risk factor for the manifestation of neurodevelopmental disorders (NDDs) such as autism spectrum disorder and schizophrenia. To further elucidate this association between MIA and NDD risk, rodent models have been used extensively across laboratories for many years. However, there are few uniform approaches for rodent MIA models which make not only comparisons between studies difficult, but some established approaches come with limitations that can affect experimental outcomes. Here, we provide researchers with a comprehensive review of common experimental variables and potential limitations that should be considered when designing an MIA study based in a rodent model. Experimental variables discussed include: innate immune stimulation using poly I:C and LPS, environmental gestational stress paradigms, rodent diet composition and sterilization, rodent strain, neonatal handling, and the inclusion of sex-specific MIA offspring analyses. We discuss how some aspects of these variables have potential to make a profound impact on MIA data interpretation and reproducibility

Optimising motor learning in infants at high risk of cerebral palsy: a pilot study

Background: The average age for the diagnosis of cerebral palsy (CP) is 19 months. Recent neuroplasticity literature suggests that intensive, task-specific intervention ought to commence as early as possible and in an enriched environment, during the critical period of neural development. Active motor interventions are effective in some populations, however the effects of active motor interventions on the motor outcomes of infants with CP have not been researched thoroughly, but pilot work is promising. The aim of this study was to determine the short- term effects of “GAME”; a new and novel goal-oriented activity-based, environmental enrichment therapy programme on the motor development of infants at high risk of CP and test study procedures for a randomized controlled trial (RCT). Methods: Pragmatic 2-group pilot RCT to assess motor outcomes, goal attainment, parent well-being and home environment quality, after 12-weeks of GAME intervention versus standard care. GAME included: creation of movement environments to elicit motor behaviours; parent training in motor learning and task analysis; frequent practice of motor tasks using a programme that was individualised to the child, was varied and focused on self-initiated movement. Data were analyzed using multiple regression. Results: Thirteen infants were consented, randomised, treated and completed the study. At study conclusion, the GAME group (n = 6) demonstrated an advantage in Total Motor Quotient of 8.05 points on the Peabody Developmental Motor Scale-2 (PDMS-2) compared to the standard care group (n = 7) (p \u3c .001). No significant differences existed between groups on any other measure. Conclusions: GAME appears to offer a promising and feasible new motor intervention for CP, with favourable short-term motor outcomes. A pressing need exists for an adequately powered RCT with long-term end points, to determine if GAME may advance these children’s motor trajectory

Space Plasma Interactions with Spacecraft Materials

Spacecraft materials on orbit are subjected to the harsh weather of space. In particular, high-energy electrons alter the chemical structure of polymers and cause charge accumulation. Understanding the mechanisms of damage and charge dissipation is critical to spacecraft construction and operational anomaly resolution. Energetic particles in space plasma break molecular bonds in polymers and create radicals that can act as space charge traps. These electron-induced chemical changes also result in changes to the spectral absorption profile of polymers on orbit. Radicals react over time, either recreating identical bonds to those in the pristine material, leading to material recovery, or creating new bonds, resulting in a new material with new physical properties. Lack of knowledge about this dynamic aging is a major impediment to accurate modeling of spacecraft behavior over its mission life. This chapter first presents an investigation of the chemical and physical properties of polyimide films (PI, Kapton-H®) during and after irradiation with high-energy (90 keV) electrons. Second, the deleterious effects of space plasma on a spacecraft component level are presented. The results of this physical/chemical collaboration demonstrate the correlation of chemical changes in PI with the dynamic nature of spacecraft material aging

CANDELS: The Contribution of the Observed Galaxy Population to Cosmic Reionization

We present measurements of the specific ultraviolet luminosity density from a sample of 483 galaxies at 6<z<8. These galaxies were selected from new deep near-infrared HST imaging from the CANDELS, HUDF09 and ERS programs. In contrast to the majority of previous analyses, which assume that the distribution of galaxy ultraviolet (UV) luminosities follows a Schechter distribution, and that the distribution continues to luminosities far below our observable limit, we investigate the contribution to reionization from galaxies which we can observe, free from these assumptions. We find that the observable population of galaxies can sustain a fully reionized IGM at z=6, if the average ionizing photon escape fraction (f_esc) is ~30%. A number of previous studies have measured UV luminosity densities at these redshifts that vary by 5X, with many concluding that galaxies could not complete reionization by z=6 unless a large population of galaxies fainter than the detection limit were invoked, or extremely high values of f_esc were present. The observed UV luminosity density from our observed galaxy samples at z=7-8 is not sufficient to maintain a fully reionized IGM unless f_esc>50%. Combining our observations with constraints on the emission rate of ionizing photons from Ly-alpha forest observations at z=6, we can constrain f_esc<34% (2-sigma) if the observed galaxies are the only contributors to reionization, or <13% (2-sigma) if the luminosity function extends to M_UV = -13. These escape fractions are sufficient to complete reionization by z=6. These constraints imply that the volume ionized fraction of the IGM becomes less than unity at z>7, consistent with a number of complementary reionization probes. If faint galaxies dominate reionization, future JWST observations will probe deep enough to see them, providing an indirect constraint on the ionizing photon escape fraction [abridged].Comment: 16 pages, 7 figures, Submitted to the Astrophysical Journa

The Lantern Vol. 15, No. 3, Summer 1947

• On Sleeping at Lectures • So You Want Security • Mild and Bitters • The Child April • Helgoland • His Majesty, Tabby • January Interval • A Friend or Two • Wish in June • The Search • Jack of 54 and Davey Jones • Song of the Earth • Donald Gay Baker • The Dilemma by the Horns • Psychologyhttps://digitalcommons.ursinus.edu/lantern/1042/thumbnail.jp

Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient

Autoimmune encephalitis (AE) is an important and treatable cause of acute encephalitis. Diagnosis of AE in a developing child is challenging because of overlap in clinical presentations with other diseases and complexity of normal behavior changes. Existing diagnostic criteria for adult AE require modification to be applied to children, who differ from adults in their clinical presentations, paraclinical findings, autoantibody profiles, treatment response, and long-term outcomes.A subcommittee of the Autoimmune Encephalitis International Working Group collaborated through conference calls and email correspondence to consider the pediatric-specific approach to AE. The subcommittee reviewed the literature of relevant AE studies and sought additional input from other expert clinicians and researchers.Existing consensus criteria for adult AE were refined for use in children. Provisional pediatric AE classification criteria and an algorithm to facilitate early diagnosis are proposed. There is also discussion about how to distinguish pediatric AE from conditions within the differential diagnosis.Diagnosing AE is based on the combination of a clinical history consistent with pediatric AE and supportive diagnostic testing, which includes but is not dependent on antibody testing. The proposed criteria and algorithm require validation in prospective pediatric cohorts.Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

Emotional valence and arousal affect reading in an interactive way: neuroimaging evidence for an approach-withdrawal framework

A growing body of literature shows that the emotional content of verbal material affects reading, wherein emotional words are given processing priority compared to neutral words. Human emotions can be conceptualised within a two-dimensional model comprised of emotional valence and arousal (intensity). These variables are at least in part distinct, but recent studies report interactive effects during implicit emotion processing and relate these to stimulus-evoked approach-withdrawal tendencies. The aim of the present study was to explore how valence and arousal interact at the neural level, during implicit emotion word processing. The emotional attributes of written word stimuli were orthogonally manipulated based on behavioural ratings from a corpus of emotion words. Stimuli were presented during an fMRI experiment while 16 participants performed a lexical decision task, which did not require explicit evaluation of a word's emotional content. Results showed greater neural activation within right insular cortex in response to stimuli evoking conflicting approach-withdrawal tendencies (i.e., positive high-arousal and negative low-arousal words) compared to stimuli evoking congruent approach vs. withdrawal tendencies (i.e., positive low-arousal and negative high-arousal words). Further, a significant cluster of activation in the left extra-striate cortex was found in response to emotional than neutral words, suggesting enhanced perceptual processing of emotionally salient stimuli. These findings support an interactive two-dimensional approach to the study of emotion word recognition and suggest that the integration of valence and arousal dimensions recruits a brain region associated with interoception, emotional awareness and sympathetic functions

Social democracy, embeddedness and decommodification: On the conceptual innovations and intellectual affiliations of Karl Polanyi

Of the several debates that revolve around the work of the economic historian and political economist Karl Polanyi, one that continues to exercise minds concerns his analysis of, and political attitudes toward, post-war capitalism and the welfare state. Simplified a little, it is a debate with two sides. To borrow Iván Szelényi's terms, one side constructs a ‘hard’ Karl Polanyi, the other a ‘soft’ one. The former advocated a socialist mixed economy dominated by redistributive mechanisms. He was a radical socialist for whom the market should never be the dominant mechanism of economic coordination. His ‘soft’ alter ego insisted that the market system remain essentially intact but be complemented by redistributive mechanisms. The ‘double movement’ – the central thesis of his ‘Great Transformation’ – acts, in this reading, as a self-correcting mechanism that moderates the excesses of market fundamentalism; its author was positioned within the social-democratic mainstream for which the only realistic desirable goal is a regulated form of capitalism. In terms of textual evidence there is much to be said for both interpretations. In this article I suggest a different approach, one that focuses upon the meaning of Polanyi's concepts in relation to their socio-political and intellectual environment

Spatio-Temporal Patterns of Barmah Forest Virus Disease in Queensland, Australia

Background Barmah Forest virus (BFV) disease is a common and wide-spread mosquito-borne disease in Australia. This study investigated the spatio-temporal patterns of BFV disease in Queensland, Australia using geographical information system (GIS) tools and geostatistical analysis. Methods/Principal Findings We calculated the incidence rates and standardised incidence rates of BFV disease. Moran's I statistic was used to assess the spatial autocorrelation of BFV incidences. Spatial dynamics of BFV disease was examined using semi-variogram analysis. Interpolation techniques were applied to visualise and display the spatial distribution of BFV disease in statistical local areas (SLAs) throughout Queensland. Mapping of BFV disease by SLAs reveals the presence of substantial spatio-temporal variation over time. Statistically significant differences in BFV incidence rates were identified among age groups (χ2 = 7587, df = 7327,p<0.01). There was a significant positive spatial autocorrelation of BFV incidence for all four periods, with the Moran's I statistic ranging from 0.1506 to 0.2901 (p<0.01). Semi-variogram analysis and smoothed maps created from interpolation techniques indicate that the pattern of spatial autocorrelation was not homogeneous across the state. Conclusions/Significance This is the first study to examine spatial and temporal variation in the incidence rates of BFV disease across Queensland using GIS and geostatistics. The BFV transmission varied with age and gender, which may be due to exposure rates or behavioural risk factors. There are differences in the spatio-temporal patterns of BFV disease which may be related to local socio-ecological and environmental factors. These research findings may have implications in the BFV disease control and prevention programs in Queensland

An open-label trial of JAK 1/2 blockade in progressive IFIH1 -associated neuroinflammation

IFIH1 gain-of-function causes a spectrum of neuroinflammatory phenotypes associated with enhanced type I interferon production and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway activation.1,2 Patients most often present in infancy, variably exhibiting spasticity, dystonia, seizures, and acquired microcephaly. We report the use of ruxolitinib, a JAK 1/2 blocker, in the treatment of early-onset, progressive neurologic disease due to an IFIH1 mutation