2,234 research outputs found

    Detail-oriented cognitive style and social communicative deficits, within and beyond the autism spectrum: independent traits that grow into developmental interdependence

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    At the heart of debates over underlying causes of autism is the "Kanner hypothesis" that autistic deficits in social reciprocity, and a cognitive/perceptual 'style' favouring detail-oriented cognition, co-vary in autistic individuals. A separate line of work indicates these two domains are normally distributed throughout the population, with autism representing an extremity. This realisation brings the Kanner debate into the realm of normative co-variation, providing more ways to test the hypothesis, and insights into typical development; for instance, in the context of normative functioning, the Kanner hypothesis implies social costs to spatial/numerical prowess

    Molecular Typing of Protease-Resistant Prion Protein in Transmissible Spongiform Encephalopathies of Small Ruminants, France, 2002–2009

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    The agent that causes bovine spongiform encephalopathy (BSE) may be infecting small ruminants, which could have serious implications for human health. To distinguish BSE from scrapie and to examine the molecular characteristics of the protease-resistant prion protein (PrPres), we used a specifically designed Western blot method to test isolates from 648 sheep and 53 goats. During 2002–2009, classical non-Nor98 transmissible spongiform encephalopathy had been confirmed among ≈1.7 million small ruminants in France. Five sheep and 2 goats that showed a PrPres pattern consistent with BSE, or with the CH1641 experimental scrapie source, were identified. Later, bioassays confirmed infection by the BSE agent in 1 of the 2 goats. Western blot testing of the 6 other isolates showed an additional C-terminally cleaved PrPres product, with an unglycosylated band at ≈14 kDa, similar to that found in the CH1641 experimental scrapie isolate and different from the BSE isolate

    Measuring the Effect of a Resuscitation Academy on Out of Hospital Cardiac Arrest Resuscitation Rates

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    According to the American Heart Association (AHA), rates of successful resuscitation after out of hospital cardiac arrest (OHCA) vary across the country. Amongst 132 counties in the United States, the rates of CPR survival to hospital discharge ranges between 3.4%-22.0%, and the rates of CPR survival with functional recovery ranges from 0.8%-20.1%. This large degree of variability between regions has been improved through programs that educate Emergency Medical Service (EMS) departments on ways to improve outcomes through an evidence-based lens. The Medic One EMS department in Seattle and King County, Washington developed a resuscitation academy (RA) that improved cardiac arrest survival from 26% in 2002 to 62% in 2013. In 2015, The New Castle County, Delaware EMS (NCCEMS) department modeled a RA after the Medic One EMS department. This study measured the effect on the number of patients experiencing return of spontaneous circulation (ROSC) and the cerebral performance category (CPC) scores for discharged patients. Data from 599 atraumatic out-of-hospital cardiac arrests (OHCA) was collected from 2009-2019, and 99 cases met Utstein inclusion criteria. Next, the study categorized if at least one RA was implemented prior to these cases to determine the RA’s effect. Implementation of one RA on ROSC outcomes yielded a significant improvement (p = .028), with a small to medium strength of effect (Cramer’s V=0.221); this indicates that the administration of at least one RA had a moderate and significant effect on increasing ROSC in patients suffering from OHCA. Administration of at least one RA did not demonstrate a significant effect on eventual patient outcomes as indicated by discharge CPC score (p = .488). This indicates that there was no statistically significant effect on the cerebral performance of patients who suffered OHCA upon discharge

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    In silico-in vitro modeling to uncover cues involved in establishing microglia identity: TGF-β3 and laminin can drive microglia signature gene expression

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    Microglia are the resident macrophages of the central nervous system (CNS) and play a key role in CNS development, homeostasis, and disease. Good in vitro models are indispensable to study their cellular biology, and although much progress has been made, in vitro cultures of primary microglia still only partially recapitulate the transcriptome of in vivo microglia. In this study, we explored a combination of in silico and in vitro methodologies to gain insight into cues that are involved in the induction or maintenance of the ex vivo microglia reference transcriptome. First, we used the in silico tool NicheNet to investigate which (CNS-derived) cues could underlie the differences between the transcriptomes of ex vivo and in vitro microglia. Modeling on basis of gene products that were found to be upregulated in vitro, predicted that high mobility group box 2 (HMGB2)- and interleukin (IL)-1β-associated signaling pathways were driving their expression. Modeling on basis of gene products that were found to be downregulated in vitro, did not lead to predictions on the involvement of specific signaling pathways. This is consistent with the idea that in vivo microenvironmental cues that determine microglial identity are for most part of inhibitory nature. In a second approach, primary microglia were exposed to conditioned medium from different CNS cell types. Conditioned medium from spheres composed of microglia, oligodendrocytes, and radial glia, increased the mRNA expression levels of the microglia signature gene P2RY12. NicheNet analyses of ligands expressed by oligodendrocytes and radial glia predicted transforming growth factor beta 3 (TGF-β3) and LAMA2 as drivers of microglia signature gene expression. In a third approach, we exposed microglia to TGF-β3 and laminin. In vitro exposure to TGF-β3 increased the mRNA expression levels of the microglia signature gene TREM2. Microglia cultured on laminin-coated substrates were characterized by reduced mRNA expression levels of extracellular matrix-associated genes MMP3 and MMP7, and by increased mRNA expression levels of the microglia signature genes GPR34 and P2RY13. Together, our results suggest to explore inhibition of HMGB2- and IL-1β-associated pathways in in vitro microglia. In addition, exposure to TGF-β3 and cultivation on laminin-coated substrates are suggested as potential improvements to current in vitro microglia culture protocols

    Optical and ultraviolet spectroscopic analysis of SN 2011fe at late times

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    We present optical spectra of the nearby Type Ia supernova SN 2011fe at 100, 205, 311, 349, and 578 days post-maximum light, as well as an ultraviolet spectrum obtained with Hubble Space Telescope at 360 days post-maximum light. We compare these observations with synthetic spectra produced with the radiative transfer code PHOENIX. The day +100 spectrum can be well fit with models which neglect collisional and radiative data for forbidden lines. Curiously, including this data and recomputing the fit yields a quite similar spectrum, but with different combinations of lines forming some of the stronger features. At day +205 and later epochs, forbidden lines dominate much of the optical spectrum formation; however, our results indicate that recombination, not collisional excitation, is the most influential physical process driving spectrum formation at these late times. Consequently, our synthetic optical and UV spectra at all epochs presented here are formed almost exclusively through recombination-driven fluorescence. Furthermore, our models suggest that the ultraviolet spectrum even as late as day +360 is optically thick and consists of permitted lines from several iron-peak species. These results indicate that the transition to the "nebular" phase in Type Ia supernovae is complex and highly wavelength-dependent.Comment: 22 pages, 21 figuress, 1 table, submitted to MNRA

    Application of Unmanned Aerial Vehicles in Emergency Medical Situations

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    Introduction One of the significant impacts on patient outcome in emergency medical situations is the response time taken for trained personnel and equipment arrival on scene. The National EMS Information System states the average response time to reach adult patients in the United States is 9.4 minutes (1). We are exploring the whether the application of Unmanned Aerial Vehicle (UAV) technology in emergency situations would shorten response time and subsequently could improve patients’ outcome In this reported on first phase (Phase 1) of an envisioned multi-stage project, we tested the ability of a UAV to properly, efficiently transport a a portable ECG device to a mock emergency site and successfully take an ECG reading when used by an untrained personnel on hand. MethodsOur UAV was a DJI Phantom 2 Vision model, a quadcopter equipped with a 14 Megapixel camera and HD video recording capabilities. The onboard camera allows for real time transmission of patient status and appearance, while the quadcopter model allows for maximum weight to lift ratio. In order to record a portable ECG, we equipped an iPhone 5 with an AliveCor Kardia mobile ECG monitor. We included an easy to use protocol for the AliveCor so that a layperson would be able to operate the machine. DataThe total flight time for 100 yards across an open field was two and a half minutes , or approximately 2 feet/second. This data shows a chi-squared distribution of 5.065, with a p-value of .01 (df=1, p\u3c.05). DiscussionDue to the statistically significant p-value, Phase 1 data demonstrates that our UAV was capable of traversing an appropriate distance in an amount of time that drastically improves upon the emergency response call time taken by traditional methods. In addition to our flight data, we were also able to properly operate the ECG and apply it to a mock patient in under 90 seconds, showing that our protocol, with instructions for usage, was clear and precise. Conclusion: This study is considered Phase 1 of a multi-stage investigation. Moving forward, we hope to improve the efficacy of our UAV, while expanding its the technological and medical capabilities, allowing it to not only carry ECG but also possibly AEDs and pharmaceuticals. Ultimately, We hope to apply such technology to emergencies in both rural and urban environments, as well as adapt it for use within the military

    Autosomal dominant hypoparathyroidism associated with short stature and premature osteoarthritis

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    Familial hypoparathyroidism is an unusual and genetically heterogeneous group of disorders that may be isolated or may be associated with congenital or acquired abnormalities in other organs or glands. We have evaluated a family with a novel syndrome of autosomal dominant hypoparathyroidism, short stature, and premature osteoarthritis. A 74-yr-old female (generation I) presented with hypoparathyroidism, a movement disorder secondary to ectopic calcification of the cerebellum and basal ganglia, and a history of knee and hip replacements for osteoarthritis. Two members of generation II and one member of generation III were also documented with hypoparathyroidism, short stature, and premature osteoarthritis evident as early as 11 yr. Because of the known association between autosomal dominant hypoparathyroidism and activating mutations of the calcium-sensing receptor (CaR) gene, further studies were performed. Sequencing of PCR-amplified genomic DNA revealed a leucine to valine substitution at position 616 in the first transmembrane domain of the CaR, which cosegregated with the disorder. However, this amino acid sequence change did not affect the total accumulation of inositol phosphates as a function of extracellular calcium concentrations in transfected HEK-293 cells. In conclusion, a sequence alteration in the coding region of the CaR gene was identified, but is not conclusively involved in the etiology of this novel syndrome. The cosegregation of hypoparathyroidism, short stature, and osteoarthritis in this kindred does suggest a genetic abnormality involving a common molecular mechanism in parathyroid, bone, and cartilage
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