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The neural mechanisms contributing to the social problems of pediatric brain tumor survivors (PBTS) are unknown. Face processing is important to social communication, social behavior, and peer acceptance. Research with other populations with social difficulties, namely autism spectrum disorder, suggests atypical brain activation in areas important for face processing. This case-controlled functional magnetic resonance imaging (fMRI) study compared brain activation during face processing in PBTS and typically developing (TD) youth.
Participants included 36 age-, gender-, and IQ-matched youth (N = 18 per group). PBTS were at least 5 years from diagnosis and 2 years from the completion of tumor therapy. fMRI data were acquired during a face identity task and a control condition. Groups were compared on activation magnitude within the fusiform gyrus for the faces condition compared to the control condition. Correlational analyses evaluated associations between neuroimaging metrics and indices of social behavior for PBTS participants.
Both groups demonstrated face-specific activation within the social brain for the faces condition compared to the control condition. PBTS showed significantly decreased activation for faces in the medial portions of the fusiform gyrus bilaterally compared to TD youth, ps ≤ .004. Higher peak activity in the left fusiform gyrus was associated with better socialization (r = .53, p < .05).
This study offers initial evidence of atypical activation in a key face processing area in PBTS. Such atypical activation may underlie some of the social difficulties of PBTS. Social cognitive neuroscience methodologies may elucidate the neurobiological bases for PBTS social behavior.
Electroencephalographic (EEG) abnormalities are greater in mild cognitive impairment (MCI) with Lewy bodies (MCI-LB) than in MCI due to Alzheimer’s disease (MCI-AD) and may anticipate the onset of dementia. We aimed to assess whether quantitative EEG (qEEG) slowing would predict a higher annual hazard of dementia in MCI across these etiologies. MCI patients (n = 92) and healthy comparators (n = 31) provided qEEG recording and underwent longitudinal clinical and cognitive follow-up. Associations between qEEG slowing, measured by increased theta/alpha ratio, and clinical progression from MCI to dementia were estimated with a multistate transition model to account for death as a competing risk, while controlling for age, cognitive function, and etiology classified by an expert consensus panel.
Over a mean follow-up of 1.5 years (SD = 0.5), 14 cases of incident dementia and 5 deaths were observed. Increased theta/alpha ratio on qEEG was associated with increased annual hazard of dementia (hazard ratio = 1.84, 95% CI: 1.01–3.35). This extends previous findings that MCI-LB features early functional changes, showing that qEEG slowing may anticipate the onset of dementia in prospectively identified MCI.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
This essay explores ideas of the untimely in connection with a queer politics in Faulkner: queer a commitment to imagining novel forms of dissident desire, pleasure, and affiliation; untimeliness an effect of the non-coincidence of chronological and political temporalities. Faulkner’s fiction is staggered temporally not only as a result of his well-known determination to recollect the traumatic past of nation, region, and individual, but also by less noticed efforts to grasp, in that past, alternative futures, some now foreclosed, others still biding their time. In Faulkner’s historical fiction like Absalom, Absalom! and Go Down, Moses, we find materializations in the past of futures that may not come to pass; in novels set in the present such as Light in August, we encounter dissident ways of life that resist modern normative constraints; in If I Forget Thee, Jerusalem another dimension of the untimely appears, in forms of futurity that beckon with unprecedented gratifications of desire while threatening the resurgence of past forms of bondage.
Psychological attachment to political parties can bias people’s attitudes, beliefs, and group evaluations. Studies from psychology suggest that self-affirmation theory may ameliorate this problem in the domain of politics on a variety of outcome measures. We report a series of studies conducted by separate research teams that examine whether a self-affirmation intervention affects a variety of outcomes, including political or policy attitudes, factual beliefs, conspiracy beliefs, affective polarization, and evaluations of news sources. The different research teams use a variety of self-affirmation interventions, research designs, and outcomes. Despite these differences, the research teams consistently find that self-affirmation treatments have little effect. These findings suggest considerable caution is warranted for researchers who wish to apply the self-affirmation framework to studies that investigate political attitudes and beliefs. By presenting the “null results” of separate research teams, we hope to spark a discussion about whether and how the self-affirmation paradigm should be applied to political topics.
Anxiety disorders are common in autism spectrum disorder (ASD) and associated with social–communication impairment and repetitive behavior symptoms. The neurobiology of anxiety in ASD is unknown, but amygdala dysfunction has been implicated in both ASD and anxiety disorders. Using resting-state functional magnetic resonance imaging, we compared amygdala–prefrontal and amygdala–striatal connections across three demographically matched groups studied in the Autism Brain Imaging Data Exchange (ABIDE): ASD with a comorbid anxiety disorder (N = 25; ASD + Anxiety), ASD without a comorbid disorder (N = 68; ASD-NoAnx), and typically developing controls (N = 139; TD). Relative to ASD-NoAnx and TD controls, ASD + Anxiety individuals had decreased connectivity between the amygdala and dorsal/rostral anterior cingulate cortex (dACC/rACC). The functional connectivity of these connections was not affected in ASD-NoAnx, and amygdala connectivity with ventral ACC/medial prefrontal cortex (mPFC) circuits was not different in ASD + Anxiety or ASD-NoAnx relative to TD. Decreased amygdala–dorsomedial prefrontal cortex (dmPFC)/rACC connectivity was associated with more severe social impairment in ASD + Anxiety; amygdala–striatal connectivity was associated with restricted, repetitive behavior (RRB) symptom severity in ASD-NoAnx individuals. These findings suggest comorbid anxiety in ASD is associated with disrupted emotion-monitoring processes supported by amygdala–dACC/mPFC pathways, whereas emotion regulation systems involving amygdala–ventromedial prefrontal cortex (vmPFC) are relatively spared. Our results highlight the importance of accounting for comorbid anxiety for parsing ASD neurobiological heterogeneity.
OBJECTIVES/GOALS: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatologic disease childhood and a cause of pain and potential disability. JIA has a strong genetic component and no known cure. The goal of this study is to evaluate allele-dependent effects of a novel JIA risk variant at 1q24.3. METHODS/STUDY POPULATION: JIA patients meeting criteria for the two most common disease subtypes (oligoarticular and RF neg polyarthritis) were genotyped using the Immunochip, an Illumina array with dense coverage of the HLA region and 186 other loci previously reported in autoimmune diseases. Phase I association findings (Hinks, 2013) and Phase II analysis (unpublished) of an expanded cohort (4,271 JIA and 14,390 controls) identified new risk loci, including rs78037977 at 1q24.3. We prioritized rs78037977 and predicted possible impacted mechanisms based on Bayesian predictions of attributable risk, the surrounding chromatin landscape, and transcription factor binding data. A luciferase reporter assay was used to assess allele-dependent enhancer activity. RESULTS/ANTICIPATED RESULTS: rs78037977 is located between FASLG and TNFSF18 at chromosome 1q24.3 is associated with JIA (p = 6.3x10−09), and explains 94% of the posterior probability at this locus; no other SNPs in linkage disequilibrium (r2>0.6). The chromatin landscape around rs78037977 contains H3K4Me1 and H3K27Ac marks, which are indicative of enhancer activity. Further, >160 transcription factors have chromatin immunoprecipitation followed by sequencing (ChIP-seq) peaks overlapping rs78037977 in various cellular contexts. In luciferase reporter assays, the region around rs78037977 containing the reference A allele had ~2-fold increased enhancer activity compared to the non-reference allele. DISCUSSION/SIGNIFICANCE OF IMPACT: This work provides in vitro evidence to support allele-dependent enhancer activity of a novel JIA-risk variant at 1q24.3. Our ongoing work investigates the effect of the DNA-containing region of rs78037977 on gene expression and differential transcription factor binding at rs78037977.
In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a “wet” person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.
This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.
Mild cognitive impairment (MCI) may gradually worsen to dementia, but often remains stable for extended periods of time. Little is known about the predictors of decline to help explain this variation. We aimed to explore whether this heterogeneous course of MCI may be predicted by the presence of Lewy body (LB) symptoms in a prospectively-recruited longitudinal cohort of MCI with Lewy bodies (MCI-LB) and Alzheimer's disease (MCI-AD).
A prospective cohort (n = 76) aged ⩾60 years underwent detailed assessment after recent MCI diagnosis, and were followed up annually with repeated neuropsychological testing and clinical review of cognitive status and LB symptoms. Latent class mixture modelling identified data-driven sub-groups with distinct trajectories of global cognitive function.
Three distinct trajectories were identified in the full cohort: slow/stable progression (46%), intermediate progressive decline (41%) and a small group with a much faster decline (13%). The presence of LB symptomology, and visual hallucinations in particular, predicted decline v. a stable cognitive trajectory. With time zeroed on study end (death, dementia or withdrawal) where available (n = 39), the same subgroups were identified. Adjustment for baseline functioning obscured the presence of any latent classes, suggesting that baseline function is an important parameter in prospective decline.
These results highlight some potential signals for impending decline in MCI; poorer baseline function and the presence of probable LB symptoms – particularly visual hallucinations. Identifying people with a rapid decline is important but our findings are preliminary given the modest cohort size.
Spotted fever group rickettsiae (SFG) are a neglected group of bacteria, belonging to the genus Rickettsia, that represent a large number of new and emerging infectious diseases with a worldwide distribution. The diseases are zoonotic and are transmitted by arthropod vectors, mainly ticks, fleas and mites, to hosts such as wild animals. Domesticated animals and humans are accidental hosts. In Asia, local people in endemic areas as well as travellers to these regions are at high risk of infection. In this review we compare SFG molecular and serological diagnostic methods and discuss their limitations. While there is a large range of molecular diagnostics and serological assays, both approaches have limitations and a positive result is dependent on the timing of sample collection. There is an increasing need for less expensive and easy-to-use diagnostic tests. However, despite many tests being available, their lack of suitability for use in resource-limited regions is of concern, as many require technical expertise, expensive equipment and reagents. In addition, many existing diagnostic tests still require rigorous validation in the regions and populations where these tests may be used, in particular to establish coherent and worthwhile cut-offs. It is likely that the best strategy is to use a real-time quantitative polymerase chain reaction (qPCR) and immunofluorescence assay in tandem. If the specimen is collected early enough in the infection there will be no antibodies but there will be a greater chance of a PCR positive result. Conversely, when there are detectable antibodies it is less likely that there will be a positive PCR result. It is therefore extremely important that a complete medical history is provided especially the number of days of fever prior to sample collection. More effort is required to develop and validate SFG diagnostics and those of other rickettsial infections.
A synthesis method to form conformal core-shell foams of metals and alloys on a carbon nanotube (CNT) scaffold by electroplating from a single bath electrolyte is demonstrated in this work. A triple cyclic pulse electrodeposition technique was used to deposit Ni and Cu layers on the CNT scaffold, and electron microscopy was then used to identify conditions amenable to conformal and island growth morphologies. Nanoindentation of the resulting metallic foam structure, using a flat punch/compression geometry, demonstrates that adding conformal metallic shells to the CNT turf to create a metal coated low density foam increases both the hardness and elastic modulus; however, once island growth initiates there is no significant subsequent increase in mechanical properties with increases in deposited metals.
A synthesis method to form foams consisting of a shell of metals conformally coated on carbon nanotube (CNT) arrays by electroplating from a single bath electrolyte is demonstrated in this work. A triple cyclic pulse electrodeposition technique was used to deposit Ni and Cu layers on the CNT arrays, and electron microscopy was then used to identify conditions amenable to semi-conformal and island growth morphologies. Nanoindentation of the resulting metallic-CNT composite foam structure, using a flat punch/compression geometry, demonstrates that adding metallic shells to the CNT turf to create a metallic low density foam increases both the hardness and elastic modulus; however, once island growth initiates there is no significant subsequent increase in mechanical properties with increases in deposited metals.
Accidental hypothermia can lead to untoward cardiac manifestations and arrest. This report presents a case series of severe accidental hypothermia with cardiac complications in three emergency patients who were treated with extracorporeal membrane oxygenation (ECMO) and survived after re-warming. The aim of this discussion was to encourage more clinicians to consider ECMO as a re-warming therapy for severe hypothermia with circulatory collapse and to prompt discussion about decreasing the barriers to its use.
NiehausMT, PechulisRM, WuJK, FreiS, HongJJ, SandhuRS, GreenbergMR. Extracorporeal Membrane Oxygenation (ECMO) for Hypothermic Cardiac Deterioration: A Case Series. Prehosp Disaster Med. 2016;31(5):570–571.
To aid in preparation of military medic trainers for a possible new curriculum in teaching junctional tourniquet use, the investigators studied the time to control hemorrhage and blood volume lost in order to provide evidence for ease of use.
Models of junctional tourniquet could perform differentially by blood loss, time to hemostasis, and user preference.
In a laboratory experiment, 30 users controlled simulated hemorrhage from a manikin (Combat Ready Clamp [CRoC] Trainer) with three iterations each of three junctional tourniquets. There were 270 tests which included hemorrhage control (yes/no), time to hemostasis, and blood volume lost. Users also subjectively ranked tourniquet performance. Models included CRoC, Junctional Emergency Treatment Tool (JETT), and SAM Junctional Tourniquet (SJT). Time to hemostasis and total blood loss were log-transformed and analyzed using a mixed model analysis of variance (ANOVA) with the users represented as random effects and the tourniquet model used as the treatment effect. Preference scores were analyzed with ANOVA, and Tukey’s honest significant difference test was used for all post-hoc pairwise comparisons.
All tourniquet uses were 100% effective for hemorrhage control. For blood loss, CRoC and SJT performed best with least blood loss and were significantly better than JETT; in pairwise comparison, CRoC-JETT (P < .0001) and SJT-JETT (P = .0085) were statistically significant in their mean difference, while CRoC-SJT (P = .35) was not. For time to hemostasis in pairwise comparison, the CRoC had a significantly shorter time compared to JETT and SJT (P < .0001, both comparisons); SJT-JETT was also significant (P = .0087). In responding to the directive, “Rank the performance of the models from best to worst,” users did not prefer junctional tourniquet models differently (P > .5, all models).
The CRoC and SJT performed best in having least blood loss, CRoC performed best in having least time to hemostasis, and users did not differ in preference of model. Models of junctional tourniquet performed differentially by blood loss and time to hemostasis.
KraghJFJr, LunatiMP, KharodCU, CunninghamCW, BaileyJA, StockingerZT, CapAP, ChenJ, AdenJK3d, CancioLC. Assessment of Groin Application of Junctional Tourniquets in a Manikin Model. Prehosp Disaster Med. 2016;31(4):358–363.