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OBJECTIVES/GOALS: Neonatal hypoxic-ischemic encephalopathy (HIE) is an acute neurologic syndrome where decreased blood flow and oxygen to the brain causes acute and chronic brain dysfunction. The only proven neuroprotective intervention for HIE is hypothermia treatment started within 6 hours of birth and 50% of survivors have long-term deficits. METHODS/STUDY POPULATION: Pre-clinical adult stroke studies demonstrated that vagus nerve stimulation (VNS) has anti-inflammatory effects and attenuates brain damage. Transcutaneous auricular VNS (taVNS) is safe and feasible in infants and may improve the motor skill of bottle feeding. We hypothesize that a combined hypothermia-taVNS treatment shortly after HIE birth will have neuroprotective effects, improve motor function, attenuate infarct volume inflammation compared to hypothermia alone. The HIE model includes ligation of the right common carotid artery in postnatal day 7 (P7) rats followed by 90min hypoxia (8% oxygen) and 2hr hypothermia. taVNS or sham taVNS was administered using a bipolar electrode placed on the auricular concha region for 30min, [30sec trains, 0.5msec duration, 20Hz frequency, followed by 4.5min breaks] RESULTS/ANTICIPATED RESULTS: Experimental groups include +HIE/+taVNS, +HIE/-taVNS, and -HIE/-taVNS. To assess motor function, grasping reflex and forelimb grip strength tasks were assessed prior to surgery through P10. Infarct volume was assessed at 72h after injury by staining coronal sections with cresyl-violet. Thirty-four rat pups underwent surgery with an 8.82% mortality rate. taVNS was well tolerated by the P7 rats when delivered below perceptual threshold (0.4-1.1mA). There was no difference in elementary motor function or infarct volume between any group. DISCUSSION/SIGNIFICANCE: Future studies will include 2.5hr hypoxia for a more severe brain injury and a -HIE/+taVNS control group. These initial pre-clinical studies in neonates are important in determining whether taVNS may translate as a treatment to improve outcomes after neonatal HIE.
Chapter 13, “Sacred Dimensions: Death and Burial,” examines burial practices in Constantinople between the fourth century and the fifteenth century. Particular attention is given to aristocratic and imperial burial practice.
Passive microwave satellite observations are used to identify the presence of surface meltwater across Antarctica at daily intervals from July 1979 to June 2020, with a focus on ice shelves. Antarctic Peninsula ice shelves have the highest number of annual days of melt, with a maximum of 89 days. Over the entire time period, there are few significant linear trends in days of melt per year. High melt years can be split into two distinct categories, those with high melt days in Dronning Maud Land and Wilkes Land, and those with high melt days in the Antarctic Peninsula and the Bellingshausen Sea sector of West Antarctica. The first pattern coincides with significant negative correlations between melt days and spring and summer Southern Annular Mode. Both patterns also form the primary modes of spatial and annual variability in the dataset observed by Principal Component Analysis. Areas experiencing extended melt for the first time in years tend to show large decreases in subsequent winter microwave emissions due to structural changes in the firn. We use this to identify the impact of novel melt events, particularly over the austral summers of 1991/92 and 2015/16 on the Ross Ice Shelf.
It was suggested that children's referent selection may not lay memory traces sufficiently strong to lead to retention of new word-object mappings. If this was the case we expect incorrect selections to be easily rectified through feedback. Previous work suggested this to be the case in toddlers at typical likelihood (TL) but not in those at elevated likelihood (EL) for autism spectrum disorder (ASD) (Bedford et al., 2013). Yet group differences in lexical knowledge may have confounded these findings. Here, TL (N = 29) and EL toddlers (N = 75) chose one of two unfamiliar objects as a referent for a new word. Both groups retained the word-referent mapping above chance when their choices were immediately reinforced but were at chance after corrective feedback. The same pattern of results was obtained when children observed another experimenter make the initial referent choice. Thus, children's referent choices lay memory traces that compete with subsequent correction; these strong word-object associations are not a result of children actively choosing potential referents for new words.
To determine the utility of the Sofia SARS rapid antigen fluorescent immunoassay (FIA) to guide hospital-bed placement of patients being admitted through the emergency department (ED).
Cross-sectional analysis of a clinical quality improvement study.
This study was conducted in 2 community hospitals in Maryland from September 21, 2020, to December 3, 2020. In total, 2,887 patients simultaneously received the Sofia SARS rapid antigen FIA and SARS-CoV-2 RT-PCR assays on admission through the ED.
Rapid antigen results and symptom assessment guided initial patient placement while confirmatory RT-PCR was pending. The sensitivity, specificity, positive predictive values, and negative predictive values of the rapid antigen assay were calculated relative to RT-PCR, overall and separately for symptomatic and asymptomatic patients. Assay sensitivity was compared to RT-PCR cycle threshold (Ct) values. Assay turnaround times were compared. Clinical characteristics of RT-PCR–positive patients and potential exposures from false-negative antigen assays were evaluated.
For all patients, overall agreement was 97.9%; sensitivity was 76.6% (95% confidence interval [CI], 71%–82%), and specificity was 99.7% (95% CI, 99%–100%). We detected no differences in performance between asymptomatic and symptomatic individuals. As RT-PCR Ct increased, the sensitivity of the antigen assay decreased. The mean turnaround time for the antigen assay was 1.2 hours (95% CI, 1.0–1.3) and for RT-PCR it was 20.1 hours (95% CI, 18.9–40.3) (P < .001). No transmission from antigen-negative/RT-PCR–positive patients was identified.
Although not a replacement for RT-PCR for detection of all SARS-CoV-2 infections, the Sofia SARS antigen FIA has clinical utility for potential initial timely patient placement.
In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process—the Qualitative Transparency Deliberations (QTD)—involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups’ final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency’s promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports—the full versions of which can be found in the Supplementary Materials—offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate—as understood by relevant research communities—to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.1
Rapid whole genome sequencing (rapid WGS) is a powerful diagnostic tool that is becoming increasingly practical for widespread clinical use. However, protocols for its use are challenging to implement. A significant obstacle to clinical adoption is that laboratory certification requires an initial research development phase, which is constrained by regulations from returning results. Regulations preventing return of results have ethical implications in cases which might impact patient outcomes. Here, we describe our experience with the development of a rapid WGS research protocol, that balanced the requirements for laboratory-validated test development with the ethical needs of clinically relevant return of results.
An intermediate-depth (1751 m) ice core was drilled at the South Pole between 2014 and 2016 using the newly designed US Intermediate Depth Drill. The South Pole ice core is the highest-resolution interior East Antarctic ice core record that extends into the glacial period. The methods used at the South Pole to handle and log the drilled ice, the procedures used to safely retrograde the ice back to the National Science Foundation Ice Core Facility (NSF-ICF), and the methods used to process and sample the ice at the NSF-ICF are described. The South Pole ice core exhibited minimal brittle ice, which was likely due to site characteristics and, to a lesser extent, to drill technology and core handling procedures.
As John Dewey observed, and contemporary moral psychology confirms, most of our moral deliberation and judgment operates via deeply rooted habits of perception, discrimination, and valuing over which we have little conscious control. These processes are intuitive, automatic, and seldom subject to reflective change. However, we are not just condemned to our reinforced biases, because we are also creatures whose brains exhibit a measure of plasticity, or what Dewey called “habits of flexibility.” Good moral deliberation, therefore, is intelligent reconstruction of habits, and the formation of new habits that make it possible for us to deal constructively with new moral problems that confront us. Moral deliberation of this sort is a process of dramatic imaginative rehearsal of possibilities for conscientiously transforming our habits, in order to deal with the new problems that arise from changed conditions. Conscientiousness is a flexible habit of reflective, empathic, and critical moral inquiry.
Identifying developmental endophenotypes on the pathway between genetics and behavior is critical to uncovering the mechanisms underlying neurodevelopmental conditions. In this proof-of-principle study, we explored whether early disruptions in visual attention are a unique or shared candidate endophenotype of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). We calculated the duration of the longest look (i.e., peak look) to faces in an array-based eye-tracking task for 335 14-month-old infants with and without first-degree relatives with ASD and/or ADHD. We leveraged parent-report and genotype data available for a proportion of these infants to evaluate the relation of looking behavior to familial (n = 285) and genetic liability (using polygenic scores, n = 185) as well as ASD and ADHD-relevant temperament traits at 2 years of age (shyness and inhibitory control, respectively, n = 272) and ASD and ADHD clinical traits at 6 years of age (n = 94).
Results showed that longer peak looks at the face were associated with elevated polygenic scores for ADHD (β = 0.078, p = .023), but not ASD (β = 0.002, p = .944), and with elevated ADHD traits in mid-childhood (F(1,88) = 6.401, p = .013, $\eta _p^2$=0.068; ASD: F (1,88) = 3.218, p = .076), but not in toddlerhood (ps > 0.2). This pattern of results did not emerge when considering mean peak look duration across face and nonface stimuli. Thus, alterations in attention to faces during spontaneous visual exploration may be more consistent with a developmental endophenotype of ADHD than ASD. Our work shows that dissecting paths to neurodevelopmental conditions requires longitudinal data incorporating polygenic contribution, early neurocognitive function, and clinical phenotypic variation.
The incidence of dementia in Black, Asian and minority ethnic (BAME) groups is increasing in the UK, with concern about underdiagnosis and late presentation.
By reviewing referrals to memory clinics from Leicester City we examined whether the following differed by ethnicity: the proportion with a diagnosis of dementia, type of dementia and severity at presentation.
We examined referrals between 2010 and 2017: all those whose ethnicity was recorded as Black (n = 131) and a random sample of 260 Asian and 259 White British referrals. Severity of dementia was assessed by record review. Odds ratios (ORs) were adjusted for general practice, age, gender and year of referral.
A diagnosis of dementia was recorded in 193 (74.5%) White British, 96 (73.3%) Black and 160 (61.5%) Asian referrals. Compared with Asians, White British had twice the adjusted odds of a dementia diagnosis (OR = 1.99 (1.23–3.22). Of those with dementia, Alzheimer's disease was more common in White British (57.0%) than in Asian (43.8%) and Black referrals (51.0%): adjusted OR White British versus Asian 1.76 (1.11–2.77). Of those with dementia, the proportion with moderate/severe disease was highest in White British (66.8%), compared with 61.9% in Asian and 45.8% in Black groups. The adjusted OR for the White versus Black groups was 2.03 (1.10–3.72), with no significant difference between Asian and White British groups.
Differences in confirmed dementia suggest general practitioners have a lower threshold for referral for possible dementia in some BAME groups. Unlike other centres, we found no evidence of greater severity at presentation in Asian and Black groups.
The study of planning in second language (L2) writing research is heavily influenced by two research domains: (a) early research on cognition in first language (L1) composing processes and (b) second language acquisition (SLA) research. The first research domain has been instrumental in determining the specific systems and processes involved in composing and has led to widely accepted models of L1 writing (Bereiter & Scardamalia, 1987*; Flower & Hayes, 1980*; Hayes, 1996, 2012) as well as a widely accepted model of the interaction between working memory and L1 writing systems (Kellogg, 1996*; Kellogg, Whiteford, Turner, Cahill, & Mertens, 2013). The influence of these early studies is still felt in process approaches to composition instruction commonly implemented in L1 and L2 writing classes. The second research domain—SLA and more specifically task-based language teaching/learning—has come to view planning as a feature of task complexity that can be manipulated to facilitate the production of language that is complex (syntactically and/or lexically), accurate, and/or fluent (Robinson, 2011*; Skehan, 1998*; Skehan & Foster, 2001). This research timeline traces the study of planning in L2 writing in each of these domains by reviewing key L1 and L2 writing research over the last 30-plus years and by highlighting each study's findings. Prior to presenting the timeline, the following sections provide backgrounds in each of the domains noted above and situate planning within those domains.
Fossil fishes are among the rarest in volcanic oceanic islands, their presence providing invaluable data for the understanding of more general (palaeo)biogeographical patterns and processes. Santa Maria Island (Azores Archipelago) is renowned for its palaeontological heritage, with representatives of several phyla, including the Chordata. We report on the fossil fishes, resulting in an increase in the number of Pliocene fishes from the Azores to 11 taxa: seven Chondrichthyes and at least four Actinopterygii. The genus Sparisoma is reported for the first time in the fossil record. The presence of fossil remains of the parrotfish Sparisoma cretense in Last Interglacial outcrops is significant, because it posits a setback for the theory that most of the present-day Azorean marine species colonized the area after the last glacial episode. Our multidisciplinary approach combines palaeontological data with ecological and published genetic data, offering an alternative interpretation. We suggest that most of the Azorean shallow-water subtropical and temperate marine species living in the archipelago during the Last Interglacial were not affected by the decrease in sea surface temperatures during the last glacial episode. We also predict low genetic diversity for fish species presently living in the Azores and ecologically associated with fine sediments, as a result of the remobilization and sediment transport to abyssal depths, during the Last Glacial episode; these are viewed as post-glacial colonizers or as ‘bottleneck’ survivors from the Last Glaciation.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.