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Childhood acute arterial ischemic stroke (AIS) is diagnosed at a median of 23 hours post-symptom onset, delaying treatment. Pediatric stroke pathways can expedite diagnosis. Our goal was to understand the similarities and differences between Canadian pediatric stroke protocols with the aim of optimizing AIS management.
We contacted neurologists at all 16 Canadian pediatric hospitals regarding AIS management. Established protocols were analyzed for similarities and differences in eight domains.
Response rate was 100%. Seven (44%) centers have an established AIS protocol and two (13%) have a protocol under development. Seven centers do not have a protocol; two redirect patients to adult neurology, five rely on a case-by-case approach for management. Analysis of the seven protocols revealed differences in: 1) IV-tPA dosage: age-dependent 0.75–0.9 mg/kg (N = 1) versus age-independent 0.9 mg/kg (N = 6), with maximum doses of 75 mg (N = 1) or 90 mg (N = 6); 2) IV-tPA lower age cut-off: 2 years (N = 5) versus 3 or 10 years (each N = 1); 3) IV-tPA exclusion criteria: PedNIHSS score <4 (N = 3), <5 (N = 1), <6 (N = 3); 4) first choice of pre-treatment neuroimaging: computed tomography (CT) (N = 3), magnetic resonance imaging (MRI) (N = 2) or either (N = 2); 5) intra-arterial tPA use (N = 3) and; 6) mechanical thrombectomy timeframe: <6 hour (N = 3), <24 hour (N = 2), unspecified (N = 2).
Although 44% of Canadian pediatric hospitals have established AIS management pathways, several differences remain among centers. Some criteria (dosage, imaging) reflect adult AIS literature. Canadian expert consensus regarding IV-tPA and endovascular treatment should be established to standardize and implement AIS protocols across Canada.
Recent drilling successes on Rutford Ice Stream in West Antarctica demonstrate the viability of hot water drilling subglacial access holes to depths >2000 m. Having techniques to access deep subglacial environments reliably paves the way for subglacial lake exploration beneath the thick central West Antarctic Ice Sheet. An ideal candidate lake, overlain by ~2650 m of ice, identified by Centro de Estudios Científicos (CECs), Chile, has led to collaboration with British Antarctic Survey to access Subglacial Lake CECs (SLCECs). To conform with the Scientific Committee on Antarctic Research code of conduct, which provides a guide to responsible scientific exploration and stewardship of these pristine systems, any access drilling must minimise all aspects of contamination and disturbance of the subglacial environment. To meet these challenges, along with thicker ice and 2000 m elevation, pumping and water treatment systems developed for the Subglacial Lake Ellsworth project, together with new diesel generators, additional water heating and longer drill hose, are currently being integrated with the BEAMISH hot water drill. A dedicated test season near SLCECs will commission the new clean hot water drill, with testing and validation of all clean operating procedures. A subsequent season will then access SLCECs cleanly.
Head impact exposure (HIE) in youth football is a public health concern. The objective of this study was to determine if one season of HIE in youth football was related to cognitive changes.
Over 200 participants (ages 9–13) wore instrumented helmets for practices and games to measure the amount of HIE sustained over one season. Pre- and post-season neuropsychological tests were completed. Test score changes were calculated adjusting for practice effects and regression to the mean and used as the dependent variables. Regression models were calculated with HIE variables predicting neuropsychological test score changes.
For the full sample, a small effect was found with season average rotational values predicting changes in list-learning such that HIE was related to negative score change: standardized beta (β) = -.147, t(205) = -2.12, and p = .035. When analyzed by age clusters (9–10, 11–13) and adding participant weight to models, the R2 values increased. Splitting groups by weight (median split), found heavier members of the 9–10 cohort with significantly greater change than lighter members. Additionaly, significantly more participants had clinically meaningful negative changes: X2 = 10.343, p = .001.
These findings suggest that in the 9–10 age cluster, the average seasonal level of HIE had inverse, negative relationships with cognitive change over one season that was not found in the older group. The mediation effects of age and weight have not been explored previously and appear to contribute to the effects of HIE on cognition in youth football players.
Turbulent fluxes make a substantial and growing contribution to the energy balance of ice surfaces globally, but are poorly constrained owing to challenges in estimating the aerodynamic roughness length (z0). Here, we used structure from motion (SfM) photogrammetry and terrestrial laser scanning (TLS) surveys to make plot-scale 2-D and 3-D microtopographic estimations of z0 and upscale these to map z0 across an ablating mountain glacier. At plot scales, we found spatial variability in z0 estimates of over two orders of magnitude with unpredictable z0 trajectories, even when classified into ice surface types. TLS-derived surface roughness exhibited strong relationships with plot-scale SfM z0 estimates. At the glacier scale, a consistent increase in z0 of ~0.1 mm d−1 was observed. Space-for-time substitution based on time since surface ice was exposed by snow melt confirmed this gradual increase in z0 over 60 d. These measurements permit us to propose a scale-dependent temporal z0 evolution model where unpredictable variability at the plot scale gives way to more predictable changes of z0 at the glacier scale. This model provides a critical step towards deriving spatially and temporally distributed representations of z0 that are currently lacking in the parameterisation of distributed glacier surface energy balance models.
OBJECTIVES/GOALS: Epilepsy with myoclonic-atonic seizures (EMAS) is a childhood onset epilepsy disorder characterized by seizures with sudden loss of posture, or drop seizures. Our objective was to use short-read genome sequencing in 40 EMAS trios to better understand variants contributing to the development of EMAS. METHODS/STUDY POPULATION: Eligibility for the cohort included a potential diagnosis of EMAS by child neurology faculty at Children’s Hospital Colorado. Exclusion criteria included lack of drop seizures upon chart review or structural abnormality on MRI. Some individuals had prior genetic testing and priority for genome sequencing was given to individuals without clear genetic diagnosis based on previous testing. We analyzed single nucleotide variants (SNVs), small insertions and deletions (INDELs), and larger structural variants (SVs) from trio genomes and determined those that were likely contributory based on standardized American College of Medical Genetics (ACMG) criteria. RESULTS/ANTICIPATED RESULTS: Our initial analysis focused on variants in coding regions of known epilepsy-associated genes. We identified pathogenic or likely pathogenic variants in 6 different individuals involving 6 unique genes. Of these, 5 are de novo SNVs or INDELs and 1 is a de novo SV. One of these involve a de novo heterozygous variant in an X-linked gene (ARHGEF9) in a female individual. We hypothesize the skewed X-inactivation may result in primarily expression of the pathogenic variant. We anticipate identifying additional candidate variants in coding regions of genes previously not associated with EMAS or pediatric epilepsies as well as in noncoding regions of the genome. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite the genetic heterogeneity of EMAS, our initial analysis identified de novo pathogenic or likely pathogenic variants in 15% (6/40) of our cohort. As the cost continues to decline, short read genome sequencing represents a promising diagnostic tool for EMAS and other pediatric onset epilepsy syndromes. CONFLICT OF INTEREST DESCRIPTION: The authors have no conflicts of interest to disclose. SD has consulted for Upsher-Smith, Biomarin and Neurogene on an unrelated subject matter. GLC holds a research collaborative grant with Stoke therapeutics on unrelated subject matter.
Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
Surgical site infections (SSIs) are among the most common healthcare-associated infections in low- and middle-income countries. To encourage establishment of actionable and standardized SSI surveillance in these countries, we propose simplified surveillance case definitions. Here, we use NHSN reports to explore concordance of these simplified definitions to NHSN as ‘reference standard.’
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Palmer amaranth is the most common and troublesome weed in North Carolina sweetpotato. Field studies were conducted in Clinton, NC, in 2016 and 2017 to determine the critical timing of Palmer amaranth removal in ‘Covington’ sweetpotato. Palmer amaranth was grown with sweetpotato from transplanting to 2, 3, 4, 5, 6, 7, 8, and 9 wk after transplanting (WAP) and maintained weed-free for the remainder of the season. Palmer amaranth height and shoot dry biomass increased as Palmer amaranth removal was delayed. Season-long competition by Palmer amaranth interference reduced marketable yields by 85% and 95% in 2016 and 2017, respectively. Sweetpotato yield loss displayed a strong inverse linear relationship with Palmer amaranth height. A 0.6% and 0.4% decrease in yield was observed for every centimeter of Palmer amaranth growth in 2016 and 2017, respectively. The critical timing for Palmer amaranth removal, based on 5% loss of marketable yield, was determined by fitting a log-logistic model to the relative yield data and was determined to be 2 WAP. These results show that Palmer amaranth is highly competitive with sweetpotato and should be managed as early as possible in the season. The requirement of an early critical timing of weed removal to prevent yield loss emphasizes the importance of early-season scouting and Palmer amaranth removal in sweetpotato fields. Any delay in removal can result in substantial yield reductions and fewer premium quality roots.
We report on the successful demonstration of a 150 J nanosecond pulsed cryogenic gas cooled, diode-pumped multi-slab Yb:YAG laser operating at 1 Hz. To the best of our knowledge, this is the highest energy ever recorded for a diode-pumped laser system.
Depression and chronic inflammatory medical conditions have been linked to impaired cognitive ability. However despite frequent comorbidity, their combined association with cognitive ability has rarely been examined.
This study examined associations between self-reported depression and chronic inflammatory diseases and their interaction with cognitive performance in 456,748 participants of the UK Biobank, adjusting for sociodemographic and lifestyle factors. Numbers with available data ranged from 94,899 to 453,208 depending on the cognitive test.
Self-reported depression was associated with poorer performance compared to controls in several cognitive tests (fully adjusted models, reaction time: B = 6.08, 95% CI = 5.09, 7.07; pairs matching: incidence rate ratio = 1.02, 95% CI = 1.02, 1.03; Trail Making Test B: B = 1.37, 95% CI = 0.88, 1.87; Digit Symbol Substitution Test (DSST): B = −0.35, 95% CI = −0.44, −0.27). Self-reported chronic inflammatory conditions were associated with slower reaction time (B = 3.79, 95% CI = 2.81, 4.78) and lower DSST scores (B = −0.21, 95% CI = −0.30, −0.13). No interaction effects were observed.
In this large, population-based study we provide evidence of lower cognitive performance in both depression and a comprehensive category of chronic inflammatory conditions. Results are consistent with additive effects of both types of disorder on cognitive ability. Clinicians should be aware of such effects, particularly as cognitive impairment is linked to poorer disease outcomes and quality of life.
Propagating inhomogeneous electromagnetic waves called surface plasmon polaritons (SPPs) can be excited by free-space beams on corrugated conducting surfaces at resonance angles determined by corrugation period, permittivity, and optical frequency. SPPs are coupled to and co-propagate with surface charge displacements. Complete electrical isolation of individual conducting corrugations prevents the charge displacement necessary to sustain an SPP, such that excitation resonances of traveling SPPs are absent. However, SPPs can be excited via electric induction if a smooth conducting surface exists below and nearby the isolated conducting corrugations. The dependence of SPP excitation resonances on that separation is experimentally investigated here at long-wave infrared wavelengths. We find that excitation resonances for traveling SPPs broaden and disappear as the dielectric’s physical thickness is increased beyond ~1% of the free-space wavelength. The resonance line width increases with refractive index and optical thickness of the dielectric.
Sulfur-bearing monazite-(Ce) occurs in silicified carbonatite at Eureka, Namibia, forming rims up to ~0.5 mm thick on earlier-formed monazite-(Ce) megacrysts. We present X-ray photoelectron spectroscopy data demonstrating that sulfur is accommodated predominantly in monazite-(Ce) as sulfate, via a clino-anhydrite-type coupled substitution mechanism. Minor sulfide and sulfite peaks in the X-ray photoelectron spectra, however, also indicate that more complex substitution mechanisms incorporating S2– and S4+ are possible. Incorporation of S6+ through clino-anhydrite-type substitution results in an excess of M2+ cations, which previous workers have suggested is accommodated by auxiliary substitution of OH– for O2–. However, Raman data show no indication of OH–, and instead we suggest charge imbalance is accommodated through F– substituting for O2–. The accommodation of S in the monazite-(Ce) results in considerable structural distortion that may account for relatively high contents of ions with radii beyond those normally found in monazite-(Ce), such as the heavy rare earth elements, Mo, Zr and V. In contrast to S-bearing monazite-(Ce) in other carbonatites, S-bearing monazite-(Ce) at Eureka formed via a dissolution–precipitation mechanism during prolonged weathering, with S derived from an aeolian source. While large S-bearing monazite-(Ce) grains are likely to be rare in the geological record, formation of secondary S-bearing monazite-(Ce) in these conditions may be a feasible mineral for dating palaeo-weathering horizons.
In patients with β-lactam allergies, administration of non–β-lactam surgical prophylaxis is associated with increased risk of infection. Although many patients self-report β-lactam allergies, most are unconfirmed or mislabeled. A quality improvement process, utilizing a structured β-lactam allergy tool, was implemented to improve the utilization of preferred β-lactam surgical prophylaxis.
Cognitive impairment is strongly linked with persistent disability in people with mood disorders, but the factors that explain cognitive impairment in this population are unclear.
To estimate the total effect of (a) bipolar disorder and (b) major depression on cognitive function, and the magnitude of the effect that is explained by potentially modifiable intermediate factors.
Cross-sectional study using baseline data from the UK Biobank cohort. Participants were categorised as having bipolar disorder (n = 2709), major depression (n = 50 975) or no mood disorder (n = 102 931 and n = 105 284). The outcomes were computerised tests of reasoning, reaction time and memory. The potential mediators were cardiometabolic disease and psychotropic medication. Analyses were informed by graphical methods and controlled for confounding using regression, propensity score-based methods and G-computation.
Group differences of small magnitude were found on a visuospatial memory test. Z-score differences for the bipolar disorder group were in the range −0.23 to −0.17 (95% CI −0.39 to −0.03) across different estimation methods, and for the major depression group they were approximately −0.07 (95% CI −0.10 to −0.03). One-quarter of the effect was mediated via psychotropic medication in the bipolar disorder group (−0.05; 95% CI −0.09 to −0.01). No evidence was found for mediation via cardiometabolic disease.
In a large community-based sample in middle to early old age, bipolar disorder and depression were associated with lower visuospatial memory performance, in part potentially due to psychotropic medication use. Mood disorders and their treatments will have increasing importance for population cognitive health as the proportion of older adults continues to grow.
Declaration of interest
I.J.D. is a UK Biobank participant. J.P.P. is a member of the UK Biobank Steering Committee.
We have derived absolute proper motions of stars in the Galactic bulge region combining the VVV InfraRed Astrometric Catalogue (VIRAC) and Gaia. We use the proper motions to study the kinematic structure of the bulge both integrated along the line-of-sight and in magnitude intervals using red clump stars as standard candles. In parallel we compare to a made-to-measure barred dynamical model, folding in the VIRAC selection function, to understand and interpret the structures that we observe. The barred dynamical model, which contains a boxy/peanut bulge, and has a pattern speed of 37.5 kms−1 kpc−1, is able to reproduce all structures impressively well.
Breastfeeding may reduce obesity risk, but this association could be confounded by breastfeeding families’ characteristics. We investigated if body composition differs at birth among infants who were either exclusively breast- or formula-fed. We hypothesized the two groups would differ in body composition, even at birth, prior to their post-natal feeding experience. Healthy primiparous carrying singleton pregnancy were recruited at 15 weeks’ gestation. PEA POD® measured body composition within 72 hours of delivery and infant feeding was prospectively captured. Out of the 1,152 infants recruited, 117 (10.2%) and 239 (20.7%) went on to be either exclusively breast- or formula-fed, respectively. Breastfed infants were heavier at birth, but their percentage fat mass (FM) was lower than that of exclusively formula-fed infants (covariate adjusted β = −1.91 percentage points of FM; 95% CI −2.82 to −1.01). Differences in intra-uterine exposures, irrespective of early diet, may partly explain an infant’s obesity risk.
Icequakes at or near the bed of a glacier have the potential to allow us to investigate the interaction of ice with the underlying till or bedrock. Understanding this interaction is important for studying basal sliding of glaciers and ice streams, a critical process in ice dynamics models used to constrain future sea-level rise projections. However, seismic observations on glaciers can be dominated by seismic energy from surface crevassing. We present a method of automatically detecting basal icequakes and discriminating them from surface crevassing, comparing this method to a commonly used spectrum-based method of detecting icequakes. We use data from Skeidararjökull, an outlet glacier of the Vatnajökull Ice Cap, South-East Iceland, to demonstrate that our method outperforms the commonly used spectrum-based method. Our method detects a higher number of basal icequakes, has a lower rate of incorrectly identifying crevassing as basal icequakes and detects an additional, spatially independent basal icequake cluster. We also show independently that the icequakes do not originate from near the glacier surface. We conclude that the method described here is more effective than currently implemented methods for detecting and discriminating basal icequakes from surface crevassing.
Field and greenhouse studies were conducted in 2016 and 2017 to determine sweetpotato tolerance to herbicides applied to plant propagation beds. Herbicide treatments included PRE application of flumioxazin (107 g ai ha−1), S-metolachlor (800 g ai ha−1), fomesafen (280 g ai ha−1), flumioxazin plus S-metolachlor (107 g ai ha−1 + 800 g ai ha−1), fomesafen plus S-metolachlor (280 g ai ha−1 + 800 g ai ha−1), fluridone (1,120 or 2,240 g ai ha−1), fluridone plus S-metolachlor (1,120 g ai ha−1 + 800 g ai ha−1), napropamide (1,120 g ai ha−1), clomazone (420 g ai ha−1), linuron (560 g ai ha−1), linuron plus S-metolachlor (560 g ai ha−1 + 800 g ai ha−1), bicyclopyrone (38 or 49.7 g ai ha−1), pyroxasulfone (149 g ai ha−1), pre-mix of flumioxazin plus pyroxasulfone (81.8 g ai ha−1 + 104.2 g ai ha−1), or metribuzin (294 g ai ha−1). Paraquat plus non-ionic surfactant (280 g ai ha−1 + 0.25% v/v) POST was also included. After plants in the propagation bed were cut and sweetpotato slip number, length, and weight had been determined, the slips were then transplanted to containers and placed either in the greenhouse or on an outdoor pad to determine any effects from the herbicide treatments on initial sweetpotato growth. Sweetpotato slip number, length, and/or weight were affected by flumioxazin with or without S-metolachlor, S-metolachlor with or without fomesafen, clomazone, and all fluridone treatments. In the greenhouse studies, initial root growth of plants after transplanting was inhibited by fluridone (1,120 g ai ha−1) and fluridone plus S-metolachlor. However, by 5 wk after transplanting few differences were observed between treatments. Fomesafen, linuron with or without S-metolachlor, bicyclopyrone (38 or 49.7 g ai ha−1), pyroxasulfone with or without flumioxazin, metribuzin, and paraquat did not cause injury to sweetpotato slips in any of the studies conducted.