COVID-19 has had a calamitous effect on the global community. Despite intense study, the immunologic response to the infection is only partially understood. In addition to older age and ethnicity, ...patients with comorbidities including obesity, diabetes, hypertension, coronary artery disease, malignancy, renal, and pulmonary disease may experience severe outcomes. Some patients with primary immunodeficiency (PID) and secondary immunodeficiency also appear to be at increased risk from COVID-19. In addition to vulnerability to SARS-CoV-2, patients with PIDs often have chronic pulmonary disease and may not respond to vaccines, which exacerbates their long-term risk. Patients with common variable immunodeficiency disorders, the most frequent symptomatic PID in adults and children, have a spectrum of B- and T-cell defects. It may be possible to stratify their risk for severe COVID-19 based on age, ethnicity, the severity of the T-cell defect, and the presence of other comorbidities. Patients with common variable immunodeficiency disorders and other immunodeficiencies are at risk for Chronic COVID-19, a dangerous stalemate between a suboptimal immune response and SARS-CoV-2. Intra-host viral evolution could result in the rapid emergence of vaccine-resistant mutants and variants of high consequence; it is a public health emergency. Vaccination and prevention of Chronic COVID-19 in immunodeficient patients is therefore of the utmost priority. Having a reliable diagnostic assay for T-cell immunity to SARS-CoV-2 is critical for evaluating responses to vaccines in these patients. New treatments for SARS-CoV-2 such as NZACE2-Pātari are likely to be particularly beneficial for immunodeficient patients, especially those who fail to mount a robust T-cell response to COVID-19 vaccines.
Purpose: This was an investigation of the dimensionality of oral and written language to test the hypothesis that a two-factor model with sound/word and sentence/discourse language levels would best ...fit language and literacy data for a population-based sample in the school-age years. Method: A stratified secondary data set of 1,500 participants was drawn randomly from a larger nationally representative U.S. data set (N = 1,853) gathered during standardization of the Test of Integrated Language and Literacy Skills. A sample of 254 students with prior diagnoses of language and literacy disorders (LLD) was drawn from the full data set. Confirmatory factor analysis was used to compare the hypothesized two-factor model with other theoretically possible models. Results: The hypothesized two-factor language-levels model had an acceptable-to-good fit to the full data set, as did the three-factor model, with verbal memory added. High interfactor correlation between verbal memory and sentence/ discourse constructs, as well as a preference for parsimony, led to the acceptance of the two-factor model as best. This language-levels model had a good fit to the data at ages 8-11 years, and an excellent fit at ages 12-18 years, but only a poor fit for ages 6-7 years (yet still better than other two-factor or unitary models). It had a reasonable fit for students with LLD, although the three-factor model fit their data slightly better. Conclusions: Oral and written language abilities during the school-age years are best explained by a two-factor model with sound/word and sentence/ discourse language levels and memory as a contributing factor. Implications for identifying and treating language and literacy disorders as multidimensional rather than categorical are discussed.
The emergence of COVID-19 virus has led to a pandemic with staggering morbidity and mortality. There is evidence showing that pre-existing conditions and environmental factors are associated with ...worse COVID-19 outcomes. Among these conditions, altitude is of particular interest. Altitude has been shown to influence the morbidity and mortality of multiple chronic pathologies such as cardiovascular disease, chronic obstructive pulmonary disease and lung cancer. COVID-19 fatality rate has been associated with as altitude as well, but findings are disputed. Therefore, we revisit this assessment with a comprehensive analysis of the relationship between COVID-19 fatality rates and altitude for the Mountain region of the United States while considering the effect of additional comorbidities and sociodemographic factors. A Generalized Additive Model (GAM) approach using one year of county data adjusted by population density was performed to evaluate associations within states and for the whole region. Our analysis revealed a consistent effect where COVID-19 case-fatality rate is decreased with higher altitude, even when controlling for pre-existing conditions and certain demographic variables. In summary, the work presented provides evidence that suggests that the protective effects of high altitude are likely to be influenced by physiologic factors but demographic trends that are associated with life at high altitude must also be considered.
Osteoarthritis (OA) is a multifactorial disease with etiological heterogeneity. The objective of this study was to classify OA subgroups by generating metabolomic phenotypes from human synovial ...fluid.
Post mortem synovial fluids (n = 75) were analyzed by high performance-liquid chromatography mass spectrometry (LC-MS) to measure changes in the global metabolome. Comparisons of healthy (grade 0), early OA (grades I-II), and late OA (grades III-IV) donor populations were considered to reveal phenotypes throughout disease progression.
Global metabolomic profiles in synovial fluid were distinct between healthy, early OA, and late OA donors. Pathways differentially activated among these groups included structural deterioration, glycerophospholipid metabolism, inflammation, central energy metabolism, oxidative stress, and vitamin metabolism. Within disease states (early and late OA), subgroups of donors revealed distinct phenotypes. Synovial fluid metabolomic phenotypes exhibited increased inflammation (early and late OA), oxidative stress (late OA), or structural deterioration (early and late OA) in the synovial fluid.
These results revealed distinct metabolic phenotypes in human synovial fluid, provide insight into pathogenesis, represent novel biomarkers, and can move toward developing personalized interventions for subgroups of OA patients.
Abstract
We present a survey of how the spectral features of black hole X-ray binary systems depend on spin, accretion rate, viewing angle, and Fe abundance when predicted on the basis of ...first-principles physical calculations. The power-law component hardens with increasing spin. The thermal component strengthens with increasing accretion rate. The Compton bump is enhanced by higher accretion rate and lower spin. The Fe K
α
equivalent width grows sublinearly with Fe abundance. Strikingly, the K
α
profile is more sensitive to accretion rate than to spin because its radial surface brightness profile is relatively flat, and higher accretion rate extends the production region to smaller radii. The overall radiative efficiency is at least 30%–100% greater than as predicted by the Novikov–Thorne model.
The Chicago Defender ceased its print publication in 2019 (but remains online) and the Johnson Publishing Company—publishers of Jet and (until 2016) Ebony—was liquidated in the same year. Longtime ...Black residents of Chicago found the habits and manners of these "'down home' people" to shatter their sense of "middle-class respectability," and the resulting conversations in the Defender reveal the extent to which readers and the newspaper sought to police the behavior of new arrivals (84, 79). The placement of works like "Karintha" in the international journal Broom's Mayan issue shows how the networks of Cane involve "not only an expanded geography" but also an opportunity to think about the networks of Wai Chee Dimock's "deep time," which occasions a discussion of Toomer's invocation of the "Dixie Pike" as a network that runs across both time and space as it charts the history of enslavement (147).
The Daily Mile is a physical activity programme made popular by a school in Stirling, Scotland. It is promoted by the Scottish Government and is growing in popularity nationally and internationally. ...The aim is that each day, during class time, pupils run or walk outside for 15 min (~1 mile) at a self-selected pace. It is anecdotally reported to have a number of physiological benefits including increased physical activity, reduced sedentary behaviour, increased fitness and improved body composition. This study aimed to investigate these reports.
We conducted a quasi-experimental repeated measures pilot study in two primary schools in the Stirling Council area: one school with, and one without, intention to introduce the Daily Mile. Pupils at the control school followed their usual curriculum. Of the 504 children attending the schools, 391 children in primary classes 1-7 (age 4-12 years) at the baseline assessment took part. The follow-up assessment was in the same academic year. Outcomes were accelerometer-assessed average daily moderate to vigorous intensity physical activity (MVPA) and average daily sedentary behaviour, 20-m shuttle run fitness test performance and adiposity assessed by the sum of skinfolds at four sites. Valid data at both time points were collected for 118, 118, 357 and 327 children, respectively, for each outcome.
After correction for age and gender, significant improvements were observed in the intervention school relative to the control school for MVPA, sedentary time, fitness and body composition. For MVPA, a relative increase of 9.1 min per day (95% confidence interval or 95%CI 5.1-13.2 min, standardised mean difference SMD = 0.407, p = 0.027) was observed. For sedentary time, there was a relative decrease of 18.2 min per day (10.7-25.7 min, SMD = 0.437, p = 0.017). For the shuttle run, there was a relative increase of 39.1 m (21.9-56.3, SMD = 0.236, p = 0.037). For the skinfolds, there was a relative decrease of 1.4 mm (0.8-2.0 mm, SMD = 0.246, p = 0.036). Similar results were obtained when a correction for socioeconomic groupings was included.
The findings show that in primary school children, the Daily Mile intervention is effective at increasing levels of MVPA, reducing sedentary time, increasing physical fitness and improving body composition. These findings have relevance for teachers, policymakers, public health practitioners, and health researchers.
is a major cause of community-acquired pneumonia. There are limited data in the United States on the molecular epidemiological characteristics of
We collected 446
-positive specimens from 9 states ...between August 2012 and October 2018. Culture, antimicrobial susceptibility testing, P1 subtyping, and multilocus VNTR (variable-number tandem repeats) analysis (MLVA) were performed to characterize the isolates. Macrolide-resistant
(MRMp) was detected in 37 (8.3%) specimens. P1 subtype 2 (P1-2) was the predominant P1 subtype (59.8%). P1 subtype distribution did not change significantly chronologically or geographically. The macrolide resistance rate in P1 subtype 1 (P1-1) samples was significantly higher than that in P1-2 (12.9% versus 5.5%). Six P1-2 variants were identified, including two novel types, and variant 2c was predominant (64.6%). P1-2 variants were distributed significantly differently among geographic regions. Classical P1-2 was more frequent in lower respiratory tract specimens and had longer
trinucleotide repeats. Classical P1-2 was most common in MRMp (35.7%), while variant 2c was most common in macrolide-susceptible
(67.5%). Fifteen MLVA types were identified; 3-5-6-2 (41.7%), 4-5-7-2 (35.3%), and 3-6-6-2 (16.6%) were the major types, and four MLVA clusters were delineated. The distribution of MLVA types varied significantly over time and geographic location. The predominant MLVA type switched from 4-5-7-2 to 3-5-6-2 in 2015. MLVA type was associated with P1 subtypes and P1-2 variant types but not with macrolide resistance. To investigate the
genotype shift and its impact on clinical presentations, additional surveillance programs targeting more diverse populations and prolonged sampling times are required.
We present a formulation for a local cooling function to be employed in the diffuse, hot corona region of 3D GRMHD simulations of accreting black holes. This new cooling function calculates the ...cooling rate due to inverse Compton scattering by considering the relevant microphysics in each cell in the corona and approximating the radiation energy density and Compton temperature thereby integrating over the thermal seed photon flux from the disk surface. The method either assumes the ion and electron temperatures are equal (1T) or calculates them separately (2T) using an instantaneous equilibrium approach predicated on the actual relevant rate equations (Coulomb and Compton). The method is shown to be consistent with a more detailed ray-tracing calculation where the bulk of the cooling occurs, but is substantially less costly to perform. As an example, we apply these methods to a harm3d simulation of a 10M , non-spinning black hole, accreting at nominally 1% the Eddington value. This new approach leads to radiative efficiency values 65% above Novikov-Thorne, with a larger fraction of total cooling in the corona as compared to simulations performed using the original target-temperature cooling function. Time-averaged post-processing reveals that the continuum spectral observations predicted from these simulations are qualitatively similar to actual X-ray binary data, especially so for the 1T approach, which yields a harder power-law component (Γ = 2.25) compared to the 2T version (Γ = 2.53).
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