BACKGROUND:Early-life exposure to traffic-related air pollution exacerbates childhood asthma, but it is unclear what role it plays in asthma development.
METHODS:The association between exposure to ...primary mobile source pollutants during pregnancy and during infancy and asthma incidence by ages 2 through 6 was examined in the Kaiser Air Pollution and Pediatric Asthma Study, a racially diverse birth cohort of 24,608 children born between 2000 and 2010 and insured by Kaiser Permanente Georgia. We estimated concentrations of mobile source fine particulate matter (PM2.5, µg/m), nitrogen oxides (NOX, ppb), and carbon monoxide (CO, ppm) at the maternal and child residence using a Research LINE source dispersion model for near-surface releases. Asthma was defined using diagnoses and medication dispensings from medical records. We used binomial generalized linear regression to model the impact of exposure continuously and by quintiles on asthma risk.
RESULTS:Controlling for covariates and modeling log-transformed exposure, a 2.7-fold increase in first year of life PM2.5 was associated with an absolute 4.1% (95% confidence interval, 1.6%, 6.6%) increase in risk of asthma by age 5. Quintile analysis showed an increase in risk from the first to second quintile, but similar risk across quintiles 2–5. Risk differences increased with follow-up age. Results were similar for NOX and CO and for exposure during pregnancy and the first year of life owing to high correlation.
CONCLUSIONS:Results provide limited evidence for an association of early-life mobile source air pollution with childhood asthma incidence with a steeper concentration–response relationship observed at lower levels of exposure.
An overview of metal hydride complex protonation is presented along with a discussion of using photoinduced electron transfer reactions to generate very reactive hydride complexes for which the ...protonation kinetics can be examined in detail by transient spectroscopy.
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The paper presents a brief overview of the role of metal hydride complexes in understanding the dynamics of hydrogen generation in homogeneous water reduction catalysts. In addition, the kinetics of protonation of Os(phen)2(CO)(H)+ and the one-electron reduced form of the complex, Os(phen)(phen−)(CO)(H), in acetonitrile solution were examined. The monocationic complex reacted with tosylic acid to form a distinct intermediate species which was found to be a dihydrogen complex; this went on to produce hydrogen and the solvento complex. The one-electron reduced complex was prepared by reduction of the photoexcited monocationic complex with the sacrificial donor BIH. Protonation of the reduced complex by tosylic acid occurred with a rate constant approximately 100 million times larger. The results are used to address possible mechanistic pathways of existing homogeneous catalysts.
In 2014, over 60% of medical schools were incorporating point of care ultrasound (POCUS) into their curriculum. Today, over 6 years later, many more schools are teaching POCUS or are in the planning ...stages of implementing a POCUS curriculum. In 2019, the AAMC reported that 53 schools or over one-third of US medical schools have multi-site campuses for undergraduate medical education. Implementation of a POCUS educational initiative at a multi-site campus presents unique challenges for teaching a uniform curriculum statewide. This article will discuss the POCUS curriculum and implementation process at a large multi-site institution.
We present results from the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) photometric redshift methods investigation. In this investigation, the results from 11 ...participants, each using a different combination of photometric redshift code, template spectral energy distributions (SEDs), and priors, are used to examine the properties of photometric redshifts applied to deep fields with broadband multi-wavelength coverage. The photometry used includes U-band through mid-infrared filters and was derived using the TFIT method. Comparing the results, we find that there is no particular code or set of template SEDs that results in significantly better photometric redshifts compared to others. However, we find that codes producing the lowest scatter and outlier fraction utilize a training sample to optimize photometric redshifts by adding zero-point offsets, template adjusting, or adding extra smoothing errors. These results therefore stress the importance of the training procedure. We find a strong dependence of the photometric redshift accuracy on the signal-to-noise ratio of the photometry. On the other hand, we find a weak dependence of the photometric redshift scatter with redshift and galaxy color. We find that most photometric redshift codes quote redshift errors (e.g., 68% confidence intervals) that are too small compared to that expected from the spectroscopic control sample. We find that all codes show a statistically significant bias in the photometric redshifts. However, the bias is in all cases smaller than the scatter; the latter therefore dominates the errors. Finally, we find that combining results from multiple codes significantly decreases the photometric redshift scatter and outlier fraction. We discuss different ways of combining data to produce accurate photometric redshifts and error estimates.
Abstract
Use of cool-season annual cover crops through grazing has been shown to be a potential tool in extending the grazing season, while still mitigating environmental risks associated with ...warm-season row crop production. Although data describing the effects of grazing on soil health are not novel, effects of grazing length on animal performance and cover crop production are limited. The objective was to determine cattle performance and forage production when grazing a cool-season annual cover-crop. Twelve, 1.2-ha pastures were established in a four species forage mix and randomly allocated to be grazed through either mid-February (FEB), mid-March (MAR), or mid-April (APR) with a non-grazed control (CON). Three tester steers were randomly placed in each paddock and a 1:1 forage allowance was maintained in each paddock using put-and-take steers. Animals were weighed every 30 d for determination of average daily gain (ADG). Forage was harvested bi-weekly and analyzed for forage production, neutral detergent fiber (NDF), and acid detergent fiber (ADF). Fiber fractions were measured using an ANKOM fiber analyzer (ANKOM Tech, Macedon, NY). All data were analyzed using MIXED procedure of SAS version 9.4 (SAS Inst., Cary, NC). Differences in forage mass were detected between CON and FEB (3,694.75 vs. 2,539.68 kg/ha; P < 0.003), CON and MAR (3,694.75 vs. 1,823.45 kg/ha; P < 0.001), and CON and APR (3,694.75 vs. 1,976.23 kg/ha; P < 0.001). Differences in total gain/acre were detected between APR and MAR (212.24 vs. 101.74 kg/ha; P < 0.0001), APR and FEB (212.24 vs 52.65 kg/ha; P < 0.0001), and FEB and MAR (101.74 vs. 52.65 kg/ha; P < 0.003). No differences were detected for tester ADG (1.23 kg/day, P = 0.56), NDF (44.9%, P = 0.99), or ADF (27.2%, P = 0.92) among treatments. These results indicate that cattle removal date effected forage yield and total gain/hectare.
Background
Venous thromboembolism (VTE) in trauma patients carries significant morbidity and mortality. We previously described how titrating enoxaparin dosing by anti-Xa trough levels was associated ...with a lower VTE rate. We combined this strategy with a higher initial enoxaparin dose for a majority of patients and modified the electronic medical record (EMR) to encourage immediate dosing. We sought to determine if this systems-based approach was associated with a decrease in VTE rate.
Study Design
A retrospective review was conducted of all trauma patients on prophylactic enoxaparin at an academic, Level I Trauma Center from 01/2013 to 05/2014 (PRE) and 06/2015 to 02/2018 (POST). The patients in PRE were prescribed enoxaparin 30 mg twice daily without dose adjustments. The patients in POST received 40 mg twice daily unless exclusion criteria applied, with doses titrated to maintain anti-Xa trough levels between 0.1 and 0.2 IU/mL.
Results
There were 478 patients in the PRE and 1306 in the POST. Compared to PRE, POST patients were of similar age and were as likely to present after blunt trauma, although POST patients had lower injury severity scores (10 vs. 9,
p
< 0.01). The overall VTE rate was lower in POST (6.9% vs. 3.6%,
p
< 0.01). The adjusted risk of VTE (AOR 0.61, adjusted
p
= 0.04) was lower in POST and POST was independently protective for VTE (AOR 0.54;
p
= 0.01).
Conclusion
By implementing system changes to improve enoxaparin dosing after trauma, a significant reduction in VTE rate was observed. Wider application of this strategy should be considered.
Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation. Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic ...pathway (HBP). HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis. However, its function during tumorigenesis is poorly understood. One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT). Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway. We demonstrated that HBP was required for suppressing KrasG12D-induced senescence, and targeting HBP significantly delayed KrasG12D lung tumorigenesis. To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins. O-GlcNAcylation suppressed KrasG12D oncogene-induced senescence (OIS) and accelerated lung tumorigenesis. Conversely, loss of O-GlcNAcylation delayed lung tumorigenesis. O-GlcNAcylation of proteins SNAI1 and c-MYC correlated with the EMT-HBP axis and accelerated lung tumorigenesis. Our results demonstrated that O-GlcNAcylation was sufficient and required to accelerate KrasG12D lung tumorigenesis in vivo, which was reinforced by epithelial plasticity programs.
Abstract
Objectives
The risk of attention deficit hyperactivity disorder (ADHD) following multiple exposures to anesthesia has been debated. Our objective was to systematically review the literature ...to examine the association between multiple exposures to general anesthesia before age 5 and subsequent diagnosis of ADHD.
Methods
A systematic search of EMBASE, PubMed, and SCOPUS was performed using key search terms in February 2022. We included studies that: were published after 1980, included only otherwise healthy children who experienced two or more exposures to general anesthetic before age 5, diagnosed ADHD by a medical professional before age 19 years after exposure to general anesthetic, were cross-sectional, case–control, or cohort study, and were published in English. The results (expressed as hazard ratios HR and associated 95% confidence intervals CI) were pooled using meta-analytic techniques. Studies which did not present their results as HR and 95% CI were analyzed separately. GRADE was used to determine the certainty of the findings. PRISMA guidelines were followed at each stage of the review.
Results
Eight studies (196,749 children) were included. Five reported HR and 95% CI and were subsequently pooled for meta-analysis. Multiple exposures to anesthesia were associated with diagnosis of ADHD before the 19th year of life (HR: 1.71; 95% CI: 1.59, 1.84). Two of the three studies not used in the meta-analysis also found an increased risk of ADHD diagnosis following multiple anesthetic exposures.
Conclusions
There was an association between multiple early exposures to general anesthesia and later diagnosis of ADHD.
Ribociclib, a CDK4/6 inhibitor, demonstrates preclinical antitumor activity in combination with taxanes. We evaluated the safety and efficacy of ribociclib plus docetaxel in a phase Ib/II study in ...metastatic castration-resistant prostate cancer (mCRPC).
Patients had chemotherapy-naïve mCRPC with progression on ≥ 1 androgen receptor signaling inhibitor (ARSI). The phase II primary endpoint was 6-month radiographic progression-free survival (rPFS) rate, with an alternative hypothesis of 55% versus 35% historical control. Circulating tumor cells (CTC) were collected at baseline and genomically profiled.
Forty-three patients were enrolled (N = 30 in phase II). Two dose-limiting toxicities were observed (grade 4 neutropenia and febrile neutropenia). The recommended phase II dose (RP2D) and schedule was docetaxel 60 mg/m2 every 21 days plus ribociclib 400 mg/day on days 1-4 and 8-15 with filgrastim on days 5-7. At the RP2D, neutropenia was the most common grade ≥ 3 adverse event (37%); however, no cases of febrile neutropenia were observed. The primary endpoint was met; the 6-month rPFS rate was 65.8% 95% confidence interval (CI): 50.6%-85.5%; P = 0.005 and median rPFS was 8.1 months (95% CI, 6.0-10.0 months). Thirty-two percent of evaluable patients achieved a PSA50 response. Nonamplified MYC in baseline CTCs was associated with longer rPFS (P = 0.052).
The combination of intermittent ribociclib plus every-3-weeks docetaxel demonstrated acceptable toxicity and encouraging efficacy in ARSI-pretreated mCRPC. Genomic profiling of CTCs may enrich for those most likely to derive benefit. Further evaluation in a randomized clinical trial is warranted.
Hierarchical processing requires activity propagating between higher- and lower-order cortical areas. However, functional neuroimaging studies have chiefly quantified fluctuations within regions over ...time rather than propagations occurring over space. Here, we leverage advances in neuroimaging and computer vision to track cortical activity propagations in a large sample of youth (n = 388). We delineate cortical propagations that systematically ascend and descend a cortical hierarchy in all individuals in our developmental cohort, as well as in an independent dataset of densely sampled adults. Further, we demonstrate that top-down, descending hierarchical propagations become more prevalent with greater demands for cognitive control as well as with development in youth. These findings emphasize that hierarchical processing is reflected in the directionality of propagating cortical activity and suggest top-down propagations as a potential mechanism of neurocognitive maturation in youth.
•Cortical activity systematically propagates up and down a cortical hierarchy•Bottom-up and top-down propagations are common in all participants across datasets•Top-down propagations are more common during cognitive demands•Top-down propagations become more prominent with development in youth
Hierarchical processing requires activity propagating between higher and lower-order cortical areas. However, neuroimaging studies have chiefly quantified fluctuations within fixed regions over time rather than propagations over space. We used recent advances in neuroimaging and computer vision to demonstrate that top-down propagations become more prominent during task demands and over neurodevelopment.
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