To understand the influence of a novel infectious disease epidemic on parent general attitudes about childhood vaccines.
We conducted a natural experiment utilizing cross-sectional survey data from ...parents of infants in Washington and Colorado participating in a larger trial that began on September 27, 2019. At enrollment, parents completed the short version of the Parental Attitudes about Childhood Vaccines (PACV-SF), a validated survey scored from 0 to 4, with higher scores representing more negative attitudes. The exposure variable was onset of the SARS-CoV-2 pandemic in the United States, with the before-period defined as September 27, 2019 to February 28, 2020 and the after-period defined as April 1, 2020—December 10, 2020, with the after-period further separated into proximate (April 1, 2020–July 31, 2020) and distant periods (August 1, 2020–December 10, 2020). The outcome variable was parent negative attitudes about childhood vaccines, defined as a score of ≥2 on the PACV-SF. We estimated the probability of the outcome after (vs before) the exposure using log-binomial regression with generalized estimating equations adjusted for demographic confounding variables.
Among 4562 parents, the risk of negative attitudes was lower immediately after (vs before) SARS-CoV-2 onset (adjusted risk ratio aRR = 0.58; 95% confidence interval CI, 0.36, 0.94; P = .027), but by August–December 2020, the average rate of negative attitudes was 35% higher than during April–July 2020 (aRR: 1.35; 95% CI: 1.13, 1.61; P = .0009).
A reduced risk of negative general vaccine attitudes observed immediately after SARS-CoV-2 onset was quickly attenuated.
Bioconversion of lignocellulosic resources offers an economically promising path to renewable energy. Technological challenges to achieving bioconversion include the development of cost-effective ...processes that render the cellulose and hemicellulose components of these resources to fermentable hexoses and pentoses. Natural bioprocessing of the hemicellulose fraction of lignocellulosic biomass requires depolymerization of methylglucuronoxylans. This requires secretion of endoxylanases that release xylooligosaccharides and aldouronates. Physiological, biochemical, and genetic studies with selected bacteria support a process in which a cell-anchored multimodular GH10 endoxylanase catalyzes release of the hydrolysis products, aldotetrauronate, xylotriose, and xylobiose, which are directly assimilated and metabolized. Gene clusters encoding intracellular enzymes, including α-glucuronidase, endoxylanase, β-xylosidase, ABC transporter proteins, and transcriptional regulators, are coordinately responsive to substrate induction or repression. The rapid rates of glucuronoxylan utilization and microbial growth, along with the absence of detectable products of depolymerization in the medium, indicate that assimilation and depolymerization are coupled processes. Genomic comparisons provide evidence that such systems occur in xylanolytic species in several genera, including Clostridium, Geobacillus, Paenibacillus, and Thermotoga. These systems offer promise, either in their native configurations or through gene transfer to other organisms, to develop biocatalysts for efficient production of fuels and chemicals from the hemicellulose fractions of lignocellulosic resources.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Assessing deglutitive esophagogastric junction (EGJ) relaxation is an essential focus of clinical manometry. Our aim was to apply automated algorithmic analyses to high-resolution manometry (HRM) ...studies to ascertain the optimal method for discriminating normal from abnormal deglutitive EGJ relaxation. All 473 subjects (73 controls) were studied with a 36-channel solid-state HRM assembly during water swallows. Patients were classified as: 1) achalasia, 2) postfundoplication, 3) nonachalasia with normal deglutitive EGJ relaxation, or 4) functional obstruction (preserved peristalsis with incomplete EGJ relaxation). Automated computer programs assessed the adequacy of EGJ relaxation by using progressively complex analysis routines to compensate for esophageal shortening, crural diaphragm contraction, and catheter movement, all potential confounders. The single-sensor method of assessing EGJ relaxation had a sensitivity of only 52% for detecting achalasia. Of the automated HRM analysis paradigms tested, the 4-s integrated relaxation pressure using a cutoff of 15 mmHg performed optimally with 98% sensitivity and 96% specificity in the detection of achalasia. We also identified a heterogeneous group of 26 patients with functional EGJ obstruction attributed to variant achalasia and other diverse pathology. Although further clinical experience will ultimately judge, it is our expectation that applying rigorous methodology such as described herein to the analysis of HRM studies will improve the consistency in the interpretation of clinical manometry and prove useful in guiding clinical management.
As the amount of data from genome wide association studies grows dramatically, many interesting scientific questions require imputation to combine or expand datasets. However, there are two ...situations for which imputation has been problematic: (1) polymorphisms with low minor allele frequency (MAF), and (2) datasets where subjects are genotyped on different platforms. Traditional measures of imputation cannot effectively address these problems.
We introduce a new statistic, the imputation quality score (IQS). In order to differentiate between well-imputed and poorly-imputed single nucleotide polymorphisms (SNPs), IQS adjusts the concordance between imputed and genotyped SNPs for chance. We first evaluated IQS in relation to minor allele frequency. Using a sample of subjects genotyped on the Illumina 1 M array, we extracted those SNPs that were also on the Illumina 550 K array and imputed them to the full set of the 1 M SNPs. As expected, the average IQS value drops dramatically with a decrease in minor allele frequency, indicating that IQS appropriately adjusts for minor allele frequency. We then evaluated whether IQS can filter poorly-imputed SNPs in situations where cases and controls are genotyped on different platforms. Randomly dividing the data into "cases" and "controls", we extracted the Illumina 550 K SNPs from the cases and imputed the remaining Illumina 1 M SNPs. The initial Q-Q plot for the test of association between cases and controls was grossly distorted (lambda = 1.15) and had 4016 false positives, reflecting imputation error. After filtering out SNPs with IQS<0.9, the Q-Q plot was acceptable and there were no longer false positives. We then evaluated the robustness of IQS computed independently on the two halves of the data. In both European Americans and African Americans the correlation was >0.99 demonstrating that a database of IQS values from common imputations could be used as an effective filter to combine data genotyped on different platforms.
IQS effectively differentiates well-imputed and poorly-imputed SNPs. It is particularly useful for SNPs with low minor allele frequency and when datasets are genotyped on different platforms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Early liver transplantation (LT) for alcoholic hepatitis (AH) is lifesaving but concerns regarding return to harmful alcohol use remain. We sought to identify distinct patterns of alcohol use post-LT ...to inform pre-LT candidate selection and post-LT addiction care.
Detailed post-LT alcohol use data was gathered retrospectively from consecutive patients with severe AH at 11 ACCELERATE-AH sites from 2006-2018. Latent class analysis identified longitudinal patterns of alcohol use post-LT. Logistic and Cox regression evaluated associations between patterns of alcohol use with pre-LT variables and post-LT survival. A microsimulation model estimated the effect of selection criteria on overall outcomes.
Of 153 LT recipients, 1-, 3-, and 5-year survival were 95%, 88% and 82%. Of 146 LT recipients surviving to home discharge, 4 distinct longitudinal patterns of post-LT alcohol use were identified: Pattern 1 abstinent(n = 103; 71%), pattern 2 late/non-heavy(n = 9; 6.2%), pattern 3 early/non-heavy(n = 22; 15%), pattern 4 early/heavy(n = 12; 8.2%). One-year survival was similar among the 4 patterns (100%), but patients with early post-LT alcohol use had lower 5-year survival (62% and 53%) compared to abstinent and late/non-heavy patterns (95% and 100%). Early alcohol use patterns were associated with younger age, multiple prior rehabilitation attempts, and overt encephalopathy. In simulation models, the pattern of post-LT alcohol use changed the average life-expectancy after early LT for AH.
A significant majority of LT recipients for AH maintain longer-term abstinence, but there are distinct patterns of alcohol use associated with higher risk of 3- and 5-year mortality. Pre-LT characteristics are associated with post-LT alcohol use patterns and may inform candidate selection and post-LT addiction care.
In Neh 1–6 werden Berichte über Feinde Nehemias, die vom Fortschritt beim Bau der Stadtmauer Jerusalems »hören«, oft als alte narrative Trennlinien innerhalb des Textes verstanden. Die Ähnlichkeiten ...in der Form verdeutlichen die einheitliche Absicht der Berichte, die Abweichungen jedoch scheinen die Arbeit mehrerer Hände zu verraten. Dieser Aufsatz untersucht die Komposition dieser Verse anhand form- und redaktionkritischer Methoden und schlägt eine relative Chronologie vor, wobei die Verwendung oder Auslassung von Volksbezeichnungen für »Sanballat der Horonit«, »Tobiah der Ammonit« und »Geshem der Araber« hervorgehoben werden.
A procedure is presented for analyzing postconstruction deformation of seepage barriers due to changes in the pore pressure regime after seepage barrier construction. The procedure uses the changes ...in pore pressures calculated by finite-element seepage analyses to calculate changes in buoyancy and seepage forces that occur as a result of seepage barrier construction. When the buoyancy and seepage forces are applied to a finite-element soil-structure interaction model, the result is an effective-stress analysis that rigorously models seepage effects. This paper discusses application of the procedure to five dams to calculate postconstruction deformation and stresses in seepage barriers. The results of the analyses indicate that deformation due to pore pressure regime changes is a likely mechanism causing cracking in rigid seepage barriers.
Celotno besedilo
Dostopno za:
DOBA, FGGLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
High-fat diet (HFD) consumption in female rodents causes impaired estrous cyclicity, fewer pups per litter, and dysregulation of key ovulatory genes suggesting that HFD-induced subfertility may be ...due to ovulatory dysfunction. To test this hypothesis female mice were fed chow or HFD for 10 weeks at which point ovulation and ovarian gene expression of endothelin-2 (Edn2), a gene critical for ovulation, were assessed. After 10 weeks of HFD, both mice that remained lean and those that became obese had fewer ovulated oocytes than chow controls (P = 0.041, P = 0.0030, respectively). In chow controls, Edn2 was expressed as expected with basal levels during diestrus and proestrus, increased 11.6-fold during estrus, and decreased to basal levels during metestrus. In HFD mice, Edn2 was dysregulated across the entire estrous cycle as were other Edn2 system components (endothelin converting enzyme 1 (Ece-1), and the endothelin receptors (Ednra, Ednrb)). Interestingly, we found dysregulation of key ovarian steroidogenic genes after HFD. We also found that estradiol treatment in prepubertal mice increased Edn2 expression in the ovary (P = 0.030), suggesting that impaired steroidogenesis may be involved in the HFD-induced dysregulation of ovarian Edn2. In conclusion, HFD leads to ovulatory dysfunction regardless of the development of obesity, which appears to be mediated through dysregulation of ovarian Edn2 expression.
Methamphetamine use disorder (MUD) has become a global problem due to the highly addictive nature of methamphetamine. Earlier research have demonstrated that PROK2 functions as a compensatory and ...protective response against neurotoxic stress by stimulating astrocyte reactivity. The aim of our study was to evaluate the correlation between the
gene and both MUD risk susceptibility and craving scale in the Chinese Han population.
A total of 5,282 participants (1,796 MUD patients and 3,486 controls) were recruited. Seven tag SNPs of the
gene were chosen and genotyped in the samples. Genetic association analyses were performed to capture the significant SNPs. To investigate the relationship between PROK2 levels and craving scores with the associated-SNP genotypes, we conducted a linear model.
SNP rs75433452 was significantly linked with MUD risk (
-value = 1.54 × 10
), with the A allele being positively correlated with an increased risk of MUD. Moreover, the average serum level of PROK2 decreased when more copies of the A allele were presented in both MUD patients (
-value = 4.57 × 10
) and controls (
-value = 1.13 × 10
). Furthermore, the genotypes of SNP rs75433452 were strongly correlated with the craving scores in MUD patients (
-value = 4.05 × 10
).
Our study identified a significant association signal of the
gene with MUD risk susceptibility and methamphetamine craving scores in the Chinese Han population, providing potential valuable insights into the underlying mechanisms of METH dependence.
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