Reply to Braillon: Vitamin C to Pregnant Smokers and Infant Airway Function: Missing the Forest for the Trees?
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ABSTRACT:
SUBMITTER: McEvoy CT
PROVIDER: S-EPMC6680303 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC6680308 | biostudies-literature
Project description:Vitamin C (500 mg·day-1) supplementation for pregnant smokers has been reported to increase newborn pulmonary function and infant forced expiratory flows (FEFs) at 3 months of age. Its effect on airway function through 12 months of age has not been reported. To assess whether vitamin C supplementation to pregnant smokers is associated with a sustained increased airway function in their infants through 12 months of age. This is a prespecified secondary outcome of a randomised, double-blind, placebo-controlled trial that randomised 251 pregnant smokers between 13 and 23 weeks of gestation: 125 to 500 mg·day-1 vitamin C and 126 to placebo. Smoking cessation counselling was provided. FEFs performed at 3 and 12 months of age were analysed by repeated measures analysis of covariance. FEFs were performed in 222 infants at 3 months and 202 infants at 12 months of age. The infants allocated to vitamin C had significantly increased FEFs over the first year of life compared to those allocated to placebo. The overall increased flows were: 40.2 mL·sec-1 for FEF75 (adjusted 95% CI for difference 6.6 to 73.8; p=0.025); 58.3 mL·sec-1 for FEF50 (95% CI 10.9 to 105.8; p=0.0081); and 55.1 mL·sec-1 for FEF25-75 (95% CI, 9.7 to 100.5; p=0.013). In offspring of pregnant smokers randomised to vitamin C versus placebo, vitamin C during pregnancy was associated with a small but significantly increased airway function at 3 and 12 months of age, suggesting a potential shift to a higher airway function trajectory curve. Continued follow-up is underway.
| S-EPMC8029653 | biostudies-literature
Project description:Rationale: We reported a randomized trial demonstrating daily supplemental vitamin C to pregnant smokers significantly improved newborn pulmonary function tests. The current study tests these results in a new cohort using infant pulmonary function tests. Objectives: To determine if infants of pregnant smokers randomized to daily supplemental vitamin C would have improved forced expiratory flows (FEFs) at 3 months of age compared with those randomized to placebo, and to investigate the association of the α5 nicotinic acetylcholine receptor. Methods: A randomized, double-blind, placebo-controlled trial was conducted at three centers. Two hundred fifty-one pregnant smokers were randomized at 13-23 weeks of gestation: 125 randomized to vitamin C (500 mg/d) and 126 to placebo. Measurements and Main Results: The primary outcome was FEF75 at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF50 and FEF25-75 obtained from the same expiratory curves were prespecified secondary outcomes. The infants of pregnant smokers randomized to vitamin C (n = 113) had the following FEFs at 3 months of age compared with those randomized to placebo (n = 109) as measured by FEF75 (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval [CI] for difference, -3.33 to 35.64; P = 0.10), FEF50 (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30; P = 0.02), and FEF25-75 (387.4 vs. 365.8 ml/s; adjusted 95% CI for difference, 0.92-55.34; P = 0.04). Infant FEFs seemed to be negatively associated with the maternal risk alleles for the α5 nicotinic acetylcholine receptor (rs16969968). Conclusions: Although the primary outcome of FEF75 was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF50 and FEF25-75 were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF50 and FEF25-75) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT01723696).
| S-EPMC6515875 | biostudies-literature
Project description: Not available
| S-EPMC6515870 | biostudies-literature
Project description:BackgroundIn the pursuit of a better understanding of biodiversity, evolutionary biologists rely on the study of phylogenetic relationships to illustrate the course of evolution. The relationships among natural organisms, depicted in the shape of phylogenetic trees, not only help to understand evolutionary history but also have a wide range of additional applications in science. One of the most challenging problems that arise when building phylogenetic trees is the presence of missing biological data. More specifically, the possibility of inferring wrong phylogenetic trees increases proportionally to the amount of missing values in the input data. Although there are methods proposed to deal with this issue, their applicability and accuracy is often restricted by different constraints.ResultsWe propose a framework, called PhyloMissForest, to impute missing entries in phylogenetic distance matrices and infer accurate evolutionary relationships. PhyloMissForest is built upon a random forest structure that infers the missing entries of the input data, based on the known parts of it. PhyloMissForest contributes with a robust and configurable framework that incorporates multiple search strategies and machine learning, complemented by phylogenetic techniques, to provide a more accurate inference of lost phylogenetic distances. We evaluate our framework by examining three real-world datasets, two DNA-based sequence alignments and one containing amino acid data, and two additional instances with simulated DNA data. Moreover, we follow a design of experiments methodology to define the hyperparameter values of our algorithm, which is a concise method, preferable in comparison to the well-known exhaustive parameters search. By varying the percentages of missing data from 5% to 60%, we generally outperform the state-of-the-art alternative imputation techniques in the tests conducted on real DNA data. In addition, significant improvements in execution time are observed for the amino acid instance. The results observed on simulated data also denote the attainment of improved imputations when dealing with large percentages of missing data.ConclusionsBy merging multiple search strategies, machine learning, and phylogenetic techniques, PhyloMissForest provides a highly customizable and robust framework for phylogenetic missing data imputation, with significant topological accuracy and effective speedups over the state of the art.
| S-EPMC9116704 | biostudies-literature
Project description:The cardiorenal syndrome relates to the detrimental interplay between the vascular system and the kidney. The uremic milieu induced by reduced kidney function alters the phenotype of vascular smooth muscle cells (VSMC) and promotes vascular calcification, a condition which is strongly linked to cardiovascular morbidity and mortality. Biological mechanisms involved include generation of reactive oxygen species, inflammation and accelerated senescence. A better understanding of the vasotoxic effects of uremic retention molecules may reveal novel avenues to reduce vascular calcification in CKD. The present review aims to present a state of the art on the role of uremic toxins in pathogenesis of vascular calcification. Evidence, so far, is fragmentary and limited with only a few uremic toxins being investigated, often by a single group of investigators. Experimental heterogeneity furthermore hampers comparison. There is a clear need for a concerted action harmonizing and standardizing experimental protocols and combining efforts of basic and clinical researchers to solve the complex puzzle of uremic vascular calcification.
| S-EPMC7599869 | biostudies-literature
Project description:One of the central goals of ecology is to determine the mechanisms that enable coexistence among species. Evidence is accruing that conspecific negative density dependence (CNDD), the process by which plant seedlings are unable to survive in the area surrounding adults of their same species, is a major contributor to tree species coexistence. However, for CNDD to maintain community-level diversity, three conditions must be met. First, CNDD must maintain diversity for the majority of the woody plant community (rather than merely specific groups). Second, the pattern of repelled recruitment must increase in with plant size. Third, CNDD should extend to the majority of plant life history strategies. These three conditions are rarely tested simultaneously. In this study, we simultaneously test all three conditions in a woody plant community in a North American temperate forest. We examined whether understory and canopy woody species across height categories and dispersal syndromes were overdispersed-a spatial pattern indicative of CNDD-using spatial point pattern analysis across life history stages and strategies. We found that there was a strong signal of overdispersal at the community level. Across the whole community, larger individuals were more overdispersed than smaller individuals. The overdispersion of large individuals, however, was driven by canopy trees. By contrast, understory woody species were not overdispersed as adults. This finding indicates that the focus on trees for the vast majority of CNDD studies may have biased the perception of the prevalence of CNDD as a dominant mechanism that maintains community-level diversity when, according to our data, CNDD may be restricted largely to trees.
| S-EPMC8282035 | biostudies-literature
Project description: Not available
| S-EPMC8017947 | biostudies-literature
Project description:BackgroundOncologists often refer to forest plots to determine which patient subgroups may be more likely to benefit from a therapy tested in a randomized clinical trial (RCT). We sought to empirically determine the information content of subgroup comparisons from forest plots of RCTs.MethodsWe assessed all forest plots from RCTs of therapeutic interventions presented orally at the American Society of Clinical Oncology Annual Meetings in 2020 and 2021. Subgroups were considered as showing evidence of treatment effect heterogeneity in forest plots when their confidence intervals (CIs) did not overlap with the vertical line corresponding to the main effect observed in the overall RCT cohort. Subgroups were considered as showing evidence of treatment effect homogeneity in forest plots when their CIs did not meaningfully differ, within 80-125% equivalence range, with the values compatible with the main effect. All other subgroups were considered as inconclusive.ResultsA total of 99 forest plots were presented, and only 24.2% contained one or more subgroups suggestive of treatment effect heterogeneity. A total of 81 forest plots provided enough information to evaluate treatment effect heterogeneity and homogeneity. These 81 forest plots represented a total of 1344 individual subgroups, of which 57.2% were inconclusive, 41.1% showed evidence of treatment effect homogeneity, and 1.6% yielded evidence suggestive of treatment effect heterogeneity.ConclusionThe majority of subgroup comparisons were inconclusive in this empirical analysis of forest plots used in oncology RCTs. Different strategies should be considered to improve the estimation and representation of subgroup-specific effects.
| S-EPMC9168942 | biostudies-literature
Project description:ObjectiveTo determine the implications of supplemental vitamin C for pregnant tobacco smokers and its effects on the prevalence of pediatric asthma, asthma-related mortality, and associated costs.Study designA decision-analytic model built via TreeAge compared the outcome of asthma in a theoretical annual cohort of 480,000 children born to pregnant smokers through 18 years of life. Vitamin C supplementation (500 mg/day) with a standard prenatal vitamin was compared to a prenatal vitamin (60 mg/day). Model inputs were derived from the literature. Deterministic and probabilistic sensitivity analyses assessed the impact of assumptions.ResultAdditional vitamin C during pregnancy would prevent 1637 cases of asthma at the age of 18 per birth cohort of pregnant smokers. Vitamin C would reduce asthma-related childhood deaths and save $31,420,800 in societal costs over 18 years per birth cohort.ConclusionVitamin C supplementation in pregnant smokers is a safe and inexpensive intervention that may reduce the economic burden of pediatric asthma.
| S-EPMC6414472 | biostudies-literature