Objective
Dysbiosis of the infant gut microbiota may have long‐term health consequences. This study aimed to determine the impact of maternal intrapartum antibiotic prophylaxis (IAP) on infant gut ...microbiota, and to explore whether breastfeeding modifies these effects.
Design
Prospective pregnancy cohort of Canadian infants born in 2010–2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Study.
Setting
General community.
Sample
Representative sub‐sample of 198 healthy term infants from the CHILD Study.
Methods
Maternal IAP exposures and birth method were documented from hospital records and breastfeeding was reported by mothers. Infant gut microbiota was characterised by Illumina 16S rRNA sequencing of faecal samples at 3 and 12 months.
Main outcome measures
Infant gut microbiota profiles.
Results
In this cohort, 21% of mothers received IAP for Group B Streptococcus prophylaxis or pre‐labour rupture of membranes; another 23% received IAP for elective or emergency caesarean section (CS). Infant gut microbiota community structures at 3 months differed significantly with all IAP exposures, and differences persisted to 12 months for infants delivered by emergency CS. Taxon‐specific composition also differed, with the genera Bacteroides and Parabacteroides under‐represented, and Enterococcus and Clostridium over‐represented at 3 months following maternal IAP. Microbiota differences were especially evident following IAP with emergency CS, with some changes (increased Clostridiales and decreased Bacteroidaceae) persisting to 12 months, particularly among non‐breastfed infants.
Conclusions
Intrapartum antibiotics in caesarean and vaginal delivery are associated with infant gut microbiota dysbiosis, and breastfeeding modifies some of these effects. Further research is warranted to explore the health consequences of these associations.
Tweetable
Maternal #antibiotics during childbirth alter the infant gut #microbiome.
Tweetable
Maternal #antibiotics during childbirth alter the infant gut #microbiome.
We report the first measurement of coherent elastic neutrino-nucleus scattering (CEvNS) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two ...independent analyses prefer CEvNS over the background-only null hypothesis with greater than 3σ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2±0.7)×10^{-39} cm^{2}-consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the CEvNS process and provides improved constraints on nonstandard neutrino interactions.
Summary
Background
The gut microbiota is established during infancy and plays a fundamental role in shaping host immunity. Colonization patterns may influence the development of atopic disease, but ...existing evidence is limited and conflicting.
Objective
To explore associations of infant gut microbiota and food sensitization.
Methods
Food sensitization at 1 year was determined by skin prick testing in 166 infants from the population‐based Canadian Healthy Infant Longitudinal Development (CHILD) study. Faecal samples were collected at 3 and 12 months, and microbiota was characterized by Illumina 16S rRNA sequencing.
Results
Twelve infants (7.2%) were sensitized to ≥ 1 common food allergen at 1 year. Enterobacteriaceae were overrepresented and Bacteroidaceae were underrepresented in the gut microbiota of food‐sensitized infants at 3 months and 1 year, whereas lower microbiota richness was evident only at 3 months. Each quartile increase in richness at 3 months was associated with a 55% reduction in risk for food sensitization by 1 year (adjusted odds ratio 0.45, 95% confidence interval 0.23–0.87). Independently, each quartile increase in Enterobacteriaceae/Bacteroidaceae ratio was associated with a twofold increase in risk (2.02, 1.07–3.80). These associations were upheld in a sensitivity analysis among infants who were vaginally delivered, exclusively breastfed and unexposed to antibiotics. At 1 year, the Enterobacteriaceae/Bacteroidaceae ratio remained elevated among sensitized infants, who also tended to have decreased abundance of Ruminococcaceae.
Conclusions and Clinical Relevance
Low gut microbiota richness and an elevated Enterobacteriaceae/Bacteroidaceae ratio in early infancy are associated with subsequent food sensitization, suggesting that early gut colonization may contribute to the development of atopic disease, including food allergy.
White Americans who participate in the Black Lives Matter movement, men who attended the Women’s March, and people from the Global North who work to reduce poverty in the Global South—advantaged ...group members (sometimes referred to as allies) often engage in action for disadvantaged groups. Tensions can arise, however, over the inclusion of advantaged group members in these movements, which we argue can partly be explained by their motivations to participate. We propose that advantaged group members can be motivated to participate in these movements (a) to improve the status of the disadvantaged group, (b) on the condition that the status of their own group is maintained, (c) to meet their own personal needs, and (d) because this behavior aligns with their moral beliefs. We identify potential antecedents and behavioral outcomes associated with these motivations before describing the theoretical contribution our article makes to the psychological literature.
Two once‐daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non‐valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly ...impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re‐estimate values of the models' parameters for the current AF population. An oral one‐compartment model with first‐order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase‐induced clotting time exhibited a near‐linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post‐dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum‐effect (Emax) relationship. Renal function (on prothrombin time; prothrombinase‐induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF.
Intrinsic variations of the projected density profiles of clusters of galaxies at fixed mass are a source of uncertainty for cluster weak lensing. We present a semi-analytical model to account for ...this effect, based on a combination of variations in halo concentration, ellipticity and orientation, and the presence of correlated haloes. We calibrate the parameters of our model at the 10 per cent level to match the empirical cosmic variance of cluster profiles at
$M_{200m}\approx 10^{14}\ldots 10^{15}\,h^{-1}{\,\mathrm{M}_{\odot }}$
, z = 0.25…0.5 in a cosmological simulation. We show that weak lensing measurements of clusters significantly underestimate mass uncertainties if intrinsic profile variations are ignored, and that our model can be used to provide correct mass likelihoods. Effects on the achievable accuracy of weak lensing cluster mass measurements are particularly strong for the most massive clusters and deep observations (with ≈20 per cent uncertainty from cosmic variance alone at
$M_{200m}\approx 10^{15}\,h^{-1}{\,\mathrm{M}_{\odot }}$
and z = 0.25), but significant also under typical ground-based conditions. We show that neglecting intrinsic profile variations leads to biases in the mass-observable relation constrained with weak lensing, both for intrinsic scatter and overall scale (the latter at the 15 per cent level). These biases are in excess of the statistical errors of upcoming surveys and can be avoided if the cosmic variance of cluster profiles is accounted for.
In order to study the galaxy population of galaxy clusters with photometric data, one must be able to accurately discriminate between cluster members and non-members. The redMaPPer cluster finding ...algorithm treats this problem probabilistically, focusing exclusively on the red galaxy population. Here, we utilize Sloan Digital Sky Survey (SDSS) and Galaxy And Mass Assembly spectroscopic membership rates to validate the redMaPPer membership probability estimates for clusters with z ∈ 0.1, 0.3. We find small – but correctable – biases, sourced by three different systematics. The first two were expected a priori, namely blue cluster galaxies and correlated structure along the line of sight. The third systematic is new: the redMaPPer template fitting exhibits a non-trivial dependence on photometric noise, which biases the original redMaPPer probabilities when utilizing noisy data. After correcting for these effects, we find exquisite agreement (≈1 per cent) between the photometric probability estimates and the spectroscopic membership rates, demonstrating that we can robustly recover cluster membership estimates from photometric data alone. As a byproduct of our analysis we find that on average unavoidable projection effects from correlated structure contribute ≈6 per cent of the richness of a redMaPPer galaxy cluster. This work also marks the second public release of the SDSS redMaPPer cluster catalogue.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder that affects carriers, principally males, of premutation alleles (55–200 CGG repeats) of the fragile X ...mental retardation 1 (FMR1) gene. Clinical features of FXTAS include progressive intention tremor and gait ataxia, accompanied by characteristic white matter abnormalities on MRI. The neuropathological hallmark of FXTAS is an intranuclear inclusion, present in both neurons and astrocytes throughout the CNS. Prior to the current work, the nature of the associations between inclusion loads and molecular measures (e.g. CGG repeat) was not defined. Post-mortem brain and spinal cord tissue has been examined for gross and microscopic pathology in a series of 11 FXTAS cases (males, age 67–87 years at the time of death). Quantitative counts of inclusion numbers were performed in various brain regions in both neurons and astrocytes. Inclusion counts were compared with specific molecular (CGG repeat, FMR1 mRNA level) and clinical (age of onset, age of death) parameters. In the current series, the three most prominent neuropathological characteristics are (i) significant cerebral and cerebellar white matter disease, (ii) associated astrocytic pathology with dramatically enlarged inclusion-bearing astrocytes prominent in cerebral white matter and (iii) the presence of intranuclear inclusions in both brain and spinal cord. The pattern of white matter pathology is distinct from that associated with hypertensive vascular disease and other diseases of white matter. Spongiosis was present in the middle cerebellar peduncles in seven of the eight cases in which those tissues were available for study. There is inclusion formation in cranial nerve nucleus XII and in autonomic neurons of the spinal cord. The most striking finding is the highly significant association between the number of CGG repeats and the numbers of intranuclear inclusions in both neurons and astrocytes, indicating that the CGG repeat is a powerful predictor of neurological involvement in males, both clinically (age of death) and neuropathologically (number of inclusions).
Uterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct ...a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant (P < 5 × 10
) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.
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