Background
The objectives of this study were to identify developmental trajectories of wheezing using data‐driven methodology, and to examine whether trajectory membership differentially impacts the ...effectiveness of primary preventive efforts that target modifiable asthma risk factors.
Methods
Secondary analysis of the Canadian Asthma Primary Prevention Study (CAPPS), a multifaceted prenatal intervention among children at high risk of asthma, followed from birth to 15 years. Wheezing trajectories were identified by latent class growth analysis. Predictors, intervention effects, and asthma diagnoses were examined between and within trajectory groups.
Results
Among 525 children, 3 wheeze trajectory groups were identified: Low‐Progressive (365, 69%), Early‐Transient (52, 10%), and Early‐Persistent (108, 21%). The study intervention was associated with lower odds of Early‐Transient and Early‐Persistent wheezing (P < .01). Other predictors of wheeze trajectories included, maternal asthma, maternal education, city of residence, breastfeeding, household pets, infant sex and atopy at 12 months. The odds of an asthma diagnosis were three‐fold to six‐fold higher in the Early‐Persistent vs Low‐Progressive group at all follow‐up assessments (P = .03), whereas Early‐Transient wheezing (limited to the first year) was not associated with asthma. In the Early‐Persistent group, the odds of wheezing were lower among intervention than control children (adjusted odds ratio: 0.67; 95% CI: 0.48; 0.93) at 7 years.
Conclusions
Using data‐driven methodology, children can be classified into clinically meaningful wheeze trajectory groups that appear to be programmed by modifiable and non‐modifiable factors, and are useful for predicting asthma risk. Early‐life interventions can alter some wheeze trajectories (ie, Early‐Persistent) in infancy and reduce wheezing prevalence in mid‐childhood.
Mounting evidence suggests that endorsement of psychological continuity and the afterlife increases with age. This developmental change raises questions about the cognitive biases, social ...representations, and cultural input that may support afterlife beliefs. To what extent is there similarity versus diversity across cultures in how people reason about what happens after death? The objective of this study was to compare beliefs about the continuation of biological and psychological functions after death in Tanna, Vanuatu (a Melanesian archipelago), and the United States (Austin, Texas). Children, adolescents, and adults were primed with a story that contained either natural (non‐theistic) or supernatural (theistic) cues. Participants were then asked whether or not different biological and psychological processes continue to function after death. We predicted that across cultures individuals would be more likely to endorse the continuation of psychological processes over biological processes (dualism) and that a theistic prime would increase continuation responses regarding both types of process. Results largely supported predictions; U.S. participants provided more continuation responses for psychological than biological processes following both the theistic and non‐theistic primes. Participants in Vanuatu, however, provided more continuation responses for biological than psychological processes following the theistic prime. The data provide evidence for both cultural similarity and variability in afterlife beliefs and demonstrate that individuals use both natural and supernatural explanations to interpret the same events.
In humans and other animals, the internal organs are positioned asymmetrically in the body cavity, and disruption of this body plan can be fatal in humans. The mechanisms by which internal asymmetry ...are established are presently the subject of intense study; however, the functional significance of internal asymmetry (outside the brain) is largely unexplored. Is internal asymmetry functionally significant, or merely an expedient way of packing organs into a cavity?
Like humans, Drosophila shows internal asymmetry, with the gut thrown into stereotyped folds. There is also renal asymmetry, with the rightmost pair of renal (Malpighian) tubules always ramifying anteriorly, and the leftmost pair always sitting posteriorly in the body cavity. Accordingly, transcriptomes of anterior-directed (right-side) and posterior-directed (left-side) Malpighian (renal) tubules were compared in both adult male and female Drosophila. Although genes encoding the basic functions of the tubules (transport, signalling) were uniformly expressed, some functions (like innate immunity) showed positional or gender differences in emphasis; others, like calcium handling or the generation of potentially toxic ammonia, were reserved for just the right-side or left-side tubules, respectively. These findings correlated with the distinct locations of each tubule pair within the body cavity. Well known developmental genes (like dorsocross, dachshund and doublesex) showed continuing, patterned expression in adult tubules, implying that somatic tissues maintain both left-right and gender identities throughout life. Gender asymmetry was also noted, both in defence and in male-specific expression of receptors for neuropeptide F and sex-peptide: NPF elevated calcium only in male tubules.
Accordingly, the physical asymmetry of the tubules in the body cavity is directly adaptive. Now that the detailed machinery underlying internal asymmetry is starting to be delineated, our work invites the investigation, not just of tissues in isolation, but in the context of their unique physical locations and milieux.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Examining variation in reasoning about sustainability between diverse populations provides unique insight into how group norms surrounding resource conservation develop. Cultural institutions, such ...as religious organizations and formal schools, can mobilize communities to solve collective challenges associated with resource depletion. This study examined conservation beliefs in a Western industrialized (Austin, Texas, USA) and a non‐Western, subsistence agricultural community (Tanna, Vanuatu) among children, adolescents, and adults (N = 171; n = 58 7–12‐year‐olds, n = 53 13–17‐year‐olds, and n = 60 18–68‐year‐olds). Participants endorsed or rejected four types of justifications for engaging in land and animal conservation: sustainability, moral, religious, or permissible. In both populations, participants endorsed sustainability justifications most frequently. Religious justifications increased with age in Tanna and decreased with age in Austin. Tannese participants were also more likely to endorse multiple justifications for conservation than Austin participants. Data across all justification types show a main effect of age in both communities; endorsement of conservation decreased with age in Austin, but increased with age in Tanna. Across age groups, participants were more likely to endorse the conservation of animals than land in Austin, yet equally as likely to endorse the conservation of land and animals in Tanna. Overall, these results reveal similarities and differences in the beliefs that support the conservation of natural resources across populations.
Preliminary cold spray trials have been performed using gas-atomized Al-Cr-Mn-Co-Zr alloy powder, which exhibits a nanocomposite structure with an Al matrix and 35vol% of icosahedral quasicrystalline ...dispersoids. Consolidated material produced from this powder has been shown to exhibit a remarkable combination of mechanical properties and pitting corrosion resistance. The purpose of this research was to determine whether this nanocomposite material could form the basis of a hard, corrosion-resistant coating. The powder was screened and classified to a size range of 15–34μm. Coatings of 180μm in thickness were deposited using a He carrier gas with a gun temperature and pressure of 430°C and 3.5MPa, respectively. The coatings were hard (301±25HV), dense (<1% porosity), and adherent (no interfacial cracks or debonds). X-ray diffraction and electron microscopy data show that the nanocomposite powder microstructure is retained in the coating with no decomposition of the metastable quasicrystalline dispersoids to equilibrium crystalline phases. However, there were significant changes in the grain structure of the Al, both in the coating and in the underlying substrate. The grains are refined and equiaxed in the substrate, indicating that dynamic recovery/recrystallization occurs. Severely distorted flattened Al grains arise in the coating close (<1μm) to the interface with the substrate, consistent with bonding via an adiabatic shear instability. The coating shows no pitting in 6-week salt fog exposures and seems to afford some protection to small exposed areas on adjacent bare substrate. These observations suggest that this material has very good potential to form the basis for a practical, hard, corrosion-resistant, quasicrystal-reinforced, nano-composite, cold-spray coating.
•Cold spray has been used to produce coatings from Al-Cr-Mn-Co-Zr alloy powder.•Gas-atomized powder exhibits a nanocomposite FCC Al+quasicrystal microstructure.•Phase mixture is retained in the coating with no crystallization/transformation.•Coatings are hard (301HV), dense (<1% pores), and adherent (no interfacial cracks).•Coatings also exhibit excellent resistance to salt fog pitting corrosion.
To present the first 22-months experience of transitioning to an ultrasound-first pathway for suspected midgut malrotation.
An "ultrasound-first" imaging pathway was initiated in October 2021. ...Twenty-two-months later, a search was undertaken of all <1-year-old patients with "bilious", "malrotation," or "volvulus" as the imaging indication. Reports and images from upper gastrointestinal fluoroscopy (UGI) and ultrasound were reviewed, and diagnoses and outcomes were documented.
The search yielded 101 eligible cases between October 2021 and July 2023. Of the patients, 63/101 (62%) had both ultrasound and UGI: 47/63 (75%) ultrasound first, 16/63 (25%) UGI first. Thirty-one per cent (31/101) had ultrasound only and 7/70 (10%) UGI only. The pathway diagnosed 7/8 (88%) infants with midgut malrotation with or without volvulus and one infant who had an inconclusive ultrasound examination with a suspected an internal hernia and who was found to have malrotation volvulus at surgery. Twenty-one infants who had confidently normal ultrasound examinations and who also had UGI all had a normal duodenojejunal flexure position. Ultrasound detected alternative pathology in eight children. Duodenal visualisation improved with time: 6/15 (40%) in the first 6 months to 23/34 (68%) after the first year.
The transition to ultrasound as the first diagnostic test for midgut malrotation can be done safely and effectively in a UK centre, which previously relied solely on UGI.
Wild bees provide vital pollination services for many native and agricultural plant species, yet the landscape conditions needed to support wild bee populations are not well understood or ...appreciated. We assessed the influence of landscape composition on bee abundance and species richness in apple (Malm spp.) orchards of northeastern Wisconsin during the spring flowering period. A diverse community of bee species occurs in these apple orchards, dominated by wild bees in the families Andrenidae and Halictidae and the honey bee, Apis mellifera L. Proportion of forest area in the surrounding landscape was a significant positive predictor of wild bee abundance in orchards, with strongest effects at a GIS (Geographic Information Systems) buffer distance of 1,000 m or greater. Forest area also was positively associated with species richness, showing strongest effects at a buffer distance of 2,000 m. Nonagricultural developed land (homes, lawns, etcetera) was significantly negatively associated with species richness at buffer distances >750 m and wild bee abundance in bowl traps at all distances. Other landscape variables statistically associated with species richness or abundance of wild bees included proportion area of pasture (positive) and proportion area of roads (negative). Forest area was not associated with honey bee abundance at any buffer distance. These results provide clear evidence that the landscape surrounding apple orchards, especially the proportion of forest area, affects richness and abundance of wild bees during the spring flowering period and should be a part of sustainable land management strategies in agro-ecosystems of northeastern Wisconsin and other apple growing regions.
Mechanisms driving acute food allergic reactions have not been fully characterized. We profile the dynamic transcriptome of acute peanut allergic reactions using serial peripheral blood samples ...obtained from 19 children before, during, and after randomized, double-blind, placebo-controlled oral challenges to peanut. We identify genes with changes in expression triggered by peanut, but not placebo, during acute peanut allergic reactions. Network analysis reveals that these genes comprise coexpression networks for acute-phase response and pro-inflammatory processes. Key driver analysis identifies six genes (LTB4R, PADI4, IL1R2, PPP1R3D, KLHL2, and ECHDC3) predicted to causally modulate the state of coregulated networks in response to peanut. Leukocyte deconvolution analysis identifies changes in neutrophil, naive CD4
T cell, and macrophage populations during peanut challenge. Analyses in 21 additional peanut allergic subjects replicate major findings. These results highlight key genes, biological processes, and cell types that can be targeted for mechanistic study and therapeutic targeting of peanut allergy.
The acquisition of genes by horizontal transfer can impart entirely new biological functions and provide an important route to major evolutionary innovation. Here we have used ancient gene ...reconstruction and functional assays to investigate the impact of a single horizontally transferred nucleotide transporter into the common ancestor of the Microsporidia, a major radiation of intracellular parasites of animals and humans. We show that this transporter provided early microsporidians with the ability to steal host ATP and to become energy parasites. Gene duplication enabled the diversification of nucleotide transporter function to transport new substrates, including GTP and NAD
, and to evolve the proton-energized net import of nucleotides for nucleic acid biosynthesis, growth and replication. These innovations have allowed the loss of pathways for mitochondrial and cytosolic energy generation and nucleotide biosynthesis that are otherwise essential for free-living eukaryotes, resulting in the highly unusual and reduced cells and genomes of contemporary Microsporidia.
The increased need for macromolecular therapeutics, such as peptides, proteins and nucleotides, to reach intracellular targets necessitates more effective delivery vectors and a higher level of ...understanding of their mechanism of action. Cell penetrating peptides (CPPs) can transport a range of macromolecules into cells, either through direct plasma membrane translocation or endocytosis. All known endocytic pathways involve cell-cortex remodelling, a process shown to be regulated by reorganisation of the actin cytoskeleton. Here using flow cytometry, confocal microscopy and a variety of actin inhibitors we identify how actin disorganisation in different cell types differentially influences the cellular entry of three probes: the CPP octaarginine - Alexa488 conjugate (R8-Alexa488), octaarginine conjugated Enhanced Green Fluorescent Protein (EGFP-R8), and the fluid phase probe dextran. Disrupting actin organisation in A431 skin epithelial cells dramatically increases the uptake of EGFP-R8 and dextran, and contrasts strongly to inhibitory effects observed with transferrin and R8 attached to the fluorophore Alexa488. This demonstrates that uptake of the same CPP can occur via different endocytic processes depending on the conjugated fluorescent entity. Overall this study highlights how cargo influences cell uptake of this peptide and that the actin cytoskeleton may act as a gateway or barrier to endocytosis of drug delivery vectors.
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