Developmental pathways to autism: a review of prospective studies of infants at risk

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders characterized by impairments in social interaction and communication, and the presence of restrictive and repetitive behaviors. Symptoms of ASD likely emerge from a complex interaction between pre-existing neurodevelopmental vulnerabilities and the child's environment, modified by compensatory skills and protective factors. Prospective studies of infants at high familial risk for ASD (who have an older sibling with a diagnosis) are beginning to characterize these developmental pathways to the emergence of clinical symptoms. Here, we review the range of behavioral and neurocognitive markers for later ASD that have been identified in high-risk infants in the first years of life. We discuss theoretical implications of emerging patterns, and identify key directions for future work, including potential resolutions to several methodological challenges for the field. Mapping how ASD unfolds from birth is critical to our understanding of the developmental mechanisms underlying this disorder. A more nuanced understanding of developmental pathways to ASD will help us not only to identify children who need early intervention, but also to improve the range of interventions available to them

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Evaluating Inter-Rater Reliability and Statistical Power of Vegetation Measures Assessing Deer Impact

Long-term vegetation monitoring projects are often used to evaluate how plant communities change through time in response to some external influence. Here, we evaluate the efficacy of vegetation monitoring to consistently detect changes in white-tailed deer browsing effects. Specifically, we compared inter-rater reliability (Cohen&#8217;s &#954; and Lin&#8217;s concordance correlation coefficient) between two identically trained field crews for several plant metrics used by Pennsylvania state agencies to monitor deer browsing impact. Additionally, we conducted a power analysis to determine the effect of sampling scale (1/2500th or 1/750th ha plots) on the ability to detect changes in tree seedling stem counts over time. Inter-rater reliability across sampling crews was substantial for most metrics based on direct measurements, while the observational based Deer Impact Index (DII) had only moderate inter-rater reliability. The smaller, 1/2500th ha sampling scale resulted in higher statistical power to detect changes in tree seedling stem counts due to reduced observer error. Overall, this study indicates that extensive training on plant identification, project protocols, and consistent data collection methods can result in reliable vegetation metrics useful for tracking understory responses to white-tailed deer browsing. Smaller sampling scales and objective plant measures (i.e., seedling counts, species richness) improve inter-rater reliability over subjective measures of deer impact (i.e., DII). However, considering objective plant measures when making a subjective assessment regarding deer browsing effects may also improve DII inter-rater reliability

Species_Code_List_2014

List of species names for abbreviation codes used in Tree_Data_2014.csv, Seedling_Data_2014.csv, and Cover_Data_204.cs

Tree_Data_2014

Overstory tree measurements (>=5" dbh) at 24 sampling sites at Rothrock and Bald Eagle state forests in central Pennsylvania. See Vegetation_Metadata_2014.csv and Vegetation_Metadata_2014.csv for specific column descriptions and data formatting

Data from: Soil chemistry, and not short-term (1-2 year) deer exclusion, explains understory plant occupancy in forests affected by acid deposition

The loss of species diversity and plant community structure throughout the temperate deciduous forests of North America have often been attributed to overbrowsing by white-tailed deer (Odocoileus virginanus). Slow species recovery following removal from browsing, or reduction in deer density, has been termed a legacy effect of past deer herbivory. However, vegetation legacy effects have also coincided with changes to soil chemistry throughout the northeastern United States. In this paper, we assess the viability of soil chemistry (i.e. pH, extractable nutrients, and extractable metals) and other factors (topography, light, overstory basal area, and location) as alternative explanations for a lack of vegetation recovery. We compared the relative effects of soil chemistry, site conditions, and short-term (1-2 year) deer exclusion on single-species occupancy probabilities of 10 plant taxa common to oak-hickory forests in central Pennsylvania. We found detection for all modeled species was constant and high (p > 0.65), and occupancy probability of most taxa was best explained by at least 1 soil chemistry parameter. Specifically, ericaceous competing vegetation was more likely to occupy acidic (pH < 3.5), base cation poor (K < 0.20 cmolc/kg) sites, while deer-preferred plants were less likely to occur when soil manganese exceeded 0.1 cmolc/kg. Short-term deer exclusion did not explain occupancy of any plant taxon, and site conditions were of nominal importance. This study demonstrates the importance of soil chemistry in shaping plant community composition in the northcentral Appalachians, and suggests soil as an alternative, or additional, explanation for deer vegetation legacy effects. We suggest that the reliance on phyto-indicators of deer browsing effects may overestimate the effects of browsing if those species are also limited by unfavorable soil conditions. Future research should consider study designs that address the complexity of deer forest interactions, especially in areas with complex site-vegetation histories