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Animal and human data demonstrate independent relationships between fetal growth, hypothalamic-pituitary-adrenal axis function (HPA-A) and adult cardiometabolic outcomes. While the association between fetal growth and adult cardiometabolic outcomes is well-established, the role of the HPA-A in these relationships is unclear. This study aims to determine whether HPA-A function mediates or moderates this relationship. Approximately 2900 pregnant women were recruited between 1989-1991 in the Raine Study. Detailed anthropometric data was collected at birth (per cent optimal birthweight [POBW]). The Trier Social Stress Test was administered to the offspring (Generation 2; Gen2) at 18 years; HPA-A responses were determined (reactive responders [RR], anticipatory responders [AR] and non-responders [NR]). Cardiometabolic parameters (BMI, systolic BP [sBP] and LDL cholesterol) were measured at 20 years. Regression modelling demonstrated linear associations between POBW and BMI and sBP; quadratic associations were observed for LDL cholesterol. For every 10% increase in POBW, there was a 0.54 unit increase in BMI (standard error [SE] 0.15) and a 0.65 unit decrease in sBP (SE 0.34). The interaction between participant’s fetal growth and HPA-A phenotype was strongest for sBP in young adulthood. Interactions for BMI and LDL-C were non-significant. Decomposition of the total effect revealed no causal evidence of mediation or moderation.
Fossil colobines are found in Africa, Asia, and Europe and as far back as over 12 million years ago. They are known from paleontological sites that extend well beyond their current range to northern Europe and Asia. In the late Miocene (10 – 5 Ma) they are quite rare but show a pattern of steadily increasing diversity. By Pliocene times they are considerably more diverse than today in terms of number of genera. They also span a greater range of body sizes extending from some similar to extant colobines up to at least three lineages that probably exceeded 40 Kg. Dental morphology, microwear analysis, and stable isotopes of carbon and oxygen further suggest that they had a range of diets, many likely different than extant colobines. Postcranial morphology suggests a wider range of locomotor modes as well. Finally, many seemed to have occupied more open, seasonal, and varied habitats than extant forms.
Patients presenting to hospital with suspected coronavirus disease 2019 (COVID-19), based on clinical symptoms, are routinely placed in a cohort together until polymerase chain reaction (PCR) test results are available. This procedure leads to delays in transfers to definitive areas and high nosocomial transmission rates. FebriDx is a finger-prick point-of-care test (PoCT) that detects an antiviral host response and has a high negative predictive value for COVID-19. We sought to determine the clinical impact of using FebriDx for COVID-19 triage in the emergency department (ED).
We undertook a retrospective observational study evaluating the real-world clinical impact of FebriDx as part of an ED COVID-19 triage algorithm.
Emergency department of a university teaching hospital.
Patients presenting with symptoms suggestive of COVID-19, placed in a cohort in a ‘high-risk’ area, were tested using FebriDx. Patients without a detectable antiviral host response were then moved to a lower-risk area.
Between September 22, 2020, and January 7, 2021, 1,321 patients were tested using FebriDx, and 1,104 (84%) did not have a detectable antiviral host response. Among 1,104 patients, 865 (78%) were moved to a lower-risk area within the ED. The median times spent in a high-risk area were 52 minutes (interquartile range [IQR], 34–92) for FebriDx-negative patients and 203 minutes (IQR, 142–255) for FebriDx-positive patients (difference of −134 minutes; 95% CI, −144 to −122; P < .0001). The negative predictive value of FebriDx for the identification of COVID-19 was 96% (661 of 690; 95% CI, 94%–97%).
FebriDx improved the triage of patients with suspected COVID-19 and reduced the time that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR-negative patients spent in a high-risk area alongside SARS-CoV-2–positive patients.
Recent excavations by the Ancient Southwest Texas Project of Texas State University sampled a previously undocumented Younger Dryas component from Eagle Cave in the Lower Pecos Canyonlands of Texas. This stratified assemblage consists of bison (Bison antiquus) bones in association with lithic artifacts and a hearth. Bayesian modeling yields an age of 12,660–12,480 cal BP, and analyses indicate behaviors associated with the processing of a juvenile bison and the manufacture and maintenance of lithic tools. This article presents spatial, faunal, macrobotanical, chronometric, geoarchaeological, and lithic analyses relating to the Younger Dryas component within Eagle Cave. The identification of the Younger Dryas occupation in Eagle Cave should encourage archaeologists to revisit previously excavated rockshelter sites in the Lower Pecos and beyond to evaluate deposits for unrecognized, older occupations.
Hypotension is an adverse event that may be related to systemic exposure of milrinone; however, the true exposure–safety relationship is unknown.
Using the Pediatric Trials Network multicentre repository, we identified children ≤17 years treated with milrinone. Hypotension was defined according to age, using the Pediatric Advanced Life Support guidelines. Clinically significant hypotension was defined as hypotension with concomitant lactate >3 mg/dl. A prior population pharmacokinetic model was used to simulate milrinone exposures to evaluate exposure–safety relationships.
We included 399 children with a median (quarter 1, quarter 3) age of 1 year (0,5) who received 428 intravenous doses of milrinone (median infusion rate 0.31 mcg/kg/min [0.29,0.5]). Median maximum plasma milrinone concentration was 110.7 ng/ml (48.4,206.2). Median lowest systolic and diastolic blood pressures were 74 mmHg (60,85) and 35 mmHg (25,42), respectively. At least 1 episode of hypotension occurred in 178 (45%) subjects; clinically significant hypotension occurred in 10 (2%). The maximum simulated milrinone plasma concentrations were higher in subjects with clinically significant hypotension (251 ng/ml [129,329]) versus with hypotension alone (86 ng/ml [44, 173]) versus without hypotension (122 ng/ml [57, 208], p = 0.002); however, this relationship was not retained on multivariable analysis (odds ratio 1.01; 95% confidence interval 0.998, 1.01).
We successfully leveraged a population pharmacokinetic model and electronic health record data to evaluate the relationship between simulated plasma concentration of milrinone and systemic hypotension occurrence, respectively, supporting the broader applicability of our novel, efficient, and cost-effective study design for examining drug exposure–response and –safety relationships.
In shell-secreting molluscs, age and growth rate of individuals and hence their performance can normally be measured using growth lines that are deposited in the shell throughout their lives. An annual periodicity of growth line formation of the warm-water limpet Patella depressa was established using marked and recaptured individuals from north Wales, UK. Length at age from suitably prepared shell sections was determined in limpets from non-range-edge populations and at two range edges, where different demographic attributes have been recorded. Individuals collected from their poleward range-edge in north Wales were older when compared with individuals at their range-edge in southern England. Shells collected from southern England were characterized by rapid growth with most individuals reaching >30 mm in maximum length by the fourth or fifth year, contrasting with those from north Wales, where most shells only reached this size at 7–10 years of age. Von Bertalanffy growth coefficients (K-values) were negatively related to P. depressa density, showing faster growth in lower total densities of both P. depressa and Patella vulgata combined. Higher intra-specific effects on K-values were found in P. depressa compared with its congener P. vulgata, with stronger effects in north Wales than in southern England. These results confirm differences in population patterns and individual traits between the two leading edges of P. depressa. Understanding annual growth in P. depressa over large scales could help to disentangle the processes determining differences in shell growth and age structure seen at the two range edges of this limpet species.
A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).
The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8–40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.
When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).
We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.
The Glastonbury Lake Village in Somerset, UK, is made up of 90 mounds comprising 40 roundhouses. Excavations between 1892 and 1907 revealed Iron Age structural and material remains unparalleled in Western Europe. The settlement's exact chronology, however, has remained uncertain. Here, the authors present a programme of radiocarbon and dendrochronological dating and chronological modelling on samples from recent excavations. The results indicate that the site was founded in the early second century cal BC, with the last structures being built just over a century later. This new, robust chronology can be used to date a wide range of associated material culture, and complements chronologies established for other Iron Age sites.
This article emerged as the human species collectively have been experiencing the worst global pandemic in a century. With a long view of the ecological, economic, social, and political factors that promote the emergence and spread of infectious disease, archaeologists are well positioned to examine the antecedents of the present crisis. In this article, we bring together a variety of perspectives on the issues surrounding the emergence, spread, and effects of disease in both the Americas and Afro-Eurasian contexts. Recognizing that human populations most severely impacted by COVID-19 are typically descendants of marginalized groups, we investigate pre- and postcontact disease vectors among Indigenous and Black communities in North America, outlining the systemic impacts of diseases and the conditions that exacerbate their spread. We look at how material culture both reflects and changes as a result of social transformations brought about by disease, the insights that paleopathology provides about the ancient human condition, and the impacts of ancient globalization on the spread of disease worldwide. By understanding the differential effects of past epidemics on diverse communities and contributing to more equitable sociopolitical agendas, archaeology can play a key role in helping to pursue a more just future.
There are numerous associations between psychological characteristics and political values, but it is unclear whether messages tailored to these psychological characteristics can influence political decisions. Two studies (N = 398, N = 395) tested whether psychological-based argument tailoring could influence participants’ decision-making. We constructed arguments based on the 2016 Brexit referendum; Remain supporters were presented with four arguments supporting the Leave campaign, tailored to reflect the participant’s strongest (/weakest) moral foundation (Loyalty or Fairness) or personality trait (Conscientiousness or Openness). We tested whether individuals scoring high on a trait would find the tailored arguments more persuasive than individuals scoring low on the same trait. We found clear evidence for targeting, particularly for Loyalty, but either no evidence or weak evidence, in the case of Conscientiousness, for tailoring. Overall, the results suggest that targeting political messages could be effective, but provide either no, or weak evidence that tailoring these messages influences political decision-making.
Antarctica's ice shelves modulate the grounded ice flow, and weakening of ice shelves due to climate forcing will decrease their ‘buttressing’ effect, causing a response in the grounded ice. While the processes governing ice-shelf weakening are complex, uncertainties in the response of the grounded ice sheet are also difficult to assess. The Antarctic BUttressing Model Intercomparison Project (ABUMIP) compares ice-sheet model responses to decrease in buttressing by investigating the ‘end-member’ scenario of total and sustained loss of ice shelves. Although unrealistic, this scenario enables gauging the sensitivity of an ensemble of 15 ice-sheet models to a total loss of buttressing, hence exhibiting the full potential of marine ice-sheet instability. All models predict that this scenario leads to multi-metre (1–12 m) sea-level rise over 500 years from present day. West Antarctic ice sheet collapse alone leads to a 1.91–5.08 m sea-level rise due to the marine ice-sheet instability. Mass loss rates are a strong function of the sliding/friction law, with plastic laws cause a further destabilization of the Aurora and Wilkes Subglacial Basins, East Antarctica. Improvements to marine ice-sheet models have greatly reduced variability between modelled ice-sheet responses to extreme ice-shelf loss, e.g. compared to the SeaRISE assessments.
This study provides a morphological and phylogenetic characterization of two novel species of the order Haplosporida (Haplosporidium carcini n. sp., and H. cranc n. sp.) infecting the common shore crab Carcinus maenas collected at one location in Swansea Bay, South Wales, UK. Both parasites were observed in the haemolymph, gills and hepatopancreas. The prevalence of clinical infections (i.e. parasites seen directly in fresh haemolymph preparations) was low, at ~1%, whereas subclinical levels, detected by polymerase chain reaction, were slightly higher at ~2%. Although no spores were found in any of the infected crabs examined histologically (n = 334), the morphology of monokaryotic and dikaryotic unicellular stages of the parasites enabled differentiation between the two new species. Phylogenetic analyses of the new species based on the small subunit (SSU) rDNA gene placed H. cranc in a clade of otherwise uncharacterized environmental sequences from marine samples, and H. carcini in a clade with other crustacean-associated lineages.
The adsorption and retention of phosphates in soil systems is of wide environmental importance, and understanding the surface chemistry of halloysite (a common soil clay mineral) is also of prime importance in many emerging technological applications of halloysite nanotubes (HNTs). The adsorption of phosphate anions on tubular halloysite (7 Å) has been studied to gain a greater understanding of the mechanism and kinetics of adsorption on the surface of HNTs. Two well-characterized tubular halloysites with differing morphologies have been studied: one polygonal prismatic and one cylindrical, where the cylindrical form has a greater surface area and shorter tube length. Greater phosphate adsorption of up to 42 μmol g–1 is observed on the cylindrical halloysite when compared to the polygonal prismatic sample, where adsorption reached a maximum of just 15 μmol g–1 compared to a value for platy kaolinite (KGa-2) of 8 μmol g–1. Phosphate adsorption shows strong pH dependence, and the differences in phosphate sorption between the prismatic and cylindrical morphologies suggest that phosphate absorption does not occur at the same pH-dependent alumina edge sites and that the lumen may have a greater influence on uptake for the cylindrical form.
A 53-year-old male presents with cough, fever, and myalgias for 7 days. Vitals include temperature, 38.0°C; heart rate, 110; blood pressure, 118/70 mm Hg; respiration rate, 28; and oxygen saturation 83% on room air. His only past medical history is hypertension. Your community is in the midst of the coronavirus disease 2019 (COVID-19) pandemic. The patient is hypoxic but responds to oxygen supplementation with nasal cannula and a face mask. His chest x-ray demonstrates multifocal infiltrates. Are there any therapeutic agents currently available for COVID-19?