Evaluation of association of blood and bronchoalveolar eosinophil numbers and serum total immunoglobulin E concentration with the expression of nonspecific airway reactivity in dogs

To characterize the relation between bronchoalveolar and blood eosinophil numbers, serum total IgE concentration, and nonspecific airway reactivity in healthy dogs

Late Cenozoic tephrostratigraphy offshore the southern Central American Volcanic Arc: 1. Tephra ages and provenance

We studied the tephra inventory of 18 deep sea drill sites from six DSDP/ODP legs (Legs 84, 138, 170, 202, 205, 206) and two IODP legs (Legs 334 and 344) offshore the southern Central American Volcanic Arc (CAVA). Eight drill sites are located on the incoming Cocos plate and ten drill sites on the continental slope of the Caribbean plate. In total we examined ∼840 ash-bearing horizons and identified ∼650 of these as primary ash beds of which 430 originated from the CAVA. Correlations of ash beds were established between marine cores and with terrestrial tephra deposits, using major and trace element glass compositions with respect to relative stratigraphic order. As a prerequisite for marine-terrestrial correlations we present a new geochemical data set for significant Neogene and Quaternary Costa Rican tephras. Moreover, new Ar/Ar ages for marine tephras have been determined and marine ash beds are also dated using the pelagic sedimentation rates. The resulting correlations and provenance analyses build a tephrochronostratigraphic framework for Costa Rica and Nicaragua that covers the last >8 Myr. We define 39 correlations of marine ash beds to specific tephra formations in Costa Rica and Nicaragua; from the 4.15 Ma Lower Sandillal Ignimbrite to the 3.5 ka Rincón de la Vieja Tephra from Costa Rica, as well as another 32 widely distributed tephra layers for which their specific region of origin along Costa Rica and Nicaragua can be constrained

Analysing EHR navigation patterns and digital workflows among physicians during ICU pre-rounds

Background: Some physicians in intensive care units (ICUs) report that electronic health records (EHRs) can be cumbersome and disruptive to workflow. There are significant gaps in our understanding of the physician–EHR interaction. Objective: To better understand how clinicians use the EHR for chart review during ICU pre-rounds through the characterisation and description of screen navigation pathways and workflow patterns. Method: We conducted a live, direct observational study of six physician trainees performing electronic chart review during daily pre-rounds in the 30-bed medical ICU at a large academic medical centre in the Southeastern United States. A tailored checklist was used by observers for data collection. Results: We observed 52 distinct live patient chart review encounters, capturing a total of 2.7 hours of pre-rounding chart review activity by six individual physicians. Physicians reviewed an average of 8.7 patients (range = 5–12), spending a mean of 3:05 minutes per patient (range = 1:34–5:18). On average, physicians visited 6.3 (±3.1) total EHR screens per patient (range = 1–16). Four unique screens were viewed most commonly, accounting for over half (52.7%) of all screen visits: results review (17.9%), summary/overview (13.0%), flowsheet (12.7%), and the chart review tab (9.1%). Navigation pathways were highly variable, but several common screen transition patterns emerged across users. Average interrater reliability for the paired EHR observation was 80.0%. Conclusion: We observed the physician–EHR interaction during ICU pre-rounds to be brief and highly focused. Although we observed a high degree of “information sprawl” in physicians’ digital navigation, we also identified common launch points for electronic chart review, key high-traffic screens and common screen transition patterns. Implications: From the study findings, we suggest recommendations towards improved EHR design

In utero exposure to transient ischemia-hypoxemia promotes long-term neurodevelopmental abnormalities in male rat offspring

The impact of transient ischemic-hypoxemic insults on the developing fetal brain is poorly understood despite evidence suggesting an association with neurodevelopmental disorders such as schizophrenia and autism. To address this, we designed an aberrant uterine hypercontractility paradigm with oxytocin to better assess the consequences of acute, but transient, placental ischemia-hypoxemia in term pregnant rats. Using MRI, we confirmed that oxytocin-induced aberrant uterine hypercontractility substantially compromised uteroplacental perfusion. This was supported by the observation of oxidative stress and increased lactate concentration in the fetal brain. Genes related to oxidative stress pathways were significantly upregulated in male, but not female, offspring 1 hour after oxytocin-induced placental ischemia-hypoxemia. Persistent upregulation of select mitochondrial electron transport chain complex proteins in the anterior cingulate cortex of adolescent male offspring suggested that this sex-specific effect was enduring. Functionally, offspring exposed to oxytocin-induced uterine hypercontractility showed male-specific abnormalities in social behavior with associated region-specific changes in gene expression and functional cortical connectivity. Our findings, therefore, indicate that even transient but severe placental ischemia-hypoxemia could be detrimental to the developing brain and point to a possible mitochondrial link between intrauterine asphyxia and neurodevelopmental disorders

Constraints on Earth system functioning at the Paleocene-Eocene Thermal Maximum from the marine silicon cycle

The Paleocene‐Eocene Thermal Maximum (PETM, ca. 56 Ma) is marked by a negative carbon isotope excursion (CIE) and increased global temperatures. The CIE is thought to result from the release of 13C‐depleted carbon, although the source(s) of carbon and triggers for its release, its rate of release, and the mechanisms by which the Earth system recovered are all debated. Many of the proposed mechanisms for the onset and recovery phases of the PETM make testable predictions about the marine silica cycle, making silicon isotope records a promising tool to address open questions about the PETM. We analyzed silicon isotope ratios (δ30Si) in radiolarian tests and sponge spicules from the Western North Atlantic (ODP Site 1051) across the PETM. Radiolarian δ30Si decreases by 0.6‰ from a background of 1‰ coeval with the CIE, while sponge δ30Si remains consistent at 0.2‰. Using a box model to test the Si cycle response to various scenarios, we find the data are best explained by a weak silicate weathering feedback, implying the recovery was mostly driven by nondiatom organic carbon burial, the other major long‐term carbon sink. We find no resolvable evidence for a volcanic trigger for carbon release, or for a change in regional oceanography. Better understanding of radiolarian Si isotope fractionation and more Si isotope records spanning the PETM are needed to confirm the global validity of these conclusions, but they highlight how the coupling between the silica and carbon cycles can be exploited to yield insight into the functioning of the Earth system

Oxytocin-induced birth causes sex-specific behavioral and brain connectivity changes in developing rat offspring

Despite six decades of the use of exogenous oxytocin for management of labor, little is known about its effects on the developing brain. Motivated by controversial reports suggesting a link between oxytocin use during labor and autism spectrum disorders (ASDs), we employed our recently validated rat model for labor induction with oxytocin to address this important concern. Using a combination of molecular biological, behavioral, and neuroimaging assays, we show that induced birth with oxytocin leads to sex-specific disruption of oxytocinergic signaling in the developing brain, decreased communicative ability of pups, reduced empathy-like behaviors especially in male offspring, and widespread sex-dependent changes in functional cortical connectivity. Contrary to our hypothesis, social behavior, typically impaired in ASDs, was largely preserved. Collectively, our foundational studies provide nuanced insights into the neurodevelopmental impact of birth induction with oxytocin and set the stage for mechanistic investigations in animal models and prospective longitudinal clinical studies

The Toll-Like Receptor Signaling Molecule Myd88 Contributes to Pancreatic Beta-Cell Homeostasis in Response to Injury

Commensal flora and pathogenic microbes influence the incidence of diabetes in animal models yet little is known about the mechanistic basis of these interactions. We hypothesized that Myd88, an adaptor molecule in the Toll-like-receptor (TLR) pathway, regulates pancreatic β-cell function and homeostasis. We first examined β-cells histologically and found that Myd88−/− mice have smaller islets in comparison to C57Bl/6 controls. Myd88−/− mice were nonetheless normoglycemic both at rest and after an intra-peritoneal glucose tolerance test (IPGTT). In contrast, after low-dose streptozotocin (STZ) challenge, Myd88−/−mice had an abnormal IPGTT relative to WT controls. Furthermore, Myd88−/− mice suffer enhanced β-cell apoptosis and have enhanced hepatic damage with delayed recovery upon low-dose STZ treatment. Finally, we treated WT mice with broad-spectrum oral antibiotics to deplete their commensal flora. In WT mice, low dose oral lipopolysaccharide, but not lipotichoic acid or antibiotics alone, strongly promoted enhanced glycemic control. These data suggest that Myd88 signaling and certain TLR ligands mediate a homeostatic effect on β-cells primarily in the setting of injury

Changes in the variability and periodicity of precipitation in Scotland

This paper analyses the temporal and spatial changes in the amount and variability of rainfall in Scotland. The sequential Mann–Kendall test reveals that total annual precipitation has increased across Scotland since the 1970s with increasing trends in variability beginning between the mid-1960s and the mid-1970s. Whilst temporally consistent increasing trends in precipitation totals prevail in the West, many weather stations in the East have experienced subsequent trend turning points in the following two decades, explaining the larger magnitude of the trends in western Scotland in recent decades. Trend analyses on six measures of rainfall variability indicate an increase in rainfall variability during the period 1961–2000, as measured by the intra-annual variance, the winter to summer precipitation ratio and the annual cumulative sum range, with decreasing trends observed in the number of dry days. Periodicities associated with the North Atlantic Oscillation and the Atlantic Multidecadal Oscillation could explain the observed temporal variability of rainfall