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Abstract Backgorund Tissue-engineered tracheal grafts (TETG) can be recellularized by the host or pre-seeded with host-derived cells. However, the impact of airway disease on the recellularization process is unknown. Methods In this study, we determined if airway disease alters the regenerative potential of the human tracheobronchial epithelium (hTBE) obtained by brushing the tracheal mucosa during clinically-indicated bronchoscopy from 48 pediatric and six adult patients. Results Our findings revealed that basal cell recovery and frequency did not vary by age or region. At passage 1, all samples produced enough cells to cellularize a 3.5 by 0.5 cm2 graft scaffold at low cell density (~ 7000 cells/cm2), and 43.75% could cellularize a scaffold at high cell density (~ 100,000 cells/cm2). At passage 2, all samples produced the number of cells required for both recellularization models. Further evaluation revealed that six pediatric samples (11%) and three (50%) adult samples contained basal cells with a squamous basal phenotype. These cells did not form a polarized epithelium or produce differentiated secretory or ciliated cells. In the pediatric population, the squamous basal cell phenotype was associated with degree of prematurity (

Summary: Background: Concerns remain over the long-term safety of vascular endothelial growth factor (VEGF) inhibitors to treat retinopathy of prematurity (ROP). RAINBOW is an open label randomised trial comparing intravitreal ranibizumab (in 0.2 mg and 0.1 mg doses) with laser therapy in very low birthweight infants (

We describe hepatitis C testing of 47 (2%) of 2,266 children diagnosed with perinatal hepatitis C who were exposed during 2018–2020 in 7 jurisdictions in the United States. Expected frequency of perinatal transmission is 5.8%, indicating only one third of the cases in this cohort were reported to public health authorities.

Abstract Background The merits and drawbacks of moral relevance models of addiction have predominantly been discussed theoretically, without empirical evidence of these potential effects. This study develops and evaluates a novel survey measure for assessing moral evaluations of patient substance misuse (ME-PSM). Methods This measure was tested on 524 health professionals (i.e., physicians, nurses, and other health professionals) in California (n = 173), urban France (n = 102), and urban China (n = 249). Demographic factors associated with ME-PSM were investigated using analyses of variance (ANOVAs) and t-tests, with results suggesting that ME-PSM is higher among younger health professionals, nurses (when compared with physicians and other health professionals), and Chinese health professionals (when compared with French and American health professionals). Results Results provide preliminary support for the psychometric quality of the survey measure introduced in this study, including the existence of a single latent structure and partial invariance of collected data across countries. Conclusion The survey measure for ME-PSM which was developed and tested in the current study appears to hold potential utility for use as a measure of moral views of patient substance misuse. With development, this measure may be used to examine moral evaluations, both as factors of stigma and of other clinical factors associated with the treatment of patients with substance use disorders.

Abstract Nutrient subsidies have significant impacts on ecosystems by connecting disjunct habitats, often through long‐distance animal migrations. Salmon migrations on the North Pacific coasts provide these kinds of nutrient subsidies from senescent fish at the end of their life cycle, which can have significant ecological effects on terrestrial species. This can include impacts on individuals, populations, and communities, where shifts in community composition towards plant species that indicate nitrogen‐rich soils have been documented. We investigated the effects of variation in salmon spawning density on the leaf traits of four common riparian plant species on the central coast of British Columbia, Canada. We found that all plant species had higher foliar salmon‐derived nitrogen on streams with a higher spawning density. Three of the four species had larger leaves, and one species also had higher leaf mass per area on streams with more salmon. However, we found no differences in leaf greenness or foliar percent nitrogen among our study streams. These results demonstrate that nutrient subsidies from spawning salmon can have significant impacts on the ecology, morphology, and physiology of riparian plants, which lends support to a mechanism by which certain plants are more common on productive salmon streams.

High-resolution (< 1 km) atmospheric modeling is increasingly used to study precipitation distributions in complex terrain and cryosphere–atmospheric processes. While this approach has yielded insightful results, studies over annual timescales or at the spatial extents of watersheds remain unrealistic due to the computational costs of running most atmospheric models. In this paper we introduce a high-resolution variant of the Intermediate Complexity Atmospheric Research (ICAR) model, HICAR. We detail the model development that enabled HICAR simulations at the hectometer scale, including changes to the advection scheme and the wind solver. The latter uses near-surface terrain parameters which allow HICAR to simulate complex topographic flow features. These model improvements clearly influence precipitation distributions at the ridge scale (50 m), suggesting that HICAR can approximate processes dependent on particle–flow interactions such as preferential deposition. A 250 m HICAR simulation over most of the Swiss Alps also shows monthly precipitation patterns similar to two different gridded precipitation products which assimilate available observations. Benchmarking runs show that HICAR uses 594 times fewer computational resources than the Weather Research and Forecasting (WRF) atmospheric model. This gain in efficiency makes dynamic downscaling accessible to ecohydrological research, where downscaled data are often required at hectometer resolution for whole basins at seasonal timescales. These results motivate further development of HICAR, including refinement of parameterizations used in the wind solver and coupling of the model with an intermediate-complexity snow model.

Abstract Extensive tracheal injury or disease can be life-threatening but there is currently no standard of care. Regenerative medicine offers a potential solution to long-segment tracheal defects through the creation of scaffolds that support the generation of healthy neotissue. We developed decellularized tracheal grafts (PDTG) by removing the cells of the epithelium and lamina propria while preserving donor cartilage. We previously demonstrated that PDTG support regeneration of host-derived neotissue. Here, we use a combination of microsurgical, immunofluorescent, and transcriptomic approaches to compare PDTG neotissue with the native airway and surgical controls. We report that PDTG neotissue is composed of native tracheal cell types and that the neoepithelium and microvasculature persisted for at least 6 months. Vascular perfusion of PDTG was established within 2 weeks and the graft recruited multipotential airway stem cells that exhibit normal proliferation and differentiation. Hence, PDTG neotissue recapitulates the structure and function of the host trachea and has the potential to regenerate.

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Crayfish plague is a devastating disease of European freshwater crayfish and is caused by the oomycete Aphanomyces astaci (Ap. astaci), believed to have been introduced to Europe around 1860. All European species of freshwater crayfish are susceptible to the disease, including the white-clawed crayfish Austropotamobius pallipes. Ap. astaci is primarily spread by North American crayfish species and can also disperse rapidly through contaminated wet gear moved between water bodies. This spread, coupled with competition from non-indigenous crayfish, has drastically reduced and fragmented native crayfish populations across Europe. Remarkably, the island of Ireland remained free from the crayfish plague pathogen for over 100 years, providing a refuge for A. pallipes. However, this changed in 1987 when a mass mortality event was linked to the pathogen, marking its introduction to the region. Fortunately, crayfish plague was not detected again in Ireland until 2015 when a molecular analysis linked a mass mortality event in the Erne catchment to Ap. astaci. Since then, the pathogen has appeared across the island. Between 2015 and 2023, Ap. astaci was detected in 18 water catchments, revealing multiple genotypes. Intriguingly, the pathogen in Ireland is present without its natural host species. The uneven distribution of various genetic lineages strongly suggests the human-mediated transport of zoospores via contaminated water equipment as a primary cause of spread. This review details the timeline of these events, Ap. astaci’s introduction into Ireland, and its rapid spread. As well, this review references the genotypes that have been determined, and discusses the issue of non-indigenous crayfish species in Ireland and management efforts.

Conservation of coastal biodiversity and associated ecosystem services requires protection and management for attributes of coastal wildness, which we define to include physical and ecological intactness and connectivity, native species and habitat diversity, and limited human disturbance. Coastal wildness is threatened by high demand for access to and development of coastal margins; sea level rise exacerbates this threat. As a case study, California (USA), a biodiversity hotspot, has a network of marine and terrestrial protected areas along the coast and strong coastal policy. While 35% of California’s coast has wildness attributes, only 9% of California’s coast is characterized as wild and also protected on both land and in the adjacent waters. A multi-tiered approach is needed to incorporate wild coast attributes into conservation planning and protection of coastal areas. A coastal wildness designation is needed, as well as policies that manage for wildness attributes in existing protected areas.

Abstract There is currently no suitable autologous tissue to bridge large tracheal defects. As a result, no standard of care exists for long‐segment tracheal reconstruction. Tissue engineering has the potential to create a scaffold from allografts or xenografts that can support neotissue regeneration identical to the native trachea. Recent advances in tissue engineering have led to the idea of partial decellularization that allows for the creation of tracheal scaffolds that supports tracheal epithelial formation while preserving mechanical properties. However, the ability of partial decellularization to eliminate graft immunogenicity remains unknown, and understanding the immunogenic properties of partially decellularized tracheal grafts (PDTG) is a critical step toward clinical translation. Here, we determined that tracheal allograft immunogenicity results in epithelial cell sloughing and replacement with dysplastic columnar epithelium and that partial decellularization creates grafts that are able to support an epithelium without histologic signs of rejection. Moreover, allograft implantation elicits CD8+ T‐cell infiltration, a mediator of rejection, while PDTG did not. Hence, we establish that partial decellularization eliminates allograft immunogenicity while creating a scaffold for implantation that can support spatially appropriate airway regeneration.

Abstract Objective While airway epithelial biorepositories have established roles in the study of bronchial progenitor stem (basal) cells, the utility of a bank of tracheal basal cells from pediatric patients, who have or are suspected of having an airway disease, has not been established. In vitro study of these cells can enhance options for tracheal restoration, graft design, and disease modeling. Development of a functional epithelium in these settings is a key measure. The aim of this study was the creation a tracheal basal cell biorepository and assessment of recovered cells. Methods Pediatric patients undergoing bronchoscopy were identified and endotracheal brush (N = 29) biopsies were collected. Cells were cultured using the modified conditional reprogramming culture (mCRC) method. Samples producing colonies by day 14 were passaged and cryopreserved. To explore differentiation potential, cells were thawed and differentiated using the air–liquid interface (ALI) method. Results No adverse events were associated with biopsy collection. Of 29 brush biopsies, 16 (55%) were successfully cultured to passage 1/cryopreserved. Samples with higher initial cell yields were more likely to achieve this benchmark. Ten unique donors were then thawed for analysis of differentiation. The average age was 2.2 ± 2.2 years with five donors (50%) having laryngotracheal pathology. Nine donors (90%) demonstrated differentiation capacity at 21 days of culture, as indicated by detection of ciliated cells (ACT+) and mucous cells (MUC5B+). Conclusion Pediatric tracheal basal cells can be successfully collected and cryopreserved. Recovered cells retain the ability to differentiate into epithelial cell types in vitro. Level of Evidence Level 3.

Abstract The current study utilized eye-tracking to investigate the effects of intersensory redundancy and language on infant visual attention and detection of a change in prosody in audiovisual speech. Twelve-month-old monolingual English-learning infants viewed either synchronous (redundant) or asynchronous (non-redundant) presentations of a woman speaking in native or non-native speech. Halfway through each trial, the speaker changed prosody from infant-directed speech (IDS) to adult-directed speech (ADS) or vice versa. Infants focused more on the mouth of the speaker on IDS trials compared to ADS trials regardless of language or intersensory redundancy. Additionally, infants demonstrated greater detection of prosody changes from IDS speech to ADS speech in native speech. Planned comparisons indicated that infants detected prosody changes across a broader range of conditions during redundant stimulus presentations. These findings shed light on the influence of language and prosody on infant attention and highlight the complexity of audiovisual speech processing in infancy.

Abstract Biodiversity community science projects are growing rapidly in popularity. The enormous amounts of data generated by these programs are transforming how we conduct ecological research and conservation management. However, as with other biodiversity surveys, community science datasets suffer from biases in time and locations of observations. To better use these data, we modeled the spatial biases present in the popular community science platform, iNaturalist. iNaturalist uses crowdsourcing to collect georeferenced and time‐stamped observations of all taxa worldwide. With its wealth of biodiversity data, iNaturalist is now being used to answer a broad range of questions in ecology and conservation, but little is known about the platform's spatial biases. We focus on the more than 1.75 million iNaturalist observations available (as of December 2021) from British Columbia, Canada, a region with a strong community science presence and diversity of ecosystems. Using machine learning and species distribution modeling, we examined which landscape factors (e.g., protected areas, roads, human population density, habitat zones, elevation) were most important in determining where observations are taken, and we created a predicted probability map revealing how likely different regions are to be sampled by community scientists. We found strong road biases for observations in iNaturalist, with over 94% of observations within 1 km of roads. In addition, human population density and broad habitat ecosystem zones played a large role in predicting where iNaturalist observations occur across the landscape. These methods demonstrate tools for modeling the effects of spatial biases in large opportunistic datasets that can then be used to produce more accurate species distribution and biodiversity models from community science data.

Abstract Current human donor care protocols following death by neurologic criteria (DNC) can stabilize macro-hemodynamic parameters but have minimal ability to preserve systemic blood flow and microvascular oxygen delivery. S-nitrosylated hemoglobin (SNO-Hb) within red blood cells (RBCs) is the main regulator of tissue oxygenation (StO2). Based on various pre-clinical studies, we hypothesized that brain death (BD) would decrease post-mortem SNO-Hb levels to negatively-impact StO2 and reduce organ yields. We tracked SNO-Hb and tissue oxygen in 61 DNC donors. After BD, SNO-Hb levels were determined to be significantly decreased compared to healthy humans (p = 0·003) and remained reduced for the duration of the monitoring period. There was a positive correlation between SNO-Hb and StO2 (p

Abstract Nano and microelectromechanical relays can be used in lieu of transistors to build digital integrated circuits that can operate with zero leakage current at high operating temperatures and radiation levels. Four‐terminal (4‐T) relays facilitate efficient logic circuits with greatly reduced device counts compared to three‐terminal (3‐T) relay implementations. Existing 4‐T relays, however, require two moving contacts to simultaneously land on two stationary electrodes, which can adversely impact reliability, or have complex out‐of‐plane fabrication methods that can reduce yield and increase cost while having poor scalability. In this work an in‐plane four‐terminal relay with a single moving contact is demonstrated for the first time, through successful fabrication and characterization of prototypes with a critical dimension of 1.5 µm. Body biasing is shown to reduce the pull‐in voltage of this 4‐T relay compared to a 3‐T relay with the same architecture and footprint. The potential of the 4‐T relay to build efficient logic circuits is demonstrated by fabricating and characterizing a 1‐to‐2 demultiplexer (DEMUX) circuit using only two devices, a saving of eight devices over a 3‐T relay implementation.

The exponential growth and interest in community science programs is producing staggering amounts of biodiversity data across broad temporal and spatial scales. Large community science datasets such as iNaturalist and eBird are allowing ecologists and conservation biologists to answer novel questions that were not possible before. However, the opportunistic nature of many of these enormous datasets leads to biases. Spatial bias is a common problem, where observations are biased towards points of access like roads and trails. iNaturalist-a popular biodiversity community science platform-exhibits strong spatial biases, but it is unclear how these biases affect the quality of biodiversity data collected. Thus, we tested whether fine-scale spatial bias due to sampling from trails affects taxonomic richness estimates. We compared timed transects with experienced iNaturalist observers on and off trails in British Columbia, Canada. Using generalized linear mixed models, we found higher overall taxonomic richness on trails than off trails. In addition, we found more exotic as well as native taxa on trails than off trails. There was no difference between on and off trail observations for species that are rarely observed. Thus, fine-scale spatial bias from trails does not reduce the quality of biodiversity measurements, a promising result for those interested in using iNaturalist data for research and conservation management.

Organismal movement can bring individuals, resources and novel interactions across ecosystem boundaries and into recipient habitats, thereby forming meta-ecosystems. For example, Pacific salmon ecosystems receive large marine-derived nitrogen subsidies during annual spawning events, which can have a wide range of effects on aquatic and terrestrial plant species and communities. In this study, we evaluate the effects of cross-ecosystem nutrient subsidies on terrestrial plant growth and reproduction. We conducted a large-scale field experiment with four treatments: (i) addition of a pink salmon (Oncorhynchus gorbuscha) carcass, (ii) addition of the drift seaweed rockweed (Fucus distichus), (iii) addition of both salmon + rockweed, and (iv) a control. We examined treatment effects on leaf nitrogen and fitness-associated floral traits in four common estuarine wildflower species. We found elevated leaf ∂15N in all plant species and all sampling years in treatments with salmon carcass additions but did not observe any differences in leaf per cent nitrogen. We also observed larger leaf area in two species, a context-dependent increase in floral display area in two species, and a limited increase in plant seed set in response to both salmon carcass treatments. In sum, our study suggests that marine nutrients can affect terrestrial plant growth and reproduction.

Abstract Marine‐derived resource subsidies can generate intrapopulation variation in the behaviors and diets of terrestrial consumers. How omnivores respond, given their multiple trophic interactions, is not well understood. We sampled mice (Peromyscus keeni) and their food sources at five sites on three islands of the Central Coast of British Columbia, Canada, to test predictions regarding variation in the spatial behavior and consumption of marine‐subsidized foods among individuals. About 50% of detections (n = 27 recaptures) occurred at traps closest to shoreline (25 m), with capture frequencies declining significantly inland (up to 200 m). Stable isotope signatures (δ13C and δ15N), particularly δ15N, in plant foods, forest arthropod prey, and mouse feces were significantly enriched near shorelines compared with inland, while δ13C patterns were more variable. Bayesian isotope mixing models applied to isotope values in mouse hair indicated that over one‐third (35–37%) of diet was comprised of beach‐dwelling arthropods, a marine‐derived food source. Males were more abundant near the shoreline than females and consumed more marine‐derived prey, regardless of reproductive status or availability of other food sources. Our results identify how multiple pathways of marine nutrient transfer can subsidize terrestrial omnivores and how subsets of recipient populations can show variation in spatial and dietary response.

Abstract Chronic lung disease has been attributed to stem cell aging and/or exhaustion. We investigated these mechanisms using mouse and human tracheobronchial tissue‐specific stem cells (TSC). In mouse, chromatin labeling and flow cytometry demonstrated that naphthalene (NA) injury activated a subset of TSC. These activated TSC continued to proliferate after the epithelium was repaired and a clone study demonstrated that ~96% of activated TSC underwent terminal differentiation. Despite TSC attrition, epithelial repair after a second NA injury was normal. The second injury accelerated proliferation of previously activated TSC and a nucleotide‐label retention study indicated that the second injury recruited TSC that were quiescent during the first injury. These mouse studies indicate that (a) injury causes selective activation of the TSC pool; (b) activated TSC are predisposed to further proliferation; and (c) the activated state leads to terminal differentiation. In human TSC, repeated proliferation also led to terminal differentiation and depleted the TSC pool. A clone study identified long‐ and short‐lived TSC and showed that short‐lived TSC clones had significantly shorter telomeres than their long‐lived counterparts. The TSC pool was significantly depleted in dyskeratosis congenita donors, who harbor mutations in telomere biology genes. The remaining TSC had short telomeres and short lifespans. Collectively, the mouse and human studies support a model in which epithelial injury increases the biological age of the responding TSC. When applied to chronic lung disease, this model suggests that repeated injury accelerates the biological aging process resulting in abnormal repair and disease initiation.

IntroductionIn spite of promising medical, sociological, and engineering strategies and interventions to reduce the burden of disease, malaria remains a source of significant morbidity and mortality, especially among children in sub-Saharan Africa. In particular, progress in the development and administration of chemotherapeutic agents is threatened by evolved resistance to most of the antimalarials currently in use, including artemisinins.MethodsThis study analyzed the prevalence of mutations associated with antimalarial resistance in Plasmodium falciparum from 95 clinical samples collected from individuals with clinically confirmed malaria at a hospital in Bo, Sierra Leone between May 2017 and December 2018. The combination of polymerase chain reaction amplification and subsequent high throughput DNA sequencing was used to determine the presence of resistance-associated mutations in five P. falciparum genes – pfcrt, pfmdr1, pfdhfr, pfdhps and pfkelch13. The geographic origin of parasites was assigned using mitochondrial sequences.ResultsRelevant mutations were detected in the pfcrt (22%), pfmdr1 (>58%), pfdhfr (100%) and pfdhps (>80%) genes while no resistance-associated mutations were found in the pfkelch13 gene. The mitochondrial barcodes were consistent with a West African parasite origin with one exception indicating an isolate imported from East Africa.DiscussionDetection of the pfmdr1 NFSND haplotype in 50% of the samples indicated the increasing prevalence of strains with elevated tolerance to artemeter + lumefantrine (AL) threatening the combination currently used to treat uncomplicated malaria in Sierra Leone. The frequency of mutations linked to resistance to antifolates suggests widespread resistance to the drug combination used for intermittent preventive treatment during pregnancy.

Perceptual narrowing is a domain-general process in which infants move from a broad sensitivity to a wide range of stimuli to developing expertise within often experienced native stimuli (Maurer & Werker, 2014). One outcome of this is the own-race bias, characterized by an increasing difficulty in discriminating other-race faces with age and experience for those raised in a racially homogenous environment (Anzures, Quinn, Pascalis, Slater, Tanaka, & Lee, 2013). Theorists have proposed that this is due to a categorization-individuation process, wherein infants begin to categorize non-native stimuli but continue to individuate native stimuli (Hugenberg, Young, Bernstein, & Sacco, 2010; Nelson, 2001). Exposure to multiple exemplars during initial learning has been found to facilitate infant categorization of other-species faces while exposure to a single exemplar does not (Dixon, Reynolds, Romano, Roth, Stumpe, Guy, & Mosteller, 2019). The goal of this study was to investigate the effects of initial learning conditions on infants' ability to individuate and categorize own- and other-race faces. Ten-month-old infants were familiarized with a single exemplar or multiple exemplars of own- or other-race faces. Event-related potentials (ERPs) were recorded while infants were presented with the familiar face(s) they were exposed to during familiarization, novel faces from the same race used during familiarization, and novel faces from a race other than the one used in familiarization. Infants familiarized with a single exemplar, regardless of race, showed significant differences in both the Nc component (Negative central, associated with visual attention) and the LSW (late slow wave, associated with recognition memory) between familiar and novel faces at the subordinate-level category of race. No differences were found across familiarization conditions for the P400 component associated with face processing. Infants familiarized with multiple exemplars showed no evidence of discriminating faces at the categorical or individual level. Results suggest that, in contrast to other-species faces, infants at this age may process human faces more efficiently when familiarized with a single exemplar. The implications of the current findings are discussed in relation to the impact of initial learning conditions on infants' ability to individuate and categorize own- and other-species faces and social implications of infants' processing of other-race faces.

Abstract When Pacific salmon (Oncorhynchus spp.) spawn and die, they deliver marine‐derived nutrient subsidies to freshwater and riparian ecosystems. These subsidies can alter the behavior, productivity, and abundance of recipient species and their habitats. Isotopes, such as nitrogen‐15 (15N), are often used to trace the destination of marine‐derived nutrients in riparian habitats. However, few studies have tested for correlations between stable isotopes and physiological responses of riparian organisms. We examined whether increases in δ15N in terrestrial insect bodies adjacent to salmon spawning habitat translate to changes in percent nitrogen content and body size. This involved comparisons between distance from a salmon‐bearing river, marine‐derived nutrients in soils and insects, soil moisture content, and body size and nitrogen content in two common beetle families (Coleoptera: Curculionidae, Carabidae). As predicted, δ15N in riparian soils attenuated with distance from the river but was unaffected by soil moisture. This gradient was mirrored by δ15N in the herbivorous curculionid beetles, whereas carabid beetles, which feed at a higher trophic level and are more mobile, did not show discernable patterns in their δ15N content. Additionally, neither distance from the river nor body δ15N content was related to beetle body size. We also found that nitrogen‐15 was not correlated with total percent nitrogen in insect bodies, meaning that the presence of spawning salmon did not increase the percent nitrogen content of these insects. We conclude that while salmon‐derived nutrients had entered terrestrial food webs, the presence of δ15N alone did not indicate meaningful physiological changes in these insects in terms of percent nitrogen nor body size. While stable isotopes may be useful tracers of marine‐derived nutrients, they cannot necessarily be used as a proxy for physiologically important response variables.

Dr. Angela Y. Davis is a political activist, academician, and writer who has navigated and discussed issues of race, class, gender, and USA social policies across her 75 years of life. Davis’s activism established her as the icon of a larger social movement and further related to her decision-making and legacy. Using psychobiographical methods, data were gathered through publicly available sources to explore Davis’s personal, professional, and representational life, as well as understand Davis’s lived experience through a socio-cultural-historical perspective. Two established theories, Social Cognitive Career Theory and Politicized Collective Identity model, were applied to Davis’s life. Findings suggested that in addition to her unique intersectional identities, a confluence of factors including growing up in a family of activists, incarceration, Federal Bureau of Investigation (FBI) surveillance, Communist Party involvement, marginalization within activist spaces, and practicing radical self-care impacted Davis committing to a life as an activist, academic, and the leader of a social movement.

Summary: Travel represents a major cost for many animals so there should be selection pressure for it to be efficient – at minimum cost. However, animals sometimes exceed minimum travel costs for reasons that must be correspondingly important. We use Dynamic Body Acceleration (DBA), an acceleration-based metric, as a proxy for movement-based power, in tandem with vertical velocity (rate of change in depth) in a shark (Rhincodon typus) to derive the minimum estimated power required to swim at defined vertical velocities. We show how subtraction of measured DBA from the estimated minimum power for any given vertical velocity provides a “proxy for power above minimum” metric (PPAmin), highlighting when these animals travel above minimum power. We suggest that the adoption of this metric across species has value in identifying where and when animals are subject to compelling conditions that lead them to deviate from ostensibly judicious energy expenditure.

Mucosecretory lung disease compromises airway epithelial function and is characterized by goblet cell hyperplasia and ciliated cell hypoplasia. Goblet and ciliated cell types are derived from tracheobronchial stem/progenitor cells via a Notch-dependent mechanism. Although specific arrays of Notch receptors regulate cell fate determination, the function of the ligands Jagged1 (JAG1) and JAG2 is unclear. This study examined JAG1 and JAG2 function using human air-liquid-interface cultures that were treated with γ-secretase complex (GSC) inhibitors, neutralizing peptides/antibodies, or WNT/β-catenin pathway antagonists/agonists. These experiments revealed that JAG1 and JAG2 regulated cell fate determination in the tracheobronchial epithelium; however, their roles did not adhere to simple necessity and sufficiency rules. Biochemical studies indicated that JAG1 and JAG2 underwent posttranslational modifications that resulted in generation of a JAG1 C-terminal peptide and regulated the abundance of full-length JAG2 on the cell surface. GSC and glycogen synthase kinase 3 were implicated in these posttranslational events, but WNT agonist/antagonist studies and RNA-Seq indicated a WNT-independent mechanism. Collectively, these data suggest that posttranslational modifications create distinct assemblies of JAG1 and JAG2, which regulate Notch signal strength and determine the fate of tracheobronchial stem/progenitor cells.

Abstract Although marine subsidies often enrich terrestrial ecosystems, their influence is known to be context‐dependent. Additionally, the multitrophic impact of marine subsidies has not been traced through food webs across physically diverse islands. Here, we test predictions about how island characteristics can affect marine enrichment of food web constituents and how nutrients flow through island food webs. To evaluate enrichment and trace marine nutrients across food webs, we used stable isotopes of soil, flora, and fauna (n = 4752 samples) collected from 97 islands in British Columbia, Canada. Island area was the strongest predictor of enrichment across taxa; we found that samples were more 15N‐rich on smaller islands. Enrichment declined with distance from shore but less so on small islands, implying a higher per‐unit‐area subsidy effect. These area and distance‐to‐shore effects were taxon‐specific, and nearly twice as strong in basal food web groups. We also found that increases in δ15N correlated with increases in %N in basal trophic groups, as well as in songbirds, implying biologically relevant uptake of a potentially limiting nutrient. Path analysis demonstrated that subsidies in soil flow through plants and detritivores, and into upper‐level consumers. Our results reveal an interplay between island biogeography and marine subsidies in shaping island food webs through bottom‐up processes.

The world’s largest extant fish, the whale shark Rhincodon typus, is one of the most-studied species of sharks globally. The discovery of predictable aggregation sites where these animals gather seasonally or are sighted year-round – most of which are coastal and juvenile-dominated – has allowed for a rapid expansion of research on this species. The most common method for studying whale sharks at these sites is photographic identification (photo-ID). This technique allows for long-term individual-based data to be collected which can, in turn, be used to evaluate population structure, build population models, identify long-distance movements, and assess philopatry and other population dynamics. Lagged identification rate (LIR) models have fewer underlying assumptions than more traditional capture mark recapture approaches, making them more broadly applicable to marine taxa, especially far-ranging megafauna species like whale sharks. However, the increased flexibility comes at a cost. Parameter estimations based on LIR can be difficult to interpret and may not be comparable between areas with different sampling regimes. Using a unique data-set from the Philippines with ~8 years of nearly continuous survey effort, we were able to derive a metric for converting LIR residency estimates into more intuitive days-per-year units. We applied this metric to 25 different sites allowing for the first quantitatively-meaningful comparison of sightings-derived residence among the world’s whale shark aggregations. We validated these results against the only three published acoustic residence metrics (falling within the ranges established by these earlier works in all cases). The results were then used to understand residency behaviours exhibited by the sharks at each site. The adjusted residency metric is an improvement to LIR-based population modelling, already one of the most widely used tools for describing whale shark aggregations. The standardised methods presented here can serve as a valuable tool for assessing residency patterns of whale sharks, which is crucial for tailored conservation action, and can cautiously be tested in other taxa.

We tested composite tracheal grafts (CTG) composed of a partially decellularized tracheal graft (PDTG) combined with a 3-dimensional (3D)-printed airway splint for use in long-segment airway reconstruction. CTG is designed to recapitulate the 3D extracellular matrix of the trachea with stable mechanical properties imparted from the extraluminal airway splint. We performed segmental orthotopic tracheal replacement in a mouse microsurgical model. MicroCT was used to measure graft patency. Tracheal neotissue formation was quantified histologically. Airflow dynamic properties were analyzed using computational fluid dynamics. We found that CTG are easily implanted and did not result in vascular erosion, tracheal injury, or inflammation. Graft epithelialization and endothelialization were comparable with CTG to control. Tracheal collapse was absent with CTG. Composite tracheal scaffolds combine biocompatible synthetic support with PDTG, supporting the regeneration of host epithelium while maintaining graft structure.

The pet trade in aquatic organisms is a significant source of non-indigenous species introductions. In comparison with ornamental animals, unintentionally transported invertebrate assemblages are easily overlooked by traders and keepers. Moreover, hitchhiking species detection and identification is difficult even for experts. The densities of “hitchhikers” in aquaria may be relatively higher than those in the wild. These phenomena are known in freshwater aquaria but poorly studied in marine ones. We found 17 species of non-ornamental marine invertebrates in one of the leading importers of aquarium species in the Czech Republic in November 2017. The set comprised six gastropods, two bivalves, three cnidarians, two echinoderms, two crustaceans, and two polychaete worms. In one case, a symbiont was also detected, associated with the host “hitchhiker”. No “live rocks” are traded by the surveyed wholesaler. Thus, the found animals were not imported together with this item as larvae or eggs. Contrary to the transport of targeted ornamental species, it is clear that transport of “hitchhikers” is occurring despite standard legislative regulations and should be brought to the attention of conservationists, wildlife managers, policymakers and other stakeholders.

Abstract Objective Stool repositories are a valuable resource for retrospective analyses including quantitative PCR assays to distinguish between asymptomatic shedding and clinical disease. The suitability of archival specimens for this purpose is unclear and requires assessment. We conducted a pilot study to evaluate pathogen detection by TaqMan Array Card (TAC) in travelers’ diarrhea (TD) stool specimens stored for 1–13 years, as well as the impact of transporting specimens on Whatman FTA Elute cards (FTA Cards) on detection. Results The positive percent agreement (PPA) for TAC on stool vs. microbiologic testing was lower than our a priori PPA estimate of 80% for most pathogens: Shigella spp. (100% [95%CI 69–100%]), enterotoxigenic E coli (ETEC) (63% [95%CI 49–75%]), Campylobacter spp. (66% [95%CI 43–85%]) and Norovirus (37% [95%CI 16–61%]). Use of the FTA card resulted in a further reduction of PPA. Our findings suggest that archival specimens may lead to insensitive detection on quantitative PCR assays due to degradation of nucleic acid with prolonged storage, although our limited sample size precluded us from evaluating the impact of storage duration on nucleic acid yield. Additional studies are needed to understand the impact of storage duration on quantitative PCR data.

Respiratory system damage is the primary cause of mortality in individuals who are exposed to vesicating agents including sulfur mustard (SM). Despite these devastating health complications, there are no fielded therapeutics that are specific for such injuries. Previous studies reported that SM inhalation depleted the tracheobronchial airway epithelial stem cell (TSC) pool and supported the hypothesis, TSC replacement will restore airway epithelial integrity and improve health outcomes for SM-exposed individuals. TSC express Major Histocompatibility Complex (MHC-I) transplantation antigens which increases the chance that allogeneic TSC will be rejected by the patient’s immune system. However, previous studies reported that Beta-2 microglobulin (B2M) knockout cells lacked cell surface MHC-I and suggested that B2M knockout TSC would be tolerated as an allogeneic graft. This study used a Cas9 ribonucleoprotein (RNP) to generate B2M-knockout TSC, which are termed Universal Donor Stem Cells (UDSC). Whole genome sequencing identified few off-target modifications and demonstrated the specificity of the RNP approach. Functional assays demonstrated that UDSC retained their ability to self-renew and undergo multilineage differentiation. A preclinical model of SM inhalation was used to test UDSC efficacy and identify any treatment-associated adverse events. Adult male Sprague-Dawley rats were administered an inhaled dose of 0.8 mg/kg SM vapor which is the inhaled LD50 on day 28 post-challenge. On recovery day 2, vehicle or allogeneic Fisher rat UDSC were delivered intravenously (n = 30/group). Clinical parameters were recorded daily, and planned euthanasia occurred on post-challenge days 7, 14, and 28. The vehicle and UDSC treatment groups exhibited similar outcomes including survival and a lack of adverse events. These studies establish a baseline which can be used to further develop UDSC as a treatment for SM-induced airway disease.

Abstract In their native range, Pacific salmon (Oncorhynchus spp.) have strong interactions with a multitude of species due to the annual pulse of marine‐derived nutrients that they deliver to streams and forests when they spawn and die. Over the past few decades, Chinook salmon (Oncorhynchus tshawytscha) has established non‐native populations throughout the Patagonia region of southern South America. Here, we provide the first assessment of the pathways through which salmon‐derived nutrients enter stream and forest food webs in Patagonia by surveying multiple streams in southern Chile to identify invertebrate and vertebrate consumers of salmon carcasses and summarizing all documented trophic interactions of Chinook salmon in Patagonia. Blowflies (Calliphoridae) were the dominant colonizer of carcasses in the riparian zone, and midge flies (Chironomidae) were the most common invertebrate on submerged carcasses. Camera trap monitoring in the riparian zone revealed consumption of carcasses or carcass‐associated invertebrates by the insectivorous passerine bird “chucao” (Scelorchilis rubecula), small rodents (black rat Rattus rattus, house mouse Mus musculus, and/or colilargo Oligoryzomys longicaudatus), the South American fox “culpeo” (Lycalopex culpaeus), and the invasive American mink (Neovison vison). A mink was filmed transferring a carcass from stream to streambank, indicating that vertebrate scavenging likely increases the degree to which marine‐derived nutrients enter terrestrial food webs. The native taxa that consume salmon are closely related to species that benefit from salmon consumption in North America, suggesting that the pathways of salmon nutrient incorporation in North American food webs have functionally re‐emerged in South America. Similarly, non‐native trout (Oncorhynchus mykiss and Salmo trutta) and mink consume salmon in Patagonia, and their eco‐evolutionary history of coexistence with salmon could mean that they are preadapted for salmon consumption and could thus be key beneficiaries of this invasion. Expanded monitoring of the abundance and impacts of salmon will be vital for understanding how these novel inputs of marine‐derived nutrients alter Patagonian food webs.

Conservation and management of mobile marine species requires an understanding of how movement behaviour and space-use varies among individuals and populations, and how intraspecific differences influence exposure to anthropogenic threats. Because of their long-distance movements, broad distribution and long lifespan, whale sharks (Rhincodon typus) can encounter multiple, cumulative threats. However, we lack knowledge on how sharks at different aggregations use their habitats, and how geographic variation in anthropogenic threats influences their vulnerability to population decline. Using movement data from 111 deployments of satellite-linked tags, we examined how whale sharks at five aggregations in the Indian Ocean varied in their exposure to six anthropogenic impacts known to threaten this endangered species. Tagged sharks were detected in territorial waters of 24 countries, and international waters, with individuals travelling up to 11,401 km. Despite long-distance movements, tagged sharks from each aggregation occupied mutually exclusive areas of the Indian Ocean, where they encountered different levels of anthropogenic impacts. Sharks in the Arabian Gulf had the greatest proximity to oil and gas platforms, and encountered the warmest sea surface temperatures and highest levels of shipping, pollution and ocean acidification, while those from the Maldives and Mozambique aggregations had the highest exposure to fishing and human population impacts respectively. Our findings highlight the need for aggregation-specific conservation efforts to mitigate regional threats to whale sharks. Multinational coordination is essential for implementing these efforts beyond national jurisdictions and tackling issues of global conservation concern, including the consequences of climate change and an expanding human population.

The average body size of salmon has declined rapidly over recent decades. Here the authors quantify changes in body size distributions for Pacific salmon in Alaska and examine the causes and consequences of size declines for ecosystems, food security, and commercial fisheries.

Abstract Background Campylobacter jejuni is a leading cause of bacterial diarrhea worldwide, and increasing rates of fluoroquinolone (FQ) resistance in C. jejuni are a major public health concern. The rapid detection and tracking of FQ resistance are critical needs in developing countries, as these antimicrobials are widely used against C. jejuni infections. Detection of point mutations at T86I in the gyrA gene by real-time polymerase chain reaction (RT-PCR) is a rapid detection tool that may improve FQ resistance tracking. Methods C. jejuni isolates obtained from children with diarrhea in Peru were tested by RT-PCR to detect point mutations at T86I in gyrA. Further confirmation was performed by sequencing of the gyrA gene. Results We detected point mutations at T86I in the gyrA gene in 100% (141/141) of C. jejuni clinical isolates that were previously confirmed as ciprofloxacin-resistant by E-test. No mutations were detected at T86I in gyrA in any ciprofloxacin-sensitive isolates. Conclusions Detection of T86I mutations in C. jejuni is a rapid, sensitive, and specific method to identify fluoroquinolone resistance in Peru. This detection approach could be broadly employed in epidemiologic surveillance, therefore reducing time and cost in regions with limited resources.

Abstract Objective: Schools are an important setting for skin cancer prevention. An intervention for implementation of school sun safety policy, Sun Safety Schools (SSS), was evaluated. Methods: Primary schools (n=118) in California school districts that had already adopted a sun safety policy were enrolled in a study with a randomised controlled design. Half of the schools were randomised to SSS intervention (N=58). Parents completed an online post‐test. Results: More parents in intervention schools received information about sun safety (mean=26.3%, sd=3.1%, p=0.017) and children more frequently wore sun‐protective clothing when not at school (mean=2.93, sd=0.03, p=0.033) than in control schools (mean=18.0%, sd=2.5%; mean=2.83, sd=0.03, respectively). In schools where principals reported implementing sun safety practices, parents reported that children spent less time outdoors at midday (mean=14.78 hours, sd=0.25, p=0.033) and fewer were sunburned (mean=12.7%, sd=1.1%, p=0.009) than in non‐implementing schools (M=16.3 hours, sd=0.67; mean=21.2%, sd=3.8%, respectively). Parents who received sun safety information (mean=3.08, sd=0.04, p=0.008) reported more child sun protection than parents not receiving information (mean=2.96, sd=0.02). Conclusions: A school district sun protection policy and support for implementation increased dissemination of sun safety information to parents and student sun safety. Implications for public health: Technical assistance for sun safety policies may increase sun protection of children.

Designing reliable, scalable and energy efficient data storage systems that can operate in extreme temperatures, remains a challenge. Here, the authors demonstrate a nanoelectromechanical relay that does not exhibit pull-in instability for reliable reprogrammable non-volatile memory operation.

A 12 year-old female spayed felid presented after a 35 day history of right eye pain. On examination, a sub-epithelial opacity was identified in the cornea. A lamellar keratectomy was performed and histopathological analysis revealed low numbers of 2x4um, Gram, Hamatoxylin-eosin and Gomori methanamine-silver positive spores. Transmission electron microscopy found ultrastructural findings consistent with the phylum Microspora. To the author's knowledge, this is only the second case of microsporidial stromal keratitis reported in a felid. Keywords: Microsporidial, Fungal, Keratitis, Feline, Veterinary

Abstract Background Malaria continues to affect over 200 million individuals every year, especially children in Africa. Rapid and sensitive detection and identification of Plasmodium parasites is crucial for treating patients and monitoring of control efforts. Compared to traditional diagnostic methods such as microscopy and rapid diagnostic tests (RDTs), DNA based methods, such as polymerase chain reaction (PCR) offer significantly higher sensitivity, definitive discrimination of Plasmodium species, and detection of mixed infections. While PCR is not currently optimized for routine diagnostics, its role in epidemiological studies is increasing as the world moves closer toward regional and eventually global malaria elimination. This study demonstrates the field use of a novel, ambient temperature-stabilized, multiplexed PCR assay in a small hospital setting in Sierra Leone. Methods Blood samples from 534 febrile individuals reporting to a hospital in Bo, Sierra Leone, were tested using three methods: a commercial RDT, microscopy, and a Multiplex Malaria Sample Ready (MMSR) PCR designed to detect a universal malaria marker and species-specific markers for Plasmodium falciparum and Plasmodium vivax. A separate PCR assay was used to identify species of Plasmodium in samples in which MMSR detected malaria, but was unable to identify the species. Results MMSR detected the presence of any malaria marker in 50.2% of all tested samples with P. falciparum identified in 48.7% of the samples. Plasmodium vivax was not detected. Testing of MMSR P. falciparum-negative/universal malaria-positive specimens with a panel of species-specific PCRs revealed the presence of Plasmodium malariae (n = 2) and Plasmodium ovale (n = 2). The commercial RDT detected P. falciparum in 24.6% of all samples while microscopy was able to detect malaria in 12.8% of tested specimens. Conclusions Wider application of PCR for detection of malaria parasites may help to fill gaps existing as a result of use of microscopy and RDTs. Due to its high sensitivity and specificity, species coverage, room temperature stability and relative low complexity, the MMSR assay may be useful for detection of malaria and epidemiological studies especially in low-resource settings.

Summary: Understanding the formulation and manufacturing parameters that lead to higher energy density and longevity is critical to designing energy-dense graphite electrodes for battery applications. A limited dataset that includes 27 different formulation, manufacturing protocols, and performance properties is reported. Input parameters from formulation and manufacturing are varied: slurry composition, mixing protocol, electrode coating gap size, drying temperature, coating speed, and calendering. Measurable outputs from the rheological characteristics, adhesion, and electrochemical testing are recorded. A database with the inputs and output parameters is populated and used to train an artificial intelligence model. Validation of the model is performed upon test data and an optimized electrode formulation and manufacturing process predicted. The electrode manufactured using the model process shows excellent cycle life and capacity agreement to prediction. The data model can be used to predict and design the formulation and manufacturing process to produce thick, high-coat-weight, graphite-based electrodes.

Lithium-ion battery electrode design and manufacture is a multi-faceted process where the link between underlying physical processes and manufacturing outputs is not yet fully understood. This is in part due to the many parameters and variables involved and the lack of complete data sets under different processing conditions. The slurry coating step has significant implications for electrode design and advanced metrology offers opportunities to improve understanding and control at this stage. Here, metrology options for slurry coating are reviewed as well as opportunities for in-line integration, discussing the benefits of combining advanced metrology to provide comprehensive characterisation, improve understanding and feed into predictive design models. There is a comprehensive range of metrology which needs little improvement to provide the relevant quantifiable measures during coating, with one exception of particle sizing, where more precise, in-line measurement would be beneficial. However, there is a lack of studies that bring together the latest advancements in electrode coating metrology which is crucial to understanding the interdependency of myriad processing and product parameters. This review highlights the need for a comprehensive metrological picture whose value would be much greater than the sum of its parts for the next generation of multiphysics and data-driven models.

Abstract Pacific salmon (Oncorhynchus spp.) carcasses can fertilize riparian forests with marine‐derived nutrients when populations make their annual return to natal streams to spawn; however, the strength of this cross‐system linkage likely varies substantially among years due to the interannual fluctuations in abundance that characterize most salmon populations. Here, we used a 36‐yr time series (1984–2019) of satellite imagery and salmon abundance estimates to assess spatiotemporal associations between forest greenness (a measure of plant productivity) and adult sockeye salmon (Oncorhynchus nerka) abundance in the lower Adams River, British Columbia, Canada. The Adams River sockeye population displays a quadrennial pattern of abundance, with a dominant cohort that spawns every four years in numbers that are typically two to three orders of magnitude larger than non‐dominant cohorts. We found that variation in forest greenness was consistently explained best by models including dominant cohort year, whereas models lacking an index of salmon abundance were the lowest‐ranked. Greenness of riparian vegetation increased by an average of 0.015 NDVI units (approximately 1%) in the summer after a dominant cohort return, and this effect on greenness persisted into the subsequent fall (11–13 months after spawning). The positive association between quadrennial pulses of salmon and riparian greenness occurred in plots both within 30 m of the stream and 95–125 m away from the stream, indicating that the spatial extent of fertilization may occur well beyond areas directly adjacent to the riverbank. These results suggest that forests respond to cyclical variation in salmon abundance and that overwinter storage of marine‐derived nutrients within catchments allows plants to capitalize on these nutrients in the following growing season. Continued advances in remote sensing technology will enhance our understanding of cross‐system resource linkages and can inform the ecosystem‐based management of Pacific salmon.

Preventable healthcare-associated harm results in significant morbidity and mortality in the United States, costing nearly 400 000 patient lives annually. The Institute for Healthcare Improvement provides high-quality educational resources tailored for working healthcare professionals. One such resource is the Certified Professional in Patient Safety (CPPS™) review course, which equips professionals with advanced proficiency in 5 core patient safety domains. The CPPS™ certification is the only interprofessional, patient safety science credential recognized worldwide. In 2010, the Lucian Leape Institute at the National Patient Safety Foundation described the critical need for medical students to participate in patient safety solutions as well. However, equivalent patient safety credentialing remains challenging for students in the preclinical and clinical stages of training to obtain. To address this growing dilemma, the Texas College of Osteopathic Medicine (TCOM) piloted the first-of-its-kind CPPS™ course with 10 medical students to test a novel, academic-level approach to patient safety curriculum. Medical students showed large gains in performance on the post-test (83.18% ± 26.12%) compared to the pre-test (46.46% ± 27.18%) ( P

Decellularized tracheal scaffolds offer a potential solution for the repair of long-segment tracheal defects. However, complete decellularization of trachea is complicated by tracheal collapse. We created a partially decellularized tracheal scaffold (DTS) and characterized regeneration in a mouse model of tracheal transplantation. All cell populations except chondrocytes were eliminated from DTS. DTS maintained graft integrity as well as its predominant extracellular matrix (ECM) proteins. We then assessed the performance of DTS in vivo. Grafts formed a functional epithelium by study endpoint (28 days). While initial chondrocyte viability was low, this was found to improve in vivo . We then used atomic force microscopy to quantify micromechanical properties of DTS, demonstrating that orthotopic implantation and graft regeneration lead to the restoration of native tracheal rigidity. We conclude that DTS preserves the cartilage ECM, supports neo-epithelialization, endothelialization and chondrocyte viability, and can serve as a potential solution for long-segment tracheal defects.