Radar for Europa Assessment and Sounding: Ocean to Near-Surface (REASON).

The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon. REASON will investigate processes governing this material exchange by characterizing the distribution of putative non-ice material (e.g., brines, salts) in the subsurface, searching for an ice-ocean interface, characterizing the ice shell's global structure, and constraining the amplitude of Europa's radial tidal deformations. REASON will accomplish these science objectives using a combination of radar measurement techniques including altimetry, reflectometry, sounding, interferometry, plasma characterization, and ranging. Building on a rich heritage from Earth, the moon, and Mars, REASON will be the first ice-penetrating radar to explore the outer solar system. Because these radars are untested for the icy worlds in the outer solar system, a novel approach to measurement quality assessment was developed to represent uncertainties in key properties of Europa that affect REASON performance and ensure robustness across a range of plausible parameters suggested for the icy moon. REASON will shed light on a never-before-seen dimension of Europa and - in concert with other instruments on Europa Clipper - help to investigate whether Europa is a habitable world.

Oil and gas development exposure and atrial fibrillation exacerbation: a retrospective study of atrial fibrillation exacerbation using Colorado's all payer claims dataset.

Introduction: Emerging risk factors for atrial fibrillation (AF) incidence and episodes (exacerbation), the most common and clinically significant cardiac arrhythmia, include air and noise pollution, both of which are emitted during oil and natural gas (O&G) well site development. Methods: We evaluated AF exacerbation risk and proximity to O&G well site development by employing a novel data source and interrupted time-series design. We retrospectively followed 1,197 AF patients living within 1-mile of an O&G well site (at-risk of exposure) and 9,764 patients living >2 miles from any O&G well site (unexposed) for AF claims in Colorado's All Payer Claims Dataset before, during, and after O&G well site development. We calculated AF exacerbation risk with multi-failure survival analysis. Results: The analysis of the total study population does not provide strong evidence of an association between AF exacerbation and proximity to O&G wells sites during (HR = 1.07, 95% CI: 0.94, 1.22) or after (HR = 1.01, 95% CI: 0.88, 1.16) development. However, AF exacerbation risk differed by patient age and sex. In patients >80 years living within 0.39 miles (2,059 feet) of O&G well site development, AF exacerbation risk increased by 83% (HR = 1.83, 95% CI: 1.25, 2.66) and emergency room visits for an AF event doubled (HR = 2.55, 95% CI: 1.50, 4.36) during development, with risk increasing with proximity. In female patients living within 0.39 miles of O&G well site development, AF exacerbation risk increased by 56% percent (95% CI: 1.13, 2.15) during development. AF exacerbation risk did not persist past the well development period. We did not observe increased AF exacerbation risk in younger or male patients. Discussion: The prospect that proximity to O&G well site development, a significant noise and air pollution source, may increase AF exacerbation risk in older and female AF patients requires attention. These findings support appropriate patient education to help mitigate risk and development of mitigation strategies and regulations to protect the health of populations in O&G development regions.

Associations between COVID-19 therapies and outcomes in rural and urban America: A multisite, temporal analysis from the Alpha to Omicron SARS-CoV-2 variants.

PURPOSE: To investigate the enduring disparities in adverse COVID-19 events between urban and rural communities in the United States, focusing on the effects of SARS-CoV-2 vaccination and therapeutic advances on patient outcomes. METHODS: Using National COVID Cohort Collaborative (N3C) data from 2021 to 2023, this retrospective cohort study examined COVID-19 hospitalization, inpatient death, and other adverse events. Populations were categorized into urban, urban-adjacent rural (UAR), and nonurban-adjacent rural (NAR). Adjustments included demographics, variant-dominant waves, comorbidities, region, and SARS-CoV-2 treatment and vaccination. Statistical methods included Kaplan-Meier survival estimates, multivariable logistic, and Cox regression. FINDINGS: The study included 3,018,646 patients, with rural residents constituting 506,204. These rural dwellers were older, had more comorbidities, and were less vaccinated than their urban counterparts. Adjusted analyses revealed higher hospitalization odds in UAR and NAR (aOR 1.07 [1.05-1.08] and 1.06 [1.03-1.08]), greater inpatient death hazard (aHR 1.30 [1.26-1.35] UAR and 1.37 [1.30-1.45] NAR), and greater risk of other adverse events compared to urban dwellers. Delta increased, while Omicron decreased, inpatient adverse events relative to pre-Delta, with rural disparities persisting throughout. Treatment effectiveness and vaccination were similarly protective across all cohorts, but dexamethasone post-ventilation was effective only in urban areas. Nirmatrelvir/ritonavir and molnupiravir better protected rural residents against hospitalization. CONCLUSIONS: Despite advancements in treatment and vaccinations, disparities in adverse COVID-19 outcomes persist between urban and rural communities. The effectiveness of some therapeutic agents appears to vary based on rurality, suggesting a nuanced relationship between treatment and geographic location while highlighting the need for targeted rural health care strategies.

High economic inequality is linked to greater moralization.

Throughout the 21st century, economic inequality is predicted to increase as we face new challenges, from changes in the technological landscape to the growing climate crisis. It is crucial we understand how these changes in inequality may affect how people think and behave. We propose that economic inequality threatens the social fabric of society, in turn increasing moralization-that is, the greater tendency to employ or emphasize morality in everyday life-as an attempt to restore order and control. Using longitudinal data from X, formerly known as Twitter, our first study demonstrates that high economic inequality is associated with greater use of moral language online (e.g. the use of words such as "disgust", "hurt", and "respect'). Study 2 then examined data from 41 regions around the world, generally showing that higher inequality has a small association with harsher moral judgments of people's everyday actions. Together these findings demonstrate that economic inequality is linked to the tendency to see the world through a moral lens.

Cyanotoxin accumulation and growth patterns of biocrust communities under variable environmental conditions.

Biocrusts dominate the soil surface in deserts and are composed of diverse microbial communities that provide important ecosystem services. Cyanobacteria in biocrusts produce many secondary metabolites, including the neurotoxins BMAA, AEG, DAB, anatoxin-a(S) (guanitoxin), and the microcystin hepatotoxins, all known or suspected to cause disease or illness in humans and other animals. We examined cyanobacterial growth and prevalence of these toxins in biocrusts at millimeter-scales, under a desert-relevant illumination gradient. In contrast to previous work, we showed that hydration had an overall positive effect on growth and toxin accumulation, that nitrogen was not correlated with growth or toxin production, and that phosphorus enrichment negatively affected AEG and BMAA concentrations. Excess illumination positively correlated with AEG, and negatively correlated with all other toxins and growth. Basic pH negatively affected only the accumulation of BMAA. Anatoxin-a(S) (guanitoxin) was not correlated with any tested variables, while microcystins were not detected in any of the samples. Concerning toxin pools, AEG and BMAA were good predictors of the presence of one another. In a newly conceptualized scheme, we integrate aspects of biocrust growth and toxin pool accumulations with arid-relevant desertification drivers.

Metagenome-enabled models improve genomic predictive ability and identification of herbivory-limiting genes in sweetpotato.

Plant-insect interactions are often influenced by host- or insect-associated metagenomic community members. The relative abundance of insects and the microbes that modulate their interactions were obtained from sweetpotato (Ipomoea batatas) leaf-associated metagenomes using quantitative reduced representation sequencing and strain/species-level profiling with the Qmatey software. Positive correlations were found between whitefly (Bemisia tabaci) and its endosymbionts (Candidatus Hamiltonella defensa, Candidatus Portiera aleyrodidarum, and Rickettsia spp.) and negative correlations with nitrogen-fixing bacteria that implicate nitric oxide in sweetpotato-whitefly interaction. Genome-wide associations using 252 975 dosage-based markers, and metagenomes as a covariate to reduce false positive rates, implicated ethylene and cell wall modification in sweetpotato-whitefly interaction. The predictive abilities (PA) for whitefly and Ocypus olens abundance were high in both populations (68%-69% and 33.3%-35.8%, respectively) and 69.9% for Frankliniella occidentalis. The metagBLUP (gBLUP) prediction model, which fits the background metagenome-based Cao dissimilarity matrix instead of the marker-based relationship matrix (G-matrix), revealed moderate PA (35.3%-49.1%) except for O. olens (3%-10.1%). A significant gain in PA after modeling the metagenome as a covariate (gGBLUP, ≤11%) confirms quantification accuracy and that the metagenome modulates phenotypic expression and might account for the missing heritability problem. Significant gains in PA were also revealed after fitting allele dosage (≤17.4%) and dominance effects (≤4.6%). Pseudo-diploidized genotype data underperformed for dominance models. Including segregation-distorted loci (SDL) increased PA by 6%-17.1%, suggesting that traits associated with fitness cost might benefit from the inclusion of SDL. Our findings confirm the holobiont theory of host-metagenome co-evolution and underscore its potential for breeding within the context of G × G × E interactions.

Removing the FDA's Boxed Hepatotoxicity Warning and Liver Function Testing Requirement for Ambrisentan.

Importance: Endothelin receptor antagonists are first-line therapy for pulmonary arterial hypertension (PAH). The first 2 agents approved in the class, bosentan and ambrisentan, initially carried boxed warnings for hepatotoxicity and required monthly liver function tests (LFTs) as part of a risk evaluation and mitigation strategy (REMS); however, in 2011, as further safety data emerged on ambrisentan, the boxed hepatotoxicity warning and LFT requirements were removed. Objective: To analyze changes in the use of and LFT monitoring for ambrisentan and bosentan after changes to the ambrisentan labeling and REMS. Design, Setting, and Participants: This serial cross-sectional study used data from 3 longitudinal health care insurance claims databases-Medicaid, Optum's deidentified Clinformatics Data Mart, and Merative Marketscan-to perform an interrupted time series analysis of prescription fills and LFTs for patients taking ambrisentan and bosentan. Participants were patients filling prescriptions for ambrisentan and bosentan from July 1, 2007, to December 31, 2018. Data analysis was performed from April 2021 to August 2023. Exposure: Removal of the boxed warning for hepatotoxicity and the REMS LFT monitoring requirements on ambrisentan in March 2011. Main Outcomes and Measures: The primary outcomes were use of ambrisentan (ie, individuals with at least 1 dispensing per 1 000 000 individuals enrolled in the 3 datasets) vs bosentan and LFT monitoring (ie, proportion of initiators with at least 1 ordered test) before initiation and before the first refill. Results: A total of 10 261 patients received a prescription for ambrisentan during the study period (7442 women [72.5%]; mean [SD] age, 52.6 [17.6] years), and 11 159 patients received a prescription for bosentan (7931 women [71.1%]; mean [SD] age, 47.7 [23.7] years). Removal of the ambrisentan boxed hepatotoxicity warning and LFT monitoring requirement was associated with an immediate increase in the use of ambrisentan (1.50 patients per million enrollees; 95% CI, 1.08 to 1.92 patients per million enrollees) but no significant change in the use of bosentan. There were reductions in recorded LFTs before drug initiation (13.1% absolute decrease; 95% CI, -18.2% to -8.0%) and before the first refill (26.4% absolute decrease; 95% CI, -34.4% to -18.5%) of ambrisentan but not bosentan. Conclusions and Relevance: In this serial cross-sectional study of ambrisentan, labeling changes and removal of the REMS-related LFT requirement were associated with shifts in prescribing and testing behavior for ambrisentan but not bosentan. Further clinician education may be needed to maximize the benefits of REMS programs and labeling warnings designed to ensure the safe administration of high-risk medications.

Information avoidance: An interchangeable strategy of self-protection.

Across two studies, using five samples (N = 1,850), we examined whether health information avoidance-the deliberate decision to remain ignorant of available but unwanted personal health information-serves a defensive purpose and is interchangeable with other defensive strategies. We tested this idea by examining the relationship between health information avoidance-both as a dispositional tendency and deliberate decision-and feedback derogation. In Study 1, we experimentally demonstrated that a situation known to reduce defensiveness-self-uncertainty-decreased both proactive avoidance and reactive defensiveness relative to a control group. Study 2 demonstrated, across four samples, that people with a greater defensive orientation toward personal health information were more likely to derogate health information. These results are consistent with the idea that feedback derogation replaced the decision to avoid feedback. Together, results suggest that health information avoidance is likely part of a broader self-protective system and is replaceable with other motivated self-protection strategies.

Correction: Towards control of excitonic coupling in DNA-templated Cy5 aggregates: the principal role of chemical substituent hydrophobicity and steric interactions.

Correction for 'Towards control of excitonic coupling in DNA-templated Cy5 aggregates: the principal role of chemical substituent hydrophobicity and steric interactions' by Sebastián A. Díaz et al., Nanoscale, 2023, 15, 3284-3299. https://doi.org/10.1039/D2NR05544A.

Pan-Evo: The Evolution of Information and Biology's Part in This.

Many people wonder whether biology, including humans, will benefit or experience harm from new developments in information such as artificial intelligence (AI). Here, it is proposed that biological and non-biological information might be components of a unified process, 'Panevolution' or 'Pan-Evo', based on four basic operations-innovation, transmission, adaptation, and movement. Pan-Evo contains many types of variable objects, from molecules to ecosystems. Biological innovation includes mutations and behavioural changes; non-biological innovation includes naturally occurring physical innovations and innovation in software. Replication is commonplace in and outside biology, including autocatalytic chemicals and autonomous software replication. Adaptation includes biological selection, autocatalytic chemicals, and 'evolutionary programming', which is used in AI. The extension of biological speciation to non-biological information creates a concept called 'Panspeciation'. Panevolution might benefit or harm biology, but the harm might be minimal if AI and humans behave intelligently because humans and the machines in which an AI resides might split into vastly different environments that suit them. That is a possible example of Panspeciation and would be the first speciation event involving humans for thousands of years. This event will not be particularly hostile to humans if humans learn to evaluate information and cooperate better to minimise both human stupidity and artificial simulated stupidity (ASS-a failure of AI).

A new method for ecologists to estimate heterozygote excess and deficit for multi-locus gene families.

The fixation index, F IS, has been a staple measure to detect selection, or departures from random mating in populations. However, current Next Generation Sequencing (NGS) cannot easily estimate F IS, in multi-locus gene families that contain multiple loci having similar or identical arrays of variant sequences of ≥1 kilobase (kb), which differ at multiple positions. In these families, high-quality short-read NGS data typically identify variants, but not the genomic location, which is required to calculate F IS (based on locus-specific observed and expected heterozygosity). Thus, to assess assortative mating, or selection on heterozygotes, from NGS of multi-locus gene families, we need a method that does not require knowledge of which variants are alleles at which locus in the genome. We developed such a method. Like F IS, our novel measure, 1 H IS, is based on the principle that positive assortative mating, or selection against heterozygotes, and some other processes reduce within-individual variability relative to the population. We demonstrate high accuracy of 1 H IS on a wide range of simulated scenarios and two datasets from natural populations of penguins and dolphins. 1 H IS is important because multi-locus gene families are often involved in assortative mating or selection on heterozygotes. 1 H IS is particularly useful for multi-locus gene families, such as toll-like receptors, the major histocompatibility complex in animals, homeobox genes in fungi and self-incompatibility genes in plants.

Commercial markups on pediatric oncology drugs at 340B pediatric hospitals.

Eligible pediatric hospitals can purchase clinician-administered drugs at discounted rates through the 340B Drug Pricing Program and charge payers prices exceeding drug acquisition costs, but the magnitude of these markups is not known. In a study of newly approved oncology drugs at pediatric 340B hospitals, median negotiated prices ranged from 102% (interquartile range [IQR]: 91%-156%) of average sales price (ASP) at Phoenix Children's Hospital to 630% (IQR: 526%-630%) at Driscoll Children's Hospital. Pediatric hospitals participating in the federal 340B Drug Pricing Program can extract steep payments on new drugs from commercial insurers, though with wide variation between and within hospitals.

Evolutionary genomic analyses of canine E. coli infections identify a relic capsular locus associated with resistance to multiple classes of antimicrobials.

Infections caused by antimicrobial-resistant Escherichia coli are the leading cause of death attributed to antimicrobial resistance (AMR) worldwide, and the known AMR mechanisms involve a range of functional proteins. Here, we employed a pan-genome wide association study (GWAS) approach on over 1,000 E. coli isolates from sick dogs collected across the US and Canada and identified a strong statistical association (empirical P < 0.01) of AMR, involving a range of antibiotics to a group 1 capsular (CPS) gene cluster. This cluster included genes under relaxed selection pressure, had several loci missing, and had pseudogenes for other key loci. Furthermore, this cluster is widespread in E. coli and Klebsiella clinical isolates across multiple host species. Earlier studies demonstrated that the octameric CPS polysaccharide export protein Wza can transmit macrolide antibiotics into the E. coli periplasm. We suggest that the CPS in question, and its highly divergent Wza, functions as an antibiotic trap, preventing antimicrobial penetration. We also highlight the high diversity of lineages circulating in dogs across all regions studied, the overlap with human lineages, and regional prevalence of resistance to multiple antimicrobial classes. IMPORTANCE: Much of the human genomic epidemiology data available for E. coli mechanism discovery studies has been heavily biased toward shiga-toxin producing strains from humans and livestock. E. coli occupies many niches and produces a wide variety of other significant pathotypes, including some implicated in chronic disease. We hypothesized that since dogs tend to share similar strains with their owners and are treated with similar antibiotics, their pathogenic isolates will harbor unexplored AMR mechanisms of importance to humans as well as animals. By comparing over 1,000 genomes with in vitro antimicrobial susceptibility data from sick dogs across the US and Canada, we identified a strong multidrug resistance association with an operon that appears to have once conferred a type 1 capsule production system.

Prophylactic Antibiotic Choice and Deep Infection in Lower Extremity Endoprosthetic Reconstruction: Comparison of Cefazolin, Cefazolin-Vancomycin, and Alternative Regimens.

INTRODUCTION: Infection is a common mode of failure in lower extremity endoprostheses. The Prophylactic Antibiotic Regimens in Tumor Surgery trial reported that 5 days of cefazolin had no difference in surgical site infection compared with 24 hours of cefazolin. Our purpose was to evaluate infection rates of patients receiving perioperative cefazolin monotherapy, cefazolin-vancomycin dual therapy, or alternative antibiotic regimens. METHODS: A single-center retrospective review was conducted on patients who received lower extremity endoprostheses from 2008 to 2021 with minimum 1-year follow-up. Three prophylactic antibiotic regimen groups were compared: cefazolin monotherapy, cefazolin-vancomycin dual therapy, and alternative regimens. The primary outcome was deep infection, defined by a sinus tract, positive culture, or clinical diagnosis. Secondary outcomes were revision surgery, microorganisms isolated, and superficial wound issues. RESULTS: The overall deep infection rate was 10% (30/294) at the median final follow-up of 3.0 years (IQR 1.7 to 5.4). The deep infection rates in the cefazolin, cefazolin-vancomycin, and alternative regimen groups were 8% (6/72), 10% (18/179), and 14% (6/43), respectively (P = 0.625). Patients not receiving cefazolin had an 18% deep infection rate (6/34) and 21% revision surgery rate (7/34) compared with a 9% deep infection rate (24/260) (P = 0.13) and 12% revision surgery rate (31/260) (P = 0.17) in patients receiving cefazolin. In those not receiving cefazolin, 88% (30/34) were due to a documented penicillin allergy, only two being anaphylaxis. All six patients in the alternative regimen group who developed deep infections did not receive cefazolin secondary to nonanaphylactic penicillin allergy. CONCLUSION: The addition of perioperative vancomycin to cefazolin in lower extremity endoprosthetic reconstructions was not associated with a lower deep infection rate. Patients who did not receive cefazolin trended toward higher rates of deep infection and revision surgery, although not statistically significant. The most common reason for not receiving cefazolin was a nonanaphylactic penicillin allergy, highlighting the continued practice of foregoing cefazolin unnecessarily.

Preoperative Identification and Outcomes of Vascular Variants on Surgery for Chronic Pancreatitis.

INTRODUCTION: Surgeries for chronic pancreatitis are tailored based on disease process and either include parenchymal-preserving surgeries or total pancreatectomy with or without islet cell autotransplantation. It is critical to account for vascular variants as injuries to these are associated with short- and long-term morbidity and mortality. There is a lack of contemporary data on the true incidence of aberrant arterial anatomy, and it is likely to be underreported by nonhepatobiliary radiologists. METHODS: This study is a retrospective analysis of all patients undergoing pancreatic resections for chronic pancreatitis at the single center. The presence of vascular variants was compared between standard reporting and preoperative imaging review by a hepatobiliary radiologist and surgeon. Primary outcomes were operative time and blood loss. RESULTS: Of the 72 pancreatic resections for chronic pancreatitis, 50 (69%) satisfied inclusion criteria. Three of fifty (6%) had vascular anomalies reported on standard reporting while 11 (22%) had vascular anomalies identified on preoperative imaging review and confirmed at surgery. Hence, only 27% of patients with variant vascular anatomy were reported on standard imaging. There was no significant difference in operative times or blood loss between those with and without known vascular anomalies. CONCLUSIONS: Pancreatic resection is a complex undertaking as long-standing inflammation distorts anatomic planes and increases opportunity for inadvertent vascular injury especially if there are aberrant vessels. In this study, we found that anatomic vascular variants are oftentimes not reported. Dedicated surgical planning with review of cross-sectional imaging identified all cases of anatomic variants resulting in no difference in operative time or incidence of intraoperative hemorrhage.

Review of Connections in the clinic: Relational narratives from team-based primary care.

Reviews the book, Connections in the Clinic: Relational Narratives from Team-Based Primary Care edited by Randall Reitz, Laura E. Sudano, and Mark P. Knudson (2021). This book is an edited collection of poems and stories reflecting the personal nature of the mission, vision, and practice of integrated primary care. This collection reflects the biopsychosocial model, which has been growing steadily in research and practice over the last few decades. These stories from the frontlines illustrate the increased awareness of the strong mind-body-interpersonal and team connections that are a critical part of a successful primary care system. This book is intended to be inspirational for anyone working in a primary care clinic. The editors describe the central purpose of the book is to find meaning in the relationships that are created in team-based primary care. This is a book where these stories are collected to expand our recognition and appreciation of the full diversity of patterns in our personal and work lives. The collection of stories is intended to inspire readers to actively practice their own reflections and learnings and encourages sharing them with others. (PsycInfo Database Record (c) 2024 APA, all rights reserved).