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Abstract Human space exploration poses inherent risks to astronauts’ health, leading to molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these changes bear similarities to those observed during the aging process on Earth. However, our understanding of the connection between these molecular shifts and disease development in space remains limited. Frailty syndrome, a clinical syndrome associated with biological aging, has not been comprehensively investigated during spaceflight. To bridge this knowledge gap, we leveraged murine data obtained from NASA’s GeneLab, along with astronaut data gathered from the JAXA and Inspiration4 missions. Our objective was to assess the presence of biological markers and pathways related to frailty, aging, and sarcopenia within the spaceflight context. Through our analysis, we identified notable changes in gene expression patterns that may be indicative of the development of a frailty-like condition during space missions. These findings suggest that the parallels between spaceflight and the aging process may extend to encompass frailty as well. Consequently, further investigations exploring the utility of a frailty index in monitoring astronaut health appear to be warranted.

Abstract Our previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing and transcriptomic analysis on 3D microvessel cell cultures exposed to simulated deep space radiation (0.5 Gy of Galactic Cosmic Radiation) with and without the antagonists to three microRNAs: miR-16-5p, miR-125b-5p, and let-7a-5p (i.e., antagomirs). Significant reduction of inflammation and DNA double strand breaks (DSBs) activity and rescue of mitochondria functions are observed after antagomir treatment. Using data from astronaut participants in the NASA Twin Study, Inspiration4, and JAXA missions, we reveal the genes and pathways implicated in the action of these antagomirs are altered in humans. Our findings indicate a countermeasure strategy that can potentially be utilized by astronauts in spaceflight missions to mitigate space radiation damage.

​​​​​​​The ability to detect and quantify methane emissions from offshore platforms is of considerable interest in providing actionable feedback to industrial operators. While satellites offer a distinctive advantage for remote sensing of offshore platforms which may otherwise be difficult to reach, offshore measurements of methane from satellite instruments in the shortwave infrared are challenging due to the low levels of diffuse sunlight reflected from water surfaces. Here, we use the GHGSat satellite constellation in a sun glint configuration to detect and quantify methane emissions from offshore targets around the world. We present a variety of examples of offshore methane plumes, including the largest single emission at (84 000 ± 24 000) kg h−1 observed by GHGSat from the Nord Stream 2 pipeline leak in 2022 and the smallest offshore emission measured from space at (180 ± 130) kg h−1 in the Gulf of Mexico. In addition, we provide an overview of the constellation's offshore measurement capabilities. We measure a median column precision of 2.1 % of the background methane column density and estimate a detection limit, from analytical modelling and orbital simulations, that varies between 160 and 600 kg h−1 depending on the latitude and season.

Introduction: Each year the number of combined heart-liver transplants (HLT) increases, with two distinct patient populations proceeding down this pathway. The first are patients with congenital heart disease (CHD), most commonly single ventricle patients palliated with Fontan. The second group are those with long standing congestive hepatopathy, amyloidosis, hemochromatosis, or alcohol induced myopathies and liver disease.One argument for HLT has been the low rate of rejection even among sensitized patients, with reported rejection rates ranging from 0% to 31%. Historically, those with CHD have been highly sensitized which in some cases may prevent or at least delay transplantation. As such, a recent consensus statement by Emamaulee et al. suggest that “there may be an immunological benefit to proceed with HLT with significantly fewer acute cellular and humoral rejection episodes”. The aim of this study is to demonstrate that HLT patients remain at risk for rejection and have required treatment for it. Results: There were 15 patients who underwent HLT from January 2017 to February 2022. Of the four patients who did not have CHD, none were considered sensitized, and all underwent induction with basiliximab per our institutional protocol. One of these had rejection. Rejection episodes were identified in four of the 11 CHD patients (36%) patients. Conclusions: In our study of 15 HLT, including 11 CHD patients (73% denied transplant at ≥ 1 center) demonstrated a higher rate of rejection than previously reported. While theoretically, HLT may mitigate the likelihood of rejection, the risk still exists, and patients benefit from close monitoring commensurate with single organ transplant.

TAE Technologies’ fifth-generation fusion device, C-2W (also called ‘Norman’), is the world’s largest compact-toroid device and has made significant progress in field-reversed configuration (FRC) plasma performance. C-2W produces record breaking, macroscopically stable, high-temperature advanced beam-driven FRC plasmas, dominated by injected fast particles and sustained in steady state, which is primarily limited by neutral-beam (NB) pulse duration. The NB power supply system has recently been upgraded to extend the pulse length from 30 ms to 40 ms, which allows for a longer plasma lifetime and thus better characterization and further enhancement of FRC performance. An active plasma control system is routinely used in C-2W to produce consistent FRC performance as well as for reliable machine operations using magnet coils, edge-biasing electrodes, gas injection and tunable-energy NBs. Google’s machine learning framework for experimental optimization has also been routinely used to enhance plasma performance. Dedicated plasma optimization experimental campaigns, particularly focused on the external magnetic field profile and NB injection (NBI) optimizations, have produced a superior FRC plasma performance; for instance, achieving a total plasma energy of ∼13 kJ, a trapped poloidal magnetic flux of ∼16 mWb (based on the rigid-rotor model) and plasma sustainment in steady state up to ∼40 ms. Furthermore, under some operating conditions, the electron temperature of FRC plasmas at a quiescent phase has successfully reached up to ∼1 keV at the peak inside the FRC separatrix for the first time. The overall FRC performance is well correlated with the NB and edge-biasing systems, where higher total plasma energy is obtained with higher NBI power and applied voltage on biasing electrodes. C-2W operations have now reached a mature level where the machine can produce hot, stable, long-lived, and repeatable plasmas in a well-controlled manner.

In this work, the influence of selected alloying variations on Zn-assisted liquid metal embrittlement (LME) susceptibility of Zn-coated advanced high strength steels (AHSS) is investigated. Cold-rolled AHSS alloys of different carbon (C), manganese (Mn), silicon (Si), and aluminum (Al) concentrations were continuous-annealed to generate a third generation AHSS microstructure (composed of martensite and retained austenite) via quenching and partitioning. High temperature tension tests using simulated spot-weld thermomechanical cycles revealed no significant influence of C and Mn variations on the Zn-LME susceptibility of AHSS. On the other hand, Zn-LME susceptibility was strongly correlated with the Si content of AHSS. A direct comparison of the (reacted) coating microstructures of the Si-alloyed and Low-Si AHSS variants revealed that Si in the AHSS substrate suppresses Fe–Zn alloying reactions and retards the nucleation and growth of Fe-Zn intermetallic phases at the coating-substrate interface in these spot weld simulations. The suppressed intermetallic formation at elevated Si concentrations is consistent with phase equilibria considerations in the Fe-Zn-Si ternary system. In the context of Zn-assisted LME, therefore, Si is hypothesized to aggravate LME behavior by increasing the liquid Zn availability for embrittlement and promoting direct contact between liquid Zn and the AHSS steel substrate.

Background: Students often harbour negative attitudes towards research methods and statistics courses, and such attitudes may be associated with harmful cognitive and behavioural responses. Research on these effects has been restricted to the investigation of direct links between attitudes towards statistics, statistics anxiety, academic procrastination, and course performance. Aims: This study sought to examine the interconnected impact of attitudes towards statistics, statistics anxiety, and procrastination, on course performance in a cohesive model. It was predicted that attitudes towards statistics would indirectly affect statistical performance via statistics anxiety and procrastination in a sequential manner. Sample: The sample comprised 171 undergraduate psychology students from Australian universities. Methods: An online questionnaire collected information on participant demographics, attitudes towards statistics, statistics anxiety, procrastinatory behaviours, and performance in participants most recently completed statistics course. Data were collected cross-sectionally. All responses were anonymous. Results: A sequential mediation analysis revealed a significant indirect effect of statistics anxiety and procrastination, controlling for age and gender. The results showed that more negative attitudes towards statistics are associated with greater statistics anxiety, which is in turn associated with greater procrastination, and finally with lower statistical performance. Conclusions: It was concluded that students who view their statistics courses as a threatening experience may fail to see value in their statistical education, which is associated with heightened statistics anxiety, increased avoidance of course-related activities, and in turn poorer course performance. Practical implications of the findings are also discussed.

BackgroundGiven the public release of large language models, research is needed to explore whether older adults would be receptive to personalized medication advice given by artificial intelligence (AI) tools. ObjectiveThis study aims to identify predictors of the likelihood of older adults stopping a medication and the influence of the source of the information. MethodsWe conducted a web-based experimental survey in which US participants aged ≥65 years were asked to report their likelihood of stopping a medication based on the source of information using a 6-point Likert scale (scale anchors: 1=not at all likely; 6=extremely likely). In total, 3 medications were presented in a randomized order: aspirin (risk of bleeding), ranitidine (cancer-causing chemical), or simvastatin (lack of benefit with age). In total, 5 sources of information were presented: primary care provider (PCP), pharmacist, AI that connects with the electronic health record (EHR) and provides advice to the PCP (“EHR-PCP”), AI with EHR access that directly provides advice (“EHR-Direct”), and AI that asks questions to provide advice (“Questions-Direct”) directly. We calculated descriptive statistics to identify participants who were extremely likely (score 6) to stop the medication and used logistic regression to identify demographic predictors of being likely (scores 4-6) as opposed to unlikely (scores 1-3) to stop a medication. ResultsOlder adults (n=1245) reported being extremely likely to stop a medication based on a PCP’s recommendation (n=748, 60.1% [aspirin] to n=858, 68.9% [ranitidine]) compared to a pharmacist (n=227, 18.2% [simvastatin] to n=361, 29% [ranitidine]). They were infrequently extremely likely to stop a medication when recommended by AI (EHR-PCP: n=182, 14.6% [aspirin] to n=289, 23.2% [ranitidine]; EHR-Direct: n=118, 9.5% [simvastatin] to n=212, 17% [ranitidine]; Questions-Direct: n=121, 9.7% [aspirin] to n=204, 16.4% [ranitidine]). In adjusted analyses, characteristics that increased the likelihood of following an AI recommendation included being Black or African American as compared to White (Questions-Direct: odds ratio [OR] 1.28, 95% CI 1.06-1.54 to EHR-PCP: OR 1.42, 95% CI 1.17-1.73), having higher self-reported health (EHR-PCP: OR 1.09, 95% CI 1.01-1.18 to EHR-Direct: OR 1.13 95%, CI 1.05-1.23), having higher confidence in using an EHR (Questions-Direct: OR 1.36, 95% CI 1.16-1.58 to EHR-PCP: OR 1.55, 95% CI 1.33-1.80), and having higher confidence using apps (EHR-Direct: OR 1.38, 95% CI 1.18-1.62 to EHR-PCP: OR 1.49, 95% CI 1.27-1.74). Older adults with higher health literacy were less likely to stop a medication when recommended by AI (EHR-PCP: OR 0.81, 95% CI 0.75-0.88 to EHR-Direct: OR 0.85, 95% CI 0.78-0.92). ConclusionsOlder adults have reservations about following an AI recommendation to stop a medication. However, individuals who are Black or African American, have higher self-reported health, or have higher confidence in using an EHR or apps may be receptive to AI-based medication recommendations.

Background: Allergic rhinitis (AR) is a highly prevalent disease. We aimed to assess the symptoms that physicians who see patients with AR perceive as the most bothersome in their patients. Methods: We performed a cross-sectional study based on an online questionnaire sent to all members of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative. The survey included questions on the physicians' perceptions of patients’ AR symptoms as well as of their own AR symptoms. Results: Among 401 respondents, 155 (38.7%) reported having AR. ARIA members reported nasal symptoms to be the most frequent (89.7%) and bothersome (80.0%) symptoms experienced by themselves. Likewise, nasal symptoms were reported by ARIA members as the most frequent (94.8% in members with AR vs 96.0% in members without AR) and bothersome (57.0% in members with AR vs 67.9% in members without AR) in their patients. We found a significant association (p = 0.001) between physicians’ own symptoms and those perceived as the most bothersome in their patients. Conclusion: Physicians perceive nasal symptoms to be the most frequent and the most bothersome symptoms in AR patients. The physicians' personal experiences with AR may influence their perception of patients’ symptoms.

IntroductionPredators, such as sharks, play important ecological roles in coastal ecosystems when abundant and these roles change over ontogeny. However, these shifts in ecological role are often not evaluated in light of feeding performance. Bite force is an ecologically relevant metric of feeding performance that has been associated with a species’ foraging niche, which may serve as a key factor that constrains prey selection both within and among sympatric species.MethodsThis study applies an interdisciplinary approach to discern the ecomechanical relationships of sympatric bull (Carcharhinus leucas), blacktip (Carcharhinus limbatus), and bonnethead sharks (Sphyrna tiburo) using feeding biomechanics and bulk stable isotopes (δ13C, δ15N). We sought to (1) estimate theoretical bite force and scaling patterns over ontogeny of each species, (2) quantify niche breadth and overlap among species, and (3) characterize the relationship between ecological niche shifts and changes in bite force over ontogeny.ResultsImportantly, we found that smaller conspecifics exhibited positive allometric scaling of bite force, whereas larger conspecifics exhibited isometric scaling. Associations between bite force and ontogenetic niche shifts in habitat and diet were found in bull and bonnethead sharks, but not in blacktip sharks. Additionally, isotopic niche breadth was greatest in generalist bull sharks, followed by specialist bonnethead and blacktip sharks.DiscussionThese findings highlight animal performance measures as critical drivers ofecological relationships both within and among species. Size-based differences in bite force scaling should be considered when evaluating feeding performance in other taxa, which may be an important determinant of ontogenetic dietary shifts.

The primary aim of this study was to establish the feasibility of implementing a larger RCT designed to evaluate the effect of financial incentives on HCV treatment initiation among persons receiving opioid agonist therapy and/or who have injected drugs in the prior six months. ETHOS Engage is an observational cohort of participants recruited from drug treatment and needle and syringe programs in Australia. Among 11 drug and alcohol clinics, participants who were HCV RNA-positive were randomized (1:1) to receive standard of care or a AUD $60 gift card at treatment initiation. Regarding feasibility, 100% (57/57) of eligible participants enrolled to take part. Twenty-eight participants were randomised to the financial incentive arm (AUD $60 gift card) plus standard of care and 29 participants to the standard of care arm. In this pilot RCT (n = 57), median age was 42 years (IQR 37–49), 63% were male (n = 36), 35% Indigenous (n = 20) and 36% (n = 21) reported injecting drugs daily in the past month. Twelve weeks post-study enrolment, 11 (39%) participants in the financial incentive arm and 17 (59%) participants in the standard of care arm initiated HCV treatment. Findings indicate high feasibility among people who inject drugs to be randomised to receive financial incentives to initiate HCV treatment.

IntroductionDigital health technologies are increasingly being used in emergency medicine, many of which utilize smartphones and computers. Patient willingness to use these modalities is an important factor in successful implementation. Therefore, this study aimed to assess emergency department (ED) patients' use of and attitudes towards technology.MethodsThis was a pooled sub-analysis of ED patients (≥18 years old) that were enrolled in two studies evaluating the ED patient experience in response to novel technological interventions. Participants completed the Media and Technology Usage and Attitudes Scale (MTUAS) that assessed computer and smartphone ownership; frequency of use of phone calls, texting, email, and smartphones; and anxiety and dependence attitudes on these technologies.ResultsOne hundred and forty-four participants completed the survey. Mean age was 47.2 years (SD 17.94); 61.8% were female; and 61.1% were white. There was high usage of smartphones (93.1%) and computers (74.3%). Participants most frequently used phone calling and texting and least commonly used email. Participants had a positive attitude (mean 3.9/5, SD 0.68) towards the use of these technologies.DiscussionED patients reported high ownership of smartphones and computers, had a positive attitude towards their use, and had varying frequency with which they used different technologies. Future studies can use this information to inform the development of digital health interventions that utilize technologies that patients find most acceptable.

Abstract Objectives Queuing theory suggests that signing up for multiple patients at once (batching) can negatively affect patients’ length of stay (LOS). At academic centers, resident assignment adds a second layer to this effect. In this study, we measured the rate of batched patient assignment by resident physicians, examined the effect on patient in‐room LOS, and surveyed residents on underlying drivers and perceptions of batching. Methods This was a retrospective study of discharged patients from August 1, 2020 to October 27, 2020, supplemented with survey data conducted at a large, urban, academic hospital with an emergency medicine training program in which residents self‐assign to patients. Time stamps were extracted from the electronic health record and a definition of batching was set based on findings of a published time and motion study. Results A total of 3794 patients were seen by 28 residents and ultimately discharged during the study period. Overall, residents batched 23.7% of patients, with a greater rate of batching associated with increasing resident seniority and during the first hour of resident shifts. In‐room LOS for batched assignment patients was 15.9 minutes longer than single assignment patients (P value

Objective: Although there is evidence for the association between air pollution and decreased lung function in children, evidence for adolescents and young adults is scarce. For a peri-urban area in India, we evaluated the association of ambient PM2.5 and household air pollution with lung function for young adults who had recently attained their expected maximum lung function. Methods: We measured, using a standardized protocol, forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) in participants aged 20–26 years from the third follow-up of the population-based APCAPCS cohort (2010–2012) in 28 Indian villages. We estimated annual average PM2.5 outdoors at residence using land-use regression. Biomass cooking fuel (a proxy for levels of household air pollution) was self-reported. We fitted a within-between linear-mixed model with random intercepts by village, adjusting for potential confounders. Results: We evaluated 1,044 participants with mean age of 22.8 (SD = 1) years (range 20–26 years); 327 participants (31%) were female. Only males reported use of tobacco smoking (9% of all participants, 13% of males). The mean ambient PM2.5 exposure was 32.9 (SD = 2.8) µg/m3; 76% reported use of biomass as cooking fuel. The adjusted association between 1 µg/m3 increase in PM2.5 was −27 ml (95% CI, −89 to 34) for FEV1 and −5 ml (95% CI, −93 to 76) for FVC. The adjusted association between use of biomass was −112 ml (95% CI, −211 to −13) for FEV1 and −142 ml (95% CI, −285 to 0) for FVC. The adjusted association was of greater magnitude for those with unvented stove (−158 ml, 95% CI, −279 to −36 for FEV1 and −211 ml, 95% CI, −386 to −36 for FVC). Conclusions: We observed negative associations between ambient PM2.5 and household air pollution and lung function in young adults who had recently attained their maximum lung function.

Cities emit the majority of greenhouse gas emissions globally and are increasingly committing to aggressive mitigation actions. Cities are also experiencing poor—and in some cases worsening—air quality, contributing to large disease burdens for adults and children. Integrated planning frameworks can help cities leverage and prioritize measures that achieve climate, air quality, and health benefits simultaneously. We developed and applied an integrated climate action planning process that includes air quality, utilizing Pathways-AQ, a new assessment tool, in six pilot cities: Accra, Ghana; Addis Ababa, Ethiopia; Buenos Aires, Argentina; the metropolitan area of Guadalajara, Mexico; Johannesburg, South Africa; and Lima, Peru. Implementing the “ambitious” greenhouse gas reduction scenarios in these cities' climate action plans would reduce in-city contributions to fine particulate matter (PM2.5) concentrations and would avoid 230–1,040 annual premature deaths per city, by 2050. This new integrated climate action planning process revealed the importance of (i) geographic scales of analysis, (ii) data integration across climate and air quality, (iii) local civic engagement, and (iv) nuanced health messaging. Rapidly scaling up and applying this integrated approach can broaden the group of municipal stakeholders involved in climate-related planning goals, potentially leading to greater ambition by integrating climate, air pollution, and health objectives.

How circuits self-assemble starting from neuronal stem cells is a fundamental question in developmental neurobiology. Here, we addressed how neurons from different stem cell lineages wire with each other to form a specific circuit motif. In Drosophila larvae, we combined developmental genetics (twin-spot mosaic analysis with a repressible cell marker, multi-color flip out, permanent labeling) with circuit analysis (calcium imaging, connectomics, network science). For many lineages, neuronal progeny are organized into subunits called temporal cohorts. Temporal cohorts are subsets of neurons born within a tight time window that have shared circuit-level function. We find sharp transitions in patterns of input connectivity at temporal cohort boundaries. In addition, we identify a feed-forward circuit that encodes the onset of vibration stimuli. This feed-forward circuit is assembled by preferential connectivity between temporal cohorts from different lineages. Connectivity does not follow the often-cited early-to-early, late-to-late model. Instead, the circuit is formed by sequential addition of temporal cohorts from different lineages, with circuit output neurons born before circuit input neurons. Further, we generate new tools for the fly community. Our data raise the possibility that sequential addition of neurons (with outputs oldest and inputs youngest) could be one fundamental strategy for assembling feed-forward circuits.

As ACE2 is the critical SARS-CoV-2 receptor, we hypothesized that aerosol administration of clinical grade soluble human recombinant ACE2 (APN01) will neutralize SARS-CoV-2 in the airways, limit spread of infection in the lung, and mitigate lung damage caused by deregulated signaling in the renin-angiotensin (RAS) and Kinin pathways. Here, after demonstrating in vitro neutralization of SARS-CoV-2 by APN01, and after obtaining preliminary evidence of its tolerability and preventive efficacy in a mouse model, we pursued development of an aerosol formulation. As a prerequisite to a clinical trial, we evaluated both virus binding activity and enzymatic activity for cleavage of Ang II following aerosolization. We report successful aerosolization for APN01, retaining viral binding as well as catalytic RAS activity. Dose range-finding and IND-enabling repeat-dose aerosol toxicology testing were conducted in dogs. Twice daily aerosol administration for two weeks at the maximum feasible concentration revealed no notable toxicities. Based on these results, a Phase I clinical trial in healthy volunteers has now been initiated (NCT05065645), with subsequent Phase II testing planned for individuals with SARS-CoV-2 infection.

Obesity is a significant factor for increased morbidity and mortality upon infection with SARS-CoV-2. Because of the higher potential for negative outcomes following infection of individuals with obesity, the impact of body mass index (BMI) on vaccine immunogenicity and efficacy is an important public health concern. Few studies have measured the magnitude and durability of the vaccine-specific response in relation to BMI. We measured the receptor binding domain (RBD)-specific serum IgG and surrogate neutralizing titers in a cohort of 126 vaccinated individuals with no clinical history or serological evidence of previous SARS-CoV-2 infection 50 and 200 days following vaccination. BMI had no significant impact on RBD-specific IgG titers and surrogate neutralizing titers 50 days following immunization, and leptin levels had no correlation with the response to immunization. Two hundred days following immunization, antibody titers in all groups had declined by approximately 90%. The responses were also similar between male and female participants and did not significantly vary across age groups. These results indicate that the magnitude and durability of the antibody response to mRNA-based vaccines are unaffected by BMI in this cohort.