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Abstract Earth experienced the strongest geomagnetic storm in 20 years over 10–13 May 2024. The Ap and Dst geomagnetic indices were 273 and −291.94 nT on 11 May. The Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the Thermosphere‐Ionosphere‐Mesosphere Energetics and Dynamics satellite observed significant enhancement in thermospheric infrared emission at 15, 5.3, 4.3, and 1.27 μm. On 11 May the daily global power radiated by nitric oxide (NO) at 5.3 μm was 1.41 TW and by carbon dioxide (CO2) at 15 μm was 1.35 TW. These are the largest single day power values observed by SABER in 22 years and the first time the daily power radiated by NO exceeded that of CO2. The total infrared power (above background) radiated during the storm was 2.64 TW (2.28 × 1017 J). Significant enhancement in limb radiance observed at 4.3 μm (to 250 km tangent height) is likely indicative of NO + formation during the storm.

Abstract Time series of radiative cooling of the upper mesosphere and lower thermosphere (UMLT) by carbon dioxide (CO2) are examined for evidence of trends over 20 years. Radiative cooling rates in K day−1 provided by the SABER instrument are converted to time series of infrared power radiated from three distinct layers between 0.1 hPa and 0.0001 hPa (65–105 km). Linear regression against time and a predictor for solar variability provides estimates of the trend in exiting longwave radiation (ELR) from these layers. Trends in ELR are not significantly different from zero at 95% or 99% confidence in each layer. These results demonstrate energy conservation in the UMLT on decadal time scales and show that the UMLT continues to radiate the same amount of energy it receives despite cooling and contracting over two decades. These results are enabled by the long‐term stability of the SABER instrument calibration.

Abstract Twenty‐two years (2002–2023) of infrared radiative cooling rate data derived from the SABER instrument on the NASA TIMED satellite are presented. Global daily and global annual infrared power (Watts, W) emitted by nitric oxide (NO) and carbon dioxide (CO2) illustrate the variability of the geospace environment on timescales from days to decades. The 11‐year solar cycle (SC) is evident in the global power data and in vertical profiles of infrared cooling rates (nW/m3). The global annual power radiated by NO and CO2 are larger in 2023 than at any time since 2003 and 2002, respectively. The to‐date peak in NO infrared power in SC 25 is larger than in SC 24, is comparable to SC 20, but is less than in SCs 18–19 and 21–23. Two geomagnetic storms in 2023 radiated more than 1 TW and are in the top 10 strongest storms observed by SABER.

Abstract Microfluidic 3D cell culture devices that enable the recapitulation of key aspects of organ structures and functions in vivo represent a promising preclinical platform to improve translational success during drug discovery. Essential to these engineered devices is the spatial patterning of cells from different tissue types within a confined microenvironment. Traditional fabrication strategies lack the scalability, cost‐effectiveness, and rapid prototyping capabilities required for industrial applications, especially for processes involving thermoplastic materials. Here, an approach to pattern fluid guides inside microchannels is introduced by establishing differential hydrophilicity using pressure‐sensitive adhesives as masks and a subsequent selective coating with a biocompatible polymer. Optimal coating conditions are identified using polyvinylpyrrolidone, which resulted in rapid and consistent hydrogel flow in both the open‐chip prototype and the fully bonded device containing additional features for medium perfusion. The suitability of the device for dynamic 3D cell culture is tested by growing human hepatocytes in the device under controlled fluid flow for a 14‐day period. Additionally, the study demonstrated the potential of using the device for pharmaceutical high‐throughput screening applications, such as predicting drug‐induced liver injury. The approach offers a facile strategy of rapid prototyping thermoplastic microfluidic organ chips with varying geometries, microstructures, and substrate materials.

Artisanal small-scale mines (ASMs) in the Amazon Rainforest are an important cause of deforestation, forest degradation, biodiversity loss, sedimentation in rivers, and mercury emissions. Satellite image data are widely used in environmental decision-making to monitor changes in the land surface, but ASMs are difficult to map from space. ASMs are small, irregularly shaped, unevenly distributed, and confused (spectrally) with other land clearance types. To address this issue, we developed a reliable and efficient ASM detection method for the Tapajós River Basin of Brazil—an important gold mining region of the Amazon Rainforest. We enhanced detection in three key ways. First, we used the time-series segmentation (LandTrendr) Google Earth Engine (GEE) Application Programming Interface to map the pixel-wise trajectory of natural vegetation disturbance and recovery on an annual basis with a 2000 to 2019 Landsat image time series. Second, we segmented 26 textural features in addition to 5 spectral features to account for the high spatial heterogeneity in ASM pixels. Third, we trained and tested a Random Forest model to detect ASMs after eliminating irrelevant and redundant features with the Variable Selection Using Random Forests “ensemble of ensembles” technique. The out-of-bag error and overall accuracy of the final Random Forest was 3.73 and 92.6%, which are comparable to studies mapping large industrial mines with the normalized difference vegetation index (NDVI) and LandTrendr. The most important feature in our study was NDVI, followed by textural features in the near and shortwave infrared. Our work paves the way for future ASM regulation through large area monitoring from space with free and open-source GEE and operational satellites. Studies with sufficient computational resources can improve ASM monitoring with advanced sensors consisting of spectral narrow bands (Sentinel-2, Environmental Mapping and Analysis Program, PRecursore IperSpettrale della Missione Applicativa) and deep learning.

Abstract Background Our aim was to extend traditional parametric models used to extrapolate survival in cost-effectiveness analyses (CEAs) by integrating individual-level patient data (IPD) from a clinical trial with estimates from experts regarding long-term survival. This was illustrated using a case study evaluating survival of patients with triple-class exposed relapsed/refractory multiple myeloma treated with the chimeric antigen receptor (CAR) T cell therapy idecabtagene vicleucel (ide-cel, bb2121) in KarMMa (a phase 2, single-arm trial). Methods The distribution of patients expected to be alive at 3, 5, and 10 years given the observed survival from KarMMa (13.3 months of follow-up) was elicited from 6 experts using the SHeffield ELicitation Framework. Quantities of interest were elicited from each expert individually, which informed the consensus elicitation including all experts. Estimates for each time point were assumed to follow a truncated normal distribution. These distributions were incorporated into survival models, which constrained the expected survival based on standard survival distributions informed by IPD from KarMMa. Results Models for ide-cel that combined KarMMa data with expert opinion were more consistent in terms of survival as well as mean survival at 10 years (survival point estimates under different parametric models were 29–33% at 3 years, 5–17% at 5 years, and 0–6% at 10 years) versus models with KarMMa data alone (11–39% at 3 years, 0–25% at 5 years, and 0–11% at 10 years). Conclusion This case study demonstrates a transparent approach to integrate IPD from trials with expert opinion using traditional parametric distributions to ensure long-term survival extrapolations are clinically plausible.

As online courses become more common, practitioners are in need of clear guidance on how to translate best educational practices into web-based instruction. Moreover, student engagement is a pressing concern in online courses, which often have high levels of dropout. Our goals in this work were to experimentally study routine instructional design choices and to measure the effects of these choices on students' subjective experiences (engagement, mind wandering, and interest) in addition to objective learning outcomes. Using randomized controlled trials, we studied the effect of varying instructional activities (namely, assessment and a step-through interactive) on participants' learning and subjective experiences in a lesson drawn from an online immunology course. Participants were recruited from Amazon Mechanical Turk. Results showed that participants were more likely to drop out when they were in conditions that included assessment. Moreover, assessment with minimal feedback (correct answers only) led to the lowest subjective ratings of any experimental condition. Some of the negative effects of assessment were mitigated by the addition of assessment explanations or a summary interactive. We found no differences between the experimental conditions in learning outcomes, but we did find differences between groups in the accuracy of score predictions. Finally, prior knowledge and self-rated confusion were predictors of post-test scores. Using student behavior data from the same online immunology course, we corroborated the importance of assessment explanations. Our results have a clear implication for course developers: the addition of explanations to assessment questions is a simple way to improve online courses.

Abstract The ability of satellite instruments to accurately observe long‐term changes in atmospheric temperature depends on many factors including the absolute accuracy of the measurement, the stability of the calibration of the instrument, the stability of the satellite orbit, and the stability of the numerical algorithm that produces the temperature data. We present an example of algorithm instability recently discovered in the temperature data set from the SABER instrument on the NASA TIMED satellite. The instability resulted in derived temperatures that were substantially colder than anticipated from mid‐December 2019 to mid‐2022. This algorithm‐induced change in temperature over 1 to 2 years corresponded to the expected temperature change over several decades from increasing anthropogenic CO2. This paper highlights the importance of algorithm stability in developing Geospace Data Records (GDRs) for Earth’s mesosphere and lower thermosphere. A corrected version (Version 2.08) of the temperatures from SABER is described.

Abstract Purpose Spinal metastases are indicative of progressive cancer which can lead to vertebral body fractures and spinal cord compression. Radiofrequency ablation (RFA) treatment is infrequently used in patients with refractory pain. The aim of this systematic review is to determine the clinical efficacy of RFA, with the scope of using it as front-line management of spinal metastases. Methods Electronic databases were searched (to July 2020) for studies evaluating RFA treatment for spinal metastases in adults. Measured outcomes were pain (primary), disability, health-related quality of life (HRQOL), complications, tumour control and mortality. Study inclusion, data extraction and risk of bias using the ROBIN-I tool were assessed. Meta-analysis was conducted for pooled results with homogeneity, and narrative synthesis was conducted otherwise. Results 15 studies were included. RFA reduces pain scores at 3–5 weeks [standardised mean difference (SMD 2.24, 95% confidence intervals (CI) 1.55–2.93], 3–4 months (SMD 3.00, 95% CI 1.11–4.90) and 5–6 months (SMD 3.54, 95% CI 1.96–5.11). RFA is effective in reducing disability/improving HRQOL in the short-term but longer-term efficacy remains unclear. 13.2% cases reported local tumour control failure (2.5 months–5 year follow-up) whereas mortality was 23.6% (follow-up of up to 1 year). Conclusion Low quality evidence has proven RFA to be safe and effective in reducing pain and disability, especially in the short-term. RFA may be routinely implemented in all cases involving refractory pain or radiotherapy-resistant tumours but controlled trials are required to compare the efficacy of RFA to current frontline treatments. PROSPERO protocol registration number: CRD42020202377.

Abstract The SABER instrument on the National Aeronautics and Space Administration Thermosphere‐Ionosphere‐Mesosphere Energetics and Dynamics satellite continues to provide a long‐term record of Earth's stratosphere, mesosphere, and lower thermosphere. The SABER data are being used to examine long‐term changes and trends in temperature, water vapor, and carbon dioxide. A tacit, central assumption of these analyses is that the SABER instrument radiometric calibration is not changing with time; that is, the instrument is stable. SABER stratospheric temperatures and those derived from Global Positioning System Radio Occultation measurements are compared to examine SABER's stability. Global Positioning System Radio Occultation measurements are inherently stable due to the accuracy and traceability of the measured phase delay rate to the Système Internationale definition of the second. Differences in global annual mean SABER and COSMIC lower stratospheric temperatures show little significant change with time in the 11 years spanning 2007–2017. From this analysis we infer that SABER temperatures are stable to better than 0.1 to 0.2 K per decade.

How a craft work may have effects both on the transformed material and on the person who experiences it? This article explores the hypothesis that the transformation activity of a material can have lasting effects on personal identity. Beyond the acquisition of professional skills, what does the work of interaction with the wood stimulate? What is left of it several years later? During professional learning, these effects occur more clearly because of their novelty. Through the analysis of excerpts from the narrative of life of two people of very different profile, appears retrospectively what played a significant role during their apprenticeship in carpentry-cabinetmaking. The technique of interview for explicitation of action (Vermersch, 2003), combined with an experiential preparation of research, has made it possible to bring out the richness of personal experience in the interaction with things.

Abstract Background In addition to determining static states of gene expression (high vs. low), it is important to characterize their dynamic status. For example, genes with H3K27me3 chromatin marks are not only suppressed but also poised for activation. However, the responsiveness of genes to perturbations has never been studied systematically. To distinguish gene responses to specific factors from responsiveness in general, it is necessary to analyze gene expression profiles of cells responding to a large variety of disturbances, and such databases did not exist before. Results We estimated the responsiveness of all genes in mouse ES cells using our recently published database on expression change after controlled induction of 53 transcription factors (TFs) and other genes. Responsive genes (N = 4746), which were readily upregulated or downregulated depending on the kind of perturbation, mostly have regulatory functions and a propensity to become tissue-specific upon differentiation. Tissue-specific expression was evaluated on the basis of published (GNF) and our new data for 15 organs and tissues. Non-responsive genes (N = 9562), which did not change their expression much following any perturbation, were enriched in housekeeping functions. We found that TF-responsiveness in ES cells is the best predictor known for tissue-specificity in gene expression. Among genes with CpG islands, high responsiveness is associated with H3K27me3 chromatin marks, and low responsiveness is associated with H3K36me3 chromatin, stronger tri-methylation of H3K4, binding of E2F1, and GABP binding motifs in promoters. Conclusions We thus propose the responsiveness of expression to perturbations as a new way to define the dynamic status of genes, which brings new insights into mechanisms of regulation of gene expression and tissue specificity.

We cannot assume that youngsters will be drawn to a study of the past on their own initiative, and the public education system has dismissed the study of history as irrelevant. Native-born Americans cannot gain the same insights through osmosis that foreign-born citizens acquire through supervised study. (MT)

Mammalian stress granules (SGs) contain stalled translation preinitiation complexes that are assembled into discrete granules by specific RNA-binding proteins such as G3BP. We now show that cells lacking both G3BP1 and G3BP2 cannot form SGs in response to eukaryotic initiation factor 2α phosphorylation or eIF4A inhibition, but are still SG-competent when challenged with severe heat or osmotic stress. Rescue experiments using G3BP1 mutants show that phosphomimetic G3BP1-S149E fails to rescue SG formation, whereas G3BP1-F33W, a mutant unable to bind G3BP partner proteins Caprin1 or USP10, rescues SG formation. Caprin1/USP10 binding to G3BP is mutually exclusive: Caprin binding promotes, but USP10 binding inhibits, SG formation. G3BP interacts with 40S ribosomal subunits through its RGG motif, which is also required for G3BP-mediated SG formation. We propose that G3BP mediates the condensation of SGs by shifting between two different states that are controlled by the phosphorylation of S149 and by binding to Caprin1 or USP10.

To examine transcription factor (TF) network(s), we created mouse ESC lines, in each of which 1 of 50 TFs tagged with a FLAG moiety is inserted into a ubiquitously controllable tetracycline-repressible locus. Of the 50 TFs, Cdx2 provoked the most exten- sive transcriptome perturbation in ESCs, followed by Esx1, Sox9, Tcf3, Klf4, and Gata3. ChIP-Seq revealed that CDX2 binds to promoters of upregulated target genes. By contrast, genes downregulated by CDX2 did not show CDX2 binding but were enriched with binding sites for POU5F1, SOX2, and NANOG. Genes with binding sites for these core TFs were also down-regulated by the induction of at least 15 other TFs, suggesting a common initial step for ESC differentiation mediated by interference with the binding of core TFs to their target genes. These ESC lines provide a fundamental resource to study biological networks in ESCs and mice. [ABSTRACT FROM AUTHOR]

Objective: The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) is designed to evaluate the longitudinal outcome of patients with bipolar disorder. The STEP-BD disease-management model is built on evidence-based practices and a collaborative care approach designed to maximize specific and nonspecific treatment mechanisms. This prospective study examined the longitudinal relationships between patients' satisfaction with care, levels of hope, and life functioning in the first 1000 patients to enter STEP-BD. Methods: The study used scores from the Care Satisfaction Questionnaire, Beck Hopelessness Scale, Range of Impaired Functioning Tool, Young Mania Rating Scale, and Montgomery-Asberg Depression Rating Scale at 5 time points during a 1-year interval. Analyses tested mediational pathways between care satisfaction, hope, and life functioning, depression, and mania using mixed-effects (random and fixed) regression models. Results: Increases in care satisfaction were associated with decreased hopelessness (P < .01) but not related to symptoms of depression or mania. Similarly, decreased hopelessness was associated with better life functioning (P < .01) but not related to symptoms of depression or mania. Depression was independently associated with poorer life functioning (P < .0001). Conclusions: This study provided support for the hypothesized mediational pathway between care satisfaction, hopelessness, and life functioning. Findings suggest that providing care that maximizes patient hope may be important. By so doing, patients might overcome the learned helplessness/hopelessness that often accompanies a cyclical illness and build a realistic illness-management strategy. [ABSTRACT FROM AUTHOR]

Despite the availability of psychosocial evidence-based practices (EBPs), treatment and outcomes for persons with mental disorders remain suboptimal. Replicating Effective Programs (REP), an effective implementation strategy, still resulted in less than half of sites using an EBP. The primary aim of this cluster randomized trial is to determine, among sites not initially responding to REP, the effect of adaptive implementation strategies that begin with an External Facilitator (EF) or with an External Facilitator plus an Internal Facilitator (IF) on improved EBP use and patient outcomes in 12 months. This study employs a sequential multiple assignment randomized trial (SMART) design to build an adaptive implementation strategy. The EBP to be implemented is life goals (LG) for patients with mood disorders across 80 community-based outpatient clinics (N = 1,600 patients) from different U.S. regions. Sites not initially responding to REP (defined as <50% patients receiving ≥3 EBP sessions) will be randomized to receive additional support from an EF or both EF/IF. Additionally, sites randomized to EF and still not responsive will be randomized to continue with EF alone or to receive EF/IF. The EF provides technical expertise in adapting LG in routine practice, whereas the on-site IF has direct reporting relationships to site leadership to support LG use in routine practice. The primary outcome is mental health-related quality of life; secondary outcomes include receipt of LG sessions, mood symptoms, implementation costs, and organizational change. This study design will determine whether an off-site EF alone versus the addition of an on-site IF improves EBP uptake and patient outcomes among sites that do not respond initially to REP. It will also examine the value of delaying the provision of EF/IF for sites that continue to not respond despite EF., Psychology