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Learning to descend stairs requires motor and cognitive capacities on the part of infants and opportunities for practice and assurance of safety offered by caregivers. The American Academy of Pediatrics prescribes the age strategy to teach toddlers to safely descend stairs but without much consideration for individual differences in infants' skills or caregivers' techniques. The purpose of this study was to observe the natural ways in which caregivers teach infants to descend stairs at home and the extent to which infants abide. Of particular interest was to examine the dynamic nature of caregivers' teaching and infants' learning over the session with attention to individual differences. Dyads (N = 59) were videorecorded on Zoom for 10 min interacting on stairs at home in the United States, Brazil, Canada, Italy, and Spain. Infants (n = 30 girls, 29 boys; 13-month-olds ± 1 week) were novice walkers (M = 2.04 months walking experience). Caregivers used a variety of teaching strategies and focused on "backing" and "scooting." Infants were more likely to heed caregivers' guidance when caregivers provided hands-on support and verbal encouragement suggesting infants were engaged and responsive to caregivers' overtures. Infants' walking experience predicted change in descent strategy over the session. Although infants did not show evidence of learning over the session, consistent caregiver instruction suggested caregivers were persistent, if not effective, teachers. Teaching and learning motor skills in a potentially risky task creates a unique opportunity for interaction, allowing infants and caregivers to learn from one another.

#MeToo hails the comeback of the decried “subject of feminism”: if not women as unified subjects, at least women subjects united across class, race, and even sexual orientation dividing lines, through the common experience of sexual violence at the hands of men. It warns us, then, it seems, against taking too quick a break from feminism. The outcry, and its repeated occasions, sound like a vindication of Catharine Mackinnon’s understanding of sexuality as a universal apparatus of male domination. Yet, a closer look at some of the scenes leading up to the drama that now goes by this name, complicates the matter at stake. Domination and seduction may overlap where sexuality is concerned, causing the subject of desire and the “subject of feminism” to split, but they needn’t coincide. A new theory – and practice – of seduction may be called for in order to bridge the gap between the two “subjects”.

Abstract The dataset presents a 43 year-long reanalysis of pollen seasons for three major allergenic genera of trees in Europe: alder (Alnus), birch (Betula), and olive (Olea). Driven by the meteorological reanalysis ERA5, the atmospheric composition model SILAM predicted the flowering period and calculated the Europe-wide dispersion pattern of pollen for the years 1980–2022. The model applied an extended 4-dimensional variational data assimilation of in-situ observations of aerobiological networks in 34 European countries to reproduce the inter-annual variability and trends of pollen production and distribution. The control variable of the assimilation procedure was the total pollen release during each flowering season, implemented as an annual correction factor to the mean pollen production. The dataset was designed as an input to studies on climate-induced and anthropogenically driven changes in the European vegetation, biodiversity monitoring, bioaerosol modelling and assessment, as well as, in combination with intra-seasonal observations, for health-related applications.

Infant motor development is affected by the sociocultural context in which it takes place. Because societal and cultural practices are dynamic, this exploratory study examined whether the ages at which infants typically learned to crawl, cruise, and walk changed over the past 3 decades. We compiled archival data from 1,306 infants born between January 31, 1992, and December 10, 2021. Parents originally reported milestone onsets in interviews and by using diaries. For each motor milestone, a linear regression model predicted the onset age using birth date. Segmented regression analyses inspected changes in slopes over time. Covariates included rural/urban housing, gestation age, season of birth, and birth weight. Infants' average crawling, cruising, and walking onset ages changed over time. After controlling for the covariates, infants' crawling onset age steadily increased until 2012, after which crawling onset age decreased. Infants' cruising onset age increased from 1991 to 2001, after which cruising onset age remained stable. After controlling for the covariates, infants' walking onset increased until 2015, after which walking onset age decreased. Thus, when infants were born explained a small but significant amount of variability in infant motor skill onset. While the current study showed that motor development changed over the years, motor development is just a model system for development more generally: Cohort effects may be pervasive across developmental domains. Using motor development as a model system for studying change suggests that generational effects due to a changing society may be pervasive across developmental domains.

Some double-blind, placebo-controlled trials have shown that Azelastine (Aze) high dose (0.15%) was effective in seasonal (SAR) and perennial allergic rhinitis (PAR). However, there was no long-term comparison between Aze 0.15% and intranasal corticosteroids (INCS) on safety and quality of life in perennial allergic rhinitis.An open-label, active-controlled, parallel-group one-year study comparing mometasone furoate and Aze 0.15% in adults assessed safety over 1 year. Efficacy using the 28-item rhino-conjunctivitis quality of life questionnaire (RQLQ) was a secondary end point.A total of 703 patients were randomized and 687 (97.7%) were included in the intent-to-treat (ITT) population. The present formulation was shown to be safe with long-term use over 12 months, with a mean duration of exposure of 270.7 days.Over the one-year period, there was no significant difference for any RQLQ domains between Aze and mometasone furoate (MF) for all evaluations (baseline, 6, 9, and 12 months). This study suggests that Aze 0.15% and MF display a similar improvement of RQLQ ( 2.80 [2.78] for Aze 0.15% vs 2.81 [2.75] for MF). Clinical trial registry number: NCT00720382.

Background Gastric carcinomas (GC) are aggressive malignancies, and only ~15% of patients respond to anti-programmed cell death (ligand) 1 (PD-(L)1) monotherapy. However, Epstein-Barr virus (EBV)-associated GCs (~5–10% of GCs) often harbor PD-L1 and PD-L2 chromosomal amplifications and robust CD8+ T cell infiltrates, and respond at a high rate to anti-PD-1. The current study compares the tumor immune microenvironments (TiMEs) of EBV+ versus EBV(−) GCs.Methods Over 1000 cases of primary invasive GCs were screened to identify 25 treatment-naïve specimens for study (11 EBV+, 14 EBV(−)). Quantitative immunohistochemistry (IHC) was conducted for markers of immune cell subsets and co-regulatory molecules. Gene expression profiling (GEP) was performed on RNAs isolated from macrodissected areas of CD3+ T cell infiltrates abutting PD-L1+ stromal/tumor cells, using multiplex quantitative reverse transcriptase PCR for a panel of 122 candidate immune-related genes.Results IHC revealed that 17/25 GCs contained PD-L1+ stromal cells, with no significant difference between EBV+/- specimens; however, only 3/25 specimens (all EBV+) contained PD-L1+ tumor cells. CD8+ T cell densities were higher in EBV+ versus EBV(−) tumors (p=0.044). With GEP normalized to the pan-leukocyte marker PTPRC/CD45, EBV+ GCs overexpressed ITGAE (CD103, marking intraepithelial T cells and a dendritic cell subset) and the interferon-inducible genes CXCL9 and IDO1. In contrast, EBV(−) tumors overexpressed several functionally-related gene groups associated with myeloid cells (CD163, IL1A, NOS2, RIGI), immunosuppressive cytokines/chemokines (CXCL2, CXCR4, IL10, IL32), coinhibitory molecules (HAVCR2/TIM-3 and VSIR/VISTA), and adenosine pathway components (ENTPD1/ CD39 and NT5E/CD73). Notably, compared with EBV+ GCs, EBV(−) GCs also overexpressed components of the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway associated with cancer-promoting inflammation, including PTGS2/COX-2 (most highly upregulated gene, 32-fold, p=0.005); prostaglandin receptors PTGER1 (EP1; up 21-fold, p=0.015) and PTGER4 (EP4; up twofold, p=0.022); and the major COX-2-inducing cytokine IL1B (up 11-fold, p=0.019). Consistent with these findings, COX-2 protein expression trended higher in EBV(−) versus EBV+ GCs (p=0.068).Conclusions While certain markers of immunosuppression are found in the GC TiME regardless of EBV status, EBV(−) GCs, which are much more common than EBV+ GCs, overexpress components of the COX-2/PGE2 pathway. These findings provide novel insights into the immune microenvironments of EBV+ and EBV(−) GC, and offer potential targets to overcome resistance to anti-PD-(L)1 therapies.

Abstract Aim To adopt a novel artificial intelligence (AI) optical coherence tomography (OCT)-based program to identify the presence of biomarkers associated with central serous chorioretinopathy (CSC) and whether these can differentiate between acute and chronic central serous chorioretinopathy (aCSC and cCSC). Methods Multicenter, observational study with a retrospective design enrolling treatment-naïve patients with aCSC and cCSC. The diagnosis of aCSC and cCSC was established with multimodal imaging and for the current study subsequent follow-up visits were also considered. Baseline OCTs were analyzed by an AI-based platform (Discovery® OCT Fluid and Biomarker Detector, RetinAI AG, Switzerland). This software allows to detect several different biomarkers in each single OCT scan, including subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective foci (HF) and flat irregular pigment epithelium detachment (FIPED). The presence of SRF was considered as a necessary inclusion criterion for performing biomarker analysis and OCT slabs without SRF presence were excluded from the analysis. Results Overall, 160 eyes of 144 patients with CSC were enrolled, out of which 100 (62.5%) eyes were diagnosed with cCSC and 60 eyes (34.5%) with aCSC. In the OCT slabs showing presence of SRF the presence of biomarkers was found to be clinically relevant (> 50%) for HF and FIPED in aCSC and cCSC. HF had an average percentage of 81% (± 20) in the cCSC group and 81% (± 15) in the aCSC group (p = 0.4295) and FIPED had a mean percentage of 88% (± 18) in cCSC vs. 89% (± 15) in the aCSC (p = 0.3197). Conclusion We demonstrate that HF and FIPED are OCT biomarkers positively associated with CSC when present at baseline. While both HF and FIPED biomarkers could aid in CSC diagnosis, they could not distinguish between aCSC and cCSC at the first visit. AI-assisted biomarker detection shows promise for reducing invasive imaging needs, but further validation through longitudinal studies is needed.

Fast X-ray transients (FXTs) are a new observational class of phenomena with no clear physical origin. This is at least partially a consequence of limited multiwavelength follow-up of this class of transients in real time. Here we present deep optical ( g - and i -band) photometry with Keck, and prompt radio observations with the Very Large Array of FXT 210423 obtained at δ t ≈ 14–36 days since the X-ray trigger. We use these multiband observations, combined with publicly available data sets, to constrain the presence and physical properties of on-axis and off-axis relativistic jets such as those that can be launched by neutron star mergers and tidal disruption events, which are among the proposed theoretical scenarios of FXTs. Considering a wide range of possible redshifts z ≤ 3.5, circumstellar medium density n = 10 ^−6 –10 ^−1 cm ^−3 , and isotropic-equivalent jet kinetic energy E _k _,iso = 10 ^48 –10 ^55 erg, we find that we can rule out wide jets with opening angle θ _j = 15° viewed within 10° off-axis. For more collimated jets ( θ _j = 3°) we can only rule out on-axis ( θ _obs = 0°) orientations. This study highlights the constraining power of prompt multiwavelength observations of FXTs discovered in real time by current (e.g., Einstein Probe) and future facilities.

Abstract Background Tumor regression following immune checkpoint blockade (ICB) is often associated with immune-related adverse events (irAEs), marked by inflammation in non-cancerous tissues. This study was undertaken to investigate the functional relationship between anti-tumor and anti-self immunity, to facilitate irAE management while promoting anti-tumor immunity. Methods Multiple biopsies from tumor and inflamed tissues were collected from a patient with melanoma experiencing both tumor regression and irAEs on ICB, who underwent rapid autopsy. Immune cells infiltrating melanoma lesions and inflamed normal tissues were subjected to gene expression profiling with multiplex qRT-PCR for 122 candidate genes. Subsequently, immunohistochemistry was conducted to assess the expression of 14 candidate markers of immune cell subsets and checkpoints. TCR-beta sequencing was used to explore T cell clonal repertoires across specimens. Results While genes involved in MHC I/II antigen presentation, IFN signaling, innate immunity and immunosuppression were abundantly expressed across specimens, irAE tissues over-expressed certain genes associated with immunosuppression (CSF1R, IL10RA, IL27/EBI3, FOXP3, KLRG1, SOCS1, TGFB1), including those in the COX-2/PGE2 pathway (IL1B, PTGER1/EP1 and PTGER4/EP4). Immunohistochemistry revealed similar proportions of immunosuppressive cell subsets and checkpoint molecules across samples. TCRseq did not indicate common TCR repertoires across tumor and inflammation sites, arguing against shared antigen recognition between anti-tumor and anti-self immunity in this patient. Conclusions This comprehensive study of a single patient with melanoma experiencing both tumor regression and irAEs on ICB explores the immune landscape across these tissues, revealing similarities between anti-tumor and anti-self immunity. Further, it highlights expression of the COX-2/PGE2 pathway, which is known to be immunosuppressive and potentially mediates ICB resistance. Ongoing clinical trials of COX-2/PGE2 pathway inhibitors targeting the major COX-2 inducer IL-1B, COX-2 itself, or the PGE2 receptors EP2 and EP4 present new opportunities to promote anti-tumor activity, but may also have the potential to enhance the severity of ICB-induced irAEs.

Background:. The aim of this study was to compare the use of pedicled local (PFs) versus random pattern flaps (RpFs) in foot and ankle reconstruction in patients with chronic, nonhealing wounds. Methods:. A single-center, retrospective review of 204 patients with 118 PFs and 86 RpFs was performed. The primary outcome included rates of limb salvage. Results:. PFs were used more often in the hindfoot (44.1% versus 30.2%, P = 0.045), lateral and medial surface (39.8% versus 18.6%, P = 0.001), and wounds containing exposed bone and hardware (78.8% versus 62.8%, P = 0.018). RpFs were used more for forefoot (19.8% versus 10.2%, P = 0.053) and plantar defects (58.1% versus 30.3%, P = 0.000). RpFs had a higher rate of immediate success (100% versus 95.8%, P = 0.053), with no significant differences in rate of long-term limb salvage (77.1% versus 69.8%, P = 0.237). PFs had higher rates of ischemia requiring intervention (11.0% versus 3.5%, P = 0.048). RpFs had a higher rate of minor amputations (15.12% versus 6.8%, P = 0.053) but similar rates of major amputation (15.1% versus 16.1%, P = 0.848). There were no significant differences in rates of mortality or ambulatory status. Conclusions:. Both RpFs and PFs remain reliable options to reconstruct defects of the foot and ankle. Optimizing the use of each flap type should consider wound characteristics. RpFs are preferred for dorsal and plantar defects, whereas PFs are protective for minor infections and preferred for deeper wounds despite a higher rate of partial necrosis.

We present the first deep X-ray observations of luminous fast blue optical transient (LFBOT) AT 2018cow at ∼3.7 yr since discovery, together with the reanalysis of the observation at δ t ∼ 220 days. X-ray emission is significantly detected at a location consistent with AT 2018cow. The very soft X-ray spectrum and sustained luminosity are distinct from the spectral and temporal behavior of the LFBOT in the first ∼100 days and would possibly signal the emergence of a new emission component, although a robust association with AT 2018cow can only be claimed at δ t ∼ 220 days, while at δ t ∼ 1350 days contamination of the host galaxy cannot be excluded. We interpret these findings in the context of the late-time panchromatic emission from AT 2018cow, which includes the detection of persistent, slowly fading UV emission with ν L _ν ≈ 10 ^39 erg s ^−1 . Similar to previous works (and in analogy with arguments for ultraluminous X-ray sources), these late-time observations are consistent with thin disks around intermediate-mass black holes (with M _• ≈ 10 ^3 –10 ^4 M _☉ ) accreting at sub-Eddington rates. However, differently from previous studies, we find that smaller-mass black holes with M _• ≈ 10–100 M _☉ accreting at ≳the Eddington rate cannot be ruled out and provide a natural explanation for the inferred compact size ( R _out ≈ 40 R _☉ ) of the accretion disk years after the optical flare. Most importantly, irrespective of the accretor mass, our study lends support to the hypothesis that LFBOTs are accretion-powered phenomena and that, specifically, LFBOTs constitute electromagnetic manifestations of super-Eddington accreting systems that evolve to ≲Eddington over a ≈100-day timescale.

Abstract The U.S. Global Change Research Program reports that the frequency and intensity of extreme heat are increasing globally. Studies of the impact of climate change on child health often exclude sleep, despite its importance for healthy growth and development. To address this gap in the literature, we studied the impact of unusually high temperatures in the summer of 2022 on infants’ sleep. Sleep was assessed objectively using Nanit camera monitors in infants’ homes. Generally, sleep was not impacted when temperatures stayed below 88° but was negatively impacted when temperatures reached over 100°. Compared to non-heatwave nights, infants had less total sleep, less efficient sleep, took longer to fall asleep, had more fragmented sleep, and parents’ visits were more frequent during the night. Following peaks in temperature, sleep metrics rebounded to better than average compared to non-peak nights, suggesting that infants compensated for disrupted sleep by sleeping more and with fewer interruptions once the temperature dropped below 85°. Increased instances of disrupted sleep in infancy have important implications for psychological health and development. Climate disruptions such as heat waves that create occasional or ongoing sleep disruptions can leave infants vulnerable and unprepared for learning.

Abstract Background Advanced practice physiotherapy (APP) models of care where physiotherapists are primary contact emergency department (ED) providers are promising models of care to improve access, alleviate physicians’ burden, and offer efficient centered patient care for patients with minor musculoskeletal disorders (MSKD). Objectives To compare the effectiveness of an advanced practice physiotherapist (APPT)-led model of care with usual ED physician care for persons presenting with a minor MSKD, in terms of patient-related outcomes, health care resources utilization, and health care costs. Methods This trial is a multicenter stepped-wedge cluster randomized controlled trial (RCT) with a cost analysis. Six Canadian EDs (clusters) will be randomized to a treatment sequence where patients will either be managed by an ED APPT or receive usual ED physician care. Seven hundred forty-four adults with a minor MSKD will be recruited. The main outcome measure will be the Brief Pain Inventory Questionnaire. Secondary measures will include validated self-reported disability questionnaires, the EQ-5D-5L, and other health care utilization outcomes such as prescription of imaging tests and medication. Adverse events and re-visits to the ED for the same complaint will also be monitored. Health care costs will be measured from the perspective of the public health care system using time-driven activity-based costing. Outcomes will be collected at inclusion, at ED discharge, and at 4, 12, and 26 weeks following the initial ED visit. Per-protocol and intention-to-treat analyses will be performed using linear mixed models with a random effect for cluster and fixed effect for time. Discussion MSKD have a significant impact on health care systems. By providing innovative efficient pathways to access care, APP models of care could help relieve pressure in EDs while providing efficient care for adults with MSKD. Trial registration ClinicalTrials.gov NCT05545917 . Registered on September 19, 2022

BackgroundAzelastine hydrochloride (AZE) is a selective, non-sedating H1 antagonist with anti-inflammatory and mast cell stabilizing properties, which can be used as an alternative to intranasal corticosteroids. The objective of this study was to evaluate the efficacy of the new formulation of 0.15% AZE compared to that of the placebo at a dosage of two sprays per nostril twice daily for 4 weeks in patients with perennial allergic rhinitis (PAR).Materials and methodsA total of 581 subjects were randomized in this double-blind (DB) placebo-controlled trial (NCT00712920) that compared 0.10% (1,096 μg daily) and 0.15% AZE (1,644 μg daily) to the placebo in PAR patients. The study consisted of a 7-day single-blind placebo lead-in period and a 28-day DB treatment period. The primary endpoint was the change from baseline in the 12-h reflective total nasal symptom score (rTNSS) for the entire 28-day study period of 0.15% AZE, two sprays per nostril BID compared to the placebo. The efficacy and safety of 0.15% AZE were compared to the placebo.ResultsLeast square (LS) mean improvement from baseline in the morning (AM) and evening (PM) combined rTNSS was statistically significant for the 0.15% AZE group (p = 0.04) compared to the placebo group. LS mean improvement from baseline in the AM and PM combined rTNSS was 4.10 (4.26) units for 0.15% AZE and 3.81 (3.99) for 0.10% AZE. For individual symptoms, there was a statistically significant change in the LS mean (p = 0.04) improvement from baseline on the 12-h reflective assessment for the 0.15% AZE group for runny nose. Further numerical improvements were shown for itchy nose, nasal congestion, runny nose, and sneezing compared to the placebo. No deaths or serious adverse events related to the study medication were reported.ConclusionThe present formulation of 0.15% AZE is safe and effective in relieving PAR symptoms. It effectively relieves nasal and non-nasal symptoms. Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT00712920.

Abstract Preliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were included. Plasma protein levels were quantified using mass spectrometry and erythrocyte omega-3 PUFA levels were quantified using gas chromatography. We examined the relationship between change in polyunsaturated PUFAs (between baseline and 6-month follow-up) and follow-up plasma proteins. Using mediation analysis, we investigated whether plasma proteins mediated the relationship between change in omega-3 PUFAs and clinical outcomes. A 6-months change in omega-3 PUFAs was associated with 24 plasma proteins at follow-up. Pathway analysis revealed the complement and coagulation pathway as the main biological pathway to be associated with change in omega-3 PUFAs. Moreover, complement and coagulation pathway proteins significantly mediated the relationship between change in omega-3 PUFAs and clinical outcome at follow-up. The inflammatory protein complement C5 and protein S100A9 negatively mediated the relationship between change in omega-3 PUFAs and positive symptom severity, while C5 positively mediated the relationship between change in omega-3 and functional outcome. The relationship between change in omega-3 PUFAs and cognition was positively mediated through coagulation factor V and complement protein C1QB. Our findings provide evidence for a longitudinal association of omega-3 PUFAs with complement and coagulation protein changes in the blood. Further, the results suggest that an increase in omega-3 PUFAs decreases symptom severity and improves cognition in the CHR state through modulating effects of complement and coagulation proteins.

Enhanced emission in the months to years preceding explosion has been detected for several core-collapse supernovae (SNe). Though the physical mechanisms driving the emission remain hotly debated, the light curves of detected events show long-lived (≥50 days), plateau-like behavior, suggesting hydrogen recombination may significantly contribute to the total energy budget. The Vera C. Rubin Observatory’s Legacy Survey of Space and Time (LSST) will provide a decade-long photometric baseline to search for this emission, both in binned pre-explosion observations after an SN is detected and in single-visit observations prior to the SN explosion. In anticipation of these searches, we simulate a range of eruptive precursor models to core-collapse SNe and forecast the discovery rates of these phenomena in LSST data. We find a detection rate of ∼40–130 yr ^−1 for SN IIP/IIL precursors and ∼110 yr ^−1 for SN IIn precursors in single-epoch photometry. Considering the first three years of observations with the effects of rolling and observing triplets included, this number grows to a total of 150–400 in binned photometry, with the highest number recovered when binning in 100 day bins for 2020tlf-like precursors and in 20 day bins for other recombination-driven models from the literature. We quantify the impact of using templates contaminated by residual light (from either long-lived or separate precursor emission) on these detection rates, and explore strategies for estimating baseline flux to mitigate these issues. Spectroscopic follow-up of the eruptions preceding core-collapse SNe and detected with LSST will offer important clues to the underlying drivers of terminal-stage mass loss in massive stars.

We present radio observations of 23 optically discovered tidal disruption events (TDEs) on timescales of ∼500–3200 days postdiscovery. We detect nine new TDEs that did not have detectable radio emission at earlier times, indicating a late-time brightening after several hundred (and up to 2300) days; an additional seven TDEs exhibit radio emission whose origin is ambiguous or may be attributed to the host galaxy or an active galactic nucleus. We also report a new rising component in one TDE previously detected in the radio at ∼10 ^3 days. While the radio emission in some of the detected TDEs peaked on a timescale ≈2–4 yr, over half of the sample still show rising emission. The range of luminosities for the sample is ∼10 ^37 –10 ^39 erg s ^−1 , about 2 orders of magnitude below the radio luminosity of the relativistic TDE Sw J1644+57. Our data set indicates ∼40% of all optical TDEs are detected in radio hundreds to thousands of days after discovery, and that this is probably more common than early radio emission peaking at ∼10 ^2 days. Using an equipartition analysis, we find evidence for a delayed launch of the radio-emitting outflows, with delay timescales of ∼500–2000 days, inferred velocities of ≈0.02–0.15 c , and kinetic energies of ∼10 ^47 –10 ^49 erg. We rule out off-axis relativistic jets as a viable explanation for this population, and conclude delayed outflows are a more likely explanation, possibly from delayed disk formation. We conclude late radio emission marks a fairly ubiquitous but heretofore overlooked phase of TDE evolution.

We present 1–12 GHz Karl G. Jansky Very Large Array observations of nine off-nuclear persistent radio sources (PRSs) in nearby ( z ≲ 0.055) dwarf galaxies, along with high-resolution European VLBI Network observations for one of them at 1.7 GHz. We explore the plausibility that these PRSs are associated with fast radio burst (FRB) sources by examining their properties—physical sizes, host-normalized offsets, spectral energy distributions (SEDs), radio luminosities, and light curves—and compare them to those of the PRSs associated with FRB 20121102A and FRB 20190520B, two known active galactic nuclei (AGN), and one likely AGN in our sample with comparable data, as well as other radio transients exhibiting characteristics analogous to FRB-PRSs. We identify a single source in our sample, J1136+2643, as the most promising FRB-PRS, based on its compact physical size and host-normalized offset. We further identify two sources, J0019+1507 and J0909+5655, with physical sizes comparable to FRB-PRSs, but which exhibit large offsets and flat spectral indices potentially indicative of a background AGN origin. We test the viability of neutron star wind nebula and hypernebula models for J1136+2643 and find that the physical size, luminosity, and SED of J1136+2643 are broadly consistent with these models. Finally, we discuss the alternative interpretation that the radio sources are instead powered by accreting massive black holes, and we outline future prospects and follow-up observations for differentiating between these scenarios.

Preceding a core-collapse supernova (CCSN), various processes produce an increasing amount of neutrinos of all flavors characterized by mounting energies from the interior of massive stars. Among them, the electron antineutrinos are potentially detectable by terrestrial neutrino experiments such as KamLAND and Super-Kamiokande (SK) via inverse beta decay interactions. Once these pre-supernova (pre-SN) neutrinos are observed, an early warning of the upcoming CCSN can be provided. In light of this, KamLAND and SK, both located in the Kamioka mine in Japan, have been monitoring pre-SN neutrinos since 2015 and 2021, respectively. Recently, we performed a joint study between KamLAND and SK on pre-SN neutrino detection. A pre-SN alert system combining the KamLAND detector and the SK detector was developed and put into operation, which can provide a supernova alert to the astrophysics community. Fully leveraging the complementary properties of these two detectors, the combined alert is expected to resolve a pre-SN neutrino signal from a 15 M _⊙ star within 510 pc of the Earth at a significance level corresponding to a false alarm rate of no more than 1 per century. For a Betelgeuse-like model with optimistic parameters, it can provide early warnings up to 12 hr in advance.

The tidal disruption event (TDE) AT2022cmc represents the fourth known example of a relativistic jet produced by the tidal disruption of a stray star, providing a unique probe of the formation and evolution of relativistic jets in otherwise dormant supermassive black holes (SMBHs). Here we present deep, late-time Chandra observations of AT2022cmc extending to t _obs ≈ 400 days after disruption. Our observations reveal a sudden decrease in the X-ray brightness by a factor of ≳14 over a factor of ≈2.3 in time, and a deviation from the earlier power-law decline with a steepening α ≳ 3.2 ( F _X ∝ t ^− ^α ), steeper than expected for a jet break, and pointing to the cessation of jet activity at t _obs ≈ 215 days. Such a transition has been observed in two previous TDEs (Swift J1644+57 and Swift J2058+05). From the X-ray luminosity and the timescale of jet shut-off, we parameterize the mass of the SMBH in terms of unknown jet efficiency and accreted mass fraction parameters. Motivated by the disk–jet connection in active galactic nuclei, we favor black hole masses ≲10 ^5 M _⊙ (where the jet and disk luminosities are comparable), and disfavor larger black holes (in which extremely powerful jets are required to outshine their accretion disks). We additionally estimate a total accreted mass of ≈0.1 M _⊙ . Applying the same formalism to Swift J1644+57 and Swift J2058+05, we favor comparable black hole masses for these TDEs of ≲ a few × 10 ^5 M _⊙ , and suggest that jetted TDEs may preferentially form from lower-mass black holes when compared to nonrelativistic events, owing to generally lower jet and higher disk efficiencies at higher black hole masses.

Abstract Background Natalizumab and fingolimod are used as high-efficacy treatments in relapsing–remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. Methods Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. Results Overall, 5,148 relapsing–remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. Conclusions This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

Abstract On 03 February 2022, SpaceX launched 49 Starlink satellites, 38 of which re‐entered the atmosphere on or about 07 February 2022 due to unexpectedly high atmospheric drag. We use empirical model (NRLMSIS, JB08, and HASDM) outputs as well as solar extreme ultraviolet occultation and high‐fidelity accelerometer data to show that thermospheric density was at least 20%–30% higher at 210 km relative to the 9 days prior to the launch due to consecutive geomagnetic storms related to solar eruptions from NOAA AR12936 on 29 January 2022. We model the orbital altitude and in‐track position of a Starlink‐like satellite in a low‐drag configuration at 200 km during minor (G1) and extreme (G5) geomagnetic storms to show that an extreme storm would have at least a factor of two higher impact, with cumulative in‐track errors on the order of 10,000 km after a 5‐day duration extreme storm. Comparison of the JB08 and NRL MSIS models relative to the HASDM model during modeled historical minor and extreme geomagnetic storms shows that in‐track errors on the order of 100 km per day at 250 km, decreasing to cumulative errors on the order of 1 km per day at 550 km during geomagnetic storms. We conclude that full‐physics, data assimilative, coupled models of the magnetosphere and upper atmosphere, as well as new operational satellite missions providing “nowcasting” data to launch controllers, space traffic coordinators, and satellite operators, are needed to prevent similar—or worse—orbital system impacts during future geomagnetic storms.

We present the discovery and extensive follow-up of a remarkable fast-evolving optical transient, AT 2022aedm, detected by the Asteroid Terrestrial impact Last Alert Survey (ATLAS). In the ATLAS o band, AT 2022aedm exhibited a rise time of 9 ± 1 days, reaching a luminous peak with M _g ≈ −22 mag. It faded by 2 mag in the g band during the next 15 days. These timescales are consistent with other rapidly evolving transients, though the luminosity is extreme. Most surprisingly, the host galaxy is a massive elliptical with negligible current star formation. Radio and X-ray observations rule out a relativistic AT 2018cow–like explosion. A spectrum in the first few days after explosion showed short-lived He ii emission resembling young core-collapse supernovae, but obvious broad supernova features never developed; later spectra showed only a fast-cooling continuum and narrow, blueshifted absorption lines, possibly arising in a wind with v ≈ 2700 km s ^−1 . We identify two further transients in the literature (Dougie in particular, as well as AT 2020bot) that share similarities in their luminosities, timescales, color evolution, and largely featureless spectra and propose that these may constitute a new class of transients: luminous fast coolers. All three events occurred in passive galaxies at offsets of ∼4–10 kpc from the nucleus, posing a challenge for progenitor models involving massive stars or black holes. The light curves and spectra appear to be consistent with shock breakout emission, though this mechanism is usually associated with core-collapse supernovae. The encounter of a star with a stellar-mass black hole may provide a promising alternative explanation.

We present the results from a multiyear radio campaign of the superluminous supernova (SLSN) SN 2017ens, which yielded the earliest radio detection of an SLSN to date at the age of ∼3.3 yr after explosion. SN 2017ens was not detected at radio frequencies in the first ∼300 days but reached L _ν ≈ 10 ^28 erg s ^−1 cm ^−2 Hz ^−1 at ν ∼ 6 GHz, ∼1250 days post explosion. Interpreting the radio observations in the context of synchrotron radiation from the supernova shock interaction with the circumstellar medium (CSM), we infer an effective mass-loss rate $\dot{M}\approx {10}^{-4}\,{M}_{\odot }\,{\mathrm{yr}}^{-1}$ at r ∼ 10 ^17 cm from the explosion’s site, for a wind speed of v _w = 50–60 km s ^−1 as measured from optical spectra. These findings are consistent with the spectroscopic metamorphosis of SN 2017ens from hydrogen poor to hydrogen rich ∼190 days after explosion reported by Chen et al. SN 2017ens is thus an addition to the sample of hydrogen-poor massive progenitors that explode shortly after having lost their hydrogen envelope. The inferred circumstellar densities, implying a CSM mass up to ∼0.5 M _☉ , and low velocity of the ejection suggest that binary interactions (in the form of common-envelope evolution and subsequent envelope ejection) play a role in shaping the evolution of the stellar progenitors of SLSNe in the ≲500 yr preceding core collapse.

Supervised Machine Learning (ML) models for solar flare prediction rely on accurate labels for a given input data set, commonly obtained from the GOES/XRS X-ray flare catalog. With increasing interest in utilizing ultraviolet (UV) and extreme ultraviolet (EUV) image data as input to these models, we seek to understand if flaring activity can be defined and quantified using EUV data alone. This would allow us to move away from the GOES single pixel measurement definition of flares and use the same data we use for flare prediction for label creation. In this work, we present a Solar Dynamics Observatory (SDO) Atmospheric Imaging Assembly (AIA)-based flare catalog covering flare of GOES X-ray magnitudes C, M and X from 2010 to 2017. We use active region (AR) cutouts of full disk AIA images to match the corresponding SDO/Helioseismic and Magnetic Imager (HMI) SHARPS (Space weather HMI Active Region Patches) that have been extensively used in ML flare prediction studies, thus allowing for labeling of AR number as well as flare magnitude and timing. Flare start, peak, and end times are defined using a peak-finding algorithm on AIA time series data obtained by summing the intensity across the AIA cutouts. An extremely randomized trees (ERT) regression model is used to map SDO/AIA flare magnitudes to GOES X-ray magnitude, achieving a low-variance regression. We find an accurate overlap on 85% of M/X flares between our resulting AIA catalog and the GOES flare catalog. However, we also discover a number of large flares unrecorded or mislabeled in the GOES catalog.

Here, the authors use in vivo site-specific crosslinking to provide molecular-level insight into how the fungal Hsp70 chaperone system — the Ssb:Ssz1:Zuo1 triad — assists the folding process for the nascent peptide chain emerging from the ribosome tunnel.