GRB 110918A is the brightest long GRB detected by Konus-WIND during its 19 years of continuous observations and the most luminous GRB ever observed since the beginning of the cosmological era in ...1997. We report on the final IPN localization of this event and its detailed multiwavelength study with a number of space-based instruments. The prompt emission is characterized by a typical duration, a moderare \(E_{peak}\) of the time-integrated spectrum, and strong hard-to-soft evolution. The high observed energy fluence yields, at z=0.984, a huge isotropic-equivalent energy release \(E_{iso}=(2.1\pm0.1)\times10^{54}\) erg. The record-breaking energy flux observed at the peak of the short, bright, hard initial pulse results in an unprecedented isotropic-equivalent luminosity \(L_{iso}=(4.7\pm0.2)\times10^{54}\)erg s\(^{-1}\). A tail of the soft gamma-ray emission was detected with temporal and spectral behavior typical of that predicted by the synchrotron forward-shock model. Swift/XRT and Swift/UVOT observed the bright afterglow from 1.2 to 48 days after the burst and revealed no evidence of a jet break. The post-break scenario for the afterglow is preferred from our analysis, with a hard underlying electron spectrum and ISM-like circumburst environment implied. We conclude that, among multiple reasons investigated, the tight collimation of the jet must have been a key ingredient to produce this unusually bright burst. The inferred jet opening angle of 1.7-3.4 deg results in reasonable values of the collimation-corrected radiated energy and the peak luminosity, which, however, are still at the top of their distributions for such tightly collimated events. We estimate a detection horizon for a similar ultraluminous GRB of \(z\sim7.5\) for Konus-WIND, and \(z\sim12\) for Swift/BAT, which stresses the importance of GRBs as probes of the early Universe.
Background:
Post-extubation dysphagia is associated with an increased incidence of nosocomial pneumonias, longer hospitalizations, and higher re-intubation rates. The purpose of this study was to ...determine if it is necessary to delay swallow evaluation for 24 hours post-extubation.
Methods:
A prospective investigation of swallowing was conducted at 1, 4, and 24 hours post-extubation to determine if it is necessary to delay swallow evaluation following intubation. Participants were 202 adults from 5 different intensive care units (ICU).
Results:
A total of 166 of 202 (82.2%) passed the Yale Swallow Protocol at 1 hour post-extubation, with an additional 11 (177/202; 87.6%) at 4 hours, and 8 more (185/202; 91.6%) at 24 hours. Only intubation duration ≥4 days was significantly associated with nonfunctional swallowing.
Conclusions:
We found it is not necessary to delay assessment of swallowing in individuals who are post-extubation. Specifically, the majority of patients in our study (82.2%) passed a swallow screening at 1 hour post-extubation.
Since the onset of the COVID-19 pandemic, all facets of palliative care provision for patients with serious illness have faced unparalleled challenges.
We describe our palliative care program's ...response to the increased clinical volume associated with the pandemic by adapting workflows for inpatient and outpatient palliative care teams caring for oncology and nononcology populations.
During the initial surge, the demand for palliative care consultation for patients affected by SARS-CoV-2 was high, accounting for 75% of all inpatient palliative care referral requests for oncology and nononcology patients. Furthermore, our ambulatory clinic experienced a 40% increase in visits for complex oncology patients between February and December of 2020.
This article highlights transformations in palliative care delivery implemented in response to the pandemic and reflects on how these transformations have shaped our current care delivery models. We further delineate our intentional reliance on key population health principles to drive ongoing innovation in palliative care provision across our clinical teams.
Brown Norway rats were exposed by intratracheal instillation of saline, carbon black (CB), or diesel exhaust particles (DEP) (5 mg/kg) on day 1, followed by exposure to ovalbumin (OVA, 90 mg/m 3) or ...saline for 30 minutes on days 1, 8, 15, and 29. Animals were sacrificed on day 30. The DEP, CB, or OVA exposure alone did not result in abnormal levels of inflammatory cells, lactate dehydrogenase (LDH), or total protein in the lavage fluid. In combined OVA-DEP or OVA-CB exposure, however, these markers were significantly increased. The adjuvant effect of CB and DEP on OVA sensitization was evidenced by the marked increases in serum OVA-specific IgG (5.6-fold) and IgE (3.5-4 fold) levels, and the increase in interleukin-4 (IL-4) mRNA levels in lung tissue. The OVA exposure markedly reduced glutathione (GSH) levels in both cell types. In combined DEP-OVA exposure, the level of GSH in lymphocytes was further decreased, indicating a possible interactive effect between DEP and OVA exposures. These results show that both DEP and CB augmented OVA-induced allergic sensitization, and that particle composition of DEP may not be a critical factor for the adjuvant effect. OVA exposure causes significant depletion of intracellular GSH in lymphocytes, which may play a key role in OVA-mediated immune responses.
Background
We characterize the incidence and 5‐year survival of children and adolescents with neuroblastoma stratified by demographic and clinical factors based on the comprehensive data from United ...States Cancer Statistics (USCS) and the National Program of Cancer Registries (NPCR).
Methods
We analyzed the incidence of neuroblastoma from USCS (2003–2019) and survival data from NPCR (2001–2018) for patients less than 20 years old. Incidence trends were calculated by average annual percent change (AAPC) using joinpoint regression. Differences in relative survival were estimated comparing non‐overlapping confidence intervals (CI).
Results
We identified 11,543 primary neuroblastoma cases in USCS. Age‐adjusted incidence was 8.3 per million persons 95% CI: 8.2, 8.5, with an AAPC of 0.4% 95% CI: −0.1, 0.9. Five‐year relative survival from the NPCR dataset (n = 10,676) was 79.7% 95% CI: 78.9, 80.5. Patients aged less than 1 year had the highest 5‐year relative survival (92.5%). Five‐year relative survival was higher for non‐Hispanic White patients (80.7%) or Hispanic patients (80.8%) compared to non‐Hispanic Black patients (72.6%).
Conclusion
Neuroblastoma incidence was stable during 2003–2019. Differences in relative survival exist by sex, age, race/ethnicity, and stage; patients who were male, older, non‐Hispanic Black, or with distant disease had worse survival. Future studies could seek to assess the upstream factors driving disparities in survival, and evaluate interventions to address inequities and improve survival across all groups.
The TNF family cytokine TL1A (Tnfsf15) costimulates T cells and type 2 innate lymphocytes (ILC2) through its receptor DR3 (Tnfrsf25). DR3-deficient mice have reduced T cell accumulation at the site ...of inflammation and reduced ILC2-dependent immune responses in a number of models of autoimmune and allergic diseases. In allergic lung disease models, immunopathology and local Th2 and ILC2 accumulation is reduced in DR3-deficient mice despite normal systemic priming of Th2 responses and generation of T cells secreting IL-13 and IL-4, prompting the question of whether TL1A promotes the development of other T cell subsets that secrete cytokines to drive allergic disease. In this study, we find that TL1A potently promotes generation of murine T cells producing IL-9 (Th9) by signaling through DR3 in a cell-intrinsic manner. TL1A enhances Th9 differentiation through an IL-2 and STAT5-dependent mechanism, unlike the TNF-family member OX40, which promotes Th9 through IL-4 and STAT6. Th9 differentiated in the presence of TL1A are more pathogenic, and endogenous TL1A signaling through DR3 on T cells is required for maximal pathology and IL-9 production in allergic lung inflammation. Taken together, these data identify TL1A-DR3 interactions as a novel pathway that promotes Th9 differentiation and pathogenicity. TL1A may be a potential therapeutic target in diseases dependent on IL-9.
Background
Transfusion of long‐stored red blood cells (RBCs) is associated with decreased in vivo RBC recovery, delivery of RBC breakdown products, and increased morbidity and mortality. Reducing the ...burden of this RBC “storage lesion” is a major challenge in transfusion medicine. Additive solution‐7 (AS‐7) is a new RBC storage solution designed to improve RBC metabolism by providing phosphate and increasing buffering capacity.
Study Design and Methods
Storage quality in AS‐7 was measured in a prospective, randomized, three‐center trial using units of whole blood from healthy human subjects whose RBCs were stored for up to 56 days in AS‐7 (n = 120) or for 42 days in the control solution AS‐1 (n = 60).
Results
Hemolysis and shedding of protein‐containing microvesicles were significantly reduced in RBCs stored in AS‐7 for 42 and 56 days compared with RBCs stored in AS‐1. Autologous in vivo recoveries of RBCs stored in AS‐7 was 88 ± 5% at 42 days (n = 27) and 82 ± 3% at 56 days (n = 27), exceeding recoveries of RBCs stored in currently used solutions.
Conclusion
Increasing the phosphate, pH range, and buffer capacity of a RBC storage system allowed RBCs to be stored better and longer than currently approved storage systems. AS‐7 ameliorates the long‐term storage lesion resulting in significantly increased viability in vitro and in vivo.
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