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Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization of prehospital blood products, (3) use of hemostatic adjuncts, (4) tourniquet use, (5) prehospital airway and blood pressure management, and (6) conventional coagulation tests or thromboelastography-guided resuscitation. A total of 21 recommendations are detailed in this article: 2 clinical recommendations, 14 expert consensus statements, and 5 good practice statements. The statement, the panel's voting outcome, and the rationale for each statement intend to give pediatric trauma providers the latest evidence and guidance to care for pediatric trauma patients experiencing hemorrhagic shock. With a broad multidisciplinary representation, the Pediatric Traumatic Hemorrhagic Shock Consensus Conference systematically evaluated the literature and developed clinical recommendations, expert consensus, and good practice statements concerning topics in traumatically injured pediatric patients with hemorrhagic shock.

Current American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) and European Society of Cardiology (ESC) guidelines recommend different strategies to avoid low-yield admissions in patients with syncope.The purpose of this study was to directly compare the safety and efficacy of applying admission criteria of both guidelines to patients presenting with syncope to the emergency department in 2 multicenter studies.The international BASEL IX (BAsel Syncope EvaLuation) study (median age 71 years) and the U.S. SRS (Improving Syncope Risk Stratification in Older Adults) study (median age 72 years) were investigated. Primary endpoints were sensitivity/specificity for the adjudicated diagnosis of cardiac syncope (BASEL IX only) and 30-day major adverse cardiovascular events (30d-MACE).Among 2560 patients in the BASEL IX and 2085 in SRS studies, ACC/AHA/HRS and ESC criteria recommended admission for a comparable number of patients in BASEL IX (27% vs 28%), but ACC/AHA/HRS criteria less often in SRS (19% vs 32%; P.01). Recommendations were discordant in ∼25% of patients. In BASEL IX, sensitivity for cardiac syncope and 30d-MACE among patients without admission criteria was comparable for ACC/AHA/HRS and ESC criteria (64% vs 65%, P = .86; and 67% vs 71%, P = .15, respectively). In SRS, sensitivity for 30d-MACE was lower with ACC/AHA/HRS (54%) vs ESC criteria (88%; P.001). Similarly, specificity for cardiac syncope and 30d-MACE in BASEL IX was comparable for both guidelines, but in SRS the ACC/AHA/HRS guidelines showed a higher specificity for 30d-MACE than the ESC guidelines.ACC/AHA/HRS and ESC guidelines showed disagreement regarding admission for 1 in 4 patients and had only modest sensitivity, all indicating possible opportunities for improvements.

There is strong evidence in adult literature that tranexamic acid (TXA) given within 3 hours from injury is associated with improved outcomes. The evidence for TXA use in injured children is limited to retrospective studies and one prospective observational trial. Two studies in combat settings and one prospective civilian US study have found association with improved mortality. These studies indicate the need for a randomized controlled trial to evaluate the efficacy of TXA in injured children and to clarify appropriate timing, dose and patient selection. Additional research is also necessary to evaluate trauma-induced coagulopathy in children. Recent studies have identified three distinct fibrinolytic phenotypes following trauma (hyperfibrinolysis, physiologic fibrinolysis, and fibrinolytic shutdown), which can be identified with viscohemostatic assays. Whether viscohemostatic assays can appropriately identify children who may benefit or be harmed by TXA is also unknown.

The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage; however, the drug has not been evaluated in a trial in injured children. We evaluated the feasibility of a large-scale trial evaluating the effects of TXA in children with severe hemorrhagic injuries.Severely injured children (0 up to 18A total of 31 patients were randomized with a mean age of 10.7 years (standard deviation [SD] 5.0 years) and 22 (71%) patients were male. The mean time from injury to randomization was 2.4 hours (SD 0.6 hours). Sixteen (52%) patients had isolated brain injuries and 15 (48%) patients had isolated torso injuries. The enrollment rate using EFIC was 1.34 patients per site per month. All eligible enrolled patients received study intervention (9 patients TXA 15 mg/kg bolus dose, 10 patients TXA 30 mg/kg bolus dose, and 12 patients placebo) and had the primary outcome measured. No statistically significant differences in any of the clinical outcomes were identified.Based on enrollment rate, protocol adherence, and measurement of the primary outcome in this pilot trial, we confirmed the feasibility of conducting a large-scale, randomized trial evaluating the efficacy of TXA in severely injured children with hemorrhagic brain and/or torso injuries using EFIC.

A deep survey of the Large Magellanic Cloud at ~0.1-100TeV photon energies with the Cherenkov Telescope Array is planned. We assess the detection prospects based on a model for the emission of the galaxy, comprising the four known TeV emitters, mock populations of sources, and interstellar emission on galactic scales. We also assess the detectability of 30 Doradus and SN 1987A, and the constraints that can be derived on the nature of dark matter. The survey will allow for fine spectral studies of N157B, N132D, LMC P3, and 30 Doradus C, and half a dozen other sources should be revealed, mainly pulsar-powered objects. The remnant from SN 1987A could be detected if it produces cosmic-ray nuclei with a flat power-law spectrum at high energies, or with a steeper index 2.3-2.4 pending a flux increase by a factor >3-4 over ~2015-2035. Large-scale interstellar emission remains mostly out of reach of the survey if its >10GeV spectrum has a soft photon index ~2.7, but degree-scale 0.1-10TeV pion-decay emission could be detected if the cosmic-ray spectrum hardens above >100GeV. The 30 Doradus star-forming region is detectable if acceleration efficiency is on the order of 1-10% of the mechanical luminosity and diffusion is suppressed by two orders of magnitude within, Accepted for publication in MNRAS. Corresponding authors: Pierrick Martin, Maria Isabel Bernardos Martin, Fabio Iocco

To present consensus statements and supporting literature for plasma and platelet transfusions in critically ill children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children.Not applicable.Critically ill neonates and children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage.None.A panel of eight experts developed expert-based statements for plasma and platelet transfusions in critically ill neonates and children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed one good practice statement and six expert consensus statements.The lack of evidence precludes proposing recommendations on monitoring of the coagulation system and on plasma and platelets transfusion in critically ill pediatric patients with severe trauma, severe traumatic brain injury, or nontraumatic intracranial hemorrhage.

Study objectiveThe objective of this study was to conduct a systematic review and meta-analysis of the diagnostic accuracy of the clinical signs, symptoms, laboratory investigations, and imaging modalities commonly used in patients with clinically suspected renal colic.MethodsWe conducted this systematic reviewand meta-analysisaccording to an a priori, registered protocol (PROSPERO CRD42017055153). A literature search was performed using MEDLINE and EMBASE from inception to July 2, 2020. We assessed the risk of bias using Quality Assessment of Diagnostic Accuracy Studies-2, calculated likelihood ratios (LRs), and applied a random-effects model for meta-analysis.ResultsAmong 7641 references screened, 76 were included in the systematic review and 53 were included in the meta-analyis. The overall pooled prevalence for ureteral stones was 63% (95% confidence interval [CI], 58%-67%). No individual demographic feature, symptom, or sign when present had an LR+ ≥2.0 for identifying ureterolithiasis. A (Sex, Timing and Origin of pain, race, presence or absence of Nausea, and Erythrocytes) STONE score ≥10 increased (sensitivity 0.49, specificity 0.91, LR 5.3 [95% CI, 4.1-6.7]) and a STONE score&nbsp

Background: Research networks need access to EMS data to conduct pilot studies and determine feasibility of prospective studies. Combining data across EMS agencies is complicated and costly. Leveraging the National EMS Information System (NEMSIS) to extract select agencies’ data may be an efficient and cost-effective method of providing network-level data. Objective: Describe the process of creating a Pediatric Emergency Care Applied Research Network (PECARN) specific NEMSIS data set and determine if these data were nationally representative. Methods: We established data use agreements (DUAs) with EMS agencies participating in PECARN to allow for agency identification through NEMSIS. Using 2019 NEMSIS version 3.4.0 data for EMS events with patients 18 years old and younger, we compared PECARN NEMSIS data to national NEMSIS data. Analyzed variables were selected for their ability to characterize events. No statistical analyses were utilized due to the large sample, instead, differences of ±5% were deemed clinically meaningful. Results: DUAs were established for 19 EMS agencies, creating a PECARN data set with 305,188 EMS activations of which 17,478 (5.7%) were pediatric. Of the pediatric activations, 17,140 (98.1%) were initiated through 9-1-1 and 9,487 (55.4%) resulted in transport by the documenting agency. The national data included 36,288,405 EMS activations of which 2,152,849 (5.9%) were pediatric. Of the pediatric activations 1,704,141 (79.2%) were initiated through 9-1-1 and 1,055,504 (61.9%) were transported by the documenting agency. Age and gender distributions were similar between the two groups, but the PECARN-specific data under-represents Black and Latinx patients. Comparison of EMS provider primary impressions revealed that three of the five most common were similar with injury being the most prevalent for both data sets along with mental/behavioral health and seizure. Conclusion: We demonstrated that NEMSIS can be leveraged to create network specific data sets. PECARN’s EMS data were similar to the national data, though racial/ethnic minorities and some primary impressions may be under-represented. Additionally, more EMS activations in PECARN study areas originated through 9-1-1 but fewer were transported by the documenting agency. This is likely related to the type of participating agencies, their ALS response level, and the diversity of the communities they serve.

The objectives of this study were to implement and examine the potential capture rate of a novel instrument, the Expanded Cannabis Inventory, in a population of emergency department (ED) patients presenting after motor vehicle collisions (MVC).Study participants who presented to the ED after MVC were recruited from three hospitals in cannabis-legal states (Denver, CO; Portland, OR; and Sacramento, CA). Research assistants (RAs) administered the Expanded Cannabis Inventory, which includes a wide variety of products that have become readily available in states where cannabis is legal, in addition to assessments related to patient demographic characteristics, general health, cannabis attitudes, and dependency measures. RAs also obtained blood samples for delta-9-THC and metabolites.Among 692 participants who provided responses to questions about cannabis use, 292 (42%) reported past-year use. Seventy-eight (27%) of those identified as using cannabis were only captured due to items in the expanded instrument. These patients were more likely to be White and were more likely to perceive daily use to be of high risk. Fewer had Cannabis Use Disorder Inventory Test (CUDIT) scores consistent with hazardous cannabis use. However, more of the patients only captured by the expanded instrument had high measured blood levels of delta-9-THC on samples obtained in the ED.Changing cannabis use patterns must be reflected in our measurements for clinical practice, research, and surveillance. Instruments that are the current standard in clinical practice capture limited data and may no longer perform well enough to identify a complete cohort or to provide insight into the health behaviors of patients.

OBJECTIVE: We evaluated the acceptability of the Pediatric Quality of Life Inventory (PedsQL) and other outcomes as the primary outcomes for a pediatric hemorrhagic trauma trial (TIC-TOC) among clinicians. METHODS: We conducted a mixed-methods study that included an electronic questionnaire followed by teleconference discussions. Participants confirmed or rejected the PedsQL as the primary outcome for the TIC-TOC trial and evaluated and proposed alternative primary outcomes. Responses were compiled and a list of themes and representative quotes was generated. RESULTS: 73 of 91 (80%) participants completed the questionnaire. 61 (84%) participants agreed that the PedsQL is an appropriate primary outcome for children with hemorrhagic brain injuries. 32 (44%) participants agreed that the PedsQL is an acceptable primary outcome for children with hemorrhagic torso injuries, 27 (38%) participants were neutral, and 13 (18%) participants disagreed. Several themes were identified from responses, including that the PedsQL is an important and patient-centered outcome but may be affected by other factors, and that intracranial hemorrhage progression assessed by brain imaging (among patients with brain injuries) or blood product transfusion requirements (among patients with torso injuries) may be more objective outcomes than the PedsQL. CONCLUSIONS: The PedsQL was a well-accepted proposed primary outcome for children with hemorrhagic brain injuries. Traumatic intracranial hemorrhage progression was favored by a subset of clinicians. A plurality of participants also considered the PedsQL an acceptable outcome for selection for pediatric trauma clinical trial children with hemorrhagic torso injuries. Blood product transfusion requirement was favored by fewer participants.

Background and Purpose: Early detection of large vessel occlusion (LVO) stroke optimizes endovascular therapy and improves outcomes. Clinical stroke severity scales used for LVO identification have variable accuracy. We investigated a portable LVO-detection device (PLD), using electroencephalography and somatosensory-evoked potentials, to identify LVO stroke. Methods: We obtained PLD data in suspected patients with stroke enrolled prospectively via a convenience sample in 8 emergency departments within 24 hours of symptom onset. LVO discriminative signals were integrated into a binary classifier. The National Institutes of Health Stroke Scale was documented, and 4 prehospital stroke scales were retrospectively calculated. We compared PLD and scale performance to diagnostic neuroimaging. Results: Of 109 patients, there were 25 LVO (23%), 38 non-LVO ischemic (35%), 14 hemorrhages (13%), and 32 stroke mimics (29%). The PLD had higher sensitivity (80% [95% CI, 74–85]) and similar specificity (80% [95% CI, 77–83]) to all prehospital scales at their predetermined high probability LVO thresholds. The PLD had high discrimination for LVO ( C -statistic=0.88). Conclusions: The PLD identifies LVO with superior accuracy compared with prehospital stroke scales in emergency department suspected stroke. Future studies need to validate the PLD’s potential as an LVO triage aid in prehospital undifferentiated stroke populations.

Super-Kamiokande has been searching for neutrino bursts characteristic of core-collapse supernovae continuously, in real time, since the start of operations in 1996. The present work focuses on detecting more distant supernovae whose event rate may be too small to trigger in real time, but may be identified using an offline approach. The analysis of data collected from 2008 to 2018 found no evidence of distant supernovae bursts. This establishes an upper limit of 0.29 yr−1 on the rate of core-collapse supernovae out to 100 kpc at 90% C.L. For supernovae that fail to explode and collapse directly to black holes the limit reaches to 300 kpc.

Current guidelines for treating cardiac arrest recommend administering 1 mg of epinephrine every 3–5 min. However, this interval is based solely on expert opinion. We aimed to investigate the impact of the epinephrine administration interval (EAI) on resuscitation outcomes in adults with cardiac arrest. We systematically reviewed the PubMed, EMBASE, and Scopus databases. We included studies comparing different EAIs in adult cardiac arrest patients with reported neurological outcomes. Pooled estimates were calculated using the IVhet meta-analysis, and the heterogeneities were assessed using Q and I2 statistics. We evaluated the study risk of bias and overall quality using validated bias assessment tools. Three studies were included. All were classified as “good quality” studies. Only two reported the primary outcome. Compared with a recommended EAI of 3–5 min, a favorable neurological outcome was not significantly different in patients with the other frequencies: for 5 min, OR 1.01 (95% CI: 0.55–1.87). For survival to hospital discharge, administering epinephrine for less than 3 min was not associated with a good outcome (OR 1.66, 95% CI: 0.89–3.10). Moreover, EAI of >5 min did not pose a benefit (OR 0.87, 95% CI: 0.68–1.11). Our review showed that EAI during CPR was not associated with better hospital outcomes. Further clinical trials are necessary to determine the optimal dosing interval for epinephrine in adults with cardiac arrest.

In order to improve Super-Kamiokande's neutron detection efficiency and to thereby increase its sensitivity to the diffuse supernova neutrino background flux, 13 tons of $\rm Gd_2(\rm SO_4)_3\cdot \rm 8H_2O$ (gadolinium sulfate octahydrate) was dissolved into the detector's otherwise ultrapure water from July 14 to August 17, 2020, marking the start of the SK-Gd phase of operations. During the loading, water was continuously recirculated at a rate of 60 m$^3$/h, extracting water from the top of the detector and mixing it with concentrated $\rm Gd_2(\rm SO_4)_3\cdot \rm 8H_2O$ solution to create a 0.02% solution of the Gd compound before injecting it into the bottom of the detector. A clear boundary between the Gd-loaded and pure water was maintained through the loading, enabling monitoring of the loading itself and the spatial uniformity of the Gd concentration over the 35 days it took to reach the top of the detector. During the subsequent commissioning the recirculation rate was increased to 120 m$^3$/h, resulting in a constant and uniform distribution of Gd throughout the detector and water transparency equivalent to that of previous pure-water operation periods. Using an Am-Be neutron calibration source the mean neutron capture time was measured to be $115\pm1$ $\mu$s, which corresponds to a Gd concentration of $111\pm2$ ppm, as expected for this level of Gd loading. This paper describes changes made to the water circulation system for this detector upgrade, the Gd loading procedure, detector commissioning, and the first neutron calibration measurements in SK-Gd., Comment: 37 pages, 19 Figures, Accepted for publication in Nucl. Instrum. Meth. A

We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218±9 μs. We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218 \pm 9 \mu s.

STUDY OBJECTIVE:In the current era of frequent chest computed tomography (CT) for adult blunt trauma evaluation, many minor injuries are diagnosed, potentially rendering traditional teachings obsolete. We seek to update teachings in regard to thoracic spine fracture by determining how often such fractures are observed on CT only (ie, not visualized on preceding trauma chest radiograph), the admission rate, mortality, and hospital length of stay of thoracic spine fracture patients, and how often thoracic spine fractures are clinically significant. METHODS:This was a preplanned analysis of prospectively collected data from the NEXUS Chest CT study conducted from 2011 to 2014 at 9 Level I trauma centers. The inclusion criteria were older than 14 years, blunt trauma occurring within 6 hours of emergency department (ED) presentation, and chest imaging (radiography, CT, or both) during ED evaluation. RESULTS:Of 11,477 enrolled subjects, 217 (1.9%) had a thoracic spine fracture; 181 of the 198 thoracic spine fracture patients (91.4%) who had both chest radiograph and CT had their thoracic spine fracture observed on CT only. Half of patients (49.8%) had more than 1 level of thoracic spine fracture, with a mean of 2.1 levels (SD 1.6 levels) of thoracic spine involved. Most patients (62%) had associated thoracic injuries. Compared with patients without thoracic spine fracture, those with it had higher admission rates (88.5% versus 47.2%; difference 41.3%; 95% confidence interval 36.3% to 45%), higher mortality (6.3% versus 4.0%; difference 2.3%; 95% confidence interval 0 to 6.7%), and longer length of stay (median 9 versus 6 days; difference 3 days; P

Background The NEXUS Chest CT clinical decision rules (CDRs) have been proposed to safely guide selective chest CT use in blunt trauma evaluation. We conducted a cost-effectiveness analysis of the NEXUS Chest CT CDR to determine its impact on missed injuries, cost, and radiation exposure. Methods We constructed a decision model comparing two strategies: implementation of the NEXUS Chest CDR vs. usual care in the evaluation of adults with blunt trauma. We derived probabilities, clinical outcomes, effective radiation dose (ERD) from the NEXUS Chest CT validation cohort and costs from the Charge-master at the primary study site. Our primary outcomes were cost and effective radiation dose (ERD) per missed clinically significant injury (CSI). Results Using a hypothetical cohort of 1000 adults with blunt chest trauma in each arm, the base case model projected that the implementation of the CDR would result in 161 fewer chest CTs, 0.08 additional missed CSIs, a cost savings of $136,432 and a decrease in 1435 mSv, as compared to Usual Care. To detect one additional CSI, the Usual Care strategy would require 2015 more chest CTs with a cost of $1.8 million and 17,934 mSv more radiation. Conclusions Compared to usual care, implementation of the NEXUS Chest CT Major CDR in the evaluation of adults with blunt trauma would greatly reduce CT associated costs and radiation exposure with a slight increased risk of missed CSIs.

Objectives The CRASH-2 trial demonstrated that tranexamic acid (TXA) in adults with significant traumatic hemorrhage safely reduces mortality. Given that the CRASH-2 trial did not include U.S. sites, our objective was to evaluate patient characteristics, TXA dosing strategies, and the incidence of mortality and adverse events in adult trauma patients receiving TXA at a U.S. Level I trauma center in the post-CRASH-2 era. Methods We conducted a retrospective study that included patients aged 18 years or older who received TXA after an acute injury from July 2014 to June 2017. We excluded patients who received TXA orally, patients who received TXA for elective surgical procedures or nontrauma indications, patients who received it 8 hours or longer after the time of injury, and patients with cardiac arrest at time of emergency department arrival. Trained abstractors collected data from the trauma registry and hospital electronic medical records. Our primary outcome measures were in-hospital death and acute thromboembolic events within 28 days from injury. Results We included 273 patients with a mean (±SD) age of 43.8 (±18.7) years. The mean (±SD) time of administration of TXA from time of injury was 1.55 (±1.2) hours with 229 patients (83.9%) receiving TXA within 3 hours. The overall mortality within 28 days from injury was 12.8% (95% confidence interval [CI] = 8.9% to 16.7%), which was similar compared to that in the CRASH-2 trial (14.5%, 95% CI = 13.9% to 15.2%). The incidence of acute thromboembolic events was 6.6% (95% CI = 3.7% to 9.5%), which was higher than that in the CRASH-2 trial (2.0%, 95% CI = 1.73% to 2.27%). Patients in our cohort also received surgery (64.8% vs. 47.9%) and blood transfusions (74.0% vs. 50.4%) more frequently than those in the CRASH-2 cohort. Conclusions Adult trauma patients receiving TXA had similar incidences of death but higher incidences of thromboembolic events compared to the CRASH-2 trial. Variation in patient characteristics, injury severity, TXA dosing, and surgery and transfusion rates could explain these observed differences. Further research is necessary to provide additional insight into the incidence and risk factors of thromboembolic events in TXA use.

BackgroundOlder adults with isolated rib fractures are often admitted to an intensive care unit (ICU) because of presumedly increased morbidity and mortality. However, evidence-based guidelines are limited. We sought to identify characteristics of these patients that predict the need for ICU care.Materials and methodsWe analyzed patients ≥50y old at our center during 2013-2017 whose only indication for ICU admission, if any, was isolated rib fractures. The primary outcome was any critical care intervention (e.g., intubation) or adverse event (e.g., hypoxemia) (CCIE) based on accepted critical care guidelines. We used stepwise logistic regression to identify characteristics that predict CCIEs.ResultsAmong 401 patients, 251 (63%) were admitted to an ICU. Eighty-three patients (33%) admitted to an ICU and 7 (5%) admitted to the ward experienced a CCIE. The most common CCIEs were hypotension (10%), frequent respiratory therapy (9%), and oxygen desaturation (8%). Predictors of CCIEs included incentive spirometry

Author(s): Yu, Louis; Baumann, Brigitte M; Raja, Ali S; Mower, William R; Langdorf, Mark I; Medak, Anthony J; Anglin, Deirdre R; Hendey, Gregory W; Nishijima, Daniel; Rodriguez, Robert M | Abstract: BACKGROUND:In the era of frequent head-to-pelvis computed tomography (CT) for adult blunt trauma evaluation, we sought to update teachings regarding aortic injury by determining 1) the incidence of aortic injury; 2) the proportion of patients with isolated aortic injury (without other concomitant thoracic injury); 3) the clinical implications of aortic injury (hospital mortality, length of stay [LOS], and rate of surgical interventions); and 4) the screening value of traditional risk factors/markers (such as high-energy mechanism and widened mediastinum on chest x-ray [CXR]) for aortic injury, compared to newer criteria from the recently developed NEXUS Chest CT decision instrument (DI). METHODS:We conducted a preplanned analysis of patients prospectively enrolled in the NEXUS Chest studies at 10 Level I trauma centers with the following inclusion criteria: age g 14nyears, blunt trauma within 6nhours of ED presentation, and receiving chest imaging duringnED trauma evaluation. RESULTS:Of 24,010 enrolled subjects, 42 (0.17%, 95% confidence interval [CI]n= 0.13% to 0.24%) had aortic injury. Most patients (79%, 95% CIn= 64% to 88%) had an associated thoracic injury, with rib fractures, pneumothorax/hemothorax, and pulmonary contusion occurring most frequently. Compared to patients without aortic injury this cohort had similar mortality (9.5%, 95% CIn= 3.8% to 22.1% vs. 5.8%, 95% CIn= 5.4% to 6.3%), longer median hospital LOS (11ndays vs. 3ndays, pnln0.01), and higher median Injury Severity Score (29 vs. 5, pnln0.001). High-energy mechanism and widened mediastinum on CXR had low sensitivity for aortic injury (76% [95% CIn= 62% to 87%] and 33% [95% CIn= 21% to 49%], respectively), compared to the NEXUS Chest CT DI (sensitivity 100% [95% CIn= 92% to 100%]). CONCLUSIONS:Aortic injury is rare in adult ED blunt trauma patients who survive to receive imaging. Most ED aortic injury patients have associated thoracic injuries and survive to hospital discharge.nWidened mediastinum on CXR and high-energy mechanism have relatively low screening sensitivity for aortic injury, but the NEXUS Chest DI detected all cases.

ObjectiveTo evaluate the cost-effectiveness of planned observation on cranial CT use in children with minor head trauma.DesignPlanned secondary analysis of a multicentre prospective observation study.SettingAustralia and New Zealand.PatientsAn analytic cohort of 18 471 children aged InterventionA plan for observation and immediate CT scan were documented after the initial assessment. The planned observation group included those with planned observation and no immediate plan for CT.Main outcome measuresTaking an Australian public-funded healthcare perspective, we estimated the cost-effectiveness of planned observation on the adjusted mean costs per child and CT use reduction by net benefit regression analysis using ordinary least squares with robust SEs and bootstrapping. All costs presented in 2018 euros.ResultsPlanned observation in 4945 (27%) children was cost-saving of €85 (95% CI −120 to −51) with 10.4% lower CT use (95% CI 9.6 to 11.2). This strategy was cost-saving for the PECARN high-risk (−€757 (95% CI −961 to −554)) and intermediate-risk (−€52 (95% CI −99 to −4.3)) categories, with 43% (95% CI 39 to 47) and 11% (95% CI 9.6 to 12.4) lower CT use, respectively. The very low-risk category incurred more cost of €86 (95% CI 67 to 104) with planned observation and 0.05% lower CT use (95% CI −0.61 to 0.71).ConclusionPlanned ED observation in selected children with minor head trauma is cost-effective for reducing CT use for the PECARN intermediate-risk and high-risk categories.Trial registration numberACTRN12614000463673.

Full list of authors: Acciari, V. A.; Ansoldi, S.; Antonelli, L. A.; Arbet Engels, A.; Artero, M.; Asano, K.; Babić, A.; Baquero, A.; Barres de Almeida, U.; Barrio, J. A.; Batković, I.; Becerra González, J.; Bednarek, W.; Bellizzi, L.; Bernardini, E.; Bernardos, M.; Berti, A.; Besenrieder, J.; Bhattacharyya, W.; Bigongiari, C.; Blanch, O.; Bošnjak, Ž.; Busetto, G.; Carosi, R.; Ceribella, G.; Cerruti, M.; Chai, Y.; Chilingarian, A.; Cikota, S.; Colak, S. M.; Colombo, E.; Contreras, J. L.; Cortina, J.; Covino, S.; D'Amico, G.; D'Elia, V.; da Vela, P.; Dazzi, F.; de Angelis, A.; de Lotto, B.; Delfino, M.; Delgado, J.; Delgado Mendez, C.; Depaoli, D.; di Pierro, F.; di Venere, L.; Do Souto Espiñeira, E.; Dominis Prester, D.; Donini, A.; Doro, M.; Fallah Ramazani, V.; Fattorini, A.; Ferrara, G.; Fonseca, M. V.; Font, L.; Fruck, C.; Fukami, S.; García López, R. J.; Garczarczyk, M.; Gasparyan, S.; Gaug, M.; Giglietto, N.; Giordano, F.; Gliwny, P.; Godinović, N.; Green, J. G.; Green, D.; Hadasch, D.; Hahn, A.; Heckmann, L.; Herrera, J.; Hoang, J.; Hrupec, D.; Hütten, M.; Inada, T.; Inoue, S.; Ishio, K.; Iwamura, Y.; Jiménez, I.; Jormanainen, J.; Jouvin, L.; Kajiwara, Y.; Karjalainen, M.; Kerszberg, D.; Kobayashi, Y.; Kubo, H.; Kushida, J.; Lamastra, A.; Lelas, D.; Leone, F.; Lindfors, E.; Lombardi, S.; Longo, F.; López-Coto, R.; López-Moya, M.; López-Oramas, A.; Loporchio, S.; Machado de Oliveira Fraga, B.; Maggio, C.; Majumdar, P.; Makariev, M.; Mallamaci, M.; Maneva, G.; Manganaro, M.; Maraschi, L.; Mariotti, M.; Martínez, M.; Mazin, D.; Menchiari, S.; Mender, S.; Mićanović, S.; Miceli, D.; Miener, T.; Minev, M.; Miranda, J. M.; Mirzoyan, R.; Molina, E.; Moralejo, A.; Morcuende, D.; Moreno, V.; Moretti, E.; Neustroev, V.; Nigro, C.; Nilsson, K.; Nishijima, K.; Noda, K.; Nozaki, S.; Ohtani, Y.; Oka, T.; Otero-Santos, J.; Paiano, S.; Palatiello, M.; Paneque, D.; Paoletti, R.; Paredes, J. M.; Pavletić, L.; Peñil, P.; Perennes, C.; Persic, M.; Prada Moroni, P. G.; Prandini, E.; Priyadarshi, C.; Puljak, I.; Ribó, M.; Rico, J.; Righi, C.; Rugliancich, A.; Saha, L.; Sahakyan, N.; Saito, T.; Sakurai, S.; Satalecka, K.; Saturni, F. G.; Schmidt, K.; Schweizer, T.; Sitarek, J.; Šnidarić, I.; Sobczynska, D.; Spolon, A.; Stamerra, A.; Strom, D.; Strzys, M.; Suda, Y.; Surić, T.; Takahashi, M.; Tavecchio, F.; Temnikov, P.; Terzić, T.; Teshima, M.; Tosti, L.; Truzzi, S.; Tutone, A.; Ubach, S.; van Scherpenberg, J.; Vanzo, G.; Vazquez Acosta, M.; Ventura, S.; Verguilov, V.; Vigorito, C. F.; Vitale, V.; Vovk, I.; Will, M.; Wunderlich, C.; Zarić, D.; Baack, D.; Balbo, M.; Biederbeck, N.; Biland, A.; Bretz, T.; Buss, J.; Dorner, D.; Eisenberger, L.; Elsaesser, D.; Hildebrand, D.; Iotov, R.; Mannheim, K.; Neise, D.; Noethe, M.; Paravac, A.; Rhode, W.; Schleicher, B.; Sliusar, V.; Walter, R.; D'Ammando, F.; Horan, D.; Lien, A. Y.; Baloković, M.; Madejski, G. M.; Perri, M.; Verrecchia, F.; Leto, C.; Lähteenmäki, A.; Tornikoski, M.; Ramakrishnan, V.; Järvelä, E.; Vera, R. J. C.; Chamani, W.; Villata, M.; Raiteri, C. M.; Gupta, A. C.; Pandey, A.; Fuentes, A.; Agudo, I.; Casadio, C.; Semkov, E.; Ibryamov, S.; Marchini, A.; Bachev, R.; Strigachev, A.; Ovcharov, E.; Bozhilov, V.; Valcheva, A.; Zaharieva, E.; Damljanovic, G.; Vince, O.; Larionov, V. M.; Borman, G. A.; Grishina, T. S.; Hagen-Thorn, V. A.; Kopatskaya, E. N.; Larionova, E. G.; Larionova, L. V.; Morozova, D. A.; Nikiforova, A. A.; Savchenko, S. S.; Troitskiy, I. S.; Troitskaya, Y. V.; Vasilyev, A. A.; Merkulova, O. A.; Chen, W. P; Samal, M.; Lin, H. C.; Moody, J. W.; Sadun, A. C.; Jorstad, S. G.; Marscher, A. P.; Weaver, Z. R.; Feige, M.; Kania, J.; Kopp, M.; Kunkel, L.; Reinhart, D.; Scherbantin, A.; Schneider, L.; Lorey, C.; Acosta-Pulido, J. A.; Carnerero, M. I.; Carosati, D.; Kurtanidze, S. O.; Kurtanidze, O. M.; Nikolashvili, M. G.; Chigladze, R. A.; Ivanidze, R. Z.; Kimeridze, G. N.; Sigua, L. A.; Joner, M. D.; Spencer, M.; Giroletti, M.; Marchili, N.; Righini, S.; Rizzi, N.; Bonnoli, G.; MAGIC Collaboration; Fact Collaboration.-- This is an Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., Aims. We present a detailed characterisation and theoretical interpretation of the broadband emission of the paradigmatic TeV blazar Mrk 421, with a special focus on the multi-band flux correlations. Methods. The dataset has been collected through an extensive multi-wavelength campaign organised between 2016 December and 2017 June. The instruments involved are MAGIC, FACT, Fermi-LAT, Swift, GASP-WEBT, OVRO, Medicina, and Metsahovi. Additionally, four deep exposures (several hours long) with simultaneous MAGIC and NuSTAR observations allowed a precise measurement of the falling segments of the two spectral components. Results. The very-high-energy (VHE; E 100 GeV) gamma rays and X-rays are positively correlated at zero time lag, but the strength and characteristics of the correlation change substantially across the various energy bands probed. The VHE versus X-ray fluxes follow dierent patterns, partly due to substantial changes in the Compton dominance for a few days without a simultaneous increase in the X-ray flux (i.e., orphan gamma-ray activity). Studying the broadband spectral energy distribution (SED) during the days including NuSTAR observations, we show that these changes can be explained within a one-zone leptonic model with a blob that increases its size over time. The peak frequency of the synchrotron bump varies by two orders of magnitude throughout the campaign. Our multi-band correlation study also hints at an anti-correlation between UV-optical and X-ray at a significance higher than 3. A VHE flare observed on MJD 57788 (2017 February 4) shows gamma-ray variability on multi-hour timescales, with a factor ten increase in the TeV flux but only a moderate increase in the keV flux. The related broadband SED is better described by a two-zone leptonic scenario rather than by a one-zone scenario.We find that the flare can be produced by the appearance of a compact second blob populated by high energetic electrons spanning a narrow range of Lorentz factors, from 0 min = 2104 to 0 max = 6105. © 2021 Georg Thieme Verlag. All rights reserved., The MAGIC Collaboration would like to thank the Instituto de Astrofísica de Canarias for the excellent working conditions at the Observatorio del Roque de los Muchachos in La Palma. The financial support of the German BMBF, MPG and HGF; the Italian INFN and INAF; the Swiss National Fund SNF; the ERDF under the Spanish Ministerio de Ciencia e Innovación (MICINN) (FPA2017-87859-P, FPA2017-85668-P, FPA2017-82729-C6-5-R, FPA2017-90566-REDC, PID2019-104114RB-C31, PID2019-104114RB-C32, PID2019-105510GB-C31,PID2019-107847RB-C41, PID2019-107847RB-C42, PID2019-107847RB-C44, PID2019-107988GB-C22); the Indian Department of Atomic Energy; the Japanese ICRR, the University of Tokyo, JSPS, and MEXT; the Bulgarian Ministry of Education and Science, National RI Roadmap Project DO1-268/16.12.2019 and the Academy of Finland grant nr. 320045 is gratefully acknowledged. This work was also supported by the Spanish Centro de Excelencia “Severo Ochoa” SEV-2016-0588, SEV-2017-0709 and CEX2019-000920-S, and “María de Maeztu” CEX2019-000918-M, the Unidad de Excelencia “María de Maeztu” MDM-2015-0509-18-2 and the “la Caixa” Foundation (fellowship LCF/BQ/PI18/11630012) and by the CERCA program of the Generalitat de Catalunya; by the Croatian Science Foundation (HrZZ) Project IP-2016-06-9782 and the University of Rijeka Project 13.12.1.3.02; by the DFG Collaborative Research Centers SFB823/C4 and SFB876/C3; the Polish National Research Centre grant UMO-2016/22/M/ST9/00382; and by the Brazilian MCTIC, CNPq and FAPERJ. The important contributions from ETH Zurich grants ETH-10.08-2 and ETH-27.12-1 as well as the funding by the Swiss SNF and the German BMBF (Verbundforschung Astro- und Astroteilchenphysik) and HAP (Helmoltz Alliance for Astroparticle Physics) are gratefully acknowledged. Part of this work is supported by Deutsche Forschungsgemeinschaft (DFG) within the Collaborative Research Center SFB 876 “Providing Information by Resource-Constrained Analysis”, project C3. We are thankful for the very valuable contributions from E. Lorenz, D. Renker and G. Viertel during the early phase of the project. We thank the Instituto de Astrofísica de Canarias for allowing us to operate the telescope at the Observatorio del Roque de los Muchachos in La Palma, the Max-Planck-Institut für Physik for providing us with the mount of the former HEGRA CT3 telescope, and the MAGIC collaboration for their support. The Fermi LAT Collaboration acknowledges generous ongoing support from a number of agencies and institutes that have supported both the development and the operation of the LAT as well as scientific data analysis. These include the National Aeronautics and Space Administration and the Department of Energy in the United States, the Commissariat à l’Energie Atomique and the Centre National de la Recherche Scientifique/Institut National de Physique Nucléaire et de Physique des Particules in France, the Agenzia Spaziale Italiana and the Istituto Nazionale di Fisica Nucleare in Italy, the Ministry of Education, Culture, Sports, Science and Technology (MEXT), High Energy Accelerator Research Organization (KEK) and Japan Aerospace Exploration Agency (JAXA) in Japan, and the K. A. Wallenberg Foundation, the Swedish Research Council and the Swedish National Space Board in Sweden. Additional support for science analysis during the operations phase is gratefully acknowledged from the Istituto Nazionale di Astrofisica in Italy and the Centre National d’Études Spatiales in France. This work performed in part under DOE Contract DE-AC02-76SF00515. This work made use of data from the NuSTAR mission, a project led by the California Institute of Technology, managed by the Jet Propulsion Laboratory, and funded by the National Aeronautics and Space Administration. We thank the NuSTAR Operations, Software, and Calibration teams for support with the execution and analysis of these observations. This research has made use of the NuSTAR Data Analysis Software (NuSTARDAS) jointly developed by the ASI Science Data Center (ASDC; Italy) and the California Institute of Technology (USA). This research has also made use of the XRT Data Analysis Software (XRTDAS) developed under the responsibility of the ASI Science Data Center (ASDC), Italy. A.A.E and D.P acknowledge support from the Deutsche Forschungs gemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC-2094 – 390783311. M. B. acknowledges support from the YCAA Prize Postdoctoral Fellowship and from the Black Hole Initiative at Harvard University, which is funded in part by the Gordon and Betty Moore Foundation (grant GBMF8273) and in part by the John Templeton Foundation. This publication makes use of data obtained at the Metsähovi Radio Observatory, operated by Aalto University in Finland. This research has made use of data from the OVRO 40-m monitoring program (Richards et al. 2011) which is supported in part by NASA grants NNX08AW31G, NNX11A043G, and NNX14AQ89G and NSF grants AST-0808050 and AST-1109911. I.A. acknowledges financial support from the Spanish “Ministerio de Ciencia e Innovación” (MCINN) through the “Center of Excellence Severo Ochoa” award for the Instituto de Astrofísica de Andalucía-CSIC (SEV-2017-0709). Acquisition and reduction of the MAPCAT data was supported in part by MICINN through grants AYA2016-80889-P and PID2019-107847RB-C44. The MAPCAT observations were carried out at the German-Spanish Calar Alto Observatory, which is jointly operated by Junta de Andalucía and Consejo Superior de Investigaciones Científicas. C.C. acknowledges support from the European Research Council (ERC) under the European Union Horizon 2020 research and innovation program under the grant agreement No 771282. This research was partially supported by the Bulgarian National Science Fund of the Ministry of Education and Science under grants KP-06-H28/3 (2018), KP-06-H38/4 (2019) and KP-06-KITAJ/2 (2020). We acknowledge support by Bulgarian National Science Fund under grant DN18-10/2017 and National RI Roadmap Projects DO1-277/16.12.2019 and DO1-268/16.12.2019 of the Ministry of Education and Science of the Republic of Bulgaria. This research was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract No 451-03-68/2020-14/200002). G.D. acknowledges observing grant support from the Institute of Astronomy and Rozhen NAO BAS through the bilateral joint research project “Gaia Celestial Reference Frame (CRF) and fast variable astronomical objects” (2020–2022, head – G. Damljanovic). The BU group was supported in part by NASA Fermi guest investigator program grants 80NSSC19K1505 and 80NSSC20K1566. This study was based in part on observations conducted using the 1.8 m Perkins Telescope Observatory (PTO) in Arizona, which is owned and operated by Boston University. This article is partly based on observations made with the LCOGT Telescopes, one of whose nodes is located at the Observatorios de Canarias del IAC on the island of Tenerife in the Observatorio del Teide. This article is also based partly on data obtained with the STELLA robotic telescopes in Tenerife, an AIP facility jointly operated by AIP and IAC. The Abastumani team acknowledges financial support by the Shota Rustaveli National Science Foundation under contract FR-19-6174. Based on observations with the Medicina telescope operated by INAF – Istituto di Radioastronomia.

Trauma is a major cause of morbidity and mortality in older adults and will become more common as the population ages. Tranexamic acid (TXA) is a lysine analogue frequently used in the setting of significant trauma with hemorrhage. The aim of this study is to investigate the heterogeneity of treatment effect of TXA as it relates to patient age during trauma care.We included patients from the CRASH-2 trial who were randomized within 3 h of injury. Patients were stratified into age groups26 years, 26 to 35 years, 36 to 45 years, 46 to 55 years, and 55 years. Multiple logistic regression models were utilized to evaluate adjusted odds ratios (OR) with 95% confidence intervals (CI) for mortality. Heterogeneity of treatment effect was evaluated using Akaike and Bayesian information criteria to determine the optimum logistic regression model after which a Wald Chi-square test was utilized to evaluate statistical significance.On univariate analysis, TXA administration decreased mortality within the26 years cohort (decrease of 2.1%, 95% CI 0.2 to 4.0), 46 to 55 years cohort (decrease 6.7%, 95% CI 2.7 to 10.7), and 55 years cohort (decrease of 5.3%, 95% CI 0.4 to 10.3). On adjusted analysis, when compared to the 36 to 45 years cohort, the26 year cohort experienced a decreased mortality (OR 0.72, 95% CI 0.62 to 0.85) whereas the55 year cohort experienced increased mortality (OR 1.8, 95% CI 1.5 to 2.2). Assessment for heterogeneity of treatment effect of TXA administration between groups approached but did not reach statistical significance (p = 0.11).Mortality related to trauma increases with age, however, there does not appear to be heterogeneity of treatment effect for TXA administration among different age groups.

Trauma is the leading cause of childhood death in the United States. Our goal was to determine the effectiveness of tranexamic acid (TXA) in improving survival in pediatric trauma.MEDLINE (OVID), Embase (OVID), Cochrane Central Register databases, CINAHL (EBSCO), Web of Science (Clarivate Analytics), and grey literature sources were searched for publications reporting survival and safety outcomes in children receiving TXA in acute trauma, with no language restrictions, published until February 11, 2021. Two independent researchers assessed studies for eligibility, bias, and quality. Data on the study setting, injury type, participants, design, interventions, TXA dosing and outcomes were extracted. The primary outcome was survival in children who received TXA following trauma. Forest plots of effect estimates were constructed for each study. Heterogeneity was assessed and data were pooled by meta-analysis using a random-effects model.Fourteen articles met inclusion criteria - six single-institution and eight multicentre retrospective cohort studies. Overall, TXA use was not associated with increased survival in pediatric trauma (adjusted odds ratio [aOR]: 0.61, 95% CI: 0.30-1.22) after adjustment for patient-level variables, such as injury severity. Increased survival was documented in the subset of children experiencing trauma in combat settings (aOR for mortality: 0.31, 95% CI: 0.14-0.68). There were no differences in the odds of thromboembolic events (OR 1.15, 95% CI: 0.46-2.87) in children who received TXA versus not.The utility of TXA in children with trauma is unclear. Guidelines supporting TXA use in pediatric trauma may not be based on the available evidence of its use in this context. Rigorous trials measuring survival and other meaningful outcomes and exploring optimal TXA dosing are urgently needed. Study Registration (PROSPERO): CRD42020157683.

A previous study demonstrated that the Pediatric Quality of Life Inventory, a health-related quality-of-life instrument consisting of physical and psychosocial domain scores, reliably differentiates between children with varying severities of traumatic brain injuries (N = 729) 3, 12, and 24 mos after injury. However, the Pediatric Quality of Life Inventory physical domain score alone may simplify evaluation outcomes in physical rehabilitation and clinical research when comparing different trauma interventions. Therefore, we performed a secondary analysis to evaluate and compare the discriminative capacity of traumatic brain injury severity for changes in the overall Pediatric Quality of Life Inventory or the Pediatric Quality of Life Inventory physical domain score alone. We used linear mixed models to assess the change of outcome scores from baseline compared with arm-injury controls. Somers' D was calculated to compare discriminatory capacity with injury severity as a predictor of change in Pediatric Quality of Life Inventory outcome scores. We found that traumatic brain injury severity in children can be differentiated by the Pediatric Quality of Life Inventory physical domain score alone. However, at all follow-up time points, traumatic brain injury severity had higher discriminatory capacity for changes in the overall Pediatric Quality of Life Inventory. Our results suggest that the overall Pediatric Quality of Life Inventory should be used preferentially in children with traumatic brain injuries, although further investigation of the physical domain is warranted in conditions where physical injuries may predominate.

Full list of authors: Acciari, V. A.; Ansoldi, S.; Antonelli, L. A.; Arbet Engels, A. ; Artero, M.; Asano, K.; Baack, D.; Babić, A.; Baquero, A.; Barres de Almeida, U.; Barrio, J. A.; Batković, I.; Becerra González, J.; Bednarek, W.; Bellizzi, L.; Bernardini, E.; Bernardos, M.; Berti, A.; Besenrieder, J.; Bhattacharyya, W.; Bigongiari, C.; Biland, A.; Blanch, O.; Bošnjak, Ž.; Busetto, G.; Carosi, R.; Ceribella, G.; Cerruti, M.; Chai, Y.; Chilingarian, A.; Cikota, S.; Colak, S. M.; Colombo, E.; Contreras, J. L.; Cortina, J.; Covino, S.; D'Amico, G.; D'Elia, V.; da Vela, P.; Dazzi, F.; de Angelis, A.; de Lotto, B.; Delfino, M.; Delgado, J.; Delgado Mendez, C.; Depaoli, D.; Pierro, F. Di; Venere, L. Di; Do Souto Espiñeira, E.; Dominis Prester, D.; Donini, A.; Dorner, D.; Doro, M.; Elsaesser, D.; Fallah Ramazani, V.; Fattorini, A.; Ferrara, G.; Fonseca, M. V.; Font, L.; Fruck, C.; Fukami, S.; García López, R. J.; Garczarczyk, M.; Gasparyan, S.; Gaug, M.; Giglietto, N.; Giordano, F.; Gliwny, P.; Godinović, N.; Green, J. G.; Green, D.; Hadasch, D.; Hahn, A.; Heckmann, L.; Herrera, J.; Hoang, J.; Hrupec, D.; Hütten, M.; Inada, T.; Inoue, S.; Ishio, K.; Iwamura, Y.; Jiménez, I.; Jormanainen, J.; Jouvin, L.; Kajiwara, Y.; Karjalainen, M.; Kerszberg, D.; Kobayashi, Y.; Kubo, H.; Kushida, J.; Lamastra, A.; Lelas, D.; Leone, F.; Lindfors, E.; Lombardi, S.; Longo, F.; López-Coto, R.; López-Moya, M.; López-Oramas, A.; Loporchio, S.; Machado de Oliveira Fraga, B.; Maggio, C.; Majumdar, P.; Makariev, M.; Mallamaci, M.; Maneva, G.; Manganaro, M.; Mannheim, K.; Maraschi, L.; Mariotti, M.; Martínez, M.; Mazin, D.; Menchiari, S.; Mender, S.; Mićanović, S.; Miceli, D.; Miener, T.; Minev, M.; Miranda, J. M.; Mirzoyan, R.; Molina, E.; Moralejo, A.; Morcuende, D.; Moreno, V.; Moretti, E.; Neustroev, V.; Nigro, C.; Nilsson, K.; Nishijima, K.; Noda, K.; Nozaki, S.; Ohtani, Y.; Oka, T.; Otero-Santos, J.; Paiano, S.; Palatiello, M.; Paneque, D.; Paoletti, R.; Paredes, J. M.; Pavletić, L.; Peñil, P.; Perennes, C.; Persic, M.; Prada Moroni, P. G.; Prandini, E.; Priyadarshi, C.; Puljak, I.; Rhode, W.; Ribó, M.; Rico, J.; Righi, C.; Rugliancich, A.; Saha, L.; Sahakyan, N.; Saito, T.; Sakurai, S.; Satalecka, K.; Saturni, F. G.; Schleicher, B.; Schmidt, K.; Schweizer, T.; Sitarek, J.; Šnidarić, I.; Sobczynska, D.; Spolon, A.; Stamerra, A.; Strom, D.; Strzys, M.; Suda, Y.; Surić, T.; Takahashi, M.; Tavecchio, F.; Temnikov, P.; Terzić, T.; Teshima, M.; Tosti, L.; Truzzi, S.; Tutone, A.; Ubach, S.; van Scherpenberg, J.; Vanzo, G.; Vazquez Acosta, M.; Ventura, S.; Verguilov, V.; Vigorito, C. F.; Vitale, V.; Vovk, I.; Will, M.; Wunderlich, C.; Zarić, D.; Bissaldi, E.; Bonnoli, G.; Cutini, S.; D'Ammando, F.; Nabizadeh, A.; Marchini, A.; Orienti, M.; MAGIC Collaboration., We report here on the first multiwavelength (MWL) campaign on the blazar TXS 1515-273, undertaken in 2019 and extending from radio to very-high-energy gamma-rays (VHE). Up until now, this blazar had not been the subject of any detailed MWL observations. It has a rather hard photon index at GeV energies and was considered a candidate extreme high-synchrotron-peaked source. MAGIC observations resulted in the first-time detection of the source in VHE with a statistical significance of 7.6σ. The average integral VHE flux of the source is 6 ± 1 per cent of the Crab nebula flux above 400 GeV. X-ray coverage was provided by Swift-XRT, XMM-Newton, and NuSTAR. The long continuous X-ray observations were separated by ∼9 h, both showing clear hour scale flares. In the XMM-Newton data, both the rise and decay time-scales are longer in the soft X-ray than in the hard X-ray band, indicating the presence of a particle cooling regime. The X-ray variability time-scales were used to constrain the size of the emission region and the strength of the magnetic field. The data allowed us to determine the synchrotron peak frequency and classify the source as a flaring high, but not extreme synchrotron-peaked object. Considering the constraints and variability patterns from the X-ray data, we model the broad-band spectral energy distribution. We applied a simple one-zone model, which could not reproduce the radio emission and the shape of the optical emission, and a two-component leptonic model with two interacting components, enabling us to reproduce the emission from radio to VHE band. © 2021 The Author(s) Published by Oxford University Press on behalf of Royal Astronomical Society., The financial support of the German BMBF, MPG, and HGF; the Italian INFN and INAF; the Swiss National Fund SNF; the ERDF under the Spanish Ministerio de Ciencia e Innovacion (MICINN) (FPA201787859-P, FPA2017-85668-P, FPA2017-82729-C6-5-R, FPA201790566-REDC, PID2019-104114RB-C31, PID2019-104114RB-C32, PID2019-105510GB-C31, PID2019-107847RB-C41, PID2019107847RB-C42, PID2019-107847RB-C44, PID2019-107988GBC22); the Indian Department of Atomic Energy; the Japanese ICRR, the University of Tokyo, JSPS, and MEXT; the Bulgarian Ministry of Education and Science, National RI Roadmap Project DO1268/16.12.2019 and the Academy of Finland grant nr. 317637 and 320045 are gratefully acknowledged. This work was also supported by the Spanish Centro de Excelencia `Severo Ochoa' SEV-20160588, SEV-2017-0709 and CEX2019-000920-S, and `Maria de Maeztu' CEX2019-000918-M, the Unidad de Excelencia `Maria de Maeztu' MDM-2015-0509-18-2 and the `la Caixa' Foundation (fellowshipLCF/BQ/PI18/11630012), by the Croatian Science Foundation (HrZZ) Project IP-2016-06-9782 and the University of Rijeka Project 13.12.1.3.02, by the DFG Collaborative Research Centers SFB823/C4 and SFB876/C3, the Polish National Research Centre grant UMO-2016/22/M/ST9/00382 and by the Brazilian MCTIC, CNPq, and FAPERJ. The Fermi-LAT Collaboration acknowledges generous ongoing support from a number of agencies and institutes that have supported both the development and the operation of the LAT as well as scientific data analysis. These include the National Aeronautics and Space Administration and the Department of Energy in the United States, theCommissariat à l'Energie Atomique and the Centre National de la Recherche Scientifique/Institut National de Physique Nucleaire et de Physique des Particules in France, the Agenzia Spaziale Italiana and the Istituto Nazionale di Fisica Nucleare in Italy, the Ministry of Education, Culture, Sports, Science and Technology (MEXT), High Energy Accelerator Research Organization (KEK) and Japan Aerospace Exploration Agency (JAXA) in Japan, and the K. A. Wallenberg Foundation, the Swedish Research Council and the Swedish National Space Board in Sweden. Additional support for science analysis during the operations phase from the following agencies is also gratefully acknowledged: the Istituto Nazionale di Astrofisica in Italy and the Centre National d'Etudes Spatiales in France.

The Super-Kamiokande detector can be used to search for neutrinos in time coincidence with gravitational waves detected by the LIGO-Virgo Collaboration (LVC). Both low-energy ($7-100$ MeV) and high-energy ($0.1-10^5$ GeV) samples were analyzed in order to cover a very wide neutrino spectrum. Follow-ups of 36 (out of 39) gravitational waves reported in the GWTC-2 catalog were examined; no significant excess above the background was observed, with 10 (24) observed neutrinos compared with 4.8 (25.0) expected events in the high-energy (low-energy) samples. A statistical approach was used to compute the significance of potential coincidences. For each observation, p-values were estimated using neutrino direction and LVC sky map ; the most significant event (GW190602_175927) is associated with a post-trial p-value of $7.8\%$ ($1.4\sigma$). Additionally, flux limits were computed independently for each sample and by combining the samples. The energy emitted as neutrinos by the identified gravitational wave sources was constrained, both for given flavors and for all-flavors assuming equipartition between the different flavors, independently for each trigger and by combining sources of the same nature., Comment: 16 pages, 5 figures. v2: adding corrections from The Astrophysical Journal review

Importance In patients with acute spontaneous or traumatic intracranial hemorrhage, early hemostasis is thought to be critical to minimize ongoing bleeding. However, research evaluating hemostatic therapies has been hampered by a lack of standardized clinical trial outcome measures. Objective To identify appropriate primary outcomes for phase 2 and 3 clinical trials of therapies aimed at reducing acute intracranial bleeding. Evidence Review A comprehensive review of all previous clinical trials of hemostatic therapy for intracranial bleeding was performed, and studies measuring the frequency, risk factors, and association of intracranial bleeding with outcome of hemorrhage growth were included. Findings A hierarchy of 3 outcome measures is recommended, with the first choice being a global patient-centered clinical outcome scale measured 30 to 180 days after the event; the second, a combined clinical and radiographic end point associating hemorrhage expansion with a poor patient-centered outcome at 24 hours or later; and the third, a radiographic measure of hemorrhage expansion at 24 hours alone. Additional recommendations stress the importance of separating various subtypes of bleeding when possible, early treatment within a standardized treatment window, and the routine use of computerized planimetry comparing continuous measures of absolute and relative hemorrhage growth as either a primary or secondary end point. Conclusions and Relevance Standardization of outcome measures in studies of intracranial bleeding and hemostatic therapy will support comparative effectiveness research and meta-analysis, with the goal of accelerating the translation of research into clinical practice. The 3 outcome measures proposed in this consensus statement could help this process.

The radioactivity background are among the most dangerous background for low energy neutrino analysis in Super-Kamiokande (SK), like the solar neutrino analysis. Among them, the main contribution is coming from $^{222}$Rn, which is spread in the detector's water due to the water source and to the photo multiplier (PMT) emanations. Up to now, its exact distribution in the detector was not known. Using our knowledge of the radon concentration in the detector water, and the SK-IV solar data, we developed a model of the radon distribution in the detector. The uncertainty on the Rn concentration associated with this model was estimated to be $\sim0.1$ mBq/m$^{3}$

Background Federal exception from informed consent (EFIC) procedures allow studies to enroll patients with time-sensitive, life-threatening conditions when written consent is not feasible. Our objective was to compare enrollment rates with and without EFIC in a trial of tranexamic acid (TXA) for children with hemorrhagic injuries. Methods We conducted a four-center randomized controlled pilot and feasibility trial evaluating TXA in children with severe hemorrhagic brain and/or torso injuries. We initiated the trial enrolling patients without EFIC. After 3 months of enrollment, we met our a priori futility threshold and paused the trial to incorporate EFIC procedures and obtain regulatory approval. We then restarted the trial allowing EFIC if the guardian was unable to provide timely written consent. We used descriptive statistics to compare characteristics of eligible patients approached with and without EFIC procedures. We also calculated the time delay to restart the trial using EFIC. Results We enrolled 1 of 15 (6.7%) eligible patients (0.17 per site per month) prior to using EFIC procedures. Of the 14 missed eligible patients, 7 (50%) were not enrolled because guardians were not present or were injured and unable to provide written consent. After obtaining approval for EFIC, we enrolled 30 of 48 (62.5%) eligible patients (1.34 per site per month). Of these 30 patients, 22 (73.3%) were enrolled with EFIC. Of the 22, no guardians refused written consent after randomization. There were no significant differences in the eligibility rate and patient characteristics enrolled with and without EFIC procedures. Across all sites, the mean delay to restart the trial using EFIC procedures was 12 months. Conclusions In a multicenter trial of severely injured children, the use of EFIC procedures greatly increased the enrollment rate and was well accepted by guardians. Initiating the trial without EFIC procedures led to a significant delay in enrollment.

Background A pediatric field triage strategy that meets the national policy benchmark of ≥95% sensitivity would likely improve health outcomes but increase heath care costs. Our objective was to compare the cost-effectiveness of current pediatric field triage practices to an alternative field triage strategy that meets the national policy benchmark of ≥95% sensitivity. Study design We developed a decision-analysis Markov model to compare the outcomes and costs of the two strategies. We used a prospectively collected cohort of 3507 (probability weighted, unweighted n = 2832) injured children transported by 44 emergency medical services (EMS) agencies to 28 trauma and non-trauma centers in the Northwestern United States from 1/1/2011 to 12/31/2011 to derive the alternative field triage strategy and to populate model probability and cost inputs for both strategies. We compared the two strategies by calculating quality adjusted life years (QALYs) and health care costs over a time horizon from the time of injury until death. We set an incremental cost-effectiveness ratio threshold of less than $100,000 per QALY for the alternative field triage to be a cost-effective strategy. Results Current pediatric field triage practices had a sensitivity of 87.4% (95% confidence interval [CI] 71.9 to 95.0%) and a specificity of 82.3% (95% CI 81.0 to 83.5%) and the alternative field triage strategy had a sensitivity of 97.3% (95% CI 82.6 to 99.6%) and a specificity of 46.1% (95% CI 43.8 to 48.4%). The alternative field triage strategy would cost $476,396 per QALY gained compared to current pediatric field triage practices and thus would not be a cost-effective strategy. Sensitivity analyses demonstrated similar findings. Conclusion Current field triage practices do not meet national policy benchmarks for sensitivity. However, an alternative field triage strategy that meets the national policy benchmark of ≥95% sensitivity is not a cost-effective strategy.