Interobserver Agreement in the Clinical Assessment of Children With Blunt Abdominal Trauma

Objectives The objective was to determine the interobserver agreement of historical and physical examination findings assessed during the emergency department (ED) evaluation of children with blunt abdominal trauma. Methods This was a planned substudy of a multicenter, prospective cohort study of children younger than 18 years of age evaluated for blunt abdominal trauma. Patients were excluded if injury occurred more than 24 hours prior to evaluation or if computed tomography (CT) imaging was obtained at another hospital prior to transfer to a study site. Two clinicians independently recorded their clinical assessments of a convenience sample of patients onto data collection forms within 60 minutes of each other and prior to CT imaging (if obtained) or knowledge of laboratory results. The authors categorized variables as either subjective symptoms (i.e., patient history) or objective findings (i.e., physical examination). For each variable recorded by the two observers, the agreement beyond that expected by chance was estimated, using the kappa (κ) statistic for categorical variables and weighted κ for ordinal variables. Variables with 95% lower confidence limits (LCLs) κ ≥ 0.4 (moderate agreement or better) were considered to have acceptable agreement. Results A total of 632 pairs of physician observations were obtained on 23 candidate variables. Acceptable agreement was achieved in 16 (70%) of the 23 variables tested. For six subjective symptoms, κ ranged from 0.48 (complaint of shortness of breath) to 0.90 (mechanism of injury), and only the complaint of shortness of breath had a 95% LCL κ < 0.4. For the 17 objective findings, κ ranged from –0.01 (pelvis instability) to 0.82 (seat belt sign present). The 95% LCL for κ was <0.4 for flank tenderness, abnormal chest auscultation, suspicion of alcohol or drug intoxication, pelvis instability, absence of bowel sounds, and peritoneal irritation. Conclusions Observers can achieve at least acceptable agreement on the majority of historical and physical examination variables in children with blunt abdominal trauma evaluated in the ED. Those variables are candidates for consideration for development of a clinical prediction rule for intra‐abdominal injury in children with blunt trauma. Resumen Concordancia Interobservador en la Valoración Clínica de los Niños con Traumatismo Abdominal Cerrado Objetivos Determinar la concordancia interobservador de los hallazgos de la historia clínica y la exploración física obtenidos durante la valoración de los niños con traumatismo abdominal de alta energía en el servicio de urgencias (SU). Metodología Se diseñó un subestudio de un estudio de cohorte prospectivo y multicéntrico de niños de 18 años o menos evaluados por traumatismo abdominal cerrado. Se excluyeron los pacientes si el traumatismo había ocurrido más de 24 horas antes de la primera valoración, o si las imágenes de la tomografía computarizada (TC) se obtuvieron en otro hospital previamente a trasladarse al lugar del estudio. Dos clínicos recogieron de forma independiente su valoración clínica en un formulario de datos, de una muestra de conveniencia de pacientes, en los primeros 60 minutos, y previamente a las imágenes de la TC (si ésta se realizó) o al conocimiento de los resultados del laboratorio. Se clasificaron las variables como síntomas subjetivos (ej.: historia del paciente) o hallazgos objetivos (ej.: exploración física). Para cada variable recogida por los dos observadores, se estimó la concordancia más allá de la esperada por el azar usando el índice kappa (κ) para las variables categóricas y índice κ ponderado para las variables ordinales. Se consideró que existía una concordancia aceptable para las variables con una κ ≥ 0,4 (concordancia moderada o buena) en el límite inferior del intervalo de confianza del 95% (IC 95%). Resultados Se obtuvieron 632 pares de observaciones clínicas en 23 variables candidatas. Se alcanzó la concordancia aceptable en 16 (70%) de ellas. Para los seis síntomas subjetivos, el rango de κ fue de 0,48 (queja de dificultad respiratoria) a 0,90 (mecanismo de la lesión), y sólo la queja de dificultad respiratoria tuvo una κ < 0,4 en el límite inferior del IC 95%. Para los 17 hallazgos objetivos, el rango de κ fue desde ‐0,01 (inestabilidad pelvis) a 0,82 (presencia del signo del cinturón de seguridad). El dolor en el flanco, la auscultación torácica alterada, la sospecha de intoxicación por alcohol o tóxicos, la inestabilidad de pelvis, la ausencia de ruidos intestinales y la irritación peritoneal tuvieron una κ < 0,4 en el límite inferior del IC 95%. Conclusiones Los observadores pueden alcanzar al menos una concordancia aceptable en la mayoría de las variables de la historia clínica y la exploración física en los niños con traumatismo abdominal cerrado evaluado en el SU. Estas variables son candidatas para considerarse en el desarrollo de una regla de predicción clínica para la lesión intrabdominal en los niños con traumatismo de cerrado.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98339/1/acem12132.pd

The Structure of the {\beta} Leonis Debris Disk

We combine nulling interferometry at 10 {\mu}m using the MMT and Keck Telescopes with spectroscopy, imaging, and photometry from 3 to 100 {\mu}m using Spitzer to study the debris disk around {\beta} Leo over a broad range of spatial scales, corresponding to radii of 0.1 to ~100 AU. We have also measured the close binary star o Leo with both Keck and MMT interferometers to verify our procedures with these instruments. The {\beta} Leo debris system has a complex structure: 1.) relatively little material within 1 AU; 2.) an inner component with a color temperature of ~600 K, fitted by a dusty ring from about 2 to 3 AU; and 3.) a second component with a color temperature of ~120 K fitted by a broad dusty emission zone extending from about ~5 AU to ~55 AU. Unlike many other A-type stars with debris disks, {\beta} Leo lacks a dominant outer belt near 100 AU.Comment: 14 page body, 3 page appendix, 15 figure

Comparison of Clinician Suspicion Versus a Clinical Prediction Rule in Identifying Children at Risk for Intra‐abdominal Injuries After Blunt Torso Trauma

ObjectivesEmergency department (ED) identification and radiographic evaluation of children with intra‐abdominal injuries who need acute intervention can be challenging. To date, it is unclear if a clinical prediction rule is superior to unstructured clinician judgment in identifying these children. The objective of this study was to compare the test characteristics of clinician suspicion with a derived clinical prediction rule to identify children at risk of intra‐abdominal injuries undergoing acute intervention following blunt torso trauma.MethodsThis was a planned subanalysis of a prospective, multicenter observational study of children (50% prior to knowledge of abdominal computed tomography (CT) scanning (if performed). Intra‐abdominal injuries undergoing acute intervention were defined by a therapeutic laparotomy, angiographic embolization, blood transfusion for abdominal hemorrhage, or intravenous fluid administration for 2 or more days in those with pancreatic or gastrointestinal injuries. Patients were considered to be positive for clinician suspicion if suspicion was documented as ≥1%. Suspicion ≥ 1% was compared to the presence of any variable in the prediction rule for identifying children with intra‐abdominal injuries undergoing acute intervention.ResultsClinicians recorded their suspicion in 11,919 (99%) of 12,044 patients enrolled in the parent study. Intra‐abdominal injuries undergoing acute intervention were diagnosed in 203 (2%) patients. Abdominal CT scans were obtained in the ED in 2,302 of the 2,667 (86%, 95% confidence interval [CI] = 85% to 88%) enrolled patients with clinician suspicion ≥1% and in 3,016 of the 9,252 (33%, 95% CI = 32% to 34%) patients with clinician suspicion  50% previamente a conocer la tomografía computarizada (TC) abdominal (si fue realizada). La LIA con necesidad de intervención urgente se definió como laparotomía terapéutica, embolización angiográfica, transfusión de sangre por hemorragia intrabdominal o administración de fluidos intravenosos durante 2 o más días en aquéllos con lesiones pancreáticas o gastrointestinales. Los pacientes se consideraron positivos para la sospecha clínica si la sospecha se documentó como ≥1%. La sospecha > 1% se comparó con la presencia de cualquier variable en la regla de predicción para la identificación de niños con LIA con necesidad de una intervención urgente.ResultadosLos clínicos documentaron su sospecha en 11.919 (99%) de los 12.044 pacientes incluidos en el estudio original. La LIA con necesidad de intervención urgente se diagnosticó en 203 (2%) pacientes. Las TC abdominales se obtuvieron en el SU en 2.302 de los 2.667 pacientes (86%, IC95% = 85% a 88%) incluidos con sospecha clínica ≥1%; y en 3.016 de los 9.252 pacientes (33%, IC95% = 32% a 34%) con sospecha clínica < 1%. La sensibilidad de la regla de predicción para LIA con necesidad de intervención aguda fue mayor que la sospecha clínica ≥1% (197 de 203, 97,0%, IC95% = 93,7% a 98,9%, frente a 168 de 203, 82,8%, IC95% = 76,9% a 87,7%, respectivamente; diferencia de 14,2%, IC95% = 8,6% a 20,0%). La especificidad de la regla de predicción, sin embargo, fue menor que la sospecha clínica (4,979 de los 11.716, 42,5%, IC95% = 41,6% a 43,4%, frente a 9,217 de los 11.716, 78,7%, IC95% = 77,9% a 79,4%, respectivamente; diferencia de –36,2%, IC95% = –37,3% a –35,0%). Treinta y cinco de los pacientes con sospecha clínica < 1% (0,4%, IC95% = 0,3% a 0,5%) tuvieron LIA con necesidad de intervención urgente.ConclusionesLa regla de predicción clínica derivada tuvo una sensibilidad mayor de forma significativa, pero menor especificidad que la sospecha clínica para la identificación de niños con necesidad de una intervención urgente. La mayor especificidad de la sospecha clínica, sin embargo, no se tradujo en la práctica clínica, ya que los clínicos obtuvieron más frecuentemente TC abdominales en los pacientes que consideraron de muy bajo riesgo. Si se validase, esta regla de predicción puede ayudar en la toma de decisiones clínicas sobre el uso de TC abdominal en los niños con traumatismo torácico cerrado.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113736/1/acem12739.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113736/2/acem12739_am.pd

Beam mask and sliding window-facilitated deep learning-based accurate and efficient dose prediction for pencil beam scanning proton therapy

Purpose: To develop a DL-based PBSPT dose prediction workflow with high accuracy and balanced complexity to support on-line adaptive proton therapy clinical decision and subsequent replanning. Methods: PBSPT plans of 103 prostate cancer patients and 83 lung cancer patients previously treated at our institution were included in the study, each with CTs, structure sets, and plan doses calculated by the in-house developed Monte-Carlo dose engine. For the ablation study, we designed three experiments corresponding to the following three methods: 1) Experiment 1, the conventional region of interest (ROI) method. 2) Experiment 2, the beam mask (generated by raytracing of proton beams) method to improve proton dose prediction. 3) Experiment 3, the sliding window method for the model to focus on local details to further improve proton dose prediction. A fully connected 3D-Unet was adopted as the backbone. Dose volume histogram (DVH) indices, 3D Gamma passing rates, and dice coefficients for the structures enclosed by the iso-dose lines between the predicted and the ground truth doses were used as the evaluation metrics. The calculation time for each proton dose prediction was recorded to evaluate the method's efficiency. Results: Compared to the conventional ROI method, the beam mask method improved the agreement of DVH indices for both targets and OARs and the sliding window method further improved the agreement of the DVH indices. For the 3D Gamma passing rates in the target, OARs, and BODY (outside target and OARs), the beam mask method can improve the passing rates in these regions and the sliding window method further improved them. A similar trend was also observed for the dice coefficients. In fact, this trend was especially remarkable for relatively low prescription isodose lines. The dose predictions for all the testing cases were completed within 0.25s

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Assignment of epidemiological lineages in an emerging pandemic using the pangolin tool.

Funder: Oxford Martin School, University of OxfordThe response of the global virus genomics community to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been unprecedented, with significant advances made towards the 'real-time' generation and sharing of SARS-CoV-2 genomic data. The rapid growth in virus genome data production has necessitated the development of new analytical methods that can deal with orders of magnitude of more genomes than previously available. Here, we present and describe Phylogenetic Assignment of Named Global Outbreak Lineages (pangolin), a computational tool that has been developed to assign the most likely lineage to a given SARS-CoV-2 genome sequence according to the Pango dynamic lineage nomenclature scheme. To date, nearly two million virus genomes have been submitted to the web-application implementation of pangolin, which has facilitated the SARS-CoV-2 genomic epidemiology and provided researchers with access to actionable information about the pandemic's transmission lineages

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): study protocol for a pilot randomized controlled trial.

BACKGROUND: Trauma is the leading cause of morbidity and mortality in children in the United States. The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage, however, the drug has not been evaluated in a clinical trial in severely injured children. We designed the Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC) trial to evaluate the feasibility of conducting a confirmatory clinical trial that evaluates the effects of TXA in children with severe trauma and hemorrhagic injuries. METHODS: Children with severe trauma and evidence of hemorrhagic torso or brain injuries will be randomized to one of three arms: (1) TXA dose A (15 mg/kg bolus dose over 20 min, followed by 2 mg/kg/hr infusion over 8 h), (2) TXA dose B (30 mg/kg bolus dose over 20 min, followed by 4 mg/kg/hr infusion over 8 h), or (3) placebo. We will use permuted-block randomization by injury type: hemorrhagic brain injury, hemorrhagic torso injury, and combined hemorrhagic brain and torso injury. The trial will be conducted at four pediatric Level I trauma centers. We will collect the following outcome measures: global functioning as measured by the Pediatric Quality of Life (PedsQL) and Pediatric Glasgow Outcome Scale Extended (GOS-E Peds), working memory (digit span test), total amount of blood products transfused in the initial 48 h, intracranial hemorrhage progression at 24 h, coagulation biomarkers, and adverse events (specifically thromboembolic events and seizures). DISCUSSION: This multicenter trial will provide important preliminary data and assess the feasibility of conducting a confirmatory clinical trial that evaluates the benefits of TXA in children with severe trauma and hemorrhagic injuries to the torso and/or brain. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT02840097 . Registered on 14 July 2016