The IPD-IMGT/HLA Database.

It is 24 years since the IPD-IMGT/HLA Database, http://www.ebi.ac.uk/ipd/imgt/hla/, was first released, providing the HLA community with a searchable repository of highly curated HLA sequences. The database now contains over 35 000 alleles of the human Major Histocompatibility Complex (MHC) named by the WHO Nomenclature Committee for Factors of the HLA System. This complex contains the most polymorphic genes in the human genome and is now considered hyperpolymorphic. The IPD-IMGT/HLA Database provides a stable and user-friendly repository for this information. Uptake of Next Generation Sequencing technology in recent years has driven an increase in the number of alleles and the length of sequences submitted. As the size of the database has grown the traditional methods of accessing and presenting this data have been challenged, in response, we have developed a suite of tools providing an enhanced user experience to our traditional web-based users while creating new programmatic access for our bioinformatics user base. This suite of tools is powered by the IPD-API, an Application Programming Interface (API), providing scalable and flexible access to the database. The IPD-API provides a stable platform for our future development allowing us to meet the future challenges of the HLA field and needs of the community.

Lymphatic endothelial cell RXRα is critical for 9-cis-retinoic acid-mediated lymphangiogenesis and prevention of secondary lymphedema.

Secondary lymphedema is a debilitating disease characterized by abnormal soft tissue swelling and caused by lymphatic system dysfunction. Despite a high prevalence of secondary lymphedema after cancer treatments, current management is supportive and there are no approved therapeutic agents that can thwart disease progression. We have previously demonstrated that 9-cis-retinoic acid (9-cisRA) has the potential to be repurposed for lymphedema as it mitigates disease by promoting lymphangiogenesis at the site of lymphatic injury. Although the efficacy of 9-cisRA has been demonstrated in previous studies, the mechanism of action is not completely understood. In this study, we demonstrate that when RXRα is specifically deleted in lymphatic endothelial cells, 9-cisRA fails to induce lymphangiogenesis in vitro and prevent pathologic progression of postsurgical lymphedema in vivo. These findings demonstrate that downstream nuclear receptor RXRα plays a critical role in the therapeutic efficacy of 9-cisRA in postsurgical lymphedema.

Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic Expansion.

BACKGROUND: Mutations in PIEZO1 (Piezo type mechanosensitive ion channel component 1) cause human lymphatic malformations. We have previously uncovered an ORAI1 (ORAI calcium release-activated calcium modulator 1)-mediated mechanotransduction pathway that triggers lymphatic sprouting through Notch downregulation in response to fluid flow. However, the identity of its upstream mechanosensor remains unknown. This study aimed to identify and characterize the molecular sensor that translates the flow-mediated external signal to the Orai1-regulated lymphatic expansion. METHODS: Various mutant mouse models, cellular, biochemical, and molecular biology tools, and a mouse tail lymphedema model were employed to elucidate the role of Piezo1 in flow-induced lymphatic growth and regeneration. RESULTS: Piezo1 was found to be abundantly expressed in lymphatic endothelial cells. Piezo1 knockdown in cultured lymphatic endothelial cells inhibited the laminar flow-induced calcium influx and abrogated the flow-mediated regulation of the Orai1 downstream genes, such as KLF2 (Krüppel-like factor 2), DTX1 (Deltex E3 ubiquitin ligase 1), DTX3L (Deltex E3 ubiquitin ligase 3L,) and NOTCH1 (Notch receptor 1), which are involved in lymphatic sprouting. Conversely, stimulation of Piezo1 activated the Orai1-regulated mechanotransduction in the absence of fluid flow. Piezo1-mediated mechanotransduction was significantly blocked by Orai1 inhibition, establishing the epistatic relationship between Piezo1 and Orai1. Lymphatic-specific conditional Piezo1 knockout largely phenocopied sprouting defects shown in Orai1- or Klf2- knockout lymphatics during embryo development. Postnatal deletion of Piezo1 induced lymphatic regression in adults. Ectopic Dtx3L expression rescued the lymphatic defects caused by Piezo1 knockout, affirming that the Piezo1 promotes lymphatic sprouting through Notch downregulation. Consistently, transgenic Piezo1 expression or pharmacological Piezo1 activation enhanced lymphatic sprouting. Finally, we assessed a potential therapeutic value of Piezo1 activation in lymphatic regeneration and found that a Piezo1 agonist, Yoda1, effectively suppressed postsurgical lymphedema development. CONCLUSIONS: Piezo1 is an upstream mechanosensor for the lymphatic mechanotransduction pathway and regulates lymphatic growth in response to external physical stimuli. Piezo1 activation presents a novel therapeutic opportunity for preventing postsurgical lymphedema. The Piezo1-regulated lymphangiogenesis mechanism offers a molecular basis for Piezo1-associated lymphatic malformation in humans.

Thermal Energy Transport in Oxide Nuclear Fuel.

To efficiently capture the energy of the nuclear bond, advanced nuclear reactor concepts seek solid fuels that must withstand unprecedented temperature and radiation extremes. In these advanced fuels, thermal energy transport under irradiation is directly related to reactor performance as well as reactor safety. The science of thermal transport in nuclear fuel is a grand challenge as a result of both computational and experimental complexities. Here we provide a comprehensive review of thermal transport research on two actinide oxides: one currently in use in commercial nuclear reactors, uranium dioxide (UO2), and one advanced fuel candidate material, thorium dioxide (ThO2). In both materials, heat is carried by lattice waves or phonons. Crystalline defects caused by fission events effectively scatter phonons and lead to a degradation in fuel performance over time. Bolstered by new computational and experimental tools, researchers are now developing the foundational work necessary to accurately model and ultimately control thermal transport in advanced nuclear fuels. We begin by reviewing research aimed at understanding thermal transport in perfect single crystals. The absence of defects enables studies that focus on the fundamental aspects of phonon transport. Next, we review research that targets defect generation and evolution. Here the focus is on ion irradiation studies used as surrogates for damage caused by fission products. We end this review with a discussion of modeling and experimental efforts directed at predicting and validating mesoscale thermal transport in the presence of irradiation defects. While efforts in these research areas have been robust, challenging work remains in developing holistic tools to capture and predict thermal energy transport across widely varying environmental conditions.

Association of outcomes in point-of-care lung ultrasound for bronchiolitis in the pediatric emergency department.

BACKGROUND: Acute bronchiolitis (AB) is the most common lower respiratory tract infection in infants. Objective scoring tools and plain film radiography have limited application, thus diagnosis is clinical. The role of point-of-care lung ultrasound (LUS) is not well established. OBJECTIVE: We sought to characterize LUS findings in infants presenting to the pediatric ED diagnosed with AB, and to identify associations between LUS and respiratory support (RS) at 12 and 24 h, maximum RS during hospitalization, disposition, and hospital length of stay (LOS). METHODS: Infants ≤12 months presenting to the ED and diagnosed with AB were enrolled. LUS was performed at the bedside by a physician. Lungs were divided into 12 segments and scanned, then scored and summated (min. 0, max. 36) in real time accordingly: 0 - A lines with <3 B lines per lung segment. 1 - ≥3 B lines per lung segment, but not consolidated. 2 - consolidated B lines, but no subpleural consolidation. 3 - subpleural consolidation with any findings scoring 1 or 2. Chart review was performed for all patients after discharge. RS was categorized accordingly: RS (room air), low RS (wall O2 or heated high flow nasal cannula <1 L/kg), and high RS (heated high flow nasal cannula ≥1 L/kg or positive pressure). RESULTS: 82 subjects were enrolled. Regarding disposition, the mean (SD) LUS scores were: discharged 1.18 (1.33); admitted to the floor 4.34 (3.62); and admitted to the ICU was 10.84 (6.54). For RS, the mean (SD) LUS scores at 12 h were: no RS 1.56 (1.93), low RS 4.34 (3.51), and high RS 11.94 (6.17). At 24 h: no RS 2.11 (2.35), low RS 4.91 (3.86), and high RS 12.64 (6.48). Maximum RS: no RS 1.22 (1.31), low RS 4.11 (3.61), and high RS 10.45 (6.16). Mean differences for all dispositions and RS time points were statistically significant (p < 0.05, CI >95%). The mean (SD) hospital LOS was 84.5 h (SD 62.9). The Pearson correlation coefficient (r) comparing LOS and LUS was 0.489 (p < 0.0001). CONCLUSION: Higher LUS scores for AB were associated with increased respiratory support, longer LOS, and more acute disposition. The use of bedside LUS in the ED may assist the clinician in the management and disposition of patient's diagnosed with AB.

Characterizing applications, exposure risks, and hazard communication for engineered nanomaterials in construction.

BACKGROUND: Engineered nanomaterials (ENMs) may pose health risks to workers. Objectives were to characterize ENM applications in construction, identify exposure scenarios, and evaluate the quality of safety data sheets (SDSs) for nano-enabled construction products. METHODS: SDSs and product data were obtained from a public database of nano-enabled construction products. Descriptive statistics were calculated for affected trades, product categories, and types of ENMs. A sample of SDSs (n = 33) was evaluated using modified criteria developed by NIOSH researchers. Bulk analysis via transmission electron microscopy characterized nanoparticles in a subset of products. RESULTS: Companies report using >50 ENMs in construction products. ENM composition could not be determined via SDSs for 38.1% of the 907 products examined. Polymers and metal oxides tied for most frequently reported ENMs (n = 87, 9.6%). Nano silica, graphene, carbon nanotubes, and silver nanoparticles were also frequently reported. Most of the products were paints and coatings (n = 483, 53.3%), followed by pre-market additives, cementitious materials, insulation, and lubricants. Workers in twenty construction trades are likely to handle nano-enabled products, these particularly encompass cement and brick masons, painters, laborers, carpenters, glaziers, and insulators. A wide range of exposure scenarios were identified. SDSs were classified as satisfactory (18%), in need of improvement (12%), or in need of significant improvement (70%). Bulk analyses revealed discrepancies between actual ENM composition and those in SDSs. DISCUSSION AND CONCLUSION: There has been significant progress investigating risks to construction workers posed by ENMs, but SDSs need major improvements. This study provides new insights on the use of ENMs in construction, exposure risks, and hazard communication.

Machine learning in computational histopathology: Challenges and opportunities.

Digital histopathological images, high-resolution images of stained tissue samples, are a vital tool for clinicians to diagnose and stage cancers. The visual analysis of patient state based on these images are an important part of oncology workflow. Although pathology workflows have historically been conducted in laboratories under a microscope, the increasing digitization of histopathological images has led to their analysis on computers in the clinic. The last decade has seen the emergence of machine learning, and deep learning in particular, a powerful set of tools for the analysis of histopathological images. Machine learning models trained on large datasets of digitized histopathology slides have resulted in automated models for prediction and stratification of patient risk. In this review, we provide context for the rise of such models in computational histopathology, highlight the clinical tasks they have found success in automating, discuss the various machine learning techniques that have been applied to this domain, and underscore open problems and opportunities.

Contact with Wet Cement-A Preventable Cause of Chemical Burn: Case Report and Discussion.

GENERAL PURPOSE: To review the management of a patient with a chemical burn from wet cement. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Recognize the clinical presentation of a patient with a chemical burn from contact with wet cement.2. Describe features related to the pathophysiology of alkali burns from wet cement.3. Select the proper decontamination procedure after exposure to wet cement.4. Identify steps in the treatment of a patient with a chemical burn from contact with wet cement.

Alkali burn from wet cement is an often unrecognized and completely preventable chemical injury. The prevalence of cement burns is likely underestimated because of a lack of awareness and knowledge among both individuals who work with cement and healthcare providers. Chemical injuries have important differences compared with thermal burns: they are usually produced by longer exposure to noxious agents as opposed to short-term exposure that is quickly stopped. As a result, first aid approaches are different. Chemical burns from cement can be avoided with adequate skin and eye protection as well as immediate first aid if contact occurs. Manufacturers of bagged cement place warning notices on packaging, but these can be small and go unnoticed by consumers. Construction workers and amateur do-it-yourselfers should avoid direct contact with cement for any prolonged amount of time. Watertight boots, gloves, and clothing will prevent contact, and any accidental splash on exposed skin should be immediately washed away. Education and awareness of the consequences of cement burns are the best prevention.

The Landscape of NIAID-funded Observational COVID-19 Cohort Studies.

The spread of SARS-CoV-2 since late 2019 represented an unprecedented public health emergency, which included a need to fully understand COVID-19 disease across all ages and populations. In response, the US National Institute of Allergy and Infectious Diseases (NIAID) rapidly funded epidemiology studies that monitored COVID-19. However, the diversity and breadth of the populations studied in NIAID-funded COVID-19 observational cohorts were not easy to extrapolate because of siloed approaches to collect and report data within NIAID. Here, we describe the effort to develop a harmonized cohort study reporting tool that includes common epidemiological data elements as well as NIAID priorities. We report its implementation to analyze metadata from 58 COVID-19 cohort studies funded February 2020 to June 2021, visualize key metadata including geographic distribution, study duration, participant demographics, sample types collected, and scientific priorities addressed. A bibliographic analysis highlights the scientific publications and citations across these funded studies and demonstrates their enormous impact on the COVID-19 field. These analyses highlight how common data elements and reporting tools can assist funding agencies to capture the landscape and potential gaps during public health responses and how they can assist in decision making.

Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study.

Ivosidenib (AG-120) and enasidenib (AG-221) are targeted oral inhibitors of the mutant isocitrate dehydrogenase (mIDH) 1 and 2 enzymes, respectively. Given their effectiveness as single agents in mIDH1/2 relapsed or refractory acute myeloid leukemia (AML), this phase 1 study evaluated the safety and efficacy of ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed mIDH1/2 AML. Ivosidenib 500 mg once daily and enasidenib 100 mg once daily were well tolerated in this setting, with safety profiles generally consistent with those of induction and consolidation chemotherapy alone. The frequency of IDH differentiation syndrome was low, as expected given the concurrent administration of cytotoxic chemotherapy. In patients receiving ivosidenib, the frequency and grades of QT interval prolongation were similar to those observed with ivosidenib monotherapy. Increases in total bilirubin were more frequently observed in patients treated with enasidenib, consistent with this inhibitor's known potential to inhibit UGT1A1, but did not appear to have significant clinical consequences. In patients receiving ivosidenib (n = 60) or enasidenib (n = 91), end-of-induction complete remission (CR) rates were 55% and 47%, respectively, and CR/CR with incomplete neutrophil or platelet recovery (CR/CRi/CRp) rates were 72% and 63%, respectively. In patients with a best overall response of CR/CRi/CRp, 16/41 (39%) receiving ivosidenib had IDH1 mutation clearance and 15/64 (23%) receiving enasidenib had IDH2 mutation clearance by digital polymerase chain reaction; furthermore, 16/20 (80%) and 10/16 (63%), respectively, became negative for measurable residual disease by multiparameter flow cytometry. This trial was registered at www.clinicaltrials.gov as #NCT02632708.

Treatment of Hypertrophic Burn Scars With Laser Therapy: A Review of Adverse Events.

ABSTRACT: Hypertrophic scarring, characterized by excessive scar tissue formation, is a debilitating outcome that significantly impairs physical and psychosocial recovery after burn injury. Hypertrophic scarring affects a substantial proportion of burn survivors, with reported prevalence as high as 70%. Fractional CO 2 laser (FCL) therapy, a therapy commonly used in acne scar treatment or skin rejuvenation, has become popular in treating hypertrophic scars. Little is known regarding FCL's adverse events for burn scar treatment. We hypothesize that FCL is a safe treatment modality with minimal adverse events in the management of hypertrophic burn scars. This is a retrospective chart review of adverse events after FCL at 2 centers within a single institution. Burn patients undergoing FCL between May 1, 2019, and June 1, 2021 were included. Demographics, injury etiology, laser treatment details, and adverse events were collected. A total of 170 patients, 77 (45.3%) males and 93 (54.7%) females, underwent 544 FCL therapies for burn scars. The average number of treatments per patient was 3 ± 2.23, with a range of 1 to 17 sessions. From the total 544 laser therapy sessions, 13 adverse events (2.4%) were reported. There were 5 reports (0.9%) of increased postprocedural pain and 1 report (0.2%) of increased paresthesia/numbness to laser site. Three instances (0.6%) of increased erythema and 4 reports (0.7%) of epidermal sloughing or blistering were reported. All but 5 patients (2.9%) reported improvements to scar symptoms. This study demonstrates minimal adverse events associated with FCL for hypertrophic burn scar treatment.

IPD-IMGT/HLA Database.

The IPD-IMGT/HLA Database, http://www.ebi.ac.uk/ipd/imgt/hla/, currently contains over 25 000 allele sequence for 45 genes, which are located within the Major Histocompatibility Complex (MHC) of the human genome. This region is the most polymorphic region of the human genome, and the levels of polymorphism seen exceed most other genes. Some of the genes have several thousand variants and are now termed hyperpolymorphic, rather than just simply polymorphic. The IPD-IMGT/HLA Database has provided a stable, highly accessible, user-friendly repository for this information, providing the scientific and medical community access to the many variant sequences of this gene system, that are critical for the successful outcome of transplantation. The number of currently known variants, and dramatic increase in the number of new variants being identified has necessitated a dedicated resource with custom tools for curation and publication. The challenge for the database is to continue to provide a highly curated database of sequence variants, while supporting the increased number of submissions and complexity of sequences. In order to do this, traditional methods of accessing and presenting data will be challenged, and new methods will need to be utilized to keep pace with new discoveries.

Developing an Extubation strategy for the difficult pediatric airway-Who, when, why, where, and how?

Comprehensive airway management of the pediatric patient with a difficult airway requires a plan for the transition back to a patent and protected airway. Multiple techniques are available to manage the periextubation period. Equally important is performing a comprehensive risk assessment and developing a strategy that optimizes the likelihood of safe extubation. This includes team-focused communication of the desired goals, critical steps in the process, and potential responses in the case of failed extubation. This review summarizes extubation of pediatric patients with difficult airways along with one suggested framework to manage this challenging period.

Isolated Medial Maxillary Buttress Displacement in Naso-Orbito-Ethmoid Fractures: A Surgical Indication to Resolve Nasal Airway Obstruction.

PURPOSE: The aim of this study was to present a case series emphasizing low medial maxillary (pyriform) buttress displacement in naso-orbito-ethmoid (NOE) fractures as an operative indication, in the absence of the typical NOE surgical indications (medial canthus displacement, midface bony comminution, nasal bone collapse, and orbital indications), to prevent nasal airway obstruction. METHODS: Five cases of minor NOE fractures are reviewed, where only the low medial maxillary buttress was displaced. The typical surgical indications for NOE repair were absent. RESULTS: In each case, the pyriform buttress was medially and posteriorly displaced, creating nasal airway obstruction in each patient. The medial canthal tendons were all nondisplaced, there was no diplopia, and the other 2 cardinal buttresses (infraorbital rim and nasofrontal junction) were minimally displaced or greensticked. In the acute setting, patients were treated with open reduction and internal fixation. With delayed presentation, septorhinoplasty or osteotomy and fixation were used. Among the patients who had adequate follow-up, nasal airway obstruction was resolved. CONCLUSIONS: This series suggests that, in NOE fractures with isolated displacement at the medial maxillary buttress, nasal airway obstruction should be considered an operative indication (independent of the classical indications) in order to prevent or resolve nasal airway obstruction.

Intravenous Tranexamic Acid is Associated With a Clinically Significant Reduction in Blood Loss in Craniosynostosis Surgery.

ABSTRACT: Blood loss is a potential cause of morbidity and mortality in craniosynostosis surgery. Recent reports have suggested that the use of tranexamic acid (TXA), an antifibrinolytic agent, mitigates this blood loss. A retrospective cohort study of patients undergoing craniosynostosis surgery at a tertiary craniofacial hospital in Sydney was undertaken. Primary outcomes were blood loss and transfusion requirements. Two groups were compared: those who received intravenous prophylactic TXA and those who underwent surgery without TXA. Statistical analysis was performed with Student t test and the Mann-Whitney U test for nonparametric results. We identified 206 patients who underwent craniosynostosis surgery over an 8 year period; 78 control patients and 128 patients that received TXA. Tranexamic acid was found to result in a weight-adjusted calculated blood loss mean difference of 9.6 ml/kg across all procedures (P = 0.0332 95% confidence interval 0.7734-18.4266). The actual blood loss reduction achieved with TXA was 6.7 ml/kg in spring cranioplasties, compared to 15.2 ml/kg in fronto-orbital remodeling procedures. There was a statistically and clinically significant reduction in postoperative transfusion incidence, with transfusions required in 27% of controls and 6% of TXA patients (P < 0.0001). The number needed to treat to prevent giving a unit of blood postoperatively was 4.8. There were no incidences of TXA-specific complications. This study found that TXA is a safe and effective method of decreasing blood loss and transfusion requirements in patients undergoing craniosynostosis surgery. The clinical benefit of TXA is particularly evident in the more invasive craniosynostosis surgeries.

Point-of-Care Ultrasound for Central Venous Assessment in the Emergency Department: A Prospective Study Comparing the Femoral and Internal Jugular Veins.

OBJECTIVES: The objective of this study was to estimate the width, height, and depth of the femoral vein (FV) and internal jugular vein (IJV), both sites of potential central line placement in children, using point-of-care ultrasound. METHODS: This was a prospective observational study. Point-of-care ultrasound was used to measure the width, height, and depth of the right FV and IJV in 100 children. The primary outcome was a comparison of the widths of the FV and the IJV in the same child. Our primary hypothesis was that the IJV would be wider than the FV. Secondary outcome measures included comparison of the heights and depths the FV and IJV and description of vessel overlap frequency between the 2 sites. RESULTS: A total of 106 children were enrolled, with 6 subjects excluded, and equally divided into 5 age groups (0-30 days, 1-24 months, 2-5 years, 6-11 years, and 12-17 years). The FV/IJV width ratios (95% confidence interval) by age were 0.58 (0.49-0.68), 0.53 (0.43-0.66), 0.57 (0.49-0.67), 0.68 (0.55-0.85), and 0.73 (0.62-0.85), all P < 0.002. The FV/IJV height ratios were <1 in all age groups, with P < 0.003 in the 4 youngest age groups. The FV/IJV depth ratios were >1 in 6 to 11 years (P = 0.018) and 12 to 17 years (P < 0.001). CONCLUSIONS: The IJV was significantly wider and taller than the FV in the same child in all age groups. The FV was significantly deeper than the IJV in children 6 years and older. This supports the use of the IJV as a potential site when placing ultrasound-guided central lines in children.

A Novel 3-Dimensional Printing Fabrication Approach for the Production of Pediatric Airway Models.

BACKGROUND: Pediatric airway models currently available for use in education or simulation do not replicate anatomy or tissue responses to procedures. Emphasis on mass production with sturdy but homogeneous materials and low-fidelity casting techniques diminishes these models' abilities to realistically represent the unique characteristics of the pediatric airway, particularly in the infant and younger age ranges. Newer fabrication technologies, including 3-dimensional (3D) printing and castable tissue-like silicones, open new approaches to the simulation of pediatric airways with greater anatomical fidelity and utility for procedure training. METHODS: After ethics approval, available/archived computerized tomography data sets of patients under the age of 2 years were reviewed to identify those suitable for designing new models. A single 21-month-old subject was selected for 3D reconstruction. Manual thresholding was then performed to produce 3D models of selected regions and tissue types within the dataset, which were either directly 3D-printed or later cast in 3D-printed molds with a variety of tissue-like silicones. A series of testing mannequins derived using this multimodal approach were then further refined following direct clinician feedback to develop a series of pediatric airway model prototypes. RESULTS: The initial prototype consisted of separate skeletal (skull, mandible, vertebrae) and soft-tissue (nasal mucosa, pharynx, larynx, gingivae, tongue, functional temporomandibular joint [TMJ] "sleeve," skin) modules. The first iterations of these modules were generated using both single-material and multimaterial 3D printing techniques to achieve the haptic properties of real human tissues. After direct clinical feedback, subsequent prototypes relied on a combination of 3D printing for osseous elements and casting of soft-tissue components from 3D-printed molds, which refined the haptic properties of the nasal, oropharyngeal, laryngeal, and airway tissues, and improved the range of movement required for airway management procedures. This approach of modification based on clinical feedback resulted in superior functional performance. CONCLUSIONS: Our hybrid manufacturing approach, merging 3D-printed components and 3D-printed molds for silicone casting, allows a more accurate representation of both the anatomy and functional characteristics of the pediatric airway for model production. Further, it allows for the direct translation of anatomy derived from real patient medical imaging into a functional airway management simulator, and our modular design allows for modification of individual elements to easily vary anatomical configurations, haptic qualities of components or exchange components to replicate pathology.

Delayed Diagnosis of Injury in Pediatric Trauma Patients at a Level I Trauma Center.

BACKGROUND: Trauma care per Advanced Trauma Life Support addresses immediate threats to life. Occasionally, delays in injury diagnosis occur. Delayed diagnosis of injury (DDI) is a common quality indicator in trauma care, and pediatric DDI data are sparse. OBJECTIVE: Our aim was to describe the DDI rate in a severely injured pediatric trauma population and identify any factors associated with DDI in the pediatric population. METHODS: A prospective cohort of trauma activations in 0- to 16-year-old patients admitted to a pediatric level I trauma center over 12 months with injuries prospectively recorded were followed during admission to identify DDI. RESULTS: A total of 170 trauma activations were enrolled. Twelve patients had type I DDI (7.1%), 15 patients had type II DDI (8.8%), and 5 patients had both type I and type II DDI (2.9%). DDI patients had twice as many injuries and higher Injury Severity Scores (ISS) as non-DDI patients. DDI patients were more likely to require intensive care unit (ICU) admission, longer hospital stay, and ventilator support. Controlling for age and ISS in multivariate analysis, the number of injuries found and requiring a ventilator were significantly associated with DDI. CONCLUSIONS: This prospective study found a type I DDI rate of 7.1% and a type II DDI rate of 8.8% in the pediatric population. DDI patients had a greater number of injuries, higher ISS, higher rate of ICU admission, and were more likely to require mechanical ventilation. This study adds prospective data to the pediatric DDI literature, increases provider awareness of pediatric DDI, and lays the foundation for future study and quality improvement.

Occupational exposure risk during spraying of biocidal paint containing silver nanoparticles.

The study assessed potential to exceed occupational exposure limits while spraying paint with and without a silver nanoparticle biocidal additive. A tradesperson performed the tasks in a sealed chamber with filtered air supply. Integrated air sampling entailed transmission electron microscopy with energy dispersive X-ray analysis, direct-reading of particle number concentrations, and determination of silver mass concentration by NIOSH Method 7300. Silver nanoparticles were primarily embedded in paint spray droplets but also observed as isolated particles. Using an α-level of 0.05, median nanoparticle number concentrations did not differ significantly when spraying conventional vs. biocidal paint, although statistically significant differences were observed at specific particle size ranges <100 nm. The geometric mean concentration of total silver while spraying biocidal paint (n = 6) was 2.1 µg/m3 (95% CI: 1.5-2.8 µg/m3), and no respirable silver was detected (<0.50 µg/m3). The results address a lack of silver nanoparticle exposure data in construction and demonstrate the feasibility of a practical sampling approach. Given similar conditions, the measurements suggest a low probability of exceeding a proposed silver nanoparticle exposure limit of 0.9 µg/m3 as an airborne 8-hr time-weighted average respirable mass concentration. A full workday of exposure to respirable silver at the highest possible level in this study (<0.50 µg/m3) would not exceed the exposure limit, although limitations in comparing short task-based exposures to an 8-hr exposure limit must be noted. There was airflow in the study chamber, whereas exposure levels could increase over time in work environments lacking adequate ventilation. Potential to exceed the exposure limit hinged upon the respirable fraction of the paint mist, which could vary by material and application method. Additional research would improve understanding of silver nanoparticle exposure risks among construction trades, and biological responses to these exposures. Given the potential for exposure variability on construction jobsites, safety and health professionals should be cognizant of methods to assess and control silver nanoparticle exposures.

Association of Follow-Up After an Emergency Department Visit for Mental Illness with Utilization Based Outcomes.

Follow-up within 30 days of an emergency department (ED) visit for mental illness is a new and widely-used quality measure. However, no empirical evidence validates associations between follow-up and subsequent utilization based outcomes. Using Massachusetts all payer claims data, we identified insured individuals with an ED visit for mental illness. Multivariate regression analysis estimated associations between follow-up within 30 days after an ED visit for mental illness with costs, hospitalizations, and additional ED visits in 180 days following the index visit. 63,814 index ED visits were included (56.5% female, mean [SD] age 38.0 [12.1] years, 48% Medicaid covered). 31% of index ED principal diagnoses were for major depressive disorder, 3% schizophrenia, 5% bipolar disorder, 34% anxiety disorder, 0.6% post-traumatic stress disorder, 8% other psychoses, and 19% other mental illness diagnoses. Only 33% of patients had a follow-up visit for mental illness within 30 days. Adjusted regression analyses show timely follow-up is associated with increased costs in the 180 days after (average marginal effect = $1622; 95% confidence interval [CI] 1459, 1786), an increased probability of inpatient hospitalization (2.7 percentage points; 95% CI 0.021, 0.032), and a small reduction in the probability of at least one additional ED visit (- 1.7 percentage points; 95% CI - 0.026 to 0.009). Overall follow-up rates are low; follow-up within 30 days of an ED visit for mental illness is associated with increased costs and increased probability of hospitalization in the follow-up period. It is not known whether increased rates of utilization improve patient outcomes, potentially by receiving appropriate more intensive care.