Headache that will not go away...Third ED visit is the charm?

Subdural hematoma is an uncommon complication of epidural analgesia or diagnostic lumbar puncture. Headache is a common complaint for patients with either a subdural hematoma or a post-dural puncture headache. Because post-dural puncture headaches are commonly seen in the Emergency Department, the potential to miss more serious pathology arises. We present the case of a young female who suffered bilateral subdural hematomas following epidural analgesia during childbirth. She presented twice to the Emergency Department and was treated for a post-dural puncture headache before computed tomography imaging revealed the diagnosis on the third Emergency Department encounter. This case highlights the importance of exploring all potential diagnoses when a patient presents with a headache after either epidural analgesia or a diagnostic lumbar puncture, especially if the patient returns after unsuccessful treatment for a presumptive post-dural puncture headache.

RNAseq of INOCA patients identifies innate, invariant, and acquired immune changes: potential autoimmune microvascular dysfunction.

Background: Ischemia with non-obstructive coronary arteries (INOCA) is a major clinical entity that involves potentially 20%-30% of patients with chest pain. INOCA is typically attributed either to coronary microvascular disease and/or vasospasm, but is likely distinct from classical coronary artery disease (CAD). Objectives: To gain insights into the etiology of INOCA and CAD, RNA sequencing of whole blood from patients undergoing both stress testing and elective invasive coronary angiography (ICA) was conducted. Methods: Stress testing and ICA of 177 patients identified 40 patients (23%) with INOCA compared to 39 controls (stress-, ICA-). ICA+ patients divided into 38 stress- and 60 stress+. RNAseq was performed by Illumina with ribosomal RNA depletion. Transcriptome changes were analyzed by DeSeq2 and curated by manual and automated methods. Results: Differentially expressed genes for INOCA were associated with elevated levels of transcripts related to mucosal-associated invariant T (MAIT) cells, plasmacytoid dendritic cells (pcDC), and memory B cells, and were associated with autoimmune diseases such as rheumatoid arthritis. Decreased transcripts were associated with neutrophils, but neutrophil transcripts, per se, were not less abundant in INOCA. CAD transcripts were more related to T cell functions. Conclusions: Elevated transcripts related to pcDC, MAIT, and memory B cells suggest an autoimmune component to INOCA. Reduced neutrophil transcripts are likely attributed to chronic activation leading to increased translation and degradation. Thus, INOCA could result from stimulation of B cell, pcDC, invariant T cell, and neutrophil activation that compromises cardiac microvascular function.

Blood RNA Biomarkers Identify Bacterial and Biofilm Coinfections in COVID-19 Intensive Care Patients.

Purpose: Secondary opportunistic coinfections are a significant contributor to morbidity and mortality in intensive care unit (ICU) patients, but can be difficult to identify. Presently, new blood RNA biomarkers were tested in ICU patients to diagnose viral, bacterial, and biofilm coinfections. Methods: COVID-19 ICU patients had whole blood drawn in RNA preservative and stored at -80°C. Controls and subclinical infections were also studied. Droplet digital polymerase chain reaction (ddPCR) quantified 6 RNA biomarkers of host neutrophil activation to bacterial (DEFA1), biofilm (alkaline phosphatase [ALPL], IL8RB/CXCR2), and viral infections (IFI27, RSAD2). Viral titer in blood was measured by ddPCR for SARS-CoV2 (SCV2). Results: RNA biomarkers were elevated in ICU patients relative to controls. DEFA1 and ALPL RNA were significantly higher in severe versus incidental/moderate cases. SOFA score was correlated with white blood cell count (0.42), platelet count (-0.41), creatinine (0.38), and lactate dehydrogenase (0.31). ALPL RNA (0.59) showed the best correlation with SOFA score. IFI27 (0.52) and RSAD2 (0.38) were positively correlated with SCV2 viral titer. Overall, 57.8% of COVID-19 patients had a positive RNA biomarker for bacterial or biofilm infection. Conclusions: RNA biomarkers of host neutrophil activation indicate the presence of bacterial and biofilm coinfections in most COVID-19 patients. Recognizing coinfections may help to guide the treatment of ICU patients.

History and Prospects of Drug Discovery and Development Collaboration between Industry and Academia.

Research collaborations and licensing deals are critical for the discovery and development of life-saving drugs. This practice has been ongoing since the inception of the pharmaceutical industry. The current process of drug discovery and development is complex, regulated, and highly regimented, having evolved over time. Academia excels in the discovery of fundamental scientific concepts and biological processes, while industry excels in translational science and product development. Potential for collaboration exists at every step of the drug discovery and development continuum. This perspective walks through such collaborative activities, provides examples, and offers tips for potential collaborations.

Association of Body Surface Area With Access to Deceased Donor Liver Transplant and Novel Allocation Policies.

Importance: Small waitlist candidates are significantly less likely than larger candidates to receive a liver transplant. Objective: To investigate the magnitude of the size disparity and test potential policy solutions. Design, Setting, and Participants: A decision analytical model was generated to match liver transplant donors to waitlist candidates based on predefined body surface area (BSA) ratio limits (donor BSA divided by recipient BSA). Participants included adult deceased liver transplant donors and waitlist candidates in the Organ Procurement and Transplantation Network database from June 18, 2013, to March 20, 2020. Data were analyzed from January 2021 to September 2021. Exposures: Candidates were categorized into 6 groups according to BSA from smallest (group 1) to largest (group 6). Waitlist outcomes were examined. A match run was created for each donor under the current acuity circle liver allocation policy, and the proportion of candidates eligible for a liver based on BSA ratio was calculated. Novel allocation models were then tested. Main Outcomes and Measures: Time on the waitlist, assigned Model for End-Stage Liver Disease (MELD) score, and proportion of patients undergoing a transplant were compared by BSA group. Modeling under the current allocation policies was used to determine baseline access to transplant by group. Simulation of novel allocation policies was performed to examine change in access. Results: There were 41 341 donors (24 842 [60.1%] male and 16 499 [39.9%] female) and 84 201 waitlist candidates (53 724 [63.8%] male and 30 477 [36.2%] female) in the study. The median age of the donors was 42 years (IQR, 28-55) and waitlist candidates, 57 years (IQR, 50-63). Females were overrepresented in the 2 smallest BSA groups (7100 [84.0%] and 7922 [61.1%] in groups 1 and 2, respectively). For each increase in group number, waitlist time decreased (234 days [IQR, 48-700] for group 1 vs 179 days [IQR, 26-503] for group 6; P < .001) and the proportion of the group undergoing transplant likewise improved (3890 [46%] in group 1 vs 4932 [57%] in group 6; P < .001). The smallest 2 groups of candidates were disadvantaged under the current acuity circle allocation model, with 37% and 7.4% fewer livers allocated relative to their proportional representation on the waitlist. Allocation of the smallest 10% of donors (by BSA) to the smallest 15% of candidates overcame this disparity, as did performing split liver transplants. Conclusions and Relevance: In this study, liver waitlist candidates with the smallest BSAs had a disadvantage due to size. Prioritizing allocation of smaller liver donors to smaller candidates may help overcome this disparity.

Necrotizing Soft Tissue Infections (NSTI): Pearls and Pitfalls for the Emergency Clinician.

BACKGROUND: Skin and soft tissue infections are common emergency department (ED) presentations. These infections cover a wide spectrum of disease, from simple cellulitis to necrotizing fasciitis. Despite the commonality, a subset of skin and soft tissue infections known as necrotizing soft tissue infections (NSTIs) can cause significant morbidity and mortality. OBJECTIVE: This review evaluates the current evidence regarding the presentation, evaluation, and management of NSTI from the ED perspective. DISCUSSION: NSTIs are commonly missed diagnoses. History and physical examination findings are inconsistent, and the risk factors for this high mortality disease are common amongst ED populations. Laboratory evaluation and the Laboratory Risk in Necrotizing Fasciitis (LRINEC) score is helpful but is insufficient to rule out the disease. Imaging modalities including ultrasound, computed tomography, and magnetic resonance imaging are highly sensitive and specific, but may delay definitive management. The gold standard for diagnosis includes surgical exploration. Surgical intervention and empiric broad-spectrum antibiotic coverage are the foundations of treatment. Adjuvant therapies including hyperbaric oxygen and intravenous immunoglobulin have not yet been proven to be beneficial or to improve outcome. CONCLUSION: NSTIs are associated with significant morbidity and mortality. Knowledge of the history, examination, evaluation, and management is vital for emergency clinicians.

Research data infrastructure for high-throughput experimental materials science.

The High-Throughput Experimental Materials Database (HTEM-DB, htem.nrel.gov) is a repository of inorganic thin-film materials data collected during combinatorial experiments at the National Renewable Energy Laboratory (NREL). This data asset is enabled by NREL's Research Data Infrastructure (RDI), a set of custom data tools that collect, process, and store experimental data and metadata. Here, we describe the experimental data flow from the RDI to the HTEM-DB to illustrate the strategies and best practices currently used for materials data at NREL. Integration of the data tools with experimental instruments establishes a data communication pipeline between experimental researchers and data scientists. This work motivates the creation of similar workflows at other institutions to aggregate valuable data and increase their usefulness for future machine learning studies. In turn, such data-driven studies can greatly accelerate the pace of discovery and design in the materials science domain.

Clinical Policy: Critical Issues in the Management of Adult Patients Presenting to the Emergency Department With Community-Acquired Pneumonia.

This clinical policy from the American College of Emergency Physicians is a revision of the 2009 "Clinical Policy: Critical Issues in the Management of Adult Patients Presenting to the Emergency Department With Community-Acquired Pneumonia." A writing subcommittee conducted a systematic review of the literature to derive evidence-based recommendations to answer the following clinical questions: (1) In the adult emergency department patient diagnosed with community-acquired pneumonia, what clinical decision aids can inform the determination of patient disposition? (2) In the adult emergency department patient with community-acquired pneumonia, what biomarkers can be used to direct initial antimicrobial therapy? (3) In the adult emergency department patient diagnosed with community-acquired pneumonia, does a single dose of parenteral antibiotics in the emergency department followed by oral treatment versus oral treatment alone improve outcomes? Evidence was graded and recommendations were made based on the strength of the available data.

Synthesis of Tunable SnS-TaS2 Nanoscale Superlattices.

Nanoscale superlattices represent a compelling platform for designed materials as the specific identity and spatial arrangement of constituent layers can lead to tunable properties. A number of kinetically stabilized, nonepitaxial superlattices with almost limitless structural tunability have been reported in telluride and selenide chemistries but have not yet been extended to sulfides. Here, we present SnS-TaS2 nanoscale superlattices with tunable layer architecture. Layered amorphous precursors are prepared as thin films programmed to mimic the targeted superlattice; subsequent low temperature annealing activates self-assembly into crystalline nanocomposites. We investigate structure and composition of superlattices comprised of monolayers of TaS2 and 3-7 monolayers of SnS per repeating unit. Furthermore, a graded precursor preparation approach is introduced, allowing stabilization of superlattices with multiple stacking sequences in a single preparation. Controlled synthesis of the architecture of nanoscale superlattices is a critical path toward tuning their exotic properties and enabling integration with electronic, optical, or quantum devices.

Ternary nitride semiconductors in the rocksalt crystal structure.

Inorganic nitrides with wurtzite crystal structures are well-known semiconductors used in optical and electronic devices. In contrast, rocksalt-structured nitrides are known for their superconducting and refractory properties. Breaking this dichotomy, here we report ternary nitride semiconductors with rocksalt crystal structures, remarkable electronic properties, and the general chemical formula Mgx TM 1-xN (TM = Ti, Zr, Hf, Nb). Our experiments show that these materials form over a broad metal composition range, and that Mg-rich compositions are nondegenerate semiconductors with visible-range optical absorption onsets (1.8 to 2.1 eV) and up to 100 cm2 V-1⋅s-1 electron mobility for MgZrN2 grown on MgO substrates. Complementary ab initio calculations reveal that these materials have disorder-tunable optical absorption, large dielectric constants, and electronic bandgaps that are relatively insensitive to disorder. These ternary Mgx TM 1-xN semiconductors are also structurally compatible both with binary TMN superconductors and main-group nitride semiconductors along certain crystallographic orientations. Overall, these results highlight Mgx TM 1-xN as a class of materials combining the semiconducting properties of main-group wurtzite nitrides and rocksalt structure of superconducting transition-metal nitrides.

COMBIgor: Data-Analysis Package for Combinatorial Materials Science.

Combinatorial experiments involve synthesis of sample libraries with lateral composition gradients requiring spatially resolved characterization of structure and properties. Because of the maturation of combinatorial methods and their successful application in many fields, the modern combinatorial laboratory produces diverse and complex data sets requiring advanced analysis and visualization techniques. In order to utilize these large data sets to uncover new knowledge, the combinatorial scientist must engage in data science. For data science tasks, most laboratories adopt common-purpose data management and visualization software. However, processing and cross-correlating data from various measurement tools is no small task for such generic programs. Here we describe COMBIgor, a purpose-built open-source software package written in the commercial Igor Pro environment and designed to offer a systematic approach to loading, storing, processing, and visualizing combinatorial data. It includes (1) methods for loading and storing data sets from combinatorial libraries, (2) routines for streamlined data processing, and (3) data-analysis and -visualization features to construct figures. Most importantly, COMBIgor is designed to be easily customized by a laboratory, group, or individual in order to integrate additional instruments and data-processing algorithms. Utilizing the capabilities of COMBIgor can significantly reduce the burden of data management on the combinatorial scientist.

An Inter-Laboratory Study of Zn-Sn-Ti-O Thin Films using High-Throughput Experimental Methods.

High-throughput experimental (HTE) techniques are an increasingly important way to accelerate the rate of materials research and development for many technological applications. However, there are very few publications on the reproducibility of the HTE results obtained across different laboratories for the same materials system, and on the associated sample and data exchange standards. Here, we report a comparative study of Zn-Sn-Ti-O thin films materials using high-throughput experimental methods at National Institute of Standards and Technology (NIST) and National Renewable Energy Laboratory (NREL). The thin film sample libraries were synthesized by combinatorial physical vapor deposition (cosputtering and pulsed laser deposition) and characterized by spatially resolved techniques for composition, structure, thickness, optical, and electrical properties. The results of this study indicate that all these measurement techniques performed at two different laboratories show excellent qualitative agreement. The quantitative similarities and differences vary by measurement type, with 95% confidence interval of 0.1-0.2 eV for the band gap, 24-29 nm for film thickness, and 0.08 to 0.37 orders of magnitude for sheet resistance. Overall, this work serves as a case study for the feasibility of a High-Throughput Experimental Materials Collaboratory (HTE-MC) by demonstrating the exchange of high-throughput sample libraries, workflows, and data.

Negative-pressure polymorphs made by heterostructural alloying.

The ability of a material to adopt multiple structures, known as polymorphism, is a fascinating natural phenomenon. Various polymorphs with unusual properties are routinely synthesized by compression under positive pressure. However, changing a material's structure by applying tension under negative pressure is much more difficult. We show how negative-pressure polymorphs can be synthesized by mixing materials with different crystal structures-a general approach that should be applicable to many materials. Theoretical calculations suggest that it costs less energy to mix low-density structures than high-density structures, due to less competition for space between the atoms. Proof-of-concept experiments confirm that mixing two different high-density forms of MnSe and MnTe stabilizes a Mn(Se,Te) alloy with a low-density wurtzite structure. This Mn(Se,Te) negative-pressure polymorph has 2× to 4× lower electron effective mass compared to MnSe and MnTe parent compounds and has a piezoelectric response that none of the parent compounds have. This example shows how heterostructural alloying can lead to negative-pressure polymorphs with useful properties-materials that are otherwise nearly impossible to make.

An open experimental database for exploring inorganic materials.

The use of advanced machine learning algorithms in experimental materials science is limited by the lack of sufficiently large and diverse datasets amenable to data mining. If publicly open, such data resources would also enable materials research by scientists without access to expensive experimental equipment. Here, we report on our progress towards a publicly open High Throughput Experimental Materials (HTEM) Database (htem.nrel.gov). This database currently contains 140,000 sample entries, characterized by structural (100,000), synthetic (80,000), chemical (70,000), and optoelectronic (50,000) properties of inorganic thin film materials, grouped in >4,000 sample entries across >100 materials systems; more than a half of these data are publicly available. This article shows how the HTEM database may enable scientists to explore materials by browsing web-based user interface and an application programming interface. This paper also describes a HTE approach to generating materials data, and discusses the laboratory information management system (LIMS), that underpin HTEM database. Finally, this manuscript illustrates how advanced machine learning algorithms can be adopted to materials science problems using this open data resource.

Redox-Mediated Stabilization in Zinc Molybdenum Nitrides.

We report on the theoretical prediction and experimental realization of new ternary zinc molybdenum nitride compounds. We used theory to identify previously unknown ternary compounds in the Zn-Mo-N systems, Zn3MoN4 and ZnMoN2, and to analyze their bonding environment. Experiments show that Zn-Mo-N alloys can form in broad composition range from Zn3MoN4 to ZnMoN2 in the wurtzite-derived structure, accommodating very large off-stoichiometry. Interestingly, the measured wurtzite-derived structure of the alloys is metastable for the ZnMoN2 stoichiometry, in contrast to the Zn3MoN4 stoichiometry, where ordered wurtzite is predicted to be the ground state. The formation of Zn3MoN4-ZnMoN2 alloy with wurtzite-derived crystal structure is enabled by the concomitant ability of Mo to change oxidation state from +VI in Zn3MoN4 to +IV in ZnMoN2, and the capability of Zn to contribute to the bonding states of both compounds, an effect that we define as "redox-mediated stabilization". The stabilization of Mo in both the +VI and +IV oxidation states is due to the intermediate electronegativity of Zn, which enables significant polar covalent bonding in both Zn3MoN4 and ZnMoN2 compounds. The smooth change in the Mo oxidation state between Zn3MoN4 and ZnMoN2 stoichiometries leads to a continuous change in optoelectronic properties-from resistive and semitransparent Zn3MoN4 to conductive and absorptive ZnMoN2. The reported redox-mediated stabilization in zinc molybdenum nitrides suggests there might be many undiscovered ternary compounds with one metal having an intermediate electronegativity, enabling significant covalent bonding, and another metal capable of accommodating multiple oxidation states, enabling stoichiometric flexibility.

Pott's Disease in a Patient with Subtle Red Flags.

BACKGROUND: Tuberculosis (TB) is now rare in developed countries; however, it is an important diagnosis for the Emergency Physician to be able to make. Classically thought of as a respiratory disease, TB can present in other ways, making it more challenging to recognize. CASE REPORT: We report the case of a 41-year-old woman who presented to the Emergency Department with a 4-week history of back pain. A diagnosis of T12 osteomyelitis and right psoas muscle abscess was made after magnetic resonance imaging. The concurrent finding raised concern for TB as psoas muscle abscess is usually found along with spinal TB. A computed tomography-guided fine-needle aspiration confirmed the diagnosis. This patient's social history was negative for many of the classic predisposing factors associated with TB: immunosuppression, personal travel, crowded living conditions. Repeated investigation into the patient's history revealed a visit several months prior from a family member from Vietnam who had been treated for TB. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important for Emergency Physicians to be aware of the relatively high incidence of TB as a cause for concurrent psoas abscess and vertebral osteomyelitis.

High-fraction brookite films from amorphous precursors.

Structure-specific synthesis processes are of key importance to the growth of polymorphic functional compounds such as TiO2, where material properties strongly depend on structure as well as chemistry. The robust growth of the brookite polymorph of TiO2, a promising photocatalyst, has been difficult in both powder and thin-film forms due to the disparity of reported synthesis techniques, their highly specific nature, and lack of mechanistic understanding. In this work, we report the growth of high-fraction (~95%) brookite thin films prepared by annealing amorphous titania precursor films deposited by pulsed laser deposition. We characterize the crystallization process, eliminating the previously suggested roles of substrate templating and Na helper ions in driving brookite formation. Instead, we link phase selection directly to film thickness, offering a novel, generalizable route to brookite growth that does not rely on the presence of extraneous elements or particular lattice-matched substrates. In addition to providing a new synthesis route to brookite thin films, our results take a step towards resolving the problem of phase selection in TiO2 growth, contributing to the further development of this promising functional material.

Novel phase diagram behavior and materials design in heterostructural semiconductor alloys.

Structure and composition control the behavior of materials. Isostructural alloying is historically an extremely successful approach for tuning materials properties, but it is often limited by binodal and spinodal decomposition, which correspond to the thermodynamic solubility limit and the stability against composition fluctuations, respectively. We show that heterostructural alloys can exhibit a markedly increased range of metastable alloy compositions between the binodal and spinodal lines, thereby opening up a vast phase space for novel homogeneous single-phase alloys. We distinguish two types of heterostructural alloys, that is, those between commensurate and incommensurate phases. Because of the structural transition around the critical composition, the properties change in a highly nonlinear or even discontinuous fashion, providing a mechanism for materials design that does not exist in conventional isostructural alloys. The novel phase diagram behavior follows from standard alloy models using mixing enthalpies from first-principles calculations. Thin-film deposition demonstrates the viability of the synthesis of these metastable single-phase domains and validates the computationally predicted phase separation mechanism above the upper temperature bound of the nonequilibrium single-phase region.