Density Measurements of Molten LiF-BeF2 and LiF-BeF2-LaF3 Salt Mixtures by Neutron Radiography.

The densities of eutectic (LiF)2-BeF2 and mixtures of this salt (FLiBe) with LaF3 were measured by dilatometry and by neutron attenuation from 673 K to 1,073 K. Because LaF3 has a limited solubility in FLiBe, it was necessary to determine the amount of LaF3 in solution before the density could be determined. The FLiBe density determination was favorably benchmarked against the literature data. A simple comparison was not available for the LaF3-FLiBe mixtures, so extrapolation of published data was necessary based on analysis using the Molten Salt Thermal Properties Database-Thermochemistry, or MSTDB-TC, developed by the US Department of Energy. Solubilities for LaF3 in FLiBe ranged from 1 to 4 mol % over 673 to 1,073 K. The salt system was heated and cooled over 24 h to evaluate potential changes in composition and hysteresis during the measurement. Changes in the meniscus were observed, and these were included in the correction for density determinations. Salt surface tension may have led to supersaturation of LaF3 in the salt because the solubility curve was nonlinear with respect to the inverse temperature, as would be expected for an ideal system. Surface tension measurements are currently underway to test this hypothesis.

Multivariate Analysis of Risk Factors for In-Hospital Dislocation Following Primary Total Hip Arthroplasty.

Background: Early dislocation following primary total hip arthroplasty (THA) is a rare but devastating complication and represents a source of patient morbidity and financial burden to the healthcare system. The objective of this study was to identify patient characteristics and comorbidities that are associated with increased early in-hospital dislocation rates following primary THA. Methods: A retrospective cohort study was conducted using patient data from the Nationwide Inpatient Sample (NIS) database; we identified patients who had undergone THA from 2016 to 2019 and compared those with an early periprosthetic dislocation prior to discharge to those without. The patient characteristics and comorbidities were compared using univariate analysis with a subsequent investigation of statistically significant variables using multivariate analysis. The variables were compared using chi square, Fisher's exact test, and independent sample t-tests with data assessed using odds ratio with 95% confidence intervals. Results: A total of 5151 patients sustained an early dislocation compared to 362,743 who did not. Those who sustained an in-hospital dislocation were more likely to share the following characteristics: female sex (OR 1.21, p < 0.01), age > 70 (OR 1.45, p < 0.01), Caucasian ethnicity (OR 1.22, p < 0.01), SLE (OR 1.87, p < 0.01), and Parkinson's disease (OR 1.93, p < 0.01). Certain characteristics were also associated with decreased odds of having an in-hospital dislocation including elective surgery (OR 0.14, p < 0.01), tobacco use (OR 0.8, p < 0.01), diabetes without complications (OR 0.87, p < 0.01), and a history of heart valve replacement (OR 0.81, p < 0.01). The length of stay was significantly longer (4.7 days vs. 2.3 days) as was the total hospital charges (USD $101,517 vs. USD $66,388) for the early in-hospital dislocation group. Conclusions: Several patient characteristics and comorbidities are associated with early in-hospital dislocation episodes following total hip arthroplasty including female sex, age > 70, non-elective surgery, SLE, and Parkinson's. This information may be useful to help guide intraoperative implant selection and/or postoperative protocol in select patient populations to limit early instability as well as decrease the financial burden associated with this postoperative complication.

Versatile, in-line optical oxygen tension sensors for continuous monitoring during ex vivo kidney perfusion.

Integration of physiological sensing modalities within tissue and organ perfusion systems is becoming a steadily expanding field of research, aimed at achieving technological breakthrough innovations that will expand the sites and clinical settings at which such systems can be used. This is becoming possible in part due to the advancement of user-friendly optical sensors in recent years, which rely both on synthetic, luminescent sensor molecules and inexpensive, low-power electronic components for device engineering. In this article we report a novel approach towards enabling automated, continuous monitoring of oxygenation during ex vivo organ perfusion, by combining versatile flow cell components and low-power, programmable electronic readout devices. The sensing element comprises a 3D printed, miniature flow cell with tubing connectors and an affixed oxygen-sensing thin film material containing in-house developed, brightly-emitting metalloporphyrin phosphor molecules embedded within a polymer matrix. Proof-of-concept validation of this technology is demonstrated through integration within the tubing circuit of a transportable medical device for hypothermic oxygenated machine perfusion of extracted kidneys as a model for organs to be preserved as transplants.

Illustrated State-of-the-Art Capsules of the ISTH 2024 Congress.

Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand. This year's Congress marks the first time that the International Society on Thrombosis and Haemostasis has held its flagship scientific meeting in Southeast Asia and is the first to be organized by an international Planning Committee. The Bangkok program will feature innovative science and clinical updates from around the world, reflecting the diversity and multidisciplinary growth of our field. In these illustrated SOA capsules, you will find an exploration of novel models of thrombosis and bleeding and biomaterial discoveries that can trigger or block coagulation. Thromboinflammation is now understood to drive many disease states, and the SOA speakers cover cellular and coagulation responses to COVID-19 and other infections. The theme of crosstalk between coagulation and inflammation expands with capsules on protein S signaling, complement, and fibrinolytic inhibitors. Novel agents for hemophilia and thrombosis prevention are introduced. Challenging clinical conditions are also covered, such as inherited platelet disorders and antiphospholipid antibody syndrome. The scientific program in Bangkok will also showcase the work of clinicians and scientists from all parts of the world and chronicle real-world challenges. For example, 2 SOA capsules address the diagnosis and management of von Willebrand disease in low-income settings. Take some time to browse through these short illustrated reviews; we're sure that you'll be entertained, educated, and inspired to further explore the world of thrombosis and hemostasis.

The impact of prior ACL reconstruction on total knee arthroplasty outcomes: a retrospective matched cohort study.

INTRODUCTION: Discrepant data exists regarding the outcomes following total knee arthroplasty (TKA) with a prior anterior cruciate reconstruction (ACLR). The purpose of our study was to compare surgical and medical outcomes in the patients with prior ACLR undergoing TKAs compared to a matched control group of the patients who had undergone TKAs without prior ACLR. We hypothesized that the patients with prior ACLR would have inferior clinical outcomes. MATERIAL/METHODS: We retrospectively queried the PearlDiver-database for patients who underwent TKA following ACLR from 2011 to 2020. We used propensity-score matching to create two cohorts. The two-sided independent t-test and Chi-Squared test were used. RESULTS: We identified 2,174 patients who had prior ACLR before the TKAs. There were another 1,348,870 patients who did not have ACLR before the TKAs. After matching, each group had 2,171 patients. The ACLR-TKA group had significantly lower rates of aseptic revision at 2 years (1.2% vs. 4.0%, OR 0.3, p < 0.01), PJI requiring antibiotic spacer at 2 years (0.3% vs. 0.8%, OR 0.35, p = 0.02), and MUA at 90 days (0.4% vs. 7.5%, OR 0.05, p < 0.01). The rate of wound disruption was lower for the ACLR-TKA group at 90 days (p = 0.03) as were several medical complications including AKI at 90 days (p < 0.01), DVT at 90 days (p < 0.01), pneumonia at 90 days (0.04), and required blood transfusion at 90 days (p < 0.01). CONCLUSION: These results differed from our expectations. Within the limitations of the study, we are unable to determine the factors for the lower complications in the ACLR-TKA group. The data from this study are different from what had been reported in the previous studies.

Spatially Resolved Raman Spectroscopic Investigation of Uranyl Fluoride: A Case Study in the Importance of Instrument Optimization.

Raman spectroscopy is an emerging technique for rapid and nondestructive analysis of nuclear materials for forensic and nonproliferation applications as it is a powerful tool for distinguishing multiple chemical forms of materials with similar stoichiometries. Recent developments in spectroscopic software have enabled rapid data collection with high-speed Raman spectroscopic mapping capabilities. However, some uranium-rich materials are susceptible to degradation in humid air and/or laser-induced phase transformations. To mitigate environmental or measurement-related sample degradation of potential samples of interest, we have taken a systematic approach to define optimized data collection parameters for high-throughput measurements of uranyl fluoride (UO2F2), which is an important intermediate material in the nuclear fuel cycle. First, we systematically describe the influence of optical magnification (5× to 100×), laser power, and exposure time on obtained signal for identical particles of UO2F2 and find that at low laser power and exposure times, comparable signal is obtained regardless of optical magnification. Second, we ensure sample integrity during data collection, and third, collect spectroscopic maps that employ optimized parameters to reduce the time required to obtain spatially resolved spectroscopic information. Reductions of 90% and 99% in measurement times are discussed as they relate to differences in resolving spectroscopic features of particles in identical mapping areas. During this work, we found that additional data processing options were needed and thus developed a customized Python script for importing, processing, analyzing, and visualizing Raman spectroscopic map data.

Neutrophil-mediated Inflammatory Plasminogen Degradation, Rather Than High Plasminogen-Activator Inhibitor-1, May Underly Failures and Inefficiencies of Intrapleural Fibrinolysis.

BACKGROUND: Complex pleural space infections often require treatment with multiple doses of intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease, with treatment failure frequently necessitating surgery. Pleural infections are rich in neutrophils, and neutrophil elastase degrades plasminogen, the target substrate of tPA, that is required to generate fibrinolysis. We hypothesized that pleural fluid from patients with pleural space infection would show high elastase activity, evidence of inflammatory plasminogen degradation, and low fibrinolytic potential in response to tPA that could be rescued with plasminogen supplementation. RESEARCH QUESTION: Does neutrophil elastase degradation of plasminogen contribute to intrapleural fibrinolytic failure? STUDY DESIGN AND METHODS: We obtained infected pleural fluid and circulating plasma from hospitalized adults (n = 10) with institutional review board approval from a randomized trial evaluating intrapleural fibrinolytics vs surgery for initial management of pleural space infection. Samples were collected before the intervention and on days 1, 2, and 3 after the intervention. Activity assays, enzyme-linked immunosorbent assays, and Western blot analysis were performed, and turbidimetric measurements of fibrinolysis were obtained from pleural fluid with and without exogenous plasminogen supplementation. Results are reported as median (interquartile range) or number (percentage) as appropriate, with an α value of .05. RESULTS: Pleural fluid elastase activity was more than fourfold higher (P = .02) and plasminogen antigen levels were more than threefold lower (P = .04) than their corresponding plasma values. Pleural fluid Western blot analysis demonstrated abundant plasminogen degradation fragments consistent with elastase degradation patterns. We found that plasminogen activator inhibitor 1 (PAI-1), the native tPA inhibitor, showed high antigen levels before the intervention, but the overwhelming majority of this PAI-1 (82%) was not active (P = .003), and all PAI-1 activity was lost by day 2 after the intervention in patients receiving intrapleural tPA and deoxyribonuclease. Finally, using turbidity clot lysis assays, we found that the pleural fluid of 9 of 10 patients was unable to generate a significant fibrinolytic response when challenged with tPA and that plasminogen supplementation rescued fibrinolysis in all patients. INTERPRETATION: Our findings suggest that inflammatory plasminogen deficiency, not high PAI-1 activity, is a significant contributor to intrapleural fibrinolytic failure. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03583931; URL: www. CLINICALTRIALS: gov.

Disentangling cell-intrinsic and extrinsic factors underlying gene expression evolution.

Chimeras have played a foundational role in biology, for example by enabling the classification of developmental processes into those driven intrinsically by individual cells versus those driven extrinsically by their extracellular environment. Here, we extend this framework to decompose evolutionary divergence in gene expression and other quantitative traits into cell-intrinsic, extrinsic, and intrinsic-extrinsic interaction components. Applying this framework to reciprocal rat-mouse chimeras, we found that the majority of gene expression divergence is attributable to cell-intrinsic factors, though extrinsic factors also play an integral role. For example, a rat-like extracellular environment extrinsically up-regulates the expression of a key transcriptional regulator of the endoplasmic reticulum (ER) stress response in some but not all cell types, which in turn strongly predicts extrinsic up-regulation of its target genes and of the ER stress response pathway as a whole. This effect is also seen at the protein level, suggesting propagation through multiple regulatory levels. We also demonstrate that our framework is applicable to a cellular trait, neuronal differentiation, and estimated the intrinsic and extrinsic contributions to its divergence. Finally, we show that imprinted genes are dramatically mis-expressed in species-mismatched environments, suggesting that mismatch between rapidly evolving intrinsic and extrinsic mechanisms controlling gene imprinting may contribute to barriers to interspecies chimerism. Overall, our conceptual framework opens new avenues to investigate the mechanistic basis of evolutionary divergence in gene expression and other quantitative traits in any multicellular organism.

Uranium Single Particle Analysis for Simultaneous Fluorine and Uranium Isotopic Determinations via Laser-Induced Breakdown Spectroscopy/Laser Ablation-Multicollector-Inductively Coupled Plasma-Mass Spectrometry.

Uranyl fluoride (UO2F2) particles (<20 µm) were subjected to first-of-its-kind analysis via simultaneous laser-induced breakdown spectroscopy (LIBS) and laser ablation multi-collector inductively coupled plasma-mass spectrometry (LA-MC-ICP-MS). Briefly, a nanosecond pulsed high-energy laser was focused onto the sample (particle) surface. In a single laser pulse, the UO2F2 particle was excited/ionized within the microplasma volume, and the emission of light was collected via fiber optics such that emission spectroscopy could be employed for the detection of uranium (U) and fluorine (F). The ablated particle was simultaneously transported into the MC-ICP-MS for high precision isotopic (i.e., 234U, 235U, and 238U) analysis. This method, LIBS/LA-MC-ICP-MS was optimized and employed to rapidly measure 80+ UO2F2 particles, which were subjected to different calcination processes, which results in varying degrees of F loss from the individual particles. In measuring the particles, the average F/U ratios for the populations treated at 100 and 500 °C were 2.78 ± 1.28 and 1.01 ± 0.50, respectively, confirming loss of F through the calcination process. The average 235U/238U on the particle populations for the 100 and 500 °C were 0.007262 (22) and 0.007231 (23), which was determined to be <0.2% from the expected value. The 234U/238U ratios on the same particles were 0.000053 (11) and 0.000050 (10) for the 100 and 500 °C, respectively, <10% from the expected value. Notably, each population was analyzed in under 5 min, demonstrating the truly rapid analysis technique presented here.

Positive Bacterial Cultures on Spinal Wound Closure Do Not Predict Postoperative Outcomes.

BACKGROUND: Complex surgical back wounds represent significant morbidity in patients who have undergone spinal procedures requiring closure or revision by plastic surgeons. This study aimed to assess the utility of bacterial wound culture data for predicting surgical outcomes of wound management. METHODS: This study is a single-institution retrospective review of consecutive patients who required plastic surgery intervention for wound infection following spinal procedures between the years 2010 and 2021 (n = 70). Statistical analysis was performed for demographics, comorbidities, perioperative laboratory studies, and treatment methods. The primary outcomes of interest were rate of postoperative complications after soft tissue reconstruction and reconstructive failure. The secondary outcome of interest was time to healing in number of days. RESULTS: The overall complication rate after wound closure was 31.4%, with wound infection in 12.9%, seroma in 10%, dehiscence in 12.9%, and hematoma in 1.4%. Increasing number of debridements before wound closure increased the likelihood of a surgical complication of any kind (odds ratio [OR], 1.772; 95% confidence interval [CI], 1.045-3.002). Positive wound cultures before reconstruction were associated with development of seroma only (OR, 0.265; 95% CI, 0.078-0.893). Use of incisional vacuum-assisted closure devices significantly decreased the odds of postoperative wound dehiscence (OR, 0.179; 95% CI, 0.034-0.904) and increased odds of healing (hazard ratio, 3.638; 95% CI, 1.547-8.613). CONCLUSIONS: Positive wound cultures were not significantly associated with negative outcomes after complex closure or reconstruction of infected spinal surgical wounds. This finding emphasizes the importance of clinical judgment with a multidisciplinary approach to complex surgical back wounds over culture data for wound closure timing.

Effects of two-step golf swing drills on rhythm and clubhead speed in competitive juniors.

Vertical and horizontal rhythms are crucial aspects of a dynamic golf swing, and the two-step swing drills (TSSD) were specifically designed to promote rhythmic unloading and loading of the legs. The purpose of this study was to evaluate the effects of a TSSD training session on the swing rhythm and clubhead speed (CHS) among competitive junior golfers (3.1 ± 4.4 hcp). The driver swings (7 swings each) of 10 competitive junior golfers (aged 15-18) were captured before and after a TSSD session consisting of four stages (lasting less than 45 minutes). Post-TSSD training, there were significant increases in CHS (p < .001), maximum unweighting (p = .006), the trail-side push (p = .009), the horizontal motion ranges of the body and pelvis (p = .005-.031), the upward/downward motion range of the body in the backswing (p = .042/.024), and the backswing/downswing angular velocity peaks of the axle-chain system (p < .033). The stepping-like leg actions primarily facilitated horizontal motion rhythm over vertical motion and unweighting over push in terms of ground interaction. These findings suggest that TSSD can serve as an effective method for developing a rhythmic and dynamic motion pattern while increasing CHS.

Validation of the Wiedemann-Franz Law in Solid and Molten Tungsten above 2000 K through Thermal Conductivity Measurements via Steady-State Temperature Differential Radiometry.

We measure the thermal conductivity of solid and molten tungsten using steady state temperature differential radiometry. We demonstrate that the thermal conductivity can be well described by application of Wiedemann-Franz law to electrical resistivity data, thus suggesting the validity of Wiedemann-Franz law to capture the electronic thermal conductivity of metals in their molten phase. We further support this conclusion using ab initio molecular dynamics simulations with a machine-learned potential. Our results show that at these high temperatures, the vibrational contribution to thermal conductivity is negligible compared to the electronic component.

Quantifying platinum binding on protein-functionalized magnetic microparticles using single particle-ICP-TOF-MS.

This work describes an analytical procedure, single particle-inductively coupled plasma-time-of-flight-mass spectrometry (SP-ICP-TOF-MS), that was developed to determine the platinum binding efficiency of protein-coated magnetic microparticles. SP-ICP-TOF-MS is advantageous due to its ability to quasi-simultaneously detect all nuclides (7Li-242Pu), allowing for both platinum and iron (composition of magnetic microparticles) to be measured concurrently. This method subsequently allows for the differentiation between bound and unbound platinum. The 1 µm magnetic microparticles were fully characterized for their iron concentration, particle concentration, and trace element composition by bulk digestion-ICP-MS and SP-ICP-TOF-MS. The results of both approaches agreed with the certificate values. Using the single particle methodology the platinum loading was quantified to be to 0.18 ± 0.02 fg per particle and 0.32 ± 0.02 fg per particle, for the streptavidin-coated and azurin-coated microparticles, respectively. Both streptavidin-coated and the azurin-coated microparticles had a particle-platinum association of >65%. Platinum bound samples were also analyzed via bulk digestion-based ICP-MS. The bulk ICP-MS results overestimated platinum loading due to free platinum in the samples. This highlights the importance of single particle analysis for a closer inspection of platinum binding performance. The SP-ICP-TOF-MS approach offers advantages over typical bulk digestion methods by eliminating laborious sample preparation, enabling differentiation between bound/unbound platinum in a solution, and quantification of platinum on a particle-by-particle basis. The procedure presented here enables quantification of metal content per particle, which could be broadly implemented for other single particle applications.

Aluminothermic reduction of CeO2: mechanism of an economical route to aluminum-cerium alloys.

Cerium oxide is a low-value byproduct of rare-earth mining yet constitutes the largest fraction of the rare earth elements. The reduction of cerium oxide by liquid aluminum is proposed as an energy- and cost-efficient route to produce high-strength Al-Ce alloys. This work investigated the mechanism of a multi-step reduction reaction to facilitate the industrial adaptation of the process. Differential scanning calorimetry in combination with time-resolved synchrotron diffraction data uncovered the rate-limiting reaction step as the origin of the reported temperature dependence of reduction efficiency. This is the first in situ study of a metallothermic reaction mechanism and will serve as guidance for cost- and energy efficient industrial process control.

Differentiating Pathologic from Physiologic Fibrinolysis: Not as Simple as Conventional Thrombelastography.

BACKGROUND: Conventional rapid thrombelastography (rTEG) cannot differentiate fibrinolysis shutdown from hypofibrinolysis, as both of these patient populations have low fibrinolytic activity. Tissue plasminogen activator (tPA) TEG can identify depletion of fibrinolytic inhibitors, and its use in combination with rTEG has the potential to differentiate all 3 pathologic fibrinolytic phenotypes after trauma. We hypothesize tPA-TEG and rTEG in combination can further stratify fibrinolysis phenotypes postinjury to better stratify risk for mortality. STUDY DESIGN: Adult trauma patients (981) with both rTEG and tPA-TEG performed less than 2 hours postinjury were included. rTEG lysis at 30 minutes after maximum amplitude (LY30) was used to initially define fibrinolysis phenotypes (hyperfibrinolysis >3%, physiologic 0.9% to 3%, and shutdown <0.9%), with Youden Index then used to define pathologic extremes of tPA-TEG LY30 (tPA sensitive [depletion of fibrinolytic inhibitors] vs resistant) resulting in 9 groups that were assessed for risk of death. RESULTS: The median New Injury Severity Score was 22, 21% were female, 45% had penetrating injury, and overall mortality was 13%. The tPA-TEG LY30 inflection point for increased mortality was >35.5% (tPA sensitive, odds ratio mortality 9.2, p < 0.001) and <0.3% (tPA resistance, odds ratio mortality 6.3, p = 0.04). Of the 9 potential fibrinolytic phenotypes, 5 were associated with increased mortality. Overall, the 9 phenotypes provided a significantly better prediction of mortality than rTEG or tPA-TEG alone (areas under the operating characteristics curves = 0.80 vs 0.63 and 0.75, respectively, p < 0.0001). These could be condensed to 3 pathologic phenotypes (true hyperfibrinolysis, early fibrinolysis shutdown, and hypofibrinolysis). CONCLUSIONS: The combination of rTEG and tPA-TEG increases the ability to predict mortality and suggests patient-specific strategies for improved outcomes.

Mapping of uranium particles on J-type swipes with microextraction-ICP-MS.

A microextraction liquid sampling system coupled to a quadrupole inductively coupled plasma-mass spectrometer (ICP-MS) was utilized to spatially discern uranium particles, isotopically, on a cellulose-based swipe material (i.e., J-type swipe). These types of swipes are often used by the International Atomic Energy Agency (IAEA) as part of their environmental sampling program. A grid was created such that extraction locations covered the center circle (n = 34 without overlapping). Uranium (U) particulates (<20 µm) of varying U isotopic abundance and chemical form (i.e., uranyl fluoride and uranyl nitrate hexahydrate) were mechanically placed on the swipes in random locations and detected via the microextraction-ICP-MS methodology. Heat maps were subsequently generated to show the placement of the particulate with their respective intensity and isotopic determination. This detection of the uranium particulates, via isotopic determination, agreed with reference values for these materials. Additionally, depleted (235U/238U = 0.002) uranium particulates were placed directly within a clay matrix, on the swipe surface, and subjected to analysis by microextraction-ICP-MS. The mapping of the swipe demonstrated, for the first time, the employment of the microextraction-ICP-MS method for extracting sample from a complex matrix, and correctly identifying the uranium isotopic composition. This example ultimately demonstrates the utility of the methodology for detecting particles of interest in complex matrices.

Cell-type-specific cis-regulatory divergence in gene expression and chromatin accessibility revealed by human-chimpanzee hybrid cells.

Although gene expression divergence has long been postulated to be the primary driver of human evolution, identifying the genes and genetic variants underlying uniquely human traits has proven to be quite challenging. Theory suggests that cell-type-specific cis-regulatory variants may fuel evolutionary adaptation due to the specificity of their effects. These variants can precisely tune the expression of a single gene in a single cell-type, avoiding the potentially deleterious consequences of trans-acting changes and non-cell type-specific changes that can impact many genes and cell types, respectively. It has recently become possible to quantify human-specific cis-acting regulatory divergence by measuring allele-specific expression in human-chimpanzee hybrid cells-the product of fusing induced pluripotent stem (iPS) cells of each species in vitro. However, these cis-regulatory changes have only been explored in a limited number of cell types. Here, we quantify human-chimpanzee cis-regulatory divergence in gene expression and chromatin accessibility across six cell types, enabling the identification of highly cell-type-specific cis-regulatory changes. We find that cell-type-specific genes and regulatory elements evolve faster than those shared across cell types, suggesting an important role for genes with cell-type-specific expression in human evolution. Furthermore, we identify several instances of lineage-specific natural selection that may have played key roles in specific cell types, such as coordinated changes in the cis-regulation of dozens of genes involved in neuronal firing in motor neurons. Finally, using novel metrics and a machine learning model, we identify genetic variants that likely alter chromatin accessibility and transcription factor binding, leading to neuron-specific changes in the expression of the neurodevelopmentally important genes FABP7 and GAD1. Overall, our results demonstrate that integrative analysis of cis-regulatory divergence in chromatin accessibility and gene expression across cell types is a promising approach to identify the specific genes and genetic variants that make us human.

Fibrinolysis Resistance After Injury Is a Risk Factor for a Hospital-Acquired Pneumonia-Like Disease Pattern.

Background: Pneumonia is associated with increased morbidity and costs in the intensive care unit (ICU). Its early identification is key for optimal outcomes, but early biomarkers are lacking. Studies suggest that fibrinolysis resistance (FR) after major abdominal surgery is linked to an increased risk of infection. Patients and Methods: Patients in a randomized controlled trial for hemorrhagic shock were evaluated for FR. Fibrinolysis resistance was quantified by thrombelastography with exogenous tissue plasminogen activator (tPA-TEG) at 24- and 48-hours post-injury and measuring LY30 (%). A receiver-operating characteristics (ROC) curve analysis was used to identify a cutoff for increased risk of pneumonia, which was then validated in ICU patients at risk for venous thromboembolism (VTE). Multivariable logistic regression was used to control for confounders. Results: Forty-nine patients in the hemorrhagic shock cohort had tPA-TEGs at 24- and 48-hours (median ISS, 27; 7% pneumonia). A composite tPA-TEG LY30 of less than 4% at 24 and 48 hours was found to be the optimal cutoff for increased risk of pneumonia. This cohort had a seven-fold increased rate of pneumonia (4% vs. 28%; p = 0.048). Eighty-eight patients in the VTE cohort had tPA-TEGs at 24 and 48 hours post-ICU admission (median ISS, 28; 6% pneumonia). The tPA-TEG LY30 of less than 4% was associated with a 10-fold increased rate of pneumonia (19% vs. 1.5%; p = 0.002). In patients with traumatic brain injury, the same association was found (33% vs. 3.2%; p = 0.006). Adjusting for confounders, the tPA-TEG persisted as a substantial risk factor for pneumonia (adjusted odds ratio [OR], 35.7; 95% confidence interval [CI], 1.9-682; p = 0.018). Conclusions: Fibrinolysis resistance quantified by tPA-TEG within 48 hours of ICU admission is associated with an increased risk of pneumonia in patients in hemorrhagic shock and those at risk for VTE. Prospective validation of the tPA-TEG LY30 optimal cutoff for pneumonia and further investigation into whether endogenous FR is a cause of an altered immunity is warranted.

Corrigendum: Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies.

[This corrects the article DOI: 10.3389/fimmu.2023.1230049.].