A Catalytic Method for the Enantioselective Synthesis of α-Quaternary Ketones, α-Ketoesters and Aldehydes.

A practical method for the efficient and enantioselective preparation of versatile ketones and aldehydes that contain an α-quaternary stereocenter is described. Reactions utilize simple carboxylic acid or ester starting materials, a monodentate chiral phosphine, and afford a variety of aryl, alkenyl, alkynyl, and alkyl-substituted ketone and aldehyde products in 25-94 % yield and 90 : 10 to >99 : 1 enantiomeric ratio. Reactions proceed by acyl substitution with in situ formed chiral allylic nucleophiles, and display selectivity and conversion dependence on a protic additive. The utility of the approach is demonstrated through several product transformations.

Analysis of Admission Thromboelastogram Profiles in 1369 Male and Female Trauma Patients.

INTRODUCTION: Recent studies have demonstrated a hypercoagulable thromboelastrogram (TEG) in female trauma patients compared with males, conferring a possible survival advantage. We hypothesized that TEG profiles would reveal a relative hypercoagulable state in female compared with male trauma patients. METHODS: A prospective review was conducted on all adult trauma patients admitted to the trauma service at an American College of Surgeons-verified level I trauma center from December 2019 to June 2021 who, per our institutional protocol, received a thrombelastotgraphy on their initial arrival to the trauma center if classified as a level I or II trauma activation. The thromboelastography values of male and female trauma patients were compared as the primary outcome variables of interest. The secondary outcomes investigated were hospital length of stay, surgical interventions, and ventilatory requirement. RESULTS: A total of 1369 patients met inclusion criteria, with 878 (64.1%) male and 491 (35.9%) female. Female patients had a higher median alpha angle (74.8 versus 72.6°, P < 0.001), maximum amplitude (69.3 versus 66.2 mm, P < 0.001), and shorter median K time (1.0 versus 1.2 s, P < 0.001). Female patients had a shorter hospital length of stay (4 versus 5 d, P < 0.001), had a lower rate of surgical intervention (14.6% versus 25.5%, P < 0.001), and had lower rates of mechanical ventilation (19.3% versus 39.5%, P < 0.001). CONCLUSIONS: Female trauma patients were found to have hypercoagulable indices on TEG at the time of initial trauma evaluation compared with males. Intrinsic differences in sex coagulation profiles should be further investigated to optimize modern resuscitation strategies.

Overutilization of Helicopter Emergency Medical Services in Central Gulf Coast Region Results in Unnecessary Expenditure.

INTRODUCTION: When appropriately used, helicopter emergency medical services (HEMSs) allow for timely delivery of severely injured patients to definitive care. Inappropriate utilization of HEMSs results in increased cost to the patient and trauma system. The purpose of this study was to review current HEMS criteria in the central Gulf Coast region and evaluate for potential areas of triage refinement and cost savings. We hypothesized that a significant number of patients received potentially unwarranted HEMS transport. METHODS: A retrospective cohort study of all patients with trauma arriving to a level I trauma center by helicopter over 28 mo was performed; 381 patients with trauma and with HEMS transport from the scene were included. Data were collected from prehospital sources, as well as hospital chart review for each patient. The primary outcome was the rate of unwarranted HEMS transport. RESULTS: A total of 381 adult patients with trauma transported by the HEMS were analyzed, of which 34% were deemed potentially nonwarranted transports. The significant factors correlating with warranted HEMS transport included age, multiple long bone fractures, penetrating mechanism, and vehicle ejection. Insurance demographics did not correlate to transport modality. Many of these patients were transported from a location within the same county or the county adjacent to the trauma center. When comparing patients transported by ground and HEMSs from the same scene, no time savings were identified. Unwarranted transports at the trauma center represented an estimated health care expenditure of over $3 million. CONCLUSIONS: HEMSs may be overused in the central Gulf Coast region, creating the risk for a substantial resource and financial burden to the trauma system. Further collaboration is needed to establish HEMS triage criteria, that is, more appropriate use of resources.

Transarterial Radioembolization for Hepatocellular Carcinoma with Major Vascular Invasion: A Nationwide Propensity Score-Matched Analysis with Target Trial Emulation.

PURPOSE: To examine National Cancer Database (NCDB) data to comparatively evaluate overall survival (OS) between patients undergoing transarterial radioembolization (TARE) and those undergoing systemic therapy for hepatocellular carcinoma with major vascular invasion (HCC-MVI). METHODS: One thousand five hundred fourteen patients with HCC-MVI undergoing first-line TARE or systemic therapy were identified from the NCDB. OS was compared using propensity score-matched Cox regression and landmark analysis. Efficacy was also compared within a target trial framework. RESULTS: TARE usage doubled between 2010 and 2015. Intervals before treatment were longer for TARE than for systemic therapy (mean [median], 66.5 [60] days vs 46.8 (35) days, respectively, P < .0001). In propensity-score-matched and landmark-time-adjusted analyses, TARE was found to be associated with a hazard ratio of 0.74 (95 % CI, 0.60-0.91; P = .005) and median OS of 7.1 months (95 % CI, 5.0-10.5) versus 4.9 months (95 % CI, 3.9-6.5) for systemically treated patients. In an emulated target trial involving 236 patients with unilobular HCC-MVI, a low number of comorbidities, creatinine levels <2.0 mg/dL, bilirubin levels <2.0 mg/dL, and international normalized ratio <1.7, TARE was found to be associated with a hazard ratio of 0.57 (95 % CI, 0.39-0.83; P = .004) and a median OS of 12.9 months (95 % CI, 7.6-19.2) versus 6.5 months (95 % CI, 3.6-11.1) for the systemic therapy arm. CONCLUSIONS: In propensity-score-matched analyses involving pragmatic and target trial HCC-MVI cohorts, TARE was found to be associated with significant survival benefits compared with systemic therapy. Although not a substitute for prospective trials, these findings suggest that the increasing use of TARE for HCC-MVI is accompanied by improved OS. Further trials of TARE in patients with HCC-MVI are needed, especially to compare with newer systemic therapies.

Variable social organization is ubiquitous in Artiodactyla and probably evolved from pair-living ancestors.

Previous studies to understand the evolution of interspecific variation in mammalian social organization (SO; composition of social units) produced inconsistent results, possibly by ignoring intraspecific variation. Here we present systematic data on SO in artiodactyl populations, coding SO as solitary, pair-living, group-living, sex-specific or variable (different kinds of SOs in the same population). We found that 62% of 245 populations and 83% of species (83/100) exhibited variable SO. Using Bayesian phylogenetic mixed-effects models, we simultaneously tested whether research effort, habitat, sexual dimorphism, breeding seasonality or body size predicted the likelihood of different SOs and inferred the ancestral SO. Body size and sexual dimorphism were strongly associated with different SOs. Contingent on the small body size (737 g) and putative sexual monomorphism of the earliest fossil artiodactyl, the ancestral SO was most likely to be pair-living (probability = 0.76, 95% CI = 0-1), followed by variable (p = 0.19, 95% CI = 0-0.99). However, at body size values typical of extant species, variable SO becomes the dominant form (p = 0.74, 95% CI = 0.18-1.00). Distinguishing different kinds of 'variable' highlights transitions from SOs involving pair-living to SOs involving solitary and/or group-living with increasing body size and dimorphism. Our results support the assumption that ancestral artiodactyl was pair-living and highlight the ubiquity of intraspecific variation in SO.

Capillary Leveling of Freestanding Liquid Nanofilms.

We report on the capillary-driven leveling of a topographical perturbation at the surface of a freestanding liquid nanofilm. The width of a stepped surface profile is found to evolve as the square root of time. The hydrodynamic model is in excellent agreement with the experimental data. In addition to exhibiting an analogy with diffusive processes, this novel system serves as a precise nanoprobe for the rheology of liquids at interfaces in a configuration that avoids substrate effects.

Large area high-speed metrology SPM system.

We present a large area high-speed measuring system capable of rapidly generating nanometre resolution scanning probe microscopy data over mm(2) regions. The system combines a slow moving but accurate large area XYZ scanner with a very fast but less accurate small area XY scanner. This arrangement enables very large areas to be scanned by stitching together the small, rapidly acquired, images from the fast XY scanner while simultaneously moving the slow XYZ scanner across the region of interest. In order to successfully merge the image sequences together two software approaches for calibrating the data from the fast scanner are described. The first utilizes the low uncertainty interferometric sensors of the XYZ scanner while the second implements a genetic algorithm with multiple parameter fitting during the data merging step of the image stitching process. The basic uncertainty components related to these high-speed measurements are also discussed. Both techniques are shown to successfully enable high-resolution, large area images to be generated at least an order of magnitude faster than with a conventional atomic force microscope.

Cartilage boundary lubrication synergism is mediated by hyaluronan concentration and PRG4 concentration and structure.

BACKGROUND: Proteoglycan 4 (PRG4) and hyaluronan (HA) are key synovial fluid constituents that contribute synergistically to cartilage boundary lubrication; however, the effects of their concentrations as well as their structure, both of which can be altered in osteoarthritis, on this functional synergism are unknown. The objectives of this study were to evaluate cartilage boundary lubricating ability of 1) PRG4 + HA in solution at constant HA concentration in a range of PRG4 concentrations, 2) constant PRG4 concentration in a range of HA concentrations, 3) HA + reduced/alkylated (R/A) PRG4, and 4) hylan G-F 20 + PRG4. METHODS: Static and kinetic friction coefficients (µ(static,Neq), <µ(kinetic,Neq)>) were measured using a previously characterized cartilage-cartilage boundary mode friction test for the following concentrations of purified PRG4 and HA: Test 1: HA (1.5 MDa, 3.3 mg/mL) + PRG4 from 4.5 - 1500 µg/mL; Test 2: PRG4 (450, 150, 45 µg/mL) + HA (1.5 MDa) from 0.3 - 3.3 mg/mL. Test 3: hylan G-F 20 (3. 3 mg/mL) + PRG4 (450 µg/mL). Test 4: HA (3.3 mg/mL) + R/A PRG4 (450 µg/mL). ANOVA was used to compare lubricants within (comparing 6 lubricants of interest) and between (comparing 3 lubricants of interest) test sequences, with Tukey and Fishers post-hoc testing respectively. RESULTS: This study demonstrates that both PRG4 and HA concentration, as well as PRG4 disulfide-bonded structure, can alter the cartilage boundary lubricating ability of PRG4 + HA solutions. The boundary lubricating ability of high MW HA + PRG4 solutions was limited by very low concentrations of PRG4. Decreased concentrations of high MW HA also limited the cartilage boundary lubricating ability of HA + PRG4 solutions, with the effect exacerbated by low PRG4 concentrations. The reduction of friction by addition of PRG4 to a cross-linked HA viscosupplement product, but not with addition of R/A PRG4 to HA, is consistent with a non-covalent mechanism of interaction where tertiary and quaternary PRG4 structure are important. CONCLUSIONS: Collectively, these results demonstrate that deficiency of either or both PRG4 and HA, or alterations in PRG4 structure, may be detrimental to SF cartilage boundary lubricating function. This study provides further insight into the nature of cartilage boundary lubrication and advancement towards potential formulation of new intra-articular biotherapeutic treatments for osteoarthritis using PRG4 ± HA.

Submersible optical sensors exposed to chemically dispersed crude oil: wave tank simulations for improved oil spill monitoring.

In situ fluorometers were deployed during the Deepwater Horizon (DWH) Gulf of Mexico oil spill to track the subsea oil plume. Uncertainties regarding instrument specifications and capabilities necessitated performance testing of sensors exposed to simulated, dispersed oil plumes. Dynamic ranges of the Chelsea Technologies Group AQUAtracka, Turner Designs Cyclops, Satlantic SUNA and WET Labs, Inc. ECO, exposed to fresh and artificially weathered crude oil, were determined. Sensors were standardized against known oil volumes and total petroleum hydrocarbons and benzene-toluene-ethylbenzene-xylene measurements-both collected during spills, providing oil estimates during wave tank dilution experiments. All sensors estimated oil concentrations down to 300 ppb oil, refuting previous reports. Sensor performance results assist interpretation of DWH oil spill data and formulating future protocols.

Increasing the Rate of Venous Thromboembolism Chemoprophylaxis Administration Using the Electronic Medical Record.

Introduction: Venous thromboembolism (VTE) remains a leading cause of preventable harm among hospitalized patients. Pharmacologic VTE prophylaxis reduces the rate of in-hospital VTE by 60%, but medication administration is often missed for various reasons. Electronic medical record (EMR) prompts may be a useful tool to decrease withholding of critical VTE chemoprophylaxis medications. Methods: In August 2021, an EMR prompt was implemented at a tertiary referral academic medical center mandating nursing staff to contact a provider for approval before withholding VTE chemoprophylaxis. A pre-intervention group from August 2020 to August 2021 was compared to a post-intervention group from August 2021 to August 2022. Rates of VTE chemoprophylaxis withholding were compared between the groups with a P < .01 considered significant. Results: A total of 16,395 patients prescribed VTE chemoprophylaxis were reviewed, with 13,395 (81.7%) receiving low molecular weight heparin. Of the 16,395 patients included, 10,701 (65.3%) were medical and 5694 (34.7%) were surgical. Patients in the pre-intervention cohort (n = 8803) and post-intervention cohort (n = 7592) were similar in hospital length of stay and duration of DVT prophylaxis. In the post-intervention group, the frequency of surgical patients with at least one missed dose had increased by 4.2% (P = .002), with the trauma and acute care surgery (TACS) show an increase of 6.6% (P < .001). However, the frequency of medical patients and non-TACS patients with missed doses decreased by 3.1% (P = .002) and 1.0% (<.001), respectively. Conclusions: EMR prompts appear to be a low-cost intervention that increases the rate of VTE prophylaxis administration among medical and elective surgery patients.

Implementation of a novel peer review academy by Surgery and the Association of Women Surgeons.

BACKGROUND: A novel Peer Review Academy was developed as a collaborative effort between the Association of Women Surgeons and the journal Surgery to provide formal training in peer review. We aimed to describe the outcomes of this initiative using a mixed methods approach. METHODS: We developed a year-long curriculum with monthly online didactic sessions. Women surgical trainee mentees were paired 1:1 with rotating women surgical faculty mentors for 3 formal peer review opportunities. We analyzed pre-course and post-course surveys to evaluate mentee perceptions of the academy and assessed changes in mentee review quality over time with blinded scoring of unedited reviews. Semi-structured interviews were conducted upon course completion. RESULTS: Ten women surgical faculty mentors and 10 women surgical trainees from across the United States and Canada successfully completed the Peer Review Academy. There were improvements in the mentees' confidence for all domains of peer review evaluated, including overall confidence in peer review, study novelty, study design, analytic approach, and review formatting (all, P ≤ .02). The mean score of peer review quality increased over time (59.2 ± 10.8 vs 76.5 ± 9.4; P = .02). In semi-structured interviews, important elements were emphasized across the Innovation, Implementation Process, and Individuals Domains, including the values of (1) a comprehensive approach to formal peer review education; (2) mentoring relationships between women faculty and resident surgeons; and (3) increasing diversity in the scientific peer review process. CONCLUSION: Our novel Peer Review Academy was feasible on a national scale, resulting in significant qualitative and quantitative improvements in women surgical trainee skillsets, and has the potential to grow and diversify the existing peer review pool.

Chondroitin sulfate, dermatan sulfate, and hyaluronic acid differentially modify the biophysical properties of collagen-based hydrogels.

Fibrillar collagens and glycosaminoglycans (GAGs) are structural biomolecules that are natively abundant to the extracellular matrix (ECM). Prior studies have quantified the effects of GAGs on the bulk mechanical properties of the ECM. However, there remains a lack of experimental studies on how GAGs alter other biophysical properties of the ECM, including ones that operate at the length scales of individual cells such as mass transport efficiency and matrix microstructure. This study focuses on the GAG molecules chondroitin sulfate (CS), dermatan sulfate (DS), and hyaluronic acid (HA). CS and DS are stereoisomers while HA is the only non-sulfated GAG. We characterized and decoupled the effects of these GAG molecules on the stiffness, transport, and matrix microarchitecture properties of type I collagen hydrogels using mechanical indentation testing, microfluidics, and confocal reflectance imaging, respectively. We complement these biophysical measurements with turbidity assays to profile collagen aggregate formation. Surprisingly, only HA enhanced the ECM indentation modulus, while all three GAGs had no effect on hydraulic permeability. Strikingly, we show that CS, DS, and HA differentially regulate the matrix microarchitecture of hydrogels due to their alterations to the kinetics of collagen self-assembly. In addition to providing information on how GAGs define key physical properties of the ECM, this work shows new ways in which stiffness measurements, microfluidics, microscopy, and turbidity kinetics can be used complementarily to reveal details of collagen self-assembly and structure. STATEMENT OF SIGNIFICANCE: Collagen and glycosaminoglycans (GAGs) are integral to the structure, function, and bioactivity of the extracellular matrix (ECM). Despite widespread interest in collagen-GAG composite hydrogels, there is a lack of quantitative understanding of how different GAGs alter the biophysical properties of the ECM across tissue, cellular, and subcellular length scales. Here we show using mechanical, microfluidic, microscopy, and analytical methods and measurements that the GAG molecules chondroitin sulfate, dermatan sulfate, and hyaluronic acid differentially regulate the mechanical, transport, and microstructural properties of hydrogels due to their alterations to the kinetics of collagen self-assembly. As such, these results will inform improved design and utilization of collagen-based scaffolds of tailored composition, mechanical properties, molecular availability due to mass transport, and microarchitecture.

Growth of preschool age children receiving daily inhaled corticosteroids.

Data on the effects of inhaled corticosteroid (ICS) on linear growth in children <5 years old are limited with conflicting results from existing studies. This study was designed to investigate growth effects of inhaled corticosteroid use in children <5 years of age treated for asthma with ICS administered through a valved holding chamber (VHC). A retrospective cohort study was performed of 145 children in three treatment groups: (1) metered-dose inhaler (MDI) containing ultrafine beclomethasone dipropionate (n = 62), (2) MDI containing fluticasone propionate (n = 32), and (3) oral montelukast sodium (n = 51). Children <5 years of age between 2000 and 2009 treated for asthma with one of the three drugs were included in the study. Linear mixed model analysis was used to examine and compare growth during sustained treatment with each of the three medications. The three treatment groups did not differ significantly in their effect on growth rates (p = 0.64). However, female subjects had significantly slower growth than male subjects (p = 0.017), and the addition of intranasal corticosteroids (INS; p = 0.013) and the presence of atopy (p = 0.015) had a significant negative effect on growth. In children <5 years of age receiving maintenance therapy for chronic asthma, low-to-medium doses of ultrafine beclomethasone or fluticasone administered through a VHC were not associated with growth inhibition compared with children receiving oral montelukast. A small but statistically significant decrease in growth was seen in subjects with positive skin testing to inhalant allergens in female subjects and in subjects receiving INS.

Measuring nanoscale forces with living probes.

Optical trapping techniques have been used to investigate fundamental biological processes ranging from the identification of the processive mechanisms of kinesin and myosin to understanding the mechanics of DNA. To date, these investigations have relied almost exclusively on the use of isotropic probes based on colloidal microspheres. However, there are many potential advantages in utilizing more complex probe morphologies: use of multiple trapping points enables control of the interaction volume; increasing the distance between the optical trap and the sample minimizes photodamage in sensitive biological materials; and geometric anisotropy introduces the potential for asymmetric surface chemistry and multifunctional probes. Here we demonstrate that living cells of the freshwater diatom Nitzschia subacicularis Hustedt can be exploited as advanced probes for holographic optical tweezing applications. We characterize the optical and material properties associated with the high shape anisotropy of the silica frustule, examine the trapping behavior of the living algal cells, and demonstrate how the diatoms can be calibrated for use as force sensors and as force probes in the presence of rat B-cell hybridoma (11B11) cells.

Nationwide, Multioperator Self-Exclusion and Psychiatric Comorbidity in Patients with Gambling Disorder: A Retrospective Chart Review Study from a Regional Treatment Unit.

Gambling disorder is an addictive disorder that has been shown to have a detrimental effect on an individual's health, social, and financial situations. Voluntary self-exclusion is one way for patients to reduce harm in gambling disorder, but breaching one's self-exclusion appears to be common. In January 2019, Sweden launched a nationwide, multioperator self-exclusion instrument called Spelpaus (literally "game break"). Spelpaus is unique to Sweden, and there is limited research on the use of this type of nationwide, multioperator self-exclusion services, also in relation to gambling disorder and mental health. There is a reason to follow the clinical picture of treatment seeking for gambling disorder over time, and this study aims to explore clinical characteristics of patients seeking clinical gambling disorder treatment, including sex distribution and mental health comorbidity, as well as the use of Spelpaus amongst patients with gambling disorder and how frequently users gambled despite ongoing self-exclusion, in relation to sex and psychiatric comorbidities. A retrospective chart study was carried out on patients presenting to a regional gambling disorder treatment unit. Information regarding self-exclusions using Spelpaus, gambling despite self-exclusion, and the method of gambling despite self-exclusion as well as psychiatric comorbidities were extracted from medical records. Females were markedly more likely to report overall psychiatric comorbidities (48% vs. 25% among males, p < 0.001), affective, neurotic/anxiety-related (p < 0.001), and behavioral/emotional (p = 0.028) diagnoses and more likely to have two or more diagnoses excluding gambling disorder (p = 0.001). From 120 patients from whom information regarding self-exclusion was present, 114 (95%) had chosen to self-exclude. From the 114 self-excluders, 67 reported to have gambled despite self-exclusion, with unregistered websites being the most common method. Self-exclusion was not significantly related to sex (p = 0.146) or to psychiatric comorbidities (p = 0.178). In conclusion, psychiatric comorbidity was particularly common in female gambling disorder patients and gambling despite self-exclusion was common. Gambling regulations should be improved to help self-excluders avoid being able to gamble on unlicensed gambling operators. Further research should focus on sex differences and the association with psychiatric comorbidities.

Management of Internal Mammary Artery Injuries Associated With the Nuss Procedure.

The minimally invasive repair of pectus excavatum (MIRPE), or Nuss procedure, is regarded as the gold standard technique for the treatment of symptomatic pectus excavatum. Minimally invasive repair of pectus excavatum is regarded as a low-risk operation with a reported life-threatening complication rate estimated at around 0.1%. Presented are three cases of right internal mammary artery injury (RIMA) after MIRPE resulting in massive hemorrhage in both the acute and chronic postoperative setting and subsequent management strategies. Exploratory thoracoscopy and angioembolization were utilized which achieved prompt hemostasis and allowed for complete patient recovery.

Hypofibrinogenemic Massive Transfusion Trauma Patients Experience Worse Outcomes.

INTRODUCTION: Uncontrolled hemorrhage accounts for up to 40% of trauma-related mortality. Previous reports demonstrate that decreased fibrinogen levels during traumatic hemorrhage are associated with worse outcomes. Cryoprecipitate is used to replace fibrinogen for patients in hemorrhagic shock undergoing massive transfusion (MT), though the optimal ratio of cryoprecipitate to fresh frozen plasma (FFP), packed red blood cells (PRBCs), and platelets remains undefined. The purpose of this study is to investigate the effect of admission fibrinogen level and the use of cryoprecipitate on outcomes in trauma patients undergoing MT. METHODS: A prospective practice management guideline was established to obtain fibrinogen levels on adult trauma patients undergoing MT at a level I trauma center from December 2019 to December 2021. Ten units of cryoprecipitate were administered every other round of MT. Thromboelastography (TEG) was also obtained at the initiation and completion of MT. Patient demographic, injury, transfusion, and outcome data were collected. Hypofibrinogenemic (<200 mg/dL) patients at initiation of MT were compared to patients with a level of 200 mg/dL or greater. RESULTS: A total of 96 out of 130 patients met criteria and underwent MT with a median admission fibrinogen of 170.5 mg/dL. Hypofibrinogenemia was associated with elevated INR (1.26 vs 1.13, P < .001) and abnormal TEG including decreased alpha angle (68.1 vs 73.3, P < .001), increased K time (1.7 vs 1.1, P < .001), and decreased max amplitude (58 vs 66, P < .001). Patients with hypofibrinogenemia received more PRBC (10 vs 7 U, P = .002), FFP (9 vs 6 U, P = .003), and platelets (2 vs 1 U, P = .004) during MT. Hypofibrinogenemic patients demonstrated greater mortality than patients with normal levels (50% vs 23.5%, P = .021). Older age, decreased GCS, and elevated injury severity score (ISS) were risk factors for mortality. Increased fibrinogen was associated with lower odds of mortality (P = .001). Age, ISS, and fibrinogen level remained significantly associated with mortality in a multivariable analysis. Overall, fibrinogen in post-MT survivors showed an increase in median level compared to admission (231 vs 177.5 mg/dL, P < .001). CONCLUSION: Trauma patients undergoing MT with decreased admission fibrinogen demonstrate increased mortality. Other mortality risk factors include older age, decreased GCS, and higher ISS. Patients with increased fibrinogen levels had lower odds of mortality in a multivariable model. Post-MT survivors demonstrated significantly higher fibrinogen levels than pre-MT patients. Hypofibrinogenemic patients also had worse TEG parameters and required more PRBCs, FFP, and platelets during MT. Further studies are needed to assess the optimal volume of fibrinogen replacement with cryoprecipitate during MT to improve trauma patient mortality.

Ultrasound may safely replace chest radiograph after tube thoracostomy removal in trauma patients.

INTRODUCTION: A chest radiograph (CXR) is routinely obtained in trauma patients following tube thoracostomy (TT) removal to assess for residual pneumothorax (PTX). New literature supports the deference of a radiograph after routine removal procedure. However, many surgeons have hesitated to adopt this practice due to concern for patient welfare and medicolegal implications. Ultrasound (US) is a portable imaging modality which may be performed rapidly, without radiation exposure, and at minimal cost. We hypothesized that transitioning from CXR to US following TT removal in trauma patients would prove safe and provide superior detection of residual PTX. MATERIALS AND METHODS: A practice management guideline was established calling for the performance of a CXR and bedside US 2 h after TT removal in all adult trauma patients diagnosed with PTX at a level 1 trauma center. Surgical interns completed a 30-minute, US training course utilizing a handheld US device. US findings were interpreted and documented by the surgical interns. CXRs were interpreted by staff radiologists blinded to US findings. Data was retrospectively collected and analyzed. RESULTS: Eighty-nine patients met inclusion criteria. Thirteen (15%) post removal PTX were identified on both US and CXR. An additional 11 (12%) PTX were identified on CXR, and 5 (6%) were identified via US, for a total of 29 PTX (33%). One patient required re-intervention; the recurrent PTX was detected by both US and CXR. For all patients, using CXR as the standard, US displayed a sensitivity of 54.2%, specificity of 92.3%, negative predictive value of 84.5%, and positive predictive value of 72.2%. The cost of care for the study cohort may have been reduced over $9,000 should US alone have been employed. CONCLUSION: Bedside US may be an acceptable alternative to CXR to assess for recurrent PTX following trauma TT removal.

Two centuries of southwest Iceland annually-resolved marine temperature reconstructed from Arctica islandica shells.

Iceland's exposure to major ocean current pathways of the central North Atlantic makes it a useful location for developing long-term proxy records of past marine climate. Such records provide more detailed understanding of the full range of past variability which is necessary to improve predictions of future changes. We constructed a 225-year (1791-2015 CE) master shell growth chronology from 29 shells of Arctica islandica collected at 100 m water depth in southwest Iceland (Faxaflói). The growth chronology provides a robust age model for shell oxygen isotope (δ18Oshell) data produced at annual resolution for 251 years (1765-2015 CE). The temperature reconstruction derived from δ18Oshell shows coherence with May-October local surface temperature records and sea surface temperatures in the North Atlantic region, suggesting it is a useful proxy indicator of water temperature variability at 100 m depth within Faxaflói. Field correlations between the shell-based records and gridded sea surface temperature data reveal strong positive correlations between the 1-year lagged shell growth and temperatures within the subpolar gyre post-1972, suggesting a delayed influence of subpolar gyre dynamics on ecological indicators in southwest Iceland in recent decades. However, the shell growth chronology and δ18Oshell record generally show relatively weak and insignificant correlations with larger region climate indices including the Atlantic Multidecadal Variability, North Atlantic Oscillation, and East Atlantic pattern. Therefore the interannual variations in the newly produced shell-based records appear to reflect more local to regional dynamics around southwest Iceland than large-scale modes of climate variability.

Identification of Genetic and Genomic Influences on Progressive Ethanol Consumption in Diversity Outbred Mice.

Genetic factors play a significant role in the risk for development of alcohol use disorder (AUD). Using 3-bottle choice intermittent access ethanol (IEA), we have employed the Diversity Outbred (DO) mouse panel as a model of alcohol use disorder in a genetically diverse population. Through use of gene expression network analysis techniques, in combination with expression quantitative trait loci (eQTL) mapping, we have completed an extensive analysis of the influence of genetic background on gene expression changes in the prefrontal cortex (PFC). This approach revealed that, in DO mice, genes whose expression was significantly disrupted by intermittent ethanol in the PFC also tended to be those whose expression correlated to intake. This finding is in contrast to previous studies of both mice and nonhuman primates. Importantly, these analyses identified genes involved in myelination in the PFC as significantly disrupted by IEA, correlated to ethanol intake, and having significant eQTLs. Genes that code for canonical components of the myelin sheath, such as Mbp, also emerged as key drivers of the gene expression response to intermittent ethanol drinking. Several regulators of myelination were also key drivers of gene expression, and had significant QTLs, indicating that genetic background may play an important role in regulation of brain myelination. These findings underscore the importance of disruption of normal myelination in the PFC in response to prolonged ethanol exposure, that genetic variation plays an important role in this response, and that this interaction between genetics and myelin disruption in the presence of ethanol may underlie previously observed behavioral changes under intermittent access ethanol drinking such as escalation of consumption.