Application Times, Placement Accuracy, and User Ratings of Commercially Available Manual and Battery-Powered Intraosseous Catheters in a High Bone Density Cadaveric Swine Model.

INTRODUCTION: Intraosseous (IO) infusion, the pressurized injection of fluids into bone through a catheter, is a life-preserving resuscitative technique for treating trauma patients with severe hemorrhage. However, little is known regarding the application times, placement accuracy, and end-user ratings of battery-powered and manual IO access devices. This study was specifically designed to fill these knowledge gaps on six FDA-approved IO access devices. MATERIALS AND METHODS: Three experienced U.S. Navy Emergency Medicine residents each placed commercially available 15-gauge IO catheters in cadaveric swine (Sus scrofa) proximal humeri and sternums in a randomized prospective experimental design. Devices included the battery-powered EZ-IO Rapid Infuser and the manual Jamshidi IO, PerSys NIO, SAM Manual IO, Tactical Advanced Lifesaving IO Needle (TALON), and PYNG First Access for Shock and Trauma 1 (30 trials per device, 10 per user, 210 total trials). Application times, placement accuracy in medullary (zone 1) and trabecular (zone 2) bone while avoiding cortical (zone 3) bone, and eight subjective user ratings were analyzed using ANOVA and nonparametric statistics at P < .05. RESULTS: The EZ-IO demonstrated the fastest application times, high rates in avoiding zone 3, and the highest user ratings (P < .0001). The TALON conferred intermediate placement times, highest rates of avoiding zone 3, and second-highest user ratings. The SAM Manual IO and Jamshidi performed poorly, with mixed results for the PerSys NIO and PYNG First Access for Shock and Trauma 1. CONCLUSIONS: The battery-powered EZ-IO performed best and remains the IO access device of choice. The present findings suggest that the TALON should be considered as a manual backup to the EZ-IO.

Ultrasound Localization of Resuscitative Endovascular Balloon Occlusion of the Aorta in a Human Cadaver Model.

OBJECTIVE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a method of gaining proximal control of noncompressible torso hemorrhage (NCTH). Catheter placement is traditionally confirmed with fluoroscopy, but few studies have evaluated whether ultrasound (US) can be used. METHODS: Using a pressurized human cadaver model, a certified REBOA placer was shown one of four randomized cards that instructed them to place the REBOA either correctly or incorrectly in Zone 1 (the distal thoracic aorta extending from the celiac artery to the left subclavian artery) or Zone 3 (in the distal abdominal aorta, from the aortic bifurcation to the lowest renal artery). Once the REBOA was placed, 10 US-trained locators were asked to confirm balloon placement via US. The participants were given 3 minutes to determine whether the catheter had been correctly placed, repeating this 20 times on two cadavers. RESULTS: Overall, US exhibited an average sensitivity of 83%, specificity of 76%, and accuracy of 80%. For Zone 1, US showed a sensitivity of 78% and specificity of 83%, and for Zone 3, a sensitivity of 88% and specificity of 76%. In addition, US exhibited a likelihood positive ratio (LR+) of 3.73 and a likelihood negative ratio (LR-) of 0.22 for either position, with similar numbers for Zone 1 (+4.57, -0.26) and Zone 3 (+3.16, -0.16). CONCLUSION: Ultrasound could prove to be a useful tool for confirming placement of a REBOA catheter, especially in austere environments.

New approach to undergraduate quality improvement.

BACKGROUND: While quality improvement (QI) is an essential component to modern day clinical practice, some foundation doctors fail to engage. This is compounded by a lack of formalised undergraduate QI teaching. We trial an undergraduate active learning workshop and evaluate it using a concurrent triangulation mixed methods design. APPROACH: We constructed a 2-hour interactive QI workshop utilising near-peer educators for third year undergraduate medical students. Our workshop demonstrated an exemplary project and a template featuring evidenced-based QI tools to grasp key concepts. Informal support was provided for student QI projects, undertaken in small peer groups. Utility was assessed using linked pre-and-post event questionnaires with Likert scales, free text thematic analysis and project completion rates. EVALUATION: We recruited 74 students to attend our workshops delivered over 3 months. We achieved high event satisfaction and significant improvements on baseline confidence. Free text comments suggested students perceive QI as an important part of the undergraduate curriculum, described barriers to engagement and the value they place on project autonomy. The workshop eased student feelings of anxiety and intimidation regarding change ideas. Nine projects were completed with one winning a poster prize at a regional conference. IMPLICATIONS: We demonstrate a popular resource light model that can be scaled up to a variety of centres. Targeting QI teaching at the undergraduate level may be instrumental in developing QI culture in health care systems and address barriers to postgraduate involvement. Our study furthers the understanding of undergraduate students' perspectives of QI and demand for further sessions.

COVID-19 Associated Thyroid Storm: A Case Report.

INTRODUCTION: The distinction between coronavirus disease 2019 (COVID-19) and thyroid storm can be extremely difficult to determine on clinical grounds alone as there is significant overlap between the signs and symptoms of each. CASE REPORT: We present a case of a patient with thyroid storm triggered by underlying COVID-19 infection. CONCLUSION: Infection with severe acute respiratory syndrome coronavirus 2 is linked to dysregulation of the thyroid gland through numerous mechanisms, although thyroid storm triggered by COVID-19 appears rare, with only a single case previously identified in the literature.

Mapping multiple endocrine disrupting activities in Virginia rivers using effect-based assays.

Water sources are frequently contaminated with natural and anthropogenic substances having known or suspected endocrine disrupting activities; however, these activities are not routinely measured and monitored. Phenotypic bioassays are a promising new approach for detection and quantitation of endocrine disrupting chemicals (EDCs). We developed cell lines expressing fluorescent chimeric constructs capable of detecting environmental contaminants which interact with multiple nuclear receptors. Using these assays, we tested water samples collected in the summers of 2016, 2017 and 2018 from two major Virginia rivers. Samples were concentrated 200× and screened for contaminants interacting with the androgen (AR), glucocorticoid (GR), aryl hydrocarbon (AhR) and thyroid receptors. Among 45 tested sites, over 70% had AR activity and 60% had AhR activity. Many sites were also positive for GR and TRß activation (22% and 42%, respectively). Multiple sites were positive for more than one type of contaminants, indicating presence of complex mixtures. These activities may negatively impact river ecosystems and consequently human health.

Comparison of thromboelastography versus conventional coagulation tests in simulated Crotalus atrox envenomation using human blood.

INTRODUCTION: Pit viper bites are a source of significant morbidity and mortality. Pit viper bites can cause venom-induced consumptive coagulopathy (VICC), typically evaluated with laboratory-based conventional coagulation tests (CCTs). However, CCTs require a laboratory and average 1 h to conduct. Thromboelastography (TEG) provides real-time, point-of-care tests of coagulation that are fast and require no separate laboratory facilities, which could be advantageous in both hospital and austere settings. However, the relative efficacy of TEG versus CCTs was unclear, particularly at low venom concentrations. Therefore, the objectives of this study were to test human blood with various concentrations of pit viper venom using CCTs and TEG to determine dose-dependent changes, lowest observed effect concentration (LOEC), and sensitivity to detecting samples out of normal diagnostic range. METHODS: Blood samples from 20 volunteers were mixed with varying concentrations of western diamond back rattlesnake (Crotalus atrox) venom based on the mouse LD50IV (none, 0.5%, 1%, 2%, 33%, 66%, and 100% LD50IV). Samples were split and assessed with both CCTs including prothrombin time (PT), international normalized ratio (INR), partial thromboplastin time (PTT), fibrinogen, and D-dimer, along with TEG measures of reaction time (R), kinetic time (K), rate of clot formation (α-angle), and clot strength (MA). Data were analyzed as dose-dependent concentration-based changes in raw values and in percent of samples exceeding diagnostic thresholds using ANOVA and nonparametric statistics at the p < .05 threshold. RESULTS: All evaluations showed significant concentration-dependent changes, and 100% of samples exceeded diagnostic thresholds at 33%LD50IV and above, save D-dimer. At 0.5%LD50IV, R, K, α-angle, PT, and INR were significantly different from controls, and at 1%LD50IV, mean values exceeded diagnostic thresholds for R, K, α-angle, MA, PT, and INR, but not for PTT, D-dimer, or fibrinogen. At 2%LD50IV, 100% of samples were out of normal range for K, α-angle, and PT. CONCLUSION: TEG is effective in coagulopathy evaluations of in vitro simulated pit viper envenomation. At low venom concentrations, TEG performed as well or better than the majority of CCTs. These findings provide empirical evidence supporting the use of TEG to rapidly and accurately evaluate VICC.

Transcriptional Bursting and Co-bursting Regulation by Steroid Hormone Release Pattern and Transcription Factor Mobility.

Genes are transcribed in a discontinuous pattern referred to as RNA bursting, but the mechanisms regulating this process are unclear. Although many physiological signals, including glucocorticoid hormones, are pulsatile, the effects of transient stimulation on bursting are unknown. Here we characterize RNA synthesis from single-copy glucocorticoid receptor (GR)-regulated transcription sites (TSs) under pulsed (ultradian) and constant hormone stimulation. In contrast to constant stimulation, pulsed stimulation induces restricted bursting centered around the hormonal pulse. Moreover, we demonstrate that transcription factor (TF) nuclear mobility determines burst duration, whereas its bound fraction determines burst frequency. Using 3D tracking of TSs, we directly correlate TF binding and RNA synthesis at a specific promoter. Finally, we uncover a striking co-bursting pattern between TSs located at proximal and distal positions in the nucleus. Together, our data reveal a dynamic interplay between TF mobility and RNA bursting that is responsive to stimuli strength, type, modality, and duration.

Impact of Nitrogen Application Rate on Switchgrass Yield, Production Costs, and Nitrous Oxide Emissions.

Switchgrass ( L.) has been promoted as a potential feedstock for cellulosic biofuel in the United States. Switchgrass is known to respond to N fertilizer, but optimal rates remain unclear. Given the potential nonlinear response of nitrous oxide (NO) emissions to N inputs, N additions to switchgrass above optimal levels could have large impacts on the greenhouse gas balance of switchgrass-based biofuel. Additionally, N additions are likely to have large impacts on switchgrass production costs. Yield, N removal, and net returns were measured in switchgrass receiving 0 to 200 kg N ha in Manhattan, KS, from 2012 to 2014. Emissions of NO were measured in the 0- to 150-kg N ha treatments. Total emissions of NO increased from 0.2 to 3.0 kg NO-N ha as N inputs increased from 0 to 150 kg N ha. The 3-yr averages of fertilizer-induced emission factors were 0.7, 2.1, and 2.6% at 50, 100, and 150 kg N ha, respectively. Removal of N at harvest increased linearly with increasing N rate. Switchgrass yields increased with N inputs up to 100 to 150 kg N ha, but the critical N level for maximum yields decreased each year, suggesting that N was being applied in excess at higher N rates. Net returns were maximized at 100 kg N ha at both a high and low urea cost (US$394.71 and $945.91 ha, respectively). These results demonstrate that N inputs were necessary to increase switchgrass productivity, but rates exceeding optimal levels resulted in excessive NO emissions and increased costs for producers.

Hsp72 Is an Intracellular Target of the α,ß-Unsaturated Sesquiterpene Lactone, Parthenolide.

The electrophilic natural product parthenolide has generated significant interest as a model for potential chemotherapeutics. Similar to other α,ß-unsaturated carbonyl electrophiles, parthenolide induces the heat shock response in leukemia cells, potentially through covalent adduction of heat shock proteins. Other thiol-reactive electrophiles have also been shown to induce the heat shock response as well as to covalently adduct members of the heat shock protein family, such as heat shock protein 72 (Hsp72). To identify sites of modification of Hsp72 by parthenolide, we used high-resolution tandem mass spectrometry to detect 10 lysine, histidine, and cysteine residues of recombinant Hsp72 as modified in vitro by 10 and 100 µM parthenolide. To further ascertain that modification of Hsp72 by parthenolide occurs inside cells and not simply as an in vitro artifact, an alkyne-labeled derivative of parthenolide was synthesized to enable enrichment and detection of protein targets of parthenolide using copper-catalyzed [3 + 2] azide-alkyne cycloaddition. The alkyne-labeled parthenolide derivative displays an half maximal inhibitory concentration (IC50) in undifferentiated acute monocytic leukemia cells (THP-1) of 13.1 ± 1.1 µM, whereas parthenolide has an IC50 of 4.7 ± 1.1 µM. Concentration dependence of protein modification by the alkyne-parthenolide derivative was demonstrated, as well as in vitro adduction of Hsp72. Following treatment of THP-1 cells in culture by the alkyne-parthenolide, adducted proteins were isolated with neutravidin resin and detected by immunoblotting in the enriched protein fraction. Hsp70 proteins were detected in the enriched proteins, indicating that Hsp70 proteins were adducted intracellularly by the alkyne-parthenolide derivative.

High rates of growth recorded for hawksbill sea turtles in Anegada, British Virgin Islands.

Management of species of conservation concern requires knowledge of demographic parameters, such as rates of recruitment, survival, and growth. In the Caribbean, hawksbill turtles (Eretmochelys imbricata) have been historically exploited in huge numbers to satisfy trade in their shells and meat. In the present study, we estimated growth rate of juvenile hawksbill turtles around Anegada, British Virgin Islands, using capture-mark-recapture of 59 turtles over periods of up to 649 days. Turtles were recaptured up to six times, having moved up to 5.9 km from the release location. Across all sizes, turtles grew at an average rate of 9.3 cm year(-1) (range 2.3-20.3 cm year(-1)), and gained mass at an average of 3.9 kg year(-1) (range 850 g-16.1 kg year(-1)). Carapace length was a significant predictor of growth rate and mass gain, but there was no relationship between either variable and sea surface temperature. These are among the fastest rates of growth reported for this species, with seven turtles growing at a rate that would increase their body size by more than half per year (51-69% increase in body length). This study also demonstrates the importance of shallow water reef systems for the developmental habitat for juvenile hawksbill turtles. Although growth rates for posthatching turtles in the pelagic, and turtles larger than 61 cm, are not known for this population, the implications of this study are that Caribbean hawksbill turtles in some areas may reach body sizes suggesting sexual maturity in less time than previously considered.

Emergency department patient knowledge, opinions, and risk tolerance regarding computed tomography scan radiation.

BACKGROUND: Computed tomography (CT) scanning use for emergency department (ED) patients has increased exponentially since its inception. STUDY OBJECTIVES: This study aimed to determine what patients view as the risk of radiation from CT scans, their risk tolerance and preference for alternative testing, and their opinions about informed consent and malpractice regarding CT scans. METHODS: A 25-question survey was administered to a random convenience sample of ED patients aged ≥ 18 years by trained research associates. RESULTS: There were 487 patients approached to be surveyed; 78 patients were excluded, leaving 409 patients (84.0%) responding. Mean patient age was 40.5 (standard deviation [SD] 16.8) years, and 51.5% were female. Three hundred ninety of 409 (95.4%) believed doctors should explain the risks and benefits of CT, and 316/409 (77.3%) thought an informed consent form should be signed. One hundred seventy-nine of 409 (43.8%) patients recognized that there was more radiation from a CT scan than a single chest x-ray study. Three hundred twenty-four of 409 (79.2%) preferred CT angiography over lumbar puncture to exclude subarachnoid hemorrhage. To diagnose appendicitis, 199/409 (48.7%) preferred an ultrasound first even if it meant needing a subsequent confirmatory CT, and 193/409 (47.2%) preferred a CT right away. One hundred sixty-nine of 409 (41.3%) patients would still like to have a CT scan of the head after head trauma even if their physician did not believe the test was indicated. CONCLUSION: This study elucidates patient preference and knowledge regarding CT scans. Overall, patients have a poor understanding of CT scan radiation, and desire to have risks explained to them as informed consent prior to the scan.

Reconstruction of paternal genotypes over multiple breeding seasons reveals male green turtles do not breed annually.

For species of conservation concern, knowledge of key life-history and demographic components, such as the number and sex ratio of breeding adults, is essential for accurate assessments of population viability. Species with temperature-dependent sex determination can produce heavily biased primary sex ratios, and there is concern that adult sex ratios may be similarly skewed or will become so as a result of climate warming. Prediction and mitigation of such impacts are difficult when life-history information is lacking. In marine turtles, owing to the difficultly in observing males at sea, the breeding interval of males is unknown. It has been suggested that male breeding periodicity may be shorter than that of females, which could help to compensate for generally female-biased sex ratios. Here we outline how the use of molecular-based paternity analysis has allowed us, for the first time, to assess the breeding interval of male marine turtles across multiple breeding seasons. In our study rookery of green turtles (Chelonia mydas), 97% of males were assigned offspring in only one breeding season within the 3-year study period, strongly suggesting that male breeding intervals are frequently longer than 1year at this site. Our results also reveal a sex ratio of breeding adults of at least 1.3 males to each female. This study illustrates the utility of molecular-based parentage inference using reconstruction of parental genotypes as a method for monitoring the number and sex ratio of breeders in species where direct observations or capture are difficult.

Turtle mating patterns buffer against disruptive effects of climate change.

For organisms with temperature-dependent sex determination (TSD), skewed offspring sex ratios are common. However, climate warming poses the unique threat of producing extreme sex ratio biases that could ultimately lead to population extinctions. In marine turtles, highly female-skewed hatchling sex ratios already occur and predicted increases in global temperatures are expected to exacerbate this trend, unless species can adapt. However, it is not known whether offspring sex ratios persist into adulthood, or whether variation in male mating success intensifies the impact of a shortage of males on effective population size. Here, we use parentage analysis to show that in a rookery of the endangered green turtle (Chelonia mydas), despite an offspring sex ratio of 95 per cent females, there were at least 1.4 reproductive males to every breeding female. Our results suggest that male reproductive intervals may be shorter than the 2-4 years typical for females, and/or that males move between aggregations of receptive females, an inference supported by our satellite tracking, which shows that male turtles may visit multiple rookeries. We suggest that male mating patterns have the potential to buffer the disruptive effects of climate change on marine turtle populations, many of which are already seriously threatened.

Population genetics and morphological comparisons of migratory European (Hirundo rustica rustica) and sedentary East-Mediterranean (Hirundo rustica transitiva) barn swallows.

Speciation processes are largely determined by the relative strength of divergent selection versus the magnitude of gene flow. The barn swallow (Hirundo rustica) has a broad geographic distribution that encompasses substantial geographic variation in morphology and behavior. The European (H. r. rustica) and East-Mediterranean (H. r. transitiva) subspecies are closely related, despite differing in morphological and life-history traits. To explore patterns of genetic differentiation and gene flow, we compared morphological and genetic variation among the nonmigratory breeding population of H. r. transitiva from Israel and the migratory population of H. r. rustica that passes through Israel and compared it with the genetic differentiation between H. r. transitiva from Israel and a breeding population of H. r. rustica from the United Kingdom that uses a different migratory flyway. Mitochondrial haplotype network analysis suggests that the European and East-Mediterranean populations are intermixed, although there was low but significant genetic differentiation between the subspecies based on both mitochondrial (F(ST) = 0.025-0.033) and microsatellite (F(ST) = 0.009-0.014) loci. Coalescent-based analyses suggest recent divergence and substantial gene flow between these populations despite their differences in morphological and behavioral traits. The results suggest that these subspecies are undergoing a differentiation process in the face of gene flow, with selection possibly operating on sexually selected traits.

Low variation in the polymorphic Clock gene poly-Q region despite population genetic structure across barn swallow (Hirundo rustica) populations.

Recent studies of several species have reported a latitudinal cline in the circadian clock gene, Clock, which influences rhythms in both physiology and behavior. Latitudinal variation in this gene may hence reflect local adaptation to seasonal variation. In some bird populations, there is also an among-individual association between Clock poly-Q genotype and clutch initiation date and incubation period. We examined Clock poly-Q allele variation in the Barn Swallow (Hirundo rustica), a species with a cosmopolitan geographic distribution and considerable variation in life-history traits that may be influenced by the circadian clock. We genotyped Barn Swallows from five populations (from three subspecies) and compared variation at the Clock locus to that at microsatellite loci and mitochondrial DNA (mtDNA). We found very low variation in the Clock poly-Q region, as >96% of individuals were homozygous, and the two other alleles at this locus were globally rare. Genetic differentiation based on the Clock poly-Q locus was not correlated with genetic differentiation based on either microsatellite loci or mtDNA sequences. Our results show that high diversity in Clock poly-Q is not general across avian species. The low Clock variation in the background of heterogeneity in microsatellite and mtDNA loci in Barn Swallows may be an outcome of stabilizing selection on the Clock locus.

Independent colonization of multiple urban centres by a formerly forest specialist bird species.

Urban areas are expanding rapidly, but a few native species have successfully colonized them. The processes underlying such colonization events are poorly understood. Using the blackbird Turdus merula, a former forest specialist that is now one of the most common urban birds in its range, we provide the first assessment of two contrasting urban colonization models. First, that urbanization occurred independently. Second, that following initial urbanization, urban-adapted individuals colonized other urban areas in a leapfrog manner. Previous analyses of spatial patterns in the timing of blackbird urbanization, and experimental introductions of urban and rural blackbirds to uncolonized cities, suggest that the leapfrog model is likely to apply. We found that, across the western Palaearctic, urban blackbird populations contain less genetic diversity than rural ones, urban populations are more strongly differentiated from each other than from rural populations and assignment tests support a rural source population for most urban individuals. In combination, these results provide much stronger support for the independent urbanization model than the leapfrog one. If the former model predominates, colonization of multiple urban centres will be particularly difficult when urbanization requires genetic adaptations, having implications for urban species diversity.

Isolation and characteristics of 10 microsatellite markers from the endangered coconut crab (Birgus latro).

The coconut crab (Birgus latro), an endangered marine-dispersed crustacean, is facing severe and probably accelerating population extinction worldwide, but biological information on its conservation remains deficient. In order to reveal the genetic structure of B. latro, 10 microsatellite loci were developed. A high degree of polymorphism was observed with a mean number of alleles per locus of 16.9. The mean expected heterozygosities were also high, ranging from 0.742 to 0.965. The observed heterozygosities ranged from 0.210 to 0.925. Departures from Hardy-Weinberg equilibrium were observed at five loci after the Bonferroni correction. These hypervariable markers will be utilized to study the genetic diversity and conservation of B. latro throughout its distribution range in the Pacific and Indian Oceans.

Winter resource wealth drives delayed dispersal and family-group living in western bluebirds.

Delayed dispersal, where offspring remain with parents beyond the usual period of dependence, is the typical route leading to formation of kin-based cooperative societies. The prevailing explanations for why offspring stay home are variation in resource wealth, in which offspring of wealthy parents benefit disproportionately by staying home, and nepotism, where the tendency for parents to be less aggressive and share food with offspring makes home a superior place to wait to breed. These hypotheses are not strict alternatives, as only wealthy parents have sufficient resources to share. In western bluebirds, Sialia mexicana, sons usually delay dispersal until after winter, gaining feeding advantages through maternal nepotism in a familial winter group. Experimentally reducing resource wealth (mistletoe) by half on winter territories caused sons to disperse in summer, even though their parents remained on the territory during the winter. Only 8% of sons remained with their parents on mistletoe-removal territories compared to 50% of sons on control territories (t(9,10)=3.33, p<0.005). This study is the first to demonstrate that experimentally reducing wealth of a natural food resource reduces delayed dispersal, facilitating nepotism and family-group living. The results clarify the roles of year-round residency, resource limitation and relative wealth outside the breeding season in facilitating the formation of kin-based cooperative societies.

Learned kin recognition cues in a social bird.

In many cooperatively breeding birds, kin selection has an important role in the evolution and maintenance of social behaviour, and 'helpers' can maximize indirect fitness gains by preferentially allocating care to close relatives. Although there is evidence for kin-biased helping behaviour in several species, the mechanism of kin recognition underlying this behaviour is poorly understood. Vocalizations are the most commonly used cues in avian recognition systems, but the effectiveness of vocal signals as reliable recognition cues must depend on how they are acquired. However, there have been no experimental studies of the development of vocal recognition cues in cooperative birds; indeed, the ontogeny of all bird vocalizations other than song is poorly known in any species. Here, we show that cooperatively breeding long-tailed tits (Aegithalos caudatus) can discriminate between kin and non-kin according to the individual-specific characteristics of contact calls, and show experimentally that individuals learn these calls from provisioning adults during the nestling period. Finally, we show that the pattern of cooperative behaviour in this species is consistent with the use of recognition cues learned through association.