Though many individual transcription factors are known to regulate hematopoietic differentiation, major aspects of the global architecture of hematopoiesis remain unknown. Here, we profiled gene ...expression in 38 distinct purified populations of human hematopoietic cells and used probabilistic models of gene expression and analysis of
cis-elements in gene promoters to decipher the general organization of their regulatory circuitry. We identified modules of highly coexpressed genes, some of which are restricted to a single lineage but most of which are expressed at variable levels across multiple lineages. We found densely interconnected
cis-regulatory circuits and a large number of transcription factors that are differentially expressed across hematopoietic states. These findings suggest a more complex regulatory system for hematopoiesis than previously assumed.
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► Gene expression profiles for 38 states of human hematopoietic differentiation ► Expression organized in modules: lineage-specific or reused across lineages ► Transcription factors target each other in densely interconnected circuits ► Dozens of regulators of hematopoiesis identified and functionally validated
Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI.
To determine whether tranexamic acid ...treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI.
Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher.
Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309).
The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 moderate disability or good recovery) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 no disability to 30 death), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events.
Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 74% male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; 90% 1-sided confidence limit for benefit, -0.9%; P = .16; 97.5% 1-sided confidence limit for harm, 10.2%; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% 95% CI, -7.9% to 2.1%; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 95% CI, -2.5 to 0.7; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% 95% CI, -12.8% to 2.1%; P = .16).
Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended.
ClinicalTrials.gov Identifier: NCT01990768.
This study investigates the utility of an off-the-shelf, consumer-grade unmanned aerial vehicle (UAV) for invasive species mapping in a lacustrine fringe environment. Specifically, this work sought ...to determine whether such a UAV would be capable of creating accurate maps of the extent of patches of an invasive plant, yellow flag iris (Iris pseudacorus L.), more efficiently than could be accomplished by a traditional field survey, which is often considered in the literature to provide the most accurate maps. The study was conducted at two lakes in the central interior of British Columbia. The UAV used in this study was a DJI Phantom 3 Professional that can acquire images using the built-in 12.4 MP digital camera. This UAV was selected because it is representative of the type of aerial platform that is easily accessible to invasive plant managers in terms of cost, ease of use, and lack of legal restrictions. Three methods of mapping the yellow flag iris were compared: (1) field survey, (2) manual interpretation of the raw UAV-acquired imagery and the orthoimage created from these data, and (3) pixel-based classification of the orthoimage created from the UAV imagery using a random forest classifier. The results revealed that, at both lakes considered, manual interpretation of the UAV-acquired imagery produced the most accurate maps of yellow flag iris infestation, with a false-positive and false-negative classification rate of less than 1%.
The mosquito, Aedes aegypti, is highly anthropophilic and transmits debilitating arboviruses within human populations and between humans and non-human primates. Female mosquitoes are attracted to ...sources of blood by responding to odor plumes that are emitted by their preferred hosts. Acidic volatile compounds, including carboxylic acids, represent particularly salient odors driving this attraction. Importantly, carboxylic acids are major constituents of human sweat and volatiles generated by skin microbes. As such, they are likely to impact human host preference, a dominant factor in disease transmission cycles. A more complete understanding of mosquito host attraction will necessitate the elucidation of molecular mechanisms of volatile odor detection that function in peripheral sensory neurons. Recent studies have shown that members of the variant ionotropic glutamate receptor gene family are necessary for physiological and behavioral responses to acidic volatiles in Aedes. In this study, we have identified a subfamily of variant ionotropic receptors that share sequence homology across several important vector species and are likely to be activated by carboxylic acids. Moreover, we demonstrate that selected members of this subfamily are activated by short-chain carboxylic acids in a heterologous cell expression system. Our results are consistent with the hypothesis that members of this receptor class underlie acidic volatile sensitivity in vector mosquitoes and provide a frame of reference for future development of novel mosquito attractant and repellent technologies.
Two-dimensional (2D) inorganic materials have emerged as exciting platforms for (opto)electronic, thermoelectric, magnetic, and energy storage applications. However, electronic redox tuning of these ...materials can be difficult. Instead, 2D metal–organic frameworks (MOFs) offer the possibility of electronic tuning through stoichiometric redox changes, with several examples featuring one to two redox events per formula unit. Here, we demonstrate that this principle can be extended over a far greater span with the isolation of four discrete redox states in the 2D MOFs Li x Fe3(THT)2 (x = 0–3, THT = triphenylenehexathiol). This redox modulation results in 10,000-fold greater conductivity, p- to n-type carrier switching, and modulation of antiferromagnetic coupling. Physical characterization suggests that changes in carrier density drive these trends with relatively constant charge transport activation energies and mobilities. This series illustrates that 2D MOFs are uniquely redox flexible, making them an ideal materials platform for tunable and switchable applications.
To address emergency department overcrowding operational research seeks to identify efficient processes to optimize flow of patients through the emergency department. Vertical flow refers to the ...concept of utilizing and assigning patients virtual beds rather than to an actual physical space within the emergency department to care of low acuity patients. The aim of this study is to evaluate the impact of vertical flow upon emergency department efficiency and patient satisfaction.
Prospective pre/post-interventional cohort study of all intend-to-treat patients presenting to the emergency department during a two-year period before and after the implementation of a vertical flow model.
In total 222,713 patient visits were included in the analysis with 107,217 patients presenting within the pre-intervention and 115,496 in the post-intervention groups. The results of the regression analysis demonstrate an improvement in throughput across the entire ED patient population, decreasing door to departure time by 17 min (95% CI 15–18) despite an increase in patient volume. No statistically significant difference in patient satisfaction scores were found between the pre- and post-intervention.
Initiation of a vertical split flow model was associated with improved ED efficiency.
Objective
The purpose of this study was to evaluate the subsequent health resource utilization (HRU) between patients with migraine who received opioid medications at their emergency department (ED) ...visits (“opioid recipients”) versus patients with migraine who did not receive opioid medications at their ED visits (“non‐recipients”).
Background
Previous studies have found that opioid use is common among patients with migraine at emergency settings. Medication overuse, especially the use of opioids, is associated with migraine progression, which can ultimately lead to substantial health resource use and costs. There is limited evidence on opioid use specifically in emergency settings and its impact on future HRU among people with migraine.
Method
This retrospective cohort study used electronic health record data from the Baylor Scott & White Health between December 2013 and April 2017. Adult patients who had at least 6 months of continuous enrollment before (baseline or pre‐index) and after (follow‐up) the first date they had an ED visit with a diagnosis of migraine (defined as index date) were enrolled in the study. Opioid use and HRU during follow‐up period between opioid recipients and non‐recipients were summarized and compared.
Results
A total of 788 patients met the eligibility criteria and were included in this study. During the 6‐month follow‐up period, compared to patients with migraine who were non‐recipients at their index ED visits, opioid recipients had significantly more all‐cause (3.6 SD = 6.3 vs. 1.9 SD = 4.8, p < 0.0001) and migraine‐related (1.6 SD = 4.2 vs. 0.6 SD = 2.1, p < 0.0001) opioid prescriptions (RXs), and more all‐cause (2.6 SD = 4.3 vs. 1.6 SD = 2.6, p = 0.002) and migraine‐related (0.6 SD = 1.4 vs. 0.3 SD = 0.8, p = 0.001) ED visits. In addition, opioid recipients had higher risk of future migraine‐related ED visits controlling for covariates (HR = 1.49, 95% CI = 1.09–2.03, p = 0.013). Factors that were significantly (p < 0.05) related to future migraine‐related ED visits include previous opioid use (HR = 2.12, 95% CI = 1.24–3.65, p = 0.007), previous ED visits (HR = 2.38, 95% CI = 1.23–4.58, p = 0.010), hypertension (HR = 1.46, 95% CI = 1.07–2.00, p = 0.017), age between 45 and 64 years (HR = 0.68, 95% CI = 0.48–0.97, p = 0.033), female sex (HR = 1.82, 95% CI = 1.12–2.86, p = 0.015), and tobacco use disorder (HR = 1.45, 95% CI = 1.07–1.97, p = 0.017). Sub‐analyses were restricted to the group of patients who were opioid naïve at baseline (n = 274, defined as having ≤1 opioid RXs during the 6‐month pre‐index period). Patients who were baseline opioid naïve but received opioids during their index ED visits were more likely to have future migraine‐related ED visits compared to patients who were baseline opioid naïve and did not receive any opioids during their index ED visits, controlling for covariates (HR = 2.90, 95% CI = 1.54–5.46, p = 0.001).
Conclusion
Opioid use among patients with migraine presenting to the ED is associated with increased future HRU, which highlights the need for optimizing migraine management in emergency settings.
Cobalt chromium (CoCr) is the most commonly used material in TKA; however, the use of oxidized zirconium (OxZr) implants has increased. The advantages to this material demonstrated in basic science ...studies have not been borne out in clinical studies to date.
In the setting of the American Joint Replacement Registry (AJRR), how do revision rates differ between CoCr and OxZr after primary TKA?
The AJRR was accessed for all primary TKAs performed between 2012 and 2020 for osteoarthritis, resulting in 441,605 procedures (68,506 with OxZr and 373,099 with CoCr). The AJRR is the largest joint replacement registry worldwide and collects procedure-specific details, making it ideal for large-scale comparisons of implant materials in the United States. Competing risk survival analyses were used to evaluate the all-cause revision rates of primary TKAs, comparing CoCr and OxZr implants. Data from the Centers for Medicare and Medicaid Services claims from 2012 to 2017 were also cross-referenced to capture additional revisions from other institutions. Revision rates were tabulated and subclassified by indication. Multivariate Cox regression was used to account for confounding variables such as age, gender, region, and hospital size.
After controlling for confounding variables, there were no differences between the OxZr and CoCr groups in terms of the rate of all-cause revision at a mean follow-up of 46 ± 23 months and 44 ± 24 months for CoCr and OxZr implants, respectively (hazard ratio 1.055 95% confidence interval 0.979 to 1.137; p = 0.16) The univariate analysis demonstrated increased rates of revisions for pain and instability in the OxZr group (p = 0.003 and p < 0.001, respectively).
These findings suggest there is no difference in all-cause revision between OxZr and CoCr implants in the short-term to mid-term. However, further long-term in vivo studies are needed to monitor the safety and all-cause revision rate of OxZr implants compared with those of CoCr implants. OxZr implants may be favorable in patients who have sensitivity to metal. Despite similar short-term to mid-term all-cause revision rates to CoCr implants, because of the limitations of this study, definitive recommendations for or against the use of OxZr cannot be made.
Level III, therapeutic study.
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