Association of Patient Sex and Pregnancy Status With Naloxone Administration During Emergency Department Visits

OBJECTIVE: To evaluate the association of sex and pregnancy status with rates of naloxone administration during opioid overdose-related emergency department (ED) visits using the Nationwide Emergency Department Sample (NEDS). METHODS: A retrospective cohort study was conducted using NEDS 2016 and 2017 datasets. Eligible records included men and women, 15–49 years of age, with an opioid overdose-related ED visit; records for women were stratified by pregnancy status (ICD-10 O codes). A multivariable logistic regression model was used to assess the primary outcome of naloxone administration (CPT code: J2310). Secondary outcomes included subsequent admission and mortality. A subgroup analysis compared pregnant women who did versus did not receive naloxone. RESULTS: Records from 443,714 men, 304,364 non-pregnant women, and 25,056 pregnant women were included. Non-pregnant women had lower odds for naloxone administration (1.70% vs 2.10%; aOR: 0.86(0.83–0.89)) and mortality (2.21% vs 2.99%; aOR: 0.71(0.69–0.73)) but higher odds of subsequent admission (30.22% vs 27.18%; aOR: 1.04(1.03–1.06)) compared with men. Pregnant women had lower odds for naloxone administration (0..27% vs 1.70%; aOR: 0.16(0.13–0.21)) and mortality (0.41% vs 2.21%; aOR: 0.28(0.23–0.35)) but higher odds of subsequent admission (40.50% vs 30.22%; aOR: 2.04(2.00–2.10)) compared with non-pregnant women. Pregnant women who received naloxone had higher odds of mortality (14% vs 0.39%; aOR: 6.30(2.11–18.78)) compared with pregnant women who did not receive naloxone. Pregnant women who did not receive naloxone were more likely to have Medicaid as their expected insurance payer, be in the lowest quartile of median household income for residence ZIP code, and have a concurrent mental health diagnosis compared with pregnant women who did receive naloxone. CONCLUSION: Reproductive-aged non-pregnant and pregnant women were less likely to receive naloxone during opioid overdose-related ED visits compared to reproductive-aged men. Naloxone administration for reproductive-aged women should be prioritized in the efforts to reduce opioid- and pregnancy-related morbidity and mortality in the United States

Basin tectonic history and paleo-physiography of the pelagian platform, northern Tunisia, using vitrinite reflectance data

Constraining the thermal, burial and uplift/exhumation history of sedimentary basins is crucial in the understanding of upper crustal strain evolution and also has implications for understanding the nature and timing of hydrocarbon maturation and migration. In this study, we use Vitrinite Reflectance (VR) data to elucidate the paleo‐physiography and thermal history of an inverted basin in the foreland of the Atlasic orogeny in Northern Tunisia. In doing so, it is the primary aim of this study to demonstrate how VR techniques may be applied to unravel basin subsidence/uplift history of structural domains and provide valuable insights into the kinematic evolution of sedimentary basins. VR measurements of both the onshore Pelagian Platform and the Tunisian Furrow in Northern Tunisia are used to impose constraints on the deformation history of a long‐lived structural feature in the studied region, namely the Zaghouan Fault. Previous work has shown that this fault was active as an extensional structure in Lower Jurassic to Aptian times, before subsequently being inverted during the Late Cretaceous Eocene Atlas I tectonic event and Upper Miocene Atlas II tectonic event. Quantifying and constraining this latter inversion stage, and shedding light on the roles of structural inheritance and the basin thermal history, are secondary aims of this study. The results of this study show that the Atlas II WNW‐ESE compressive event deformed both the Pelagian Platform and the Tunisian Furrow during Tortonian‐Messinian times. Maximum burial depth for the Pelagian Platform was reached during the Middle to Upper Miocene, i.e. prior to the Atlas II folding event. VR measurements indicate that the Cretaceous to Ypresian section of the Pelagian Platform was buried to a maximum burial depth of ~3 km, using a geothermal gradient of 30°C/km. Cretaceous rock samples VR values show that the hanging wall of the Zaghouan Fault was buried to a maximum depth of <2 km. This suggests that a vertical km‐scale throw along the Zaghouan Fault pre‐dated the Atlas II shortening, and also proves that the fault controlled the subsidence of the Pelagian Platform during the Oligo‐Miocene. Mean exhumation rates of the Pelagian Platform throughout the Messinian to Quaternary were in the order of 0.3 mm/year. However, when the additional effect of Tortonian‐Messinian folding is accounted for, exhumation rates could have reached 0.6-0.7 mm/year

Anatomically and functionally distinct lung mesenchymal populations marked by Lgr5 and Lgr6

The diversity of mesenchymal cell types in the lung that influence epithelial homeostasis and regeneration is poorly defined. We used genetic lineage tracing, single-cell RNA sequencing, and organoid culture approaches to show that Lgr5 and Lgr6, well-known markers of stem cells in epithelial tissues, are markers of mesenchymal cells in the adult lung. Lgr6+ cells comprise a subpopulation of smooth muscle cells surrounding airway epithelia and promote airway differentiation of epithelial progenitors via Wnt-Fgf10 cooperation. Genetic ablation of Lgr6+ cells impairs airway injury repair in vivo. Distinct Lgr5+ cells are located in alveolar compartments and are sufficient to promote alveolar differentiation of epithelial progenitors through Wnt activation. Modulating Wnt activity altered differentiation outcomes specified by mesenchymal cells. This identification of region- and lineage-specific crosstalk between epithelium and their neighboring mesenchymal partners provides new understanding of how different cell types are maintained in the adult lung.This work was supported by (J.-H.L. and J.C.) Wellcome Trust and the Royal Society (107633/Z/15/Z), European Research Council Starting Grant (679411), and the Cambridge Stem Cell Institute Core grant (07922/Z/11/Z) from Wellcome Trust and Medical Research Council; (J.-H.L.) the Hope Funds for Cancer Research; (M.P.) American Lung Association (400553); (A.R.) Howard Hughes Medical Institute, the Klarman Cell Observatory, and NCI grant 1U24CA180922; (A.R., T.T., and T.J.) the Koch Institute Core grant P30-CA14051 from the NCI; (T.T.) the National Cancer InstituteK99 CA187317, the Sigrid Juselius Foundation, the Hope Funds for Cancer Research; (T.J.) a Howard Hughes Medical Institute Investigator, a David H. Koch Professor of Biology and a Daniel K. Ludwig Scholar; and (C.F.K.) R01 HL090136, R01 HL132266, R01 HL125821, U01 HL100402, Harvard Stem Cell Institute, Alfred and Gilda Slifka, Gail and Adam Slifka, and the CFMS Fund

A randomized trial provided new evidence on the accuracy and efficiency of traditional vs. electronically annotated abstraction approaches in systematic reviews

Abstract Objectives Data Abstraction Assistant (DAA) is a software for linking items abstracted into a data collection form for a systematic review to their locations in a study report. We conducted a randomized cross-over trial that compared DAA-facilitated single-data abstraction plus verification ("DAA verification"), single data abstraction plus verification ("regular verification"), and independent dual data abstraction plus adjudication ("independent abstraction"). Study Design and Setting This study is an online randomized cross-over trial with 26 pairs of data abstractors. Each pair abstracted data from six articles, two per approach. Outcomes were the proportion of errors and time taken. Results Overall proportion of errors was 17% for DAA verification, 16% for regular verification, and 15% for independent abstraction. DAA verification was associated with higher odds of errors when compared with regular verification (adjusted odds ratio [OR] = 1.08; 95% confidence interval [CI]: 0.99–1.17) or independent abstraction (adjusted OR = 1.12; 95% CI: 1.03–1.22). For each article, DAA verification took 20 minutes (95% CI: 1–40) longer than regular verification, but 46 minutes (95% CI: 26 to 66) shorter than independent abstraction. Conclusion Independent abstraction may only be necessary for complex data items. DAA provides an audit trail that is crucial for reproducible research

Measurement of the prompt J/psi and psi(2S) polarizations in pp collisions at sqrt(s) = 7 TeV

The polarizations of prompt J/psi and psi(2S) mesons are measured in proton-proton collisions at sqrt(s) = 7 TeV, using a dimuon data sample collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 4.9 inverse femtobarns. The prompt J/psi and psi(2S) polarization parameters lambda[theta], lambda[phi], and lambda[theta, phi], as well as the frame-invariant quantity lambda(tilde), are measured from the dimuon decay angular distributions in three different polarization frames. The J/psi results are obtained in the transverse momentum range 14 &lt; pt &lt; 70 GeV, in the rapidity intervals abs(y) &lt; 0.6 and 0.6 &lt; abs(y) &lt; 1.2. The corresponding psi(2S) results cover 14 &lt; pt &lt; 50 GeV and include a third rapidity bin, 1.2 &lt; abs(y) &lt; 1.5. No evidence of large transverse or longitudinal polarizations is seen in these kinematic regions, which extend much beyond those previously explored

Interplay of Nkx3.2, Sox9 and Pax3 Regulates Chondrogenic Differentiation of Muscle Progenitor Cells

Muscle satellite cells make up a stem cell population that is capable of differentiating into myocytes and contributing to muscle regeneration upon injury. In this work we investigate the mechanism by which these muscle progenitor cells adopt an alternative cell fate, the cartilage fate. We show that chick muscle satellite cells that normally would undergo myogenesis can be converted to express cartilage matrix proteins in vitro when cultured in chondrogenic medium containing TGFß3 or BMP2. In the meantime, the myogenic program is repressed, suggesting that muscle satellite cells have undergone chondrogenic differentiation. Furthermore, ectopic expression of the myogenic factor Pax3 prevents chondrogenesis in these cells, while chondrogenic factors Nkx3.2 and Sox9 act downstream of TGFß or BMP2 to promote this cell fate transition. We found that Nkx3.2 and Sox9 repress the activity of the Pax3 promoter and that Nkx3.2 acts as a transcriptional repressor in this process. Importantly, a reverse function mutant of Nkx3.2 blocks the ability of Sox9 to both inhibit myogenesis and induce chondrogenesis, suggesting that Nkx3.2 is required for Sox9 to promote chondrogenic differentiation in satellite cells. Finally, we found that in an in vivo mouse model of fracture healing where muscle progenitor cells were lineage-traced, Nkx3.2 and Sox9 are significantly upregulated while Pax3 is significantly downregulated in the muscle progenitor cells that give rise to chondrocytes during fracture repair. Thus our in vitro and in vivo analyses suggest that the balance of Pax3, Nkx3.2 and Sox9 may act as a molecular switch during the chondrogenic differentiation of muscle progenitor cells, which may be important for fracture healing

Small molecule compounds targeting the p53 pathway: are we finally making progress?

Loss of function of p53, either through mutations in the gene or through mutations to other members of the pathway that inactivate wild-type p53, remains a critically important aspect of human cancer development. As such, p53 remains the most commonly mutated gene in human cancer. For these reasons, pharmacologic activation of the p53 pathway has been a highly sought after, yet unachieved goal in developmental therapeutics. Recently progress has been made not only in the discovery of small molecules that target wild-type and mutant p53, but also in the initiation and completion of the first in-human clinical trials for several of these drugs. Here, we review the current literature of drugs that target wild-type and mutant p53 with a focus on small-molecule type compounds. We discuss common means of drug discovery and group them according to their common mechanisms of action. Lastly, we review the current status of the various drugs in the development process and identify newer areas of p53 tumor biology that may prove therapeutically useful