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To determine whether a brief leadership curriculum including high-fidelity simulation can improve leadership skills among resident physicians.This was a double-blind, randomized controlled trial among obstetrics-gynecology and emergency medicine (EM) residents across 5 academic medical centers from different geographic areas of the United States, 2015-2017. Participants were assigned to 1 of 3 study arms: the Leadership Education Advanced During Simulation (LEADS) curriculum, a shortened Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) curriculum, or as active controls (no leadership curriculum). Active controls were recruited from a separate site and not randomized to limit any unintentional introduction of materials from leadership curricula. The LEADS curriculum was developed in partnership with the Council on Resident Education in Obstetrics and Gynecology and Council of Residency Directors in Emergency Medicine as a novel way to provide a leadership toolkit. Both LEADS and the abbreviated TeamSTEPPS were designed as six 10-minute interactive web-based modules.The primary outcome of interest was the leadership performance score from the validated Clinical Teamwork Scale instrument measured during standardized high-fidelity simulation scenarios. Secondary outcomes were 9 key components of leadership from the detailed leadership evaluation measured on 5-point Likert scales. Both outcomes were rated by a blinded clinical video reviewer.One hundred ten obstetrics-gynecology and EM residents participated in this 2-year trial. Participants in both LEADS and TeamSTEPPS had statistically significant improvement in leadership scores from "average" to "good" ranges both immediately and at the 6-month follow-up, while controls remained unchanged in the "average" category throughout the study. There were no differences between LEADS and TeamSTEPPS curricula with respect to the primary outcome.Residents who participated in a brief structured leadership training intervention had improved leadership skills that were maintained at 6-month follow-up.

Airway management is an important priority in the care of critically ill children. We sought to provide updated estimates of the epidemiology of pediatric out-of-hospital airway management and ventilation interventions in the United States.We used data from the 2019 National Emergency Medical Services Information System (NEMSIS) data set. We performed a descriptive analysis of all patients 18 years receiving one or more of the following: bag-valve-mask ventilation (BVM), tracheal intubation (TI), supraglottic airway (SGA) insertion, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP) and surgical airway placement. We determined success and complication rates for each airway procedure.Among 1,148,943 pediatric patient care encounters, airway and ventilation interventions occurred in 22,637 (1,970 per 100,000 pediatric Emergency Medical Services (EMS) activations), including 64%11 years old, 56.1% male, 16.9% cardiac arrest, 16.6% injured, and 83.9% in urban areas. Airway interventions included: BVM 3,997 (17.7% of pediatric airway encounters), TI 3,165 (14.0%), SGA 582 (2.6%), CPAP/BiPAP 331 (1.5%) and surgical airway 29 (0.1%). TI success was 75.2% (95% CI 73.7-76.7%) and lowest for the 0-1 month age group (56.8%; 49.2-64.2%). SGA success was 88.0% (95% CI 85.1-90.6%). Vomiting was the most common airway complication (n = 223, 1%).BVM and advanced airway management occur in 1 of every 51 pediatric EMS encounters. BVM is the most commonly prehospital pediatric airway management technique, followed by TI and SGA insertion. These data provide contemporary perspectives of pediatric prehospital airway management.

The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products, bi-substrate analogues and the widely used small molecule C646, lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.

Objectives To determine factors associated with parents who plan to vaccinate their children against influenza next year, especially those who did not vaccinate against influenza last year using a global survey. Study Design A survey of caregivers accompanying their children 1-19 years-old in 17 Pediatric Emergency Departments (ED) in six countries at the peak of the COVID-19 pandemic. Anonymous online survey included caregiver and child demographic information, vaccination history and future intentions, and concern about the child and caregiver having COVID-19 at the time of ED visit. Results Of 2422 surveys, 1314 (54.2%) caregivers stated they plan to vaccinate their child against influenza next year, an increase of 15.8% from the prior year. Of 1459 caregivers who did not vaccinate their children last year, 418 (28.6%) plan to do so next year. Factors predicting willingness to change and vaccinate included child’s up-to-date vaccination status (adjusted odds ratio (aOR)=2.03, 95% confidence interval (CI) 1.29 – 3.32 P = .003); caregivers’ influenza vaccine history (aOR=3.26, 95% CI 2.41 – 4.40 , p< 0.010), and level of concern their child had COVID-19 (aOR=1.09, 95% CI 1.01 – 1.17, p=0.022). Conclusions Changes in risk perception due to COVID-19, and prior vaccination, may serve to influence decision-making among caregivers regarding influenza vaccination in the coming season. In order to promote influenza vaccination among children, public health programs can leverage this information.

The synthesis of (S)-N-Boc-bis(4-fluorophenyl)alanine, an intermediate in the synthesis of denagliptin, is described from the synthesis of a 12 g proof of principle sample to a >900 kg cGMP manufacturing campaign. The chiral centre was established by the asymmetric hydrogenation of the sterically crowded precursor, ethyl 2-acetamido-3,3-bis(4-fluorophenyl)acrylate. The ability to isolate the various intermediates in a physical form that would readily allow filtration, washing, and ultimately purification underpinned the successful manufacturing campaign.

The dynamic and reversible acetylation of proteins catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs) is a major epigenetic regulatory mechanism of gene transcription 1 associated with multiple diseases. While HDAC inhibitors are approved to treat certain cancers, progress on the development of drug-like HAT inhibitors has lagged 2. The HAT paralogs p300 and CBP (p300/CBP) are key transcriptional co-activators essential for a multitude of cellular processes and also implicated in human pathological conditions, including cancer 3. Current p300/CBP HAT domain inhibitors including natural products, 4 bi-substrate analogs (Lys-CoA) 5 and the widely utilized C646 6, 7 lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like p300/CBP catalytic inhibitor. We show the first high resolution (1.95Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 is acetyl-CoA competitive. A-485 selectively inhibited proliferation across lineage-specific tumor types, including several hematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen sensitive and castrate resistant prostate cancer and inhibited tumor growth in a castration resistant xenograft model. These results demonstrate the feasibility of selectively targeting the catalytic activity of histone acetyltransferases.

This article provides details of a low-temperature joining technology called friction stir welding. Friction stir welding (FSW) uses a cylindrical, shouldered tool with a profiled pin that is rotated and slowly plunged into the joint line between two pieces of sheet or plate material. According to an engineer, stir welding eliminated 60 percent of the rivets that the plane would have otherwise required. Eclipse Aviation Corp., Albuquerque, NM, is building a separate plant to house its stir welding operations for commercial production, once its plane receives certification by the US Federal Aviation Administration. FSW is a solid-state process, more like forging and extruding than to fusion welding. Since the process is solid state, the joint is not subject to any shrinkage because of phase changes. The process also introduces minimal heat into the weld, so the heat-affected zone is relatively small in comparison to arc welding.

In January 1997 the Bellevue, Washington, office of CH2M HILL, a full service engineering consulting firm, implemented a new transportation management plan (TMP), replacing an innovative TMP implemented in 1987 that had gained attention nationwide. The results were remarkable: drive-alone commuting by CH2M HILL employees dropped from 61 to 40 percent in just a few months’ time. An employee-led committee adopted the new TMP before an increase in parking fees, a condition of the company’s building lease. The committee desired to offer employees an alternative to higher parking fees. The new TMP included King County Metro’s transportation benefits package called the FlexPass, along with a host of other incentives. The combination of higher parking fees and very inexpensive access to transit and vanpools led to a successful update to an already effective program. It is important to note that the tools were largely in place to support the mode shift: The CH2M HILL office is located within a city block of the downtown Bellevue transit center; an extensive park-and-ride system supports the transit center; the building is equipped with bike racks, showers, and lockers and is served by a transportation management organization; and the company has corporate vehicles available for work-related trips. Since these favorable conditions were already in place, the combination of the transit incentive and parking cost increase changed employees’ commuting habits.