Team working in intensive care:current evidence and future endeavors

Purpose of review: It has recently been argued that the future of intensive care medicine will rely on high quality management and teamwork. Therefore, this review takes an organizational psychology perspective to examine the most recent research on the relationship between teamwork, care processes, and patient outcomes in intensive care. Recent findings: Interdisciplinary communication within a team is crucial for the development of negotiated shared treatment goals and short-team patient outcomes. Interventions for maximizing team communication have received substantial interest in recent literature. Intensive care coordination is not a linear process, and intensive care teams often fail to discuss how to implement goals, trigger and align activities, or reflect on their performance. Despite a move toward interdisciplinary team working, clinical decision-making is still problematic and continues to be perceived as a top-down and authoritative process. The topic of team leadership in intensive care is underexplored and requires further research. Summary: Based on findings from the most recent research evidence in medicine and management, four principles are identified for improving the effectiveness of team working in intensive care: engender professional efficacy, create stable teams and leaders, develop trust and participative safety, and enable frequent team reflexivity

Phase Ib study of the combination of pexidartinib (PLX3397), a CSF-1R inhibitor, and paclitaxel in patients with advanced solid tumors.

Purpose:To evaluate the safety, recommended phase II dose (RP2D) and efficacy of pexidartinib, a colony stimulating factor receptor 1 (CSF-1R) inhibitor, in combination with weekly paclitaxel in patients with advanced solid tumors. Patients and Methods:In part 1 of this phase Ib study, 24 patients with advanced solid tumors received escalating doses of pexidartinib with weekly paclitaxel (80 mg/m2). Pexidartinib was administered at 600 mg/day in cohort 1. For subsequent cohorts, the dose was increased by ⩽50% using a standard 3+3 design. In part 2, 30 patients with metastatic solid tumors were enrolled to examine safety, tolerability and efficacy of the RP2D. Pharmacokinetics and biomarkers were also assessed. Results:A total of 51 patients reported ≥1 adverse event(s) (AEs) that were at least possibly related to either study drug. Grade 3-4 AEs, including anemia (26%), neutropenia (22%), lymphopenia (19%), fatigue (15%), and hypertension (11%), were recorded in 38 patients (70%). In part 1, no maximum tolerated dose was achieved and 1600 mg/day was determined to be the RP2D. Of 38 patients evaluable for efficacy, 1 (3%) had complete response, 5 (13%) partial response, 13 (34%) stable disease, and 17 (45%) progressive disease. No drug-drug interactions were found. Plasma CSF-1 levels increased 1.6- to 53-fold, and CD14dim/CD16+ monocyte levels decreased by 57-100%. Conclusions:The combination of pexidartinib and paclitaxel was generally well tolerated. RP2D for pexidartinib was 1600 mg/day. Pexidartinib blocked CSF-1R signaling, indicating potential for mitigating macrophage tumor infiltration

Effect of Intake Air Filter Condition on Vehicle Fuel Economy

The U.S. Department of Energy (DOE) Office of Energy Efficiency and Renewable Energy and the U.S. Environmental Protection Agency (EPA) jointly maintain a fuel economy website (www.fueleconomy.gov), which helps fulfill their responsibility under the Energy Policy Act of 1992 to provide accurate fuel economy information [in miles per gallon (mpg)] to consumers. The site provides information on EPA fuel economy ratings for passenger cars and light trucks from 1985 to the present and other relevant information related to energy use such as alternative fuels and driving and vehicle maintenance tips. In recent years, fluctuations in the price of crude oil and corresponding fluctuations in the price of gasoline and diesel fuels have renewed interest in vehicle fuel economy in the United States. (User sessions on the fuel economy website exceeded 20 million in 2008 compared to less than 5 million in 2004 and less than 1 million in 2001.) As a result of this renewed interest and the age of some of the references cited in the tips section of the website, DOE authorized the Oak Ridge National Laboratory (ORNL) Fuels, Engines, and Emissions Research Center (FEERC) to initiate studies to validate and improve these tips. This report documents a study aimed specifically at the effect of engine air filter condition on fuel economy. The goal of this study was to explore the effects of a clogged air filter on the fuel economy of vehicles operating over prescribed test cycles. Three newer vehicles (a 2007 Buick Lucerne, a 2006 Dodge Charger, and a 2003 Toyota Camry) and an older carbureted vehicle were tested. Results show that clogging the air filter has no significant effect on the fuel economy of the newer vehicles (all fuel injected with closed-loop control and one equipped with MDS). The engine control systems were able to maintain the desired AFR regardless of intake restrictions, and therefore fuel consumption was not increased. The carbureted engine did show a decrease in fuel economy with increasing restriction. However, the level of restriction required to cause a substantial (10-15%) decrease in fuel economy (such as that cited in the literature) was so severe that the vehicle was almost undrivable. Acceleration performance on all vehicles was improved with a clean air filter. Once it was determined how severe the restriction had to be to affect the carbureted vehicle fuel economy, the 2007 Buick Lucerne was retested in a similar manner. We were not able to achieve the level of restriction that was achieved with the 1972 Pontiac with the Lucerne. The Lucerne's air filter box would not hold the filter in place under such severe conditions. (It is believed that this testing exceeded the design limits of the air box.) Tests were conducted at a lower restriction level (although still considerably more severe than the initial clogged filter testing), allowing the air filter to stay seated in the air box, and no significant change was observed in the Lucerne's fuel economy or the AFR over the HFET cycle. Closed-loop control in modern fuel injected vehicle applications is sophisticated enough to keep a clogged air filter from affecting the vehicle fuel economy. However for older, open-loop, carbureted vehicles, a clogged air filter can affect the fuel economy. For the vehicle tested, the fuel economy with a new air filter improved as much as 14% over that with a severely clogged filter (in which the filter was so clogged that drivability was impacted). Under a more typical state of clog, the improvement with a new filter ranged from 2 to 6%

Computerised lung sound analysis to improve the specificity of paediatric pneumonia diagnosis in resource-poor settings: protocol and methods for an observational study

Introduction: WHO case management algorithm for paediatric pneumonia relies solely on symptoms of shortness of breath or cough and tachypnoea for treatment and has poor diagnostic specificity, tends to increase antibiotic resistance. Alternatives, including oxygen saturation measurement, chest ultrasound and chest auscultation, exist but with potential disadvantages. Electronic auscultation has potential for improved detection of paediatric pneumonia but has yet to be standardised. The authors aim to investigate the use of electronic auscultation to improve the specificity of the current WHO algorithm in developing countries. Methods: This study is designed to test the hypothesis that pulmonary pathology can be differentiated from normal using computerised lung sound analysis (CLSA). The authors will record lung sounds from 600 children aged ≤5 years, 100 each with consolidative pneumonia, diffuse interstitial pneumonia, asthma, bronchiolitis, upper respiratory infections and normal lungs at a children\u27s hospital in Lima, Peru. The authors will compare CLSA with the WHO algorithm and other detection approaches, including physical exam findings, chest ultrasound and microbiologic testing to construct an improved algorithm for pneumonia diagnosis. Discussion: This study will develop standardised methods for electronic auscultation and chest ultrasound and compare their utility for detection of pneumonia to standard approaches. Utilising signal processing techniques, the authors aim to characterise lung sounds and through machine learning, develop a classification system to distinguish pathologic sounds. Data will allow a better understanding of the benefits and limitations of novel diagnostic techniques in paediatric pneumonia

CRADA Final Report for CRADA Number ORNL00-0605: Advanced Engine/Aftertreatment System R&D

Navistar and ORNL established this CRADA to develop diesel engine aftertreatment configurations and control strategies that could meet emissions regulations while maintaining or improving vehicle efficiency. The early years of the project focused on reducing the fuel penalty associated with lean NOx trap (LNT), also known as NOx adsorber catalyst regeneration and desulfation. While Navistar pursued engine-based (in-cylinder) approaches to LNT regeneration, complementary experiments at ORNL focused on in-exhaust fuel injection. ORNL developed a PC-based controller for transient electronic control of EGR valve position, intake throttle position, and actuation of fuel injectors in the exhaust system of a Navistar engine installed at Oak Ridge. Aftertreatment systems consisting of different diesel oxidation catalysts (DOCs) in conjunction with a diesel particle filter and LNT were evaluated under quasi-steady-state conditions. Hydrocarbon (HC) species were measured at multiple locations in the exhaust system with Gas chromatograph mass spectrometry (GC-MS) and Fourier transform infrared (FTIR) spectroscopy. Under full-load, rated speed conditions, injection of fuel upstream of the DOC reduced the fuel penalty for a given level of NOx reduction by 10-20%. GC-MS showed that fuel compounds were 'cracked' into smaller hydrocarbon species over the DOC, particularly light alkenes. GC-MS analysis of HC species entering and exiting the LNT showed high utilization of light alkenes, followed by mono-aromatics; branched alkanes passed through the LNT largely unreacted. Follow-on experiments at a 'road load' condition were conducted, revealing that the NOx reduction was better without the DOC at lower temperatures. The improved performance was attributed to the large swings in the NOx adsorber core temperature. Split-injection experiments were conducted with ultra-low sulfur diesel fuel and three pure HC compounds: 1-pentene, toluene, and iso-octane. The pure compound experiments confirmed the previous results regarding hydrocarbon reactivity: 1-pentene was the most efficient LNT reductant, followed by toluene. Injection location had minimal impact on the reactivity of these two compounds. Iso-octane was an ineffective LNT reductant, requiring high doses (resulting in high HC emissions) to achieve reasonable NOx conversions. Diesel fuel reactivity was sensitive to injection location, with the best performance achieved through fuel injection downstream of the DOC. This configuration generated large LNT temperature excursions, which probably improved the efficiency of the NOx storage/reduction process, but also resulted in very high HC emissions. The ORNL team demonstrated an LNT desulfation under 'road load' conditions using throttling, EGR, and in-pipe injection of diesel fuel. Flow reactor characterization of core samples cut from the front and rear of the engine-aged LNT revealed complex spatially dependent degradation mechanisms. The front of the catalyst contained residual sulfates, which impacted NOx storage and conversion efficiencies at high temperatures. The rear of the catalyst showed significant sintering of the washcoat and precious metal particles, resulting in lower NOx conversion efficiencies at low temperatures. Further flow reactor characterization of engine-aged LNT core samples established that low temperature performance was limited by slow release and reduction of stored NOx during regeneration. Carbon monoxide was only effective at regenerating the LNT at temperatures above 200 C; propene was unreactive even at 250 C. Low temperature operation also resulted in unselective NOx reduction, resulting in high emissions of both N{sub 2}O and NH{sub 3}. During the latter years of the CRADA, the focus was shifted from LNTs to other aftertreatment devices. Two years of the CRADA were spent developing detailed ammonia SCR device models with sufficient accuracy and computational efficiency to be used in development of model-based ammonia injection control algorithms.ORNL, working closely with partners at Navistar and M

ERβ Binds N-CoR in the Presence of Estrogens via an LXXLL-like Motif in the N-CoR C-terminus

Nuclear receptors (NRs) usually bind the corepressors N-CoR and SMRT in the absence of ligand or in the presence of antagonists. Agonist binding leads to corepressor release and recruitment of coactivators. Here, we report that estrogen receptor β (ERβ) binds N-CoR and SMRT in the presence of agonists, but not antagonists, in vitro and in vivo. This ligand preference differs from that of ERα interactions with corepressors, which are inhibited by estradiol, and resembles that of ERβ interactions with coactivators. ERβ /N-CoR interactions involve ERβ AF-2, which also mediates coactivator recognition. Moreover, ERβ recognizes a sequence (PLTIRML) in the N-CoR C-terminus that resembles coactivator LXXLL motifs. Inhibition of histone deacetylase activity specifically potentiates ERβ LBD activity, suggesting that corepressors restrict the activity of AF-2. We conclude that the ER isoforms show completely distinct modes of interaction with a physiologically important corepressor and discuss our results in terms of ER isoform specificity in vivo

Effects of Intermediate Ethanol Blends on Legacy Vehicles and Small Non‑Road Engines, Report 1 - Updated

In summer 2007, the U.S. Department of Energy (DOE) initiated a test program to evaluate the potential impacts of intermediate ethanol blends on legacy vehicles and other engines. The purpose of the test program is to assess the viability of using intermediate blends as a contributor to meeting national goals in the use of renewable fuels. Through a wide range of experimental activities, DOE is evaluating the effects of E15 and E20--gasoline blended with 15 and 20% ethanol--on tailpipe and evaporative emissions, catalyst and engine durability, vehicle driveability, engine operability, and vehicle and engine materials. This first report provides the results available to date from the first stages of a much larger overall test program. Results from additional projects that are currently underway or in the planning stages are not included in this first report. The purpose of this initial study was to quickly investigate the effects of adding up to 20% ethanol to gasoline on the following: (1) Regulated tailpipe emissions for 13 popular late model vehicles on a drive cycle similar to real-world driving and 28 small non-road engines (SNREs) under certification or typical in use procedures. (2) Exhaust and catalyst temperatures of the same vehicles under more severe conditions. (3) Temperature of key engine components of the same SNREs under certification or typical in-use conditions. (4) Observable operational issues with either the vehicles or SNREs during the course of testing. As discussed in the concluding section of this report, a wide range of additional studies are underway or planned to consider the effects of intermediate ethanol blends on materials, emissions, durability, and driveability of vehicles, as well as impacts on a wider range of nonautomotive engines, including marine applications, snowmobiles, and motorcycles. Section 1 (Introduction) gives background on the test program and describes collaborations with industry and agencies to date. Section 2 (Experimental Setup) provides details concerning test fuels, vehicle and SNRE selection, and test methods used to conduct the studies presented in this report. Section 3 (Results and Discussion) summarizes the vehicle and SNRE studies and presents data from testing completed to date. Section 4 (Next Steps) describes planned future activities. The appendixes provide test procedure details, vehicle and SNRE emissions standards, analysis details, and additional data and tables from vehicle and SNRE tests

Quantum-statistical transport phenomena in memristive computing architectures

The advent of reliable, nanoscale memristive components is promising for next generation compute-in-memory paradigms, however, the intrinsic variability in these devices has prevented widespread adoption. Here we show coherent electron wave functions play a pivotal role in the nanoscale transport properties of these emerging, non-volatile memories. By characterizing both filamentary and non-filamentary memristive devices as disordered Anderson systems, the switching characteristics and intrinsic variability arise directly from the universality of electron transport in disordered media. Our framework suggests localization phenomena in nanoscale, solid-state memristive systems are directly linked to circuit level performance. We discuss how quantum conductance fluctuations in the active layer set a lower bound on device variability. This finding implies there is a fundamental quantum limit on the reliability of memristive devices, and electron coherence will play a decisive role in surpassing or maintaining Moore's Law with these systems.Comment: 13 pages, 6 figure

A phase 1/2 study of the oral FLT3 inhibitor pexidartinib in relapsed/refractory FLT3-ITD-mutant acute myeloid leukemia.

FMS-like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitors (TKIs) have activity in acute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (ITD) mutations, but efficacy is limited by resistance-conferring kinase domain mutations. This phase 1/2 study evaluated the safety, tolerability, and efficacy of the oral FLT3 inhibitor PLX3397 (pexidartinib), which has activity against the FLT3 TKI-resistant F691L gatekeeper mutation in relapsed/refractory FLT3-ITD-mutant AML. Ninety patients were treated: 34 in dose escalation (part 1) and 56 in dose expansion (part 2). Doses of 800 to 5000 mg per day in divided doses were tested. No maximally tolerated dose was reached. Plasma inhibitory assay demonstrated that patients dosed with ≥3000 mg had sufficient levels of active drug in their trough plasma samples to achieve 95% inhibition of FLT3 phosphorylation in an FLT3-ITD AML cell line. Based on a plateau in drug exposure, the 3000-mg dose was chosen as the recommended phase 2 dose. The most frequently reported treatment-emergent adverse events were diarrhea (50%), fatigue (47%), and nausea (46%). Based on modified response criteria, the overall response rate to pexidartinib among all patients was 21%. Twenty-three percent of patients treated at ≥2000 mg responded. The overall composite complete response rate for the study was 11%. Six patients were successfully bridged to transplantation. Median overall survival (OS) of patients treated in dose expansion was 112 days (90% confidence interval [CI], 77-150 days), and median OS of responders with complete remission with or without recovery of blood counts was 265 days (90% CI, 170-422 days). This trial was registered at www.clinicaltrials.gov as #NCT01349049