979 research outputs found

    A Reflective Hybrid Approach to Connecting Leadership Style and Stakeholder Perspective

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    Using quantitative analysis and reflection techniques, we examine employee perception of leadership style and perceived results within organizations based in Whistler, Canada. We are primarily concerned with results in terms of organizational culture towards 3 key stakeholder groups, customers, community, and employees. The observed differences in results between transformational and transactional leadership provide a basis for enriching the mapping of leadership style to desired outcomes

    Halothane binds to druggable sites in the [Ca2+]4-calmodulin (CaM) complex, but does not inhibit [Ca2+]4-CaM activation of kinase

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    The mechanism(s) of volatile anesthetics (VA) are poorly understood. We used high resolution NMR spectroscopy to determine the structure of the halothane/calmodulin([Ca2+]4-CaM) complex, and found that halothane molecules bind in the druggable sites. We then examined whether VA binding to druggable sites in calmodulin would effect [Ca2+]4-CaM dependent activity of myosin light chain kinase. We used fluorescence assays to determine that VA effect [Ca2+]4-CaM activation of smooth-muscle-myosin-light-chain-kinase (smMLCK), but not the Kd of [Ca2+]4-CaM binding to skeletal-myosin-light-chain-kinase-peptide recognition sequence (skMLCKp). These results suggest that VA do not alter [Ca2+]4-CaM dependent MLCK activity via direct interactions with [Ca2+]4-CaM

    Procedural tool for analysing building energy performance: structural equation modelling protocol

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    Building energy performance assessment technique has become a new paradigm that plays a significant part in reducing world energy demand and greenhouse gas emissions. However, there exists a global proliferation of diverse models for assessing and benchmarking buildings. This paper proposes a single building energy performance assessment model that considered several factors that affect office building energy efficiency performances in two different countries. It aimed to develop a model that could identify building energy performance critical factors as a new technique for aggregating energy efficiency metrics for commercial buildings. It examined the relationship and interdependency between the variables as it affects buildings’ performance as a basis for developing its theoretical model. Survey questions were derived from variables obtained from the existing literature using this theoretical paper proposition. A self-administered questionnaire was used to gather data from occupants of office buildings in Nigeria and the UK. Exploratory factor analysis and structural equation modelling via confirmatory factor analysis were used to analyse the explanatory power of the measured variables and their constructs. The results identified management, strategic and operational issues as critical factors that affect building energy performance in both countries. It confirmed the relationships and interdependency of the study factors and developed a new strategy that gives them proper considerations in the operations and management of building energy. Data collected support the theoretical model, and the measurement model fits into the conceptual model. The model gives a quantitative approach that identified critical factors for improving energy management and auditing efficiency of buildings

    Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

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    Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. <p/>Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). <p/>Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. <p/>Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage

    In-Space Structural Assembly: Applications and Technology

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    As NASA exploration moves beyond earth's orbit, the need exists for long duration space systems that are resilient to events that compromise safety and performance. Fortunately, technology advances in autonomy, robotic manipulators, and modular plug-and-play architectures over the past two decades have made in-space vehicle assembly and servicing possible at acceptable cost and risk. This study evaluates future space systems needed to support scientific observatories and human/robotic Mars exploration to assess key structural design considerations. The impact of in-space assembly is discussed to identify gaps in structural technology and opportunities for new vehicle designs to support NASA's future long duration missions

    Interobserver Reliability of Three Validated Scoring Systems in the Assessment of Diabetic Foot Ulcers

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    Scoring systems for diabetic foot ulcers may be used for clinical purposes, research or audit, to help assess disease severity, plan management, and even predict outcomes. While many have been validated in study populations, little is known about their interobserver reliability. This prospective study aimed to evaluate interobserver reliability of 3 scoring systems for diabetic foot ulceration. After sharp debridement, diabetic foot ulcers were classified by a multidisciplinary pool of trained observers, using the PEDIS (Perfusion, Extent, Depth, Infection, Sensation), SINBAD (Site, Ischemia, Neuropathy, Bacterial infection, Depth), and University of Texas (UT) wound classification systems. Interobserver reliability was assessed using intraclass correlations (0 = no agreement; 1 = complete agreement). Thirty-seven patients (78.4% male) were assessed by a pool of 12 observers. Single observer reliability was slight to moderate for all scoring systems (UT 0.53; SINBAD 0.44; PEDIS 0.23-0.42), but multiple observer reliability was almost perfect (UT 0.94; SINBAD 0.91; PEDIS 0.80-0.90). The worst agreement for single observers was when scoring infection (SINBAD 0.28; PEDIS 0.28), ischemia (SINBAD 0.26; PEDIS 0.23), or both (UT 0.25); however, this improved to almost perfect agreement for multiple observers (infection: 0.83; ischemia: 0.80-0.82; both: 0.81). These classification systems may be reliably used by multiple observers, for example, when conducting research and audit. However, they demonstrate only slight to moderate reliability when used by a single observer on an individual subject and may therefore be less helpful in the clinical setting, when documenting ulcer characteristics or communicating between colleagues. </jats:p

    Variations in the slope of the psychometric functions for speech intelligibility: a systematic survey

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    Although many studies have looked at the effects of different listening conditions on the intelligibility of speech, their analyses have often concentrated on changes to a single value on the psychometric function, namely, the threshold. Far less commonly has the slope of the psychometric function, that is, the rate at which intelligibility changes with level, been considered. The slope of the function is crucial because it is the slope, rather than the threshold, that determines the improvement in intelligibility caused by any given improvement in signal-to-noise ratio by, for instance, a hearing aid. The aim of the current study was to systematically survey and reanalyze the psychometric function data available in the literature in an attempt to quantify the range of slope changes across studies and to identify listening conditions that affect the slope of the psychometric function. The data for 885 individual psychometric functions, taken from 139 different studies, were fitted with a common logistic equation from which the slope was calculated. Large variations in slope across studies were found, with slope values ranging from as shallow as 1% per dB to as steep as 44% per dB (median = 6.6% per dB), suggesting that the perceptual benefit offered by an improvement in signal-to-noise ratio depends greatly on listening environment. The type and number of maskers used were found to be major factors on the value of the slope of the psychometric function while other minor effects of target predictability, target corpus, and target/masker similarity were also found

    Sunyaev-Zel'dovich observations of galaxy clusters out to the virial radius with the Arcminute Microkelvin Imager

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    We present observations using the Small Array of the Arcminute Microkelvin Imager (AMI; 14-18 GHz) of four Abell and three MACS clusters spanning 0.171-0.686 in redshift. We detect Sunyaev-Zel'dovich (SZ) signals in five of these without any attempt at source subtraction, although strong source contamination is present. With radio-source measurements from high-resolution observations, and under the assumptions of spherical β\beta-model, isothermality and hydrostatic equilibrium, a Bayesian analysis of the data in the visibility plane detects extended SZ decrements in all seven clusters over and above receiver noise, radio sources and primary CMB imprints. Bayesian evidence ratios range from 10^{11}:1 to 10^{43}:1 for six of the clusters and 3000:1 for one with substantially less data than the others. We present posterior probability distributions for, e.g., total mass and gas fraction averaged over radii internal to which the mean overdensity is 1000, 500 and 200, r_200 being the virial radius. Reaching r_200 involves some extrapolation for the nearer clusters but not for the more-distant ones. We find that our estimates of gas fraction are low (compared with most in the literature) and decrease with increasing radius. These results appear to be consistent with the notion that gas temperature in fact falls with distance (away from near the cluster centre) out to the virial radius.Comment: 18 pages, 10 figures, submitted to MNRAS (updated authors and fixed Figure 1
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