The role of triacylglycerol in cardiac energy provision

Triacylglycerols (TAGs) constitute the main energy storage resource in mammals, by virtue of their high energy density. This in turn is a function of their highly reduced state and hydrophobicity. Limited water solubility, however, imposes specific requirements for delivery and uptake mechanisms on TAG-utilising tissues, including the heart, as well as intracellular disposition. TAGs constitute potentially the major energy supply for working myocardium, both through blood-borne provision and as intracellular TAG within lipid droplets, but also provide the heart with fatty acids (FAs) which the myocardium cannot itself synthesise but are required for glycerolipid derivatives with (non-energetic) functions, including membrane phospholipids and lipid signalling molecules. Furthermore they serve to buffer potentially toxic amphipathic fatty acid derivatives. Intracellular handling and disposition of TAGs and their FA and glycerolipid derivatives similarly requires dedicated mechanisms in view of their hydrophobic character. Dysregulation of utilisation can result in inadequate energy provision, accumulation of TAG and/or esterified species, and these may be responsible for significant cardiac dysfunction in a variety of disease states. This review will focus on the role of TAG in myocardial energy provision, by providing FAs from exogenous and endogenous TAG sources for mitochondrial oxidation and ATP production, and how this can change in disease and impact on cardiac function

A Comparison of non-coplanar three-dimensional conformal radiation therapy, intensity modulated radiation therapy, and volumetric modulated radiation therapy for the delivery of stereotactic ablative radiation therapy to peripheral lung cancer

Aim The objective of the study was to compare three noncoplanar delivery techniques (three-dimensional conformal radiation therapy [3DCRT], intensity-modulated radiation therapy [IMRT], and volumetric-modulated arc therapy [VMAT]) for the delivery of lung stereotactic ablative radiation therapy to peripheral lung tumours. Methods and Materials The plans were compared by assessing the planning target volume coverage, doses to organs at risk, high and intermediate dose constraints (D and R) and delivery times using analysis of variance for repeated measurements or Friedman's test when appropriate. Results Mean PTV54 Gy coverage was found to be 95.6%, 95.7%, and 95.6% for the 3DCRT, IMRT, and VMAT techniques, respectively. No deviations to the intermediate dose constraints were found in 65%, 65%, and 85% of the patients for the 3DCRT, IMRT, and VMAT plans, respectively. Mean treatment times (excluding setup and imaging) were 20.0 minutes (±1.67), 25.2 minutes (±2.15), and 11.7 (±2.0) minutes respectively for 3DCRT, IMRT, and VMAT. Conclusion A noncoplanar VMAT technique was found to provide superior intermediate dose sparing with comparable prescription dose coverage when compared with noncoplanar 3DCRT or IMRT. In addition, VMAT was found to reduce the treatment times of stereotactic ablative radiation therapy delivery for peripheral lung tumours

The effect of beam arrangements and the impact of non-coplanar beams on the treatment planning of stereotactic ablative radiation therapy for early stage lung cancer

<b>Introduction</b>\ud \ud - The aim of this study was to compare various coplanar and non-coplanar <i>3-dimensional conformal radiation therapy (3DCRT)</i> beam arrangements for the delivery of <i>stereotactic ablative radiation therapy (SABR)</i> to patients with early stage lung cancer, based on the dosimetric criteria from the <i>Radiation Therapy Oncology Group (RTOG)</i> 1021 protocol.\ud \ud <b>Methods</b>\ud \ud - Ten medically inoperable lung cancer patients eligible for SABR were re-planned using three different coplanar and three different non-coplanar beam arrangements. The plans were compared by assessing <i>planning target volume (PTV)</i> coverage, doses to normal tissues, the high-dose conformity (conformity index) and intermediate dose spillage as defined by the D_2cm, (the dose at any point 2 cm away from the PTV), and the R_50% (the ratio of the volume of half the prescription dose to the volume of the PTV).\ud \ud <b>Results</b>\ud \ud - Sixty plans in total were assessed. Mean PTV coverage with the prescription isodose was similar between coplanar (95.14%) and non-coplanar (95.26%) techniques (P = 0.47). There was significant difference between all coplanar and all non-coplanar fields for the R_50% (P < 0.0001) but none for the D_2cm (P = 0.19). The seven and nine field beam arrangements with two non-coplanar fields had less unacceptable protocol deviations (10 and 7) than the seven and nine field plans with only coplanar fields (13 and 8). The 13 field coplanar fields did not improve protocol compliance with eight unacceptable deviations. The 10 field non-coplanar beam arrangement achieved best compliance with the RTOG 1021 dose criteria with only one unacceptable deviation (maximum rib dose).\ud \ud <b>Conclusion</b>\ud \ud - A 3DCRT planning technique using 10 fields with ≥6 non-coplanar beams best satisfied high and intermediate dose constraints stipulated in the RTOG 1021 trial. Further investigations are required to determine if minor protocol deviations should be balanced against efficiency with the extended treatment times required to deliver non-coplanar fields and if treatment times can be improved using novel intensity modulated techniques

Provocazioni in libertà sull'art. 2346, comma 4, c.c.

<b>Introduction</b>\ud \ud - The purpose of this study was to investigate coplanar and non-coplanar <i>volumetric modulated arc therapy (VMAT)</i> delivery techniques for <i>stereotactic ablative radiation therapy (SABR)</i> to the lung.\ud \ud <b>Methods</b>\ud \ud - For ten patients who had already completed a course of radiation therapy for early stage lung cancer, three new SABR treatment plans were created using (1) a coplanar full arc (FA) technique, (2) a coplanar partial arc technique (PA) and (3) a non-coplanar technique utilising three partial arcs (NCA). These plans were evaluated using planning target volume (PTV) coverage, dose to organs at risk, and high and intermediate dose constraints as incorporated by radiation therapy oncology group (RTOG) 1021.\ud \ud <b>Results</b>\ud \ud - When the FA and PA techniques were compared to the NCA technique, on average the PTV coverage (V_54Gy) was similar (P = 0.15); FA (95.1%), PA (95.11%) and NCA (95.71%). The NCA resulted in a better conformity index (CI) of the prescription dose (0.89) when compared to the FA technique (0.88, P = 0.23) and the PA technique (0.83, P = 0.06). The NCA technique improved the intermediate dose constraints with a statistically significant difference for the D_2cm and R_50% when compared with the FA (P < 0.03 and <0.0001) and PA (P < 0.04 and <0.0001) techniques. The NCA technique reduced the maximum spinal cord dose by 2.72 and 4.2 Gy when compared to the PA and FA techniques respectively. Mean lung doses were 4.09, 4.31 and 3.98 Gy for the FA, PA and NCA techniques respectively.\ud \ud <b>Conclusion</b>\ud \ud - The NCA VMAT technique provided the highest compliance to RTOG 1021 when compared to coplanar techniques for lung SABR. However, single FA coplanar VMAT was suitable for 70% of patients when minor deviations to both the intermediate dose and organ at risk (OAR) constraints were accepted

NATO AVT-365 Lecture Series: Rotorcraft Flight Simulation Model Fidelity Improvement and Assessment

Slides and Educational Notes for the Lecture Series NATO AVT-365 which presents results from the working group AVT-296 with the same titl

Rotorcraft Flight Simulation Model Fidelity Improvement and Assessment

Rotorcraft flight dynamics simulation models require high levels of fidelity to be suitable as prime items in support of life cycle practices, particularly vehicle and control design and development, and system and trainer certification. On the civil side, both the FAA (US) and EASA (Europe) have documented criteria (metrics and practices) for assessing model and simulator fidelity as compared to flight-test data, although these have not been updated for several decades. On the military side, the related practices in NATO nations are not harmonised and often only developed for specific applications. Methods to update the models for improved fidelity are mostly ad-hoc and lack a rational and methodical approach. Modern rotorcraft system identification (SID) and inverse simulation methods have been developed in recent years that provide new approaches well suited to pilot-in-the-loop fidelity assessment and systematic techniques for updating simulation models to achieve the needed level of fidelity. To coordinate efforts and improve the knowledge in this area, STO Applied Vehicle Technology Panel Research Task Group (STO AVT-296 RTG) was constituted to evaluate update methods used by member nations to find best practices and suitability for different applications including advanced rotorcraft configurations. This report presents the findings of the AVT-296 RTG. An overview of previous rotorcraft simulation fidelity Working Groups is presented, followed by a review of the metrics that have been used in previous studies to quantify the fidelity of a flight model or the overall perceptual fidelity of a simulator. The theoretical foundations of the seven different update methods and a description of the eight flight databases (Bell 412, UH-60, Iris+, EC135, CH-47, AW139, AW109, and X2, provided by the National Research Council of Canada, US Army, Airbus Helicopters, Boeing, Leonardo Helicopter Division, and Sikorsky) used by the RTG is presented. Both time- and frequency-domain fidelity assessment methods are considered, including those in current use by simulator qualification authorities and those used in the research community. Case studies are used to show the application, utility, and limitations of the update and assessment methods to the flight-test data. The work of the RTG has shown that time- and frequency-domain SID based metrics are suitable for use for assessing the model fidelity across a wide range of rotorcraft configurations. Gain and time delay update methods work well for well-developed flight dynamics models and can be used for flight control system design, but do not provide physical insights into the sources of errors in a model. Deriving stability and control derivatives from flight-test data and nonlinear simulation models using SID provides insight into the missing dynamics of the simulation model, which can subsequently be updated using additional forces and moments to significantly improve the fidelity of the model and can be used to update models for flight simulation training application methods. Reduced order model and physics-based correction methods provide large benefits when extrapolating to other flight conditions but does require detailed flight-test data. SID can quickly provide accurate point models, if detailed flight-test data is available, which can be "stitched" together to produce models suitable for real-time piloted simulation and control design applications. However, the dependency on flight-test data means that this method is not suitable for early aircraft development activities. This documentation of rotorcraft simulation fidelity assessment and model update strategies will benefit NATO nations by allowing for common, agreed-upon best practices and recommendations, ensuring each country's flight dynamics and simulation models are of the highest calibre possible. The collaboration between industry, academia, and government laboratories has been key to the success of this RTG; this cooperation model should be adopted in future research activities. As industries strive to achieve greater efficiency and safety in their products, the fidelity of simulation should match commercial aspirations to ensure that the "right first time" ethos is fully embedded into industrial best practices. Militaries will be able to use the methods and metrics presented to set criteria that will underpin the use of modelling and simulation in certification to accelerate development and acquisition and reduce the cost of new aircraft systems, e.g. advanced high-speed rotorcraft and legacy system upgrades. The criteria may also set standards for training devices used to support the expansion of synthetic environments for training to offset the high costs of flight hours. This RTG has identified that current flight training simulator standards could be updated to use the flight model and perceptual fidelity metrics presented in this report to ensure that models are not "over-tuned" and a more rigorous method of subjective simulator assessment is adopted