Towards harmonisation of indirect effects in transport project appraisal Guidelines and current practice in Europe - miles apart

The paper deals with the appropriate treatment of indirect socio-economic effects of transport investments and policies. A central question is how assessment of indirect effects can be improved and harmonised in a European context. First, the paper describes state of the art in assessment (identifying types of indirect socio-economic effects, modelling). Secondly, an overview is presented on current practice in EU-countries. Market imperfections and cross-border effects appear as key conditions for the existence of indirect effects. The proposed starting point for analysis is therefore the total absence of market disturbances. This point of reference, however, is used in no country. The paper concludes by stressing the importance of harmonisation of transport initiative assessment, as well as elaboration on the distinction of types of effects as well as market imperfections. A very clear advantage of harmonisation in Europe would be the inclusion of cross-border effects as direct socio-economic effects in CBA where they concern national borders and not EU-borders, instead of viewing them as welfare effects ‘leaking away’ to other member countries. Especially the market imperfections characterising land markets (external effects, replacement value) and the disturbances and rigidities specific for European labour markets offer great perspectives for better analysis of transport projects and hence better decision making.

Towards Automated Benchmarking of Atomistic Forcefields: Neat Liquid Densities and Static Dielectric Constants from the ThermoML Data Archive

Atomistic molecular simulations are a powerful way to make quantitative predictions, but the accuracy of these predictions depends entirely on the quality of the forcefield employed. While experimental measurements of fundamental physical properties offer a straightforward approach for evaluating forcefield quality, the bulk of this information has been tied up in formats that are not machine-readable. Compiling benchmark datasets of physical properties from non-machine-readable sources require substantial human effort and is prone to accumulation of human errors, hindering the development of reproducible benchmarks of forcefield accuracy. Here, we examine the feasibility of benchmarking atomistic forcefields against the NIST ThermoML data archive of physicochemical measurements, which aggregates thousands of experimental measurements in a portable, machine-readable, self-annotating format. As a proof of concept, we present a detailed benchmark of the generalized Amber small molecule forcefield (GAFF) using the AM1-BCC charge model against measurements (specifically bulk liquid densities and static dielectric constants at ambient pressure) automatically extracted from the archive, and discuss the extent of available data. The results of this benchmark highlight a general problem with fixed-charge forcefields in the representation low dielectric environments such as those seen in binding cavities or biological membranes

Een algemene normtheorie toegepast op open normen in het belastingrecht

The objective of this research was to establish a theoretical method with which legal norms could be distinguished by their content. Extensive research led to the development of a general norm theory based on norm definitions that allowed for the formulation of a coherent set of legal norms, thus distinguishing between different norms. Consequently, this set is constitutive for the construction of an executable legal system which is demonstrated by applying the theory on the Dutch tax system. The general formula of a norm is given by ∀ε∈E 'imperatief^'φ, in which φ represents in algorithmic form the most recent content. This symbolic form represents all the properties of a norm and may include existing norm theories. Furthermore, it is demonstrated that every legal text can be transformed into this algorithmic form. Grenzen van fiscale soevereinitei

Maintenance spare parts planning and control : a framework for control and agenda for future research

This paper presents a framework for planning and control of the spare parts supply chain in organizations that use and maintain high-value capital assets. Decisions in the framework are decomposed hierarchically and interfaces are described. We provide relevant literature to aid decision making and identify open research topics. The framework can be used to increase the e??ciency, consistency and sustainability of decisions on how to plan and control a spare parts supply chain. Applicability of the framework in di??erent environments is investigated

To Improve Your Surgical Drilling Skills, Make Use of Your Index Fingers

BACKGROUND: Surgery has greatly benefited from various technologic advancements over the past decades. Surgery remains, however, mostly manual labor performed by well-trained surgeons. Little research has focused on improving osseous drilling techniques. The objective of this study was to compare the accuracy and precision of different orthopaedic drilling techniques involving the use of both index fingers. QUESTIONS/PURPOSES: (1) Does the shooting grip technique and aiming at the contralateral index finger improve accuracy and precision in drilling? (2) Is the effect of drilling technique on accuracy and precision affected by the experience level of the performer? METHODS: This study included 36 participants from two Dutch training hospitals who were subdivided into three groups (N = 12 per group) based on their surgical experience (that is, no experience, residents, and surgeons). The participants had no further experience with drilling outside the hospital nor were there other potential confounding variables that could influence the test outcomes. Participants were instructed to drill toward a target exit point on a synthetic bone model. There were four conditions: (1) clenched grip without aiming; (2) shooting grip without aiming; (3) clenched grip with aiming at the contralateral index finger; and (4) shooting grip aiming at the contralateral index finger. Participants were only used to a clenched grip without aiming in clinical practice. Each participant had to drill five times per technique per test, and the test was repeated after 4 weeks. Accuracy was defined as the systematic error of all measurements and was calculated as the mean of the five distances between the five exit points and the target exit point, whereas precision was defined as the random error of all measurements and calculated as the SD of those five distances. Accuracy and precision were analyzed using mixed-design analyses of variance. RESULTS: Accuracy was highest when using a clenched grip with aiming at the index finger (mean 4.0 mm, SD 1.1) compared with a clenched grip without aiming (mean 5.0 mm, SD 1.2, p = 0.004) and a shooting grip without aiming (mean 4.9 mm, SD 1.4, p = 0.015). The shooting grip with aiming at the index finger (mean 4.1 mm, SD 1.2) was also more accurate than a clenched grip without aiming (p = 0.006) and a shooting grip without aiming (p = 0.014). Shooting grip with aiming at the opposite index finger (median 2.0 mm, interquartile range [IQR] 1.2) showed the best precision and outperformed a clenched grip without aiming (median 2.9 mm, IQR 1.1, p = 0.016), but was not different than the shooting grip without aiming (median 2.2 mm, IQR 1.4) or the clenched grip with aiming (median 2.4 mm, IQR 1.3). The accuracy of surgeons (mean 4.1 mm, SD 1.1) was higher than the inexperienced group (mean 5.0 mm, SD 1.1, p = 0.012). The same applied for precision (median 2.2 mm, IQR 1.0 versus median 2.8 mm, IQR 1.4, p = 0.008). CONCLUSIONS: A shooting grip combined with aiming toward the index finger of the opposite hand had better accuracy and precision compared with a clenched grip alone. Based on this study, experience does matter, because the orthopaedic surgeons outperformed the less experienced participants. Based on our study, we advise surgeons to aim at the index finger of the opposite hand when possible and to align the ipsilateral index finger to the drill bit. LEVEL OF EVIDENCE: Level II, therapeutic study

Systeemgericht spare parts management bij de Nederlandse Koninklijke Marine

In dit artikel worden methoden ontwikkeld voor een doelgericht beheer van ‘spare parts’ bij de Nederlandse Koninklijke Marine. Daarbij gaat het in het bijzonder om reservedelen, ‘subassemblies’ en ‘assemblies’ die in geval van storing in een technisch systeem snel het defecte onderdeel of artikel kunnen vervangen. Door deze ‘repair by replacement’-strategie wordt getracht de operationele beschikbaarheid van de technische systemen zo hoog mogelijk te houden. Een cruciale vraag betreft de hoeveelheid componenten, subassemblies of assemblies die hetzij op locatie hetzij in een centraal depot in voorraad moeten worden gehouden, rekening houdend met een beperkt investeringsbudget. Dit is het vraagstuk van de initiële bevoorrading. Echter, omdat een deel van de artikelen verbruiksartikelen zijn of omdat soms onherstelbare schade aan onderdelen is ontstaan, is jaarlijks ook een budget nodig voor inkoop van nieuwe onderdelen of artikelen. Ook rond deze zogeheten exploitatiebevoorrading doen zich vragen voor met betrekking tot de optimale aanwending van een per jaar beperkt, en niet overdraagbaar, budget. Voor beide vraagstukken worden methoden ontwikkeld en getest op real life systemen bij de marine. De resultaten zijn uitermate bevredigend, in die zin dat een belangrijk hogere beschikbaarheid van systemen wordt gerealiseerd, met gelijktijdig een significante verlaging van het in voorraad geïnvesteerd vermogen

eTOX ALLIES:an automated pipeLine for linear interaction energy-based simulations

Abstract Background Computational methods to predict binding affinities of small ligands toward relevant biological (off-)targets are helpful in prioritizing the screening and synthesis of new drug candidates, thereby speeding up the drug discovery process. However, use of ligand-based approaches can lead to erroneous predictions when structural and dynamic features of the target substantially affect ligand binding. Free energy methods for affinity computation can include steric and electrostatic protein–ligand interactions, solvent effects, and thermal fluctuations, but often they are computationally demanding and require a high level of supervision. As a result their application is typically limited to the screening of small sets of compounds by experts in molecular modeling. Results We have developed eTOX ALLIES, an open source framework that allows the automated prediction of ligand-binding free energies requiring the ligand structure as only input. eTOX ALLIES is based on the linear interaction energy approach, an efficient end-point free energy method derived from Free Energy Perturbation theory. Upon submission of a ligand or dataset of compounds, the tool performs the multiple steps required for binding free-energy prediction (docking, ligand topology creation, molecular dynamics simulations, data analysis), making use of external open source software where necessary. Moreover, functionalities are also available to enable and assist the creation and calibration of new models. In addition, a web graphical user interface has been developed to allow use of free-energy based models to users that are not an expert in molecular modeling. Conclusions Because of the user-friendliness, efficiency and free-software licensing, eTOX ALLIES represents a novel extension of the toolbox for computational chemists, pharmaceutical scientists and toxicologists, who are interested in fast affinity predictions of small molecules toward biological (off-)targets for which protein flexibility, solvent and binding site interactions directly affect the strength of ligand-protein binding

Early changes in the extracellular matrix of the degenerating intervertebral disc, assessed by Fourier transform infrared imaging.

Mechanical overloading induces a degenerative cell response in the intervertebral disc. However, early changes in the extracellular matrix (ECM) are challenging to assess with conventional techniques. Fourier Transform Infrared (FTIR) imaging allows visualization and quantification of the ECM. We aim to identify markers for disc degeneration and apply these to investigate early degenerative changes due to overloading and katabolic cell activity. Three experiments were conducted; Exp 1.: In vivo, lumbar spines of seven goats were operated: one disc was injected with chondroitinase ABC (mild degeneration) and compared to the adjacent disc (control) after 24 weeks. Exp 2a: Ex vivo, caprine discs received physiological loading (n=10) or overloading (n=10) in a bioreactor. Exp 2b: Cell activity was diminished prior to testing by freeze-thaw cycles, 18 discs were then tested as in Exp 2a. In all experiments, FTIR images (spectral region: 1000-1300 cm ) of mid-sagittal slices were analyzed using multivariate curve resolution. In vivo, FTIR was more sensitive than biochemical and histological analysis in identifying reduced proteoglycan content (p=0.046) and increased collagen content in degenerated discs (p<0.01). Notably, FTIR analysis additionally showed disorganization of the ECM, indicated by increased collagen entropy (p=0.011). Ex vivo, the proteoglycan/collagen ratio decreased due to overloading (p=0.047) and collagen entropy increased (p=0.047). Cell activity affected collagen content only (p=0.044). FTIR imaging allows a more detailed investigation of early disc degeneration than traditional measures. Changes due to mild overloading could be assessed and quantified. Matrix remodeling is the first detectable step towards intervertebral disc degeneration. [Abstract copyright: Copyright © 2018. Published by Elsevier Ltd.