Evaluating megaprojects: from the “iron triangle” to network mapping

Evaluation literature has paid relatively little attention to the specific needs of evaluating large, complex industrial and infrastructure projects, often called ‘megaprojects’. The abundant megaproject governance literature, in turn, has largely focused on the so-called ‘megaproject pathologies’, i.e. the chronic budget overruns, and failure of such projects to keep to timetables and deliver the expected social and economic benefits. This article draws on these two strands of literature, identifies shortcomings, and suggests potential pathways towards an improved evaluation of megaprojects. To counterbalance the current overemphasis on relatively narrowly defined accountability as the main function of megaproject evaluation, and the narrow definition of project success in megaproject evaluation, the article argues that conceptualizing megaprojects as dynamic and evolving networks would provide a useful basis for the design of an evaluation approach better able to promote learning and to address the socio economic aspects of megaprojects. A modified version of ‘network mapping’ is suggested as a possible framework for megaproject evaluation, with the exploration of the multiple accountability relationships as a central evaluation task, designed to reconcile learning and accountability as the central evaluation functions. The article highlights the role of evaluation as an ‘emergent’ property of spontaneous megaproject ‘governing’, and explores the challenges that this poses to the role of the evaluator

The predictive role of biomarkers and genetics in childhood asthma exacerbations

Asthma exacerbations are associated with significant childhood morbidity and mortality. Recurrent asthma attacks contribute to progressive loss of lung function and can sometimes be fatal or near‐fatal, even in mild asthma. Exacerbation prevention becomes a primary target in the management of all asthmatic patients. Our work reviews current advances on exacerbation predictive factors, focusing on the role of non‐invasive biomarkers and genetics in order to identify subjects at higher risk of asthma attacks. Easy‐to‐perform tests are necessary in children; therefore, interest has increased on samples like exhaled breath condensate, urine and saliva. The variability of biomarker levels suggests the use of seriate measurements and composite markers. Genetic predisposition to childhood asthma onset has been largely investigated. Recent studies highlighted the influence of single nucleotide polymorphisms even on exacerbation susceptibility, through involvement of both intrinsic mechanisms and gene‐environment interaction. The role of molecular and genetic aspects in exacerbation prediction supports an individual‐shaped approach, in which follow‐up planning and therapy optimization take into account not only the severity degree, but also the risk of recurrent exacerbations. Further efforts should be made to improve and validate the application of biomarkers and genomics in clinical settings

Acute kidney injury (Aki) before and after kidney transplantation: Causes, medical approach, and implications for the long-term outcomes

Acute kidney injury (AKI) is a common finding in kidney donors and recipients. AKI in kidney donor, which increases the risk of delayed graft function (DGF), may not by itself jeopardize the short-and long-term outcome of transplantation. However, some forms of AKI may induce graft rejection, fibrosis, and eventually graft dysfunction. Therefore, various strategies have been proposed to identify conditions at highest risk of AKI-induced DGF, that can be treated by targeting the donor, the recipient, or even the graft itself with the use of perfusion machines. AKI that occurs early post-transplant after a period of initial recovery of graft function may reflect serious and often occult systemic complications that may require prompt intervention to prevent graft loss. AKI that develops long after transplantation is often related to nephrotoxic drug reactions. In symptomatic patients, AKI is usually associated with various systemic medical complications and could represent a risk of mortality. Electronic systems have been developed to alert transplant physicians that AKI has occurred in a transplant recipient during long-term outpatient follow-up. Herein, we will review most recent understandings of pathophysiology, diagnosis, therapeutic approach, and short-and long-term consequences of AKI occurring in both the donor and in the kidney transplant recipient

On de-bunking “Fake News” in the post-truth era : how to reduce statistical error in research

The authors note with alarm that statistical noise caused by statistical incompetence is beginning to creep into research on cost overrun in public investment projects, contaminating research with work that does not meet basic standards of validity and reliability. The paper gives examples of such work and proposes three heuristics to root out the problem. First, researchers who are not statisticians, or do not have a strong background in statistics, should abstain from doing statistical analysis, and instead rely on more experienced colleagues, preferably professional statisticians. Second, journal referees should clearly state their level of statistical proficiency to journal editors, so these can set the right referee team. Finally, journal editors should make sure that at least one referee is capable of reviewing the statistical and methodological aspects of a paper. The work under review would have benefitted from observing these simple heuristics, as would any work based on statistical analysis.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Transport and Logistic

autologous pancreatic islet transplantation in human bone marrow diabetes 2013 62 3523 3531

In the article listed above, there is an error in Fig. 3. In panel B , the immunohistochemical staining of insulin ( top middle panel

NetPyNE, a tool for data-driven multiscale modeling of brain circuits.

Biophysical modeling of neuronal networks helps to integrate and interpret rapidly growing and disparate experimental datasets at multiple scales. The NetPyNE tool (www.netpyne.org) provides both programmatic and graphical interfaces to develop data-driven multiscale network models in NEURON. NetPyNE clearly separates model parameters from implementation code. Users provide specifications at a high level via a standardized declarative language, for example connectivity rules, to create millions of cell-to-cell connections. NetPyNE then enables users to generate the NEURON network, run efficiently parallelized simulations, optimize and explore network parameters through automated batch runs, and use built-in functions for visualization and analysis - connectivity matrices, voltage traces, spike raster plots, local field potentials, and information theoretic measures. NetPyNE also facilitates model sharing by exporting and importing standardized formats (NeuroML and SONATA). NetPyNE is already being used to teach computational neuroscience students and by modelers to investigate brain regions and phenomena

Određivanje umjetnih sladila u osvježavajućim bezalkoholnim pićima i posebnim prehrambenim proizvodima metodom tekućinske kromatografije visoke djelotvornosti

This paper presents two high performance liquid chromatographic (HPLC) methods used for the separation and determination of artificial sweeteners aspartame, acesulphame K, sodium saccharin, and sodium cyclamate in beverages and special nutritional products (special food intended for specific population groups). All four compounds are soluble in aqueous solutions and can easily be separated and determined by HPLC with a diode array detector (DAD). The first method involved separation of aspartame, acesulphame K, and sodium saccharin on a C18 column with an isocratic elution of phosphate buffer and acetonitrile as mobile phase. The second method was used to separate sodium cyclamate on a C18 column with methanol and water as mobile phase. Under optimum conditions, both methods showed good analytical performance, such as linearity, precision, and recovery. The methods were successfully applied for the analysis of real samples of soft drinks and special nutritional products.Ovaj rad predstavlja dvije metode za separaciju i određivanje umjetnih sladila aspartama, acesulfama K, natrijeva saharina i natrijeva ciklamata u osvježavajućim bezalkoholnim pićima i posebnim prehrambenim proizvodima tehnikom tekućinske kromatografi je visoke djelotvornosti (HPLC). Sva četiri analita topljiva su u vodenim otopinama i lako se mogu razdvojiti i odrediti tekućinskom kromatografi jom uz primjenu detektora s nizom dioda (DAD). Prva je metoda kromatografsko razdvajanje aspartama, acesulfama K i natrij saharina na C18 koloni izokratnim ispiranjem fosfatnog pufera i acetonitrila kao mobilne faze. Druga metoda omogućava određivanje natrijeva ciklamata na C18 koloni sa metanolom i vodom kao mobilnom fazom. Pod najpovoljnijim eksperimentalnim uvjetima obadvije metode pokazale su dobre analitičke karakteristike, kao što su linearnost, preciznost i analitički povrat. Navedene su metode primijenjene za analize realnih uzoraka osvježavajućih bezalkoholnih pića i hrane za posebne prehrambene potrebe

Distinct phosphorylation requirements regulate cortactin activation by TirEPEC and its binding to N-WASP

<p>Abstract</p> <p>Background</p> <p>Cortactin activates the actin-related 2/3 (Arp2/3) complex promoting actin polymerization to remodel cell architecture in multiple processes (e.g. cell migration, membrane trafficking, invadopodia formation etc.). Moreover, it was called the Achilles' heel of the actin cytoskeleton because many pathogens hijack signals that converge on this oncogenic scaffolding protein. Cortactin is able to modulate N-WASP activation <it>in vitro </it>in a phosphorylation-dependent fashion. Thus Erk-phosphorylated cortactin is efficient in activating N-WASP through its SH3 domain, while Src-phosphorylated cortactin is not. This could represent a switch on/off mechanism controlling the coordinated action of both nucleator promoting factors (NPFs). Pedestal formation by enteropathogenic <it>Escherichia coli </it>(EPEC) requires N-WASP activation. N-WASP is recruited by the cell adapter Nck which binds a major tyrosine-phosphorylated site of a bacterial injected effector, Tir (translocated intimin receptor). Tir-Nck-N-WASP axis defines the current major pathway to actin polymerization on pedestals. In addition, it was recently reported that EPEC induces tyrosine phosphorylation of cortactin.</p> <p>Results</p> <p>Here we demonstrate that cortactin phosphorylation is absent on N-WASP deficient cells, but is recovered by re-expression of N-WASP. We used purified recombinant cortactin and Tir proteins to demonstrate a direct interaction of both that promoted Arp2/3 complex-mediated actin polymerization <it>in vitro</it>, independently of cortactin phosphorylation.</p> <p>Conclusion</p> <p>We propose that cortactin binds Tir through its N-terminal part in a tyrosine and serine phosphorylation independent manner while SH3 domain binding and activation of N-WASP is regulated by tyrosine and serine mediated phosphorylation of cortactin. Therefore cortactin could act on Tir-Nck-N-WASP pathway and control a possible cycling activity of N-WASP underlying pedestal formation.</p

OpenWorm: an open-science approach to modeling Caenorhabditis elegans.

OpenWorm is an international collaboration with the aim of understanding how the behavior of Caenorhabditis elegans (C. elegans) emerges from its underlying physiological processes. The project has developed a modular simulation engine to create computational models of the worm. The modularity of the engine makes it possible to easily modify the model, incorporate new experimental data and test hypotheses. The modeling framework incorporates both biophysical neuronal simulations and a novel fluid-dynamics-based soft-tissue simulation for physical environment-body interactions. The project's open-science approach is aimed at overcoming the difficulties of integrative modeling within a traditional academic environment. In this article the rationale is presented for creating the OpenWorm collaboration, the tools and resources developed thus far are outlined and the unique challenges associated with the project are discussed