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 Novel Object and Unusual Name (NOUN) database: a collection of novel images for use in experimental research

Many experimental research designs require images of novel objects. Here we introduce the Novel Object and Unusual Name (NOUN) Database. This database contains 64 primary novel object images and additional novel exemplars for ten basic- and nine global-level object categories. The objects’ novelty was confirmed by both self-report and a lack of consensus on questions that required participants to name and identify the objects. We also found that object novelty correlated with qualifying naming responses pertaining to the objects’ colors. Results from a similarity sorting task (and subsequent multidimensional scaling analysis on the similarity ratings) demonstrated that the objects are complex and distinct entities that vary along several featural dimensions beyond simply shape and color. A final experiment confirmed that additional item exemplars comprise both sub- and superordinate categories. These images may be useful in a variety of settings, particularly for developmental psychology and other research in language, categorization, perception, visual memory and related domains

The functional architecture of mother-infant communication, and the development of infant social expressiveness in the first two months

By two-three months, infants show active social expressions during face-to-face interactions. These interactions are important, as they provide the foundation for later emotional regulation and cognition, but little is known about how infant social expressiveness develops. We considered two different accounts. One emphasizes the contingency of parental responsiveness, regardless of its form; the other, the functional architecture account, emphasizes the preparedness of both infants and parents to respond in specific ways to particular forms of behaviour in their partner. We videotaped mother-infant interactions from one to nine weeks, and analysed them with a micro-analytic coding scheme. Infant social expressiveness increased through the nine-week period, particularly after 3 weeks. This development was unrelated to the extent of maternal contingent responsiveness, even to infant social expressions. By contrast, specific forms of response that mothers used preferentially for infant social expressions - mirroring, marking with a smile- predicted the increase in these infant behaviours over time. These results support a functional architecture account of the perceptual and behavioural predispositions of infants and parents that allows young infants to capitalize on relatively limited exposure to specific parental behaviours, in order to develop important social capacities

Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis

Background: Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest. Decidua-derived MSCs (DMSCs) are a cell population obtained from human placental extraembryonic membranes able to differentiate into the three germ layers. This study explores the therapeutic potential of DMSCs. Methods: We used the experimental autoimmune encephalomyelitis (EAE) animal model to evaluate the effect of DMSCs on clinical signs of the disease and on the presence of inflammatory infiltrates in the central nervous system. We also compared the inflammatory profile of spleen T cells from DMSC-treated mice with that of EAE control animals, and the influence of DMSCs on the in vitro definition of the Th17 phenotype. Furthermore, we analyzed the effects on the presence of some critical cell types in central nervous system infiltrates. Results: Preventive intraperitoneal injection of DMSCs resulted in a significant delay of external signs of EAE. In addition, treatment of animals already presenting with moderate symptoms resulted in mild EAE with reduced disease scores. Besides decreased inflammatory infiltration, diminished percentages of CD4+IL17+, CD11b+Ly6G+ and CD11b+Ly6C+ cells were found in infiltrates of treated animals. Early immune response was mitigated, with spleen cells of DMSC-treated mice displaying low proliferative response to antigen, decreased production of interleukin (IL)-17, and increased production of the anti-inflammatory cytokines IL-4 and IL-10. Moreover, lower RORγT and higher GATA-3 expression levels were detected in DMSC-treated mice. DMSCs also showed a detrimental influence on the in vitro definition of the Th17 phenotype. Conclusions: DMSCs modulated the clinical course of EAE, modified the frequency and cell composition of the central nervous system infiltrates during the disease, and mediated an impairment of Th17 phenotype establishment in favor of the Th2 subtype. These results suggest that DMSCs might provide a new cell-based therapy for the control of multiple sclerosis.This work was sponsored by grants from Acción Estratégica en Salud (PI13/00297 and PI11/00581), the Neurosciences and Aging Foundation, the Francisco Soria Melguizo Foundation, Octopharma, and Parkinson Madrid (PI2012/0032).S

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

This is the final version of the article. Available from the publisher via the DOI in this record.Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Thrombospondins in the heart: potential functions in cardiac remodeling

Cardiac remodeling after myocardial injury involves inflammation, angiogenesis, left ventricular hypertrophy and matrix remodeling. Thrombospondins (TSPs) belong to the group of matricellular proteins, which are non-structural extracellular matrix proteins that modulate cell–matrix interactions and cell function in injured tissues or tumors. They interact with different matrix and membrane-bound proteins due to their diverse functional domains. That the expression of TSPs strongly increases during cardiac stress or injury indicates an important role for them during cardiac remodeling. Recently, the protective properties of TSP expression against heart failure have been acknowledged. The current review will focus on the biological role of TSPs in the ischemic and hypertensive heart, and will describe the functional consequences of TSP polymorphisms in cardiac disease