Taking on a wider view: public value interests of construction clients in a changing construction industry

For financial and strategic reasons, public and semi-public construction clients increasingly depend on private parties to carry out public service delivery. They subcontract operational responsibilities to private parties while remaining socio-politically responsible for ensuring public values. Public administration literature mainly addresses the importance of procedural and performance values in safeguarding public values. However, safeguarding the quality of the built environment also requires a focus on product values. In this study, we aim to increase the understanding of the meaning and significance of public values in the daily practice of public construction clients and identify the challenges they face in commissioning these seemingly opposing values. A set of semi-structured interviews with the public administrators of a variety of public and semi-public construction client organizations in the Netherlands shows that both internal and external factors influence the collaborative practices between clients and contractors. This causes a value shift from an emphasis on procedural values to managing performance and product values, indicating that clients need to take on a wider view on public values. Six main public value dilemmas were found that complicate the task of developing an open, transparent and sustainable long-term client–contractor relationship. The current contractual system, however, lacks the flexibility to facilitate this product-based value view in construction.     

The Role of the Lymphatic System in the Pathogenesis and Treatment of Inflammatory Bowel Disease

Although the number of therapeutic options for the treatment of inflammatory bowel disease (IBD) has increased in recent years, patients suffer from decreased quality of life due to non-response or loss of response to the currently available treatments. An increased understanding of the disease’s etiology could provide novel insights for treatment strategies in IBD. Lymphatic system components are generally linked to immune responses and presumably related to inflammatory diseases pathophysiology. This review aims to summarize findings on immune-mediated mechanisms in lymphoid tissues linked with IBD pathogenesis and (potential) novel treatments. Enhanced innate and adaptive immune responses were observed in mesenteric lymph nodes (MLNs) and other lymphoid structures, such as Peyer’s patches, in patients with IBD and in animal models. Furthermore, the phenomenon of lymphatic obstruction in the form of granulomas in MLNs and lymphatic vessels correlates with disease activity. There is also evidence that abnormalities in the lymphatic stromal components and lymph node microbiome are common in IBD and could be exploited therapeutically. Finally, novel agents targeting lymphocyte trafficking have been added to the treatment armamentarium in the field of IBD. Overall, gut-associated lymphoid tissue plays a key role in IBD immunopathogenesis, which could offer novel therapeutic targets.     

Bioinspired pressure actuated adhesive system

We developed a dry synthetic adhesive system inspired by gecko feet adhesion that can switch reversibly from adhesion to non-adhesion with applied pressure as external stimulus. Micropatterned polydimethylsiloxane (PDMS) surfaces with pillars of 30 μm length and 10 μm diameter were fabricated using photolithography and moulding. Adhesion properties were determined with a flat probe as a function of preload. For low and moderate applied compressive preloads, measured adhesion was 7.5 times greater than on flat controls whereas for high applied preloads adhesion dropped to very low values. In situ imaging shows that the increased preload caused the pillars to deform by bending and/or buckling and to lose their adhesive contact. The elasticity of PDMS aids the pillar recovery to the upright position upon removal of preload enabling repeatability of the switch.     

Creating trauma-informed systems: Child welfare, education, first responders, health care, juvenile justice.

Children and adolescents who are exposed to traumatic events are helped by numerous child-serving agencies, including health, mental health, education, child welfare, first responder, and criminal justice systems to assist them in their recovery. Service providers need to incorporate a trauma-informed perspective in their practices to enhance the quality of care for these children. This includes making sure that children and adolescents are screened for trauma exposure; that service providers use evidence-informed practices; that resources on trauma are available to providers, survivors, and their families; and that there is a continuity of care across service systems. This article reviews how traumatic stress impacts children and adolescents' daily functioning and how various service systems approach trauma services differently. It also provides recommendations for how to make each of these service systems more trauma informed and an appendix detailing resources in the National Child Traumatic Stress Network that have been produced to meet this objective. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Improvement of Aglycone π-Stacking Yields Nanomolar to Sub-nanomolar FimH Antagonists

Antimicrobial resistance has become a serious concern for the treatment of urinary tract infections. In this context, an anti-adhesive approach targeting FimH, a bacterial lectin enabling the attachment of E. coli to host cells, has attracted considerable interest. FimH can adopt a low/medium-affinity state in the absence and a high-affinity state in the presence of shear forces. Until recently, mostly the high-affinity state has been investigated, despite the fact that a therapeutic antagonist should bind predominantly to the low-affinity state. In this communication, we demonstrate that fluorination of biphenyl α-d -mannosides leads to compounds with perfect π–π stacking interactions with the tyrosine gate of FimH, yielding low nanomolar to sub-nanomolar K_D values for the low- and high-affinity states, respectively. The face-to-face alignment of the perfluorinated biphenyl group of FimH ligands and Tyr48 was confirmed by crystal structures as well as ¹H,¹⁵N-HSQC NMR analysis. Finally, fluorination improves pharmacokinetic parameters predictive for oral availability.     

What governs the transition to a sustainable hydrogen economy? Articulating the relationship between technologies and political institutions

There is a lack of integrated knowledge on the transition to a sustainable energy system. The paper focuses on the relationship between technologies and institutions in the field of hydrogen from the perspective of political theory. The paper unfolds four paradigms of governance: ‘Governance by policy networking’, Governance by government’, ‘Governance by corporate business’, and ‘Governance by challenge’, and looks into the major line of argument in support of these paradigms and into their possible bias with respect to hydrogen options. Each of these paradigms reveals an institutional bias in that it articulates specific opportunities for collaboration and competition in order to stimulate the transition to a sustainable hydrogen economy. The paper makes the observation that there is a compelling need to reframe fashionable discourse such as the necessary shift from government to governance or from government to market. Instead, specific questions with respect to the impact of guiding policy frameworks on innovation will highlight that neither ‘neutral’ nor ‘optimal’ frameworks for policy making exist, where competing hydrogen options are at stake. The identification of paradigms of governance maybe considered a methodological device for (participator) policy analysis.     

Cloning and Functional Characterization of Dog OCT1 and OCT2: Another Step in Exploring Species Differences in Organic Cation Transporters

OCT1 and OCT2 are polyspecific membrane transporters that are involved in hepatic and renal drug clearance in humans and mice. In this study, we cloned dog OCT1 and OCT2 and compared their function to the human and mouse orthologs. We used liver and kidney RNA to clone dog OCT1 and OCT2. The cloned and the publicly available RNA-Seq sequences differed from the annotated exon-intron structure of OCT1 in the dog genome CanFam3.1. An additional exon between exons 2 and 3 was identified and confirmed by sequencing in six additional dog breeds. Next, dog OCT1 and OCT2 were stably overexpressed in HEK293 cells and the transport kinetics of five drugs were analyzed. We observed strong differences in the transport kinetics between dog and human orthologs. Dog OCT1 transported fenoterol with 12.9-fold higher capacity but 14.3-fold lower affinity (higher K_M) than human OCT1. Human OCT1 transported ipratropium with 5.2-fold higher capacity but 8.4-fold lower affinity than dog OCT1. Compared to human OCT2, dog OCT2 showed 10-fold lower transport of fenoterol and butylscopolamine. In conclusion, the functional characterization of dog OCT1 and OCT2 reported here may have implications when using dogs as pre-clinical models as well as for drug therapy in dogs.     

Evaluation of registration methods on thoracic CT: the EMPIRE10 challenge

EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of intrapatient thoracic CT image pairs. Evaluation of nonrigid registration techniques is a nontrivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the configuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (http://empire10.isi.uu.nl). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This paper details the organization of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.