Organizing Science Society Collaborations: Coordination for Social Relevance and Scientific Excellence

Atlanta Conference on Science and Innovation Policy 2011In 2003 the Netherlands introduced 37 consortia to increase the social relevance of its science system. The consortia were given a double objective of scientific excellence and social relevance. The question is raised how consortia from different disciplines have dealt with this potential area of tension in their coordination strategy

How universities influence societal impact practices:Academics’ sense-making of organizational impact strategies

Societal impact of academic research has become a central concern of contemporary science policies. As key players in the higher education sector, universities play a crucial role in translating policy into organizational strategies, which then have the potential to shape academics' practices. This article investigates the influence that universities may have on academics' impact practices. We employ an analytical framework that combines a novel method for studying university impact strategies, sense-making theory, and insights from literature on impact. Our data consist of interviews with sixteen philosophers and anthropologists working across four universities in the Netherlands and the UK. We find that, in response to organizational goals and Human Resource Management policies, academics report changing their impact practices. We call for universities to use their influence responsibly in order to enable a broad range of impact practices

From ‘productive interactions’ to ‘enabling conditions’:The role of organizations in generating societal impact of academic research

Societal impact of academic research has been high on both policy and scientific agendas for several decades. Scholars increasingly focus on processes when analyzing societal impact, often inspired by the concept of 'productive interactions'. Building on this concept, we assert that processes do not take place in isolation. Rather, we suggest that productive interactions emerge in environments that offer conditions for these interactions to occur. This special section brings together three papers that focus on 'enabling conditions' that organizations provide to enable societal impact

Pre-Transplant Plasma Potassium as a Potential Risk Factor for the Need of Early Hyperkalaemia Treatment after Kidney Transplantation:A Cohort Study

INTRODUCTION: Plasma potassium (K+) abnormalities are common among patients with chronic kidney disease and are associated with higher rates of death, major adverse cardiac events, and hospitalization in this population. Currently, no guidelines exist on how to handle pre-transplant plasma K+ in renal transplant recipients (RTR). OBJECTIVE: The aim of this study is to examine the relation between pre-transplant plasma K+ and interventions to resolve hyperkalaemia within 48 h after kidney transplantation. METHODS: In a single-centre cohort study, we addressed the association between the last available plasma K+ level before transplantation and the post-transplant need for dialysis or use of K+-lowering medication to resolve hyperkalaemia within 48 h after renal transplantation using multivariate logistic regression analysis. RESULTS: 151 RTR were included, of whom 51 (33.8%) patients received one or more K+ interventions within 48 h after transplantation. Multivariate regression analysis revealed that a higher pre-transplant plasma K+ was associated with an increased risk of post-transplant intervention (odds ratio 2.2 [95% CI: 1.1-4.4]), independent of donor type (deceased or living) and use of K+-lowering medication within 24 h prior to transplantation). CONCLUSIONS: This study indicates that a higher pre-transplant plasma K+ is associated with a higher risk of interventions necessary to resolve hyperkalaemia within 48 h after renal transplantation. Further research is recommended to determine a cutoff level for pre-transplant plasma K+ that can be used in practice

The shapes of elongating gastruloids are consistent with convergent extension driven by a combination of active cell crawling and differential adhesion.

Gastruloids have emerged as highly useful in vitro models of mammalian gastrulation. One of the most striking features of 3D gastruloids is their elongation, which mimics the extension of the embryonic anterior-posterior axis. Although axis extension is crucial for development, the underlying mechanism has not been fully elucidated in mammalian species. Gastruloids provide an opportunity to study this morphogenic process in vitro. Here, we measure and quantify the shapes of elongating gastruloids and show, by Cellular Potts model simulations based on a novel, optimized algorithm, that convergent extension, driven by a combination of active cell crawling and differential adhesion can explain the observed shapes. We reveal that differential adhesion alone is insufficient and also directly observe hallmarks of convergent extension by time-lapse imaging of gastruloids. Finally, we show that gastruloid elongation can be abrogated by inhibition of the Rho kinase pathway, which is involved in convergent extension in vivo. All in all, our study demonstrates, how gastruloids can be used to elucidate morphogenic processes in embryonic development

Micro-costing diagnostics in oncology:from single-gene testing to whole- genome sequencing

Purpose: Predictive diagnostics play an increasingly important role in personalized medicine for cancer treatment. Whole-genome sequencing (WGS)-based treatment selection is expected to rapidly increase worldwide. This study aimed to calculate and compare the total cost of currently used diagnostic techniques and of WGS in treatment of non-small cell lung carcinoma (NSCLC), melanoma, colorectal cancer (CRC), and gastrointestinal stromal tumor (GIST) in the Netherlands. Methods: The activity-based costing (ABC) method was conducted to calculate total cost of included diagnostic techniques based on data provided by Dutch pathology laboratories and the Dutch-centralized cancer WGS facility. Costs were allocated to four categories: capital costs, maintenance costs, software costs, and operational costs. Results: The total cost per cancer patient per technique varied from € 58 (Sanger sequencing, three amplicons) to € 2925 (paired tumor-normal WGS). The operational costs accounted for the vast majority (over 90%) of the total per cancer patient technique costs. Conclusion: This study outlined in detail all costing aspects and cost prices of current and new diagnostic modalities used in treatment of NSCLC, melanoma, CRC, and GIST in the Netherlands. Detailed cost differences and value comparisons between these diagnostic techniques enable future economic evaluations to support decision-making

A self-organized model for cell-differentiation based on variations of molecular decay rates

Systemic properties of living cells are the result of molecular dynamics governed by so-called genetic regulatory networks (GRN). These networks capture all possible features of cells and are responsible for the immense levels of adaptation characteristic to living systems. At any point in time only small subsets of these networks are active. Any active subset of the GRN leads to the expression of particular sets of molecules (expression modes). The subsets of active networks change over time, leading to the observed complex dynamics of expression patterns. Understanding of this dynamics becomes increasingly important in systems biology and medicine. While the importance of transcription rates and catalytic interactions has been widely recognized in modeling genetic regulatory systems, the understanding of the role of degradation of biochemical agents (mRNA, protein) in regulatory dynamics remains limited. Recent experimental data suggests that there exists a functional relation between mRNA and protein decay rates and expression modes. In this paper we propose a model for the dynamics of successions of sequences of active subnetworks of the GRN. The model is able to reproduce key characteristics of molecular dynamics, including homeostasis, multi-stability, periodic dynamics, alternating activity, differentiability, and self-organized critical dynamics. Moreover the model allows to naturally understand the mechanism behind the relation between decay rates and expression modes. The model explains recent experimental observations that decay-rates (or turnovers) vary between differentiated tissue-classes at a general systemic level and highlights the role of intracellular decay rate control mechanisms in cell differentiation.Comment: 16 pages, 5 figure

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials

Search for Branons at LEP

We search, in the context of extra-dimension scenarios, for the possible existence of brane fluctuations, called branons. Events with a single photon or a single Z-boson and missing energy and momentum collected with the L3 detector in e^+ e^- collisions at centre-of-mass energies sqrt{s}=189-209$ GeV are analysed. No excess over the Standard Model expectations is found and a lower limit at 95% confidence level of 103 GeV is derived for the mass of branons, for a scenario with small brane tensions. Alternatively, under the assumption of a light branon, brane tensions below 180 GeV are excluded

Measurement of Exclusive rho^0 rho^0 Production in Two-Photon Collisions at High Q^2 at LEP

Exclusive rho rho production in two-photon collisions involving a single highly virtual photon is studied with data collected at LEP at centre-of-mass energies 89GeV < \sqrt{s} < 209GeV with a total integrated luminosity of 854.7pb^-1 The cross section of the process gamma gamma^* -> rho rho is determined as a function of the photon virtuality, Q^2 and the two-photon centre-of-mass energy, Wgg, in the kinematic region: 1.2GeV^2 < Q^2 < 30GeV^2 and 1.1GeV < Wgg < 3GeV