The governance of physical and social connections

It is by no means a new idea that the world we live in is an interconnected one. Centuries before Castells’ seminal trilogy ‘The Information Age’, various European philosophers adopted a systemic view in order to explain certain physical and social phenomena. The 1950s were the heyday of total systems thinking: the idea that everything is connected to everything. This led to the assumption that planning and policy making should cov

High practice variation in risk stratification, baseline oncological staging, and follow-up strategies for T1 colorectal cancers in the Netherlands

Background and study aims Based on pathology, locally resected T1 colorectal cancer (T1-CRC) can be classified as having low- or high-risk for irradicality and/or lymph node metastasis, the latter requiring adjuvant surgery. Reporting and application of pathological high-risk criteria is likely variable, with inherited variation regarding baseline oncological staging, treatment and surveillance. Methods We assessed practice variation using an online survey among gastroenterologists and surgeons participating in the Dutch T1-CRC Working Group. Results Of the 130 invited physicians, 53 % participated. Regardi

Proadrenomedullin NH(2)-terminal 20 peptide (PAMP) and adrenomedullin bind to teratocarcinoma cells.

Proadrenomedullin NH(2-)terminal 20 peptide (PAMP) and adrenomedullin (ADM) bind to teratocarcinoma cells. The effects of PAMP and ADM on teratocarcinoma cells were investigated. (125)I-PAMP bound to PA1 cells with moderate affinity (K(d) = 110 nM) to a single class of sites (B(max) = 110 000/cell). Specific (125)I-PAMP binding was inhibited by PAMP (IC(50) of 100 nM) but not ADM, calcitonin gene-related peptide (CGRP), or amylin. Specific (125)I-ADM binding was inhibited with high affinity by ADM, CGRP, and CGRP(8-37) (IC(50) values of 10, 10, and 15 nM respectively) but not PAMP or amylin. ADM elevated cAMP (ED(50) value of 100 nM), whereas PAMP had no effect on basal cAMP but inhibited the increase in cAMP caused by 10 nM ADM. Also, the increase in cAMP caused by ADM was inhibited CGRP(8-37), suggesting that ADM is binding to CGRP receptors. ADM (100 nM) stimulated transiently c-fos mRNA, whereas PAMP (1000 nM) had little effect; however, PAMP inhibited the increase in c-fos mRNA caused by ADM. ADM stimulated [(3)H]thymidine uptake into PA1 cells, whereas PAMP inhibited the increase in thymidine uptake caused by ADM. These results indicate that ADM and PAMP are both biologically active in teratocarcinoma cells

Level of motion sickness based on heart rate variability when reading inside a fully automated vehicle

This study investigates the level of experienced motion sickness when performing reading while being driven in fully automated driving under three different conditions. One condition was without any intervention while the other two conditions were with the visual (VPIS) and haptic (HPIS) peripheral information system. Both systems provided the upcoming navigational information in the lateral direction three seconds before the turning/cornering was done. It was hypothesized that with the peripheral information systems, the experienced motion sickness would be reduced compared to the condition where a peripheral information system was not present. Eighteen participants with severe motion sickness susceptibility were carefully chosen to undergo the conditions using an instrumented vehicle with the Wizard-of-Oz approach. The participants were required to read from a tablet during the whole 15-minutes of automated driving. Results from the heart rate variability (beats per minute, root means square of successive differences, and high-frequency component) indicated no statistically significant changes (p &lt; 0.05) in motion sickness found with the presence of HPIS and VPIS when performing reading when being driven in automated mode. However, results from this study were mixed and inconclusive, but overall findings indicated mild motion sickness was found in both VPIS and HPIS conditions.</p

Adrenomedullin in mammalian embryogenesis

Here are summarized data supporting that adrenomedullin (AM) is a multifunctional factor involved in the complex regulatory mechanisms of mammalian development. During rodent embryogenesis, AM is first expressed in the heart, followed by a broader but also defined spatio-temporal pattern of expression in vascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs. AM pattern of expression is suggestive of its involvement in the control of embryonic invasion, proliferation, and differentiation processes, probably through autocrine or paracrine modes of action. AM levels in fetoplacental tissues, uterus, maternal and umbilical plasma are highly increased during normal gestation. These findings in addition to other physiological and gene targeting studies support the importance of AM as a vasorelaxant factor implicated in the regulation of maternal vascular adaptation to pregnancy, as well as of fetal and fetoplacental circulations. AM is also present in amniotic fluid and milk, which is suggestive of additional functions in the maturation and immunological protection of the fetus. Altered expression of AM has been found in some gestational pathologies, although it is not yet clear whether this corresponds to causative or compensatory mechanisms. Future studies in regard to the distribution and expression levels of the molecules known to function as AM receptors, together with data on the action of complement factor H (an AM binding protein), may help to better define the roles of AM during embryonic development

Optimizing the total energy consumption and CO₂ emissions by distributing computational workload among worldwide dispersed data centers

Major internet service providers have built and are currently building the world's largest data centres (DCs), which has already resulted in significant global energy consumption. Energy saving measures, from chip to building level, have been introduced gradually in recent decades. However, there is further potential for savings by assessing the performance of different DCs on a wider scale and evaluating information technology (IT) workload distribution strategies among these DCs. This paper proposes a methodology to optimize the electricity consumption and CO2 emissions by distributing IT workload across multiple imaginary DCs. The DCs are modelled and controlled in a virtual test environment based on a building energy simulation (BES) tool (TRNSYS). A controller tool (Matlab) is used to support testing and tuning of the optimization algorithm. A case study, consisting of the distribution of IT workload across four different types of data centers in multiple locations with different climate conditions, is presented. The case study will illustrate.</p

Evolution of Non-Equilibrium Profile in Adsorbate Layer under Compressive Strain

We investigate the time evolution of an initial step profile separating a bare substrate region from the rest of the compressively strained adsorbate layer near a commensurate to incommensurate transition. The rate of profile evolution as a function of the mismatch, coverage and the strength of the substrate potential are determined by Brownian molecular dynamics simulations. We find that the results are qualitatively similar to those observed for the Pb/Si(111) system. The anomalously fast time evolution and sharpness of the non-equilibrium profile can be understood through the domain wall creation at the boundary and its subsequent diffusion into the interior of the adsorbate layer.Comment: 6 pages, 7 figures, Tribology Letter

Optimizing the total energy consumption and CO₂ emissions by distributing computational workload among worldwide dispersed data centers

Major internet service providers have built and are currently building the world's largest data centres (DCs), which has already resulted in significant global energy consumption. Energy saving measures, from chip to building level, have been introduced gradually in recent decades. However, there is further potential for savings by assessing the performance of different DCs on a wider scale and evaluating information technology (IT) workload distribution strategies among these DCs. This paper proposes a methodology to optimize the electricity consumption and CO2 emissions by distributing IT workload across multiple imaginary DCs. The DCs are modelled and controlled in a virtual test environment based on a building energy simulation (BES) tool (TRNSYS). A controller tool (Matlab) is used to support testing and tuning of the optimization algorithm. A case study, consisting of the distribution of IT workload across four different types of data centers in multiple locations with different climate conditions, is presented. The case study will illustrate.</p

Development of a Clinical Simulation Protocol for the Transfer of a Premature Fetal Manikin to the Perinatal-Life-Support System

Introduction:At present, Perinatal-Life-Support (PLS) research is progressing to offer extreme premature infants an extracorporeal environment for extended growth that mimics the natural womb closely. During the early phase development of this novel life-support technology, validation and training could be facilitated by the use of a medical simulation. By doing so, the need for animal testing can be greatly reduced. Within this abstract, the development to realize a wellorchestrated clinical simulation protocol is described, tailored to the specific needs of novel procedure(s) regarding the transfer of a premature fetus from the maternal uterus to the PLS system.Materials &amp; Methods:Throughout protocol development an iterative approach is used, initiated with a literature analysis and a review of existing obstetrics guidelines for premature births. Next, co-creation sessions and interviews with medical and engineering experts led to a holistic understanding of fetal physiology, patient and specialist needs, current procedures, task divisions, hospital resources and drug specifications. Expert feedback on drafts, checklists and an explanatory step-by-step video, led to multiple re-designs as unforeseen procedural difficulties arose. Verified with available data from literature, multiple perspectives and options were analyzed and weighed to ensure the advancement of a safe, hygienic, effective, and user-friendly simulation protocol.Results:We describe the development process of a simulation protocol and showcase an overview of the current protocol design through an infographic, outlining the different phases and tasks during a transfer procedure and the planning of involved medical experts within the operating theatre. We demonstrate that an iterative approach to protocol development for an unprecedented procedure allows for a comprehensive understanding of the challenges that a transfer to the PLS-system could bring.Conclusions:Using medical simulation during the early phase development process of the PLS-system allows us to train and validate novel practices, in particular the transfer procedure. With the demonstrated approach we aim to establish a thorough simulation protocol by providing a step-by-step plan, informed by literature and expert consultation. We expect to offer a realistic simulation training whilst also informing requirements for the future development of PLS-related devices and their validation

Adrenomedullin expression in the mouse mammary gland: evidence for the mature form in milk

Adrenomedullin (AM) is a recently identified amidated peptide produced by a variety of tissue types. We have investigated the involvement of AM and its receptor (AM-R) in developing mouse mammary glands and have examined what influence ovarian hormones have on AM and AM-R expression in this system. Tissues from ductal morphogenesis, virgin adult, pregnancy, and lactation stages were assessed for AM and AM-R by molecular, biochemical and immunohistochemical techniques. Results from these studies indicated that messenger RNA for AM and AM-R and immunoreactivity for AM were expressed in the luminal epithelium of small and large ducts and in terminal end buds. Immunoreactive AM was identified as a cytoplasm component of ductal cells, with some cells also having nuclear staining. Western blot analysis of mammary gland tissues yielded two molecular mass species (M(r) 14,000 and 18,500) of AM immunoreactivity in the mammary gland for the above developmental stages, consistent with processed intermediate and prohormone forms respectively. Ovariectomy alone or followed by hormonal treatments did not alter the expression pattern for these two proteins. By Western blot, the fully processed AM form (M(r) 6000) was identified in milk extracts from lactating glands. These data suggest a potential role for AM and its receptor in the maintenance of mammary gland homeostasis and suggests a potential role for AM in development of the newborn