6 research outputs found

    Robotically driven construction of buildings: Exploring on-demand building components production

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    Robotically Driven Construction of Buildings (RDCB) is an exploration into design to production solutions for robotically driven construction of buildings initiated by the faculties of Civil Engineering and Architecture, TU Delft and Architecture, TU Eindhoven and implemented 2014 within the 3TU Lighthouse framework. The aim of was to involve the disciplines of architecture, robotics, materials science, and structural design in order to integrate knowledge from the individual disciplines and develop new numerically controlled manufacturing techniques and building-design optimisation methods for adding creative value to buildings in a cost-effective and sustainable way.RDCB builds up on expertise developed at Hyperbody with respect to applications of robotics in architecture and this paper presents the contribution of the Robotic Building team from Hyperbody, Faculty of Architecture, TU Delft to the RDCB project. The contribution is in line with Europe’s aim to improve material and energy efficiency of buildings and efficiency of construction processes. Robotically driven construction and customised building materials have the potential to realise this in a cost-effective way and at the same time reduce accidents and health hazards for workers in the building sector. In order to achieve this RDCB is distributing materials as needed and where needed. This requires exploration of a variety of techniques and implies working with customised materials and techniques while finding the best methods of applying materials in the logic of specific force flows or thermal dissipation patterns.RDCB advances multi- and trans-disciplinary knowledge in robotically driven construction by designing and engineering new building systems for the on-demand production of customisable building components (Bier, 2014). The main consideration is that in architecture and building construction the factory of the future employs building materials and components that can be on site robotically processed and assembled

    Effect of forced-air heaters on perfusion and temperature distribution during and after open-heart surgery

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    OBJECTIVES: After cardiopulmonary bypass, patients often show redistribution hypothermia, also called afterdrop. Forced-air blankets help to reduce afterdrop. This study explores the effect of forced-air blankets on temperature distribution and peripheral perfusion. The blood perfusion data is used to explain the observed temperature effects and the reduction of the afterdrop. METHODS: Fifteen patients were enrolled in a randomised study. In the test group (n=8), forced-air warmers were used. In the control group (n=7), only passive insulation was used. Core and skin temperatures and thigh temperatures at 0, 8, 18 and 38 mm depth were measured. Laser Doppler flowmetry (LDF) was used to record skin perfusion from the big toe. Blood flow through the femoral artery was determined with ultrasound. RESULTS: Afterdrop in the test group was smaller than in the control group (1.2+/-0.2 degrees C vs 1.8+/-0.7 degrees C: P=0.04) whilst no significant difference in mean tissue thigh temperature was found between the groups. Local skin temperature was 2.5-3.0 degrees C higher when using forced-air heaters. However, skin perfusion was unaffected. Ultrasound measurements revealed that leg blood flow during the first hours after surgery was reduced to approximately 70% of pre- and peri-operative values. CONCLUSIONS: Forced-air blankets reduce afterdrop. However, they do not lead to clinical relevant changes in deep thigh temperature. LDF measurements show that forced-air heating does not improve toe perfusion. The extra heat especially favours core temperature. This is underlined by the decrease in postoperative leg blood flow, suggesting that the majority of the warmed blood leaving the heart flows to core organs and not to the peripher

    Functional analysis identifies damaging CHEK2 missense variants associated with increased cancer risk

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    Heterozygous carriers of germline loss-of-function variants in the tumor suppressor gene checkpoint kinase 2 (CHEK2) are at an increased risk for developing breast and other cancers. While truncating variants in CHEK2 are known to be pathogenic, the interpretation of missense variants of uncertain significance (VUS) is challenging. Consequently, many VUS remain unclassified both functionally and clinically. Here we describe a mouse embryonic stem (mES) cell-based system to quantitatively determine the functional impact of 50 missense VUS in human CHEK2. By assessing the activity of human CHK2 to phosphorylate one of its main targets, Kap1, in Chek2 knockout mES cells, 31 missense VUS in CHEK2 impaired protein function to a similar extent as truncating variants, and 9 CHEK2 missense VUS resulted in intermediate functional defects. Mechanistically, most VUS impaired CHK2 kinase function by causing protein instability or by impairing activation through (auto)phosphorylation. Quantitative results showed that the degree of CHK2 kinase dysfunction correlates with an increased risk for breast cancer. Both damaging CHEK2 variants as a group (OR 2,23; 95% CI 1,62-3,07; pG/p.D162G, was also identified, which co-segregated with familial prostate cancer. Altogether, these functional assays efficiently and reliably identified VUS in CHEK2 that associate with cancer.ISSN:0008-5472ISSN:1538-744

    Functional Analysis Identifies Damaging CHEK2 Missense Variants Associated with Increased Cancer Risk

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    Heterozygous carriers of germline loss-of-function variants in the tumor suppressor gene checkpoint kinase 2 (CHEK2) are at an increased risk for developing breast and other cancers. While truncating variants in CHEK2 are known to be pathogenic, the interpretation of missense variants of uncertain significance (VUS) is challenging. Consequently, many VUS remain unclassified both functionally and clinically. Here we describe a mouse embryonic stem (mES) cell-based system to quantitatively determine the functional impact of 50 missense VUS in human CHEK2. By assessing the activity of human CHK2 to phosphorylate one of its main targets, Kap1, in Chek2 knockout mES cells, 31 missense VUS in CHEK2 were found to impair protein function to a similar extent as truncating variants, while 9 CHEK2 missense VUS resulted in intermediate functional defects. Mechanistically, most VUS impaired CHK2 kinase function by causing protein instability or by impairing activation through (auto)phosphorylation. Quantitative results showed that the degree of CHK2 kinase dysfunction correlates with an increased risk for breast cancer. Both damaging CHEK2 variants as a group [OR 2.23; 95% confidence interval (CI), 1.62-3.07; P G/p.D162G, was also identified, which cosegregated with familial prostate cancer. Altogether, these functional assays efficiently and reliably identified VUS in CHEK2 that associate with cancer. Significance: Quantitative assessment of the functional consequences of CHEK2 variants of uncertain significance identifies damaging variants associated with increased cancer risk, which may aid in the clinical management of patients and carriers

    Recommendations for follow-up of muscle-invasive bladder cancer patients : A consensus by the international bladder cancer network

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    Rationale: Several guidelines exist that address treatment of patients with nonmetastatic muscle-invasive bladder cancer (MIBC). However, most only briefly mention follow-up strategies for patients and hence the treating physician is often left to infer on what the preferred follow-up schema would be for an individual patient. Herein, we aim to synthesize recommendations for follow-up of patients with MIBC for easy reference. Methods: A multidisciplinary MIBC expert panel from the International Bladder Cancer Network was assembled to critically assess currently available major guidelines on surveillance of MIBC patients. Recommendations for follow-up were extracted and critically evaluated. Important considerations for guideline assessment included both aspects of oncological and functional follow-up-frequency of visits, the use of different imaging modalities, the role of cytology and molecular markers, and the duration of follow-up. Outcome: An International Bladder Cancer Network expert consensus recommendation was constructed for the follow-up of patients with MIBC based on the currently available evidence-based data
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