Mutationen im PTS-Gen und mögliche Auswirkungen auf Funktion und Struktur der 6-Pyruvoyl-Tetrahydropterin-Synthase

Background: Research on Juvenile Idiopathic Arthritis (JIA) should support patients, caregivers/parents (carers) and clinicians to make important decisions in the consulting room and eventually to improve the lives of patients with JIA. Thus far these end-users of JIA-research have rarely been involved in the prioritisation of future research. Main body: Dutch organisations of patients, carers and clinicians will collaboratively develop a research agenda for JIA, following the James Lind Alliance (JLA) methodology. In a 'Priority Setting Partnership' (PSP), they will gradually establish a top 10 list of the most important unanswered research questions for JIA. In this process the input from clinicians, patients and their carers will be equally valued. Additionally, focus groups will be organised to involve young people with JIA. The involvement of all contributors will be monitored and evaluated. In this manner, the project will contribute to the growing body of literature on how to involve young people in agenda setting in a meaningful way. Conclusion: A JIA research agenda established through the JLA method and thus co-created by patients, carers and clinicians will inform researchers and research funders about the most important research questions for JIA. This will lead to research that really matters.</p

Dutch juvenile idiopathic arthritis patients, carers and clinicians create a research agenda together following the James Lind Alliance method: A study protocol

Background: Research on Juvenile Idiopathic Arthritis (JIA) should support patients, caregivers/parents (carers) and clinicians to make important decisions in the consulting room and eventually to improve the lives of patients with JIA. Thus far these end-users of JIA-research have rarely been involved in the prioritisation of future research. Main body: Dutch organisations of patients, carers and clinicians will collaboratively develop a research agenda for JIA, following the James Lind Alliance (JLA) methodology. In a 'Priority Setting Partnership' (PSP), they will gradually establish a top 10 list of the most important unanswered research questions for JIA. In this process the input from clinicians, patients and their carers will be equally valued. Additionally, focus groups will be organised to involve young people with JIA. The involvement of all contributors will be monitored and evaluated. In this manner, the project will contribute to the growing body of literature on how to involve young people in agenda setting in a meaningful way. Conclusion: A JIA research agenda established through the JLA method and thus co-created by patients, carers and clinicians will inform researchers and research funders about the most important research questions for JIA. This will lead to research that really matters

Building Trust: preserving an inclusive Addis Ababa

Ethiopia is a flourishing country with a rapidly growing economy and population. This is one of the reasons why the capital Addis Ababa is increasingly urbanizing. Due to the free market only providing housing for high incomes, many households live in poor conditions. In addition, these private developments are often built as gated communities out of fear of insecurity and resulting in segregation. This segregation is further enhanced by the government's Integrated Housing Development Program (IHDP), which realizes subsidized housing for middle and low incomes, but by doing so it also segregates these groups. While Addis Ababa has traditionally been an integrated city with an inclusive society, which is still of great importance for the living standard of especially low-income people. This research offers an alternative design for the current scheme of the IHDP and proposes a mixed-income neighborhood whereby stimulating mutual trust between residents through the built environment is central to the project.Addis Ababa Living LabArchitecture, Urbanism and Building Sciences | Global Housin

Modular Hybrid Coastal Protection Structure: Pilot site: Montego Bay, Jamaica

Tourism is one of the main sources of income of Jamaica. . However, at the moment the beaches are retreating. An example is the erosion of Hellshire Beach, showing a retreat of ten meters in only seven years. To preserve the beaches effectively, a new concept is requested. The main requirements of the system are wave attenuation and the marine life enhancement. The literature study showed, a variety of coastal management techniques exist. However, none of those solutions are capable of attenuating waves and enhancing marine life in an effective way. Ranking criteria are given and the following concept groups are generated: boulders, gabions, marine blocks, big (open) blocks and 'lego' (interlocking) blocks. The Multi-Criteria Analysis shows that the big (open) blocks are the most viable and two concepts are designed within this concept group: a triangular and a hexagonal block structure.In the hydrodynamic and wave models (Delft3D), a study is performed to find the relation between breakwater dimensions and wave attenuation. Also, three different conditions are modelled: daily conditions, hurricane conditions, and one-year storm conditions at the Hip-Strip in Montego Bay. Using the results from the hurricane model, the flow- and wave forces are calculated using the Morison equations for lift and drag. Three lay-outs for submerged breakwaters are tested in the model. This led to the final lay-out which is a combination of the three tested breakwaters.Following the Delft3D models, a structural analysis is done with the flow- and wave forces from the Morison equation. The structural analysis focuses on the sliding and uplift of the submerged breakwater. The hexagonal structure shows a better stability than the triangular blocks in hurricane conditions and therefore chosen as the final concept. A sensitivity analysis is performed with regard to the friction coefficient, the force-time profile and the placement errors. The placement errors turn out to be crucial and a connection between the top block and the base is needed to retain stability. The final dimensions (l x w x h) of the hexagonal blocks are 3 x 0.75 x 0.93 meter. The blocks can be made from a low strength class concrete and reinforcement is needed to provide strength during lifting. To enhance the marine life enhancement properties, fish condos of 4" and 6" are provided, the surface is made more permeable and the pH of the concrete is altered by curing.The structure shows great future potential and can be built soon. It is a state of the art structure, the stability is high, it enhances the marine life, the final dimensions will precisely agree with the drawings and there is no need for a nearby quarry. However, to all this benefits, there is also a drawback; the cost. The cost is a multiple of the conventional armour stones. Recommendations are given to bring expenses down. Placement in shallow water is preferred and replacing steel reinforcement by fibre reinforcement is worth investigating. Those recommendations will decrease the cost and will increase the viability of the Honeycomb block concept

High-Resolution Global Water Temperature Modeling

The temperature of river water plays a crucial role in many physical, chemical, and aquatic ecological processes. Despite the importance of having detailed information on this environmental variable at locally relevant scales (≤50 km), high-resolution simulations of water temperature on a large scale are currently lacking. We have developed the dynamical 1-D water energy routing model (DynWat), that solves both the energy and water balance, to simulate river temperatures for the period 1960–2014 at a nominal 10-km and 50-km resolution. The DynWat model accounts for surface water abstraction, reservoirs, riverine flooding, and formation of ice, enabling a realistic representation of the water temperature. We present a novel 10-km water temperature data set at the global scale for all major rivers, lakes, and reservoirs. Validated results against 358 stations worldwide indicate a decrease in the simulated root-mean-square error (0.2 °C) and bias (0.7 °C), going from 50- to 10-km simulations. We find an average global increase in water temperature of 0.16 °C per decade between 1960 and 2014, with more rapid warming toward 2014. Results show increasing trends for the annual daily maxima in the Northern Hemisphere (0.62 °C per decade) and the annual daily minima in the Southern Hemisphere (0.45 °C per decade) for 1960–2014. The high-resolution modeling framework not only improves the model performance, it also positively impacts the relevance of the simulations for regional-scale studies and impact assessments in a region without observations. The resulting global water temperature data set could help to improve the accuracy of decision-support systems that depend on water temperature estimates

High-Resolution Global Water Temperature Modeling

The temperature of river water plays a crucial role in many physical, chemical, and aquatic ecological processes. Despite the importance of having detailed information on this environmental variable at locally relevant scales (≤50 km), high-resolution simulations of water temperature on a large scale are currently lacking. We have developed the dynamical 1-D water energy routing model (DynWat), that solves both the energy and water balance, to simulate river temperatures for the period 1960–2014 at a nominal 10-km and 50-km resolution. The DynWat model accounts for surface water abstraction, reservoirs, riverine flooding, and formation of ice, enabling a realistic representation of the water temperature. We present a novel 10-km water temperature data set at the global scale for all major rivers, lakes, and reservoirs. Validated results against 358 stations worldwide indicate a decrease in the simulated root-mean-square error (0.2 °C) and bias (0.7 °C), going from 50- to 10-km simulations. We find an average global increase in water temperature of 0.16 °C per decade between 1960 and 2014, with more rapid warming toward 2014. Results show increasing trends for the annual daily maxima in the Northern Hemisphere (0.62 °C per decade) and the annual daily minima in the Southern Hemisphere (0.45 °C per decade) for 1960–2014. The high-resolution modeling framework not only improves the model performance, it also positively impacts the relevance of the simulations for regional-scale studies and impact assessments in a region without observations. The resulting global water temperature data set could help to improve the accuracy of decision-support systems that depend on water temperature estimates

Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells

Surgical resection of the tumor is the primary treatment of colorectal cancer patients. However, we previously demonstrated that abdominal surgery promotes the adherence of circulating tumor cells (CTC) in the liver and subsequent liver metastasis development. Importantly, preoperative treatment with specific tumor-targeting monoclonal antibodies (mAb) prevented surgery-induced liver metastasis development in rats. This study investigated whether the epidermal growth factor receptor (EGFR) represents a suitable target for preoperative antibody treatment of colorectal cancer patients undergoing surgery. The majority of patients with resectable colorectal liver metastases were shown to have EGFR + CTCs. Three different anti-EGFR mAbs (cetuximab, zalutumumab, and panitumumab) were equally efficient in the opsonization of tumor cell lines. Additionally, all three mAbs induced antibody-dependent cellular phagocytosis (ADCP) of tumor cells by macrophages at low antibody concentrations in vitro, independent of mutations in EGFR signaling pathways. The plasma of cetuximab-treated patients efficiently opsonized tumor cells ex vivo and induced phagocytosis. Furthermore, neither proliferation nor migration of epithelial cells was affected in vitro, supporting that wound healing will not be hampered by treatment with low anti-EGFR mAb concentrations. These data support the use of a low dose of anti-EGFR mAbs prior to resection of the tumor to eliminate CTCs without interfering with the healing of the anastomosis. Ultimately, this may reduce the risk of metastasis development, consequently improving long-term patient outcome significantly

Addis Ababa as a Palimpsest

The goal of the Global Housing graduation studio is to research and design housing solutions to improve the livelihood of Addis Ababa’s urban dwellers. Combining analysis, planning and design, the participants in this graduation studio are challenged to use multidisciplinary research methods and tools to elaborate design proposals for mass housing as mass welfare. The research outcomes and analytical output compiled in this book have been instrumental to support several dozens of reflexive and critical design proposals for adequate housing in Addis Ababa. More than just a compilation of material, we believe the work included in this book is also a contribution to help students, educators, practitioners and policymakers exploring and developing new standards for housing that respond to contemporary ideals of sustainability and inclusivity.This report was produced as part of the Global Housing Graduation Studio of Architecture & Dwelling from the Faculty of Architecture and the Built Environment. The studio was set up as a supportive educational component in the research project ‘Addis Ababa Living Lab’ (2019-2023), jointly funded by NWO-WOTRO and TU Delft.Architecture, Urbanism and Building Sciences | Dwellin