Nature-based solutions (NbS) are fast becoming the norm for multifunctional climate adaptation to the combined challenges of increased sea-level rise, coastal population densities, and erosion of... Show moreNature-based solutions (NbS) are fast becoming the norm for multifunctional climate adaptation to the combined challenges of increased sea-level rise, coastal population densities, and erosion of sandy shores worldwide, delivering functions such as flood prevention, recreation, and biodiversity benefits. However, it remains a challenge to the research field to inform decision-makers well on the outcomes and trade-offs of designing, planning, and managing the multifunctional NbS. This study set out to identify the information requirements by decision-makers on NbS for coastal climate adaptation. Using the Sand Motor in The Netherlands as a case study, we applied a policy science framework to distinguish four stages of decision-making to quantitatively analyse the content of functions and indicators utilized per stage in public policy documents. These stages are the ambition, political, bureaucratic, and provisioning processes. This study is the first comprehensive empirical investigation distinguishing these crucial stages of decision-making to analyse NbS information requirements. Our results show, most notably, that as the project developed through the decision-making stages, the content of the functions and indicators changed from abstract to concrete. And, with it, the content of the information required shifted significantly. These results suggest that it is crucial for academic researchers to recognize the decision-making process their information will be used in and adapt its content and level of abstraction accordingly to increase its uptake in decision-making. This study lays the groundwork for future research into the multiple dimensions of NbS decision-making and for the increased understanding of the information requirements on evaluation and trade-offs in planning, designing, and managing NbS, to increase the ability of NbS to deliver multifunctional coastal climate adaptation for sandy shores worldwide. Show less
The eighteenth-century passion to order and systematize as well as to measure and calculate has been explained as a result of both the Scientific Revolution and the emergence of centralized states.... Show moreThe eighteenth-century passion to order and systematize as well as to measure and calculate has been explained as a result of both the Scientific Revolution and the emergence of centralized states. The first, enabled the new experimental philosophy that quantified the 'sciences', while the latter created the need for statistics (e.g., demographic data). This paper explores the diffusion of the ‘quantifying spirit’ among the wider public in the eighteenth century and offers alternative explanation for the interest of the population at large in structured quantitative data. Using a corpus of 188 handwritten chronicles, produced by a heterogenous group of middle-class authors from the Low Countries, between 1500-1800, it analyses how early modern chroniclers used Western/Hindu-Arabic numerals in their writings, and under which circumstances this changed in the eighteenth century. From the analysis it appears that chroniclers used meteorological measurement and demographic data for different purposes than natural philosophers and (centralized) governments. Moreover, it transpires that the collection of quantitative data was initially stimulated by local governments, subsequently made public by various media, and picked up by the society at large and higher authorities. Show less
Learning analytics sits in the middle space between learning theory and data analytics. The inherent diversity of learning analytics manifests itself in an epistemology that strikes a balance... Show moreLearning analytics sits in the middle space between learning theory and data analytics. The inherent diversity of learning analytics manifests itself in an epistemology that strikes a balance between positivism and interpretivism, and knowledge that is sourced from theory and practice. In this paper, we argue that validation approaches for learning analytics systems should be cognisant of these diverse foundations. Through a systematic review of learning analytics validation research, we find that there is currently an over-reliance on positivistic validity criteria. Researchers tend to ignore interpretivistic criteria such as trustworthiness and authenticity. In the 38 papers we analysed, researchers covered positivistic validity criteria 221 times, whereas interpretivistic criteria were mentioned 37 times. We motivate that learning analytics can only move forward with holistic validation strategies that incorporate “thick descriptions” of educational experiences. We conclude by outlining a planned validation study using argument-based validation, which we believe will yield meaningful insights by considering a diverse spectrum of validity criteria. Show less
The problem of approximating the Pareto front of a multiobjective optimization problem can be reformulated as the problem of finding a set that maximizes the hypervolume indicator. This paper...Show moreThe problem of approximating the Pareto front of a multiobjective optimization problem can be reformulated as the problem of finding a set that maximizes the hypervolume indicator. This paper establishes the analytical expression of the Hessian matrix of the mapping from a (fixed size) collection of n points in the d-dimensional decision space (or m dimensional objective space) to the scalar hypervolume indicator value. To define the Hessian matrix, the input set is vectorized, and the matrix is derived by analytical differentiation of the mapping from a vectorized set to the hypervolume indicator. The Hessian matrix plays a crucial role in second-order methods, such as the Newton-Raphson optimization method, and it can be used for the verification of local optimal sets. So far, the full analytical expression was only established and analyzed for the relatively simple bi-objective case. This paper will derive the full expression for arbitrary dimensions (m ≥ 2 objective functions). For the practically important three-dimensional case, we also provide an asymptotically efficient algorithm with time complexity in O(n log n) for the exact computation of the Hessian Matrix’ non-zero entries. We establish a sharp bound of 12m−6 for the number of non-zero entries. Also, for the general m-dimensional case, a compact recursive analytical expression is established, and its algorithmic implementation is discussed. Also, for the general case, some sparsity results can be established; these results are implied by the recursive expression. To validate and illustrate the analytically derived algorithms and results, we provide a few numerical examples using Python and Mathematica implementations. Open-source implementations of the algorithms and testing data are made available as a supplement to this paper.Show less
The conflict between computational budget and quality of found solutions is crucial when dealing with expensive black-box optimization problems from the industry. We show that through multi... Show moreThe conflict between computational budget and quality of found solutions is crucial when dealing with expensive black-box optimization problems from the industry. We show that through multi-objective parameter tuning of the Covariance Matrix Adaptation Evolution Strategy on benchmark functions different optimal algorithm configurations can be found for specific computational budgets and solution qualities. With the obtained Pareto front, tuned parameter sets are selected and transferred to a real-world optimization problem from vehicle dynamics, improving the solution quality and budget needed. The benchmark functions for tuning are selected based on their similarity to a real-world problem in terms of Exploratory Landscape Analysis features. Show less
Background: The Mayo protocol for liver transplantation in patients with unresectable perihilar cholangiocarcinoma is based on strict selection and neoadjuvant chemoradiotherapy. The role of... Show moreBackground: The Mayo protocol for liver transplantation in patients with unresectable perihilar cholangiocarcinoma is based on strict selection and neoadjuvant chemoradiotherapy. The role of neoadjuvant chemoradiotherapy in this scenario remains unclear. The aim of this study was to compare outcomes after transplantation for perihilar cholangiocarcinoma using strict selection criteria, either with or without neoadjuvant chemoradiotherapy. Methods: This was an international, multicentre, retrospective cohort study of patients who underwent transplantation between 2011 and 2020 for unresectable perihilar cholangiocarcinoma using the Mayo selection criteria and receiving neoadjuvant chemoradiotherapy or not receiving neoadjuvant chemoradiotherapy. Endpoints were post-transplant survival, post-transplant morbidity rate, and time to recurrence. Results: Of 49 patients who underwent liver transplantation for perihilar cholangiocarcinoma, 27 received neoadjuvant chemoradiotherapy and 22 did not. Overall 1-, 3-, and 5-year post-transplantation survival rates were 65 per cent, 51 per cent and 41 per cent respectively in the group receiving neoadjuvant chemoradiotherapy and 91 per cent, 68 per cent and 53 per cent respectively in the group not receiving neoadjuvant chemoradiotherapy (1-year hazards ratio (HR) 4.55 (95 per cent c.i. 0.98 to 21.13), P = 0.053; 3-year HR 2.07 (95 per cent c.i. 0.78 to 5.54), P = 0.146; 5-year HR 1.71 (95 per cent c.i. 0.71 to 4.09), P = 0.229). Hepatic vascular complications were more frequent in the group receiving neoadjuvant chemoradiotherapy compared with the group not receiving neoadjuvant chemoradiotherapy (nine of 27 versus two of 22, P = 0.045). In multivariable analysis, tumour recurrence occurred less frequently in the group receiving neoadjuvant chemoradiotherapy (HR 0.30 (95 per cent c.i. 0.09 to 0.97), P = 0.044). Conclusion: In selected patients undergoing liver transplantation for perihilar cholangiocarcinoma, neoadjuvant chemoradiotherapy resulted in a lower risk of tumour recurrence, but was associated with a higher rate of early hepatic vascular complications. Adjustments in neoadjuvant chemoradiotherapy reducing the risk of hepatic vascular complications, such as omitting radiotherapy, may further improve the outcome in patients undergoing liver transplantation for perihilar cholangiocarcinoma.This international, multicentre study presents for the first time, to the best of our knowledge, a comparison of two cohorts of patients who underwent transplantation for unresectable perihilar cholangiocarcinoma using the Mayo Clinic selection criteria and either received neoadjuvant chemoradiotherapy or did not receive neoadjuvant chemoradiotherapy. Neoadjuvant chemoradiotherapy resulted in a lower risk of tumour recurrence, but was associated with a higher rate of early hepatic vascular complications. Adjustments in neoadjuvant chemoradiotherapy reducing the risk of hepatic vascular complications may further improve the outcome in patients undergoing liver transplantation for perihilar cholangiocarcinoma. Show less
Saturation is considered the state-of-the-art method for computing fixpoints with decision diagrams. We present a relatively simple decision diagram operation called REACH that also computes... Show moreSaturation is considered the state-of-the-art method for computing fixpoints with decision diagrams. We present a relatively simple decision diagram operation called REACH that also computes fixpoints. In contrast to saturation, it does not require a partitioning of the transition relation. We give sequential algorithms implementing the new operation for both binary and multi-valued decision diagrams, and moreover provide parallel counterparts. We implement these algorithms and experimentally compare their performance against saturation on 692 model checking benchmarks in different languages. The results show that the REACH operation often outperforms saturation, especially on transition relations with low locality. In a comparison between parallelized versions of REACH and saturation we find that REACH obtains comparable speedups up to 16 cores, although falls behind saturation at 64 cores. Finally, in a comparison with the state-of-the-art model checking tool ITS-tools we find that REACH outperforms ITS-tools on 29% of models, suggesting that REACH can be useful as a complementary method in an ensemble tool. Show less
The National Museum of Raqqa in Syria has suffered immensely from the ongoing violence since 2011. Much of its valuable collection of movable archaeological heritage (ca. 6000 items) is considered... Show moreThe National Museum of Raqqa in Syria has suffered immensely from the ongoing violence since 2011. Much of its valuable collection of movable archaeological heritage (ca. 6000 items) is considered lost. Starting from 500 of the most precious objects of the museum stored in the Raqqa Central Bank and stolen from there in 2013, the pilot project Focus Raqqa created a concrete, workable database to enable identification by Syrian and international police and heritage institutions. The project made a pivotal first step towards potential reconstruction of the Raqqa Museum in the future. The Raqqa museum collection included cuneiform tablets. Some of the tablets were cast before the war to allow detailed study in Europe. Today the tablets have vanished. The pilot project Scanning for Syria safeguarded information from the lost artefacts by making high-resolution three-dimensional scans of the silicone rubber moulds and subsequently physical replicas of the original objects by 3D printing. The short life expectancy (30 years) of the moulds necessitated measures for long-term preservation. The Scanning for Syria team not only succeeded at the preservation and sharing of knowledge in the academic circle. It also told the story of Syrian culture and its people to everyone for raising more voices in the united effort to keep cultural heritage safe in a zone of conflict. Show less
Objectives: Voriconazole therapeutic drug monitoring (TDM) is recommended based on retrospective data and limited prospective studies. This study aimed to investigate whether TDM-guided... Show moreObjectives: Voriconazole therapeutic drug monitoring (TDM) is recommended based on retrospective data and limited prospective studies. This study aimed to investigate whether TDM-guided voriconazole treat-ment is superior to standard treatment for invasive aspergillosis.Methods: A multicentre ( n = 10), prospective, cluster randomised, crossover clinical trial was performed in haematological patients aged >= 18 years treated with voriconazole. All patients received standard voriconazole dose at the start of treatment. Blood/serum/plasma was periodically collected after treat-ment initiation of voriconazole and repeated during treatment in both groups. The TDM group had mea-sured voriconazole concentrations reported back, with dose adjustments made as appropriate, while the non-TDM group had voriconazole concentrations measured only after study completion. The composite primary endpoint included response to treatment and voriconazole treatment discontinuation due to an adverse drug reaction related to voriconazole within 28 days after treatment initiation. Results: In total, 189 patients were enrolled in the study. For the composite primary endpoint, 74 patients were included in the non-TDM group and 68 patients in the TDM group. Here, no significant difference was found between both groups ( P = 0.678). However, more trough concentrations were found within the generally accepted range of 1-6 mg/L for the TDM group (74.0%) compared with the non-TDM group (64.0%) ( P < 0.001). Conclusions: In this trial, TDM-guided dosing of voriconazole did not show improved treatment outcome compared with standard dosing. We believe that these findings should open up the discussion for an approach to voriconazole TDM that includes drug exposure, pathogen susceptibility and host defence. Clinical trial registration: ClinicalTrials.gov registration no. NCT00893555.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ) Show less
Kapteijn, M.Y.; Kaptein, F.H.J.; Stals, M.A.M.; Klaase, E.E.; Eijk, R. van; Ruano, D.; ... ; Garcia-Ortiz, I. 2023
Background and objectives: Patients with glioblastoma have a high risk of developing venous thromboembolism (VTE). However, the role of underlying genetic risk factors remains largely unknown.... Show moreBackground and objectives: Patients with glioblastoma have a high risk of developing venous thromboembolism (VTE). However, the role of underlying genetic risk factors remains largely unknown. Therefore, the aim of this study was to discover whether genetic aberrations in glioblastoma associate with VTE risk.Methods: In this cohort study, all consecutive patients diagnosed with glioblastoma in two Dutch hospitals be-tween February 2017 and August 2020 were included. Targeted DNA next-generation sequencing of all glio-blastomas was performed for diagnostic purposes and included mutational status of the genes ATRX, BRAF, CIC, FUBP1, H3F3A, IDH1, IDH2, PIK3CA, PTEN and TP53 and amplification/gain or deletion of BRAF, CDKN2A, EGFR, NOTCH1 and PTEN. The primary outcome was VTE within three months before glioblastoma diagnosis until two years after. Cumulative incidences were determined using competing risk analysis adjusting for mor-tality. Univariable Cox regression analysis was performed to determine hazard ratios.Results: From 324 patients with glioblastoma, 25 were diagnosed with VTE. Patients with a CDKN2A deletion had a 12-month adjusted cumulative incidence of VTE of 12.5 % (95%CI: 7.3-19.3) compared with 5.4 % (95%CI: 2.6-9.6) in patients with CDKN2A wildtype (p = 0.020), corresponding to a HR of 2.53 (95%CI: 1.12-5.73, p = 0.026). No significant associations were found between any of the other investigated genes and VTE.Conclusion: This study suggests a potential role for CDKN2A deletion in glioblastoma-related VTE. Therefore, once independently validated, CDKN2A mutational status may be a promising predictor to identify glioblastoma patients at high risk for VTE, who may benefit from thromboprophylaxis. Show less
