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
Lamers, C.H.C.B.; Vidal, R.; Belbachir, N.; Stein, N. van; Bäck, T.H.W.; Paris, G. 2023
The large-scale magnetometer prospection conducted in 2021 south of the al-Najaf International Airport, Iraq, reveals the complex settlement structure of the late Antique and early Islamic site of... Show moreThe large-scale magnetometer prospection conducted in 2021 south of the al-Najaf International Airport, Iraq, reveals the complex settlement structure of the late Antique and early Islamic site of al-Ḥīra. The manual archaeo-geophysical interpretation resulted in 16 classes and the three most relevant archaeological classes will serve as a baseline for a (semi-) automated classification workflow. Show less
König, H.M.T.; Bosman, A.W.; Hoos, H.H.; Rijn, J.N. van 2023
This paper reflects on the justifications and impacts of militarism in contemporary global narcotic governance, focusing on the interrelated questions on how state leaders and elites justify state... Show moreThis paper reflects on the justifications and impacts of militarism in contemporary global narcotic governance, focusing on the interrelated questions on how state leaders and elites justify state-perpetrated violence by invoking seemingly anti-violence concepts such as peace, security, human rights, justice, democracy, and development, and how drug war perpetrators justify their actions within and outside the state apparatus. The paper demonstrates that the war-on-drugs approach institutionalizes death and militarism as the default state policy, which represses marginalized groups based on material endowments, race, and gender, while highlighting the mechanisms of justification and implementation of a war on drugs policy approach. The paper maintains that state leaders actualize a war-on-drugs approach through intensified state violence and the perpetration of an impunity culture that protects state agents from any sort of legal prosecution for their human rights abuses. Show less
Mast, D.; Broekens, D.J.; Vries, S. de; Verbeek, F.J. 2023
The Participant Journey Map (PJM) provides structured insight into participation with interactive play in (semi-) public environments. It supports understanding of participants’ behavior and was... Show moreThe Participant Journey Map (PJM) provides structured insight into participation with interactive play in (semi-) public environments. It supports understanding of participants’ behavior and was developed based on experiences with previously developed playful interfaces, related research and expert interviews. We apply the PJM to interactive playful museum exhibits and evaluate and refine it based on its usage in a situated context. We observed 672 play sessions with 6 interactive playful museum exhibits. The observation data was visualized and analyzed using the PJM. This study shows that the PJM provides a realistic representation of participant behaviour, can be used to identify stagnations and progressions in participation flow, and support identification of influencing design and contextual factors. With this paper we contribute by presenting the PJM as a well-grounded, valuable and realistic framework for evaluating and understanding participation with situated interactive play, based on post-hoc evaluation of multiple interfaces with many users. Show less
Whereas the scholarship on enslaved women’s resistance to the most intimate forms of bodily exploitation has grown over the years and developed into dif-ferent directions, not enough attention has... Show moreWhereas the scholarship on enslaved women’s resistance to the most intimate forms of bodily exploitation has grown over the years and developed into dif-ferent directions, not enough attention has been paid to the use of strategy by enslaved women. As a result, enslaved women’s resistance to bodily exploita-tions has wrongly been interpreted as impulsive. To correct this myth, this study broadly explores enslaved women’s strategic gendered resistance by looking at a variety of different sources. It looks at how enslaved women were strategic in resisting sexual abuse, it recognizes enslaved women’s adopted strategies in the practice of wet-nursing, and it explores how enslaved women thought stra-tegically about using methods of resistance such as abortion and infanticide. In an effort to combine these different sources and bring separate directions into which enslaved women’s resistance developed together, this study aims to elucidate that, without denying their victimhood, enslaved women were intel-lectually decisive and calculated in their acts and methods of resistance used when resisting the most intimate forms of bodily exploitation. Show less
Kentrotis-Zinelis, D.; Dam, D. van; Eenink, B.; Haak, N.; Jansen, H.R.J.; Kok, C. 2023
This paper presents a peculiar approach of escaping the dual gender-identity conceptualization, using bodybuilding—which is both a sports and corporeal practice—as a tool to shatter gender... Show moreThis paper presents a peculiar approach of escaping the dual gender-identity conceptualization, using bodybuilding—which is both a sports and corporeal practice—as a tool to shatter gender stereotypes. The bodies that are trans-formed as a result of this practice will be analysed and interpreted as a way to develop a relevant distinction between those bodies that are objectified on stage, due to the sport’s regulations, and those bodies that are located within an artistic and activist frame as “critical flesh.” This analysis looks at the bodies of three artists involved in the practice of bodybuilding to develop their artworks in order to discuss whether or not this corporeal identity built through muscle de-velopment creates a split in the gender discourse and in the expectations that this discourse generates. This approach is developed through the visual and conceptual support from the following artists: Cassils [they/them] (Canada-USA), Francesca Steele [they/them] (UK), and the author of this paper [she/her]. Show less
With the advancement of digital technologies, surveillance in the People’s Republic of China (PRC) has evolved from state and corporate modes towards everyday domains. This integration occurs... Show moreWith the advancement of digital technologies, surveillance in the People’s Republic of China (PRC) has evolved from state and corporate modes towards everyday domains. This integration occurs through the growing reliance of individuals on digital infrastructure in their ordinary interactions, which embodies the concept of ‘surveillance culture’. These novel surveillance methods and control mechanisms have given rise to new forms of institutional power imbalances This paper focuses on multimedia artist Cao Fei’s曹斐 (b. 1978) artwork i, mirror (2007) to explore the artistic strategies employed with updated media to reflect on the PRC’s developing surveillance culture critically. Through a thorough analysis of i.mirror, the research investigates how the artist represents the virtual body to complicate the notion of post-panoptical surveillance culture as a mechanism of control beyond the real realm. The paper examines how the body’s shifting identities, as both the object and the subject of the subtler surveillance collectively undertaken by the PRC’s authorities and civilians in their everyday lives, leads contemporary artists to explore the potential for new subjectivities in the new age of ‘digital China’. The overarching aim is to explore how contemporary Chinese artists can strategically utilise surveillance technologies as a way of political counter-surveillance to challenge systemic power asymmetries. Show less
