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Metastatic breast cancer (mBC) remains incurable and liver metastases (LM) are observed in approximately 50% of all patients with mBC. In some cases, surgical resection of breast cancer liver metastases (BCLM) is associated with prolonged survival. However, there are currently no validated marker to identify these patients. The interactions between the metastatic cancer cells and the liver microenvironment result in two main histopathological growth patterns (HGP): replacement (r-HGP), characterized by a direct contact between the cancer cells and the hepatocytes, and desmoplastic (d-HGP), in which a fibrous rim surrounds the tumor cells. In patients who underwent resection of BCLM, the r-HGP is associated with a worse postoperative prognosis than the d-HGP. Here, we aim at unraveling the biological differences between these HGP within ten patients presenting both HGP within the same metastasis. The transcriptomic analyses reveal overexpression of genes involved in cell cycle, DNA repair, vessel co-option and cell motility in r-HGP while angiogenesis, wound healing, and several immune processes were found overexpressed in d-HGP LM. Understanding the biology of the LM could open avenues to refine treatment of BC patients with LM., SCOPUS: ar.j, info:eu-repo/semantics/published

OBJECTIVE: To depict objectively measured moderate-to-vigorous physical activity (MVPA), motor performance (MP), cardiorespiratory fitness (CRF), organized sports participation, parental perceptions of vulnerability and parenting style in children with a Critical Congenital Heart Disease (CCHD), and to explore whether these factors are associated with MVPA.STUDY DESIGN: A prospective observational cohort study in 62 7-10 years old children with a CCHD.RESULTS: On average, children with CCHD spent 64 min on MVPA per day (accelerometry), 61 % met the international WHO physical activity guideline. Only 12 % had >60 min of MVPA daily. Eighteen percent had a motor delay (movement-assessment-battery-for children-II) and 38 % showed a below average CRF (cardiopulmonary exercise test using the Godfrey ramp protocol). Seventy-seven percent participated in organized sports activities at least once a week. Twenty-one percent of the parents are classified as overprotective (parent protection scale) and 7.3 % consider their child as being vulnerable (child vulnerability scale). A significant positive association was found between MVPA and MP (rs = 0.359), CRF(V̇O 2peak/ml/kg: rs = 0.472 and W peak/kg: rs = 0.396) and sports participation (rs = 0.286). Children who were perceived as vulnerable by their parents showed a significantly lower MVPA (rs = -0.302). No significant associations were found between mean MVPA and parental overprotection. CONCLUSION: Even though the majority of school aged children with a CCHD is sufficiently active, counseling parents regarding the importance of sufficient MVPA and sports participation, especially in parents who consider their child being vulnerable, could be useful. Since motor delays can be detected at an early age, motor development could be an important target to improve exercise capacity and sports participation to prevent inactivity in children with a CCHD.

Purpose: To explore the association between cardiorespiratory fitness and other physical literacy domains in children with cystic fibrosis (CF) or congenital heart disease (CHD). Methods: In 28 children with CF (n = 10) or CHD (n = 18), aged 7 to 11 years, cardiorespiratory fitness and the following physical literacy domains were measured: (a) physical competence, (b) motivation and confidence, (c) knowledge and understanding, and (d) daily behavior (ie, self-perceived moderate-to-vigorous physical activity [MVPA]). Results: Cardiorespiratory fitness was significantly associated with motivation and confidence and self-perceived MVPA. There were no other significant associations. Conclusions: Cardiorespiratory fitness is associated with self-perceived MVPA, motivation, and confidence in children with CF or CHD.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management., Ministerio de Ciencia, Innovación y Universidades (España), European Comission, Junta de Castilla y León, Instituto de Salud Carlos III, Ministerio de Economía, Comercio y Empresa (España), Federación Española de Enfermedades Raras, Departamento de Defensa (Estados Unidos), National Institutes of Health (Estados Unidos), Universidad de California (Estados Unidos), Instituto Nacional del Cáncer (Estados Unidos), Fundación "la Caixa", Agencia Estatal de Investigación, Depto. de Estadística e Investigación Operativa, Fac. de Farmacia, TRUE, pub

Open-mindedness is defined as one’s willingness and ability to consider opposing beliefs and perspectives and give them a serious, impartial consideration by setting aside one’s commitment towards one’s own beliefs and perspectives. Learning to prepare and teach open-minded lessons is a crucial skill for student teachers because it fosters an atmosphere in which pupils feel free to express their own views and to learn about the views of others. The aim of this experiment was to examine which instructional strategy best supports student teachers’ learning to prepare an open-minded citizenship education lesson. Therefore, participants (n = 176) processed an instruction on how to prepare an open-minded citizenship education lesson through learning by teaching on video, preparing to teach, or re-study (control condition), and as a post-test designed a lesson plan. We examined the completeness and accuracy of the explanations of the instructional content, feelings of social presence and arousal, open-mindedness levels, the completeness and accuracy of the lesson plans, and the conceptual knowledge of the instructional content. In addition, the lesson plans were graded on overall quality. Results showed that all participants scored higher on open-mindedness as measured with the Actively Open-minded Thinking scale after the experiment than before the experiment. Participants in the control condition prepared significantly more accurate and complete open-minded lessons than participants in the other two conditions, suggesting they have gained better understanding of the instructional content. There were no significant differences between the conditions on the other outcome measures.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

http://journals.openedition.org/frontieres/1725, info:eu-repo/semantics/published

Le château en ruines de Walhain-Saint-Paul (Brabant Wallon, Belgique), implanté sur l’ancienne frontière entre le Duché de Brabant et le Comté de Namur, fait l’objet de recherches conjointes entre l’UCLouvain (Belgique) et l’Eastern Illinois University (USA) depuis 1998. L’étude interdisciplinaire du site ainsi que les campagnes de fouilles successives permettent aujourd’hui de documenter l’organisation des bâtiments internes à la haute-cour, dont le phasage et les articulations ont été investigués au sein d’un mémoire de master en 2019. Après l’édification du donjon au début du 12ème siècle, des remparts au cours du 13ème siècle, de grands travaux de réaménagement au 16ème siècle semblent pérenniser les fonctions des différents espaces de la haute-cour. Les structures internes à ces bâtiments, telles que des fours, documentées tant par l’archéologie que par les sources historiques, principalement connues dans leur phase moderne, permettent de postuler la spécialisation des espaces, suivant des fonctions résidentielles, de services et artisanales, au sein de la haute-cour du château.

Background and Purpose: Evidence regarding radiation-induced lymphopenia and its negative impact on oncological outcome is incrementing. Therefore, the aim of this study is to evaluate the feasibility of lymphocyte-rich organs at risk (LOAR) sparing in pelvic irradiation for localized prostate cancer and to estimate its impact on the effective dose to circulating immune cells (EDIC). Materials and Methods: Twenty patients with pelvic nodal and prostate or prostate bed irradiation were included. The following bone marrow (BM) structures were delineated as LOARs using semi-automatic segmentation: lumbosacral spine (Ls-BM), ilium (Il-BM), lower pelvis (Lp-BM), and the combined whole-pelvis (Wp-BM). Twenty new lymphocyte sparing treatment plans (LS plans) were calculated, optimizing doses to LOARs while maintaining strict coverage of the targets and respecting standard OARs dose constraints. Finally, we elaborated an EDIC calculation model for pelvic irradiation. Results: LS plans showed a statistically significant dose decrease for LOAR compared to standard of care plans without compromising target coverage nor classic OAR dose constraints: in prostate plans, the V40Gy for Ls-BM, Il-BM, and Lp-BM was decreased by 23 %, 36 %, 52 % respectively. For prostate bed plans, the V40Gy for Ls-BM, Il-BM, and Lp-BM was decreased by 25 %, 59 %, 56 %, respectively. For Wp-BM, the V10Gy, V20Gy, and Dmean have been decreased by 3 %, 14 %, 15 %, and by 5 %, 15 %, 17 %, respectively for prostate and prostate bed plans. A statistically significant decrease in EDIC was seen for LS plans in both groups. Conclusions: We successfully demonstrated the feasability of lympocyte-sparing treatment planning in pelvic irradiation, also proposing a model for EDIC calculation., SCOPUS: ar.j, info:eu-repo/semantics/published

The world is currently facing a pandemic and global challenges such as climate change, poverty, hunger, biodiversity loss, ocean acidification and inequalities. In this context, it follows that societies have forgotten a worrying old problem: pollution in all its shapes and forms. Thus, a plan must be devised to deal with the effects of chemical, physical and biological pollution. Such a strategy, however, should not ignore the syndemic caused by the interaction of pollution with the rest of the environmental, social, political, economic and health problems humanity has to deal with. Likewise, it should consider starting the intervention at the local scale, i.e. from the communities up. In this paper we present the conclusions of a series of collaborations that we have published in this journal, as well as our strategy for tackling polluting processes at the community level in highly vulnerable regions that we have named Humanitarian Scenarios, which include not only human communities but also the rest of nature’s living beings (Total Health scheme). We have called this initiative Integrated Monitoring System for Polluted Communities (SIVICCO) since it incorporates a set of concepts and tools for preventing the negative effects of pollution in all its forms and in all communities. SIVICCO is an integrated strategy but, above all, the expression of a new civic spirit based on the active participation of communities from a human rights perspective., Actualmente, el mundo enfrenta una pandemia y retos globales como el cambio climático, la pobreza, el hambre, la pérdida de la biodiversidad, la acidificación de los océanos y las desigualdades. En este contexto, se infiere que las sociedades hayan olvidado un problema antiguo y preocupante, la contaminación en todas sus formas. Es así entonces, que debe establecerse un plan para afrontar los efectos de la contaminación química, física y biológica. Sin embargo, dicha estrategia no debe ignorar la sindemia causada por la interacción de la contaminación con el resto de los problemas ambientales, sociales, políticos, económicos y sanitarios que enfrenta la humanidad. Asimismo, debe contemplar el reto de iniciar la intervención desde la escala local, es decir, desde la comunidad. En este trabajo, presentamos las conclusiones de una serie de colaboraciones que hemos publicado en esta revista. Así como una estrategia generada para intervenir procesos contaminantes a nivel comunitario en regiones de alta vulnerabilidad que hemos definido como Escenarios Humanitarios, incluyendo no solamente a las comunidades humanas, sino al resto de los seres vivos de la naturaleza (esquema de Salud Total). Esta iniciativa ha sido denominada como Sistema de Vigilancia Integrada para Comunidades Contaminadas (SIVICCO), ya que incorpora un conjunto de conceptos y herramientas para prevenir los efectos negativos de la contaminación en todas sus formas y en todas las comunidades. SIVICCO representa una estrategia integrada, pero sobre todo, la expresión de un nuevo civismo basado en la participación activa del colectivo comunitario con una perspectiva de derechos humanos., Atualmente, o mundo enfrenta uma pandemia e desafios globais, como as alterações climáticas, a pobreza, a fome, a perda de biodiversidade, a acidificação dos oceanos e as desigualdades. Neste contexto, infere-se que as sociedades esqueceram um problema antigo e preocupante, a poluição em todas as suas formas. Assim, deve ser estabelecido um plano para lidar com os efeitos da contaminação química, física e biológica. No entanto, esta estratégia não deve ignorar a sindemia causada pela interação da poluição com os demais problemas ambientais, sociais, políticos, económicos e de saúde que a humanidade enfrenta. Da mesma forma, deve contemplar o desafio de iniciar a intervenção a partir da escala local, ou seja, da comunidade. Neste trabalho, apresentamos as conclusões de uma série de colaborações que publicámos nesta revista. Assim como uma estratégia gerada para intervir em processos poluidores a nível comunitário em regiões de alta vulnerabilidade que definimos como Cenários Humanitários, incluindo não apenas comunidades humanas, mas também todos os seres vivos da natureza (esquema de Saúde Global). Essa iniciativa foi denominada de Sistema Vigilância Integrada para Comunidades Contaminadas (SIVICCO), pois incorpora um conjunto de conceitos e ferramentas para prevenir os efeitos negativos da poluição em todas as suas formas e em todas as comunidades. O SIVICCO representa uma estratégia integrada, mas sobretudo, a expressão de um novo civilismo baseado na participação ativa do grupo comunitário com uma perspetiva de direitos humanos.

The use of cardiopulmonary exercise testing in pediatrics provides critical insights into potential physiological causes of unexplained exercise-related complaints or symptoms, as well as specific pathophysiological patterns based on physiological responses or abnormalities. Clinical interpretation of the results of a cardiopulmonary exercise test in pediatrics requires specific knowledge with regard to pathophysiological responses and interpretative strategies that can be adapted to address concerns specific to the child's medical condition or disability. In this review, the authors outline the 7-step interpretative approach that they apply in their outpatient clinic for diagnostic, prognostic, and evaluative purposes. This approach allows the pediatric clinician to interpret cardiopulmonary exercise testing results in a systematic order to support their physiological reasoning and clinical decision making.

Les ruines du château de Walhain-Saint-Paul, monument médiéval du Brabant wallon remontant au XIIIe siècle, ont fait l’objet de plusieurs campagnes de fouilles archéologiques depuis 1998, menées par l’Université catholique de Louvain en collaboration avec une université américaine de l’Illinois. En ce Moyen Âge troublé, Walhain constituait une des pièces du système de défense à la frontière entre le duché de Brabant et le comté de Namur. Après la Renaissance, le château devient avec le temps une simple résidence administrative. Resté en relativement bon état jusqu’au XVIIIe siècle, c’est une tempête qui le détruit presqu’entièrement dans les années 1790, époque où c’est plutôt la Révolution qui mettait à bas châteaux, églises et autres abbayes. Le XIXe et le début du XXe siècles voient le château, outrage suprême, réduit à l’état de carrière pour les habitants des environs. Alizé Van Brussel, assistante-doctorante en archéologie à l’Université catholique de Louvain, en collaboration avec Laurent Verslype, professeur dans cette même université, livre dans ce Bulletin une Étude des vestiges archéologiques de la haute-cour et de l’organisation des espaces à la période moderne.

BACKGROUND AND AIMS: The Hippo pathway and its downstream effectors YAP and TAZ (YAP/TAZ) are heralded as important regulators of organ growth and regeneration. However, different studies provided contradictory conclusions about their role during regeneration of different organs, ranging from promoting proliferation to inhibiting it. Here we resolve the function of YAP/TAZ during regeneration of the liver, where Hippo’s role in growth control has been studied most intensely. METHODS: We evaluated liver regeneration after carbon tetrachloride toxic liver injury in mice with conditional deletion of Yap/Taz in hepatocytes and/or biliary epithelial cells, and measured the behavior of different cell types during regeneration by histology, RNA sequencing, and flow cytometry. RESULTS: We found that YAP/TAZ were activated in hepatocytes in response to carbon tetrachloride toxic injury. However, their targeted deletion in adult hepatocytes did not noticeably impair liver regeneration. In contrast, Yap/Taz deletion in adult bile ducts caused severe defects and delay in liver regeneration. Mechanistically, we showed that Yap/Taz mutant bile ducts degenerated, causing cholestasis, which stalled the recruitment of phagocytic macrophages and the removal of cellular corpses from injury sites. Elevated bile acids activated pregnane X receptor, which was sufficient to recapitulate the phenotype observed in mutant mice. CONCLUSIONS: Our data show that YAP/TAZ are practically dispensable in hepatocytes for liver development and regeneration. Rather, YAP/TAZ play an indirect role in liver regeneration by preserving bile duct integrity and securing immune cell recruitment and function.

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV-VSD have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2'-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino-acid residues from the hypervariable E region of the capsid in the cultured viruses did not support the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose-response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4-0.6 µM, TI = 21; 2CMC EC50, 2.7-5.3 µM, TI > 18; NITD-008, 0.5 to 0.9 µM, TI > 111. Investigation of these antivirals for the treatment of FCV-VSD is warranted.

The aim of this experiment was to examine the effect of different instructional strategies on student teachers’ confirmation bias. Confirmation bias refers to the selectivity in finding and using evidence that fits one’s own beliefs or hypotheses while neglecting evidence that is opposite to one’s own beliefs or hypotheses (Nickerson, 1998). Dutch student teachers (n = 141) took a confirmation bias pre-test and were then randomly assigned to three conditions; teaching on video (TOV), preparing to teach (PTT) and re-study (CC). All participants received text-based instruction on confirmation bias and how it can be mitigated. They also practised with confirmation bias tasks and they received feedback on their answers. Subsequently, participants in the TOV and PTT conditions prepared a lesson about the instructional content and in the TOV condition they taught this lesson on video. After the learning phase, TOV and PTT participants completed a social presence questionnaire. All participants completed an arousal questionnaire and a confirmation bias post-test and a transfer test. The results showed that confirmation bias was reduced to a similar extent in all conditions. Results also showed that the quality of the prepared lesson was highest for TOV participants suggesting they had gained better understanding of the confirmation bias than PTT participants. Furthermore, in contrast to our expectations, PTT participants reported highest social presence scores. TOV participants experienced higher arousal levels compared to CC participants. Transfer scores did not differ between conditions. We discuss theoretical explanations of the findings from the present study.

Here we present a series of supplemental datasets that complement our study entitled "A Systems Genetics approach to identify genetic markers of cardiotoxicity due to anthracyclines in cancer patients." The datasets presented here were used to generate the main and supplementary figures and tables of the indicated study. The study consists of the identification of genetic markers of cardiotoxicity due to anthracyclines (CDA). CDA is a complex genesis disease or complex trait, and because of this, there is a component of missing heritability. Therefore, it is not possible to identify genetic markers associated with CDA risk. Here, we propose that molecular subphenotypes associated with the CDA may be a strategy for identifying some of this missing heritability and risk markers associated with it. A similar strategy could be applied to identify markers of other diseases of complex genesis. This study is done using a genetically heterogeneous cohort of mice that developed breast cancer and was treated with doxorubicin or a combined treatment of doxorubicin and docetaxel. The mouse cohort was generated by backcrossing, so each mouse is genetically unique. Post-chemotherapy heart damage was assessed by quantifying fibrosis's cardiac area and the thickness of myocardial fibers. The genetic regions associated with CDA were assessed by massive genotyping and genetic linkage analysis. Several molecular subphenotypes were quantified in the myocardium, and their association with the CDA was evaluated. Subsequently, we identified which of them were most statistically associated with CDA in multivariate models. Moreover, which complex trait loci (QTLs) associated with molecular subphenotypes best explained CDA. This strategy served to identify in the cohort of mice genes whose allelic forms could be candidates for the risk of CDA. Allelic variants of these genes were evaluated in four cohorts of cancer patients treated with anthracyclines and whose CDA was evaluated by echocardi

Clinical management of renal artery stenosis has seen a major shift, after randomised clinical trials have shown no group benefit of endovascular intervention relative to optimal medical control. However, the inclusion criteria of these trials have been criticised for focusing on a subset of patients with atherosclerotic renal artery stenosis where intervention was unlikely to be beneficial. Moreover, new imaging and computational techniques have become available, which have the potential to improve identification of patients that will respond to interventional treatment. This review addresses the challenges associated with clinical decision making in patients with renal artery stenosis. Opportunities for novel diagnostic techniques to improve patient selection are discussed, along with ongoing Dutch studies and network initiatives that investigate these strategies.

Compte-rendu de la fouille en 2018 d'une fosse d'extraction au comblement de l'époque contemporaine.

Clinical management of renal artery stenosis has seen a major shift, after randomised clinical trials have shown no group benefit of endovascular intervention relative to optimal medical control. However, the inclusion criteria of these trials have been criticised for focusing on a subset of patients with atherosclerotic renal artery stenosis where intervention was unlikely to be beneficial. Moreover, new imaging and computational techniques have become available, which have the potential to improve identification of patients that will respond to interventional treatment. This review addresses the challenges associated with clinical decision making in patients with renal artery stenosis. Opportunities for novel diagnostic techniques to improve patient selection are discussed, along with ongoing Dutch studies and network initiatives that investigate these strategies.

Unbiased reasoning is considered an essential critical thinking skill that students need to possess to face the future challenges in their work and life. Confirmation bias, which is the tendency to selectively attend to information that is consistent with held beliefs, presents a significant thread to unbiased reasoning. An effective strategy to reduce confirmation bias is the 'consider-the-opposite'-strategy (COS). The central question of this pre-registered study was whether providing elaborative, worked example feedback after COS practice would lead to a better performance on previously practised and transfer tasks than correct-answer feedback. Participants were 132 university students who took a confirmation bias pre-test, watched an instructional video on COS afterwards and next received either worked example feedback or correct answer feedback on practice tasks, practised only, watched the instruction only or received no treatment. Finally, all participants took a learning test assessing their skill to avoid confirmation bias, and a transfer test assessing whether they could apply this acquired skill to problems containing other biases. Results revealed no differences on the learning test between both feedback conditions, but students who received feedback scored significantly higher on the confirmation bias problems than students who did not receive feedback. We carried out our pre-registered analysis plan, but due to the low reliability of particularly the pre-test, we carried out an additional exploratory analysis on subsets of post-test items and a subset of transfer test items. Results on learning revealed the same pattern as the planned analyses. However, we found no differences between any of the conditions on transfer.

This volume gathers the work of the Brussels Discourse Theory Group, a group of critical media and communication scholars that deploy discourse theory as a theoretical backbone and an analytical research perspective. The book seeks to show the value and applicability of discourse-theoretical analysis (DTA) within the field of media and communication studies, through a variety of case studies that highlight both the radical contingent nature and the hegemonic workings of media and communication practices.

The introduction to the edited volume Communication and Discourse Theory aims to reflect on the interaction between discourse theory and the study of media and communication, as well as the Brussels Discourse Theory Group’s contribution to it. The chapter starts with a summary of the main tenets of Laclau and Mouffe’s discourse theory, and touches upon its methodological/analytical translation in discourse-theoretical analysis (DTA). The next main part of the chapter discusses how discourse theory has been put to use for the analysis of communication and media, distinguishing four thematic areas: (1) communication, rhetoric, and media strategies; (2) discourses in media organizations; (3) media identities, practices, and institutions; and (4) media and agonistic democracy. In the next part, two areas that are currently being developed in the group, and have thus far remained under-developed, are singled out theoretically as well as empirically, from a discourse-theoretical perspective. This includes the relation between the discursive and the material, and the relation between media, communication, and audiences. Finally, the chapter provides a short overview of the other chapters in this book.

The introduction to the edited volume Communication and Discourse Theory aims to reflect on the interaction between discourse theory and the study of media and communication, as well as the Brussels Discourse Theory Group’s contribution to it. The chapter starts with a summary of the main tenets of Laclau and Mouffe’s discourse theory, and touches upon its methodological/analytical translation in discourse-theoretical analysis (DTA). The next main part of the chapter discusses how discourse theory has been put to use for the analysis of communication and media, distinguishing four thematic areas: (1) communication, rhetoric, and media strategies; (2) discourses in media organizations; (3) media identities, practices, and institutions; and (4) media and agonistic democracy. In the next part, two areas that are currently being developed in the group, and have thus far remained under-developed, are singled out theoretically as well as empirically, from a discourse-theoretical perspective. This includes the relation between the discursive and the material, and the relation between media, communication, and audiences. Finally, the chapter provides a short overview of the other chapters in this book.

BACKGROUND AND AIM: Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) cause significant adverse events including thyroid dysfunction, mainly hypothyroidism, in a considerable proportion of patients. In a series of metastatic renal cell carcinoma (mRCC) patients treated with sunitinib, we aimed to study the correlation between hypothyroidism and single nucleotide polymorphisms (SNPs) in genes involved in sunitinib pharmacokinetics and pharmacodynamics. PATIENTS AND METHODS: We included 79 mRCC patients who started sunitinib between November 2005 and March 2016. Serum thyroid function markers were collected at start and during sunitinib therapy. Germ-line DNA genotyping for 16 SNPs in 8 candidate genes was performed. Endpoints were time to increase in thyroid stimulating hormone (TSH) and time to decrease in T4 or free T4 (FT4) on day 1 and day 28 of each sunitinib cycle. RESULTS: Patients with the ABCG2 rs2231142 CC-genotype had a significantly longer time-to-TSH-increase on day 1 (11 vs. 5 cycles; p = 0.0011), and time-to-T4/FT4-decrease on day 1 (not reached vs. 10 cycles; p = 0.013) and day 28 (28 vs. 7 cycles; p = 0.03) compared to CA-carriers. Patients with the CYP3A5 rs776746 GG-genotype had a significantly longer time-to-TSH-increase at day 1 compared to GA-patients: 11 vs. 5 cycles (p = 0.0071). Significant associations were also found between PDGFRA rs35597368 and rs1800812 and time-to-TSH-increase at day 28. CONCLUSION: Polymorphism rs2231142 in the efflux pump ABCG2 is associated with hypothyroidism in mRCC patients treated with sunitinib.

BACKGROUND: There are no validated markers that predict response or resistance in patients with metastatic clear-cell renal cell carcinoma (mccRCC) treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors such as sunitinib and pazopanib. Recently, single nucleotide polymorphism (SNP) rs2981582 in Fibroblast Growth Factor Receptor 2 (FGFR2) was found to be associated with clinical outcome in patients with mccRCC treated with pazopanib and sunitinib. We aimed to validate these findings in patients treated with sunitinib. MATERIALS AND METHODS: Germline DNA was collected in patients with mccRCC starting first-line systemic therapy with sunitinib. SNP rs2981582 in FGFR2 C>T was genotyped. Association of the genotype with response rate, tumor shrinkage, median progression-free survival (mPFS), and median overall survival (mOS) was studied. RESULTS: We collected clinical data from 154 patients with available germline DNA. Baseline prognostic markers were well-balanced between both subgroups. Patients with the TT genotype had a poorer outcome compared with patients with the CT/CC genotype. The median shrinkage of selected tumor target lesions during treatment with sunitinib was -16% versus -31% (P = .002), mPFS was 8 versus 15 months (P = .0007), and mOS was 22 versus 33 months (P = .04), respectively. On multivariate analysis, rs2981582 remained an independent predictor of PFS (hazard ratio, 2.858; 95% confidence interval, 1.659-4.923; P < .0001) and OS (hazard ratio, 1.795; 95% confidence interval, 1.003-3.212; P = .049). CONCLUSION: Polymorphism rs2981582 in FGFR2 is correlated to PFS and OS in patients with mccRCC treated with sunitinib. Prospective validation of the impact of this SNP is warranted.

Le château en ruines de Walhain-Saint-Paul (Brabant Wallon, Belgique), implanté sur l’ancienne frontière entre le Duché de Brabant et le Comté de Namur, fait l’objet de recherches conjointes entre l’UCLouvain (Belgique) et l’Eastern Illinois University (USA) depuis 1998. L’étude interdisciplinaire du site ainsi que les campagnes de fouilles successives permettent aujourd’hui de documenter l’organisation des bâtiments internes à la haute-cour, dont le phasage et les articulations ont été investigués au sein d’un mémoire de master en 2019. Après l’édification du donjon au début du 12ème siècle, des remparts au cours du 13ème siècle, de grands travaux de réaménagement au 16ème siècle semblent pérenniser les fonctions des différents espaces de la haute-cour. Les structures internes à ces bâtiments, telles que des fours, documentées tant par l’archéologie que par les sources historiques, principalement connues dans leur phase moderne, permettent de postuler la spécialisation des espaces, suivant des fonctions résidentielles, de services et artisanales, au sein de la haute-cour du château.