Patients with the mesenchymal subtype colorectal cancer (CRC) have a poor prognosis, in particular patients with stroma-rich tumors and aberrant SMAD4 expression. We hypothesized that interactions... Show morePatients with the mesenchymal subtype colorectal cancer (CRC) have a poor prognosis, in particular patients with stroma-rich tumors and aberrant SMAD4 expression. We hypothesized that interactions between SMAD4-deficient CRC cells and cancer-associated fibroblasts provide a biological explanation. In transwell invasion assays, fibroblasts increased the invasive capacity of SMAD4-deficient HT29 CRC cells, but not isogenic SMAD4-proficient HT29 cells. A TGF-beta/BMP-specific array showed BMP2 upregulation by fibroblasts upon stimulation with conditioned medium from SMAD4-deficient CRC cells, while also stimulating their invasion. In a mouse model for experimental liver metastasis, the co-injection of fibroblasts increased metastasis formation of SMAD4-deficient CRC cells (p = 0.02) but not that of SMAD4-proficient CRC cells. Significantly less metastases were seen in mice co-injected with BMP2 knocked-down fibroblasts. Fibroblast BMP2 expression seemed to be regulated by TRAIL, a factor overexpressed in SMAD4-deficient CRC cells. In a cohort of 146 stage III CRC patients, we showed that patients with a combination of high stromal BMP2 expression and the loss of tumor SMAD4 expression had a significantly poorer overall survival (HR 2.88, p = 0.04). Our results suggest the existence of a reciprocal loop in which TRAIL from SMAD4-deficient CRC cells induces BMP2 in fibroblasts, which enhances CRC invasiveness and metastasis. Show less
Motivation Only 27% of computer and mathematical scientists in the United States and 18% of IT specialists in Europe are women. The under-representation of women in the field of Computer Science is... Show moreMotivation Only 27% of computer and mathematical scientists in the United States and 18% of IT specialists in Europe are women. The under-representation of women in the field of Computer Science is, among other things, influenced by stereotypes of computer scientists. These stereotypes include being male, asocial and having an (obsessive) interest in computers. Even though stereotypical beliefs can develop at an early age, research on children’s stereotypes of computer scientists is sparse and inconclusive. Objectives Stereotypes we hold can be implicit or unconscious beliefs, or explicit or conscious beliefs. In this study, we focus on children’s implicit and explicit stereotypes regarding computer scientists’ gender, social skills and interests. We also study whether explaining what a computer scientist does affects these stereotypes. Method We study the implicit stereotypes through the reduced-length Child Implicit Association Test and the explicit stereotypes through self-reported absolute and relative Likert scale questions. We gathered data on 564 children between the age of 7 and 18 who were visiting a science museum. The participants in the experiment group (n=352) watch a video of either a man or woman explaining what a computer scientist does at the start of the study. Results We found weak implicit stereotypical beliefs on computer scientists’ social skills and moderate implicit stereotypical beliefs on computer scientists’ interests. We also found explicit stereotypes on computer scientists’ gender, social skills and interests. Measuring the effects of the intervention, we found significant differences between the control and experiment group in their explicit stereotypes on computer scientists’ social skills. Discussion The amount of scientific work on children’s stereotypes regarding computer scientists is still limited. Applying the reduced-length Child Implicit Association Test to measure children’s stereotypes on computer scientists has, to our knowledge, not been done before. Understanding children’s stereotypes and how to tackle them contributes to closing the gender gap in Computer Science. Show less
Vries, F.E. de; Wit, S. de; Cath, D.C.; Werf, Y.D. van der; Borden, V. van der; Rossum, T. van; ... ; Heuvel, O.A. van den 2013
Background Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to... Show moreBackground Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries. Methods We merged data on demographics, CD4 cell counts, viral-load measurements, hepatitis C co-infection status, smoking status, date of death, and whether death was AIDS-related or not from 23 European and North American cohorts. We calculated standardised mortality ratios (SMRs) standardised by age, sex, and year, stratifying by risk group. Data were included for patients aged 20-59 years who had at least one CD4 count greater than 350 cells per mu L while ART naive. All pre-ART CD4 counts greater than 350 cells per mu L from January, 1990, to December, 2004, were included. We investigated mortality for four risk groups men who have sex with men, heterosexual people, injecting drug users, and those at other or unknown risk. The association between CD4 cell count and death rate was investigated by use of Poisson regression methods. Findings Data were analysed for 40 830 patients contributing 80 682 person-years of follow-up. Of 419 deaths, 401 were used in the SMR analysis: 100 men who have sex with men (SMR 1.30 , 95% CI 1.06-1 58); 68 heterosexual people (2.94, 2.28-3.73); 203 injecting drug users (9.37, 8.13-10.75); and 30 in the other or unknown risk category (4.57, 3.09-6.53). Compared with CD4 counts of 350-499 cells per mu L, death rate was lower in patients with counts of 500-699 cells per mu L (adjusted rate ratio 0-77, 95% CI 0.61-0.95) and counts of 700 cells per mu L (0.66, 0.52-0.85). Interpretation In HIV-infected ART-naive patients with high CD4 cell counts, death rates were raised compared with the general population. In men who have sex with men this was modest, suggesting that a substantial proportion of the increased risk in other groups is due to confounding by other factors. Even though the increased risk is small, new studies of potential benefits of ART in this group are merited. Show less
Woiski, M.; Visser, S. de; Vugt, H. van; Dijkman, A.; Schuitemaker, N.; Meir, C. van; ... ; Hermens, R. 2018
Moving beyond existing approaches that largely deal with the biophysical consequences of climate change realities in Africa, this book explores an alternative perspective that traces climate change... Show moreMoving beyond existing approaches that largely deal with the biophysical consequences of climate change realities in Africa, this book explores an alternative perspective that traces climate change as a travelling idea. It focuses on how globally constructed discourses on climate change find their way to the local level in the Bamenda Grassfields of Cameroon, thereby seeking to understand how these discursive practices lead to social transformations, and to new configurations of power. In the translation process from the 'global' to the 'local' level a continuous modification and appropriation of the idea of climate change takes place that finally leads to a concrete implementation of climate change related projects and sensitization campaigns. Hence, it is argued that in this increasingly interconnected and mediated world people in Africa (and elsewhere in the world) do not solely adapt to a changing climate, but also adapt to a changing discourse about the climate. Travelling between traditional rulers and their palaces, to the world of NGOs, journalists and ordinary farmers this study brings the reader on a captivating journey, that reveals how climate change engages in a variety of ways with different lifeworlds, revitalizes local cosmologies, gives birth to a new development paradigm, and moreover how it evokes apocalyptic anxieties and trajectories of blame at the grassroots level. Show less
Friis-Moller, N.; Thiebaut, R.; Reiss, P.; Weber, R.; Monforte, A.D.; Wit, S. de; ... ; DAD Study Grp 2010
Aims HIV-infected patients receiving combination antiretroviral therapy may experience metabolic complications, potentially increasing their risk of cardiovascular diseases (CVDs). Furthermore,... Show moreAims HIV-infected patients receiving combination antiretroviral therapy may experience metabolic complications, potentially increasing their risk of cardiovascular diseases (CVDs). Furthermore, exposures to some antiretroviral drugs seem to be independently associated with increased CVD risk. We aimed to develop cardiovascular risk-assessment models tailored to HIV-infected patients. Methods and results Prospective multinational cohort study. The data set included 22 625 HIV-infected patients from 20 countries in Europe and Australia who were free of CVD at entry into the Data collection on Adverse Effects of Anti-HIV Drugs Study. Using cross-validation methods, separate models were developed to predict the risk of myocardial infarction, coronary heart disease, and a composite CVD endpoint. Model performance was compared with the Framingham score. The models included age, sex, systolic blood pressure, smoking status, family history of CVD, diabetes, total cholesterol, HDL cholesterol and indinavir, lopinavir/r and abacavir exposure. The models performed well with area under the receiver operator curve statistics of 0.783 (range 0.642-0.820) for myocardial infarction, 0.776 (0.670-0.818) for coronary heart disease and 0.769 (0.695-0.824) for CVD. The models estimated more accurately the outcomes in the subgroups than the Framingham score. Conclusion Risk equations developed from a population of HIV-infected patients, incorporating routinely collected cardiovascular risk parameters and exposure to individual antiretroviral therapy drugs, might be more useful in estimating CVD risks in HIV-infected persons than conventional risk prediction models. Eur J Cardiovasc Prev Rehabil 17:491-501 (C) 2010 The European Society of Cardiology Show less
Sjoerds, Z.; Brink, W. van den; Wit, S. de; Beekman, A.T.F.; Penninx, B.W.J.H.; Veltman, D.J. 2014
According to ideomotor theory, goal-directed action involves the active perceptual anticipation of actions and their associated effects. We used multivariate analysis of fMRI data to test if... Show moreAccording to ideomotor theory, goal-directed action involves the active perceptual anticipation of actions and their associated effects. We used multivariate analysis of fMRI data to test if preparation of an action promotes precision in the perceptual representation of the action. In addition, we tested how reward magnitude modulates this effect. Finally, we examined how expectation and uncertainty impact neural precision in the motor cortex. In line with our predictions, preparation of a hand or face action increased the precision of neural activation patterns in the extrastriate body area (EBA) and fusiform face area (FFA), respectively. The size of this effect of anticipation predicted individuals' efficiency at performing the prepared action. In addition, increasing reward magnitude increased the precision of perceptual representations in both EBA and FFA although this effect was limited to the group of participants that learned to associate face actions with high reward. Surprisingly, examination of representations in the hand motor cortex and face motor cortex yielded effects in the opposite direction. Our findings demonstrate that the precision of representations in visual and motor areas provides an important neural signature of the sensorimotor representations involved in goal-directed action. Show less
Passive social media use (PSMU)—for example, scrolling through social media news feeds—has been associated with depression symptoms. It is unclear, however, if PSMU causes depression symptoms or... Show morePassive social media use (PSMU)—for example, scrolling through social media news feeds—has been associated with depression symptoms. It is unclear, however, if PSMU causes depression symptoms or vice versa. In this study, 125 students reported PSMU, depression symptoms, and stress 7 times daily for 14 days. We used multilevel vector autoregressive time-series models to estimate (a) contemporaneous, (b) temporal, and (c) between-subjects associations among these variables. (a) More time spent on PSMU was associated with higher levels of interest loss, concentration problems, fatigue, and loneliness. (b) Fatigue and loneliness predicted PSMU across time, but PSMU predicted neither depression symptoms nor stress. (c) Mean PSMU levels were positively correlated with several depression symptoms (e.g., depressed mood and feeling inferior), but these associations disappeared when controlling for all other variables. Altogether, we identified complex relations between PSMU and specific depression symptoms that warrant further research into potentially causal relationships. Show less
Meulen, A.N. van der; Hermans, F.F.J.; Aivaloglou, E.; Aldewereld, A.; Heemskerk, B.; Smit, M.; ... ; Wit, S. de 2021
Computer science education (CSEd) research within K-12 makes extensive use of empirical studies in which children participate. Insight in the demographics of these children is important for the... Show moreComputer science education (CSEd) research within K-12 makes extensive use of empirical studies in which children participate. Insight in the demographics of these children is important for the purpose of understanding the representativeness of the populations included. This literature review studies the demographics of subjects included in K-12 CSEd studies. We have manually inspected the proceedings of three of the main international CSEd conferences: SIGCSE, ITiCSE and ICER, of five years (2014–2018), and selected all papers pertaining to K-12 CSEd experiments. This led to a sample of 134 papers describing 143 studies. We manually read these papers to determine the demographic information that was reported on, investigating the following categories: age/grade, gender, race/ethnic background, location, prior computer science experience, socio-economic status (SES), and disability. Our findings show that children from the United States, boys and children without computer science experience are included most frequently. Race and SES are frequently not reported on, and for race as well as for disabilities there appears a tendency to report these categories only when they deviate from the majority. Further, for several demographic categories different criteria are used to determine them. Finally, most studies take place within schools. These insights can be valuable to correctly interpret current knowledge from K-12 CSEd research, and furthermore can be helpful in developing standards for consistent collection and reporting of demographic information in this community. Show less
