Mesenchymal stromal cells (MSCs) and colorectal cancer - a troublesome twosome for the anti-tumour immune response?

The tumour microenvironment (TME) is an important factor in determining the growth and metastasis of colorectal cancer, and can aid tumours by both establishing an immunosuppressive milieu, allowing the tumour avoid immune clearance, and by hampering the efficacy of various therapeutic regimens. The tumour microenvironment is composed of many cell types including tumour, stromal, endothelial and immune cell populations. It is widely accepted that cells present in the TME acquire distinct functional phenotypes that promote tumorigenesis. One such cell type is the mesenchymal stromal cell (MSC). Evidence suggests that MSCs exert effects in the colorectal tumour microenvironment including the promotion of angiogenesis, invasion and metastasis. MSCs immunomodulatory capacity may represent another largely unexplored central feature of MSCs tumour promoting capacity. There is considerable evidence to suggest that MSCs and their secreted factors can influence the innate and adaptive immune responses. MSC-immune cell interactions can skew the proliferation and functional activity of T-cells, dendritic cells, natural killer cells and macrophages, which could favour tumour growth and enable tumours to evade immune cell clearance. A better understanding of the interactions between the malignant cancer cell and stromal components of the TME is key to the development of more specific and efficacious therapies for colorectal cancer. Here, we review and explore MSC- mediated mechanisms of suppressing anti-tumour immune responses in the colon tumour microenvironment. Elucidation of the precise mechanism of immunomodulation exerted by tumour-educated MSCs is critical to inhibiting immunosuppression and immune evasion established by the TME, thus providing an opportunity for targeted and efficacious immunotherapy for colorectal cancer growth and metastasis

Psychometric properties of the Actively Open-minded Thinking scale

The Actively Open-minded Thinking scale (AOT; Stanovich & West, 2007) is a questionnaire that is used to measure the disposition towards rational thinking as a single psychological trait. Yet, despite its frequent use, also in abbreviated form, it is still unclear whether sumscores of the AOT can actually be used to order individuals on their disposition towards actively open-minded thinking and whether the questionnaire can be validly shortened. The present study aimed to obtain a valid and shorter AOT. We conducted Mokken scale analyses on the (Dutch) AOT using two samples of higher education students (N = 930; N = 509). Our analyses showed that none of the 41 items could discriminate sufficiently between respondents with varying latent trait levels. Furthermore, no item-set of the AOT could be obtained to validly order individuals on the assumed latent trait, which is a crucial assumption when using it in research. Consequently, it is questionable whether scores on the AOT provide insights into the concept it aims to measure

Identifying Characteristics Associated with Higher Education Teachers’ Cognitive Reflection Test Performance and Their Attitudes towards Teaching Critical Thinking

The aim of this study was to identify characteristics that are related to higher education teachers' (N ¼ 263) Cognitive Reflection Test (CRT) performance, which assesses an important aspect of critical thinking (CT), and their attitudes towards teaching CT more generally. Results of a structural equation model showed that a stronger disposition towards effortful thinking, teaching in a more technological domain, and a higher level of education were related to a better CRT performance. Thinking dispositions were also related to teachers’ perceived relevance of teaching CT. Confidence in CRT performance rather than actual performance was related to perceived competence in teaching CT

Physicians' opinion and practice with the continuous use of sedatives in the last days of life

CONTEXT: There are few international studies about the continuous use of sedatives (CUS) in the last days of life. OBJECTIVES: We aim to describe the experiences and opinions regarding CUS of physicians caring for terminally ill patients in seven countries. METHODS: Questionnaire study about practices and experiences with CUS in the last days of life among physicians caring for terminally ill patients in Belgium (N=175), Germany (N=546), Italy (N=214), Japan (N=513), the Netherlands (N=829), United Kingdom (N=114) and Singapore (N=21). RESULTS: The overall response rate was 22%. Of the respondents, 88-99% reported that they had clinical experience of CUS in the last 12 months. More than 90% of respondents indicated that they mostly used midazolam for sedation. The use of sedatives to relieve suffering in the last days of life was considered acceptable in cases of physical suffering (87-99%). This percentage was lower but still substantial in cases of psycho-existential suffering in the absence of physical symptoms (45-88%). These percentages were lower when the prognosis was at least several weeks (22- 66% for physical suffering and 5-42% for psycho-existential suffering). Of the respondents, 10% or less agreed with the statement that CUS is unnecessary because suffering can be alleviated with other measures. A substantial proportion (41-95%) agreed with the statement that a competent patient with severe suffering has the right to demand the use of sedatives in the last days of life. CONCLUSION: Many respondents in our study considered CUS acceptable for the relief of physical and psycho-existential suffering in the last days of life. The acceptability was lower regarding CUS for psycho-existential suffering and regarding CUS for patients with a longer life expectancy. FUNDING: Ministry of Education, Culture, Sports, Science and Technology, Japan KEY MESSAGE: : This questionnaire study among physicians caring for terminally ill patients showed that many considered the continuous use of sedatives acceptable to relieve physical and psycho-existential suffering in the last days of life. Respondents' regarded the practice as less acceptable in patients with a longer life expectancy

Learning to Avoid Biased Reasoning: Effects of Interleaved Practice and Worked Examples

It is yet unclear which teaching methods are most effective for improving critical thinking (CT) skills and especially for the ability to avoid biased reasoning. Two experiments (laboratory: N = 85; classroom: N = 117), investigated the effect of practice schedule (interleaved/blocked) on students’ learning and transfer of unbiased reasoning, and whether it interacts with practice-task format (worked-examples/problems). After receiving CT-instructions, participants practiced in: (1) a blocked schedule with worked examples, (2) an interleaved schedule with worked examples, (3) a blocked schedule with problems, or (4) an interleaved schedule with problems. In both experiments, learning outcomes improved after instruction/practice. Surprisingly, there were no indications that interleaved practice led to better learning/transfer than blocked practice, irrespective of task format. The practice-task format did matter for novices’ learning: worked examples were more effective than low-assistance practice problems, which demonstrates –for the first time–that the worked-example effect also applies to novices’ learning to avoid biased reasoning

Effects of Self-explaining on Learning and Transfer of Critical Thinking Skills

Critical thinking is considered to be an important competence for students and graduates of higher education. Yet, it is largely unclear which teaching methods are most effective in supporting the acquisition of critical thinking skills, especially regarding one important aspect of critical thinking: avoiding biased reasoning. The present study examined whether creating desirable difficulties in instruction by prompting students to generate explanations of a problem-solution to themselves (i.e., self-expl

Building the Flexible Firm: How to Remain Competitive

Building the Flexible Firm: How to Remain Competitiv

The determinants of expatriate staffing by Japanese multinationals in Asia: control, learning and vertical business groups

We empirically examine the determinants of the decision whether or not to appoint an expatriate as the managing director of overseas affiliates for a sample of 844 Japanese manufacturing affiliates operating in Asia in 1995. Confirmation is found for hypotheses derived both from a control and coordination perspective on expatriation and from a knowledge creation and learning perspective. Strategic dependence of the parent on the affiliate increases the propensity to appoint expatriates, whereas localisation of the affiliate reduces it. Organisational experience in the country, both by the affiliate and by the firm, increases the probability that host country nationals will be appointed. Inter-firm relationships within vertical keiretsu groups impact on expatriation policies through inter-organisational knowledge exchange in host countries and the mitigation of localisation requirements owing to intra-group transactions