Development of metacognitive skills in young adolescents : a bumpy ride to the high road

This thesis shows the final results of a longitudinal project where the same participants (12 to 15 yrs.) were followed for three consecutive years. The first objective of this study was to investigate the development of both quantity and quality of metacognitive skills. The second objective was to establish whether the development of metacognitive skills is intelligence-related or relatively intelligence-independent. Finally, the generality vs. domain-specificity of developing metacognitive skills was investigated. While thinking aloud, participants performed two different tasks representing two different domains: A text-studying task and a problem-solving task. Participants__ intellectual ability was assessed, as well as their metacognitive skills and learning performance for both domains separately. In summary, this thesis has shown that (1) Metacognitive skills do increase spontaneously in frequency and quality during young adolescence, albeit not continuously. The various subscales of metacognitive skillfulness do not develop at the same pace; (2) Metacognitive skills have their own contribution to the prediction of learning performance, on top of intellectual ability. The relation between intellectual ability and metacognitive skills as predictors of learning performance is not affected by development between 12 and 15 yrs.; (3) Around the age of 15 yrs. metacognitive skills become fully general.LEI Universiteit LeidenDevelopmental pathways of social-emotional and cognitive functioning - ou

Pet-related bacterial zoonotic infections:Three cases of severe infections in the immunocompromised host

Pets can have many positive effects on their owners. However, close contact with pets offers optimal conditions for transmission of micro-organisms. Especially immunocompromised patients are at risk for zoonotic infections. Here we describe the diagnosis, microbiology and treatment of three patients with severe zoonotic infections with Helicobacter canis, Pasteurella multocida and Capnocytophaga canimorsus. With this case report we would like to emphasize the importance of awareness for pet-related zoonotic infections in immunocompromised patients

Point Projection Mapping System for Tracking, Registering, Labeling and Validating Optical Tissue Measurements

Validation of newly developed optical tissue sensing techniques for tumor detection during cancer surgery requires an accurate correlation with histological results. Additionally, such accurate correlation facilitates precise data labeling for developing high-performance machine-learning tissue classification models. In this paper, a newly developed Point Projection Mapping system will be introduced, which allows non-destructive tracking of the measurement locations on tissue specimens. Additionally, a framework for accurate registration, validation, and labeling with histopathology results is proposed and validated on a case study. The proposed framework provides a more robust and accurate method for tracking and validation of optical tissue sensing techniques, which saves time and resources compared to conventional techniques available

Evaluation of an imaging-based in vitro screening platform for estrogenic activity with OECD reference chemicals

Estrogen receptor alpha (ERα) is often a primary target of endocrine disrupting chemicals (EDCs) and therefore several biochemical and cell-based assays for the detection of chemicals with estrogenic properties have been developed in the past. However, the current approaches are not suitable for the monitoring of pathway activation dynamics, and they are mostly based on expression constructs that lack physiological promoter regulation. We recently developed MCF7 fluorescent reporter cell lines of 3 different green fluorescent protein (GFP)-tagged ERα target genes: GREB1, PGR and TFF1. These reporters are under control of the full physiological promoter region and allow the monitoring of dynamic pro-proliferative pathway activation on a single cell level using a live-cell imaging set-up. In this study, we systematically characterized the response of these reporters to a full reference compound set of known estrogenic and non-estrogenic chemicals as defined by the Organization for Economic Co-Operation and Development (OECD). We linked activation of the pro-proliferative ERα pathway to a potential adverse outcome by additionally monitoring cell cycle progression and proliferation. The correct classification of the OECD reference compounds showed that our reporter platform has the same sensitivity and specificity as other validated artificial ERα pathway reporters, such as the ERα CALUX and VM7 Luc ER TA assay. By monitoring several key events (i.e. ER target activation, cell cycle progression and proliferation), and subsequently determining Point-of-Departure (POD) values, our reporter panel can be used in high-throughput testing for a physiologically more relevant, quantitative temporal endocrine modulation analysis to improve human carcinogen risk assessment.Toxicolog

Size and depth of residual tumor after neoadjuvant chemoradiotherapy in rectal cancer – implications for the development of new imaging modalities for response assessment

With the shift towards organ preserving treatment strategies in rectal cancer it has become increasingly important to accurately discriminate between a complete and good clinical response after neoadjuvant chemoradiotherapy (CRT). Standard of care imaging techniques such as CT and MRI are well equipped for initial staging of rectal tumors, but discrimination between a good clinical and complete response remains difficult due to their limited ability to detect small residual vital tumor fragments. To identify new promising imaging techniques that could fill this gap, it is crucial to know the size and invasion depth of residual vital tumor tissue since this determines the requirements with regard to the resolution and imaging depth of potential new optical imaging techniques. We analyzed 198 pathology slides from 30 rectal cancer patients with a Mandard tumor regression grade 2 or 3 after CRT that underwent surgery. For each patient we determined response pattern, size of the largest vital tumor fragment or bulk and the shortest distance from the vital tumor to the luminal surface. The response pattern was shrinkage in 14 patients and fragmentation in 16 patients. For both groups combined, the largest vital tumor fragment per patient was smaller than 1mm for 38% of patients, below 0.2mm for 12% of patients and for one patient as small as 0.06mm. For 29% of patients the vital tumor remnant was present within the first 0.01mm from the luminal surface and for 87% within 0.5mm. Our results explain why it is difficult to differentiate between a good clinical and complete response in rectal cancer patients using endoscopy and MRI, since in many patients submillimeter tumor fragments remain below the luminal surface. To detect residual vital tumor tissue in all patients included in this study a technique with a spatial resolution of 0.06mm and an imaging depth of 8.9mm would have been required. Optical imaging techniques offer the possibility of detecting majority of these cases due to the potential of both high-resolution imaging and enhanced contrast between tissue types. These techniques could thus serve as a complimentary tool to conventional methods for rectal cancer response assessment.</p

Identification of mitochondrial toxicants by combined in silico and in vitro studies: a structure-based view on the adverse outcome pathway

Toxicolog

Size and depth of residual tumor after neoadjuvant chemoradiotherapy in rectal cancer – implications for the development of new imaging modalities for response assessment

With the shift towards organ preserving treatment strategies in rectal cancer it has become increasingly important to accurately discriminate between a complete and good clinical response after neoadjuvant chemoradiotherapy (CRT). Standard of care imaging techniques such as CT and MRI are well equipped for initial staging of rectal tumors, but discrimination between a good clinical and complete response remains difficult due to their limited ability to detect small residual vital tumor fragments. To identify new promising imaging techniques that could fill this gap, it is crucial to know the size and invasion depth of residual vital tumor tissue since this determines the requirements with regard to the resolution and imaging depth of potential new optical imaging techniques. We analyzed 198 pathology slides from 30 rectal cancer patients with a Mandard tumor regression grade 2 or 3 after CRT that underwent surgery. For each patient we determined response pattern, size of the largest vital tumor fragment or bulk and the shortest distance from the vital tumor to the luminal surface. The response pattern was shrinkage in 14 patients and fragmentation in 16 patients. For both groups combined, the largest vital tumor fragment per patient was smaller than 1mm for 38% of patients, below 0.2mm for 12% of patients and for one patient as small as 0.06mm. For 29% of patients the vital tumor remnant was present within the first 0.01mm from the luminal surface and for 87% within 0.5mm. Our results explain why it is difficult to differentiate between a good clinical and complete response in rectal cancer patients using endoscopy and MRI, since in many patients submillimeter tumor fragments remain below the luminal surface. To detect residual vital tumor tissue in all patients included in this study a technique with a spatial resolution of 0.06mm and an imaging depth of 8.9mm would have been required. Optical imaging techniques offer the possibility of detecting majority of these cases due to the potential of both high-resolution imaging and enhanced contrast between tissue types. These techniques could thus serve as a complimentary tool to conventional methods for rectal cancer response assessment

A quantitative AOP of mitochondrial toxicity based on data from three cell lines

Adverse Outcome Pathways (AOPs) are increasingly used to support the integration of in vitro data in hazard assessment for chemicals. Quantitative AOPs (qAOPs) use mathematical models to describe the relationship between key events (KEs). In this paper, data obtained in three cell lines, LHUMES, HepG2 and RPTEC/TERT1, using similar experimental protocols, was used to calibrate a qAOP of mitochondrial toxicity for two chemicals, rotenone and deguelin. The objectives were to determine whether the same qAOP could be used for the three cell types, and to test chemical-independence by cross-validation with a dataset obtained on eight other chemicals in LHUMES cells. Repeating the calibration approach for both chemicals in three cell lines highlighted various practical difficulties. Even when the same readouts of KEs are measured, the mathematical functions used to describe the key event relationships may not be the same. Cross-validation in LHUMES cells was attempted by estimating chemical-specific potency at the molecular initiating events and using the rest of the calibrated qAOP to predict downstream KEs: toxicity of azoxystrobin, carboxine, mepronil and thifluzamide was underestimated. Selection of most relevant readouts and accurate characterization of the molecular initiating event for cross-validation are critical when designing in vitro experiments targeted at calibrating qAOPs.Toxicolog