Genetic and Epigenetic Traits as Biomarkers in Colorectal Cancer

Colorectal cancer is a major health burden, and a leading cause of cancer-related deaths in industrialized countries. The steady improvements in surgery and chemotherapy have improved survival, but the ability to identify high- and low-risk patients is still somewhat poor. Molecular biology has, over the years, given insight into basic principles of colorectal cancer initiation and development. These findings include aberrations increasing risk of tumor development, genetic changes associated with the stepwise progression of the disease, and errors predicting response to a specific treatment. Potential biomarkers in colorectal cancer are extensively studied, and how the molecular aberrations relate to clinical features. Yet, little of this knowledge has been possible to transfer into clinical practice. In this review, an overview of colorectal cancer genetics will be given, as well as how aberrations found in this tumor type are proposed as biomarkers for risk prediction, as diagnostic tools, for prognosis or prediction of treatment outcome.publishedVersio

Some prognosticc factors for the therapy of patients with Non-Hodgkin's Lymphomas

A number of factors influencing the results of therapy and the outcome of disease for patients with non-Hodgkin's lymphomas have been reviewed. Clearly these factors have a restricted prognostic value in a large number of cases, because of a lack of precise information on most factors involved, and on the significance of the relations between these factors and still unknown factors. In the following chapters some variables influencing the prognosis of the disease have been studied in more detail. The group of low-grade malignant lymphomas, in particular the follicular centre cell tumours, are characterized by a heterogeneous clinical behaviour. Attempts to define subgroups with a uniform clinical course on either immunological grounds, cytokinetic data, or the clinical stage have not been very successful. In the chapters II and III the significance of a more precise histocytological analysis for the prognosis under therapy is presented. In the treatment of high-grade malignant lymphomas the lack of results has led to a progressive intensification of chemotherapy regimens. Factors like histology and immunological markers did not seem to have a really important role until now. The most important condition was to achieve a complete remission, giving a better chance for prolonged survival and eventually cure. The moderate improvements with aggressive chemotherapy now show that some cytologically defined subgroups have a different course under therapy, and also that the amount of total tumour load is important for the results of treatment. However, the intensive chemotherapy protocols needed have a high treatment related toxicity, and the initial survival is also reduced by a high mortality rate. Side effects often prevent effective therapy because dose reduction or lengthening of the interval between the courses have to be instituted. Since at the start of the study the most important prognostic factors in high-grade NHL seemed to be the tumour mass and the induction of a CR, a new induction regimen was developed on the basis of the studies of Skipper et al .138 This combined pulse administration of corticosteroids and S-phase specific drugs, preceding conventional therapy. The purpose was to achieve a fast initial tumour load reduction with less toxicity, as described in chapter IV. The individual responses to identical chemotherapy is variable because of insufficient pharmacokinetic and cell kinetic data. Cell kinetic data in non-Hodgkin's lymphoma are limited because representative material is difficult to obtain. Polyamine excretion in urine can give information about cell growth and cell break down processes. When polyamines are determined in all spontaneous voided urine samples, this can be used as a continuous monitoring model of tumour cell kinetics. We attempted with such a model to obtain information on the individual responses to the cytostatic drugs used in the treatment regimen of the foregoing chapter. In chapter V the results are described of polyamine measurements before and during treatment with S-phase specific drugs of patients with a high-grade malignant lymphoma. ... Zie: Summary

Edutainment and entrepreneurship : a field experiment on youth in Tanzania

The aim of our thesis is to examine an innovative way to educate people in developing countries about business training. This paper analyses whether the edutainment show Ruka Juu, broadcasted in Tanzania in the spring of 2011, has had an informational or inspirational impact on youth in Tanzania when it comes to entrepreneurship. We find that Ruka Juu has led to increased business knowledge for male viewers who have not watched similar shows before, indicating that the show has had an informational impact. In addition we find an inspiration to learn more about business related topics for females. If an edutainment show like Ruka Juu successfully can express its educational approach, it can help create employment opportunities in developing countries

DIZZYNET 2020: basic and clinical vestibular research united

Objective!#!To investigate diagnostic accuracy of a nerve ultrasound (US) protocol that is individualized to a patient's clinical deficits for the differentiation of amyotrophic lateral sclerosis with predominant lower motoneuron disease (ALS/LMND) and multifocal motor neuropathy (MMN).!##!Methods!#!Single-center, prospective, examiner-blinded, diagnostic study in two cohorts. Cohort I (model development): Convenience sample of subjects with ALS/LMND or MMN according to revised El-Escorial or EFNS guidelines. Cohort II (model validation): Consecutively recruited treatment-naïve subjects with suspected diagnosis of ALS/LMND or MMN. Cutoffs for 28 different US values were determined by Receiver Operating Curve (ROC) in cohort I. Area Under The Curve (AUC) of US was compared to nerve conduction studies (NCS). Diagnostic accuracy of US protocols, individualized according to clinical deficits, was compared to former rigid non-individualized protocols and to random examination site selection in cohort II.!##!Results!#!48 patients were recruited. In cohort I (28 patients), US had higher ROC AUCs than NCS, US 0.82 (0.12) (mean (standard deviation)), NCS (compound muscle action potential (CMAP) 0.60 (0.09), p < .001; two-sided t-test). US models based on the nerve innervating the clinically most affected muscles had higher correct classification rates (CCRs, 93%) in cohort II than former rigid protocols (85% and 80%), or models with random measurement site selection (66% and 80%).!##!Conclusions!#!Clinically guided US protocols for differentiation of ALS/LMND from MMN increase diagnostic accuracy when compared to clinically unguided protocols. They also require less measurements sites to achieve this accuracy