Effectively sampling rectal mucus and assessing the validity of a DNA methylation assay in the detection of colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers in the Western world. Screening for CRC using faecal occult blood test (FOBT) is well established. There is evidence that DNA based stool tests may be more effective than FOBT. Hypothesis The hypothesis is that in patients with CRC, rectal mucus may contain DNA derived from colonic tumours. It is speculated that quantitative or qualitative assessment of DNA in rectal mucus may permit an improved method of CRC screening. Aims Using surgically resected specimens of colonic tumours: To assess the feasibility and reliability of measuring DNA in mucus samples To compare different devices to measure mucus DNA To assess the amount of mucus DNA at various distances from colonic tumours In patients with CRC and controls: To compare the amount of DNA in rectal mucus Using a panel of 3 DNA methylation markers, to compare the rectal mucus DNA methylation profile between patients with CRC and controls Methods Surgical colectomy specimens were obtained from 25 patients with CRC. The feasibility and repeatability of measuring mucus DNA amounts was established using different buffer solutions, different storage techniques and different sampling devices. Mucus DNA amounts were measured at tumour sites and various distances proximal and distal to the tumour. 58 patients referred to a colorectal outpatient clinic with suspected CRC were assessed. Rectal mucus samples were obtained using a balloon device introduced through a proctoscope. All patients were investigated by colonoscopy to clarify the presence or absence of a CRC. The amount of DNA in the mucus samples was measured. The presence of three DNA methylation markers (NDRG4, TFP12 and GATA4) was assessed in all samples. All studies were approved by the local ethics committee. Results Reliable measurement of DNA from mucus samples was established using balloon, foam and brush devices and a cell lysate buffer. Higher amounts of DNA in surgical specimens were found distal to tumours compared to proximally. In patients with CRC the amount of DNA in rectal mucus was higher than in controls (no disease or benign polyps). The three DNA methylation marker panel had a sensitivity of 87% and specificity of 27.5% for the detection of CRC. Conclusions The results are consistent with the hypothesis that DNA detected in rectal mucus is derived from proximal tumours. Higher levels of rectal mucus DNA are obtained from patients with CRC than from controls. The selected DNA methylation panel was not sufficiently useful in our sample group to be of use as a screening technique, due to poor specificity. Further work is in progress to compare DNA abnormalities in resected tumour tissue with DNA from rectal mucus in the same patients. Future work may be required to improve the panel of DNA abnormalities assessed

Essays on the quality of institutions and economic performance

This thesis builds a model to describe the process of institutional change in which the probability of revolution depends on the state of the economy and the level of education in the society. The model generates two cases. First, when the cost of revolution is lower than the cost of the recession,institutional change will occur. The magnitude of the negative shock,sufficient to cause a revolution, depends on education; the higher the level of education in the society the lower the magnitude of the negative shock. The second case, when the cost of a revolution is higher than the cost of a negative shock, generates a mechanism of marginal institutional changes. Those who hold the power can adjust the quality of institutions to avoid a revolution; the magnitude of the changes necessary to prevent a revolution depends positively on both the magnitude of the shock and the level of education in the society. Both cases predict that institutional improvement is associated with increasing levels of education. We then test the prediction of our model. First, in a dynamic panel analysis of 86 developing countries, the system GMM results demonstrate that the quality of institutions will increase by 10% if years of schooling increase by one standard deviation. This result is confirmed by two separate bias correction estimations (BCFE and LSDV). Second, we use an EU crossregional dataset of the Quality of Government to examine the determinants of institutional quality in European regions. Using the share of atheists in every region as an instrument for education, our IV estimations confirm the prediction of our model. More education leads to better institutions. Additionally, our findings confirm other existing theories of the political and social determinants of the quality of institutions and demonstrate that this phenomenon is not confined to developing countries or even post-communist economies

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide