Libyan breast cancer: Health services and biology. Diagnosis delay and prognostic value of DNA pploidy, S-phase fraction, and Ki-67 and Bcl-2 immunohistochemistry

The aim of this study was to investigate the diagnosis delay and its impact on the stage of disease. The study also evaluated a nuclear DNA content, immunohistochemical expression of Ki-67 and bcl-2, and the correlation of these biological features with the clinicopathological features and patient outcome. 200 Libyan women, diagnosed during 2008–2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. Also retrospective preclinical and clinical data were collected from medical records on a form (questionnaire) in association with the interview. Tumor material of the patients was collected and nuclear DNA content analysed using DNA image cytometry. The expression of Ki-67 and bcl-2 were assessed using immunohistochemistry (IHC). The studies described in this thesis show that the median of diagnosis time for women with breast cancer was 7.5 months and 56% of patients were diagnosed within a period longer than 6 months. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was also associated with initial breast symptom(s) that did not include a lump, old age, illiteracy, and history of benign fibrocystic disease. The patients who showed diagnosis delay had bigger tumour size (p<0.0001), positive lymph nodes (p<0.0001), and high incidence of late clinical stages (p<0.0001). Biologically, 82.7% of tumors were aneuploid and 17.3% were diploid. The median SPF of tumors was 11% while the median positivity of Ki-67 was 27.5%. High Ki-67 expression was found in 76% of patients, and high SPF values in 56% of patients. Positive bcl-2 expression was found in 62.4% of tumors. 72.2% of the bcl-2 positive samples were ER-positive. Patients who had tumor with DNA aneuploidy, high proliferative activity and negative bcl-2 expression were associated with a high grade of malignancy and short survival. The SPF value is useful cell proliferation marker in assessing prognosis, and the decision cut point of 11% for SPF in the Libyan material was clearly significant (p<0.0001). Bcl-2 is a powerful prognosticator and an independent predictor of breast cancer outcome in the Libyan material (p<0.0001). Libyan breast cancer was investigated in these studies from two different aspects: health services and biology. The results show that diagnosis delay is a very serious problem in Libya and is associated with complex interactions between many factors leading to advanced stages, and potentially to high mortality. Cytometric DNA variables, proliferative markers (Ki-67 and SPF), and oncoprotein bcl-2 negativity reflect the aggressive behavior of Libyan breast cancer and could be used with traditional factors to predict the outcome of individual patients, and to select appropriate therapy.

Periprocedural prognostic factors in coronary interventions – retrospective studies

Background: Approximately 11,000 revascularization procedures, either percutaneous coronary interventions (PCI) or coronary artery bypass grafting surgery (CABG), are performed yearly in Finland for coronary artery disease. Periprocedural risk factors for mortality and morbidity as well as long-term outcome have been extensively studied in general populations undergoing revascularization. Treatment choice between PCI and CABG in many high risk groups and risk-stratification, however, needs clarification and there is still room for improvement in periprocedural outcomes. Materials and methods: Cohorts of patients from Finnish hospitals revascularized between 2001 and 2011 were retrospectively analyzed. Patient records were reviewed for baseline variables and postprocedural outcomes (stroke, myocardial infarction, quality of life measured by the EQ-5D –questionnaire, repeat revascularization, bleeding episodes). Data on date and mode of death was acquired from Statistics Finland. Statistical analysis was performed to identify predictors of adverse events and compare procedures. Results: Postoperative administration of blood products (red blood cells, fresh frozen plasma, platelets) after isolated CABG independently and dose-dependently increases the risk of stroke. Patients 80 years or older who underwent CABG had better survival at 5 years compared to those who underwent PCI. After adjusting for baseline differences survival was similar. Patients on oral anticoagulation (OAC) for atrial fibrillation (AF) treated with CABG had better survival and overall outcome at 3 years compared to PCI patients. There was no difference in incidence of stroke or bleeding episodes. Differences in outcome remained significant after adjusting for propensity score. Lower health-related quality of life (HRQOL) scores as measured by the visual analogue scale (VAS) of the EQ-5D questionnaire at 6 months after CABG predicted later major adverse cardiac and cerebrovascular events (MACCE). Deteriorating function and VAS scores between 0 and 6 months on the EQ-5D also independently predicted later MACCE. Conclusions: Administration of blood products can increase the risk of stroke after CABG and liberal use of transfusions should be avoided. In the frail subpopulations of patients on OAC and octogenarians CABG appears to offer superior long-term outcome as compared to PCI. Deteriorating HRQOL scores predict later adverse events after CABG. Keywords: percutaneous coronary intervention, coronary artery bypass grafting, age over 80, transfusion, anticoagulants, coronary artery disease, health-related quality of life, outcome.

Insiders´ views as a predictor of stock performance : can insider trading be used to predict stock performance on the United States stock market?

This thesis studies the possibility of using information on insiders’ transactions to forecast future stock returns after the implementation of Sarbanes Oxley Act in July 2003. Insider transactions between July 2003 and August 2009 are analysed with regression tests to identify the relationships between insiders’ transactions and future stock returns. This analysis is complemented with rudimentary bootstrapping procedures to verify the robustness of the findings. The underlying assumption of the thesis is that insiders constantly receive pieces of information that indicate future performance of the company. They may not be allowed to trade on large and tangible pieces of information but they can trade on accumulation of smaller, intangible pieces of information. Based on the analysis in the thesis insiders’ profits were found not to differ from the returns from broad stock index. However, their individual transactions were found to be linked to future stock returns. The initial model was found to be unstable but some of the predictive power could be sacrificed to achieve greater stability. Even after sacrificing some predictive power the relationship was significant enough to allow external investors to achieve abnormal profits after transaction costs and taxes. The thesis does not go into great detail about timing of transactions. Delay in publishing insiders’ transactions is not taken into account in the calculations and the closed windows are not studied in detail. The potential effects of these phenomena are looked into and they do not cause great changes in the findings. Additionally the remuneration policy of an insider or a company is not taken into account even though it most likely affects the trading patterns of insiders. Even with the limitations the findings offer promising opportunities for investors to improve their investment processes by incorporating additional information from insiders’ transaction into their decisions. The findings also raise questions on how insider trading should be regulated. Insiders achieve greater returns than other investors based on superior information. On the other hand, more efficient information transfer could warrant more lenient regulation. The fact that insiders’ returns are dominated by the large investment stake they maintain all the time in their own companies also speaks for more leniency. As Sarbanes Oxley Act considerably modified the insider trading landscape, this analysis provides information that has not been available before. The thesis also constitutes a thorough analysis of insider trading phenomenon which has previously been somewhat separated into several studies.

Survival competencies in SMEs in changing business environments

The thesis examines the competencies that enable business survival in changing business environments from the perspective of Russian and Finnish micro, small, and medium-sized enterprises in the field of forest industry. Additionally, it studies the competence transformation necessary in SMEs for successful continuation of business operations when a firm considers transferring its business to another industry. The dissertation builds a holistic firm-level view of survival competencies for SMEs facing changes in their business environments. The holistic firm-level view of competencies includes both the individual-level and the firm-level perspectives, regardless of the position of the person in a firm. The findings highlight the importance of high-level individual competencies and the ability to perform versatile tasks in a firm. In addition, continuous business environment scanning, self-evaluation of personal competencies, willingness to renew and change, open-mindedness, and a readiness to network, are competencies that belong to and need to be taken care of by everybody – employees and employers - in a firm. In addition to previous competencies, an ability to manage every-day business also needs to be embedded in SME owners/managers. Furthermore, Russian SMEs seem to be more proactive in change situations, when compared with Finnish SMEs, which are used to operate in a more stable business environment. In conclusion, it can be said that the thesis adds to SME literature by introducing the concept of ‘SME-level competencies’, a combination of previously discussed organisational and networking competencies which are needed in order to survive through change. Furthermore, the thesis concludes with new competence classifications, such as operational and change competencies, which offer new information concerning the required competencies by which a firm may reduce the resistance to change that can hinder business renewal. For SME practitioners, the study suggests proper preparation and proactive operations in their business to reduce the influence of endless changes, and reminds SME owners/managers that changes are, however, a significant source of new business opportunities. For educational players, the study suggests upgrading educational and training systems by improving the training as regards attitudes towards work, and especially training in the comprehensive working abilities needed in SMEs to master diverse tasks. Finally, for public actors the study suggests providing stronger support to entrepreneurs by boosting SMEs entrepreneurial conditions and the existing business possibilities in change situations. This can be done by encouraging a legislative and entrepreneurial climate that responds better to the demands of SMEs.

Forecasting with social media – Using Facebook likes to predict the results of the 2015 Finnish Parliamentary elections

Already one-third of the human population uses social media on a daily basis. The biggest social networking site Facebook has over billion monthly users. As a result, social media services are now recording unprecedented amount of data on human behavior. The phenomenon has certainly caught the attention of scholars, businesses and governments alike. Organizations around the globe are trying to explore new ways to benefit from the massive databases. One emerging field of research is the use of social media in forecasting. The goal is to use data gathered from online services to predict offline phenomena. Predicting the results of elections is a prominent example of forecasting with social media, but regardless of the numerous attempts, no reliable technique has been established. The objective of the research is to analyze how accurately the results of parliament elections can be forecasted using social media. The research examines whether Facebook “likes” can be effectively used for predicting the outcome of the Finnish parliament elections that took place in April 2015. First a tool for gathering data from Facebook was created. Then the data was used to create an electoral forecast. Finally, the forecast was compared with the official results of the elections. The data used in the research was gathered from the Facebook walls of all the candidates that were running for the parliament elections and had a valid Facebook page. The final sample represents 1131 candidates and over 750000 Facebook “likes”. The results indicate that creating a forecast solely based on Facebook “likes” is not accurate. The forecast model predicted very dramatic changes to the Finnish political landscape while the official results of the elections were rather moderate. However, a clear statistical relationship between “likes” and votes was discovered. In conclusion, it is apparent that citizens and other key actors of the society are using social media in an increasing rate. However, the volume of the data does not directly increase the quality of the forecast. In addition, the study faced several other limitations that should be addressed in future research. Nonetheless, discovering the positive correlation between “likes” and votes is valuable information that can be used in future studies. Finally, it is evident that Facebook “likes” are not accurate enough and a meaningful forecast would require additional parameters.

Life without Phd? – Phd Oxygen Sensor Proteins in Hypoxic Carcinoma Cell Survival

The microenvironment within the tumor plays a central role in cellular signaling. Rapidly proliferating cancer cells need building blocks for structures as well as nutrients and oxygen for energy production. In normal tissue, the vasculature effectively transports oxygen, nutrient and waste products, and maintains physiological pH. Within a tumor however, the vasculature is rarely sufficient for the needs of tumor cells. This causes the tumor to suffer from lack of oxygen (hypoxia) and nutrients as well as acidification, as the glycolytic end product lactate is accumulated. Cancer cells harbor mutations enabling survival in the rough microenvironment. One of the best characterized mutations is the inactivation of the von Hippel-Lindau protein (pVHL) in clear cell renal cell carcinoma (ccRCC). Inactivation causes constitutive activation of hypoxia-inducible factor HIF which is an important survival factor regulating glycolysis, neovascularization and apoptosis. HIFs are normally regulated by HIF prolyl hydroxylases (PHDs), which in the presence of oxygen target HIF α-subunit to ubiquitination by pVHL and degradation by proteasomes. In my thesis work, I studied the role of PHDs in the survival of carcinoma cells in hypoxia. My work revealed an essential role of PHD1 and PHD3 in cell cycle regulation through two cyclin-dependent kinase inhibitors (CKIs) p21 and p27. Depletion of PHD1 or PHD3 caused a cell cycle arrest and subjected the carcinoma cells to stress and impaired the survival.