Soveltuvuuskokeella täydennetty opiskelijavalinta : Seurantatutkimus eräiden sosiaali- ja terveysalan teknisluonteisten koulutusohjelmien (apuvälinetekniikka, hammastekniikka ja optometria) opiskelijavalinnan toteuttamisesta

Aptitude-based student selection: A study concerning the admission processes of some technically oriented healthcare degree programmes in Finland (Orthotics and Prosthetics, Dental Technology and Optometry). The data studied consisted of conveniencesamples of preadmission information and the results of the admission processes of three technically oriented healthcare degree programmes (Orthotics and Prosthetics, Dental Technology and Optometry) in Finland during the years 1977-1986 and 2003. The number of the subjects tested and interviewed in the first samples was 191, 615 and 606, and in the second 67, 64 and 89, respectively. The questions of the six studies were: I. How were different kinds of preadmission data related to each other? II. Which were the major determinants of the admission decisions? III. Did the graduated students and those who dropped out differ from each other? IV. Was it possible to predict how well students would perform in the programmes? V. How was the student selection executed in the year 2003? VI. Should clinical vs. statistical prediction or both be used? (Some remarks are presented on Meehl's argument: "Always, we might as well face it, the shadow of the statistician hovers in the background; always the actuary will have the final word.") The main results of the study were as follows: Ability tests, dexterity tests and judgements of personality traits (communication skills, initiative, stress tolerance and motivation) provided unique, non-redundant information about the applicants. Available demographic variables did not bias the judgements of personality traits. In all three programme settings, four-factor solutions (personality, reasoning, gender-technical and age-vocational with factor scores) could be extracted by the Maximum Likelihood method with graphical Varimax rotation. The personality factor dominated the final aptitude judgements and very strongly affected the selection decisions. There were no clear differences between graduated students and those who had dropped out in regard to the four factors. In addition, the factor scores did not predict how well the students performed in the programmes. Meehl's argument on the uncertainty of clinical prediction was supported by the results, which on the other hand did not provide any relevant data for rules on statistical prediction. No clear arguments for or against the aptitude-based student selection was presented. However, the structure of the aptitude measures and their impact on the admission process are now better known. The concept of "personal aptitude" is not necessarily included in the values and preferences of those in charge of organizing the schooling. Thus, obviously the most well-founded and cost-effective way to execute student selection is to rely on e.g. the grade point averages of the matriculation examination and/or written entrance exams. This procedure, according to the present study, would result in a student group which has a quite different makeup (60%) from the group selected on the basis of aptitude tests. For the recruiting organizations, instead, "personal aptitude" may be a matter of great importance. The employers, of course, decide on personnel selection. The psychologists, if consulted, are responsible for the proper use of psychological measures.

Stem Cell Markers in Cancer: Do They Have Clinical Significance?

In cancer, a subpopulation of malignant cells expresses markers of normal stem cells. These cells have the potential of initiating tumor growth and therefore also tumor recurrence. Thus, these cells are called cancer stem cells. A myriad of markers have been applied to identify these cells, but no single marker can be found exclusively in cancer stem cells. In many types of cancer, clinical recurrence and tumor progression are the main causes of mortality, despite intense oncological treatment. It has been proposed that the presence of cancer stem cells causes this resistance to therapy. The scope of this thesis is to investigate the role of stem cell markers and genes in the clinical setting. Especially, the aim was to elucidate the clinical significance of stem cell markers as novel prognostic and diagnostic tools in cancer. Tumor biopsy material from central nervous system tumors (oligodendroglioma, astrocytoma and glioblatoma), neural crest derived tumors (pheochromocytomas) and oral carcinoma was screened for stem cell markers. Initially, 15 stem cell markers were screened in a test series of gliomas. The markers applied for expanded tumor analyses (in 305 cases of glioma, 42 cases of pheochromocytoma, and 73 cases of oral carcinoma) were BMI-1, Snail, p16, mdm2, and c-Myc. Data on marker expression was compared with clinical and pathological parameters. In gliomas, BMI-1 expression was found in nearly all tumors analyzed, but the frequency of BMI-1 expressing cells was highly variable, ranging from 1 to 100%. In oligodendroglioma, BMI-1 expression was identified as a prognostic marker independent of tumor grade and clinical parameters. In pheochromocytoma, Snail expression was shown to distinguish between the metastatic and non-metastatic forms of the tumor. Snail expression was seen only in metastatic tumors, whereas non-metastatic tumors did not commonly express Snail. Finally, in oral carcinoma, BMI-1 expression was seen in roughly 80% of tumors, and Snail expression was high or very high in all cases. The lack of BMI-1 expression was associated with early relapse in oral carcinoma.

Blood pressure lowering effects of Lactobacillus helveticus fermented milk containing bioactive peptides Ile-Pro-Pro and Val-Pro-Pro; mechanistic, kinetic and clinical studies

The purpose of the present study was to evaluate the effects of Lactobacillus helveticus fermented milk (peptide milk) containing the casein-derived tripeptides Isoleucyl-prolyl-proline (Ile-Pro-Pro) and Valyl-prolyl-proline (Val-Pro-Pro) on blood pressure and vascular function in hypertensive subjects. The peptide milk lowered systolic and diastolic blood pressure in long-term use in hypertensive subjects when blood pressure was measured by using 24-hour ambulatory blood pressure measurement (ABPM). The blood pressure lowering effect was seen with the dose of 50 mg of tripeptides, and a tendency for lowering blood pressure was also observed when the dose was 5 mg. No adverse effects compared to the placebo group were reported or detected in laboratory analysis. The effect of the peptide milk on arterial stiffness was shown using two different methods, the ambulatory arterial stiffness index (AASI) and pulse wave analysis (PWA). According to the AASI, arterial stiffness was significantly reduced in the peptide milk group compared to the baseline level, but the difference was not significant compared to the placebo group. PWA showed that the peptide milk reduced arterial stiffness significantly compared to the placebo group. Endothelium-independent relaxation (nitroglycerin) and endothelium-dependent relaxation (salbutamol) did not differ between the groups. The blood pressure lowering mechanisms of the tripeptides and the kinetics of Ile-Pro-Pro were investigated using spontaneously hypertensive rats (SHR) and Sprague-Dawley rats. Previous studies have suggested that the blood pressure lowering effect of the tripeptides Ile-Pro-Pro and Val-Pro-Pro is based on angiotensin-converting enzyme inhibition, but the present findings did not agree with these previous studies. It was shown in SHR that calcium, potassium and magnesium may also have an important role in attenuating the development of hypertension as part of the peptide milk effect. In addition, the present study suggests indirectly that improved endothelial nitric oxide release capacity is not the mechanism by which peptide milk mediates its favourable circulatory effects. The kinetics of Ile-Pro-Pro were studied using adult Sprague-Dawley rats. The results showed that orally administered Ile-Pro-Pro is absorbed at least partly intact from the gastrointestinal tract. Radiolabelled Ile-Pro-Pro was distributed in different tissues and considerable radioactivity levels were found in tissues related to the renin-angiotensin system (RAS), adrenals, aorta and kidneys. Ile-Pro-Pro does not bind to plasma proteins, and therefore it is possible that its blood pressure lowering effect is mediated by free Ile-Pro-Pro. In conclusion, consumption of the peptide milk lowers blood pressure and reduces arterial stiffness in hypertensive subjects. Ile-Pro-Pro can be absorbed partly intact from the gastrointestinal tract and might accumulate in tissues related to the RAS. The precise blood pressure lowering mechanism of peptide milk remains to be studied.

The influence of HIV infection to the periodontium; a clinical, microbiological, and enzymological study

The main targets of human immunodeficiency virus (HIV) are CD4 receptors of CD4+ lymphocytes and many other cells such as monocytes/macrophages, megakaryocytes, peripheral blood dendritic cells, follicular dendritic cells (DC), epidermal Langerhans cells, and astrocytes. Infection and killing of CD4+ lymphocytes or false reaction of the body to HIV infection and the spontaneous apoptosis of CD4+ lymphocytes decrease CD4+ lymphocyte counts leading to immunosuppression, further disease progression, and appearance of opportunistic infections and malignancies. Oral manifestations are considered to be among the first signs of HIV infection. Enhanced degradation of extracellular matrix and basement membrane components in oral diseases including periodontitis is caused by Zn-dependent enzymes called matrix metalloproteinases (MMPs). The levels and degrees of activation of MMP-1, -2, -3, -7, -8, -9, -25, -26, tissue inhibitors of MMPs (TIMP)-1 and -2, and myeloperoxidase (MPO) and collagenolytic/gelatinolytic activities, and also Ig A, -G, and -M, total protein, and albumin levels in a two-year follow-up were studied from salivary samples. The expression of MMP-7, -8, -9, -25, and -26 immunoreactivities in gingival tissue specimens were studied. Healthy HIV-negative subjects served as controls. All studied clinical periodontal parameters and microbiological evaluation of the periodontopathogens showed that periodontal health of the HIV-positive patients was moderately decreased in comparison to the healthy controls. The levels of Candida in the periodontal pockets and salivary MPO increased with the severity of HIV infection. Immunoreactivities and levels of MMPs and TIMPs, and MMP activities (collagenase, gelatinase) were enhanced in the HIV-positive patient salivary samples relative to the healthy controls regardless of the phase of HIV infection. However, these parameters did not reflect periodontal status in a similar way as in the generally healthy periodontitis patients. Salivary total protein, albumin, IgA, -G, and -M levels were significantly higher in all phases of HIV infection compared to the controls, and salivary total protein, IgG and IgM levels remained higher after two years follow-up, partly correlating with the disease progression and which may reflect the leakage of serum components into the mouth and thus a decreased mucosal barrier. Salivary analyses of MMPs and TIMPs with immunohistochemical analyses showed that HIV infection could predispose to periodontal destruction when compared with healthy controls or the body s defence reactions associated with HIV infection may have been reflected or mediated by MMPs.

Temporomandibular disorders and related psychosocial factors in non-patients : A survey and a clinical follow-up study based on the RDC/TMD

Temporomandibular disorders (TMD) and psychosocial factors reportedly associate. The underlying factors remain partially obscure, however, and further studies are required to clarify the relationships. The aims of this study were thus to assess in a non-patient working population the prevalence of TMD and related symptoms, and to clinically diagnose and follow the natural courses of TMD over a one-year period. In addition, possible comorbidity of temporomandibular and/or neck muscle pain and perceived stress and their impact on work performance were investigated, as well as how various psychosocial aspects relate to TMD. A questionnaire was mailed to all 30- to 55-year-old employees of the Finnish Broadcasting Company Ltd. whose employment in the Helsinki area had lasted at least five years (n = 1784). Of the 1339 subjects, who returned the questionnaire, 241 were examined according to the RDC/TMD and standard neck muscle palpation methods. Clinical signs of temporomandibular and/or neck muscle pain were found in 118 subjects. One-year follow-up TMD examinations were conducted on 211 subjects. The prevalence of frequent painless TMJ-related symptoms was 10%, orofacial pain 7%, neck pain 38%, and headache 15%. TMD diagnoses were: myofascial pain (13%), disc displacements (16%), and arthralgia, osteoarthritis, osteoarthrosis (4%). Chronic myofascial pain was present in 7% and chronic disc displacement with reduction in 11% of the subjects. Symptoms were significantly associated with almost all the studied psychosocial symptoms. Reduced work performance was significantly positively associated with continuous pain, severity of pain, and health stress perception, and according to logistic regression, somatization with the probability of having chronic myofascial pain. It could be concluded based on the results of this study among a non-patient working population that TMD and related symptoms are common and associated with psychosocial factors. Moreover, myofascial pain and disc displacement with reduction are the most common diagnoses of TMD. In addition, self-reported health related stress, and continuous pain in temporomandibular and/or neck muscles are associated with reduced work performance, and somatization is significantly associated with chronic myofascial pain.

Molecular and clinical characteristics of tricarboxylic acid cycle-associated tumors

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare, dominantly inherited tumor predisposition syndrome characterized by benign cutaneous and uterine (ULM) leiomyomas, and sometimes renal cell cancer (RCC). A few cases of uterine leiomyosarcoma (ULMS) have also been reported. Mutations in a nuclear gene encoding fumarate hydratase (FH), an enzyme of the mitochondrial tricarboxylic acid cycle (TCA cycle), underlie HLRCC. As a recessive condition, germline mutations in FH predispose to a neurological defect, FH deficiency (FHD). Hereditary paragangliomatosis (HPGL) is a dominant disorder associated with paragangliomas and pheochromocytomas. Inherited mutations in three genes encoding subunits of succinate dehydrogenase (SDH), also a TCA cycle enzyme, predispose to HPGL. Both FH and SDH seem to act as tumor suppressors. One of the consequences of the TCA cycle defect is abnormal activation of HIF1 pathway ( pseudohypoxia ) in the HLRCC and HPGL tumors. HIF1 drives transcription of genes encoding e.g. angiogenetic factors which can facilitate tumor growth. Recently hypoxia/HIF1 has been suggested to be one of the causes of genetic instability as well. One of the aims of this study was to broaden the clinical definers of HLRCC. To determine the cancer risk and to identify possible novel tumor types associated with FH mutations eight Finnish HLRCC/FHD families were extensively evaluated. The extension of the pedigrees and the Finnish Cancer Registry based tumor search yielded genealogical and cancer data of altogether 868 individuals. The standardized incidence ratio-based comparison of HLRCC/FHD family members with general Finnish population revealed 6.5-fold risk for RCC. Moreover, risk for ULMS was highly increased. However, according to the recent and more stringent diagnosis criteria of ULMS many of the HLRCC uterine tumors previously considered malignant are at present diagnosed as atypical or proliferative ULMs (with a low risk of recurrence). Thus, the formation of ULMS (as presently defined) in HLRCC appears to be uncommon. Though increased incidence was not observed, interestingly the genetic analyses suggested possible association of breast and bladder cancer with loss of FH. Moreover, cancer cases were exceptionally detected in an FHD family. Another clinical finding was the conventional (clear cell) type RCC of a young Spanish HLRCC patient. Conventional RCC is distinct from the types previously observed in this syndrome but according to these results, FH mutation may underlie some of young conventional cancer cases. Secondly, the molecular pathway from defective TCA cycle to tumor formation was intended to clarify. Since HLRCC and HPGL tumors display abnormally activated HIF1, the hypothesis on the link between HIF1/hypoxia and genetic instability was of interest to study in HLRCC and HPGL tumor material. HIF1α (a subunit of HIF1) stabilization was confirmed in the majority of the specimens. However, no repression of MSH2, a protein of DNA mismatch repair system, or microsatellite instability (MSI), an indicator of genetic instability, was observed. Accordingly, increased instability seems not to play a role in the tumorigenesis of pseudohypoxic TCA cycle-deficient tumors. Additionally, to study the putative alternative functions of FH, a recently identified alternative FH transcript (FHv) was characterized. FHv was found to contain instead of exon 1, an alternative exon 1b. Differential subcellular distribution, lack of FH enzyme activity, low mRNA expression compared to FH, and induction by cellular stress suggest FHv to have a role distinct from FH, for example in apoptosis or survival. However, the physiological significance of FHv requires further elucidation.

Novel Insights into the Molecular Genetic Background of Colorectal Tumors

Many of the genes predisposing to highly penetrant colorectal cancer (CRC) syndromes, including hereditary non-polyposis colorectal cancer (MLH1, MSH2, MSH6, PMS2), familial adenomatous polyposis (APC), Peutz-Jeghers syndrome (LKB1), juvenile polyposis (SMAD4, BMPR1A), MYH-associated polyposis (MYH), and Cowden syndrome (PTEN) have already been discovered. Identification of these genes has allowed a more precise classification of the hereditary CRC syndromes and provided a means for predictive genetic testing and surveillance. Some of the genes are also involved in sporadic cancer forms, and therefore the investigation of the rare CRC syndromes has been a breakthrough for general cancer research. Despite the accumulating knowledge on hereditary cancer syndromes, a significant number of familial CRCs remain molecularly unexplained after genetic testing, reflecting the possibility of other predisposing genes or existence of novel syndromes. Moreover, genetic variants conferring low-penetrance risk are still largely unknown. In this study, we examined the role of some new high- and low-penetrance alleles on CRC predisposition. We identified disease causing MYH mutations in a subset (9%) of patients with APC and AXIN2 mutation negative adenomatous polyposis. Due to differences in the pattern of inheritance and clinical manifestation, screening for mutations in MYH is beneficial in view of genetic counselling and surveillance. A novel functionally deficient MYH founder mutation A459D was identified in the Finnish population, and this finding had immediate clinical implications for genetic counselling of at risk families. Many patients with hamartomatous polyposis remain without molecular diagnosis due to atypical phenotypes. We therefore sought to classify 49 patients with unexplained hamartomatous or hyperplastic/mixed polyposis by extensive molecular analyses of PTEN, LKB1, BMPR1A, SMAD4, ENG, BRAF, MYH, and BHD along with revision of polyp histology. Mutations were identified in 11/49 (22%) of the patients. In 6 cases the molecular diagnosis was re-classified guiding surveillance and decisions for prophylactic surgery. Re-evaluation of polyp histology with subsequent more accurate selection of candidate gene analyses is beneficial and can be recommended for patients with unexplained polyposis. Furthermore, germline mutations in ENG underlying juvenile polyposis were described for the first time, characterizing a possible novel genetically defined form of hereditary CRC. Association analyses on two putative low-penetrance alleles, NOD2 3020insC and MDM2 SNP309 were performed in a population-based series of 1042 Finnish CRC patients and in cancer-free controls. In contrast to previous results, NOD2 3020insC did not associate with CRC or age at disease onset in the Finnish population. These data suggest that NOD2 3020insC alone might not be sufficient for CRC predisposition. MDM2 SNP309 was as common in the CRC cohort as in the healthy controls. Interesting trends, however, were observed, which after correction for multiple testing did not reach statistical significance. SNP309 was more common in female CRC patients and a trend towards an earlier age at disease onset was observed in women with SNP309. Subsequent studies have supported this observation and SNP309 could affect gender- or hormone-related tumorigenesis. Finally, a large-scale unbiased effort was designed to characterize the complete mutatome of CRC with microsatellite instability (MSI). Using an approach combining expression microarray and genome database searches, we were able to identify putative MSI target genes. Further characterization of one of the genes suggested that it might play a role also in microsatellite stable CRC and Peutz-Jeghers syndrome pathogenesis.

Silvicultural decisions based on simulation-optimization systems

Forest management is facing new challenges under climate change. By adjusting thinning regimes, conventional forest management can be adapted to various objectives of utilization of forest resources, such as wood quality, forest bioenergy, and carbon sequestration. This thesis aims to develop and apply a simulation-optimization system as a tool for an interdisciplinary understanding of the interactions between wood science, forest ecology, and forest economics. In this thesis, the OptiFor software was developed for forest resources management. The OptiFor simulation-optimization system integrated the process-based growth model PipeQual, wood quality models, biomass production and carbon emission models, as well as energy wood and commercial logging models into a single optimization model. Osyczka s direct and random search algorithm was employed to identify optimal values for a set of decision variables. The numerical studies in this thesis broadened our current knowledge and understanding of the relationships between wood science, forest ecology, and forest economics. The results for timber production show that optimal thinning regimes depend on site quality and initial stand characteristics. Taking wood properties into account, our results show that increasing the intensity of thinning resulted in lower wood density and shorter fibers. The addition of nutrients accelerated volume growth, but lowered wood quality for Norway spruce. Integrating energy wood harvesting into conventional forest management showed that conventional forest management without energy wood harvesting was still superior in sparse stands of Scots pine. Energy wood from pre-commercial thinning turned out to be optimal for dense stands. When carbon balance is taken into account, our results show that changing carbon assessment methods leads to very different optimal thinning regimes and average carbon stocks. Raising the carbon price resulted in longer rotations and a higher mean annual increment, as well as a significantly higher average carbon stock over the rotation.

A dynamic programming model for optimising feeding and slaughter decisions regarding fattening pigs

Costs of purchasing new piglets and of feeding them until slaughter are the main variable expenditures in pig fattening. They both depend on slaughter intensity, the nature of feeding patterns and the technological constraints of pig fattening, such as genotype. Therefore, it is of interest to examine the effect of production technology and changes in input and output prices on feeding and slaughter decisions. This study examines the problem by using a dynamic programming model that links genetic characteristics of a pig to feeding decisions and the timing of slaughter and takes into account how these jointly affect the quality-adjusted value of a carcass. The model simulates the growth mechanism of a pig under optional feeding and slaughter patterns and then solves the optimal feeding and slaughter decisions recursively. The state of nature and the genotype of a pig are known in the analysis. The main contribution of this study is the dynamic approach that explicitly takes into account carcass quality while simultaneously optimising feeding and slaughter decisions. The method maximises the internal rate of return to the capacity unit. Hence, the results can have vital impact on competitiveness of pig production, which is known to be quite capital-intensive. The results suggest that producer can significantly benefit from improvements in the pig's genotype, because they improve efficiency of pig production. The annual benefits from obtaining pigs of improved genotype can be more than €20 per capacity unit. The annual net benefits of animal breeding to pig farms can also be considerable. Animals of improved genotype can reach optimal slaughter maturity quicker and produce leaner meat than animals of poor genotype. In order to fully utilise the benefits of animal breeding, the producer must adjust feeding and slaughter patterns on the basis of genotype. The results suggest that the producer can benefit from flexible feeding technology. The flexible feeding technology segregates pigs into groups according to their weight, carcass leanness, genotype and sex and thereafter optimises feeding and slaughter decisions separately for these groups. Typically, such a technology provides incentives to feed piglets with protein-rich feed such that the genetic potential to produce leaner meat is fully utilised. When the pig approaches slaughter maturity, the share of protein-rich feed in the diet gradually decreases and the amount of energy-rich feed increases. Generally, the optimal slaughter weight is within the weight range that pays the highest price per kilogram of pig meat. The optimal feeding pattern and the optimal timing of slaughter depend on price ratios. Particularly, an increase in the price of pig meat provides incentives to increase the growth rates up to the pig's biological maximum by increasing the amount of energy in the feed. Price changes and changes in slaughter premium can also have large income effects. Key words: barley, carcass composition, dynamic programming, feeding, genotypes, lean, pig fattening, precision agriculture, productivity, slaughter weight, soybeans