Free PAPP-A: a Novel Marker in Acute Coronary Syndrome Patients

In recent years, one important objective of cardiovascular research has been to find new markers that would improve the risk stratification and diagnosis of patients presenting with symptoms of acute coronary syndrome (ACS). Pregnancy-associated plasma protein A (PAPP-A) is a large metalloproteinase involved in insulin-like growth factor signalling. It is expressed in various tissues and seems to be involved in many physiological and pathological processes, such as folliculogenesis, bone formation, wound healing, pregnancy and atherosclerosis. The aim of this thesis was to investigate PAPP-A in ACS patients. Circulating concentrations of PAPP-A had been previously shown to be elevated in ACS. In this study it was revealed that the form of PAPP-A causing this elevation was the free noncomplexed PAPP-A. Thus, the form of PAPP-A in the circulation of ACS patients differed from the complexed PAPP-A form abundantly present in the circulation during pregnancy. A point-of-care method based on time-resolved immunofluorometric assays was developed, which enabled the rapid detection of free PAPP-A. The method was found to perform well with serum and heparin plasma samples as well as with heparinized whole blood samples. With this method the concentrations of free PAPP-A in healthy individuals were shown to be negligible. When the clinical performance of the method was evaluated with serum samples from ACS patients, it was shown that the free PAPP-A concentration in the admission sample was an independent predictor of myocardial infarction and death. Moreover, as a prognostic marker, free PAPP-A was revealed to be superior to total PAPPA, i.e. the combination of free and complexed PAPP-A, which has been measured by the other groups in this field. As heparin products are widely used as medication in ACS patients, the effect of heparin products on free PAPP-A molecule and circulating concentrations were also investigated in this study. It was shown that intravenous administration of low molecular weight or unfractionated heparin elicits a rapid release of free PAPP-A into the circulation in haemodialysis patients and patients undergoing angiography. Moreover, the interaction between PAPP-A and heparin was confirmed in gel filtration studies. Importantly, the patients included in the clinical evaluation of the free PAPP-A detection method developed had not received any heparin product medication before the admission sample and thus the results were not affected by the heparin effect. In conclusion, free PAPP-A was identified as a novel marker associated with ACS. The point-of-care methods developed enable rapid detection of this molecule which predicts adverse outcome when measured in the admission sample of ACS patients. However, the effect revealed of heparin products on circulating PAPP-A concentrations should be acknowledged when further studies are conducted related to free or total PAPP-A in ACS.

La relación entre el aprendizaje léxico y el desarrollo gramatical

El presente trabajo se centra en estudiar la relación que existe entre el desarrollo de léxico y el de la morfosintaxis. Concretamente pretendemos explorar el tipo de vocabulario que mejor predice el desarrollo de la morfología verbal y el de la complejidad gramatical, así como establecer el tipo de relación entre desarrollo léxico y desarrollo morfosintáctico. La muestra comprende 517 niños de edades comprendidas entre los 18 meses y los 30 meses. Los datos se han recogido a partir de la adaptación al catalán del instrumento MacArthur-Bates Communicative Development Inventories (CDI). Los resultados muestran que el mejor predictor del desarrollo morfológico y gramatical es el vocabulario de clase cerrada, conjuntamente con el vocabulario general. Por otra parte, se observa una relación predominantemente lineal entre el desarrollo del léxico y el desarrollo morfosintáctico

Spatial and Spectral Separability of Grasslands in the inner Turku Archipelago using Landsat Thematic Mapper Satellite Imagery

The present study investigates the spatial and spectral discrimination potential for grassland patches in the inner Turku Archipelago using Landsat Thematic Mapper satellite imagery. The spatial discrimination potential was computed through overlay analysis using official grassland parcel data and a hypothetical 30 m resolution satellite image capturing the site. It found that Landsat TM imagery’s ability to retrieve pure or near-pure pixels (90% purity or more) from grassland patches smaller than 1 hectare was limited to 13% success, compared to 52% success when upscaling the resolution to 10 x 10 m pixel size. Additionally, the perimeter/area patch metric is proposed as a predictor for the suitability of the spatial resolution of input imagery. Regression analysis showed that there is a strong negative correlation between a patch’s perimeter/area ratio and its pure pixel potential. The study goes on to characterise the spectral response and discrimination potential for the five main grassland types occurring in the study area: recreational grassland, traditional pasture, modern pasture, fodder production grassland and overgrown grassland. This was done through the construction of spectral response curves, a coincident spectral plot and a contingency matrix as well as by calculating the transformed divergence for the spectral signatures, all based on training samples from the TM imagery. Substantial differences in spectral discrimination potential between imagery from the beginning of the growing season and the middle of summer were found. This is because the spectral responses for these five grassland types converge as the peak of the growing season draws nearer. Recreational grassland shows a consistent discrimination advantage over other grassland types, whereas modern pasture is most easily confused. Traditional pasture land, perhaps the most biologically valuable grassland type, can be spectrally discriminated from other grassland types with satisfactory success rates provided early growing season imagery is used.

Hypoxia-associated biomarkers in rectal cancer treated by preoperative radiotherapy or chemoradiotherapy

Hypoksiaan liittyvät biologiset merkkiaineet leikkausta edeltävällä sädehoidolla tai kemosädehoidolla hoidetussa peräsuolisyövässä Peräsuolensyöpä on yleinen pahanlaatuinen kasvain. Leikkausta edeltävä sädehoito annetaan yleensä T3-T4-kasvaimille. Tutkimuksella pyrittiin selvittämään, voidaanko kasvaimen hapenpuutteeseen liittyvillä biologisilla merkkiaineilla arvioida peräsuolisyövän ennustetta leikkausta edeltävän sädehoidon tai kemosädehoidon jälkeen. Tällaisia merkkiaineita ovat hapenpuutteen vaikutuksesta aktivoituva HIF-1alfa hiilihappoanhydraasi IX (CA IX), sokerin kuljetukseen solussa osallistuva GLUT-1 sekä solun tukirankaproteiini ezrin. Tutkimukseen otettiin 178 potilasta, jotka olivat saaneet ennen leikkausta lyhyen (n=77) tai pitkän sädehoidon (n=10), pitkän sädehoidon ja solunsalpaajahoidon (n=37) tai ei mitään hoitoa (n=54). Lisäksi osalta leikkausta edeltävää sädehoitoa saaneelta potilaalta tutkittiin hoitoja edeltävät, diagnostiset näytteet (n=80). Tutkimuksessa käytettiin immunehistokemiallisia värjäysmenetelmiä. Kasvaimen regressiota (TRG) arvioitiin pitkän sädehoidon jälkeisistä näytteistä. Leikkausnäytteissä negatiivinen/heikko CA IX intensiteetti liittyi sekä pidempään tautispesifiseen (p=0.034) että tautivapaaseen elinaikaan (p=0.003) ja pitkän sädehoidon jälkeen HIF-1alfa-negatiivisuus pidempään tautispesifiseen (p=0.001) sekä negatiivinen/heikko GLUT-1 pidempään tautivapaaseen elinaikaan (p=0.066). Voimakas ezrin-ilmentymä diagnostisissa näytteissä liittyi lyhyempään tautivapaaseen ja tautispesifiseen (p=0.027 ja p=0.002) ennusteeseen. Monimuuttuja-analyysissä vahva CA IX intensiteetti leikkausnäytteissä ennusti itsenäisesti huonompaa tautivapaata ja tautispesifistä selviytymistä. Erinomainen TRG liittyi negatiiviseen/heikkoon CA IX- (p=0.057), ezrin- (p=0.012) ja GLUT-1 -ilmentymään (p=0.013) leikkausnäytteissä. Kun kaikki neljä merkkiainetta analysoitiin yhdessä monimuuttuja-analyysissä, CA IX intensiteetti leikkausnäytteissä ennusti itsenäisesti tautispesifistä elinaikaa. Voimakas CA IX-ilmentymä leikkausnäytteissä ja positiivinen HIF-1alfa- ja vahva GLUT-1-ilmentymä pitkän sädehoidon jälkeisissä leikkausnäytteissä sekä vahva ezrin-ilmentymä diagnostisissa näytteissä liittyivät epäsuotuisaan ennusteeseen. Monimuuttujaanalyysissä kohtalainen/voimakas CA IX intensiteetti leikkausnäytteissä ennusti itsenäisesti huonompaa tautivapaata ja tautispesifistä elinaikaa. CA IX on vahva biologinen merkkiaine peräsuolisyövässä.

Understanding the Racial Nature of Police and Immigrant Relations In Finland. The Case of Africans in Turku

The focus of this study is to examine the role of police and immigrants’ relations, as less is known about this process in the country. The studies were approached in two different ways. Firstly, an attempt was made to examine how immigrants view their encounters with the police. Secondly, the studies explored how aware the police are of immigrants’ experiences in their various encounters and interactions on the street level. An ancillary aim of the studies is to clarify, analyse and discuss how prejudice and stereotypes can be tackled, thereby contributing to the general debate about racism and discrimination for better ethnic relations in the country. The data in which this analysis was based is on a group of adults (n=88) from the total of 120 Africans questioned for the entire study (n=45) police cadets and (n=6) serving police officers from Turku. The present thesis is a compilation of five articles. A summary of each article findings follows, as the same data was used in all five studies. In the first study, a theoretical model was developed to examine the perceived knowledge of bias by immigrants resulting from race, culture and belief. This was also an attempt to explore whether this knowledge was predetermined in my attempt to classify and discuss as well as analyse the factors that may be influencing immigrants’ allegations of unfair treatment by the police in Turku. The main finding shows that in the first paper there was ignorance and naivety on the part of the police in their attitudes towards the African immigrant’s prior experiences with the police, and this may probably have resulted from stereotypes or their lack of experience as well as prior training with immigrants where these kinds of experience are rampant in the country (Egharevba, 2003 and 2004a). In exploring what leads to stereotypes, a working definition is the assumption that is prevalent among some segments of the population, including the police, that Finland is a homogenous country by employing certain conducts and behaviour towards ethnic and immigrant groups in the country. This to my understanding is stereotype. Historically this was true, but today the social topography of the country is changing and becoming even more complex. It is true that, on linguistic grounds, the country is multilingual, as there are a few recognised national minority languages (Swedish, Sami and Russian) as well as a number of immigrant languages including English. Apparently it is vital for the police to have a line of communication open when addressing the problem associated with immigrants in the country. The second paper moved a step further by examining African immigrants’ understanding of human rights as well as what human rights violation means or entails in their views as a result of their experiences with the police, both in Finland and in their country of origin. This approach became essential during the course of the study, especially when the participants were completing the questionnaire (N=88), where volunteers were solicited for a later date for an in-depth interview with the author. Many of the respondents came from countries where human rights are not well protected and seldom discussed publicly, therefore understanding their views on the subject can help to explain why some of the immigrants are sceptical about coming forward to report cases of batteries and assaults to the police, or even their experiences of being monitored in shopping malls in their new home and the reason behind their low level of trust in public authorities in Finland. The study showed that knowledge of human rights is notably low among some of the participants. The study also found that female respondents were less aware of human rights when compared with their male counterparts. This has resulted in some of the male participants focussing more on their traditional ways of thinking by not realising that they are in a new country where there is equality in sexes and lack of respect on gender terms is not condoned. The third paper focussed on the respondents’ experiences with the police in Turku and tried to explore police attitudes towards African immigrant clients, in addition to the role stereotype plays in police views of different cultures and how these views have impacted on immigrants’ views of discriminatory policing in Turku. The data is the same throughout the entire studies (n=88), except that some few participants were interviewed for the third paper thirty-five persons. The results showed that there is some bias in mass-media reports on the immigrants’ issues, due to selective portrayal of biases without much investigation being carried out before jumping to conclusions, especially when the issues at stake involve an immigrant (Egharevba, 2005a; Egharevba, 2004a and 2004b). In this vein, there was an allegation that the police are even biased while investigating cases of theft, especially if the stolen property is owned by an immigrant (Egharevba, 2006a, Egharevba, 2006b). One vital observation from the respondents’ various comments was that race has meaning in their encounters and interaction with the police in the country. This result led the author to conclude that the relation between the police and immigrants is still a challenge, as there is rampant fear and distrust towards the police by some segments of the participating respondents in the study. In the fourth paper the focus was on examining the respondents’ view of the police, with special emphasis on race and culture as well as the respondents’ perspective on police behaviour in Turku. This is because race, as it was relayed to me in the study, is a significant predictor of police perception (Egharevba, 2005a; Egharevba and Hannikianen, 2005). It is a known scientific fact that inter-group racial attitudes are the representation of group competition and perceived threat to power and status (Group-position theory). According to Blumer (1958) a sense of group threat is an essential element for the emergence of racial prejudice. Consequently, it was essential that we explored the existing relationship between the respondents and the police in order to have an understanding of this concept. The result indicates some local and international contextual issues and assumptions that were of importance tackling prejudice and discrimination as it exists within the police in the country. Moreover, we have to also remember that, for years, many of these African immigrants have been on the receiving end of unjust law enforcement in their various countries of origin, which has resulted in many of them feeling inferior and distrustful of the police even in their own country of origin. While discussing the issues of cultural difference and how it affects policing, we must also keep in mind the socio-cultural background of the participants, their level of language proficiency and educational background. The research data analysed in this study also confirmed the difficulties associated with cultural misunderstandings in interpreting issues and how these misunderstandings have affected police and immigrant relations in Finland. Finally, the fifth paper focussed on cadets’ attitudes towards African immigrants as well as serving police officers’ interaction with African clients. Secondly, the police level of awareness of African immigrants’ distrustfulness of their profession was unclear. For this reason, my questions in this fifth study examined the experiences and attitudes of police cadets and serving police officers as well as those of African immigrants in understanding how to improve this relationship in the country. The data was based on (n=88) immigrant participants, (n=45) police cadets and 6 serving police officers from the Turku police department. The result suggests that there is distrust of the police in the respondents’ interaction; this tends to have galvanised a heightened tension resulting from the lack of language proficiency (Egharevba and White, 2007; Egharevba and Hannikainen, 2005, and Egharevba, 2006b) The result also shows that the allegation of immigrants as being belittled by the police stems from the misconceptions of both parties as well as the notion of stop and search by the police in Turku. All these factors were observed to have contributed to the alleged police evasiveness and the lack of regular contact between the respondents and the police in their dealings. In other words, the police have only had job-related contact with many of the participants in the present study. The results also demonstrated the complexities caused by the low level of education among some of the African immigrants in their understanding about the Finnish culture, norms and values in the country. Thus, the framework constructed in these studies embodies diversity in national culture as well as the need for a further research study with a greater number of respondents (both from the police and immigrant/majority groups), in order to explore the different role cultures play in immigrant and majority citizens’ understanding of police work.

Commitment to military service among Finnish conscripts

This research establishes the primary components, predictors, and consequences of organizational commitment in the military context. Specifically, the research examines commitment to the military service among Finnish conscripts and whether initial affective commitment prior to service predicts later commitment, attitudes, behavior, and performance, and, furthermore, analyzes the changes in commitment and its possible outcomes. The data were collected from records as well as by surveys from 1,387 rank and file soldiers, immediately after they reported for duty, near the end of basic training, and near the end of 6 to 12 months of service. The data covered a wide array of predictor variables, including background items, attitudes toward conscription, mental and physical health, sociability, training quality, and leadership. Moreover, the archival data included such items as rank, criminal record, performance ratings, and the number of medical examines and exemptions. The measures were further refined based on the results of factor analysis and reliability tests. The results indicated that initial commitment significantly corresponded with expected adjustment, intentions to stay in the military, and acceptance of authority. Moreover, initial commitment moderately related to personal growth, perceived performance, and the number of effective service days at the end of service. During basic training, affective commitment was mostly influenced by challenging training, adjustment experiences, regimentation, and unit climate. At the end of service, committed soldiers demonstrated more personal growth and development in service, had higher-level expected performance, and less malingering during their service. Additionally, they had significantly more positive attitudes toward national defense. The results suggest that affective commitment requires adequate personal adjustment, experiences of personal growth and development, and satisfaction with unit dynamics and training. This research contributes to the theoretical discussion on organizational commitment and the will to defend the nation and advances developing models to support and manage conscript training, education, leadership, and personnel policy. This is achieved by determining the main factors and variables, including their relative strength, that affect commitment to the military service. These findings may also facilitate in designing programs aimed at reducing unwanted discharges and inadequate performance. In particular, these results provide tools for improving conscripts’ overall attachment to and identification with the military service.

Computational methods for tactical simulations

Tämä taktiikan tutkimus keskittyy tietokoneavusteisen simuloinnin laskennallisiin menetelmiin, joita voidaan käyttää taktisen tason sotapeleissä. Työn tärkeimmät tuotokset ovat laskennalliset mallit todennäköisyyspohjaisen analyysin mahdollistaviin taktisen tason taistelusimulaattoreihin, joita voidaan käyttää vertailevaan analyysiin joukkue-prikaatitason tarkastelutilanteissa. Laskentamallit keskittyvät vaikuttamiseen. Mallit liittyvät vahingoittavan osuman todennäköisyyteen, jonka perusteella vaikutus joukossa on mallinnettu tilakoneina ja Markovin ketjuina. Edelleen näiden tulokset siirretään tapahtumapuuanalyysiin operaation onnistumisen todennäköisyyden osalta. Pienimmän laskentayksikön mallinnustaso on joukkue- tai ryhmätasolla, jotta laskenta-aika prikaatitason sotapelitarkasteluissa pysyisi riittävän lyhyenä samalla, kun tulokset ovat riittävän tarkkoja suomalaiseen maastoon. Joukkueiden mies- ja asejärjestelmävahvuudet ovat jakaumamuodossa, eivätkä yksittäisiä lukuja. Simuloinnin integroinnissa voidaan käyttää asejärjestelmäkohtaisia predictor corrector –parametreja, mikä mahdollistaa aika-askelta lyhytaikaisempien taistelukentän ilmiöiden mallintamisen. Asemallien pohjana ovat aiemmat tutkimukset ja kenttäkokeet, joista osa kuuluu tähän väitöstutkimukseen. Laskentamallien ohjelmoitavuus ja käytettävyys osana simulointityökalua on osoitettu tekijän johtaman tutkijaryhmän ohjelmoiman ”Sandis”- taistelusimulointiohjelmiston avulla, jota on kehitetty ja käytetty Puolustusvoimien Teknillisessä Tutkimuslaitoksessa. Sandikseen on ohjelmoitu karttakäyttöliittymä ja taistelun kulkua simuloivia laskennallisia malleja. Käyttäjä tai käyttäjäryhmä tekee taktiset päätökset ja syöttää nämä karttakäyttöliittymän avulla simulointiin, jonka tuloksena saadaan kunkin joukkuetason peliyksikön tappioiden jakauma, keskimääräisten tappioiden osalta kunkin asejärjestelmän aiheuttamat tappiot kuhunkin maaliin, ammuskulutus ja radioyhteydet ja niiden tila sekä haavoittuneiden evakuointi-tilanne joukkuetasolta evakuointisairaalaan asti. Tutkimuksen keskeisiä tuloksia (kontribuutio) ovat 1) uusi prikaatitason sotapelitilanteiden laskentamalli, jonka pienin yksikkö on joukkue tai ryhmä; 2) joukon murtumispisteen määritys tappioiden ja haavoittuneiden evakuointiin sitoutuvien taistelijoiden avulla; 3) todennäköisyyspohjaisen riskianalyysin käyttömahdollisuus vertailevassa tutkimuksessa sekä 4) kokeellisesti testatut tulen vaikutusmallit ja 5) toimivat integrointiratkaisut. Työ rajataan maavoimien taistelun joukkuetason todennäköisyysjakaumat luovaan laskentamalliin, kenttälääkinnän malliin ja epäsuoran tulen malliin integrointimenetelmineen sekä niiden antamien tulosten sovellettavuuteen. Ilmasta ja mereltä maahan -asevaikutusta voidaan tarkastella, mutta ei ilma- ja meritaistelua. Menetelmiä soveltavan Sandis -ohjelmiston malleja, käyttötapaa ja ohjelmistotekniikkaa kehitetään edelleen. Merkittäviä jatkotutkimuskohteita mallinnukseen osalta ovat muun muassa kaupunkitaistelu, vaunujen kaksintaistelu ja maaston vaikutus tykistön tuleen sekä materiaalikulutuksen arviointi.

Testing Futures Market Efficiency and Optimal Hedge Ratio Estimation: Evidence from Futures and Options on RTS

This study investigates futures market efficiency and optimal hedge ratio estimation. First, cointegration between spot and futures prices is studied using Johansen method, with two different model specifications. If prices are found cointegrated, restrictions on cointegrating vector and adjustment coefficients are imposed, to account for unbiasedness, weak exogeneity and prediction hypothesis. Second, optimal hedge ratios are estimated using static OLS, and time-varying DVEC and CCC models. In-sample and out-of-sample results for one, two and five period ahead are reported. The futures used in thesis are RTS index, EUR/RUB exchange rate and Brent oil, traded in Futures and options on RTS.(FORTS) For in-sample period, data points were acquired from start of trading of each futures contract, RTS index from August 2005, EUR/RUB exchange rate March 2009 and Brent oil October 2008, lasting till end of May 2011. Out-of-sample period covers start of June 2011, till end of December 2011. Our results indicate that all three asset pairs, spot and futures, are cointegrated. We found RTS index futures to be unbiased predictor of spot price, mixed evidence for exchange rate, and for Brent oil futures unbiasedness was not supported. Weak exogeneity results for all pairs indicated spot price to lead in price discovery process. Prediction hypothesis, unbiasedness and weak exogeneity of futures, was rejected for all asset pairs. Variance reduction results varied between assets, in-sample in range of 40-85 percent and out-of sample in range of 40-96 percent. Differences between models were found small, except for Brent oil in which OLS clearly dominated. Out-of-sample results indicated exceptionally high variance reduction for RTS index, approximately 95 percent.

Does hyperglycemia in pregnancy change fetal kidney growth?: a longitudinal prospective study

PURPOSE: To measure fetal renal volume in normoglycemic and hyperglycemic pregnancies. METHODS: A longitudinal prospective study was conducted and included 92 hyperglycemic and 339 normoglycemic pregnant women attended at the prenatal service of a hospital from Rio de Janeiro State. Ultrasound examinations were performed to estimate gestational age at baseline and the kidney volume was estimated using the prolate ellipsoid volume equation. RESULTS: Fetal kidney volume growth between normoglycemic and hyperglycemic pregnancies are significantly different. The fetal kidney volume growth in pregnancy is positively correlated with gestational age explained by these predictor equations, by group: normal renal volume = exp (6.186+0.09×gestational week); hyperglycemic renal volume = exp (6.978+0.071×gestational week) and an excessive growth pattern for hyperglycemic pregnancies may be established according to gestational age. CONCLUSION: This is important for early detection of abnormalities in pregnancy, particularly in diabetic mothers.

Factors associated with the onset of hypertension in women of 50 years of age or more in a city in Southeastern Brazil

PURPOSE:To evaluate factors associated with hypertension in Brazilian women of 50 years of age or more.METHODS:A cross-sectional population based study using self-reports. A total of 622 women were included. The association between sociodemographic, clinical and behavioral factors and the woman's age at the onset of hypertension was evaluated. Data were analyzed according to cumulative continuation rates without hypertension, using the life-table method and considering annual intervals. Next, a Cox multiple regression analysis model was adjusted to analyze the occurrence rates of hypertension according to various predictor variables. Significance level was pre-established at 5% (95% confidence level) and the sampling plan (primary sampling unit) was taken into consideration.RESULTS:Median age at onset of hypertension was 64.3 years. Cumulative continuation rate without hypertension at 90 years was 20%. Higher body mass index (BMI) at 20–30 years of age was associated with a higher cumulative occurrence rate of hypertension over time (coefficient=0.078; p<0.001). Being white was associated with a lower cumulative occurrence rate of hypertension over time (coefficient= -0.439; p=0.003), while smoking >15 cigarettes/day was associated with a higher rate over time (coefficient=0.485; p=0.004).CONCLUSION:The results of the present study highlight the importance of weight control in young adulthood and of avoiding smoking in preventing hypertension in women aged ≥50 years.

Imaging of Tumour Microenvironment for the Planning of Oncological Therapies Using Positron Emission Tomography

Tumour cells differ from normal tissue cells in several important ways. These differences, like for example changed energy metabolism, result in altered microenvironment of malignant tumours. Non-invasive imaging of tumour microenvironment has been at the centre of intense research recently due to the important role that this changed environement plays in the development of malignant tumours and due to the role it plays in the treatment of these tumours. In this respect, perhaps the most important characteristics of the tumour microenvironment from this point of view are the lack of oxygen or hypoxia and changes in blood flow (BF). The purpose of this thesis was to investigate the processes of energy metabolism, BF and oxygenation in head and neck cancer and pancreatic tumours and to explore the possibilities of improving the methods for their quantification using positron emission tomography (PET). To this end [18F]EF5, a new PET tracer for detection of tumour hypoxia was investigated. Favourable uptake properties of the tracer were observed. In addition, it was established that the uptake of this tracer does not correlate with the uptake of existing tracers for the imaging of energy metabolism and BF, so the information about the presence of tissue hypoxia cannot therefore be obtained using tracers such as [18F]FDG or [15O]H2O. These results were complemented by the results of the follow-up study in which it was shown that the uptake of [18F]EF5 in head and neck tumours prior to treatment is also associated with the overall survival of the patients, indicating that tumour hypoxia is a negative prognostic factor and might be associated with therapeutic resistance. The influences of energy metabolism and BF on the survival of patients with pancreatic cancer were investigated in the second study. The results indicate that the best predictor of survival of patients with pancreatic cancer is the relationship between energy metabolism and BF. These results suggest that the cells with high metabolic activity in a hypoperfused tissue have the most aggressive phenotype.

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.

Spontaneous Focusing on Quantitative Relations and the Development of Rational Number Conceptual Knowledge

The aim of the present set of studies was to explore primary school children’s Spontaneous Focusing On quantitative Relations (SFOR) and its role in the development of rational number conceptual knowledge. The specific goals were to determine if it was possible to identify a spontaneous quantitative focusing tendency that indexes children’s tendency to recognize and utilize quantitative relations in non-explicitly mathematical situations and to determine if this tendency has an impact on the development of rational number conceptual knowledge in late primary school. To this end, we report on six original empirical studies that measure SFOR in children ages five to thirteen years and the development of rational number conceptual knowledge in ten- to thirteen-year-olds. SFOR measures were developed to determine if there are substantial differences in SFOR that are not explained by the ability to use quantitative relations. A measure of children’s conceptual knowledge of the magnitude representations of rational numbers and the density of rational numbers is utilized to capture the process of conceptual change with rational numbers in late primary school students. Finally, SFOR tendency was examined in relation to the development of rational number conceptual knowledge in these students. Study I concerned the first attempts to measure individual differences in children’s spontaneous recognition and use of quantitative relations in 86 Finnish children from the ages of five to seven years. Results revealed that there were substantial inter-individual differences in the spontaneous recognition and use of quantitative relations in these tasks. This was particularly true for the oldest group of participants, who were in grade one (roughly seven years old). However, the study did not control for ability to solve the tasks using quantitative relations, so it was not clear if these differences were due to ability or SFOR. Study II more deeply investigated the nature of the two tasks reported in Study I, through the use of a stimulated-recall procedure examining children’s verbalizations of how they interpreted the tasks. Results reveal that participants were able to verbalize reasoning about their quantitative relational responses, but not their responses based on exact number. Furthermore, participants’ non-mathematical responses revealed a variety of other aspects, beyond quantitative relations and exact number, which participants focused on in completing the tasks. These results suggest that exact number may be more easily perceived than quantitative relations. As well, these tasks were revealed to contain both mathematical and non-mathematical aspects which were interpreted by the participants as relevant. Study III investigated individual differences in SFOR 84 children, ages five to nine, from the US and is the first to report on the connection between SFOR and other mathematical abilities. The cross-sectional data revealed that there were individual differences in SFOR. Importantly, these differences were not entirely explained by the ability to solve the tasks using quantitative relations, suggesting that SFOR is partially independent from the ability to use quantitative relations. In other words, the lack of use of quantitative relations on the SFOR tasks was not solely due to participants being unable to solve the tasks using quantitative relations, but due to a lack of the spontaneous attention to the quantitative relations in the tasks. Furthermore, SFOR tendency was found to be related to arithmetic fluency among these participants. This is the first evidence to suggest that SFOR may be a partially distinct aspect of children’s existing mathematical competences. Study IV presented a follow-up study of the first graders who participated in Studies I and II, examining SFOR tendency as a predictor of their conceptual knowledge of fraction magnitudes in fourth grade. Results revealed that first graders’ SFOR tendency was a unique predictor of fraction conceptual knowledge in fourth grade, even after controlling for general mathematical skills. These results are the first to suggest that SFOR tendency may play a role in the development of rational number conceptual knowledge. Study V presents a longitudinal study of the development of 263 Finnish students’ rational number conceptual knowledge over a one year period. During this time participants completed a measure of conceptual knowledge of the magnitude representations and the density of rational numbers at three time points. First, a Latent Profile Analysis indicated that a four-class model, differentiating between those participants with high magnitude comparison and density knowledge, was the most appropriate. A Latent Transition Analysis reveal that few students display sustained conceptual change with density concepts, though conceptual change with magnitude representations is present in this group. Overall, this study indicated that there were severe deficiencies in conceptual knowledge of rational numbers, especially concepts of density. The longitudinal Study VI presented a synthesis of the previous studies in order to specifically detail the role of SFOR tendency in the development of rational number conceptual knowledge. Thus, the same participants from Study V completed a measure of SFOR, along with the rational number test, including a fourth time point. Results reveal that SFOR tendency was a predictor of rational number conceptual knowledge after two school years, even after taking into consideration prior rational number knowledge (through the use of residualized SFOR scores), arithmetic fluency, and non-verbal intelligence. Furthermore, those participants with higher-than-expected SFOR scores improved significantly more on magnitude representation and density concepts over the four time points. These results indicate that SFOR tendency is a strong predictor of rational number conceptual development in late primary school children. The results of the six studies reveal that within children’s existing mathematical competences there can be identified a spontaneous quantitative focusing tendency named spontaneous focusing on quantitative relations. Furthermore, this tendency is found to play a role in the development of rational number conceptual knowledge in primary school children. Results suggest that conceptual change with the magnitude representations and density of rational numbers is rare among this group of students. However, those children who are more likely to notice and use quantitative relations in situations that are not explicitly mathematical seem to have an advantage in the development of rational number conceptual knowledge. It may be that these students gain quantitative more and qualitatively better self-initiated deliberate practice with quantitative relations in everyday situations due to an increased SFOR tendency. This suggests that it may be important to promote this type of mathematical activity in teaching rational numbers. Furthermore, these results suggest that there may be a series of spontaneous quantitative focusing tendencies that have an impact on mathematical development throughout the learning trajectory.

Quantification and Clinical Relevance of Cystatin C

An aging population and increasing rates of diabetes mellitus contribute to a high prevalence of kidney dysfunction – approximately 10 percent of adults in developed countries have chronic kidney disease (CKD). CKD is a progressive loss of kidney function and this remains permanent. Early recognition of this condition is important for prevention or impeding severe adverse cardiac and renal outcomes. Cystatin C is a low molecular weight cysteine protease inhibitor that has emerged as a biomarker of kidney function. The special potential of plasma cystatin C in this setting is related to its independency of muscle mass, which is a remarkable limitation of the traditional marker creatinine. Cystatin C is a sensitive marker in diagnosing mild and moderate CKD, especially in small children, in the elderly and in conditions where muscle mass is affected. Cystatin C is quantified with immunoassays, mainly based on particle-enhanced nephelometry (PENIA) or turbidimetry (PETIA). The aim of this study was to develop a rapid and reliable assay for quantification of human cystatin C in plasma or serum by utilizing time-resolved fluorescence-based immunoassay methods. This was accomplished by utilizing different antibodies, including polyclonal and 7 monoclonal antibodies against cystatin C. Different assay designs were tested and the best assay was further modified to a dry-reagent double monoclonal assay run on an automated immunonalyzer. This assay was evaluated for clinical performance in estimating reduced kidney function and in predicting risk of adverse outcomes in patients with non-ST elevation acute coronary syndrome. Of the tested assay designs, heterogeneous non-competitive assay had the best performace and was chosen to be developed further. As an automated double monoclonal assay, this assay enabled a reliable measurement of clinically relevant cystatin C concentrations. It also showed a stronger concordance with the reference clearance method than the conventional PETIA method in patients with reduced kidney function. Risk of all-cause mortality and combined events, defined by death and myocardial infarction, increased with higher cystatin C and cystatin C remained an independent predictor of death and combined events after adjustment to nonbiochemical baseline factors. In conclusion, the developed dry-reagent double monoclonal assay allows rapid and reliable quantitative measurement of cystatin C. As measured with the developed assay, cystatin C is a potential predictor of adverse outcomes in cardiac patients.

Biomass and mineralmass estimates in a "cerrado" ecosystem

This work aimed to develop allometric equations for tree biomass estimation, and to determine the site biomass in different "cerrado" ecosystems. Destructive sampling in a "campo cerrado" (open savanna) was carried out at the Biological Reserve of Moji-Guaçu, State of São Paulo, southeastern Brazil. This "campo cerrado" (open savanna) grows under a tropical climate and on acid, low nutrient soils. Sixty wood plants were cut to ground level and measurements of diameter, height and weight of leaves and stems were taken. We selected the best equations among the most commonly used mathematical relations according to R² values, significance, and standard error. Both diameter (D) and height (H) showed good relationship with plant biomass, but the use of these two parameters together (DH and D²H) provided the best predictor variables. The best equations were linear, but power and exponential equations also showed high R² and significance. The applicability of these equations is discussed and biomass estimates are compared with other types of tropical savannas. Mineralmass was also estimated. "Cerrados" proved to have very important carbon reservoirs due to their great extent. In addition, high land-use change that takes place nowadays in the "cerrado" biome may significantly affect the global carbon cycle.