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  • Pöyhönen, Samuli (Helsingin yliopisto, 2013)
    The articles comprising this dissertation concern classification and concept formation in the social and behavioral sciences. In particular, the emphasis in the study is on the philosophical analysis of interdisciplinary settings created by the recent intellectual developments on the interfaces between the social sciences, psychology, and neuroscience. The need for a systematic examination of the problems of conceptual coordination and integration across disciplinary boundaries is illustrated by focusing on phenomena whose satisfactory explanation requires drawing together the theoretical resources from a variety of disciplines. In philosophy, questions regarding the nature of scientific concepts have often been framed in terms of theories of natural kinds. For this reason, analysis of the notion of natural kind as well as examination of how theories of natural kinds should be connected to recent philosophical accounts of scientific explanation and mechanisms form the core of the study. Building on contemporary discussions on these topics in the philosophy of biology, the philosophy of cognitive science, and the philosophy of the social sciences, the articles develop a mechanistic theory of natural kinds in the social and behavioral sciences, and scrutinize its applicability and usefulness as a theory of conceptual change in interdisciplinary settings. The study suggests that, although the mechanistic theory cannot account for the functioning of the whole range of scientific concepts, interweaving biological, cognitive, and social mechanisms in the manner suggested by the mechanistic theory offers a naturalistic and non-reductionist basis for conceptualizing epistemic coordination across disciplinary boundaries.
  • Aaltonen, Terhi (Helsingin yliopisto, 2013)
    Almost 40 years ago, a cheese-making process was described in which milk was concentrated to the final total solids content of cheese and no whey draining was made after coagulation. This full concentration (FC) process has since been used in soft cheese-making. However in semi-hard and hard cheese-making concentrated whey proteins have had negative effect on cheese flavor and texture and therefore the technique has not been used for these products. Development of filtration techniques has made it possible to fractionate milk components. Concentration of the major cheese components, fat and casein, is possible with microfiltration (MF). The aim of this study was to develop an FC cheese process using MF and evaporation steps. Cheese-making with the FC process consists of whey protein removal and standardization of lactose and calcium contents. During whey protein removal plasmin (PL) was activated and its heat stability was increased. Protein hydrolysis by PL before cheese-making may reduce cheese yield and coagulation properties and therefore the FC process must be continuous. The calcium-protein ratio affects the final structure of cheese and can be standardized with acidification and filtration steps. During FC of milk, the viscosity of retentate increases and its processability decreases. It was found that acidification reduced the viscosity of retentate and slowed the increase of viscosity during concentration. This observation may be important for FC process development. Secondary proteolysis of FC cheese was apparently at a low level, because no free amino acids (FAA) were found at the end of ripening. Added peptidase increased the FAA content in cheese and with enzyme addition it was possible to alter the ripening process. However, peptidase addition also changed lactose fermentation, and therefore the microbiological composition of LAB changed in cheese. The effects of CaCl2 addition on FC cheese ripening were studied. It was found that CaCl2 addition increased the growth of LAB, probably due to delayed lysis of LAB. It appears that standardization of calcium content is essential to control lyses caused by LAB, which affect cheese ripening.
  • Kilpivaara, Outi (Helsingin yliopisto, 2007)
    Breast and colorectal cancers, are common types of cancer, with over two million newly diagnosed cases annually worldwide. Cancer is a genetic disease and defects in DNA integrity restoring functions make a significant contribution to cancer risk. CHEK2 is a checkpoint kinase functioning as a regulator of cell cycle checkpoints, apoptosis, and DNA repair in response to DNA double-strand breaks. The aim of this study was to evaluate the role of CHEK2 in breast cancer predisposition in Finnish breast cancer families and in breast cancer risk at the population level. We were interested in the clinical and biological characteristics of the breast tumors associated with the CHEK2 germline mutations or aberrant CHEK2 protein expression and the effect on survival of patients with these CHEK2 defects. We also assessed the role of CHEK2 mutations, namely 1100delC and I157T, in colorectal cancer susceptibility in Finland. CHEK2 I157T was found to be a low-penetrance breast cancer susceptibility allele, conferring a 1.4-fold risk for carriers. Reduced or absent CHEK2 protein expression was observed in one-fifth of breast tumors from patients unselected for family history, implying that defective CHEK2 signaling contributes to tumorigenesis. Reduction in CHEK2 expression was more common in tumors with larger diameter and ER expression, but with regard to other tumor characteristics and prognosis of a patient no association was observed. Results from comparison of CHEK2 1100delC carrier tumors with noncarrier tumors were in line with the findings from the CHEK2 expression study. Tumors from CHEK2 1100delC carriers were more often of higher grade than tumors from noncarriers, and they also tended to be ER-positive more often, although generally 1100delC status does not seem to radically affect the tumor characteristics. Our results suggest that CHEK2 1100delC may not be a susceptibility allele for CRC, although a very small effect cannot be excluded. Furthermore, CHEK2 1100delC is equally frequent in HBCC (hereditary breast and colorectal cancer) phenotype families and in breast cancer families. Over 1000 CRC cases were screened for CHEK2 I157T, and a significantly higher frequency of I157T was observed among both familial and sporadic CRC cases. The relation of CHEK2 I157T with familial CRC has not been studied previously. CHEK2 I157T seems to be a susceptibility allele for both familial and sporadic CRC, conferring a 1.5-fold risk for carriers of this variant. CHEK2 I157T has been proposed to have a role as a multiple cancer susceptibility allele, which is supported by our results since we observed a trend towards higher frequency of the variant among cases with multiple primary tumors or those with a family history of cancer. During the last five years CHEK2 has established its role as an important cancer susceptibility gene. It has become apparent that CHEK2 is a low-penetrance susceptibility gene for several cancer types, significantly contributing to familial cancer risk as well as to cancer risk at the population level.
  • Jakovleva, Natalia (Helsingin yliopisto, 2012)
    This study is a historical and semantic description of the notion of the human document (document humain), borrowed by Russian critics from the literary theory of French Naturalism. To this day the term remains current in the Russian language in fictional and scholarly texts, mostly in the humanities. Becoming something of a cliché, however, it has lost its strict, narrow sense. This book details the evolution of the notion over the relatively long period of its existence. The term itself was invented by two French writers the Goncourt brothers, whose works were less known to Russian readers than, for instance, the ideas of Hyppolite Taine, where one could find semantically similar formulas. Meanwhile the texts of Emile Zola achieved particular popularity in Russia, and the human document played a key role in Zola s aesthetics, especially in his theory of the experimental novel . For Zola the human document rejected the ideology of Romanticism with its orientation on inventive and captivating fictions. It is a noteworthy fact that Zola s works devoted to the experimental novel were first published in Russian, since the French writer was collaborating with Russian periodicals. At the same time, similar expressions were wide spread in Russian critical discourse: for example, the prominent and influential critic Nikolay Mikhaylovsky oft en used synonyms like documents about the human, and one can find other derivatives like female document or Parisian document . On the other hand, Russian reception of Zola s declared interest in psychic physiology and human degradation was also negative, and in the end of the nineteenth century the human document acquired a range of pejorative connotations. As Naturalist theories were gradually becoming obsolete and disappearing, the term s semantic associations were markedly transformed. The 1910s were a crucial period in its history. Although one can find the term in the texts of Russian Naturalists like the prolific writer Aleksandr Amfiteatrov, it was no longer strictly connected with this aesthetical and intellectual tradition. Displaced and half-forgotten, human document appears in the contexts of women s literature , memoirs, and even autobiographies about the 1905 revolution. Now it was associated with different documentary genres, such as diaries and confessions, as with the literary strategy of frank or true expression. This suggests that the term was becoming a part of the rhetoric of anti-literature . As a result, the positive ideal of frank testimony was combined with psychic physiology s negative associations, and this ambiguity allowed the application of the term to a certain set of specific subjects. For example, it was connected with the marginal hero of the age , i.e. the time of decadence and social decline (the revolutionary, the scoundrel, the cynic, and so on). The 1920s and 1930s were the heyday of the human document . The term was rarely used in early Soviet literature but flourished among Russian emigre writers. Thanks to the older generation, who actively took part in pre-revolutionary literary discussions, this cliche gradually returned to the pages of émigré periodicals. In the 1930s, as in Zola s time, it assumed the form of a literary manifesto and united different circles of young Russian writers, mostly in France. Human document became a keyword in the famous discussion between two prominent figures of the Paris emigration, Vladislav Khodasevich and Georgy Adamovich, who considered the goal of a new literature to be the return to raw, frank self-expression. This new development in the history of the term was partly supported by the interest of contemporary French writers like Louis-Ferdinand Celine in naturalistic literary devices. In this period human document became a kind of synonym for a certain sort of poetry which was called the Parisian note . It is not unusual that this cliché sometimes appeared in Soviet criticism as a means of describing and then belittling émigré literature. It arose in the mid-1960s, probably after the polemics about frankness in literature and then was borrowed by literary scholar Lydia Ginzburg, who worked on the history of documentary genres in Russian literature.
  • Sillanpää, Markus (Helsingin yliopisto, 2006)
    Recent epidemiological studies have shown a consistent association of the mass concentration of urban air thoracic (PM10) and fine (PM2.5) particles with mortality and morbidity among cardiorespiratory patients. However, the chemical characteristics of different particulate size ranges and the biological mechanisms responsible for these adverse health effects are not well known. The principal aims of this thesis were to validate a high volume cascade impactor (HVCI) for the collection of particulate matter for physicochemical and toxicological studies, and to make an in-depth chemical and source characterisation of samples collected during different pollution situations. The particulate samples were collected with the HVCI, virtual impactors and a Berner low pressure impactor in six European cities: Helsinki, Duisburg, Prague, Amsterdam, Barcelona and Athens. The samples were analysed for particle mass, common ions, total and water-soluble elements as well as elemental and organic carbon. Laboratory calibration and field comparisons indicated that the HVCI can provide a unique large capacity, high efficiency sampling of size-segregated aerosol particles. The cutoff sizes of the recommended HVCI configuration were 2.4, 0.9 and 0.2 μm. The HVCI mass concentrations were in a good agreement with the reference methods, but the chemical composition of especially the fine particulate samples showed some differences. This implies that the chemical characterization of the exposure variable in toxicological studies needs to be done from the same HVCI samples as used in cell and animal studies. The data from parallel, low volume reference samplers provide valuable additional information for chemical mass closure and source assessment. The major components of PM2.5 in the virtual impactor samples were carbonaceous compounds, secondary inorganic ions and sea salt, whereas those of coarse particles (PM2.5-10) were soil-derived compounds, carbonaceous compounds, sea salt and nitrate. The major and minor components together accounted for 77-106% and 77-96% of the gravimetrically-measured masses of fine and coarse particles, respectively. Relatively large differences between sampling campaigns were observed in the organic carbon content of the PM2.5 samples as well as the mineral composition of the PM2.5-10 samples. A source assessment based on chemical tracers suggested clear differences in the dominant sources (e.g. traffic, residential heating with solid fuels, metal industry plants, regional or long-range transport) between the sampling campaigns. In summary, the field campaigns exhibited different profiles with regard to particulate sources, size distribution and chemical composition, thus, providing a highly useful setup for toxicological studies on the size-segregated HVCI samples.
  • Saarnio, Karri (Helsingin yliopisto, 2013)
    Biomass burning has lately started to attract attention because there is a need to decrease the carbon dioxide (CO2) emissions from the combustion of fossil fuels. Biomass is considered as CO2 neutral fuel. However, the burning of biomass is one of the major sources of fine particles both at the local and global scale. In addition to the use of biomass as a fuel for heat energy production, biomass burning emissions can be caused, e.g. by slash-and-burn agriculture and wild open-land fires. Indeed, the emissions from biomass burning are crucially important for the assessment of the potential impacts on global climate and local air quality and hence on human health. The chemical composition of fine particles has a notable influence on these impacts. The overall object of this thesis was to gain knowledge on the chemistry of fine particles that originate from biomass burning as well as on the contribution of biomass burning emissions to the ambient fine particle concentrations. For this purpose novel analytical methods were developed and tested in this thesis. Moreover, the thesis is based on ambient aerosol measurements that were carried out in six European countries at 12 measurement sites during 2002 2011. Additionally, wood combustion experiments were conducted in a laboratory. The measurements included a wide range of techniques: filter and impactor samplings, offline chemical analyses (chromatographic and mass spectrometric techniques, thermal-optical method), and online measurements of particles physical properties and chemical composition (incl. particle number and mass concentrations and size distributions, concentrations of carbonaceous components, water-soluble ions, and tracer compounds). This thesis presents main results of different studies aimed towards chemical characterisation of fine particle emissions from biomass burning. It was found that wood combustion had a significant influence on atmospheric fine particle concentrations in the Helsinki Metropolitan Area in the cold season. Especially in the residential areas local wood combustion emissions were occasionally substantial. A notable contribution of particles originating from wood combustion was detected both at suburban and urban areas caused by emissions that were distributed regionally or they were long-range transported. In addition to the wood combustion emissions, transported smokes from open-land fires in Russia and the Baltic countries affected the air quality in Helsinki in the warm season. Source-specific tracer compounds were used in the thesis for identifying the biomass burning source of fine particles. The most used tracer compounds were anhydrosugars (levoglucosan, mannosan, and galactosan) that originate specifically in the pyrolysis of cellulose and hemicelluloses, the main components of plant biomass. In summary, the sampling and analytical methods needed for the online chemical characterisation of fine particles from biomass burning were developed in order to provide precise and prompt high-time-resolution information on biomass burning emissions. The results and the implications of this thesis provide new information on the concentrations and sources of fine particles in the boreal region.
  • Lukkari, Kaarina (Helsingin yliopisto, 2008)
    Chemical characteristics and behaviour of sediment phosphorus in the northeastern Baltic Sea Eutrophication is a severe environmental problem in the Baltic Sea, especially in the Gulf of Finland and the Archipelago Sea, and it is enhanced by the release of phosphorus (P) from bottom sediments. The release of P from sediment reserves largely depends on the occurrence of P in different chemical forms and on the prevailing conditions, especially on the presence of oxygen. This study examines the chemical character and the vertical distribution of sediment P in two shallow estuaries, in shallow coastal sediments overlain by oxic near-bottom water, and in poorly oxygenated open sea sediments in the northeastern Baltic Sea. The objective was to evaluate how much of the sediment P is buried and removed from the nutrient cycle, and how much of it is in forms that can be released from the sediment to the overlaying water over time. Relationships between the distribution of the different P forms and the chemical and physical properties of the sediment, sediment pore water, and near-bottom water were determined in order to examine the behaviour of P at the sediment-water interface. The results show that the chemical character of sediment P varied in the different areas. Generally, in the outer estuaries and in the organic-rich coastal areas in the eastern Gulf of Finland, the sediments were higher in P than the sediments in the poorly oxygenated open sea areas in the central and western Gulf. The estuary sediments that received erosion-transported material were characterised by P bound to hydrated oxides of iron and aluminum. Iron-bound P is sensitive to changes in redox-conditions, but part of it was buried in the estuaries, possibly because of high sedimentation rates and incomplete reduction of iron. The open sea sediments in the central and western Gulf of Finland were dominated by apatite-P, which was also abundant in the areas strongly affected by sediment transportation. The burial of sediment P was most effective in the areas rich in apatite-P, which is a relatively stable form of P in sediment. In the eastern Gulf of Finland, organic P forms predominated in the organic-rich sediments. A part of these P forms will be buried, while part will be degraded in the long term, releasing soluble P to the pore water. In the poorly oxygenated areas, iron compounds at the sediment surface are not able to retain P released during mineralisation of organic matter or reduction-induced dissolution of iron-compounds in deep sediment layers. However, in the shallow coastal areas overlain by oxic near-bottom water, the organic-rich surface sediment can also become temporarily reduced and release P from the sediment to the overlaying water. The considerable variation in the chemical composition of sediment P reserves in the northeastern Baltic Sea proved that it is an important factor and should be taken into account when evaluating the release of sediment P and the role of P reserves in bottom sediments in eutrophication.
  • Carbone, Samara (Helsingin yliopisto, 2014)
    Fine particles affect climate change in complex ways that are not fully understood and were verified to be harmful to animal and human health. For these reasons information concerning their composition is important to understand their behaviour and to elaborate strategies to mitigate air pollution in urban environments. The overall objective of this study was to investigate in more detail chemical characteristics of ambient particulate matter (PM) and its sources. Studies made in laboratory and during field were used to study composition of fresh emissions, changes during aging, and finally composition of submicron PM (PM1) observed in ambient air. For that the field studies were performed at three different sites: rural, urban, and background urban with the HR-ToF-AMS and ACSM, instruments that measured only the non-refractory PM1 (NR-PM1). For this reason the new SP-AMS was further characterized in order to evaluate its feasi-bility to detect trace metals. The use of the positive matrix factorization (PMF) has shown useful in the identification of PM sources. Thus, the PMF was applied to the mass spectrometers datasets and 11 different components of the organic aerosol (OA) were identified, 6 types of oxygenated OAs (OOAs), one containing substantial organosulfate fragments from methanesulfonic acid (MSA), long-range transported biomass burning OA (LRT-BBOA), nitrogen-containing OA (NOA), local BBOA, coffee roastery OA (CROA), and hydrocarbon-like OA (HOA). The last three most likely represented the primary organic aerosol (POA), while the others represented the secondary OA (SOA). The OM was dominated by aerosol particles of secondary origin (65%). The investigation of different properties of the PM1 revealed more information about its composition and sources. A comparison of the AMS data with those from additional instrumentation indicated that most of the PM1 was non-refractory. The water-solubility of the OM indicated that the low-volatility OOA (LV-OOA) and the LRT-BBOA were the most water-soluble components. The SV-OOA presented clear semi-volatile character when investigated as a function of the local air temperature, decreasing in concentration with the air temperature increase. Concerning the aerosol neutralization, in most sites the results indicated enough ammonium to neutralize the major inorganic anions, except for Helsinki during wintertime when the aerosol particles were acidic most of the time. The size-resolved chemical composition was investigated in detail to different episodes and revealed internally and externally mixed aerosol particles in two different modes, an accumulation (~470 nm) and a lower mode (~130nm). The different modes were composed of different compounds and suggested a rather acidic lower mode mainly dominated by nitrate most likely from local traffic emissions. The laboratory experiments accomplished with the SP-AMS successfully confirmed the feasibility of detection of trace metals. 13 different metals were identified through the determination of isotopic patterns. Furthermore, the negative mass defect, typical from metals, was observed useful in their identification in the mass spectrum. The measurement of trace metals by the SP-AMS represents a step forward in the study of sources and might be extremely useful in the next source apportionment studies.
  • Timonen, Hilkka (Helsingin yliopisto, 2011)
    In order to evaluate the influence of ambient aerosol particles on cloud formation, climate and human health, detailed information about the concentration and composition of ambient aerosol particles is needed. The dura-tion of aerosol formation, growth and removal processes in the atmosphere range from minutes to hours, which highlights the need for high-time-resolution data in order to understand the underlying processes. This thesis focuses on characterization of ambient levels, size distributions and sources of water-soluble organic carbon (WSOC) in ambient aerosols. The results show that in the location of this study typically 50-60 % of organic carbon in fine particles is water-soluble. The amount of WSOC was observed to increase as aerosols age, likely due to further oxidation of organic compounds. In the boreal region the main sources of WSOC were biomass burning during the winter and secondary aerosol formation during the summer. WSOC was mainly attributed to a fine particle mode between 0.1 - 1 μm, although different size distributions were measured for different sources. The WSOC concentrations and size distributions had a clear seasonal variation. Another main focus of this thesis was to test and further develop the high-time-resolution methods for chemical characterization of ambient aerosol particles. The concentrations of the main chemical components (ions, OC, EC) of ambient aerosol particles were measured online during a year-long intensive measurement campaign conducted on the SMEAR III station in Southern Finland. The results were compared to the results of traditional filter collections in order to study sampling artifacts and limitations related to each method. To achieve better a time resolution for the WSOC and ion measurements, a particle-into-liquid sampler (PILS) was coupled with a total organic carbon analyzer (TOC) and two ion chromatographs (IC). The PILS-TOC-IC provided important data about diurnal variations and short-time plumes, which cannot be resolved from the filter samples. In summary, the measurements made for this thesis provide new information on the concentrations, size distribu-tions and sources of WSOC in ambient aerosol particles in the boreal region. The analytical and collection me-thods needed for the online characterization of aerosol chemical composition were further developed in order to provide more reliable high-time-resolution measurements.
  • Saarikoski, Sanna (Helsingin yliopisto, 2008)
    It has been known for decades that particles can cause adverse health effects as they are deposited within the respiratory system. Atmospheric aerosol particles influence climate by scattering solar radiation but aerosol particles act also as the nuclei around which cloud droplets form. The principal objectives of this thesis were to investigate the chemical composition and the sources of fine particles in different environments (traffic, urban background, remote) as well as during some specific air pollution situations. Quantifying the climate and health effects of atmospheric aerosols is not possible without detailed information of the aerosol chemical composition. Aerosol measurements were carried out at nine sites in six countries (Finland, Germany, Czech, Netherlands, Greece and Italy). Several different instruments were used in order to measure both the particulate matter (PM) mass and its chemical composition. In the off-line measurements the samples were collected first on a substrate or filter and gravimetric and chemical analysis were conducted in the laboratory. In the on-line measurements the sampling and analysis were either a combined procedure or performed successively within the same instrument. Results from the impactor samples were analyzed by the statistical methods. This thesis comprises also a work where a method for the determination carbonaceous matter size distribution by using a multistage impactor was developed. It was found that the chemistry of PM has usually strong spatial, temporal and size-dependent variability. In the Finnish sites most of the fine PM consisted of organic matter. However, in Greece sulfate dominated the fine PM and in Italy nitrate made the largest contribution to the fine PM. Regarding the size-dependent chemical composition, organic components were likely to be enriched in smaller particles than inorganic ions. Data analysis showed that organic carbon (OC) had four major sources in Helsinki. Secondary production was the major source in Helsinki during spring, summer and fall, whereas in winter biomass combustion dominated OC. The significant impact of biomass combustion on OC concentrations was also observed in the measurements performed in Central Europe. In this thesis aerosol samples were collected mainly by the conventional filter and impactor methods which suffered from the long integration time. However, by filter and impactor measurements chemical mass closure was achieved accurately, and a simple filter sampling was found to be useful in order to explain the sources of PM on the seasonal basis. The online instruments gave additional information related to the temporal variations of the sources and the atmospheric mixing conditions.
  • Wang, Chang-Fang (Helsingin yliopisto, 2015)
    Anticancer drugs inhibit the cancer growth by killing the rapidly dividing cancer cells. However, anticancer drugs also kill the dividing healthy cells and cause severe damage to healthy tissues. More specific delivery of the cancer drugs to the cancer tissue can increase the drug delivery efficiency and reduce the drug s side effects. Nanocarriers can increase the solubility of poorly-water soluble anticancer drugs and be modified for targeted drug delivery and theranostic applications. For efficient drug delivery, the drug loading capacity has been one of the key issues for the development of nanoparticle (NP)-based drug delivery systems. The biocompatible and biodegradable porous silicon (PSi) nanomaterial presents high drug loading capacity and tunable surface chemistry which renders it an ideal candidate as a drug delivery carrier. Chemical surface modification, which is one of the approaches to improve the nanomaterials properties, can lead to a stable nanosystem for further drug delivery applications. The main aim of this dissertation was to employ chemical approaches and surface modified PSi nanoparticles (NPs) to improve the drug delivery efficiency for potential cancer therapy applications. Incorporating targeting moieties to the surfaces of the nanocarriers, such as targeting peptides, can increase the nanocarrier s accumulation into the cancer tissue after the intravenous administration. In this thesis, surface modification of amine-terminated PSi NPs was achieved with targeting peptides (RGDS and iRGD) via strain-promoted azide-alkyne cycloaddition click reaction. The functionalization of the PSi NPs with the targeting peptides did not comprise the drug loading capacity, but enhanced the cellular uptake and the drug delivery efficacy of the PSi NPs in vitro. In addition to the targeting NP surface modifications, a multifunctional nanosystem was prepared with simultaneous fluorescence- and radio-labeling, and iRGD surface modification of the carboxylic acid-terminated PSi NPs. Both labelings were accessible for the in vivo biodistribution evaluation in mice by single-photon emission computed tomography and X-ray computed tomography, and ex vivo by immunofluorescence staining, respectively. The iRGD modification enhanced the tumor uptake of the PSi NPs after the intravenous administration. In order to reduce the plasma protein adsorption onto the PSi NPs, five bioactive molecules (peptides and hydrophilic anti-fouling polymers) were used to modify the surface of alkyne-terminated PSi NPs using copper-catalized click chemistry. Dextran 40 kDa modified PSi NPs presented enhanced cellular uptake and the least protein adsorption of all the tested NPs. Furthermore, the chemical conjugation of drug molecules was studied. The targeting peptides were successfully conjugated to antisense interleukin-6 via copper-catalyzed [3+2] azide-alkyne cycloaddition for targeted angiogenic anti-inflammation in cancer. Finally, anticancer drug methotrexate (MTX) was chemically conjugated to the cationic PSi NPs and demonstrated to increase the cellular uptake of MTX with up to 96 h sustained drug release. A hydrophobic anti-angiogenic drug, sorafenib, was also loaded to the MTX-conjugated PSi NPs, and the dissolution rate of this drug was considerably increased. In conclusion, in this thesis different chemical approaches were used to biofunctionalize PSi NPs and to prepare drug-conjugates formulations for potential anti-cancer applications.
  • Kautio, Anna-Liisa (Helsingin yliopisto, 2012)
    The present study aimed to investigate the effect of amitriptyline in prevention and treatment of chemo-therapy-induced peripheral neuropathy (CIPN). The secondary aims were to evaluate the prevalence and discomfort of CIPN in a clinical cohort predisposed to neurotoxic chemotherapy agents, grading of neu-rotoxicity, and the changes in intraepidermal nerve fiber (IENF) density during the neurotoxic chemo-therapy treatment. The study included three cancer patient populations treated with neurotoxic chemotherapy. The first study population was screened from 448 patients aged 20 to 70 years who were treated with neurotoxic chemotherapy, of whom 152 reported neuropathic symptoms and were hence eligible for evaluation of the burden of neuropathic symptoms. Of that cohort 33 patients with sensory neuropathic symptoms (numbness, tingling or pain) of at least moderate severity were randomised to the treatment study. The third study population consists of 104 patients without previous neuropathy who started neurotoxic chemotherapy and were randomized to the prevention study. The fifth study investigating IENF density consisted of 12 patients starting adjuvant chemotherapy with taxanes or platinum derivatives. Fifty-nine percent of the screened patients reported neuropathic symptoms. Tingling (71 %), numbness (58 %), impaired sensory function (46 %) and pain in hands and feet (40 %) were the most common symptoms. Neuropathic symptoms were the third most commonly reported adverse effect symptoms. Every third patient (37 %) with neuropathic symptoms ranked them as the most troublesome symptom. Comparing the NCI-CTC sensory and Oxaliplatin Scales the progression of the toxicity from mild (grade 1 or 2) to moderate or severe (grade 3 or 4) was detected more frequently with the Oxaliplatin Scale. Neither the treatment study nor the prevention study showed significant difference between the amitriptyline and placebo groups in the intensity of the neuropathic symptoms during the follow-up. However, amitriptyline significantly improved quality of life measured with the EORTC QLQ-C30 compared with placebo in treatment study. Reduced IENF density was found in 8/12 patients at base-line. During the follow-up IENF density increased significantly in six of them and remained unchanged in two. No association was found between neuropathic symptoms and IENF count.
  • Hintsa, Taina (Helsingin yliopisto, 2008)
    Work stress is after musculoskeletal disorders the second most common work-related health problem in the European Union, affecting 28% of EU employees. Furthermore, a 50% excessive cardiovascular disease risk among employees with work stress is reported. High job demands combined with low job control according to the Job Demands-Job Control model, or high effort combined with low rewards according to Effort-Reward Imbalance model, are likely to produce work stress in the majority of employees. Atherosclerotic wall thickening is a validated marker of an increased risk of cardiovascular disease. This study examined the role of childhood and adolescent factors as antecedents of work stress and early atherosclerosis, and in the relationship between them. The Cardiovascular Risk in Young Finns Study, (the CRYF project) started in 1980 when the participants were at the age of three to 18 years. Follow-ups have been conducted every three years until 1992, after that in 1997 and 2001, and the latest is ongoing in 2008. The participants parents reported their socioeconomic position in 1980 and 1983, and their life satisfaction in 1983. Biological risk factors were measured in 1980 and 2001. Type A behaviour was reported in 1986, 1989 and 2001. In the 2001 follow-up when the participants were aged 24 to 39, work stress was assessed from responses to questionnaires on job demands-job control and effort-reward imbalance, and education. Ultrasound measurement of the carotid intima-media thickness (CIMT) was used to assess atherosclerosis. There were 755, 746, 1014 and 494 participants in studies I-IV, respectively. The results showed that low parental socioeconomic position and parental life dissatisfaction during childhood and adolescence predicted higher levels of job strain 18 years later, and that education mediated the relationship between parental socioeconomic position and job strain. Childhood and adolescent family factors were not related to the effort-reward imbalance. Parental life satisfaction was associated with high rewards at work among the men, and high parental socioeconomic position was associated with high reward among the women. Among the men, the eagerness-energy component of Type A behaviour across different developmental periods predicted increased CIMT. Among the women, hard-driving component of Type A behaviour predicted decreased CIMT. Low leadership characteristic in adolescence and early adulthood was associated with both high job strain and increased CIMT, and attenuated the relationship between job strain and CIMT to non-significance in men. The current findings add to the literature on the relationship between job strain and health literature in adopting a developmental perspective. The results imply that work stress does not completely originate from work. There are childhood and adolescent environmental and dispositional effects on work stress and CIMT several years later, and these partly seem to operate through educational attainment.
  • Alatupa, Saija (Helsingin yliopisto, 2013)
    Social exclusion, in general, is seen as a long-term process that is multidimensional and cumulative. It includes educational, occupational, social, normative and the exercise of power; the present study focused on the first three of these dimensions. They were chosen, because they are closely related to the other dimensions of exclusion (normative and the exercise of power) and because they were most relevant from the public health view. Particular interest was to find those less serious factors of the exclusion process that can still be influenced. Thus, the aim of the present study was to examine in two large population-based samples childhood and adolescence characteristics that may be involved in the process of educational, occupational or social exclusion. It was hypothesized that 1) social status among classmates is related to temperament and that social status is associated with higher self-esteem. Further expectations were that 2) disruptive childhood behaviour is associated with both poor school performance at comprehensive school and 3) a lower socioeconomic position in adulthood and that 4) poor school performance associates with obesity in adulthood. The findings supported the hypotheses. Adolescent s self-perception of their social self-esteem was highly associated with social and general self-esteem, whereas the association with family self-esteem was lower in magnitude. It was shown that different aspects of self-esteem have a different impact on a person s social status in general. Disruptive childhood behaviour was associated with poor school performance throughout the school years, but its impact first started in middle childhood. Within these associations a gender-related difference was also found: hyperactivity was negatively associated with girls school performance, while aggression was detrimental for boys school success. Disruptive childhood behaviour further associated with educational and occupational status in adulthood, but it had no effect on income. Childhood aggression predicted educational and occupational status in adulthood, whereas hyperactivity only had an effect on education. A gender-related association was also found between poor school performance and adulthood obesity: poor school performance was a risk factor for women s health. To sum up, it was shown that early behaviour and school performance are associated with later socioeconomic and health-related outcomes. These finding suggest that the roots of detrimental development can already be found in childhood. From the perspective of public health and its improvement, identifying those children at risk is highly relevant.
  • Hammarén-Malmi, Sari (Helsingin yliopisto, 2007)
    Background: Otitis media (OM) is one of the most common childhood diseases. Approximately every third child suffers from recurrent acute otitis media (RAOM), and 5% of all children have persistent middle ear effusion for months during their childhood. Despite numerous studies on the prevention and treatment of OM during the past decades, its management remains challenging and controversial. In this study, the effect of adenoidectomy on the risk for OM, the potential risk factors influencing the development of OM and the frequency of asthma among otitis-prone children were investigated. Subjects and methods: One prospective randomized trial and two retrospective studies were conducted. In the prospective trial, 217 children with RAOM or chronic otitis media with effusion (COME) were randomized to have tympanostomy with or without adenoidectomy. The age of the children at recruitment was between 1 and 4 years. RAOM was defined as having at least 3 episodes of AOM during the last 6 months or at least 5 episodes of AOM during the last 12 months. COME was defined as having persistent middle ear effusion for 2-3 months. The children were followed up for one year. In the first retrospective study, the frequency of childhood infections and allergy was evaluated by a questionnaire among 819 individuals. In the second retrospective study, data of asthma diagnosis were analysed from hospital discharge records of 1616 children who underwent adenoidectomy or had probing of the nasolacrimal duct. Results: In the prospective randomized study, adenoidectomy had no beneficial effect on the prevention of subsequent episodes of AOM. Parental smoking was found to be a significant risk factor for OM even after the insertion of tympanostomy tubes. The frequencies of exposure to tobacco smoke and day-care attendance at the time of randomization were similar among children with RAOM and COME. However, the frequencies of allergy to animal dust and pollen and parental asthma were lower among children with COME than those with RAOM. The questionnaire survey and the hospital discharge data revealed that children who had frequent episodes of OM had an increased risk for asthma. Conclusions: The first surgical intervention to treat an otitis-prone child younger than 4 years should not include adenoidectomy. Interventions to stop parental smoking could significantly reduce the risk for childhood RAOM. Whether an otitis-prone child develops COME or RAOM, seems to be influenced by genetic predisposition more strongly than by environmental risk factors. Children who suffer from repeated upper respiratory tract infections, like OM, may be at increased risk for developing asthma.
  • Gyllenberg, David (Helsingin yliopisto, 2012)
    Early identification of individuals who later develop psychiatric problems requiring psychotropic medication and psychiatric hospital treatment has implications for prevention. The aims of this thesis are to describe the cumulative incidence of psychotropic medication use from age 12 to age 25, and to study factors at age eight that predict psychotropic medication use and psychiatric hospital treatment between age 12 and 25. A representative random sample of all children born in 1981 and alive at age eight in 1989 was primarily selected in 1989 (6,017 of 60,007; 10%). At age eight, 5,813 children were assessed using questionnaires (97% of 6,017). The parents and the teacher completed questionnaires with items concerning family structure, parental education level, conduct problems, hyperactive problems, emotional symptoms, bullying, and victimization of bullying behavior. The children themselves completed questions regarding depressive symptoms, bullying, and victimization of bullying behavior. Between 1994 and 2005, when the participants were 12-13 to 24-25 years old, the personal identification numbers of 5,525 subjects (92% of 6,017) were linked to the nationwide Drug Prescription Register and the nationwide Finnish Hospital Discharge Register. Information about psychotropic medication use and psychiatric hospital treatment between age 12 and 25 was collected from these registers. The main results in the thesis are that more than every seventh subject had used psychotropic medications by age 25, and that psychotropic medication use and psychiatric hospital treatment are strongly associated with psychiatric symptoms at age eight. Depressive symptoms predicted treatment of depressive disorders and non-intact family structure predicted a wide range of different psychiatric treatments in both sexes. Among males, particularly acting-out behaviors, while among females, especially depressive and anxiety symptoms and being a victim of bullying behavior predicted antipsychotic use, antidepressant use, and psychiatric hospital treatment by age 25. The study shows that a considerable proportion of the population has used psychotropic medication at some point by age 25. The novel result that the psychiatric outcomes are partly predicted differently among males versus females, should be further studied using large population-based cohorts. If the results are replicated and screening of mental health problems is implemented in primary schools, sex-specific screening strategies might be warranted.
  • Mannerkoski, Minna (Helsingin yliopisto, 2009)
    The need for special education (SE) is increasing. The majority of those whose problems are due to neurodevelopmental disorders have no specific aetiology. The aim of this study was to evaluate the contribution of prenatal and perinatal factors and factors associated with growth and development to later need for full-time SE and to assess joint structural and volumetric brain alterations among subjects with unexplained, familial need for SE. A random sample of 900 subjects in full-time SE allocated into three levels of neurodevelopmental problems and 301 controls in mainstream education (ME) provided data on socioeconomic factors, pregnancy, delivery, growth, and development. Of those, 119 subjects belonging to a sibling-pair in full-time SE with unexplained aetiology and 43 controls in ME underwent brain magnetic resonance imaging (MRI). Analyses of structural brain alterations and midsagittal area and diameter measurements were made. Voxel-based morphometry (VBM) analysis provided detailed information on regional grey matter, white matter, and cerebrospinal fluid (CSF) volume differences. Father’s age ≥ 40 years, low birth weight, male sex, and lower socio-economic status all increased the probability of SE placement. At age 1 year, one standard deviation score decrease in height raised the probability of SE placement by 40% and in head circumference by 28%. At infancy, the gross motor milestones differentiated the children. From age 18 months, the fine motor milestones and those related to speech and social skills became more important. Brain MRI revealed no specific aetiology for subjects in SE. However, they had more often ≥ 3 abnormal findings in MRIs (thin corpus callosum and enlarged cerebral and cerebellar CSF spaces). In VBM, subjects in full-time SE had smaller global white matter, CSF, and total brain volumes than controls. Compared with controls, subjects with intellectual disabilities had regional volume alterations (greater grey matter volumes in the anterior cingulate cortex bilaterally, smaller grey matter volume in left thalamus and left cerebellar hemisphere, greater white matter volume in the left fronto-parietal region, and smaller white matter volumes bilaterally in the posterior limbs of the internal capsules). In conclusion, the epidemiological studies emphasized several factors that increased the probability of SE placement, useful as a framework for interventional studies. The global and regional brain MRI findings provide an interesting basis for future investigations of learning-related brain structures in young subjects with cognitive impairments or intellectual disabilities of unexplained, familial aetiology.