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  • Siikamäki, Heli (Helsingin yliopisto, 2015)
    Study I analyzed Finnish travellers health problems abroad during 2010 2012. Information was drawn from a database kept by an assistance organization of insurance companies covering 95% of Finnish cases requiring aid abroad. The study included 50 710 cases. These data were compared to numbers of Finnish travellers from the Official Statistics of Finland to calculate incidences of illness and injury at various destinations. The most common diagnostic categories proved to be infections (60%) and injuries (14%); the most frequent diagnoses were acute gastroenteritis (23%) and respiratory infections (21%). Incidence was high in Africa, southern Europe plus the eastern Mediterranean, and Asia. Pre-travel counselling appears advisable also for visitors to southern Europe. Means for preventing gastrointestinal and respiratory infections are needed. Study II explored the final diagnoses of returning travellers with fever. This retrospective investigation comprised 462 febrile adults returning from malaria-endemic areas admitted to the Helsinki University Central Hospital emergency room during 2005 2009. The most common diagnostic categories were acute diarrhoeal disease (27%), systemic febrile illness (15%), and respiratory illness (15%). One traveller in four had a potentially life-threatening illness; septicemia proved as common as malaria (5% vs. 4%); one in ten had more than one diagnosis. The results suggest that the diagnostic protocol in tertiary hospital should in addition to malaria smears comprise blood cultures, influenza rapid test, and HIV test. Study III analyzed surveillance data on malaria cases reported to the National Infectious Disease Register 1995 2008 totalling 484 cases, and related them to travel statistics and antimalarial drug sales. The number of visits to malaria-endemic areas increased, whereas malaria cases did not, and a decreasing trend appeared in antimalarial drug sales. Infections were mostly acquired in Africa (76%). The most common species was Plasmodium falciparum (61%). Of all cases, 42% proved of foreign origin; in 89%, the infection was contracted in the region of birth, implying that immigrants visiting friends and relatives constitute a risk group with a particular need for pre-travel advice. Study IV analyzed in detail the background information on malaria cases diagnosed in Finland 2003 2011. The data included 265 cases, 54% of whom were born in malaria-endemic countries, and 86% currently lived in non-endemic regions. Of those born in non-endemic regions, 81% had received pre-travel advice, but only 20% of those born in endemic ones. Among travellers infected with P. falciparum, 4% reported regular use of appropriate chemoprophylaxis, yet individual rechecking by interview revealed that none had been fully compliant. These data suggest that, if taken conscientiously, mefloquine, atovaquone/proguanil, and doxycycline are effective as chemoprophylaxis against P. falciparum malaria.
  • Knaster, Peter (Helsingin yliopisto, 2015)
    Chronic pain is a long-lasting burdensome condition. Comorbid psychological symptoms are common in chronic pain patients and they tend to worsen the treatment outcome. The aim of this cross-sectional study was to assess the prevalence of psychiatric comorbidity in chronic pain patients and to assess the associations between chronic pain, anxiety, anger, and depression. The study participants in the study were one hundred consecutive chronic pain patients referred to the Meilahti Pain Clinic of Helsinki University Hospital. The subjects were interviewed with the Structured Clinical Interview for DSM-IV for Axis I disorders (SCID-I). In addition self-report questionnaires were used in the assessment. Most (75%) patients had at least one lifetime mental disorder. The prevalence of major depressive disorder (MDD) was 37% and of a specific anxiety disorder 25% over the past 12 months. The psychiatric comorbidity was associated with increased pain intensity, measured by Visual Analogue Scale (VAS). The majority (77%) of the anxiety disorders had their onset before the onset of pain, whereas only 37% of the mood disorders preceded pain onset. The Harm Avoidance (HA) scale of the Temperament and Character Inventory (TCI) of Cloninger was associated with pain-related anxiety measured with Pain Anxiety Symptom Scale-20. The pain intensity influenced the strength of the association between the Harm Avoidance HA4 subscale and pain-related anxiety. Higher pain intensity was associated with stronger association between the variables. Likewise, pain intensity influenced the association between anger management and depression. A tendency to inhibit angry feelings was associated the somatic and physical symptoms of depression, measured by a two-factor model of the Beck Depression Inventory (BDI). The association was stronger in patients with higher pain intensity. Chronic pain patients with current MDD scored higher in both the somatic and cognitive-emotional subscales of the BDI compared with those without MDD. However, the somatic-physical-related items were more strongly associated with the diagnosis of MDD. Psychiatric disorders are common in chronic pain patients. Because of their influence on the chronic pain treatment and outcome, their thorough assessment is important. The linking mechanisms between chronic pain and the psychiatric disorders and symptoms are complicated and there is an overlap between the constructs. Clear boundaries between pain, anxiety and depression can be difficult to draw, which can be a reflection of the common background mechanisms such as common neural circuits and neurotransmitters.
  • Arovuori, Kyösti (Helsingin yliopisto, 2015)
    This dissertation analyses the effectiveness of the Common Agricultural Policy of the European Union. The motivation of this study arises from the fact that there is a lack of empirical research on the effects of policy instruments on the stated policy objectives. In addition, most of the analysis in the literature has focused on the policy objective to secure farmers incomes and, thus, on the efficiency of income redistribution. The policy effectiveness is defined as the ability of agricultural policy to respond to the stated policy objectives, given the general economic and structural conditions under which the policies operate. In this study, an empirical analysis of the effects of implemented policies and policy reforms on the stated policy objectives in the Common Agricultural Policy of the European Union is conducted. The analysis is carried out at the EU15 level and the time period analysed ranges from 1975 to 2007. In the empirical part, an econometric model utilising panel data for the EU15 countries is built. In the model, the development of the defined policy target variables is explained with policy variables and a set of economic and structural control variables. The results show that policy target variables have, in general, developed in the desired direction. The productivity of agriculture has increased, markets have been stable, self-sufficiency ratios have been achieved and the real term food prices have declined. However, farmers incomes have mostly declined. The implemented agricultural policy reforms have improved the policy effectiveness in general. The main contribution of the implemented reforms has been to the use of resources in agriculture. A policy shift from coupled price support to direct payments has released resources from agriculture to be utilised in other sectors. On the other hand, policy reforms have led to increasing price variation. This is a self-explanatory impact in the sense that administrative price setting was reduced and later on abolished in the policy reforms. According to this study, the impact of agricultural policy on the policy objectives is multifunctional. The implemented policy instruments may also have worked in the opposite direction compared to the targets set. While agricultural policies have clearly contributed to increasing agricultural productivity, they have also absorbed resources into the sector which could have been utilised more efficiently in other sectors. The country-level heterogeneity of economic and agricultural structures has increased especially due to the recent enlargements of the EU from EU15 to EU28. The analysis in this study shows that country-level heterogeneity has a significant impact on the development of policy target variables. Although the implemented policy reforms have made a contribution towards the desired direction and improved the effectiveness of the policies, it is a major challenge for future agricultural policies to effectively tackle the different structures.
  • Louhimo, Riku (Helsingin yliopisto, 2015)
    Cancer is one of the leading causes of death in industrialized nations and its incidence is steadily increasing due to population aging. Cancer constitutes a group of diseases characterized by unwanted cellular growth which results from random genomic alterations and environmental exposure. Diverse genomic and epigenomic alterations separately and jointly regulate gene expression and stimulate and support neoplastic growth. More effective treatment, earlier and more accurate diagnosis, and improved management of cancer are important for public health and well-being. Technological improvements in data measurement, storing and transport capability are transforming cancer research to a data-intensive field. The large increases in the quality and quantity of data for the analysis and interpretation of experiments has made employing computational and statistical tools necessary. Data integration - the combination of different types of measurement data - is a valuable computational tool for cancer research because data integration improves the interpretability of data-driven analytics and can thereby provide novel prognostic markers and drug targets. I have developed two computational data integration tools for large-scale genomic data and a simulator framework for testing a specific type of data integration algorithm. The first computational method, CNAmet, enhances the interpretation of genomic analysis results by integrating three data levels: gene expression, copy-number alteration, and DNA methylation. The second computational method, GOPredict, uses a knowledge discovery approach to prioritize drugs for patient cohorts thereby stratifying patients into potentitally drug-sensitive subgroups. Using the simulator framework, we are able to compare the performance of integration algorithms which integrate gene copy-number data with gene expression data to find putative cancer genes. Our experimental results indicate in simulated, cell line, and primary tumor data that well-performing integration algorithms for gene copy-number and expression data use and process genomic data appropriately. Applying these methods to diffuse large B-cell lymphoma, integrative analysis of copy-number and expression data helps to uncover a gene with putative prognostic utility. Furthermore, analysis of glioblastoma brain cancer data with CNAmet suggests that a number of known cancer genes, including the epidermal growth factor receptor, are highly expressed due to co-occuring alterations in their promoter DNA methylation and copy-number. Finally, integration of publicly available molecular and literature data with GOPredict suggests that treating patients with FGFR inhibitors in breast cancer and CDK inhibitors in ovarian cancer could support standard drug therapies. Collectively, the methods developed here and their application to varied molecular cancer data sets illustrates the benefits of data integration in cancer genomics.
  • Terhonen, Eeva-Liisa (Helsingin yliopisto, 2015)
    Scots pine (Pinus sylvestris) and Norway spruce (Picea abies) cover large areas in boreal regions with significant economic importance to Finnish forest industry. Approximately 15% of the spruce trees felled in Finland are rotten and thus commercially less valuable. The majority of this conifer wood decay is due to the root and butt rot pathogen Heterobasidion annosum sensu lato. Extensive logging of conifer forests has changed the environment into favouring this pathogen in stands where it originally has been rare. The saprotrophic fungus Phlebiopsis gigantea has for several years been used as a biocontrol agent against H. annosum s.l. in spruce and pine stumps. A major problem is that, although the effectiveness of P. gigantea as a biocontrol agent has empirically been shown, the long-term biological effect of this fungus on other decomposing wood microbiota has not been proven. The first objective of this thesis is to evaluate the impact of the only biocontrol agent used against root and butt rot fungus (H. annosum s.l.) on other resident microflora of Norway spruce stumps. An additional objective is to screen and identify other potentially novel bioagents that can be deployed for the biocontrol of the conifer pathogen. To find out whether the P. gigantea treatment impacts the overall diversity of other non-target stump microbes we used the 454- pyrosequencing approach. Samples were collected from forest sites previously pre-treated with P. gigantea either one, six or 13 years ago. Similarly samples were collected from untreated stumps within the same forest site over the same period of time. The results revealed that initial application of the biocontrol agent influenced the fungal species composition, but the overall fungal diversity was not affected and no statistical differences were observed between treated and non-treated stumps in the mycobiota. The biocontrol treatment significantly decreased the initial bacterial richness in the stumps, but the bacterial community gradually recovered and the negative effect of P. gigantea was attenuated. In parallel to the above studies, I further explored the potential of finding other novel biocontrol agents for use in managing the disease caused by the root rot pathogen Heterobasidion parviporum. This necessitated isolation studies of fungal root endophytes from forestry sites such as pristine mires and drained peatlands where the spread of H. annosum s.l. species have not been commonly reported. A total of 113 isolates of fungal root endophytes were obtained from non-mycorrhizal P. abies roots, which were assigned to 15 different operational taxonomic units (OTUs). Nineteen of the isolates (17%) inhibited the growth of the conifer root rot pathogen in vitro. From these, two isolates were further used to test the potential inhibitory effects during interaction, in vitro, with H. parviporum. Additionally, the metabolites secreted by the selected root endophytes were extracted and the inhibitory effects on these pathogenic fungi were assayed. The secreted metabolites were further chemically analysed using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). These results give new information from the new possibilities to protect the valuable seedling roots from root rot. The results of the thesis provide new information to facilitate better management and protection of these forest sites from H. annosum s.l. as well as support the continued used of P. gigantea for stump pre-treatment in Finnish forests.
  • Li, Jianyong (Helsingin yliopisto, 2015)
    Assessing the numerical relationships among pollen spectra, human influence and climate is a critical prerequisite for obtaining reliable and robust pollen-based quantitative reconstructions for past climatic variations and human-induced environmental changes. Here, modern pollen data from small river catchments in human-influenced mountainous ecosystems of northern China are collected to investigate the pollen/vegetation/land-use relationships. The effects of human influence index (HII) in comparison with key climate variables on influencing modern pollen distribution are evaluated using a continental-scale dataset. The importance of different climate variables accounting for modern pollen distribution is quantified for identifying the determinant variables that can be reconstructed in different bioclimatic regions of China. Furthermore, pollen-based calibration models for HII and climate parameters are developed and applied to a set of fossil pollen data for quantitative human influence and climate reconstructions. In addition, the bias caused by long-term and intensive human influence on vegetation in quantitative pollen-based palaeoclimatic reconstructions is examined, and pollen-based climate reconstructions are used to validate the reliability of climate model simulations. The results reveal that pollen assemblages from surface sediment samples in the Tuoliang and Qipanshan catchments from northern China are dominated by Artemisia, Chenopodiaceae, Pinus and Selaginella sinensis. Pollen types indicative of human activities such as Cerealia-type are common but not abundant. Artemisia and Chenopodiaceae percentages decline with decreasing altitude, whereas Pinus and S. sinensis percentages increase, suggesting that saccate Pinus pollen and S. sinensis spores can be transported further than non-saccate pollen types and that pollen sorting is taking place over water transportation. There is a positive linear relationship between percentages of Cerealia-type pollen and proportions of farmland, whereas correlation between percentages of trees, shrubs and herbs pollen and proportions of woodland, scrubland and grassland respectively is poor. This can be attributed to the differences in pollen productivity, deposition and dispersal. These findings may provide the basis for a modeling approach to reconstruct past land-cover changes at small catchment scale in northern China. The effects of HII on accounting for modern pollen distribution are smaller than annual precipitation (PANN) or annual average temperature (TANN) in most regions of China, with the exception of east-central China that has a significant pollen–HII relationship. The quantified importance of six climate variables (PANN; TANN; actual/potential evapotranspiration ratio, Alpha; mean temperature of the warmest month, MTWA; mean temperature of the coldest month, MTCO; annual sum of the growing degree days above 5 °C, GDD5) for the geographical distribution of modern pollen data differs among regions in China. Hydrological variables are more important than temperature-related variables in north-western and -eastern China and the Tibetan Plateau, whilst temperature-related variables are dominant in east-central and southern China. This suggests that the critical climate variables which can be optimally reconstructed from pollen data vary regionally in China. These regional differences are common to other large-scale surface pollen datasets and need to be taken into considerations in pollen-based climate reconstructions. The calibration models for HII, PANN and TANN show good statistical performances and are applied to a fossil pollen sequence from Lake Tianchi in east-central China. The inferred HII increases abruptly at 1100 cal. yr BP and remains high until present-day. Correspondingly, the reconstructed PANN shows a sudden decrease since 1100 cal. yr BP, whereas TANN displays an increase. However, other independent palaeoclimatic records mostly contradict the reconstructed climatic trends for the last 1100 years, suggesting that the Tianchi climate reconstructions for this period are biased by the intensification of human influence. This bias probably occurs in other palaeoclimatic reconstructions using pollen data from other regions where human impact on vegetation is also intensive and long-lasting. The calibration models for the summer monsoon precipitation (Pjja) also exhibit good predictive performances and are applied to a set of fossil pollen data from monsoonal China. The Holocene Pjja reconstructions from northern China are stacked to one record, showing that Pjja increases since 9500 cal. yr BP, reaches the maximum at 7000–4000 cal. yr BP, and falls down to present-day. The reconstructions are compared with Pjja simulations from the Kiel Climate Model (KCM). The model output and reconstructions are different for the early-Holocene for which the model suggests higher Pjja. The simulated Pjja changes for the Holocene summer monsoon maximum (HSMM) are lower than the reconstructed changes. The increasing or decreasing Pjja trends before or after the HSMM are more pronounced in the reconstructions than in the model results. Other palaeoclimatic data show substantial Holocene monsoon precipitation changes. This suggests that the KCM underestimates the magnitude of the summer monsoon precipitation changes. The results obtained in this work highlight the necessity for critically assessing the modern pollen/human-influence/climate relationships at various spatial scales and can be used to improve the correctness and robustness of pollen-based climate and human influence reconstructions in China and other regions of the world with large-scale surface pollen datasets. The pollen-based calibration models and their forthcoming applications can be employed to further quantitatively explore the past environmental changes and climatic dynamics and to validate the accuracy of climate model output.
  • Venhoranta, Heli (Helsingin yliopisto, 2015)
    Dairy cattle breeding programs rely heavily on artificial insemination (AI). The AI enables intense selection for desired traits, but the use of few elite bulls carries a risk that inherited defects may proliferate in the population. The emergence of inherited defects is a recurrent issue in cattle breeding and rapid identification and management of genetic defects are crucial for preventing economic losses and maintaining good animal welfare. Modern molecular genetics techniques enable efficient detection of causative mutations, information which is needed for DNA testing. In this study, we investigated three inherited congenital bovine defects and located causative mutations for these diseases. 1. A microdeletion in PEG3 domain causes intrauterine growth restriction and stillbirths to almost half of the pregnancies sired by a single Ayrshire AI bull. The deletion, when inherited from the sire, is semi-lethal but the female mutation carriers can breed normally. The deletion truncates the 3 end of the non-coding maternally imprinted MIMT1 transcript and also causes expression changes in other genes of the domain. The expression changes of hundreds of genes in the foetal side of the placenta were also demonstrated. 2. Inherited gonadal hypoplasia with incomplete penetrance in Northern Finncattle and Swedish Mountain breed is associated with homozygosity for the Cs29 allele. This allele is an ectopic segment that is duplicated and translocated from chromosome 6 to 29 and encompasses the KIT gene. Cs29 allele is associated with colour sidedness in various cattle breeds, which coheres with the results that gonadal hypoplasia is connected with white coat colour. The KIT gene is known to regulate the migration of the germ cells and precursors of melanocytes. 3. A new recessive developmental disorder defined as PIRM (ptosis, intellectual disability, retarded growth and mortality) in Ayrshire breed was associated with single base substitution in the UBE3B gene. Mutation causes in-frame exon skipping, resulting in an altered protein lacking 40 amino acids, which likely comprises protein function. In humans, mutations in the UBE3B gene are associated with Kaufman oculocerebrofacial syndrome, with similar pathological effects as for PIRM syndrome. The UBE3B mutation may be connected with the AH1 haplotype, which is associated with reduced fertility and has a carrier frequency of 26.1% in the North American Ayrshire population. The mutations related to these three defects or syndromes can now be easily tested for. The results can be used to avoid risky matings, cull carriers and provide a veterinary diagnostic. The expression analyses proved that the mutations in Ayrshires also affected the RNA expression of the respective mutated gene or even hundreds of other genes. The described genotype-phenotype associations can be used as a basis for approaches to locate quantitative trait loci in cattle or provide new insights into developmental biology and inform translational research across species.
  • Autio, Karoliina (Helsingin yliopisto, 2015)
    Cancer is one of the most common reasons for death in dogs, cats and humans. New therapeutic modalities are necessary to improve disease outcome. One promising approach is oncolytic virotherapy. Until now, the only oncolytic virus evaluated in a clinical trial in veterinary medicine has been canine oncolytic adenovirus, but a clinical trial has been started with oncolytic vaccinia virus (VV) in pet dogs. In cats, oncolytic viruses have not been evaluated in clinical settings. Tumour treatment in dogs and cats could also serve as a model for human cancer therapy. The purpose of the thesis was to evaluate preclinically whether genetically modified oncolytic VV and Semliki Forest virus (SFV) could offer a new treatment modality for dogs and cats. Oncolytic VV was rendered tumour selective by a dual ablation of vaccinia growth factor and thymidine kinase, making it more cancer-specific than previously used VVs in veterinary research. To further increase the efficacy of the VV, an immunostimulatory gene, CD40L, was added to the virus backbone. Avirulent SFV A7(74) has a natural trophism for cancer cells and was not genetically manipulated. Both viruses infected and killed tested cancer cell lines, and VV also infected most of the primary surgical tumour tissues tested. In the nude mouse xenograft model, double deleted VV (vvdd) significantly reduced tumour growth. Interestingly, when in intact monolayers, SCCF1 cells were not killed by VV, but secreted infectious, morphologically abnormal virions. One dog experienced a possible seizure after VV administration, but no other serious adverse events occurred. Vaccinia DNA declined quickly in the blood after virus administration, but was still detectable one week later by qPCR. Only samples taken directly after the VV infusion contained infectious virus, which was not found in any other blood, saliva, urine or faecal samples. Necropsies did not reveal any pathological changes associated with virus administrations. In conclusion, our results show that oncolytic VV and SFV can infect and kill tested canine cancer cell lines, and that VV has antitumoral activity in the mouse xenograft model and it can infect fresh tumour biopsies. In addition, intravenous administration of the viruses did not induce life-threatening adverse events in healthy dogs. These agents thus warrant further evaluation in veterinary medicine.
  • von Boehm, Jukka (2015)
    The study analyses the performance history and Wirkungsgeschichte of Richard Wagner s Lohengrin (premiered 1850) in Germany and Russia in the 20th century. In Wagner s opera the mysterious knight arrives in medieval Brabant, where the people receive him as their redeemer . Lohengrin became one of Adolf Hitler s favourite operas. Through analysis of Lohengrin s influence, the study casts light on a broad and complex theme: how did Wagner s ideas and art become intertwined with Nazi ideology? Or how were they received in the context of other radical societal experiments, namely Soviet and East German socialism? This examination of different interpretations of the same text (Lohengrin) on stage and through its reception will reveal prevailing societal attitudes, taboos, values and hopes. Case study I discusses the reception of a few nationalist themes in Lohengrin. Specifically, the focus is on ultra-nationalist projections onto Lohengrin, which emerged during the resurgence of late 19th-century German Hurrah-patriotism and Nazi ideology. The focus of Case study II is on Heinz Tietjen s direction of Lohengrin at the Bayreuth Festival during the Third Reich (1936). The study demonstrates how Tietjen embedded Nazi ideology in his reading. Case study III takes another look at Lohengrin s influence on Soviet and East German socialism. The study scrutinises the ambivalent role of Lohengrin in the context of a dogmatic communist cultural policy that valued (socialist) realism. Another theme discussed is the problematic relationship of Lohengrin to the German Democratic Republic and its anti-fascism. Case study IV analyses Peter Konwitschny s innovative direction of Lohengrin in 1998. Characteristic of the deconstructive style of German director s theatre , the opera was set in a school classroom before the outbreak of the First World War. Konwitschny s interpretation offers an excellent case for analysing strategies by which a modern direction can take up the challenge of ideologically ambivalent opera. The study challenges the commonly oversimplified narrative that presents Wagner as a forerunner of Hitler and Nazism. Although there was irrational potential in Lohengrin, which became topical in the Third Reich, the relationship between Wagner s opera and National Socialism is much more complex, including the fact that Wagner s utopian ideas in Lohengrin also inspired the left. The main primary sources consist of German archival material, newspapers and journals.
  • Lehtonen, Heini (Helsingin yliopisto, 2015)
    This thesis examines language use in interaction among adolescents in two junior high schools in Eastern Helsinki. The pupils represent several ethnic backgrounds, and some twenty different first languages are spoken in the schools. The thesis analyses the ways in which the adolescents position themselves and each other with regard to social categories related to ethnicity, gender, and style, focusing on the linguistic resources used in the positioning. The attitudes vis-a-vis linguistic diversity and asymmetry are explored as well. The research questions are as follows: 1) How does a linguistic feature become a social indexical? 2) How do (linguistic) styles get enregistered? 3) How are ownership and foreignness of language negotiated and construed? The thesis participates in the current discussions on ways of conceptualizing multilingualism in the globalization era. Questions of immigration and second language acquisition, learning and teaching are discussed from a sociolinguistic point of view. Theoretically and methodologically, the thesis encompasses the fields of linguistic ethnography, interactional sociolinguistics, and the sociolinguistics of globalization. The data consist of 1) field notes and a field diary, 2) recorded interviews with 37 adolescents, 3) several audio and video recordings of spontaneous interaction during both the lessons and the breaks, and 4) retrospective interviews. The analysis shows the adolescents orientating to the categories of Finns and foreigners , but the meaning of these categorizations is construed in local stylistic practices and does not necessarily resemble to the similar labels used in public discourses. Ethnicity, gender, and enregistered styles (such as hip hop) intertwine in such ways, that the participation in local stylistic practices may guarantee a stronger ownership of linguistic resources than one s ethnic background. All types of linguistic features (phonetic, prosodic, morphological, syntactic, lexical) were found to function as social indexicals. Frequent resources that stand out and establish social relationships between participants are especially likely to develop into social indexicals. As a part of local social practices and in the metapragmatic accounts commenting the practices, linguistic features get associated to specific social personae and their characteristics, and get enregistered to styles. Social indexicals are employed in stylized performances that bring another s voice into the interaction. The stylisations serve as a resource for stance-taking, but also as metapragmatic accounts of the features employed in them. The questions of who knows Finnish or does not know Finnish are negotiated both explicitly and implicitly. One of the implicit means of such negotiations are the stylized bad Finnish performances, where the adolescents carnevalize the stereotypical representations of immigrants or non-native Finns .
  • Selim, Shaimaa (Helsingin yliopisto, 2015)
    The objective of the research described in this thesis was to increase the understanding of the transcriptional adaptations of genes encoding proteins, which have key roles in lipid and glucose metabolism, insulin signalling and inflammation, in situations of overfeeding energy during the dry period in dairy cows and summer grazing season in mares. Emphasis was placed on the potential to decrease metabolic disorders and to improve animal nutritional management and health. In the experiment I, dairy cows were fed a grass silage based diet either on a controlled energy level (on average 99 MJ/d metabolizable energy (ME), n = 8) during the last six weeks of the dry period or high energy level (on average 141 MJ/d ME, n = 8) for the first three weeks and then gradually decreasing energy allowance during three weeks to 99 MJ/d ME by parturition. In experiment II, dairy cows were fed ad libitum either grass silage (144 MJ/d ME, n = 8) or a mixture of grass silage, wheat straw and rapeseed meal (TMR, 55%: 40%: 5%, 109 MJ/d ME, n = 8) during the 8-wk dry period. Liver and adipose tissue biopsies and blood samples were collected during the transition period in experiments I and II. In the experiment III, the impact of grazing either on cultivated high-yielding pasture (CG) or semi-natural grassland pasture (NG) on fat deposition, insulin resistance status and adipose tissue gene expression of Finnhorse mares was studied. Body measurements, intravenous glucose tolerance tests (IVGTT), and sampling for the determination of neck and tailhead adipose tissue gene expressions were conducted in May and September. In experiments I and II, overfed cows had greater total dry matter and ME intakes and ME balance before parturition than control cows, but no differences were observed after calving. Increases in body weight and body condition score were greater in the overfed cows of the experiment II during the dry period. In the experiment I, there was greater plasma insulin and lower glucagon/insulin ratio in overfed cows than in control cows, while in the experiment II, there were no differences in blood parameters between overfed and TMR group during the transition period. Down-regulation of key genes linked to hepatic gluconeogenesis and fatty acid β-oxidation in the overfed group of cows in the experiment I was found, suggesting impaired liver function compared to a controlled energy diet. In the experiment II, ad libitum feeding of grass silage throughout the dry period may have attenuated the increase of hepatic gluconeogenic capacity from propionate compared to a controlled TMR diet. However, there was no difference in the expression of genes related to hepatic glucose release during the transition period (II). In adipose tissue, there was some evidence that the level of energy overfeeding may have exacerbated the inflammatory status postpartum and temporarily decreased lipogenesis very near parturition relative to control energy diet (I). In the experiment II, prepartal ad libitum feeding of grass silage decreased lipogenesis and insulin sensitivity early postpartum compared to the TMR control group. In the experiment III, CG mares had higher median body condition score and body weight, and larger waist circumference than NG mares at the end of grazing. In September, greater basal and peak insulin concentrations, and faster glucose clearance rate during IVGTT were observed in CG mares than in NG mares. In addition, a greater decrease in plasma non-esterified fatty acids during IVGTT was noticed in CG mares. There were no differences in the expression of genes related to insulin resistance, inflammation and lipogenesis between the two groups. Significant temporal differences in the expression profiles of genes related to insulin resistance and lipogenesis were observed during the grazing season. Grazing on CG had moderate effects on responses during IVGTT, but did not exacerbate insulin resistance. In conclusion, overfeeding energy with concomitant weight gain moderately altered the expression of genes related to insulin resistance, inflammation and lipogenesis in adipose tissue of dairy cows. Prepartal overfeeding energy affected the expression of genes related to hepatic gluconeogenesis and fatty acid oxidation in dairy cows, but the extent of these effects differed depending on the dietary composition during the close-up period (e.g. feeding of cereal grain). In mares, the diets with variable energy content did not affect the expression of insulin resistance- or inflammation-related genes, although mares were different in their body condition scores.
  • Marinkovic, Ivan (Helsingin yliopisto, 2015)
    Intracerebral hemorrhage (ICH) represents the subtype of stroke carrying the most detrimental outcome and highest mortality. It is clearly underinvestigated and lacks an effective treatment except supportive management measures. The dismal outcomes of ICH are clearly associated with the mass effect of hematoma accompanied with dynamic perihematomal edema (PHE) and potential intraventricular bleeding (IVH), which is often complicated by development of hydrocephalus. In this thesis, we aimed to develop novel therapy modalities, which apart from experimental conditions, might be found effective in clinical scenario, and successfully implemented in ICH treatment clinical protocols in the future. In study (I), we utilized autologous blood injection model and magnetic resonance imaging (MRI) follow-up. Following the induction of deep right hemispheric hematoma of 75uL of volume, we performed decompressive craniectomy (DC) at 1 h, 6 h, and 24 h time points, aiming at diminishing high intracranial pressure (ICP) after the bleeding event. Control group did not undergo DC procedure. Decompressive craniectomy was found effective in reducing mortality and improving overall neurobehavioral outcome and mortality in all the 3 treatment groups. Effect of DC was most pronounced in the early craniectomy group (1 h). In study (II), we aimed to examine how deleterious is the influence of tissue plasminogen activator (tPA) in experimental ICH scenario, and whether the adverse tPA effects could be antagonized by the clinically safe mast-cell stabilizer chromoglycate. Animals were divided in four groups. We utilized intrahemispheric collagenase injection rat ICH model and MRI follow-up imaging up to 72h. Group 1 received tPA only, whereas Group 2 and Group 3 besides tPA received chromoglycate in single or double dose. Group 4 was used as a control having ICH, but receiving saline only. TPA-treated animals did not have significantly larger hematomas or hemispheric expansion even though been characterized by worse overall outcome. Application of chromoglycate in high dose mitigated detrimental outcomes present in the group being treated with tPA only, and diminished the extent of hemispheric expansion. This encourages further research to potentially establish "blind" thrombolysis concept coupled with concomitant application of MC inhibitors, as we could show that injurious tPA effects were successfully abolished by concomitant MC stabilization in experimental ICH scenario. In the third study (III), we decided to develop a novel combined ICH + intraventricular hemorrhage (IVH) model in the rat as such a model does not exist besides the fact that approximately 40% of all ICHs in human patients are complicated by presence of intraventricular hemorrhage which is known to worsen prognosis. We utilized different blood volumes of 100-250uL in modified autologous blood injection model to induce deep intrahemispheric ICH to establish a fully novel experimental approach of ICH followed by IVH. We performed 1-week MRI follow-up and consistent neurobehavioral evaluation at 24 h, 48 h, 72 h, and 1 week after hemorrhage. Using MRI, we identified the presence of hydrocephalus in all experimental subjects, and its progressive tendency during entire follow-up. The most prominent hemispheric expansion and the most pronounced hydrocephalus were present in experimental groups with >200uL blood injection. This model was reliable and highly reproducible, demonstrating promising initial point for ICH+IVH experimental research. These two novel treatment strategies established in our studies give promise for further refinements and potential applications in human patients. The novel ICH+IVH model we established in rat models may serve as an improved model for future experimental studies as it mimics human disease scenarios better than the existing models.
  • Hänninen, Timo (Helsingin yliopisto, 2015)
    Controlling integral operators by dyadic model operators, and studying the boundedness of dyadic operators on Lebesgue spaces are central themes in dyadic harmonic analysis. This dissertation consists of an introductory part and five articles contributing to these themes. Many operators of harmonic analysis can be dominated by positive dyadic operators by using Lerner's median oscillation decomposition. In the first and fifth article, we extend this decomposition to Banach space valued functions and non-doubling measures. Dyadic shifts and paraproducts are dyadic model operators for Calderón-Zygmund operators. In the second article, we study the boundedness of these operators on unweighted Lebesgue spaces in an abstract operator-valued setting. We prove that operator-valued dyadic shifts are bounded, and we characterize the boundedness of operator-valued dyadic paraproducts. Furthermore, we extend Hytönen's dyadic representation theorem, which states that every Calderón-Zygmund operator can be represented by dyadic shifts and paraproducts, to the operator-valued setting. In the third article, we characterize the boundedness of linear and bilinear positive dyadic operators from a weighted Lebesgue space to another. We consider the case that the Lebesgue exponent of the range side is strictly less than the Lebesgue exponent of the domain side. We show that, in this range of the exponents, the Sawyer testing condition is insufficient for the boundedness. We introduce a sequential testing condition, of which the Sawyer testing condition can be viewed as an endpoint case, and prove that this testing condition is both sufficient and necessary for the boundedness. No characterization in the bilinear case was available until this article. Furthermore, we show that the sequential testing condition is necessary for the boundedness of any positive linear or bilinear operator, and hence it may be helpful in charactering the boundedness of other operators as well. In the fourth article, we characterize the boundedness of positive dyadic operators from a weighted Lebesgue space to another in an abstract operator-valued setting. The purpose is to understand which kind of testing condition is needed in this setting. We prove that an operator-valued positive dyadic operator is bounded if and only if the operator and its adjoint are each bounded on the class of all functions localized on dyadic cubes and taking values on a unit sphere. Furthermore, we show that the boundedness on unweighted Lebesgue spaces is characterized by an endpoint case of this condition. We work directly with Lebesgue spaces, without using interpolation between endpoint spaces. In the second article, we give new (in our opinion simple) proofs for the key tools that we use: decoupling inequality for martingale differences and a variant of Pythagoras' theorem for Lebesgue spaces.
  • Sandboge, Samuel (Helsingin yliopisto, 2015)
    Background. A small birth size, an indicator of a suboptimal intrauterine environment, is a risk factor for several non-communicable diseases (NCDs), a risk that in many cases is modified by childhood growth patterns. Regional variation in NCD prevalence could partly have its origin in early development. Lifestyle factors further influence NCD prevalence. Aims. We aimed to explore the associations between early growth and adult resting metabolic rate (RMR), body composition, non-alcoholic fatty liver disease (NAFLD), and hypertension. We also studied the associations between fructose intake and NAFLD, and differences in birth size between Helsinki and the Åland Islands. Subjects and methods. The Helsinki Birth Cohort Study consists of 13345 individuals born in Helsinki in 1934‒44. Detailed records are available for all participants including information on maternal and birth characteristics and measurements of childhood body size. 2003 individuals participated in a clinical study in 2001‒04 and 1083 of these additionally participated in a follow-up study in 2006‒08. The Åland records include 1697 births for the years 1937‒44. Results. The association between birth weight and RMR was inverse among women and quadratic among men. A higher attained adult weight than expected, based on weight and height measurements before age 11 years and adult height, was associated with higher adult body fat content. The odds ratio (OR) for NAFLD was 18.5 (95% CI 10.1; 33.6) among those who belonged to the lowest BMI tertile at age 2 years and subsequently were obese as adults, compared to those who were still lean or normal weight as adults. NAFLD was most common among individuals with the lowest dietary fructose intake. Systolic blood pressure (SBP) and the presence of hypertension were inversely associated with linear (height) growth between ages 2 and 11 years. Relative weight gain after age 11 years was positively associated with SBP. Ålandic babies born 1937‒44 were 87 grams (95% CI 61; 111) heavier and 0.4 cm (95% CI 0.3; 0.5) longer than their Helsinki peers. Conclusions. A more pronounced increase in relative weight after age 11 years than would be expected from previous body size, was positively associated with body fat content, NAFLD, and hypertension. Conversely, several growth measurements before age 11 years were negatively associated with the outcomes studied. None of the studied individuals were obese in childhood. Instead, a larger relative childhood body size in this group most likely represents a more beneficial childhood environment. Contrary to previous findings, we found that individuals with the highest fructose intake were least likely to suffer from NAFLD. We found a small but significant difference in birth size between the Åland Islands and Helsinki for the years 1937‒44.
  • Müller, Susann (Helsingin yliopisto, 2015)
    Biogeochemical processes in sea ice and the ice-water interface depend on abiotic processes and biological activity. Abiotic processes in sea ice are controlled by the crystallization process of freezing water and the associated formation of saline brine. Also the heat budget of sea ice and the resulting changes in abiotic properties such as porosity and salinity need to be taken into account. The dissolved fraction of sea ice brines contain ions and dissolved organic matter (DOM). Ions are rejected from the ice by diffusion and gravity drainage whereas dissolved organic matter with highly complex and diverse chemical composition can react in many ways with other molecules and surfaces. Hence, the present work compares the behavior of different fractions of DOM to the ones of salts during initial sea ice formation. Controlled tank studies were combined with natural sea ice sampling to exclude the disadvantages of both systems such as the effects of small-scale experiments, artificial additions in tank experiments and the unknown history of natural samples. The studies were conducted with brackish sea ice from the Baltic Sea with its high nutrient and DOM concentrations, but also with oceanic sea ice from the North Sea and the Arctic Ocean. This allows a general conclusion about the behavior of solutes during the formation of sea ice. The present studies indicate that the major seawater ions are significantly fractionated due to differential diffusion and coupled diffuse-convective salt transport through the brine channel network. Ions with a lower diffusivity than Cl¯, in this study SO42¯, Ca+ and Mg2+, remained longer in the brine channel network and got therefore enriched in sea ice relative to Cl¯. K+, on the other hand, diffused faster than Cl¯ and was depleted in sea ice in this study. The behavior of DOM in sea ice was more complex compared to ions because of the complex structure of DOM and the effect of secondary processes on DOM, such as biological production and degradation in sea ice. The quantification of DOM is challenging since only certain fractions such as chromophoric DOM can be measured instead of estimating the total concentration of DOM. Nevertheless, the present studies on DOM in sea ice from Baltic and North Sea water indicated enrichment of DOM compared to sea water ions. The magnitude of this enrichment was higher than expected from diffusion and convection following the transport of salts. The enrichment varied among DOM fractions with highest enrichment of amino-acid like DOM and lowest enrichment of humic-like substances. The results therefore suggest that additional processes, such as selective drainage that depends on the chemical properties of the DOM molecules, affect the enrichment of DOM in sea ice. The optical properties of sea ice were used to develop a bio-optical model. The model estimates the primary production in Baltic Sea ice based on the absorption by particles and chromophoric DOM and the quantum yield for C fixation calculated from photosynthesis-irradiance curves. The results were compared to in situ primary production measurements. The combination of modelled primary production estimates and the measurements of optical properties and primary production in different types of Baltic Sea ice gave a good overview over bio-optical properties in Baltic Sea ice and can be used as a tool to improve different parameters of ecosystem models.
  • Tokariev, Anton (Helsingin yliopisto, 2015)
    In humans the few months surrounding birth comprise a developmentally critical period characterised by the growth of major neuronal networks as well as their initial tuning towards more functionally mature large-scale constellations. Proper wiring in the neonatal brain, especially during the last trimester of pregnancy and the first weeks of postnatal life, relies on the brain’s endogenous activity and remains critical throughout one’s life. Structural or functional abnormalities at the stage of early network formation may result in a neurological disorder later during maturation. Functional connectivity measures based on an infant electroencephalographic (EEG) time series may be used to monitor these processes. A neonatal EEG is temporally discrete and consists of events (e.g., spontaneous activity transients (SATs)) and the intervals between them (inter-SATs). During early maturation, communication between areas of the brain may be transmitted through two distinct mechanisms: synchronisation between neuronal oscillations and event co-occurrences. In this study, we proposed a novel algorithm capable of assessing the coupling on both of these levels. Our analysis of real data from preterm neonates using the proposed algorithm demonstrated its ability to effectively detect functional connectivity disruptions caused by brain lesions. Our results also suggest that SAT synchronisation represents the dominant means through which inter-areal cooperation occurs in an immature brain. Structural disturbances of the neuronal pathways in the brain carry a frequency selective effect on the functional connectivity decreasing at the event level. Next, we used mathematical models and computational simulations combined with real EEG data to analyse the propagation of electrical neuronal activity within the neonatal head. Our results show that the conductivity of the neonatal skull is much higher than that found in adults. This leads to greater focal spread of cortical signals towards the scalp and requires high-density electrode meshes for quality monitoring of neonatal brain activity. Additionally, we show that the specific structure of the neonatal skull fontanel does not represent a special pathway for the spread of electrical activity because of the overall high conductivity of the skull. Finally, we demonstrated that the choice of EEG recording montage may strongly affect the fidelity of non-redundant neuronal information registration as well as the output of functional connectivity analysis. Our simulations suggest that high-density EEG electrode arrays combined with mathematical transformations, such as the global average or current source density (CSD), provide more spatially accurate details about the underlying cortical activity and may yield results more robust against volume conduction effects. Furthermore, we provide clear instruction regarding how to optimise recording montages for different numbers of sensors.
  • Pekkonen, Pirita (Helsingin yliopisto, 2015)
    Human tumorigenesis is a process in which a normal cell needs to acquire multiple characteristics to become malignant and metastatic. In short, these so called cancer hallmarks include increased proliferation and cell survival, as well as the ability to invade into the surroundings, induce angiogenesis, and finally metastasize to distant sites. These traits are regulated in a variety of different ways. However, some embryonic signaling pathways, including the Notch pathway, are able to regulate many of these processes. Furthermore, it has been shown that these signaling pathways can be deregulated in cancer, and that their untimely activation can lead to malignancies. In this study, Kaposi's sarcoma herpesvirus (KSHV) associated malignancies, namely Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), as well as melanoma have been used as model cancers. In all these malignancies, the tumor cells show alterations in cell identity and lineage marker expression, i.e. signs of cellular de- or transdifferentiation. In addition, the Notch pathway has been shown to be overly active in all of them. Thus, this thesis has focused on how the pro-tumorigenic traits are affected by cell plasticity and reprogramming in these cancers, and how the signaling pathways leading to these phenotypes, most notably Notch, are in turn regulated. Firstly, the results show that in vivo expression of a KSHV oncogene, viral (v-)cyclin, leads to activation of Notch signaling through Notch3 upregulation as well as fine-tuning of the NF-κB pathway through Cdk6 mediated phosphorylation. These changes in turn lead to defects in T-lymphocyte differentiation and immune functions, as well as to the development of T-cell lymphomas. Secondly, this work demonstrates that KSHV infection in primary lymphatic endothelial cells (LECs) in three dimensional (3D) cell culture model leads to activation of a morphogenic process, endothelial to mesenchymal transition (EndMT), and increased invasiveness through activation of the Notch pathway and matrix metalloproteinase MT1-MMP. Lastly, the data show that the changes in cell plasticity contributing to tumorigenic traits are not confined to virally induced cancers. Melanoma cell interaction with LECs leads to activation of the Notch pathway and increased adhesive, invasive, and metastatic properties of the tumor cells. In conclusion, the results show that regulation of cell plasticity through the Notch pathway takes place in different types of cancers, and it can affect several steps of tumorigenesis. A thorough and comprehensive understanding of the processes discovered herein may help develop better and more efficient treatments for these largely fatal malignancies.
  • Lindahl, Jan (Helsingin yliopisto, 2015)
    Jan Lindahl: MANAGEMENT OF PELVIC RING INJURIES Unstable pelvic ring injuries are relatively rare injuries, but they constitute a major cause of death and disability in high-energy polytrauma patients Massive hemorrhage is the leading cause of potentially preventable death following a blunt pelvic trauma. The overall aim of surgical treatment for unstable pelvic ring injuries is to restore the pelvic anatomy and perform neural decompression, thus allowing normal function with a low rate of complications. This doctoral thesis was initiated to investigate the outcomes of acute and definitive management strategies for unstable pelvic ring injuries. The first study investigated the radiological and functional results of treating type B and C pelvic injuries with an anterior external fixation frame. The second study focused on identifying factors for early predictions of mortality-related outcome and prognosis in patients with pelvic fracture-related arterial bleeding that were treated with transcatheter angiographic embolization (TAE). The third study investigated the outcomes of type C pelvic fractures treated with standardized reduction and internal fixation methods. The fourth study evaluated outcomes and identified prognostic factors for operatively-treated, H-shaped sacral fractures with spinopelvic dissociation. Study I showed that an anterior external fixator failed to achieve and properly maintain reduction in 75% of type B open book injuries and in nearly all (95%) type C pelvic ring injuries. Therefore, an external frame is not a suitable method of treatment for the most unstable pelvic ring injuries as a definitive treatment. The current clinical applications of anterior pelvic external fixators comprise the resuscitation phase, initial fracture stabilization phase, and sometimes, in complex injuries (type C), the definitive phase for fixation of the anterior part of the pelvic ring, in conjunction with posterior internal fixation. Study II of pelvic fracture related arterial bleedings showed that the worst prognosis was related to exsanguinating bleeding from the main trunk of the internal or external iliac artery (large pelvic arteries) or from multiple branches of the internal or external iliac vasculature (high vessel size score). Definitive control of arterial bleeding was achieved with TAE in all patients. In massive hemorrhage with several bleeding arteries uni- or bilaterally, it is reasonable to use non-selective embolization by promptly occluding the main trunk of the internal iliac artery, either uni- or bilaterally. Study III of operatively treated type C pelvic fractures revealed that, internal fixation of injuries in the posterior and anterior pelvic ring provided excellent or good radiological results in 90% of cases. Additionally, because a reduction with displacement less than or equal to 5 mm was more often associated with a good functional outcome, that should be the goal of operative management. However, the prognosis is also often dependent on associated injuries, particularly a permanent lumbosacral plexus injury. The results favoured internal fixation of all the injured elements of the pelvis for improved stability and a more accurate anatomical result in the entire pelvic ring. The H-shaped sacral fracture with spinopelvic dissociation is a rare injury pattern. Study IV revealed that lumbopelvic fixation was a reliable treatment method. The study also showed that neurological recovery and clinical outcome were associated with the degree of initial translational displacement of the transverse sacral fracture component. Permanent neurological deficits were more frequent and the clinical outcome was worst in completely displaced transverse sacral fractures. An accurate operative reduction of all sacral fracture components was associated with better neurological recovery and clinical outcome. We conclude, that with appropriate treatment of unstable pelvic ring injuries, and associated injuries in other organs, it is possible to achieve better survival rates and functional results, and to reduce long-term disability.
  • Franti, Lasse (Helsingin yliopisto, 2015)
    The gauge/gravity duality connects the dynamics of gravity theories in the bulk with the dynamics of field theories on the boundary. In this thesis we introduce two thermalization scenarios and investigate them using a suitable holographic description. We will first study the thermalization of equal-time correlators and entanglement entropy in a hyperscaling violating AdS-Lifshitz-Vaidya metric. This work verifies the agreement between numerical procedures and preceding analytical predictions and generalises the previous studies of thermalization in this kind of situations. In the latter part we will use the duality to describe the quark-qluon plasma created in heavy ion collisions. The anisotropic plasma is modelled by introducing anisotropies into the source on the gravity side and letting them evolve according to the equations of motion. The boundary dynamics is extracted by finding the boundary stress-energy tensor. The results agree with the conventional models. The situations considered here are rather simple but this work demonstrates the applicability of holography in the anisotropic case.
  • Lepojärvi, Jason (Helsingin yliopisto, 2015)
    C. S. Lewis (1898-1963) was one of the most influential Christian thinkers of the twentieth century with continuing relevance into the twenty-first. Despite growing academic interest in Lewis, many fields of inquiry remain largely unmapped in Lewis scholarship today. This compilation dissertation, consisting of an introductory overview together with four stand-alone but connected essays, extends critical understanding of Lewis's contribution to the theology of love. In three of the four essays, Lewis's theology of love is compared to and contrasted with that of Anders Nygren (1890-1978); and in one, that of Augustine of Hippo. Using systematic textual analysis, the essays evaluate Lewis's key concepts, argumentation, and presuppositions. Nygren, the Swedish Lutheran theologian and bishop of Lund, has virtually dominated modern theological discussion of love. His antithesis between selfless and gratuitous Christian love and self-seeking and needful Pagan love, or agape and eros respectively, became enormously influential in twentieth century theology. Lewis was initially shaken up by Nygren's work, and it took him decades to formulate his own model, above all in Surprised by Joy (1955) and The Four Loves (1960). It is shown that Lewis constructed not only his theology of love, but also his theology of spiritual desire as a form of love, in conscious opposition to Nygren. Lewis's theology of love challenges the denigration of eros and its separation from agape. Nygren's predestinarianism is also rejected. Lewis devises his own vocabulary, avoids the use of eros and agape in Nygren's sense, and hardly ever mentions Nygren by name. All this suggests a deliberate apologetic strategy to bypass certain defences of his readers and to avoid Nygren-dependency. Despite their incommensurate love-taxonomies, Lewis's need-love/gift-love and Nygren's eros/agape have often been treated as parallels. This longstanding assumption is shown to be in need of greater nuance. The study demonstrates that Lewis's concept of spiritual longing, which he calls Joy, is relevant to the Nygren debate and serves as a potent variant for Nygren's eros. However, no one thing in Lewis's mental repertoire can serve as a perfect translation of Nygren's eros, because for Lewis it is an abstract caricature cut off from real life. In Lewis's theological vision, contra Nygren, spiritual longing, far from obfuscating the Gospel, is a God-given desire that prepares the way for it. Lewis is not free from the occasional hyperbole or blind spot. For instance, his argument that romantic love is not eudaimonistic is shown to be somewhat convoluted, and his famous disagreement with Augustine is possibly based on a misunderstanding. A perennial feature in Lewis's understanding of love, reflected in all four essays, is the ambiguity of love. Love is not something pejorative, but neither is it an infallible moral compass. God is love, but love is not God.