Väitöskirjat: Recent submissions

Now showing items 1-20 of 7241
  • Harjunen, Ville Johannes (Helsingin yliopisto, 2019)
    Emotional expressions as manifested in facial movements, voice, and touch are a crucial part of face-to-face interaction. The majority of existing neuroscientific research on emotional expressions concerns the perception of unimodal emotional cues, such as facial emotional expressions. In natural face-to-face interaction, however, emotions are often expressed as compounds of facial, tactile, prosodic, and postural cues. How the brain processes such multimodal emotional information remains poorly understood. The aim of the current dissertation is to investigate how emotional expressions conveyed consecutively via face and touch are integrated in perceptual processing and decision-making. Four studies were conducted to measure event-related brain potentials (ERPs) and autonomic nervous system responses to simulated touches and facial emotional expression stimuli. The first two studies used virtual reality to investigate how a virtual agent’s facial emotional expressions influenced the way the agent’s subsequent touch was perceived (Study I) and whether the receiver’s individual characteristics influenced this visuo-tactile affective modulation (Study II). Touch perception was measured using self-reports, somatosensory-evoked potentials (SEPs), and cardiac orienting responses (ORs), and the individual characteristics were indexed by behavioural inhibition system sensitivity (BIS) and gender. Study III investigated whether receiving a touch influenced the processing of a subsequent emotional face picture presented on the computer screen. Here, face-evoked ERPs, ORs, and facial electromyography were measured. Finally, the Study IV examined whether a virtual agent’s touch and emotional facial expressions influence receivers’ decision-making and offer-related ORs in an economic decision-making game. Additionally, the study examined whether the receivers’ behavioural inhibition/approach system (BAS/BIS) sensitivities and sensitivity to unfair treatment moderated persuasiveness of nonverbal cues. Study I revealed that happy, angry, and sad facial expressions resulted in amplified SEPs around 20–50 ms after touch onset, whereas in later latencies (250–650 ms), the angry facial expression amplified and the happy expression decreased the SEP amplitudes. In Study II, men with high BIS were found to perceive touch from male agents as especially intense if accompanied by happy, angry, of fearful facial expressions, and they showed pronounced cardiac OR to all the touches. Study III demonstrated that receiving a computer-generated touch did not modulate emotional face processing in any of the measured indices. Finally, in Study IV, people were found to accept unfair offers more often if the agent smiled or touched them before making the offer. The touch had a stronger persuasive influence in people with low sensitivity to unfairness and low approach tendency, whereas the effect of facial expressions was moderated by BIS. Altogether, the findings of the dissertation reveal that a sender’s facial emotional expressions modulate subsequent touch perception at a very early stage and that the modulation is based on different emotional information in different temporal stages. In addition, the findings suggest that motivational tendencies and gender influence the manner in which people perceive a sender’s multimodal emotional expressions and make decisions thereafter. These findings are valuable for basic research, but their implications extend also to the development of novel clinical interventions and social virtual reality applications.
  • Pokki, Heidi (2019)
    Fish stocks in the Baltic Sea are an important natural resource for Finland; targeted by both commercial and recreational fishermen. Fisheries managers require data on the economic value of commercial and recreational fisheries for decision making and to assess the economic sustainability of fisheries. The volume of recreational catch of salmon in Finland is greater than the volume of commercial catch. However, there is marginally information available on the recreational value of salmon angling. These data deficiencies hinder the possibility of fishery managers to make optimal regulatory decisions concerning fish stocks. Additionally, the angler preferences and related angler profiles should be consid-ered in the decision making process as the reaction to different management measures can vary considerably depending on the angler type. This thesis contributes to the alleviation of the existing data deficiencies by contributing knowledge on the economic state of marine commercial fisheries and on the economic value of salmon angling. Defining an economic value is often ambiguous as the valuation methods involve inaccuracies which affect the reliability of the estimates. Therefore, it would be benefi-cial for the data end users to understand the consequences of the choices made in the estimation process in order to interpret the results correctly for decision making. In this thesis, the application of two different valuation methods: the perpetual in-ventory method and the travel cost method is described for defining the value of capital and recreational fishing in Finland. The perpetual inventory method is applied for estimating the capital value of the marine commercial fishing fleet of Finland. The thesis describes the justification for the choices made in the estimation process and how these choices affect the results. In addition, the differences between economic and financial analysis are discussed. Moreover, the thesis describes the value estimation of salmon angling in the River Teno and the River Tornionjoki employing the travel cost method. The studies use a two-step estimation procedure, which considers the potential endogeneity of on-site time per fishing trip. The case study of salmon angling in the River Tornionjoki explores the influence of angler profiles on the fishing behavior; the length of a fishing trip and the number of trips taken. The results show that the importance of increasing catch rate for the recreational benefit obtained by the angler is smaller than expected and the importance of salmon catch differs between the Teno and Tornionjoki rivers. In the River Teno, the experience of catching salmon in the previous season increased, on average, the number of fishing trips during the following season. In the River Tornionjoki the higher catch rate reduced the average number of fishing trips and the length of a trip during the season. The results presented in this thesis can be utilized for e.g. bio-economic modeling, assessing the sustainability of commercial fisheries of Finland, evaluating the implementation of EU common fisheries policy, and defining river specific fishing regulations.
  • Pollari, Marjukka (Helsingin yliopisto, 2019)
    Primary testicular lymphoma is a rare and aggressive lymphoma entity presenting in an immune-privileged site of the testis and most commonly representing diffuse large B-cell lymphoma (DLBCL). Due to the rareness of the disease, no randomized clinical trials have been conducted and the currently recognized standard of care is based on retrospective analysis and few phase II trials. During the last years, tumor-related immunity has been the focus of many studies, and the emergence of targeted therapies and checkpoint inhibitors has significantly modulated the field of cancer therapies. The role of distinct tumor-infiltrating immune cell subtypes and their immunophenotypes has not, however, been thoroughly studied in testicular DLBCL (T-DLBCL). The aims of this study were to evaluate the efficacy of different treatment modalities among T-DLBCL patients identified from the pathology databases of three university hospitals in Finland and the Danish lymphoma registry as well as to characterize tumor-infiltrating immune cell subtypes, their phenotypes and distribution in the TME, and to associate the findings with known clinical and biological risk factors and survival in T-DLBCL. The efficacy of different treatment modalities was evaluated by comparing the patient outcomes of altogether 189 Finnish and Danish T-DLBCL patients. Among these patients, intravenously (IV) administered central nervous system (CNS) -targeted chemotherapy and treatment of the contralateral testis translated into significantly longer patient survival, especially among elderly patients. Intrathecally (IT) administered CNS prophylaxis had no effect on the patient outcome, and rituximab seemed to be beneficial among high-risk (International Prognostic Index (IPI) score 3-5) T-DLBCL patients. In our patient material, the overall CNS relapse rate was low, and no differences in the risk of CNS relapse could be observed between patients treated with different treatment modalities. However, the use of IV CNS-targeted chemotherapy significantly improved the systemic control of lymphoma. Tumor-infiltrating immune cell subtypes, their phenotypes and distribution in the TME were studied using gene expression analysis and multiplex immunohistochemistry (mIHC) on tissue microarray (TMA) slides of 60–79 Finnish T-DLBCL patients. We observed that higher expression of 121 T-lymphocyte signature genes enriched for T-lymphocyte markers associated with significantly longer survival of T-DLBCL patients. The association with survival was especially evident among rituximab-treated T-DLBCL patients and could also be seen in an independent cohort of 96 primary DLBCL patients. We observed a great variation in the distribution of distinct tumor-infiltrating lymphocyte (TIL) phenotypes. Higher proportions of CD3+ TILs in general, CD4+ TILs, and CD8+ cytotoxic T-lymphocytes (CTLs) translated into better outcome. Higher proportions of programmed cell death-1 (PD-1) expressing CD4+ TILs and CTLs associated with significantly longer patient survival. Despite the overall favorable prognostic impact of high TIL content, a subpopulation of FoxP3+T-bet+ double-positive regulatory T-cells (Tregs) could be identified to have a significant adverse effect on patient outcome. We were able to show that a large proportion of both tumor-associated macrophages (TAMs) and lymphoma cells expressed programmed cell death ligand 1 (PD-L1), and higher proportions of PD-L1+CD68+ TAMs associated with longer survival. The content of PD-L1+CD68+ TAMs correlated with the content of PD-1+CD4+ TILs and PD-1+ CTLs, and the proportion of PD-L1+CD68- cells did not have an effect on the outcome of T-DLBCL patients. In conclusion, our results support the use of the currently recognized standard of care with anthracycline-based immunochemotherapy and IV CNS-targeted chemotherapy with prophylactic treatment of the contralateral testis as the first-line treatment of patients with T-DLBCL. The results of our biological studies provide novel information on tumor-infiltrating immune cell subtypes, their phenotypes, and their association with survival among patients with T-DLBCL.
  • Rämö, Joel (Helsingin yliopisto, 2019)
    Despite decades of progress in primary prevention and treatment of acute coronary syndromes and strokes, cardiovascular disease (CVD) remains the leading cause of death and loss of disability-adjusted life years in Western countries. In this thesis, we sought to identify risk stratifying factors beyond the traditional measures of body mass index (BMI) and dyslipidemia. In particular, we focused on the role of hepatic steatosis in obesity, and on the family history of patients with hyperlipidemia. We quantified circulating metabolites during an oral glucose tolerance test in BMI-discordant (ΔBMI ≥ 3 kg/m2) monozygotic twin pairs based on the presence of concomitant liver fat discordance. Liver fat -discordant cotwins exhibited greater putatively atherogenic differences in metabolomic parameters across a wide range of molecular classes, including lipoproteins, fatty acids, amino acids and glycoproteins. We also observed several putatively atherogenic differences between liver fat -concordant twin pairs, suggesting that increased BMI without concomitant liver fat accumulation may not be entirely neutral with respect to CVD risk. We performed the first comprehensive genotyping analysis of familial combined hyperlipidemia (FCH), a common familial hyperlipidemia typically characterized by elevations in total cholesterol or triglycerides. We observed rare high-impact variants in the APOE or APOA5 genes in only a few (3%) of hyperlipidemic family members. Almost a third of hyperlipidemic family members had elevated polygenic burden for LDL-C or triglycerides, similar to population samples with comparable lipid levels. Next, we estimated incident CVD risk in an overlapping cohort of hyperlipidemic families. We focused on common familial hyperlipidemias characterized by high LDL cholesterol or triglyceride levels after excluding individuals with monogenic FH. In our study, such familial hyperlipidemias conferred increased coronary artery disease and CVD risk, but the elevation in risk was similar to that observed in population-ascertained hyperlipidemias. Additionally, we observed highly similar lipidomic profiles consisting of 151 circulating lipid species between individuals with familial and population-ascertained hyperlipidemias. Our results add to existing support for hepatic steatosis as a more discerning stratifying CVD risk factor among individuals with increased BMI. Our findings on FCH and familial aggregation of high LDL cholesterol or triglyceride levels suggest that they share similar and overlapping pathophysiology with common population-ascertained hyperlipidemias, and may not confer differential CVD risk.
  • Mohan, Nitinder (Helsingin yliopisto, 2019)
    Cloud computing has created a radical shift in expanding the reach of application usage and has emerged as a de-facto method to provide low-cost and highly scalable computing services to its users. Existing cloud infrastructure is a composition of large-scale networks of datacenters spread across the globe. These datacenters are carefully installed in isolated locations and are heavily managed by cloud providers to ensure reliable performance to its users. In recent years, novel applications, such as Internet-of-Things, augmented-reality, autonomous vehicles etc., have proliferated the Internet. Majority of such applications are known to be time-critical and enforce strict computational delay requirements for acceptable performance. Traditional cloud offloading techniques are inefficient for handling such applications due to the incorporation of additional network delay encountered while uploading pre-requisite data to distant datacenters. Furthermore, as computations involving such applications often rely on sensor data from multiple sources, simultaneous data upload to the cloud also results in significant congestion in the network. Edge computing is a new cloud paradigm which aims to bring existing cloud services and utilities near end users. Also termed edge clouds, the central objective behind this upcoming cloud platform is to reduce the network load on the cloud by utilizing compute resources in the vicinity of users and IoT sensors. Dense geographical deployment of edge clouds in an area not only allows for optimal operation of delay-sensitive applications but also provides support for mobility, context awareness and data aggregation in computations. However, the added functionality of edge clouds comes at the cost of incompatibility with existing cloud infrastructure. For example, while data center servers are closely monitored by the cloud providers to ensure reliability and security, edge servers aim to operate in unmanaged publicly-shared environments. Moreover, several edge cloud approaches aim to incorporate crowdsourced compute resources, such as smartphones, desktops, tablets etc., near the location of end users to support stringent latency demands. The resulting infrastructure is an amalgamation of heterogeneous, resource-constrained and unreliable compute-capable devices that aims to replicate cloud-like performance. This thesis provides a comprehensive collection of novel protocols and platforms for integrating edge computing in the existing cloud infrastructure. At its foundation lies an all-inclusive edge cloud architecture which allows for unification of several co-existing edge cloud approaches in a single logically classified platform. This thesis further addresses several open problems for three core categories of edge computing: hardware, infrastructure and platform. For hardware, this thesis contributes a deployment framework which enables interested cloud providers to effectively identify optimal locations for deploying edge servers in any geographical region. For infrastructure, the thesis proposes several protocols and techniques for efficient task allocation, data management and network utilization in edge clouds with the end-objective of maximizing the operability of the platform as a whole. Finally, the thesis presents a virtualization-dependent platform for application owners to transparently utilize the underlying distributed infrastructure of edge clouds, in conjunction with other co-existing cloud environments, without much management overhead.
  • Tuononen, Minttu (Helsingin yliopisto, 2019)
    Synoptic situation and different meteorological phenomena can highly affect renewable energy production. Investigating different phenomena will give new information on the occurrence and characteristics of specific phenomena and their impacts on renewable energy applications. Different observational data sets and numerical models can be widely used in different phases of renewable energy projects; from planning of the project to help with the operation and the maintenance of the existing wind or solar field. In this thesis a meteorological phenomena, a low-level jet, is investigated. Thesis comprises analysis of the climatological occurrence of low-level jets, their characteristics and forcing mechanisms, as well as numerical model capability to capture the phenomena. In addition, solar radiation forecasts obtained from the operational numerical weather prediction model are evaluated and the role of cloud cover forecast skill in solar radiation forecast error is investigated. Long data sets of observational data: mainly Doppler wind lidar, ceilometer, and solar radiation observations, are used, in addition to reanalysis and operational numerical weather prediction model data. A low-level jet is a wind phenomenon that can affect wind energy production. Nighttime low-level jets are a commonly known boundary-layer phenomenon occurring during stably stratified conditions over flat terrain. In this thesis, new information on the occurrence, characteristics, and forcing mechanisms of a low-level jet was gained in different conditions: in Northern Hemisphere mid-latitude and polar regions based on reanalysis data and at two different sites in Finland and Germany based on long-term Doppler lidar observations. The low-level jet identification algorithms developed in these studies can be used to repeat the studies by using different models covering different areas or at any site operating a Doppler lidar. The low-level jet identification algorithm for Doppler lidar data can also be applied to operationally detect low-level jets, which is useful information for example from wind energy point-of-view. Solar radiation and cloud cover forecasts were evaluated at one site in Finland based on long time-series of solar radiation and ceilometer observations. The role of cloud cover forecast in solar radiation forecast error is investigated. The solar radiation and cloud cover forecasts were obtained from operational numerical weather prediction model that can be used to predict the expected power production at solar field day-ahead. It was found that there is a positive bias in the forecast incoming solar radiation even if the cloud cover forecast is correct. The study can guide model improvements as the bias is likely due to underestimation in the forecast cloud liquid water content or incorrect representation of cloud optical properties. The methods created in this study can be applied to hundreds of sites globally. In addition, the algorithms developed in this study can be further used in different applications in the field of renewable energy, for example to detect potential in-cloud icing conditions.
  • Toivari, Miika (Helsingin yliopisto, 2019)
    The aims of the present study were to identify the characteristics of facial fractures in geriatric patients and to compare them with younger adults. The hypotheses were that the causes and resulting types of facial fractures are different, and that geriatric patients are more severely injured than younger controls. The present study focused on three different patient populations, diagnosed and treated for facial fractures at a level I trauma center and at the Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki, Finland. The study included patients with all types of facial fractures (Studies I and II), with a unilateral orbital fracture (Study III), and with a unilateral ZMO fracture (Study IV). The commonest cause of facial fractures in geriatric patients was falling on the ground, whereas younger adults commonly sustained their injuries due to assault (Studies I to IV). Midfacial fractures were significantly more common in geriatric than younger adult patients (Study I). Orbital fractures were significantly more often extensive among geriatric than younger adult patients (Study III). Associated injuries (AIs) in general, multiple AIs, and mortality were significantly more frequent among the elderly when compared to younger controls (Study II). In patients diagnosed with isolated ZMO fractures, AIs in general and traumatic brain injuries (TBI) in particular were significantly more frequent among the geriatric than the younger control group (Study IV). The causes and resulting types of facial injuries differ between geriatric patients and younger adults, and midfacial fractures need to be meticulously excluded in geriatric patients. The frequency and severity of AIs in geriatric facial trauma requires systematic trauma assessment, repeated examination of patient’s condition, and care in collaboration with several specialties.
  • Hildén, Jockum (Helsingin yliopisto, 2019)
    This study explores how one of the most talked about regulations in the internet policy domain was drafted. The General Data Protection Regulation (GDPR) has been widely regarded as one of the most lobbied pieces of legislation in the history of the European Union (EU). This raises two questions: What policy alternatives were put forth by the EU institutions in the course of the GDPR’s legislative process, and how did they correspond to the ideas, issues and frames promoted by interest representatives? What does the influence of organized interests and stakeholders in GDPR decision-making reveal about the democratic legitimacy of the process? Drawing on new institutionalism, this research traces the evolution of the GDPR, comparing the different EU institutions’ iterations of the new law with the positions of interest representatives, and simultaneously situating the GDPR in the history of data protection policy. The results reveal that business groups dominated the public consultations prior to the Commission’s draft proposal, but the Commission’s approach was more closely aligned with the positions of civil society. Members of the European Parliament were, on the contrary, highly susceptible to the influence of business interests, until public salience of information privacy increased owing to Edward Snowden’s revelations of governmental mass surveillance by the National Security Agency. These revelations made it possible for policy entrepreneurs to push for stronger rules on data protection. However, public salience would not have a significant impact on the Council, which was mostly aligned with the interests of businesses and concerned with maintaining public interest exceptions. The final GDPR was more reminiscent of the Council’s position than the Parliament’s first reading, demonstrating that in many instances, business interests prevailed. This result should not be understood as mere resistance to policy change, but rather that a big data paradigm, which encourages the collection, processing and exchange of personal data in the name of progress, security and innovation, structured and constrained the available policy options. Therefore, the answer to the second question is that the institutionalized inclusion of stakeholders in the early stages of the process did not negatively impact its legitimacy, but the opaqueness and overall tendency to support business interests in the Council critically challenge the democratic legitimacy of the GDPR’s legislative process.
  • Engelberg, Matti (Helsingin yliopisto, 2019)
    The dissertation discusses the recent EU directive on preventive restructuring (‘Directive on Preventive Restructuring’, 2019/1023), its adoption in EU member states, and the English company law scheme of arrangement (‘Scheme of Arrangement’ or ’Scheme’), analysing the best preventive restructuring model for Finland and other Nordic countries. The principal method of the research is the regulation theory in law and economics; yet by using the comparative law method, optimal frameworks are outlined to develop, de lege ferenda, legislation for ensuring efficient legal protection against abuse of holdout positions relating to debt or equity instruments. The English law Scheme of Arrangement is a court approved compromise or arrangement between a company and its shareholders or creditors or any class of them, that operates in a solvent or a financially distressed situation. When viewed from a Nordic and continental European perspective, the English regime is a highly flexible company law tool that can be used, among other things, in a preventive restructuring to protect a company and a majority of its same class debt holders from hold-out minority dissenters. Its increased importance as a tool for preventive restructuring coincides with the diversification of financing sources over the past decade since the financial crisis. The economic impact of rescue and recovery frameworks in the EU has been analysed in the preparatory works of the Directive on Preventive Restructuring: an estimated 200 000 firms go bankrupt each year in the EU (this being 600 on a daily basis), resulting in 1.7 million direct job losses every year. According to the reasoning of the preparative works, a significant percentage of firms and related jobs could be saved, if preventive procedures existed in all Member States. Scheme of Arrangement framework is analysed in the research also from an insolvency law viewpoint. This is important, particularly as the new Directive on Preventive Restructuring derives from the insolvency law angle. Hence, the directive is setting standards for minimum harmonisation, and emphasises flexibility for the Member States to have several frameworks available. Further flexibility may be provided, inter alia through company law, as such a framework would be available for a company and its stakeholders, in case there is any need for a compromise or arrangement between the company and its shareholders or creditors or any class of them. The principal thesis of the dissertation is that the current Finnish and Nordic legislation does not provide adequate protection for a company and its key stakeholders against abuse of holdout positions by the minority of any same class finance instrument. Both the US and the English law provide such workout-tools, which would be useful for the Nordic jurisdictions as well. An availability of a workout-framework for restructuring has been outlined in a study of the European Law Institute as an important element in law. This would safeguard, that only creditors, whose rights would be altered, would be involved in the court process, and the company would otherwise be able to continue its’ operations without interference. The recent Finnish and Swedish legal writing on insolvency law has analysed debt to equity swaps, i.e. possibilities, in an insolvency scenario, to swap debt into equity, also against the will of the existing shareholders. Finnish Government has also conducted an international comparative study on debt-to-equity conversion as part of the Government’s analyses and research activities. Under English law, Schemes of Arrangement provide a useful tool for the debt-to-equity swaps in insolvency, but still protect the interests of all stakeholders amicably. Hence, Scheme of Arrangement framework could provide a solution to this practical problem with the current Nordic legislation. As a conclusion, the dissertation presents a figure illustrating in a hypothetical showing the matrix of the financial and economic condition of a company and the related needs for preventive and restructuring legal frameworks for a company and its stakeholders. Based on the theory of path dependency, the author concludes that the legislative changes presented in the dissertation would be justified, as the estimated benefits of the reform would supersede the costs involved. Therefore, the legislators should consider the presented reform to company law, noting that this would require a good understanding of the fundamental changes. By doing so, the Finnish and Nordic legislators should be well positioned to follow the principles of the Directive on Preventive Restructuring.
  • Pooch, Fabian (Helsingin yliopisto, 2019)
    Poly(2-oxazoline)s consist of a -(CH2-CH2-N)- main chain and an N-acyl substituent. They were reported for the first time in 1966/67. They have been investigated in the bulk, in solutions and in dispersions. The recent interest lies primarily in their chemical versatility and their potential for nanomedical applications. Tailoring materials for such specific applications requires a sound knowledge of their phase behaviors, which depends on intensive parameters. Amongst others, composition and temperature are of particular interest. The phase behaviors of poly(2-propyl-2-oxazoline)s (PPOxs) will be the main focus of this thesis. PPOx homopolymers are investigated as well as block copolymers (BCPs) and blends of poly(2-isopropyl-2-oxazoline) (PiPOx) and poly(lactide) (PLA). The first part describes the synthesis of the polymers. The PPOxs are prepared by cationic ring opening polymerization. They are linear, narrowly dispersed, and bear at the termini one methyl- and one azide-group. Semi-crystalline as well as amorphous PLA is synthesized by ring opening polymerization of L-lactide and DL-lactide, respectively. The linear PLAs are terminated with one propargyl- and one hydroxyl-group. Coupling of the azido- and alkyne-functional homopolymers gives a library of 18 PiPOx-b-PLA BCPs. This approach allows to compare the phase behaviors of the BCPs with those of the individual components. The next part is dedicated to a study of the solution properties of three PPOx homopolymers, namely poly(2-n-propyl-2-oxazoline) (PnPOx), poly(2-cyclopropyl-2-oxazoline) (PcyPOx) and PiPOx in water, in methanol and in water/methanol mixtures. Nuclear magnetic resonance (NMR) spectroscopy of the three polymers reveals significant differences in the side-group’s rotational freedom. Unexpectedly, these differences are reflected in the calorimetric assessment of the coil-to-globule phase transition. The phase diagrams in respect to the water/methanol composition are constructed based on transmittance measurements. Methanol is a good solvent up to its boiling point for the three PPOxs. The solubility of PnPOx in water decreases when up to 40 vol% methanol is added. This behavior termed “cononsolvency” was first reported for ternary polymer/water/methanol mixtures of poly(N-isopropyl acrylamide), a structural isomer of PnPOx and PiPOx. PiPOx and PcyPOx do not exhibit cononsolvency in the investigated ternary system. The PPOxs’ solution behaviors depend on the rotational freedom of the side-groups. In the third part, the bulk phase behavior of PiPOx, its blends with PLA, and PiPOx-b-PLA BCPs is studied. The PiPOx volume fractions in the BCPs varies from 14 to 82 %. PiPOx and PLA are miscible based on the single glass transition criterion and small angle x-ray scattering at a temperature above the melting points of the two polymers. Infrared spectroscopy indicates an attractive dipole-dipole interaction between the carbonyl moieties of the PiPOx amide and the carbonyl of the PLA ester. PiPOx and the stereo-regular PLLA are semi-crystalline. The influence of the miscibility on the crystallization is investigated by polarized optical microscopy, differential scanning calorimetry and wide-angle x-ray scattering. It is found that the presence of PLA increases the crystallization rate of PiPOx. In contrast, PLLA remains amorphous in most of the BCPs. The last part focuses on aqueous dispersions of the self-assembled PiPOx-b-PLA BCPs. The dispersions were prepared by adding a solution of a BCP in THF to water, a non-solvent of PLA but a solvent of PiPOx at low temperature. Contrary to expectation PiPOx resides in the particle interior, together with PLA. It does not form a shell of hydrated chains around the PLA core. This conclusion was attained on the basis of NMR spectroscopy and evaluation of the thermo-responsive properties of the BCP particle dispersions in water. At room temperature the particles are colloidally stable for 20 days at least. The particle morphology is investigated by cryogenic transmission electron microscopy, light scattering and small angle neutron scattering. The particles are spherical and permeated with water over the wide PiPOx volume fraction. Short segments of PiPOx reside on the particle/water interface and stabilize the dispersion. The thermo-responsive properties of the dispersions depend on the configuration and length of these segments. Attractive interactions between soluble and insoluble block are an important factor for the self-assembly of amphiphilic BCPs.
  • Tiihonen, Eeva (Helsingin yliopisto, 2019)
    University of Helsinki, Faculty of Educational Sciences, Helsinki Studies in Education, number 56 In this study, leadership is studied through relationship-based and shared phenomenon in early childhood education. The purpose of the research is to describe, interpret and create an understanding of leadership implementation. The focus is on working community relationships and how leadership is shared in the Early Childhood Unit. Leadership is approached through relationship modeling both as a supervisor relationship and as a relationship between employees. Theoretical starting points are relational leadership and shared leadership in a pedagogical context in early childhood education. In relational leadership, leadership is seen to be a phenomenon that arises in interaction. Shared leadership is defined as an activity that employees can participate in. The study was conducted in the Early Childhood Unit in Helsinki, which included a day care center manager and 29 employees. The leader of the Kindergarten and all the employees participated in the study. The study did not target children. This Early Childhood Unit consisted of two physically working kindergartens. The research is based on qualitative data. The collection of research material was carried out using a thematic focus group interviews and a method of empathy-based stories. The analysis was based on content analysis. According to the study, leadership takes place in different forms of interaction and these relationships allow for the sharing of leadership. As the major outcome of the study a leadership relationship model was developed. It consisted of the following leadership relationships: empowering interaction relationship, leadership in confidence, leadership in partnership and leadership as an authority relationship. In the study, relationships are described as separate in order to allow a detailed examination of them. In reality, relationships are interrelated and implemented holistically. Keywords: distributed leadership, shared leadership, leadership, leadership relationships, qualitative research, narrative perspective, pedagogical leadership, relationship leadership, early childhood education
  • Rakkolainen, Ilmari (Helsingin yliopisto, 2019)
    Severe burn injury is one of the most devastating traumas with its direct tissue destruction, triggering a systemic inflammation and numerous cytokine-mediated alterations of homeostasis. Acute kidney injury (AKI) is a common sequela in severe burns and substantially increases the risk of death. The focus of this thesis was to investigate novel biomarkers of AKI: neutrophil gelatinase-associated lipocalin (NGAL) (I) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (II) in primary diagnostics of AKI. The thesis also investigated the risk factors for AKI development after severe burn injury and factors affecting the outcome (III), as well the need for long-term renal replacement therapy (RRT) after severe burn injury and possible association of burn injury and cause of death (COD) (IV). Studies I and II enrolled 19 consecutive patients treated at Helsinki Burn Centre between March 2013 and September 2014. Plasma NGAL levels elevated over time in the majority of patients. Out of 19 patients, 17 showed elevated plasma NGAL levels (>150 ng/ml). Two patients showed high NGAL levels (>600ng/ml) without AKI. The area under the curve (AUC) was 0.62 in predicting AKI during the first week after a burn injury, whereas serum creatinine (SCr) and cystatin C (CysC) showed notably better diagnostic accuracy. A multivariable regression model showed that the NT-proBNP was correlated with the volume of infused fluids and age but found a negative correlation between the body mass index (BMI) and NT-proBNP levels. NT-proBNP increased over time in all patients. The variation between patients was substantial, and even more variation was observed in patients who developed AKI. No association between AKI and high NT-proBNP was discovered. Study III found that 27.3% of patients developed AKI during the intensive care unit (ICU) stay, defined by an absolute SCr value of at least 120 μmol/l (1.4 mg/dl). 11.2% required RRT, and 19.8% of patients succumbed during their hospital stay. AKI patients showed 52.9% mortality compared to 7.4% of non-AKI patients. Age, TBSA%, sepsis and rhabdomyolysis were independent risk factors for AKI. Age, TBSA% and AKI were risk factors for death during an ICU stay. The RRT had no effect on the significantly reduced mortality in AKI patients. AKI was associated with increased mortality, even in minor burns, and mortality increased substantially in major burns. The prognosis of major burns was relatively good without AKI, though the majority of patients developed AKI in major burns (>50% burned TBSA). Study IV included 68 burn patients who had received RRT in the Helsinki Burn Centre between November 1988 and December 2015. The need for RRT subsided before discharge in 81.3% of survivors. 6.3% of survivors needed RRT for over three months. 35.7% of deaths occurred because of burns, 7.1% because of kidney failure and 57.1% of deaths occurred for any other reason. One patient developed chronic kidney disease (CKD) and succumbed during follow-up. The study showed CKD as a rare event after burn injury and RRT. It remains possible, however, that a prior burn injury may potentially enhance future development of AKI due to other reasons.
  • Anton, Emil (Helsingin yliopisto, 2019)
    This dissertation explores the thought of Joseph Ratzinger/Pope Benedict XVI on the theology of religions and interreligious dialogue. It consists of an introductory overview and four peer-reviewed articles. With a systematic analysis of key concepts, structures, and arguments, the dissertation contributes to a better understanding of a less appreciated area of Ratzinger’s theology. The two events that dominate commentaries as well as popular imagination on Ratzinger/Benedict’s contribution to the theology of religions and interreligious dialogue are the publication of Dominus Iesus in 2000 and the 2006 lecture at the University of Regensburg, both of which caused an uproar. More attention should be paid to Ratzinger’s personal theology of religions as expressed in his books, as well as to the 188 texts from Benedict XVI’s pontificate that relate to interreligious dialogue. Contrary to those who have tried to portray Ratzinger as a soteriological exclusivist, I argue that he is an optimistic restrictivist inclusivist, allowing for the salvation of a great number of non-Christians while not considering other religions instruments of salvation as such. Ratzinger’s inclusivism is structured around an objective and a subjective aspect, the vicarious representation of Christ and the Church (Stellvertretung) and some sort of a pistis or openness to God in the subject. A reinterpretation of purgatory provides the final solution to the salvation of “the many”. Ratzinger’s opposition to John Paul II’s interreligious Assisi meetings and his negativity about the Asiatic religions have also been exaggerated. Despite a strong juxtaposition between the theistic and mystical paths in the world of religions, Ratzinger hopes for an integration of the best elements of the mystical religions, and while cautious about multireligious and interreligious prayer, he provides criteria for their right realisation. A contradiction seems to emerge between Ratzinger/Benedict’s emphasis on truth as the ultimate goal of interreligious dialogue and his apparent endorsement of the idea that interreligious dialogue, or theological dialogue, is actually impossible. At the end of his papacy, Benedict maintains that interreligious dialogue does not seek to convert another, even though it should always aim at drawing closer to the truth. Pope Benedict XVI’s most central message to representatives of other religions concerns peace and non-violence, coupled with a call to a common witness to spiritual values in a secular society. Religiously motivated violence remains a central challenge for interreligious dialogue.
  • Yaman, Sezin Gizem (Helsingin yliopisto, 2019)
    Software experiments are presently often used by big technology pioneers, such as Microsoft, Facebook and Google, in order to learn about their users and to guide their research and development activities. Continuous experimentation (CE) is reported to be an integral part of software development in these organisations, however, how they transitioned to the approach is not publicly shared. Therefore, there is a lack of guidance for other organisations that are willing to adopt CE. In the current competitive markets, investing time and money in a new approach might be risky for these organisations, especially if they do not know how to initiate this transition process. This dissertation focuses on how organisations can initiate the transition towards CE, i.e., an approach to enhance development decisions by running experiments in an iterative and sustainable fashion. The dissertation was designed to acquire descriptive and observational knowledge through empirical studies and was con- ducted in three main phases. First, we designed and ran multiple-case studies to investigate how CE can be introduced to existing software company development teams, who want to run their first systematic experiments. We extracted descriptive knowledge from the introduction process and composed lessons learned to act as guidelines. In the second phase, we conducted a survey study with practitioners from four Nordic software companies, in order to better understand their attitudes and perception towards experiment-driven development, user involvement and ethics. Examining the results at role-to-role levels gave us an understanding of commonalities and distinctions stemming from different job functions. Furthermore, we identified patterns from the data that describe what trends exist across the dataset with respect to experiment-driven software development. Finally, in the last phase of the study, we conducted a single-case study with a mobile gaming company to investigate how CE functions as an organisational mechanism throughout the development life-cycle. The findings show that transitioning towards CE is a learning process that can be facilitated well by guidance, utilising existing resources and starting with small experiments with potentially enormous impact. Furthermore, by investigating the point of view of practitioners, we observed that software experiments represent different concepts, for instance, A/B tests and user interviews. We also observed that the role of the practitioner has a big impact not only on how experiments are understood, but also how individuals perceive the ethics involved in the experiments. For example, while managers are more cautious about company-customer relationships, UX designers were found to allow exceptions to user notification during experiments. In addition, we discovered that companies might understand and adopt experiment-driven development differently, for in- stance, influenced by their business contexts. Lastly, by examining a company’s CE practices, we found that experiments can take different forms given the development stage, and the organisational mechanism can be established to fit both the needs of the business domain and organisational goals. One of the biggest challenges of adopting CE, inaccessible real users, can be overcome with alter- native methods, such as proxy users, especially early in the development, when experiments are important in determining product value. Highly competitive markets can put pressure on organisations to avoid risks and costs when adopting a new approach. In this dissertation, we learned that by and large, software organisations and development teams can initiate their transition towards CE in an efficient and economical way. Furthermore, we conclude that the transition is a learning process that improves with practice and has to adapt to the organisational goals and contexts. The influence of human factors, such as the finding that individual perception of experiments and ethics is correlated with job functions indicates that CE is a multi-disciplinary research field, where individuals should be studied as well as experimentation processes. Software engineering research needs further studies to validate the findings in different contexts.
  • Lopez Cazalilla, Alvaro (Helsingin yliopisto, 2019)
    Low and medium energy ion irradiation can induce different structures over the surface of semiconductors and metals depending on the parameters used for the irradiation of the surfaces. Different mathematical models have been developed in the last decades to explain the formation reasons of such structures, such as nano-dots or ripples, and to predict the pattern wavelength. These theories have been discussed and tested for several years. In this work, computational methods are used in order to predict and observe such effects. First, a mathematical model, which uses as an input the results from the computational methods, is applied to predict the pattern wavelength and at which angle the regime changes from stable to unstable. Moreover, a relaxation method to remove the background displacement in amorphous silicon, which affects the prediction is presented. Second, a simulation model of sequential irradiation consisting of the irradiation of a segment of the surface, and speeding-up the eventual modification of the surface is developed. The simulation outputs at ultra-low energy are compared with experimental results. The use of the same model at higher energies and applied to aluminum allows us to obtain conclusions on the reason of pattern formation in both materials at different energies and irradiation angles. The last part of this work contains the results obtained from homogeneously distributed irradiation. The irradiation is performed according to an accelerated molecular dynamics method which reduces the time span between impacts and allows us to reach higher fluences. This latter method allowed us to observe the direct ripple-formation and the propagation of the pattern on the surface for the first time. This study allows to explain and observe the different stages before the eventual ripple formation.
  • Orav, Ester (Helsingin yliopisto, 2019)
    Neural circuits emerge when neurons become connected by synaptic contacts. In rodents, this process begins already before birth and continues during the first postnatal weeks. The initial steps of synapse formation are guided by intrinsic molecular cues. The emerging synaptic contacts are then refined and fine-tuned by activity-dependent mechanisms. Kainate-type glutamate receptors (KARs) are involved in synapse formation and refinement during this “critical period” by regulating neurotransmitter release and neuronal excitability in both principal cells and interneurons in a developmentally restricted manner. Functional KAR tetramers are assembled from various combinations of five core subunits GluK1-5 and supplemented with auxiliary subunits, Neuropilin and tolloid-like proteins (NETO) 1 and 2 that are not part of the pore-forming receptor. KAR interaction with NETOs affects multiple aspects of KARs like subcellular localization of the receptor complex, receptor gating and current kinetics, and even KAR affinity to main agonists, kainate and glutamate. Despite the accumulating evidence emphasizing the functional significance of NETOs in regulating KAR functions in the adult brain, the role of NETO/KAR complex in the immature brain remains elusive. The main aim of this study was to clarify the physiological significance of NETO/KAR complex in the maturation of hippocampal circuitry. First, we found that NETO1 is an important regulator of physiologically relevant KAR activity at immature glutamatergic synapses. NETO1 deficiency significantly reduced axonal delivery of KARs resulting in loss of presynaptic KAR function and delayed maturation of CA3-CA1 synapses. At the network level, NETO1 deficiency caused impaired synchronization between areas CA3 and CA1 of the hippocampus. This phenotype was fully rescued by GluK1c expression at CA3 principal neurons, emphasizing the role of NETO1 and axonal GluK1-containing immature-type KARs in the development of CA3-CA1 synapses. Next, we showed that NETO1 is necessary for the dendritic delivery of KAR subunits and for formation of KAR-containing synapses in cultured GABAergic neurons. In CA3 interneurons, loss of NETO1 disrupted postsynaptic and metabotropic KAR signaling, while a subpopulation of ionotropic KARs in the somatodendritic compartment remained functional. NETO1 was not necessary to maintain the excitability of the immature CA3 network at physiological levels. However, kainate-dependent modulation of network bursts and GABAergic transmission in the developing hippocampus was significantly impaired in the absence of NETO1. In conclusion, these new findings elucidate the cellular mechanisms and physiological significance of NETO/KAR interaction in hippocampal principal cells and interneurons during the first week of postnatal development. This early period of neural network development is extremely sensitive to external stimuli. Accordingly, disturbances in circuit structure or activity patterns that take place during this “critical period” could predispose to neuropsychiatric disorders later in life.
  • Ruutu, Piia (Helsingin yliopisto, 2019)
    Supporting the schooling of children and adolescents in psychiatric care and the perceived effects of a hospital school period The aim of this study is to describe the schooling of students who have psychiatric disorders, to evaluate what kind of impact a hospital school pedagogy has on the students’ schooling and to identify both supportive and exclusionary practices in the Finnish school system. This study has both quantitative and qualitative components. The Finnish National Follow-Up Study 2009-2014 (SOS survey) contains students’ (n=251) and teachers’ (n = 247) survey as-sessments of schooling before a hospital school period, at the end of the period and at follow-up 3-6- months later. Interviews of former hospital school students (n=22) and their parent´s (n=17) were conducted between 2013 and 2016. Hospital school as part of a child’s overall rehabilitation had a positive impact on their school-ing but the effect decreased slightly at the follow-up 3-6 months later. Logistic regression analysis was used to identify factors that could explain the student’s low or high assessment in the follow-up phase. Research interviews made it possible to understand the results in a deeper way and gave a more personal perspective on the results. Participants identified both supportive and harmful practices in the Finnish school system. These results can be used to develop schooling practices in Finland. It is important to find out what kinds of factors support the inclusion of students and their families and to identify exclusionary and harmful practices. The study identifies key devel-opment needs and suggests solutions to them. The interviews showed that participants had received support in schools, but there was varia-tion in the availability of support. Help and support was not available until the school situation had become very problematic and there was a lack of early interventions. In addition, there were variations in the number and quality of school interventions. Externalizing students had a lot of school-based interventions on their school path, but the interventions often suffered from a lack of planning and control. The support and interventions of internalizing students in school were minimal or absent. Based on the SOS survey and interviews, students who had psychiatric disorders had a higher risk of school refusal and of being excluded from school. In this research the participants were asked to identify the factors behind school refusal and exclusion. As a result of this, a student typology was developed that can help to design better interventions and support for these stu-dents. A supportive school atmosphere, good relationships between students and adults in school, at least one schoolmate, co-operation with parents and tailor-made, flexible solutions support the schooling of students who have psychiatric disorders. In addition, the school personnel’s ability to regulate the child’s stress levels with the parents and other caregivers is important. Developing school-based interventions to support these children will be essential in the future. Schools and basic education require practices that help identify and implement school-based interventions. This dissertation gives voice to children, adolescents and their parents. With their views, it is possible to develop hospital school pedagogy and basic education practices as well as services for families more generally. Keywords: perceived effects, experiences, school refusal, hospital school pedagogy, follow-up study
  • Mukrimin, Mukrimin (Helsingin yliopisto, 2019)
    Forests are the hotspots of Earth’s biodiversity, providing habitats to animals and resources to humans, protecting watersheds, preventing soil degradation, and mitigating climate change. In fact, forest disturbance is mainly caused by biotic and abiotic stresses, which affect both the primary metabolic components required for growth, development, and reproduction and secondary metabolites (defense-related chemical compounds) of trees. In the Northern Hemisphere, including Finland, members of the fungal group Heterobasidion annosum species complex are the most important pathogens of conifer trees causing serious economic losses for forest industries. The existing control and management strategies against this pathogen do not lead to 100% protection. To gain better insights and knowledge of Heterobasidion–conifer tree interactions, I investigated the impact of pathogen infection on the resident mycobiota in naturally infected trees as well as performed an analysis of fungal community structure under field conditions. Fourier transform infrared spectroscopy (FT-IR) analysis was also performed to discriminate between asymptomatic and symptomatic trees. In a parallel study, I investigated the genetic variants that could be associated with the control of necrotic lesions caused by H. parviporum inoculation among selected clonal lines of Norway spruce. Additionally, the expression level of a subset of selected genes involved in terpene, stilbene and flavonoid biosynthesis and programmed cell death in Scots pine trees with varying levels of resistance was further assessed. Mycobiome analysis demonstrated significant differences in the structure of fungal communities residing within symptomatic and asymptomatic Norway spruce trees. The results provided novel insight into the interactions between fungal plant pathogens and resident plant mycobiota. The FT-IR spectroscopy analysis was able to discriminate between symptomatic and asymptomatic Heterobasidion-infected Norway spruce trees. Other findings in terms of genetic and chemical markers revealed ten single nucleotide polymorphisms (SNPs) associated with eight genes. The identified SNPs were significantly associated with larger lesions in response to H. parviporum inoculation in Norway spruce saplings. In Scots pine, genes with higher expression levels predicted to encode α-pinene synthase, geranyl diphosphate synthase (GPPS), and metacaspase 5 (MC5) were associated with trees exhibiting high levels of necrotic lesion formation in response to fungal inoculation. Concentrations of two terpenoid compounds (β-caryophyllene and α-humulene) were significantly negatively correlated with lesion size. These results can be used in further studies to elucidate potential biomarkers in conifer tree genetic resistance research. Keywords: Heterobasidion, Norway spruce, Scots pine, tree-pathogen interactions, mycobiome analysis, FT-IR spectroscopy, gene expression, terpenoid, chemical markers
  • Aro, Karoliina (Helsingin yliopisto, 2019)
    Nearly all humans acquire a human papillomavirus (HPV) infection during their lifetime. The vast majority of HPV infections regress spontaneously, even the precancerous lesions (intraepithelial neoplasias) of the female genital tract that HPV causes. Precancerous cervical lesions are treated with local excision, because the progressive or regressive nature of an individual lesion remains unknown. These procedures have a 90% initial cure rate but may predispose to preterm birth. Prophylactic HPV vaccines targeting the two most common HPV types in cervical cancer (HPV 16 and 18) have been available for a little over a decade. A near eradication of HPV infections and precancerous lesions has been demonstrated a decade after vaccination in adolescence; however, the full effect of mass vaccination, especially on cancer rates, will only be seen decades later. Characterising the prevaccination era HPV-type distribution can aid the assessment of the effect of vaccinations and refine screening strategies. Our study of 1279 women assessed for abnormal cytology found a distinct, age-related polarisation of HPV types. Histological high-grade cervical disease was diagnosed in 503 women, and two thirds of cases in young women were attributed to HPV16/18, whereas it was only found in one third of women ≥45. Other high-risk types and even HPV negativity were more common than HPV16/18 in the older women. We performed a meta-analysis on the outcomes of untreated cervical intraepithelial neoplasia grade 2 (CIN2). Summary estimates from 36 studies showed the overall regression rate at two years to be 50% and the progression rate 18%. The two-year regression rate was 60% and the progression rate was 11% in a subgroup analysis of women <30 years of age (approximately 1000 women). Overall progression to invasive cancer was rare (0.5%, n=15/3160). In addition, we assessed the performance of a DNA methylation panel (S5 classifier) in predicting progression of untreated histological CIN2 in a prospective cohort study of 149 women (18-30 years of age). S5 was independently able to predict progression even when adjusted for age, initial cytology, cigarette smoking, and HPV16/18 status. Vaginal intraepithelial neoplasia (VAIN) is more uncommon than CIN. Contemporary treatment is mostly laser vaporisation, but recurrence occurs in up to a third. HPV persistence is associated with recurrence. We recruited 30 women with high-grade VAIN into a randomised trial comparing the efficacy of self-administered vaginal immunomodulator imiquimod, laser vaporisation, and expectant management. No progressions were observed during the follow-up, and histological regression rates showed no significant differences between the study arms. HPV clearance, however, was significantly more common in the imiquimod arm (63%) than in the laser arm (11%).
  • Iso-Markku, Paula (Helsingin yliopisto, 2019)
    Physical activity (PA) has been associated with better cognition or decreased dementia incidence in many earlier studies. Since both PA and cognition are, to a large extent, heritable traits, the association found in earlier studies may be confounded by genetic selection. The aim of this thesis study was to ascertain whether midlife PA is associated with late-life dementia mortality and cognition and if objectively measured late-life PA is associated with late-life cognition and whether the possible associations are contributable to genetic factors and childhood shared environment. The thesis study was implemented in the older Finnish Twin Cohort. Vigorous PA and the volume of PA have been reported in questionnaires in 1975 and 1981. Dementia mortality was followed from the time of the questionnaire in 1981 to the end of the year 2011 (n=21,524). All participants over 65 years of age were offered the possibility to participate in a telephone cognition interview. The cognition interview participants born in 1940–1944 were also offered the possibility to participate in accelerometer monitorings. The participation rates for questionnaires in 1975 and 1981, cognition interviews and accelerometer monitorings were high considering the length of the follow-up (89%, 84%, 78% and 54% among twins alive and with an address in Finland). In the accelerometer study, there was a trend toward a slightly selected population regarding better education and healthier lifestyle. Among the 21,524 twins followed for dementia mortality, there were 353 dementia deaths. Long-term vigorous PA was associated with decreased dementia mortality (hazard ratio (HR) in the fully adjusted model 0.60, 95% confidence intervals (CI) 0.39 – 0.93). The volume of PA and long-term quantitative physical inactivity were not significantly associated with dementia mortality. Among 3050 twins aged 65 years and older and who had participated in cognition interviews, 204 had cognitive impairment. Long-term vigorous PA was significantly associated with better cognition (beta estimate 0.91, 95% CI 0.47 – 1.35), belonging to the most inactive quintile in both questionnaire years 1975 and 1981 was inversely associated with cognition, and volume of PA was not significantly associated with cognition. Late-life objectively measured light PA was positively and sedentary behavior inversely associated with late-life cognition, but the effect sizes were small. In analyses comparing twins with their co-twins, the point estimates were quite similar to those found at the individual level but were statistically non-significant. The number of twin pairs discordant for PA and dementia mortality or cognition was very small. The results indicate that midlife vigorous activity is significantly associated with decreased dementia mortality and better late-life cognition, but the associations are likely to be explained in part by genetic factors and childhood shared environment. The association of objectively measured PA and cognition in late-life seems weak and, also, explained in part by genetic factors and childhood shared environment.