Cognitive Functioning in Alcohol and Other Substance Use Disorders in Young Adulthood : A Genetic Epidemiological Study

Alcohol and other substance use disorders (SUDs) result in great costs and suffering for individuals and families and constitute a notable public health burden. A multitude of factors, ranging from biological to societal, are associated with elevated risk of SUDs, but at the level of individuals, one of the best predictors is a family history of SUDs. Genetically informative twin and family studies have consistently indicated this familial risk to be mainly genetic. In addition, behavioral and temperamental factors such as early initiation of substance use and aggressiveness are associated with the development of SUDs. These familial, behavioral and temperamental risk factors often co-occur, but their relative importance is not well known. People with SUDs have also been found to differ from healthy controls in various domains of cognitive functioning, with poorer verbal ability being among the most consistent findings. However, representative population-based samples have rarely been used in neuropsychological studies of SUDs. In addition, both SUDs and cognitive abilities are influenced by genetic factors, but whether the co-variation of these traits might be partly explained by overlapping genetic influences has not been studied. Problematic substance use also often co-occurs with low educational level, but it is not known whether these outcomes share part of their underlying genetic influences. In addition, educational level may moderate the genetic etiology of alcohol problems, but gene-environment interactions between these phenomena have also not been widely studied. The incidence of SUDs peaks in young adulthood rendering epidemiological studies in this age group informative. This thesis investigated cognitive functioning and other correlates of SUDs in young adulthood in two representative population-based samples of young Finnish adults, one of which consisted of monozygotic and dizygotic twin pairs enabling genetically informative analyses. Using data from the population-based Mental Health in Early Adulthood in Finland (MEAF) study (n=605), the lifetime prevalence of DSM-IV any substance dependence or abuse among persons aged 21—35 years was found to be approximately 14%, with a majority of the diagnoses being alcohol use disorders. Several correlates representing the domains of behavioral and affective factors, parental factors, early initiation of substance use, and educational factors were individually associated with SUDs. The associations between behavioral and affective factors (attention or behavior problems at school, aggression, anxiousness) and SUDs were found to be largely independent of factors from other domains, whereas daily smoking and low education were still associated with SUDs after adjustment for behavioral and affective factors. Using a wide array of neuropsychological tests in the MEAF sample and in a subsample (n=602) of the population-based FinnTwin16 (FT16) study, consistent evidence of poorer verbal cognitive ability related to SUDs was found. In addition, participants with SUDs performed worse than those without disorders in a task assessing psychomotor processing speed in the MEAF sample, whereas no evidence of more specific cognitive deficits was found in either sample. Biometrical structural equation models of the twin data suggested that both alcohol problems and verbal ability had moderate heritabilities (0.54—0.72), and that their covariation could be explained by correlated genetic influences (genetic correlations -0.20 to -0.31). The relationship between educational level and alcohol problems, studied in the full epidemiological FT16 sample (n=4,858), was found to reflect both genetic correlation and gene-environment interaction. The co-occurrence of low education and alcohol problems was influenced by overlapping genetic factors. In addition, higher educational level was associated with increased relative importance of genetic influences on alcohol problems, whereas environmental influences played a more important role in young adults with lower education. In conclusion, SUDs, especially alcohol abuse and dependence, are common among young Finnish adults. Behavioral and affective factors are robustly related to SUDs independently of many other factors, and compared to healthy peers, young adults who have had SUDs during their life exhibit significantly poorer verbal cognitive ability, and possibly less efficient psychomotor processing. Genetic differences between individuals explain a notable proportion of individual differences in risk of alcohol dependence, verbal ability, and educational level, and the co-occurrence of alcohol problems with poorer verbal cognition and low education is influenced by shared genetic backgrounds. Finally, various environmental factors related to educational level in young adulthood moderate the relative importance of genetic factors influencing the risk of alcohol problems, possibly reflecting differences in social control mechanisms related to educational level.

Population projection for Namibia 2011-2020 - With an estimation of the impact of HIV/AIDS

This study presents a population projection for Namibia for years 2011–2020. In many countries of sub-Saharan Africa, including Namibia, the population growth is still continuing even though the fertility rates have declined. However, many of these countries suffer from a large HIV epidemic that is slowing down the population growth. In Namibia, the epidemic has been severe. Therefore, it is important to assess the effect of HIV/AIDS on the population of Namibia in the future. Demographic research on Namibia has not been very extensive, and data on population is not widely available. According to the studies made, fertility has been shown to be generally declining and mortality has been significantly increasing due to AIDS. Previous population projections predict population growth for Namibia in the near future, yet HIV/AIDS is affecting the future population developments. For the projection constructed in this study, data on population is taken from the two most recent censuses, from 1991 and 2001. Data on HIV is available from HIV Sentinel Surveys 1992–2008, which test pregnant women for HIV in antenatal clinics. Additional data are collected from different sources and recent studies. The projection is made with software (EPP and Spectrum) specially designed for developing countries with scarce data. The projection includes two main scenarios which have different assumptions concerning the development of the HIV epidemic. In addition, two hypothetical scenarios are made: the first considering the case where HIV epidemic would never have existed and the second considering the case where HIV treatment would never have existed. The results indicate population growth for Namibia. Population in the 2001 census was 1.83 million and is projected to result in 2.38/2.39 million in 2020 in the first two scenarios. Without HIV, population would be 2.61 million and without treatment 2.30 million in 2020. Urban population is growing faster than rural. Even though AIDS is increasing mortality, the past high fertility rates still keep young adult age groups quite large. The HIV epidemic shows to be slowing down, but it is still increasing the mortality of the working-aged population. The initiation of HIV treatment in 2004 in the public sector seems to have had an effect on many projected indicators, diminishing the impact of HIV on the population. For example, the rise of mortality is slowing down.

Koneellisen annosjakelupalvelun aloittaminen - lääkehoidon tarkistus ja sen vaikutus potilaan lääkehoitoon

Farmaseuttisilla palveluilla tarkoitetaan apteekkien palveluita, joissa hyödynnetään apteekin farmaseuttisen henkilökunnan tietoja ja taitoja. Farmaseuttiset palvelut voidaan jakaa farmaseuttisiin perus- ja erityispalveluihin. Farmaseuttiset peruspalvelut kattavat apteekkien lakisääteiset tehtävät, kun taas farmaseuttisilla erityispalveluilla pyritään ottamaan aktiivisempi rooli asiakkaan terveyden edistämisessä. Koneellinen annosjakelupalvelu on farmaseuttinen erityispalvelu. Koneellisessa annosjakelupalvelussa lääkkeet jaetaan kerta-annospusseihin annostusajankohdan mukaan. Kun uusi asiakas aloittaa koneellinen annosjakelupalvelun, tarkistetaan asiakkaan lääkitys yhteensopimattomien ja turhien lääkkeiden osalta. Palvelun aloitushetkellä huomioidaan myös lääkevalmisteiden sopivuus koneelliseen annosjakeluun sekä tarkistetaan valmisteiden annosteluajankohdat. Koneellisessa annosjakelupalvelussa asiakkaan lääkehoidosta muodostetaan lääkityskortti, josta kokonaislääkehoito on helppo tarkistaa. Erikoistyön tavoitteena oli selvittää millainen lääkehoidon arviointi tai tarkistus koneellisen annosjakelupalvelun aloittamisen yhteydessä tehdään ja miten palvelun aloittavien asiakkaiden kokonaislääkehoitotieto saadaan selvitettyä. Lisäksi selvitettiin millaisia muutoksia lääkehoitoihin tehdään palvelun aloittamisen yhteydessä, mitkä ovat muutosten syyt sekä millainen on asiakkaan kokonaislääkehoito. Kyselylomake lähetettiin kaikkiin apteekkeihin, jotka tilasivat koneellista annosjakelua sopimusvalmistuksena Espoonlahden apteekilta syyskuussa 2010. Tutkimus suoritettiin semistrukturoidulla kirjallisella kyselyllä, joka sisälsi sekä avoimia kysymyksiä että monivalintakysymyksiä. Kyselyyn saatiin 147 vastausta ja vastausprosentiksi muodostui 45. Vastauksia kyselyyn saatiin koko Mannersuomen alueelta ja kaikkien kokoluokkien apteekeilta. Koneellisen annosjakelupalvelun aloittavat henkilöt ovat pääasiassa iäkkäitä, jotka ovat kotihoidon piirissä, asuvat hoitokodissa tai palveluasumisen yksikössä. Asiakkaiden lääkitystietojen keräämisessä hyödynnetään lääkityskorttia, mutta lääkityskortin tietoja päivitetään myös muista lähteistä. Asiakkaiden lääkityksille tehdään useimmiten lääkehoidon tarkistus moniammatillisena yhteistyönä. Lääkehoidolle tehdyt muutokset johtuvat pääasiassa lääkevaihdosta, annosjakelukoneen lääkevalikoimasta tai puolittamisen välttämisestä. Lääkehoidoissa on vain vähän yhteisvaikutuksia, jotka johtavat lääkevalmisteen käytön lopettamiseen. Lääkehoidon tarkistuksella ei ollut suurta vaikutusta asiakkaiden käyttämien lääkevalmisteiden määrään. Palvelun aloittamisen jälkeen asiakkaalla on käytössään keskimäärin 11 lääkevalmistetta, joista seitsemää jaellaan koneellisesti. Lääkeaineryhmistä eniten käytettyjä ovat hermostoon vaikuttavat sekä sydän- ja verisuonisairauksien lääkkeet, joita kumpaakin on käytössä keskimäärin kolme jokaisella uudella koneellisen annosjakelupalvelun asiakkaalla sekä palvelun aloittamista ennen että sen jälkeen.

Mammalian Mat1 subunit of Transcription Factor IIH in gene-specific and general transcription

All protein-encoding genes in eukaryotes are transcribed into messenger RNA (mRNA) by RNA Polymerase II (RNAP II), whose activity therefore needs to be tightly controlled. An important and only partially understood level of regulation is the multiple phosphorylations of RNAP II large subunit C-terminal domain (CTD). Sequential phosphorylations regulate transcription initiation and elongation, and recruit factors involved in co-transcriptional processing of mRNA. Based largely on studies in yeast models and in vitro, the kinase activity responsible for the phosphorylation of the serine-5 (Ser5) residues of RNAP II CTD has been attributed to the Mat1/Cdk7/CycH trimer as part of Transcription Factor IIH. However, due to the lack of good mammalian genetic models, the roles of both RNAP II Ser5 phosphorylation as well as TFIIH kinase in transcription have provided ambiguous results and the in vivo kinase of Ser5 has remained elusive. The primary objective of this study was to elucidate the role of mammalian TFIIH, and specifically the Mat1 subunit in CTD phosphorylation and general RNAP II-mediated transcription. The approach utilized the Cre-LoxP system to conditionally delete murine Mat1 in cardiomyocytes and hepatocytes in vivo and and in cell culture models. The results identify the TFIIH kinase as the major mammalian Ser5 kinase and demonstrate its requirement for general transcription, noted by the use of nascent mRNA labeling. Also a role for Mat1 in regulating general mRNA turnover was identified, providing a possible rationale for earlier negative findings. A secondary objective was to identify potential gene- and tissue-specific roles of Mat1 and the TFIIH kinase through the use of tissue-specific Mat1 deletion. Mat1 was found to be required for the transcriptional function of PGC-1 in cardiomyocytes. Transriptional activation of lipogenic SREBP1 target genes following Mat1 deletion in hepatocytes revealed a repressive role for Mat1apparently mediated via co-repressor DMAP1 and the DNA methyltransferase Dnmt1. Finally, Mat1 and Cdk7 were also identified as a negative regulators of adipocyte differentiation through the inhibitory phosphorylation of Peroxisome proliferator-activated receptor (PPAR) γ. Together, these results demonstrate gene- and tissue-specific roles for the Mat1 subunit of TFIIH and open up new therapeutic possibilities in the treatment of diseases such as type II diabetes, hepatosteatosis and obesity.

The Church and Its Boundaries : A Study of the Special Commission on Orthodox Participation in the WCC

The relationship between the Orthodox Churches and the World Council of Churches (WCC) became a crisis just before the 8th Assembly of the WCC in Harare, Zimbabwe in 1998. The Special Commission on Orthodox Participation in the WCC (SC), inaugurated in Harare, worked during the period 1999 2002 to solve the crisis and to secure the Orthodox participation in the WCC. The purpose of this study is: 1) to clarify the theological motives for the inauguration of the SC and the theological argumentation of the Orthodox criticism; 2) to write a reliable history and analysis of the SC; 3) to outline the theological argumentation, which structures the debate, and 4) to investigate the ecclesiological questions that arise from the SC material. The study spans the years 1998 to 2006, from the WCC Harare Assembly to the Porto Alegre Assembly. Hence, the initiation and immediate reception of the Special Commission are included in the study. The sources of this study are all the material produced by and for the SC. The method employed is systematic analysis. The focus of the study is on theological argumentation; the historical context and political motives that played a part in the Orthodox-WCC relations are not discussed in detail. The study shows how the initial, specific and individual Orthodox concerns developed into a profound ecclesiological discussion and also led to concrete changes in WCC practices, the best known of which is the change to decision-making by consensus. The Final Report of the SC contains five main themes, namely, ecclesiology, decision-making, worship/common prayer, membership and representation, and social and ethical issues. The main achievement of the SC was that it secured the Orthodox membership in the WCC. The ecclesiological conclusions made in the Final Report are twofold. On the one hand, it confirms that the very act of belonging to the WCC means the commitment to discuss the relationship between a church and churches. The SC recommended that baptism should be added as a criterion for membership in the WCC, and the member churches should continue to work towards the mutual recognition of each other s baptism. These elements strengthen the ecclesiological character of the WCC. On the other hand, when the Final Report discusses common prayer, the ecclesiological conclusions are much more cautious, and the ecclesiological neutrality of the WCC is emphasized several times. The SC repeatedly emphasized that the WCC is a fellowship of churches. The concept of koinonia, which has otherwise been important in recent ecclesiological questions, was not much applied by the SC. The comparison of the results of the SC to parallel ecclesiological documents of the WCC (Nature and Mission of the Church, Called to Be the One Church) shows that they all acknowledge the different ecclesiological starting points of the member churches, and, following that, a variety of legitimate views on the relation of the Church to the churches. Despite the change from preserving the koinonia to promises of eschatological koinonia, all the documents affirm that the goal of the ecumenical movement is still full, visible unity.

Production process of Scots pine.

The accompanying collective research report is the result of the research project in 1986­90 between The Finnish Academy and the former Soviet Academy of Sciences. The project was organized around common field work in Finland and in the former Soviet Union and theoretical analyses of tree growth determining processes. Based on theoretical analyses, dynamic stand growth models were made and their parameters were determined utilizing the field results. Annual cycle affects the tree growth. Our theoretical approach was based on adaptation to local climate conditions from Lapland to South Russia. The initiation of growth was described as a simple low and high temperature accumulation driven model. Linking the theoretical model with long term temperature data allowed us to analyze what type of temperature response produced favorable outcome in different climates. Initiation of growth consumes the carbohydrate reserves in plants. We measured the dynamics of insoluble and soluble sugars in the very northern and Karelian conditions. Clear cyclical pattern was observed but the differences between locations were surprisingly small. Analysis of field measurements of CO2 exchange showed that irradiance is the dominating factor causing variation in photosynthetic rate in natural conditions during summer. The effect of other factors is so small that they can be omitted without any considerable loss of accuracy. A special experiment carried out in Hyytiälä showed that the needle living space, defined as the ratio between the shoot cylindric volume and needle surface area, correlates with the shoot photosynthesis. The penetration of irradiance into Scots pine canopy is a complicated phenomenon because of the movement of the sun on the sky and the complicated structure of branches and needles. A moderately simple but balanced forest radiation regime submodel was constructed. It consists of the tree crown and forest structure, the gap probability calculation and the consideration of spatial and temporal variation of radiation inside the forest. The common field excursions in different geographical regions resulted in a lot of experimental data of regularities of woody structures. The water transport seems to be a good common factor to analyse these properties of tree structure. There are evident regressions between cross-sectional areas measured at different locations along the water pathway from fine roots to needles. The observed regressions have clear geographical trends. For example, the same cross-sectional area can support three times higher needle mass in South Russia than in Lapland. Geographical trends can also be seen in shoot and needle structure. Analysis of data published by several Russian authors show, that one ton of needles transpire 42 ton of water a year. This annual amount of transpiration seems to be independent of geographical location, year and site conditions. The produced theoretical and experimental material is utilised in the development of stand growth model that describes the growth and development of Scots pine stands in Finland and the former Soviet Union. The core of the model is carbon and nutrient balances. This means that carbon obtained in photosynthesis is consumed for growth and maintenance and nutrients are taken according to the metabolic needs. The annual photosynthetic production by trees in the stand is determined as a function of irradiance and shading during the active period. The utilisation of the annual photosynthetic production to the growth of different components of trees is based on structural regularities. Since the fundamental metabolic processes are the same in all locations the same growth model structure can be applied in the large range of Scots pine. The annual photosynthetic production and structural regularities determining the allocation of resources have geographical features. The common field measurements enable the application of the model to the analysis of growth and development of stands growing on the five locations of experiments. The model enables the analysis of geographical differences in the growth of Scots pine. For example, the annual photosynthetic production of a 100-year-old stand at Voronez is 3.5 times higher than in Lapland. The share consumed to needle growth (30 %) and to growth of branches (5 %) seems to be the same in all locations. In contrast, the share of fine roots is decreasing when moving from north to south. It is 20 % in Lapland, 15 % in Hyytiälä Central Finland and Kentjärvi Karelia and 15 % in Voronez South Russia. The stem masses (115­113 ton/ha) are rather similar in Hyytiälä, Kentjärvi and Voronez, but rather low (50 ton/ha) in Lapland. In Voronez the height of the trees reach 29 m being in Hyytiälä and Kentjärvi 22 m and in Lapland only 14 m. The present approach enables utilization of structural and functional knowledge, gained in places of intensive research, in the analysis of growth and development of any stand. This opens new possibilities for growth research and also for applications in forestry practice.

Strategic Sales Process Adaptation: Relationship Orientation of the Sales Process in a Business-to-Business Context

Although previous research has recognised adaptation as a central aspect in relationships, the adaptation of the sales process to the buying process has not been studied. Furthermore, the linking of relationship orientation as mindset with adaptation as a strategy and forming the means has not been elaborated upon in previous research. Adaptation in the context of relationships has mostly been studied in relationship marketing. In sales and sales management research, adaptation has been studied with reference to personal selling. This study focuses on adaptation of the sales process to strategically match it to the buyer’s mindset and buying process. The purpose of this study is to develop a framework for strategic adaptation of the seller’s sales process to match the buyer’s buying process in a business-to-business context to make sales processes more relationship oriented. In order to arrive at a holistic view of adaptation of the sales process during relationship initiation, both the seller and buyer are included in an extensive case analysed in the study. However, the selected perspective is primarily that of the seller, and the level focused on is that of the sales process. The epistemological perspective adopted is constructivism. The study is a qualitative one applying a retrospective case study, where the main sources of information are in-depth semi-structured interviews with key informants representing the counterparts at the seller and the buyer in the software development and telecommunications industries. The main theoretical contributions of this research involve targeting a new area in the crossroads of relationship marketing, sales and sales management, and buying and purchasing by studying adaptation in a business-to-business context from a new perspective. Primarily, this study contributes to research in sales and sales management with reference to relationship orientation and strategic sales process adaptation. This research fills three research gaps. Firstly, linking the relationship orientation mindset with adaptation as strategy. Secondly, extending adaptation in sales from adaptation in selling to strategic adaptation of the sales process. Thirdly, extending adaptation to include facilitation of adaptation. The approach applied in the study, systematic combining, is characterised by continuously moving back and forth between theory and empirical data. The framework that emerges, in which linking mindset with strategy with mindset and means forms a central aspect, includes three layers: purchasing portfolio, seller-buyer relationship orientation, and strategic sales process adaptation. Linking the three layers enables an analysis of where sales process adaptation can make a contribution. Furthermore, implications for managerial use are demonstrated, for example how sellers can avoid the ‘trap’ of ad-hoc adaptation. This includes involving the company, embracing the buyer’s purchasing portfolio, understanding the current position that the seller has in this portfolio, and possibly educating the buyer about advantages of adopting a relationship-oriented approach.

Arabidopsis GRI is involved in the regulation of cell death induced by extracellular ROS

Reactive oxygen species (ROS) have important functions in plant stress responses and development. In plants, ozone and pathogen infection induce an extracellular oxidative burst that is involved in the regulation of cell death. However, very little is known about how plants can perceive ROS and regulate the initiation and the containment of cell death. We have identified an Arabidopsis thaliana protein, GRIM REAPER (GRI), that is involved in the regulation of cell death induced by extracellular ROS. Plants with an insertion in GRI display an ozone-sensitive phenotype. GRI is an Arabidopsis ortholog of the tobacco flower-specific Stig1 gene. The GRI protein appears to be processed in leaves with a release of an N-terminal fragment of the protein. Infiltration of the N-terminal fragment of the GRI protein into leaves caused cell death in a superoxide-and salicylic acid-dependent manner. Analysis of the extracellular GRI protein yields information on how plants can initiate ROS-induced cell death during stress response and development.