Psychosocial aspects of cleft lip and palate. Implications for parental education

Lectio praecursoria

Associations between alexithymia and mental well-being in adolescents

Nuorten tunneilmaisun yhteys psyykkiseen oireiluun Aleksitymialla tarkoitetaan persoonallisuuden piirteistöä, jolle on tyypillistä heikko kyky tunnistaa ja ilmaista tunteita sekä vähäinen mielikuvitus ja konkreettinen, ulkokohtainen ajattelutapa. Tämän tutkimuksen tarkoituksena on tarkastella aleksitymian yhteyttä psyykkiseen oireiluun nuorilla sekä tutkia aleksitymian kehittymiselle altistavia yksilöllisiä lapsuudenaikaisia tekijöitä. Tutkimusaineisto koostui aiempaan nuorten syömishäiriöoireilua tarkastelevaan tutkimukseen osallistuneista nuorista (n = 320) ja heille satunnaisotannalla poimituista verrokeista (n = 640). Seurantakyselyssä käytettiin vastaajan itsensä täytettäviä mittareita ja aineisto kerättiin postikyselynä. Yhteensä 729 henkilöä (78 %) palautti lomakkeen täytettynä, muodostaen näin lopullisen tutkimusaineiston. Tyttöjä vastanneista oli 74 % ja poikia 26 %. Aineiston keski-ikä oli 19 vuotta tämän tutkimuksen aikaan. Aineistosta oli käytettävissä neuvolatiedot syntymästä lähtien. Tutkimusaineistossa todettiin aleksitymian yleisyydeksi tytöillä 8,2 % ja pojilla 8,5 %. Sukupuolten välillä ei todettu eroa 20-osioisella Toronto Alexithymia Scale-kyselyllä (TAS-20) pistemäärissä (tytöillä 44.7 ja pojilla 46.0). Syömishäiriöoireiden todettiin olevan yleisempiä aleksityymisillä nuorilla verrattuna ei-aleksityymisiin. Syömishäiriöoireita mitattiin SCOFF-mittarilla (“Sick”, “Control”, “One”, “Fat”, “Food”). Aleksityymisten nuorten keskimääräinen SCOFF-pistemäärä oli merkitsevästi korkeampi kuin ei-aleksityymisten ja SCOFF-positiivisten (pistemäärä vähintään 2) osuus oli aleksityymisten ryhmässä kolminkertainen ei-aleksityymisten ryhmään verrattuna. Myös ahdistuneisuuden todettiin olevan yhteydessä aleksitymiaan nuorilla. Ahdistuneisuutta mitattiin State-Trait Anxiety Inventory-mittarilla (STAI) ja lisäksi mitattiin masennusoireita ja alkoholinkäyttöä. Aleksityymisten nuorten STAI-pisteet olivat merkitsevästi korkeammat kuin eialeksityymisten. Ahdistuneet aleksityymiset nuoret olivat myös yleisemmin masentuneita ja käyttivät runsaammin alkoholia kuin yhtä ahdistuneet ei-aleksityymiset nuoret. Tutkimuksessa selvitettiin aleksitymian yhteyttä sosiaaliseen tukeen sekä koettuun vanhempien hoivaan ja ylisuojelevaisuuteen. Käytetyt mittarit olivat Multidimensional Scale of Perceived Social Support ja Parental Bonding Instrument. Aleksitymia oli merkitsevästi yhteydessä sekä heikompaan koettuun sosiaaliseen tukeen – erityisesti ystäviltä saatavaan − että korkeampaan vanhempien ylisuojelevaisuuteen. Tutkimuksessa käytettiin 5-vuotisneuvolatarkastuksen tietoja sen arviointiin, mitkä kehitykselliset tekijät saattavat olla yhteydessä aleksitymian ilmenemiseen. Puheenkehityksen ongelmien todettiin olevan miehillä selvästi yhteydessä aleksitymiaan. Tutkimuksen perusteella aleksityymisillä nuorilla esiintyy ei-aleksityymisiin ikätovereihin verrattuna selvästi yleisemmin psyykkisiä oireita. Koska aleksitymia heikentää hoitovastetta todennäköisesti myös nuorilla, tulisi aleksitymian mahdollisuus selvittää tehokkaasti psyykkisesti oireilevilla nuorilla. Lisääntyvä tutkimustieto aleksitymian kehittymisestä mahdollistaa riskitapausten varhaisemman tunnistamisen ja tilanteeseen puuttumisen.

Interactions between genes and alcohol on aggressive behavior and anger related traits : the oxytocin receptor gene as a candidate

Alkoholberusning är en av de starkaste riskfaktorerna för aggressivt beteende. Alla individer blir dock inte aggressiva under alkoholberusning. I sin doktorsavhandling undersökte Johansson ifall individens genetiska uppsättning kan förklara skillnader i vem som reagerar på alkohol med ökat aggressivt beteende och ilska och vem som inte gör det. Resultaten visade att individer som är bärare av en viss variant av genen som kodar för oxytocinets receptorer är i högre grad benägna att uppvisa aggressivt beteende än andra när de är alkoholberusade. Sambandet mellan alkohol och ilska påverkades även av individens genetiska uppsättning av två oxytocinreceptorgenvarianter, vilket antyder att dessa genvarianter även påverkar benägenheten att känna ilska under alkoholberusning. Oxytocinet, som fungerar både som ett hormon och en neurotransmittor, har i tidigare studier visats ha breda effekter på sociala förmågor hos människan, såsom förmåga till igenkännande av andras känslouttryck. Resultaten är de första att hos människan experimentellt påvisa att vissa individer beter sig mer aggressivt än andra när de är berusade, beroende på individens genetiska uppsättning. ”Det är viktigt att komma ihåg att genens effekt i det här fallet inte är av en sådan natur att den direkt och ofrånkomligen orsakar aggressivt beteende. Med andra ord är det orimligt i detta fall att tänka att en individ skulle tillmätas ansvarsfrihet i exempelvis ett våldsbrottmål om hon bär på en viss variant av denna gen”, påpekar Johansson. Oxytocinreceptorgenens effekter analyserades i två olika urval. I ett experimentellt upplägg indelades 116 män slumpässigt i två grupper: en grupp som tilldelades alkoholhaltiga drycker, och en kontrollgrupp som tilldelades alkoholfria drycker. Aggressivt beteende mättes med ett laboratorietest där försökspersonerna fick bestraffa en fiktiv motspelare genom att spela upp motbjudande ljud för denne. Resultaten replikerades i ett populationsbaserat urval av män och kvinnor (n = 3755) vilka besvarat frågor om deras aggressiva beteenden, ilska, och alkoholanvändning.

Fetal alcohol spectrum disorders in Finnish children and adolescents : diagnosis, cognition, behavior, adaptation and brain metabolic alterations

Alcohol consumption during pregnancy can potentially affect the developing fetus in devastating ways, leading to a range of physical, neurological, and behavioral alterations most accurately termed Fetal Alcohol Spectrum Disorders (FASD). Despite the fact that it is a preventable disorder, prenatal alcohol exposure today constitutes a leading cause of intellectual disability in the Western world. In Western countries where prevalence studies have been performed the rates of FASD exceed, for example, autism spectrum disorders, Down’s syndrome and cerebral palsy. In addition to the direct effects of alcohol, children and adolescents with FASD are often exposed to a double burden in life, as their neurological sequelae are accompanied by adverse living surroundings exposing them to further environmental risk. However, children with FASD today remain remarkably underdiagnosed by the health care system. This thesis forms part of a larger multinational research project, The Collaborative Initiative on Fetal Alcohol Spectrum Disorders (the CIFASD), initiated by the National Institute of Alcohol Abuse and Alcoholism (NIAAA) in the U.S.A. The general aim of the present thesis was to examine a cohort of children and adolescents growing up with fetal alcohol-related damage in Finland. The thesis consists of five studies with a broad focus on diagnosis, cognition, behavior, adaptation and brain metabolic alterations in children and adolescents with FASD. The participants consisted of four different groups: one group with histories of prenatal exposure to alcohol, the FASD group; one IQ matched contrast group mostly consisting of children with specific learning disorder (SLD); and two typically-developing control groups (CON1 and CON2). Participants were identified through medical records, random sampling from the Finnish national population registry and email alerts to students. Importantly, the participants in the present studies comprise a group of very carefully clinically characterized children with FASD as the studies were performed in close collaboration with leading experts in the field (Prof. Edward Riley and Prof. Sarah Mattson, Center for Behavioral Teratology, San Diego State University, U.S.A; Prof. Eugene Hoyme, Sanford School of Medicine, University of South Dakota, U.S.A.). In the present thesis, the revised Institute of Medicine diagnostic criteria for FASD were tested on a Finnish population and found to be a reliable tool for differentiating among the subgroups of FASD. A weighted dysmorphology scoring system proved to be a valuable additional adjunct in quantification of growth deficits and dysmorphic features in children with FASD (Study 1). The purpose of Study 2 was to clarify the relationship between alcohol-related dysmorphic features and general cognitive capacity. Results showed a significant correlation between dysmorphic features and cognitive capacity, suggesting that children with more severe growth deficiency and dysmorphic features have more cognitive limitations. This association was, however, only moderate, indicating that physical markers and cognitive capacity not always go hand in hand in individuals with FASD. Behavioral problems in the FASD group proved substantial compared to the typically developing control group. In Study 3 risk and protective factors associated with behavioral problems in the FASD group were explored further focusing on diagnostic and environmental factors. Two groups with elevated risks for behavioral problems emerged: length of time spent in residential care and a low dysmorphology score proved to be the most pervasive risk factor for behavioral problems. The results underscore the clinical importance of appropriate services and care for less visibly alcohol affected children and highlight the need to attend to children with FASD being raised in institutions. With their background of early biological and psychological impairment compounded with less opportunity for a close and continuous caregiver relationship, such children seem to run an especially great risk of adverse life outcomes. Study 4 focused on adaptive abilities such as communication, daily living skills and social skills, in other words skills that are important for gradually enabling an independent life, maintain social relationships and allow the individual to become integrated into society. The results showed that adaptive abilities of children and adolescents growing up with FASD were significantly compromised compared to both typically-developing peers and IQ-matched children with SLD. Clearly different adaptive profiles were revealed where the FASD group performed worse than the SLD group, who in turn performed worse than the CON1 group. Importantly, the SLD group outperformed the FASD group on adaptive behavior in spite of comparable cognitive levels. This is the first study to compare adaptive abilities in a group of children and adolescents with FASD relative to both a contrast group of IQ-matched children with SLD and to a group of typically-developing peers. Finally, in Study 5, through magnetic resonance spectroscopic imaging (MRS) evidence of longstanding neurochemical alterations were observed in adolescents and young adults with FASD related to alcohol exposure in utero 14-20 years earlier. Neurochemical alterations were seen in several brain areas: in frontal and parietal cortices, corpus callosum, thalamus and frontal white matter areas as well as in the cerebellar dentate nucleus. The findings are compatible with neuropsychological findings in FASD. Glial cells seemed to be more affected than neurons. In conclusion, more societal efforts and resources should be focused on recognizing and diagnosing FASD, and supporting subgroups with elevated risk of poor outcome. Without adequate intervention children and adolescents with FASD run a great risk of marginalization and social maladjustment, costly not only to society but also to the lives of the many young people with FASD.

The role of emotional state, sexual arousal, and alcohol intoxication as situational factors associated with adults’ online sexual contact with children and adolescents

In the present study we explored whether and how the situational factors; emotional states, sexual arousal, and alcohol intoxication influenced the propensity in adults to engage in online sexual contact with children (13 or younger) and adolescents (14 – 17 year olds). The results were compared to a group of adults that had engaged in online sexual contact with adults only (18 or older). We also looked at the variation over time within these situational factors during the online sexual contact with a child, an adolescent, or an adult. The present study was an online self-report survey to the adult populations in Finland, Sweden, and Germany, with a final sample (N = 776) of women and men who were active on the Internet. The participants were asked to report whether, how, and with whom they had engaged in online sexual contact. The results showed that more men than women reported online sexual contact with persons of all age groups, and that the situational factors; emotional states and sexual arousal influenced the propensity in both women and men to engage in online sexual contact with children and adolescents. However, the effects of alcohol intoxication were small and significant only for men. These results indicate that higher levels of emotional state and sexual arousal might increase the propensity to go against social norms and contact children and adolescents online for sexual purposes, but it can also imply that that those who look for online sexual contact online with children and adolescents, are more emotionally and/or sexually aroused than the group that only seek adult company or that these are post-hoc explanations for such sexual activities.

Lipase and omega-transaminase catalysis in preparation of alcohol and amine enantiomers

Enantiopure intermediates are of high value in drug synthesis. Biocatalysis alone or combined with chemical synthesis provides powerful tools to access enantiopure compounds. In biocatalysis, chemo-, regio- and enantioselectivity of enzymes are combined with their inherent environmentally benign nature. Enzymes can be applied in versatile chemical reactions with non-natural substrates under synthesis conditions. Immobilization of an enzyme is a crucial part of an efficient biocatalytic synthesis method. Successful immobilization enhances the catalytic performance of an enzyme and enables its reuse in successive reactions. This thesis demonstrates the feasibility of biocatalysis in the preparation of enantiopure secondary alcohols and primary amines. Viability and synthetic usability of the studied biocatalytic methods have been addressed throughout this thesis. Candida antarctica lipase B (CAL-B) catalyzed enantioselective O-acylation of racemic secondary alcohols was successfully incorporated with in situ racemization in the dynamic kinetic resolution, affording the (R)-esters in high yields and enantiopurities. Side reactions causing decrease in yield and enantiopurity were suppressed. CAL-B was also utilized in the solvent-free kinetic resolution of racemic primary amines. This method produced the enantiomers as (R)-amides and (S)-amines under ambient conditions. An in-house sol-gel entrapment increased the reusability of CAL-B. Arthrobacter sp. omega-transaminase was entrapped in sol-gel matrices to obtain a reusable catalyst for the preparation enantiopure primary amines in an aqueous medium. The obtained heterogeneous omega-transaminase catalyst enabled the enantiomeric enrichment of the racemic amines to their (S)-enantiomers. The synthetic usability of the sol-gel catalyst was demonstrated in five successive preparative kinetic resolutions.

Nordic alcohol policy in Europe: the adaptation of Finland’s, Sweden’s and Norway’s alcohol policies to a new policy framework, 1994-2013

The purpose of this thesis is to study how and to which extent Finland, Sweden and Norway have adapted their alcohol policies to the framework imposed to them by the EU and the European Economic Area (EEA) since the mid-1990s. This is done by studying the underlying mechanisms that have influenced the formation of alcohol policy in the Nordic countries in that period. As a part of this analysis main differences in alcohol policies and alcohol consumption between the three countries are assessed and the phenomenon of cross-border trade with alcohol is discussed. The study examines also the development of Finnish, Norwegian and Swedish alcohol policies between 1994 and 2012 and compares the Nordic alcohol policies with other alcohol policies in Europe as the situation was in 2012. The time frame of the study spans from the mid-1990s to the end of 2013 and is divided into three phases. Studying the role of the Europeanisation process on the formation of alcohol policies has a key role in the analysis. Besides alcohol policies, the analyses comprise the development of alcohol consumption and cross-border trade with alcohol. In addition, a quantitative scale constructed to measure the strictness of alcohol policies is utilised in the analyses. The results from the scale are used to substantiate the qualitative analysis and to test whether the stereotypical view of a strict Nordic alcohol policy is still true. The results from the study clearly corroborate earlier findings on the significance of Europeanisation and the Single Market for the development of alcohol policies in the Nordic countries. Free movement of goods and unhindered competition have challenged the principle of disinterest and enabled private profit seeking in alcohol trade. The Single Market has also contributed to the increase in availability of alcohol and made it more difficult for the Nordic EU member states to maintain restrictive alcohol policies. All in all, alcohol policies in the Nordic countries are more liberal in 2013 than they were in 1994. Norway, being outside the EU has, however, managed to maintain a stricter alcohol policy than Finland and Sweden. Norway has also been spared from several EU directives that have affected Finland and Sweden, the most remarkable being the abolishment of the travellers’ import quotas for alcohol within the EU. Due to its position as a non-EU country Norway has been able to maintain high alcohol taxes without being subjected to a ”race to the bottom” regarding alcohol taxes the same way as Finland and Sweden. Finland distinguishes as the country that has liberalised its alcohol policy most during the study period. The changes in alcohol policies were not only induced by Europeanisation and the Single Market, but also by autonomous decision-making and political processes in the individual countries. Furthermore, the study shows that alcohol policy measures are implemented more widely in Europe than before and that there is a slow process of convergence going on regarding alcohol policy in Europe. Despite this, alcohol policies in the Nordic countries are still by far the strictest in all of Europe. From a Europeanisation perspective, the Nordic countries were clearly on the receiving end during the first two study phases (1994–2007), having more to adjust to rules from the EU and the Single Market than having success in uploading and shaping alcohol policy on the European and international field. During the third and final study phase (2008–2013), however, the Nordic countries have increasingly succeeded in contributing to shape the alcohol policy arena in the EU and also more widely through the WHOs global alcohol strategy. The restrictive Nordic policy tradition on which the current alcohol policies in Finland, Sweden and Norway were built on has still quite a solid evidence base. Although the basis of the restrictive alcohol policy has crumbled somewhat during the past twenty years and the policies have become less effective, nothing prevents it from being the base for alcohol policy in the Nordic countries even in the long term. In the future, all that is needed for an effective and successful alcohol policy is a solid evidence base, enough political will and support from the general public.

Parental and Successor Liability in EU Competition Law Infringements

Under EU competition law, parent companies may be held jointly and severally liable for the competition law infringements committed by their subsidiaries. The possibility of holding parent companies liable demonstrates a significant exception from the idea of separate legal entities. However, it is not the only deviation developed under EU competition law. In cases, where the legal entity responsible for the anti-competitive conduct has changed its form, liability can be attributed to the new operator, in particular, to its successor. The principles of legal certainty and legitimate expectations are issues that surround the doctrines of parental and successor liability. The aim of this thesis is to present a comprehensive comparative analysis of the parental and successor liability doctrines and to clarify the conditions under which it is possible to attribute liability for the infringements of EU competition law. The main purpose is therefore to demonstrate the problems related to the allocation of liability and to discuss whether these liability principles, established to assure the effective enforcement of the EU competition rules, are good solutions. The research methods used in this thesis are the legal dogmatic approach and the comparative law approach. The former enables the possibility of using the case law and legislation as a framework in which the difficulties concerning the application of parental and successor liability can be discussed while the latter ensures the comparison of the characteristics and judgments. The doctrines of parental and successor liability are both well established, but the application practice has caused several difficulties. These problems derive from, inter alia, the broadness and disjointed developed of the doctrines. There has been much recent case law dealing with these issues and having the potential to open up a considerable risk and to allocate strict liability for parent and successor companies.