Genetics of inherited small vessel diseases – in search of a novel small vessel disease and modifiers of the clinical course of CADASIL

The genetic and environmental risk factors of vascular cognitive impairment are still largely unknown. This thesis aimed to assess the genetic background of two clinically similar familial small vessel diseases (SVD), CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) and Swedish hMID (hereditary multi-infarct dementia of Swedish type). In the first study, selected genetic modifiers of CADASIL were studied in a homogenous Finnish CADASIL population of 134 patients, all carrying the p.Arg133Cys mutation in NOTCH3. Apolipoprotein E (APOE) genotypes, angiotensinogen (AGT) p.Met268Thr polymorphism and eight NOTCH3 polymorphisms were studied, but no associations between any particular genetic variant and first-ever stroke or migraine were seen. In the second study, smoking, statin medication and physical activity were suggested to be the most profound environmental differences among the monozygotic twins with CADASIL. Swedish hMID was for long misdiagnosed as CADASIL. In the third study, the CADASIL diagnosis in the Swedish hMID family was ruled out on the basis of genetic, radiological and pathological findings, and Swedish hMID was suggested to represent a novel SVD. In the fourth study, the gene defect of Swedish hMID was then sought using whole exome sequencing paired with a linkage analysis. The strongest candidate for the pathogenic mutation was a 3’UTR variant in the COL4A1 gene, but further studies are needed to confirm its functionality. This study provided new information about the genetic background of two inherited SVDs. Profound knowledge about the pathogenic mutations causing familial SVD is also important for correct diagnosis and treatment options.

Late-onset spinal motor neuronopathy- a new neuromuscular disease

The aim of this study was to clarify the clinical phenotype of late-onset spinal motor neuronopathy (LOSMoN), an adult-onset autosomal dominant lower motor neuron disorder identified first in two families in Eastern Finland, in order to clarify its genetic background. Motor neuron disorders (MNDs) are characterized by dysfunction and premature death of motor neurons in the brain and spinal cord. MNDs can manifest at any age of the human lifespan, ranging from pre- or neonatal forms such as spinal muscular atrophy type I (SMA I) to those preferentially affecting the older age groups exemplified by sporadic amyotrophic lateral sclerosis (ALS). With a combination of genetic linkage analysis and genome sequencing using DNA from a total of 55 affected members of 17 families and a whole genome scan, we were able to show that LOSMoN is caused by the c.197G>T p.G66V mutation in the gene CHCHD10. This study showed that LOSMoN has very characteristic features that help to differentiate it from other more malignant forms of motor neuron disease, such as ALS, which was erroneously diagnosed in many patients in our cohort. Lack of fibrillations in the first dorsal interosseus muscle on EMG and extensive grouping of non-atrophic type IIA/2A fibers on muscle biopsy were shown to be common findings in LOSMoN, but rare or absent in ALS patients. The results of this study will help clinicians recognize the characteristic phenotype of LOSMoN disease and thus improve their diagnostic accuracy, and will also allow physicians to provide adequate genetic counseling for patients.

Corporate green image communication through public disclosures and social media

Today, companies need to mind the environment in all their actions. Policies, regulations and growing pressure from environmentally conscious public are driving corporations to invest increasingly in their green images. Communication plays a key role in forming and maintaining that image. This thesis explores how six selected companies communicate about their environmental efforts and activities, and its linkage to their green images, in annual and sustainability reports and in Facebook. The companies come from the U.S. and Europe and operate in three different industries: ICT, oil and gas, and aerospace & defense. Qualitative and quantitative content analyses are conducted to examine 36 reports and 121 Facebook messages, collected from the period of 2010-2014, and from 2005 for comparison. The results show that although the quality and quantity of environmental disclosure is increasing, there is still room for improvement. Overall, disclosure in the ICT sector is on the highest level. The European companies disclose more and on average have stronger green images than the American ones. Emissions and ways to reduce them is by far the most covered topic in both continents and in all three industry sectors. The messages in Facebook are closer to advertising, and overall the platform is utilized surprisingly little.

Litteracitet i fem högstadieungdomars en-till-en-datorpraktiker

The study focuses on five lower secondary school pupils’ daily use of their one-toone computers, the overall aim being to investigate literacy in this form of computing. Theoretically, the study is rooted in the New Literacy tradition with an ecological perspective, in combination with socio-semiotic theory in a multimodal perspective. New Literacy in the ecological perspective focuses on literacy practices and place/space and on the links between them. Literacy is viewed as socially based, in specific situations and in recurring social practices. Socio-semiotic theory embodying the multimodal perspective is used for the text analysis. The methodology is known as socio-semiotic ethnography. The ethnographic methods encompass just over two years of fieldwork with participating observations of the five participants’ computing activities at home, at school and elsewhere. The participants, one boy and two girls from the Blue (Anemone) School and two girls from the White (Anemone) School, were chosen to reflect a broad spectrum in terms of sociocultural and socioeconomic background. The study shows the existence of a both broad and deep variation in the way digital literacy features in the participants’ one-to-one computing. These variations are associated with experience in relation to the home, the living environment, place, personal qualities and school. The more varied computer usage of the Blue School participants is connected with the interests they developed in their homes and living environments and in the computing practices undertaken in school. Their more varied usage of the computer is reflected in their broader digital literacy repertoires and their greater number and variety of digital literacy abilities. The Blue School participants’ text production is more multifaceted, covers a wider range of subjects and displays a broader palette of semiotic resources. It also combines more text types and the texts are generally longer than those of the White School participants. The Blue School girls have developed a text culture that is close to that of the school. In their case, there is clear linkage between school-initiated and self-initiated computing activities, while other participants do not have the same opportunities to link and integrate self-initiated computing activities into the school context. It also becomes clear that the Blue School girls can relate and adapt their texts to different communicative practices and recipients. In addition, the study shows that the Blue School girls have some degree of scope in their school practice as a result of incorporating into it certain communicative practices that they have developed in nonschool contexts. Quite contrary to the hopes expressed that one-to-one computing would reduce digital inequality, it has increased between these participants. Whether the same or similar results apply in a larger perspective, on a more structural level, is a question that this study cannot answer. It can only draw attention to the need to investigate the matter. The study shows in a variety of ways that the White School participants do not have the same opportunity to develop their digital literacy as the Blue School participants. In an equivalence perspective, schools have a compensational task to perform. It is abundantly clear from the study that investing in one-to-one projects is not enough to combat digital inequality and achieve the digitisation goals established for school education. Alongside their investments in technology, schools need to develop a didactic that legitimises and compensates for the different circumstances of different pupils. The compensational role of schools in this connection is important not only for the present participants but also for the community at large, in that it can help to secure a cohesive, open and democratic society.