Movement is a prerequisite for normal fetal development and growth. Intrauterine movement restrictions cause a broad spectrum of disorders in which the unifying feature is a reduction or lack of fetal movement, giving rise to the term fetal akinesia deformations sequence (FADS [OMIM 208150]). FADS corresponds to a clinically and genetically heterogeneous constellation of properties and is characterized by multiple joint contractures, facial abnormalities, and lung hypoplasia as a result of the decreased in utero movement of the fetuses. Affected babies are often prematurely and stillborn, and those born alive typically die within minutes or hours after birth. The genetic causes for this fatal disorder are ill-defined as a genetic diagnosis is rarely executed, but mutations in three genes, namely RAPSN, DOK7, and MUSK, as well as in the subunits of the muscular nicotinic acetylcholine receptor (AChR) have been described. These mutations are thought to affect neuromuscular junctions, although this has not been proven experimentally.The nucleoporin NUP88 is a constituent of the nuclear pore complex (NPC), the gate for all trafficking between the nucleus and the cytoplasm. NUP88 resides on both the cytoplasmic and the nuclear side of NPCs, and it is found in two distinct subcomplexes. It associates with NUP214 and NUP62 on the cytoplasmic face, while on the nuclear side NUP88 binds NUP98 and the intermediate filament protein lamin A. The NUP88-NUP214-NUP62 complex plays an essential role in the nuclear export of a subset of proteins and pre-ribosomes, which is mediated by the nuclear export receptor CRM1. NUP88 in particular somewhat participates in the nuclear export of NF-κB proteins in a CRM1-dependent manner. Moreover, NUP88 is frequently overexpressed in a variety of human cancers, and its role in cancer appears linked to the deregulation of the anaphase-promoting complex. Here, we report the first Mendelian disorders caused by mutations in NUP88 and with that the first lethal developmental human disease due to mutations in a nuclear pore component. We demonstrate that biallelic mutations in NUP88 are likely to cause fetal akinesia of the Pena-Shokeir subtype. We confirm in zebrafish that loss of NUP88 impairs movement and the mutations identified in the affected individuals resemble a loss-of-function phenotype. We show that loss of NUP88 affects expression and localization of rapsyn, the protein encoded by RAPSN, in human and mouse cell lines, and patient samples. Consistent with altered rapsyn, AChR clustering and neuromuscular junction formation in zebrafish are abnormal. We therefore propose that defective NUP88 function cause FADS by affecting neuromuscular junction formation.Keywords: Nuclear pore complex, NUP88, Fetal Akinesia Deformation Sequence, rapsyn, acetylcholine receptor clustering, synaptic transmission, fetal development, inherited developmental disorder. / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

PhD (Psychology) / Department of Psychology. / Attention Deficit Hyperactivity Disorder (ADHD) is the most common diagnosed neurocognitive behavioural developmental disorder among school going–age children. ADHD in most instances is found to comorbid with internalising disorders such as anxiety and depression, therefore causing impairment on behaviour, emotions, academic, social and many areas of functioning. The existence of comorbid internalising disorders complicates the presentation of ADHD symptoms than if it was pure ADHD. The aim of the study was to explore the comorbidity of internalising disorders and ADHD symptoms. The study investigated whether children with ADHD have more symptoms of anxiety and depression than children without ADHD. The study went further to investigate whether children with ADHD have low self-esteem than children without ADHD. Also, that internalising comorbidities (anxiety and depression) are more prevalent in girls than in boys who have more externalising comorbidities which are Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) and anger issues. The null hypotheses further showed that, children with ADHD do not have more symptoms of anxiety and depression than children without ADHD. Moreover, children with ADHD have no lower self-esteem than children without ADHD. Also, internalising disorders (anxiety and depression) are not prevalent in girls than in boys who do not exhibit more externalising disorders which are Oppositional Defiant Disorder (ODD), Conduct Disorder (CD) and anger issues. The study was conducted in Lepelle-Nkumpi Municipality in Lebowakgomo sub circuit. A total of 250 children (94 boys and 156 girls, aged 6 – 12) who were purposively selected participated in the study. A total of 125 clinically diagnosed ADHD were matched to 125 control group for age and gender. Participants were assessed on a battery consisting of Parent/Teacher Disruptive Behavioural Rating Scale (DBD), which was used to assess the presence and degree of ADHD- related symptoms (inattention and hyperactive/ impulsive); Oppositional Defiant Disorder and Conduct Disorder and Beck Youth Inventory Second Edition (BYI II), which was used to assess emotional and psychological issues that children experience. ADHD scores obtained on the DBD scale were correlated with scores obtained on BYI II scale. The study only focused on learners from primary schools in Lepelle-Nkumpi in Lebowakgomo sub circuit. In this research study, children who were reported to have a history of neurological problems such as head injurie, epilepsy, cerebral palsy or severe psychiatric disorders were excluded from the study. The results were analysed using the analysis of variance (ANOVA) and post hoc benferoni analysis to determine the significant difference within ADHD subtypes. Results of the study showed that children with ADHD had comorbid internalising disorders (anxiety and depression) when compared to their neurotypical group. Both boys and girls with a clinical diagnosis of ADHD showed symptoms of anxiety and depression. More symptoms of anxiety and depression were observed within the ADHD-HI, ADHD-PI and ADHD-C subtypes. Comorbid internalising disorders (anxiety and depression) were also associated with impairments with ADHD symptom, in particular inattention. Children with ADHD also showed more symptoms of low self-esteem when compared to their neurotypical group. Both boys and girls showed significant difference level of low self-esteem in all ADHD subtypes (ADHD-HI, ADHD-PI and ADHD-PI). The results further revealed that both boys and girls equally showed symptoms of comorbid internalising disorders (anxiety and depression), whereas girls showed significantly more symptoms of externalising comorbidities such as ODD, CD and anger issues. In conclusion, the findings suggest that the comorbidity of internalising disorders in a clinically diagnosed child with ADHD worsens or complicates the child’s expected normal functioning unlike when the child was presenting with only ADHD. The results further suggest that a child with clinical diagnosis has double impairment as a result of many impairments which are occurring at the same time. Moreover, the existence of externalising comorbidities which are salient in girls with ADHD may require proper screening and assessment. / NRF

AbstractThe purpose of this study is to illustrate how Work-based Learning (WBL) is handled in Special Education High Schools. With this purpose in mind, four questions have been formulated and they focus on what proportion of the total amount of high school students in the Special Education High School National Program who is completing their WBL according to governmental regulations, what challenges the WBL managers experience in working with WBL, what reasons the WBL managers see as decisive for students not completing their WBL and what benefits the WBL managers see with WBL. To answer the study’s purpose and questions, a survey was conducted, where we looked for respondents on a nationwide level. Data from the survey was analyzed with the help of a theoretical basis that we chose. This theory was based on three different perspectives on special education; the compensatory, the critical and the dilemma perspective by Nilholm (2007). A total of 127 respondents were included in the study and there were respondents from all three parts of Sweden; Norrland, Svealand and Götaland. The majority of respondents work as vocational teachers, Special Ed teachers working with the developmentally disabled and high school level teachers. The results showed that compulsory WBL education is an important part of the Special Education High School National Program, but at the same time difficult to implement due to lack of time, lack of internships and students’ individual abilities to complete a WBL. / SammanfattningSyftet med denna studie är att belysa hur styrdokumentens krav när det gäller arbetsplatsförlagt lärande (APL) hanteras i gymnasiesärskolan. Kopplat till syftet har fyra frågeställningar formulerats och de fokuserar på hur stor andel av det totala elevantalet på gymnasiesärskolans nationella program som genomför sin APL enligt styrdokumentens krav i dagsläget, vilka utmaningar de APL-ansvariga upplever sig möta i arbetet med APL, vilka orsaker de APL-ansvariga ser som avgörande för att eleven inte genomför sin APL, vilken nytta de APL-ansvariga ser med APL. För att besvara studiens syfte och frågeställningar genomfördes en enkätundersökning, där vi sökte efter informanter på ett rikstäckande plan. Data från enkäten analyserades med hjälp av en av oss vald teoretisk utgångspunkt. Denna teori utgick från tre olika perspektiv på specialpedagogik; det kompensatoriska, det kritiska och dilemmaperspektivet av Nilholm (2007).  Det var sammanlagt 127 informanter som ingick i enkätstudien och det fanns informanter hemmahörande från alla tre landsdelar i Sverige, Norrland, Svealand och Götaland. Majoriteten av informanterna arbetar som yrkeslärare, speciallärare mot utvecklingsstörning och ämneslärare på gymnasienivå. Resultatet visade att den obligatoriska APL utbildningen är en viktig del av ett nationellt program i gymnasiesärskolan, men den är samtidigt svår att genomföra på grund av tidsbrist för uppdraget, brist på APL-platser och elevernas individuella förutsättningar att klara av en APL.

Syftet är att undersöka konsekvenser för barn, unga och unga vuxna i åldern 0-25 år som växer upp tillsammans med syskon som har funktionsnedsättning. Dessutom är syftet att identifiera betydande faktorer för att uppnå ökad kunskap om hur professionella inom hälsooch sjukvård kan utveckla arbetet och bemötandet till barnen och deras familjer. Studiens teoretiska ramverk är Eriksons åtta utvecklingsfaser och Marcias identitetsstatusmodell som berör människors identitetsutveckling ur ett psykosocialt perspektiv samt copingstrategier för att hantera sin situation. Studien är utformad som en integrativ litteraturstudie, vilket innebär att vetenskapligt material med både kvalitativ och kvantitativ metod samlas in. Samtliga artiklar bearbetas och sammanställs genom tematisk analysmetod. Resultatet visar att målgruppen löper ökad risk för sociala konsekvenser, emotionell överbelastning och psykisk ohälsa. Resultatet tyder på att syskon med funktionsnedsättningen i sig inte bidrar till ökad psykisk ohälsa hos barnet, däremot eventuella konsekvenser av funktionsnedsättningen. Det framträder även positiva konsekvenser som utvecklad stresshantering, ökat tålamod samt värderingar om respekt för andra trots olikheter. Framträdande risk- och skyddsfaktorer är tillgång till socialt stöd, föräldrar, diagnosens karaktär och ålder. Utöver konsekvenser som mätbar hälsa framkommer även att identitetsutvecklingen kan påverkas och således även copingstrategiernas betydelse för att hantera situationen på ett framgångsrikt sätt. / The following study aims to investigate the consequences for children aged 0-25 growing up with a sibling with a developmental disorder. In addition, the study intends to identify significant factors to achieve knowledge on how professionals in healthcare can develop the work and treatment with the children and their families. The study's theoretical framework is a psychosocial perspective on identity development and coping strategies. The study is designed as an integrative review in which both qualitative and quantitative data have been included. The data is processed and compiled through thematic analysis. The results show that growing up with a sibling with a developmental disorder can be related to higher risk of social consequences, emotional overload and mental illness. The results indicate that it’s the potential consequences of the disorder that is the main reason for the higher risk of mental illness. There are also positive consequences such as developed stress management, increased patience and values about respect for others despite differences. Identified prominent factors are social support, parents, the diagnosis and age. Identity development can be affected and thus also the importance of coping strategies for managing the situation in a successful way.

No description available.

The diploma thesis The influence of early diagnosis for family of children with ASD deals with problems with autistic spectrum disorders diagnostics. It is focused on families with ASD children. It also maps the period before the diagnosis. The main aim is to show the preceding situation and consequences after the diagnosis of one of the autistic spectrum disorders in the family. The thesis works with both, the psychic impacts influencing family members, but also many other factors. The acquired information is based on the narrative conversation with parents. It speaks about the first displayed symptoms and the attempt to solve the occurring problems. It also speaks about possible seeing doctors, and if so, what specialists and what approaches and diagnoses they met. Last but not least the thesis is interested in those who informed the family about ASD as the first, when it was diagnosed and the change of family life after the diagnosis.

No description available.