The purpose of this thesis is to query the legitimacy of offering preimplantation genetic diagnostic (PGD) testing against Down's syndrome on the basis of United Kingdom (UK) law and policies. I will argue that extending PGD testing for Down’s syndrome as a permissible use of this technology does not (straightforwardly) adhere with the Human Fertilisation and Embryology Authority (HFEA) Code of Practice's stated factors which are to be considered when assessing the appropriateness of PGD applications. Indeed, due consideration of the evidence given in the relevant literature about the capacities and quality of life possible for persons living with Down's syndrome would seriously call into question the validity of a positive judgment recommending PGD as a treatment service for Down's syndrome according to the current UK regulatory instruments. I end the thesis by considering why the HFEA's relatively recent decision to limit client access according to an exclusive list of "serious" and therefore "in principle" test-worthy genetic conditions—understood as legitimate applications for PGD—stands to entrench prejudice, stigma, social bias, and unfair discrimination against the disadvantaged social group of persons living with Down's syndrome.

This thesis explored attachment in individuals with intellectual disability (ID). It investigated the role attachment may have in presenting difficulties such as challenging behaviour, which is an area much researched within other populations. It also considered parental well-being in the early years following diagnosis and the implications this may have for attachment development. Paper 1 describes a systematic review of the literature on parental response and adaptation to a child’ diagnosis of an ID in the early years. The news of a child’s diagnosis can be met with a range of intense emotions however, existing research reports conflicting outcomes regarding the nature of parental reactions and the psychological impact that may result. 12 studies were reviewed with one study demonstrating a strong methodology. The review found that the comparison groups used within studies had an important bearing on how effectual parental response and adaptation appeared. Due to the limited literature available and the methodological variation within the reviewed studies, no clear conclusions could be drawn. Paper 2 describes an empirical study which investigated the contribution of attachment behaviour to engagement in challenging behaviour, whilst considering other variables, in adults with ID. 22 service staff completed assessment questionnaires which examined service user attachment behaviour, level of adaptive ability, challenging behaviour and other variables. The relationships between particular variables were analysed. Results showed that level of adaptive ability was significantly related to attachment behaviour and challenging behaviour. Attachment behaviour was also significantly related to challenging behaviour, particularly social withdrawal and lethargy. However, when adaptive behaviour was controlled for the significance of these relationships disappeared. Therefore attachment behaviour did appear to contribute to challenging behaviour but less significantly than level of adaptive ability. The nature of the interaction between these three key variables is unclear and requires further research. Findings support the implementation of effective attachment based interventions alongside evidence based behavioural strategies. This would be particularly important for those at high risk of attachment and behavioural difficulties, which current and previous findings suggest may be those with ASD and those with lower levels of ability. Paper 3 describes the strengths and limitations of the systematic review and empirical paper. The research process, findings and clinical implications from each of the previous papers are discussed and reflected upon.

Orientador: Daniela Atili Brandini / Resumo: A qualidade de vida é a percepção do indivíduo sobre sua posição na vida e em relação aos seus objetivos, expectativas, padrões e preocupações representando seu grau de satisfação. Cuidar de pacientes com Sídrome de Down (SD) demanda tarefas complexas, delicadas e sofridas que somadas as responsabilidades diárias, podem gerar um impacto na qualidade de vida. Além disso, toda sobrecarga, pode causar estresse social e trazer sentimentos de ansiedade e depressão, em longo prazo, ao cuidador de um portador da SD. Assim, o objetivo foi avaliar a qualidade de vida, ansiedade, estresse e depressão de cuidadores de pacientes com ou sem síndrome de Down. O estudo foi conduzido com uma amostra de 144 participantes, que serão divididos entre dois grupos denominados GC (Grupo Controle) e GSD (Grupo Síndrome de Down). No GC, participou do estudo cuidadores de crianças com desenvolvimento normal de uma escola pública, numa faixa etária de 4 a 8 anos e no GSD, participou do estudo cuidadores principais de pacientes com SD, numa faixa etária de 4 a 30 anos de idade. Para coleta de dados foram utilizados 5 questionários para identificação do cuidador, avaliação da qualidade de vida (WHOQOL-Bref), avaliação de depressão (BDI), avaliação de ansiedade (BAI) e avaliação de estresse (LIPP). Para a análise dos dados foram identificadas categorias referentes ao perfil do cuidador, e foi utilizado teste Qui-quadrado com post hoc Bonferroni modificado com nível de significância de p ≤ 0,05, para compa... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Orientador: Fátima Elisabeth Denari / Resumo: Esta pesquisa tem como objetivo analisar as expressões e percepções de jovens com Síndrome de Down a respeito do afeto e da própria sexualidade. A metodologia abordada priorizou a escuta de adolescentes, tendo o afeto, sexualidade, a deficiência e a deficiência como categorias principais de análise, configurando-se como uma pesquisa qualitativa fundamentada na abordagem descritiva. Para tanto, foram realizadas três oficinas, com quatro jovens que apresentavam Síndrome de Down entre 18 e 22 anos. Os participantes frequentam o Centro de Atendimento Especializado Exclusivo, interior de São Paulo. Além da discussão, recorreu-se na confecção de desenhos e imagens em temas cotidianos, contemplando aspectos decorrentes da expressão não-verbal. A análise dos dados demonstrou a existência de uma educação sexual repressora para alguns jovens, apesar da faixa etária e constituição biológica lhes conferirem condições. Porém, a presente pesquisa apontou que muitos veem sua sexualidade de maneira positiva. Constatou-se, assim, os valores e as atitudes relacionadas ao afeto e a sexualidade podem ser transmitidos e assimilados pelas pessoas com Síndrome de Down, que favorece o aprendizado em comportamentos partilhados, tornando-os socialmente aceitos no contexto que fazem parte. Conclui-se que a limitação cognitiva, quando leve ou moderada, não impede a realização na inserção de programas referentes à educação sexual, demonstra prioridade, entendendo que a sexualidade é dimensão presente dur... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This research aims to analyze the expressions and perceptions of young people with Down Syndrome regarding affection and sexuality itself. The approached methodology prioritized listening to adolescents, with affection, sexuality, disability and handicap as main categories of analysis, configuring itself as a qualitative research based on the descriptive approach. To this end, three workshops were held, with four young people who had Down Syndrome between 18 and 22 years old. Participants attend the Exclusive Specialized Service Center, in the interior of São Paulo. In addition to the discussion, we made use of drawings and images in everyday themes, contemplating aspects arising from non-verbal expression. The analysis of the data demonstrated the existence of a repressive sex education for some young people, despite the age group and biological constitution giving them conditions. However, the present research showed that many see their sexuality in a positive way. Thus, it was found that the values and attitudes related to affection and sexuality can be transmitted and assimilated by people with Down Syndrome, which favors learning in shared behaviors, making them socially accepted in the context they are part of. It is concluded that the cognitive limitation, when mild or moderate, does not prevent the realization of the insertion of programs related to sexual education, demonstrates priority, understanding that sexuality is present dimension during all human development,... (Complete abstract click electronic access below) / Mestre

There is some discrepancy on how differential reinforcement of other behavior (DRO) and response cost (RC) affect responding within the context of token economies. We evaluated DRO and two variations of response cost with and without verbal feedback to decrease response errors in the context of academic skills for three children diagnosed with Down syndrome. The results suggest that a token economy intervention alone, with or without verbal feedback, was not effective for 2 of 3 participants. Gestural prompting was required to reduce response errors for those 2 participants and is possibly responsible for reducing response errors for the third participant.

Title: Postural Stability in Adults with Down Syndrome Objectives: The goal of the thesis was to compare postural stability in individuals with Down syndrome and the control group comprising of healthy individuals, and to compare postural stability in adult men with Down syndrome and adult women with Down syndrome. Methods: The empirical part of the thesis was based on data collected from a pressure sensing platform MobileMat 3140 by Tekscan. The study was made up of 52 probands (30 men and 22 women). The probands were separated into the experimental and the control group based on their Down syndrome diagnosis. The experimental group consisted of 11 men and 15 women, with the average age being 38,4 ± 8,7 years, the average height 156 ± 7,2 cm, and the average weight 75,1 ± 16,2 kg. Similarly, the control group consisted of 11 men and 15 women, with the average age being 38,8 ± 9,2 years, the average height 175 ± 10,1 cm, and the average weight 78,9 ± 14,5 kg. The participants were measured in four modifications of the bipedal stance: wide base of support with the eyes open; wide base of support with the eyes closed; narrow base of support with the eyes open; narrow base of support with the eyes closed. Each measuring session took 30 seconds. Results: Six parameters of postural stability were...

Advances in Down syndrome (DS) research depend on the availability of mouse models that replicate the genetic landscape and resulting phenotypes of DS which allow for experimental manipulation to correlate cellular and molecular changes with behavior, in a way that is not possible with human studies alone. These models have been a critical component in understanding the underlying mechanism of the intellectual disability in people with Down syndrome. The Ts(1716)65Dn (Ts65Dn) mouse is one of the most commonly used models as it recapitulates many of the phenotypes seen in individuals with Down syndrome, including neuroanatomical changes and impaired learning and memory. Although Ts65Dn exhibits a number of traits also present in DS, studies have produced variable results across time that call into question the validity of Ts65Dn and its use as a tool for studying Down syndrome. As Ts65Dn is the platform employed to gather preclinical evidence for treatments of DS, a critical assessment regarding the validity of the model over time is necessary. In this study, we conduct a rigorous and comprehensive, comparative analysis of multiple cohorts from the Ts65Dn line to assess the stability and reproducibility of neuroanatomical and behavioral characteristics. We measured gross anatomical brain and body size, neuronal density in the hippocampus and cerebellum, alterations to oligodendrocyte maturation and myelination, acquisition of developmental milestones, and learning and memory performance using the Morris water maze. Our results show a significant amount of variability in Ts65Dn, both across as well as within cohorts. Inconsistent phenotypes in Ts65Dn mice highlight specific cautions and caveats for use of these mice when studying Down syndrome and suggest it is not always the most appropriate model system to use. In addition to phenotypic variability, a major pitfall of the Ts65Dn model is the unintended triplication of 60 non-DS-related genes and the unknown consequences on resulting phenotypes. Recent advances in gene editing strategies have allowed for the gene dosage normalization of those 60 genes and the generation of a new mouse model of Down syndrome, Ts66YAH. As this newly developed line has not yet been characterized, we conducted an analysis complimentary to our study of Ts65Dn to investigate the utility of Ts66YAH for Down syndrome research. We found Ts66YAH mice show no measurable neuroanatomical changes, developmental delays, or learning and memory deficits suggesting that the deleted non-DS-related genes do influence the phenotypes seen in Ts65Dn. Although Ts66YAH is a more genetically representative model of Down syndrome compared to Ts65Dn, it does not exhibit disease relevant phenotypes and therefore, may not be a suitable model for studying DS. The various downfalls identified in the present study may be impacting other mouse models of DS as well and thus, our analysis of Ts65Dn across time and comparative study of Ts66YAH illustrate the need for careful use and increased rigor to ensure translational and reproducible results when working with all mouse models of Down syndrome.

AFRIKAANS: Die doel van hierdie studie is om 'n beter begrip te verkry van die wyse waarop ouers hulle rolle konstrueer by die insluiting van 'n leerder met Downsindroom. Die studie is in die Suid-Afrikaanse konteks ondemeem met 'n aantal ouers van kinders met Downsindroom, wat tans in Gr. 1, Gr. 2 of Gr. 3 in verskeie skole in Gauteng ingesluit is. Die rol wat hierdie ouers self gekonstrueer het voor en tydens die insluiting van hul kinders, is verken en geïdentifiseer d.m.v. semi-gestruktureerde onderhoudvoering volgens 'n kwalitatiewe navorsingsontwerp. Vraelyste, veldnotas en oudiobandopnames het dee1 uitgemaak van die data-insamelingstegnieke wat gebruik is. Die resultate van die studie dui daarop dat ouers hulle rolle op 'n multi-fasettige wyse konstrueer. Hierdie studie se bydrae is primer gesetel in die uitbreiding van teorie, veral in terme van die rolle van ouers by insluitende onderwys van kinders met Downsindroom. Hierdie bydrae word in hierdie studie grafies voorgestel. ENGLISH: The purpose of this study is to understand the way in which parents construct their roles in the inclusion of their child with Down's Syndrome. The study was conducted in the South-African context with the parents of children with Down's Syndrome, who are currently included in Gr. 1, Gr. 2 or Gr. 3 in different schools in Gauteng. The role that these parents constructed before and during the inclusion of their children, was examined and identified by means of semi-structured interviews according to a qualitative research design. Questionnaires, field notes and audiotape recordings were used as part of the data collecting methods. Results from this study indicate that parents construct their roles in a multifaceted manner. The primary contribution of this study is towards the expansion of the theoretical knowledge about the role of parents in inclusive education of learners with Down syndrome. This contribution is presented graphically in this study. / Dissertation (MEd (Orthodidactics))--University of Pretoria, 2001. / Educational Psychology / unrestricted

Background: Prevalence of metabolic disturbances is higher among individuals with neurodevelopmental disorders (NDDs), yet this association has been poorly studied. Investigation into human disease remains challenging, as a complete pathophysiological understanding relies on accurate modeling and highly controlled variables. As such, genetically engineered mouse models are increasingly used to gain insight into the biology of human NDDs, but preclinical research focus has been mainly on behavioral and neurophysiological abnormalities. Mouse models engineered to embody human-equivalent genetic variations can display discrepancies to human phenotypes, therefore a thorough characterization of mouse phenotypes must be conducted in order to evaluate how accurately a mouse model embodies a human phenotype. Also, mouse models can help discover unsuspected abnormalities that can be further validated in humans. Objective: In this study, we sought to investigate the metabolic alterations derived from NDD-associated genetic polymorphisms in previously-validated genetic mouse models. Due to the similarities in NDD-associated phenotypic expression, we hypothesized that our NDDs of interest would express similar metabolic signatures. Further, we anticipated that we might uncover unknown metabolic anomalies, and that sex may alter these differences. Methods: We used the Comprehensive Lab Animal Monitoring System coupled to EchoMRI, as well as quantification of key plasma metabolites by liquid chromatography-mass spectrometry to characterize and compare basal metabolism in three mouse models of NDDs, namely Down syndrome (Dp(16)Yey/+ mice), 16p11.2 deletion syndrome (16p11.2df/+ mice) and Fragile X syndrome (Fmr1-/- KO mice) and their wild-type (WT) counterparts. Results: Our study reveals that each mouse model expresses a unique metabolic signature that is sex-specific, independent of the amount of food consumed and minimally influenced by physical activity. We found striking differences in body composition, respiratory exchange ratio, caloric expenditure and concentrations of circulating plasma metabolites related to mitochondrial function. Conclusion: Providing novel insight into NDD-associated metabolic alterations provides a basis for future studies aimed at understanding physiological mechanisms and provides a point of reference for research aimed at detecting changes in response to intervention.

Bakgrund: Varje år föds det 110-120 barn med Downs syndrom (DS) i Sverige. DS är orsakat av en kromosomrubbning, orsaken till detta är ännu oklart. Att bli föräldrar till barn med DS drabbar hela familjen och för med sig många känslor som ofta är negativa. Barnet är ofta i stort behov av stöd och hjälp av sina föräldrar men också av andra professioner. Det är viktigt att göra föräldrarna delaktiga och se familjen som en helhet. Metod: Metoden som valts för examensarbetet är en litteraturöversikt. Syfte: Undersöka föräldrars upplevelse av att ha ett barn med DS. Resultat: I resultatet hittas fyra kategorier, det blev inte som vi tänkt oss, hur information ges har betydelse, behov av kontinuitet samt acceptans och anpassning. Det framkommer i resultatet att föräldrar ofta har negativa känslor och att det är svårt att acceptera sitt barns diagnos. Sjuksköterskan spelar en stor roll för familjens vård och det är sjuksköterskans ansvar att ge stöd och relevant information. Konklusion:Föräldrars upplevelser är stark förankrade i känslorna kring den första tiden. Mycket negativa känslor som sedan övergår i positiva känslor när acceptans och förståelse för deras nya situation infunnit sig. / Background: Every year, 110-120 children are born with DS in Sweden. DS is caused by a chromosome disorder, the cause of this is still unclear. Becoming parents to children with DS affects the whole family and brings with it many emotions that are often negative. The child is often in great need of support and help from his parents but also other professions. It is important to involve the parents and see the family as a unit. Method: The method chosen for the degree project is a literature review. Purpose: To investigate parents' experience when they have a child with DS. Results: In the result, four categories were found, it did not turn out as we expected, how information is given is important, need for continuity and acceptance and adaptation. The results show that parents often have negative feelings and that it is difficult to accept their child's diagnosis. The nurse plays a major role in the family's care and it is the nurse's responsibility to provide support and relevant information. Conclusion: Parents' experiences are strongly rooted in their feelings. Negative feelings that then become positive when acceptance and understanding has occurred.