Vi har genomfört en kvalitativ intervjustudie om föräldrars erfarenheter av en vardag tillsammans med ett barn som har Downs syndrom, i synnerhet när det gäller barnets ungdomstid. Den insamlade empirin har tolkats med hjälp av Beckers (2006) teori om avvikelse, Goffmans (2001) teori om stigma samt Goffmans (2009) teori om interaktion i det vardagliga sociala livet. Föräldern ingår i ett allmänt system av normalitet, såsom övriga samhällsmedlemmar. Studiens fokus ligger på förälderns agerande utefter detta i förhållande till den situation som barnets funktionsnedsättning för med sig. Downs syndrom medför en utvecklingsstörning, vilket innebär att barnets kroppsliga och mentala utveckling inte alltid är i fas med varandra. En följd av detta är att småbarns- och ungdomstiden förlängs, vilket föräldrarna i vår studie upplever som en svårighet. Svårigheten ligger bland annat i att barnets självständighetsutveckling skiljer sig från det som i allmänhet anses vara normalt och därmed skiljer sig även förälderns roll i denna utveckling. Studien visar att föreställningar om normalitet ständigt är närvarande i föräldrarnas berättelser. / We have made a qualitative interview study about parents' experiences of every day life with a child who has Down syndrome, particularly with regard to the child's youth. The empirical data collected has been interpreted using Becker's (2006) theory of deviance, Goffman's (2001) theory of stigma and Goffman's (2009) theory of interaction in everyday social life. The parent are included in a general system of normality, just as any other member of society. The focus of the study is parent's acting in relation to normality and to the situation that the child's disability causes. Down syndrome results in a development disorder, which means that child's physical and mental development not always is in phase with each other. This causes an extension of the childhood and youth, which the parents in our study perceive as difficult. The difficulty lies among other things in that the child's development of independence differs from what is generally considered to be normal and that the parent's role in this development consequently also differs. The study shows that ideas of normality are constantly present in the parents' narratives.

Background: Assessment of dementia in adults with intellectual disabilities poses specific challenges. Firstly, there is a paucity of validated, standardised and appropriate neuropsychological assessments of memory for adults with intellectual disabilities. Secondly, there are difficulties determining whether performance on neuropsychological assessments are attributable to preexisting intellectual disabilities, ‘normal’ ageing or part of a dementing process. A systematic review was therefore carried out to examine if there are memory changes associated with ‘normal’ ageing in the Down syndrome population. Following this an exploratory empirical research project was undertaken to examine one aspect of construct validity (i.e. convergent validity) of an associative memory test in a sample of adults with intellectual disabilities. This research project is presented as a journal article titled ‘Convergent validity of the Visual Association Test (VAT) in adults with intellectual disabilities’. Methods: 40 participants aged between 18-45 years were recruited from Community Learning Disability Teams. Participants completed the VAT and subtests of the modified Cambridge Cognitive Examination (CAMCOG-DS). IQ was assessed using the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV). Correlational analysis of the test variables were carried out. Participants with a diagnosis of dementia were excluded from the study. Results: All participants performed well on the VAT irrespective of age, gender or IQ. It was well received by participants. No significant correlations were found between the VAT and the subtests of the CAMCOG-DS or with the subtests of the WAIS-IV. Therefore, there was no evidence of convergent validity with this test in this sample of participants. Conclusions: While the VAT was found to be an easy, quick test to use with people with intellectual disabilities and all participants scored above ‘floor’ level, it was not found to have convergent validity with the CAMCOG-DS. Further research is needed to determine if the VAT represents a useful tool for assessment with this population.

Thesis (M Sport Sc (Sport Science)--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: Functional fitness refers to the physical capacity to perform normal everyday activities safely and independently without undue fatigue. More specifically, functional fitness refers to having adequate strength, flexibility, mobility and endurance to execute essential tasks efficiently and effortlessly. Being functionally fit is important for all populations, but even more so for populations at risk for loosing functional capacity such as the elderly, disabled, and those with chronic medical conditions. Down syndrome individuals form part of the intellectually disabled population and show even more marked reductions in physical and functional capacities when compared to this already functionally limited population. Most DS individuals live sedentary lives, are obese, and age prematurely. For these reasons it is important to develop their functional capacities optimally. Although standardised tests are available for youngsters with intellectual disability, this is not the case for DS individuals. This study therefore endeavoured to describe the physical and functional fitness capacity of DS adults and to determine how much individual physical attributes contribute to functional capacity. 17 items, of which the validity and reliability have been determined, were included in the test battery. This included 2 balance tests, 2 flexibility tests, 2 coordination tests, 5 muscular strength and endurance tests, 2 functional tasks and an aerobic test. A total of 371 individuals from DS centres and institutions across seven provinces in South Africa volunteered to participate in the study. The study sample was categorised according to gender and four different age groups (18-25, 26-35, 36-45, >45 years) for further analysis. DS men were taller, heavier and had a greater arm span and sitting height than DS women. The majority of the participants were either overweight or obese. DS men performed significantly better on all but three tests compared to the women. The women performed better on the sit- and- reach flexibility test and the chair stand test, however, differences were not statistically significant. Physical test items correlated significantly and strongly to functional performance in 9 items for DS men and 5 items for DS women. Importantly, balance items correlated stronger with functional performance in DS women than in DS men. This is not a new finding and suggests that separate training programs should be developed for DS men and DS women. This is the first study of its kind in South Africa and confirms the findings of previous studies that DS adults have both low physical and functional capacities. They are particularly weak in terms of basic endurance and strength, which have been shown are trainable variables in DS individuals. The study also provides valuable criterion referenced values for an adult DS population. This information will assist health professionals in tailoring appropriate training programs to address functional limitations, as well as the negative health consequences associated with ageing. This special population thus need the assistance of sport scientists, as well as the community, to integrate them into special training and activity programs to improve their quality of life. / AFRIKAANSE OPSOMMING : Funksionele fiksheid verwys na die fisieke kapasiteit om alledaagse aktiwiteite op ‘n veilige en onafhanklike wyse uit te voer sonder om oormatige vermoeienis te ervaar. Meer spesifiek beteken funksionele fiksheid dat ‘n person voldoende krag, lenigheid, beweeglikheid en uithouvermoë besit om essensiële take doeltreffend en moeiteloos te voltooi. Alle populasies behoort funksioneel fiks te wees, maar dit is self meer belangrik vir populasies wat die risiko het om hul funksionele kapasiteit te verloor, soos bejaardes, persone met gestremdhede en diegene met kroniese mediese toestande. Down sindroom individue is deel van die populasie met intellektueel gestremdhede en hulle het selfs meer fisieke en funksionele beperkinge as die intellektueel gestremdes. Die meeste persone met DS het ‘n onaktiewe leefstyl, is vetsugtig en ervaar premature veroudering. Vir hierdie redes is dit uiters belangrik om hulle funksionele kapasiteit optimaal te ontwikkel. Hoewel gestandaardiseerde toetse beskikbaar is vir jong persone met intellektueel gestremdhede, is dit nie die geval met DS individue nie. Hierdie studie was ‘n poging om die fisieke en funksionele fiksheidkapasiteit van DS volwassenes te beskryf en te bepaal tot watter mate fisieke eienskappe funksionele kapasiteit bepaal. 17 items, waarvan die geldigheid en herhaalbaarheid bepaal is, is ingelsuit in die toetsbattery. Dit het die volgende ingesluit: 2 balanstoetse, 2 lenigheidstoetse, 2 koordinasietoetse. 5 spierkrag en uithouvermoë toetse, 2 funksionale take en een aërobiese toets. ‘n Totaal van 371 individue van DS sentrums en instellings in sewe provinsies in Suid Afrika het vrywillig ingestem om aan die studie deel te neem. Die steekproef is volgens geslag en ouderdom in vier kategorieë verdeel (18-25, 26-35, 36-45, >45 jaar) vir verdere analise. DS mans was langer, swaarder en het ‘n langer armlengte en sithoogte gehad as DS vroue. Die meerderheid van die deelnemers was of oorgewig of vetsugtig. DS mans het beduidend beter as die vroue gevaar in al die toetse, behalwe drie. Die vroue het beter gevaar in die sit en strek lenigheidstoets en die stoel opstaan toets, maar die verskille was nie statisties betekenisvol nie. Nege fisieke toetsitems vir mans het sterk en betekenisvol gekorreleer met funksionele kapasiteit, terwyl 5 items vir vroue betekenisvolle korrelasies gewys het. Balans items het sterker met funksionele kapasiteit in vroue as in mans gekorreleer. Hierdie is nie ‘n nuwe bevinding nie en bevestig dat verskillende oefenprogramme vir DS mans en vroue ontwikkel moet word. Hierdie is die eerste studie van sy soort in Suid Afrika en bevestig die resultate van vorige studies dat DS volwassenes beide lae fisieke en funksionele kapasiteite het. Hulle is veral swak ten opsigte van basiese uithouvermoë en spierkrag, maar beide hierdie veranderlikes kan by DS persone ingeoefen word. Hierdie studie voorsien ook waardevolle kriterium verwysingswaardes vir ‘n volasse DS populasie. Hierdie inligting kan persone in die gesondheidsberoepe help om gepaste oefenprogramme saam te stel om die funksionele beperkings en negatiewe gesondheidsgevolge wat met veroudering geassosieer word, aan te spreek. Hierdie spesiale populasie benodig dus die hulp van sportwetenskaplikes, sowel as die gemeenskap, om hulle te integreer in spesiale oefen- en aktiwiteitsprogramme om sodoende hulle kwaliteit van lewe te verbeter.

Thesis (MEd(Psych))--University of Stellenbosch, 2002. / ENGLISH ABSTRACT: The literacy development of learners with special educational needs has traditionally been approached from a behaviouristic framework, which led to the reductionistic teaching of language, focussing on smaller units and sub-skills in order to facilitate a simplification of the learning process. During the 80's changes in the area of literacy development occurred, placing the focus on the whole language approach. This approach (embedded in a constructivistic framework) emphasises the holistic and integrated nature of the language and literacy system, which seems to hold advantages for learners with special educational needs. This also includes learners with Down Syndrome since literature shows that a phonetic approach (which is reductionistic in nature) does not seem to benefit these learners in terms of literacy development and support. The purpose of this study therefore was to ascertain the usefulness of the whole language approach in the development of literacy skills of a , learner with Down Syndrome. This was accomplished by means of a literature review and learner support twice a week. The research methology took the form of a single case study consisting of a learner with Down Syndrome within an inclusive classroom. The qualitative nature of the research, which were descriptive and explanatory, made it possible to provide a rich holistic description of the findings. Data derived from various sources were analyzed according to the constant comparative method in order to identify the main and sub-categories. The findings of the study showed real development in the literacy skills of the learner with Down Syndrome. Noticeable, was the fact that the learner's reading skills developed faster in relation to the other skills. This is supported by the literature review. A fifth dimension, namely personal development was identified which promoted development on the cognitive as well as affective area. Although the scope of the study was limited, it seemed that the whole language a / AFRIKAANSE OPSOMMING: Geletterdheidsontwikkeling van leerders met spesiale onderwysbehoeftes is tradisioneel vanuit 'n behavioristiese raamwerk benader, wat daartoe aanleiding gegee het dat taal gereduseer is tot kleiner eenhede en subvaardighede ten einde die leerproses te vergemaklik. Gedurende die tagtigerjare het veranderinge op die gebied van geletterdheidsontwikkeling plaasgevind, wat die fokus op die geheeltaalbenadering geplaas het. Hierdie benadering (gesetel in die konstruktivistiese verwysingsraamwerk) lê klem op die holistiese en geïntegreerde aard van die taal- en geletterdheidsisteem, wat blyk om voordeel vir leerders met spesiale onderwysbehoefte in te hou. Dit sluit ook die leerder met Downsindroom in, aangesien literatuur daarop wys dat die fonetiese benadering (reduksionisties van aard) nie blyk om tot voordeel van hierdie leerders se geletterdheidsontwikkeling en -ondersteuning te strek nie. Die doel van die studie was gevolglik om die bruikbaarheid van die geheeltaalbenadering in die ondersteuning van 'n leerder met Downsindroom se geletterdheidsvaardighede te ondersoek. Dit is by wyse van In literatuuroorsig en leerondersteuningsessies op 'n tweeweeklikse basis gedoen. Die navorsingsmetodiek het die vorm van 'n enkel gevallestudie aangeneem, bestaande uit 'n leerder met Downsindroom in 'n inklusiewe klaskamer. Die kwalitatiewe aard van die navorsing, wat beskrywend, verkennend en verklarend is, het dit moontlik gemaak om 'n ryk holistiese beskrywing van die bevindinge te gee. Data afkomstig van verskeie bronne is volgens die konstante vergelykende metode geanaliseer ten einde die hoofkategorieë en subkategorieë te identifiseer. Die bevindinge van die studie het gedui op 'n beduidende ontwikkeling van die die leerder met Downsindroom se geletterdheidsvaardighede. Opmerklik was die feit dat die leerder se leesvaardighede, in vergelyking met die ander geletterdheidsvaardighede, vinniger ontwikkel het. Dit word deur die literatuuroorsig ondersteun. 'n Vyfde dimensie, naamlik persoonsontwikkeling, is geïdentifiseer wat ontwikkeling op kognitiewe sowel as affektiewe gebied bevorder het. Alhoewel die omvang van die studie beperk was, blyk dit dat die geheeltaalbenadering tot voordeel van die leerder met Downsindroom se geletterdheidsontwikkeling strek.

published_or_final_version / abstract / toc / Educational Psychology / Master / Master of Social Sciences

Children with Down syndrome (DS) are reported to experience difficulty with spoken and written language which can persist through the lifespan. However, little is known about the spoken and written language profiles of children with DS in the New Zealand social and education environment, and a thorough investigation of these profiles has yet to be conducted. The few controlled interventions to remediate language deficits in children with DS that are reported in the literature typically focus on remediation of a single language domain, with the effectiveness of interventions which integrate spoken and written language goals yet to be explored for this population. The experiments reported in this thesis aim to address these areas of need. The following questions are asked 1) What are the phonological awareness, speech, language and literacy skills of New Zealand children with DS? 2) What are the home and school literacy environments of New Zealand children with DS and how do they support written language development? and 3) What are the immediate and longer term effects of an integrated phonological awareness intervention on enhancing aspects of spoken and written language development in young children with DS? These questions will be addressed through the following chapters. The first experiment (presented in Chapter 2) was conducted in two parts. Part 1 consisted of the screening of the early developing phonological awareness, letter knowledge, and decoding skills of 77 primary school children with DS and revealed considerable variability between participants on all measures. Although some children were able to demonstrate mastery of the phoneme identity and letter knowledge skills, floor effects were also apparent. Data were analysed by age group (5 - 8 years and 9 -14 years) which revealed increased performance with maturation, with older children outperforming their younger peers on all measures. Approximately one quarter of all children were unable to decode any words, 6.6% demonstrated decoding skills at a level expected for 7 - 8 year old children and one child demonstrated decoding skills at an age equivalent level. Significant relationships between decoding skills and letter knowledge were found to exist. In Part 2 of the experiment, 27 children with DS who participated in the screening study took part in an in-depth investigation into their speech, phonological awareness, reading accuracy and comprehension and narrative language skills. Results of the speech assessments revealed the participants’ speech was qualitatively and quantitatively similar to the speech of younger children with typical development, but that elements of disorder were also evident. Results of the phonological awareness measures indicated participants were more successful with blending than with segmentation at both sentence and syllable level. Rhyme generation scores were particularly low. Reading accuracy scores were in advance of reading comprehension, with strong relationships demonstrated between reading accuracy and phonological awareness and letter knowledge. Those children who were better readers also had better language skills, producing longer sentences and using a greater number of different words in their narratives. The production of more advanced narrative structures was restricted to better readers. In the second experiment (presented in Chapter 3), the home literacy environment of 85 primary school aged children with DS was investigated. Parents of participants completed a questionnaire which explored the frequency and duration of literacy interactions, other ways parents support and facilitate literacy, parents’ priorities for their children at school, and the child’s literacy skills. Results revealed that the homes of participants were generally rich in literacy resources, and that parents and children read together regularly, although many children were reported to take a passive role duding joint story reading. Many parents also reported actively teaching their child letter names and sounds and encouraging literacy development in other ways such as language games, computer use, television viewing and library access. Writing at home was much less frequent than reading, and the allocation of written homework was much less common than reading homework. In the third experiment (presented in Chapter 4), the school literacy environment of 87 primary school aged children with DS (identified in the second experiment) was explored. In a parallel survey to the one described in Chapter 3, the teachers of participants completed a questionnaire which explored the frequency and duration of literacy interactions, the role of the child during literacy interactions, the child’s literacy skills, and other ways literacy is supported. The results of the questionnaire revealed nearly all children took part in regular reading instruction in the classroom although the amount of time reportedly dedicated to reading instruction was extremely variable amongst respondents. The average amount of time spent on reading instruction was consistent with that reported nationally and in advance of the international average for Year 5 children. Reading instruction was typically given in small groups or in a one on one setting and included both ‘top-down’ and bottom up’ strategies. Children were more likely to be assigned reading homework compared to written homework, with writing activities and instruction reported to be particularly challenging. In the fourth experiment (reported in Chapter 5), the effectiveness of an experimental integrated phonological awareness intervention was evaluated for ten children with DS, who ranged in age from 4;04 to 5;05 (M = 4;11, SD = 4.08 months). The study employed a multiple single-subject design to evaluate the effect of the intervention on participants’ trained and untrained speech measures, and examined the development of letter knowledge and phonological awareness skills. The 18 week intervention included the following three components; 1. parent implemented print referencing during joint story reading, 2. speech goals integrated with letter knowledge and phoneme awareness activities conducted by the speech-language therapist (SLT) in a play based format, and 3. letter knowledge and phoneme awareness activities conducted by the computer specialist (CS) adapted for presentation on a computer. The intervention was implemented by the SLT and CS at an early intervention centre during two 20 minute sessions per week, in two 6 week therapy blocks separated by a 6 week break (i.e. 8 hours total). The parents implemented the print referencing component in four 10 minute sessions per week across the 18 week intervention period (approximately 12 hours total). Results of the intervention revealed all ten children made statistically significant gains on their trained and untrained speech targets with some children demonstrating transfer to other phonemes in the same sound class. Six children demonstrated gains in letter knowledge and nine children achieved higher scores on phonological awareness measures at post-intervention, however all phonological awareness scores were below chance. The findings demonstrated that dedicating some intervention time to facilitating the participants’ letter knowledge and phonological awareness was not at the expense of speech gains. The fifth experiment (presented in Chapter 6) comprises a re-evaluation of the speech, phonological awareness, and letter knowledge, and an evaluation of the decoding and spelling development in children with DS who had previously participated in an integrated phonological awareness intervention (see Chapter 5), after they had subsequently received two terms (approximately 20 weeks) of formal schooling. Speech accuracy was higher at follow-up than at post-intervention on standardised speech measures and individual speech targets for the group as a whole, with eight of the ten participants demonstrating increased scores on their individual speech targets. Group scores on both letter knowledge measures were higher at follow-up than at post-intervention, with nine participants maintaining or improving on post-intervention performance. The majority of participants exhibited higher phonological awareness scores at follow-up on both the phoneme level assessments, with above chance scores achieved by five participants on one of the tasks, however, scores on the rhyme matching task demonstrated no evidence of growth. Some transfer of phonological awareness and letter knowledge was evident, with five children able to decode some words on the single word reading test and three children able to represent phonemes correctly in the experimental spelling task. The emergence of these early literacy skills highlighted the need for ongoing monitoring of children’s ability to transfer their improved phonological awareness and letter knowledge to decoding and spelling performance. In the sixth experiment (presented in Chapter 7) the long term effects of the integrated phonological awareness intervention was evaluated for one boy with DS aged 5;2 at the start of the intervention. The study monitored Ben’s speech and literacy development up to the age of 8;0 (34 months post pre-school intervention) which included two years of formal schooling. Ben demonstrated sustained growth on all measures with evidence of a growing ability to transfer letter-sound knowledge and phoneme-grapheme correspondences to the reading and spelling process. The results indicated an intervention which is provided early and which simultaneously targets speech, letter knowledge and phonological awareness goals provides a promising alternative to conventional therapy, and that integrating spoken and written therapy goals for children with DS can be effective in facilitating development in both domains. This thesis provides evidence that the spoken and written language abilities of New Zealand children with DS exhibit a pattern of delay and disorder that is largely consistent with those of children with DS from other countries reported in the literature. The home and school literacy environments of children in New Zealand with DS are rich in literacy resources and are, for the most part, supportive of their literacy development. The immediate and longer term results of the integrated phonological awareness intervention suggest that it is possible to achieve significant and sustained gains in speech, letter knowledge and phonological awareness which may contribute to the remediation of the persistent and compromised spoken and written language profile characteristic of individuals with DS.

Behavioral data in individuals with Down syndrome (DS) and mouse models of the syndrome suggest impaired object processing. In this study we examined the component processes that may contribute to object memory deficits. A neuropsychological test battery was administered to individuals with DS (n=28), including tests targeting perirhinal cortex (PRC) and prefrontal cortex (PFC) function, tests of perception (i.e., convexity based figure ground perception), and tests of memory (object recognition and object-in-place learning). To compare to individuals with DS, the same number of typically developing chronological age (CA, n=28) and mental age-matched (MA, n=28) controls were recruited. We observed object memory deficits in DS (p<0.001). In contrast, the DS group showed relatively intact use of convexity when making figure-ground judgments and spared PRC-dependent function, as compared to MA control. In addition, measures of PFC function seemed to be related to performance on object recognition tasks. These findings suggest that the inputs into the MTL from low and high level perceptual processing streams may be intact in DS. The object memory deficits we observed might reflect impaired PFC function.

The research presented in this thesis combined a number of aims. One was to investigate in detail the early typical development of individual cognitive domains including attention, literacy and numeracy, and consequently to investigate whether domain-general attentional abilities constrain the development of either literacy or numeracy skills in preschool to school-age children. A further aim was to test the development of the same cognitive processes in two groups of children with developmental disorders of known genetic origin; Down syndrome (DS) and Williams syndrome (WS). A combination of standardised tests, novel experimental paradigms, and questionnaire measures were employed in pursuit of these aims, and children were assessed both cross-sectionally and longitudinally one year later. In typically developing (TD) children, novel findings pointed to differential influences of cognitive constructs of sustained and selective attention on the one hand, and executive attention on the other, on reading and numeracy abilities longitudinally. In both of the atypically developing groups of children, novel and individual patterns of developmental relationships emerged in the domains of attention, literacy and numeracy. In addition, the investigation of cross-domain relationships between attentional abilities and literacy and numeracy skills evidenced typical patterns in DS children, but atypical patterns in WS children. These findings emphasize the importance of cross-syndrome, cross-domain, and fully developmental research to understand both typical and atypical profiles of cognitive development. Furthermore, teaching practice, early identification of difficulties, and interventions should consider the wider implications of potential constraints of broader cognitive domains, such as attention, on learning.

Background: Children with Down syndrome (DS) have increased risk for developing AML (DS-AMKL), and they usually experience severe therapy-related toxicities compared to non DS-AMKL. Refractory/ relapsed disease has very poor outcome, and patients would benefit from novel, less toxic, therapeutic strategies that overcome resistance. Relapse/resistance are linked to cancer stem cells with high aldehyde dehydrogenase (ALDH) activity. The purpose of the present work was to study less toxic alternative therapeutic agents for relapsed/refractory DS-AMKL. Methods: Fourteen AML cell lines including the DS-AMKL CMY and CMK from relapsed/refractory AML were used. Cytarabine (Ara-C), bortezomib (BTZ), disulfiram/copper (DSF/Cu2+) were evaluated for cytotoxicity, depletion of ALDH-positive cells, and resistance. BTZ-resistant CMY and CMK variants were generated by continuous BTZ treatment. Cell viability was assessed using CellTiter-Glo((R)), ALDH activity by ALDELUOR(TM), and proteasome inhibition by western blot of ubiquitinated proteins and the Proteasome-Glo(TM) Chymotrypsin-Like (CT-like) assay, apoptosis by Annexin V Fluos/Propidium iodide staining, and mutations were detected using PCR, cloning and sequencing. Results: Ara-C-resistant AML cell lines were sensitive to BTZ and DSF/Cu2+. The Ara-C-resistant DS-AMKL CMY cells had a high percentage of ALDHbright "stem-like" populations that may underlie Ara-C resistance. One percent of these cells were still resistant to BTZ but sensitive to DSF/Cu2+. To understand the mechanism of BTZ resistance, BTZ resistant (CMY-BR) and (CMK-BR) were generated. A novel mutation PSMB5 Q62P underlied BTZ resistance, and was associated with an overexpression of the beta 5 proteasome subunit. BTZ-resistance conferred increased resistance toAra-C due to G1 arrest in the CMY-BR cells, which protected the cells from S-phase damage by Ara-C. CMY-BR and CMK-BR cells were cross-resistant to CFZ and MG-132 but sensitive to DSF/Cu2+. In this setting, DSF/Cu2+ induced apoptosis and proteasome inhibition independent of CT-like activity inhibition. Conclusions: We provide evidence that DSF/Cu2+ overcomes Ara-C and BTZ resistance in cell lines from DS-AMKL patients. A novel mutation underlying BTZ resistance was detected that may identify BTZ-resistant patients, who may not benefit from treatment with CFZ or Ara-C, but may be responsive to DSF/Cu2+. Our findings support the clinical development of DSF/Cu2+ as a less toxic efficacious treatment approach in patients with relapsed/refractory DS-AMKL.

The aim of this experiment was to study whether completing a questionnaire either related or unrelated to various aspects of the workplace could induce different implicit and explicit stereotypic associations with Down syndrome. Subjects read one of three questionnaires before completing a task designed to measure implicit associations. The task consisted of photo primes of faces belonging to individuals with Down syndrome and typically developing individuals, followed by an evaluative decision task with adjectives related to the stereotype dimensions of warmth and competence. Following the implicit task, participants were asked directly about their associations between Down syndrome and each of the target traits. It was hypothesized that Down syndrome would be systematically associated with low competence, regardless of the context primed, but that it would be associated with greater warmth when morale-related aspects of the workplace were primed than when efficiency-related aspects of the workplace were primed. These hypotheses were not supported, and questionnaire type did not seem to prime specific associations in the implicit task. However, consistent with past research, Down syndrome was associated with high ratings of warmth on the explicit measure, and implicit results suggest Down syndrome may be implicitly associated with greater warmth as well. Methodological limitations of the study are discussed, as well as possible directions for future research.