Pluralism, Community and Civil Society at Regional Level : An Analysis from a Viewpoint of Historical Research

textabstractOBJECTIVE. The purpose of this article is to present and discuss the susceptibilityweighted imaging signal characteristics of the normal pediatric brain and those of a variety of pediatric brain pathologic abnormalities. CONCLUSION. Its high susceptibility for blood products, iron depositions, and calcifications makes susceptibility-weighted imaging an important additional sequence for the diagnostic workup of pediatric brain pathologic abnormalities. Compared with conventional MRI sequences, susceptibility-weighted imaging may show lesions in better detail or with higher sensitivity. Familiarity with the pediatric susceptibility-weighted imaging signal variance is essential to prevent misdiagnosis

Development, behaviour and autism in individuals with SMC1A variants

Introduction: Development and behaviour in Cornelia de Lange Syndrome (CdLS), including autism characteristics, have been described infrequently stratified to genetic cause and only a few studies have considered behavioural characteristics in relation to developmental level. Here, we describe the behavioural phenotype in individuals with CdLS with SMC1A variants. Methods: We performed an international, interdisciplinary study on 51 individuals with SMC1A variants. Results of questionnaire studies are compared to those in individuals with Down Syndrome and with Autism Spectrum Disorder. Results on cognition and self-injurious behaviour (SIB) are compared to those in individuals with CdLS caused by NIPBL variants. For Dutch participants with SMC1A variants we performed direct in-person assessments of cognition, autism, and added an interview and questionnaire on adaptive behaviour and sensory processing. Results: Individuals with SMC1A variants show a higher cognitive level and less SIB than individuals with NIPBL variants. Individuals with SMC1A variants without classic CdLS phenotype but with a Rett-like phenotype show more severe intellectual disability and more SIB compared to those with a CdLS phenotype. Autism is less present if outcomes in direct in-person assessments are evaluated taking developmental level into account compared to results based on a questionnaire. Conclusions: Behaviour in individuals with CdLS should be evaluated taking genetic cause into account. Detailed interdisciplinary approaches are of clinical importance to inform tailored care and may eventually improve quality of life of patients and families

Six-Minute Walk Test in Patients With Down Syndrome:Validity and Reproducibility

Contains fulltext : 81543.pdf (publisher's version ) (Closed access)OBJECTIVES: To examine the validity of the six-minute walk test (6MWT) as a tool to evaluate functional exercise performance in patients with Down syndrome (DS). DESIGN: Comparison of the six-minute walk distance (6MWD) in 2 distinct groups of DS patients: with and without severe cardiac disease. To test reproducibility, a group of patients with DS performed the 6MWT twice. SETTING: Tertiary referral centers for patients with congenital heart defects and outpatient clinics for people with intellectual disabilities. PARTICIPANTS: Adult patients with DS with (n=29) and without (n=52) severe cardiac disease categorized by cardiac echocardiography. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Distance walked on the 6MWT. RESULTS: The mean 6MWD in the group with severe cardiac disease was 289+/-104 m and in the group without severe cardiac disease 280+/-104 m (P=.70). Older age, female sex, and severe level of intellectual disability were all found to be independently and significantly correlated with a lower 6MWD (r=.67, P<.001). The paired 6MWD was not significantly different (310+/-88 m vs 317+/-85 m; P=.40) in patients who performed the 6MWT twice. The coefficient of variation was 11%. CONCLUSIONS: The 6MWD between the 2 groups was not significantly different. However, the walking distance inversely correlated with the level of intellectual disability. Therefore, the 6MWT is not a valid test to examine cardiac restriction in adult patients with DS

What Factors Influence Non‑Participation Most in Colorectal Cancer Screening? A Discrete Choice Experiment

Background and Objective Non-participation in colorectal cancer (CRC) screening needs to be decreased to achieve its full potential as a public health strategy. To facilitate successful implementation of CRC screening towards unscreened individuals, this study aimed to quantify the impact of screening and individual characteristics on non-participation in CRC screening. Methods An online discrete choice experiment partly based on qualitative research was used among 406 representatives of the Dutch general population aged 55–75 years. In the discrete choice experiment, respondents were ofered a series of choices between CRC screening scenarios that difered on fve characteristics: efectiveness of the faecal immunochemical screening test, risk of a false-negative outcome, test frequency, waiting time for faecal immunochemical screening test results and waiting time for a colonoscopy follow-up test. The discrete choice experiment data were analysed in a systematic manner using random-utility-maximisation choice processes with scale and/or preference heterogeneity (based on 15 individual characteristics) and/or random intercepts. Results Screening characteristics proved to infuence non-participation in CRC screening (21.7–28.0% non-participation rate), but an individual’s characteristics had an even higher impact on CRC screening non-participation (8.4–75.5% nonparticipation rate); particularly the individual’s attitude towards CRC screening followed by whether the individual had participated in a cancer screening programme before, the decision style of the individual and the educational level of the individual. Our fndings provided a high degree of confdence in the internal–external validity. Conclusions This study showed that although screening characteristics proved to infuence non-participation in CRC screening, a respondent’s characteristics had a much higher impact on CRC screening non-participation. Policy makers and physicians can use our study insights to improve and tailor their communication plans regarding (CRC) screening for unscreened individuals

Delineation of phenotypes and genotypes related to cohesin structural protein RAD21

RAD21 encodes a key component of the cohesin complex, and variants in RAD21 have been associated with Cornelia de Lange Syndrome (CdLS). Limited information on phenotypes attributable to RAD21 variants and genotype–phenotype relationships is currently published. We gathered a series of 49 individuals from 33 families with RAD21 alterations [24 different intragenic sequence variants (2 recurrent), 7 unique microdeletions], including 24 hitherto unpublished cases. We evaluated consequences of 12 intragenic variants by protein modelling and molecular dynamic studies. Full clinical information was available for 29 individuals. Their phenotype is an attenuated CdLS phenotype compared to that caused by variants in NIPBL or SMC1A for facial morphology, limb anomalies, and especially for cognition and behavior. In the 20 individuals with limited clinical information, additional phenotypes include Mungan syndrome (in patients with biallelic variants) and holoprosencephaly, with or without CdLS characteristics. We describe several additional cases with phenotypes including sclerocornea, in which involvement of the RAD21 variant is uncertain. Variants were frequently familial, and genotype–phenotype analyses demonstrated striking interfamilial and intrafamilial variability. Careful phenotyping is essential in interpreting consequences of RAD21 variants, and protein modeling and dynamics can be helpful in determining pathogenicity. The current study should be helpful when counseling families with a RAD21 variation.Spanish Ministry of Science, Innovation and Universities/State Research Agency RTC-2017-6494-1 and RTI2018-094434-B-I00 (MCIU/AEI/FEDER, UE) as well as funds from the European JPIAMR-VRI network “CONNECT” to PG-