'I want support, not comments': children's perspectives on supports in their lives

Supports are a major part of the daily lives of children with special educational needs who participate in general education schools. Little attention has been paid to how they experience supports. Six children and their peers who were interviewed appreciated supports because they remove restrictions in activities due to the impairment. However, the analysis also shows how these positive supports can have negative psycho-emotional repercussions, and that they are less focused on addressing disabling barriers. The children’s accounts demonstrate the ambiguous and situated nature of supports, and need for the children to be able to direct supports as ‘chief partners’ in the inclusion process

Voice characteristics in adults with neurofibromatosis type 1

Introduction and aims of the study: Change or loss of voice in patients with neurofibromatosis type 1 (NF1) has been associated with head and neck neurofibromas. However, laryngeal involvement in NF1 is rare and voice abnormalities have also been reported in absence of such a tumor. Authors mention the occurrence of deviations in voice quality (such as breathiness, hoarseness, harshness, presence of a creak) and problems in regulating pitch and loudness. These studies are mainly based on perceptual evaluations. Therefore, the purpose of this study was to examine the voice characteristics of adult NF1 patients without laryngeal manifestations using a multiparameter approach. Methods: A total of 22 NF1 patients (age range 17-64 years) and 22 controls (age range 18-67 years) participated in the study. The patient group consisted of 9 males (mean age 39,33 years) and 13 females (mean age 32,69 years). The control group consisted of 12 males (mean age 38,00 years) and 10 females (mean age 32,90 years). Voice characteristics were evaluated using aerodynamic, voice range and acoustic measurements. These measurements allowed us to determine the Dysphonia Severity Index (DSI). Additionally, participants were asked to complete the Voice Handicap Index (VHI), a questionnaire concerning voice-related quality of life. Results: Vital capacity was significantly reduced in NF1 patients compared with controls. Also, the frequency and intensity range were significantly narrower in the patient group compared with controls. The narrower frequency and intensity range were due to a significantly lower highest frequency and a significantly lower highest intensity respectively. Additionally, male NF1 patients showed a significantly higher lowest intensity compared with male controls. Further, during reading, female NF1 patients exhibited a significantly smaller standard deviation of the mean frequency compared with female controls. This trend was also observed in the male NF1 patients compared with male controls. However, a significant difference could not be demonstrated. Finally, DSI scores were significantly lower and VHI values were significantly higher in both sexes of the patient group compared with controls. Conclusion: NF1 patients appear to have a vocal quality that is worse compared with controls. In particular, it seems that NF1 patients have reduced laryngeal possibilities with respect to fundamental frequency and sound intensity compared with controls. They are also more likely to present a more marked psychosocial voice impact compared with controls

qBase relative quantification framework and software for management and automated analysis of real-time quantitative PCR data

Although quantitative PCR (qPCR) is becoming the method of choice for expression profiling of selected genes, accurate and straightforward processing of the raw measurements remains a major hurdle. Here we outline advanced and universally applicable models for relative quantification and inter-run calibration with proper error propagation along the entire calculation track. These models and algorithms are implemented in qBase, a free program for the management and automated analysis of qPCR data

Home death for children dying in six European countries

Aim: Guidelines on pediatric palliative care underline that care at the end of life of chronically ill children should preferably be provided in the child’s home situation. Till present, no European data at population level are available for place of death of children. The aim of this study was to compare proportions of home death for children in six European countries and investigate relation between place of death and sociodemographic and clinical factors. Method: Data were collected from death certificates of all deceased children aged 1-17 in Belgium (BE), the Netherlands (NL), Norway (NO), England (E), Wales (W) (2003) and Italy (IT) (2002). Gender, cause (cancer, natural non-cancer and external) and place of death (home vs. outside home) and sociodemographic factors (socio-economic status (SES), degree of urbanization and number of hospital beds in the area) were included in the analyses. Data were analyzed using frequencies and multivariate logistic regression. Results: A total of 3.187 deaths were included in the analyses, 534 (16,8%) died from cancer. The proportion of home deaths was 19,6% (IT), 20,5% (E), 20,6% (W), 21,0% (NO), 23,8% (BE) and 28,6% (NL). Home death was more likely for children dying from cancer in BE, NL, E and W, for children with high SES in BE, in areas with low number of hospital beds in IT, and for boys in NL. Conclusion: The proportion of home deaths for children differs between studied countries. In most, but not all, countries children dying from cancer had better odds of dying at home than those not dying from cancer. Although acknowledging the influence of culture in the differences, studying care provisions in countries with higher proportions of home deaths, particularly in chronically ill children, can be helpful to identify factors facilitating terminally ill children to die at home. Early involvement of palliative care and equal access to these services can be important in this context. Funding: IWT-Flanders

Recessive osteogenesis imperfecta caused by LEPRE1 mutations: clinical documentation and identification of the splice form responsible for prolyl 3-hydroxylation

Abstract: Background: Recessive forms of osteogenesis imperfecta (OI) may be caused by mutations in LEPRE1, encoding prolyl 3-hydroxylase-1 (P3H1) or in CRTAP, encoding cartilage associated protein. These proteins constitute together with cyclophilin B (CyPB) the prolyl 3-hydroxylation complex that hydroxylates the Pro986 residue in both the type I and type II collagen alpha 1-chains. Methods: We screened LEPRE1, CRTAP and PPIB (encoding CyPB) in a European/Middle Eastern cohort of 20 lethal/severe OI patients without a type I collagen mutation. Results: Four novel homozygous and compound heterozygous mutations were identified in LEPRE1 in four probands. Two probands survived the neonatal period, including one patient who is the eldest reported patient (17(7/12) years) so far with P3H1 deficiency. At birth, clinical and radiologic features were hardly distinguishable from those in patients with autosomal dominant (AD) severe/lethal OI. Follow-up data reveal that the longer lived patients develop a severe osteochondrodysplasia that overlaps with, but has some distinctive features from, AD OI. A new splice site mutation was identified in two of the four probands, affecting only one of three LEPRE1 mRNA splice forms, detected in this study. The affected splice form encodes a 736 amino acid (AA) protein with a "KDEL'' endoplasmic reticulum retention signal. While western blotting and immunocytochemical analysis of fibroblast cultures revealed absence of this P3H1 protein, mass spectrometry and SDS-urea-PAGE data showed severe reduction of alpha 1(I) Pro986 3-hydroxylation and overmodification of type I (pro) collagen chains in skin fibroblasts of the patients. Conclusion: These findings suggest that the 3-hydroxylation function of P3H1 is restricted to the 736AA splice form

Helical mutations in type I collagen that affect the processing of the amino-propeptide result in an Osteogenesis Imperfecta/Ehlers-Danlos Syndrome overlap syndrome

Background: Whereas mutations affecting the helical domain of type I procollagen classically cause Osteogenesis Imperfecta (OI), helical mutations near the amino (N)-proteinase cleavage site have been suggested to result in a mixed OI/Ehlers-Danlos syndrome (EDS)-phenotype. Methods: We performed biochemical and molecular analysis of type I (pro-) collagen in a cohort of seven patients referred with a clinical diagnosis of EDS and showing only subtle signs of OI. Transmission electron microscopy of the dermis was available for one patient. Results: All of these patients harboured a COL1A1 / COL1A2 mutation residing within the most N-terminal part of the type I collagen helix. These mutations affect the rate of type I collagen N-propeptide cleavage and disturb normal collagen fibrillogenesis. Importantly, patients with this type of mutation do not show a typical OI phenotype but mainly present as EDS patients displaying severe joint hyperlaxity, soft and hyperextensible skin, abnormal wound healing, easy bruising, and sometimes signs of arterial fragility. In addition, they show subtle signs of OI including blue sclerae, relatively short stature and osteopenia or fractures. Conclusion: Recognition of this distinct phenotype is important for accurate genetic counselling, clinical management and surveillance, particularly in relation to the potential risk for vascular rupture associated with these mutations. Because these patients present clinical overlap with other EDS subtypes, biochemical collagen analysis is necessary to establish the correct diagnosis