Der österreichische Islam: Entwicklung, Tendenzen und Möglichkeiten

'Etwa 350.000 Muslime und Musliminnen leben in Österreich. Aus dieser Präsenz ergeben sich mehrere Fragen. Ein kurzer Abriss der historischen Entwicklung bis in die Gegenwart steht am Anfang des Artikels. Die quantitative Entwicklung der muslimischen Bevölkerung in den letzten Jahren wird anhand der Ergebnisse der letzten Volkszählungen aufgezeigt. Wie Muslime und Musliminnen ihre Religion in Österreich erleben und praktizieren, welche Bedeutung die Religion im Alltagsleben hat, wird in der Folge ebenso beleuchtet wie Geschlechterbeziehungen und die Situation muslimischer Jugendlicher. Abschließend wird die Frage erörtert, ob es einen spezifisch österreichischen Islam gibt und inwieweit dieser sogar als ein zukunftsweisendes Konzept für Europa gelten kann.' (Autorenreferat)'About 350,000 Muslims live in Austria. This fact addresses several issues. First, the article summarizes the historical development and census results since 1981. Second, the modes conducting and living their religion, differentiated between female and male Muslims, are discussed - the importance of religion in daily life as well as gender relations and the situation of adolescent Muslims, often already in the second or third generation. Finally, the article raises the question, whether a specific type of 'Austrian Islam' exists that has the potential to be qualified as a forward-looking and trend-setting concept for Europe.' (author's abstract)

Investigation of a Monturaqui Impactite by Means of Bi-Modal X-ray and Neutron Tomography

X-ray and neutron tomography are applied as a bi-modal approach for the 3D characterisation of a Monturaqui impactite formed by shock metamorphism during the impact of an iron meteorite with the target rocks in the Monturaqui crater (Chile). The particular impactite exhibits structural heterogeneities on many length scales: its composition is dominated by silicate-based glassy and crystalline materials with voids and Fe/Ni-metal and oxihydroxides particles generally smaller than 1 mm in diameter. The non-destructive investigation allowed us to apply a novel bi-modal imaging approach that provides a more detailed and quantitative understanding of the structural and chemical composition compared to standard single mode imaging methods, as X-ray and neutron interaction with matter results in different attenuation coefficients with a non-linear relation. The X-ray and neutron data sets have been registered, and used for material segmentation, porosity and metallic content characterization. The bimodal data enabled the segmentation of a large number of different materials, their morphology as well as distribution in the specimen including the quantification of volume fractions. The 3D data revealed an evaporite type of material in the impactite not noticed in previous studies. The present study is exemplary in demonstrating the potential for non-destructive characterisation of key features of complex multi-phase objects such as impactites

Development of a complex intervention to improve participation of nursing home residents with joint contractures: a mixed-method study

Joint contractures in nursing home residents limit the capacity to perform daily activities and restrict social participation. The purpose of this study was to develop a complex intervention to improve participation in nursing home residents with joint contractures

Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA

AIM: Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents. Circulating free (cfDNA) and circulating tumour DNA (ctDNA) are promising biomarkers for disease surveillance and prognostication in several cancer types; however, few such studies are reported for OS. The purpose of this study was to discover and validate methylation-based biomarkers to detect plasma ctDNA in patients with OS and explore their utility as prognostic markers. METHODS: Candidate CpG markers were selected through analysis of methylation array data for OS, non-OS tumours and germline samples. Candidates were validated in two independent OS datasets (n = 162, n = 107) and the four top-performing markers were selected. Methylation-specific digital droplet PCR (ddPCR) assays were designed and experimentally validated in OS tumour samples (n = 20) and control plasma samples. Finally, ddPCR assays were applied to pre-operative plasma and where available post-operative plasma from 72 patients with OS, and findings correlated with outcome. RESULTS: Custom ddPCR assays detected ctDNA in 69% and 40% of pre-operative plasma samples (n = 72), based on thresholds of one or two positive markers respectively. ctDNA was detected in 5/17 (29%) post-operative plasma samples from patients, which in four cases were associated with or preceded disease relapse. Both pre-operative cfDNA levels and ctDNA detection independently correlated with overall survival (p = 0.0015 and p = 0.0096, respectively). CONCLUSION: Our findings illustrate the potential of mutation-independent methylation-based ctDNA assays for OS. This study lays the foundation for multi-institutional collaborative studies to explore the utility of plasma-derived biomarkers in the management of OS

Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations

Chondrosarcoma (CS) is a rare tumour type and the most common primary malignant bone cancer in adults. The prognosis, currently based on tumour grade, imaging and anatomical location, is not reliable, and more objective biomarkers are required. We aimed to determine whether the level of circulating tumour DNA (ctDNA) in the blood of CS patients could be used to predict outcome. In this multi-institutional study, we recruited 145 patients with cartilaginous tumours, of which 41 were excluded. ctDNA levels were assessed in 83 of the remaining 104 patients, whose tumours harboured a hotspot mutation in IDH1/2 or GNAS. ctDNA was detected pre-operatively in 31/83 (37%) and in 12/31 (39%) patients postoperatively. We found that detection of ctDNA was more accurate than pathology for identification of high-grade tumours and was associated with a poor prognosis; ctDNA was never associated with CS grade 1/atypical cartilaginous tumours (ACT) in the long bones, in neoplasms sited in the small bones of the hands and feet or in tumours measuring less than 80 mm. Although the results are promising, they are based on a small number of patients, and therefore, introduction of this blood test into clinical practice as a complementary assay to current standard-of-care protocols would allow the assay to be assessed more stringently and developed for a more personalised approach for the treatment of patients with CS

Sarcoma and the 100,000 Genomes Project: our experience and changes to practice

The largest whole genome sequencing (WGS) endeavour involving cancer and rare diseases was initiated in the UK in 2015 and ran for 5 years. Despite its rarity, sarcoma ranked third overall among the number of patients' samples sent for sequencing. Herein, we recount the lessons learned by a specialist sarcoma centre that recruited close to 1000 patients to the project, so that we and others may learn from our experience. WGS data was generated from 597 patients, but samples from the remaining approximately 400 patients were not sequenced. This was largely accounted for by unsuitability due to extensive necrosis, secondary to neoadjuvant radiotherapy or chemotherapy, or being placed in formalin. The number of informative genomes produced was reduced further by a PCR amplification step. We showed that this loss of genomic data could be mitigated by sequencing whole genomes from needle core biopsies. Storage of resection specimens at 4 °C for up to 96 h overcame the challenge of freezing tissue out of hours including weekends. Removing access to formalin increased compliance to these storage arrangements. With over 70 different sarcoma subtypes described, WGS was a useful tool for refining diagnoses and identifying novel alterations. Genomes from 350 of the cohort of 597 patients were analysed in this study. Overall, diagnoses were modified for 3% of patients following review of the WGS findings. Continued refinement of the variant-calling bioinformatic pipelines is required as not all alterations were identified when validated against histology and standard of care diagnostic tests. Further research is necessary to evaluate the impact of germline mutations in patients with sarcoma, and sarcomas with evidence of hypermutation. Despite 50% of the WGS exhibiting domain 1 alterations, the number of patients with sarcoma who were eligible for clinical trials remains small, highlighting the need to revaluate clinical trial design

MYC amplifications are common events in childhood osteosarcoma.

Funder: Bone Cancer Research Trust; Id: http://dx.doi.org/10.13039/100011719Funder: The Tom Prince Cancer TrustFunder: Wellcome Trust; Id: http://dx.doi.org/10.13039/100010269Funder: Jean Shanks Foundation – Pathological Society Clinical FellowshipFunder: UCL Experimental Cancer CentreFunder: UCLH Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100012317Funder: National Institute for Health Research; Id: http://dx.doi.org/10.13039/501100000272Osteosarcoma, the most common primary malignant tumour of bone, affects both children and adults. No fundamental biological differences between paediatric and adult osteosarcoma are known. Here, we apply multi-region whole-genome sequencing to an index case of a 4-year-old child whose aggressive tumour harboured high-level, focal amplifications of MYC and CCNE1 connected by translocations. We reanalysed copy number readouts of 258 cases of high-grade osteosarcoma from three different cohorts and identified a significant enrichment of focal MYC, but not CCNE1, amplifications in children. Furthermore, we identified four additional cases of MYC and CCNE1 coamplification, highlighting a rare driver event which warrants further investigation. Our findings indicate that amplification of the MYC oncogene is a major driver of childhood osteosarcoma, while CCNE1 appears recurrently amplified independent of age

A genetic model for central chondrosarcoma evolution correlates with patient outcome

Background Central conventional chondrosarcoma (CS) is the most common subtype of primary malignant bone tumour in adults. Treatment options are usually limited to surgery, and prognosis is challenging. These tumours are characterised by the presence and absence of IDH1 and IDH2 mutations, and recently, TERT promoter alterations have been reported in around 20% of cases. The effect of these mutations on clinical outcome remains unclear. The purpose of this study was to determine if prognostic accuracy can be improved by the addition of genomic data, and specifically by examination of IDH1, IDH2, and TERT mutations. Methods In this study, we combined both archival samples and data sourced from the Genomics England 100,000 Genomes Project (n = 356). Mutations in IDH1, IDH2, and TERT were profiled using digital droplet PCR (n = 346), whole genome sequencing (n=68), or both (n = 64). Complex events and other genetic features were also examined, along with methylation array data (n = 84). We correlated clinical features and patient outcomes with our genetic findings. Results IDH2-mutant tumours occur in older patients and commonly present with high-grade or dedifferentiated disease. Notably, TERT mutations occur most frequently in IDH2-mutant tumours, although have no effect on survival in this group. In contrast, TERT mutations are rarer in IDH1-mutant tumours, yet they are associated with a less favourable outcome in this group. We also found that methylation profiles distinguish IDH1- from IDH2-mutant tumours. IDH wild-type tumours rarely exhibit TERT mutations and tend to be diagnosed in a younger population than those with tumours harbouring IDH1 and IDH2 mutations. A major genetic feature of this group is haploidisation and subsequent genome doubling. These tumours evolve less frequently to dedifferentiated disease and therefore constitute a lower risk group. Conclusions Tumours with IDH1 or IDH2 mutations or those that are IDHwt have significantly different genetic pathways and outcomes in relation to TERT mutation. Diagnostic testing for IDH1, IDH2, and TERT mutations could therefore help to guide clinical monitoring and prognostication