Simulating the Genetics Clinic of the Future - whether undergoing whole-genome sequencing shapes professional attitudes

Whole-genome sequencing (WGS) can provide valuable health insight for research participants or patients. Opportunities to be sequenced are increasing as direct-to- consumer (DTC) testing becomes more prevalent, but it is still fairly unusual to have been sequenced. We offered WGS to fourteen professionals with pre-existing familiarity with an interest in human genetics - healthcare, science, policy and art. Participants received a hard drive containing their personal sequence data files (.BAM,. gvcf), without further explanation or obligation, to consider how experiencing WGS firsthand might influence their professional attitudes. We performed semi-structured pre- and post-sequencing interviews with each participant to identify key themes that they raised after being sequenced. To evaluate how their experience of the procedure evolved over time, we also conducted a questionnaire to gather their views 3 years after receiving their genomic data. Participants were generally satisfied with the experience (all 14 participants would choose to participate again). They mostly decided to participate out of curiosity (personal) and to learn from the experience (professional). Whereas most participants slightly developed their original perspective on genetic data, a small selection of them radically changed their views over the course of the project. We conclude that personal experience of sequencing provides an interesting alternative perspective for experts involved in leading, planning, implementing or researching genome sequencing services. Moreover, the personal experience may provide professionals with a better understanding of the challenges visitors of the Genetics Clinic of the Future may face.Peer reviewe

"D'Anstalt" Außerfamiliäre Kinderbetreuung im 19. und beginnenden 20. Jahrhundert : Die Geschichte des Kindergartens in Österreich am Fallbeispiel Telfs

Arbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüftInnsbruck, Univ., Masterarb., 2019(VLID)456842

Die relative Einkommensentwicklung der EU-Beitrittswerber: Endbericht ; Studie im Auftrag des Bundesministeriums für wirtschaftliche Angelegenheiten

aus dem Inhaltsverzeichnis: Einleitung; Analyse des Konvergenzprozesses in den Regionen Österreich-Ungarns 1870-1910; Analyse des Wachstumsprozesses in den postkommunistischen Ländern; Grundlagen der Konvergenzdebatte; Empirische Ergebnisse; Konsequenzen der Konvergenz für den Außenhandel; Konsequenzen der Konvergenz für Direktinvestitionen; Konsequenzen der Konvergenz für die Migration; Zusammenfassung; Anhang

Spectrum of novel mutations found in Waardenburg syndrome types 1 and 2: implications for molecular genetic diagnostics

Objectives: Till date, mutations in the genes PAX3 and MITF have been described in Waardenburg syndrome (WS), which is clinically characterised by congenital hearing loss and pigmentation anomalies. Our study intended to determine the frequency of mutations and deletions in these genes, to assess the clinical phenotype in detail and to identify rational priorities for molecular genetic diagnostics procedures. Design: Prospective analysis. Patients: 19 Caucasian patients with typical features of WS underwent stepwise investigation of PAX3 and MITF. When point mutations and small insertions/deletions were excluded by direct sequencing, copy number analysis by multiplex ligation-dependent probe amplification was performed to detect larger deletions and duplications. Clinical data and photographs were collected to facilitate genotype-phenotype analyses. Setting: All analyses were performed in a large German laboratory specialised in genetic diagnostics. Results: 15 novel and 4 previously published heterozygous mutations in PAX3 and MITF were identified. Of these, six were large deletions or duplications that were only detectable by copy number analysis. All patients with PAX3 mutations had typical phenotype of WS with dystopia canthorum (WS1), whereas patients with MITF gene mutations presented without dystopia canthorum (WS2). In addition, one patient with bilateral hearing loss and blue eyes with iris stroma dysplasia had a de novo missense mutation (p. Arg217Ile) in MITF. MITF 3-bp deletions at amino acid position 217 have previously been described in patients with Tietz syndrome (TS), a clinical entity with hearing loss and generalised hypopigmentation. Conclusions: On the basis of these findings, we conclude that sequencing and copy number analysis of both PAX3 and MITF have to be recommended in the routine molecular diagnostic setting for patients, WS1 and WS2. Furthermore, our genotype-phenotype analyses indicate that WS2 and TS correspond to a clinical spectrum that is influenced by MITF mutation type and position

Genetic Mapping of Variation in Spatial Learning in the Mouse

Introduction The effect of genetic mutations on spatial learning has been studied extensively using transgenic techniques (Chen and Tonegawa, 1997), but there have been fewer attempts to identify the genetic variants responsible for differences in spatial learning between inbred strains of mice (Crawley et al., 1997), variants that may well occur in a different set of genes from those so far subjected to transgenic analysis. For instance, genetic mapping performed in an inbred strain cross detected almost no overlap in the chromosomal location of known mutants and genes affecting variation in circadian rhythm (Shimomura et al., 2001). A similar result for the analysis of spatial learning would open a pathway for the eventual identification of novel genes involved in learning and memory processes. Although the molecular characterization of loci influencing phenotypic variation in inbred strain crosses has proved to be more difficult than initially anticipated (Flint and Mott, 2001), p

Implementing pharmacogenomics decision support across seven European countries: The Ubiquitous Pharmacogenomics (U-PGx) project

Clinical pharmacogenomics (PGx) has the potential to make pharmacotherapy safer and more effective by utilizing genetic patient data for drug dosing and selection. However, widespread adoption of PGx depends on its successful integration into routine clinical care through clinical decision support tools, which is often hampered by insufficient or fragmented infrastructures. This paper describes the setup and implementation of a unique multimodal, multilingual clinical decision support intervention consisting of digital, paper-, and mobile-based tools that are deployed across implementation sites in seven European countries participating in the Ubiquitous PGx (U-PGx) project.(VLID)472881

Pharmacogenomics decision support in the U-PGx project: Results and advice from clinical implementation across seven European countries.

BackgroundThe clinical implementation of pharmacogenomics (PGx) could be one of the first milestones towards realizing personalized medicine in routine care. However, its widespread adoption requires the availability of suitable clinical decision support (CDS) systems, which is often impeded by the fragmentation or absence of adequate health IT infrastructures. We report results of CDS implementation in the large-scale European research project Ubiquitous Pharmacogenomics (U-PGx), in which PGx CDS was rolled out and evaluated across more than 15 clinical sites in the Netherlands, Spain, Slovenia, Italy, Greece, United Kingdom and Austria, covering a wide variety of healthcare settings.MethodsWe evaluated the CDS implementation process through qualitative and quantitative process indicators. Quantitative indicators included statistics on generated PGx reports, median time from sampled upload until report delivery and statistics on report retrievals via the mobile-based CDS tool. Adoption of different CDS tools, uptake and usability were further investigated through a user survey among healthcare providers. Results of a risk assessment conducted prior to the implementation process were retrospectively analyzed and compared to actual encountered difficulties and their impact.ResultsAs of March 2021, personalized PGx reports were produced from 6884 genotyped samples with a median delivery time of twenty minutes. Out of 131 invited healthcare providers, 65 completed the questionnaire (response rate: 49.6%). Overall satisfaction rates with the different CDS tools varied between 63.6% and 85.2% per tool. Delays in implementation were caused by challenges including institutional factors and complexities in the development of required tools and reference data resources, such as genotype-phenotype mappings.ConclusionsWe demonstrated the feasibility of implementing a standardized PGx decision support solution in a multinational, multi-language and multi-center setting. Remaining challenges for future wide-scale roll-out include the harmonization of existing PGx information in guidelines and drug labels, the need for strategies to lower the barrier of PGx CDS adoption for healthcare institutions and providers, and easier compliance with regulatory and legal frameworks