Qualitätskriterien transdisziplinärer Forschung : ein Leitfaden für die formative Evaluation von Forschungsprojekten

Transdisziplinäre Forschung befasst sich mit lebensweltlichen Problemstellungen. Bei der Forschungsarbeit müssen Experten/innen aus verschiedenen Fächern bzw. Disziplinen und aus der Praxis zusammenwirken, um die komplexe Problematik umfassend behandeln zu können. Diese Vielfalt, die besondere Formen der Kooperation, der Differenzierung und Integration, Methoden und Theorien impliziert, bringt es mit sich, dass gängige, bei der fachbezogenen Bewertung hinreichende Verfahren der Evaluation und der Qualitätssicherung nicht unmittelbar auf solche Forschungsvorhaben übertragen werden können. Diesem Mangel an Kriterien und Methoden der Evaluation begegnet Evalunet, das Evaluationsnetzwerk für transdisziplinäre Forschung, mit dem vorgelegten Leitfaden für die Forschungspraxis, der vor allem ausführlich beschriebene Qualitätskriterien enthält und ebenso Aussagen zu methodischen und Verfahrensfragen macht. Er ist aus der empirischen Auswertung konkreter transdisziplinärer Forschungsprojekte und unter Mithilfe zahlreicher Experten und Expertinnen aus verschiedenen Fachrichtungen entstanden. Der Leitfaden dient dem Zweck der Evaluation von transdisziplinären Forschungsprojekten, wobei dieses Instrument auf den Aspekt des Lernens aus dem Evaluationsvorgang (formative Evaluation) zugeschnitten ist und bei der Aus- und Bewertung auf einen Diskurs setzt (diskursive Evaluation). Neben einer Evaluierung mittels der ausführlich beschriebenen Detailkriterien ist auch eine weniger aufwändige Evaluation mit Hilfe einer Kriterienauswahl (Basiskriterien) möglich. Die Qualitätskriterien können auch für die Konzipierung neuer transdisziplinärer Forschungsvorhaben genutzt werden.Transdisciplinary research projects investigate problems from everyday life. Experts from various disciplines and practitioners from the practical field in question have to co-operate to cope with the problem appropriately. Multiple forms of co-operation, differentiation and integration, methods and theories are significant for such projects. So conventional methods of disciplinary evaluation cannot be transferred and applied directly. In this situation, Evalunet, the Network for Transdisciplinary Evaluation, offers this guide, which provides researchers with very detailed evaluation criteria and descriptions of evaluation methods and practices. The criteria and procedures were identified in an empirical process by evaluating a number of transdisciplinary research projects. In this process, the Evalunet team was supported by numerous experts from various research areas. The main purpose of the guide is to provide guidance for the evaluation of transdisciplinary research projects. The criteria mainly support discursive evaluation processes that initiate learning processes for researchers and evaluators (formative evaluation). A set with a reduced number of criteria (Basiskriterien) offers a basic procedure for the evaluation, while the larger set with more detailed criteria (Detailkriterien) provides explanations and assistance in making a judgement. Criteria can also be used for conceiving and constructing new research projects

A cross-sectional controlled developmental study of neuropsychological functions in patients with glutaric aciduria type I

Background: Glutaric aciduria type I (GA-I) is an inherited metabolic disease due to deficiency of glutaryl-CoA dehydrogenase (GCDH). Cognitive functions are generally thought to be spared, but have not yet been studied in detail. Methods: Thirty patients detected by newborn screening (n = 13), high-risk screening (n = 3) or targeted metabolic testing (n = 14) were studied for simple reaction time (SRT), continuous performance (CP), visual working memory (VWM), visual-motor coordination (Tracking) and visual search (VS). Dystonia (n = 13 patients) was categorized using the Barry-Albright-Dystonia Scale (BADS). Patients were compared with 196 healthy controls. Developmental functions of cognitive performances were analysed using a negative exponential function model. Results: BADS scores correlated with speed tests but not with tests measuring stability or higher cognitive functions without time constraints. Developmental functions of GA-I patients significantly differed from controls for SRT and VS but not for VWM and showed obvious trends for CP and Tracking. Dystonic patients were slower in SRT and CP but reached their asymptote of performance similar to asymptomatic patients and controls in all tests. Asymptomatic patients did not differ from controls, except showing significantly better results in Tracking and a trend for slower reactions in visual search. Data across all age groups of patients and controls fitted well to a model of negative exponential development. Conclusions: Dystonic patients predominantly showed motor speed impairment, whereas performance improved with higher cognitive load. Patients without motor symptoms did not differ from controls. Developmental functions of cognitive performances were similar in patients and controls. Performance in tests with higher cognitive demand might be preserved in GA-I, even in patients with striatal degeneration

Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host

Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV

Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

Intraocular pressure and ocular pulse amplitude using dynamic contour tonometry and contact lens tonometry

BACKGROUND: The new Ocular Dynamic Contour Tonometer (DCT), investigational device supplied by SMT (Swiss Microtechnology AG, Switzerland) allows simultaneous recording of intraocular pressure (IOP) and ocular pulse amplitude (OPA). It was the aim of this study to compare the IOP results of this new device with Goldmann tonometry. Furthermore, IOP and OPA measured with the new slitlamp-mounted DCT were compared to the IOP and OPA measured with the hand-held SmartLens(®), a gonioscopic contact lens tonometer (ODC Ophthalmic Development Company AG, Switzerland). METHODS: Nineteen healthy subjects were included in this study. IOP was determined by three consecutive measurements with each of the DCT, SmartLens(®), and Goldmann tonometer. Furthermore, OPA was measured three times consecutively by DCT and SmartLens(®). RESULTS: No difference (P = 0.09) was found between the IOP values by means of DCT (mean: 16.6 mm Hg, median: 15.33 mm Hg, SD: +/- 4.04 mm Hg) and Goldmann tonometry (mean: 16.17 mm Hg, median: 15.33 mm Hg, SD: +/- 4.03 mm Hg). The IOP values of SmartLens(® )(mean: 20.25 mm Hg, median: 19.00 mm Hg, SD: +/- 4.96 mm Hg) were significantly higher (P = 0.0008) both from Goldmann tonometry and DCT. The OPA values of the DCT (mean: 3.08 mm Hg, SD: +/- 0.92 mm Hg) were significantly lower (P = 0.0003) than those obtained by SmartLens(® )(mean: 3.92 mm Hg, SD: +/- 0.83 mm Hg). CONCLUSIONS: DCT was equivalent to Goldmann applanation tonometry in measurement of IOP in a small group of normal subjects. In contrast, SmartLens(® )(contact lens tonometry) gave IOP readings that were significantly higher compared with Goldmann applanation tonometer readings. Both devices, DCT and SmartLens(® )provide the measurement of OPA which could be helpful e.g. for the management of glaucoma

Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision

Glutaric aciduria type 1 is a rare inherited neurometabolic disorder of lysine metabolism caused by pathogenic gene variations in GCDH (cytogenic location: 19p13.13), resulting in deficiency of mitochondrial glutaryl-CoA dehydrogenase (GCDH) and, consequently, accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid and glutarylcarnitine detectable by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Depending on residual GCDH activity, biochemical high and low excreting phenotypes have been defined. Most untreated individuals present with acute onset of striatal damage before age 3 (to 6) years, precipitated by infectious diseases, fever or surgery, resulting in irreversible, mostly dystonic movement disorder with limited life expectancy. In some patients, striatal damage develops insidiously. In recent years, the clinical phenotype has been extended by the finding of extrastriatal abnormalities and cognitive dysfunction, preferably in the high excreter group, as well as chronic kidney failure. Newborn screening is the prerequisite for pre-symptomatic start of metabolic treatment with low lysine diet, carnitine supplementation and intensified emergency treatment during catabolic episodes, which, in combination, have substantially improved neurologic outcome. In contrast, start of treatment after onset of symptoms cannot reverse existing motor dysfunction caused by striatal damage. Dietary treatment can be relaxed after the vulnerable period for striatal damage, that is, age 6 years. However, impact of dietary relaxation on long-term outcomes is still unclear. This third revision of evidence-based recommendations aims to re-evaluate previous recommendations (Boy et al., J Inherit Metab Dis, 2017;40(1):75-101; Kolker et al., J Inherit Metab Dis 2011;34(3):677-694; Kolker et al., J Inherit Metab Dis, 2007;30(1):5-22) and to implement new research findings on the evolving phenotypic diversity as well as the impact of non-interventional variables and treatment quality on clinical outcomes

Envelhecimento (in)ativo e desenvolvimento emocional em reclusos

Este projeto pretende apresentar o contributo do programa de Exercício Físico e do Desenvolvimento Emocional nos reclusos. Para isso optamos por desenvolver um estudo de carácter Quantitativo, Exploratório, Quasi - Experimental, Longitudinal e Descritivo. A amostra é constituída por 20 reclusos do Estabelecimento Prisional de Izeda, com idade média de 41,10±10,19 anos, distribuída entre os 24 e os 67 anos. Dos 20 reclusos, 9 foram designados para integrarem o Grupo de Investigação e os restantes o Grupo de Controlo. A seleção foi feita de forma aleatória. O Grupo de Investigação foi submetido a um programa de atividades de duas a três sessões semanais, durante 8 semanas, tendo cada sessão a duração de 1:15 Horas. Foi aplicada a escala EVCE e o questionário SF-36v2, com a complementaridade das avaliações do estado funcional dos reclusos. As características psicométrica obtidas na escala EVCE e no questionário SF-36v2 permitem-nos verificar que neste estudo se obtem uma boa consistência interna. Após a realização das sessões de intervenção, verificamos que não houve alterações estatisticamente significativas entre os parâmetros do Grupo de Controlo e o Grupo de Investigação. Desta forma, podemos concluir que o programa de intervenção teria melhores resultados se tivesse uma duração maior ao longo do tempo.This project aims to present the contribution of an Exercise Program and of an Emotional Development Program in prison. For this study we chose to develop a Quantitative Explorational, Quasi - Experimental, Descriptive and Longitudinal. The sample consists of 20 inmates of the Izeda Prison, with a mean age of 41.10± 10.19 years, distributed between 24 and 67 years. Of the 20 inmates, nine were appointed to serve on the Research Group and the remaining To the Control Group. The selection was done randomly. The Research Group has undergone program of activities two to three times per week for 8 weeks, with each session lasting 1h15m. EVCE scale and SF-36v2 were applied, the functional status of the inmates was assessed. The psychometric characteristics obtained in EVCE scale and SF-36v2 allow us to verify that this study gives a good internal consistency. After completion of intervention sessions, we found that there were no statistically significant changes between the parameters of the Control Group and Research Group. Thus, we can conclude that the intervention program would have better results if it had a longer duration over tim