Austria. Report on the drug situation 2006.

Commissioned each year by the EMCCDA and produced by the national focal points of the Reitox network, the National reports draw an overall picture of the drug phenomenon at national level in each EU Member State. These data are key information to the EMCCDA and are an important resource, among others, for the compilation of its Annual repor

An investigation into the controls on fracture tortuosity in rock sequences and the impact on fluid flow in the upper crust

Fractures are ubiquitous in geological sequences, and play an important role in the movement of fluids in the earth’s crust, particularly in fields such as hydrogeology, petroleum geology and volcanology. When predicting or analysing fluid flow, fractures are often simplified as a set of smooth parallel plates. In reality, they exhibit tortuosity on a number of scales: Fine-scale tortuosity, or roughness, is the product of the small-scale (µm – mm) irregularities in the fracture surface, whereas large-scale (> mm) tortuosity occurs as a result of anisotropy and heterogeneity within the host formation that leads to the formation of irregularities in the fracture surfaces. It is important to consider such tortuosity when analysing processes that rely on the movement (or hindrance) of fluids flowing through fractures in the subsurface. Such processes include fluid injection into granitic plutons for the extraction of heat in Engineered Geothermal Systems, or the injection of CO2 into reservoirs overlain by fine-grained mudrocks acting as seals in Carbon Capture and Storage projects. Although it is generally assumed that tortuosity is controlled by factors such as grain size, mineralogy and fracture mode, a systematic study of how these factors quantitatively affect tortuosity is currently lacking. Furthermore, in anisotropic rocks the fracture orientation with respect to any inherent anisotropy is also likely to affect tortuosity. In order to address this gap, we have induced fractures in a selection of different rock types (mudrocks, sandstones and carbonates) using the Brazil disk method, and imaged the fracture surfaces using both a digital optical microscope and X-ray Computed Tomography. Using these methods we are able to characterise both the fine-scale (roughness) and large-scale tortuosity. In order to understand the effect of fracture orientation on tortuosity we have also analysed fractures induced at different angles to bedding in samples of a highly anisotropic mudrock taken from South Wales, UK. Results indicate that fine-scale tortuosity is highly dependent on the fracture orientation with regards to the bedding plane, with fractures normal to bedding being rougher than those induced parallel to bedding. Finally, in order to measure the effect of tortuosity on fluid flow, we have carried out a series of core flooding experiments on a subset of fractured samples showing that fracture transmissivity decreases with increasing tortuosity

The association between use of electronic media and prevalence of headache in adolescents: results from a population-based cross-sectional study

Background: Use of electronic media, i.e. mobile phones, computers, television, game consoles or listening to music, is very common, especially amongst adolescents. There is currently a debate about whether frequent use of these media might have adverse effects on health, especially on headaches, which are among the most-reported health complaints in adolescents. The aim of the present study was to assess associations between frequent use of electronic media and the prevalence of different types of headache in adolescents. Methods: Data were derived from a population-based sample (n = 1,025, ages 13-17 years). Type of headache (i.e. migraine, tension-type headache, unclassifiable headache) was ascertained by standardized questionnaires for subjects reporting headache episodes at least once per month during the last six months. Duration of electronic media use was assessed during personal interviews. Associations were estimated with logistic regression models adjusted for age group, sex, family condition and socio-economic status. Results: Most of the adolescents used computers (85%), watched television (90%) or listened to music (90%) daily, otherwise only 23% of the participants used their mobile phones and only 25% played with game consoles on a daily basis. A statistically significant association between listening to music and any headache (odds ratio 1.8; 95% confidence interval 1.1-3.1 for 30 minutes per day, 2.1; 1.2-3.7 for 1 to 2 hours per day; 2.0; 1.2-3.5 for 3 hours and longer listening to music per day) was observed. When stratifying for type of headache, no statistically significant association was seen. Conclusions: Apart from an association between listening to music on a daily basis and overall headache, no consistent associations between the use of electronic media and different types of headache were observed

Nurr1 Modulation Mediates Neuroprotective Effects of Statins

The ligand-sensing transcription factor Nurr1 emerges as a promising therapeutic target for neurodegenerative pathologies but Nurr1 ligands for functional studies and therapeutic validation are lacking. Here pronounced Nurr1 modulation by statins for which clinically relevant neuroprotective effects are demonstrated, is reported. Several statins directly affect Nurr1 activity in cellular and cell-free settings with low micromolar to sub-micromolar potencies. Simvastatin as example exhibits anti-inflammatory effects in astrocytes, which are abrogated by Nurr1 knockdown. Differential gene expression analysis in native and Nurr1-silenced cells reveals strong proinflammatory effects of Nurr1 knockdown while simvastatin treatment induces several neuroprotective mechanisms via Nurr1 involving changes in inflammatory, metabolic and cell cycle gene expression. Further in vitro evaluation confirms reduced inflammatory response, improved glucose metabolism, and cell cycle inhibition of simvastatin-treated neuronal cells. These findings suggest Nurr1 involvement in the well-documented but mechanistically elusive neuroprotection by statins

miR-9-5p in Nephrectomy Specimens is a Potential Predictor of Primary Resistance to First-Line Treatment with Tyrosine Kinase Inhibitors in Patients with Metastatic Renal Cell Carcinoma

Approximately 20-30% of patients with metastatic renal cell carcinoma (mRCC) in first-line treatment with tyrosine kinase inhibitors (TKIs) do not respond due to primary resistance to this drug. At present, suitable robust biomarkers for prediction of a response are not available. Therefore, the aim of this study was to evaluate a panel of microRNAs (miRNAs) in nephrectomy specimens for use as predictive biomarkers for TKI resistance. Archived formalin-fixed, paraffin embedded nephrectomy samples from 60 mRCC patients treated with first-line TKIs (sunitinib, n = 51; pazopanib, n = 6; sorafenib, n = 3) were categorized into responders and non-responders. Using the standard Response Evaluation Criteria in Solid Tumors, patients with progressive disease within 3 months after the start of treatment with TKI were considered as non-responders and those patients with stable disease and complete or partial response under the TKI treatment for at least 6 months as responders. Based on a miRNA microarray expression profile in the two stratified groups of patients, seven differentially expressed miRNAs were validated using droplet digital reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) assays in the two groups. Receiver operating characteristic curve analysis and binary logistic regression of response prediction were performed. MiR-9-5p and miR-489-3p were able to discriminate between the two groups. MiR-9-5p, as the most significant miRNA, improved the correct prediction of primary resistance against TKIs in comparison to that of conventional clinicopathological variables. The results of the decision curve analyses, Kaplan-Meier analyses and Cox regression analyses confirmed the potential of miR-9-5p in the prediction of response to TKIs and the prediction of progression-free survival after the initiation of TKI treatment

How to classify, diagnose, treat and follow-up extragonadal germ cell tumors? A systematic review of available evidence

Purpose To present the current evidence and the development of studies in recent years on the management of extragonadal germ cell tumors (EGCT). Methods A systematic literature search was conducted in Medline and the Cochrane Library. Studies within the search period (January 2010 to February 2021) that addressed the classifcation, diagnosis, prognosis, treatment, and follow-up of extragonadal tumors were included. Risk of bias was assessed and relevant data were extracted in evidence tables. Results The systematic search identifed nine studies. Germ cell tumors (GCT) arise predominantly from within the testis, but about 5% of the tumors are primarily located extragonadal. EGCT are localized primarily mediastinal or retroperitoneal in the midline of the body. EGCT patients are classifed according to the IGCCCG classifcation. Consecutively, all mediastinal non-seminomatous EGCT patients belong to the “poor prognosis” group. In contrast mediastinal seminoma and both retroperitoneal seminoma and non-seminoma patients seem to have a similar prognosis as patients with gonadal GCTs and metastasis at theses respective sites. The standard chemotherapy regimen for patients with a EGCT consists of 3–4 cycles (good vs intermediate prognosis) of bleomycin, etoposid, cisplatin (BEP); however, due to their very poor prognosis patients with non-seminomatous mediastinal GCT should receive a dose-intensifed or high-dose chemotherapy approach upfront on an individual basis and should thus be referred to expert centers Ifosfamide may be exchanged for bleomycin in cases of additional pulmonary metastasis due to subsequently planned resections. In general patients with non-seminomatous EGCT, residual tumor resection (RTR) should be performed after chemotherapy. Conclusion In general, non-seminomatous EGCT have a poorer prognosis compared to testicular GCT, while seminomatous EGGCT seem to have a similar prognosis to patients with metastatic testicular seminoma. The current insights on EGCT are limited, since all data are mainly based on case series and studies with small patient numbers and non-comparative studies. In general, systemic treatment should be performed like in testicular metastatic GCTs but upfront dose intensifcation of chemotherapy should be considered for mediastinal non-seminoma patients. Thus, EGCT should be referred to interdisciplinary centers with utmost experience in the treatment of germ cell tumors

Can magnetic resonance imaging replace conventional computerized tomography for follow-up of patients with testicular cancer? A systematic review

Purpose Follow-up protocols for patients with testicular cancer (TC) have significantly reduced the number of cross-sectional imaging studies to reduce radiation exposure. At present, it is unclear whether magnetic resonance imaging (MRI) could replace conventional computerized tomography (CT) imaging. The objective of this study is to summarize the scientific evidence on this topic and to review guideline recommendations with regard to the use of MRI. Methods A systematic literature review was performed searching Medline and Cochrane databases for prospective studies on patients with TC in the follow-up care (last search in February 2021). Additionally, guideline recommendations for TC were screened. Data extraction and quality assessment of included studies were performed and used for a descriptive presentation of results. Results A total of four studies including two ongoing trials were identified. Overall, the scientific evidence of prospective comparative studies is based on 102 patients. Data suggest that abdominal imaging with MRI can replace conventional CT for detection of lymph node metastasis of the retroperitoneum to spare radiation exposure and contrast media application. However, experienced radiologists are needed. Clinical guidelines are aware of the risk of diagnosis-induced secondary malignancy due to CT imaging and some have adapted their recommendations accordingly. Results of the two ongoing trials on 738 patients are expected soon to provide more reliable results on this topic. Conclusions There is growing evidence that abdominopelvic MRI imaging can replace CT imaging during follow-up of patients with TC in order to reduce radiation exposure and diagnosis-induced secondary malignancy