Simulative basic investigation for a new forming process punch-hole-rolling

Future products will require new forming processes in order to meet the increasing requirements for innovative products. These processes will enable new possibilities in product manufacturing and the control of product properties beyond geometry control. For this purpose, a new process called punch-hole-rolling has been developed, which enables the production of a double-sided collar in thin sheet structures. Punch-hole-rolling is a two-stage process combination of conventional shear cutting and novel rolling which is carried out in one tool. The process combination allows to derive product data from the punching process for the control of the flexible hole-rolling in order to control product properties such as geometry, hardness and microstructure. In order to increase the process understanding and classification, an FE-simulation is built and validated by experiments

Enantioselektive Synthese von (1S,4R)-4-Hydroxycyclopent-2-enyl-acetat durch enzym-katalysierte Veresterung von cis-Cyclopent-2-en-1,4-diol mit Acetanhydrid. Gaschromatographische Untersuchungen zum Reaktionsmechanismus

(1S,4R)-4-Hydroxycyclopent-2-enyl-acetate (1), an attractive starting material for the synthesis of prostaglandins, was readily prepared by an enzyme-catalyzed interesterification procedure using acetic anhydride as acylation agent. As the chemical yield of the chiral monoacylation product is rather low (45%), we investigated the acylation mechanism of this reaction to optimize the product output. Kinetic measurements were carried out by means of gas chromatography on a chiral stationary phase, synthesized by methylation of β-cyclodextrin

The energy source of the filaments around the giant galaxy NGC1275

The brightest galaxy in the nearby Perseus cluster, NGC1275, is surrounded by a network of filaments. These were first observed through their Halpha emission but are now known to have a large molecular component with a total mass approaching 10^11Msun of gas. The filaments are embedded in hot intracluster gas and stretch over 80 kpc. They have an unusual low excitation spectrum which is well modelled by collisional heating and ionization by secondary electrons. Here we note that the surface radiative flux from the outer filaments is close to the energy flux impacting on them from particles in the hot gas. We propose that the secondary electrons within the cold filaments, which excite the observed submillimetre through UV emission, are due to the hot surrounding gas efficiently penetrating the cold gas through reconnection diffusion. Some of the soft X-ray emission seen from the filaments is then due to charge exchange, although this is insufficient to account for all the observed X-ray flux. The filaments are complex with multiphase gas. Interpenetration of hot and cold gas leads to the filaments growing in mass, at a rate of up to 100Msunpyr. The lack of soft X-ray cooling emission in cool core clusters is then due to the non-radiative cooling of hot gas on mixing with cold gas around and within the central galaxy.Comment: 7 pages, 4 figures, MNRAS in pres

Spatial and Settlement Development Adapted to Climate Change in Strasshof an der Nordbahn (Lower Austria)

Climate change, increasing urbanisation and densification, not only in inner-city areas, require new approaches and solutions to improve liveability and act against the consequences of climate change, primarily noticeable in cities and their surrounding areas. The introduced projects "Strasshof 2021" and "Strasshof. Klimafit!" (both funded by the Austrian Climate and Energy Fund, Klima- und Energiefonds, under the Smart Cities Initiative in Austria) deal with climate change adaptation measures, exemplified by the Austrian municipality of Strasshof an der Nordbahn, using instruments of spatial planning, such as land development plans, construction plans, zoning plans etc., focussing on soil bioengineering measures to infiltrate rainwater as well as climate-effective design of roadside greenery using a selection of plants appropriate to the climate. Within the exploratory project "Strasshof 2021. Preparation of climate change-adapted planning instruments and processes for a Smart Village" the municipality of Strasshof examined in cooperation with the project team, how certain climate change adaptation measures could be specifically requested and regulated in the municipality's development plan, including how compliance and implementation of these measures could then be monitored by the municipality. At the level of the land development plan, criteria were developed suitable for implementing climate change-adapted settlement developments. Existing experiences were transferred to Strasshof and measures and options for climate change-adapted rainwater management were developed. For example, potential implementations of the sponge city principle, adapted to the local conditions (no canal for draining rainwater, very permeable soil) were examined in Strasshof. Based on the assessment of potential areas to establish green structures and roadside greenery in Strasshof, measures and options for climate change adapted planting and vegetation in public spaces and on buildings were analysed. A list of "climate-fit" trees (trees that are well-adapted to the changing climate) for public areas as well as for private gardens was drawn up. "Strasshof. Klimafit! Strasshof as a lighthouse: EVAPO+ green walls, green infiltration troughs, empowerment and practical transfer" is a lighthouse demonstration project that stimulates processes for climate change measures by empowering other municipalities and small towns. The project aims to implement resilient, multifunctional and "climate-fit" solutions that respond to heat and heavy rain, improve the microclimate, increase the quality of life and living while promoting biodiversity and species diversity in existing areas of the municipality. With these measures, Strasshof can act against climate change consequences and improve the liveability of the population. The transferability of the demonstrations shall be guaranteed with the help of various regional, national and international exchange forums. In cooperation with other Austrian municipalities, the lessons learned from Strasshof will be reflected and transferred to the regional network "Climate-Fit Small Towns and Municipalities" along with step-by-step instructions for climate-fit municipalities

Reworked remains of mosasauroids (Pythonomorpha, Squamata) in the Pleistocene of Pinilla del Valle (Madrid, Spain)

Proyecto de Investigación: "Evolución de la dieta de los homínidos"Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEComunidad de Madridpu

Combined antibiotic stewardship and infection control measures to contain the spread of linezolid-resistant Staphylococcus epidermidis in an intensive care unit

Background The unrestricted use of linezolid has been linked to the emergence of linezolid-resistant Staphylococcus epidermidis (LRSE). We report the effects of combined antibiotic stewardship and infection control measures on the spread of LRSE in an intensive care unit (ICU). Methods Microbiological data were reviewed to identify all LRSE detected in clinical samples at an ICU in southwest Germany. Quantitative data on the use of antibiotics with Gram-positive coverage were obtained in defined daily doses (DDD) per 100 patient-days (PD). In addition to infection control measures, an antibiotic stewardship intervention was started in May 2019, focusing on linezolid restriction and promoting vancomycin, wherever needed. We compared data from the pre-intervention period (May 2018–April 2019) to the post-intervention period (May 2019–April 2020). Whole-genome sequencing (WGS) was performed to determine the genetic relatedness of LRSE isolates. Results In the pre-intervention period, LRSE were isolated from 31 patients (17 in blood cultures). The average consumption of linezolid and daptomycin decreased from 7.5 DDD/100 PD and 12.3 DDD/100 PD per month in the pre-intervention period to 2.5 DDD/100 PD and 5.7 DDD/100 PD per month in the post-intervention period (p = 0.0022 and 0.0205), respectively. Conversely, vancomycin consumption increased from 0.2 DDD/100 PD per month to 4.7 DDD/100 PD per month (p < 0.0001). In the post-intervention period, LRSE were detected in 6 patients (4 in blood cultures) (p = 0.0065). WGS revealed the predominance of one single clone. Conclusions Complementing infection control measures by targeted antibiotic stewardship interventions was beneficial in containing the spread of LRSE in an ICU

DNA-Methylome based Tumor Hypoxia Classifier Identifies HPV-negative Head & Neck Cancer Patients at Risk for Locoregional Recurrence After Primary Radiochemotherapy

BACKGROUND Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in Head and Neck Squamous Cell Carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia. METHODS A DNA methylome-based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA-HNSCC cohort based on matched assignments using gene expression-based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of Human Papilloma Virus (HPV)-negative HNSCC patients treated with primary radiochemotherapy (RCHT). RESULTS While hypoxia-GSEs failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (LR, HR=4.3, p=0.001) and overall survival (OS, HR=2.34, p=0.03) but not distant metastasis (DM) after RCHT in the both cohorts. Hypoxia-M status was inversely associated with CD8 T-cells infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR=1.83, p=0.04), underscoring the breadth of this classifier for predicting tumor hypoxia status. CONCLUSIONS Our findings highlight an unexplored avenue for DNA Methylation-based classifiers as biomarkers of tumoral hypoxia for identifying high-risk features in patients with HNSCC tumors. TRIAL REGISTRATION Retrospective observational study from the German Cancer Consortium (DKTK-ROG), not interventional

Estrogen- and Progesterone (P4)-Mediated Epigenetic Modifications of Endometrial Stromal Cells (EnSCs) and/or Mesenchymal Stem/Stromal Cells (MSCs) in the Etiopathogenesis of Endometriosis

Endometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Grand Challenges in global eye health: a global prioritisation process using Delphi method

Background We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenge