Prospective evaluation of quality of life effects in patients undergoing palliative radiotherapy for brain metastases

Background: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. Methods: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. Results: At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. Conclusions: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information

Involvement of the Cytokine MIF in the Snail Host Immune Response to the Parasite Schistosoma mansoni

We have identified and characterized a Macrophage Migration Inhibitory Factor (MIF) family member in the Lophotrochozoan invertebrate, Biomphalaria glabrata, the snail intermediate host of the human blood fluke Schistosoma mansoni. In mammals, MIF is a widely expressed pleiotropic cytokine with potent pro-inflammatory properties that controls cell functions such as gene expression, proliferation or apoptosis. Here we show that the MIF protein from B. glabrata (BgMIF) is expressed in circulating immune defense cells (hemocytes) of the snail as well as in the B. glabrata embryonic (Bge) cell line that has hemocyte-like features. Recombinant BgMIF (rBgMIF) induced cell proliferation and inhibited NO-dependent p53-mediated apoptosis in Bge cells. Moreover, knock-down of BgMIF expression in Bge cells interfered with the in vitro encapsulation of S. mansoni sporocysts. Furthermore, the in vivo knock-down of BgMIF prevented the changes in circulating hemocyte populations that occur in response to an infection by S. mansoni miracidia and led to a significant increase in the parasite burden of the snails. These results provide the first functional evidence that a MIF ortholog is involved in an invertebrate immune response towards a parasitic infection and highlight the importance of cytokines in invertebrate-parasite interactions

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe

Gender Dimensions in UGC and VGI: A Desk-Based Study. GI_Forum 2013 – Creating the GISociety|

Much user generated content (UGC) is produced or reproduced by volunteers. Many UGC platforms exist nowadays to facilitate the process of co-production. The majority of them, however, show a gender imbalance of their contributors’ communities, including platforms for collecting Volunteered Geographic Information (VGI). Causes of this gender imbalance have not yet been elaborated sufficiently. In order to identify some of these factors which influence women’s participation in UGC platforms, case studies were carried out to compare different spatially explicit, spatially implicit, and non-spatial UGC projects. The case study analysis is based on a conceptual framework used to analyse participants’ motivations for contributing VGI in reference to gender. The findings suggest several criteria related to the imbalance of female and male contributors in the field of VGI

Gender Dimensions in UGC and VGI: A Desk-Based Study. GI_Forum 2013 – Creating the GISociety|

Much user generated content (UGC) is produced or reproduced by volunteers. Many UGC platforms exist nowadays to facilitate the process of co-production. The majority of them, however, show a gender imbalance of their contributors’ communities, including platforms for collecting Volunteered Geographic Information (VGI). Causes of this gender imbalance have not yet been elaborated sufficiently. In order to identify some of these factors which influence women’s participation in UGC platforms, case studies were carried out to compare different spatially explicit, spatially implicit, and non-spatial UGC projects. The case study analysis is based on a conceptual framework used to analyse participants’ motivations for contributing VGI in reference to gender. The findings suggest several criteria related to the imbalance of female and male contributors in the field of VGI

Potential carbon footprint reduction for reclaimed asphalt pavement innovations : Lca methodology, best available technology, and near-future reduction potential

The carbon footprints of asphalt mixtures with increasing reclaimed asphalt pavement (RAP) content were estimated using a life-cycle assessment methodology. Three asphalt mixtures with different applications and technical requirements, namely porous asphalt (PA), stone mastic asphalt (SMA), and asphalt concrete (AC), were included. The technology leaps needed to achieve asphalt mixtures containing up to 93% RAP were modelled. Mixtures containing up to 57% RAP were hot-mix asphalts (175 °C), while mixtures containing more RAP were produced at 135 °C and 105 °C. The energy requirements and their respective carbon footprints were calculated based on the heat capacity of the aggregates, RAP, and other bituminous materials. Furthermore, the effects of changing the country’s electricity mix were also evaluated. A potential carbon footprint reduction of between 55% and 64% was found for one tonne of asphalt containing 93% RAP and produced at 105 °C compared to the 0% RAP mixture produced at 175 °C. Considering the uncertainty of this technology at its early stage of development, the reduction could be as low as 45% or as high as 79%. Changing the electricity mix to one that is likely to be implemented until 2030 in the Netherlands further reduces the footprint by 10%.</p

Multifocal epilepsy in children is associated with increased long-distance functional connectivity: An explorative EEG-fMRI study

Objective: Multifocal epileptic activity is an unfavourable feature of a number of epileptic syndromes (Lennox-Gastaut syndrome, West syndrome, severe focal epilepsies) which suggests an overall vulnerability of the brain to pathological synchronization. However, the mechanisms of multifocal activity are insufficiently understood. This explorative study investigates whether pathological connectivity within brain areas of the default mode network as well as thalamus, brainstem and retrosplenial cortex may predispose individuals to multifocal epileptic activity. Methods: 33 children suffering from multifocal and monofocal (control group) epilepsies were investigated using EEG-fMRI recordings during sleep. The blood oxygenated level dependent (BOLD) signal of 15 regions of interest was extracted and temporally correlated (resting-state functional connectivity). Results: Patients with monofocal epilepsies were characterized by strong correlations between the corresponding interhemispheric homotopic regions. This pattern of correlations with pronounced short-distance and weak long-distance functional connectivity resembles the connectivity pattern described for healthy children. Patients with multifocal epileptic activity, however, demonstrated significantly stronger correlations between a large number of regions of the default mode network as well as thalamus and brainstem, with a significant increase in long-distance connectivity compared to children with monofocal epileptic activity. In the group of patients with multifocal epilepsies there were no differences in functional connectivity between patients with or without Lennox-Gastaut syndrome. Conclusion: This explorative study shows that multifocal activity is associated with generally increased long-distance functional connectivity in the brain. It can be suggested that this pronounced connectivity may represent either a risk to pathological over-synchronization or a consequence of the multifocal epileptic activity.Fil: Siniatchkin, Michael. Christian-Albrechts-Universität zu Kiel; AlemaniaFil: Moehring, Jan. Christian-Albrechts-Universität zu Kiel; AlemaniaFil: Kroeher, Bianca. Christian-Albrechts-Universität zu Kiel; AlemaniaFil: Galka, Andreas. Christian-Albrechts-Universität zu Kiel; AlemaniaFil: Ondarza, Gisela von. Christian-Albrechts-Universität zu Kiel; AlemaniaFil: Moeller, Friederike. Christian-Albrechts-Universität zu Kiel; AlemaniaFil: Wolff, Stephan. Christian-Albrechts-Universität zu Kiel; AlemaniaFil: Tagliazucchi, Enzo Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Christian-Albrechts-Universität zu Kiel; AlemaniaFil: Steinmann, Elisabeth. Christian-Albrechts-Universität zu Kiel; AlemaniaFil: Boor, Rainer. Christian-Albrechts-Universität zu Kiel; AlemaniaFil: Stephani, Ulrich. Christian-Albrechts-Universität zu Kiel; Alemani

A Combination of CRISPR/Cas9 and Standardized RNAi as a Versatile Platform for the Characterization of Gene Function

Traditional loss-of-function studies in Drosophila suffer from a number of shortcomings, including off-target effects in the case of RNA interference (RNAi) or the stochastic nature of mosaic clonal analysis. Here, we describe minimal in vivo GFP interference (miGFPi) as a versatile strategy to characterize gene function and to conduct highly stringent, cell type-specific loss-of-function experiments in Drosophila. miGFPi combines CRISPR/Cas9-mediated tagging of genes at their endogenous locus with an immunotag and an exogenous 21 nucleotide RNAi effector sequence with the use of a single reagent, highly validated RNAi line targeting this sequence. We demonstrate the utility and time effectiveness of this method by characterizing the function of the Polymerase I (Pol I)-associated transcription factor Tif-1a, and the previously uncharacterized gene MESR4, in the Drosophila female germline stem cell lineage. In addition, we show that miGFPi serves as a powerful technique to functionally characterize individual isoforms of a gene. We exemplify this aspect of miGFPi by studying isoform-specific loss-of-function phenotypes of the longitudinals lacking (lola) gene in neural stem cells. Altogether, the miGFPi strategy constitutes a generalized loss-of-function approach that is amenable to the study of the function of all genes in the genome in a stringent and highly time effective manner