The European Added Value of EU Spending: Can the EU Help its Member States to Save Money? Exploratory Study

Critical public debt levels have forced EU member states to pursue fiscal consolidation. Yet, there is a flip side to the austerity policies being administered to overcome the sovereign debt crisis. Cut backs in social transfers and public service delivery erode the social welfare architecture of the European economic model. Growing social insecurity, in turn, challenges European integration. Ever declining popular approval rates for the EU speak for themselves. In addition, the scaling back of public investments seems not to be an option either. This only further strangles what is left as potential for growth

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

The genomic and transcriptional landscape of primary central nervous system lymphoma

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations

The genomic and transcriptional landscape of primary central nervous system lymphoma

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)

The value of Positron-Emission-Tomography with 2-deoxy-2[18F]Fluoro-D-Glucose in children with Sarcoma and Wilms-Tumor (PET2003-Study)

Ziel der Arbeit: Evaluation der Wertigkeit der Positronen-Emissions- Tomographie (PET) mit 2-deoxy-2[18F]Fluoro-D-Glukose (FDG) für das Staging bei Kindern und Jugendlichen mit malignen Sarkomen (Ewing-Sarkom [EWS], Osteosarkom [OS], Weichteilsarkom [RMS]) und Wilms-Tumoren (WT). In einem weiteren Schritt wurden als sekundäre Studienziele der Stellenwert für das Therapiemonitoring und die Rezidivdiagnostik analysiert. Methoden: Es wurden 46 Patienten (weiblich: n=22; männlich: n=24; mittleres Alter: 12,9 (± 4,2) Jahre; Altersspanne: 1-18 Jahre) mit Sarkomen (EWS: n=23; OS: n=11; RMS: n=12) und 12 Patienten mit WT (weiblich: n=5; männlich: n=7; mittleres Alter: 5,9 Jahre; Altersspanne: 1-19 Jahre; primärer WT: n=9; Rezidiv: n=3) aus 4 Institutionen in die prospektive Multizenterstudie „PET2003“ eingeschlossen. Zusätzlich zur protokollgemäß durchgeführten konventionellen Diagnostik (CIM) wurde eine Ganzkörper-FDG-PET im Rahmen des Stagings sowie zum Therapiemonitoring nach neoadjuvanter Chemotherapie und nach Abschluss der Therapie durchgeführt. Die Ergebnisse der beiden Modalitäten wurden verglichen und der Einfluss der FDG-PET auf das jeweilige Therapieregime ermittelt. Als Referenzstandard diente der Entscheid eines interdisziplinären Truth Panels, welchem alle klinischen Daten inklusive der Histologie sowie die Ergebnisse aller bildgebenden Verfahren zur Verfügung standen. Ergebnisse: Im Initialstaging (n=46) der Sarkome konnten CIM und FDG-PET alle Primärtumoren konkordant nachweisen. Bei den Lymphknotenmetastasen zeigte sich eine Überlegenheit der FDG-PET (Sensitivität 95% vs. 25%), welche sich am deutlichsten in der Gruppe der RMS manifestierte (Sensitivität 93% vs. 36%). Unabhängig von der Tumorentität zeigte sich eine Unterlegenheit bei der Detektion von Lungenmetastasen (Sensitivität 25% vs. 100%). Für den Nachweis ossärer Filiae ergab sich eine signifikant höhere Sensitivität (88% vs. 37%; p=<0,01) der FDG-PET bei den EWS, während sich bei den OS kein signifikanter Unterschied zeigte (90% vs. 81%). Die PET bewirkte eine Therapieänderung in 30% der Fälle (EWS: n=7; OS: n=1, RMS: n=2). Für das Ansprechen auf die Therapie (n=27) konnte die FDG-PET bei den OS Responder und Non-Responder mittels SUVmax-Reduktion (AUC=0,967; p=0,009) bei einem cut-off von 62% (Sensitivität 100%; Spezifität, 83%; Korrektheit, 91%) signifikant voneinander trennen und war dem Parameter MRT-Tumorvolumenreduktion überlegen (AUC=0,5; p=1; Sensitivität, 40%; Spezifität, 100%; Korrektheit, 73%). Bei den EWS konnten beide Modalitäten keine signifikante Trennung der Patientengruppen erreichen (PET: AUC=0,614; p=0,571; CIM: AUC=0,479; p=0,953). Bei den WT zeigten CIM und FDG-PET die gleiche Korrektheit (9/9) für das Initialstaging der primären WT. Ferner zeigte sich ein Vorteil bei der Rezidiverfassung (1/3), für das nichtinvasive Grading (1/9 Patienten mit anaplastischer Histologie) sowie für die kombinierte Analyse von FDG-PET und CIM (Side-by- Side-Analyse) bei der Abschlussuntersuchung (3/5). Schlussfolgerung: Bei den EWS und den RMS hat die FDG-PET durch zusätzliche Detektion von Knochen- und Lymphknotenmetastasen einen relevanten Einfluss auf das Therapieregime. Für die Beurteilung des Ansprechens auf die Therapie ist die FDG-PET der lokalen MRT bei den OS überlegen, wohingegen bei den EWS beide Verfahren eine eingeschränkte Wertigkeit aufweisen. Bei den WT ergeben sich mögliche Vorteile zur Ausbreitungsdiagnostik in der Rezidivsituation und zum non-invasiven Grading.Aim: Evaluation of Positron-Emission-Tomography with 2-deoxy-2[18F]Fluoro-D-Glucose for staging in children with sarcoma (Ewing- Sarcoma [EWS], Osteosarcoma [OS], Soft Tissue Sarcoma [RMS]) and Wilms-Tumors (WT). Furthermore, the value for monitoring of response to treatment and for the detection of recurrent disease was evaluated as secondary aims of the study. Patients/Methods: 46 patients (female: n=22; male: n=24; mean age: 12,9 (± 4,2) years; range: 1-18 years) with sarcoma (EWS: n=23; OS: n=11; RMS: n=12) and 12 patients with WT (female: n=5; male: n=7; mean age: 5,9 years; range: 1-19 years; primary WT: n=9; recurrent WT: n=3) from 4 institutions were enrolled into the prospective multicentric study „PET2003“. Additionally to the conventional diagnostic algorithm (CIM) patients were examined with whole-body FDG-PET for initial staging as well as for monitoring of response to therapy and after the therapeutic management. The results of both modalities were compared and the impact of FDG-PET on the therapeutic management evaluated. The standard of reference consisted of all imaging material, follow-up data as well as histopathology, and was determined by an interdisciplinary tumor board. Results: FDG-PET and CIM were equally effective in the detection of primary tumors (accuracy, 100%). Concerning the detection of lymph node metastases, FDG-PET showed a superior sensitivity (sensitivity 95% vs. 25%), which was even more pronounced in the subgroup of RMS patients (sensitivity 93% vs. 36%). For lung metastases, CIM was superior to FDG-PET in all subgroups (sensitivity 25% vs. 100%). The detection of bone metastases revealed a significantly higher sensitivity (88% vs. 37%; p=<0,01) of FDG-PET in EWS patients, whereas there was no significant difference in OS patients (90% vs. 81%). FDG-PET led to a change of therapy in 30% of cases (EWS: n=7; OS: n=1, RMS: n=2). For monitoring of response to treatment (n=27), FDG-PET significantly discriminated Responders and Non-Responders using the SUVmax- Reduktion (AUC=0,967; p=0,009; cut-off=62%) in the subgroup of OS patients (sensitivity 100%; specificity, 83%; accuracy, 91%) and was superior to the volume-reduction measured by MRI (AUC=0,5; p=1; sensitivity, 40%; specificity, 100%; accuracy, 73%). In EWS both modalities could not discriminate Responders and Non-Responders (PET: AUC=0,614; p=0,571; CIM: AUC=0,479; p=0,953). In WT CIM and FDG-PET were equally effective for initial staging (9/9) of primary WT. FDG-PET was advantageous in staging of recurrent disease (1/3), for noninvasive Grading (1/9) as well as for the combined analysis of FDG-PET and CIM (Side-by-Side-Analysis) after therapeutic management (3/5). Conclusion: In EWS and RMS patients FDG-PET has a relevant impact on the therapeutic management. For the evaluation of response to treatment, FDG-PET is superior to local MRI in OS, whereas both modalities showed limited value in EWS patients. In WT patients, there are possible advantages of FDG-PET for staging of recurrent disease and for noninvasive grading