Outcome of 11 children with ependymoblastoma treated within the prospective HIT-trials between 1991 and 2006

Ependymoblastoma is a rare malignant brain tumor of early childhood. Data on clinical behavior and optimal treatment strategies are scarce. We report on 11 consecutively treated children with centrally confirmed diagnosis of CNS ependymoblastoma, registered between February 1994 and October 2006 to the prospective GPOH-HIT multicenter brain tumor trials, and treated by multimodal regimens. Median age at diagnosis was 3.5years (range, 1.8-5.6years), and the median follow-up of survivors was 5.9years (range, 2.2-12.7years). Initial stage was M0 in 9, and M0/1 (no cerebrospinal fluid examination done) in 2 patients. Gross-total tumor resection was achieved in 7 patients, incomplete resection in 4 patients. Further primary therapy included chemotherapy in all patients, craniospinal radiotherapy in 5 patients and high-dose chemotherapy in 2 patients. Tumor response to chemotherapy was observed in 1 of 4 evaluable patients. Tumor progression occurred in 7 patients after a median time of 5.0months (range, 2.5-19.2months). Five-year progression-free survival was 36.4% (±14.5%), 5-year overall survival 30.3% (±15.9%). Of 4 survivors, 3 had gross-total tumor resection, and all were treated by either craniospinal radiotherapy and/or high-dose chemotherapy with autologous blood stem cell rescue. Prognosis of children with ependymoblastoma is poor, but sustained remissions have been achieved after multimodal treatment. Considerable diagnostic discrepancies between local and central pathologists underscore the importance of central review. Further studies are needed to improve survival of children with this rare malignant central nervous system tumo

Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007

Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64% (genetic analyses, FISH, MLPA, sequencing) up to 97% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46% (+/- 0.10) and 45% (+/- 0.09), respectively. Serious adverse events and one treatment-related death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU-RHAB provides the best available basis for phase I/II clinical trials

Geographical Perspectives on Transport and Ageing

In terms of ageing, we are living in unprecedented times. People across the globe are living longer than ever before and societies are ageing at increasing rates. In low to middle income countries reductions in mortality at young ages have fuelled this growth. A person born today in Brazil, for example, can expect to live 20 years longer than someone born 50 years ago (WHO, 2015). For the first time life expectancy across the globe is over 60 years of age. In high Income countries, someone born now can expect to live up to around 80 years of age on average (ONS, 2015). There are not simply a growing number of older people, but also a growing number of older people as a total percentage of the population due to people living longer and declining birth rates in many countries. Across Europe, for example, people aged over 65 years will account for 29.5% of the population in 2060 compared to around 19% now (EUROSTAT, 2017). The share of those aged 80 years or above across Europe will almost triple by 2060 (EUROSTAT, 2017)The macro level demographics and associated trends mask big differences within the ageing populations. There can be as much as 10 years difference in life expectancy within high income countries, for example in the UK someone born a baby boy born in Kensington and Chelsea has a life expectancy of 83.3 years, compared with a boy born in Glasgow who has a life expectancy of 10 years lower (73.0 years) (ONS, 2015). For newborn baby girls, life expectancy is highest in Chiltern at 86.7 years and 8 years lower Glasgow at 78.5 years (ONS, 2015; NRS, 2016). There is also considerable variation within cities, spatially and socially.This volume brings together contributions from a broad range of human geographers, with different disciplinary perspectives of transport and ageing. This chapter outlines some of the key contemporary issues for an ageing society in terms of transport and mobility, highlights the importance of considering transport and mobility for ageing populations and outlines the contribution that a geographical approach can offer to studies of transport and ageing

The evidence base for circulating tumour DNA blood-based biomarkers for the early detection of cancer: a systematic mapping review

Background: The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to those interested in early cancer detection, as well as to those wishing to monitor tumour progression or diagnose the presence of activating mutations to guide treatment. In 2014, the UK Early Cancer Detection Consortium undertook a systematic mapping review of the literature to identify blood-based biomarkers with potential for the development of a non-invasive blood test for cancer screening, and which identified this as a major area of interest. This review builds on the mapping review to expand the ctDNA dataset to examine the best options for the detection of multiple cancer types. Methods: The original mapping review was based on comprehensive searches of the electronic databases Medline, Embase, CINAHL, the Cochrane library, and Biosis to obtain relevant literature on blood-based biomarkers for cancer detection in humans (PROSPERO no. CRD42014010827). The abstracts for each paper were reviewed to determine whether validation data were reported, and then examined in full. Publications concentrating on monitoring of disease burden or mutations were excluded. Results: The search identified 94 ctDNA studies meeting the criteria for review. All but 5 studies examined one cancer type, with breast, colorectal and lung cancers representing 60% of studies. The size and design of the studies varied widely. Controls were included in 77% of publications. The largest study included 640 patients, but the median study size was 65 cases and 35 controls, and the bulk of studies (71%) included less than 100 patients. Studies either estimated cfDNA levels non-specifically or tested for cancer-specific mutations or methylation changes (the majority using PCR-based methods). Conclusion: We have systematically reviewed ctDNA blood biomarkers for the early detection of cancer. Pre-analytical, analytical, and post-analytical considerations were identified which need to be addressed before such biomarkers enter clinical practice. The value of small studies with no comparison between methods, or even the inclusion of controls is highly questionable, and larger validation studies will be required before such methods can be considered for early cancer detection

Neutrale und robuste Zink-Halogenido-Guanidin-Komplexe für die Ringöffnungspolymerisation von rac-Lactid

Due to the increasing use of petrochemical based plastics and the corresponding disadvantages an alternative has to be found. Polylactide (PLA) is a biodegradable polymer and is produced from renewable raw materials. Tin octanoate, which is toxic for the human organism, is nowadays commercially used as catalyst in the industrial PLA synthesis. This catalyst must therefore be replaced by a non-toxic alternative metal (e. g. zinc). Useful ligands are neutral guanidines which show high nucleophilicity, positive donor properties and great combination options of different substituents and bridging units.This dissertation thesis focuses on the optimisation of new aliphatic and aromatic hybridguanidine and aliphatic, chiral bisguanidine ligands with varying bridging units. The reaction of the ligand systems with zinc salts leads to novel zinc halide complexes, which were in detail characterized by means of X-ray crystallography, NMR, IR spectroscopy and mass spectrometer. Afterwards they were compared among each other. The obtained zinc halide complexes polymerise technical lactide after short reaction times without solvent to a colourless polymer which is of large importance for all industrial usecases. Besides, the chirality of the ligands should have an impact on the tacticity of the PLA so that the mechanical properties of the polylactide can be varied. A comparison between chiral bisguanidine and hybrid guanidine complexes relating to polymerisation of lactide and the influence of the bridging unit and of different zinc salts has been elaborated. In addition end group analyses by means of Maldi-ToF measurements were carried out, which provided crucial information for mechanism clarification. To clarify the molecular structures, density functional theory (DFT) calculations and natural bond orbital (NBO) analysis have been performed. The calculated donor-acceptor interactions of the complexes were compared and the donor strength of the coordinating nitrogen atoms was analysed. The influence of the quality of the lactide monomer and the addition of a coinitiator was investigated with two different setups in detail. In addition, one bis(chelate)-complex was tested in the polymerisation which shows outstanding activity in lactide polymerisation. In cooperation with the working group Kögerler robust bis(chelate) zinc complexes with anionic Schiff base ligands were successfully applied as catalysts for the ring-opening polymerisation of lactide

Economic dimensions of geological CO2 storage: key factors in an assessment of sub-seafloor and continental sequestration options

Geological sequestration offers long term storage opportunities that differ in terms of technical capacity and characteristics, and in terms of economic costs and benefits. In this paper we outline a simple economic framework that reflects the planning problem for sequestering CO2 in alternative geological sinks and highlights the differences in the environmental risks and the economic costs of alternative sinks. The marginal costs of alternative geological sequestration options must be compared to measures of marginal benefits that take into account the probability of local and global environmental risks and other regulatory requirements. We direct our discussion of an application of this framework to the case of geological sequestration in deep-sea basalts and provide an initial assessment of how this framework could be implemented to quantify the long-term economic costs relative to other continental geological storage options