Radium-223 in combination with paclitaxel in cancer patients with bone metastases : safety results from an open-label, multicenter phase Ib study

Purpose Concomitant treatment with radium-223 and paclitaxel is a potential option for cancer patients with bone metastases; however, myelosuppression risk during coadministration is unknown. This phase Ib study in cancer patients with bone metastases evaluated the safety of radium-223 and paclitaxel. Methods Eligible patients had solid tumor malignancies with >= 2 bone metastases and were candidates for paclitaxel. Treatment included seven paclitaxel cycles (90 mg/m(2) per week intravenously per local standard of care; 3 weeks on/1 week off) plus six radium-223 cycles (55 kBq/kg intravenously; one injection every 4 weeks, starting at paclitaxel cycle 2). The primary end point was percentage of patients with grade 3/4 neutropenia or thrombocytopenia during coadministration of radium-223 and paclitaxel (cycles 2, 3) versus paclitaxel alone (cycle 1). Results Of 22 enrolled patients, 15 were treated (safety population), with 7 completing all six radium-223 cycles. Treated patients had primary cancers of breast (n = 7), prostate (n = 4), bladder (n = 1), non-small cell lung (n = 1), myxofibrosarcoma (n = 1), and neuroendocrine (n = 1). No patients discontinued treatment from toxicity of the combination. In the 13 patients who completed cycle 3, the rates of grade 3 neutropenia in cycles 2 and 3 were 31% and 8%, respectively, versus 23% in cycle 1; there were no cases of grade 4 neutropenia or grade 3/4 thrombocytopenia. Breast cancer subgroup safety results were similar to the overall safety population. Conclusion Radium-223 was tolerated when combined with weekly paclitaxel, with no clinically relevant additive toxicities. This combination should be explored further in patients with bone metastases.Peer reviewe

Effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis

BACKGROUND: Pain and impaired mobility because of osteoarthritis (OA) is common in dogs and humans. Efficacy studies of analgesic drug treatment of dogs with naturally occurring OA may be challenging, as a caregiver placebo effect is typically evident. However, little is known about effect sizes of common outcome-measures in canine clinical trials evaluating treatment of OA pain. Forty-nine client-owned dogs with hip OA were enrolled in a randomized, double-blinded placebo-controlled prospective trial. After a 1 week baseline period, dogs were randomly assigned to a treatment (ABT-116 – transient receptor potential vanilloid 1 (TRPV1) antagonist, Carprofen – non-steroidal anti-inflammatory drug (NSAID), Tramadol - synthetic opiate, or Placebo) for 2 weeks. Outcome-measures included physical examination parameters, owner questionnaire, activity monitoring, gait analysis, and use of rescue medication. RESULTS: Acute hyperthermia developed after ABT-116 treatment (P < 0.001). Treatment with carprofen (P ≤ 0.01) and tramadol (P ≤ 0.001) led to improved mobility assessed by owner questionnaire. Nighttime activity was increased after ABT-116 treatment (P = 0.01). Kinetic gait analysis did not reveal significant treatment effects. Use of rescue treatment decreased with treatment in the ABT-116 and Carprofen groups (P < 0.001). Questionnaire score and activity count at the end of treatment were correlated with age, clinical severity at trial entry, and outcome measure baseline status (S(R) ≥ ±0.40, P ≤ 0.005). Placebo treatment effects were evident with all variables studied. CONCLUSION: Treatment of hip OA in client-owned dogs is associated with a placebo effect for all variables that are commonly used for efficacy studies of analgesic drugs. This likely reflects caregiver bias or the phenomenon of regression to the mean. In the present study, outcome measures with significant effects also varied between groups, highlighting the value of using multiple outcome measures, as well as an a priori analysis of effect size associated with each measure. Effect size data from the present study could be used to inform design of future trials studying analgesic treatment of canine OA. Our results suggest that analgesic treatment with ABT-116 is not as effective as carprofen or tramadol for treatment of hip arthritis pain in client-owned dogs

Cultural appropriation of spaces and things

This proceedings volume gathers papers presented at the symposium “Cultural Appropriation of Spaces and Things” held in Siegen, Germany in October 2019. All over the world, children are confronted with an increasingly complicated and fast-moving world. Children need elementary cultural techniques and skills to shape their own lives and enable them to find individual interpretations of meaning. In addition to the acquisition of classical cultural techniques such as arithmetic, writing and reading, the competent handling of spaces and things – through manifold processes of appropriation and reflection – is crucial. It forms the basis and prerequisite for the development of competences or abilities that are suitable for understanding the dimensions, the complexity and changeability of their world and enable them to critically deal with associated problems and find appropriate solutions. The aim of the conference was to find suitable ways for children all over the world for a methodically and didactically guided examination of their natural, social and technical environment. At the same time, the aim was to achieve a mutual enrichment of monodisciplinary research accesses. It also included a self-critical reflection of one’s own culturally shaped approaches of research.Contents: Martin Gröger, Christian Prust, Alexandra Flügel: Preface LECTURES Alexandre Avelino Giffoni Junior, Sebastião Lázaro Pereira, Alberto Barella Netto: Haus Früher Hilfen UniRV: A historic building in process in the heart of Brazil Hyeongjoo Kim: Designing and Applying the Moral Turing Test for Korean Children Karen Barfod and Peer Daugbjerg: Teaching Science and Mathematics Outside the Classroom, a pilot study on assessing inquiry-based practices Jan Höper: Towards integrated science education by using mobile technologies outdoors WORKSHOPS Mareike Janssen: Exploring the things of life: First insights into chemical processes with sparkling water as an example Julia Gaffron, Martin Gröger: Children like to experiment, many teachers apparently do not Volker Heck: Alexander von Humboldt - The Voyage to the Americas as an approach to science in Primary School Thomas Sukopp: Interculturality in Philosophy Education: Challenges and Prospects of Education for Sustainable Development in Primary Schools POSTERS André Dorn, Martin Gröger: ESD in general studies -prospective general studies teachers deal with the educational concept of ESD in a student-oriented and cooperative manner Andree Georg: From Carlowitz to Sustainable Development and Education for Sustainable Development Irina Landrock: Children at NS Memorial Sites Dr. Markus Schaal: Martha Muchow in the Context of the New Sociology of Childhood What Can a Classic Still Teach Us Today? Martin Gröger: Open air laboratory FLEX – Starting to learn chemistry in a near-natural learning environment Martin Gröger: FoodLAB - a molecular gastronomic experimental laboratory in teacher training Martin Gröger: How Alexander von Humboldt saw the world from a chemist’s point of view Matthias Weipert: Extracurricular learning locations in the historical perspective of general studies - the example of the Wendener Hütte Mirko Schommer: Spatial Orientation - Competence expectations and common misconceptions based on map projections Sarah Gaubitz: Options for handling complex problems of global change from the perspective of primary school children Swaantje Brill: Museum Field Trips in Primary School: An Approach to Children’s Perspectives Urs Gießelmann and Uta Birkhölzer: The “Hauberg” as an extracurricular learning locatio

The mortality after release from incarceration consortium (MARIC): Protocol for a multi-national, individual participant data meta-analysis

Introduction More than 30 million adults are released from incarceration globally each year. Many experience complex physical and mental health problems, and are at markedly increased risk of preventable mortality. Despite this, evidence regarding the global epidemiology of mortality following release from incarceration is insufficient to inform the development of targeted, evidence-based responses. Many previous studies have suffered from inadequate power and poor precision, and even large studies have limited capacity to disaggregate data by specific causes of death, sub-populations or time since release to answer questions of clinical and public health relevance. Objectives To comprehensively document the incidence, timing, causes and risk factors for mortality in adults released from prison. Methods We created the Mortality After Release from Incarceration Consortium (MARIC), a multi-disciplinary collaboration representing 29 cohorts of adults who have experienced incarceration from 11 countries. Findings across cohorts will be analysed using a two-step, individual participant data meta-analysis methodology. Results The combined sample includes 1,337,993 individuals (89% male), with 75,795 deaths recorded over 9,191,393 person-years of follow-up. Conclusions The consortium represents an important advancement in the field, bringing international attention to this problem. It will provide internationally relevant evidence to guide policymakers and clinicians in reducing preventable deaths in this marginalized population

The InterPro protein families database: the classification resource after 15 years

The InterPro database (http://www.ebi.ac.uk/interpro/) is a freely available resource that can be used to classify sequences into protein families and to predict the presence of important domains and sites. Central to the InterPro database are predictive models, known as signatures, from a range of different protein family databases that have different biological focuses and use different methodological approaches to classify protein families and domains. InterPro integrates these signatures, capitalizing on the respective strengths of the individual databases, to produce a powerful protein classification resource. Here, we report on the status of InterPro as it enters its 15th year of operation, and give an overview of new developments with the database and its associated Web interfaces and software. In particular, the new domain architecture search tool is described and the process of mapping of Gene Ontology terms to InterPro is outlined. We also discuss the challenges faced by the resource given the explosive growth in sequence data in recent years. InterPro (version 48.0) contains 36 766 member database signatures integrated into 26 238 InterPro entries, an increase of over 3993 entries (5081 signatures), since 201

InterPro in 2011: new developments in the family and domain prediction database

InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interface

InterPro: the integrative protein signature database

The InterPro database (http://www.ebi.ac.uk/interpro/) integrates together predictive models or ‘signatures' representing protein domains, families and functional sites from multiple, diverse source databases: Gene3D, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY and TIGRFAMs. Integration is performed manually and approximately half of the total ∼58 000 signatures available in the source databases belong to an InterPro entry. Recently, we have started to also display the remaining un-integrated signatures via our web interface. Other developments include the provision of non-signature data, such as structural data, in new XML files on our FTP site, as well as the inclusion of matchless UniProtKB proteins in the existing match XML files. The web interface has been extended and now links out to the ADAN predicted protein-protein interaction database and the SPICE and Dasty viewers. The latest public release (v18.0) covers 79.8% of UniProtKB (v14.1) and consists of 16 549 entries. InterPro data may be accessed either via the web address above, via web services, by downloading files by anonymous FTP or by using the InterProScan search software (http://www.ebi.ac.uk/Tools/InterProScan/

Open science resources for the discovery and analysis of Tara Oceans data

Le " Tara Expéditions" organise des expéditions pour étudier et comprendre l'impact des changements climatiques sur nos océans.International audienceThe Tara Oceans expedition (2009–2013) sampled contrasting ecosystems of the world oceans, collecting environmental data and plankton, from viruses to metazoans, for later analysis using modern sequencing and state-of-the-art imaging technologies. It surveyed 210 ecosystems in 20 biogeographic provinces, collecting over 35,000 samples of seawater and plankton. The interpretation of such an extensive collection of samples in their ecological context requires means to explore, assess and access raw and validated data sets. To address this challenge, the Tara Oceans Consortium offers open science resources, including the use of open access archives for nucleotides (ENA) and for environmental, biogeochemical, taxonomic and morphological data (PANGAEA), and the development of on line discovery tools and collaborative annotation tools for sequences and images. Here, we present an overview of Tara Oceans Data, and we provide detailed registries (data sets) of all campaigns (from port-to-port), stations and sampling events