bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase III randomized controlled study of daratumumab, bortezomib, and dexamethasone (DVd) versus bortezomib and dexamethasone (Vd) in patients (pts) with relapsed or refractory multiple myeloma (RRMM): CASTOR study.
Authors: Palumbo Antonio , Chanan-Khan Asher Alban Akmal , Weisel Katja , Nooka Ajay K. , Masszi Tamas , Beksac Meral , Spicka Ivan , Hungria Vania T.M. , Mateos María-Victoria , Mark Tomer Martin , Qi Ming , Schecter Jordan Mark , Amin Himal , Qin Xiang , Deraedt William , Ahmadi Tahamtan , Spencer Andrew , Sonneveld Pieter 
Published: May 2017

LBA4 Background: Daratumumab (D), a human anti-CD38 IgGκ mAb, induces deep and durable responses with a favorable safety profile in RRMM pts. We report a pre-specified interim analysis of the first randomized controlled study of D (CASTOR; NCT02136134). Methods: Pts with ≥1 prior line of therapy were randomized (1:1) to 8 cycles (q3w) of bortezomib (V)/dexamethasone (d) (V: 1.3 mg/m2sc on Days 1, 4, 8, 11; d: 20 mg po on Days 1, 2, 4, 5, 8, 9, 11, 12) ± D (16 mg/kg iv qw in Cycles 1-3, Day 1 of Cycles 4-8, then q4w until progression). Primary endpoint was PFS. Results: 498 pts (DVd, 251; Vd, 247) were randomized. Baseline demographics and disease characteristics were well balanced. Pts received a median of 2 prior lines of therapy (range 1-10). 66% received prior V; 76% received prior IMiD; 48% received prior PI and IMiD; 33% were IMiD-refractory; 32% were refractory to last line of prior therapy. With median follow-up of 7.4 months, D significantly improved median PFS (61% reduction in risk of progression) and TTP for DVd vs Vd (Table). D significantly increased ORR (83% vs 63%, P <0.0001), and doubled rates of ≥VGPR (59% vs 29%, P <0.0001), and ≥CR (19% vs 9%, P= 0.0012) for DVd vs Vd, respectively; median duration of response was NR vs 7.9 months, respectively. Most common (>25%) AEs (DVd/Vd) were thrombocytopenia (59%/44%), peripheral sensory neuropathy (47%/ 38%), diarrhea (32%/22%) and anemia (26%/31%). Most common grade 3/4 AEs (>10%) were thrombocytopenia (45%/33%), anemia (14%/16%), neutropenia (13%/4%). 7%/9% of pts discontinued due to a TEAE. D-associated infusion-related reactions (45% of pts) mostly occurred during the first infusion; most were grade 1/2 (grade 3/4, 9%/0%). Conclusions: D significantly improved PFS, TTP, and ORR in combination with Vd vs Vd alone. DVd doubled both VGPR and sCR/CR rates vs Vd alone. Safety of DVd is consistent with the known safety profile of D and Vd. The addition of D to Vd should be considered a new standard of care for RRMM pts currently receiving Vd alone. Clinical trial information: NCT02136134. [Table: see text]
ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma.
Authors: Neoptolemos John P. , Palmer Dan , Ghaneh Paula , Valle Juan W. , Cunningham David , Wadsley Jonathan , Meyer Tim , Anthoney Alan , Glimelius Bengt , Falk Stephen , Segersvard Ralf , Izbicki Jakob R. , Middleton Gary William , Ross Paul J. , Wasan Harpreet , Mcdonald Alec , Crosby Tom David Lewis , Psarelli Eftychia Eirini , Hammel Pascal , Buchler Markus W. 
Published: May 2017

LBA4006 Background: The ESPAC-3 trial compared adjuvant GEM with 5-fluorouracil/folinic acid for resected pancreatic cancer. GEM is the standard of care based on similar survival and less toxicity. ESPAC-4 aimed to determine whether combination chemotherapy with GEM/CAP improved survival compared to GEM monotherapy. Methods: Patients with pancreatic ductal adenocarcinoma were randomized within 12 weeks of surgery (stratified for R0/R1 resection margin status and country) to have either six 4 week cycles of IV GEM alone or GEM with oral CAP. The primary endpoint was overall survival; secondary endpoints were toxicity, relapse free survival, 2 and 5 year survival and quality of life. 722 patients (480 expected events), 361 in each arm, were needed to detect a 10% difference in 2 year survival rates with 90% power (log-rank test with 5% two-sided alpha). Results: Between Nov 10 2008 and Sep 11 2014, 732 patients were randomized with 730 included in the full analysis set (366 GEM, 364 GEM/CAP). Median age was 65 years, 57% were men. WHO performance status was 0, 1 or 2 in 42% 55% and 3% respectively. Postoperative median CA19-9 was 19 kU/L. Median maximum tumor size was 30 mm, 60% were R1 resections, 80% were node positive and 40% were poorly differentiated. On Dec 11 2015 the Independent Trial Steering Committee requested that the trial proceed to full analysis. The data freeze was on March 2 2016. Median survival (months) for patients treated with GEM/CAP was 28.0 (95% CI, 23.5 – 31.5) and 25.5 (22.7 – 27.9) for GEM. Stratified log-rank analysis revealed an HR=0.82 [95% CI, 0.68 – 0.98]; χ2 (1) = 4.61, P=0.032. 196 out of 366 GEM patients in the safety set reported 481 grade 3/4 adverse events, while 226 out of 359 GEM/CAP patients reported 608 grade 3/4 adverse events ( P=0.242). Conclusions: Adjuvant GEM/CAP for pancreatic cancer had a statistically significant improvement in survival compared to GEM monotherapy. Clinical trial information: ISRCTN96397434.
Heritage: A phase III safety and efficacy trial of the proposed trastuzumab biosimilar Myl-1401O versus Herceptin.
Authors: Rugo Hope S. , Barve Abhijit , Waller Cornelius F. , Hernandez-Bronchud Miguel , Herson Jay , Yuan Jinyu , Manikhas Alexey , Bondarenko Igor , Mukhametshina Guzel , Nemsadze Gia , Parra Joseph D. , Tiambeng Maria Luisa T. Abesamis , Baramidze Kakhaber , Akewanlop Charuwan , Vynnychenko Ihor , Sriuranpong Virote , Manillapalli Gopichand , Ray Sirshendu , Yanez Ruiz Eduardo Patricio , Pennella Eduardo J. 
Published: May 2017

LBA503 Background: Trastuzumab has revolutionized treatment of HER2+ breast cancer. Globally accessible alternatives are a critical need. We evaluated Myl-1401O, a proposed trastuzumab biosimilar, as treatment for HER2+ metastatic breast cancer (MBC), based on physicochemical analyses, nonclinical, pharmacokinetic and pharmacodynamic studies*. Methods: Heritage is a double-blind, randomized clinical trial designed to evaluate comparative efficacy and safety of Myl-1401O vs Herceptin. Eligible patients (pts) had centrally confirmed, measurable HER2+ MBC without prior chemotherapy or trastuzumab for metastatic disease. Pts were randomized to receive either Myl-1401O or Herceptin with docetaxel or paclitaxel for a minimum of 8 cycles. Trastuzumab was continued until progression. The primary endpoint was overall response (ORR) at Week 24 by blinded central evaluation using RECIST 1.1. Secondary endpoints include progression free survival (PFS), overall survival, and safety. A sample size of 456 pts was calculated to demonstrate equivalence in ORR at Week 24 for MYL-1401O vs Herceptin, defined as a 90% confidence interval (CI) for the ratio of best ORR within the equivalence margin (0.81, 1.24). Results: 500 pts were randomized, 458 were evaluable for efficacy. 44% had hormone receptor positive MBC, 84% received docetaxel. Week 24 ORR was 69.6% for Myl-14010 compared to 64% for Herceptin. The ratio of ORR was 1.09; both 90% CI (0.974-1.211) and 95% CI (0.954-1.237) were within the pre-defined equivalence margin. Median PFS is not yet reached (41 events for MYL-1401O vs 48 events for Herceptin). Safety was comparable; serious adverse events (primarily neutropenia related) occurred in 38% (MYL-1401O) vs 36% (Herceptin), with 4 fatal events in each arm. There was no significant change in cardiac function from baseline to Week 24 in either arm. Conclusions: MYL-1401O was equivalent to Herceptin, given in combination with a taxane as first-line therapy for MBC, as measured by 24 week ORR. Safety was comparable. The proposed trastuzumab biosimilar MYL-1401O could be a new treatment option for HER2+ MBC. * Presented at: British Pharmacological Society, Pharmacology Meeting; 2015 Dec 15-17; London, UK. Clinical trial information: 2011-001965-42.
Treatment Decision Regret Among Long-Term Survivors of Localized Prostate Cancer: Results From the Prostate Cancer Outcomes Study
Authors: Hoffman Richard M. , Lo Mary , Clark Jack A. , Albertsen Peter C. , Barry Michael J. , Goodman Michael , Penson David F. , Stanford Janet L. , Stroup Antoinette M. , Hamilton Ann S. 
Published: May 2017

Purpose To determine the demographic, clinical, decision-making, and quality-of-life factors that are associated with treatment decision regret among long-term survivors of localized prostate cancer. Patients and Methods We evaluated men who were age ≤ 75 years when diagnosed with localized prostate cancer between October 1994 and October 1995 in one of six SEER tumor registries and who completed a 15-year follow-up survey. The survey obtained demographic, socioeconomic, and clinical data and measured treatment decision regret, informed decision making, general- and disease-specific quality of life, health worry, prostate-specific antigen (PSA) concern, and outlook on life. We used multivariable logistic regression analyses to identify factors associated with regret. Results We surveyed 934 participants, 69.3% of known survivors. Among the cohort, 59.1% had low-risk tumor characteristics (PSA < 10 ng/mL and Gleason score < 7), and 89.2% underwent active treatment. Overall, 14.6% expressed treatment decision regret: 8.2% of those whose disease was managed conservatively, 15.0% of those who received surgery, and 16.6% of those who underwent radiotherapy. Factors associated with regret on multivariable analysis included reporting moderate or big sexual function bother (reported by 39.0%; OR, 2.77; 95% CI, 1.51 to 5.0), moderate or big bowel function bother (reported by 7.7%; OR, 2.32; 95% CI, 1.04 to 5.15), and PSA concern (mean score 52.8; OR, 1.01 per point change; 95% CI, 1.00 to 1.02). Increasing age at diagnosis and report of having made an informed treatment decision were inversely associated with regret. Conclusion Regret was a relatively infrequently reported outcome among long-term survivors of localized prostate cancer; however, our results suggest that better informing men about treatment options, in particular, conservative treatment, might help mitigate long-term regret. These findings are timely for men with low-risk cancers who are being encouraged to consider active surveillance.
Molecular insights into Adgra2/Gpr124 and Reck intracellular trafficking
Authors: Bostaille Naguissa , Gauquier Anne , Twyffels Laure , Vanhollebeke Benoit 
Published: May 2017

ABSTRACT
Adgra2, formerly known as Gpr124, is a key regulator of cerebrovascular development in vertebrates. Together with the GPI-anchored glycoprotein Reck, this adhesion GPCR (aGPCR) stimulates Wnt7-dependent Wnt/β-catenin signaling to promote brain vascular invasion in an endothelial cell-autonomous manner. Adgra2 and Reck have been proposed to assemble a receptor complex at the plasma membrane, but the molecular modalities of their functional synergy remain to be investigated. In particular, as typically found in aGPCRs, the ectodomain of Adgra2 is rich in protein-protein interaction motifs whose contributions to receptor function are unknown. In opposition to the severe ADGRA2 genetic lesions found in previously generated zebrafish and mouse models, the zebrafish ouchless allele encodes an aberrantly-spliced and inactive receptor lacking a single leucine-rich repeat (LRR) unit within its N-terminus. By characterizing this allele we uncover that, in contrast to all other extracellular domains, the precise composition of the LRR domain determines proper receptor trafficking to the plasma membrane. Using CRISPR/Cas9 engineered cells, we further show that Adgra2 trafficking occurs in a Reck-independent manner and that, similarly, Reck reaches the plasma membrane irrespective of Adgra2 expression or localization, suggesting that the partners meet at the plasma membrane after independent intracellular trafficking events.
Escapes in copepods: comparison between myelinate and amyelinate species
Authors: Buskey Edward J. , Strickler J. Rudi , Bradley Christina J. , Hartline Daniel K. , Lenz Petra H. 
Published: May 2017

ABSTRACT
Rapid conduction in myelinated nerves keeps distant parts of large organisms in timely communication. It is thus surprising to find myelination in some very small organisms. Calanoid copepods, while sharing similar body plans, are evenly divided between myelinate and amyelinate taxa. In seeking the selective advantage of myelin in these small animals, representatives from both taxa were subjected to a brief hydrodynamic stimulus that elicited an escape response. The copepods differed significantly in their ability to localize the stimulus: amyelinate copepods escaped in the general direction of their original swim orientation, often ending up closer to the stimulus. However, myelinate species turned away from the stimulus and distanced themselves from it, irrespective of their original orientation. We suggest that faster impulse conduction of myelinated axons leads to better precision in the timing and processing of sensory information, thus allowing myelinate copepods to better localize stimuli and respond appropriately.
Implementing the Care Certificate: a developmental tool or a tick-box exercise?
Authors: Gilding Moorene 
Published: May 2017

Introduction: The review into the role of healthcare support workers (HCSWs), carried out by Camilla Cavendish, resulted in the recommendation for standardised training for HCSWs ( Cavendish, 2013 ). Consequently, the ‘Care Certificate’ ( Health Education England (HEE), 2015 ) was introduced, with the aim of standardising initial training of HCSWs. However, no guidance on its implementation was provided nationally. Methodology: A ‘Day 2 Care Certificate Follow-up’ workshop was introduced by a team of clinical skills tutors in a London mental health trust, as a pilot study to evaluate the programme's effectiveness. Some 8 mandatory workshops were facilitated by tutors, 7 weeks after each group's induction. A total of 38 HCSWs and 32 clinical supervisors attended. Feedback on experiences was collated from a ‘Tabletop’ exercise, group discussions and course evaluation forms. Findings: Whereas the developmental value of completing the Care Certificate was acknowledged by attendees, there were overwhelming reports of inadequate support in clinical areas. Significant variations were identified for accessing protected time, team support and supervision. The findings suggest major systemic barriers impacting on HCSWs' achievement of the Care certificate. Discussion: Most competency-based training is supported by a framework that allows for protected time and pastoral support as part of the learning process. A good example is pre-registration courses for nurses. Student nurses are not expected to achieve their competency without adequate supernumerary time and support of their assessor (mentor). While not suggesting that HCSWs be made supernumerary throughout their ‘Care Certificate’ programme, clear guidance must be given nationally on implementation, outlining compulsory support systems to avoid the Care Certificate becoming another ‘tick-box’ exercise. Conclusion: While the Care Certificate has great potential for enhancing the educational development of HCSWs, the idea of national standardisation and a care passport is far from being a reality. Further consideration must be given to the impact of giving employers full control over implementation without clear guidance on method of delivery, quality assurance and a support framework.
John G. Brandon and ‘Coutts Brisbane’: Two Australian contributors to Sexton Blake and inter-war popular fiction
Authors: Arnold John 
Published: May 2017

Abstract
This article will look at the careers of two Australian expatriate writers, John Gordon Brandon and Robert Coutts Armour, better known as ‘Coutts Brisbane’. Both were born in Australia and both travelled to England to further their careers in their mid-to-late 20s, one in the theatre and the other as an artist. They both became, however, writers of popular fiction, especially of stories for boys, both being frequent contributors to the Sexton Blake Library. Coutts Brisbane was also a pioneer Science Fiction writer. Neither returned to Australia, but their stories and books did and it can well be argued that, despite their being known today only to collectors and a few specialists, both made interesting contributions to popular culture in England (and to Australia) in the second to fourth decades of the last century.
Travelling design: Learning from Hanoi’s craft streets through design-centred Vietnam study tours
Authors: Phuong Dinh Quoc 
Published: May 2017

Abstract
This article looks at the experiences of design students who took part in study tours of Vietnam offered as summer courses by the School of Design at Swinburne University of Technology in 2014, 2015 and 2016. It discusses the role that travel played in their design projects and their design education in general. The author suggests that looking at aspects of Vietnamese everyday life, including its built environment and local crafts, creates greater awareness and a better understanding of the social and cultural aspects of the design process. As outsiders based in Hanoi, the capital of Vietnam, over the course of the study tour the students achieved what Edward Relph (1976) called ‘empathetic insiderness’ – i.e. a willingness to be open to the significance of a place and to feel and appreciate this significance – as a result of exploring and engaging with the city’s architecture and everyday life.
Nostalgia is not what it used to be: Rural idylls and the American diner
Authors: Scully Mike 
Published: May 2017

Abstract
The author was drawn to visit the mid-western American conurbation of Minneapolis-St Paul by the long-running radio variety programme, A Prairie Home Companion (1974 – present), which gently satirises small-town rural culture. In a fine example of serendipity, he came across Mickey’s Diner, a traditional fast-food outlet that has operated in the same location continuously for almost 78 years. This became a springboard for examining the history of a uniquely American institution and its relevance to today’s cuisine and culture. It was also the chance to look at a city with a population only slightly less than that of Melbourne in a state proud of its rural and Scandinavian heritage.
Melbourne’s Tullamarine Airport and the modern jet city: ‘Your destination awaits you’
Authors: Chandu Arun , Darian Smith Kate 
Published: May 2017

Abstract
The 1960s saw the introduction of intercontinental jet aircrafts across the world. Australian Australia was eager to join this international jet set and was given its first opportunity to do so through the construction of a new airport for Melbourne. Built between 1964 and 1970, Melbourne airport, Tullamarine, was Australia’s first purpose-built jetport and the world’s first planned airport city by modernday standards. With all its cutting-edge features, Tullamarine instantly became an edifice to the jet age and the jet set, designed to be enjoyed by both travellers and visitors alike. It was a gateway to Victoria and Australia, but also allowed Victorians their first real taste of international travel. It was the starting point for many a memorable journey.
Just another day in the life of Hopalong Cassidy
Authors: Groves Derham 
Published: May 2017

Abstract
The American actor William Boyd (1895–1972) was world famous for his portrayal of Clarence E. Mulford’s fictional cowboy Hopalong Cassidy via comics, films, radio and television. In November 1954, Boyd travelled to Australia (Darwin, Melbourne, Adelaide, and Sydney) for sixteen hectic days to raise money for disabled children. ‘Just another day in the life of Hopalong Cassidy’ focuses on Friday, 12 November 1954, one of the four days that Boyd spent in Melbourne. Somewhat in the manner of French writer Georges Perec (Perec [1978] 2009), it documents Boyd’s activities on that very busy day – including his visits to the Royal Children’s Hospital, Yooralla, the Victorian School for Deaf Children, and Wirth’s Circus – from the points of view of Boyd himself and several people who either saw or met their cowboy hero on the 12th. In the process of re-telling their stories, a unique picture of everyday life in Melbourne in 1954 emerges.
Axiological relationships between audio-visual political and commercial messages in Spain from 2008 to 2015
Authors: Hernández Olmedo José Luis 
Published: May 2017

Abstract
Politics and commerce are fundamental activities for the development of a society. This article proposes that the two are interrelated, and the proof of it are the values that are included in their respective discourses. This article describes the axiological relationships of both typologies, through a rhetorical root analysis model designed to identify values. To exemplify these relationships, we will examine the spots of election cycles in Spain for 2008, 2011 and 2015. With this information, a values map will be drawn, and the function of the persuasive process in mass communication will be defined through a new construct called the Axiological Conversion Thesis (ACT). This article may be of interest to the fields of economics and politics, as it attempts to identify links between the public and the private, and concludes that according to contemporary audio-visual messages, commercial product brands and political parties have more points in common than differences.
Watchdog journalism or hush-puppy silencing? Framing the banking crisis of 2013 in Cyprus through the press
Authors: Maniou Theodora , Photiou Irene 
Published: May 2017

Abstract
From Ida Tarbell to Bob Woodward, journalists crusading for truth have bravely defended democracy from the incursions of corruption and undue influence despite being forced to live with the ‘consequences’ of their actions. In Cyprus, the debt of major Cypriot banks and their financial bailout culminated in the banking crisis of March 2013. As expected, the crisis has altered modes of everyday life and the images with which it is depicted, leading most Cypriots to a different notion of reality. This article focuses on the examination of the news items published in the daily newspapers of the highest circulation with different political alignments in March 2013, during which the bailout and austerity measures were negotiated by the Cyprus government, the parliament and the Troica. Based on the concept of investigative journalism, the article particularly examines the model of watchdog journalism and the extent to which this model can be applied to the role performance of the Press in times of crisis. Using framing analysis, this article aims to examine the way(s) in which these negotiations were communicated to the public through the Press. By identifying the specific frames they used, we attempt to investigate the possible relation(s) of the specific representations to the political/ideological orientation of each newspaper. The initial research question for this study is the following: Did the orientation of the newspapers examined steer their coverage of the crisis in general and what is the link (if any) with watchdog journalism?