bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pediatric trial of radiation/cetuximab followed by irinotecan/cetuximab in newly diagnosed diffuse pontine gliomas and high‐grade astrocytomas: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study
Authors: Macy Margaret E. , Kieran Mark W. , Chi Susan N. , Cohen Kenneth J. , MacDonald Tobey J. , Smith Amy A. , Etzl Michael M. , Kuei Michele C. , Donson Andrew M. , Gore Lia , DiRenzo Jennifer , Trippett Tanya M. , Ostrovnaya Irina , Narendran Aru , Foreman Nicholas K. , Dunkel Ira J. 
Published: May 2017

AbstractBackgroundDiffuse intrinsic pontine gliomas (DIPGs) and high‐grade astrocytomas (HGA) continue to have dismal prognoses. The combination of cetuximab and irinotecan was demonstrated to be safe and tolerable in a previous pediatric phase 1 combination study. We developed this phase 2 trial to investigate the safety and efficacy of cetuximab given with radiation therapy followed by adjuvant cetuximab and irinotecan.MethodsEligible patients of age 3–21 years had newly diagnosed DIPG or HGA. Patients received radiation therapy (5,940 cGy) with concurrent cetuximab. Following radiation, patients received cetuximab weekly and irinotecan daily for 5 days per week for 2 weeks every 21 days for 30 weeks. Correlative studies were performed. The regimen was considered to be promising if the number of patients with 1‐year progression‐free survival (PFS) for DIPG and HGA was at least six of 25 and 14 of 26, respectively.ResultsForty‐five evaluable patients were enrolled (25 DIPG and 20 HGA). Six patients with DIPG and five with HGA were progression free at 1 year from the start of therapy with 1‐year PFS of 29.6% and 18%, respectively. Fatigue, gastrointestinal complaints, electrolyte abnormalities, and rash were the most common adverse events and generally of grade 1 and 2. Increased epidermal growth factor receptor copy number but no K‐ras mutations were identified in available samples.ConclusionsThe trial did not meet the predetermined endpoint to deem this regimen successful for HGA. While the trial met the predetermined endpoint for DIPG, overall survival was not markedly improved from historical controls, therefore does not merit further study in this population.
The use of antifibrinolytics in pediatric patients with hypoproliferative thrombocytopenia
Authors: Delaney Meghan , Matthews Dana C. , Gernsheimer Terry B. 
Published: May 2017

AbstractDespite the use of evidence‐based platelet transfusion therapy during periods of hypoproliferative thrombocytopenia, a large proportion of pediatric hematology/oncology patients continue to suffer from clinically significant bleeding. Antifibrinolytic (AF) drugs have been shown in certain surgical and trauma settings to decrease bleeding, blood transfusion, and improve survival. We conducted a retrospective assessment of the safety of using AF drugs in pediatric patients with hypoproliferative thrombocytopenia at our center as well as the impact on bleeding occurrence and severity.
Severe cytokine release syndrome in a patient receiving PD‐1‐directed therapy
Authors: Rotz Seth J. , Leino Daniel , Szabo Sara , Mangino Jennifer L. , Turpin Brian K. , Pressey Joseph G. 
Published: May 2017

AbstractCytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T‐cell engaging immunotherapy. Checkpoint blockade using anti‐programmed cell death 1 (anti‐PD‐1) inhibitors is an approach to antitumor immune system stimulation. A 29‐year‐old female with alveolar soft part sarcoma developed severe CRS after treatment with anti‐PD‐1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin‐6 inhibitor tocilizumab and corticosteroids.
Differential protein expression in exosomal samples taken from trauma patients
Authors: Moyron Ron B. , Gonda Amber , Selleck Matthew J. , Luo‐Owen Xian , Catalano Richard D , O'Callahan Thomas , Garberoglio Carlos , Turay David , Wall Nathan R. 
Published: May 2017

AbstractTraumatic brain injuries (TBI) are among the most misdiagnosed and underreported types of head trauma. The potential long‐term impact of undiagnosed or incorrectly identified concussions and other head injuries are potentially devastating, as evidenced by the increasing societal burden exhibited by soldiers returning from combat and athletes in contact sports. Concussions and TBI are notoriously difficult to correctly diagnose and prognosis for these injuries is poorly understood. In order to increase the likelihood of successful diagnosis, treatment, and prediction of outcomes, a definitive differential diagnosis will need to be established. The establishment of a “trauma–specific profile” or a panel of known trauma markers will significantly aid in this goal. Small membrane vesicles called exosomes have been shown to contain proteins and injury‐specific biomarkers. In the future it is possible that they could become an important tool, utilized for their diagnostic and therapeutic potential.
Pyrethroid resistance associated with M918 L mutation and detoxifying metabolism in Aphis gossypii from Bt cotton growing regions of China
Authors: Chen Xuewei , Tie Minyuan , Chen Anqi , Ma Kangsheng , Li Fen , Liang Pingzhuo , Liu Ying , Song Dunlun , Gao Xiwu 
Published: May 2017

AbstractBACKGROUNDThe cotton aphid, Aphis gossypii (Glover), is a destructive pest that affects numerous crops throughout the world. Pyrethroid resistance has become endemic in A. gossypii populations in the cotton growing areas of China due to wide‐ spread application of insecticides. To assess the extent of pyrethroid resistance, bioassays were conducted on field populations collected from several cotton cultivation areas from 2010 to 2015. The frequency of a known resistance‐associated sodium channel mutation (M918 L) in A. gossypii was evaluated and the bioassay of bifenthrin with or without the synergist was performed to illuminate the mechanisms underlying resistance to pyrethroids.RESULTSThe field populations exhibited very high levels of resistance to both beta‐cypermethrin and deltamethrin. Pretreatment with synergists, DEF and PBO, significantly increased the toxicity of bifenthrin to cotton aphid populations collected from Bt cotton fields in China. Further, 96.8–100% of individuals with the M918 L mutation (including both RR and RS individuals) were observed in various populations, and only 2.8–3.2% of individuals with wild‐type homozygotes (SS) were detected.CONCLUSIONThe mutation M918 L in the voltage‐gated sodium channel along with detoxifying metabolism was contributed to the pyrethroid resistance in the field populations of Aphis gossypii from cotton growing regions of China. And insecticides with different modes of action should be recommended for the control of A. gossypii in the future. © 2017 Society of Chemical Industry
Protection status and national socio‐economic context shape land conversion in and around a key transboundary protected area complex in West Africa
Authors: Schulte to Bühne Henrike , Wegmann Martin , Durant Sarah M. , Ransom Chris , de Ornellas Paul , Grange Sophie , Beatty Hope , Pettorelli Nathalie 
Published: May 2017

AbstractTransboundary cooperation is being promoted as an effective way to conserve biodiversity that straddles national borders. However, monitoring the ecological outcomes of these large‐scale endeavours is challenging, and as a result, the factors and processes likely to shape their effectiveness remain poorly identified and understood. To address this knowledge gap, we tested three hypotheses pertaining to natural vegetation loss across the W‐Arly‐Pendjari protected area complex, a key biodiversity hotspot in West Africa. Using a new methodology to compare land cover change across large remote areas where independent validation data is unevenly distributed across time, we demonstrate widespread agricultural expansion outside protected areas over the past 13 years. Protected areas with high protection status appear considerably more effective at preventing land conversion than other protected areas. We moreover report marked differences in cropland expansion rates between countries, which we suggest may be linked to differences in rural population growth. Altogether, our results suggest that there can be considerable spatial heterogeneity in anthropogenic pressure across transboundary protected area complexes and call for more comprehensive assessments that capitalize on the current availability of remote sensing information.
Seismic assessment of concrete buildings reinforced with shape memory alloy materials in different stories
Authors: Shiravand M. R. , Nashtaee M. A. , Veismoradi S. 
Published: May 2017

SummaryShape memory alloy (SMA) is a unique material with many beneficial characteristics such as superelasticity and excellent resistance against corrosion. However, the high expenses related to the material costs and difficulties associated with implementation of SMAs in reinforced concrete (RC) structures may limit their usage. To decrease the costs related to SMA installation, this paper investigates the seismic performance of RC moment‐resisting frames with the intention of specifying the optimal stories for SMA utilization. To this end, RC frames with 3, 5, 7, and 9 stories are modeled and various cases are considered for SMA locations in different story levels. For each building, 4 different cases are considered including a frame with regular steel reinforcement (Steel), a frame with SMAs in all story levels (full SMA), and 2 remaining cases consist of frames with SMAs in bottom and middle story levels only. In the first part, nonlinear dynamic time history analyses are conducted to evaluate the base shear, roof displacement, interstory, and residual drift demands of the structures using 10 ground‐motion records. In the second part, the incremental dynamic analysis is employed to assess the entire range of structural dynamic behavior. By using the generated data from incremental dynamic analysis procedure, fragility evaluation is conducted on multiple limit states to provide a comprehensive performance assessment for each case. The results indicate that frames with SMA in their lower story levels performed similar to frames equipped with SMA in all story levels. However, the fragility assessments show the better performance of frames with SMA in their bottom stories versus other cases. On this basis, the costs associated with SMA fabrication could be reduced noticeably (nearly two‐thirds) without sacrificing the overall performance of the frame and its post‐earthquake serviceability.
Will the Paris Agreement accelerate the pace of change?
Authors: Morgan Jennifer , Northrop Eliza 
Published: May 2017

Since adoption of the Kyoto Protocol under the United Nations Framework Convention on Climate Change in 1997, the international climate regime has been caught in stasis. Due to a lack of direction and clarity at the policy level and deep political divides, the evolution of the international climate regime under the United Nations Framework Convention on Climate Change (UNFCCC) had failed to catch up with the changes occurring in the real economy. The momentum created ahead of COP21 in 2015 and resulting Paris Agreement has changed this, creating a new paradigm of international climate policy, politics and cooperation that is, if implemented, capable of generating the momentum needed to accelerate the pace of change and drive transformation. This new paradigm that emerged from the Paris Agreement, demonstrates the role of the United Nations in giving voice to smaller countries to create effective positive powerful coalitions and the need to invite the outside world into the process through greater participation of cities, business, investors and other non‐state actors. We outline the main policy and political shifts that the Paris Agreement represents, and explain why this new paradigm of international climate policy, politics and cooperation is key to accelerating the pace of change and keeping the world well below 2°C, and optimally 1.5°C. WIREs Clim Change 2017, 8:e471. doi: 10.1002/wcc.471This article is categorized under:

Policy and Governance > International Policy Framework
Global sensitivity analysis of the blade geometry variables on the wind turbine performance
Authors: Echeverría Fernando , Mallor Fermín , San Miguel Unai 
Published: May 2017

AbstractThe need for implementing efficient blade designs gains relevance as wind turbine developments require longer blades. The design of blade geometry, traditionally divided in 2D airfoils and spanwise distributions, is usually addressed as an optimization problem. A correct identification of the design variables is crucial to avoid unnecessary computational cost or insufficient exploration of the design space. This paper deals with the identification of the design variables that affect the wind turbine performance.First, the number of design variables for an accurate airfoil representation is resolved. A methodology, based on statistical hypothesis testing applied to the airfoil approximation errors, is presented to assess the accuracy of types of B‐splines.Second, the study is extended to chord and twist distributions besides airfoil geometry with the purpose of assessing the sensitive blade variables in the wind turbine performance. Global sensitivity analysis as multi‐variable linear regressions and variance‐based methods are used. Latin hypercube sampling is applied to generate efficient inputs. MATLAB‐based code is developed to obtain outputs: annual energy production, maximum blade tip deflection, overall sound power level and blade mass.As result of the study, a list of non‐affecting variables is deduced. These variables can be avoided in the optimization without loss of gain in the performance. The method is a powerful tool to analyse in a preliminary phase a design problem involving a high amount of variables and complex physical relations by means of combining different multi‐disciplinar calculation codes and performing statistical treatments. Copyright © 2017 John Wiley & Sons, Ltd.
Metabolic engineering of Saccharomyces cerevisiae for production of germacrene A, a precursor of beta-elemene
Authors: Hu Yating , Zhou Yongjin J , Bao Jichen , Huang Luqi , Nielsen Jens , Krivoruchko Anastasia 
Published: May 2017

Abstract
Beta-elemene, a sesquiterpene and the major component of the medicinal herb Curcuma wenyujin, has antitumor activity against various types of cancer and could potentially serve as a potent antineoplastic drug. However, its current mode of production through extraction from plants has been inefficient and suffers from limited natural resources. Here, we engineered a yeast cell factory for the sustainable production of germacrene A, which can be transformed to beta-elemene by a one-step chemical reaction in vitro. Two heterologous germacrene A synthases (GASs) converting farnesyl pyrophosphate (FPP) to germacrene A were evaluated in yeast for their ability to produce germacrene A. Thereafter, several metabolic engineering strategies were used to improve the production level. Overexpression of truncated 3-hydroxyl-3-methylglutaryl-CoA reductase and fusion of FPP synthase with GAS, led to a sixfold increase in germacrene A production in shake-flask culture. Finally, 190.7 mg/l of germacrene A was achieved. The results reported in this study represent the highest titer of germacrene A reported to date. These results provide a basis for creating an efficient route for further industrial application re-placing the traditional extraction of beta-elemene from plant sources.
“It was a lot Tougher than I Thought It would be”. A Qualitative Study on the Changing Nature of Being a Hemophilia Carrier
Authors: von der Lippe Charlotte , Frich Jan C. , Harris Anna , Solbrække Kari Nyheim 
Published: May 2017

AbstractStudies on carriers of genetic disorders mainly focus on the process of genetic testing and reproductive choices, and less on how psychosocial aspects of being a carrier change over time. Our study sought to understand more about the psychosocial aspects of hemophilia carrier status, and thereby improve counseling aiming to advance carriers’ quality of life and well‐being. We analyzed 16 in‐depth interviews from women who were carriers of hemophilia and had a son with hemophilia. Three themes emerged: Guilt and sorrow across generations; the choices and future consequences of genetic testing; and preparing to have a child with hemophilia. Experience with being a hemophilia carrier is a process that changes over time while feelings of guilt and sorrow run across generations. The carrier status may create “mothers‐in‐waiting” living at risk of having a sick child or not. The women think they are prepared to have a son with hemophilia, but experience more sadness than they expect when a son is diagnosed. Our findings suggest that health professionals, especially clinical geneticists and genetic counselors, carriers, families and patient organizations need to be aware that women's experiences of being a carrier of hemophilia changes during the biographical life course. The women may benefit from several rounds of genetic counseling at different stages of life.
Outcomes Following Operative Treatment of Adolescent Mallet Fractures
Authors: Chen Andrew T. , Conry Keegan T. , Gilmore Allison , Son-Hing Jochen P. , Liu Raymond W. 
Published: May 2017

Background Many surgeons advocate for surgical intervention of adult mallet fractures that involve either subluxation of the distal interphalangeal (DIP) joint or those that involve more than one-third of the articular surface. However, the efficacy of operative treatment and complication rates are unclear regarding the adolescent population. Questions/Purposes The goal of this study is to evaluate the clinical outcomes following operative fixation of bony mallet fractures in the adolescent population. Methods Seventeen patients with bony mallet fractures treated surgically were retrospectively reviewed. Twelve patients were treated by closed reduction with extension block pinning. The other patients underwent an open reduction and pin fixation. The average age was 15.2 years (13–18). Most injuries were sport related. The average time from injury to presentation was 17 days and from injury to surgery was 24.5 days. Nine patients had subluxation at the DIP joint and all involved at least one-third of the articular surface. Results The average time from surgery to pin removal was 28 days (19–46). All distal phalanx physis were closed or nearly closed. One patient reported pain at the final follow-up. Two patients (11.8%) had major complications. One had an extension contracture postoperatively, did not attend therapy, and re-fractured 5 months later requiring reoperation. The second was treated delayed (32 days) and lost fixation, requiring revision surgery and antibiotics for a superficial infection. Two patients with delayed treatment (32 and 44 days) had an extensor lag (11.8%). Conclusions Operative treatment of mallet fractures with subluxation or involving more than one-third of the articular surface appears effective. Pin removal 4 weeks postoperatively appears adequate. Complications occurred with delayed presentation and non-compliance.
TESTIMONY, RECOVERY AND PLAUSIBLE DENIABILITY: A RESPONSE TO PEET
Authors: Davies Alex 
Published: May 2017

ABSTRACTAccording to telling based views of testimony (TBVs), B has reason to believe that p when A tells B that p because A thereby takes public responsibility for B's subsequent belief that p. Andrew Peet presents a new argument against TBVs. He argues that insofar as A uses context-sensitive expressions to express p, A doesn't take public responsibility for B's belief that p. Since context-sensitivity is widespread, the kind of reason TBVs say we have to believe what we're told, is not widespread. Peet doesn't identify any problem with his own argument though he does attempt to limit its sceptical potential by identifying special contexts in which TBVs stand a chance of success. A more general defence of TBVs can be provided by showing Peet's argument to be unsound. I argue that Peet's argument is unsound because it requires us to wrongly suppose that speakers do far less labour than their audiences in context-sensitive linguistic communication. I aim to show why – in the context of the epistemology of testimony and the philosophy of language – it's important to recognize the labour that speakers can do, and so can be held responsible for not doing, in episodes of context-sensitive linguistic communication.
Dynamics and Stability of Pinned-Free Micropipes Conveying Fluid
Authors: Hu K. , Dai H. L. , Wang L. , Qian Q. 
Published: May 2017

AbstractIn this paper, the dynamical behavior and stability of hanging micropipes conveying fluid with pinned-free boundary conditions are investigated. For a pinned-free rigid micropipe, the dynamical system is found to be stable for various flow velocities. Particular emphasis is placed on the effects of flow velocity, mass ratio and gravity on the dynamics and flutter instability of flexible micropipe system with pinned-free boundary conditions. The governing equations for flexible micropipes are discretized using the differential quadrature method (DQM), yielding a generalized eigenvalue problem which is then solved for various flow velocities, mass ratios and gravity parameters. It is shown that, with increasing flow velocity, the flexible micropipe with pinned-free boundary conditions is stable until it becomes unstable via a Hopf bifurcation leading to flutter. The system may lose stability first in the second or third mode, mainly depending on the selected value of mass ratio. The existence of mode exchange between the second and third modes is possible. The gravity parameter of positive values causes additional restoring force and hence enhances the stability of the micropipe system; however, it can generate the complexity of stability diagrams.
Holocene climatic and environmental change on the western Tibetan Plateau revealed by glycerol dialkyl glycerol tetraethers and leaf wax deuterium-to-hydrogen ratios at Aweng Co
Authors: Li Xiumei , Wang Mingda , Zhang Yuzhi , Lei Li , Hou Juzhi 
Published: May 2017

AbstractMean annual air temperature (MAAT) and precipitation isotope records for the Holocene were obtained from the analysis of the relative distribution of branched glycerol dialkyl glycerol tetraethers and compound-specific hydrogen isotope ratios of leaf waxes from a sediment core from Aweng Co on the western Tibetan Plateau (WTP). Our results indicate that the Indian monsoon mainly influenced Aweng Co during the Holocene. During the early Holocene, when summer insolation was at a maximum, the monsoonal influence was strong and the climate was warm and wet. Both the summer and winter insolation were relatively weak, and Aweng Co was cool and dry during the middle Holocene (6–3 ka), indicating a weakening of the Indian monsoon. The southward displacement of the Intertropical Convergence Zone and relatively low atmospheric methane content may have contributed to the middle Holocene cooling on the WTP. During the late Holocene, with a further increase in winter insolation and decrease in summer insolation, the summer monsoon weakened and the MAAT on the WTP gradually increased. Depleted leaf wax hydrogen isotope ratios during the late Holocene can be attributed to accelerated glacier melting because of the elevated MAAT.