bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1
Authors: Smith Matthew , De Bono Johann , Sternberg Cora , Le Moulec Sylvestre , Oudard Stéphane , De Giorgi Ugo , Krainer Michael , Bergman Andries , Hoelzer Wolfgang , De Wit Ronald , Bögemann Martin , Saad Fred , Cruciani Giorgio , Thiery-Vuillemin Antoine , Feyerabend Susan , Miller Kurt , Houédé Nadine , Hussain Syed , Lam Elaine , Polikoff Jonathan , Stenzl Arnulf , Mainwaring Paul , Ramies David , Hessel Colin , Weitzman Aaron , Fizazi Karim 
Published: July 2016

Purpose Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC. Patients and Methods Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day. The primary end point was overall survival (OS). Bone scan response (BSR) at week 12 as assessed by independent review committee was the secondary end point; radiographic progression-free survival (rPFS) and effects on circulating tumor cells (CTCs), bone biomarkers, serum prostate-specific antigen (PSA), and symptomatic skeletal events (SSEs) were exploratory assessments. Results A total of 1,028 patients were randomly assigned to cabozantinib (n = 682) or prednisone (n = 346). Median OS was 11.0 months with cabozantinib and 9.8 months with prednisone (hazard ratio, 0.90; 95% CI, 0.76 to 1.06; stratified log-rank P = .213). BSR at week 12 favored cabozantinib (42% v 3%; stratified Cochran-Mantel-Haenszel P < .001). rPFS was improved in the cabozantinib group (median, 5.6 v 2.8 months; hazard ratio, 0.48; 95% CI, 0.40 to 0.57; stratified log-rank P < .001). Cabozantinib was associated with improvements in CTC conversion, bone biomarkers, and post–random assignment incidence of SSEs but not PSA outcomes. Grade 3 to 4 adverse events and discontinuations because of adverse events were higher with cabozantinib than with prednisone (71% v 56% and 33% v 12%, respectively). Conclusion Cabozantinib did not significantly improve OS compared with prednisone in heavily treated patients with mCRPC and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving BSR, rPFS, SSEs, CTC conversions, and bone biomarkers but not PSA outcomes.
Association of Chromosome 1q Gain With Inferior Survival in Favorable-Histology Wilms Tumor: A Report From the Children’s Oncology Group
Authors: Gratias Eric J. , Dome Jeffrey S. , Jennings Lawrence J. , Chi Yueh-Yun , Tian Jing , Anderson James , Grundy Paul , Mullen Elizabeth A. , Geller James I. , Fernandez Conrad V. , Perlman Elizabeth J. 
Published: July 2016

PurposeThe goal of this study was to analyze the association of copy number gain of 1q in favorable-histology Wilms tumors (FHWTs) with event-free survival (EFS) and overall survival (OS) within each tumor stage and with 1p and 16q copy number loss and/or loss of heterozygosity.MethodsUnilateral FHWTs from 1,114 patients enrolled in National Wilms Tumor Study-5 that were informative for 1p and 16q microsatellite markers (previously determined) and informative for 1q gain, 1p loss, and 16q loss using multiplex ligation-dependent probe amplification were analyzed.ResultsEight-year EFS was 86% (95% CI, 84% to 88%) for the entire cohort. Of 1,114 patients, 317 tumors (28%) displayed 1q gain. Eight-year EFS was 77% for those with 1q gain and 90% for those lacking 1q gain (P < .001). Eight-year OS was 88% for those with 1q gain and 96% for those lacking 1q gain (P < .001). Within each disease stage, 1q gain was associated with inferior EFS (stage I, 85% v 95%; P = .0052; stage II, 81% v 87%; P = .0775; stage III, 79% v 89%; P = .01; stage IV, 64% v 91%; P = .001). OS was significantly inferior in patients with stage I (P < .0015) and stage IV disease (P = .011). With multivariable analysis, 1q gain was associated with an increased relative risk of relapse of 2.4 (P < .001), whereas 1p loss was not, despite significance on univariable analysis.ConclusionGain of 1q is associated with inferior survival in unilateral FHWTs and may be used to guide risk stratification in future studies.
Variations in Oncologist Recommendations for Chemotherapy for Stage IV Lung Cancer: What Is the Role of Performance Status?
Authors: Tisnado Diana , Malin Jennifer , Kahn Katherine , Landrum Mary Beth , Fletcher Robert , Klabunde Carrie , Clauser Steven , Rogers Selwyn O. , Keating Nancy L. 
Published: July 2016

Purpose: Chemotherapy prolongs survival in patients with advanced non–small-cell lung cancer. However, few studies have included patients with poor performance status. This study examined rates of oncologists’ recommendations for chemotherapy by patient performance status and symptoms and how physician characteristics influence chemotherapy recommendations. Methods: We surveyed medical oncologists involved in the care of a population-based cohort of patients with lung cancer from the CanCORS (Cancer Care Outcomes Research and Surveillance) study. Physicians were queried about their likelihood to recommend chemotherapy to patients with stage IV lung cancer with varying performance status (Eastern Cooperative Oncology Group performance status 0 [good] v 3 [poor]) and presence or absence of tumor-related pain. Repeated measures logistic regression was used to estimate the independent associations of patients’ performance status and symptoms and physicians’ demographic and practice characteristics with chemotherapy recommendations. Results: Nearly all physicians (adjusted rate, 97% to 99%) recommended chemotherapy for patients with good performance status, and approximately half (adjusted rate, 38% to 53%) recommended chemotherapy for patients with poor performance status (P < .001). Compared with patient factors, physician and practice characteristics were less strongly associated with chemotherapy recommendations in adjusted analyses. Conclusion: Strong consensus among oncologists exists for chemotherapy in patients with advanced non–small-cell lung cancer and good performance status. However, the relatively high rate of chemotherapy recommendations for patients with poor performance status despite the unfavorable risk–benefit profile highlights the need for ongoing work to define high-value care in oncology and to implement and evaluate strategies to align incentives for such care.
Relationships Among Financial Distress, Emotional Distress, and Overall Distress in Insured Patients With Cancer
Authors: Meeker Caitlin R. , Geynisman Daniel M. , Egleston Brian L. , Hall Michael J. , Mechanic Karen Y. , Bilusic Marijo , Plimack Elizabeth R. , Martin Lainie P. , von Mehren Margaret , Lewis Bianca , Wong Yu-Ning 
Published: July 2016

Purpose: Recent studies have demonstrated increasing rates of financial toxicities and emotional distress related to cancer treatment. This study assessed and characterized the relationships among financial distress, emotional symptoms, and overall distress in patients with cancer. Methods: A cross-sectional sample of patients with cancer who visited our outpatient medical oncology and psychiatry clinics completed a pen-and-paper survey. The survey assessed demographics; cost concerns; and financial, emotional, and overall distress. Results: One hundred twenty insured patients completed the survey. Sixty-five percent reported clinically significant overall distress scores, with the same percentage reporting at least one emotional problem (worry, anxiety, depression, etc). Twenty-nine percent scored in the range of high to overwhelming financial distress. By using structural equation modeling, we found that financial distress was associated with overall distress. This association was both direct (accounting for 76% of the effect) and indirect (accounting for 24% of the effect) via mediation by emotional distress. Conclusion: This cohort of patients with cancer reported significant levels of emotional distress, financial distress, and overall distress. These factors were interrelated, with both financial and emotional distress contributing to overall distress. Interventions targeted at alleviating financial distress may help to decrease levels of overall distress.
Positron Emission Tomography–Computed Tomography (PET-CT) Versus No PET-CT in the Management of Potentially Resectable Colorectal Cancer Liver Metastases: Cost Implications of a Randomized Controlled Trial
Authors: Serrano Pablo E. , Gafni Amiram , Gu Chu-Shu , Gulenchyn Karen Y. , Julian Jim A. , Law Calvin , Hendler Aaron L. , Moulton Carol-Anne , Gallinger Steven , Levine Mark N. 
Published: July 2016

Purpose: To evaluate whether positron emission tomography (PET) combined with computed tomography (PET-CT) is cost saving, or cost neutral, compared with conventional imaging in management of patients with resectable colorectal cancer liver metastases. Methods: Cost evaluation of a randomized trial that compared the effect of PET-CT on surgical management of patients with resectable colorectal cancer liver metastases. Health care use data ≤ 1 year after random assignment was obtained from administrative databases. Cost analysis was undertaken from the perspective of a third-party payer (ie, Ministry of Health). Mean costs with 95% credible intervals (CrI) were estimated by using a Bayesian approach. Results: The estimated mean cost per patient in the 263 patients who underwent PET-CT was $45,454 CAD (range, $1,340 to $181,420) and in the 134 control patients, $40,859 CAD (range, $279 to $293,558), with a net difference of $4,327 CAD (95% CrI, −$2,207 to $10,614). The primary cost driver was hospitalization for liver surgery (difference of $2,997 CAD for PET-CT; 95% CrI, −$2,144 to $8,010), which was mainly a result of a longer length of hospital stay for the PET-CT arm (median, 7 v 6 days; P = .03) and a higher postoperative complication rate (20% v 10%; P = .01). Baseline characteristics were similar between groups, including the number of liver segments involved with cancer, number of segments resected, and type of liver resection performed. No difference in survival was detected between arms. Conclusion: PET-CT was associated with limited clinical benefit and a nonsignificant increased cost. Universal funding of PET-CT in the management of patients with resectable colorectal cancer liver metastases does not seem justified.
Survival and Toxicity After Cisplatin Plus Etoposide Versus Carboplatin Plus Etoposide for Extensive-Stage Small-Cell Lung Cancer in Elderly Patients
Authors: Hatfield Laura A. , Huskamp Haiden A. , Lamont Elizabeth B. 
Published: July 2016

Purpose:Elderly patients with cancer are under-represented in clinical trials and risk greater toxicity from chemotherapy. These patients and their physicians need better evidence to decide among guideline-recommended regimens. We test whether patients with extensive-stage small-cell lung cancer (ES SCLC) have noninferior survival and less hospital-based health care after carboplatin/etoposide compared with cisplatin/etoposide.Methods:We analyzed SEER-Medicare data for beneficiaries with ES SCLC diagnosed at age 67 years and older between 1995 and 2009. Among patients treated with first-line chemotherapy in the ambulatory setting, 831 received cisplatin/etoposide and 2,846 received carboplatin/etoposide. Propensity score matching (2:1 ratio) yielded 778 cisplatin/etoposide and 1,502 carboplatin/etoposide patients.Results:Survival was nearly identical in the two groups: 35.7 weeks for cisplatin/etoposide and 35.9 weeks for carboplatin/etoposide. The hazard ratio of 1 (95% CI, 0.91 to 1.09) excluded our prespecified threshold, indicating noninferiority. Mortality at 6 months was indistinguishable: 35% for cisplatin/etoposide and 34% for carboplatin/etoposide. After carboplatin/etoposide, patients were less likely to be admitted to a hospital (80% v 86%, P < .001) and had fewer hospitalizations (median 1 v 2, odds ratio 0.76, 95% CI, 0.65 to 0.9), ED visits (median 1 v 2, odds ratio 0.82, 95% CI, 0.7 to 0.96), and ICU stays (median 0 v 0, odds ratio 0.82, 95% CI, 0.69 to 0.99).Conclusion:First-line carboplatin/etoposide is associated with similar survival and less subsequent hospital-based health care use than cisplatin/etoposide among elderly patients with ES SCLC treated in ambulatory settings.
Focal adhesion kinase is required for actin polymerization and remodeling of the cytoskeleton during sperm capacitation
Authors: Roa-Espitia Ana L. , Hernández-Rendón Eva R. , Baltiérrez-Hoyos Rafael , Muñoz-Gotera Rafaela J. , Cote-Vélez Antonieta , Jiménez Irma , González-Márquez Humberto , Hernández-González Enrique O. 
Published: July 2016

ABSTRACTSeveral focal adhesion proteins are known to cooperate with integrins to link the extracellular matrix to the actin cytoskeleton; as a result, many intracellular signaling pathways are activated and several focal adhesion complexes are formed. However, how these proteins function in mammalian spermatozoa remains unknown. We confirm the presence of focal adhesion proteins in guinea pig spermatozoa, and we explore their role during capacitation and the acrosome reaction, and their relationship with the actin cytoskeleton. Our results suggest the presence of a focal adhesion complex formed by β1-integrin, focal adhesion kinase (FAK), paxillin, vinculin, talin, and α-actinin in the acrosomal region. Inhibition of FAK during capacitation affected the protein tyrosine phosphorylation associated with capacitation that occurs within the first few minutes of capacitation, which caused the acrosome reaction to become increasingly Ca2+ dependent and inhibited the polymerization of actin. The integration of vinculin and talin into the complex, and the activation of FAK and paxillin during capacitation, suggests that the complex assembles at this time. We identify that vinculin and α-actinin increase their interaction with F-actin while it remodels during capacitation, and that during capacitation focal adhesion complexes are structured. FAK contributes to acrosome integrity, likely by regulating the polymerization and the remodeling of the actin cytoskeleton.
A STUDY OF THE UNDERGROWTH VEGETATION OF SEMPU ISLAND, EAST JAVA, INDONESIA
Authors: SADILI ASEP , KARTAWINATA KUSWATA 
Published: July 2016

SADILI, A. & KARTAWINATA, K. 2016. A study of the undergrowth vegetation of Sempu Island, East Java, Indonesia. Reinwardtia 15(1): 1 - 9. — A study of forest floor vegetation in coastal forest (site 1) and inland lowland forest (site 2) was carried out at the Sempu Island Nature Reserve, Malang Regency, East Java. The objective of the study is to obtain data on plant species diversity, species composition and structure of the forest floor vegetation. In each site the vegetation was sampled with a plot of 1 m × 50 m, which was divided into 50 subplots of 1 m × 1 m each. Overall from the two plots we recorded 59 species, 57 genera and 39 families. Shannon-Wienner diversity indices (H’) were relatively high. i.e., 4.47 in Plot 1 and 3.2 in Plot 2, with a mean of 3.84. The number of the seedlings of shrubs and trees was greater than that of the herbaceous species. The families having the highest number of species were Euphorbiaceae (6 species) and Fabaceae (5 species). Based on dominant species the vegetation in Plot 1 was designated as Scleria lithosperma-Asystasia nemorum community type, while in Plot 2 Pterospermum javanicum-Knema sp. community type. The similarity index between these community types was only 18%. Only P. javanicum showed a good regeneration and the regeneration of other species in the two community types was poor, indicating unclear floristic changes in the forest of the Sempu Island.
REGENERATION STRATEGIES OF PALMS (ARECACEAE) IN RESPONSE TO CYCLONIC DISTURBANCES
Authors: LATIFAH DIAN , CONGDON ROBERT A. , HOLTUM JOSEPH A. 
Published: July 2016

LATIFAH, D., CONGDON, R. A. & HOLTUM, J. A. 2016. Regeneration strategies of palms (Arecaceae) in response to cyclonic disturbances. Reinwardtia 15 (1): 43 ? 59. — Tropical cyclones may act as important ecological drivers in northern Australia including north Queensland, as several cyclones impact this region each year between November and May. Extensive research has been conducted to investigate how regeneration of rainforest plant communities respond to frequent cyclonic disturbances. However, there have been few such studies on palms although they are important components of many rainforests. This research aimed to investigate the effects of canopy gaps following cyclonic disturbance (case study: Cyclone Larry) on regeneration of Arenga australasica (H. Wendl. & Drude) S. T. Blake ex H. E. Moore, Calamus australis Mart., C. moti F. M. Bailey, Hydriastele wendlandiana (F. Muell.) H. Wendl. & Drude and Licuala ramsayi var. ramsayi (F. Muell.) H. Wendl. & Drude. The field research was carried out at five sites in three areas located in northern Queensland: Tam O’Shanter/Djiru National Park, Clump Mountain National Park and Kurrimine Beach Conservation Park. Observations were made of recruitment, growth rate, leaf turnover and life history. We found that responses of palm regeneration following cyclonic disturbance varied among study sites; however, the recruitment of several species was favoured in gaps created by cyclones. The results also provide information on the various stages in the life cycle of the study palms.
Limits in 𝒫ℳℱ of Teichmüller geodesics
Authors: Chaika Jon , Masur Howard , Wolf Michael 
Published: July 2016

Abstract
In this paper we consider the limit set in Thurston’s compactification

𝒫
⁢
ℳ
⁢
ℱ

{\mathcal{P}\kern-2.27622pt\mathcal{M}\kern-0.284528pt\mathcal{F}}

of Teichmüller space of some Teichmüller geodesics defined by quadratic differentials with minimal but not uniquely ergodic vertical foliations.
We show that
(a) there are quadratic differentials so that the limit set of the geodesic
is a unique point,
(b) there are quadratic differentials so that the limit set is a line segment,
(c) there are quadratic differentials so that the vertical foliation is ergodic and there is a line segment as limit set, and
(d) there are quadratic differentials so that the vertical foliation is ergodic and there is a unique point as its limit set.
These give examples of divergent Teichmüller geodesics whose limit sets overlap and Teichmüller geodesics that
stay a bounded distance apart but whose limit sets are not equal. A byproduct of our methods is a construction of a Teichmüller geodesic and a simple closed curve γ so that the hyperbolic length of the geodesic in the homotopy class of γ varies between increasing and decreasing on an unbounded sequence of time intervals along the geodesic.
Rational connectivity and analytic contractibility
Authors: Brown Morgan , Foster Tyler 
Published: July 2016

Abstract
Let

k

{{k}}

be an algebraically closed field of characteristic 0, and let

f
:

X
→
Y

{f:X\to Y}

be a morphism of smooth projective varieties over the ring

k
⁢

(

(
t
)

)

{k((t))}

of formal Laurent series. We prove that if a general geometric fiber of f is rationally connected, then the induced map

f
an

:

X
an

→

Y
an

{f^{\mathrm{an}}:X^{\mathrm{an}}\to Y^{\mathrm{an}}}

between the Berkovich analytifications of X and Y is a homotopy equivalence. Two important consequences of this result are that the Berkovich analytification of any

ℙ
n

{\mathbb{P}^{n}}

-bundle over a smooth projective

k
⁢

(

(
t
)

)

{k((t))}

-variety is homotopy equivalent to the Berkovich analytification of the base, and that the Berkovich analytification of a rationally connected smooth projective variety over

k
⁢

(

(
t
)

)

{k((t))}

is contractible.
Working out multiword verbs within an Applied Cognitive Construction Grammar framework
Authors: Torres-Martínez Sergio 
Published: July 2016

AbstractThis article presents a constructionist approach to the teaching of multiword verbs. To that end, I outline a pedagogical model, Applied Cognitive Construction Grammar (ACCxG), which is deemed to provide insight into a novel classification of multiword verbs as constructions (form-function pairings). The ACCxG framework integrates four cognitively-driven rationales, namely Focus on Form, Task-based Language Teaching, Data-driven Learning, and Paper-based Data-Driven Learning. It is argued that the syntax-semantics of multiword verbs can be better understood through recourse to their relation with syntactic constructions (Argument Structure Constructions). Endorsing this rationale entails, among other things, the recognition that the same general cognitive mechanisms intervening in the construction of our experience of the world are at play during the construction of linguistic knowledge.
Recht auf Vergessen und piercing the corporate veil zugleich Anmerkungen zur Google-Entscheidung des EuGH, Rs. C-131/12 Google Spain SL und Google Inc.
Authors: Schmidt-Kessel Martin , Langhanke Carmen , Gläser Isabel , Herden Hannah Kathrin 
Published: July 2016

AbstractWith its decision in the Google-case, the Court has put essential ground rules of EU data protection law in concrete terms. It has thereby deviated in several ways from leading opinions in legal writing which may partly be due to the fact that these are not free of personal involvement. More importantly though seems the conclusion that this decision underlines in many respects that theoretical patterns of EU private law are different from those of the traditional national law - and this divergence also holds true for major parts of the public law and, of course, data protection law. The Court has interpreted the responsibility with regard to data protection law and also the criteria in Art. 4 of the Directive very broadly, which has not met with general approval before. The ECJ strictly orientated itself by the general concept that even the search engine operator requires a permit for the processing of data. This in mind, it has given the fundamental right of data protection an important role in its considering in contrast to the user’s interest in respect of use of the service and the economic interests of the operator