bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing hormone therapy effects in two RCTs and two large observational studies that used similar methods for comprehensive data collection and outcome assessment
Authors: Hartz Arthur , He Tao , Wallace Robert , Powers John 
Published: July 2013

ObjectivesProspective observational studies (OSs) that collect adequate information about confounders can validly assess treatment consequences. However, what constitutes adequate information is unknown. This study investigated whether the extensive information collected by the Women's Health Initiative (WHI) in two OSs and two randomised controlled trials (RCTs) was adequate.DesignSecondary analysis of WHI data. Cox regression was used to select from all baseline risk factors those that best predicted outcome. Cox regression that included these risk factors was used for two types of analyses: (1) comparing RCT and OS assessments of the effects of hormone therapy on outcome for participants with specific characteristics and (2) evaluating whether adjustment for measured confounders could eliminate outcome differences among datasets.SettingThe WHI included more than 800 baseline risk factors and outcomes during a median follow-up of 8 years.Participants151 870 postmenopausal women ages 50–79.Primary and secondary outcome measuresMyocardial infarction and stroke.ResultsRCT and OS results differed for the association of hormone therapy with outcome after adjusting for confounding factors and stratifying on factors that were hypothesised to modulate the effects of hormone therapy (eg, age and time since menopause) or that empirically modulated the effects of hormone therapy in this dataset (eg, blood pressure, previous coronary revascularisation and private medical insurance). Some of the four WHI datasets had significantly worse outcomes than others even after adjusting for risk and stratifying by type of hormone therapy, for example, the risk-adjusted HR for myocardial infarction was 1.37 (p<0.0001) in an RCT placebo group compared with an OS group not taking hormone therapy.ConclusionsApparently the WHI did not collect sufficient information to give reliable assessments of treatment effects. If the WHI did not collect sufficient data, it is likely that few OSs collect sufficient information.
Development of intra-basaltic lava-field drainage systems within the Faroe–Shetland Basin
Authors: Schofield Nick , Jolley David W. 
Published: July 2013

The Faroe–Shetland Basin, located on the NW continental shelf of the UK, represents arguably the last frontier area of hydrocarbon exploration of the UK territorial waters. The basin contains an aerially extensive lava sequence, which forms part of the Palaeogene-aged North Atlantic Igneous Province (NAIP). In 2004, a major oil and gas discovery was made within the Palaeocene–Eocene lavas in the form of the Rosebank Field. Unusually, the reservoir intervals are a series of intra-basaltic fluvial clastic sequences separated by basalt lava flows, hyaloclastites and volcaniclastic sediments, giving rise to a new hydrocarbon play concept. The discovery has led to an increased emphasis on trying to understand the detailed stratigraphy of the offshore lava fields within the Faroe–Shetland Basin, as well as the nature of the regional intra-basaltic drainage systems and sediments that form the reservoir intervals in Rosebank.
In this paper we show a regional integrated three-dimensional (3D) seismic and well analysis of the lava sequences within the area of the Corona Ridge, exploring the age relationships and spatial distribution of the sequence T40 and T45 Palaeocene lava field. In particular, we note the occurrence of an intra-basaltic (sequence T40, Colsay Member) drainage network that appears to represent a major drainage pathway within the Faroe–Shetland Basin lava fields.
Few published studies have dealt with drainage system development on lava but our preliminary analysis appears to indicate that lava flow-field morphology plays a dominant role in controlling the development and evolution of a drainage system.
X-ray diffraction and field portable X-ray fluorescence analysis and screening of soils: project design
Authors: Bergslien Elisa T. 
Published: July 2013

Abstract
This paper presents the preliminary results of a study investigating the application of laboratory X-ray diffraction (XRD) and field portable X-ray fluorescence (XRF) analysis of soils as screening methods for forensic comparison and generalized provenancing. The study area is the Buffalo–Niagara metropolitan region in New York, a glacially draped area of the northeastern USA. For the initial stages of this study, soils are being collected from publicly accessible areas (parks, playgrounds, etc.) for mineralogical and elemental analysis. Initially, minimal sample preparation is being applied to create specimens. An investigation of the published literature reveals that there are a number of different suggested approaches for forensic application of XRD data, not all of which appear to be appropriate to the task at hand. The data being generated in this study are being used to build a reference set for comparison studies. In addition, two simulated forensic samples were collected to test the usefulness of XRD and XRF screening for determining possible regional source areas. For one sample this method was reasonably successful in identifying the general source area, while the results for the second sample were somewhat less satisfactory. In future additional sample handing and analysis protocols will be added.
EPR Oxygen Images Predict Tumor Control by a 50% Tumor Control Radiation Dose
Authors: Elas Martyna , Magwood Jessica M. , Butler Brandi , Li Chanel , Wardak Rona , DeVries Rebekah , Barth Eugene D. , Epel Boris , Rubinstein Samuel , Pelizzari Charles A. , Weichselbaum Ralph R. , Halpern Howard J. 
Published: July 2013

Abstract
Clinical trials to ameliorate hypoxia as a strategy to relieve the radiation resistance it causes have prompted a need to assay the precise extent and location of hypoxia in tumors. Electron paramagnetic resonance oxygen imaging (EPR O2 imaging) provides a noninvasive means to address this need. To obtain a preclinical proof-of-principle that EPR O2 images could predict radiation control, we treated mouse tumors at or near doses required to achieve 50% control (TCD50). Mice with FSa fibrosarcoma or MCa4 carcinoma were subjected to EPR O2 imaging and immediately radiated to a TCD50 or TCD50 ± 10 Gy. Statistical analysis was permitted by collection of approximately 1,300 tumor pO2 image voxels, including the fraction of tumor voxels with pO2 less than 10 mm Hg (HF10). Tumors were followed for 90 days (FSa) or 120 days (MCa4) to determine local control or failure. HF10 obtained from EPR images showed statistically significant differences between tumors that were controlled by the TCD50 and those that were not controlled for both FSa and MCa4. Kaplan–Meier analysis of both types of tumors showed that approximately 90% of mildly hypoxic tumors were controlled (HF10%&lt; 10%), and only 37% (FSA) and 23% (MCa4) tumors controlled if hypoxic. EPR pO2 image voxel distributions in these approximately 0.5 mL tumors provide a prediction of radiation curability independent of radiation dose. These data confirm the significance of EPR pO2 hypoxic fractions. The 90% control of low HF10 tumors argue that 0.5 mL subvolumes of tumors may be more sensitive to radiation and may need less radiation for high tumor control rates. Cancer Res; 73(17); 5328–35. ©2013 AACR.
No Effect of Exercise on Urinary 6-Sulfatoxymelatonin and Catecholamines in Young Women Participating in a 16-Week Randomized Controlled Trial
Authors: Arikawa Andrea Y. , Thomas William , Patel Sanjay R. , Kurzer Mindy S. 
Published: July 2013

Abstract
Background: Women with breast cancer have decreased levels of melatonin or its metabolite in plasma and/or urine.
Methods: We measured serum melatonin, urinary 6-sulfatoxymelatonin, catecholamines, and cortisol in 141 sedentary young female participants in a clinical trial comparing 150 min/wk aerobic exercise for 4 months to no-exercise controls. Demographics, health surveys, body composition, sleep quality, fitness levels, and blood and urine samples were obtained at baseline and 16 weeks.
Results: There were no differences between groups at baseline in demographics, exercise, sleep habits, or study hormones. There were also no significant differences between groups in any of the hormones at 16 weeks.
Conclusion: Sixteen weeks of exercise had minimal effects on melatonin secretion of young women.
Impact: There is convincing evidence that exercise protects against breast cancer, but this does not appear to occur through changes in melatonin secretion. Cancer Epidemiol Biomarkers Prev; 22(9); 1634–6. ©2013 AACR.
AZD3514: A Small Molecule That Modulates Androgen Receptor Signaling and Function In Vitro and In Vivo
Authors: Loddick Sarah A. , Ross Sarah J. , Thomason Andrew G. , Robinson David M. , Walker Graeme E. , Dunkley Tom P.J. , Brave Sandra R. , Broadbent Nicola , Stratton Natalie C. , Trueman Dawn , Mouchet Elizabeth , Shaheen Fadhel S. , Jacobs Vivien N. , Cumberbatch Marie , Wilson Joanne , Jones Rhys D.O. , Bradbury Robert H. , Rabow Alfred , Gaughan Luke , Womack Chris , Barry Simon T. , Robson Craig N. , Critchlow Susan E. , Wedge Stephen R. , Brooks A. Nigel 
Published: July 2013

Abstract
Continued androgen receptor (AR) expression and signaling is a key driver in castration-resistant prostate cancer (CRPC) after classical androgen ablation therapies have failed, and therefore remains a target for the treatment of progressive disease. Here, we describe the biological characterization of AZD3514, an orally bioavailable drug that inhibits androgen-dependent and -independent AR signaling. AZD3514 modulates AR signaling through two distinct mechanisms, an inhibition of ligand-driven nuclear translocation of AR and a downregulation of receptor levels, both of which were observed in vitro and in vivo. AZD3514 inhibited testosterone-driven seminal vesicle development in juvenile male rats and the growth of androgen-dependent Dunning R3327H prostate tumors in adult rats. Furthermore, this class of compound showed antitumor activity in the HID28 mouse model of CRPC in vivo. AZD3514 is currently in phase I clinical evaluation. Mol Cancer Ther; 12(9); 1715–27. ©2013 AACR.
BCL-2 Hypermethylation Is a Potential Biomarker of Sensitivity to Antimitotic Chemotherapy in Endocrine-Resistant Breast Cancer
Authors: Stone Andrew , Cowley Mark J. , Valdes-Mora Fatima , McCloy Rachael A. , Sergio C. Marcelo , Gallego-Ortega David , Caldon C. Elizabeth , Ormandy Christopher J. , Biankin Andrew V. , Gee Julia M.W. , Nicholson Robert I. , Print Cristin G. , Clark Susan J. , Musgrove Elizabeth A. 
Published: July 2013

Abstract
Overexpression of the antiapoptotic factor BCL-2 is a frequent feature of malignant disease and is commonly associated with poor prognosis and resistance to conventional chemotherapy. In breast cancer, however, high BCL-2 expression is associated with favorable prognosis, estrogen receptor (ER) positivity, and low tumor grade, whereas low expression is included in several molecular signatures associated with resistance to endocrine therapy. In the present study, we correlate BCL-2 expression and DNA methylation profiles in human breast cancer and in multiple cell models of acquired endocrine resistance to determine whether BCL-2 hypermethylation could provide a useful biomarker of response to cytotoxic therapy. In human disease, diminished expression of BCL-2 was associated with hypermethylation of the second exon, in a region that overlapped a CpG island and an ER-binding site. Hypermethylation of this region, which occurred in 10% of primary tumors, provided a stronger predictor of patient survival (P = 0.019) when compared with gene expression (n = 522). In multiple cell models of acquired endocrine resistance, BCL-2 expression was significantly reduced in parallel with increased DNA methylation of the exon 2 region. The reduction of BCL-2 expression in endocrine-resistant cells lowered their apoptotic threshold to antimitotic agents: nocodazole, paclitaxel, and the PLK1 inhibitor BI2536. This phenomenon could be reversed with ectopic expression of BCL-2, and rescued with the BCL-2 inhibitor ABT-737. Collectively, these data imply that BCL-2 hypermethylation provides a robust biomarker of response to current and next-generation cytotoxic agents in endocrine-resistant breast cancer, which may prove beneficial in directing therapeutic strategy for patients with nonresectable, metastatic disease. Mol Cancer Ther; 12(9); 1874–85. ©2013 AACR.
SF3B1 Mutations Are Associated with Alternative Splicing in Uveal Melanoma
Authors: Furney Simon J. , Pedersen Malin , Gentien David , Dumont Amaury G. , Rapinat Audrey , Desjardins Laurence , Turajlic Samra , Piperno-Neumann Sophie , de la Grange Pierre , Roman-Roman Sergio , Stern Marc-Henri , Marais Richard 
Published: July 2013

Abstract
Uveal melanoma, the most common eye malignancy, causes severe visual morbidity and is fatal in approximately 50% of patients. Primary uveal melanoma can be cured by surgery or radiotherapy, but the metastatic disease is treatment refractory. To understand comprehensively uveal melanoma genetics, we conducted single-nucleotide polymorphism arrays and whole-genome sequencing on 12 primary uveal melanomas. We observed only approximately 2,000 predicted somatic single-nucleotide variants per tumor and low levels of aneuploidy. We did not observe an ultraviolet radiation DNA damage signature, but identified SF3B1 mutations in three samples and a further 15 mutations in an extension cohort of 105 samples. SF3B1 mutations were associated with good prognosis and were rarely coincident with BAP1 mutations. SF3B1 encodes a component of the spliceosome, and RNA sequencing revealed that SF3B1 mutations were associated with differential alternative splicing of protein coding genes, including ABCC5 and UQCC, and of the long noncoding RNA CRNDE.
Significance: Our data show that despite its dismal prognosis, uveal melanoma is a relatively simple genetic disease characterized by recurrent chromosomal losses and gains and a low mutational burden. We show that SF3B1 is recurrently mutated in uveal melanoma, and the mutations are associated with aberrant alternative splicing. Cancer Discov; 3(10); 1122–9. ©2013 AACR.
This article is highlighted in the In This Issue feature, p. 1083
Interpreting Secondary Cardiac Disease Variants in an Exome Cohort
Authors: Ng David , Johnston Jennifer J. , Teer Jamie K. , Singh Larry N. , Peller Lindsey C. , Wynter Jamila S. , Lewis Katie L. , Cooper David N. , Stenson Peter D. , Mullikin James C. , Biesecker Leslie G. 
Published: July 2013

Background—
Massively parallel sequencing to identify rare variants is widely practiced in medical research and in the clinic. Genome and exome sequencing can identify the genetic cause of a disease (primary results), but it can also identify pathogenic variants underlying diseases that are not being sought (secondary or incidental results). A major controversy has developed surrounding the return of secondary results to research participants. We have piloted a method to analyze exomes to identify participants at risk for cardiac arrhythmias, cardiomyopathies, or sudden death.

Methods and Results—
Exome sequencing was performed on 870 participants not selected for arrhythmia, cardiomyopathy, or a family history of sudden death. Exome data from 22 cardiac arrhythmia- and 41 cardiomyopathy-associated genes were analyzed using an algorithm that filtered results on genotype quality, frequency, and database information. We identified 1367 variants in the cardiomyopathy genes and 360 variants in the arrhythmia genes. Six participants had pathogenic variants associated with dilated cardiomyopathy (n=1), hypertrophic cardiomyopathy (n=2), left ventricular noncompaction (n=1), or long-QT syndrome (n=2). Two of these participants had evidence of cardiomyopathy and 1 had left ventricular noncompaction on echocardiogram. Three participants with likely pathogenic variants had prolonged QTc. Family history included unexplained sudden death among relatives.

Conclusions—
Approximately 0.5% of participants in this study had pathogenic variants in known cardiomyopathy or arrhythmia genes. This high frequency may be due to self-selection, false positives, or underestimation of the prevalence of these conditions. We conclude that clinically important cardiomyopathy and dysrhythmia secondary variants can be identified in unselected exomes.
Use and Associated Risks of Concomitant Aspirin Therapy With Oral Anticoagulation in Patients With Atrial Fibrillation
Authors: Steinberg Benjamin A. , Kim Sunghee , Piccini Jonathan P. , Fonarow Gregg C. , Lopes Renato D. , Thomas Laine , Ezekowitz Michael D. , Ansell Jack , Kowey Peter , Singer Daniel E. , Gersh Bernard , Mahaffey Kenneth W. , Hylek Elaine , Go Alan S. , Chang Paul , Peterson Eric D. 
Published: July 2013

Background—
The role of concomitant aspirin (ASA) therapy in patients with atrial fibrillation (AF) receiving oral anticoagulation (OAC) is unclear. We assessed concomitant ASA use and its association with clinical outcomes among AF patients treated with OAC.

Methods and Results—

The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry enrolled 10 126 AF patients from 176 US practices from June 2010 through August 2011. The study population was limited to those on OAC (n=7347). Hierarchical multivariable logistic regression models were used to assess factors associated with concomitant ASA therapy. Primary outcomes were 6-month bleeding, hospitalization, ischemic events, and mortality. Overall, 35% of AF patients (n=2543) on OAC also received ASA (OAC+ASA). Patients receiving OAC+ASA were more likely to be male (66% versus 53%;
P
<0.0001) and had more comorbid illness than those on OAC alone. More than one third of patients (39%) receiving OAC+ASA did not have a history of atherosclerotic disease, yet 17% had elevated Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding risk scores (≥5). Major bleeding (adjusted hazard ratio, 1.53; 95% confidence interval, 1.20–1.96) and bleeding hospitalizations (adjusted hazard ratio, 1.52; 95% confidence interval, 1.17–1.97) were significantly higher in those on OAC+ASA compared with those on OAC alone. Rates of ischemic events were low.

Conclusions—
Patients with AF receiving OAC are often treated with concomitant ASA, even when they do not have cardiovascular disease. Use of OAC+ASA was associated with significantly increased risk for bleeding, emphasizing the need to carefully determine if and when the benefits of concomitant ASA outweigh the risks in AF patients already on OAC.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01165710.
Recombinant activated factor VII in cardiac surgery: single-center experience
Authors: Singh Sarvesh Pal , Chauhan Sandeep , Choudhury Minati , Malik Vishwas , Choudhary Shiv Kumar 
Published: July 2013

Background the widespread off-label use of recombinant activated factor VII for the control of refractory postoperative hemorrhage continues despite a warning from the Food and Drug Administration. Although effective in reducing the need for transfusion of blood and blood products, safety concerns still prevail. Objective to compare the dosing and efficacy of recombinant activated factor VII between pediatric and adult patients, and in the operating room and intensive care unit. Methods the records of 69 patients (33 children and 36 adults) who underwent cardiovascular surgery and received recombinant activated factor VII were reviewed retrospectively. The dose of recombinant activated factor VII, mediastinal drainage, use of blood and blood products, incidence of thrombosis, and 28-day mortality were studied. Results the efficacy of recombinant activated factor VII was comparable in adults and children, despite the lower dose in adults. Prophylactic use of recombinant activated factor VII decreased the incidence of mediastinal exploration and the duration of intensive care unit stay. A 4.3% incidence of thrombotic complications was observed in this study. Conclusion the efficacious dose of recombinant activated factor VII is much less in adults compared to children. Prophylactic use of recombinant activated factor VII decreases the dose required, the incidence of mediastinal exploration, and intensive care unit stay, with no survival benefit.
Validation of quality indicators for the organization of palliative care: A modified RAND Delphi study in seven European countries (the Europall project)
Authors: Woitha Kathrin , Van Beek Karen , Ahmed Nisar , Jaspers Birgit , Mollard Jean M , Ahmedzai Sam H , Hasselaar Jeroen , Menten Johan , Vissers Kris , Engels Yvonne 
Published: July 2013

Background: Validated quality indicators can help health-care professionals to evaluate their medical practices in a comparative manner to deliver optimal clinical care. No international set of quality indicators to measure the organizational aspects of palliative care settings exists. Aim: To develop and validate a set of structure and process indicators for palliative care settings in Europe. Design: A two-round modified RAND Delphi process was conducted to rate clarity and usefulness of a previously developed set of 110 quality indicators. Setting/participants: In total, 20 multi-professional palliative care teams of centers of excellence from seven European countries. Results: In total, 56 quality indicators were rated as useful. These valid quality indicators concerned the following domains: the definition of a palliative care service (2 quality indicators), accessibility to palliative care (16 quality indicators), specific infrastructure to deliver palliative care (8 quality indicators), symptom assessment tools (1 quality indicator), specific personnel in palliative care services (9 quality indicators), documentation methodology of clinical data (14 quality indicators), evaluation of quality and safety procedures (1 quality indicator), reporting of clinical activities (1 quality indicator), and education in palliative care (4 quality indicator). Conclusion: The modified RAND Delphi process resulted in 56 international face-validated quality indicators to measure and compare organizational aspects of palliative care. These quality indicators, aimed to assess and improve the organization of palliative care, will be pilot tested in palliative care settings all over Europe and be used in the EU FP7 funded IMPACT project.