bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Calculated Crack Growth Values Using Unloading Compliance and d-c EP During SENT Testing
Authors: Hioe Y. , Kalyanam S. , Wilkowski G. M. 
Published: January 2019

SENT testing has become increasingly important in the characterization of the base, girth weld, and HAZ structural integrity for pipelines that are operational in the low temperature regions, such as the arctic. While the SENB and CT specimens have been used traditionally in the fracture toughness characterization and assessment of pipeline materials and welds, the SENT specimen is better representative of the constraint behavior of surface cracks found in service. Further, the SENT specimen is closer in representing the ductile-to-brittle transition temperature region for the pipe operation.
For strain-based design, ECA, and stress-based fracture analyses of girth weld defects, SENT test results have been found to be more representative of the constraint of a surface crack in a pipe and hence better reflects the material toughness. Typically the CTOD as a function of crack growth is used in girth weld defect analyses, but J-R curves can be calculated at the same time. While several procedures for SENT testing (DNV, Exxon Mobil, CANMET) are currently used in the industry and are based on reliable constitutive behavior, plasticity, and fracture theories and experimental methods, more recently a British Standard (BS8571:2014) has been published. In these procedures, either the d-c EP method or the unloading compliance technique are used to determine the start of ductile tearing and crack growth to arrive at fracture resistance CTOD-R and J-R curves. This paper presents results from comparisons of crack growth predictions where in both techniques were used simultaneously when conducting the SENT tests. Other unique aspects of the comparative methodologies, pros and cons of each of the two methods, guidelines for fracture resistance curve development from SENT testing, and its impact on girth weld, HAZ testing are also discussed.
Long Term Structural Integrity Considerations for Abandoned Pipelines
Authors: Finneran Shane , Prewitt T. J. , Kaufman Joel 
Published: January 2019

There has been increasing interest across the industry to better understand the possible long term risks associated with out of service pipelines. In Canada, the Canadian Energy Pipeline Association (CEPA), Petroleum Technology Alliance of Canada (PTAC), and the National Energy Board (NEB), have undertaken multiple studies to identify and assess the threats related to pipeline abandonment. [1][2][3]
The primary hazards typically identified across industry for pipeline abandonment are associated with long term corrosion degradation, potential for creation of water conduits, possible environmental impacts, and potential for pipeline collapse and associated soil subsidence. Unfortunately, little guidance is presently available to the industry for determining remaining structural capacity of a heavily corroded pipeline to establish likelihood, and possible timeline, of collapse, nor for determining possible subsidence magnitudes associated with large diameter transmission lines.
This paper presents a technical case study for an assessment approximating the remaining strength of an abandoned pipeline subject to long term corrosion degradation, considering both general metal loss, and randomized pitting and perforation growth. The work presented used a combination of finite element analyses, and existing industry models for determining load bearing capacity of an abandoned pipeline under varying levels of degradation.
Albuminuria measurement in diabetic care: a multilevel analysis measuring the influence of accreditation on institutional performance
Authors: Ghith Nermin , Merlo Juan , Frølich Anne 
Published: January 2019

BackgroundStudies assessing institutional performance regarding quality of care are frequently performed using single-level statistical analyses investigating differences between provider averages of various quality indicators. However, such analyses are insufficient as they do not consider patients’ heterogeneity around those averages. Hence, we apply a multilevel analysis of individual-patient heterogeneity that distinguishes between ‘general’ (‘latent quality’ or measures of variance) and ‘specific’ (measures of association) contextual effects. We assess general contextual effects of the hospital departments and the specific contextual effect of a national accreditation programme on adherence to the standard benchmark for albuminuria measurement in Danish patients with diabetes.MethodsFrom the Danish Adult Diabetes Database, we extracted data on 137 893 patient cases admitted to hospitals between 2010 and 2013. Applying multilevel logistic and probit regression models for every year, we quantified general contextual effects of hospital department by the intraclass correlation coefficient (ICC) and the area under the receiver operating characteristic curve (AUC) values. We evaluated the specific effect of hospital accreditation using the ORs and the change in the department variance.ResultsIn 2010, the department context had considerable influence on adherence with albuminuria measurement (ICC=21.8%, AUC=0.770), but the general effect attenuated along with the implementation of the national accreditation programme. The ICC value was 16.5% in 2013 and the rate of compliance with albuminuria measurement increased from 91.6% in 2010 to 96% in 2013.ConclusionsParallel to implementation of the national accreditation programme, departments’ compliance with the standard benchmark for albuminuria measurement increased and the ICC values decreased, but remained high. While those results indicate an overall quality improvement, further intervention focusing on departments with the lowest compliance could be considered.
Effect of local anesthetic volume (20 mL vs 30 mL ropivacaine) on electromyography of the diaphragm and pulmonary function after ultrasound-guided supraclavicular brachial plexus block: a randomized controlled trial
Authors: Bao Xiuxia , Huang Juanjuan , Feng Haorong , Qian Yuying , Wang Yajie , Zhang Qunying , Hu Huansheng , Wang Xianghe 
Published: January 2019

Background and objectivesDiaphragmatic paralysis following supraclavicular brachial plexus block (SCBPB) is ascribed to phrenic nerve palsy. This study investigated the effect of 2 volumes of 0.375% ropivacaine on efficacy of block as a surgical anesthetic and as an analgesic and examined diaphragm compound muscle action potentials (CMAPs) and pulmonary function before and after SCBPB.MethodsEighty patients scheduled for removal of hardware for internal fixation after healing of an upper limb fracture distal to the shoulder were randomized to receive ultrasound-guided SCBPC for surgical anesthesia with 20 mL (Group A) or 30 mL (Group B) 0.375% ropivacaine. The latency and amplitude of diaphragm CMAPs and forced vital capacity (FVC), FVC% predicted, and forced expiratory volume in 1 s (FEV1) were measured before and 30 min after SCBPB.ResultsBlock success as primary anesthetic in addition to analgesia was 81% in Group A and 91% in Group B. There were no obvious differences in the effectiveness of analgesia between the two groups. The mean time to onset of motor block was significantly longer in Group A (8.1±2.7 min) than in Group B (5.4 ± 2.8 min; p<0.05). The mean amplitude of the diaphragm CMAP was significantly lower in Group B than in Group A (p=0.03). The changes in FVC (Group A, − 8.1% vs Group B, −16.5%), FVC% (Group A, −8.0% vs Group B, −17.1%), and FEV1 (Group A, −9.5% vs Group B, −15.2%) from pre-SCBPB to post-SCBPB were significantly less in Group A than in Group B (all p=0.03).ConclusionsThe incidence rates of phrenic nerve palsy and diaphragm paralysis were reduced, and lung function was less impaired in patients who received 20 mL vs 30 mL of 0.375% ropivacaine without any differences in block success. Selecting a lower volume of anesthetic for nerve block may be especially beneficial in obese patients or patients with cardiopulmonary disease.Trial registration numberChiCTR-IND-17012166.
Quantitative Imaging Markers of Lung Function in a Smoking Population Distinguish COPD Subgroups with Differential Lung Cancer Risk
Authors: Lusk Christine M. , Wenzlaff Angela S. , Watza Donovan , Sieren Jessica C. , Robinette Natasha , Walworth Garrett , Petrich Michael , Neslund-Dudas Christine , Flynn Michael J. , Song Thomas , Spizarny David , Simoff Michael J. , Soubani Ayman O. , Gadgeel Shirish , Schwartz Ann G. 
Published: January 2019

Abstract

Background:
Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with respect to onset, progression, and response to therapy. Incorporating clinical- and imaging-based features to refine COPD phenotypes provides valuable information beyond that obtained from traditional clinical evaluations. We characterized the spectrum of COPD-related phenotypes in a sample of former and current smokers and evaluated how these subgroups differ with respect to sociodemographic characteristics, COPD-related comorbidities, and subsequent risk of lung cancer.

Methods:
White (N = 659) and African American (N = 520) male and female participants without lung cancer (controls) in the INHALE study who completed a chest CT scan, interview, and spirometry test were used to define distinct COPD-related subgroups based on hierarchical clustering. Seven variables were used to define clusters: pack years, quit years, FEV1/FVC, % predicted FEV1, and from quantitative CT (qCT) imaging, % emphysema, % air trapping, and mean lung density ratio. Cluster definitions were then applied to INHALE lung cancer cases (N = 576) to evaluate lung cancer risk.

Results:
Five clusters were identified that differed significantly with respect to sociodemographic (e.g., race, age) and clinical (e.g., BMI, limitations due to breathing difficulties) characteristics. Increased risk of lung cancer was associated with increasingly detrimental lung function clusters (when ordered from most detrimental to least detrimental).

Conclusions:
Measures of lung function vary considerably among smokers and are not fully explained by smoking intensity.

Impact:
Combining clinical (spirometry) and radiologic (qCT) measures of COPD defines a spectrum of lung disease that predicts lung cancer risk differentially among patient clusters.
Immunologic Correlates of the Abscopal Effect in a SMARCB1/INI1-negative Poorly Differentiated Chordoma after EZH2 Inhibition and Radiotherapy
Authors: Gounder Mrinal M. , Zhu Guo , Roshal Lev , Lis Eric , Daigle Scott R. , Blakemore Steven J. , Michaud Neil R. , Hameed Meera , Hollmann Travis J. 
Published: January 2019

Abstract

Purpose:
We sought to determine the mechanism of an exceptional response in a patient diagnosed with a SMARCB1/INI1-negative chordoma treated with tazemetostat, an EZH2 inhibitor, and followed by radiotherapy.
Patient and Methods: In an attempt to investigate the mechanism behind this apparent abscopal effect, we interrogated tumor tissues obtained over the clinical course. We utilized next-generation sequencing, standard IHC, and employed a novel methodology of multiplex immunofluorescence analysis.

Results:
We report an exceptional and durable response (2+ years) in a patient with SMARCB1-deleted, metastatic, poorly differentiated chordoma, a lethal disease with an overall survival of 6 months. The patient was treated for 4 weeks with tazemetostat, an EZH2 inhibitor, in a phase II clinical trial. At the time of progression she underwent radiation to the primary site and unexpectedly had a complete response at distant metastatic sites. We evaluated baseline and on-treatment tumor biopsies and demonstrate that tazemetostat resulted in pharmacodynamic inhibition of EZH2 as seen by decrease in histone trimethylation at H3K27. Tazemetostat resulted in a significant increase in intratumoral and stromal infiltration by proliferative (high Ki-67), CD8+ T cells, FoxP3+ regulatory T cells, and immune cells expressing checkpoint regulators PD-1 and LAG-3. These changes were pronounced in the stroma.

Conclusions:
These observations are the first demonstration in patient samples confirming that EZH2 inhibition can promote a sustained antitumor response that ultimately leads to T-cell exhaustion and checkpoint activation. This suggests that targeted alteration of the epigenetic landscape may sensitize some tumors to checkpoint inhibitors.
An Integrated Stress Response Agent that Modulates DR5-Dependent TRAIL Synergy Reduces Patient-Derived Glioma Stem Cell Viability
Authors: Sheikh Saad , Saxena Deeksha , Tian Xiaobing , Amirshaghaghi Ahmad , Tsourkas Andrew , Brem Steven , Dorsey Jay F. 
Published: January 2019

Abstract

The high incidence of glioblastoma recurrence necessitates additional therapeutic strategies. Heterogeneous populations of cells, including glioma stem cells (GSC) have been implicated in disease recurrence. GSCs are able to survive irradiation and temozolomide (TMZ) treatment due to upregulation of DNA damage pathways. One potential strategy to target treatment-resistant tumor populations may be via the integrated stress response (ISR). Modulation of the ISR pathway also allows for sensitization of treatment-resistant cells to TRAIL. We generated a novel cell-based death receptor assay to identify potent inducers of ISR-dependent DR5 expression. We used this assay to screen compounds from three commercially available libraries, and identified 1-benzyl-3-cetyl-2-methylimidazolium iodide (NH125) as a potent inducer of DR5 expression. NH125 engages the EIF2α–ATF4–CHOP axis culminating in DR5 expression at low micromolar doses. Expression of CHOP plays a critical role in NH125-mediated TRAIL synergy. Treatment of GSC with NH125 produces a marked reduction in viability when compared with other cell lines. NH125-treated GSC also synergize with lower doses of TRAIL when compared with all other cell lines tested. Transcriptional analysis of NH125-treated GSC uncovers a unique profile that involves activation of ISR and GADD45 pathways. Treatment of GSC xenografts with encapsulated PEG–PCL–NH125 leads to a sustained decrease in tumor volume.

Implications:
Taken together, these data suggest that engaging the ISR pathway represents a promising strategy to target treatment refractory GSC that have been implicated in glioblastoma recurrence.
A CD40 Agonist and PD-1 Antagonist Antibody Reprogram the Microenvironment of Nonimmunogenic Tumors to Allow T-cell–Mediated Anticancer Activity
Authors: Ma Hayley S. , Poudel Bibhav , Torres Evanthia Roussos , Sidhom John-William , Robinson Tara M. , Christmas Brian , Scott Blake , Cruz Kayla , Woolman Skylar , Wall Valerie Z. , Armstrong Todd , Jaffee Elizabeth M. 
Published: January 2019

Abstract
In cancers with tumor-infiltrating lymphocytes (TILs), monoclonal antibodies (mAbs) that block immune checkpoints such as CTLA-4 and PD-1/PD-L1 promote antitumor T-cell immunity. Unfortunately, most cancers fail to respond to single-agent immunotherapies. T regulatory cells, myeloid derived suppressor cells (MDSCs), and extensive stromal networks within the tumor microenvironment (TME) dampen antitumor immune responses by preventing T-cell infiltration and/or activation. Few studies have explored combinations of immune-checkpoint antibodies that target multiple suppressive cell populations within the TME, and fewer have studied the combinations of both agonist and antagonist mAbs on changes within the TME. Here, we test the hypothesis that combining a T-cell–inducing vaccine with both a PD-1 antagonist and CD40 agonist mAbs (triple therapy) will induce T-cell priming and TIL activation in mouse models of nonimmunogenic solid malignancies. In an orthotopic breast cancer model and both subcutaneous and metastatic pancreatic cancer mouse models, only triple therapy was able to eradicate most tumors. The survival benefit was accompanied by significant tumor infiltration of IFNγ-, Granzyme B-, and TNFα-secreting effector T cells. Further characterization of immune populations was carried out by high-dimensional flow-cytometric clustering analysis and visualized by t-distributed stochastic neighbor embedding (t-SNE). Triple therapy also resulted in increased infiltration of dendritic cells, maturation of antigen-presenting cells, and a significant decrease in granulocytic MDSCs. These studies reveal that combination CD40 agonist and PD-1 antagonist mAbs reprogram immune resistant tumors in favor of antitumor immunity.
Lin28a Regulates Pathological Cardiac Hypertrophic Growth Through Pck2-Mediated Enhancement of Anabolic Synthesis
Authors: Ma Hong , Yu Shuo , Liu Xiaojing , Zhang Yingao , Fakadej Thomas , Liu Ziqing , Yin Chaoying , Shen Weining , Locasale Jason W. , Taylor Joan M. , Qian Li , Liu Jiandong 
Published: January 2019

Background:
Hypertrophic response to pathological stimuli is a complex biological process that involves transcriptional and epigenetic regulation of the cardiac transcriptome. Although previous studies have implicated transcriptional factors and signaling molecules in pathological hypertrophy, the role of RNA-binding protein in this process has received little attention.

Methods:
Here we used transverse aortic constriction and in vitro cardiac hypertrophy models to characterize the role of an evolutionary conserved RNA-binding protein Lin28a in pathological cardiac hypertrophy. Next-generation sequencing, RNA immunoprecipitation, and gene expression analyses were applied to identify the downstream targets of Lin28a. Epistatic analysis, metabolic assays, and flux analysis were further used to characterize the effects of Lin28a and its downstream mediator in cardiomyocyte hypertrophic growth and metabolic remodeling.

Results:

Cardiac-specific deletion of
Lin28a
attenuated pressure overload–induced hypertrophic growth, cardiac dysfunction, and alterations in cardiac transcriptome. Mechanistically, Lin28a directly bound to mitochondrial phosphoenolpyruvate carboxykinase 2 (
Pck2
) mRNA and increased its transcript level. Increasing
Pck2
was sufficient to promote hypertrophic growth similar to that caused by increasing Lin28a, whereas knocking down
Pck2
attenuated norepinephrine-induced cardiac hypertrophy. Epistatic analysis demonstrated that Pck2 mediated, at least in part, the role of Lin28a in cardiac hypertrophic growth. Furthermore, metabolomic analyses highlighted the role for Lin28a and Pck2 in promoting cardiac biosynthesis required for cell growth.

Conclusions:

Our study demonstrates that Lin28a promotes pathological cardiac hypertrophy and glycolytic reprograming, at least in part, by binding to and stabilizing
Pck2
mRNA.
Unloading the Left Ventricle Before Reperfusion in Patients With Anterior ST-Segment–Elevation Myocardial Infarction
Authors: Kapur Navin K. , Alkhouli Mohamad A. , DeMartini Tony J. , Faraz Haroon , George Zachary H. , Goodwin Mark J. , Hernandez-Montfort Jaime A. , Iyer Vijay S. , Josephy Noam , Kalra Sanjog , Kaki Amir , Karas Richard H. , Kimmelstiel Carey D. , Koenig Gerald C. , Lau Evan , Lotun Kapildeo , Madder Ryan D. , Mannino Salvatore F. , Meraj Perwaiz M. , Moreland Jason A. , Moses Jeffrey W. , Kim Raymond L. , Schreiber Theodore L. , Udelson James E. , Witzke Christian , Wohns David H.W. , O’Neill William W. 
Published: January 2019

Background:
In ST-segment–elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible.

Methods:
In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging.

Results:

All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively,
P
=0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR,
P
=0.53).

Conclusions:
We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03000270.
A Stochastic Representation of Subgrid Uncertainty for Dynamical Core Development
Authors: Subramanian Aneesh , Juricke Stephan , Dueben Peter , Palmer Tim 
Published: January 2019

AbstractNumerical weather prediction and climate models comprise a) a dynamical core describing resolved parts of the climate system and b) parameterizations describing unresolved components. Development of new subgrid-scale parameterizations is particularly uncertain compared to representing resolved scales in the dynamical core. This uncertainty is currently represented by stochastic approaches in several operational weather models, which will inevitably percolate into the dynamical core. Hence, implementing dynamical cores with excessive numerical accuracy will not bring forecast gains, may even hinder them since valuable computer resources will be tied up doing insignificant computation, and therefore cannot be deployed for more useful gains, such as increasing model resolution or ensemble sizes. Here we describe a low-cost stochastic scheme that can be implemented in any existing deterministic dynamical core as an additive noise term. This scheme could be used to adjust accuracy in future dynamical core development work. We propose that such an additive stochastic noise test case should become a part of the routine testing and development of dynamical cores in a stochastic framework. The overall key point of the study is that we should not develop dynamical cores that are more precise than the level of uncertainty provided by our stochastic scheme. In this way, we present a new paradigm for dynamical core development work, ensuring that weather and climate models become more computationally efficient. We show some results based on tests done with the European Centre for Medium-Range Weather Forecasts (ECMWF) Integrated Forecasting System (IFS) dynamical core.