bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA10: Biomarker selected therapy for pancreas ductal adenocarcinoma: an emerging reality?
Authors: O'Reilly Eileen M. 
Published: December 2016

Abstract
Pancreas adenocarcinoma remains a major challenge hallmarked by several notables, including a rising incidence, modest effectiveness of current state-of-the-art therapies and a dearth of validated biomarkers for clinical decision making. With regard to germline genomics, about 5-8% of pancreas adenocarcinoma patients will harbor a mutation in BRCA2, BRCA1 and PALB2. These mutations amongst others lead to impaired DNA repair and are identified to be important biomarkers of genomic instability as well as of response to DNA damaging agents. Genomic instability, a result of deleterious mutations of genes functioning in homologous repair mediated DNA repair pathways, yields an exceptional vulnerability in cancer cells named synthetic lethality. Recent studies have elucidated that platinum agents and Poly-ADP-ribose polymerase (PARP) inhibitors may be effective to induce tumor regression in solid tumors bearing an unstable genome including pancreatic cancer. The impact of somatic BRCA mutations on response to DNA targeting agents is currently being investigated. A recent whole genome sequencing study by Waddell et al reported overlapping features in both somatic and germline mutations such as unstable genome along with possible DNA targeting agent sensitivity in both groups. This suggests that gained mutation of DNA repair genes throughout the oncogenesis process may also create synthetic lethality and a larger subset of patients may benefit from these evolving treatment approaches. The characteristics of genomic instability in pancreatic cancer along with its clinical implications and the utility of DNA targeting agents particularly PARP inhibitors as novel treatment approaches will be discussed.
Citation Format: Eileen M. O’Reilly.{Authors}. Biomarker selected therapy for pancreas ductal adenocarcinoma: an emerging reality? [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr IA10.
Abstract IA11: Pancreatic cancer biology and medicine
Authors: Tuveson David 
Published: December 2016

Abstract
Pancreatic cancer remains the most deadly of the common malignancies. To increase our basic understanding of this disease and advance medical approaches, we have recently co-developed with Hans Clevers mouse and human organoid model systems. Our organoid cultures representative of either normal or neoplastic ductal cells facilitate the systematic analysis of neoplastic biochemical cascades, provide a platform to explore therapeutic and diagnostic strategies, and also enable the reconstitution of tumor microenvironment interactions. We have found that Nrf2, a principal regulator of redox metabolism, promotes proliferation in KRAS mutant pancreatic ductal cells in part by regulating the reduced state of the cellular proteome. As a consequence of proteome oxidation, central pathways of homeostasis are impaired, including protein translation. The genes with markedly impaired translation include a number of critical proto-oncogenes. Additionally, diagnostic and therapeutic approaches have revealed new avenues to explore for early detection and disease treatment. Finally, the co-culture of organoids with pancreatic stellate cells promotes the activation of each cell type and results in the production of extracellular matrix. Co-cultures reveal distinct subtypes of stellate cells and provide an opportunity to identify and target novel mediators of the tumor microenvironment.
Citation Format: David Tuveson.{Authors}. Pancreatic cancer biology and medicine. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr IA11.
More than an anticoagulant: Do heparins have direct anti-inflammatory effects?
Authors: Poterucha Timothy J. , Libby Peter , Goldhaber Samuel Z. 
Published: December 2016

SummaryThe heparins, well-known for their anticoagulant properties, may also have anti-inflammatory effects that could contribute to their effectiveness in the treatment of venous thromboembolism and other vascular diseases. This review focuses on the inflammatory pathophysiology that underlies the development of thrombosis and the putative effects of heparin on these pathways. We present evidence supporting the use of heparin for other indications, including autoimmune disease, malignancy, and disseminated intravascular coagulation. These considerations highlight the need for further research to elucidate the mechanisms of the possible pleiotropic effects of the heparins, with a view to advancing treatments based upon heparin derivatives.
Interstitial Fibrosis, Functional Status, and Outcomes in Heart Failure With Preserved Ejection Fraction
Authors: Duca Franz , Kammerlander Andreas A. , Zotter-Tufaro Caroline , Aschauer Stefan , Schwaiger Marianne L. , Marzluf Beatrice A. , Bonderman Diana , Mascherbauer Julia 
Published: December 2016

Background—
Myocardial extracellular volume (ECV) accumulation is one of the key pathophysiologic features of heart failure with preserved ejection fraction (HFpEF). Our aims were to (1) measure ECV by cardiac magnetic resonance T1 mapping using the modified Look-Locker inversion recovery (MOLLI) sequence, (2) validate MOLLI-ECV against histology, and (3) investigate the relationship between MOLLI-ECV and prognosis in HFpEF.

Methods and Results—

One-hundred seventeen consecutive HFpEF patients underwent cardiac magnetic resonance imaging, coronary angiography, and invasive hemodynamic assessments at baseline. Eighteen patients also underwent left ventricular biopsy for histological analysis (Histo-ECV). To assess the prognostic impact of MOLLI-ECV, its association with hospitalization for heart failure/cardiac death was tested by multivariable Cox regression analysis. Histo-ECV was 30.1±4.6% and was significantly correlated with MOLLI-ECV (
R
=0.494,
P
=0.037). Patients were followed for 24.0 months (6.0–32.0 months), during which 34 had a cardiac event. By Kaplan–Meier analysis, patients with MOLLI-ECV ≥ the median (28.9%) had shorter event-free survival (log-rank,
P
=0.028). MOLLI-ECV significantly correlated with N-terminal prohormone of brain natriuretic peptide (
P
<0.001), 6-minute walk distance (
P
=0.004), New York Heart Association functional class (
P
=0.009), right atrial pressure (
P
=0.037), and stroke volume (
P
=0.043). By multivariable Cox regression analysis, MOLLI-ECV was associated with outcome among imaging variables (
P
=0.038) but not after adjustment for clinical and invasive hemodynamic parameters.

Conclusions—
We demonstrate that MOLLI-ECV in HFpEF accurately reflects histological ECV, correlates with markers of disease severity, and is associated with outcome among cardiac magnetic resonance parameters but not after adjustment for important clinical and invasive hemodynamic parameters. Nevertheless, MOLLI-ECV has the potential of becoming an important biomarker in HFpEF.
A Comprehensive Database of Flood Events in the Contiguous United States from 2002 to 2013
Authors: Shen Xinyi , Mei Yiwen , Anagnostou Emmanouil N. 
Published: December 2016

Abstract
Notwithstanding the rich record of hydrometric observations compiled by the U.S. Geological Survey (USGS) across the contiguous United States (CONUS), flood event catalogs are sparse and incomplete. Available databases or inventories are mostly survey- or report-based, impact oriented, or limited to flash floods. These data do not represent the full range of flood events occurring in CONUS in terms of geographical locations, severity, triggering weather, or basin morphometry. This study describes a comprehensive dataset consisting of more than half a million flood events extracted from 6,301 USGS flow records and radar-rainfall fields from 2002 to 2013, using the characteristic point method. The database features event duration; first- (mass center) and second- (spreading) order moments of both precipitation and flow, flow peak and percentile, event runoff coefficient, base flow, and information on the basin geomorphology. It can support flood modeling, geomorphological and geophysical impact studies, and instantaneous unit hydrograph and risk analyses, among other investigations. Preliminary data analysis conducted in this study shows that the spatial pattern of flood events affected by snowmelt correlates well with the mean annual snowfall accumulation pattern across CONUS, the basin morphometry affects the number of flood events and peak flows, and the concentration time and spreadness of the flood events can be related to the precipitation first- and second-order moments.
Condensational Growth of Drops Formed on Giant Sea-Salt Aerosol Particles
Authors: Jensen Jørgen B. , Nugent Alison D. 
Published: December 2016

Abstract
The most basic aspect of cloud formation is condensational growth onto cloud condensation nuclei (CCN). As such, condensational growth of cloud drops is often assumed to be a well-understood process described by the drop growth equation. When this process is represented in models, CCN activate into cloud drops at cloud base, and it is often assumed that drops consist of pure water or that the hygroscopic contribution after drop activation is small because of the inclusion of only small CCN. Drop growth rate in adiabatic ascent in such models is proportional to supersaturation and assumed to be inversely proportional to the drop radius, thereby making the drop spectrum narrow with altitude. However, the present study demonstrates that drop growth on giant sea-salt aerosol particles (GCCN; dry radius 0.5 m) behaves differently. For typical marine stratocumulus updrafts and for drops grown on GCCN with sizes m, these drops typically remain concentrated salt solutions. Because of this, their condensational growth is accelerated, and they rapidly attain precipitation drop sizes through condensation only. Additionally, drops formed on GCCN may also grow by condensation in cloudy downdrafts. The strong effect of condensation on GCCN is important when carried through to calculating rain-rate contribution as a function of aerosol size. GCCN larger than 2 m account for most of the rainfall rate in the modeled precipitating marine stratocumulus.
Reduction of the Entrainment Velocity by Cloud Droplet Sedimentation in Stratocumulus
Authors: de Lozar Alberto , Mellado Juan Pedro 
Published: December 2016

Abstract
The effect of sedimentation on stratocumulus entrainment is investigated using direct numerical simulations of a cloud-top mixing layer driven by radiative and evaporative cooling. The simulations focus on the meter and submeter scales that are expected to be relevant for entrainment, and the finest grid spacing is Δx = 26 cm. The entrainment velocity is investigated from the analysis of the integrated-buoyancy evolution equation, which is exactly derived from the flow evolution equations. The analysis shows that sedimentation interacts with entrainment through two different mechanisms. As previously reported, sedimentation prevents droplets from evaporating in the entrainment zone, which in turn reduces the entrainment velocity. Here it is shown that sedimentation also promotes a positive buoyancy flux that directly opposes entrainment. The strengths of both mechanisms are characterized by two different settling numbers, which allow for predicting which meteorological conditions favor the reduction of entrainment by sedimentation. These new insights allow for including sedimentation in a parameterization of the entrainment velocity. The reduction of the entrainment velocity by sedimentation predicted by the parameterization and observed in the simulations is 3 times larger than previously reported in large-eddy simulations, which implies that meter- and submeter-scale turbulence plays an important role in the interaction of entrainment with sedimentation. On the whole, analysis and simulations indicate that stratocumulus entrainment is more sensitive to the cloud droplet number density due to sedimentation than previously thought.
Pathways of Meltwater Export from Petermann Glacier, Greenland
Authors: Heuzé Céline , Wåhlin Anna , Johnson Helen L. , Münchow Andreas 
Published: December 2016

AbstractIntrusions of Atlantic Water cause basal melting of Greenland’s marine-terminating glaciers and ice shelves, such as that of Petermann Glacier, in northwest Greenland. The fate of the resulting glacial meltwater is largely unknown. It is investigated here, using hydrographic observations collected during a research cruise in Petermann Fjord and adjacent Nares Strait onboard icebreaker (I/B) Oden in August 2015. A three end-member mixing method provides the concentration of Petermann ice shelf meltwater. Meltwater from Petermann is found in all of the casts in adjacent Nares Strait, with the highest concentration along the Greenland coast in the direction of Kelvin wave phase propagation. The meltwater from Petermann mostly flows out on the northeast side of the fjord as a baroclinic boundary current, with the depth of maximum meltwater concentrations approximately 150 m and shoaling along its pathway. At the outer sill, which separates the fjord from the ambient ocean, approximately 0.3 mSv (1 Sv ≡ 106 m3 s−1) of basal meltwater leaves the fjord at depths between 100 and 300 m. The total geostrophic heat and freshwater fluxes close to the glacier’s terminus in August 2015 were similar to those estimated in August 2009, before the two major calving events that reduced the length of Petermann’s ice tongue by nearly a third and despite warmer inflowing Atlantic Water. These results provide a baseline but also highlight what is needed to assess properly the impact on ocean circulation and sea level of Greenland’s mass loss as the Atlantic Water warms up.
Doppler Correction of Wave Frequency Spectra Measured by Underway Vessels
Authors: Collins C. O. , Blomquist B. , Persson O. , Lund B. , Rogers W. E. , Thomson J. , Wang D. , Smith M. , Doble M. , Wadhams P. , Kohout A. , Fairall C. , Graber H. C. 
Published: December 2016

Abstract“Sea State and Boundary Layer Physics of the Emerging Arctic Ocean” is an ongoing Departmental Research Initiative sponsored by the Office of Naval Research (http://www.apl.washington.edu/project/project.php?id=arctic_sea_state). The field component took place in the fall of 2015 within the Beaufort and Chukchi Seas and involved the deployment of a number of wave instruments, including a downward-looking Riegl laser rangefinder mounted on the foremast of the R/V Sikuliaq. Although time series measurements on a stationary vessel are thought to be accurate, an underway vessel introduces a Doppler shift to the observed wave spectrum. This Doppler shift is a function of the wavenumber vector and the velocity vector of the vessel. Of all the possible relative angles between wave direction and vessel heading, there are two main scenarios: 1) vessel steaming into waves and 2) vessel steaming with waves. Previous studies have considered only a subset of cases, and all were in scenario 1. This was likely to avoid ambiguities, which arise when the vessel is steaming with waves. This study addresses the ambiguities and analyzes arbitrary cases. In addition, a practical method is provided that is useful in situations when the vessel is changing speed or heading. These methods improved the laser rangefinder estimates of spectral shapes and peak parameters when compared to nearby buoys and a spectral wave model.
Targeting the Opioid Pathway for Uremic Pruritus
Authors: Jaiswal Deep , Uzans Drea , Hayden Jill , Kiberd Bryce A. , Tennankore Karthik K. 
Published: December 2016

Background: Patients undergoing hemodialysis or peritoneal dialysis often experience pruritus which is associated with morbidity and mortality. One proposed treatment approach is to target the opioid pathway using either µ-opioid antagonists or κ-opioid agonists. Objective: To review the efficacy of targeting the opioid pathway for pruritus among dialysis patients (uremic pruritus). Design: Systematic review and meta-analysis. Setting/Methods: The systematic review included randomized controlled and randomized crossover trials identified in the MEDLINE, EMBASE, and Cochrane databases (1990 to June 2014) evaluating the efficacy of µ-opioid antagonists or κ-opioid agonists in the treatment of uremic pruritus. Patients: Adult (≥18 years) chronic dialysis patients. Measurements: The primary outcome being evaluated was reduction in itch severity measured on a patient-reported visual analog scale (VAS). Results: Five studies out of 3587 screened articles met the inclusion criteria. Three studies evaluated the efficacy of naltrexone, a µ-opioid antagonist, and 2 studies evaluated the efficacy of nalfurafine, a κ-opioid agonist. Duration of included studies was short, ranging from 2 to 9 weeks. Limitations: Due to the heterogeneity in reporting of outcomes, data from the studies evaluating naltrexone could not be pooled. Pooled analysis, using a random effects model, found that use of nalfurafine resulted in a 9.50 mm (95% confidence interval [CI], 6.27-12.74, P < .001) greater reduction of itch severity (measured on a 100-mm VAS) than placebo in the treatment of uremic pruritus. Conclusions: Nalfurafine holds some promise with respect to the treatment of uremic pruritus among dialysis patients. However, more long-term randomized controlled trials evaluating the efficacy of therapies targeting the opioid pathway for uremic pruritus are required.
The Geographic Distribution of Pediatric Anesthesiologists Relative to the US Pediatric Population
Authors: Muffly Matthew K. , Medeiros David , Muffly Tyler M. , Singleton Mark A. , Honkanen Anita 
Published: December 2016

BACKGROUND:
The geographic relationship between pediatric anesthesiologists and the pediatric population has potentially important clinical and policy implications. In the current study, we describe the geographic distribution of pediatric anesthesiologists relative to the US pediatric population (0–17 years) and a subset of the pediatric population (0–4 years).

METHODS:
The percentage of the US pediatric population that lives within different driving distances to the nearest pediatric anesthesiologist (0 to 25 miles, >25 to 50 miles, >50 to 100 miles, >100 to 250 miles, and >250 miles) was determined by creating concentric driving distance service areas surrounding pediatric anesthesiologist practice locations. US Census block groups were used to determine the sum pediatric population in each anesthesiologist driving distance service area. The pediatric anesthesiologist-to-pediatric population ratio was then determined for each of the 306 hospital referral regions (HRRs) in the United States and compared with ratios of other physician groups to the pediatric population. All geographic mapping and analysis was performed using ArcGIS Desktop 10.2.2 mapping software (Redlands, CA).

RESULTS:
A majority of the pediatric population (71.4%) lives within a 25-mile drive of a pediatric anesthesiologist; however, 10.2 million US children (0–17 years) live greater than 50 miles from the nearest pediatric anesthesiologist. More than 2.7 million children ages 0 to 4 years live greater than 50 miles from the nearest identified pediatric anesthesiologist. The median ratio of pediatric anesthesiologists to 100,000 pediatric population at the HRR level was 2.25 (interquartile range, 0–5.46). Pediatric anesthesiologist geographic distribution relative to the pediatric population by HRR is lower and less uniform than for all anesthesiologists, neonatologists, and pediatricians.

CONCLUSIONS:
A substantial proportion of the US pediatric population lives greater than 50 miles from the nearest pediatric anesthesiologist, and pediatric anesthesiologist-to-pediatric population ratios by HRR vary widely across the United States. These findings are important given that the new guidelines from the American College of Surgeons Children’s Surgery Verification™ Quality Improvement Program state that pediatric anesthesiologists must care for a subset of pediatric patients. Because of the geographic distribution of pediatric anesthesiologists relative to the pediatric population, access to care by a pediatric anesthesiologist may not be feasible for all children, particularly for those with limited resources or in emergent situations.
Redox Properties of Copper(I) Complex Bearing 4,7-Diphenyl-2,9-dimethyl-1,10-phenanthroline and 1,4-Bis(diphenylphosphino)butane Ligands and Effects of Light in the Presence of Chloroform
Authors: Nishikawa Michihiro , Kakizoe Daichi , Saito Yuma , Ohishi Tomoyuki , Tsubomura Taro 
Published: December 2016

Abstract
We have examined emission and redox properties of a copper(I) complex bearing a phenanthroline type ligand and the 1,4-bis(diphenylphosphino)butane ligand. Changes in the absorption spectra upon electrolysis and light irradiation in the presence of chloroform indicate the formation of bis(diimine)copper(I) complexes.
Effects of tranexamic acid on platelet function and thrombin generation (ETAPlaT): WOMAN trial sub-study
Authors: Dallaku Kastriot , Shakur Haleema , Roberts Ian , Edwards Phil , Beaumont Danielle , Delius Maria , Siegmund Braun , Gliozheni Orion , Tasha Ilir , Cenameri Saimir , Mansmann Ulrich 
Published: December 2016

Background. Postpartum haemorrhage (PPH) is a leading cause of maternal death. Tranexamic acid (TXA) has the potential to reduce bleeding and a large randomized placebo controlled trial of its effect in women with PPH (The WOMAN trial) is underway. TXA might also affect coagulation factors and platelets. Objectives. To examine the effect of TXA on thrombin generation, platelet function, fibrinogen, D-dimer and coagulation factors in women with PPH. Methods. We will conduct a sub-study within the WOMAN trial. Women with clinically diagnosed primary PPH after vaginal or caesarean delivery are eligible for inclusion. Blood samples will be collected at baseline and 30 minutes after the first dose of study treatment. Using platelet poor plasma we will measure thrombin generation, fibrinogen, D-dimer, factor V and VIII, and Von Willebrand factor. Platelet function will be evaluated in whole blood using Multiplate® tests.Outcomes. The primary outcome is the effect of TXA on thrombin generation. Secondary outcomes include the effect of TXA on platelet function, fibrinogen, D-dimer and coagulation factors.