bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Replication Study and Genome-Wide Scan of Single-Nucleotide Polymorphisms Associated with Pancreatic Cancer Risk and Overall Survival
Authors: Willis Jason A. , Olson Sara H. , Orlow Irene , Mukherjee Semanti , McWilliams Robert R. , Kurtz Robert C. , Klein Robert J. 
Published: June 2012

Abstract
Purpose: To explore the effects of single-nucleotide polymorphisms (SNP) on pancreatic cancer risk and overall survival (OS).
Experimental Design: The germ line DNA of 531 pancreatic cancer cases and 305 healthy controls from a hospital-based study was genotyped at SNPs previously reported to be associated with pancreatic cancer risk or clinical outcome. We analyzed putative risk SNPs for replication of their reported effects on risk and tested for novel effects on OS. Similarly, we analyzed putative survival-associated SNPs for replication of their reported effects on OS and tested for novel effects on risk. Finally, we conducted a genome-wide association study (GWAS) of OS using a subset of 252 cases, with two subsequent validation sets of 261 and 572 patients, respectively.
Results: Among seven risk SNPs analyzed, two (rs505922 and rs9543325) were associated with risk (P &lt; 0.05). Among 24 survival-associated SNPs analyzed, one (rs9350) was associated with OS (P &lt; 0.05). No putative risk SNPs or putative survival-associated SNPs were found to be associated with OS or risk, respectively. Furthermore, our GWAS identified a novel SNP [rs1482426, combined stage I and II, P = 1.7 × 10−6, per-allele HR, 1.74; 95% confidence interval (CI), 1.38–2.18] to be putatively associated with OS.
Conclusions: The effects of SNPs on pancreatic cancer risk and OS were replicated in our study, although further work is necessary to understand the functional mechanisms underlying these effects. More importantly, the putative association with OS identified by GWAS suggests that GWAS may be useful in identifying SNPs associated with clinical outcome in pancreatic cancer. Clin Cancer Res; 18(14); 3942–51. ©2012 AACR.
Vandetanib for the Treatment of Symptomatic or Progressive Medullary Thyroid Cancer in Patients with Unresectable Locally Advanced or Metastatic Disease: U.S. Food and Drug Administration Drug Approval Summary
Authors: Thornton Katherine , Kim Geoffrey , Maher V. Ellen , Chattopadhyay Somesh , Tang Shenghui , Moon Young Jin , Song Pengfei , Marathe Anshu , Balakrishnan Suchitra , Zhu Hao , Garnett Christine , Liu Qi , Booth Brian , Gehrke Brenda , Dorsam Robert , Verbois Leigh , Ghosh Debasis , Wilson Wendy , Duan John , Sarker Haripada , Miksinski Sarah Pope , Skarupa Lisa , Ibrahim Amna , Justice Robert , Murgo Anthony , Pazdur Richard 
Published: June 2012

Abstract
On April 6, 2011, the U.S. Food and Drug Administration approved vandetanib (Caprelsa tablets; AstraZeneca Pharmaceuticals LP) for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable, locally advanced, or metastatic disease. Vandetanib is the first drug approved for this indication, and this article focuses on the basis of approval. Approval was based on the results of a double-blind trial conducted in patients with medullary thyroid carcinoma. Patients were randomized 2:1 to vandetanib, 300 mg/d orally (n = 231), or to placebo (n = 100). The primary objective was demonstration of improvement in progression-free survival (PFS) with vandetanib compared with placebo. Other endpoints included evaluation of overall survival and objective response rate. The PFS analysis showed a marked improvement for patients randomized to vandetanib (hazard ratio = 0.35; 95% confidence interval, 0.24–0.53; P &lt; 0.0001). The objective response rate for the vandetanib arm was 44% compared with 1% for the placebo arm. The most common grade 3 and 4 toxicities (&gt;5%) were diarrhea and/or colitis, hypertension and hypertensive crisis, fatigue, hypocalcemia, rash, and corrected QT interval (QTc) prolongation. This approval was based on a statistically significant and clinically meaningful improvement in PFS. Given the toxicity profile, which includes prolongation of the QT interval and sudden death, only prescribers and pharmacies certified through the vandetanib Risk Evaluation Mitigation Strategy Program are able to prescribe and dispense vandetanib. Treatment-related risks should be taken into account when considering the use of vandetanib in patients with indolent, asymptomatic, or slowly progressing disease. Clin Cancer Res; 18(14); 3722–30. ©2012 AACR.
Expansion of a Regional ST-Segment–Elevation Myocardial Infarction System to an Entire State
Authors: Jollis James G. , Al-Khalidi Hussein R. , Monk Lisa , Roettig Mayme L. , Garvey J. Lee , Aluko Akinyele O. , Wilson B. Hadley , Applegate Robert J. , Mears Greg , Corbett Claire C. , Granger Christopher B. 
Published: June 2012

Background—
Despite national guidelines calling for timely coronary artery reperfusion, treatment is often delayed, particularly for patients requiring interhospital transfer.

Methods and Results—

One hundred nineteen North Carolina hospitals developed coordinated plans to rapidly treat patients with ST-segment–elevation myocardial infarction according to presentation: walk-in, ambulance, or hospital transfer. A total of 6841 patients with ST-segment–elevation myocardial infarction (3907 directly presenting to 21 percutaneous coronary intervention hospitals, 2933 transferred from 98 non–percutaneous coronary intervention hospitals) were treated between July 2008 and December 2009 (age, 59 years; 30% women; 19% uninsured; chest pain duration, 91 minutes; shock, 9.2%). The rate of patients not receiving reperfusion fell from 5.4% to 4.0% (
P
=0.04). Treatment times for hospital transfer patients substantially improved. First-hospital-door-to-device time for hospitals that adopted a “transfer for percutaneous coronary intervention” reperfusion strategy fell from 117 to 103 minutes (
P
=0.0008), whereas times at hospitals with a mixed strategy of transfer or fibrinolysis fell from 195 to 138 minutes (
P
=0.002). Median door-to-device times for patients presenting directly to PCI hospitals fell from 64 to 59 minutes (
P
<0.001). Emergency medical services–transported patients were most likely to reach door-to-device goals, with 91% treated within 90 minutes and 52% being treated with 60 minutes. Patients treated within guideline goals had a mortality of 2.2% compared with 5.7% for those exceeding guideline recommendations (
P
<0.001).

Conclusion—
Through extension of regional coordination to an entire state, rapid diagnosis and treatment of ST-segment–elevation myocardial infarction has become an established standard of care independently of healthcare setting or geographic location.
A Short-Term Ensemble Wind Speed Forecasting System for Wind Power Applications
Authors: Traiteur Justin J. , Callicutt David J. , Smith Maxwell , Roy Somnath Baidya 
Published: June 2012

AbstractThis study develops an adaptive, blended forecasting system to provide accurate wind speed forecasts 1 h ahead of time for wind power applications. The system consists of an ensemble of 21 forecasts with different configurations of the Weather Research and Forecasting Single Column Model and persistence, autoregressive, and autoregressive moving-average models. The ensemble is calibrated against observations for a 6-month period (January–June 2006) at a potential wind-farm site in Illinois using the Bayesian model averaging technique. The forecasting system is evaluated against observations for the July 2006–December 2007 period at the same site. The calibrated ensemble forecasts significantly outperform the forecasts from the uncalibrated ensemble as well the time series models under all environmental stability conditions. This forecasting system is computationally more efficient than traditional numerical weather prediction models and can generate a calibrated forecast, including model runs and calibration, in approximately 1 min. Currently, hour-ahead wind speed forecasts are almost exclusively produced using statistical models. However, numerical models have several distinct advantages over statistical models including the potential to provide turbulence forecasts. Hence, there is an urgent need to explore the role of numerical models in short-term wind speed forecasting. This work is a step in that direction and is likely to trigger a debate within the wind speed forecasting community.
Observational Evidence for Relationships between the Degree of Aggregation of Deep Convection, Water Vapor, Surface Fluxes, and Radiation
Authors: Tobin Isabelle , Bony Sandrine , Roca Remy 
Published: June 2012

Abstract
Tropical deep convection exhibits complex organization over a wide range of scales. This study investigates the relationships between the spatial organization of deep convection and the large-scale atmospheric state. By using several satellite datasets and reanalyses, and by defining a simple diagnostic of convective aggregation, relationships between the degree of convective aggregation and the amount of water vapor, turbulent surface fluxes, and radiation are highlighted above tropical oceans. When deep convection is more aggregated, the middle and upper troposphere are drier in the convection-free environment, turbulent surface fluxes are enhanced, and the low-level and midlevel cloudiness is reduced in the environment. Humidity and cloudiness changes lead to a large increase in outgoing longwave radiation. Cloud changes also result in reduced reflected shortwave radiation. Owing to these opposing effects, the sensitivity of the radiative budget at the top of the atmosphere to convective aggregation turns out to be weak, but the distribution of radiative heating throughout the troposphere is affected. These results suggest that feedbacks between convective aggregation and the large-scale atmospheric state might influence large-scale dynamics and the transports of water and energy and, thus, play a role in the climate variability and change. These observational findings are qualitatively consistent with previous cloud-resolving model results, except for the effects on cloudiness and reflected shortwave radiation. The proposed methodology may be useful for assessing the representation of convective aggregation and its interaction with the large-scale atmospheric state in various numerical models.
Simulation of the East Asian Summer Monsoon during the Last Millennium with the MPI Earth System Model
Authors: Man Wenmin , Zhou Tianjun , Jungclaus Johann H. 
Published: June 2012

Abstract
The decadal–centennial variations of East Asian summer monsoon (EASM) and the associated rainfall change during the past millennium are simulated using the earth system model developed at the Max Planck Institute for Meteorology. The model was driven by up-to-date reconstructions of external forcing including the recent low-amplitude estimates of solar variations. Analysis of the simulations indicates that the EASM is generally strong during the Medieval Warm Period (MWP; A.D. 1000–1100) and weak during the Little Ice Age (LIA; A.D. 1600–1700). The monsoon rainband exhibits a meridional tripolar pattern during both epochs. Excessive (deficient) precipitation is found over northern China (35°–42°N, 100°–120°E) but deficient (excessive) precipitation is seen along the Yangtze River valley (27°–34°N, 100°–120°E) during the MWP (LIA). Both similarities and disparities of the rainfall pattern between the model results herein and the proxy data have been compared, and reconstructions from Chinese historical documents and some geological evidence support the results. The changes of the EASM circulation including the subtropical westerly jet stream in the upper troposphere and the western Pacific subtropical high (WPSH) in the middle and lower troposphere are consistent with the meridional shift of the monsoon rain belt during both epochs. The meridional monsoon circulation changes are accompanied with anomalous southerly (northerly) winds between 20° and 50°N during the MWP (LIA). The land–sea thermal contrast change caused by the effective radiative forcing leads to the MWP and LIA monsoon changes. The “warmer land–colder ocean” anomaly pattern during the MWP favors a stronger monsoon, while the “colder land–warmer ocean” anomaly pattern during the LIA favors a weaker monsoon.
On the Correspondence between Short- and Long-Time-Scale Systematic Errors in CAM4/CAM5 for the Year of Tropical Convection
Authors: Xie Shaocheng , Ma Hsi-Yen , Boyle James S. , Klein Stephen A. , Zhang Yuying 
Published: June 2012

Abstract
The correspondence between short- and long-time-scale systematic errors in the Community Atmospheric Model, version 4 (CAM4) and version 5 (CAM5), is systematically examined. The analysis is based on the annual-mean data constructed from long-term “free running” simulations and short-range hindcasts. The hindcasts are initialized every day with the ECMWF analysis for the Year(s) of Tropical Convection. It has been found that most systematic errors, particularly those associated with moist processes, are apparent in day 2 hindcasts. These errors steadily grow with the hindcast lead time and typically saturate after five days with amplitudes comparable to the climate errors. Examples include the excessive precipitation in much of the tropics and the overestimate of net shortwave absorbed radiation in the stratocumulus cloud decks over the eastern subtropical oceans and the Southern Ocean at about 60°S. This suggests that these errors are likely the result of model parameterization errors as the large-scale flow remains close to observed in the first few days of the hindcasts. In contrast, other climate errors are present in the hindcasts, but with amplitudes that are significantly smaller than and do not approach their climate errors during the 6-day hindcasts. These include the cold biases in the lower stratosphere, the unrealistic double–intertropical convergence zone pattern in the simulated precipitation, and an annular mode bias in extratropical sea level pressure. This indicates that these biases could be related to slower processes such as radiative and chemical processes, which are important in the lower stratosphere, or the result of poor interactions of the parameterized physics with the large-scale flow.
Baroclinic Frontal Instabilities and Turbulent Mixing in the Surface Boundary Layer. Part I: Unforced Simulations
Authors: Skyllingstad Eric D. , Samelson R. M. 
Published: June 2012

Abstract
Interaction between mixed layer baroclinic eddies and small-scale turbulence is studied using a nonhydrostatic large-eddy simulation (LES) model. Free, unforced flow evolution is considered, for a standard initialization consisting of an 80-m-deep mixed layer with a superposed warm filament and two frontal interfaces in geostrophic balance, on a model domain roughly 5 km × 10 km × 120 m, with an isotropic 3-m computational grid. Results from these unforced experiments suggest that shear generated in narrow frontal zones can support weak three-dimensional turbulence that is directly linked to the larger-scale baroclinic waves. Two separate but closely related issues are addressed: 1) the possible development of enhanced turbulent mixing associated with the baroclinic wave activity and 2) the existence of a downscale transfer of energy from the baroclinic wave scale to the turbulent dissipation scale. The simulations show enhanced turbulence associated with the baroclinic waves and enhanced turbulent heat flux across the isotherms of the imposed frontal boundary, relative to background levels. This turbulence develops on isolated small-scale frontal features that form as the result of frontogenetic processes operating on the baroclinic wave scale and not as the result of a continuous, inertial forward cascade through the intermediate scales. Analysis of the spectrally decomposed kinetic energy budget indicates that large-scale baroclinic eddy energy is directly transferred to small-scale turbulence, with weaker forcing at intermediate scales. For fronts with significant baroclinic wave activity, cross-frontal eddy fluxes computed from correlations of fluctuations from means along the large-scale frontal axis generally agreed with simple theoretical estimates.
Impact of Tropical Cyclones on the Heat Budget of the South Pacific Ocean
Authors: Jullien S. , Menkes C. E. , Marchesiello P. , Jourdain N. C. , Lengaigne M. , Koch-Larrouy A. , Lefèvre J. , Vincent E. M. , Faure V. 
Published: June 2012

Abstract
The present study investigates the integrated ocean response to tropical cyclones (TCs) in the South Pacific convergence zone through a complete ocean heat budget. The TC impact analysis is based on the comparison between two long-term (1979–2003) oceanic simulations forced by a mesoscale atmospheric model solution in which extreme winds associated with cyclones are either maintained or filtered. The simulations provide a statistically robust experiment that fills a gap in the current modeling literature between coarse-resolution and short-term studies. The authors’ results show a significant thermal response of the ocean to at least 500-m depth, driven by competing mixing and upwelling mechanisms. As suggested in previous studies, vertical mixing largely explains surface cooling induced by TCs. However, TC-induced upwelling of deeper waters plays an unexpected role as it partly balances the warming of subsurface waters induced by vertical mixing. Below 100 m, vertical advection results in cooling that persists long after the storm passes and has a signature in the ocean climatology. The heat lost through TC-induced vertical advection is exported outside the cyclogenesis area with strong interannual variability. In addition, 60% of the heat input below the surface during the cyclone season is released back to the oceanic mixed layer through winter entrainment and then to the atmosphere. Therefore, seasonal modulation reduces the mean surface heat flux due to TCs to about 3 × 10−3 PW in this region exposed to 10%–15% of the world’s cyclones. The resulting climatological anomaly is a warming of about 0.1°C in the subsurface layer and cooling below the thermocline (less than 0.1°C).
Quantification of Cloud Microphysical Parameterization Uncertainty Using Radar Reflectivity
Authors: van Lier-Walqui Marcus , Vukicevic Tomislava , Posselt Derek J. 
Published: June 2012

Abstract
Uncertainty in cloud microphysical parameterization—a leading order contribution to numerical weather prediction error—is estimated using a Markov chain Monte Carlo (MCMC) algorithm. An inversion is performed on 10 microphysical parameters using radar reflectivity observations with vertically covarying error as the likelihood constraint. An idealized 1D atmospheric column model with prescribed forcing is used to simulate the microphysical behavior of a midlatitude squall line. Novel diagnostics are employed for the probabilistic investigation of individual microphysical process behavior vis-à-vis parameter uncertainty. Uncertainty in the microphysical parameterization is presented via posterior probability density functions (PDFs) of parameters, observations, and microphysical processes. The results of this study show that radar reflectivity observations, as expected, provide a much stronger constraint on microphysical parameters than column-integral observations, in most cases reducing both the variance and bias in the maximum likelihood estimate of parameter values. This highlights the enhanced potential of radar reflectivity observations to provide information about microphysical processes within convective storm systems despite the presence of strongly nonlinear relationships within the microphysics model. The probabilistic analysis of parameterization uncertainty in terms of both parameter and process activity PDFs suggest the prospect of a stochastic representation of microphysical parameterization uncertainty—specifically the results indicate that error may be more easily represented and estimated by microphysical process uncertainty rather than microphysical parameter uncertainty. In addition, these new methods of analysis allow for a detailed investigation of the full nonlinear and multivariate relationships between microphysical parameters, microphysical processes, and radar observations.
Impact of Geographic-Dependent Parameter Optimization on Climate Estimation and Prediction: Simulation with an Intermediate Coupled Model
Authors: Wu Xinrong , Zhang Shaoqing , Liu Zhengyu , Rosati Anthony , Delworth Thomas L. , Liu Yun 
Published: June 2012

Abstract
Because of the geographic dependence of model sensitivities and observing systems, allowing optimized parameter values to vary geographically may significantly enhance the signal in parameter estimation. Using an intermediate atmosphere–ocean–land coupled model, the impact of geographic dependence of model sensitivities on parameter optimization is explored within a twin-experiment framework. The coupled model consists of a 1-layer global barotropic atmosphere model, a 1.5-layer baroclinic ocean including a slab mixed layer with simulated upwelling by a streamfunction equation, and a simple land model. The assimilation model is biased by erroneously setting the values of all model parameters. The four most sensitive parameters identified by sensitivity studies are used to perform traditional single-value parameter estimation and new geographic-dependent parameter optimization. Results show that the new parameter optimization significantly improves the quality of state estimates compared to the traditional scheme, with reductions of root-mean-square errors as 41%, 23%, 62%, and 59% for the atmospheric streamfunction, the oceanic streamfunction, sea surface temperature, and land surface temperature, respectively. Consistently, the new parameter optimization greatly improves the model predictability as a result of the improvement of initial conditions and the enhancement of observational signals in optimized parameters. These results suggest that the proposed geographic-dependent parameter optimization scheme may provide a new perspective when a coupled general circulation model is used for climate estimation and prediction.
The Impact of Low Clouds on Surface Shortwave Radiation in the ECMWF Model
Authors: Ahlgrimm Maike , Forbes Richard 
Published: June 2012

AbstractThe long-term measurement records from the Atmospheric Radiation Measurement site on the Southern Great Plains show evidence of a bias in the ECMWF model’s surface irradiance. Based on previous studies, which have suggested that summertime shallow clouds may contribute to the bias, an evaluation of 146 days with observed nonprecipitating fair-weather cumulus clouds is performed. In-cloud liquid water path and effective radius are both overestimated in the model with liquid water path dominating to produce clouds that are too reflective. These are compensated by occasional cloud-free days in the model such that the fair-weather cumulus regime overall does not contribute significantly to the multiyear daytime mean surface irradiance bias of 23 W m−2. To further explore the origin of the bias, observed and modeled cloud fraction profiles over 6 years are classified and sorted based on the surface irradiance bias associated with each sample pair. Overcast low cloud conditions during the spring and fall seasons are identified as a major contributor. For samples with low cloud present in both observations and model, opposing surface irradiance biases are found for overcast and broken cloud cover conditions. A reduction of cloud liquid to a third for broken low clouds and an increase by a factor of 1.5 in overcast situations improves agreement with the observed liquid water path distribution. This approach of combining the model shortwave bias with a cloud classification helps to identify compensating errors in the model, providing guidance for a targeted improvement of cloud parameterizations.