bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Clinical and Pharmacokinetic Study of Aflibercept in Patients with Previously Treated Metastatic Colorectal Cancer
Authors: Tang Patricia A. , Cohen Steven J. , Kollmannsberger Christian , Bjarnason Georg , Virik Kiran , MacKenzie Mary J. , Lourenco Lillian , Wang Lisa , Chen Alice , Moore Malcolm J. 
Published: September 2012

Abstract
Purpose: Aflibercept is a recombinant fusion protein of the VEGF receptor (VEGFR) 1 and VEGFR2 extracellular domains. We assessed the safety and efficacy of aflibercept in patients with metastatic colorectal cancer (MCRC) who had received at least one prior palliative regimen.
Experimental Design: Seventy-five patients were enrolled onto this two-stage phase II trial in two cohorts, bevacizumab naïve (n = 24) and prior bevacizumab (n = 51). Aflibercept was administered at 4 mg/kg i.v. in two-week cycles. The primary endpoint was a combination of objective response rate and 16-week progression-free survival (PFS).
Results: In the bevacizumab-naïve cohort (n = 24), the best response was stable disease for 16 weeks or more in five of 24 patients. In the prior bevacizumab cohort (n = 50), one patient achieved a partial response and six patients had stable disease for 16 weeks or more. The median PFS in the bevacizumab-naïve and prior bevacizumab cohorts was two months [95% confidence interval (CI): 1.7–8.6 months] and 2.4 months (95% CI: 1.9–3.7 months), respectively. Median overall survival (OS) was 10.4 months (95% CI: 7.6–15.5) and 8.5 months (95% CI: 6.2–10.6), respectively. The most common grade 3 or higher treatment-related adverse events were hypertension, proteinuria, fatigue, and headache. Ten patients discontinued study treatment due to toxicity. Mean free to VEGF-bound aflibercept ratio was 1.82, suggesting that free aflibercept was present in sufficient amount to bind endogenous VEGF.
Conclusion: Aflibercept showed limited single-agent activity in patients with pretreated MCRC with moderate toxicity. Further study of aflibercept with chemotherapy is ongoing. Clin Cancer Res; 18(21); 6023–31. ©2012 AACR.
Clinical and Genetic Association of Serum Paraoxonase and Arylesterase Activities With Cardiovascular Risk
Authors: Tang W.H. Wilson , Hartiala Jaana , Fan Yiying , Wu Yuping , Stewart Alexandre F.R. , Erdmann Jeanette , Kathiresan Sekar ,   The CARDIoGRAM Consortium, Roberts Robert , McPherson Ruth , Allayee Hooman , Hazen Stanley L. 
Published: September 2012

Objective—
Diminished serum paraoxonase and arylesterase activities (measures of paraoxonase-1 [PON-1] function) in humans have been linked to heightened systemic oxidative stress and atherosclerosis risk. The clinical prognostic use of measuring distinct PON-1 activities has not been established, and the genetic determinants of PON-1 activities are not known.

Methods and Results—

We established analytically robust high-throughput assays for serum paraoxonase and arylesterase activities and measured these in 3668 stable subjects undergoing elective coronary angiography without acute coronary syndrome and were prospectively followed for major adverse cardiovascular events (MACE= death, myocardial infarction, stroke) over 3 years. Low serum arylesterase and paraoxonase activities were both associated with increased risk for MACE, with arylesterase activity showing greatest prognostic value (quartile 4 versus quartile 1; hazard ratio 2.63; 95% CI, 1.97–3.50;
P
<0.01). Arylesterase remained significant after adjusting for traditional risk factors, C-reactive protein, and creatinine clearance (hazard ratio, 2.20; 95% CI, 1.60–3.02;
P
<0.01), predicted future development of MACE in both primary and secondary prevention populations, and reclassified risk categories incrementally to traditional clinical variables. A genome-wide association study identified distinct single nucleotide polymorphisms within the PON-1 gene that were highly significantly associated with serum paraoxonase (1.18×10
-303
) or arylesterase (4.99×10
−116
) activity but these variants were not associated with either 3-year MACE risk in an angiographic cohort (n=2136) or history of either coronary artery disease or myocardial infarction in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis consortium (n≈80 000 subjects).

Conclusion—
Diminished serum arylesterase activity, but not the genetic determinants of PON-1 functional measures, provides incremental prognostic value and clinical reclassification of stable subjects at risk of developing MACE.
Association of Oxidative DNA Damage and C-Reactive Protein in Women at Risk for Cardiovascular Disease
Authors: Noren Hooten Nicole , Ejiogu Ngozi , Zonderman Alan B. , Evans Michele K. 
Published: September 2012

Objective—
The aim of the current study was to examine the relationship between clinical markers of inflammation and 8-oxo-7,8-dihydro-2′deoxyguanosine (8-oxodG), an oxidative stress marker, in middle-aged women drawn from the HANDLS study, a longitudinal epidemiological study.

Methods and Results—
We examined commonly assayed markers of inflammation, the DNA base adduct 8-oxodG, a marker of oxidative stress, and cardiovascular risk factors in a cohort of women matched on age and race in 3 groups (n=39 per group) who had low (<3 mg/L) high-sensitivity C-reactive protein (hsCRP), mid (>3–20 mg/L), and high (>20 mg/L) hsCRP. We found a significant relationship between hsCRP level and the oxidative stress marker, 8-oxodG. 8-oxodG was positively correlated with systolic blood pressure, pulse pressure, and interleukin-23. hsCRP was associated with obesity variables, high-density lipoprotein, serum insulin levels, interleukin-12p70 and intracellular adhesion molecule-1. Incubation of primary human endothelial cells with hsCRP generated reactive oxygen species in vitro. Furthermore, hsCRP specifically induced DNA base lesions, but not other forms of DNA damage, including single and double strand breaks.

Conclusion—
These data suggest that in women 8-oxodG is associated with hsCRP and is independently related to select cardiovascular risk factors. Our data in women suggest that hsCRP may contribute to cardiovascular disease by increasing oxidative stress.
Identifying the MJO, Equatorial Waves, and Their Impacts Using 32 Years of HIRS Upper-Tropospheric Water Vapor
Authors: Schreck Carl J. , Shi Lei , Kossin James P. , Bates John J. 
Published: September 2012

Abstract
The Madden–Julian oscillation (MJO) and convectively coupled equatorial waves are the dominant modes of synoptic-to-subseasonal variability in the tropics. These systems have frequently been examined with proxies for convection such as outgoing longwave radiation (OLR). However, upper-tropospheric water vapor (UTWV) gives a more complete picture of tropical circulations because it is more sensitive to the drying and warming associated with subsidence. Previous studies examined tropical variability using relatively short (3–7 yr) UTWV datasets. Intersatellite calibration of data from the High Resolution Infrared Radiation Sounder (HIRS) has recently produced a homogeneous 32-yr climate data record of UTWV for 200–500 hPa. This study explores the utility of HIRS UTWV for identifying the MJO and equatorial waves.
Spectral analysis shows that the MJO and equatorial waves stand out above the low-frequency background in UTWV, similar to previous findings with OLR. The fraction of variance associated with the MJO and equatorial Rossby waves is actually greater in UTWV than in OLR. Kelvin waves, on the other hand, are overshadowed in UTWV by horizontal advection from extratropical Rossby waves.
For the MJO, UTWV identifies subsidence drying in the subtropics, poleward of the convection. These dry anomalies are associated with the MJO’s subtropical Rossby gyres. MJO events with dry anomalies over the central North Pacific Ocean also amplify the 200-hPa flow pattern over North America 7 days later. These events cannot be identified using equatorial OLR alone, which demonstrates that UTWV is a useful supplement for identifying the MJO, equatorial waves.
Comparative Strengths of SCaMPR Satellite QPEs with and without TRMM Ingest versus Gridded Gauge-Only Analyses
Authors: Zhang Yu , Seo Dong-Jun , Kitzmiller David , Lee Haksu , Kuligowski Robert J. , Kim Dongsoo , Kondragunta Chandra R. 
Published: September 2012

Abstract
This paper assesses the accuracy of satellite quantitative precipitation estimates (QPEs) from two versions of the Self-Calibrating Multivariate Precipitation Retrieval (SCaMPR) algorithm relative to that of gridded gauge-only QPEs. The second version of SCaMPR uses the QPEs from Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar and Microwave Imager as predictands whereas the first version does not. The assessments were conducted for 22 catchments in Texas and Louisiana against National Weather Service operational multisensor QPE. Particular attention was given to the density below which SCaMPR QPEs outperform gauge-only QPEs and effects of TRMM ingest. Analyses indicate that SCaMPR QPEs can be competitive in terms of correlation and CSI against sparse gauge networks (with less than one gauge per 3200–12 000 km2) and over 1–3-h scale, but their relative strengths diminish with temporal aggregation. In addition, the major advantage of SCaMPR QPEs is its relatively low false alarm rates, whereas gauge-only QPEs exhibit better skill in detecting rainfall—though the detection skill of SCaMPR QPEs tends to improve at higher rainfall thresholds. Moreover, it was found that ingesting TRMM QPEs help mitigate the positive overall bias in SCaMPR QPEs, and improve the detection of moderate–heavy and particularly wintertime precipitation. Yet, it also tends to elevate the false alarm rate, and its impacts on detection rates can be slightly negative for summertime storms. The implications for adoption of TRMM and Global Precipitation Measurement (GPM) QPEs for NWS operations are discussed.
Statistical Assessment of Tropical Convection-Permitting Model Simulations Using a Cell-Tracking Algorithm
Authors: Caine Simon , Lane Todd P. , May Peter T. , Jakob Christian , Siems Steven T. , Manton Michael J. , Pinto James 
Published: September 2012

Abstract
This study presents a method for comparing convection-permitting model simulations to radar observations using an innovative object-based approach. The method uses the automated cell-tracking algorithm, Thunderstorm Identification Tracking Analysis and Nowcasting (TITAN), to identify individual convective cells and determine their properties. Cell properties are identified in the same way for model and radar data, facilitating comparison of their statistical distributions. The method is applied to simulations of tropical convection during the Tropical Warm Pool-International Cloud Experiment (TWP-ICE) using the Weather Research and Forecasting Model, and compared to data from a ground-based radar. Simulations with different microphysics and model resolution are also conducted. Among other things, the comparisons between the model and the radar elucidate model errors in the depth and size of convective cells. On average, simulated convective cells reached higher altitudes than the observations. Also, when using a low reflectivity (25 dBZ) threshold to define convective cells, the model underestimates the size of the largest cells in the observed population. Some of these differences are alleviated with a change of microphysics scheme and higher model resolution, demonstrating the utility of this method for assessing model changes.
Genesis of the Goshen County, Wyoming, Tornado on 5 June 2009 during VORTEX2
Authors: Kosiba Karen , Wurman Joshua , Richardson Yvette , Markowski Paul , Robinson Paul , Marquis James 
Published: September 2012

Abstract
The genesis of a strong and long-lived tornado observed during the second Verification of the Origins of Rotation in Tornadoes Experiment (VORTEX2) in Goshen County, Wyoming, on 5 June 2009 is studied. Mobile radar, mobile mesonet, rawinsonde, and photographic data are used to produce an integrated analysis of the evolution of the wind, precipitation, and thermodynamic fields in the parent supercell to deduce the processes that resulted in tornadogenesis. Several minutes prior to tornadogenesis, the rear-flank downdraft intensifies, and a secondary rear-flank downdraft forms and cyclonically wraps around the developing tornado. Kinematic and thermodynamic analyses suggest that horizontal vorticity created in the forward flank and hook echo is tilted and then stretched near the developing tornado. Tilting and stretching are enhanced in the developing low-level circulation as the secondary rear-flank downdraft develops, intensifies, and wraps around the circulation center. Shortly thereafter, the tornado forms. Tornadogenesis does not proceed steadily. Strengthening, weakening, and renewed intensification of the tornado are documented in photographic, reflectivity, Doppler velocity, and dual-Doppler fields and are associated with, and shortly follow, changes in the secondary rear-flank downdraft, convergence, location of the vortex relative to the updraft/downdraft couplet, tilting and stretching near and in the developing tornado, and the evolution of total circulation.
Covariance Localization with the Diffusion-Based Correlation Models
Authors: Yaremchuk Max , Nechaev Dmitry 
Published: September 2012

Abstract
Improving the performance of ensemble filters applied to models with many state variables requires regularization of the covariance estimates by localizing the impact of observations on state variables. A covariance localization technique based on modeling of the sample covariance with polynomial functions of the diffusion operator (DL method) is presented. Performance of the technique is compared with the nonadaptive (NAL) and adaptive (AL) ensemble localization schemes in the framework of numerical experiments with synthetic covariance matrices in a realistically inhomogeneous setting. It is shown that the DL approach is comparable in accuracy with the AL method when the ensemble size is less than 100. With larger ensembles, the accuracy of the DL approach is limited by the local homogeneity assumption underlying the technique. Computationally, the DL method is comparable with the NAL technique if the ratio of the local decorrelation scale to the grid step is not too large.
The mental health of internally displaced persons: An epidemiological study of adults in two settlements in Central Sudan
Authors: Salah Tarig Taha Mohamed , Abdelrahman Abdallah , Lien Lars , Eide Arne Henning , Martinez Priscilla , Hauff Edvard 
Published: September 2012

Aims: There is a scarcity of data on mental health problems among Sudanese internally displaced persons (IDPs). This study aims to assess the prevalence of mental disorders of IDPs in Sudan, and to determine and compare the association between mental disorders and socio-demographic variables between the rural and urban long-term IDP populations. Methods: This cross-sectional study was implemented in two IDP areas in Central Sudan. Data were collected during face-to-face interviews using structured questionnaires to assess socio-demographic factors and the Mini International Neuropsychiatric Interview (MINI) to determine psychiatric diagnoses. A total of 1,876 adults were enrolled from both study areas. Results: The overall prevalence of having any mental health disorder in the IDP population was 52.9%. The most common disorders were major depressive disorder (24.3%), generalized anxiety disorder (23.6%), social phobia (14.2%) and post-traumatic stress disorder (12.3%). Years of displacement and education were associated with different mental disorders between the two areas, and there were no gender differences in prevalence of mental disorders in either area. Conclusion: This study shows high prevalence rates of mental disorders in both urban and rural IDP populations in Sudan, indicating a need to explore the circumstances for these high rates and to develop appropriate responses.
Effects of Demineralized Bone Matrix on Tendon-Bone Healing in an Intra-articular Rodent Model
Authors: Lovric Vedran , Chen Dong , Yu Yan , Oliver Rema A. , Genin Francois , Walsh William R. 
Published: September 2012

Background: Techniques to improve and accelerate tendon-bone healing could be advantageous in anterior cruciate ligament (ACL) reconstruction. Effects of demineralized bone matrix (DBM) on intra-articular tendon-bone healing have not been examined. Hypothesis: Demineralized bone matrix has the potential to convey osteoinductive growth proteins to the site of healing at the tendon-bone interface. We hypothesized that the presence of DBM will result in more bone formation and hasten tendon-bone healing. Study Design: Controlled laboratory study. Methods: Fifty-six female athymic rnu/rnu (nude) rats were used. Rats were randomly allocated into 2 groups (control or treatment). The control group underwent an ACL reconstruction, while the treatment group had human DBM implanted in the tendon graft and bone tunnel before reconstruction. Rats were sacrificed at 2 (n = 8), 4 (n = 24), and 6 (n = 24) weeks for histological, and immunohistochemical (t = 2, 4, and 6 weeks), and biomechanical testing and micro–computed tomography (t = 4 and 6 weeks) end points. Results: Our findings suggest that in the presence of DBM, tendon-bone healing is augmented by increased woven bone formation and enhanced bone remodeling as indicated by histology and micro–computed tomography. This ultimately resulted in a statistically significant increase in peak load to failure of the tendon-bone interface at 4 weeks (DBM group: 5.96 ± 1.36 N; control group: 2.86 ± 0.7 N) and 6 weeks (DBM group: 9.13 ± 0.97 N; control group: 5.81 ± 1.1 N). Conclusion: Demineralized bone matrix at the tendon-bone interface promotes healing between the tendon and bone in a rodent ACL model. Clinical Relevance: Introduction of osteoinductive DBM at the tendon-bone interface during ACL reconstructive surgery may improve short-term outcomes.
Energy optimisation in manufacturing systems using virtual engineering-driven discrete event simulation
Authors: Ghani Usman , Monfared Radmehr P , Harrison Robert 
Published: September 2012

Increasing the cost of electricity and the global obligations for efficient use of energy have added additional pressure to industrial companies in an already challenging market. Manufacturing companies are adopting methods to have a greater agility to respond quicker to the market dynamics and varying demands by changing production configurations. In recent years, deploying virtual engineering design approaches and extensive simulation methods have facilitated an early insight into how a system may perform, in advance of the physical build. However, the impact of system reconfiguration on the cost of energy consumption is typically unknown. Much research has been carried out on the development of new energy-efficient drives (e.g. motors and actuators) and also the possibility of turning off the drives when idle to save energy. However, in this article, the authors propose a new method of energy saving for engineering production lines by fine tuning the low level device motions to optimise energy consumption. An integration method between virtual engineering design and simulation modelling is proposed, and as a result a simulation method for energy optimisation is developed. In this article the method of interpreting virtual design data for use in simulation modelling of a production assembly line in an automotive industry is discussed. Furthermore, a developed algorithm for optimising energy usage based on adjusting dynamic properties of the system components (e.g. accelerations, torque and mass) is discussed and the result of implementing the concept in an experimental application in the powertrain industry is reported.
The effect of enhanced curving forces on the behaviour of canted ballasted track
Authors: Priest Jeffery A , Powrie William , Le Pen Louis , Mak Patric , Burstow Mark C 
Published: September 2012

The performance of railway ballast depends not only on the characteristics of the ballast itself but also the magnitude, frequency and number of axle loads imposed by the trains running on the track it supports. Recent trends towards more frequent and faster trains have highlighted some potential limitations of ballasted railway track. In particular, the introduction of tilting trains on the UK West Coast Main Line, which allowed train operating speeds to be increased over much of the route, has coincided with the sporadic occurrence of localized areas of ballast migration. This phenomenon involves ballast particles moving from the high side of a canted section of track to the low side, exposing the sleeper ends on the high (outer) side of the curve, reducing the lateral resistance of the track and therefore increasing maintenance requirements. This paper reports the results of an investigation carried out to try to identify the underlying mechanism responsible for this behaviour. Measurements of sleeper end displacements under the passage of trains were made at two locations which had experienced ballast migration. Analysis of the measured data together with numerical modelling of the forces imposed on the track structure suggest that the increased speed and typical axle loads of the tilting trains result in larger lateral forces and larger rotation of the sleeper (in the vertical plane) than for a train consisting of a locomotive plus trailing vehicle, as was previously used on the route. It is hypothesized that this leads in turn to a slow but progressive movement of the ballast down the slope of the canted track. However, given the highly localized nature of the ballast migration sites, other factors such as an irregular sub-base stiffness and ballast depth may also contribute to the phenomenon and further work is required to determine the combinations of circumstances that may trigger this effect.