bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGFα and Amphiregulin Paracrine Network Promotes Resistance to EGFR Blockade in Colorectal Cancer Cells
Authors: Hobor Sebastijan , Van Emburgh Beth O. , Crowley Emily , Misale Sandra , Di Nicolantonio Federica , Bardelli Alberto 
Published: June 2014

Abstract
Purpose: Targeted inhibition of EGFR with the mAbs cetuximab or panitumumab is a valuable treatment for RAS wild-type colorectal cancers. The efficacy of EGFR blockade is limited by the emergence of acquired resistance often attributed to secondary KRAS mutations. Remarkably, tumor biopsies from resistant patients show that only a fraction of the resilient cells carry KRAS mutations. We hypothesized that a paracrine cross-talk driven by the resistant subpopulation may provide in trans protection of surrounding sensitive cells.
Experimental design: Conditioned medium assays and three-dimensional cocultures were used to assess paracrine networks between cetuximab-sensitive and -resistant cells. Production of EGFR ligands by cells sensitive to cetuximab and panitumumab was measured. The ability of recombinant EGFR ligands to protect sensitive cells from cetuximab was assessed. Biochemical activation of the EGFR signaling pathway was measured by Western blotting.
Results: Colorectal cancer cells sensitive to EGFR blockade can successfully grow despite cetuximab treatment when in the company of their resistant derivatives. Media conditioned by resistant cells protect sensitive parental cells from cetuximab. EGFR blockade triggers increased secretion of TGFα and amphiregulin. Increased secretion of ligands by resistant cells can sustain EGFR/ERK signaling in sensitive cells.
Conclusions: Colorectal cancer cells that develop resistance to cetuximab and panitumumab secrete TGFα and amphiregulin, which protect the surrounding cells from EGFR blockade. This paracrine protective mechanism might be therapeutically exploitable. Clin Cancer Res; 20(24); 6429–38. ©2014 AACR.
Ubiquitous Myocardial Extensions Into the Pulmonary Artery Demonstrated by Integrated Intracardiac Echocardiography and Electroanatomic Mapping
Authors: Liu Christopher F. , Cheung Jim W. , Thomas George , Ip James E. , Markowitz Steven M. , Lerman Bruce B. 
Published: June 2014

Background—
Idiopathic ventricular arrhythmias of left bundle branch block inferior axis morphology are usually localized to the right ventricular outflow tract (RVOT), presumably below the pulmonic valve (PV). However, the PV location is usually not confirmed by direct visualization.

Methods and Results—

Intracardiac echocardiography was used to visualize and tag the PV annulus, which was then integrated with 3-dimensional voltage maps of the RVOT. Distances were measured from the furthest extent of myocardial signal (bipolar voltage ≥1.5 mV) to the PV annulus. This was performed in 24 control patients and 24 prospective patients with RVOT arrhythmias. Myocardial signal beyond the PV was found in 92% of controls and 88% of RVOT arrhythmia patients (
P
=1.000). Average myocardial extension was further on the septal side than on the free wall side for control patients (5.6 mm; interquartile range [IQR], 3.6–7.7, versus 1.7 mm; IQR (−)0.1 to (+)4.0;
P
=0.002) and RVOT arrhythmia patients (5.7 mm; IQR, 2.7–7.7, versus 1.4 mm; IQR, (−)0.8 to (+)4.8;
P
=0.004). Eleven (46%) RVOT arrhythmia foci were localized beyond the valve in the pulmonary artery (median 8.2 mm above PV; IQR, 6.6–10.3 mm); these locations were confirmed as supravalvular by direct intracardiac echocardiography visualization.

Conclusions—
Myocardial voltage extension into the pulmonary artery in humans is ubiquitous and can be demonstrated in vivo using 3-dimensional integrated intracardiac echocardiography to localize the PV. These extensions frequently serve as origins of presumed RVOT arrhythmias; intracardiac echocardiography localization of the PV allows reclassification of these as pulmonary arterial arrhythmias.
Development of a Clinical Registry-Based 30-Day Readmission Measure for Coronary Artery Bypass Grafting Surgery
Authors: Shahian David M. , He Xia , O’Brien Sean M. , Grover Frederick L. , Jacobs Jeffrey P. , Edwards Fred H. , Welke Karl F. , Suter Lisa G. , Drye Elizabeth , Shewan Cynthia M. , Han Lein , Peterson Eric 
Published: June 2014

Background—
Reducing readmissions is a major healthcare reform goal, and reimbursement penalties are imposed for higher-than-expected readmission rates. Most readmission risk models and performance measures are based on administrative rather than clinical data.

Methods and Results—
We examined rates and predictors of 30-day all-cause readmission following coronary artery bypass grafting surgery by using nationally representative clinical data (2008–2010) from the Society of Thoracic Surgeons National Database linked to Medicare claims records. Among 265 434 eligible Medicare records, 226 960 (86%) were successfully linked to Society of Thoracic Surgeons records; 162 572 (61%) isolated coronary artery bypass grafting admissions constituted the study cohort. Logistic regression was used to identify readmission risk factors; hierarchical regression models were then estimated. Risk-standardized readmission rates ranged from 12.6% to 23.6% (median, 16.8%) among 846 US hospitals with ≥30 eligible cases and ≥90% of eligible Centers for Medicare and Medicaid Services records linked to the Society of Thoracic Surgeons database. Readmission predictors (odds ratios [95% confidence interval]) included dialysis (2.02 [1.87–2.19]), severe chronic lung disease (1.58 [1.49–1.68]), creatinine (2.5 versus 1.0 or lower:1.49 [1.41–1.57]; 2.0 versus 1.0 or lower: 1.37 [1.32–1.43]), insulin-dependent diabetes mellitus (1.45 [1.39–1.51]), obesity in women (body surface area 2.2 versus 1.8: 1.44 [1.35–1.53]), female sex (1.38 [1.33–1.43]), immunosuppression (1.38 [1.28–1.49]), preoperative atrial fibrillation (1.36 [1.30–1.42]), age per 10-year increase (1.36 [1.33–1.39]), recent myocardial infarction (1.24 [1.08–1.42]), and low body surface area in men (1.22 [1.14–1.30]). C-statistic was 0.648. Fifty-two hospitals (6.1%) had readmission rates statistically better or worse than expected.

Conclusions—
A coronary artery bypass grafting surgery readmission measure suitable for public reporting was developed by using the national Society of Thoracic Surgeons clinical data linked to Medicare readmission claims.
B‐Type Natriuretic Peptide Predicts 30‐Day Readmission for Heart Failure but not Readmission for Other Causes
Authors: Flint Kelsey M. , Allen Larry A. , Pham Michael , Heidenreich Paul A. 
Published: June 2014

Background

B‐type natriuretic peptide (
BNP
) is a marker for heart failure (HF) severity, but its association with hospital readmission is not well defined.

Methods and Results

We identified all hospital discharges (n=109 875) with a primary diagnosis of HF in the Veterans Affairs Health Care System from 2006 to 2009. We examined the association between admission (n=53 585), discharge (n=24 326), and change in
BNP
(n=7187) and 30‐day readmission for HF or other causes. Thirty‐day HF readmission was associated with elevated admission
BNP
, elevated discharge
BNP
, and smaller percent change in
BNP
from admission to discharge. Patients with a discharge
BNP
≥1000 ng/L had an unadjusted 30‐day HF readmission rate over 3 times as high as patients whose discharge
BNP
was ≤200 ng/L (15% vs. 4.1%).
BNP
improved discrimination and risk classification for 30‐day HF readmission when added to a base clinical model, with discharge
BNP
having the greatest effect (C‐statistic, 0.639 to 0.664 [
P
<0.0001]; net reclassification improvement, 9% [
P
<0.0001]). In contrast, 30‐day readmission for non‐HF causes was not associated with
BNP
levels during index HF hospitalization.

Conclusions

In this study of over 50 000 veterans hospitalized with a primary diagnosis of HF,
BNP
levels measured during hospitalization were associated with 30‐day HF readmission, but not readmissions for other causes. These data may help guide future study aimed at identifying the optimal timing for hospital discharge and help allocate high‐intensity, HF‐specific transitional care interventions to the patients most likely to benefit.
Fibroblast Growth Factor‐23 and Incident Coronary Heart Disease, Heart Failure, and Cardiovascular Mortality: The Atherosclerosis Risk In Communities Study
Authors: Lutsey Pamela L. , Alonso Alvaro , Selvin Elizabeth , Pankow James S. , Michos Erin D. , Agarwal Sunil K. , Loehr Laura R. , Eckfeldt John H. , Coresh Josef 
Published: June 2014

Background

Fibroblast growth factor‐23 (
FGF
‐23) is a hormone involved in phosphorous regulation and vitamin D metabolism that may be associated with cardiovascular risk, and it is a potential target for intervention. We tested whether elevated
FGF
‐23 is associated with incident coronary heart disease, heart failure, and cardiovascular mortality, even at normal kidney function.

Methods and Results
A total of 11 638 Atherosclerosis Risk In Communities study participants, median age 57 at baseline (1990–1992), were followed through 2010. Cox regression was used to evaluate the independent association of baseline serum active FGF‐23 with incident outcomes. Models were adjusted for traditional cardiovascular risk factors and estimated glomerular filtration rate. During a median follow‐up of 18.6 years, 1125 participants developed coronary heart disease, 1515 developed heart failure, and 802 died of cardiovascular causes. For all 3 outcomes, there was a threshold, whereby FGF‐23 was not associated with risk at <40 pg/mL but was positively associated with risk at >40 pg/mL. Compared with those with FGF‐23 <40 pg/mL, those in the highest FGF‐23 category (≥58.8 pg/mL) had a higher risk of incident coronary heart disease (adjusted hazard ratio, 95% CIs: 1.65, 1.40 to 1.94), heart failure (1.75, 1.52 to 2.01), and cardiovascular mortality (1.65, 1.36 to 2.01). Associations were modestly attenuated but remained statistically significant after further adjustment for estimated glomerular filtration rate. In stratified analyses, similar results were observed in African Americans and among persons with normal kidney function.

Conclusions

High levels of serum
FGF
‐23 were associated with increased risk of coronary heart disease, heart failure, and cardiovascular mortality in this large, biracial, population‐based cohort. This association was independent of traditional cardiovascular risk factors and kidney function.
Can Response-Adaptive Randomization Increase Participation in Acute Stroke Trials?
Authors: Tehranisa Jason S. , Meurer William J. 
Published: June 2014

Background and Purpose—
A response-adaptive randomization (RAR) trial design actively adjusts the ratio of participants assigned to each trial arm, favoring the better performing treatment by using outcome data from participants already in the trial. Compared with a standard clinical trial, an RAR study design has the potential to improve patient participation in acute stroke trials.

Methods—

This cross-sectional randomized survey included adult emergency department patients, age ≥18, without symptoms of stroke or other critical illness. A standardized protocol was used, and subjects were randomized to either an RAR or standard hypothetical acute stroke trial. After viewing the video describing the hypothetical trial (
http://youtu.be/cKIWduCaPZc
), reviewing the consent form, and having questions answered, subjects indicated whether they would consent to the trial. A multivariable logistic regression model was fitted to estimate the impact of RAR while controlling for demographic factors and patient understanding of the design.

Results—
A total of 418 subjects (210 standard and 208 RAR) were enrolled. All baseline characteristics were balanced between groups. There was significantly higher participation in the RAR trial (67.3%) versus the standard trial (54.5%), absolute increase: 12.8% (95% confidence interval, 3.7–22.2). The RAR group had a higher odds ratio of agreeing to research (odds ratio, 1.89; 95% confidence interval, 1.2–2.9) while adjusting for patient level factors. Trial designs were generally well understood by the participants.

Conclusions—
The hypothetical RAR trial attracted more research participation than standard randomization. RAR has the potential to increase recruitment and offer benefit to future trial participants.
The Role of Interactions between Multiscale Circulations on the Observed Zonally Averaged Zonal Wind Variability Associated with the Madden–Julian Oscillation
Authors: Sakaeda Naoko , Roundy Paul E. 
Published: June 2014

Abstract
The mechanisms driving the upper-tropospheric zonal mean intraseasonal zonal wind associated with the Madden–Julian oscillation are examined through budget analysis during boreal winter. To diagnose the role of nonlinear and cross-scale interactions, the wind fields are decomposed into three temporal bands, including the intraseasonal time scale (30–100 days), and periods shorter and longer than the intraseasonal time scales. The intraseasonal zonal mean circulation and its driving mechanisms are first examined based on the leading EOFs of the intraseasonal zonal wind. Consistent with previous studies of intraseasonal atmospheric angular momentum, the upper-troposphere zonal mean intraseasonal zonal wind anomaly begins in the tropics and propagates poleward. Results show that interaction between the background state and intraseasonal-time-scale zonally symmetric and asymmetric circulation helps drive changes in the tropical intraseasonal zonal wind and its poleward propagation. The intraseasonal anomalous circulation also modulates the characteristics of the transient eddies that induce anomalous momentum flux convergence that then helps to accelerate further the intraseasonal zonal wind in the extratropics. Results also suggest that feedbacks between the anomalous intraseasonal circulation and transient eddies have some sensitivity to event-to-event variability of the MJO.
On the Causal Relationship between Poleward Heat Flux and the Equator-to-Pole Temperature Gradient: A Cautionary Tale
Authors: Lee Sukyoung , Yoo Changhyun 
Published: June 2014

Abstract
An increase in the poleward heat or energy transport is often ascribed to a strengthening of the equator-to-pole gradient in temperature or in the top-of-the-atmosphere (TOA) net radiation. While this attribution conforms to the well-established flux–gradient relationship, a counterexample is shown here, demonstrating that a forced atmospheric circulation, triggered by enhanced convection over the western tropical Pacific warm pool and suppressed convection over the eastern tropical Pacific and Indian Oceans, can cause the equator-to-pole gradient in the TOA net radiation to increase.
Estimating Sensible and Latent Heat Fluxes Using the Integral Method from in situ Aircraft Measurements
Authors: Knuth Shelley L. , Cassano John J. 
Published: June 2014

Abstract
In September 2009, several Aerosonde unmanned aerial vehicles (UAVs) were flown from McMurdo Station to Terra Nova Bay, Antarctica, with the purpose of collecting three-dimensional measurements of the atmospheric boundary layer (ABL) overlying a polynya. Temperature, pressure, wind speed, and relative humidity measurements collected by the UAVs were used to calculate sensible and latent heat fluxes (SHF and LHF, respectively) during three flights. Fluxes were calculated over the depth of the ABL using the integral method, in which only measurements of the mean atmospheric state (no transfer coefficients) were used. The initial flux estimates assumed that the observations were Lagrangian. Subsequent fluxes were estimated using a robust and innovative methodology that included modifications to incorporate adiabatic and non-Lagrangian processes as well as the heat content below flight level. The SHF ranged from 12 to 485 W m−2, while the LHF ranged from 56 to 152 W m−2. The importance of properly measuring the variables used to calculate the adiabatic and non-Lagrangian processes is discussed. Uncertainty in the flux estimates is assessed both by varying the calculation methodology and by accounting for observational errors. The SHF proved to be most sensitive to the temperature measurements, while the LHF was most sensitive to relative humidity. All of the flux estimates are sensitive to the depth of the boundary layer over which the values are calculated. This manuscript highlights these sensitivities for future field campaigns to demonstrate the measurements most important for accurate flux estimates.
NPM, administrative reforms and public service motivation: improving the dialogue between research agendas
Authors: Bellé Nicola , Ongaro Edoardo 
Published: June 2014

This article makes use of the Italian case of administrative reform to investigate the changes in the public service motivation (PSM) of public employees and managers after two decades of new public management (NPM)-inspired reforms. It emerges that NPM reforms may be associated with a reduction of the stock of PSM; however, important qualifications apply. By providing so far entirely unavailable evidence about PSM in both the public and the private/commercial sectors in Italy, the article also contributes the empirical bases for the development of comparative research on the interrelation between trajectories of administrative reform and changes in the drivers of motivation of public servants. Points for practitioners Public management reforms may have an effect in terms of accretion or depletion of public service motivation (PSM), in its turn likely to be conducive to improved performance of the public sector. Policymakers should include in the design and evaluation of public sector reforms the potential impacts on the drivers of the motivation of public servants. PSM is also a factor that may be profoundly influential on the dynamics of reform processes, to be systematically considered by reformers in different jurisdictions.
Impact of home-delivered meal programs on diet and nutrition among older adults
Authors: Zhu Huichen , An Ruopeng 
Published: June 2014

Background: Poor diet quality and insufficient nutrient intake is of particular concern among older adults. The Older Americans Act of 1965 authorizes home-delivered meal services to homebound individuals aged 60 years and older. Objective: The purpose of this study was to review scientific evidence on the impact of home-delivered meal services on diet and nutrition among recipients. Methods: Keyword and reference searches were conducted in Cochrane Library, Google Scholar, PubMed and Web of Science. Inclusion criteria included: study design (randomized controlled trials, cohort studies, pre-post studies, or cross-sectional studies); main outcome (food and nutrient intakes); population (home-delivered meal program participants); country (US); language (articles written in English); and article type (peer-reviewed publications or theses). Results: Eight studies met the inclusion criteria, including two randomized controlled trial studies (from the same intervention), one cohort study, two pre-post studies, and three cross-sectional studies. All but two studies found home-delivered meal programs to significantly improve diet quality, increase nutrient intakes, and reduce food insecurity and nutritional risk among participants. Other beneficial outcomes include increased socialization opportunities, improvement in dietary adherence, and higher quality of life. Conclusions: Home-delivered meal programs improve diet quality and increase nutrient intakes among participants. These programs are also aligned with the federal cost-containment policy to rebalance long-term care away from nursing homes to home- and community-based services by helping older adults maintain independence and remain in their homes and communities as their health and functioning decline.
Pedometer-facilitated walking intervention shows promising effectiveness for reducing cancer fatigue: a pilot randomized trial
Authors: Mayo Nancy E , Moriello Carolina , Scott Susan C , Dawes Diana , Auais Mohammad , Chasen Martin 
Published: June 2014

Objective: Mechanisms for cancer related fatigue suggest that exercise but “not too much and not too little” could be effective. This study aimed to investigate feasibility and estimate the potential effects of a walking exercise program in people with advanced cancer and fatigue. Design: A pilot randomized trial. Setting: McGill University Health Centre (MUHC), Montreal, Canada. Subjects: People with advanced cancer undergoing interdisciplinary assessment and rehabilitation with a fatigue level of 4 to 10 on a visual analogue scale. Interventions: An 8-week fatigue-adapted, walking intervention, facilitated using a pedometer (STEPS), and offered at the same time as or after rehabilitation. Measures: Measures of fatigue, physical function and well-being were administered at entry, and 8, 16 and 24 weeks. Generalized estimating equations (GEE) estimated the odds of response for people receiving the STEPS program in comparison to the odds of response in the controls (odds ratio, OR). Results: Twenty-six persons were randomized to three groups: during rehabilitation, after rehabilitation, and usual care. For the fatigue measures the OR for STEPS offered at any time using an intention-to-treat approach was 3.68 (95%CI: 1.05-12.88); for the physical function measures, the OR was 1.40 (95%CI: 0.41- 4.79) and 2.36 (95%CI: 0.66-8.51) for the well-being measures. Conclusion: Fifty percent of eligible people were able to participate. This small trial suggests that a personalized exercise program reduces fatigue and that 100 people are needed in a full strength trial.
Systematic review of the psychometric properties of balance measures for cerebellar ataxia
Authors: Winser Stanley J , Smith Catherine M , Hale Leigh A , Claydon Leica S , Whitney Susan L , Mehta Poonam 
Published: June 2014

Objective: To review systematically the psychometric properties of balance measures for use in people with cerebellar ataxia. Data sources: Medline, AMED, CINAHL, Web of Science and EMBASE were searched between 1946 and April 2014. Review methods: Two reviewers independently searched data sources. Cerebellar-specific and generic measures of balance were considered. Included studies tested psychometric properties of balance measures in people with cerebellar ataxia of any cause. Quality of reported studies was rated using the Consensus Based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. Results: Twenty-one articles across which 16 measures had been tested were included for review. Using the COSMIN, quality of methodology in studies investigating psychometric properties of generic balance measures ( n=10) was rated predominantly as ‘poor’. Furthermore, responsiveness has not been tested for any generic measures in this population. The quality of studies investigating psychometric properties of balance sub-components of the cerebellar-specific measures ( n=6) ranged from ‘poor’ to ‘excellent’; however, Minimally Clinically Important Difference has not been determined for these cerebellar-specific measures. Conclusion: The Posture and Gait (PG) sub-component of the International Cooperative Ataxia Rating Scale (ICARS) demonstrates the most robust psychometric properties with acceptable clinical utility.