bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supercloud
Authors: Jia Qin , Shen Zhiming , Song Weijia , van Renesse Robbert , Weatherspoon Hakim 
Published: January 2015

Infrastructure as a Service (IaaS) clouds couple applications tightly with the underlying infrastructures and services. This vendor lock-in problem forces users to apply ad-hoc deployment strategies in order to tolerate cloud failures, and limits the ability of doing virtual machine (VM) migration and resource scaling across different clouds.
This paper presents the Supercloud, a cloud service comprising resources obtained from several diverse IaaS cloud providers, and discusses opportunities, limitations, and future research directions. Currently, the Supercloud has been deployed using resources from several major cloud providers, including Amazon EC2, Rackspace, HP Cloud, and some private clouds. VMs run in a virtual network and can be migrated seamlessly across different clouds, with different hypervisors and device models. Using case studies we demonstrate that, being able to deploy applications to more regions and granting more control to end-users, the Supercloud can reduce latency and cost compared to the underlying cloud providers.
Principles and Performance Characteristics of Algorithms for Live VM Migration
Authors: Svärd Petter , Hudzia Benoit , Walsh Steve , Tordsson Johan , Elmroth Erik 
Published: January 2015

Since first demonstrated by Clark et al. in 2005, live migration of virtual machines has both become a standard feature of hypervisors and created an active field of research. However, the rich ongoing research in live migration focusmainly on performance improvements to well-known techniques, most of them being variations of the Clark approach. In order to advance live migration beyond incremental performance improvements, it is important to gain a deeper understanding of the live migration problem itself and its underlying principles.
To address this issue, this contribution takes a step back and investigates the essential characteristics of live migration. The paper identifies five fundamental properties of live migration and uses these to investigate, categorize, and compare three approaches to live migration: precopy, postcopy and hybrid. The evaluated algorithms include well-known techniques derived from that of Clark as well as novel RDMA in-kernel approaches. Our analysis of the fundamental properties of the algorithms is validated by a set of experiments. In these, we migrate virtual machines with large memory sizes hosting workloads with high page dirtying rates to expose differences and limitations of the different approaches. Finally, we provide guidelines for which approach to use in different scenarios.
Thioredoxin-2 Inhibits Mitochondrial Reactive Oxygen Species Generation and Apoptosis Stress Kinase-1 Activity to Maintain Cardiac Function
Authors: Huang Qunhua , Zhou Huanjiao Jenny , Zhang Haifeng , Huang Yan , Hinojosa-Kirschenbaum Ford , Fan Peidong , Yao Lina , Belardinelli Luiz , Tellides George , Giordano Frank J. , Budas Grant R. , Min Wang 
Published: January 2015

Background—
Thioredoxin 2 (Trx2) is a key mitochondrial protein that regulates cellular redox and survival by suppressing mitochondrial reactive oxygen species generation and by inhibiting apoptosis stress kinase-1 (ASK1)–dependent apoptotic signaling. To date, the role of the mitochondrial Trx2 system in heart failure pathogenesis has not been investigated.

Methods and Results—
Western blot and histological analysis revealed that Trx2 protein expression levels were reduced in hearts from patients with dilated cardiomyopathy, with a concomitant increase in ASK1 phosphorylation/activity. Cardiac-specific Trx2 knockout mice develop spontaneous dilated cardiomyopathy at 1 month of age with increased heart size, reduced ventricular wall thickness, and a progressive decline in left ventricular contractile function, resulting in mortality due to heart failure by ≈4 months of age. The progressive decline in cardiac function observed in cardiac-specific Trx2 knockout mice was accompanied by the disruption of mitochondrial ultrastructure, mitochondrial membrane depolarization, increased mitochondrial reactive oxygen species generation, and reduced ATP production, correlating with increased ASK1 signaling and increased cardiomyocyte apoptosis. Chronic administration of a highly selective ASK1 inhibitor improved cardiac phenotype and reduced maladaptive left ventricular remodeling with significant reductions in oxidative stress, apoptosis, fibrosis, and cardiac failure. Cellular data from Trx2-deficient cardiomyocytes demonstrated that ASK1 inhibition reduced apoptosis and reduced mitochondrial reactive oxygen species generation.

Conclusions—
Our data support an essential role for mitochondrial Trx2 in preserving cardiac function by suppressing mitochondrial reactive oxygen species production and ASK1-dependent apoptosis. Inhibition of ASK1 represents a promising therapeutic strategy for the treatment of dilated cardiomyopathy and heart failure.
Cardiac Hemodynamics are Linked With Structural and Functional Features of Brain Aging: The Age, Gene/Environment Susceptibility (AGES)‐Reykjavik Study
Authors: Sabayan Behnam , van Buchem Mark A. , Sigurdsson Sigurdur , Zhang Qian , Harris Tamara B. , Gudnason Vilmundur , Arai Andrew E. , Launer Lenore J. 
Published: January 2015

Background
Advanced heart failure is linked with structural and functional alterations in the brain. It is unclear whether a graded decrease in cardiac function puts older subjects at risk for brain aging. We investigated the association between cardiac hemodynamics and features of brain aging in community‐dwelling older subjects.

Methods and Results

With data from a sub‐study (n=931 subjects, mean age 75.9 years, 47.7% male) of the Age, Gene/Environment Susceptibility (AGES)‐Reykjavik Study, we investigated the association of
MRI
measures of cardiac hemodynamics, including left ventricular stroke volume (
LVSV
) and cardiac output (
CO
) to brain characteristics. In multivariable analyses, each 10 mL lower
LVSV
was associated with 4.4 mL (95%
CI
1.9 to 6.9) lower total parenchymal brain volume (
TBV
) and 3.7 mL (95%
CI
1.8 to 5.7) lower gray matter volume (
GMV
). Likewise, each unit (L/min) lower
CO
was associated with 3.9 mL (95%
CI
0.4 to 7.4) lower
TBV
and 3.9 mL (95%
CI
0.4 to 7.4) lower
GMV
. Lower
LVSV
was associated with worse performance in processing speed (
P
=0.043) and executive function (
P
<0.001). Lower
CO
was associated with worse performance in processing speed (
P
=0.015) and executive function (
P
=0.003). Each 10 mL lower
LVSV
and each unit lower
CO
associated with a higher risk of mild cognitive impairment or dementia (odds ratio: 1.24, 95%
CI
0.99 to 1.57 and odds ratio: 1.40, 95%
CI
0.99 to 2.00, respectively).

Conclusions

A graded decrease in cardiac functioning is associated with features of brain aging
.
Older persons with cardiac or cognitive signs and symptoms may have both cardiac and cerebral diseases and should be evaluated accordingly.
Cardiac Autonomic Dysfunction: Particulate Air Pollution Effects Are Modulated by Epigenetic Immunoregulation of
Toll‐like Receptor 2
and Dietary Flavonoid Intake
Authors: Zhong Jia , Colicino Elena , Lin Xinyi , Mehta Amar , Kloog Itai , Zanobetti Antonella , Byun Hyang‐Min , Bind Marie‐Abèle , Cantone Laura , Prada Diddier , Tarantini Letizia , Trevisi Letizia , Sparrow David , Vokonas Pantel , Schwartz Joel , Baccarelli Andrea A. 
Published: January 2015

Background

Short‐term fine particles (
PM
2.5
) exposure is associated with reduced heart rate variability, a strong predictor of cardiac mortality among older people. Identifying modifiable factors that confer susceptibility is essential for intervention. We evaluated whether
Toll‐like receptor 2
(

TLR
2

) methylation, a reversible immune‐epigenetic process, and its dietary modulation by flavonoids and methyl nutrients, modify susceptibility to heart rate variability effects following
PM
2.5
exposure.

Methods and Results

We measured heart rate variability and
PM
2.5
repeatedly over 11 years (1275 total observations) among 573 elderly men from the Normative Aging Study. Blood

TLR
2

methylation was analyzed using pyrosequencing. Daily flavonoid and methyl nutrients intakes were assessed through the Food Frequency Questionnaire (
FFQ
). Every 10 μg/m
3
increase in 48‐hour
PM
2.5
moving average was associated with 7.74% (95%
CI
: −1.21% to 15.90%;
P
=0.09), 7.46% (95%
CI
: 0.99% to 13.50%;
P
=0.02), 14.18% (95%
CI
: 1.14% to 25.49%;
P
=0.03), and 12.94% (95%
CI
: −2.36% to 25.96%;
P
=0.09) reductions in root mean square of successive differences, standard deviation of normal‐to‐normal intervals, low‐frequency power, and high‐frequency power, respectively. Higher

TLR
2

methylation exacerbated the root mean square of successive differences, standard deviation of normal‐to‐normal intervals, low‐frequency, and high‐frequency reductions associated with heightened
PM
2.5
(
P
interaction
=0.006, 0.03, 0.05, 0.04, respectively). Every interquartile‐range increase in flavonoid intake was associated with 5.09% reduction in mean

TLR
2

methylation (95%
CI
: 0.12% to 10.06%;
P
=0.05) and counteracted the effects of
PM
2.5
on low frequency (
P
interaction
=0.05). No significant effect of methyl nutrients on

TLR
2

methylation was observed.

Conclusions

Higher

TLR
2

methylation may confer susceptibility to adverse cardiac autonomic effects of
PM
2.5
exposure in older individuals. Higher flavonoid intake may attenuate these effects, possibly by decreasing

TLR
2

methylation.
Analysis of Tissue Plasminogen Activator Eligibility by Sex in the Greater Cincinnati/Northern Kentucky Stroke Study
Authors: Madsen Tracy E. , Khoury Jane C. , Alwell Kathleen A. , Moomaw Charles J. , Kissela Brett M. , De Los Rios La Rosa Felipe , Woo Daniel , Adeoye Opeolu , Flaherty Matthew L. , Khatri Pooja , Ferioli Simona , Kleindorfer Dawn 
Published: January 2015

Background and Purpose—
Sex differences in recombinant tissue-type plasminogen activator (r-tPA) administration are present in some populations. It is unknown whether this is because of eligibility differences or the modifiable exclusion criterion of severe hypertension. Our aim was to investigate sex differences in r-tPA eligibility, in individual exclusion criteria, and in the modifiable exclusion criterion, hypertension.

Methods—
We included all ischemic stroke patients ≥18 years among residents of the Greater Cincinnati/Northern Kentucky region who presented to 16-area emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association (AHA) and European Cooperative Acute Stroke Study (ECASS) III guidelines.

Results—

Of 1837 ischemic strokes, 58% were women, 24% were black. Mean age in years was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex (6.8% men and 6.1% women;
P
=0.55), even after adjusting for age (7.0% and 5.9%;
P
=0.32). Similar proportions of women and men arrived beyond 3- and 4.5-hour time windows, but more women had severe hypertension. There were no sex differences in blood pressure treatment rates among those with severe hypertension (14.6% women and 20.8% men;
P
=0.21). More women were >80 years and had National Institutes of Health Stroke Scale (NIHSS) >25.

Conclusions—
Within a large, biracial population, eligibility for r-tPA was similar by sex. Women were more likely to have the modifiable exclusion criterion of severe hypertension but were not more likely to be treated. Women were more likely to have 2 of the 5 ECASS III exclusion criteria. Undertreatment of hypertension in women is a potentially modifiable contributor to reported differences in r-tPA administration.
Relationship Between Degree of Left Ventricular Dysfunction, Symptom Status, and Risk of Embolic Events in Patients With Atrial Fibrillation and Heart Failure
Authors: Sandhu Roopinder K. , Hohnloser Stefan H. , Pfeffer Marc A. , Yuan Fei , Hart Robert G. , Yusuf Salim , Connolly Stuart J. , McAlister Finlay A. , Healey Jeff S. 
Published: January 2015

Background and Purpose—
Limited data exists regarding the relationship between left ventricular systolic dysfunction (LVSD) and heart failure (HF) symptoms and embolic risk among patients with atrial fibrillation.

Methods—
Participants in the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE) trials with HF, but not randomized to oral anticoagulation, were categorized as having preserved versus reduced ejection fraction. If reduced, LVSD was classified as mild, moderate, or severe. Symptoms were quantified using New York Heart Association class.The primary outcome was a composite of stroke, transient ischemic attack, and systemic embolism.

Results—

There were 3487 antiplatelet-treated patients with HF at baseline. Of these patients, 969 (46.8%) had HF with preserved ejection fraction and 1103 (53.2%) had HF with reduced ejection fraction. During 3.6 years of mean follow-up, first occurrence of stroke, transient ischemic attack, or systemic embolism occurred in 386 patients.The strongest independent predictors of embolic events were age ≥75 years (hazard ratio 2.55; confidence interval, 1.85–3.53), prior stroke or transient ischemic attack (hazard ratio 2.07; 95% confidence interval, 1.65–2.60), and female sex (hazard ratio 1.37; confidence interval, 1.11–1.69). However, ejection fraction <0.50, degree of LVSD, and New York Heart Association class did not predict embolic events. Patients with HF with preserved ejection fraction exhibited similar risk of embolic events as those with HR with reduced ejection fraction: 4.3% versus 4.4% per 100 person-years (hazard ration 1.01; 95% confidence interval, 0.78–1.31). Risk of embolic events was similar across categories of LVSD (
P
for trend =0.96) and New York Heart Association class (
P
for trend =0.57).

Conclusion—
Among HF patients in ACTIVE, neither the presence of LVSD or degree of symptom severity influenced risk of embolic events.
Moisture Pathways into the U.S. Intermountain West Associated with Heavy Winter Precipitation Events*
Authors: Alexander Michael A. , Scott James D. , Swales Dustin , Abel Mimi R. , Mahoney Kelly , Smith Catherine A. 
Published: January 2015

AbstractTwo methods were used to identify the paths of moisture transport that reach the U.S. Intermountain West (IMW) during heavy precipitation events in winter. In the first, the top 150 precipitation events at stations located within six regions in the IMW were identified, and then back trajectories were initiated at 6-h intervals on those days at the four Climate Forecast System Reanalysis grid points nearest the stations. The second method identified the leading patterns of integrated water vapor transport (IVT) using the three leading empirical orthogonal functions of IVT over land that were first normalized by the local standard deviation. The top 1% of the associated 6-hourly time series was used to construct composites of IVT, atmospheric circulation, and precipitation. The results from both methods indicate that moisture originating from the Pacific that leads to extreme precipitation in the IMW during winter takes distinct pathways and is influenced by gaps in the Cascades (Oregon–Washington), the Sierra Nevada (California), and Peninsular Ranges (from Southern California through Baja California). The moisture transported along these routes appears to be the primary source for heavy precipitation for the mountain ranges in the IMW. The synoptic conditions associated with the dominant IVT patterns include a trough–ridge couplet at 500 hPa, with the trough located northwest of the ridge where the associated circulation funnels moisture from the west-southwest through the mountain gaps and into the IMW.
The salience of alcohol-related issues across the adult lifespan
Authors: Pettigrew Simone , Pescud Melanie 
Published: January 2015

Objective: The growing costs to the community of excessive alcohol consumption have resulted in pressure for governments and non-governmental organisations (NGOs) to develop strategies to address this problem, but they do so in a highly constrained resource environment. To provide evidence of health education approaches that may be effective across multiple drinker segments, and hence be relevant to a large number of drinkers, this study investigated the alcohol-related issues that are most salient to adult drinkers at different life stages. Method: Ten focus groups were conducted with 82 drinkers aged 18–65 years in Perth, Western Australia. Results: Sixteen categories of concerns were identified that related to three main themes of social, health and logistical issues. The youngest drinkers nominated the largest number of issues and older drinkers the least, although there were certain issues, such as concerns relating to role modelling and product quality, that became of increasing relevance with age. Conclusion: Study findings provide insights for those seeking to develop strategies to address alcohol-related harm at the population level.
Audible handheld Doppler ultrasound determines reliable and inexpensive exclusion of significant peripheral arterial disease
Authors: Alavi Afsaneh , Sibbald R Gary , Nabavizadeh Reza , Valaei Farnaz , Coutts Pat , Mayer Dieter 
Published: January 2015

Objective To determine the accuracy of audible arterial foot signals with an audible handheld Doppler ultrasound for identification of significant peripheral arterial disease as a simple, quick, and readily available bedside screening tool. Methods Two hundred consecutive patients referred to an interprofessional wound care clinic underwent audible handheld Doppler ultrasound of both legs. As a control and comparator, a formal bilateral lower leg vascular study including the calculation of Ankle Brachial Pressure Index and toe pressure (TP) was performed at the vascular lab. Diagnostic reliability of audible handheld Doppler ultrasound was calculated versus Ankle Brachial Pressure Index as the gold standard test. Results A sensitivity of 42.8%, a specificity of 97.5%, negative predictive value of 94.10%, positive predictive value of 65.22%, positive likelihood ratio of 17.52, and negative likelihood ratio of 0.59. The univariable logistic regression model had an area under the curve of 0.78. There was a statistically significant difference at the 5% level between univariable and multivariable area under the curves of the dorsalis pedis and posterior tibial models ( p < 0.001). Conclusion Audible handheld Doppler ultrasound proved to be a reliable, simple, rapid, and inexpensive bedside exclusion test of peripheral arterial disease in diabetic and nondiabetic patients.
Missing not at random models for masked clinical trials with dropouts
Authors: Kang Shan , Little Roderick J , Kaciroti Niko 
Published: January 2015

Background Missing data are an unavoidable problem in clinical trials. Most existing missing data approaches assume the missing data are missing at random. However, the missing at random assumption is often questionable when the real causes of missing data are not well known and cannot be tested from observed data. Methods We propose a specific missing not at random assumption, which we call masked missing not at random, which may be more plausible than missing at random for masked clinical trials. We formulate models for categorical and continuous outcomes under this assumption. Simulations are conducted to examine the finite sample performance of our methods and compare them with other methods. R code for the proposed methods is provided in supplementary materials. Results Simulation studies confirm that maximum likelihood methods assuming masked missing not at random outperform complete case analysis and maximum likelihood assuming missing at random when masked missing not at random is true. For the particular missing at random model where both of missing at random and masked missing not at random are satisfied, theory suggests that maximum likelihood assuming missing at random is at least as efficient as maximum likelihood assuming masked missing not at random. However, maximum likelihood assuming masked missing not at random is nearly as efficient as maximum likelihood assuming missing at random in our simulated settings. We also applied our methods to the TRial Of Preventing HYpertension study. The missing at random estimated treatment effect and its 95% confidence interval are robust to deviations from missing at random of the form implied by masked missing not at random. Conclusion Methods based on the masked missing not at random assumption are useful for masked clinical trials, either in their own right or to provide a form of sensitivity analysis for deviations from missing at random. Missing at random analysis might be favored on grounds of efficiency if the estimates based on masked missing not at random and missing at random are similar, but if the estimates are substantially different, the masked missing not at random estimates might be preferred because the mechanism is more plausible.
Role of neoadjuvant chemotherapy in muscle-invasive bladder cancer: Clinical and cost effectiveness
Authors: Goonewardene Sanchia S , Bahl Amit , Persad Raj 
Published: January 2015

Background: Bladder cancer is one of the most common cancers in the Western world, with associated significant mortality. Once proven to be muscle invasive, radical therapy is required. Objective: We reviewed the literature associated with clinical effectiveness of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer. Methods: We conducted a systematic literature review of papers related to the search terms neoadjuvant chemotherapy, muscle invasive bladder cancer and clinical effectiveness; from 1984 through April 2014. We used the search terms of (neoadjuvant chemotherapy) AND (muscle invasive bladder cancer). We included primary research, but only included secondary research if it was a systematic review or meta-analyses. Papers outside this category were not included. Results: From the literature review, we found that the benefits of neoadjuvant chemotherapy for muscle-invasive bladder cancer are wide-ranging. This includes a greatly improved response rate, including complete response and improved survival rate. Potential disadvantages of NAC include less accurate staging, delays in curative surgery (risk is greater, if delay > 12 weeks) in non-responders and the well-known fact that non-responders will fare worse, later on. Conclusions: In conclusion, NAC followed by radical therapy is the gold standard for muscle-invasive bladder tumours, for patients whom are sufficiently fit; however, there are many unanswered questions. As yet, this intervention has not been examined by the National Institute for Health and Care Excellence.