bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transparently Space Sharing a Multicore Among Multiple Processes
Authors: Creech Timothy , Barua Rajeev 
Published: November 2016

As hardware becomes increasingly parallel and the availability of scalable parallel software improves, the problem of managing multiple multithreaded applications (processes) becomes important. Malleable processes, which can vary the number of threads used as they run, enable sophisticated and flexible resource management. Although many existing applications parallelized for SMPs with parallel runtimes are in fact already malleable, deployed runtime environments provide no interface nor any strategy for intelligently allocating hardware threads or even preventing oversubscription. Prior research methods either depend on profiling applications ahead of time to make good decisions about allocations or do not account for process efficiency at all, leading to poor performance. None of these prior methods have been adapted widely in practice. This article presents the Scheduling and Allocation with Feedback (SCAF) system: a drop-in runtime solution that supports existing malleable applications in making intelligent allocation decisions based on observed efficiency without any changes to semantics, program modification, offline profiling, or even recompilation. Our existing implementation can control most unmodified OpenMP applications. Other malleable threading libraries can also easily be supported with small modifications without requiring application modification or recompilation.
In this work, we present the SCAF daemon and a SCAF-aware port of the GNU OpenMP runtime. We present a new technique for estimating process efficiency purely at runtime using available hardware counters and demonstrate its effectiveness in aiding allocation decisions.
We evaluated SCAF using NAS NPB parallel benchmarks on five commodity parallel platforms, enumerating architectural features and their effects on our scheme. We measured the benefit of SCAF in terms of sum of speedups improvement (a common metric for multiprogrammed environments) when running all benchmark pairs concurrently compared to equipartitioning—the best existing competing scheme in the literature. We found that SCAF improves on equipartitioning on four out of five machines, showing a mean improvement factor in sum of speedups of 1.04 to 1.11x for benchmark pairs, depending on the machine, and 1.09x on average.
Since we are not aware of any widely available tool for equipartitioning, we also compare SCAF against multiprogramming using unmodified OpenMP, which is the only environment available to end users today. SCAF improves on the unmodified OpenMP runtimes for all five machines, with a mean improvement of 1.08 to 2.07x, depending on the machine, and 1.59x on average.
Abstraction mechanisms for database programming
Authors: Schmidt Joachim W. , Mall Manuel 
Published: November 2016

Databases contain vast amounts of highly related data accessed by programs of considerable size and complexity. Therefore, database programming has a particular need for high level constructs that abstract from details of data access, data manipulation, and data control.
The paper investigates the suitability of several well-known abstraction mechanisms for database programming (e.g., control abstraction and functional abstraction). In addition, it presents some new abstraction mechanisms (access abstraction and transactional abstraction) particularly designed to manage typical database problems like integrity and concurrency control.
A programming language framework for designing user interfaces
Authors: Pilote Michel 
Published: November 2016

Programming Language researchers increasingly recognize that a high proportion of application development costs involve the interface with users of the application, including various dialogues, input formats, error checking, help and explanation messages, and the like. They also increasingly recognize that maintenance costs tend to overshadow development costs. These two factors even multiply their adverse effects: as the user needs evolve, it is the interface with a system which generally requires the most maintenance. The user relationship is even said to account for about 60 percent of the maintenance problem [Lientz and Swanson 81].
Surprisingly, few programming language constructs are designed to address the area of user interface design. On the contrary, traditional programming language constructs are strongly oriented towards improving programmers' effectiveness in developing the algorithmic and data manipulation aspects of an application. A programmer is basically left to reinvent each time the required procedures to deal with user commands and inputs.
Capsules
Authors: Zippel Richard 
Published: November 2016

Well organized large systems tend to consist of a large number of small pieces of code each of which captures a single semantic unit. These pieces of code are strung together to form larger semantic phrases, which are in turn components of even larger phrases. The smallest semantic units in a polynomial manipulation system might be the routines that add and multiply the coefficients of the polynomials. These routines are combined (used as subroutines) to form the routines that add and multiply polynomials, which are components in the factoring and greatest common divisor routines.
When a system is built in a top down manner, the larger phrases are formed first and are used to define the semantic components of the smaller phrases. Bottom up software design begins with the small phrases and generates the large phrases. In practice a combination of these two approaches is often used. The manner in which the routines are initially connected is usually simple, but in time the addition of new capabilities and features, and the necessities of performance enhancement generally cause the dependency structure to become quite complex.
Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1
Authors: Champiat Stéphane , Dercle Laurent , Ammari Samy , Massard Christophe , Hollebecque Antoine , Postel-Vinay Sophie , Chaput Nathalie , Eggermont Alexander , Marabelle Aurélien , Soria Jean-Charles , Ferté Charles 
Published: November 2016

Abstract
Purpose: While immune checkpoint inhibitors are disrupting the management of patients with cancer, anecdotal occurrences of rapid progression (i.e., hyperprogressive disease or HPD) under these agents have been described, suggesting potentially deleterious effects of these drugs. The prevalence, the natural history, and the predictive factors of HPD in patients with cancer treated by anti-PD-1/PD-L1 remain unknown.
Experimental Design: Medical records from all patients (N = 218) prospectively treated in Gustave Roussy by anti-PD-1/PD-L1 within phase I clinical trials were analyzed. The tumor growth rate (TGR) prior (“REFERENCE”; REF) and upon (“EXPERIMENTAL”; EXP) anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth. Associations between TGR, clinicopathologic characteristics, and overall survival (OS) were computed.
Results: HPD was defined as a RECIST progression at the first evaluation and as a ≥2-fold increase of the TGR between the REF and the EXP periods. Of 131 evaluable patients, 12 patients (9%) were considered as having HPD. HPD was not associated with higher tumor burden at baseline, nor with any specific tumor type. At progression, patients with HPD had a lower rate of new lesions than patients with disease progression without HPD (P &lt; 0.05). HPD is associated with a higher age (P &lt; 0.05) and a worse outcome (overall survival). Interestingly, REF TGR (before treatment) was inversely correlated with response to anti-PD-1/PD-L1 (P &lt; 0.05) therapy.
Conclusions: A novel aggressive pattern of hyperprogression exists in a fraction of patients treated with anti-PD-1/PD-L1. This observation raises some concerns about treating elderly patients (&gt;65 years old) with anti-PD-1/PD-L1 monotherapy and suggests further study of this phenomenon. Clin Cancer Res; 23(8); 1920–8. ©2016 AACR.
See related commentary by Sharon, p. 1879
PD-1 Suppresses Development of Humoral Responses That Protect against Tn-Bearing Tumors
Authors: Haro Marcela A. , Littrell Chad A. , Yin Zhaojun , Huang Xuefei , Haas Karen M. 
Published: November 2016

AbstractTn is a carbohydrate antigen uniquely exposed on tumor mucins and, thus, an ideal target for immunotherapy. However, it has been difficult to elicit protective antibody responses against Tn antigen and other tumor-associated carbohydrate antigens. Our study demonstrates this can be attributed to PD-1 immuno-inhibition. Our data show a major role for PD-1 in suppressing mucin- and Tn-specific B-cell activation, expansion, and antibody production important for protection against Tn-bearing tumor cells. These Tn/mucin-specific B cells belong to the innate-like B-1b cell subset typically responsible for T cell–independent antibody responses. Interestingly, PD-1–mediated regulation is B cell–intrinsic and CD4+ cells play a key role in supporting Tn/mucin-specific B-cell antibody production in the context of PD-1 deficiency. Mucin-reactive antibodies produced in the absence of PD-1 inhibition largely belong to the IgM subclass and elicit potent antitumor effects via a complement-dependent mechanism. The identification of this role for PD-1 in regulating B cell–dependent antitumor immunity to Tn antigen highlights an opportunity to develop new therapeutic strategies targeting tumor-associated carbohydrate antigens. Cancer Immunol Res; 4(12); 1027–37. ©2016 AACR.
Longer Left Ventricular Electric Delay Reduces Mitral Regurgitation After Cardiac Resynchronization Therapy
Authors: Chatterjee Neal A. , Gold Michael R. , Waggoner Alan D. , Picard Michael H. , Stein Kenneth M. , Yu Yinghong , Meyer Timothy E. , Wold Nicholas , Ellenbogen Kenneth A. , Singh Jagmeet P. 
Published: November 2016

Background—
Mitral regurgitation (MR) is associated with worse survival in those undergoing cardiac resynchronization therapy (CRT). Left ventricular (LV) lead position in CRT may ameliorate mechanisms of MR. We examine the association between a longer LV electric delay (QLV) at the LV stimulation site and MR reduction after CRT.

Methods and Results—

QLV was assessed retrospectively in 426 patients enrolled in the SMART-AV study (SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in CRT). QLV was defined as the time from QRS onset to the first large peak of the LV electrogram. Linear regression and logistic regression were used to assess the association between baseline QLV and MR reduction at 6 months (absolute change in vena contracta width and odds of ≥1 grade reduction in MR). At baseline, there was no difference in MR grade, LV dyssynchrony, or LV volumes in those with QLV above versus below the median (95 ms). After multivariable adjustment, increasing QLV was an independent predictor of MR reduction at 6 months as reflected by an increased odds of MR response (odds ratio: 1.13 [1.03–1.25]/10 ms increase QLV;
P
=0.02) and a decrease in vena contracta width (
P
<0.001). At 3 months, longer QLV (≥median) was associated with significant decrease in LV end-systolic volume (ΔLV end-systolic volume −28.2±38.9 versus −4.9±33.8 mL,
P
<0.001). Adjustment for 3-month ΔLV end-systolic volume attenuated the association between QLV and 6-month MR reduction.

Conclusions—
In patients undergoing CRT, longer QLV was an independent predictor of MR reduction at 6 months and associated with interval 3-month LV reverse remodeling. These findings provide a mechanistic basis for using an electric-targeting LV lead strategy at the time of CRT implant.
Methodology Considerations in Phase Mapping of Human Cardiac Arrhythmias
Authors: Vijayakumar Ramya , Vasireddi Sunil K. , Cuculich Phillip S. , Faddis Mitchell N. , Rudy Yoram 
Published: November 2016

Background—
Phase analysis of cardiac arrhythmias, particularly atrial fibrillation, has gained interest because of the ability to detect organized stable drivers (rotors) and target them for therapy. However, the lack of methodology details in publications on the topic has resulted in ongoing debate over the phase mapping technique. By comparing phase maps and activation maps, we examined advantages and limitations of phase mapping.

Methods and Results—
Seven subjects were enrolled. We generated phase maps and activation maps from electrocardiographic imaging–reconstructed epicardial unipolar electrograms. For ventricular signals, phase was computed with (1) pseudoempirical mode decomposition detrending and (2) a novel Moving Average (MVG) detrending approach. For atrial fibrillation signals, MVG was modified to incorporate dynamic cycle length (DCL) changes (MVG-DCL). Phase maps were visually analyzed to study phase singularity points and rotors. Results show that phase is sensitive to cycle length choice, a limitation that was addressed by the MVG-DCL algorithm. MVG-DCL was optimal for atrial fibrillation analysis. Phase maps helped to highlight high-curvature wavefronts and rotors. However, for some activation patterns, phase generated nonrotational singularity points and false rotors.

Conclusions—
Phase mapping computes singularity points and visually highlights rotors. As such, it can help to provide a clearer picture of the spatiotemporal activation characteristics during atrial fibrillation. However, it is advisable to incorporate electrogram characteristics and the time-domain activation sequence in the analysis, to prevent misinterpretation and false rotor detection. Therefore, for mapping complex arrhythmias, a combined time-domain activation and phase mapping with variable cycle length seems to be the most reliable method.
Magnetic Resonance Imaging of Cardiac Strain Pattern Following Transplantation of Human Tissue Engineered Heart Muscles
Authors: Qin Xulei , Riegler Johannes , Tiburcy Malte , Zhao Xin , Chour Tony , Ndoye Babacar , Nguyen Michael , Adams Jackson , Ameen Mohamed , Denney Thomas S. , Yang Phillip C. , Nguyen Patricia , Zimmermann Wolfram H. , Wu Joseph C. 
Published: November 2016

Background—
The use of tissue engineering approaches in combination with exogenously produced cardiomyocytes offers the potential to restore contractile function after myocardial injury. However, current techniques assessing changes in global cardiac performance after such treatments are plagued by relatively low detection ability. Since the treatment is locally performed, this detection could be improved by myocardial strain imaging that measures regional contractility.

Methods and Results—

Tissue engineered heart muscles (EHMs) were generated by casting human embryonic stem cell–derived cardiomyocytes with collagen in preformed molds. EHMs were transplanted (n=12) to cover infarct and border zones of recipient rat hearts 1 month after ischemia reperfusion injury. A control group (n=10) received only sham placement of sutures without EHMs. To assess the efficacy of EHMs, magnetic resonance imaging and ultrasound-based strain imaging were performed before and 4 weeks after transplantation. In addition to strain imaging, global cardiac performance was estimated from cardiac magnetic resonance imaging. Although no significant differences were found for global changes in left ventricular ejection fraction (control −9.6±1.3% versus EHM −6.2±1.9%;
P
=0.17), regional myocardial strain from tagged magnetic resonance imaging was able to detect preserved systolic function in EHM-treated animals compared with control (control 4.4±1.0% versus EHM 1.0±0.6%;
P
=0.04). However, ultrasound-based strain failed to detect any significant change (control 2.1±3.0% versus EHM 6.3±2.9%;
P
=0.46).

Conclusions—
This study highlights the feasibility of using cardiac strain from tagged magnetic resonance imaging to assess functional changes in rat models following localized regenerative therapies, which may not be detected by conventional measures of global systolic performance.
Association Between Physician Teamwork and Health System Outcomes After Coronary Artery Bypass Grafting
Authors: Hollingsworth John M. , Funk Russell J. , Garrison Spencer A. , Owen-Smith Jason , Kaufman Samuel A. , Pagani Francis D. , Nallamothu Brahmajee K. 
Published: November 2016

Background—
Patients undergoing coronary artery bypass grafting (CABG) must often see multiple providers dispersed across many care locations. To test whether teamwork (assessed with the bipartite clustering coefficient) among these physicians is a determinant of surgical outcomes, we examined national Medicare data from patients undergoing CABG.

Methods and Results—
Among Medicare beneficiaries who underwent CABG between 2008 and 2011, we mapped relationships between all physicians who treated them during their surgical episodes, including both surgeons and nonsurgeons. After aggregating across CABG episodes in a year to construct the physician social networks serving each health system, we then assessed the level of physician teamwork in these networks with the bipartite clustering coefficient. Finally, we fit a series of multivariable regression models to evaluate associations between a health system’s teamwork level and its 60-day surgical outcomes. We observed substantial variation in the level of teamwork between health systems performing CABG (SD for the bipartite clustering coefficient was 0.09). Although health systems with high and low teamwork levels treated beneficiaries with comparable comorbidity scores, these health systems differed over several sociocultural and healthcare capacity factors (eg, physician staff size and surgical caseload). After controlling for these differences, health systems with higher teamwork levels had significantly lower 60-day rates of emergency department visit, readmission, and mortality.

Conclusions—
Health systems with physicians who tend to work together in tightly-knit groups during CABG episodes realize better surgical outcomes. As such, delivery system reforms focused on building teamwork may have positive effects on surgical care.
Early Detection of Heart Failure Using Electronic Health Records
Authors: Ng Kenney , Steinhubl Steven R. , deFilippi Christopher , Dey Sanjoy , Stewart Walter F. 
Published: November 2016

Background—
Using electronic health records data to predict events and onset of diseases is increasingly common. Relatively little is known, although, about the tradeoffs between data requirements and model utility.

Methods and Results—
We examined the performance of machine learning models trained to detect prediagnostic heart failure in primary care patients using longitudinal electronic health records data. Model performance was assessed in relation to data requirements defined by the prediction window length (time before clinical diagnosis), the observation window length (duration of observation before prediction window), the number of different data domains (data diversity), the number of patient records in the training data set (data quantity), and the density of patient encounters (data density). A total of 1684 incident heart failure cases and 13 525 sex, age-category, and clinic matched controls were used for modeling. Model performance improved as (1) the prediction window length decreases, especially when <2 years; (2) the observation window length increases but then levels off after 2 years; (3) the training data set size increases but then levels off after 4000 patients; (4) more diverse data types are used, but, in order, the combination of diagnosis, medication order, and hospitalization data was most important; and (5) data were confined to patients who had ≥10 phone or face-to-face encounters in 2 years.

Conclusions—
These empirical findings suggest possible guidelines for the minimum amount and type of data needed to train effective disease onset predictive models using longitudinal electronic health records data.
Insulin Resistance Is a Risk Factor for Silent Lacunar Infarction
Authors: Lee Ji Eun , Shin Dong Wook , Yun Jae Moon , Kim Sang Hyuck , Nam You-Seon , Cho BeLong , Lim Jae-Sung , Jeong Han-Yeong , Kwon Hyung-Min , Park Jin-Ho 
Published: November 2016

Background and Purpose—
This study aims to investigate the association between insulin resistance (IR) and silent lacunar infarction (SLI) in healthy adults.

Methods—
We recruited 2326 healthy Korean adults who took health checkups, including a brain magnetic resonance imaging. SLI was defined as an infarction measuring 0.3 to 1.5 cm in diameter that was localized in the territory of perforating branches of cerebral arteries, as seen in the brain magnetic resonance imaging. The homeostasis model assessment–estimated insulin resistance index was used for IR estimation, and the cutoff value for its diagnosis for Koreans was 2.56.

Results—

The mean age of the study population was 56.2 years (range, 40–79 years), and 1279 subjects (55.0%) were male. The prevalence of SLI and IR was 8.1% and 18.1%, respectively. In multivariate logistic analysis, after adjusting for traditional SLI-associated risk factors, IR was positively associated with the prevalence of SLI (adjusted odds ratio, 1.69; 95% confidence interval, 1.16–2.46). The proportion of subjects with multiple SLI lesions (≥2) was also higher in the IR (+) group than that in the IR (−) group (4.3% versus 1.7%;
P
<0.001). In ordered logistic regression, IR was positively associated with an increase in SLI severity (adjusted odds ratio, 1.76; 95% confidence interval, 1.21–2.56).

Conclusions—
IR is an independent risk factor of SLI presence and its severity in Koreans. Whether improvement of IR might prevent SLI occurrence needs to be addressed by clinical trials.
Dynamical and Thermodynamical Impacts of High- and Low-Frequency Atmospheric Eddies on the Initial Melt of Arctic Sea Ice
Authors: Hegyi Bradley M. , Deng Yi 
Published: November 2016

Abstract
The role of high-frequency and low-frequency eddies in the melt onset of Arctic sea ice is investigated through an examination of eddy effects on lower-tropospheric (1000–500 hPa) meridional heat transport into the Arctic and local surface downwelling shortwave and longwave radiation. Total and eddy components of the meridional heat transport into the Arctic from 1979 to 2012 are calculated from reanalysis data, and surface radiation data are acquired from the NASA Clouds and the Earth’s Radiant Energy System (CERES) project dataset. There is a significant positive correlation between the mean initial melt date and the September sea ice minimum extent, with each quantity characterized by a negative trend. Spatially, the earlier mean melt onset date is primarily found in a region bounded by 90°E and 130°W. The decline in this region is steplike and not associated with an increase in meridional heat transport but with an earlier appearance of above-freezing temperatures in the troposphere. In most years, discrete short-duration episodes of melt onset over a large area occur. In an investigation of two of these melt episodes, a positive total meridional heat transport is associated with the peak melt, with the product of high-frequency eddy wind and mean temperature fields being the most important contributor. Additionally, there is a key positive anomaly in surface downwelling longwave radiation immediately preceding the peak melt that is associated with increased cloud cover and precipitable water. These results suggest the importance of carefully considering and properly representing atmospheric eddies when modeling the melt onset of Arctic sea ice.