bluuebunny/crossref_metadata_2025_split huggingface dataset:
Code optimizations using formally verified properties
Authors: Shi Yao , Blackham Bernard , Heiser Gernot 
Published: November 2013

Formal program verification offers strong assurance of correctness, backed by the strength of mathematical proof. Constructing these proofs requires humans to identify program invariants, and show that they are always maintained. These invariants are then used to prove that the code adheres to its specification.
In this paper, we explore the overlap between formal verification and code optimization. We propose two approaches to reuse the invariants derived in formal proofs and integrate them into compilation. The first applies invariants extracted from the proof, while the second leverages the property of program safety (i.e., the absence of bugs). We reuse this information to improve the performance of generated object code.
We evaluated these methods on seL4, a real-world formally-verified microkernel, and obtained improvements in average runtime performance (up to 28%) and in worst-case execution time (up to 25%). In macro-benchmarks, we found the performance of para-virtualized Linux running on the microkernel improved by 6-16%.
Efficient concurrency-bug detection across inputs
Authors: Deng Dongdong , Zhang Wei , Lu Shan 
Published: November 2013

In the multi-core era, it is critical to efficiently test multi-threaded software and expose concurrency bugs before software release. Previous work has made significant progress in detecting and validating concurrency bugs under a given input. Unfortunately, software testing always faces large sets of test inputs, and existing techniques are still too expensive to be applied to every test input in practice.
In this paper, we use open-source software to study how existing concurrency-bug detection tools work for a set of inputs. The study shows that an interleaving pattern, such as a data race or an atomicity violation, can often be exposed by many inputs. Consequently, existing bug detectors would inevitably waste their bug detection effort to generate duplicate bug reports, when applied to a set of inputs.
Guided by the above study, we propose a coverage metric, Concurrent Function Pairs (CFP), to efficiently approximate how interleavings overlap across inputs. Using CFP, we have designed a new approach to detecting data races and atomicity-violation bugs for a set of inputs.
Our evaluation on open-source C/C++ applications shows that our CFP-guided approach can effectively accelerate concurrency-bug detection for a set of inputs by reducing redundant detection effort across inputs.
Ironclad C++
Authors: DeLozier Christian , Eisenberg Richard , Nagarakatte Santosh , Osera Peter-Michael , Martin Milo M.K. , Zdancewic Steve 
Published: November 2013

The C++ programming language remains widely used, despite inheriting many unsafe features from C---features that often lead to failures of type or memory safety that manifest as buffer overflows, use-after-free vulnerabilities, or abstraction violations. Malicious attackers can exploit such violations to compromise application and system security.
This paper introduces Ironclad C++, an approach to bringing the benefits of type and memory safety to C++. Ironclad C++ is, in essence, a library-augmented, type-safe subset of C++. All Ironclad C++ programs are valid C++ programs that can be compiled using standard, off-the-shelf C++ compilers. However, not all valid C++ programs are valid Ironclad C++ programs: a syntactic source-code validator statically prevents the use of unsafe C++ features. To enforce safety properties that are difficult to check statically, Ironclad C++ applies dynamic checks via templated ``smart pointer'' classes.
Using a semi-automatic refactoring tool, we have ported nearly 50K lines of code to Ironclad C++. These benchmarks incur a performance overhead of 12% on average, compared to the original unsafe C++ code.
Modular monadic meta-theory
Authors: Delaware Benjamin , Keuchel Steven , Schrijvers Tom , Oliveira Bruno C.d.S. 
Published: November 2013

This paper presents 3MT, a framework for modular mechanized meta-theory of languages with effects. Using 3MT, individual language features and their corresponding definitions -- semantic functions, theorem statements and proofs-- can be built separately and then reused to create different languages with fully mechanized meta-theory. 3MT combines modular datatypes and monads to define denotational semantics with effects on a per-feature basis, without fixing the particular set of effects or language constructs.
One well-established problem with type soundness proofs for denotational semantics is that they are notoriously brittle with respect to the addition of new effects. The statement of type soundness for a language depends intimately on the effects it uses, making it particularly challenging to achieve modularity. 3MT solves this long-standing problem by splitting these theorems into two separate and reusable parts: a feature theorem that captures the well-typing of denotations produced by the semantic function of an individual feature with respect to only the effects used, and an effect theorem that adapts well-typings of denotations to a fixed superset of effects. The proof of type soundness for a particular language simply combines these theorems for its features and the combination of their effects. To establish both theorems, 3MT uses two key reasoning techniques: modular induction and algebraic laws about effects. Several effectful language features, including references and errors, illustrate the capabilities of 3MT. A case study reuses these features to build fully mechanized definitions and proofs for 28 languages, including several versions of mini-ML with effects.
Interleukin-30 Expression in Prostate Cancer and Its Draining Lymph Nodes Correlates with Advanced Grade and Stage
Authors: Di Meo Serena , Airoldi Irma , Sorrentino Carlo , Zorzoli Alessia , Esposito Silvia , Di Carlo Emma 
Published: November 2013

Abstract
Purpose: The interleukin (IL)-27 cytokine subunit p28, also called IL-30, has been recognized as a novel immunoregulatory mediator endowed with its own functions. These are currently the subject of discussion in immunology, but completely unexplored in cancer biology. We set out to investigate the role of IL-30 in prostate carcinogenesis and its effects on human prostate cancer (hPCa) cells.
Experimental Design: IL-30 expression, as visualized by immunohistochemistry and real-time reverse transcriptase PCR on prostate and draining lymph nodes from 125 patients with prostate cancer, was correlated with clinicopathologic data. IL-30 regulation of hPCa cell viability and expression of selected gene clusters was tested by flow cytometry and PCR array.
Results: IL-30, absent in normal prostatic epithelia, was expressed by cancerous epithelia with Gleason ≥ 7% of 21.3% of prostate cancer stage I to III and 40.9% of prostate cancer stage IV. IL-30 expression by tumor infiltrating leukocytes (T-ILK) was higher in stage IV that in stage I to III prostate cancer (P = 0.0006) or in control tissue (P = 0.0011). IL-30 expression in prostate draining lymph nodes (LN)-ILK was higher in stage IV than in stage I to III prostate cancer (P = 0.0031) or in control nodes (P = 0.0023). The main IL-30 sources were identified as CD68+ macrophages, CD33+/CD11b+ myeloid cells, and CD14+ monocytes. In vitro, IL-30 stimulated proliferation of hPCa cells and also downregulated CCL16/LEC, TNFSF14/LIGHT, chemokine-like factor (CKLF), and particularly CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) and greatly upregulated ChemR23/CMKLR.
Conclusions: We provide the first evidence that IL-30 is implicated in prostate cancer progression because (i) its expression by prostate cancer or T- and LN-ILK correlates with advanced disease grade and stage; and (ii) IL-30 exerts protumor activity in hPCa cells. Clin Cancer Res; 20(3); 585–94. ©2013 AACR.
Prognostic Value of Cardiovascular Magnetic Resonance Imaging Measurements Corrected for Age and Sex in Idiopathic Pulmonary Arterial Hypertension
Authors: Swift Andrew J. , Rajaram Smitha , Campbell Michael J. , Hurdman Judith , Thomas Steve , Capener Dave , Elliot Charlie , Condliffe Robin , Wild Jim M. , Kiely David G. 
Published: November 2013

Background—
There are limited data on the prognostic value of cardiovascular magnetic resonance measurements in idiopathic pulmonary arterial hypertension, with no studies investigating the impact of correction of cardiovascular magnetic resonance indices for age and sex on prognostic value.

Methods and Results—

Consecutive patients with idiopathic pulmonary arterial hypertension underwent cardiovascular magnetic resonance imaging at 1.5T. Steady-state free precession cardiac volumes and mass measurements were corrected for age, sex, and body surface area according to reference data and prognostic significance assessed. A total of 80 patients with idiopathic pulmonary arterial hypertension were identified, and 23 patients died during the mean follow-up of 32±14 months. Corrected for age, sex, and body surface area, right ventricular end-systolic volume (
P
=0.004) strongly predicted mortality, independent of World Health Organization functional class, mean right atrial pressure, cardiac index, and mixed venous oxygen saturations.

Conclusions—
Consideration should be given to correcting cardiovascular magnetic resonance measures for age, sex, and body surface area, particularly given the changing demographics of patients with idiopathic pulmonary arterial hypertension. Corrected right ventricular end-systolic volume is a strong prognostic marker in idiopathic pulmonary arterial hypertension, independent of invasively derived measurements, mean right atrial pressure cardiac index, and mixed venous oxygen saturations.
Multicenter, Randomized Trial of Quantitative Pretest Probability to Reduce Unnecessary Medical Radiation Exposure in Emergency Department Patients With Chest Pain and Dyspnea
Authors: Kline Jeffrey A. , Jones Alan E. , Shapiro Nathan I. , Hernandez Jackeline , Hogg Melanie M. , Troyer Jennifer , Nelson R. Darrel 
Published: November 2013

Background—
Use of pretest probability can reduce unnecessary testing. We hypothesize that quantitative pretest probability, linked to evidence-based management strategies, can reduce unnecessary radiation exposure and cost in low-risk patients with symptoms suggestive of acute coronary syndrome and pulmonary embolism.

Methods and Results—

This was a prospective, 4-center, randomized controlled trial of decision support effectiveness. Subjects were adults with chest pain and dyspnea, nondiagnostic ECGs, and no obvious diagnosis. The clinician provided data needed to compute pretest probabilities from a Web-based system. Clinicians randomized to the intervention group received the pretest probability estimates for both acute coronary syndrome and pulmonary embolism and suggested clinical actions designed to lower radiation exposure and cost. The control group received nothing. Patients were followed for 90 days. The primary outcome and sample size of 550 was predicated on a significant reduction in the proportion of healthy patients exposed to >5 mSv chest radiation. A total of 550 patients were randomized, and 541 had complete data. The proportion with >5 mSv to the chest and no significant cardiopulmonary diagnosis within 90 days was reduced from 33% to 25% (
P
=0.038). The intervention group had significantly lower median chest radiation exposure (0.06 versus 0.34 mSv;
P
=0.037, Mann–Whitney
U
test) and lower median costs ($934 versus $1275;
P
=0.018) for medical care. Adverse events occurred in 16% of controls and 11% in the intervention group (
P
=0.06).

Conclusions—
Provision of pretest probability and prescriptive advice reduced radiation exposure and cost of care in low-risk ambulatory patients with symptoms of acute coronary syndrome and pulmonary embolism.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01059500.
Effect of Remote Ischemic Preconditioning on Platelet Activation and Reactivity Induced by Ablation for Atrial Fibrillation
Authors: Stazi Alessandra , Scalone Giancarla , Laurito Marianna , Milo Maria , Pelargonio Gemma , Narducci Maria Lucia , Parrinello Rossella , Figliozzi Stefano , Bencardino Gianluigi , Perna Francesco , Lanza Gaetano A. , Crea Filippo 
Published: November 2013

Background—
Radiofrequency ablation of atrial fibrillation has been associated with some risk of thromboembolic events. Previous studies showed that preventive short episodes of forearm ischemia (remote ischemic preconditioning [IPC]) reduce exercise-induced platelet reactivity. In this study, we assessed whether remote IPC has any effect on platelet activation induced by radiofrequency ablation of atrial fibrillation.

Methods and Results—

We randomized 19 patients (age, 54.7±11 years; 17 male) undergoing radiofrequency catheter ablation of paroxysmal atrial fibrillation to receive remote IPC or sham intermittent forearm ischemia (control subjects) before the procedure. Blood venous samples were collected before and after remote IPC/sham ischemia, at the end of the ablation procedure, and 24 hours later. Platelet activation and reactivity were assessed by flow cytometry by measuring monocyte-platelet aggregate formation, platelet CD41 in the monocyte-platelet aggregate gate, and platelet CD41 and CD62 in the platelet gate in the absence and presence of ADP stimulation. At baseline, there were no differences between groups in platelet variables. Radiofrequency ablation induced platelet activation in both groups, which persisted after 24 hours. However, compared with control subjects, remote IPC patients showed a lower increase in all platelet variables, including monocyte-platelet aggregate formation (
P
<0.0001), CD41 in the monocyte-platelet aggregate gate (
P
=0.002), and CD41 (
P
<0.0001) and CD62 (
P
=0.002) in the platelet gate. Compared with control subjects, remote IPC was also associated with a significantly lower ADP-induced increase in all platelet markers.

Conclusions—
Our data show that remote IPC before radiofrequency catheter ablation for paroxysmal atrial fibrillation significantly reduces the increased platelet activation and reactivity associated with the procedure.
Growing Impact of Restenosis on the Surgical Treatment of Peripheral Arterial Disease
Authors: Jones Douglas W. , Schanzer Andres , Zhao Yuanyuan , MacKenzie Todd A. , Nolan Brian W. , Conte Michael S. , Goodney Philip P. ,   The Vascular Study Group of New England
Published: November 2013

Background

Patients with peripheral arterial disease often experience treatment failure from restenosis at the site of a prior peripheral endovascular intervention (
PVI
) or lower extremity bypass (
LEB
). The impact of these treatment failures on the utilization and outcomes of secondary interventions is poorly understood.

Methods and Results

In our regional vascular quality improvement collaborative, we compared 2350 patients undergoing primary infrainguinal
LEB
with 1154 patients undergoing secondary infrainguinal
LEB
(
LEB
performed after previous revascularization in the index limb) between 2003 and 2011. The proportion of patients undergoing secondary
LEB
increased by 72% during the study period (22% of all
LEBs
in 2003 to 38% in 2011,
P
<0.001). In‐hospital outcomes, such as myocardial infarction, death, and amputation, were similar between primary and secondary
LEB
groups. However, in both crude and propensity‐weighted analyses, secondary
LEB
was associated with significantly inferior 1‐year outcomes, including major adverse limb event‐free survival (composite of death, new bypass graft, surgical bypass graft revision, thrombectomy/thrombolysis, or above‐ankle amputation; Secondary LEB MALE‐free survival = 61.6% vs primary LEB MALE‐free survival = 67.5%,
P
=0.002) and reintervention or amputation‐free survival (composite of death, reintervention, or above‐ankle amputation; Secondary LEB RAO‐free survival = 58.9% vs Primary LEB RAO‐free survival 64.1%,
P
=0.003). Inferior outcomes for secondary
LEB
were observed regardless of the prior failed treatment type (
PVI
or
LEB
).

Conclusions

In an era of increasing utilization of
PVI
, a growing proportion of patients undergo
LEB
in the setting of a prior failed
PVI
or surgical bypass. When caring for patients with
peripheral arterial disease
, physicians should recognize that first treatment failure (
PVI
or
LEB
) affects the success of subsequent revascularizations.
Potential Vorticity Dynamics of Tropical Instability Vortices
Authors: Holmes Ryan M. , Thomas Leif N. , Thompson LuAnne , Darr David 
Published: November 2013

Abstract
Tropical instability vortices (TIVs) in the equatorial Pacific exhibit energetic horizontal and vertical circulation characterized by regions of high Rossby number and low Richardson number. Their strong anticyclonic vorticity and vertical shear can influence the broader-scale circulation by driving lateral mixing and vertical exchange between the ocean surface and interior. The authors use a set of nested high-resolution simulations of the equatorial Pacific, with a finest grid size of 3 km, to examine the vortex dynamics associated with TIV core water formation. TIV cores are characterized by low values of the Ertel potential vorticity (PV) as the relative vorticity is anticyclonic with magnitude comparable to the local Coriolis parameter. A study of the variation of PV and other scalars along Lagrangian fluid parcel tracks entering the TIVs shows that the low-PV water in their cores is a mix of Equatorial Undercurrent (EUC) water and North Equatorial Counter Current (NECC) water. The EUC water is characterized by strong horizontal vorticity, and thus, the baroclinic component of the PV is nonnegligible and acts as a source for the anticyclonic vorticity of TIVs. This horizontal vorticity is tilted by an ageostrophic secondary circulation associated with strain-induced frontogenesis that tends to form along the path of the EUC water that enters the vortex. Frontogenesis disrupts the cyclogeostrophic balance of the frontal flow and drives differential vertical motions across the front. These results emphasize the role of submesoscale physics in the equatorial region, which are active when both the Rossby and Richardson numbers are O(1).
High impact child abuse may predict risk of elevated suicidality during antidepressant initiation
Authors: Singh Ajeet B , Bousman Chad A , Ng Chee H , Berk Michael 
Published: November 2013

Background: Concerns have emerged that initiation of an antidepressant can lead to or exacerbate suicidality. If those more at risk could be identified prior to treatment, treatment risk benefit analysis and patient risk management could be assisted. Aims: This study investigated the role of child abuse and ongoing emotional impact from abuse on the risk of suicidality during the first week of treatment with an antidepressant. The patient sample for this study was drawn from one site of a larger pharmacogenetic study. The hypothesis was that subjects with high impact child abuse would have greater elevation of suicidality during the first week of antidepressant treatment. Methods: Fifty-one subjects were initiated on either venlafaxine (VEN) or escitalopram (ESC) for major depressive disorder (MDD) and had pre-treatment suicidality assayed with the reasons for living scale (RFLS), which was repeated after one week of treatment. Several clinical, demographic and genotype variables were controlled for. The 15-item Impact of Event Scale (IES-15) was administered to subjects reporting abuse to dichotomise the abuse group into low and high (IES-15 ≥ 26) impact groups for sub-analysis as per the scales validated rating guidelines. Results: Subjects reporting no child abuse exposure were less likely to have increased suicidality during the first week of antidepressant treatment (7.6%) compared to subjects with low impact abuse (38.5%, p = 0.041) and high impact abuse (58.3%, p = 0.009). Only high impact abuse predicted increased suicidality after adjustment for potential confounders such as depression severity (OR = 31.5, 95% CI = 1.3 to 748.7, p = 0.03). Conclusions: If these findings are replicated in larger samples, child abuse history could become an important element of assessing risk benefit balance when initiating antidepressants and may help guide the level of patient review needed during antidepressant initiation.
Measuring complexity in neurological rehabilitation: the Oxford Case Complexity Assessment Measure (OCCAM)
Authors: Troigros Odile , Béjot Yannick , Rodriguez Patricia Marquez , Shoaib Farhat , Ellis Henrietta , Wade Derick 
Published: November 2013

Objective: To investigate validity and reliability of a new measure of case complexity, the Oxford Case Complexity Assessment Measure (OCCAM). Design: Data collection on inpatients and outpatients attending for rehabilitation. In subsets, repeat assessments were undertaken two weeks apart, by clinicians unaware of initial data, and on admission and on discharge from inpatient rehabilitation. Setting: Specialist neurological rehabilitation service. Subjects: Patients receiving rehabilitation after acute onset disability. Interventions: Assessment by clinical staff as part of routine care. Measures: OCCAM, the INTERMED, Rehabilitation Complexity Scale – Extended (RCS-E), clinical judgement of complexity (0–10 numerical rating scale), length of stay and discharge destination (for inpatients). Results: For the OCCAM, the Cronbach’s α coefficient was 0.69 and item-total correlations were moderate to high except for pathology and time. The correlation coefficients with OCCAM were: INTERMED (ρ = 0.694), RCS-E (ρ = 0.736), and team judgement (ρ = 0.796). Inter-rater agreement was excellent (Weighted κ = 0.95). Correlation between admission and discharge scores was ρ = 0.917. Test–retest agreement was good (intraclass correlation coefficient 0.86). Higher mean admission scores were associated with prolonged stays (38.6 ± 12.2 versus 32.9 ± 13.7, P = 0.04) and failure to return home (48.0 ± 13.7 versus mean 32.1 ± 10.7, P < 0.001). The optimal cut-off of OCCAM to detect patients not discharged home was ≥ 34, with corresponding sensitivity and specificity of 84.6% and 62.8%, respectively. Conclusions: This preliminary evidence suggests that the OCCAM may measure case complexity reliably, and may predict rehabilitation resource used and outcome. Further research is warranted.