bluuebunny/crossref_metadata_2025 huggingface dataset:
AsyncClock
Authors: Hsiao Chun-Hung , Narayanasamy Satish , Khan Essam Muhammad Idris , Pereira Cristiano L. , Pokam Gilles A.
Published: May 2017

Asynchronous programming model is commonly used in mobile systems and Web 2.0 environments. Asynchronous race detectors use algorithms that are an order of magnitude performance and space inefficient compared to conventional data race detectors. We solve this problem by identifying and addressing two important problems in reasoning about causality between asynchronous events.

Unlike conventional signal-wait operations, establishing causal order between two asynchronous events is fundamentally more challenging as there is no common handle they operate on. We propose a new primitive named AsyncClock that addresses this problem by explicitly tracking causally preceding events, and show that AsyncClock can handle a wide variety of asynchronous causality models. We also address the important scalability problem of efficiently identifying heirless events whose metadata can be reclaimed.

We built the first single-pass, non-graph-based Android race detector using our algorithm and applied it to find errors in 20 popular applications. Our tool incurs about 6x performance overhead, which is several times more efficient than the state-of-the-art solution. It also scales well with the execution length. We used our tool to find 147 previously unknown harmful races.
An Analysis of Persistent Memory Use with WHISPER
Authors: Nalli Sanketh , Haria Swapnil , Hill Mark D. , Swift Michael M. , Volos Haris , Keeton Kimberly
Published: May 2017

Emerging non-volatile memory (NVM) technologies promise durability with read and write latencies comparable to volatile memory (DRAM). We define Persistent Memory (PM) as NVM accessed with byte addressability at low latency via normal memory instructions. Persistent-memory applications ensure the consistency of persistent data by inserting ordering points between writes to PM allowing the construction of higher-level transaction mechanisms. An epoch is a set of writes to PM between ordering points.

To put systems research in PM on a firmer footing, we developed and analyzed a PM benchmark suite called WHISPER (Wisconsin-HP Labs Suite for Persistence) that comprises ten PM applications we gathered to cover all current interfaces to PM. A quantitative analysis reveals several insights: (a) only 4% of writes in PM-aware applications are to PM and the rest are to volatile memory, (b) software transactions are often implemented with 5 to 50 ordering points (c) 75% of epochs update exactly one 64B cache line, (d) 80% of epochs from the same thread depend on previous epochs from the same thread, while few epochs depend on epochs from other threads.

Based on our analysis, we propose the Hands-off Persistence System (HOPS) to track updates to PM in hardware. Current hardware design requires applications to force data to PM as each epoch ends. HOPS provides high-level ISA primitives for applications to express durability and ordering constraints separately and enforces them automatically, while achieving 24.3% better performance over current approaches to persistence.
DCatch
Authors: Liu Haopeng , Li Guangpu , Lukman Jeffrey F. , Li Jiaxin , Lu Shan , Gunawi Haryadi S. , Tian Chen
Published: May 2017

In big data and cloud computing era, reliability of distributed systems is extremely important. Unfortunately, distributed concurrency bugs, referred to as DCbugs, widely exist. They hide in the large state space of distributed cloud systems and manifest non-deterministically depending on the timing of distributed computation and communication. Effective techniques to detect DCbugs are desired. This paper presents a pilot solution, DCatch, in the world of DCbug detection. DCatch predicts DCbugs by analyzing correct execution of distributed systems. To build DCatch, we design a set of happens-before rules that model a wide variety of communication and concurrency mechanisms in real-world distributed cloud systems. We then build runtime tracing and trace analysis tools to effectively identify concurrent conflicting memory accesses in these systems. Finally, we design tools to help prune false positives and trigger DCbugs. We have evaluated DCatch on four representative open-source distributed cloud systems, Cassandra, Hadoop MapReduce, HBase, and ZooKeeper. By monitoring correct execution of seven workloads on these systems, DCatch reports 32 DCbugs, with 20 of them being truly harmful.
Verification of a Practical Hardware Security Architecture Through Static Information Flow Analysis
Authors: Ferraiuolo Andrew , Xu Rui , Zhang Danfeng , Myers Andrew C. , Suh G. Edward
Published: May 2017

Hardware-based mechanisms for software isolation are becoming increasingly popular, but implementing these mechanisms correctly has proved difficult, undermining the root of security. This work introduces an effective way to formally verify important properties of such hardware security mechanisms. In our approach, hardware is developed using a lightweight security-typed hardware description language (HDL) that performs static information flow analysis. We show the practicality of our approach by implementing and verifying a simplified but realistic multi-core prototype of the ARM TrustZone architecture. To make the security-typed HDL expressive enough to verify a realistic processor, we develop new type system features. Our experiments suggest that information flow analysis is efficient, and programmer effort is modest. We also show that information flow constraints are an effective way to detect hardware vulnerabilities, including several found in commercial processors.
FLEP
Authors: Wu Bo , Liu Xu , Zhou Xiaobo , Jiang Changjun
Published: May 2017

GPUs are widely adopted in HPC and cloud computing platforms to accelerate general-purpose workloads. However, modern GPUs do not support flexible preemption, leading to performance and priority inversion problems in multi-tasking environments.

In this paper, we propose and develop FLEP, the first software system that enables flexible kernel preemption and kernel scheduling on commodity GPUs. The FLEP compilation engine transforms the GPU program into preemptable forms, which can be interrupted during execution and yield all or part of the streaming multi-processors (SMs) in the GPU. The FLEP runtime engine intercepts all kernel invocations and determines which kernels and how those kernels should be preempted and scheduled. Experimental results on two-kernel co-runs demonstrate up to 24.2X speedup for high-priority kernels and up to 27X improvement on normalized average turnaround time for kernels with the same priority. FLEP reduces the preemption latency by up to 41% compared to yielding the whole GPU when the waiting kernels only need several SMs. With all the benefits, FLEP only introduces 2.5% runtime overhead, which is substantially lower than the kernel slicing approach.
Pallas
Authors: Huang Jian , Allen-Bond Michael , Zhang Xuechen
Published: May 2017

Software optimization is constantly a serious concern for developing high-performance systems. To accelerate the workflow execution of a specific functionality, software developers usually define and implement a fast path to speed up the critical and commonly executed functions in the workflow. However, producing a bug-free fast path is nontrivial. Our study on the Linux kernel discloses that a committed fast path can have up to 19 follow-up patches for bug fixing, and most of them are deep semantic bugs, which are difficult to be pinpointed by existing bug-finding tools.

In this paper, we present such a new category of software bugs based on our fast-path bug study across various system software including virtual memory manager, file systems, network, and device drivers. We investigate their root causes and identify five error-prone aspects in a fast path: path state, trigger condition, path output, fault handling, and assistant data structure. We find that many of the deep bugs can be prevented by applying static analysis incorporating simple semantic information. We extract a set of rules based on our findings and build a toolkit PALLAS to check fast-path bugs. The evaluation results show that PALLAS can effectively reveal fast-path bugs in a variety of systems including Linux kernel, mobile operating system, software-defined networking system, and web browser.
Moonwalk
Authors: Khazraee Moein , Zhang Lu , Vega Luis , Taylor Michael Bedford
Published: May 2017

Cloud services are becoming increasingly globalized and data-center workloads are expanding exponentially. GPU and FPGA-based clouds have illustrated improvements in power and performance by accelerating compute-intensive workloads. ASIC-based clouds are a promising way to optimize the Total Cost of Ownership (TCO) of a given datacenter computation (e.g. YouTube transcoding) by reducing both energy consumption and marginal computation cost.

The feasibility of an ASIC Cloud for a particular application is directly gated by the ability to manage the Non-Recurring Engineering (NRE) costs of designing and fabricating the ASIC, so that it is significantly lower (e.g. 2X) than the TCO of the best available alternative.

In this paper, we show that technology node selection is a major tool for managing ASIC Cloud NRE, and allows the designer to trade off an accelerator's excess energy efficiency and cost performance for lower total cost.

We explore NRE and cross-technology optimization of ASIC Clouds for four different applications: Bitcoin mining, YouTube-style video transcoding, Litecoin, and Deep Learning. We address these challenges and show large reductions in the NRE, potentially enabling ASIC Clouds to address a wider variety of datacenter workloads. Our results suggest that advanced nodes like 16nm will lead to sub-optimal TCO for many workloads, and that use of older nodes like 65nm can enable a greater diversity of ASIC Clouds.
Mechanisms of Deubiquitinase Specificity and Regulation
Authors: Mevissen Tycho E.T. , Komander David
Published: May 2017

Protein ubiquitination is one of the most powerful posttranslational modifications of proteins, as it regulates a plethora of cellular processes in distinct manners. Simple monoubiquitination events coexist with more complex forms of polyubiquitination, the latter featuring many different chain architectures. Ubiquitin can be subjected to further posttranslational modifications (e.g., phosphorylation and acetylation) and can also be part of mixed polymers with ubiquitin-like modifiers such as SUMO (small ubiquitin-related modifier) or NEDD8 (neural precursor cell expressed, developmentally downregulated 8). Together, cellular ubiquitination events form a sophisticated and versatile ubiquitin code. Deubiquitinases (DUBs) reverse ubiquitin signals with equally high sophistication. In this review, we conceptualize the many layers of specificity that DUBs encompass to control the ubiquitin code and discuss examples in which DUB specificity has been understood at the molecular level. We further discuss the many mechanisms of DUB regulation with a focus on those that modulate catalytic activity. Our review provides a framework to tackle lingering questions in DUB biology.
Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade
Authors: Chiti Fabrizio , Dobson Christopher M.
Published: May 2017

Peptides and proteins have been found to possess an inherent tendency to convert from their native functional states into intractable amyloid aggregates. This phenomenon is associated with a range of increasingly common human disorders, including Alzheimer and Parkinson diseases, type II diabetes, and a number of systemic amyloidoses. In this review, we describe this field of science with particular reference to the advances that have been made over the last decade in our understanding of its fundamental nature and consequences. We list the proteins that are known to be deposited as amyloid or other types of aggregates in human tissues and the disorders with which they are associated, as well as the proteins that exploit the amyloid motif to play specific functional roles in humans. In addition, we summarize the genetic factors that have provided insight into the mechanisms of disease onset. We describe recent advances in our knowledge of the structures of amyloid fibrils and their oligomeric precursors and of the mechanisms by which they are formed and proliferate to generate cellular dysfunction. We show evidence that a complex proteostasis network actively combats protein aggregation and that such an efficient system can fail in some circumstances and give rise to disease. Finally, we anticipate the development of novel therapeutic strategies with which to prevent or treat these highly debilitating and currently incurable conditions.
Theorizing in Sociological Research: A New Perspective, a New Departure?
Authors: Swedberg Richard
Published: May 2017

During the last few years a number of articles and books have appeared that signal the emergence of a novel approach to the role of theory in sociology. Instead of equating theory with important studies, the main focus of this approach is how to use theory in ongoing empirical research and especially what happens before the presentation of the results. The key task is to empower the individual researcher to do better research. A word that keeps recurring, and that can also be said to summarize this approach, is theorizing. Three core ideas of this approach are discussed: Theorizing is of a practical nature, it draws on a number of basic theorizing tools (such as abduction, abstraction, and analogy), and the area covered by theorizing is considerably larger than that of conventional theory. If successful, the approach of theorizing would demand a much more active and central role for the theoretician in sociology.
Decision-Making Processes in Social Contexts
Authors: Bruch Elizabeth , Feinberg Fred
Published: May 2017

Over the past half century, scholars in the interdisciplinary field of judgment and decision making have amassed a trove of findings, theories, and prescriptions regarding the processes ordinary people enact when making choices. This body of knowledge, however, has had little influence on sociology. Sociological research on choice emphasizes how features of the social environment shape individual outcomes, not people's underlying decision processes. Our aim in this article is to provide an overview of selected ideas, models, and data sources from decision research that can fuel new lines of inquiry into how socially situated actors navigate both everyday and major life choices. We also highlight opportunities and challenges for cross-fertilization between sociology and decision research that can allow each field to expand its range of inquiry.
A common NHE3 single-nucleotide polymorphism has normal function and sensitivity to regulatory ligands
Authors: Yin Jianyi , Tse Chung-Ming , Cha Boyoung , Sarker Rafiquel , Zhu Xinjun C. , Walentinsson Anna , Greasley Peter J. , Donowitz Mark
Published: May 2017

Na+/H+exchanger NHE3 mediates the majority of intestinal and renal electroneutral sodium absorption. Dysfunction of NHE3 is associated with a variety of diarrheal diseases. We previously reported that the NHE3 gene ( SLC9A3) has more than 400 single-nucleotide polymorphisms (SNPs) but few nonsynonymous polymorphisms. Among the latter, one polymorphism (rs2247114-G>A), which causes a substitution from arginine to cysteine at amino acid position 799 (p.R799C), is common in Asian populations. To improve our understanding of the population distribution and potential clinical significance of the NHE3-799C variant, we investigated the frequency of this polymorphism in different ethnic groups using bioinformatics analyses and in a cohort of Japanese patients with cardiovascular or renal disease. We also characterized the function of human NHE3-799C and its sensitivity to regulatory ligands in an in vitro model. NHE3-799C had an allele frequency of 29.5–57.6% in Asian populations, 11.1–23.6% in European populations, and 10.2–22.7% in African populations. PS120/FLAG-NHERF2 fibroblasts stably expressing NHE3-799C had lower total protein expression but a higher percentage of surface expression than those expressing NHE3-799R. NHE3-799C had similar basal activity to NHE3-799R and was similarly stimulated or inhibited, by serum or forskolin, respectively. Tenapanor, a small-molecule NHE3 inhibitor, dose-dependently inhibited NHE3-799R and NHE3-799C activities. The IC50values of tenapanor for NHE3-799C and NHE3-799R were significantly different, but both were in the nanomolar range. These results suggest that NHE3-799C is a common variant enriched in Asian populations, is not associated with compromised function or abnormal regulation, and is unlikely to contribute to clinical disease.

NEW & NOTEWORTHY This study reports results on the functional significance of human NHE3-799C under basal conditions and in response to regulatory ligands, including a novel NHE3 inhibitor called tenapanor. We demonstrate that NHE3-799C is a common variant of NHE3 that is enriched in Asian populations; however, in contrast to our previous studies using rabbit NHE3, its presence seems to have limited clinical significance in humans and is not associated with compromised function or abnormal transport regulation.
Nonlinearities of heart rate variability in animal models of impaired cardiac control: contribution of different time scales
Authors: Silva Luiz Eduardo Virgilio , Lataro Renata Maria , Castania Jaci Airton , Silva Carlos Alberto Aguiar , Salgado Helio Cesar , Fazan Rubens , Porta Alberto
Published: May 2017

Heart rate variability (HRV) has been extensively explored by traditional linear approaches (e.g., spectral analysis); however, several studies have pointed to the presence of nonlinear features in HRV, suggesting that linear tools might fail to account for the complexity of the HRV dynamics. Even though the prevalent notion is that HRV is nonlinear, the actual presence of nonlinear features is rarely verified. In this study, the presence of nonlinear dynamics was checked as a function of time scales in three experimental models of rats with different impairment of the cardiac control: namely, rats with heart failure (HF), spontaneously hypertensive rats (SHRs), and sinoaortic denervated (SAD) rats. Multiscale entropy (MSE) and refined MSE (RMSE) were chosen as the discriminating statistic for the surrogate test utilized to detect nonlinearity. Nonlinear dynamics is less present in HF animals at both short and long time scales compared with controls. A similar finding was found in SHR only at short time scales. SAD increased the presence of nonlinear dynamics exclusively at short time scales. Those findings suggest that a working baroreflex contributes to linearize HRV and to reduce the likelihood to observe nonlinear components of the cardiac control at short time scales. In addition, an increased sympathetic modulation seems to be a source of nonlinear dynamics at long time scales. Testing nonlinear dynamics as a function of the time scales can provide a characterization of the cardiac control complementary to more traditional markers in time, frequency, and information domains.

NEW & NOTEWORTHY Although heart rate variability (HRV) dynamics is widely assumed to be nonlinear, nonlinearity tests are rarely used to check this hypothesis. By adopting multiscale entropy (MSE) and refined MSE (RMSE) as the discriminating statistic for the nonlinearity test, we show that nonlinear dynamics varies with time scale and the type of cardiac dysfunction. Moreover, as complexity metrics and nonlinearities provide complementary information, we strongly recommend using the test for nonlinearity as an additional index to characterize HRV.
The impact of ocular hemodynamics and intracranial pressure on intraocular pressure during acute gravitational changes
Authors: Nelson Emily S. , Mulugeta Lealem , Feola Andrew , Raykin Julia , Myers Jerry G. , Samuels Brian C. , Ethier C. Ross
Published: May 2017

Exposure to microgravity causes a bulk fluid shift toward the head, with concomitant changes in blood volume/pressure, and intraocular pressure (IOP). These and other factors, such as intracranial pressure (ICP) changes, are suspected to be involved in the degradation of visual function and ocular anatomical changes exhibited by some astronauts. This is a significant health concern. Here, we describe a lumped-parameter numerical model to simulate volume/pressure alterations in the eye during gravitational changes. The model includes the effects of blood and aqueous humor dynamics, ICP, and IOP-dependent ocular compliance. It is formulated as a series of coupled differential equations and was validated against four existing data sets on parabolic flight, body inversion, and head-down tilt (HDT). The model accurately predicted acute IOP changes in parabolic flight and HDT, and was satisfactory for the more extreme case of inversion. The short-term response to the changing gravitational field was dominated by ocular blood pressures and compliance, while longer-term responses were more dependent on aqueous humor dynamics. ICP had a negligible effect on acute IOP changes. This relatively simple numerical model shows promising predictive capability. To extend the model to more chronic conditions, additional data on longer-term autoregulation of blood and aqueous humor dynamics are needed.

NEW & NOTEWORTHY A significant percentage of astronauts present anatomical changes in the posterior eye tissues after spaceflight. Hypothesized increases in ocular blood volume and intracranial pressure (ICP) in space have been considered to be likely factors. In this work, we provide a novel numerical model of the eye that incorporates ocular hemodynamics, gravitational forces, and ICP changes. We find that changes in ocular hemodynamics govern the response of intraocular pressure during acute gravitational change.
Inflammatory responses to acute elevations of carbon dioxide in mice
Authors: Thom Stephen R. , Bhopale Veena M. , Hu JingPing , Yang Ming
Published: May 2017

Health risks are described from elevated indoor air carbon dioxide (CO2), which often ranges from 1,000 to 4,000 ppm, but the mechanisms are unknown. Here, we demonstrate that mice exposed for 2 h to 2,000 or 4,000 ppm CO2exhibit, respectively, 3.4 ± 0.9-fold (SE, n = 6) and 4.1 ± 0.7-fold ( n = 10) elevations in circulating microparticles (MPs); neutrophil and platelet activation, and vascular leak in brain, muscle, and distal colon. Interleukin (IL)-1β content of MPs also increases after 2,000 ppm by 3.8 ± 0.6-fold ( n = 6) and after 4,000 ppm CO2by 9.3 ± 1.1-fold ( n = 10) greater than control. CO2–induced vascular damage is abrogated by treating mice with an antibody to IL-1β or an IL-1β receptor inhibitor. Injecting naïve mice with CO2-induced MPs expressing a protein found on mature neutrophils recapitulates vascular damage as seen with elevated CO2, and destruction of MPs in CO2-exposed mice abrogates vascular injuries without altering neutrophil or platelet activation. We conclude that environmentally relevant elevations of CO2trigger neutrophils to generate MPs containing high concentrations of IL-1β that cause diffuse inflammatory vascular injury.

NEW & NOTEWORTHY Elevated levels of CO2are often found in indoor air and cause adverse health effects, but the mechanisms have not been identified. In a murine model, environmentally relevant levels of CO2were found to cause diffuse vascular damage because neutrophils are stimulated to produce microparticles that contain high concentrations of interleukin-1β.
Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows Evidence of Immune Response and Viral Replication in Young Cancer Patients
Authors: Streby Keri A. , Geller James I. , Currier Mark A. , Warren Patrick S. , Racadio John M. , Towbin Alexander J. , Vaughan Michele R. , Triplet Melinda , Ott-Napier Kristy , Dishman Devon J. , Backus Lori R. , Stockman Beth , Brunner Marianne , Simpson Kathleen , Spavin Robert , Conner Joe , Cripe Timothy P.
Published: May 2017

Purpose: HSV1716 is an oncolytic herpes simplex virus-1 (HSV-1) studied in adults via injection into the brain and superficial tumors. To determine the safety of administering HSV1716 to pediatric patients with cancer, we conducted a phase I trial of image-guided injection in young patients with relapsed or refractory extracranial cancers.

Experimental Design: We delivered a single dose of 105 to 107 infectious units of HSV1716 via computed tomography–guided intratumoral injection and measured tumor responses by imaging. Patients were eligible for up to three more doses if they achieved stable disease. We monitored HSV-1 serum titers and shedding by PCR and culture.

Results: We administered a single dose of HSV1716 to eight patients and two doses to one patient. We did not observe any dose-limiting toxicities. Adverse events attributed to virus included low-grade fever, chills, and mild cytopenias. Six of eight HSV-1 seronegative patients at baseline showed seroconversion on day 28. Six of nine patients had detectable HSV-1 genomes by PCR in peripheral blood appearing on day +4 consistent with de novo virus replication. Two patients had transient focal increases in metabolic activity on 18fluorine-deoxyglucose PET, consistent with inflammatory reactions. In one case, the same geographic region that flared later appeared necrotic on imaging. No patient had an objective response to HSV1716.

Conclusions: Intratumoral HSV1716 is safe and well-tolerated without shedding in children and young adults with late-stage, aggressive cancer. Viremia consistent with virus replication and transient inflammatory reactions hold promise for future HSV1716 studies. Clin Cancer Res; 23(14); 3566–74. ©2017 AACR.
A Mechanism Study Underlying the Protective Effects of Cyclosporine-A on Lung Ischemia-Reperfusion Injury
Authors: Li Jian''an , Yan Zhongya , Fang Qianjin
Published: May 2017

Aim: This study is aimed at validating the hypothesis that administration of cyclosporine-A (CsA) would be protective in lung ischemia-reperfusion (I/R) injury and in exploring the underlying mechanism. Methods: Rabbits were divided into 4 groups: the control, sham operation, I/R, and I/R with CsA treatment. Flow cytometry was used to measure the mitochondrial membrane potential. Laser scanning confocal microscope was used to analyze mitochondrion permeability transition pore (MPTP). The apoptotic cell was detected by the TUNEL staining. Western blot was performed to analyze the protein expression levels. Results: CsA not only attenuated the histopathologic alterations in lung and mitochondria after I/R injury, but also attenuated I/R injury through increasing MPP and inhibiting MPTP opening. Besides, CsA attenuated I/R injury through suppressing the release of cytochrome-c (CytC), inhibiting cell apoptosis and decreasing the expression levels of cyclophilin-D (Cyp-D), adenine nucleotide translocase 1 (ANT1) and voltage-dependent anion channel 1 (VDAC1). Finally, we found that Cyp-D knockdown inhibits I/R injury-induced MPTP opening and cell apoptosis. Conclusion: Our study found that the protective role of CsA on lung I/R injury depends on the inhibition of MPTP and CytC release, suppression of the activation of mitochondrial apoptosis pathway and the expressions of apoptotic-related proteins, as well as the decreased expression levels of ANT1 and VDAC1.
Molecular Insights into Covalently Stained Carious Dentine Using Solid-State NMR and ToF-SIMS
Authors: Almhöjd Ulrica S. , Lingström Peter , Nilsson Åke , Norén Jörgen G. , Siljeström Sandra , Östlund Åsa , Bernin Diana
Published: May 2017

Dyes currently used to stain carious dentine have a limited capacity to discriminate normal dentine from carious dentine, which may result in overexcavation. Consequently, finding a selective dye is still a challenge. However, there is evidence that hydrazine-based dyes, via covalent bonds to functional groups, bind specifically to carious dentine. The aim of this study was to investigate the possible formation of covalent bonds between carious dentine and 15N2-hydrazine and the hydrazine-based dye, 15N2-labelled Lucifer Yellow, respectively. Powdered dentine from extracted carious and normal teeth was exposed to the dyes, and the staining reactions were analysed using time-of-flight secondary ion mass spectrometry (ToF-SIMS), solid-state 13C-labelled nuclear magnetic resonance (NMR) and 15N-NMR spectroscopy. The results showed that 15N2-hydrazine and 15N2-labelled Lucifer Yellow both bind to carious dentine but not to normal dentine. It can thus be concluded that hydrazine-based dyes can be used to stain carious dentine and leave normal dentine unstained.
Clinical Factors Associated with Readmission among Patients with Lower Limb Cellulitis
Authors: Garg Amit , Lavian Jonathan , Lin Gloria , Sison Cristina , Oppenheim Michael , Koo Bonnie
Published: May 2017

Background: There is substantial allocation of resources directed towards evaluation and management of lower limb cellulitis (LLC) in the acute care setting. Readmission for LLC is poorly understood, and there is little evidence with which to identify patients at risk for readmission. Objective: To describe demographics, comorbidities, admission vital signs, and laboratory markers of infection among patients with LLC who are readmitted, and to investigate which among these factors is associated with readmission. Methods: A cross-sectional retrospective cohort study was performed at tertiary and community hospitals within a regional health care system in order to summarize readmission characteristics. Univariate and multivariate models were created to estimate the likelihood of independent variables being associated with LLC readmission. Results: The readmission rate was 11.2% with a median age of 68.6 years for the cohort. Increased age and subsidized insurance were associated with more frequent admissions. For every 10-year age increase, cellulitis subjects had a 14% increase in readmission odds (OR 1.14, CI 1.07-1.20). Patients with subsidized insurance had an almost twofold increased risk (OR 1.88, CI 1.42-2.50). Smoking, obesity, hypertension, diabetes mellitus, renal insufficiency, tachycardia, hypotension, leukocytosis, and neutrophilia were not more frequent in readmitted patients. Conclusions: Older age and subsidized insurance were associated with readmission whereas severity indicators for infection including abnormal vital signs and laboratory markers were not significantly associated. Factors other than severity of infection, such as socioeconomic factors, may influence clinical decisions related to readmission for LLC.
Intramuscular versus Vaginal Progesterone Administration in Medicated Frozen Embryo Transfer Cycles: A Randomized Clinical Trial Assessing Sub-Endometrial Contractions
Authors: Hershko Klement Anat , Samara Nivin , Weintraub Amir , Mitri Frederic , Bentov Yaakov , Chang Paul , Nayot Dan , Casper Robert F.
Published: May 2017

Objective: The study aimed to assess whether sub-endometrial contractility is reduced by the use of intramuscular (IM) progesterone. Design: This is a randomized clinical trial. Patients assigned to a medicated day 5 frozen embryo transfer (FET) were randomly allocated to “vaginal progesterone” or “IM progesterone”: patients randomized to the vaginal arm were treated with 200 mg micronized progesterone 3 times daily while patients randomized into the IM progesterone arm were treated with a single daily injection of 50 mg progesterone in oil. The main outcome measure was the number of sub-endometrial contractions (waves) per minute 1 day before a blastocyst embryo transfer. Results: Thirty-four patients were enrolled. The progesterone serum concentration was significantly higher in patients using the IM progesterone (85.2 ± 50.1 vs. 30.3 ± 11.2 nmol/L, respectively) but this did not translate into a lower sub-endometrial contractility (2.4 ± 4.8 vs. 1.4 ± 1.1 contraction/min, respectively). Clinical pregnancy rates were comparable between groups. The number of sub-endometrial waves was significantly lower among pregnant patients (p = 0.02). Conclusions: The use of IM progesterone in medicated FET cycles does not reduce the sub-endometrial activity compared to vaginal progesterone administration. Our data support a poor clinical pregnancy outcome with high wave activity, regardless of the progesterone mode.
Pre-End-Stage Renal Disease Care and Early Survival among Incident Dialysis Patients in the US Military Health System
Authors: Nee Robert , Fisher Evan , Yuan Christina M. , Agodoa Lawrence Y. , Abbott Kevin C.
Published: May 2017

Background: Previous reports showed an increased early mortality after chronic dialysis initiation among the end-stage renal disease (ESRD) population. We hypothesized that ESRD patients in the Military Health System (MHS) would have greater access to pre-ESRD care and hence better survival rates during this early high-risk period. Methods: In this retrospective cohort study, using the US Renal Data System database, we identified 1,256,640 patients initiated on chronic dialysis from January 2, 2004 through December 31, 2014, from which a bootstrap sample of 3,984 non-MHS incident dialysis patients were compared with 996 MHS patients. We assessed care by a nephrologist and dietitian, erythropoietin administration, and vascular access use at dialysis initiation as well as all-cause mortality as outcome variables. Results: MHS patients were significantly more likely to have had pre-ESRD nephrology care (adjusted OR [aOR] 2.9; 95% CI 2.3-3.7) and arteriovenous fistula used at dialysis initiation (aOR 2.2; 95% CI 1.7-2.7). Crude mortality rates peaked between the 4th and the 8th week for both cohorts but were reduced among MHS patients. The baseline adjusted Cox model showed significantly lower death rates among MHS vs. non-MHS patients at 6, 9, and 12 months. This survival advantage among MHS patients was attenuated after further adjustment for pre-ESRD nephrology care and dialysis vascular access. Conclusions: MHS patients had improved survival within the first 12 months compared to the general ESRD population, which may be explained in part by differences in pre-ESRD nephrology care and vascular access types.
Is Regular Screening for Intracranial Aneurysm Necessary in Patients with Autosomal Dominant Polycystic Kidney Disease? A Systematic Review and Meta-analysis
Authors: Zhou Zien , Xu Ying , Delcourt Candice , Shan Jiehui , Li Qiang , Xu Jianrong , Hackett Maree L.
Published: May 2017

Background: The prevalence of intracranial aneurysm in patients with autosomal dominant polycystic kidney disease (ADPKD) is higher than that among the general population. We performed a systematic review and meta-analysis on the prevalence and natural history of intracranial aneurysm among patients with ADPKD. Methods: Medline, Embase, Web of Science and Scopus, from inception to July 2016, were searched for studies reporting the occurrence of intracranial aneurysms among participants with ADPKD. Two authors independently assessed the eligibility of all retrieved studies and extracted data. Information on the prevalence of intracranial aneurysms and their natural history in participants with ADPKD was collected from all included studies. Results: Fifteen studies with 1,490 participants with ADPKD were pooled to study about the prevalence of intracranial aneurysm in participants with ADPKD, and the prevalence rate was found to be 10% (95% CI 7-13%). Studies from China, Japan and Europe (Germany, Poland) reported a higher prevalence of intracranial aneurysm. Having a family history of haemorrhagic stroke or intracranial aneurysm was a risk factor for aneurysm occurrence. Twenty-three percent (95% CI 15-31%) of the participants had multiple aneurysms. Most of the aneurysms were small (<6 mm) and located in the anterior circulation. Five studies with 171 participants (83 with 106 aneurysms at baseline and 88 without) were analyzed to understand the natural history of aneurysms, with an incidence of aneurysm growth, new aneurysm and aneurysm rupture of 1.84% (followed up for 435 person-years), 0.57% (1,227 person-years) and 0.13% (792 person-years) respectively. Conclusions: Screening for intracranial aneurysm is recommended in patients with ADPKD when there is a family history of haemorrhagic stroke or intracranial aneurysm and when they are from China, Japan or Europe (Germany, Poland). Based on existing data, regular imaging follow-up is not supported. High-quality, prospective studies are needed in the future.
Capela Santa Maria dos Anjos: uma obra alternativa
Authors: Carranza Edite Galote
Published: May 2017

Celebrando cem anos de nascimento da arquiteta Lina Bo Bardi, seu trabalho continua incitando a curiosidade de pesquisadores, artistas e arquitetos de todo o mundo, devido tanto à qualidade, à subjetividade artística, às ideias, aos ideais e à filosofia de fundo como à amplitude da obra nas áreas de cenografia, design, crítica, museologia e arquitetura. Entre suas obras arquitetônicas, a Capela Santa Maria dos Anjos, de 1978, em Vargem Grande Paulista, SP, merece maior atenção. Embora possa ser considerada singela, a Capela é uma obra densa e representativa da Arquitetura Alternativa ao status quo arquitetônico paulista. Este artigo analisa a Capela e sua relação com os conceitos de nacional-popular e Te-Ato, a fé franciscana e as culturas erudita e popular, a fim de contribuir para o melhor entendimento da obra que dialoga com a cena cultural e política da época.
Percutaneous Coronary Intervention of Saphenous Vein Graft
Authors: Redfors Björn , Généreux Philippe , Witzenbichler Bernhard , McAndrew Thomas , Diamond Jamie , Huang Xin , Maehara Akiko , Weisz Giora , Mehran Roxana , Kirtane Ajay J. , Stone Gregg W.
Published: May 2017

Background—

Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVGs) has historically been associated with a high risk of adverse ischemic events, but there is a paucity of contemporary data on the second-generation drug-eluting stent use within SVG, and the relative importance of high platelet reactivity (HPR) in SVG PCI versus native lesion PCI is unknown. We studied ischemic and bleeding events after SVG PCI and their association with HPR.

Methods and Results—

Subjects in the prospective, multicenter ADAPT-DES study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) were stratified according to whether they had PCI of an SVG or a non-SVG lesion. Two-year outcomes were compared between groups using univariate and multivariable Cox proportional hazards models. HPR was defined as on-clopidogrel P2Y12 platelet reaction units >208 as measured by the VerifyNow assay; major adverse cardiac events were defined as the composite of cardiac death, myocardial infarction, or stent thrombosis. Among 8582 subjects in ADAPT-DES, 405 (4.7%) had SVG PCI. SVG PCI was independently associated with a higher 2-year risk of major adverse cardiac events (adjusted hazard ratio, 2.34; 95% confidence interval, 1.69–3.23;
P
<0.0001), ischemia-driven target vessel revascularization (adjusted hazard ratio, 1.82; 95% confidence interval, 1.37–2.42;
P
<0.0001), and stent thrombosis (adjusted hazard ratio, 2.26; 95% confidence interval, 1.42–3.59;
P
=0.0006), but not of bleeding (adjusted hazard ratio, 0.99; 95% confidence interval, 0.68–1.46;
P
=0.97). There was no statistical interaction between HPR and SVG PCI in regard to major adverse cardiac events (adjusted
P
interaction
=0.99).

Conclusions—

SVG PCI is associated with a considerably higher risk of 2-year adverse ischemic events, with HPR conferring similar risk in SVG and non-SVG PCI. More potent and longer antiplatelet therapy may be beneficial for patients undergoing SVG PCI.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00638794.
Geographical Difference of the Interaction of Sex With Treatment Strategy in Patients With Multivessel Disease and Left Main Disease
Authors: Sotomi Yohei , Onuma Yoshinobu , Cavalcante Rafael , Ahn Jung-Min , Lee Cheol Whan , van Klaveren David , de Winter Robbert J. , Wykrzykowska Joanna J. , Farooq Vasim , Morice Marie-Claude , Steyerberg Ewout W. , Park Seung-Jung , Serruys Patrick W.
Published: May 2017

Background—

The impact of sex on clinical outcomes of percutaneous coronary intervention and coronary artery bypass graft for patients with multivessel coronary disease and unprotected left main disease could be dissimilar between Western and Asian populations.

Methods and Results—

To assess clinical outcomes after percutaneous coronary intervention or coronary artery bypass graft in women and men with multivessel coronary disease and unprotected left main disease, a pooled analysis (n=3280) was performed using the patient-level data from 3 large randomized trials: SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery), PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and BEST (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) trials. The primary end point was all-cause death. Of 3280 patients, 794 patients (24.2%) were women. The median follow-up period was 1806 days (1611–1837 days). In women, a high heterogeneity of the treatment effect among the 3 trials was found for all-cause death (
I
2
>50%), whereas in men, it was consistent across the 3 trials. In the Western trial (SYNTAX), female sex favored coronary artery bypass graft compared with percutaneous coronary intervention (hazard ratio
(percutaneous coronary intervention)
2.213; 95% confidence interval, 1.242–3.943;
P
=0.007), whereas in the Asian women (PRECOMBAT and BEST), the treatment effect was neutral between both strategies. Sex interaction with treatment strategy was evident in the Western trial (
P
interaction
=0.019) but not in the Asian trials (PRECOMBAT
P
interaction
=0.469 and BEST
P
interaction
=0.472;
I
2
=58%).

Conclusions—

The present meta-analysis suggested the presence of the heterogeneous sex–treatment interaction across Asian and Western trials. Considering the ongoing globalization of our medical practice, the heterogeneity of the sex–treatment interaction needs to be well recognized and taken into account during the decision making of the treatment strategy.

Clinical Trial Registrations—

URL:
https://www.clinicaltrials.gov
. Unique identifiers: NCT00114972, NCT00997828, NCT00422968.
American College of Cardiology/American Heart Association (ACC/AHA) Class I Guidelines for the Treatment of Cholesterol to Reduce Atherosclerotic Cardiovascular Risk: Implications for US Hispanics/Latinos Based on Findings From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Qureshi Waqas T. , Kaplan Robert C. , Swett Katrina , Burke Gregory , Daviglus Martha , Jung Molly , Talavera Gregory A. , Chirinos Diana A. , Reina Samantha A. , Davis Sonia , Rodriguez Carlos J.
Published: May 2017

Background

The prevalence estimates of statin eligibility among Hispanic/Latinos living in the United States under the new 2013 American College of Cardiology/American Heart Association (
ACC
/
AHA
) cholesterol treatment guidelines are not known.

Methods and Results

We estimated prevalence of statin eligibility under 2013
ACC
/
AHA
and 3rd National Cholesterol Education Program Adult Treatment Panel (
NCEP
/
ATP III
) guidelines among Hispanic Community Health Study/Study of Latinos (n=16 415; mean age 41 years, 40% males) by using sampling weights calibrated to the 2010 US census. We examined the characteristics of Hispanic/Latinos treated and not treated with statins under both guidelines. We also redetermined the statin‐therapy eligibility by using black risk estimates for Dominicans, Cubans, Puerto Ricans, and Central Americans. Compared with
NCEP
/
ATP III
guidelines, statin eligibility increased from 15.9% (95%
CI
15.0–16.7%) to 26.9% (95%
CI
25.7–28.0%) under the 2013
ACC
/
AHA
guidelines. This was mainly driven by the ≥7.5% atherosclerotic cardiovascular disease risk criteria (prevalence 13.9% [95%
CI
13.0–14.7%]). Of the participants eligible for statin eligibility under
NCEP
/
ATP III
and
ACC
/
AHA
guidelines, only 28.2% (95%
CI
26.3–30.0%) and 20.6% (95%
CI
19.4–21.9%) were taking statins, respectively. Statin‐eligible participants who were not taking statins had a higher prevalence of cardiovascular risk factors compared with statin‐eligible participants who were taking statins. There was no significant increase in statin eligibility when atherosclerotic cardiovascular disease risk was calculated by using black estimates instead of recommended white estimates (increase by 1.4%,
P
=0.12) for Hispanic/Latinos.

Conclusions

The eligibility of statin therapy increased consistently across all Hispanic/Latinos subgroups under the 2013
ACC
/
AHA
guidelines and therefore will potentially increase the number of undertreated Hispanic/Latinos in the United States.
Genetic Drivers of von Willebrand Factor Levels in an Ischemic Stroke Population and Association With Risk for Recurrent Stroke
Authors: Williams Stephen R. , Hsu Fang-Chi , Keene Keith L. , Chen Wei-Min , Dzhivhuho Godfrey , Rowles Joe L. , Southerland Andrew M. , Furie Karen L. , Rich Stephen S. , Worrall Bradford B. , Sale Michèle M.
Published: May 2017

Background and Purpose—

von Willebrand factor (vWF) plays an important role in thrombus formation during cerebrovascular damage. We sought to investigate the potential role of circulating vWF in recurrent cerebrovascular events and identify genetic contributors to variation in vWF level in an ischemic stroke population.

Methods—

We analyzed the effect of circulating vWF on risk of recurrent stroke using survival models in the VISP trial (Vitamin Intervention for Stroke Prevention) and the use of vWF in reclassification over traditional factors. We conducted a genome-wide association study) with imputation, based on 1000 Genomes Project data, for circulating vWF levels and then interrogated loci previously associated with vWF levels. We performed expression quantitative trait locus analysis for vWF across different tissues.

Results—

Elevated vWF levels were associated with increased risk for recurrent stroke in VISP. Adding vWF to traditional clinical parameters also improved recurrent stroke risk prediction. We identified single-nucleotide polymorphisms significantly associated with circulating vWF at the
ABO
locus (
P
<5×10
−8
) and replicated findings from previous genetic associations of vWF levels in humans. Expression quantitative trait locus analyses demonstrate that most associated
ABO
single-nucleotide polymorphisms were also associated with
vWF
gene expression.

Conclusions—

Elevated vWF levels are associated with recurrent stroke in VISP. In the VISP population, genetic determinants of vWF levels that impact
vWF
gene expression were identified. These data add to our knowledge of the pathophysiologic and genetic basis for recurrent stroke risk and may have implications for clinical care decision making.
Pseudogapping as Pseudo-VP-Ellipsis
Authors: Kubota Yusuke , Levine Robert
Published: May 2017

In this article, we propose an analysis of pseudogapping in Hybrid Type-Logical Categorial Grammar (Hybrid TLCG; Kubota 2010 ; Kubota and Levine 2012 ). Pseudogapping poses a particularly challenging problem for previous analyses in both the transformational and the nontransformational literature. We argue that the flexible syntax-semantics interface of Hybrid TLCG enables an analysis of pseudogapping that synthesizes the key insights of both transformational and nontransformational approaches, at the same time overcoming the major difficulties of each type of approach.