Manual code maintenance of large code bases is tedious, time-consuming, and error-prone. To enable the engineering of source code maintenance tools for Ada, a mature infrastructure that provides capabilities for parsing, unparsing, semantic analysis, and transformations is needed. This work discusses our progress of adding Ada support to ROSE, a mature source-to-source translation infrastructure. The paper discusses the design of ROSE, the extensions required for adding Ada, difficulties we encountered with processing existing code bases, and several prototype analysis and translation tools enabled by the new Ada support in ROSE.

The aim of this study is to assess the additional benefit of contrast-enhanced ultrasound (CEUS) over conventional ultrasonography (US) in identifying intra-testicular abnormalities among observers of different experiences. In this study, 91 focal testicular lesions (46 neoplastic, 45 non-neoplastic) imaged with gray-scale US/Doppler US and CEUS were classified using a 5-point scale. Three experienced and four inexperienced observers rated each lesion using gray-scale/color Doppler US alone and then with the addition of CEUS. Improved diagnostic specificity and accuracy with the addition of CEUS was observed for both experienced (specificity: 71.1% vs. 59.3%, p = 0.005; accuracy: 83.5% vs. 76.9%, p = 0.003) and inexperienced observers (specificity: 75.6% vs. 51.7%, p = 0.005; accuracy: 80.2% vs. 72.0%, p < 0.001). Significant inter-observer variability between the experienced and inexperienced observers when assessing conventional US alone was eliminated with the addition of CEUS. CEUS improves diagnostic accuracy of focal intra-testicular lesions for both experienced and inexperienced observers and reduces inter-observer variability in inexperienced operators.

The aim of this study was to prospectively evaluate the diagnostic performance of strain elastography for the assessment of liver fibrosis in patients with chronic liver disease using Ishak (0-6) histology stage as a reference standard. Ninety-eight consecutive patients with suspected chronic liver disease scheduled for liver biopsy (n = 78) or histologically confirmed cirrhosis (n = 20) were enrolled. Liver fibrosis Index (LF Index) calculated by strain elastography, liver stiffness by transient elastography and serum fibrosis markers (aspartate aminotransferase-to-platelet ratio index and King's Score) were measured. Spearman's correlation coefficient between the LF Index, liver stiffness, serum fibrosis markers and fibrosis stage were calculated and compared using areas under the receiver-operating characteristics (AUROCs) curves. Among 73 patients who underwent strain elastography, there was weak correlation between fibrosis stage and the LF Index (Spearman's: rho = 0.385 for Ishak score; P = 0.001). Among 52 patients who underwent strain elastography and transient elastography, the AUROC values using LF Index, transient elastography, aspartate aminotransferase-to-platelet ratio index and King's Score for diagnosing significant fibrosis (Ishak score >= 3) were 0.79, 0.87, 0.86 and 0.85, respectively (P < 0.0001) and for diagnosing severe fibrosis/cirrhosis (Ishak score >= 5) were 0.83, 0.94, 0.92 and 0.92, respectively (P < 0.0001). When comparing the diagnostic performance using LF Index, transient elastography, aspartate aminotransferase-to-platelet ratio index and King's Score, transient elastography shows a significantly higher AUROC value than LF Index in detecting severe fibrosis (P = 0.0149). The diagnostic performance of LF Index calculated by strain elastography was not statistically significantly different to the other noninvasive tests for the assessment of significant liver fibrosis but inferior to transient elastography for the assessment of severe fibrosis/cirrhosis.

Purpose To identify the minimum number of measurements required for the noninvasive assessment of liver fibrosis by using point shear-wave elastography (pSWE) and determine whether the use of a reliability indicator such as interquartile range [IQR]-to-median ratio will affect diagnostic performance. Materials and Methods Ten liver shear-wave velocity (SWV) measurements by pSWE were obtained in 232 participants. Interclass correlation coefficients (ICC) between the median of the first two through the first nine measurements and all 10 measurements were calculated; the minimum number of measurements with ICC greater than 0.95 versus all 10 measurements was determined. The diagnostic performance of the minimum number of measurements and 10 measurements in identifying significant (Ishak stage, ≥3) and severe fibrosis or cirrhosis (Ishak stage, ≥5) was compared by using areas under the receiver operating characteristic curve. These were compared between measurements that demonstrated higher or lower reliability (IQR-to-median ratio of ≤ 30% and IQR-to-median ratio of > 30%, respectively). Results Compared with 10 measurements, a minimum of six SWV measurements was required. The overall area under the curve for diagnosing significant (areas under the receiver operating characteristic curve, 0.828 vs 0.839; P = .487) and severe fibrosis or cirrhosis (0.953 vs 0.969, respectively; P = .145) did not differ according to number of measurements (six vs 10); a median of six measurements resulted in only limited disagreement (nine of 232 [3.9%]) versus histologic evaluation. When using 10 measurements, higher reliability measurements showed a lower percentage of discordance between pSWE and significant fibrosis and severe fibrosis or cirrhosis (22 [14.7%] and three [2.0%] of 150 cases, respectively) compared with lower reliability measurements (26 [31.7%] and eight [9.8%] of 82 cases, respectively). Significant fibrosis was an independent predictor for lower reliability (hazard ratio, 2.22; P < .020). Conclusion A limited number of SWV measurements (median six vs median 10) were required for the assessment of liver fibrosis by using pSWE. The number of measurements had less influence on the diagnostic accuracy compared with lower reliability measurements. © RSNA, 2018 Online supplemental material is available for this article.

Objectives-Two-dimensional shear wave elastography (2D-SWE) imaging for the noninvasive assessment of tissue stiffness was assessed for reproducibility in healthy volunteers in quantifying liver elasticity, compared with an established point shear wave elastography (p-SWE) technique also known as virtual touch quantification (VTQ) (SIEMENS).Methods-Eleven healthy volunteers were examined by four experienced operators on two occasions, separated by two weeks (sessions A and B). Ten 2D-SWE using LOGIQ E9 and p-SWE measurements using VTQ (in meters per second) were consecutively taken from deep portions of liver segments 5 or 6 away from vascular structures, using standard techniques. Inter-and intra-observer agreement was assessed by intraclass coefficient (ICC).Results-A total of 880 2D-SWE and p-SWE velocities were recorded. Mean values from the four operators ranged between 1.188 and 1.196 m/s for 2D-SWE and 1.170 to 1.207 m/s for p-SWE. Interobserver reproducibility was good for both sessions with ICCs of 0.88 and 0.93 (2D-SWE) and 0.87 and 0.93 (p-SWE). The overall intra-operator reproducibility between sessions A and B was good for both pSWE and 2D-SWE with ICC of 0.87 and 0.83, respectively. For inter-and intraobserver variability, the ICC was more than or equal to 0.71, indicating that the results were reliable. There was a strong and significant correlation between the 2D-SWE and p-SWE measurements (r = 0.87, P = .0006), but their velocities did not agree equally across different velocities.Conclusions-Two-dimensional SWE using LOGIQ E9 is a reliable and reproducible method for measuring elasticity in healthy volunteers and has a similar degree of reliability as p-SWE using VTQ, but absolute measurements from the two techniques should not be used interchangeably.

IMPORTANCE The non-vitamin K antagonist oral anticoagulants (NOACs) apixaban, dabigatran, edoxaban, and rivaroxaban are administered in fixed doses without anticoagulant monitoring. Randomized trials show that unmonitored NOAC therapy is at least as effective as and safer than dose-adjusted warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. Subgroup analyses indicate that plasma drug levels or anticoagulant activity of the NOACs predict stroke and bleeding. This review examines the historical basis for anticoagulant monitoring, discusses methods to measure and interpret drug levels, and critically assesses the role of routine laboratory monitoring in the management of NOAC therapy. OBSERVATIONS The predictable anticoagulant response of NOACs has provided the pharmacological basis for their administration in fixed doses without routine coagulation monitoring. Although it is possible to accurately measure NOAC drug levels, within-patient variability complicates interpretation of these results. Furthermore, patient characteristics, such as age and renal function, confound the association between NOAC drug levels and clinical outcomes. Information is lacking on the optimal drug level in particular patient groups (eg, elderly, the renally impaired, and those with high bleeding risk), the appropriate dose adjustment to achieve expected levels, and whether routine laboratory monitoring and dose adjustment will improve clinical outcomes. A benefit of a management strategy that incorporates routine therapeutic drug monitoring and dose adjustment over current standard-of-care metrics without such monitoring remains unproven. CONCLUSIONS AND RELEVANCE Robust evidence from patients with atrial fibrillation randomized to NOACs or warfarin demonstrates that unmonitored NOAC therapy is at least as effective and safe as monitored warfarin, with lower rates of intracranial hemorrhage and reduced mortality. Further research is required to determine whether routine laboratory monitoring might provide a net benefit for patients. Until such data are available, clinicians should continue to prescribe NOACs in fixed doses without routine monitoring.

Importance The non–vitamin K antagonist oral anticoagulants (NOACs) apixaban, dabigatran, edoxaban, and rivaroxaban are administered in fixed doses without anticoagulant monitoring. Randomized trials show that unmonitored NOAC therapy is at least as effective as and safer than dose-adjusted warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. Subgroup analyses indicate that plasma drug levels or anticoagulant activity of the NOACs predict stroke and bleeding. This review examines the historical basis for anticoagulant monitoring, discusses methods to measure and interpret drug levels, and critically assesses the role of routine laboratory monitoring in the management of NOAC therapy. Observations The predictable anticoagulant response of NOACs has provided the pharmacological basis for their administration in fixed doses without routine coagulation monitoring. Although it is possible to accurately measure NOAC drug levels, within-patient variability complicates interpretation of these results. Furthermore, patient characteristics, such as age and renal function, confound the association between NOAC drug levels and clinical outcomes. Information is lacking on the optimal drug level in particular patient groups (eg, elderly, the renally impaired, and those with high bleeding risk), the appropriate dose adjustment to achieve expected levels, and whether routine laboratory monitoring and dose adjustment will improve clinical outcomes. A benefit of a management strategy that incorporates routine therapeutic drug monitoring and dose adjustment over current standard-of-care metrics without such monitoring remains unproven. Conclusions and Relevance Robust evidence from patients with atrial fibrillation randomized to NOACs or warfarin demonstrates that unmonitored NOAC therapy is at least as effective and safe as monitored warfarin, with lower rates of intracranial hemorrhage and reduced mortality. Further research is required to determine whether routine laboratory monitoring might provide a net benefit for patients. Until such data are available, clinicians should continue to prescribe NOACs in fixed doses without routine monitoring.

Optimizing applications for the next generation of super-computers requires next generation compilers. These compilers need to provide an abstraction for the developer to describe the inner working of applications. And, next generation compilers need to be able to intelligently apply optimizations to a wide variety of algorithms solved by scientific applications. They need to optimize applications for any workload targeting any architecture. In this paper, we present an important component of any next generation supercomputer compiler that we call TileK. TileK is a tile abstraction used to generate distributed kernels from nested loops. It provides a high-level abstraction used to decompose the iteration space of loop nests. Its directives-based language enables an effective and efficient placement of multi-dimensional computations on the 3D topology of accelerators (e.g. graphics processing units, GPUs). We implemented both the tile abstraction and the kernel generator in ROSE Compiler. We used TileK to parallelize linear algebra kernels and stencils, targeting multicore CPUs (pThread) and GPUs (OpenCL). TileK enabled us to explore and evaluate a large optimization space of many versions of these kernels for varying input sizes. Our results shows that the selection of a given optimization for a specific input size is a challenging problem.

This paper presents a system for automatically supporting the optimization of stencil kernels on emerging Non-Uniform Memory Access (NUMA) many-core architectures, through a combined compiler + runtime approach. In particular, we use a pragma-driven compiler to recognize the special structures and optimization needs of stencil computations and thereby to automatically generate low-level code that efficiently utilize the data placement and management support of a C++ runtime on top of NUMA API, a programming interface to the NUMA policy supported by the Linux kernel. Our results show that through automated specialization of code generation, this approach provides a combined benefit of performance, portability, and productivity for developers.

The most widely used resiliency approach today, based on Checkpoint and Restart (C/R) recovery, is not expected to remain viable in the presence of the accelerated fault and error rates in future Exascale-class systems. In this paper, we introduce a series of pragma directives and the corresponding source-to-source transformations that are designed to convey to a compiler, and ultimately a fault-aware run-time system, key information about the tolerance to memory errors in selected sections of an application. These directives, implemented in the ROSE compiler infrastructure, convey information about storage mapping and error tolerance but also amelioration and recovery using externally provided functions and multi-threading. We present preliminary results of the use of a subset of these directives for a simple implementation of the conjugate-gradient numerical solver in the presence of uncorrected memory errors, showing that it is possible to implement simple recovery strategies with very low programmer effort and execution time overhead.

Article, see p 648 Pharmacological thromboprophylaxis given for up to 14 days reduces the risk of venous thromboembolism in hospitalized medical patients.1 Because the risk of thromboembolism remains elevated for at least several weeks after an acute medical illness, randomized trials have evaluated the role of extending prophylaxis for up to 1 month. Their results indicate that extended thromboprophylaxis with enoxaparin, apixaban, or rivaroxaban reduces the risk of venous thromboembolism but results in more bleeding and does not produce a net benefit.2–4 Based on these data, current guidelines do not recommend extending thromboprophylaxis beyond the period of patient immobilization or acute hospital stay.5APEX (Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban) is the latest trial6 to evaluate extended thromboprophylaxis in acutely ill medical patients. In total, 7513 patients (mean age, 76 years) who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (20 or 40 mg once daily) for 6 to 14 days or the nonvitamin K antagonist oral anticoagulant (NOAC), betrixaban (40 or 80 mg once daily), for 35 to 42 days6: 11% of patients were hospitalized with an acute ischemic stroke and 45% with acute heart failure,6 a known risk factor for stroke7; …

HomeCirculationVol. 135, No. 7Is There a Role for Betrixaban to Prevent Stroke in Medically Ill Patients? Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBIs There a Role for Betrixaban to Prevent Stroke in Medically Ill Patients? Daniel J. Quinlan, MBBS, John W. Eikelboom, MBBS and Robert G. Hart, MD Daniel J. QuinlanDaniel J. Quinlan From Department of Radiology, Kings College Hospital, London, United Kingdom (D.J.Q.); and Population Health Research Institute, Hamilton Health Sciences and Department of Medicine, McMaster University, Ontario, Canada (J.W.E., R.G.H.). Search for more papers by this author , John W. EikelboomJohn W. Eikelboom From Department of Radiology, Kings College Hospital, London, United Kingdom (D.J.Q.); and Population Health Research Institute, Hamilton Health Sciences and Department of Medicine, McMaster University, Ontario, Canada (J.W.E., R.G.H.). Search for more papers by this author and Robert G. HartRobert G. Hart From Department of Radiology, Kings College Hospital, London, United Kingdom (D.J.Q.); and Population Health Research Institute, Hamilton Health Sciences and Department of Medicine, McMaster University, Ontario, Canada (J.W.E., R.G.H.). Search for more papers by this author Originally published14 Feb 2017https://doi.org/10.1161/CIRCULATIONAHA.116.026170Circulation. 2017;135:656–658Article, see p 648Pharmacological thromboprophylaxis given for up to 14 days reduces the risk of venous thromboembolism in hospitalized medical patients.1 Because the risk of thromboembolism remains elevated for at least several weeks after an acute medical illness, randomized trials have evaluated the role of extending prophylaxis for up to 1 month. Their results indicate that extended thromboprophylaxis with enoxaparin, apixaban, or rivaroxaban reduces the risk of venous thromboembolism but results in more bleeding and does not produce a net benefit.2–4 Based on these data, current guidelines do not recommend extending thromboprophylaxis beyond the period of patient immobilization or acute hospital stay.5APEX (Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban) is the latest trial6 to evaluate extended thromboprophylaxis in acutely ill medical patients. In total, 7513 patients (mean age, 76 years) who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (20 or 40 mg once daily) for 6 to 14 days or the nonvitamin K antagonist oral anticoagulant (NOAC), betrixaban (40 or 80 mg once daily), for 35 to 42 days6: 11% of patients were hospitalized with an acute ischemic stroke and 45% with acute heart failure,6 a known risk factor for stroke7; 16.6% of patients had a history of atrial fibrillation; and 19.4% of betrixaban patients received the lower 40 mg dose largely because of concomitant administration of strong P-glycoprotein inhibitors. Compared with standard duration enoxaparin, extended prophylaxis with betrixaban resulted in a 1.7% absolute reduction in venous thromboembolic events without an increase in major bleeding.In this issue of Circulation, Gibson and colleagues8 report the results of a separate secondary analysis from APEX that explored the effect of extended betrixaban prophylaxis on the risk of first-ever or recurrent stroke among patients enrolled in the trial. Stoke outcomes for this post hoc analysis were accessed through 77 days of follow-up (last visit at ≤47 days of exposure plus 30 days after discontinuation to capture any rebound events after drug discontinuation) and were independently adjudicated by an expert committee blinded to treatment allocation. The results demonstrate that extended-duration betrixaban compared with enoxaparin reduced all-cause stroke (ischemic, hemorrhagic, or uncertain type) by almost one half (relative risk 0.56, 95% confidence interval 0.3–0.96, P=0.032), equivalent to an absolute risk reduction of 0.43% and a number of needed to treat of 232. The effect of betrixaban on stroke was explained by a reduction in ischemic stroke with no difference in hemorrhagic stroke. The reduction in ischemic stroke was confined to patients hospitalized with acute heart failure or noncardioembolic ischemic stroke (Table), and most of the benefit accrued after the first 10 days, corresponding to the time during which betrixaban was being compared with placebo. About one half of all patients enrolled in the APEX trial received some form of antiplatelet therapy, mostly aspirin. It is likely that most of the patients with prior stroke were receiving aspirin, but these data were not reported. Few additional events were observed in patients with a history of atrial fibrillation.Table. Ischemic Stroke Outcomes in APEX at 77 Days Follow-upParticipantsBetrixabanEnoxaparin/PlaceboRelative Risk (P Value)All participants, number of events1834 Rate at 77 days follow-up, %0.480.910.53 (0.026) Annualized rate, % per y2.64.6Those with congestive heart failure or ischemic stroke as index event, number of events1329 Rate at 77 days follow-up, %0.631.380.45 (0.014) Annualized rate, % per y3.06.5Other APEX participants, number of events55The results of this subanalysis of the APEX trial are important for at least 3 reasons. First, they demonstrate an unexpectedly high rate of new or recurrent ischemic stroke of 0.91% during the first 3 months (annualized rate of 4.6% per year) in hospitalized medical patients receiving standard enoxaparin prophylaxis, this rate being even higher among patients presenting with heart failure or ischemic stroke (1.38%, annualized rate of 6.5% per year). These rates are even higher than those seen in trials of patients with atrial fibrillation who received NOACs for stroke prevention (1.1%–2.1% per year).9Second, these data demonstrate for the first time that a NOAC reduces the risk of ischemic stroke in patients without known atrial fibrillation, most of whom were presumably treated with aspirin.Third, the effects of betrixaban on stroke are dose-dependent; all of the benefits were seen in those who received the 80 mg dose, whereas the 40 mg dose did not provide any advantages compared with enoxaparin or placebo.What are the implications for clinical practice? Although this report of the effect of extended betrixaban prophylaxis on stroke is encouraging, the results are based on a post hoc analysis and should be considered hypothesis-generating. Previous medical prophylaxis trials have not separately reported stroke outcomes,2–4 and none of the NOACs have as of yet been approved for prophylaxis in medical patients. The US Food and Drug Administration is considering an application for the licensing of betrixaban for extended-duration prophylaxis of venous thromboembolism in acutely ill medical patients.10Several studies currently underway may further clarify the role of NOACs for stroke prevention in patients without known atrial fibrillation. The MARINER trial (Rivaroxaban on the Venous Thromboembolic Risk in Posthospital Discharge Patients) is investigating the effect of extended-duration rivaroxaban in hospitalized medical patients,11 but it is unclear whether stroke is a prespecified secondary outcome. The COMMANDER HF trial (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure) is investigating rivaroxaban for stroke prevention in patients with a history of heart failure and underlying coronary heart disease.12 Other trials are investigating the efficacy and safety of dabigatran and rivaroxaban, respectively, for secondary stroke prevention in patients presenting with ischemic stroke in the absence of known atrial fibrillation or an indication for anticoagulation.13,14Anticoagulant therapy with warfarin has been previously evaluated in patients with heart failure or previous noncardioembolic stroke with disappointing results.15–17 The results presented by the APEX investigators highlight the urgent need for more effective secondary prevention therapies in these patients and provide the first evidence that a NOAC may reduce stroke in this population.DisclosuresDr Quinlan has served as a consultant and received honoraria from Bayer, Boehringer Ingelheim, and Sanofi. Dr Eikelboom has received honoraria and research support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Janssen, and Pfizer. Dr Hart receives research support and research stipends from Bayer Healthcare and Bristol-Myers Squibb.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Circulation is available at http://circ.ahajournals.org.Correspondence to: Daniel J. Quinlan, MBBS, Department of Radiology, King’s College Hospital, Denmark Hill, London, SE5 9RS, United Kingdom. E-mail [email protected]References1. Dentali F, Douketis JD, Gianni M, Lim W, Crowther MA.Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients.Ann Intern Med. 2007; 146:278–288.CrossrefMedlineGoogle Scholar2. Hull RD, Schellong SM, Tapson VF, Monreal M, Samama MM, Nicol P, Vicaut E, Turpie AG, Yusen RD; EXCLAIM (Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization) study. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial.Ann Intern Med. 2010; 153:8–18. doi: 10.7326/0003-4819-153-1-201007060-00004.CrossrefMedlineGoogle Scholar3. Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, Weitz JI; ADOPT Trial Investigators. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients.N Engl J Med. 2011; 365:2167–2177. doi: 10.1056/NEJMoa1110899.CrossrefMedlineGoogle Scholar4. Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients.N Engl J Med. 2013; 368:513–523. doi: 10.1056/NEJMoa1111096.CrossrefMedlineGoogle Scholar5. Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, Cook DJ, Balekian AA, Klein RC, Le H, Schulman S, Murad MH; American College of Chest Physicians. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence- based clinical practice guidelines.Chest. 2012; 141:e195S–e226S. doi: 10.1378/chest.11–2296.CrossrefMedlineGoogle Scholar6. Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM; APEX investigators. Extended thromboprophylaxis with betrixaban in acutely ill medical patients.N Engl J Med. 2016; 375:534–544. doi: 10.1056/NEJMoa1601747.CrossrefMedlineGoogle Scholar7. Ferreira JP, Girerd N, Alshalash S, Konstam MA, Zannad F.Antithrombotic therapy in heart failure patients with and without atrial fibrillation: update and future challenges.Eur Heart J. 2016; 37:2455–2464. doi: 10.1093/eurheartj/ehw213.CrossrefMedlineGoogle Scholar8. Gibson CM, Chi G, Halaby R, Korjian S, Daaboul Y, Jain P, Arbetter D, Goldhaber SZ, Hull R, Hernandez AF, Gold A, Bandman O, Harrington RA, Cohen AT; On Behalf of the APEX Investigators. Extended-duration betrixaban reduces the risk of stroke versus standard-dose enoxaparin among hospitalized medically ill patients: an APEX trial substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban).Circulation. 2017; 135:648–656. doi: 10.1161/CIRCULATIONAHA.116.025427.LinkGoogle Scholar9. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM.Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.Lancet. 2014; 383:955–962. doi: 10.1016/S0140-6736(13)62343-0.CrossrefMedlineGoogle Scholar10. Portola Pharmaceuticals. Portola Pharmaceuticals submits new drug application to U.S. FDA for betrixaban for extended duration prophylaxis of venous thromboembolism in acute medically ill patients.Press release, October 25, 2016. http://investors.portola.com/phoenix.zhtml?c=198136&p=irol-newsArticle&ID=2215503. Accessed November 7, 2016.Google Scholar11. Raskob GE, Spyropoulos AC, Zrubek J, Ageno W, Albers G, Elliott CG, Halperin J, Haskell L, Hiatt WR, Maynard GA, Peters G, Spiro T, Steg PG, Suh EY, Weitz JI.The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE. Design, rationale, and clinical implications.Thromb Haemost. 2016; 115:1240–1248. doi: 10.1160/TH15-09-0756.CrossrefMedlineGoogle Scholar12. Zannad F, Greenberg B, Cleland JG, Gheorghiade M, van Veldhuisen DJ, Mehra MR, Anker SD, Byra WM, Fu M, Mills RM.Rationale and design of a randomized, double-blind, event-driven, multicentre study comparing the efficacy and safety of oral rivaroxaban with placebo for reducing the risk of death, myocardial infarction or stroke in subjects with heart failure and significant coronary artery disease following an exacerbation of heart failure: the COMMANDER HF trial.Eur J Heart Fail. 2015; 17:735–742. doi: 10.1002/ejhf.266.MedlineGoogle Scholar13. University of Alberta. Dabigatran following transient ischemic attack and minor stroke (DATAS II).In: ClinicalTrials.gov [Internet]. Bethesda, MD: National Library of Medicine (US); 2000. https://clinicaltrials.gov/ct2/show/NCT02295826 NLM Identifier: NCT02295826.Google Scholar14. Yang F, Jiang W, Bai Y, Han J, Liu X, Zhang G, Zhao G.Treatment of Rivaroxaban versus Aspirin for Non-disabling Cerebrovascular Events (TRACE): study protocol for a randomized controlled trial.BMC Neurol. 2015; 15:195. doi: 10.1186/s12883-015-0453-7.CrossrefMedlineGoogle Scholar15. Mohr JP, Thompson JL, Lazar RM, Levin B, Sacco RL, Furie KL, Kistler JP, Albers GW, Pettigrew LC, Adams HP, Jackson CM, Pullicino P; Warfarin-Aspirin Recurrent Stroke Study Group. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke.N Engl J Med. 2001; 345:1444–1451. doi: 10.1056/NEJMoa011258.CrossrefMedlineGoogle Scholar16. Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ, Hertzberg VS, Frankel MR, Levine SR, Chaturvedi S, Kasner SE, Benesch CG, Sila CA, Jovin TG, Romano JG; Warfarin-Aspirin Symptomatic Intracranial Disease Trial investigators. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis.N Engl J Med. 2005; 352:1305–1316. doi: 10.1056/NEJMoa043033.CrossrefMedlineGoogle Scholar17. Kumar G, Goyal MK.Warfarin versus aspirin for prevention of stroke in heart failure: a meta-analysis of randomized controlled clinical trials.J Stroke.Cerebrovasc Dis. 2013; 22:1279–1287. doi: 10.1016/j.jstrokecerebrovasdis.2012.09.015.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Knotts T and Mousa S (2019) Anticoagulation in Venous Thromboembolism Prophylaxis in Medically Ill Patients: Potential Impact of NOACs, American Journal of Cardiovascular Drugs, 10.1007/s40256-019-00329-5, 19:4, (365-376), Online publication date: 1-Aug-2019. February 14, 2017Vol 135, Issue 7 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.116.026170PMID: 28193799 Originally publishedFebruary 14, 2017 KeywordsEditorialsstrokebetrixabananticoagulantPDF download Advertisement

The fully automatic generation of code that establishes the reversibility of arbitrary C/C++ code has been a target of research and engineering for more than a decade as reverse computation has become a central notion in large scale parallel discrete event simulation (PDES). The simulation models that are implemented for PDES are of increasing complexity and size and require various language features to support abstraction, encapsulation, and composition when building a simulation model. In this paper we focus on parallel simulation models that are written in C++ and present an approach and an evaluation for a fully automatically generated reversible code for a kinetic Monte-Carlo application implemented in C++. Although a significant runtime overhead is introduced with our technique, the assurance that the reverse code is generated automatically and correctly, is an enormous win that allows simulation model developers to write forward event code using the entire C++ language, and have that code automatically transformed into reversible code to enable parallel execution with the Rensselaer's Optimistic Simulation System (ROSS).

Purpose: Two-dimensional shear wave elastography (2D-SWE) (Logic E9, GE Healthcare) is a new imaging technique for the non-invasive assessment of tissue stiffness. This study assesses the utility of 2D-SWE in assessing liver fibrosis in patients with chronic liver disease by comparing performance against quantitative acoustic radiation force impulse (ARFI) imaging (Acuson S3000; Siemens).

The C Programming Language is known for being an efficient language that can be compiled on almost any architecture and operating system. However the absence of dynamic safety checks and a relatively weak type system allows programmer oversights that are hard to spot. In this paper, we present RTC, a runtime monitoring tool that instruments unsafe code and monitors the program execution. RTC is built on top of the ROSE compiler infrastructure. RTC finds memory bugs and arithmetic overflows and underflows, and run-time type violations. Most of the instrumentations are directly added to the source file and only require a minimal runtime system. As a result, the instrumented code remains portable. In tests against known error detection benchmarks, RTC found 98% of all memory related bugs and had zero false positives. In performance tests conducted with well known algorithms, such as binary search and MD5, we determined that our tool has an average run-time overhead rate of 9.7× and memory overhead rate of 3.5×.

Domain specific languages (DSLs) offer an attractive path to program large-scale, heterogeneous parallel computers since application developers can leverage high-level annotations defined by DSLs to efficiently express algorithms without being distracted by low-level hardware details. However, performance of DSL programs heavily relies on how well a DSL implementation, including compilers and runtime systems, can exploit knowledge across multiple layers of software/hardware environments for optimizations. The knowledge ranges from domain assumptions, high-level DSL semantics, to low-level hardware features. Traditionally, such knowledge is either implicitly assumed or represented using ad-hoc approaches, including narrative text, source-level annotations, or customized software and hardware specifications in high performance computing (HPC). The lack of a formal, uniform, extensible, reusable and scalable knowledge management approach is becoming a major obstacle to efficient DSLs implementations targeting fast-changing parallel architectures. In this paper, we present a novel DSL implementation paradigm using an ontology-based knowledge base to formally and uniformly exploit the knowledge needed for optimizations. An ontology is a formal and explicit knowledge representation to describe concepts, properties, and individuals in a domain. During the past decades, a wide range of ontology standards and tools have been developed to help users capture, share, utilize and reason domain knowledge. Using modern ontology techniques, we design a knowledge base capturing concepts and properties of a problem domain, DSL programs, and hardware architectures. Compiler interfaces are also defined to allow interactions with the knowledge base to assist program analysis, optimization and code generation. Our preliminary evaluation using stencil computation shows the feasibility and benefits of our approach.

Trustworthy supercomputing depends on advanced program optimizations to deliver high performance and ways to determine how modications to a program impact its behavior. The rst is important to allow its application on supercomputers, the latter important for cybersecurity. We must be able to track and identify any changes to programs and analyze what the source of the change was. This might be manual changes, or changes introduced by a compiler (in an optimization), or a combination of both.

The Department of Energy has a wide range of large-scale, parallel scientific applications running on cutting-edge high-performance computing systems to support its mission and tackle critical science challenges. A recent trend in these high-performance computing systems is to add commodity accelerators, such as Nvidia GPUs and Intel Xeon Phi coprocessors, into computer nodes so we can achieve increased performance without exceeding the limited power budget. However, it is well-known in the high-performance computing community that porting existing applications to accelerators is a difficult task given the numerous set of unique hardware features and the general complexity of software. In this paper, we share our experiences of using the OpenMP Accelerator Model to port two stencil applications to exploit Nvidia GPUs. Introduced as part of the OpenMP 4.0 specification, the OpenMP accelerator model provides a set of directives for users to specify semantics related to accelerators so that compilers and runtime systems can automatically handle repetitive and error-prone accelerator programming tasks, including code transformations, work scheduling, data management, reduction, and so on. Using a prototype compiler implementation based on the ROSE source-to-source compiler framework, we report the problems we encountered during the porting process, our solutions, and the obtained performance. Productivity is also evaluated. Our experience shows that the existing OpenMP Accelerator Model can effectively help programmers leverage accelerators. However, complex data types and non-canonical control structures can pose challenges for programmers to productively apply accelerator directives.

Computational accelerators, such as manycore NVIDIA GPUs, Intel Xeon Phi and FPGAs, are becoming common in work-stations, servers and supercomputers for scientific and engineering applications. Efficiently exploiting the massive parallelism these accelerators provide requires the designs and implementations of productive programming models. In this paper, we explore support of multiple accelerators in high-level programming models. We design novel language extensions to OpenMP to support offloading data and computation regions to multiple accelerators (devices). These extensions allow for distributing data and computation among a list of devices via easy-to-use interfaces, including specifying the distribution of multi-dimensional arrays and declaring shared data regions among accelerators. Computation distribution is realized by partitioning a loop iteration space among accelerators. We implement mechanisms to marshal/unmarshal and to move data of non-contiguous array subregions and shared regions between accelerators without involving CPUs. We design reduction techniques that work across multiple accelerators. Combined compiler and runtime support is designed to manage multiple GPUs using asynchronous operations and threading mechanisms. We implement our solutions for NVIDIA GPUs and demonstrate through example OpenMP codes the effectiveness of our solutions for performance improvement.

Extreme-scale computing involves hundreds of millions of threads with multi-level parallelism running on large-scale hierarchical and heterogeneous hardware. In POSIX threads and OpenMP applications, some key behaviors occurring in runtime such as thread failure, busy waiting, and exit need to be accurately and timely detected. However, for the most of these applications, there are lack of unified and efficient detection mechanisms to do this. In this paper, a heartbeat-based behavior detection mechanism for POSIX threads (Pthreads) and OpenMP applications (HBTM) is proposed. In the design, two types of implementations are conducted, centralized and decentralized respectively. In both implementations, unified API has been designed to guarantee the generality of the mechanism. Meanwhile, a ring-based detection algorithm is designed to ease the burden of the centra thread at runtime. To evaluate the mechanism, the NAS Parallel Benchmarks (NPB) are used to test the performance of the HBTM. The experimental results show that the HBTM supports detection of behaviors of POSIX threads and OpenMP applications while acquiring a short latency and near 1% overhead.