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It is convenient for designers to get the buckling loads of sparse stiffened panels quickly by using engineering calculation method to analyze the stability of composite stiffened panels, but it is still unable to meet the accuracy requirements of analysis of dense stiffened panels. The buckling loads of stiffened panels are closely related to the buckling modes. Based on capturing and analyzing the Compressive Buckling waveforms of T-shaped densely stiffened panels, this paper presents a formula for calculating the buckling loads according to the geometric coefficients. The results are very similar to those of finite element simulation, and can be used to calculate the buckling loads of sparse and dense stiffened panels with different stiffeners.

Background The association of postimplant tricuspid regurgitation (TR) and heart failure (HF) hospitalization in patients without HF and preexisting abnormal TR and TR pressure gradient (PG) remain unclear. Hypothesis This study aimed to explore the clinical outcomes of progressive postimplant TR after permanent pacemaker (PPM) implantation. Methods A total of 1670 patients who underwent a single ventricular or dual‐chamber transvenous PPM implantation at our hospital between January 2003 and December 2017 were included in the study. Patients with prior valvular surgery, history of HF, and baseline abnormal TR and TRPG were excluded. Finally, a total of 1075 patients were enrolled in this study. Progressive TR was defined as increased TR grade of ≥2 degrees and TRPG of >30 mmHg after implant. Results In 198 (18.4%) patients (group 1) experienced progressive postimplant TR and elevated TRPG, whereas 877 patients (group 2) did not have progressive postimplant TR. Group 1 had larger change in postimplant TRPG (group 1 vs. group 2; 12.8 ± 9.6 mmHg vs. 1.1 ± 7.6 mmHg; p

Objective Right ventricular (RV) septal pacing is considered a better pacing procedure compared with traditional apical pacing. This study aimed to investigate agreement among computed tomography (CT), three-dimensional echocardiography (3D-echo), and fluoroscopy for evaluating the tip of the RV pacing lead in the non-apical position in patients with permanent pacemaker implantation. Methods Fifty-four patients were prospectively enrolled. Data on patients’ characteristics and imaging findings were analyzed. The agreement rate in distinguishing the RV septal lead position among the three imaging modalities was determined. Results Thirty-three (61%) patients were men and the median age was 76 years. Overall, the agreement rate among the three imaging modalities was 87% (47/54; Kappa ratio: 0.734). The agreement of 3D-echo compared with thoracic CT (Kappa ratio: 0.893) was better than that for thoracic CT and fluoroscopy (Kappa ratio: 0.658). Agreement between fluoroscopy and 3D-echo was lowest (Kappa ratio: 0.632). Conclusions Agreement in evaluating the position of the septal lead between thoracic CT and 3D-echo is better than that between other imaging modalities. Our findings indicate that 3D-echo imaging might be the best imaging tool for defining the tip of the RV non-apical lead position and be useful for guiding positioning of the RV lead.

As the scale of VLSI circuits increases rapidly, multi-FPGA prototyping systems have been widely used for logic verification. Due to the limited number of connections between FPGAs, however, the routability of prototyping systems is a bottleneck. As a consequence, timing division multiplexing (TDM) technique has been proposed to improve the usability of prototyping systems, but it causes a dramatic increase in system delay. In this paper, we propose ALIFRouter, a practical architecture-level inter-FPGA router, to improve the chip performance by reducing the corresponding system delay. ALIFRouter consists of three major stages, including i) routing topology generation, ii) TDM ratio assignment, and iii) system delay optimization. Additionally, a multi-thread parallelization method is integrated into the three stages to improve the efficiency of ALIFRouter. With the proposed algorithm, major performance indicators of multi-FPGA systems such as signal multiplexing ratio can be improved significantly.

A prominent circadian variation is present in atrial fibrillation (AF) attacks that may be related to the expression of circadian clock genes. Little is known about the expression of circadian clock genes in AF. We prospectively enrolled 73 patients who had received pacemaker implantation, in order to define the burden of atrial high-rate episodes (AHREs) accurately. AF was diagnosed clinically in 43 (59%) patients (15 with persistent AF and 28 with paroxysmal AF). The expression levels of circadian clock genes of peripheral blood leukocytes were checked. There were more males and patients with a larger left atrial (LA) size and lower expression levels of BMAL1, CRY2, NR1D1, NR1D2, PER2, RORA, RORC, and TIM genes in persistent AF group than in other groups. There was a significant correlation between higher AHRE burden and larger LA size and between higher AHRE burden and decreased expression of circadian clock genes in patients with AF. LA volume and the expression of CRY1, NR1D1, and RORA are significantly associated with AHRE burden. However, the underlying mechanism needs to be elucidated in further studies.

As the scale of VLSI circuits and fabrication costs increase rapidly, multi-FPGA prototyping systems are widely adopted in industry to make logic verification faster and cheaper. Since routing signals can usually exceed the number of I/O pins in an FPGA, timing division multiplexing (TDM) technique is required to solve this problem. FPGA routing for developing a prototyping system is a big challenge due to the signal delay of TDM. This paper presents MSFRoute, a multi-stage FPGA routing framework for timing division multiplexing technique, to optimize the signal delay and the routability for prototyping systems. In this work, a TDM ratios assignment algorithm with an efficient parallelization method is proposed to optimize inter-FPGA signal delay. Meanwhile, we propose a practical system clock period optimization method to solve critical signal delay problem. Experimental results show that our routing framework reduces TDM ratios by up to 88.3% with an average reduction rate of 41.8%. With the proposed parallelization method, total flow of MSFRoute can get up to 4.38X speedup with a 2.77X speedup on average.

Background The impact of electrocardiography (ECG) morphology on clinical outcomes in patients with non-ST segment elevation myocardial infarction (NSTEMI) receiving percutaneous coronary intervention (PCI) is unknown. This study investigated whether different ST morphologies had different clinical outcomes in patients with NSTEMI receiving PCI. Methods This retrospective study analyzed record-linked data of 362 patients who had received PCI for NSTEMI between January 2008 and December 2010. ECG revealed ST depression in 67 patients, inverted T wave in 91 patients, and no significant ST-T changes in 204 patients. The primary endpoint was long-term all-cause mortality. The secondary endpoint was long-term cardiac death and non-fatal major adverse cardiac events. Results Compared to those patients whose ECG showed an inverted T wave and non-specific ST-T changes, patients whose ECG showed ST depression had more diabetes mellitus, advanced chronic kidney disease (CKD) and left main artery disease, as well as more in-hospital mortality, cardiac death and pulmonary edema during hospitalization. Patients with ST depression had a significantly higher rate of long-term total mortality and cardiac death. Finally, multiple stepwise Cox regression analysis showed that an advanced Killip score, age, advanced CKD, prior percutaneous transluminal coronary angioplasty and ST depression were independent predictors of the primary endpoint. Conclusions Among NSTEMI patients undergoing coronary angiography, those with ST depression had more in-hospital mortality and cardiac death. Long-term follow-up of patients with ST depression consistently reveals poor outcomes.

Aims Anticoagulation therapy is indicated to prevent stroke in atrial flutter (AFL) and atrial fibrillation (AF) patients. However, the outcomes of solitary AFL patients may differ from those with AFL who develop AF during follow-up. This study aimed to investigate the differences in clinical outcomes: (i) among patients with solitary AFL, AF, and AFL developing AF thereafter and (ii) between solitary AFL patients with vs. without anticoagulation therapy. Methods and results This nationwide cohort study enrolled patients with solitary AFL, solitary AF, and AFL developing AF from a 12 years National Health Insurance Research Database in Taiwan. There were 230 367 patients without anticoagulation therapy in the solitary AF cohort, 8064 in the solitary AFL cohort, and 4495 in the AFL with AF cohort. The AFL with AF and solitary AF cohorts had higher incidences of ischaemic stroke and major bleeding than the solitary AFL cohort. Solitary AFL patients with anticoagulation therapy had a lower ischaemic stroke rate than those without (P

Obstructive sleep apnea syndrome (OSAS) is an important risk factor for atrial fibrillation (AF). GJA1 gene encoding connexin43, a major protein in cardiac gap junctions, plays a crucial role in the synchronized contraction of the heart and in cardiac arrhythmia. However, little is known regarding the role of GJA1 expression in the incidence of AF in patients with OSAS. All prospectively enrolled OSAS patients underwent polysomnography, electrocardiography, a 24-h Holter test, and echocardiography. Moderate-to-severe OSAS was defined as an apnea-hypopnea index (AHI) ≥ 15. Exosomes were purified from the plasma of all OSAS patients and incubated in HL-1 cells to investigate the effect of exosomes from patients with and without AF on GJA1 expression. A total of 129 patients were recruited for this study, 26 were excluded due to an AHI &lt, 15. Of the 103 enrolled patients, 21 had AF, and 82 did not. Multivariate analysis showed diabetes mellitus, lower sleep efficiency, lower left ventricular ejection fraction, and larger left atrial (LA) size were independent predictors of AF occurrence in OSAS patients. The area under the receiver operating characteristic curve for LA with a size ≥38.5 mm for predicting AF occurrence in OSAS patients was 0.795 (95% confidence interval [0.666, 0.925]), p &lt, 0.001). GJA1 expression in HL-1 cells incubated with exosomes from OSAS patients with AF was lower than that with exosomes from patients without AF after controlling for age and sex and was negatively correlated with the AHI and oxygen desaturation index (ODI), especially during the non-rapid eye movement period (NREM) of OSAS patients with AF (all p &lt, 0.05). LA size was an independent predictor of AF occurrence in OSAS patients. The AHI and ODI in the NREM period of OSAS patients with AF were negatively correlated with GJA1 expression in HL-1 cells, which offers a hint that GJA1 may play a crucial role in the development of AF in patients with OSAS.

For multi-feature fusion in automatic recognition of pavement distress images, we proposed a multi-feature fusion method based on manifold learning. In this method, the intrinsic features o...

To investigate the postprocedural cardiovascular events and vascular outcomes, including hand ischemia and neurological compromise, after transulnar (TU) catheterization in ipsilateral radial artery occlusion.Previous randomized trials have shown that the transulnar (TU) approach for coronary angiogram and intervention has safety and outcomes similar to those of the transradial (TR) approach. However, the safety of the TU procedure when ipsilateral radial artery occlusion occurs is unknown.We retrospectively reviewed 87 TU cases with ipsilateral radial artery occlusion confirmed by a forearm angiogram. Eighty percent of these patients had a history of ipsilateral radial artery cannulation or surgery. We avoided the use of over-sized sheaths or applied a sheathless approach during surgery.No ulnar artery occlusion was observed by subsequent Doppler ultrasound or pulse oximetry. No patient developed hand ischemia or serious complications requiring surgery or blood transfusion during the follow-up period of 32.2 ± 24.0 months. Review of the preprocedural forearm angiograms showed that 95.7% of the patients possessed significant collaterals supplying flow from the interosseous artery to the occluded radial artery remnant. Thus, the blood circulation to the palmar arch and digital vessels was maintained even when the ulnar artery was temporarily occluded by an in-dwelling ulnar arterial sheath.TU catheterization was safe in patients with coexisting ipsilateral radial artery occlusions and feasible for use in complex intervention procedures. Cautious manipulation of ulnar artery cannulation and hemostasis helped decrease the risk of hand ischemia.

Low-energy impurity diffusion in a host material is often regarded as an adiabatic process, characterized by its adiabatic potential energy barrier. Here we show that the diffusion process in semiconductors can involve nonadiabatic electron excitations, rending it to be a more complicated process. Impurity diffusion in a device at working temperature can pump one electron up from localized impurity state into the host conduction band and causes the impurity to be a dynamic donor since it temporarily loses its electron to the host. This nonadiabatic process, against a common belief, fundamentally change the diffusion behavior, including its barrier height and diffusion path. Although we mainly demonstrate this process with Au metal impurity in bulk Si through time-dependent density functional theory simulations, we believe this could be a rather common phenomenon as it is shown that the similar phenomena also exist in Zn, Cd impurities diffusion in bulk Si, and Ti diffusion in $\mathrm{Ti}{\mathrm{O}}_{2}$. We believe this study can open up a new direction of inquiry for such diffusion behavior in semiconductor.

Detailed routing becomes the most complicated and runtime consuming stage in the physical design flow as technology nodes advance. Due to the inaccessibility of advanced routing rules and industrial designs, it is hard to conduct detailed routing academic researches using the modern real-world designs. ISPD18 hosts the first detailed routing contest [1] and releases a set of benchmarks synthesized by industrial tools with practical routing rules. ISPD18 contest spurs detailed routing researches and provides students the opportunity to become familiar with the industrial designs and rules. On top of ISPD18 detailed routing contest, we host another detailed routing contest in ISPD19 [2] to consider several advanced routing rules and make the contest problem one step closer to the real-world routing challenges in advanced technology nodes. ISPD19 detailed routing contest encourages participants to use double-cut vias to improve yield and result quality. In addition, in order to drive the development of efficient routing frameworks, the deterministic multithreading feature is encouraged but optional in this contest.

AimsThe clinical outcome and threshold of oral anticoagulation differs between patients with solitary atrial flutter (AFL) and those with AFL developing atrial fibrillation (AF) (AFL-DAF). We therefore investigated previously unevaluated predictors of AF development in patients with AFL, and also the predictive values of risk scores in predicting the occurrence of AF and ischaemic stroke.Methods and resultsParticipants were those diagnosed with AFL between 1 January 2001 and 31 December 2013. Patients were classified into solitary AFL and AFL-DAF groups during follow-up. Finally, 4101 patients with solitary AFL and 4101 patients with AFL-DAF were included after 1:1 propensity score matching with CHA2DS2-VASc scores and their components, AFL diagnosis year and other comorbidities. The group difference in the prevalence of ischaemic stroke/transient ischaemic attack (TIA) and congestive heart failure (CHF) was substantial, that of vascular disease was moderate, and that of diabetes and hypertension was negligible. Therefore, we reweighted the component of heart failure as 2 (the same with stroke/TIA) and vascular disease as 1 in the proposed A2C2S2-VASc score. The proposed A2C2S2-VASc and CHA2DS2-VASCscores showed patients with AFL who had higher delta scores and follow-up scores had higher risk of AF development. The delta score outperformed the follow-up score in both scoring systems in predicting ischaemic stroke.ConclusionThis study showed that new-onset CHF, stroke/TIA and vascular disease were predictors of AF development in patients with AFL. The dynamic score and changes in both CHA2DS2-VASCand the proposed A2C2S2-VASc score could predict the development of AF and ischaemic stroke.

Background MicroRNAs (miRs) regulate gene expression in heart failure. Circulating miRs as biomarkers for heart failure in mitral regurgitation patients (MR) remain unexplored. Methods This case–control study enrolled 32 MR patients with heart failure, 16 asymptomatic MR patients, and 12 control subjects without heart failure. We used next generation sequencing to study the gene expression profiles in the sera, and quantitative RT-PCR to study serum and tissue miRs in the left atria. Results Next generation sequencing analysis and enrichment analysis showed that 25 miRs were differentially expressed in the sera of MR patients with heart failure compared to control subjects. The circulating miR-148b-3p (p=0.002) and miR-409-3p (p=0.010) were significantly down-regulated in the MR patients with heart failure compared to control subjects. However, only circulation miR-148b-3p was significantly down-regulated in the MR patients without heart failure compared to control subjects (p=0.009). The tissue miR-409-3p was significantly down-regulated in the MR patients with heart failure compared to 3 purchased normal controls (p=0.041). Notably, the tissue RASGRP3 mRNA, target gene of miR-409-3p, was significantly up-regulated in the MR patients with heart failure compared to normal controls (p=0.010). The tissue FRY (p=0.010) and GADD45A (p=0.010) mRNAs, target genes of miR-148b-3p, were significantly up-regulated in the MR patients with heart failure compared to normal controls. Conclusions Circulating miR-148b-3p might serve as biomarker for future development of heart failure and miR-409-3p might serve as biomarker for incident heart failure in MR patients.

Supplemental Digital Content is available in the text, Atrial fibrillation (AF) is a major independent risk factor of stroke and anticoagulation therapy is needed in patients with AF after ischemic stroke. However, the detection rate of AF is low after ischemic stroke. Developing a prediction model for newly diagnosed AF after ischemic stroke will help to assess the subclinical AF. We identified 98,103 patients with diabetes mellitus (DM) and 261,893 patients without DM, who were not AF history and admitted for newly ischemic stroke from the National Health Insurance Research Database in Taiwan. The prediction model for 3-year incidence of AF after ischemic stroke was derived from multivariate logistic regression and also the accuracy rate of the prediction model was compared with CHA2DS2-VASC and CHADS2 scores as a reference. Four thousand nine hundred seventy six patients in the DM cohort and 16,127 patients in the non-DM cohort developed AF during 3 years of follow-up. The variables in the point-based prediction model for non-DM patients (range: -3–28), included age, heart failure, coronary artery disease, gout, obstructive pulmonary disease, hypertension, female, and statin use, while those for DM patients (range: -2–30) included age, heart failure, coronary artery disease, chronic kidney disease, hypertension, obstructive pulmonary disease, and statin use. Compared to the CHADS2 and CHA2DS2-VASc scoring systems, this scoring system was better at predicting 3-year risk of AF after ischemic stroke in both cohorts. This model might be useful in evaluating the benefit of insertable cardiac monitor implantation and anticoagulation agents in individual patients after ischemic stroke.

Background: There are few reports about non-vitamin K antagonist oral anticoagulant (NOAC) treatment for resolution of left atrium (LA) or left atrial appendage (LAA) thrombus. LAA thrombus is an important cause of cardiogenic cerebral thromboembolism, and the detection rate increases due to more and more patients receiving catheter ablation. However, the results from NOAC use for LA or LAA thrombus are still unknown in real-world practice. The aim of this study was to discover the resolution of LA or LAA thrombus after anticoagulant treatment in real-world practice. Method: From January 2013 to December 2016, a total 864 patients underwent transesophageal echocardiography (TEE), and 41 cases of LA or LAA thrombus were detected in our hospital. Among them, a total of 22 patients underwent follow-up TEE to detect the resolution of LA or LAA thrombus. Result: The average age of the study patients was 72.0 ± 11 years old, and 61% were male. The average CHA2DS2-VASc scores were 3.76 ± 2.01 points. A total of 22 patients underwent follow-up TEE, and 19 (86.4%) patients presented LA or LAA thrombus resolution. The average resolution duration was 258.47 ± 218.17 days. One-year all-cause mortality was 4.9%, and the incidence of ischemic stroke was 4.9%. Most physicians favored titration of the dosage of NOAC or warfarin in real-world practice. Conclusion: In real-world practice, most physicians favored titration of the dosage of NOAC or warfarin for LA or LAA thrombus. LA or LAA thrombus could exist if the patient received a reduced dose of NOAC. High frequency of LAA or LA thrombi could resolve, and a low incidence of ischemic stroke occurred after adjustment of oral anticoagulant treatment.

In advanced technology nodes, detailed routing becomes the most complicated and runtime consuming stage. To spur detailed routing research, ISPD 2018 initial detailed routing contest is hosted and it is the first ISPD contest on detailed routing problem. In this contest, the benchmarks synthesized by industrial tool and library are released, which consider the design rules like spacing table, cut spacing, end-of-line spacing, and min-area rules. In addition, the global routing guide is provided associated to each benchmark, and detailed routers are required to honor the routing guides as much as possible meanwhile minimize design-rule-checking (DRC) violations. The biggest benchmark released in this contest has near-millions of nets, so the runtime and memory scalability for detailed routers need to be well addressed. To reduce routers' runtime, the deterministic multithreading framework is encouraged but optional in this contest.

Background. Left atrial enlargement is a mortality and heart failure risk factor in primary mitral regurgitation (MR) patients. Pig models of MR have shown differential expression of genes linked to the renin-angiotensin system. Therefore, the aim of this study was to investigate the key genes of the renin-angiotensin that are expressed differentially in the left atrial myocardium in MR patients. Methods. Quantitative RT-PCR was used to compare gene expression in the renin-angiotensin system in the left atrium in MR patients, aortic valve disease patients, and normal subjects. Results. Plasma angiotensin II concentrations did not significantly differ between MR patients and aortic valve disease patients (P=0.582). Compared to normal controls, however, MR patients had significantly downregulated expressions of angiotensin-converting enzyme, angiotensin I converting enzyme 2, type 1 angiotensin II receptor, glutamyl aminopeptidase, angiotensinogen, cathepsin A (CTSA), thimet oligopeptidase 1, neurolysin, alanyl aminopeptidase, cathepsin G, leucyl/cystinyl aminopeptidase (LNPEP), neprilysin, and carboxypeptidase A3 in the left atrium. The MR patients also had significantly upregulated expressions of MAS1 oncogene (MAS1) and mineralocorticoid receptor compared to normal controls. Additionally, in comparison with aortic valve disease patients, MR patients had significantly downregulated CTSA and LNPEP expression and significantly upregulated MAS1 expression in the left atrium. Conclusions. Expressions of genes in the renin-angiotensin system, especially CTSA, LNPEP, and MAS1, in the left atrium in MR patients significantly differed from expressions of these genes in aortic valve disease patients and normal controls. Notably, differences in expression were independent of circulating angiotensin II levels. The results of this study provide a rationale for pharmacological therapies or posttranslational regulation therapies targeting genes expressed differentially in the renin-angiotensin system to remedy structural remodeling associated with atrial enlargement and heart failure progression in patients with MR.

Apoptosis occurs in atrial cardiomyocytes in mitral and tricuspid valve disease. The purpose of this study was to examine the respective roles of the mitochondrial and tumor necrosis factor-α receptor associated death domain (TRADD)-mediated death receptor pathways for apoptosis in the atrial cardiomyocytes of heart failure patients due to severe mitral and moderate-to-severe tricuspid regurgitation. This study comprised eighteen patients (7 patients with persistent atrial fibrillation and 11 in sinus rhythm). Atrial appendage tissues were obtained during surgery. Three purchased normal human left atrial tissues served as normal controls. Moderately-to-severely myolytic cardiomyocytes comprised 59.7±22.1% of the cardiomyocytes in the right atria and 52.4±12.9% of the cardiomyocytes in the left atria of mitral and tricuspid regurgitation patients with atrial fibrillation group and comprised 58.4±24.8% of the cardiomyocytes in the right atria of mitral and tricuspid regurgitation patients with sinus rhythm. In contrast, no myolysis was observed in the normal human adult left atrial tissue samples. Immunohistochemical analysis showed expression of cleaved caspase-9, an effector of the mitochondrial pathways, in the majority of right atrial cardiomyocytes (87.3±10.0%) of mitral and tricuspid regurgitation patients with sinus rhythm, and right atrial cardiomyocytes (90.6±31.4%) and left atrial cardiomyocytes (70.7±22.0%) of mitral and tricuspid regurgitation patients with atrial fibrillation. In contrast, only 5.7% of cardiomyocytes of the normal left atrial tissues showed strongly positive expression of cleaved caspase-9. Of note, none of the atrial cardiomyocytes in right atrial tissue in sinus rhythm and in the fibrillating right and left atria of mitral and tricuspid regurgitation patients, and in the normal human adult left atrial tissue samples showed cleaved caspase-8 expression, which is a downstream effector of TRADD of the death receptor pathway. Immunoblotting of atrial extracts showed that there was enhanced expression of cytosolic cytochrome c, an effector of the mitochondrial pathways, but no expression of membrane TRADD and cytosolic caspase-8 in the right atrial tissue of mitral and tricuspid regurgitation patients with sinus rhythm, and right atrial and left atrial tissues of mitral and tricuspid regurgitation patients with atrial fibrillation. Taken together, this study showed that mitochondrial pathway for apoptosis was activated in the right atria in sinus rhythm and in the left and right atria in atrial fibrillation of heart failure patients due to mitral and tricuspid regurgitation, and this mitochondrial pathway activation may contribute to atrial contractile dysfunction and enlargement in this clinical setting.

To avoid producing unroutable placement solutions, many state-of-the-art routability-driven placers iteratively invoke global routers to evaluate their placement solutions, and then perform routability optimization. However, using a global router to evaluate hard-to-route placement solutions may spend considerable runtime and it cannot guarantee that a placement is truly unroutable to any router. This paper presents an unroutable placement recognizer based on a window-based unroutable region recognition algorithm and a length-bounded unroutable panel recognition (UPR) algorithm, which can confirm some placements that are exactly unroutable among a set of hard-to-route placements. In addition, if a placement is recognized to be unroutable, the recognizer can report a lower bound of total overflow for the placement. The experimental results reveal that the unroutable region recognition algorithm can find out 16 placements that are definitely unroutable among 23 widely used hard-to-route global routing benchmarks. Moreover, when a scenic constraint is considered, the UPR algorithm can find out a few more placements that are also unroutable.

Background Hypertension is common among patients who have undergone liver transplantation and is a major contributor to cardiovascular events. Few studies have studied the risk factors associated with post–liver transplantation (LT) hypertension. This prospective study assessed the prevalence of post-LT hypertension and associated preoperative risk factors. Methods From May 2008 to December 2009, 79 normotensive adult patients (≥18 years old) who underwent living-donor LT with a median follow up of 4.79 ± 0.88 years were enrolled. Patients' pre-LT demographics, clinical data, pre-LT diabetes, and immunosuppressive agents used after LT were studied for their association with post-LT hypertension. Results The prevalence of post-LT hypertension was 49.4%. The independent risk factors for post–living-donor LT hypertension were pre-LT systolic blood pressure (SBP; odds ratio [OR], 1.04; 95% confidence interval [CI], 1.00–1.09; P = .039) and post-LT administration of mammalian target of rapamycin (mTOR) inhibitors (OR, 4.08; 95% CI, 1.40–11.94; P = .010). Pre-LT diabetes had a negative predictive value (OR, 0.15; 95% CI, 0.03–0.74; P = .019). Neither age, male sex, smoking, pre-LT serum cholesterol and triglyceride levels, tacrolimus, nor glucocorticoid was associated with post-LT hypertension. Conclusions The prevalence of hypertension is high after LT. Higher pre-LT SBP and post-LT mTOR inhibitor administration predispose patients to post-LT hypertension.

Background This study aimed to evaluate the longitudinal changes in cardiac structure and function in incident-automated peritoneal dialysis (APD) patients. Methods We conducted a 2-year prospective, randomized, open-label, parallel-group study to compare the efficacy of icodextrin solution versus glucose-based solution. Echocardiography was performed at baseline, 1 and 2 years. Echocardiographic parameters over 2 years were evaluated for each group, using the Friedman test. Generalized linear regression analysis was used to test the associations between baseline clinical variables and echocardiographic changes, and a multivariate model was used to analyze cardiac function between the two groups. Results A total of 43 APD patients were enrolled in the beginning of this study. Twenty patients in the icodextrin group (ICO) and 18 patients in the glucose group (GLU) completed the study. In left ventricular (LV) systolic function measurements, ejection fraction (EF) increased significantly in the GLU group. Measurements of LV diastolic function and septal early mitral annulus velocity (EMV) increased significantly from baseline to 24-months in the ICO group (5.43–5.51 ms). The GLU group showed a significant decrease in peak early diastolic velocity (EDV) (70.67–68.25 cm/s), but a significant increase in septal EMV (5.94–7.57 ms) from baseline to 24-months. No significant association was found between the baseline clinical variables and echocardiographic changes within 24 months in the generalized linear regression analysis. Multivariate models were used to investigate changes in the four primary endpoints, namely, myocardial performance index (MPI), left ventricular ejection fraction (LVEF), deceleration time (DT), and E/e′ ratio. These primary endpoints show no significant association with the baseline values in both the ICO and GLU groups. Conclusion The present study demonstrates that long-dwell icodextrin solution can maintain reasonable cardiac structure and function in incident-APD patients. Trial registration ISRCTN14931270 (retrospectively registered on 23/03/2018).

This paper addresses a delay-driven layer assignment problem with consideration of via delay and coupling effect in the global routing stage. A negotiation-based framework is proposed to balance delay, congestion, and via count. Coupling capacitance is considered using a probabilistic look-up table. Finally, the proposed algorithm uses both parallel wires and wide wires to reduce wire delay. The effectiveness of our layer assignment algorithm is supported by extensive experimental results.

Traditional solutions to antenna effect, such as jumper insertion and diode insertion performed at post-route stage may produce extra vias and degrade circuit performance. Previous work suggests combining layer assignment, jumper insertion, and diode insertion together to achieve a better design quality with less additional cost. Based on our observations on global and local antenna violations, this paper proposes an antenna-safe single-net layer assignment (AS-SLA), which first enumerates all antenna-safe layer assignment solutions of a net, and then extracts the minimum-cost one for the net. AS-SLA can minimize via count and separators as well. In addition, an antenna avoidance layer assignment flow (AALA) adopting AS-SLA as its kernel not only avoids global antenna violations, but also eliminates local antenna violations. Experimental results reveal that, in 16 benchmarks, AALA can yield ten antenna-violation-free assignments, while the algorithms of other works yield no antenna-violation-free assignment. However, AALA performs about seven times slower than other antenna-aware layer assignment algorithm. Accordingly, two acceleration techniques are proposed to reduce the runtime of AALA by 57.6%.

Hepatocellular carcinoma (HCC) with intracavitary metastasis to the heart is rare. The incidence of HCC with right atrial metastasis is less than 6% at autopsy. Reports of HCC with right ventricular metastasis without inferior vena cava and right atrial metastasis are rarer. The diagnosis of metastasis of HCC into the cardiac cavity might be overlooked because the symptoms are neither apparent nor specific. Here, we report a patient with metastasis of HCC into the right ventricle cavity. The patient was in a disease-free status and experienced lower limbs oedema and gradual shortness of breath.

Modern global routers employ various routing methods to improve routing speed and quality. Maze routing is the most time-consuming process for existing global routing algorithms. This paper presents two bounded-length maze routing (BLMR) algorithms (optimal-BLMR and heuristic-BLMR) that perform much faster routing than traditional maze routing algorithms. In addition, a rectilinear Steiner minimum tree aware routing scheme is proposed to guide heuristic-BLMR and monotonic routing to build a routing tree with shorter wirelength. This paper also proposes a parallel multithreaded collision-aware global router based on a previous sequential global router (SGR). Unlike the partitioning-based strategy, the proposed parallel router uses a task-based concurrency strategy. Finally, a 3-D wirelength optimization technique is proposed to further refine the 3-D routing results. Experimental results reveal that the proposed SGR uses less wirelength and runs faster than most of other state-of-the-art global routers with a different set of parameters , , , . Compared to the proposed SGR, the proposed parallel router yields almost the same routing quality with average 2.71 and 3.12-fold speedup on overflow-free and hard-to-route cases, respectively, when running on a 4-core system.

As VLSI technology shrinks to fewer tracks per standard cell, e.g., from 10-track to 7.5-track libraries (and lesser for 7nm), there has been a rapid increase in the usage of multiple-row cells like two- and three-row flip-flops, buffers, etc., for design closure. Additionally, the usage of multi-bit flip-flops or flop trays to save power creates large cells that further complicate critical design tasks, such as placement. Detailed placement happens to be a key optimization transform, which is repeatedly invoked during the design closure flow to improve design parameters, such as, wirelength, timing, and local wiring congestion. Advanced node designs, with hundreds of thousands of multiple-row cells, require a paradigm change for this critical design closure transform. The traditional approach of fixing multiple-row cells during detailed placement and only optimizing the locations of single-row standard cells can no longer obtain appreciable quality of results. It is imperative to have new techniques that can simultaneously optimize both multiple- and single-row high cell locations during detailed placement. In this paper, we propose a new density-aware detailed placer for heterogeneous-sized netlists. Our approach consists of a chain move scheme that generalizes the movement of heterogeneous-sized cells as well as a nested dynamic programming based approach for wirelength and density optimization. Experimental results demonstrate the effectiveness of these techniques in wirelength minimization and density smoothing compared with the most recent detailed placer for designs with heterogeneous-sized cells.

Head-mounted virtual reality and augmented reality displays a.k.a. VR/AR goggles created a revolutionary multimedia genre that is seeking ever-broadening applications and novel natural human interfaces. Adding neuromonitoring and neurofeedback to this genre is expected to introduce a new dimension to user interaction with the cyber-world. This study presents the development of a Neuromonitoring VR/AR Goggle armed with electroence-phalo-gram and electrooculogram sensors, programmable milli-Ampere current stimulators and wireless fog/cloud computing support. Beside of its potential use in mitigating cybersickness, this device may have potential applications in augmented cognition ranging from feedback-controlled perceptual training to on-line learning and virtual social interactions. A prototype of the device has been made from a Samsung Gear VR for S6. This study explains its technical design to ensure precision data sampling, synchronous event marking, real-time signal processing and big data cloud computing support. This study also demonstrates the effective-ness in measuring the event-related potentials during a visual oddball experiment.

The present study reports a case of a 64-year-old man was admitted for sudden collapse. On auscultation, new grade 4/6 continuous murmur were detected and was best heard along the right sternal border. Blood culture yielded Staphylococcus haemolyticus and Escherichia coli. Despite appropriate antibiotic treatment, the patient’s condition deteriorated and he developed multiple organ failure. Transesophageal echocardiography revealed echofree spaces with periannular abscess, and two perforations at the noncoronary sinus of Valsalva aneurysms. This case was about an unusual case of prosthetic aortic valve infectious endocarditis with periannular abscess formation and noncoronary sinus of Valsalva aneurysms rupturing into the right atrium and right ventricle.

Routability has become a very challenging issue in a modern VLSI design flow. Many works use global routing to estimate the routability in the early design stages. However, global routing cannot accurately capture local congestion, so it is hard to detect the detailed routability issue. To more accurately estimate the detailed-routing routability, this paper presents a track-assignment-based routability estimator. In this work, wire segments called iroutes are extracted from a global routing result, and then the proposed negotiation-based algorithm assigns these iroutes to proper tracks and minimizes the overlaps between the iroutes. Based on the assignment result, we can judge which regions may have critical routability issues by seeing where more overlaps reside.

The increasing complexity of interconnection designs has enhanced the importance of research into global routing when seeking high-routability (low overflow) results or rapid search paths that report wirelength estimations to a placer. This work presents two routing techniques, namely circular fixed-ordering monotonic routing and evolution-based rip-up and rerouting using a two-stage cost function in a high-performance congestion-driven 2-D global router. We also propose two efficient via-minimization methods, namely congestion relaxation by layer shifting and rip-up and reassignment, for a dynamic programming-based layer assignment. Experimental results demonstrate that our router achieves performance similar to the first two winning routers in ISPD 2008 Routing Contest in terms of both routability and wirelength at a 1.05 × and 18.47 × faster routing speed. Moreover, the proposed layer assignment achieves fewer vias and shorter wirelength than congestion-constrained layer assignment (COLA).

Background Oxidative stress is linked with several cardiovascular diseases. However, the NADPH oxidase activity in severe mitral regurgitation patients with and without atrial fibrillation has not yet been explored. Methods This study involved 16 adult patients (eight patients with persistent atrial fibrillation and eight with sinus rhythm) with severe mitral and moderate-to-severe tricuspid regurgitation and five control patients without mitral and tricuspid disease. Atrial tissues of the right and left atrial appendages were obtained during surgery. Superoxide anion production was measured by lucigenin-enhanced chemiluminescence, and the expression of nox2 containing NADPH oxidase mRNA was measured by quantitative real-time RT-PCR. Additionally, immunohistochemical study was performed. Results NADPH-stimulated superoxide release was significantly higher than basal superoxide production from right [5671.9±3498.7 vs. 232.7±70.0 relative light units per second per milligram of protein (RLU s −1 mg protein −1 ), P =.008) and left atrial homogenates (6475.1±1890.8 vs. 229.0±79.6 RLU s −1 mg protein −1 , P =.008) in atrial fibrillation patients. The NADPH-stimulated superoxide release from right atrial homogenates was also significantly higher than basal superoxide production in sinus patients (6809.1±1327.1 vs. 244.2±65.5 RLU s −1 mg protein −1 , P =.008). Additionally, there was a borderline significant correlation between NADPH-stimulated superoxide production from left atrial homogenates and left atrial sizes ( r =0.683, P =.062) in atrial fibrillation patients. Membrane-bound nox2 containing NADPH oxidase mRNA expression was increased and was similar in both the atrial fibrillation patients and sinus patients. The NADPH-stimulated superoxide production in right atrial homogenates in control atrial samples was 1863.7±137.2 RLU s −1 mg protein −1 . Immunohistochemical study demonstrated increased expression of nox2 in myocytes with moderate-to-severe myolysis and hypertrophy. Conclusions Results of this study demonstrate that membrane-bound nox2 containing NADPH oxidase activity and expression in the atrial myocardium is increased in patients with severe mitral regurgitation, possibly contributing to atrial remodeling in this clinical setting.

Background The reported presence of DNA breaks, based on a positive reaction to the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end-labelling (TUNEL) assay, in fibrillating human right atria of cardiac valve disease may suggest apoptotic myocyte death. However, TUNEL positivity may reflect conditions other than cell death. Methods This study comprised 27 adult patients (14 patients with persistent atrial fibrillation and 13 in sinus rhythm) with significant mitral and tricuspid valve diseases. Atrial tissues were obtained during surgery. Results Immunohistochemical study demonstrated that 31.1±12.2% of the myocytes had TUNEL-positive nuclei in the fibrillating right atria whereas 37.4±23.2% of the myocytes had TUNEL-positive nuclei in the right atrial myocardium in sinus rhythm ( p =0.505). However, most nuclei of TUNEL-positive myocytes in the right atria also expressed proliferating cell nuclear antigen (PCNA), an indicator of DNA replication and repair but never Ki-67, a replication-associated antigen (TUNEL + /PCNA + vs. TUNEL + /PCNA − , 30.5±10.8% vs. 1.2±1.5%, p =0.005, in the atrial fibrillation group and 32.8±18.6% vs. 4.6±8.1%, p =0.003, in the sinus group), suggesting that most TUNEL-positive myocytes were undergoing DNA repair. In addition, the incidence of TUNEL-positive myocytes significantly and positively correlated with the incidence of PCNA-positive myocytes ( r =0.5, p r =0.661, p Conclusions Cell death by apoptosis occurs in a small percentage of atrial cardiomyocytes in mitral and tricuspid valve diseases and DNA repair is more important and preserves the cardiomyocytes.

Eur J Clin Invest 2011; 41 (3): 299–307 Abstract Background Myolysis of atrial cardiomyocytes occurs in patients with severe mitral and tricuspid regurgitation. This morphological remodelling may involve autophagy. Methods This study comprised 20 patients (10 with long-standing persistent atrial fibrillation and 10 with sinus rhythm) with severe mitral and tricuspid regurgitation. Atrial appendageal tissues were obtained during surgery. The appearance of autophagosomes (LC3B) in myocytes can reflect autophagy induction. Complement 9 is used as a reliable marker of oncosis. Results In the fibrillating right atria, 68·4 ± 18·9% of total myocytes showed moderate-to-severe myolysis, while 64·2 ± 15·8% of total myocytes comprised these cells in right atrial myocardium with sinus rhythm. Immunohistochemical study revealed LC3B-positive myocytes in 8·0% of myocytes without myolysis, 11·9% of myocytes with mild myolysis and 49·4% of myocytes with moderate-to-severe myolysis in right atrial myocardium with sinus rhythm (P

The optimal right ventricular pacing site remains controversial. The aim of this study was to assess how acute right ventricular outflow tract (RVOT) pacing affects global left ventricular function and intraventricular dyssynchrony of the left ventricle.Thirty-six patients with sick sinus syndrome and intact intrinsic atrioventricular conduction were enrolled. All patients underwent dual-chamber permanent pacemaker implantation, with the atrial lead placed in the right atrial appendage and the right ventricle lead positioned at the septal site of the RVOT. Chamber size, dyssynchrony index, myocardial performance index, and global left ventricular ejection fraction were determined using transthoracic two-dimensional echocardiography, tissue Doppler echocardiography, and real-time three-dimensional echocardiography.RVOT pacing increased the myocardial performance index (0.42 +/- 0.21 with RVOT pacing vs 0.35 +/- 0.21 without RVOT pacing, P = .002) and decreased the global left ventricular ejection fraction on real-time 3-dimensional echocardiography (51.4 +/- 6.2% with RVOT pacing vs 55.9 +/- 7.1% without RVOT pacing, P = .001). Intraventricular dyssynchrony of the left ventricle induced by RVOT pacing was determined by increased septal-to-posterior wall motion delay (69.7 +/- 54.0 ms with RVOT pacing vs 22.8 +/- 22.3 ms without RVOT pacing, P.0001), increased systolic and diastolic dyssynchrony by tissue Doppler echocardiography, and increased systolic dyssynchrony index when assessed using real-time three-dimensional echocardiography (5.56 +/- 1.74% with RVOT pacing vs 4.05 +/- 1.61% without RVOT pacing, P.0001).Acute RVOT pacing adversely affects left ventricular function and increases intraventricular dyssynchrony in patients with sick sinus syndrome.

Objective The aim of this study was to examine the serum oxidative stress in patients with severe mitral regurgitation. Design and methods This study analyzed serum oxidative stress index in patients with severe mitral regurgitation [persistent atrial fibrillation (AF) or sinus rhythm], paroxysmal lone AF patients and healthy subjects. Results The serum oxidative stress index was significantly higher in the mitral regurgitation AF group and sinus group than in the lone AF group and healthy subjects (p

Previous study demonstrated that the percentage of circulating endothelial progenitor cells was reduced in patients with coronary artery disease. However, the relationship of the percentage of circulating endothelial progenitor cells to the severity of coronary artery disease has not been investigated. The percentages of circulating endothelial progenitor cells were measured in 78 consecutive patients with unstable angina, as well as in 32 healthy volunteers. Dual-stained cells expressing CD34 and vascular endothelial growth factor receptor-2 were judged to be endothelial progenitor cells and were analyzed using flow cytometry. On stepwise multiple linear regression analysis, the percentages of circulating endothelial progenitor cells were independently decreased in patients with unstable coronary artery disease compared with those in the healthy volunteers (P < 0.05). Among patients with unstable coronary artery disease, the percentage of patients with at least one occluded vessel was significantly higher in patients with multi-vessel disease than in patients with single-vessel disease (P < 0.04). On stepwise multiple linear regression analysis, the percentages of circulating endothelial progenitor cells were independently decreased in patients with multi-vessel coronary artery disease compared with those in patients with single-vessel coronary artery disease (P < 0.03). Among patients with unstable coronary artery disease, the percentage of circulating endothelial progenitor cells was significantly related to the severity of coronary artery disease.

Interposer-based 3D ICs (or known as 2.5D ICs) have been seen as an alternative approach to true 3D stacked ICs, which mount multiple dies on a silicon interposer and route signals between dies by the interconnects in the interposer. However, the floorplan of dies on the interposer and the signal assignment for macro-bumps and TSVs will largely impact the wirelength of the interconnects in a 2.5D IC. Because long interconnects would degrade the performance of 2.5D ICs, the multi-die floorplanning problem and signal assignment problem for 2.5D ICs are critical. This paper presents an enumeration-based algorithm and a network-flow-based algorithm to solve the multi-die floorplanning and signal assignment problems in a 2.5D IC, respectively. Also, to speed up the floorplanning and signal assignment algorithms, several acceleration techniques are proposed. The experimental results reveal that this work can effectively reduce the total wirelength in a 2.5D IC and the acceleration techniques can significantly speed up the proposed algorithms.

Placement consists of three stages: global placement, legalization, and detailed placement (DP). Recently, most research works have concentrated on improving global placement and legalization, but innovations in DP have been rarely seen. ICCAD13 held a DP contest that formulates the emerging placement issues into a bin-utilization metric and maximum cell displacement constraint. This paper presents a detailed placer that can effectively reduce both half-perimeter wirelength and the peak bin-utilization under the displacement constraint. The proposed lazy-update based incremental density profit function supports efficient cell swapping. Combination of lazy-update density profit function and Density-Driven Swap lets our placer achieve AOFP of 0 for the majority of the ICCAD13 test cases. The placer presented produces the best placement results among the top3 teams in the ICCAD13 contest.

Wire sizing can be used to reduce the delays of critical nets. However, because of the forbidden pitch issue in sub-20nm designs, wide wires may no longer be an attractive solution because of the restrictive wire spacing requirement from advanced lithography. In this work, we investigate the suitability of the parallel wiring technique, in which multiple parallel wires are used to route the same net, as an alternative to routing a net using a single wide wire. In particular, we study the trade offs between parasitics, timing, power, and routing resources. Our study reveals that wire sizing using both parallel wires and wide wires can be advantageous. Moreover, if high layout densities are required, parallel wiring can be a viable approach in solving timing problems for sub-20nm designs.

Antenna effect is an important issue that critically impacts the reliability and yield of integrated circuits. The dynamic-programming-based (DP-based) layer assignment method has been adopted to minimize antenna violation by enumerating all possible solutions and pruning inferior solutions. However, the complexities of modern circuits have significantly increased, likely causing the DP-based method to consume much more runtime and memory space. In this paper, we propose a skillful method to effectively Diminish Antenna effect in Layer Assignment Stage (DALAS). Unlike previous work that needs to search for separator locations and thus requires exploring much more solution space, DALAS does not need to search for separator locations and can deal with local and global antenna effects while trying to keep total via count and total overflow minimal. Experiment results show that DALAS is the first work to expel all antenna violations with similar via count to that produced by previous works [3][5] for the benchmarks in ISPD'08 Global Routing Contest.

To avoid producing unroutable placement solutions, many state-of-the-art routability-driven placers iteratively invoke global routers to evaluate their placement solutions and then perform routability optimization. However, using a global router to evaluate hard-to-route placement solutions may spend considerable runtime and it cannot guarantee that a placement is truly unroutable to any router. This paper presents an unroutable placement recognizer based on a window-based layout scanning algorithm, which can confirm some placements that are exactly unroutable among a set of hard-to-route placements. In addition, if a placement is recognized to be unroutable, the recognizer can point out unroutable regions and report a lower bound of total overflow for the placement. The experimental results reveal that the proposed recognizer can find out 16 placements that are definitely unroutable among 23 widely used hard-to-route global routing benchmarks.

Obstructive sleep apnea syndrome (OSAS) has been considered to be an important predisposing factor for cardiovascular disease. This study aims to investigate the impact of OSAS on cardiac function and remodeling in patients without congestive heart failure.A total of 79 patients with sleep disordered breathing, preserved systolic function, and normal pro-brain natriuretic peptide level were enrolled. Sixty-five patients were classified to have moderate to severe OSAS (apnea-hypopnea index [AHI] ≥ 15/h), while the other 14 patients with mild or no OSAS (AHI15/h) served as control subjects. Baseline clinical and polysomnographic variables as well as tissue Doppler imaging and three-dimensional echocardiographic parameters were obtained.The body mass index, neck circumference, Epworth Sleepiness Scale, desaturation index, arousal index, and snoring index were significantly higher in patients with moderate to severe OSAS than those without (p0.05). The left atrial size, mitral A-wave velocity, and left ventricular end-diastolic volume were significantly larger, while E/A ratio was lower in patients with moderate to severe OSAS than those without (p0.05). Notably, AHI in REM sleep was significantly correlated with the aortic root size, E/A ratio, left ventricular volume, and stroke volume. In addition, the area under the receiver operator characteristic curve for AHI in REM sleep ≥ 32.3/h was 0.647 (95% CI [0.525, 0.769]) in predicting the development of left ventricular diastolic dysfunction. AHI in REM sleep ≥ 32.3/h was the only independent variant in predicting diastolic dysfunction after adjusting the variables including age, gender, hypertension, and body mass index.Patients with moderate to severe OSAS tend to have cardiac dysfunction revealed by echocardiography. High AHI in REM sleep is significantly associated with cardiovascular remodeling and ventricular diastolic dysfunction, and may be a potential variable to predict cardiac dysfunction.

In an attempt to develop safe and robust methods for monitoring migraineurs' brain states, we explores the feasibility of using white, red, green and blue LED lights flickering around their critical flicker fusion (CFF) frequencies as foveal visual stimuli for inducing steady-state visual evoked potentials (SSVEP) and causing discernible habituation trends. After comparing the habituation indices, the multi-scale entropies and the time dependent intrinsic correlations of their SSVEP signals, we reached a tentative conclusion that sharp red and white light pulses flickering barely above their CFF frequencies can replace commonly used 13Hz stimuli to effectively cause SSVEP habituation among normal subjects. Empirical results showed that consecutive short bursts of light can produce more consistent responses than a single prolonged stimulation. Since these high frequency stimuli do not run the risk of triggering migraine or seizure attacks, further tests of these stimuli on migraine patients are warranted in order to verify their effectiveness.

Routability has become a critical issue in VLSI design flow. To avoid producing an unroutable design, many placers [4-7] invoke global routers to get a congestion map and then move cells to reduce congestion based on this map. However, as cells move, the accuracy of the congestion map degrades, thereby affecting the effectiveness of the placer in minimizing congestions. Moreover, most global routers [8-13] ignore local congestion. If placers are guided by these routers, it may produce hard-to-route placement solutions in terms of detailed routing. This work develops a routability optimizer, called Ropt, to reduce both global and local routing congestion levels of a given placement. Based on a local-routability-aware routing model, Ropt builds a global routing instance to obtain global and local congestion information for guiding global re-placement. In addition, this work presents a new legalization scheme to preserve the global routing instance after legalization. Finally, local detailed placement further minimizes the local congestion and wirelength. For the evaluation of Ropt, we use an academic global router and a commercial router to obtain both global and detailed routing results, respectively. Experimental results reveal that Ropt can improve the routing quality (in terms of congestion, wirelength, and violation) and routing runtime of a given placement solution.

To address the routability issue, routing congestion estimators (RCE) become essential in industrial design flow. Recently, several RCEs [1-4] based on global routing engines are developed, but they typically ignore the effects of routing on timing so that the identified routing paths may be overlong and thus impractical. To be aware of the timing issues, our proposed global-routing-based RCE obeys the layer directive and scenic constraints to respectively limit the routing layers and the maximum routing wirelength of the potentially timing-critical nets. To handle the scenic constrains, we propose a novel method based on a relaxation-legalization scheme. Also, because the work in [5] reveals that congestion ratio is a better indicator than overflow to evaluate routability, this work focuses on minimizing the congestion ratio rather than overflows. As will be shown, the problem of minimizing congestion ratio is more complicated than minimizing overflows, so we develop a new rip-up and rerouting scheme to reduce congestion and further to approach a target congestion ratio. Moreover, to fit the demands of practical uses, this work presents a control utility to trade off runtime and quality, which is an essential function to an industrial RCE tool. Experiments reveal that the proposed RCE is faster and more accurate than another industrial global-routing-based RCE.