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Phase Change Memory (PCM), with its better scaling potential compared to DRAM, is seen as a promising candidate to replace or complement DRAM. The heat generated from a RESET programming pulse to a PCM cell can disturb the neighboring cells which are not being programmed. Write disturbance (WD) poses a critical reliability challenge in high-density PCM memory with scaling below 20nm process technology node. Increasing the intra-cell space can eliminate the WD, however, it reduces the storage density which counteracts the benefits of scalability in PCM. Due to its dependence on the type of programming operation and the state of the neighboring cell, WD is a data-dependent problem. Exploiting this property, encoding techniques have been proposed to reduce the frequency of WD-vulnerable data patterns. These techniques, however, do not eliminate the WD in an array and ultimately rely on the VnC method to ensure reliable memory operation. This paper introduces a novel architecture, based on encoding and multi-level programming characteristics of PCM, to eliminate the intra-array WD in PCM. Our evaluation of the proposed architecture shows an average reduction of 57% in the number of writes (to service one write request) over the previous state-of-the-art.

Background Tigecycline is an antibiotic that well tolerated for treating complicated infections. It has received attention as an anti-cancer agent and expected to solve two major obstacles, sides effects that accompany chemotherapy and drug resistance, in the breast cancer treatment. However, previous studies reported that the levels in the blood are typically low of tigecycline, so higher doses are needed to treat cancer, that may increase the risk of side effects. To achieve better anti-cancer effects for tigecycline, we need to find a novel adjunct agent. Methods In this study, we used different concentration of pyrvinium pamoate combined with tigecycline to treat cell. And assess the effect of two drugs in inhibit cell proliferation, induce cell autophagy, or increase cell apoptosis to evaluate the consequent of combined therapy. Results We observed that after the combined therapy, the cell cycle arrest at G1/s phase, the level of p21 increased, but decreased the levels of CDK2. Others, two drugs via different mechanisms to inhibit cancer cell proliferation and with selective cytotoxic to different cell lines. That could enhance the effect of breast cancer treatment. Conclusion Combining low dose of tigecycline use with pyrvinium pamoate is a novel approach for breast cancer treatment. Appropriate combined therapy in breast cancer is recommended to improve outcomes. Other problems like drug resistance occur in patients or the microbes surrounding breast tissues would confer susceptibility to cancers then influence the effectiveness of treatment, which could be improved through combined therapy.

We aimed to evaluate the long-term risk of ischemic stroke/systemic embolism of hyperthyroidism-related AF.This retrospective population-based cohort study included records of 1,034,099 atrial fibrillation patients between 2005 and 2016 from the Korean National Health Insurance Service database. After exclusion, we identified 615,724 oral anticoagulation-naïve patients aged ≥18 years with new-onset non-valvular atrial fibrillation, of whom 20,773 had hyperthyroidism-related atrial fibrillation. After 3:1 propensity score matching, ischemic stroke and systemic embolism occurrences were compared between hyperthyroidism-related and non-hyperthyroidism-related ("nonthyroidal") atrial fibrillation patients.After exclusion, we identified 615,724 oral anticoagulation-naïve AF patients of whom 20,773 had hyperthyroidism-related AF. Median follow-up duration was 5.9 years. Hyperthyroidism-related AF patients had significantly higher risks of ischemic stroke and systemic embolism than nonthyroidal AF patients (1.83 vs 1.62 per 100-person year, hazard ratio[HR], 1.13; 95% confidence interval[CI], 1.07 to 1.19; P0.001). This risk was 36% higher in hyperthyroidism-related than in nonthyroidal AF patients within 1 year of atrial fibrillation diagnosis (3.65 vs 2.67 per 100-person year, HR, 1.36; 95% CI, 1.24 - 1.50; P0.001). This difference was also observed in the CHAHyperthyroidism-related AF patients have high risks of ischemic stroke and systemic embolism like nonthyroidal AF, especially when initially diagnosed. This risk is reduced by treating hyperthyroidism.

Several antimicrobial combination therapies are used to treat multiple drug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii infections. A novel antibiotic, eravacycline, shows a higher potency than tigecycline. The efficacies of eravacycline-based therapies have not yet been evaluated. We demonstrated the effectiveness of eravacycline- and tigecycline-based combination therapies in XDR and especially tigecycline resistant A. baumannii. Thirteen eligible isolates were selected from 642 non-duplicate Acinetobacter blood isolates from four medical centres in 2010-2014. Tigecycline/imipenem and eravacycline/imipenem combinations were simultaneously effective against some isolates in vitro with fractional inhibitory concentration index of 0.5. In contrast, eravacycline- and tigecycline-based combination therapies provided no additional benefits in mouse survival compared to those for monotherapy. In summary, colistin is still the final resort for XDR-A. baumannii treatment according to the sensitivities. Owning to rapid development of resistance in A. baumannii, novel antibiotics are urgently needed.

Background The efficacy of implantable cardioverter defibrillators (ICDs) for primary prevention is controversial in patients with nonischemic heart failure (HF). We evaluated the mortality and predictors of mortality in patients with prophylactic ICD implantation for ischemic and nonischemic HF. Methods From 2008 to 2017, 1097 patients (667, nonischemic HF and 430, ischemic HF) who underwent prophylactic ICD implantation, were identified from the Korean National Health Insurance Service database. We used propensity score overlap weighting to correct the differences between two groups. Results Those with ischemic HF were older (67.0 ± 10.1 vs 61.8 ± 14.2 years), more often male (71.4% vs 63.7%), and had more comorbidities than patients with nonischemic HF. During a median follow‐up of 37.3 months (interquartile range [IQR], 14.2‐53.8 months), all‐cause mortality was higher in unweighted patients with ischemic HF than in those with nonischemic HF (10.9 vs 6.4 per 100 person‐years; hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.38‐2.20; P, In contemporary HF patients undergoing prophylactic ICD implantation in Korea, all‐cause, cardiac, and non‐cardiac mortality rates were similar between patients with non‐ischemic and ischemic HF when weighting is performed to account for differences in patient characteristics. Therefore, the benefit of prophylactic ICD therapy in HF patients should not be restricted to ischemic patients.

Next-generation memories have been actively researched to replace the existing memories like DRAM and flash in deep sub-micron process technology. Unlike the conventional charge-based memories, next-generation memories utilize the resistive properties of different materials to store and read a data. Among the next-generation memories, Phase Change Memory (PCM) is seen as a good choice for future memory systems, given its good read performance, process compatibility and scaling potential. To enhance the storage density, multi-level cell (MLC) operation is seemed promising which can store more than one bit in each PCM cell. However, MLC operation significantly degrades the reliability of PCM, thus requiring a strong Error Correction Code (ECC) to guarantee correct memory operation. The use of heavyweight ECC comes at cost of significant degradations in storage density, performance and energy efficiency. In this article, we propose a heterogeneous PCM architecture which uses both multi-level cell and single-level cell (SLC) together for a single word line. With highly-reliable SLC cells, the overall array reliability is enhanced. To improve the reliability further, a dynamic self-encoding/decoding scheme is performed before the data is written to the PCM cells. The dynamic scheme automatically determines the locations of MLC and SLC cells and sets the corresponding resistance levels to be programmed. Since the proposed encoding/decoding scheme does not require any additional stages or storages for encoding and decoding, the overhead is negligible. The improved reliability allows to use lighter ECC scheme which in turn helps to improve performance and energy efficiency of the MLC PCM. The experimental results show that the reliability is improved by approximately $10^6$ 10 6 times compared to the conventional 4LC and more than $10^3$ 10 3 times compared to the existing encoding methods. The performance improvement is 21.5 percent over the conventional 4LC and is more than 4.1 percent higher than the prior encoding techniques. The proposed method is 30.3 percent more energy efficient than the conventional 4LC and this is similar or higher than other energy efficiency improvement methods.

Atrial fibrillation (AF), the most common cardiac arrhythmia in the elderly population, has been associated with an impairment of cognitive function and an increased risk of dementia. Even though there does not appear to be solid evidence that any specific treatment prevents or delays AF-associated cognitive decline, evidence is accumulating regarding the possible treatment strategies for preventing dementia. Oral anticoagulation, especially non-vitamin K antagonist oral anticoagulants rather than warfarin use, has been suggested to be associated with reduced risk of dementia. Successfully maintaining sinus rhythm using catheter ablation might be also helpful in preventing subsequent dementia in patients with AF. In this review, we critically appraise the proposed treatment strategies for preventing AF-associated cognitive decline.

Background Catheter ablation is more effective than antiarrhythmic drug therapy alone in patients with atrial fibrillation (AF). However, there are limited data on the outcomes of AF ablation according to sex. The purpose of this study was to evaluate gender differences in the actual outcomes after catheter ablation for atrial fibrillation. Methods Of 801,710 patients with AF in the Korean National Health Insurance Service database, we identified 9175 patients without valvular heart disease who underwent AF ablation between 2006 and 2015 and assessed 30-day safety and one-year effectiveness outcomes according to sex. Results Of the 9175 patients who underwent AF ablation, 2206 (24%) were female. Women, compared to men, were older (60.8 ± 10.2 vs. 56.0 ± 10.5 years), had higher CHA2DS2-VASc (3.5 ± 1.7 vs. 2.0 ± 1.6), higher HAS-BLED (2.6 ± 1.3 vs. 2.4 ± 1.2), and higher Charlson comorbidity index scores (3.8 ± 2.6 vs. 3.1 ± 2.5) (p Conclusion Women who underwent AF ablation did not differ from men in terms of the risk of complications and all-cause hospitalization in this study. The small increased risk in women reported in previous studies may be related to residual confounding, particularly from insufficient control for age and comorbidities.

Infections caused by extensively drug-resistant (XDR) Acinetobacter nosocomialis have become a challenging problem. The frequent use of colistin as the last resort drug for XDR bacteria has led to the emergence of colistin-resistant A. nosocomialis (ColRAN) in hospitals. The mechanism of colistin resistance in A. nosocomialis remains unclear. This study aimed to investigate the mechanisms underlying colistin resistance in clinical ColRAN isolates. We collected 36 A. nosocomialis isolates from clinical blood cultures, including 24 ColRAN and 12 colistin-susceptible A. nosocomialis (ColSAN). The 24 ColRAN isolates clustered with ST1272 (13), ST433 (eight), ST1275 (two), and ST410 (one) by multilocus sequence typing. There was a positive relationship between pmrCAB operon expression and colistin resistance. Further analysis showed that colistin resistance was related to an amino acid substitution, Ser253Leu in PmrB. By introducing a series of recombinant PmrB constructs into a PmrB knockout strain and protein structural model analyses, we demonstrated that the association between Ser253Leu and Leu244 in PmrB was coupled with colistin resistance in ColRAN. To the best of our knowledge, this is the first study demonstrating that the key amino acid Ser253Leu in PmrB is associated with overexpression of the pmrCAB operon and hence colistin resistance. This study provides insight into the mechanism of colistin resistance in A. nosocomialis.

Background Infections are the most common complications among hospitalized severe burn patients. However, limited literature reports early effective predictors of bloodstream infections (BSI) among burn patients. This study aimed to identify cost-effective biomarkers and valuable clinical scoring systems in the emergency department (ED) for the prediction of subsequent BSI in mass burn casualties. Methods In 2015, a flammable cornstarch-based powder explosion resulted in 499 burn casualties in Taiwan. A total of 35 patients were admitted at Taipei Veterans General Hospital. These severe burn patients (median total body surface area [TBSA] 54%) were young and previously healthy. We assessed the potential of various parameters to predict subsequent BSI, including initial laboratory tests performed at the ED, TBSA, and multiple scoring systems. Results Fourteen patients (40.0%) had subsequent BSI. The most common causative pathogen was the Acinetobacter baumannii (Ab) group, mostly carbapenem resistant and associated with a poor outcome. The area under the receiver operating characteristic curve revealed that the revised Baux score, TBSA, and initial white blood cell count had excellent discrimination ability in predicting subsequent BSI (0.898, 0.889, and 0.821, respectively). The rate of subsequent BSI differed significantly at the cut-off points of revised Baux score >76, TBSA >55%, and WBC count >16,200/mm3. Conclusion The initial WBC count at the ED, TBSA, and revised Baux score were good and cost-effective biomarkers for predicting subsequent BSI after burn injuries.

Background Sinoatrial node dysfunction and atrial fibrillation (AF) frequently coexist and interact with each other, often to initiate and perpetuate each other. Objective To determine the effect of AF on the incidence and risk of sick sinus syndrome (SSS). Methods The association of incident AF with the development of incident SSS was assessed from 2004 to 2014 in 302,229 SSS- and pacemaker-free subjects aged ≥60 years in the Korea National Health Insurance Service-Senior cohort. Results During an observation period of 1,854,800 person-years, incident AF was observed in a total of 12,797 subjects (0.69%/year). The incidence of SSS was 3.4 and 0.2 per 1000 person-years in the propensity score matched incident AF and no-AF groups, respectively. After adjustment, the significantly increased risk of SSS was observed in the incident AF group, with a hazard ratio (HR) of 13.4 (95% confidence interval [CI]: 8.4-21.4). This finding was consistently observed after censoring for heart failure (HR, 16.0; 95% CI: 9.2-28.0) or heart failure/myocardial infarction (HR, 16.6; 95% CI: 9.3-29.7). Incident AF also was associated with an increased risk of pacemaker implantation related with both SSS (HR, 21.8; 95% CI: 8.7-18.4) and atrioventricular (AV) block (HR, 9.5; 95% CI: 4.9-18.4). These results were consistent regardless of sex and comorbidities. Conclusion Incident AF was associated with more than ten times increased risk of SSS in an elderly population regardless of comorbidities. The risk of pacemaker implantations related with both sinus node dysfunction and AV block was increased in the elderly population with incident AF. This article is protected by copyright. All rights reserved.

Objective: The excess risk of atrial fibrillation in relation to the presence of proteinuria associated with hypertension has not been well elucidated. We aimed to determine the effect of hypertension and/or proteinuria on the incidence of atrial fibrillation. Second, we evaluated whether the associations with temporal changes in proteinuria status on the incidence of atrial fibrillation. Methods and results: A total of 85 434 participants with hypertension and 125 912 participants without hypertension with age at least 60 years from the Korea National Health Insurance Service-Senior cohort were included. Amongst controls (participants without proteinuria and hypertension), hypertension only, proteinuria only, and hypertension with proteinuria groups, the adjusted incidences of atrial fibrillation were 0.51, 0.69. 0.78 and 0.99 per 100 person-years, respectively after inverse probability of treatment weighting. Compared with controls, the weighted risks of atrial fibrillation in the hypertension only, proteinuria only and hypertension with proteinuria groups were increased by 37% (hazard ratio 1.37, 95% confidence interval, CI 1.30–1.44, P = 0.001), 55% (hazard ratio 1.55, 95% CI 1.28–1.88, P

Diabetes mellitus (DM) is considered an independent risk factor for atrial fibrillation (AF). The excess risk in relation to the presence of proteinuria has not been well elucidated. Our aim was to determine the association between the incidence of AF and proteinuria in diabetic population. A total of 240,499 individuals aged ≥ 60 years from the Korea National Health Insurance Service-Senior cohort from 2004 to 2014 were included. 4.2% of individuals with DM and 3.7% of controls were diagnosed with AF during a median follow-up period of 7.2 years. Amongst controls (participants without proteinuria and DM), DM only, proteinuria only, and DM with proteinuria groups, the crude incidences of AF were 0.58, 0.70, 0.96, 1.24 per 100 person-years respectively. Compared with controls, the weighted risk of AF was increased by 11% (hazard ratio = 1.11, 95% confidence interval = 1.02–1.20, P = .001), 48% (hazard ratio = 1.48, 95% confidence interval = 1.30–1.69, P

BACKGROUND It is unclear whether catheter ablation is beneficial for frail elderly patients with atrial fibrillation (AF). This study evaluated the effect of ablation on outcomes in frail elderly patients with AF.Methods and Results:From the Korean National Health Insurance Service database, 194,928 newly diagnosed AF patients were treated with ablation or medical therapy (rhythm or rate control) between 2005 and 2015. Among these patients, the study included 1,818 (ablation; n=119) frail and 1,907 (ablation; n=230) non-frail elderly (≥75 years) patients. Propensity score matching was used to correct for differences between groups. During 28 months (median) follow up, the risk of all-cause death, composite outcome (all-cause death, heart failure admission, stroke/systemic embolism, and sudden cardiac arrest), and each outcome did not change after ablation in frail elderly patients. However, in non-frail elderly patients, ablation was associated with a lower risk of all-cause death (3.5 and 6.2 per 100 person-years; hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.30-0.79; P=0.004), and composite outcome (6.9 and 11.2 per 100 person-years; HR 0.54; 95% CI 0.38-0.75; P

Objective The ‘Atrial fibrillation Better Care’ (ABC) pathway has been recently proposed as a holistic approach for the comprehensive management of patients with atrial fibrillation (AF). We performed a systematic review of current evidence for the use of the ABC pathway on clinical outcomes. Methods and Results We performed a systematic review and meta-analysis according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and EMBASE were searched for studies reporting the prevalence of ABC-pathway-adherent management in AF patients, and its impact on clinical outcomes (all-cause death, cardiovascular death, stroke, and major bleeding). Meta-analysis of odds ratio (OR) was performed with random-effects models; subgroup analysis and meta-regression were performed to account for heterogeneity. Among the eight studies included, we found a pooled prevalence of ABC-adherent management of 21% (95% confidence interval, CI: 13–34%), with a high grade of heterogeneity, explained by the increasing adherence to each ABC criterion. Patients treated according to the ABC pathway showed a lower risk of all-cause death (OR: 0.42; 95% CI: 0.31–0.56), cardiovascular death (OR: 0.37; 95% CI: 0.23–0.58), stroke (OR: 0.55; 95% CI: 0.37–0.82) and major bleeding (OR: 0.69; 95% CI: 0.51–0.94), with moderate heterogeneity. Prevalence of comorbidities was moderators of heterogeneity for all-cause and cardiovascular death, while longer follow-up was associated with increased effectiveness for all outcomes. Conclusion Adherence to the ABC pathway was suboptimal, being adopted in one in every five patients. Adherence to the ABC pathway was associated with a reduction in the risk of major adverse outcomes.

ObjectiveTo evaluate whether baseline and changes in cardiovascular health (CVH) were related to incident atrial fibrillation (AF) risk in the elderly population.MethodsFrom the Korea National Health Insurance Service-Senior cohort, we included 208 598 participants without prior AF (median age: 70 (IQR 66–74) years; 90 916 (43.6%) men) who underwent national health check-ups between 1 January 2005 and 31 December 2012. Using the six metrics of the American Heart Association, participants were categorised as having low, moderate and high CVH.ResultsOver a median follow-up of 7.2 years, 7818 cases of incident AF occurred. In multivariable analysis, moderate (HR: 0.90; 95% CI: 0.86 to 0.94) and high (HR: 0.81; 95% CI: 0.73 to 0.91) CVH status at baseline were associated with a lower risk of incident AF. However, in 109 695 participants with changes in CVH between the first and second check-ups, the direction of change in CVH scores showed no consistent association with future AF incidence. In newly diagnosed participants with AF, the incidence of the composite outcome (stroke, major bleeding and all-cause death) decreased with every 1-point increase in the baseline CVH score (HR: 0.94; 95% CI: 0.89 to 0.99).ConclusionsIn the general elderly population, better baseline CVH metrics were associated with lower incident AF risk. In participants with newly diagnosed AF, better CVH was also associated with lower incidence of future composite outcomes. However, the direction of change in CVH status within 2 years showed an inconsistent influence on incident AF risk.

Currently, the semiconductor manufacturing industry is seeing rapid movement from 2D planar to 3D FinFET technology. Among SCE-enhanced scaled fin structures, depending on stress engineering to increase mobility, merged elevated source–drain (eSD) epi structures are widely used because they can maximize device performance by reducing Rsd. While there is active research on device and epi own defects related to eSD process, there is no study on yield effect. Smart manufacturing (SM) applications, which form the core of Industry 4.0, are difficult to find in bulk-FinFETs, and it is difficult to find hidden systematic defects of complex three-dimensional structures using limited analyses such as in-line monitoring and abnormal trend detection. In this study, we investigate the root-cause of gate to eSD short, which is the primary FinFET yield detractor, and we obtain an optimized solution to improve yield by 25.2% without performance degradation. These improvements are accomplished using our in-house SM platform that consists of four components: a virtual integration (VI) module for defining defects such as physical connection, void, and not open; a hot spot module for identifying the location of needed process control; an advanced analytics module including algorithms for selecting key features and predicting the fail bit; and an optimizer module that can co-optimize yield and performance.

Author's summary Atrial fibrillation (AF) has been associated with an increased risk of dementia. Although there does not appear to be solid evidence that any specific treatment prevents or delays AF-associated cognitive decline, evidence is accumulating regarding the possible treatment strategies for preventing dementia. In this review, we summarize the evidence linking AF to dementia and critically appraise the proposed treatment strategies., Atrial fibrillation (AF) is the most common form of arrhythmia in the elderly population and increases stroke risk by a factor of 4- to 5-fold. There is increasing evidence to suggest that incident AF may contribute to the development of dementia, independent of overt stroke. In particular, relatively younger patients with AF are more prone to dementia development than older patients with AF. Evidence is accumulating regarding the possible treatment strategies for preventing dementia in patients with AF. Oral anticoagulation may be effective for reducing the risk of dementia, even in patients with low stroke risks. Among oral anticoagulants, the use of non-vitamin K antagonists have been associated with a considerably decreased risk of dementia than warfarin. Moreover, successful catheter ablation for AF has also been associated with decreased dementia risk compared to medical therapy, suggesting that restoration of sinus rhythm, and not the ablation procedure itself, as the important mechanism in the prevention of AF-associated dementia. Among midlife patients with AF, there appeared to be a U-shaped association of blood pressure (BP) and a linear association of hypertension with dementia risk. A BP of 120 to 129/80 to 84 mmHg has been identified as the optimal range. Finally, integrated management of AF was associated with a reduced risk of dementia in AF patients.

Purpose Cardiovascular health (CVH) status is associated with several cardiovascular outcomes; however, correlations between changes in CVH status and risk of sudden cardiac death (SCD) are unknown. We aimed to evaluate associations between changes in CVH status and risk of SCD and all-cause death in older adults. Materials and methods We used data from the Korea National Health Insurance Service-Senior cohort database (2005-2012). Six metrics from the American Heart Association (smoking, body mass index, physical activity, blood pressure, total cholesterol, and fasting blood glucose) were used to calculate CVH scores. Changes in CVH status between two health checkups were categorized as low to low, low to high, high to low, and high to high. Results We included 105200 patients whose CVH status for an initial and follow-up health checkup (2-year interval) was available. During a median of 5.2 years of follow-up after a second health checkup, 688 SCDs occurred. Compared to patients with a persistent low CVH status, those with a consistently high CVH status had a reduced risk of SCD [adjusted hazard ratio (HR), 0.69; 95% confidence interval (CI), 0.56-0.86] and all-cause death (adjusted HR, 0.74; 95% CI, 0.69-0.78). The risk of all-cause death followed similar trends. However, an inconsistent linear relationship was observed for changes in CVH status and the risk of SCD, but not of all-cause death. Conclusion Maintaining a high CVH status was associated with future risks of SCD and all-cause death among an older adult population.

Hand-gesture based control has enormous potential both theoretically and for practical applications due to its convenience and intuitiveness. This study presents a real-time interactive control system for household appliances. The interactive control system allowing wireless control of household appliances using a combination of 11 hand gestures and 2 waving motions is tested on hundreds of samples. It is implemented using a regular personal computer (PC) and existing digital single processing (DSP) platforms. The evaluation results show that the system performs efficiently reaching an accuracy recognition rate of 91% and spending around 30 seconds to complete the control operation for household appliances. The contributions of this work are both academic (1) successful demonstration of the integration of algorithms for solving image detection, processing, and pattern recognition, and practical (2) showing its feasibility and using commonly available hardware and software configurations for practical uses, and finally (3) establishing a mechanism for intuitively interactive control system that facilitates smart living.

Objectives Acinetobacter seifertii, a new member of the Acinetobacter baumannii group, has emerged as a cause of severe infections in humans. We investigated the clinical and molecular characteristics of A. seifertii. Patients and methods This retrospective study enrolled 80 adults with A. seifertii bloodstream infection (BSI) at four medical centres over an 8 year period. Species identification was confirmed by MALDI-TOF MS, rpoB sequencing and WGS. Molecular typing was performed by MLST. Clinical information, antimicrobial susceptibility and the mechanisms of carbapenem and colistin resistance were analysed. Transmissibility of the carbapenem-resistance determinants was examined by conjugation experiments. Results The main source of A. seifertii BSI was the respiratory tract (46.3%). The 28 day and in-hospital mortality rates of A. seifertii BSI were 18.8% and 30.0%, respectively. High APACHE II scores and immunosuppressant therapy were independent risk factors for 28 day mortality. The most common MLST type was ST553 (58.8%). Most A. seifertii isolates were susceptible to levofloxacin (86.2%), and only 37.5% were susceptible to colistin. Carbapenem resistance was observed in 16.3% of isolates, mostly caused by the plasmid-borne ISAba1-blaOXA-51-like genetic structure. A. seifertii could transfer various carbapenem-resistance determinants to A. baumannii, Acinetobacter nosocomialis and other A. seifertii isolates. Variations of pmrCAB and lpxCAD genes were not associated with colistin resistance of A. seifertii. Conclusions Levofloxacin and carbapenems, but not colistin, have the potential to be the drug of choice for A. seifertii infections. A. seifertii can transfer carbapenem-resistance determinants to other species of the A. baumannii group and warrants close monitoring.

Background The impact of appropriate antimicrobial therapy for A. baumannii bacteremic pneumonia has not been well established due to the inclusion of the three phenotypically indistinguishable Acinetobacter species and confounding factors including underlying diseases and severity of infection. This retrospective study aimed to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality in A. baumannii bacteremic pneumonia patients after adjusting for risk factors. Methods This study was conducted at five medical centers in Taiwan between July 2012 and June 2016. A. baumannii species identification was performed using reference molecular methods. Risk factors for 14-day mortality were analyzed via logistic regression. The interaction between the Acute Physiology and Chronic Health Evaluation (APACHE) II score and appropriate antimicrobial therapy was assessed using the logistic model. Results A total of 336 patients with monomicrobial A. baumannii bacteremic pneumonia were included in this study. The overall 14-day mortality rate was 47.3%. The crude mortality of appropriate antimicrobial therapy was 35.9% (57 of 151 patients). Appropriate antimicrobial therapy was associated with a lower mortality after multivariate adjustment (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.34–0.97; p = 0.04), and the effect was influenced by APACHE II score (OR for interaction term, 0.0098; 95% CI, 0.0005–0.1885; p = 0.002). Further analysis demonstrated that appropriate antimicrobial therapy significantly reduced 14-day mortality among the patients with an APACHE II score > 35 (OR 0.0098; 95% CI 0.0005–0.1885). Conclusion Appropriate antimicrobial therapy decreases 14-day mortality of the most severely ill patients with A. baumannii bacteremic pneumonia.

Background The benefit of integrated care management was unknown in frail atrial fibrillation (AF) patients. This study evaluated whether compliance with the atrial fibrillation Better Care (ABC) pathway for integrated care management would improve clinical outcomes in frail AF patients. Methods From the Korea National Health Insurance Service database, 262,987 nonvalvular AF patients were enrolled between 1 January 2005 and 31 December 2015. For each patient, the Hospital Frailty Risk Score and category were calculated retrospectively using all available ICD‐10 diagnostic codes. Patients were divided into three frailty‐based risk categories: low (15 points, n = 4,104). Results Over a mean follow‐up of 5.9 (interquartile range 3.2, 9.4) years, in high frailty risk patients, the ABC group had lower rates of all‐cause death (6.5 vs 17.5 per 100 person‐years, P, Compliance with the simple ABC pathway is associated with improved outcomes in AF patients with high frailty risk.

Hemoglobin level determines blood viscosity and as hemoglobin level rises, blood pressure rises. However, hemoglobin level in individuals is not fixed and change in hemoglobin is affected by various clinical conditions. The purpose of this study is to investigate whether the hemoglobin variability affects the development of hypertension using Korean cohort database. This study was conducted with 94,798 adults (age ≥ 40 years) who visited the health screening in 2006 or 2007 (index year) and had at least 3 health screenings from 2002 to 2007. Hemoglobin variability was assessed by 3 indices of coefficient of variation (CV), standard deviation, and variability independent of the mean. Cox proportional hazard regression analysis was performed for each index of quartile groups (Q1–Q4). A total of 29,145 participants (30.7%) had the incidence of hypertension during a median follow-up of 7.4 ± 2.5 years. In the multivariable adjusted model, the hazard ratio and 95% confidence interval for incidence of hypertension of Q2, Q3, and Q4 compared with Q1 of hemoglobin variability CV were 1.014 [0.981–1.047], 1.064 [1.030–1.099] and 1.094 [1.059–1.131] respectively. The results were consistent in various sensitivity and subgroup analyses. This study showed that hemoglobin variability could be associated with hypertension development.

This primarily interview-based study explores the perspectives of published applied linguists around the world on what has facilitated their success in reaching multiple readerships. The focus, more specifically, is on scholars in non-English-dominant settings, a number of whom have made a commitment to both inter- and intranational academic publication, and their perceptions of intercultural rhetoric issues salient in various linguacultural contexts. The findings indicated that such scholars were divided in their views on whether or not there are considerable differences in the rhetorical expectations of international Anglophone and more region-specific, or intranational, journal audiences. What this study’s participants shared was an appreciation of the complexities of authorial cross-contextual negotiation of multiple research worlds, only some of which are Anglophone.

Clock network plays the most significant role in power consumption in IC design. Since a clock network normally has a high switching ratio, power optimization of the clock network is one of the best solutions to minimize dynamic power and total power in modern IC designs. The clock network is synthesized based on an initial flip-flop placement. The number of clock buffers and their sizes are decided by the initial placement. Moreover, clock wires, which are the major sources of clock power consumption, are also constructed based on the flip-flop placement. As a result, the flip-flop placement determines the quality of the clock network. In this article, we propose a new clock network optimization method to reduce the dynamic power consumption of clock network. The method first creates virtual tiles over the entire design area and selects the most effective columns to align flip-flops in lines. Once the effective columns are determined, flip-flops are relocated based on the virtual tiles in the columns considering the minimum moving distance. By aligning flip-flops, it is possible to significantly reduce both wire capacitance and wire length. Since it does not change the clock structure, unlike the conventional clock network optimization techniques which use multibit flip-flop or register bank, there is no degradation in timing or other constraints. Experimental results show that the proposed method reduces the wire capacitance, wire length, and via count up to 23.2%, 10.2%, and 16.4%, respectively, in five industrial intellectual property (IP) designs. The reduction in clock network power is 14.1% on average.

Static random access memory (SRAM)-based ternary content-addressable memory (TCAM) on field-programmable gate arrays (FPGAs) is used for packet classification in software-defined networking (SDN) and OpenFlow applications. SRAMs implementing TCAM contents constitute the major part of a TCAM design on FPGAs, which are vulnerable to soft errors. The protection of SRAM-based TCAMs against soft errors is challenging without compromising critical path delay and maintaining a high search performance. This brief presents a low-cost and low-response-time technique for the protection of SRAM-based TCAMs. This technique uses simple, single-bit parity for fault detection which has a minimal critical path overhead. This technique exploits the binary-encoded TCAM table maintained in SRAM-based TCAMs for update purposes to implement a low-response-time error-correction mechanism at low cost. The error-correction process is carried out in the background, allowing lookup operations to be performed simultaneously, thus maintaining a high search performance. The proposed technique provides protection against soft errors with a response time of 293 ns, whereas maintaining a search rate of 222 million searches per second on a $1024\times40$ size TCAM on Artix-7 FPGA.

Background/purposes: Infective endocarditis (IE) is an important cause of morbidity and mortality in hemodialysis (HD) patients. Data on the differences in the microbiological features as well as clinical characteristics and outcomes of HD and non-HD patients with IE are limited. Methods: Medical records of patients (aged over 20 years) with IE were retrospectively reviewed from January 2008 to June 2017 in a tertiary care center in Northern Taiwan. Those with definite or possible IE were included in the study. The clinical characteristics, microbiological results, echocardiographic findings and outcomes of patients were analyzed. Results: Of the 183 patients with definite or possible IE, 47 had undergone HD and 136 had not. Advanced age (67.3 vs. 61.5 years, p = 0.027), more female gender (51.1% vs. 33.8%, p = 0.036), comorbidities (a high Charlson comorbidity index, 8.17 vs. 4.21, p

The existing charge-based memories like DRAM and flash are reaching their scaling limits. Phase change memory (PCM) is one of the most promising emerging memory technologies due to its good scalability and low leakage power. Multi-level cell (MLC) operation in PCM, which stores two or more bits in a single cell, is necessary to achieve a high storage density. However, a reduced resistance range in multiple storage levels of MLC PCM, introduces a lot of soft errors because of the resistance drift phenomenon. The poor reliability of MLC PCM requires strong error correction codes (ECC) which could severely degrade the storage density and performance. In this paper, we propose a cost-effective reliable MLC PCM architecture for improving MLC PCM reliability, storage density and performance. The proposed architecture exploits the data-dependent nature of resistance drift problem to reduce the ECC overhead. A simple state mapping is used to generate virtual data, which is half of the actual data size. ECC parity bits are generated based on virtual data bits instead of actual message bits, thus resulting in a reduced number of cells for parity bits. This improves the reliability and storage density of MLC PCM. The performance is also improved by minimizing the ECC overhead. Simulation results show an improvement of about 104 times in reliability and 10.9% in storage density compared to a conventional MLC PCM which uses a typical error correction scheme. Performance and energy efficiency are also improved up to 13.7% and 10%, respectively, by the proposed architecture.

Background: Clinical characteristics and risk factors for mortality of Acinetobacter bacteremia in cirrhotic patients have not been investigated. Methods: Acinetobacter bacteremia cases from four medical centers were collected from 2009 to 2014, to compare between patients with and without liver cirrhosis. Risk factors for mortality of Acinetobacter bacteremia among cirrhotic patients were identified using multivariate logistic regression. Results: Among the patients with Acinetobacter bacteremia, 72 had liver cirrhosis and 816 had not. Patients with cirrhosis were younger (57.5 [50–71] vs. 72 [50.25–71], p

Neuromorphic computing systems consist of neurons and synapses with limited programmability, and neural networks are modified to be mapped for such a system. In order to map a perceptron with a large number of connections into a hardware neuron with a fixed, small number of synapses, it is decomposed into a tree of perceptrons, which substantially affects the neuron usage and predictive performance. In this paper, we propose two decomposition algorithms that take advantage of plastic connections and the dynamic scaling capability of neurons. One algorithm based on sorting considers the neuron usage first, and the other algorithm based on packing considers the predictive performance first. Our experimental results on two popular deep convolutional neural networks showed that the sorting-based algorithm substantially improved the accuracy at no cost of neurons compared to a previous work, and the packing-based algorithm improved it even further at a small cost of neurons.

Deep learning using deep neural networks is taking machine intelligence to the next level in computer vision, speech recognition, natural language processing, etc. Brain-like hardware platforms for the brain-inspired computational models are being studied, but the maximum size of neural networks they can evaluate is often limited by the number of neurons and synapses equipped with the hardware. This paper presents two techniques, factorization and pruning, that not only compress the models but also maintain the form of the models for the execution on neuromorphic architectures. We also propose a novel method to combine the two techniques. The proposed method shows significant improvements in reducing the number of model parameters over standalone use of each method while maintaining the performance. Our experimental results show that the proposed method can achieve ${30\times }$ reduction rate within 1% budget of accuracy for the largest layer of AlexNet.

Background/Aims Atrial arrhythmia (AA) occasionally occurs after lung transplantation (LT); however, risk factors for AA and their impact on clinical outcomes are inconsistent. We aimed to investigate the incidence, predisposing factors, and clinical outcomes of AA after LT. Methods We retrospectively evaluated 153 consecutive patients who underwent LT between January 2010 and August 2016. An AA episode was defined as a documented atrial fibrillation (AF), atrial flutter, or atrial tachycardia on 12-lead electrocardiography or episodes lasting ≥ 30 seconds on telemetry monitoring. Results The mean follow-up time was 22.0 ± 19.1 months. Postoperative AA occurred in 46 patients (30.1%) after LT. Patients with postoperative AA were older, had larger body surface area, and had an increased incidence of paroxysmal AF prior to transplantation, idiopathic pulmonary fibrosis, and postoperative tracheostomy than patients without AA. Preoperative right atrial pressure (RAP) (odds ratio [OR], 1.19; p = 0.005) and longer periods of mechanical ventilation (OR, 1.03; p = 0.008) were found to be independent risk factors for AA after surgery. Development of AA was a significant predictor of long-term overall mortality (hazard ratio, 2.75; p = 0.017). Conclusions Patients with elevated preoperative RAP and long-term ventilator care had a higher risk of AA after LT. Further, AA after LT was associated with poor long-term survival.

Hemoglobin variability is known to be associated with mortality in patients with chronic renal failure and cardiovascular disease. However, the effect of hemoglobin variability on mortality in the general population has not yet been studied. We aimed to investigate the association between hemoglobin variability and mortality using Korean cohort from National Health Insurance Service-Health Screening 2002–2015 database. This study was conducted on 182,757 adults who underwent more than 4 health screenings from 2002 to 2009. Hemoglobin variability was assessed by 3 indices of coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM). Cox proportional hazard regression analysis was performed for each index of quartile groups (Q1–Q4). The hazard ratio and 95% confidence interval^l for all-cause mortality comparing Q2, Q3 and Q4 with Q1 of hemoglobin variability CV in the multivariable adjusted model were 1.07 [0.96–1.20], 1.18 [1.06–1.31] and 1.43 [1.29–1.58] respectively. As the 5% CV, SD, and VIM increased, the hazard ratio for mortality increased by 1.08 [1.06–1.10] in the multivariable adjusted model. Hemoglobin variability is not only important predictor in patients with chronic renal failure and cardiovascular disease but could also be considered as a useful predictor of mortality in the general population.

Deep Neural Networks (DNNs) have been found to outperform conventional programming approaches in several applications such as computer vision and natural language processing. Efficient hardware architectures for deploying DNNs on edge devices have been actively studied. Emerging memory technologies with their better scalability, non-volatility, and good read performance are ideal candidates for DNNs which are trained once and deployed over many devices. Emerging memories have also been used in DNNs accelerators for efficient computations of dot-product. However, due to immature manufacturing and limited cell endurance, emerging resistive memories often result in reliability issues like stuck-at faults, which reduce the chip yield and pose a challenge to the accuracy of DNNs. Depending on the state, stuck-at faults may or may not cause error. Fault-tolerance of DNNs can be enhanced by reducing the impact of errors resulting from the stuck-at faults. In this work, we introduce simple and light-weight Intra-block Address remapping and weight encoding techniques to improve the fault-tolerance for DNNs. The proposed schemes effectively work at the network deployment time while preserving the network organization and the original values of the parameters. Experimental results on state-of-the-art DNN models indicate that, with a small storage overhead of just 0.98%, the proposed techniques achieve up to 300× stuck-at faults tolerance capability on Cifar10 dataset and 125× on Imagenet datatset, compared to the baseline DNNs without any fault-tolerance method. By integrating with the existing schemes, the proposed schemes can further enhance the fault resilience of DNNs.

mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. We immunized rhesus macaques at weeks 0 and 4 and assessed immune responses over one year in blood, upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID50 at weeks 6 (peak) and 48 (challenge), respectively. Antibody binding titers also decreased in bronchoalveolar lavage (BAL). Four days after challenge, virus was unculturable in BAL and subgenomic RNA declined ∼3-log10 compared to control animals. In nasal swabs, sgRNA declined 1-log10 and virus remained culturable. Anamnestic antibody responses (590-fold increase) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.

Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare premature aging disorder characterized by short stature and atherosclerosis-induced death within teenage years. A 13-year-old male diagnosed with HGPS was administered three intravenous infusions of allogeneic cord blood (CB) cells from unrelated donors at four-month intervals to evaluate the safety and its therapeutic efficacy. Adverse events were monitored in addition to height, weight, laboratory blood tests, joint range of motion (ROM), and carotid Doppler. Cytokine and receptor assays were also performed. The patient exhibited an increase in growth rate for both height and weight. One year after therapy initiation, evident amelioration in pulse wave velocity, bilateral maximal intima-media thickness, and dyslipidemic status were observed, which were in abrupt aggravation prior to treatment. Further, an increase in flexibility occurred in some joints of the upper extremities. No serious adverse events were observed throughout the study period and one year beyond. A molecular assay revealed downregulation of proinflammatory and atherosclerosis, representing cytokine expressions following the administration of CB cells. This is the first reported case of an allogeneic CB trial in a patient with HGPS showing therapeutic effects of CB with improvements in anthropometric measures, joint ROM with amelioration of atherosclerosis, and dyslipidemia induced by anti-inflammatory and anti-atherosclerotic responses.

Background: Healthcare-associated infections (HAIs) cause increases in length of stay, mortality, and healthcare costs. A previous study conducted in Taiwan obtained similar results to those reported in Korea and Japan in 2015. Changes in microorganisms have been noted in recent years. Understanding the recent condition of HAIs in intensive care units (ICUs) can enable healthcare providers to develop effective infection control protocols to reduce HAIs. Methods: We used the Taiwan Nosocomial Infection Surveillance System to evaluate the incidence densities of HAIs, the proportions of causative pathogens, and the proportions of antimicrobial resistance (AMR). The Poisson regression model was constructed to incidence density, and the chi-square test was used to assess proportion. Results: The incidence density of HAIs decreased 5.7 to 5.4 per 1000 person-days. However, the proportions of Klebsiella pneumoniae and Enterococcus faecium significantly increased. In addition, the proportions of carbapenem-resistant K. pneumoniae and vancomycin-resistant Enterococcus faecium significantly increased over time. Conclusion: Analysis of the microorganisms involved in HAIs in ICUs showed elevated proportions of K. pneumoniae and E. faecium with AMR. Infection control protocols have been implemented for several years and require improvements regarding environmental cleanliness and medical staff prevention.

BACKGROUND: Effects of abdominal obesity on outcomes of atrial fibrillation (AF) ablation remains ill-defined. Here, we evaluated the impact of abdominal obesity on the long-term efficacy and safety of catheter AF ablation among Korean patients.METHODS: We utilised the Korean National Health Insurance Service database to identify patients who underwent AF ablation. Abdominal obesity was defined as waist circumference ≥90 cm (males) and ≥85 cm (females). The primary endpoint was AF recurrence and secondary endpoints were ischaemic stroke, intracranial haemorrhage and death. Additionally, safety endpoints of peri-procedural complications were studied.RESULTS: Among 5397 patients (median age 58 [IQR 51-65] years; 23.6% females), abdominal obesity was present in 1759 (32.6%). The rate of AF recurrence was not statistically different between the groups at 1-year (10.3 vs 8.7 events/100-PYs, P = .078), though abdominal obesity was associated with significantly higher rates of AF recurrence at 3-year (7.6 vs 6.3 events/100-PYs, P = .008) and 6-year (6.3 vs 5.2 events/100-PYs, P = .004) follow-ups. Kaplan-Meier survival analysis found significantly higher rates of AF recurrence in patients with obesity based on body mass index (BMI) and waist circumference (log-rank for trend P = .006). Using multivariable regression analysis, obesity by both BMI and waist circumference was an independent predictor for AF recurrence (HR 1.21 [95% CI, 1.05-1.40]), after accounting for other risk factors. There was a trend for increased rates of ischaemic stroke at 3-year and 6-year follow-ups in patients with abdominal obesity. Furthermore, this group of patients had a greater rate of intracranial haemorrhage. All-cause death was comparable between both groups. Total peri-procedural complications were not associated with abdominal obesity.CONCLUSION: Abdominal obesity as indicated by waist circumference was associated with a greater burden of concomitant diseases and an independent risk factor for long-term redo AF intervention following catheter ablation but had no effects on total peri-procedural complications.

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 - 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.mRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of existing vaccines and therapeutic antibodies and underscores the need for additional antibody-based tools that potently neutralize variants by targeting multiple sites of the spike protein. We isolated 216 monoclonal antibodies targeting SARS-CoV-2 from plasmablasts and memory B cells collected from patients with coronavirus disease 2019. The three most potent antibodies targeted distinct regions of the receptor binding domain (RBD), and all three neutralized the SARS-CoV-2 Alpha and Beta variants. The crystal structure of the most potent antibody, CV503, revealed that it binds to the ridge region of SARS-CoV-2 RBD, competes with the angiotensin-converting enzyme 2 receptor, and has limited contact with key variant residues K417, E484, and N501. We designed bispecific antibodies by combining nonoverlapping specificities and identified five bispecific antibodies that inhibit SARS-CoV-2 infection at concentrations of less than 1 ng/ml. Through a distinct mode of action, three bispecific antibodies cross-linked adjacent spike proteins using dual N-terminal domain–RBD specificities. One bispecific antibody was greater than 100-fold more potent than a cocktail of its parent monoclonals in vitro and prevented clinical disease in a hamster model at a dose of 2.5 mg/kg. Two bispecific antibodies in our panel comparably neutralized the Alpha, Beta, Gamma, and Delta variants and wild-type virus. Furthermore, a bispecific antibody that neutralized the Beta variant protected hamsters against SARS-CoV-2 expressing the E484K mutation. Thus, bispecific antibodies represent a promising next-generation countermeasure against SARS-CoV-2 variants of concern.

Anti-HIV broadly neutralizing antibodies (bNAbs) may favor development of antiviral immunity by engaging the immune system during immunotherapy. Targeting integrin α4β7 with an anti-α4β7 monoclonal antibody (Rh-α4β7) affects immune responses in SIV/SHIV-infected macaques. To explore the therapeutic potential of combining bNAbs with α4β7 integrin blockade, SHIVSF162P3-infected, viremic rhesus macaques were treated with bNAbs only (VRC07-523LS and PGT128 anti-HIV antibodies) or a combination of bNAbs and Rh-α4β7 or were left untreated as a control. Treatment with bNAbs alone decreased viremia below 200 copies/ml in all macaques, but seven of eight macaques (87.5%) in the bNAbs-only group rebounded within a median of 3 weeks (95% CI: 2 to 9). In contrast, three of six macaques treated with a combination of Rh-α4β7 and bNAbs (50%) maintained a viremia below 200 copies/ml until the end of the follow-up period; viremia in the other three macaques rebounded within a median of 6 weeks (95% CI: 5 to 11). Thus, there was a modest delay in viral rebound in the macaques treated with the combination antibody therapy compared to bNAbs alone. Our study suggests that α4β7 integrin blockade may prolong virologic control by bNAbs in SHIVSF162P3-infected macaques.

Diabetes mellitus (DM) is considered an independent risk factor for atrial fibrillation (AF). The excess risk in relation to the presence of proteinuria has not been well elucidated. Our aim was to determine the association between the incidence of AF and proteinuria in diabetic population. A total of 240,499 individuals aged ≥ 60 years from the Korea National Health Insurance Service-Senior cohort from 2004 to 2014 were included. 4.2% of individuals with DM and 3.7% of controls were diagnosed with AF during a median follow-up period of 7.2 years. Amongst controls (participants without proteinuria and DM), DM only, proteinuria only, and DM with proteinuria groups, the crude incidences of AF were 0.58, 0.70, 0.96, 1.24 per 100 person-years respectively. Compared with controls, the weighted risk of AF was increased by 11% (hazard ratio = 1.11, 95% confidence interval = 1.02-1.20, P = .001), 48% (hazard ratio = 1.48, 95% confidence interval = 1.30-1.69, P .001), and 66% (hazard ratio = 1.66, 95% confidence interval = 1.26-2.18, P .001) in the DM only, proteinuria only, and DM with proteinuria groups, respectively (P for trend .001). Degree of proteinuria in diabetic patients was associated with a significantly higher rate of incident AF in dose dependent manner. Thus, assessing proteinuria by a simple urine dipstick test could provide a useful adjunct to risk assessment for AF in elderly population with DM.

Several studies reported that aspirin can potentially help prevent infection and serious complications of coronavirus disease (COVID-19), but no study has elucidated a definitive association between aspirin and COVID-19. This study aims to investigate the association between aspirin and COVID-19.This case-control study used demographic, clinical, and health screening laboratory test data collected from the National Health Insurance Service database. Patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until June 4, 2020, were matched with control patients using propensity score matching according to their SARS-CoV-2 status, the composite of complications, and death. The composite of complications included intensive care unit admission, use of vasopressors, high-flow oxygen therapy, renal replacement therapy, extracorporeal membrane oxygenation, and death. Exposure to aspirin was defined as having a prescription for aspirin for more than 14 days, including the index date. After matching, multivariable-adjusted conditional logistic regression analysis was performed. To confirm the robustness of this study, we used 2 study groups, 3 propensity score matching methods, and 3 models for conditional logistic regression analyses.The crude odds ratio and 95% confidence interval for SARS-CoV-2 infection between the groups without and with exposure to aspirin were 1.21 (1.04-1.41), but the adjusted odds ratios (95% confidence interval) were not significant. There was no association between aspirin exposure and COVID-19 status. Multiple statistical analyses, including subgroup analysis, revealed consistent results. Furthermore, the results of analysis for complications and death were not significant. Aspirin exposure was not associated with COVID-19-related complications and mortality in COVID-19 patients.In this nationwide population-based case-control study, aspirin use was not associated with SARS-CoV-2 infection or related complications. With several ongoing randomized controlled trials of aspirin in COVID-19 patients, more studies would be able to confirm the effectiveness of aspirin in COVID-19.

Global warming is predominantly caused by methane (CH4) and carbon dioxide (CO2) emissions. CH4 is estimated to have a global warming potential (GWP) of 28–36 over 100 years. Its impact on the greenhouse effect cannot be overstated. In this report, a dual-bed eight-step pressure swing adsorption (PSA) process was used to simulate the separation of high-purity CH4 as renewable energy from biogas (36% CO2, 64% CH4, and 100 ppm H2S) in order to meet Taiwan’s natural gas pipeline standards (&gt, 95% CH4 with H2S content &lt, 4 ppm). Three selectivity parameters were used to compare the performance of the adsorbents. In the simulation program, the extended Langmuir–Freundlich isotherm was used for calculating the equilibrium adsorption capacity, and the linear driving force model was used to describe the gas adsorption kinetics. After the basic case simulation and design of experiments (DOE) for the laboratory-scale PSA, we obtained a top product CH4 purity of 99.28% with 91.44% recovery and 0.015 ppm H2S purity, and the mechanical energy consumption was estimated to be 0.86 GJ/ton-CH4. Lastly, a full scale PSA process simulation was conducted for the commercial applications with 500 m3/h biogas feed, and the final CH4 product with a purity of 96.1%, a recovery of 91.39%, and a H2S content of 1.14 ppm could be obtained, which can meet the standards of natural gas pipelines in Taiwan.

SARS-CoV-2 mutations may diminish vaccine-induced protective immune responses, and the durability of such responses has not been previously reported. Here, we present a comprehensive assessment of the impact of variants B.1.1.7, B.1.351, P.1, B.1.429, and B.1.526 on binding, neutralizing, and ACE2-blocking antibodies elicited by the vaccine mRNA-1273 over seven months. Cross-reactive neutralizing responses were rare after a single dose of mRNA-1273. At the peak of response to the second dose, all subjects had robust responses to all variants. Binding and functional antibodies against variants persisted in most subjects, albeit at low levels, for 6 months after the primary series of mRNA-1273. Across all assays, B.1.351 had the greatest impact on antibody recognition, and B.1.1.7 the least. These data complement ongoing studies of clinical protection to inform the potential need for additional boost vaccinations., One-Sentence Summary: Most mRNA-1273 vaccinated individuals maintained binding and functional antibodies against SARS-CoV-2 variants for 6 months.

Background This study examines changes in the ideal cardiovascular health (CVH) status and whether these changes are associated with incident cardiovascular disease (CVD) and mortality in the elderly Asian population. Methods and Results In the Korea National Health Insurance Service–Senior cohort aged ≥60 years, 208 673 participants without prior CVD, including 109 431 who showed changes in CVH status, were assessed. The association of the changes in cardiovascular risk factors with incident CVD was assessed from 2004 to 2014 in the elderly (aged 60–74 years) and very elderly (≥75 years) groups. During the follow‐up period (7.1 years for CVD and 7.2 years for mortality), 19 429 incident CVD events and 24 225 deaths occurred. In both the elderly and very elderly participants, higher CVH status resulted in a lower risk of CVD and mortality. In the very elderly participants, compared with consistently low CVH, consistently high CVH (subhazard ratio, 0.41; 95% CI, 0.23–0.73) was associated with a lower risk of CVD. This trend was consistently observed in the elderly population. In the very elderly participants, total cholesterol level was not informative enough for the prediction of CVD events. In both the elderly and very elderly groups, body mass index and total cholesterol were not informative enough for the prediction of all‐cause mortality. Conclusions In both the elderly and very elderly Asian populations without CVD, a consistent relationship was observed between the improvement of a composite metric of CVH and the reduced risk of CVD. Body mass index and total cholesterol were not informative enough for the prediction of all‐cause mortality in both the elderly and very elderly groups.

Background The long-term risks of thromboembolism and mortality are unknown in patients who survived following atrial fibrillation (AF) newly diagnosed during critical care. Methods Using the Korean National Health Insurance Service database, we identified 30,869 adults who survived for > 6 months following AF newly diagnosed during critical care (ICU-AF), 269,751 control subjects with non-ICU AF (AF-control), and 439,868 control subjects without AF (No-AF) from 2005 to 2013. We performed propensity score matching and compared the risks of stroke/systemic embolism and all-cause mortality. Results The adjusted hazard ratios (HRs) for long-term stroke/systemic embolism in the patients with ICU-AF were 0.93 (95% CI, 0.88-0.98) compared with the AF-control group and 1.50 (95% CI, 1.42-1.60) compared with the No-AF group. The adjusted HRs of the ICU-AF group for long-term mortality were 1.73 (95% CI, 1.70-1.83) and 3.20 (95% CI, 3.08-3.33) compared with the AF-control and No-AF groups, respectively. The risks of stroke/systemic embolism and mortality were significantly higher in the ICU-AF group than in the No-AF group after excluding patients with AF recurrence (adjusted HR, 1.08; 95% CI, 1.01-1.17), regardless of the causes of critical care and cardiovascular or noncardiovascular surgery. Conclusions The patients who survived following AF newly diagnosed during critical care remained at a higher risk of long-term stroke/systemic embolism and mortality than the patients without AF regardless of AF recurrence and the causes of critical care. Close follow-up and continuous anticoagulation might be needed for these patients.

Although exercise prevents cardiovascular disease and mortality, vigorous exercise and endurance athletics can cause atrial fibrillation (AF). However, no large cohort study has assessed the relationship between physical activity and AF in the general population. We assessed the effect of physical activity at different energy expenditures on the incidence of AF. We studied 501,690 individuals without pre-existing AF (mean age, 47.6 ± 14.3 years; 250,664 women [50.0%]) included in the Korean National Health Insurance Service database. The physical activity level was assessed using a standardized self-reported questionnaire at baseline. During a median follow-up of 4 years, 3,443 participants (1,432 women [41.6%]) developed AF. The overall incidence of AF at follow-up was 1.79 per 1,000 person-years. The subjects who met the recommended physical activity level (500–1,000 metabolic equivalent task [MET] minutes/week) had a 12% decreased AF risk (adjusted hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.80–0.97), but not the insufficiently (1–500 MET-minutes/week; HR: 0.94, 95% CI: 0.86–1.03) and highly active subjects (≥1,000 MET-minutes/week; HR: 0.93, 95% CI: 0.85–1.03). The recommended minimum key target range of physical activity level was associated with the maximum benefit for reduced AF risk in the general population. The dose-response relationship between physical activity level and AF risk showed a U-shaped pattern. Although exceeding the key target range attenuated this benefit, it did not increase the AF risk beyond that during inactivity.