Droplet migration: quantitative comparisons with experiment

An important practical feature of simulating droplet migration computationally, using the lubrication approach coupled to a disjoining pressure term, is the need to specify the thickness, H, of a thin energetically stable wetting layer, or precursor lm, over the entire substrate. The necessity that H be small in order to improve the accuracy of predicted droplet migration speeds, allied to the need for mesh resolution of the same order as H near wetting lines, increases the computational demands signicantly. To date no systematic investigation of these requirements on the quantitative agreement between prediction and experimental observation has been reported. Accordingly, this paper combines highly ecient Multigrid methods for solving the associated lubrication equations with a parallel computing framework, to explore the eect of H and mesh resolution. The solutions generated are compared with recent experimentally determined migration speeds for droplet ows down an inclined plane

Possible role of bonding angle and orbital mixing in iron pnictide superconductivity: Comparative electronic structure studies of LiFeAs and Sr2VO3FeAs

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Thirty-Day Clinical Outcome of Primary Percutaneous Intervention Versus Fibrinolysis Followed by Coronary Angiography in ST-Segment Elevation Myocardial Infarction

Background: Primary percutaneous coronary intervention (PCI)is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI). However, timely PCI cannot be offered to many patients. Objective: The purpose of this study was to compare the 30-day clinical outcome of primary PCI strategy and fibrinolysis followed by coronary angiography strategy in STEMI patients. Methods: This was a prospective, observational, single center study. All patients admitted for STEMI from 1 January 2016 to 30 November 2016 were screened for the study. Patients were divided into 2 reperfusion strategies: primary PCI or fibrinolysis followed by coronary angiography. Primary outcome was composite of all-cause mortality at 30 days. Results: A total of 178 patients were identified: 33 (18.5%) underwent primary PCI and 145 (81.5%) underwent fibrinolysis first. The median door-to-balloon time in the primary PCI group was 161.0 minutes (IQR 84.5). The median time from fibrinolysis-to-arrival at catheterization lab was 1738 minutes (IQR 901). The median total ischaemic time was 369 min (IQR 524) and 210 (IQR 247) for the primary PCI and fibrinolysis first group respectively (p=0.002). Kaplan-Meier survival analysis for 30-day all-cause mortality was 24.2% vs 9.7% respectively in primary PCI and fibrinolysis group p=0.018). Multivariate Linear Regression showed that Killip Class and LVEF were independent predictors of 30-day all-cause mortality. Reperfusion strategy was not associated with 30-day all-cause mortality (p=0.216). Conclusions: The clinical outcome of primary PCI strategy in STEMI is not better than fibrinolysis followed by coronary angiography strategy when timely PCI cannot be performed

Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study

Background. CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study. Materials and Methods. Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and the outcome of treatment with immune-modulating medication (IMM) was evaluated. Results. The analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal (14.5%) and hepatic (14.1%) events; the majority were grade 1/2, with 10.7% of patients experiencing grade 3/4 events. One patient had grade 5 pneumonitis. Median (range) TTO ranged from 3.6 (0.1–59.9) weeks for skin sTRAEs to 47.6 (47.1–48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs resolved, with median (range) TTR ranging from 3.7 (0.1–123.3+) weeks for gastrointestinal sTRAEs to 28.4 (0.1–79.1) weeks for endocrine sTRAEs. Most gastrointestinal and all hepatic events resolved with treatment in accordance with established toxicity management algorithms. In 57 patients (40%), sTRAEs were managed with IMM. Reoccurrence of sTRAEs was uncommon following rechallenge with nivolumab. Conclusion. Nivolumab demonstrated a manageable safety profile in this analysis of patients with advanced HCC. A majority of sTRAEs resolved with treatment

Comparison of Resting PD/PA with Fractional Flow Reserve Using a Monorail Pressure Catheter

Background: The RXi™ system (ACIST Medical Systems, MN, USA) is a new Fractional Flow Reserve (FFR) technology utilising an ultrathinmonorail microcatheter (Navvus®; ACIST Medical Systems) with an optical pressure sensor located close to the distal catheter tip. FFR measurement using monorail microcatheter is comparable to the conventional pressure wires. However, the predictive value of resting distal coronary artery pressure/aortic pressure (Pd/Pa) on hyperemic FFR value in the real world practice is unknown. Objective: To explore the diagnostic accuracy of resting Pd/Pa in relation to hyperemic FFR using the monorail pressure catheter. Methods: Resting Pd/Pa and FFR were measured using monorail pressure catheter in 67 consecutive patients with intermediate coronary artery lesions (30% to 80% diameter stenoses) between 01-03-2016 to 17-01-2017. Of 121 studied lesions, 29 (23.97%) were excluded because of no hyperemic FFR due to postive resting Pd/Pa (n=17), severe or non-critical stenosis (n=11) and suboptimal acquisition (n=1), leaving 92 lesions for final analysis. Hyperemic FFR was induced with intracoronary adenosine. The selection of coronary wire and the dose of intracoronary nitroglycerine were at the operators’ discretions. Results: Bland-Altman plots showed a moderate degree of scatter between Pd/Pa and FFR value. On average, Pd/Pa exceeded FFR by 0.066 (-0.09 to +0.22). Receiver-operating characteristic curves of the resting Pd/Pa with FFR≤0.80 as the reference variable showed an area under the curve of 0.78 (95% confidence intervals 0.680 to 0.881, pb0.001), with a diagnostic accuracy of 79.3% when the resting Pd/Pa was ≤0.86. Certain cutoff values of Pd/Pa can reliably predict whether hyperemic FFR was positive or negative (FFR cutoff≤0.80). Resting Pd/Pa value of N0.96 had a negative predictive value (NPV) of 100% and sensitivity of 100%; the resting Pd/Pa value of ≤0.82 had a positive predictive value (PPV) of 100% and specificity of 98.3%. These were consistent regardless of coronary vessel, location of lesion or degree of diameter stenosis. Conclusions: Certain range of resting Pd/Pa measured by monorail pressure catheter had excellent NPV and sensitivity or excellent PPV and specificity to predict hyperemic FFR. Clinical outcome studies are required to determine whether the results might obviate the need for hyperemia in selected patients

Impact of Myocardial Viability Assessed by Delayed Enhancement Cardiovascular Magnetic Resonance on Clinical Outcomes in Real World Practice

Background: Delayed enhancement cardiovascular magnetic resonance imaging (DeCMRI) has become the preferred method for viability assessment. It is well established that viable dysfunctional myocardium has the potential for functional recovery after revascularization. Objective: Our objective is to evaluate whether viability assessment by DeCMRI affects clinical outcome in daily clinical practice. Methodology:We retrospectively studied 132 consecutive patients (114 male, mean age 59 ± 10 years) with ischaemic cardiomyopathy (Mean LVEF: 29.1 ± 14%) who underwent CMRI viability testing from 1st Jan-31st Dec 2015 in our centre. Patientswere divided into 3 groups: Group A: Viable myocardium- optimal medical therapy only (38.6%); B: Viable myocardium- revascularization done (29.5%); and C: Nonviable myocardium (29.5%). Results: Mean age for groups A, B and C were 61.2, 58.3, 56.2 years respectively, p=0.048. The proportion of triple vessel disease in each of the groups were 56.1%, 54.5% and 38.5% (p=0.44); whereas left main involvement was 31.7%, 21.2% and 19.2% respectively (p=0.43). Majority of group C patients did not undergo revascularisation (90%). Group B had statistically significant EF improvement (5.5%, SD 11.9) compared to Group A (-0.6%, SD 6.7) and Group C (-1.2%, SD 9.8), p value 0.014. Mortality at 1 year was significantly higher in Group A compared to Group Band C (31.4%, 7.7% and 12.8% respectively, p=0.009). MACE rates were also increased in Group A compared to the other two groups (41.2%, 20.5% and 27.0%, p=0.09). Odds Ratio for MACE was 3.01 (95% Cl 1.22 - 7.45) for Group A vs B and 2.8 (95% Cl 1.1 - 6.9) for Group A vs C. Conclusion: Patients with viable myocardium who did not undergo revascularization (group A) had the worst prognosis, even when compared to those with non-viable myocardium; with significantly higher 1-year mortality. Although not statistically significant, there was also a trend towards higher MACE in these patients. These findings emphasize that patients with poor LV function but viable myocardium need to undergo revascularisation and that optimal medical therapy alone is not sufficient

Prognostic Value of N-terminal B-type Natriuretic Peptide in Patients with Acute Myocardial Infarction: A Multicenter Study

Background: Several models have been developed to help the clinician in risk stratification for Acute Coronary Syndrome (ACS),such as the TIMI and GRACE risk scores. However, there is conflicting evidence for the prognostic value of NT-ProBNP in acute myocardial infarction (AMI). Objective: (1) To explore the association of NT-proBNP with 30-day clinical outcome in AMI patients. (2) To compare the prognostic value of NT-proBNP with TIMI and GRACE risk scores in AMI patients. Methods: We conducted a multicenter, prospective observational study recruiting patients presented with AMI between 29-October-2015 and 14-January-2017, involving 1 cardiology referral centre and 4 non-cardiology hospitals. NT-proBNP level (Alere Triage®, US)was measured within 24 hours fromthe diagnosis of AMI. Patientswere followed-up for 1 month. Results: A total of 186 patients were recruited, 143 from tertiary cardiology centre and 43 from non-cardiology hospitals. Mean age was 54.7±10.0 years, 87.6% male and 64% were STEMI. The NT-proBNP level ranged from 60 to 16700pg/ml, with a median of 714pg/ml. Using the 75th centile as the cutoff, Kaplan-Meier survival analysis for the 30-day cardiac related mortality was significantly higher for patient with NT-proBNP level of ≥1600pg/ml (6.4% vs. 0.7%, p=0.02). Cox-regression analysis showed that NT-proBNP level of ≥1600pg/ml was an independent predictor of 30-day cardiac related mortality, regardless of TIMI risk score, GRACE score, LV ejection fraction and study hospitals (HR 9.274, p=0.054, 95%CI 0.965, 89.161). Readmission for heart failure at 30-day was also higher for patient with NT-proBNP level of ≥1600pg/ml (HR 9.308, p=0.053, 95%CI 0.969, 89.492). NT-proBNP level was not associated with all-cause mortality, risk of readmission for ACS, arrhythmia and stroke (pN0.05). By adding 50 score to GRACE risk score for NT-proBNP level of ≥1600pg/ml, combination of GraceNT-proBNP scores of more than 200 appeared to be a better independent predictor for 30-day cardiac related mortality (HR:28.28, p=0.004, 95%CI 2.94, 272.1). ROC analysis showed that this new score had 75% sensitivity and 91.2% specificity in predicting 30-day cardiac related mortality (AUC 0.791, p=0.046). Conclusions: NT-proBNP is a useful point-of-care risk stratification biomarker in AMI. It can be combined to the current risk score model for better risk stratification in AMI patients

Exploring definitions and predictors of severe asthma clinical remission post-biologic in adults

Peer reviewe

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings