Stepwise Gradient Research Articles

Laparoscopic Complete Excision of the Posterior Muscular Cuff: Technique Refinements and Comparison With Stepwise Gradient Muscular Cuff Cutting for Hirschsprung Disease.

ObjectivesOur institution had modified the Soave pull-through procedure using laparoscopic stepwise gradient muscular cuff cutting (LSGC) for Hirschsprung disease (HSCR). However, we found that a few children still suffered from obstructive symptoms and enterocolitis during the follow-up. Previous studies suggested that these symptoms might be caused by the retained muscular cuff. The purpose of this study was to employ a modified procedure of laparoscopic complete excision of the posterior muscular cuff (LCEPC) for HSCR and compare it with the laparoscopic stepwise gradient cutting muscular cuff (LSGC) procedure.MethodsOur institution records of 83 patients with classic form HSCR who underwent LSGC or LCEPC between August 2014 and July 2018 at the Pediatric Surgery Department of Zunyi Medical University (Zunyi, China) were carefully reviewed (LSGC, n = 52; LCEPC, n = 31). In the present study, we compared the postoperative complications and defecation functions of the two groups. All patients were followed-up (1–5 years, with an average of 2 years).ResultsThere were no differences regarding the operation time and the length of hospitalization between groups, while the anal dissection time in the LCEPC group (22.4 ± 4.8 min) was shorter than that of the LSGC group (45.5 ± 7.5 min) (p < 0.001). The postoperative complication of soiling was significantly increased in six patients (19.4%) in the LCEPC group compared with two patients (3.8%) in the LSGC group (p = 0.021). However, the total incidence of enterocolitis (two patients, 6.5%) was significantly decreased in the LCEPC group compared with the LSGC group (12 patients, 23.1 %) (p = 0.050). For anastomotic stricture, muscular cuff infection, and constipation, there were no significant differences between the two groups. No patients experienced bladder paralysis and incontinence postoperatively in this study. Anorectal manometries presented that the anorectal resting pressure was significantly lower in the LCEPC group (14.8 ± 2.7 mmHg) than the LSGC group (22.0 ± 3.8 mmHg), (p < 0.001).ConclusionThe laparoscopic complete excision of the posterior muscular cuff method was demonstrated as safe and efficient, with a decrease in the incidence of enterocolitis, although it may increase the number of soiling incidents in the short period post-surgery owing to a dissected partial internal anal sphincter.

Temporary Mechanical Circulatory Support Bridging Strategies And Post-operative Outcomes In Acute Decompensated Heart Failure-related Cardiogenic Shock Patients Undergoing Heart Transplantation Or Durable Left Ventricular Assist Device Implantation: A Society Of Thoracic Surgeons Database Analysis

Introduction Temporary mechanical circulatory support (TMCS) bridging strategies are increasingly used for acute decompensated heart failure-related cardiogenic shock (ADHF-CS). However, the impact of bridging approach on post-operative outcomes in ADHF-CS patients who receive a durable left ventricular assist device (LVAD) or heart transplant (HT) is unknown. Methods Durable LVAD or HT recipients from July 1, 2014 to December 31, 2019 with pre-operative ADHF-CS were identified in the Society of Thoracic Surgeons Adult Cardiac Surgery Database and stratified by pre-operative TMCS strategy. Associations between TMCS strategies and post-operative outcomes were evaluated using propensity-score matching and adjustment for pre-selected covariates (pre-operative hemoglobin, platelets, albumin, bilirubin, international normalized ratio, creatinine, cardiopulmonary resuscitation, and operative status). Results A total of 8,777 ADHF-CS patients were bridged to LVAD (5,975; 68%) or HT (2,802; 32%). The composite of operative/30-day death following LVAD or HT was highest in patients managed with VA ECMO (22%) and lowest in those managed without TMCS (7%), with a stepwise gradient of incidence by level of hemodynamic support (Figure, top). Other post-operative outcomes including major bleeding, cerebrovascular accident, cardiac arrest, prolonged mechanical ventilation, renal failure, and sepsis/pneumonia followed a similar pattern. However, after propensity score matching and adjustment, there were no differences in the odds of operative/30-day death or major bleeding with IABP versus no TMCS (Figure, bottom). While there was no difference in operative/30-day death, odds of major bleeding were lower with catheter-based MCS compared with IABP (OR 0.70, 95% CI 0.53 - 0.92). Conclusion ADHF-CS patients experience high rates of cardiac and non-cardiac adverse events post- LVAD and HT. A crude relationship between TMCS bridging strategy and post-operative outcomes was observed. However, after adjustment, pre-operative TMCS bridging strategy did not independently confer risk of near-term post-operative mortality among ADHF-CS patients who underwent HT or durable LVAD implantation. Temporary mechanical circulatory support (TMCS) bridging strategies are increasingly used for acute decompensated heart failure-related cardiogenic shock (ADHF-CS). However, the impact of bridging approach on post-operative outcomes in ADHF-CS patients who receive a durable left ventricular assist device (LVAD) or heart transplant (HT) is unknown. Durable LVAD or HT recipients from July 1, 2014 to December 31, 2019 with pre-operative ADHF-CS were identified in the Society of Thoracic Surgeons Adult Cardiac Surgery Database and stratified by pre-operative TMCS strategy. Associations between TMCS strategies and post-operative outcomes were evaluated using propensity-score matching and adjustment for pre-selected covariates (pre-operative hemoglobin, platelets, albumin, bilirubin, international normalized ratio, creatinine, cardiopulmonary resuscitation, and operative status). A total of 8,777 ADHF-CS patients were bridged to LVAD (5,975; 68%) or HT (2,802; 32%). The composite of operative/30-day death following LVAD or HT was highest in patients managed with VA ECMO (22%) and lowest in those managed without TMCS (7%), with a stepwise gradient of incidence by level of hemodynamic support (Figure, top). Other post-operative outcomes including major bleeding, cerebrovascular accident, cardiac arrest, prolonged mechanical ventilation, renal failure, and sepsis/pneumonia followed a similar pattern. However, after propensity score matching and adjustment, there were no differences in the odds of operative/30-day death or major bleeding with IABP versus no TMCS (Figure, bottom). While there was no difference in operative/30-day death, odds of major bleeding were lower with catheter-based MCS compared with IABP (OR 0.70, 95% CI 0.53 - 0.92). ADHF-CS patients experience high rates of cardiac and non-cardiac adverse events post- LVAD and HT. A crude relationship between TMCS bridging strategy and post-operative outcomes was observed. However, after adjustment, pre-operative TMCS bridging strategy did not independently confer risk of near-term post-operative mortality among ADHF-CS patients who underwent HT or durable LVAD implantation.

Formation and function of OmpG or OmpA-incorporated liposomes using an in vitro translation system

Outer membrane proteins (OMPs), located on the outer membrane of gram-negative bacteria, have a β-strand structure and form nanopores, which allow passage of ions, sugars, and small molecules. Recently, OMPs have been used as sensing elements to detect biological molecules. OMPs are normally expressed and purified from Escherichia coli (E. coli). Although the cell-free synthesis of OMPs, such as OmpA and OmpG, is achieved in the presence of liposomes and periplasmic chaperones, the amount of OmpA and OmpG incorporated into the nano-sized liposomes is not clear. In this study, after in vitro translation, the incorporation of OmpG into purified nano-sized liposomes with various lipid compositions was investigated. Liposomes containing the synthesized OmpG were purified using a stepwise sucrose density gradient. We report that liposomes prepared with the E. coli lipid extract (PE/PG) had the highest amount of OmpG incorporated compared to liposomes with other lipid compositions, as detected by recording the current across the OmpG containing liposomes using the patch clamp technique. This study reveals some of the requirements for the insertion and refolding of OMPs synthesized by the in vitro translation system into lipid membranes, which plays a role in the biological sensing of various molecules.

Analysis and experimental demonstration of temperature step gradients in preparative liquid chromatography

The amount of substance adsorbed on solid surface depends on temperature. Therefore, the migration velocities of the solutes in a chromatographic column can be altered by introducing temperature gradients. Such gradients designed to change retention behaviours can be exploited to improve the separation performances in preparative chromatography. To describe key process features, we used analytical solutions of the equilibrium model with instant stepwise shift of temperature. To achieve a more realistic description, the equilibrium dispersion model was additionally applied to treat finite column efficiencies. The effect of temperature gradients was illustrated experimentally using two identical columns sequentially connected. Temperature of the second column was modulated by thermostats. Wide pulse injections of a single component led to instructive elution profiles in a preliminary investigation. The observations were found to be in qualitative agreement with predictions of the equilibrium dispersion model. Subsequently, the separation of a ternary model mixture was investigated considering a simple two-step temperature gradient. To support the quantitative analysis and to identify suitable switching and cycle times, the temperature dependencies of the Henry constants were determined by short pulse injections. A meaningful variation of the parameters of the temperature gradient is required for adjusting the cycle times, which is the time difference between two consecutive injections that needs to shorten. Decreasing this time is connected with a desirable increase in process productivity. The results achieved revealed that relatively simple to implement stepwise temperature gradients offer an option to improve and fine-tune the performance of repetitive batch chromatography.

Stepwise Gradient Copolymers of n-Butyl Acrylate and Isobornyl Acrylate by Emulsion RAFT Copolymerizations

Gradient copolymers of n-butyl acrylate (nBA) and isobornyl acrylate (IBA) were prepared using reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization. Gradient copolymerizations were conducted using stepwise monomer addition such that the system was monomer-starved. Using the stepwise monomer addition process with a fixed comonomer ratio during the polymerization allows for pre-specified gradient compositions to be obtained. The structural properties of copolymers were confirmed via kinetic investigations and two-dimensional chromatography. 1H nuclear magnetic resonance (NMR) characterization revealed the gradient behavior of the prepared copolymers. The degree of change in monomer composition along the copolymer chain strongly affects the thermal properties of the final polymer product. Thus, gradient copolymers were examined to determine how the strength of the gradient impacts the glass-transition temperature (Tg). Comparisons were also made between the gradient copolymers and their corresponding statistical copolymers and homopolymers. Differential scanning calorimetry analysis of gradient copolymers demonstrated that such copolymers had much broader glass-transition regions compared to homopolymers and statistical copolymers. Furthermore, both the midpoint of the transition (i.e., Tg) and the breadth of the transition were found to be predeterminable through a judicious choice of the comonomer feed composition and the steepness of the comonomer feed in the subsequent monomer additions.

Combining computer vision score and conventional meat quality traits to estimate the intramuscular fat content using machine learning in pigs

Intramuscular fat content (IMF%) is an important factor that affects the quality of pork. The traditional testing method (Soxhlet extraction) is accurate; however, it has a long preprocessing time. In this study, a total of 1481 photographs of 200 pigs' loin muscles were used to obtain a computer vision score (IIMF %). Then, actual IMF%, meat color, marbling score, pH value, and drip loss of 200 pigs were measured. Stepwise regression (SR) and gradient boosting machine (GBM) were used to construct the estimation model of IMF%. The results showed that the correlation coefficients between IMF% and IIMF%, marbling score, backfat thickness, percentage of moisture (POM), and pH value were 0.68, 0.64, 0.48, 0.45, and 0.25, respectively. The model accuracies of SR and GBM base on residuals distribution were 0.875 and 0.89, respectively. This study presents a method for estimating IMF% using computer vision technology and meat quality traits.

Antimicrobial and antioxidant activity of proteins isolated from Melipona beecheii honey

Proteins from Melipona beecheii honey were purified by concanavalin A (conA) affinity chromatography and eluted with a stepwise glucose gradient into fractions named F2-F5. The conA-unbound fraction (F1) was further separated by molecular exclusion into fractions named MbF1-1,2 and MbF1-3. All fractions were evaluated for antibacterial activity against foodborne pathogens and antioxidant capacity. F1 fraction possessed highest antimicrobial activity against S. aureus, L. monocytogenes, S. Typhimurium, E. coli and P. aeruginosa with MIC’s 1.4 ± 0.2, 15 ± 1, 39 ± 2, 1 ± 0.1, and 75 ± 2 µg/mL, respectively. F1, MbF1-1,2 and MbF1-3 had bactericidal effect except against P. aeruginosa. When the antioxidant capacity of the fractions was determined, F2 had the highest antioxidant activity measured by DPPH radical scavenging activity (IC50 = 2.4 ± 0.4 µg/µL) and reducing power of Fe(III) (IC50 = 1.8 ± 0.2 µg/µL). We provide evidence that M. beecheii honey proteins possess broad spectrum antibacterial and antioxidant activity, the latter probably through their reducing agent and free radical scavenger properties.

Serial Assessment of High-Sensitivity Cardiac Troponin and the Effect of Dapagliflozin in Patients With Heart Failure With Reduced Ejection Fraction: An Analysis of the DAPA-HF Trial.

Circulating high-sensitivity cardiac troponin T (hsTnT) predominantly reflects myocardial injury, and higher levels are associated with a higher risk of worsening heart failure and death in patients with heart failure with reduced ejection fraction. Less is known about the prognostic significance of changes in hsTnT over time, the effects of dapagliflozin on clinical outcomes in relation to baseline hsTnT levels, and the effect of dapagliflozin on hsTnT levels. DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) was a randomized, double-blind, placebo-controlled trial of dapagliflozin (10 mg daily) in patients with New York Heart Association class II to IV symptoms and left ventricular ejection fraction ≤40% (median follow-up, 18.2 months). hsTnT (Roche Diagnostics) was measured at baseline in 3112 patients and at 1 year in 2506 patients. The primary end point was adjudicated worsening heart failure or cardiovascular death. Clinical end points were analyzed according to baseline hsTnT and change in hsTnT from baseline to 1 year. Comparative treatment effects on clinical end points with dapagliflozin versus placebo were assessed by baseline hsTnT. The effect of dapagliflozin on hsTnT was explored. Median baseline hsTnT concentration was 20.0 (25th-75th percentile, 13.7-30.2) ng/L. Over 1 year, 67.9% of patients had a ≥10% relative increase or decrease in hsTnT concentrations, and 43.5% had a ≥20% relative change. A stepwise gradient of higher risk for the primary end point was observed across increasing quartiles of baseline hsTnT concentration (adjusted hazard ratio Q4 versus Q1, 3.44 [95% CI, 2.46-4.82]). Relative and absolute increases in hsTnT over 1 year were associated with higher subsequent risk of the primary end point. The relative reduction in the primary end point with dapagliflozin was consistent across quartiles of baseline hsTnT (P-interaction=0.55), but patients in the top quartile tended to have the greatest absolute risk reduction (absolute risk difference, 7.5% [95% CI, 1.0%-14.0%]). Dapagliflozin tended to attenuate the increase in hsTnT over time compared with placebo (relative least squares mean reduction, -3% [-6% to 0%]; P=0.076). Higher baseline hsTnT and greater increase in hsTnT over 1 year are associated with worse clinical outcomes. Dapagliflozin consistently reduced the risk of the primary end point, irrespective of baseline hsTnT levels. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

A Rapid, Reliable RP-UPLC Method for Large-Scale Analysis of Wheat HMW-GS Alleles.

High-molecular-weight glutenin subunits (HMW-GS) account for only 10% of total wheat storage proteins, but play an important role in the processing quality of wheat flour. Therefore, identifying HMW-GS alleles associated with good end-use quality provides important information for wheat breeders. To rapidly, accurately and reproducibly identify HMW-GS, we established an optimized reversed-phase ultra-performance liquid chromatography (RP-UPLC) method. Separation parameters were optimized using an ACQUITY UPLC Protein BEH C4 column and stepwise ACN gradient, and the separation patterns and retention times (RTs) of 22 subunits were comparatively analyzed in 16 standard wheat cultivars. All HMW-GS proteins were well separated within about 5.5 min, and all analyses were complete within 12 min. We distinguished the 16 subunits based on RT, although three subunits in 1Bx (1Bx7/1Bx7OE and 1Bx17) and three subunits in 1By (1By8*, 1By9 and 1By15) had overlapping RTs; these were differentiated by SDS-PAGE. To distinguish 1Bx7 and 1Bx7OE, which differ in protein abundance, RP-UPLC was combined with PCR analysis of DNA junction markers. The optimized method was successfully applied to determine HMW-GS alleles in a large collection of bread wheat germplasm (1787 lines). This protocol is an appropriate option for selecting lines harboring favorable HMW-GS alleles in wheat breeding.

Dual-gating pH-responsive membranes with the heterogeneous structure for whey protein fractionation

Whey protein is a mixture of globular proteins with high nutritional value and excellent functional properties availability. Purified individual whey proteins exhibit better functionality than in their original mixture, thus there is an increasing interest in developing more efficient methods to recover individual whey protein fractions, especially membrane technology. However, whey protein fractionation from the protein mixture is still a huge challenge for membrane separation. Herein, a dual-gating pHresponsive membrane with the heterogeneous structure was developed for whey protein fractionation. The heterogeneous structure of the membranes was obtained by grafting the dimethylaminoethyl methacrylate (DMAEMA) and 4-vinylpyridine (4VP) near the topside and inside the pores of the ethylene vinyl alcohol copolymer (EVAL) membranes based on selective modification of grafting sites. The PDMAEMA and P4VP gates responded to pH individually and provided a multi-stage regulation of the surface charge and sieving property of the membranes. The major whey protein fractionation from the mixture could be achieved by single dual-gating pH-responsive membrane via the sequential stepwise pH gradient from 3.0 to 8.0. The α-Lactalbumin (α-La), β-Lactoglobulin (β-Lg), lactoferrin (LF) and bovine serum albumin (BSA) were separated and enriched in the permeate at pH 3.0, 4.2, 6.4 and 8.0 by the diafiltration process, respectively. This work not only proposed a novel concept of pHresponsive membrane, but also offered a sustainable solution to fractionate the whey protein from the complicated mixture.

Early childhood adversity and non-affective psychosis: a study of refugees and international adoptees in Sweden.

Previous Scandinavian studies have shown increased levels of psychiatric morbidity in young refugees and international adoptees with an origin outside Europe. This study investigated their risk of non-affective psychotic disorders (NAPD) and whether this risk is influenced by early childhood adversity, operationalised as age at adoption/residency, and/or gender. Register study in Swedish national cohorts born 1972-1990 including 21 615 non-European international adoptees, 42 732 non-European refugees that settled in Sweden at age 0-14 years and 1 610 233 Swedish born. The study population was followed from age 18 to year 2016 for hospitalisations with a discharge diagnosis of NAPD. Hazard ratios (HRs) were calculated in gender stratified Cox regression models, adjusted for household income at age 17. The adjusted risks of NAPD were 2.33 [95% confidence interval (CI) 2.07-2.63] for the international adoptees and 1.92 (1.76-2.09) for the former child refugees, relative to the Swedish-born population. For the international adoptees there was a stepwise gradient for NAPD by age of adoption from adjusted HR 1.66 (1.29-2.03) when adopted during the first year of life to adjusted HR 4.56 (3.22-6.46) when adopted at ages 5-14 years, with a similar risk pattern in women and men. Age at residency did not influence the risk of NAPD in the refugees, but their male to female risk ratio was higher than in Swedish-born and the adoptees. The risk pattern in the international adoptees gives support to a link between early childhood adversity and NAPD. Male gender increased the risk of NAPD more among the refugees.

Effect of stepwise gradient on dynamic failure of composite sandwich beams with metal foam core subject to low-velocity impact

Dynamic failure behaviors of fully clamped and simply supported composite sandwich beams with stepwise gradient foam cores subject to low-velocity impact have been investigated experimentally. The sandwich beams with uniform foam core, positive-gradient foam core and negative-gradient foam core are designed and manufactured. The experimental results show that the mass distributions of cores have significant effect on the failure modes. The low-density foam layer at the impact end would lead to local failure mode of indentation or face fracture, while the high-density foam layer at the impact end would bring about global failure mode of combined core shear and debonding. The simply supported graded sandwich beam exhibits softening post-failure behavior, while the fully clamped graded sandwich beam displays hardening post-failure behavior. The initial strengths of fully clamped and simply supported sandwich beams with negative-gradient foam core are the highest, while the subsequent strength of the fully clamped sandwich beams with positive-gradient foam core is the highest. Among all gradient distributions of foam cores, the impact resistance of the fully clamped composite sandwich beams with negative-gradient foam cores design is the highest.

Reversed-phase pH gradient thin-layer chromatography of biologically active substances with controlled developing solvent velocity

For the first time, stepwise pH gradient thin-layer chromatograms of biologically active substances with controlled developing solvent velocity are presented and described in the paper. Change in buffer pH of the mobile phase solution influences retardation, selectivity, and shape of the separated substances' spots. The conducted research has confirmed that the mobile phase's pH gradient could be an essential factor to optimize the conditions of the separation of substances in reversed-phase high-performance thin-layer chromatography. The reproducibility of the gradient retardation factor values of separated substance zones is satisfactory.

Isolation of a starfish myorelaxant peptide (SMP) isotype from the pyloric caeca of Patiria pectinifera

Peptides are naturally occurring biological molecules that are found in all living organisms. These biologically active peptides play a key role in various biological processes. The aim of this study is the extraction and the purification of bioactive materials that induce relaxation of an apical muscle from the pyloric caeca of Patiria pectinifera. The acidified pyloric caeca extract was partially separated by the solid phase extraction using a stepwise gradient on Sep-Pak C18 cartridge. Among the fractions, materials eluted with 60% methanol/0.1% trifluoroacetic acid was put a thorough of a series of high performance liquid chromatography (HPLC) steps to isolate a neuropeptide with relaxation activity. The purified compound was eluted at 28% acetonitrile in 0.1% trifluoroacetic acid with retention time of 25.8 min on the CAPCELL-PAK C18 reversed-phase column. To determine the molecular weight and the amino acid sequence of the purified peptide, LC-MS and Edman degradation method were used, respectively. The primary structure of the peptide was determined to be FGMGGAYDPLSAGFTD which corresponded to the amino acid sequence of a starfish myorelaxant peptide (SMP) isotype (SMPb) found in the cDNA sequence encoding SMPa and its isotypes. In this study, a muscle relaxant neuropeptide (SMPb) has been isolated from pyloric caeca of starfish P. pectinifera. This is the first report of SMPb isolation on the protein level from P. pectinifera.

Fluorimetric determination of the enantiomers of vigabatrin, an antiepileptic drug, by reversed-phase HPLC with a novel diastereomer derivatization reagent.

Herein, determination of an antiepileptic drug, (±)-vigabatrin (VB), was performed by reversed-phase HPLC with fluorimetric detection using a newly designed and synthesized fluorescence derivatization reagent, 2,5-dioxopyrrolidin-1-yl (4-{[(2-nitrophenyl)sulfonyl]oxy}-6-(3-oxomorpholino)quinoline-2-carbonyl)prolinate [Ns-MOK-(R)- or (S)-Pro-OSu]. During the derivatization of VB with Ns-MOK-(R)-Pro-OSu at 60°C, the nosyl (Ns) group, which was introduced to protect a phenolic hydroxy group, was released within 30 min to produce MOK-(R)-Pro-VB, which was detected fluorimetrically at 448 nm with an excitation wavelength of 333 nm. The VB enantiomers were separated on an octadecylsilica (ODS) column with a resolution value of 5.57, because Ns-MOK-(R)-Pro-OSu bears an optically active D-proline structure. A complete separation of MOK-(R)-Pro-(R)- and -(S)-VB enantiomers was achieved on the ODS column within 40 min using stepwise gradient elution, and the detection limits were ~0.80 and 0.37 pmol on the column, respectively. The proposed HPLC with fluorimetric detection method was successfully used for determining VB enantiomers in VB-spiked human serum following solid-phase extraction with an anion-exchange cartridge.

Time to Clinical Benefit of Dapagliflozin and Significance of Prior Heart Failure Hospitalization in Patients With Heart Failure With Reduced Ejection Fraction

Dapagliflozin has been shown to reduce the risk of cardiovascular death or worsening heart failure (HF) in patients with chronic HF and reduced ejection fraction (HFrEF). However, clinical inertia often underlies deferred initiation of effective therapies. To examine timing of onset of clinical benefit with dapagliflozin and magnitude as a function of proximity to prior HF hospitalization. This is a secondary analysis of a completed multinational trial. The Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure trial was a double-blind, placebo-controlled randomized clinical trial of dapagliflozin in patients with chronic HFrEF (n = 4744). From February 2017 to August 2018, the study enrolled patients in New York Heart Association classes II through IV and with left ventricular ejection fraction of 40% or less; the median (range) follow-up time was 18.2 (0-27.8) months. Hazard ratios (HRs) were calculated for the primary efficacy outcome with dapagliflozin vs placebo by time following randomization. Efficacy and safety of dapagliflozin were assessed according to the timing of the most recent HF hospitalization prior to trial enrollment. None. Composite of cardiovascular death or worsening HF. A total of 4744 patients were included (1109 women [23.4%]; mean [SD] age, 66.3 [10.9] years). The reduction in the primary outcome with dapagliflozin was rapidly apparent, with a sustained statistically significant benefit by 28 days after randomization (HR at 28 days, 0.51 [95% CI, 0.28-0.94]; P = .03). A total of 2251 patients (47.4%) had been previously hospitalized for HF, and 1301 (27.4%) had been hospitalized within 12 months prior to enrollment. Among patients treated with placebo, there was a stepwise gradient of risk for the primary outcome according to timing of most recent HF hospitalization, with 2-year Kaplan-Meier rates of 21.1%, 25.3%, and 33.8% (adjusted P = .003) for patients with a prior HF hospitalization never, more than 12 months ago, and 12 or fewer months ago, respectively. Across these subgroups, dapagliflozin reduced the relative risk of the primary outcome by 16% (HR, 0.84 [95% CI, 0.69-1.01]), 27% (HR, 0.73 [95% CI, 0.54-0.99]), and 36% (HR, 0.64 [95% CI, 0.51-0.80]), respectively (P = .07 for trend). Accordingly, patients with a more recent HF hospitalization tended to experience greater absolute risk reductions with dapagliflozin at 2 years: 2.1% (95% CI, -1.9% to 6.1%), 4.1% (95% CI, -3.6% to 11.7%), and 9.9% (95% CI, 3.3%-16.5%), respectively (P = .05 for trend). In this study, treatment with dapagliflozin was associated with rapid reduction in the risk of cardiovascular death or worsening HF, with a sustained statistically significant benefit emerging very early after randomization. Patients with a more recent HF hospitalization were at particularly high risk and experienced greater relative and absolute risk reductions with dapagliflozin. ClinicalTrials.gov Identifier NCT03036124.

974 Non-invasive transabdominal assessment of In-Utero fetal oxygen saturation in a hypoxic lamb model

Fetal heart rate monitoring is a poor predictor of fetal hypoxia due to its high false-positive rate. Utilizing a novel transabdominal fetal pulse oximeter (TFO), this study aimed to demonstrate the feasibility of non-invasive and direct assessment of fetal arterial blood oxygen saturation in-utero (SaO2) in a hypoxic lamb model. Fetal hypoxia was induced in 3 gravid term ewes (137.3±3.2 days gestation) by placing an inflatable balloon catheter in the infrarenal aorta via the common femoral artery (Fig 1). A fetal carotid arterial line was placed for continuous hemodynamic monitoring and arterial blood gases (ABG). The uterus was closed around the right fetal forelimb, and the laparotomy was closed, leaving the limb exposed for conventional pulse oximetry. The fetus’s depth from the ewe’s skin was determined, and the TFO device was placed on the ewe’s abdomen. The aortic balloon catheter was inflated in a stepwise fashion to decrease the ewe’s distal mean arterial pressure (dMAP) in 5mmHg increments. At each step, dMAP was maintained for 10 min, and fetal ABGs were recorded at 2.5, 5, and 10-min marks. The balloon was fully deflated after two consecutive measurements of fetal SaO2 <15%. The fetus was recovered for 45 min, and the stepwise gradient was repeated for a second round. At each dMAP level, the average fetal oxygen saturation measured by the TFO (SpO2) was compared to the average fetal SaO2. TFO measurements of fetal SpO2 were compared to fetal SaO2 (Fig 2A) and were found to be highly correlative (R=0.64 and p<0.0001) (Fig 2B). The ex-utero conventional clinical pulse oximeter readings from the exposed forelimb had a weak correlation with fetal SaO2 (R=0.16 and p<0.0003). Fetal depth, composed of ewe’s abdominal wall and uterine wall thickness, was 15.0±4.3mm (SD). The novel TFO device can measure fetal SaO2 based on the high correlation of SpO2 and SaO2 despite intervening maternal anatomy. TFO can potentially improve the accuracy of fetal hypoxia detection. Future research will focus on intrapartum validation in lamb models and human pregnancies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Abstract 17185: Burden and Prognostic Significance of Thrombocytopenia in the Cardiac Intensive Care Unit: Insights From the Critical Care Cardiology Trials Network (CCCTN) Registry

Introduction: Thrombocytopenia is associated with poor outcomes in general medical intensive care unit (ICU) populations; however, the burden and prognostic significance of thrombocytopenia in cardiac ICU (CICU) populations have not been rigorously studied. Methods: The Critical Care Cardiology Trials Network (CCCTN) is an investigator-initiated multicenter network of CICUs (n=25) in North America. Consecutive admissions to the CICU during annual snapshots (mostly 2 months) were submitted to the coordinating center (TIMI Study Group, Boston, MA) between September 2017 and September 2019. Patients were stratified by platelet counts on admission to the CICU and nadir platelet counts. Thrombocytopenia was classified as mild (100-149 K/uL), moderate (50-99 K/uL), or severe (&lt;50 K/uL). Results: Of 8206 CICU admissions with complete laboratory data, 21.7% had thrombocytopenia (platelets &lt;150 K/uL) on admission and 38.4% had thrombocytopenia at any point during their CICU course ( Fig-left ). Among those with normal platelet counts on admission (n=6423), 21.3% developed thrombocytopenia during their CICU course. Patients with thrombocytopenia on admission were more likely to have active cancer, underlying liver disease, and CKD as compared to those who did not (each p&lt;0.001). Among patients with cardiogenic shock (n=1478), 56.8% had thrombocytopenia (mild: 28.6%; moderate: 19.4%; severe: 8.9%). Among patients managed with mechanical circulatory support (MCS) (n=926), 65.0% had thrombocytopenia (mild: 27.0%; moderate: 24.3%; severe: 13.7%). There were stepwise gradients of increasing CICU and in-hospital mortality associated with lower nadir platelet counts (p-trend &lt;0.001) ( Fig-right ). Conclusions: Thrombocytopenia is common in CICU patients, including more than half of patients with cardiogenic shock and those managed with MCS. Thrombocytopenia is an adverse prognostic marker in CICU patients.

Step-wise multi-grained augmented gradient boosting decision trees for credit scoring

Credit scoring is an important financial tool for banks to determine whether to issue the loan to potential borrowers. Ensemble algorithms, which mainly can be divided into bagging ensembles and boosting ensembles, have shown great promise for credit scoring. However, some problems need to be further addressed: (1) Bagging-type algorithms enrich the feature diversity while keep the training target unchanged. However, these methods acting as feature augmentation process that highly rely on the training targets may increase the statistical similarity of the prediction results. (2) Though boosting-type ensemble algorithms avoid the problem of high prediction similarity, boosting algorithms always work on the original credit features leading to the lack of feature diversity. (3) A more intelligent credit risk management system should well balance the accuracy and its interpretability. Based on the above considerations, in this study, a step-wise multi-grained augmented gradient boosting decision trees (mg-GBDT) is proposed for credit scoring. In the proposed method, a multi-grained scanning is introduced for feature augmentation, which enriches the input feature of GBDT; the GBDT-based step-wisely optimization mechanism ensures low-deviation of credit scoring; besides, the proposed method inherits the good interpretability of tree-based structure, which provides intuitive reference results for policy-makers. Experiments on 6 credit datasets show that the proposed method outperforms classic GBDT. Moreover, numerical results indicate that mg-GBDT provides an alternative to neural network-based feature enhancement. Finally, the global interpretation results and the visualized decision path demonstrate that mg-GBDT can be a good choice for accurate credit scoring interpretation.

Simultaneous Quantification of κ-Carrageenan Oligosaccharides of DP 3, 5 and 7 by LC-MS/MS: Application to an in vitro Absorption Study

Carrageenans are widely utilized in many commercial applications such as the food and pharmaceutical industry, due to their excellent functional properties. In this study, a sensitive LC-MS/MS method was developed to determine κ-3, κ-5, and κ-7 carrageenan oligosaccharides simultaneously. Optimum MRM transitions for κ-3, κ-5, and κ-7 carrageenan oligosaccharides were (645.079→565.111, [M-H]−), (515.137→474.946, [M-2H]2−), and (471.484→445, [M-3H]3−), respectively. Chromatographic separation was performed on an Amide column coupled with a guard column operated at 60 °C under stepwise gradient elution. The linearity of the LC-MS/MS method for κ-3, κ-5, and κ-7 carrageenan oligosaccharides, evaluated over the concentration range of 0.10–20.0 µmol L−1, was excellent. The precisions of the method for κ-3, κ-5, and κ-7 carrageenan oligosaccharides were from 0.91% to 9.66%, and the inter-day precisions were from 0.92% to 10.5%. Validation of the LC-MS/MS method indicated that the method was precise and in line with the CFDA guidance. This method has been successfully applied to an in vitro absorption study.