Outcome-Stratified Analysis of Biomarker Trajectories for Patients Infected With Severe Acute Respiratory Syndrome Coronavirus 2.

Longitudinal trajectories of vital signs and biomarkers during hospital admission of patients with COVID-19 remain poorly characterized despite their potential to provide critical insights about disease progression. We studied 1884 patients with severe acute respiratory syndrome coronavirus 2 infection from April 3, 2020, to June 25, 2020, within 1 Maryland hospital system and used a retrospective longitudinal framework with linear mixed-effects models to investigate relevant biomarker trajectories leading up to 3 critical outcomes: mechanical ventilation, discharge, and death. Trajectories of 4 vital signs (respiratory rate, ratio of oxygen saturation (Spo2) to fraction of inspired oxygen (Fio2), pulse, and temperature) and 4 laboratory values (C-reactive protein (CRP), absolute lymphocyte count (ALC), estimated glomerular filtration rate, and D-dimer) clearly distinguished the trajectories of patients with COVID-19. Before any ventilation, log(CRP), log(ALC), respiratory rate, and Spo2-to-Fio2 ratio trajectories diverge approximately 8-10 days before discharge or death. After ventilation, log(CRP), log(ALC), respiratory rate, Spo2-to-Fio2 ratio, and estimated glomerular filtration rate trajectories again diverge 10-20 days before death or discharge. Trajectories improved until discharge and remained unchanged or worsened until death. Our approach characterizes the distribution of biomarker trajectories leading up to competing outcomes of discharge versus death. Moving forward, this model can contribute to quantifying the joint probability of biomarkers and outcomes when provided clinical data up to a given moment.

Seroprevalence of SARS-CoV-2 Antibodies in Rhode Island From a Statewide Random Sample.

Objectives. To characterize statewide seroprevalence and point prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Rhode Island.Methods. We conducted a cross-sectional survey of randomly selected households across Rhode Island in May 2020. Antibody-based and polymerase chain reaction (PCR)-based tests for SARS-CoV-2 were offered. Hispanics/Latinos and African Americans/Blacks were oversampled to ensure adequate representation. Seroprevalence estimations accounted for test sensitivity and specificity and were compared according to age, race/ethnicity, gender, housing environment, and transportation mode.Results. Overall, 1043 individuals from 554 households were tested (1032 antibody tests, 988 PCR tests). The estimated seroprevalence of SARS-CoV-2 antibodies was 2.1% (95% credible interval [CI] = 0.6, 4.1). Seroprevalence was 7.5% (95% CI = 1.3, 17.5) among Hispanics/Latinos, 3.8% (95% CI = 0.0, 15.0) among African Americans/Blacks, and 0.8% (95% CI = 0.0, 2.4) among non-Hispanic Whites. Overall PCR-based prevalence was 1.5% (95% CI = 0.5, 3.1).Conclusions. Rhode Island had low seroprevalence relative to other settings, but seroprevalence was substantially higher among African Americans/Blacks and Hispanics/Latinos. Rhode Island sits along the highly populated northeast corridor, making our findings broadly relevant to this region of the country. Continued monitoring via population-based sampling is needed to quantify these impacts going forward.

Classification using ensemble learning under weighted misclassification loss.

Binary classification rules based on covariates typically depend on simple loss functions such as zero-one misclassification. Some cases may require more complex loss functions. For example, individual-level monitoring of HIV-infected individuals on antiretroviral therapy requires periodic assessment of treatment failure, defined as having a viral load (VL) value above a certain threshold. In some resource limited settings, VL tests may be limited by cost or technology, and diagnoses are based on other clinical markers. Depending on scenario, higher premium may be placed on avoiding false-positives, which brings greater cost and reduced treatment options. Here, the optimal rule is determined by minimizing a weighted misclassification loss/risk. We propose a method for finding and cross-validating optimal binary classification rules under weighted misclassification loss. We focus on rules comprising a prediction score and an associated threshold, where the score is derived using an ensemble learner. Simulations and examples show that our method, which derives the score and threshold jointly, more accurately estimates overall risk and has better operating characteristics compared with methods that derive the score first and the cutoff conditionally on the score especially for finite samples.

Enhancing microbial fuel cell (MFC) performance in treatment of solid potato waste by mixed feeding of boiled potato and waste activated sludge.

The effects of mixed feeding of boiled potato and waste activated sludge (WAS) on the performance of a microbial fuel cell (MFC) in treating solid potato waste were investigated. The coulombic efficiency (CE) of four MFCs fed with potato cubes containing 0, 48.7, 67.3 and 85.6% of boiled potato was 53.5, 70.5, 92.7 and 71.1%, respectively, indicating enhanced electricity generation and the existence of an optimum mixing ratio. The hydrolysis rate estimated using a first-order sequential hydrolysis model increased from 0.061 to 0.191 day-1, leading to shortening of the startup time for current density reaching its maximum from 25 to 5 days. The final chemical oxygen demand (COD) removal reached 85%. The CE of seven MFCs, fed with raw potato alone, sterilized/unsterilized WAS alone, and four mixed samples of raw potato with sterilized WAS at ratios of 2:1 and 4:1 and unsterilized WAS at 2:1 and 4:1, was found to be 6.1, 43.6, 0.3, 31.0, 16.5, 0.9 and 31.1%, respectively. The hydrolysis rate increased from 0.056 to 0.089 day-1, and the final COD removal changed from 39.5 to 89.6% following the order: potato alone > mixture of potato & WAS > sterilized WAS alone > unsterilized WAS alone.

Ultrastructural characteristics and morphological relationships of cardiomyocytes and telocytes in the myocardium of the bullfrog (Rana catesbeiana).

Telocytes (TCs) are distinctive interstitial cells due to their characteristic structures and heterogeneity. They are suggested to participate in tissue repair/regeneration. TCs have been identified in many organs of various mammals. However, data on TCs in lower animals are still very limited. In this work, TCs were identified in the myocardium of the bullfrog (Rana catesbeiana) by light and transmission electron microscopy (TEM). The structural relationships between TCs and neighbouring cell types were measured using the ImageJ (FiJi) morphometric software. TCs with slender Tps (telepodes) were located around cardiomyocytes (CMC). TEM revealed TCs with long Tps in the stroma between CMC. The homocellular tight junctions were observed between the Tps. The Tps were also very close to the neighbouring CMC. The distance between Tps and CMC was 0.15 ± 0.08 µm. Notably, Tps were observed to adhere to the periphery of the satellite cells. The Tps and the satellite cells established heterocellular structural connections by tight junctions. Additionally, Tps were frequently observed in close proximity to mast cells (MCs). The distance between the Tps and the MCs was 0.19 ± 0.09 µm. These results confirmed that TCs are present in the myocardium of the bullfrog, and that TCs established structural relationships with neighbouring cell types, including satellite cells and MCs. These findings provide the anatomical evidence to support the note that TCs are involved in tissue regeneration.

Population-Based Estimates and Predictors of Child and Adolescent Linkage to HIV Care or Death in Western Kenya.

BACKGROUND: Population-level estimates of linkage to HIV care among children and adolescents (CAs) can facilitate progress toward 95-95-95 goals. SETTING: This study was conducted in Bunyala, Chulaimbo, and Teso North subcounties, Western Kenya. METHODS: Linkage to care was defined among CAs diagnosed with HIV through Academic Model Providing Access to Healthcare (AMPATH)'s home-based counseling and testing initiative (HBCT) by merging HBCT and AMPATH Medical Record System data. Using follow-up data from Bunyala, we examined factors associated with linkage or death, using weighted multinomial logistic regression to account for selection bias from double-sampled visits. Based on the estimated model, we imputed the trajectory for each person in 3 subcounties until a simulated linkage or death occurred or until the end of 8 years when an individual was simulated to be censored. RESULTS: Of 720 CAs in the analytic sample, 68% were between 0 and 9 years and 59% were female. Probability of linkage among CAs in the combined 3 subcounties was 48%-49% at 2 years and 64%-78% at 8 years while probability of death was 13% at 2 years and 19% at 8 years. Single or double orphanhood predicted linkage (adjusted odds ratio [aOR]: 2.66, 95% confidence interval [CI]: 1.33 to 5.32) and death (aOR: 9.85 [95% CI: 2.21 to 44.01]). Having a mother known to be HIV-positive also predicted linkage (aOR = 1.94, 95% CI: 0.97 to 3.86) and death (aOR: 14.49, 95% CI: 3.32 to 63.19). CONCLUSION: HIV testers/counselors should continue to ensure linkage among orphans and CAs with mothers known to be HIV-positive and also to support other CAs to link to HIV care.

Glucose-6-phosphate dehydrogenase-deficient mice have increased renal oxidative stress and increased albuminuria.

Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway and the principal source of NADPH, a major cellular reductant, and is central to cell survival. Our previous work showed that diabetes and increased aldosterone are acquired forms of G6PD deficiency, leading to decreased G6PD activity and NADPH levels and damage to kidney tissue and endothelial cells. In this study, G6PD-deficient mice were studied to test the hypothesis that decreased G6PD activity per se can cause changes similar to those seen in the acquired conditions of G6PD deficiency. Results show that as compared with control mice, G6PD-deficient mice had increased oxidative stress, as manifested by decreased NADPH levels and decreased GSH levels, and increased markers of lipid peroxidation. G6PD-deficient mice had increased protein kinase C activity, increased nuclear factor-kappaB activity, and increased urinary albumin levels, all of which is similar to changes seen in diabetic mice. Changes persisted as the mice aged, as old G6PD-deficient mice (17-20 mo) had higher urine albumin levels and also had evidence for increased apoptosis in the renal cortex. These results show that decreased G6PD activity per se is sufficient to cause changes similar to those seen in diabetic mice.

Population-based estimates of engagement in HIV care and mortality using double-sampling methods following home-based counseling and testing in western Kenya.

INTRODUCTION: Data on engagement in HIV care from population-based samples in sub-Saharan Africa are limited. The objective of this study was to use double-sampling methods to estimate linkage to HIV care, ART initiation, and mortality among all adults diagnosed with HIV by a comprehensive home-based counseling and testing (HBCT) program in western Kenya. METHODS: HBCT was conducted door-to-door from December 2009 to April 2011 in three sub-counties of western Kenya by AMPATH (Academic Model Providing Access to Healthcare). For those identified as HIV-positive, data were merged with electronic medical records to determine engagement with HIV care. A randomly-drawn follow-up sample of 120 adults identified via HBCT who had not linked to care as of June 2015 in Bunyala sub-county were visited by trained fieldworkers to ascertain HIV care engagement and vital status. Double-sampled data were used to generate, via multinomial regression, predicted probabilities of engagement in care and mortality among those whose status could not be ascertained by matching with the electronic medical records in the three catchments. RESULTS: Incorporating information from the double-sampling yielded estimates of prospective linkage to HIV care that ranged from 40-45%. Mortality estimates of those who did not engage in care following HBCT ranged from 12-16%. Among those who linked to care following HBCT, between 72-81% initiated ART. DISCUSSION: In settings without universal national identifiers, rates of linkage to care from community-based programs may be subject to substantial underestimation. Follow-up samples of those with missing information can be used to partially correct this bias, as has been demonstrated previously for mortality among those who were lost-to-care programs. There is a need for harmonized data systems across health systems and programs.

Synergistic effect of mixing cationic and nonionic surfactants on corrosion inhibition of mild steel in HCl: Experimental and theoretical investigations.

We studied the inhibition performances of IMB (imidazoline quaternary salt (IM) and benzotriazole (BTAH)) and IMO (IM and octyl phenol ethoxylates (OP)) mixtures as inhibitors of L245 steel placed in 10 vol% HCl solution at 298 K using experimental methods and theoretical calculations. We found that the mixtures adsorb on the steel by an endothermic spontaneous process, and the adsorption model follows Langmuir isotherm. The mixtures exhibit good synergistic inhibition effect, and the inhibition efficiency enhanced in turn (IMB < IMO). The relationship between synergistic effect of organic inhibitors and their energetic position of molecular frontier orbitals was discussed.

Improved HIV-1 Viral Load Monitoring Capacity Using Pooled Testing With Marker-Assisted Deconvolution.

OBJECTIVE: Improve pooled viral load (VL) testing to increase HIV treatment monitoring capacity, particularly relevant for resource-limited settings. DESIGN: We developed marker-assisted mini-pooling with algorithm (mMPA), a new VL pooling deconvolution strategy that uses information from low-cost, routinely collected clinical markers to determine an efficient order of sequential individual VL testing and dictates when the sequential testing can be stopped. METHODS: We simulated the use of pooled testing to ascertain virological failure status on 918 participants from 3 studies conducted at the Academic Model Providing Access to Healthcare in Eldoret, Kenya, and estimated the number of assays needed when using mMPA and other pooling methods. We also evaluated the impact of practical factors, such as specific markers used, prevalence of virological failure, pool size, VL measurement error, and assay detection cutoffs on mMPA, other pooling methods, and single testing. RESULTS: Using CD4 count as a marker to assist deconvolution, mMPA significantly reduces the number of VL assays by 52% [confidence interval (CI): 48% to 57%], 40% (CI: 38% to 42%), and 19% (CI: 15% to 22%) compared with individual testing, simple mini-pooling, and mini-pooling with algorithm, respectively. mMPA has higher sensitivity and negative/positive predictive values than mini-pooling with algorithm, and comparable high specificity. Further improvement is achieved with additional clinical markers, such as age and time on therapy, with or without CD4 values. mMPA performance depends on prevalence of virological failure and pool size but is insensitive to VL measurement error and VL assay detection cutoffs. CONCLUSIONS: mMPA can substantially increase the capacity of VL monitoring.

Switching to once-daily liraglutide from twice-daily exenatide further improves glycemic control in patients with type 2 diabetes using oral agents.

OBJECTIVE: To evaluate efficacy and safety of switching from twice-daily exenatide to once-daily liraglutide or of 40 weeks of continuous liraglutide therapy. RESEARCH DESIGN AND METHODS: When added to oral antidiabetes drugs in a 26-week randomized trial (Liraglutide Effect and Action in Diabetes [LEAD]-6), liraglutide more effectively improved A1C, fasting plasma glucose, and the homeostasis model of beta-cell function (HOMA-B) than exenatide, with less persistent nausea and hypoglycemia. In this 14-week extension of LEAD-6, patients switched from 10 microg twice-daily exenatide to 1.8 mg once-daily liraglutide or continued liraglutide. RESULTS: Switching from exenatide to liraglutide further and significantly reduced A1C (0.32%), fasting plasma glucose (0.9 mmol/l), body weight (0.9 kg), and systolic blood pressure (3.8 mmHg) with minimal minor hypoglycemia (1.30 episodes/patient-year) or nausea (3.2%). Among patients continuing liraglutide, further significant decreases in body weight (0.4 kg) and systolic blood pressure (2.2 mmHg) occurred with 0.74 episodes/patient-year of minor hypoglycemia and 1.5% experiencing nausea. CONCLUSIONS: Conversion from exenatide to liraglutide is well tolerated and provides additional glycemic control and cardiometabolic benefits.

Effects of N-acetyl-cysteine on endothelial function and inflammation in patients with type 2 diabetes mellitus.

Endothelial dysfunction has been associated with premature vascular disease. There is increasing data that N-acetyl-cysteine (NAC) may prevent or improve endothelial dysfunction. The aim of this study was to assess the effects of NAC on endothelial function in patients with type 2 diabetes mellitus, a population at high risk for endothelial dysfunction. Twenty-four patients with diabetes mellitus were assigned randomly to initial therapy with either 900 mg NAC or placebo twice daily in a double-blind, cross-over study design. Flowmediated vasodilation (FMD) of the brachial artery was assessed at baseline, after four weeks of therapy, after a four-week wash-out period, and after another four weeks on the opposite treatment. Plasma and red blood cell glutathione levels and high-sensitivity C-reactive protein (CRP) were measured at all four visits. At baseline, FMD was moderately impaired (3.7±2.9%). There was no significant change in FMD after four weeks of NAC therapy as compared to placebo (0.1±3.6% vs. 1.2±4.2%). Similarly, there was no significant change in glutathione levels. However, median CRP decreased from 2.35 to 2.14 mg/L during NAC therapy (p=0.04), while it increased from 2.24 to 2.65 mg/L with placebo. No side effects were noted during the treatment period. In this double-blind, randomized cross-over study, four weeks of oral NAC therapy failed to improve endothelial dysfunction in patients with diabetes mellitus. However, NAC therapy decreased CRP levels, suggesting that this compound may have some efficacy in reducing systemic inflammation.

Introduction of hyperglycemia and dyslipidemia in the pathogenesis of diabetic vascular complications.

Hyperglycemia and dyslipidemia are significant and independent risk factors for the vascular complications in patients with diabetes. They have been suggested to cause cardiovascular pathologic changes in diabetic states through the following molecular mechanisms: formation and accumulation of advanced glycation end products; increased oxidative stress; activation of protein kinase C pathway; increased activity of hexosamine pathway; and vascular inflammation and the impairment of insulin action in the vascular tissues.

Diabetes causes inhibition of glucose-6-phosphate dehydrogenase via activation of PKA, which contributes to oxidative stress in rat kidney cortex.

The incidence of diabetic nephropathy has been increasing. Studies have shown that oxidative stress (due to increased oxidant production and/or decreased antioxidant activity) is a critical underlying mechanism. The principal intracellular reductant is NADPH whose production is mainly dependent on glucose-6-phosphate dehydrogenase (G6PD) activity. Our work in cultured cells previously showed that high glucose caused activation of protein kinase A (PKA) and subsequent phosphorylation and inhibition of G6PD activity and hence decreased NADPH (Zhang Z, Apse K, Pang J, and Stanton RC. J Biol Chem 275:40042-40047, 2000). The purpose of this study was to determine whether these findings occur in diabetic rats (induced by streptozotocin) compared with control. G6PD activity and accordingly NADPH levels and glutathione levels were significantly decreased in diabetic kidneys compared with control kidneys. Lipid peroxidation was significantly increased, which correlated with decreased G6PD activity (r = 0.48). G6PD expression was significantly reduced, which correlated with decreased G6PD activity (r = 0.72). PKA activity and serine phosphorylation of G6PD were significantly increased and were closely correlated with decreased G6PD activity (r = 0.51 for PKA activity; r = 0.93 for serine phosphorylation of G6PD). Insulin treatment and/or correction of hyperglycemia ameliorated the changes caused by diabetes. In conclusion, chronic hyperglycemia caused inhibition of G6PD activity via decreased expression and increased phosphorylation of G6PD, which therefore led to increased oxidative stress.