Vaccine Efficacy in Adults in a Respiratory Syncytial Virus Challenge Study.

BACKGROUND: Although human respiratory syncytial virus (RSV) is an important cause of illness and death in older adults, no RSV vaccine has been licensed. METHODS: In a phase 2a study, we randomly assigned healthy adults (18 to 50 years of age), in a 1:1 ratio, to receive a single intramuscular injection of either bivalent prefusion F (RSVpreF) vaccine or placebo. Approximately 28 days after injection, participants were inoculated intranasally with the RSV A Memphis 37b challenge virus and observed for 12 days. The per-protocol prespecified primary end points were the following: reverse-transcriptase-quantitative polymerase-chain-reaction (RT-qPCR)-confirmed detectable RSV infection on at least 2 consecutive days with at least one clinical symptom of any grade from two categories or at least one grade 2 symptom from any category, the total symptom score from day 1 to discharge, and the area under the curve (AUC) for the RSV viral load in nasal-wash samples measured by means of RT-qPCR from day 2 after challenge to discharge. In addition, we assessed immunogenicity and safety. RESULTS: After participants were inoculated with the challenge virus, vaccine efficacy of 86.7% (95% CI, 53.8 to 96.5) was observed for symptomatic RSV infection confirmed by any detectable viral RNA on at least 2 consecutive days. The median AUC for the RSV viral load (hours × log10 copies per milliliter) as measured by RT-qPCR assay was 0.0 (interquartile range, 0.0 to 19.0) in the vaccine group and 96.7 (interquartile range, 0.0 to 675.3) in the placebo group. The geometric mean factor increase from baseline in RSV A-neutralizing titers 28 days after injection was 20.5 (95% CI, 16.6 to 25.3) in the vaccine group and 1.1 (95% CI, 0.9 to 1.3) in the placebo group. More local injection-site pain was noted in the vaccine group than in the placebo group. No serious adverse events were observed in either group. CONCLUSIONS: RSVpreF vaccine was effective against symptomatic RSV infection and viral shedding. No evident safety concerns were identified. These findings provide support for further evaluation of RSVpreF vaccine in a phase 3 efficacy study. (Funded by Pfizer; EudraCT number, 2020-003887-21; ClinicalTrials.gov number, NCT04785612.).

Reduced Respiratory Syncytial Virus Load, Symptoms, and Infections: A Human Challenge Trial of MVA-BN-RSV Vaccine.

BACKGROUND: Respiratory syncytial virus (RSV) causes significant disease burden in older adults. MVA-BN-RSV is a novel poxvirus-vectored vaccine encoding internal and external RSV proteins. METHODS: In a phase 2a randomized double-blind, placebo-controlled trial, healthy participants aged 18 to 50 years received MVA-BN-RSV or placebo, then were challenged 4 weeks later with RSV-A Memphis 37b. Viral load was assessed from nasal washes. RSV symptoms were collected. Antibody titers and cellular markers were assessed before and after vaccination and challenge. RESULTS: After receiving MVA-BN-RSV or placebo, 31 and 32 participants, respectively, were challenged. Viral load areas under the curve from nasal washes were lower (P = .017) for MVA-BN-RSV (median = 0.00) than placebo (median = 49.05). Total symptom scores also were lower (median = 2.50 and 27.00, respectively; P = .004). Vaccine efficacy against symptomatic, laboratory-confirmed or culture-confirmed infection was 79.3% to 88.5% (P = .022 and .013). Serum immunoglobulin A and G titers increased approximately 4-fold after MVA-BN-RSV vaccination. Interferon-γ-producing cells increased 4- to 6-fold after MVA-BN-RSV in response to stimulation with the encoded RSV internal antigens. Injection site pain occurred more frequently with MVA-BN-RSV. No serious adverse events were attributed to vaccination. CONCLUSIONS: MVA-BN-RSV vaccination resulted in lower viral load and symptom scores, fewer confirmed infections, and induced humoral and cellular responses. CLINICAL TRIALS REGISTRATION: NCT04752644.

Empagliflozin Disrupts a Tnfrsf12a-Mediated Feed Forward Loop That Promotes Left Ventricular Hypertrophy.

PURPOSE: Although the cardioprotective benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors are now widely appreciated, the mechanisms underlying these benefits remain unresolved. Tumor necrosis factor receptor superfamily member 12a (Tnfrsf12a) is a receptor for tumor necrosis factor superfamily member 12 (Tnfsf12). Tnfrsf12a is highly inducible and plays a key role in the development of cardiac hypertrophy and heart failure. Here we set out to determine if SGLT2 inhibition affects the Tnfsf12/Tnfrsf12a system in the stressed myocardium. METHODS: C57BL/6N mice that had undergone sham or transverse aortic constriction (TAC) surgery were treated with either the SGLT2 inhibitor empagliflozin (400 mg/kg diet; 60-65 mg/kg/day) or standard chow alone and were followed for 8 weeks. Tnfrsf12a expression in mouse hearts was assessed by in situ hybridization, qRT-PCR, and immunoblotting. RESULTS: Left ventricular (LV) mass, end-systolic volume, and end-diastolic volume were all increased in TAC mice and were significantly lower with empagliflozin. Myocyte hypertrophy and interstitial fibrosis in TAC hearts were similarly attenuated with empagliflozin. Tnfrsf12a expression was upregulated in mouse hearts following TAC surgery but not in the hearts of empagliflozin-treated mice. In cultured cardiomyocytes, Tnfrsf12a antagonism attenuated the increase in cardiomyocyte size that was induced by phenylephrine. CONCLUSION: Empagliflozin attenuates LV enlargement in mice with hypertrophic heart failure. This effect may be mediated, at least in part, by a reduction in loading conditions which limits upregulation of the inducible, proinflammatory, and prohypertrophic TNF superfamily receptor, Tnfrsf12a. Disruption of the Tnfsf12/Tnfrsf12a feed forward system may contribute to the cardioprotective benefits of SGLT2 inhibition.

The SGLT2i Dapagliflozin Reduces RV Mass Independent of Changes in RV Pressure Induced by Pulmonary Artery Banding.

BACKGROUND: Sodium glucose linked transporter 2 (SGLT2) inhibition not only reduces morbidity and mortality in patients with diagnosed heart failure but also prevents the development of heart failure hospitalization in those at risk. While studies to date have focused on the role of SGLT2 inhibition in left ventricular failure, whether this drug class is efficacious in the treatment and prevention of right heart failure has not been explored. HYPOTHESIS: We hypothesized that SGLT2 inhibition would reduce the structural, functional, and molecular responses to pressure overload of the right ventricle. METHODS: Thirteen-week-old Fischer F344 rats underwent pulmonary artery banding (PAB) or sham surgery prior to being randomized to receive either the SGLT2 inhibitor: dapagliflozin (0.5 mg/kg/day) or vehicle by oral gavage. After 6 weeks of treatment, animals underwent transthoracic echocardiography and invasive hemodynamic studies. Animals were then terminated, and their hearts harvested for structural and molecular analyses. RESULTS: PAB induced features consistent with a compensatory response to increased right ventricular (RV) afterload with elevated mass, end systolic pressure, collagen content, and alteration in calcium handling protein expression (all p < 0.05 when compared to sham + vehicle). Dapagliflozin reduced RV mass, including both wet and dry weight as well as normalizing the protein expression of SERCA 2A, phospho-AMPK and LC3I/II ratio expression (all p < 0.05). SIGNIFICANCE: Dapagliflozin reduces the structural, functional, and molecular manifestations of right ventricular pressure overload. Whether amelioration of these early changes in the RV may ultimately lead to a reduction in RV failure remains to be determined.

Late intervention in the remnant kidney model attenuates proteinuria but not glomerular filtration rate decline.

AIM: The use of animal models to predict the response to new therapies in humans is a vexing issue in nephrology. Unlike patients with chronic kidney disease (CKD), few rodent models develop a progressive decline in glomerular filtration rate (GFR) so that experimental studies frequently report a reduction in proteinuria as the primary efficacy outcome. Moreover, while humans present with established kidney disease that continues to progress, many experimental studies investigate therapies in the prevention rather than in a therapeutic setting. METHODS: We used the remnant kidney (subtotal nephrectomy [SNX]) rat model that develops a decline in GFR in conjunction with heavy proteinuria and hypertension along with the histological hallmarks of CKD in humans, glomerulosclerosis and tubulointerstitial fibrosis. Using agents that had been shown to improve GFR as well as proteinuria in the prevention setting, angiotensin-converting enzyme (ACE) inhibition with enalapril and SIRT1 activation with SRT3025, treatment was initiated 6 weeks after SNX. RESULTS: While enalapril reduced blood pressure, proteinuria and histological injury, it did not improve GFR, as measured by inulin clearance. SRT3025 improved neither GFR nor structural damage despite a reduction in proteinuria. CONCLUSION: These findings demonstrate that neither a reduction in proteinuria nor a reversal of structural damage in the kidney will necessarily translate to a restoration of kidney function.

Identification of behaviour patterns in waste collection and disposal during the first wave of COVID-19 in Regina, Saskatchewan, Canada.

The novel coronavirus (2019-nCov) has had significant impacts on almost every aspect of daily life. From 'stay-at-home' orders to the progressive lifting of restrictions, the COVID-19 pandemic has had unprecedented effects on consumer behaviours and waste disposal habits. The purpose of this short communication is to examine time series waste collection and disposal data in a mid-sized Canadian city to understand how behavioural changes have affected municipal waste management. The results suggest that private waste disposal increased during the pandemic. This may be due to people doing home renovations in order to accommodate working from home. Furthermore, it appears that changes in consumer habits destabilized the consistency of waste disposal tonnage when compared to the same time period in 2019. When considering curbside residential waste collection, there was also an increase in tonnage. This may be the result of more waste being generated at home due to changes in eating and cooking habits, and cleaning routine. Finally, the ratio of residential waste collection to total disposal is examined. More residential waste is being generated, which may have environmental and operational effects, especially related to collection and transportation. The results from this study are important from an operational perspective, and will help planners and policy makers to better prepare for changes in the waste stream due to pandemics or other emergencies.

Challenges to COVID-19 vaccine supply chain: Implications for sustainable development goals.

The COVID-19 outbreak has demonstrated the diverse challenges that supply chains face to significant disruptions. Vaccine supply chains are no exception. Therefore, it is elemental that challenges to the COVID-19 vaccine supply chain (VSC) are identified and prioritized to pave the way out of this pandemic. This study combines the decision-making trial and evaluation laboratory (DEMATEL) method with intuitionistic fuzzy sets (IFS) to explore the key challenges of the COVID-19 VSC. The IFS theory tackles the uncertainty of key challenges while DEMATEL addresses the interlaced causal relationships among crucial challenges to the COVID-19 VSC. This work identifies 15 challenges and reveals that 'Limited number of vaccine manufacturing companies', 'Inappropriate coordination with local organizations', 'Lack of vaccine monitoring bodies', 'Difficulties in monitoring and controlling vaccine temperature', and 'Vaccination cost and lack of financial support for vaccine purchase' are the most critical challenges. The causal interactions along with mutual relationships among these challenges are also scrutinized, and implications for sustainable development goals (SDGs) are drawn. The results offer practical guidelines for stakeholders and government policy makers around the world to develop an improved VSC for the COVID-19 virus.

Heart Rate Reduction Improves Right Ventricular Function and Fibrosis in Pulmonary Hypertension.

The potential benefit of heart rate reduction (HRR), independent of ß-blockade, on right ventricular (RV) function in pulmonary hypertension (PH) remains undecided. We studied HRR effects on RV fibrosis and function in PH and RV pressure-loading models. Adult rats were randomized to 1) sham controls, 2) monocrotaline (MCT)-induced PH, 3) SU5416 + hypoxia (SUHX)-induced PH, or 4) pulmonary artery banding (PAB). Ivabradine (IVA) (10 mg/kg/d) was administered from 2 weeks after PH induction or PAB. Exercise tolerance, echocardiography, and pressure-volume hemodynamics were obtained at a terminal experiment 3 weeks later. RV myocardial samples were analyzed for putative mechanisms of HRR effects through fibrosis, profibrotic molecular signaling, and Ca++ handling. The effects of IVA versus carvedilol on human induced pluripotent stem cell-derived cardiomyocytes beat rate and relaxation properties were evaluated in vitro. Despite unabated severely elevated RV systolic pressures, IVA improved RV systolic and diastolic function, profibrotic signaling, and RV fibrosis in PH/PAB rats. RV systolic-elastance (control, 121 ± 116; MCT, 49 ± 36 vs. MCT+IVA, 120 ± 54; PAB, 70 ± 20 vs. PAB+IVA, 168 ± 76; SUHX, 86 ± 56 vs. SUHX +IVA, 218 ± 111; all P < 0.05), the time constant of RV relaxation, echo indices of RV function, and fibrosis (fibrosis: control, 4.6 ± 1%; MCT, 13.4 ± 6.5 vs. MCT+IVA, 6.7 ± 2.6%; PAB, 11.4 ± 4.5 vs. PAB+IVA, 6.4 ± 5.1%; SUHX, 10 ± 4.6 vs. SUHX+IVA, 3.9 ± 2.2%; all P < 0.001) were improved by IVA versus controls. IVA had a dose-response effect on induced pluripotent stem cell-derived cardiomyocytes beat rate by delaying Ca++ loss from the cytoplasm. In experimental PH or RV pressure loading, HRR improves RV fibrosis, function, and exercise endurance independent of ß-blockade. The balance between adverse tachycardia and bradycardia requires further study, but judicious HRR may provide a promising strategy to improve RV function in clinical PH.

Load-independent effects of empagliflozin contribute to improved cardiac function in experimental heart failure with reduced ejection fraction.

BACKGROUND AND AIMS: Sodium-glucose linked cotransporter-2 (SGLT2) inhibitors reduce the likelihood of hospitalization for heart failure and cardiovascular death in both diabetic and non-diabetic individuals with reduced ejection fraction heart failure. Because SGLT2 inhibitors lead to volume contraction with reductions in both preload and afterload, these load-dependent factors are thought to be major contributors to the cardioprotective effects of the drug class. Beyond these effects, we hypothesized that SGLT2 inhibitors may also improve intrinsic cardiac function, independent of loading conditions. METHODS: Pressure-volume (P-V) relationship analysis was used to elucidate changes in intrinsic cardiac function, independent of alterations in loading conditions in animals with experimental myocardial infarction, a well-established model of HFrEF. Ten-week old, non-diabetic Fischer F344 rats underwent ligation of the left anterior descending (LAD) coronary artery to induce myocardial infarction (MI) of the left ventricle (LV). Following confirmation of infarct size with echocardiography 1-week post MI, animals were randomized to receive vehicle, or the SGLT2 inhibitor, empagliflozin. Cardiac function was assessed by conductance catheterization just prior to termination 6 weeks later. RESULTS: The circumferential extent of MI in animals that were subsequently randomized to vehicle or empagliflozin groups was similar. Empagliflozin did not affect fractional shortening (FS) as assessed by echocardiography. In contrast, load-insensitive measures of cardiac function were substantially improved with empagliflozin. Load-independent measures of cardiac contractility, preload recruitable stroke work (PRSW) and end-systolic pressure volume relationship (ESPVR) were higher in rats that had received empagliflozin. Consistent with enhanced cardiac performance in the heart failure setting, systolic blood pressure (SBP) was higher in rats that had received empagliflozin despite its diuretic effects. A trend to improved diastolic function, as evidenced by reduction in left ventricular end-diastolic pressure (LVEDP) was also seen with empagliflozin. MI animals treated with vehicle demonstrated myocyte hypertrophy, interstitial fibrosis and evidence for changes in key calcium handling proteins (all p < 0.05) that were not affected by empagliflozin therapy. CONCLUSION: Empagliflozin therapy improves cardiac function independent of loading conditions. These findings suggest that its salutary effects are, at least in part, due to actions beyond a direct effect of reduced preload and afterload.

The α11 integrin mediates fibroblast-extracellular matrix-cardiomyocyte interactions in health and disease.

Excessive cardiac interstitial fibrosis impairs normal cardiac function. We have shown that the α11ß1 (α11) integrin mediates fibrotic responses to glycated collagen in rat myocardium by a pathway involving transforming growth factor-ß. Little is known of the role of the α11 integrin in the developing mammalian heart. Therefore, we examined the impact of deletion of the α11 integrin in wild-type mice and in mice treated with streptozotocin (STZ) to elucidate the role of the α11 integrin in normal cardiac homeostasis and in the pathogenesis of diabetes-related fibrosis. As anticipated, cardiac fibrosis was reduced in α11 integrin knockout mice (α11(-/-); C57BL/6 background) treated with STZ compared with STZ-treated wild-type mice (P < 0.05). Unexpectedly, diastolic function was impaired in both vehicle and STZ-treated α11(-/-) mice, as shown by the decreased minimum rate of pressure change and prolonged time constant of relaxation in association with increased end-diastolic pressure (all P < 0.05 compared with wild-type mice). Accordingly, we examined the phenotype of untreated α11(-/-) mice, which demonstrated a reduced cardiomyocyte cross-sectional cell area and myofibril thickness (all P < 0.05 compared with wild-type mice) and impaired myofibril arrangement. Immunostaining for desmin and connexin 43 showed abnormal intermediate filament organization at intercalated disks and impaired gap-junction development. Overall, deletion of the α11 integrin attenuates cardiac fibrosis in the mammalian mouse heart and reduces ECM formation as a result of diabetes. Furthermore, α11 integrin deletion impairs cardiac function and alters cardiomyocyte morphology. These findings shed further light on the poorly understood interaction between the fibroblast-cardiomyocyte and the ECM.

Early outgrowth cells release soluble endocrine antifibrotic factors that reduce progressive organ fibrosis.

Adult bone marrow-derived cells can improve organ function in chronic disease models, ostensibly by the release of paracrine factors. It has, however, been difficult to reconcile this prevailing paradigm with the lack of cell retention within injured organs and their rapid migration to the reticuloendothelial system. Here, we provide evidence that the salutary antifibrotic effects of bone marrow-derived early outgrowth cells (EOCs) are more consistent with an endocrine mode of action, demonstrating not only the presence of antifibrotic factors in the plasma of EOC-treated rats but also that EOC conditioned medium (EOC-CM) potently attenuates both TGF-ß- and angiotensin II-induced fibroblast collagen production in vitro. To examine the therapeutic relevance of these findings in vivo, 5/6 subtotally nephrectomized rats, a model of chronic kidney and heart failure characterized by progressive fibrosis of both organs, were randomized to receive i.v. injections of EOC-CM, unconditioned medium, or 10(6) EOCs. Rats that received unconditioned medium developed severe kidney injury with cardiac diastolic dysfunction. In comparison, EOC-CM-treated rats demonstrated substantially improved renal and cardiac function and structure, mimicking the changes found in EOC-treated animals. Mass spectrometric analysis of EOC-CM identified proteins that regulate cellular functions implicated in fibrosis. These results indicate that EOCs secrete soluble factor(s) with highly potent antifibrotic activity, that when injected intravenously replicate the salutary effects of the cells themselves. Together, these findings suggest that an endocrine mode of action may underlie the effectiveness of cell therapy in certain settings and portend the possibility for systemic delivery of cell-free therapy.

Prediction of photovoltaic waste generation in Canada using regression-based model.

The global surge in photovoltaic (PV) installations and the resulting increase in PV waste are a growing concern. The aims of this study include predicting the volume of photovoltaic waste in Canada. The forecasting of solar waste volume employed linear regression, 2nd order polynomial regression, and power regression models. The study's results indicate that Canada is on the verge of facing challenges related to the end-of-life treatment of photovoltaic modules in the coming years due to the significant growth in PV capacity over recent decades. According to the analysis, for early loss, the PV waste volume in 2045 could range from 180,000 MT to 270,000 MT, and for regular loss, it could range from 160,000 MT to 180,000 MT. This research is anticipated to assist relevant government agencies in assessing the prospective volume of PV waste to establish a sustainable and resilient PV waste management plan for Canada. These findings may shed light on the feasibility of a circular economy and advocate for the involvement of all stakeholders in a carefully coordinated strategy to mitigate potential environmental impacts and optimize resource utilization efficiency.

Bilateral nephrectomy impairs cardiovascular function and cerebral perfusion in a rat model of acute hemodilutional anemia.

Anemia and renal failure are independent risk factors for perioperative stroke, prompting us to assess the combined impact of acute hemodilutional anemia and bilateral nephrectomy (2Nx) on microvascular brain Po2 (PBro2) in a rat model. Changes in PBro2 (phosphorescence quenching) and cardiac output (CO, echocardiography) were measured in different groups of anesthetized Sprague-Dawley rats (1.5% isoflurane, n = 5-8/group) randomized to Sham 2Nx or 2Nx and subsequently exposed to acute hemodilutional anemia (50% estimated blood volume exchange with 6% hydroxyethyl starch) or time-based controls (no hemodilution). Outcomes were assessed by ANOVA with significance assigned at P < 0.05. At baseline, 2Nx rats demonstrated reduced CO (49.9 ± 9.4 vs. 66.3 ± 19.3 mL/min; P = 0.014) and PBro2 (21.1 ± 2.9 vs. 32.4 ± 3.1 mmHg; P < 0.001) relative to Sham 2Nx rats. Following hemodilution, 2Nx rats demonstrated a further decrease in PBro2 (15.0 ± 6.3 mmHg, P = 0.022). Hemodiluted 2Nx rats did not demonstrate a comparable increase in CO after hemodilution compared with Sham 2Nx (74.8 ± 22.4 vs. 108.9 ± 18.8 mL/min, P = 0.003) that likely contributed to the observed reduction in PBro2. This impaired CO response was associated with reduced fractional shortening (33 ± 9 vs. 51 ± 5%) and increased left ventricular end-systolic volume (156 ± 51 vs. 72 ± 15 µL, P < 0.001) suggestive of systolic dysfunction. By contrast, hemodiluted Sham 2Nx animals demonstrated a robust increase in CO and preserved PBro2. These data support the hypothesis that the kidney plays a central role in maintaining cerebral perfusion and initiating the adaptive increase in CO required to optimize PBro2 during acute anemia.NEW & NOTEWORTHY This study has demonstrated that bilateral nephrectomy acutely impaired cardiac output (CO) and microvascular brain Po2 (PBro2), at baseline. Following acute hemodilution, nephrectomy prevented the adaptive increase in CO associated with acute hemodilution leading to a further reduction in PBro2, accentuating the degree of cerebral tissue hypoxia. These data support a role for the kidney in maintaining PBro2 and initiating the increase in CO that optimized brain perfusion during acute anemia.

Stormwater Infrastructure Resilience Assessment against Seismic Hazard Using Bayesian Belief Network.

Resilient stormwater infrastructure is one of the fundamental components of resilient and sustainable cities. For this, the resilience assessment of stormwater infrastructure against earthquake hazards is crucial for municipal authorities. The objective of this study is to develop a resilience assessment framework for stormwater pipe infrastructure against seismic hazards. A Bayesian belief network (BBN)-based stormwater infrastructure resilience model is constructed based on the published literature and expert knowledge. The developed framework is implemented in the city of Regina, Canada, to assess the city's stormwater pipe infrastructure resilience. The outcome of the model indicates that proposed BBN-based stormwater infrastructure resilience model can effectively quantify uncertainties and handle the nonlinear relationships between several reliability and recovery factors. The model is also capable of identifying the most sensitive and vulnerable stormwater pipes within the network.

Analysis of barriers to photovoltaic waste management to achieve net-zero goal of Canada.

Photovoltaic (PV) installations are experiencing a worldwide exponential upsurge, and the subsequent PV waste is a growing concern. This study identifies and analyzes the critical barriers to PV waste management to achieve the net-zero goal of Canada. The barriers are pinpointed through a literature review and examined by formulating a framework integrating three methods: rough analytical hierarchy process, decision-making trial and evaluation laboratory, and interpretive structural modeling. The findings show that the barriers have complex causal interrelationships with the irregular generation of PV waste and waste collection center as the two crucial barriers with the highest driving powers and causal effects on others. The anticipated outcome of this research is to assist relevant government organizations and managers in assessing the connections between obstacles related to photovoltaic (PV) waste management, with the aim of developing a viable net-zero strategy for Canada.

DJ-1 Deficiency Protects against Sepsis-Induced Myocardial Depression.

Oxidative stress is considered one of the early underlying contributors of sepsis-induced myocardial depression. DJ-1, also known as PARK7, has a well-established role as an antioxidant. We have previously shown, in a clinically relevant model of polymicrobial sepsis, DJ-1 deficiency improved survival and bacterial clearance by decreasing ROS production. In the present study, we investigated the role of DJ-1 in sepsis-induced myocardial depression. Here we compared wildtype (WT) with DJ-1 deficient mice at 24 and 48 h after cecal ligation and puncture (CLP). In WT mice, DJ-1 was increased in the myocardium post-CLP. DJ-1 deficient mice, despite enhanced inflammatory and oxidative responses, had an attenuated hypertrophic phenotype, less apoptosis, improved mitochondrial function, and autophagy, that was associated with preservation of myocardial function and improved survival compared to WT mice post-CLP. Collectively, these results identify DJ-1 as a regulator of myocardial function and as such, makes it an attractive therapeutic target in the treatment of early sepsis-induced myocardial depression.

Benchmarking Canadian solid waste management system integrating fuzzy analytic hierarchy process (FAHP) with efficacy methods.

Solid waste management is a recent challenge for both developed and developing countries because of urbanization and population growth. This research aims to identify and compare the economic efficiency of Canadian waste management systems integrating the fuzzy analytic hierarchy process (FAHP) with the efficacy method. Six economic indicators-diversion gross domestic product (DGDP) ratio, gross domestic product (GDP) of all industries, GDP of Sector 562, diversion rate, waste management output indicator, and diversion size indicator-are considered in this study. Initially, the FAHP method was used to calculate the indicator weights, and the efficacy method then ranked the DGDP ratio as the most influential factor for the GDP-related indicators. The DGDP ratio and diversion rate were determined to be most critical in the assessment of the economic efficiency of a solid waste management system in Canada. The result also revealed that the economic performance of the waste management systems of Nova Scotia, British Columbia, and Ontario are better compared to those of other provinces. The outcome of this study will aid the government and provincial organizations in establishing an effective solid waste management plan to improve their overall performance.

Yard waste prediction from estimated municipal solid waste using the grey theory to achieve a zero-waste strategy.

Yard waste is one of the key components of municipal solid waste and can play a vital role in implementing zero-waste strategy to achieve sustainable municipal solid waste management. Therefore, the objective of this study is to predict yard waste generation using the grey theory from the predicted municipal solid waste generation. The proposed model is implemented using municipal solid waste generation data from the City of Winnipeg, Canada. To identify the generation factors that influence municipal solid waste generation and yard waste generation, a correlation analysis is performed among eight socio-economic factors and six climatic factors. The GM (1, 1) model is utilized to predict individual factors with overall MAPE values of 0.06%-10.39% for the in-sample data, while the multivariable GM (1, N) grey model is employed to forecast the quarterly level of municipal solid waste generation with overall MAPE values of 5.64%-7.54%. In this study, grey models predict quarterly yard waste generation from the predicted municipal solid waste generation values using only twelve historical data points. The results indicate that the grey model (based on the error matrices) performs better than the linear and nonlinear regression-based models. The outcome of this study will support the City of Winnipeg's sustainable planning for yard waste management in terms of budgeting, resource allocation, and estimating energy generation.

Evaluating factors contributing to the failure of information system in the banking industry.

The increasing use of Information Technology (IT) has led to many security and other related failures in the banks and other financial institutions in Bangladesh. In this paper, we investigated the factors contributing to the failurein the IT system of the banking industry in Bangladesh. Based on the experts' opinions and weight on the specified evaluating criteria, an empirical test was conducted using a rough set theory to produce a framework for the IT system failure factors. In this study, an extended approach involving the integration of rough set theory based flexible Failure Mode and Effect Analysis (FMEA) and the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) has beenapplied to help the managers of the corresponding field to identify the factors responsible for the failure of the IT system in the banking industries and then prioritize them accordingly, for the ease of decision-making.In this research, eleven such failure factors were identified, which were then quantitatively analyzed to facilitate managers in crucial decision-making. It was observed that cyber-attack, database hack risks, server failure, network interruption, broadcast data error, and virus effect were the most significant factors for the failure of the IT system. The framework developed in this research can be utilized to assist in efficient decision-makingin other serviceindustries where IT systems play a key role. To the best of the knowledge, this is the first study thatempirically tested key failure factors of the IT system for the banking sector using an integrated method.