Aggressive Targets Research Articles

Damage to the Vascular Endothelium as a Leading Mechanism of COVID-19 Systemic Pathology

An analysis of the molecular and pathophysiological mechanisms of COVID-19 is presented. The endothelium of blood vessels, a kind of “endocrine tree” of the lungs and other organs in which important pathophysiological processes are concentrated, is considered as the target of the aggressive effects of the SARS-CoV-2 coronavirus. Since the main cellular target of viral aggression is the ACE2 enzyme, consideration of its role is the main line of discussion. Coronavirus blocks the activity of ACE2, a natural producer of angiotensins peptides, thus disrupting the balance of hemovascular control. Under normal conditions this mission is performed by the ACE/ACE2 complex, enzymes that control the synthesis and physiological activity of angiotensins and bradykinin peptides. Changes in the ACE/ACE2 axis ratios and cytokine stress are associated with endothelial dysfunction and a number of vascular disorders. The STORM-2 concept is proposed for the first time. According to the concept, the cause of severe organ pathology is the violation of hemostasis, transcellular diffusion, and maintenance of blood pressure.

Pharmacokinetics and Monte Carlo Simulation of Meropenem in Critically Ill Adult Patients Receiving Extracorporeal Membrane Oxygenation.

Objectives: There have been few clinical studies of ECMO-related alterations of the PK of meropenem and conflicting results were reported. This study investigated the pharmacokinetics (PK) of meropenem in critically ill adult patients receiving extracorporeal membrane oxygenation (ECMO) and used Monte Carlo simulations to determine appropriate dosage regimens. Methods: After a single 0.5 or 1 g dose of meropenem, 7 blood samples were drawn. A population PK model was developed using nonlinear mixed-effects modeling. The probability of target attainment was evaluated using Monte Carlo simulation. The following treatment targets were evaluated: the cumulative percentage of time during which the free drug concentration exceeds the minimum inhibitory concentration of at least 40% (40% fT>MIC), 100% fT>MIC, and 100% fT>4xMIC. Results: Meropenem PK were adequately described by a two-compartment model, in which creatinine clearance and ECMO flow rate were significant covariates of total clearance and central volume of distribution, respectively. The Monte Carlo simulation predicted appropriate meropenem dosage regimens. For a patient with a creatinine clearance of 50–130 ml/min, standard regimen of 1 g q8h by i. v. infusion over 0.5 h was optimal when a MIC was 4 mg/L and a target was 40% fT>MIC. However, the standard regimen did not attain more aggressive target of 100% fT>MIC or 100% fT>4xMIC. Conclusion: The population PK model of meropenem for patients on ECMO was successfully developed with a two-compartment model. ECMO patients exhibit similar PK with patients without ECMO. If more aggressive targets than 40% fT>MIC are adopted, dose increase may be needed.

A Behavioral Economics-Electronic Health Record Module to Promote Appropriate Diabetes Management in Older Adults: Protocol for a Pragmatic Cluster Randomized Controlled Trial.

BackgroundThe integration of behavioral economics (BE) principles and electronic health records (EHRs) using clinical decision support (CDS) tools is a novel approach to improving health outcomes. Meanwhile, the American Geriatrics Society has created the Choosing Wisely (CW) initiative to promote less aggressive glycemic targets and reduction in pharmacologic therapy in older adults with type 2 diabetes mellitus. To date, few studies have shown the effectiveness of combined BE and EHR approaches for managing chronic conditions, and none have addressed guideline-driven deprescribing specifically in type 2 diabetes. We previously conducted a pilot study aimed at promoting appropriate CW guideline adherence using BE nudges and EHRs embedded within CDS tools at 5 clinics within the New York University Langone Health (NYULH) system. The BE-EHR module intervention was tested for usability, adoption, and early effectiveness. Preliminary results suggested a modest improvement of 5.1% in CW compliance.ObjectiveThis paper presents the protocol for a study that will investigate the effectiveness of a BE-EHR module intervention that leverages BE nudges with EHR technology and CDS tools to reduce overtreatment of type 2 diabetes in adults aged 76 years and older, per the CW guideline.MethodsA pragmatic, investigator-blind, cluster randomized controlled trial was designed to evaluate the BE-EHR module. A total of 66 NYULH clinics will be randomized 1:1 to receive for 18 months either (1) a 6-component BE-EHR module intervention + standard care within the NYULH EHR, or (2) standard care only. The intervention will be administered to clinicians during any patient encounter (eg, in person, telemedicine, medication refill, etc). The primary outcome will be patient-level CW compliance. Secondary outcomes will measure the frequency of intervention component firings within the NYULH EHR, and provider utilization and interaction with the BE-EHR module components.ResultsStudy recruitment commenced on December 7, 2020, with the activation of all 6 BE-EHR components in the NYULH EHR.ConclusionsThis study will test the effectiveness of a previously developed, iteratively refined, user-tested, and pilot-tested BE-EHR module aimed at providing appropriate diabetes care to elderly adults, compared to usual care via a cluster randomized controlled trial. This innovative research will be the first pragmatic randomized controlled trial to use BE principles embedded within the EHR and delivered using CDS tools to specifically promote CW guideline adherence in type 2 diabetes. The study will also collect valuable information on clinician workflow and interaction with the BE-EHR module, guiding future research in optimizing the timely delivery of BE nudges within CDS tools. This work will address the effectiveness of BE-inspired interventions in diabetes and chronic disease management.Trial RegistrationClinicalTrials.gov NCT04181307; https://clinicaltrials.gov/ct2/show/NCT04181307International Registered Report Identifier (IRRID)DERR1-10.2196/28723

The micro–meso–macro architecture of a proposed collaborative emergent strategy for the hydrogen market

Abstract In 2018, an intergovernmental climate-change panel concluded that, to maintain a global temperature increases of <1.5oC, net-zero greenhouse-gas emissions would be required by 2050. Since then, >110 countries have pledged net-zero carbon ambitions by 2050 and hydrogen has been identified at national levels as key to achieving this. Governments have pledged >US$ 70 billion to further advance hydrogen infrastructure and technology, with an additional investigation on >200 proposed hydrogen-based projects expecting completion before 2030, totalling a value of US$ 300 billion. Reaching these aggressive targets will require a disciplined cohesion of collaborative strategies to develop an integrated macro infrastructure system. This article discusses the current infancy of the hydrogen market, introduces and defines a new ‘collaborative emergent strategy’ based on the emergent strategy concept by Mintzberg and Waters, and links its developmental viability through a staged micro–meso–macro architecture. Successful strategic business case studies and current market opportunities across multiple industries are reviewed as they all vie for a strategic early market position.

LDL cholesterol target achievement in heterozygous familial hypercholesterolemia patients according to 2019 ESC/EAS lipid guidelines: Implications for newer lipid-lowering treatments

BackgroundThe 2019 European guidelines (ESC/EAS) for the treatment of dyslipidaemias recommend more aggressive targets for low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). Current lipid-lowering treatment is often inadequate to achieve these targets. MethodsData from the HELLAS-FH registry were analysed to assess achievement of LDL-C targets in adults with FH based on the 2019 ESC/EAS guidelines. In patients who had not achieved LDL-C target, the maximally reduced LDL-C value was calculated after theoretical switch to rosuvastatin/ezetimibe 40/10 mg/day. The percentage of patients who remained candidates for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) was then calculated. ResultsPatients (n = 1694, mean age 50.8 ± 14.7 years) had LDL-C levels 242 ± 71 mg/dL (6.3 ± 1.8 mmol/L) at diagnosis. Most treated patients were receiving statins (97.5%) and about half were on additional ezetimibe (47.5%). Based on the 2019 ESC/EAS guidelines the percentage of patients achieving LDL-C goals was only 2.7%. Following theoretical up titration to rosuvastatin/ezetimibe 40/10 mg, LDL-C target achievement rate would increase to 5.9%. In this scenario, most patients (55.9%) would be eligible for PCSK9i treatment. Following theoretical administration of a PCSK9i, LDL-C target achievement rate would rise to 57.6%. However, 42.4% of patients would still be eligible for further LDL-C lowering treatment. ConclusionsMost FH patients do not reach new LDL-C targets even if on maximum intensity statin/ezetimibe treatment. In this case, more than half of FH patients are candidates for PCSK9i therapy and a considerable proportion may still require additional LDL-C lowering.

Association of body mass index with non-achievement of target low-density lipoprotein level in older patients at very high cardiovascular risk: a multicentre study

Abstract Introduction Low-density lipoprotein cholesterol (LDL-c) is a well-established risk factor for atherosclerotic cardiovascular disease. Nonetheless, the association of body mass index (BMI) with non-achievement of target LDL-c level in older patients with type 2 diabetes (T2D) at very high cardiovascular risk is unknown. Purpose To investigate whether BMI is associated with non-achievement of target LDL-c level in older patients with T2D at very high cardiovascular risk. Methods From December 2019 to June 2020, in this multicentre prospective cross-sectional study, we enrolled 733 consecutive outpatients aged ≥60 years with T2D at very high cardiovascular risk in whom LDL-c levels could be measured after any stable lipid-lowering therapy for ≥6 months. Achievement of target lipid level was assessed based on the 2019 guidelines of the European Society of Cardiology for dyslipidaemia. Factors associated with non-achievement of target LDL-c level were determined using logistic regression analysis. Results Of the total cases (age, 68.6±7.2 years; men, 51.3%), 654 patients (89.2%) did not achieve an aggressive target LDL-c level of <1.4 mmol/L. Target non-high-density lipoprotein cholesterol level of <2.2 mmol/L and triglyceride level of <1.7 mmol/L were not achieved in 87.9% and 56.2% of the patients, respectively. In the multivariate model, BMI was the only factor associated with failure to achieve target LDL-c level, but not other factors such as age, sex, education level, smoking, and comorbidities. The adjusted odds ratio were 0.88 (95% confidence interval [95% CI], 0.24–3.21; P=0.84) for underweight, 1.57 (95% CI, 0.87–2.81; P=0.13) for overweight, and 2.63 (95% CI, 1.43–4.83; P=0.002) for obesity (normal weight was set as reference) status. Conclusions Non-achievement of target LDL-c level is highly prevalent in older patients with T2D at very high cardiovascular risk. Obesity, defined by BMI, can be a factor associated with non-achievement of the target. The findings highlight the importance of management of lipid levels in older patients with T2D. Funding Acknowledgement Type of funding sources: None. Figure 1

The changing nature of hydroclimatic risks across South Africa

We present results from large ensembles of projected twenty-first century changes in seasonal precipitation and near-surface air temperature for the nation of South Africa. These ensembles are a result of combining Monte Carlo projections from a human-Earth system model of intermediate complexity with pattern-scaled responses from climate models of the Coupled Model Intercomparison Project Phase 5 (CMIP5). These future ensemble scenarios consider a range of global actions to abate emissions through the twenty-first century. We evaluate distributions of surface-air temperature and precipitation change over three sub-national regions: western, central, and eastern South Africa. In all regions, we find that without any emissions or climate targets in place, there is a greater than 50% likelihood that mid-century temperatures will increase threefold over the current climate’s two-standard deviation range of variability. However, scenarios that consider more aggressive climate targets all but eliminate the risk of these salient temperature increases. A preponderance of risk toward decreased precipitation (3 to 4 times higher than increased) exists for western and central South Africa. Strong climate targets abate evolving regional hydroclimatic risks. Under a target to limit global climate warming to 1.5 °C by 2100, the risk of precipitation changes within South Africa toward the end of this century (2065–2074) is commensurate to the risk during the 2030s without any global climate target. Thus, these regional hydroclimate risks over South Africa could be delayed by 30 years and, in doing so, provide invaluable lead-time for national efforts to prepare, fortify, and/or adapt.

Political, economic, social, technological, legal and environmental dimensions of electric vehicle adoption in the United States: A social-media interaction analysis

Many governments have begun to adopt aggressive targets for electric vehicles. However, studies of the drivers of electric vehicle (EV) adoption are scarce. Social media interactions can provide a new data-driven vantage point to explore such drivers. This study uses data from 36,000 public posts on Facebook to investigate intersectionality in EV-communication as per the Political, Economic, Social, Technological, Legal and Environmental (PESTLE) categories. A computational social science methodology was adopted using a mixed-method application of social network analysis and machine learning-based topic modelling through Latent Dirichlet Allocation algorithm on a 600,000-text corpus extracted from the Facebook posts. Results showed that political, economic, and legal posts had dense clusters around the technology policy of EV, the institutional discourse of electrification of the federal vehicle fleet, and tax and credit framework politics. The environmental and social dimensions had a higher discourse for social justice, clean air, and better health and well-being. A market shift towards EV as a service industry was observed in the technology and economics-related posts. These findings can help policymakers, and planners design contextualised energy policy for influencing EV adoption in the U.S. and other countries.

Association of thrombophilia prospective detection with hemocompatibility related outcomes in left ventricular assist device patients.

Inherited thrombophilias represent a concerning risk factor due to a proclivity to an aberrant clot formation. However, in patients with left ventricular assist device (LVAD), their impact on bleeding and thrombotic complications remains still poorly understood. The aim of the present study was to evaluate the effect of thrombophilic mutation directed anticoagulation therapy on adverse clinical outcomes in LVAD patients. About 138 consecutive patients indicated for LVAD implant (HeartMate II, Abbott, Plymouth, USA) were prospectively screened for three major thrombophilic mutations: factor II (prothrombin), factor V Leiden, and homozygous methylenetetrahydrofolate reductase (MTHFR). Subsequently, discordant individualized anticoagulation targets of INR 2.5-3.0 in thrombophilia positive and INR 1.8-2.2 in negative patients were established; notably without anti-platelet agents given the center standard of care. Mean age was 50 ± 12.7 years, 83% male. Mean duration of support was 464.5 days (SD 482.9; SEM 41.1) and median of 310 days (IQR 162; 546). Full thrombophilia positive cohort analysis has not revealed any significant impact on event free survival. In contrast, detailed analysis of specific thrombophilias subsets has revealed Factor II prothrombin mutation as a significant predisposition for the pump thrombosis risk (SHR 10.48; p = 0.001) despite more aggressive prespecified anticoagulation target. Moreover, the incidence of bleeding events in prothrombin group was also significantly increased (SHR 6.0; p = 0.03). Our observations suggest that specific thrombophilias in LVAD patients may pose different intensity predisposition for thrombotic complications. Factor II (prothrombin) positive mutation was identified as significant risk factor associated with the pump thrombosis.

Long-term health impacts attributable to PM2.5 and ozone pollution in China's most polluted region during 2015–2020

During the Thirteenth Five-Year Plan Period (2016–2020), China has made great efforts to control the air pollution in its most polluted regions: Beijing-Tianjin-Hebei and surrounding regions (BTHS) and Fen-Wei Plain (FWP). This study assesses the PM2.5- and ozone-related health impacts in BTHS and FWP cities from 2015 to 2020. Results show the PM2.5-health impact of BTHS and FWP cities decreased by 17.14% between 2015 and 2020, the ozone-related health impact increased over 90% contemporaneously. Significant health risk improvements mainly occurred in 2017 and 2018, showing efficient air pollution prevention and control. Health impacts in BTHS cities have been higher than in FWP cities. Air pollution problem analysis shows BTHS has strictly investigated and dealt with the problems, especially in Beijing, Tianjin, and Hebei cities. Health benefits by achieving two concentration targets (of PM2.5 and ozone) from 2021 to 2025 are evaluated. The achievement of aggressive and general concentration targets will help continue the decline of PM2.5-related health impacts and reverse the growth of ozone-related health impacts. The present study could support controlling the health risks attributable to PM2.5 and ozone pollution in BTHS and FWP cities, especially for developing two-pollutant concentration targets and collaborative control strategy.

Measuring pollutant emissions of cattle breeding and its spatial-temporal variation in China

The rapid development of animal husbandry has resulted in serious pollution issues in the livestock and poultry breeding industry, increasing the cost of environmental management. This issue is particularly prominent in China due to its rapid economic development, significant domestic consumption, and aggressive carbon neutrality targets. This study analyses pollution emissions and spatial-temporal variation in China's cattle breeding industry. Using an emission coefficient method and panel data of 31 Chinese provinces/municipalities between 2002 and 2017, we measure the total volume of pollutant emissions from China's cattle breeding industry and five major pollutants: chemical oxygen demand, total nitrogen, total phosphorus, copper, and zinc. We also analyse the dynamic variation of the spatial distribution. The results show that both the total emissions volume and emissions of the five major pollutants have decreased to different extents, among which chemical oxygen demand has decreased the fastest. Spatial divergence is strengthened as the heavy pollution areas have moved from the southeast to the northwest of the country. This study contributes to current research by its focus on the cattle breading industry and by our improvements to the pollutant emission measurement method.

ПРОГНОСТИЧЕСКИЕ МАРКЕРЫ У ПАЦИЕНТОВ С ТИМУСНЕЗАВИСИМОЙ И ТИМУСЗАВИСИМОЙ МИАСТЕНИЕЙ

Objective. To assess the presence of specific markers in patients with thymus-independent and thymus-dependent myasthenia gravis for choosing treatment tactics. Methods. The presence of specific markers was assessed in 138 patients with thymus-independent (M - myasthenia gravis without thymus changes) and thymus-dependent (MH - myasthenia gravis with thymus hyperplasia, MT - myasthenia gravis with thymoma). The method ELISA (the content of antibodies to subunits 1 and 7 nAChR in blood serum, to 7 nAChR subunit in thymocyte mitochondria, a detectablelevel of antinuclear antibody(ANA), immunofluorescence (ANA glow) and flow cytometry (expression of CD14+CD11c+and CD14 + HLA-DR +) has been used. Results. The relationship between the clinical phenotypes of myasthenia gravis and the variants of HLA diplotypes was revealed: in young patients with thymus-independent myasthenia gravis (M), a high heterogeneity of the genotypic markers HLA-DR (DR1, DR2, DR3, DR5, DR7) was detected. Patients with thymus-dependent myasthenia (MT) had only the HLA DR2 and HLA DR7 diplo- and haplotypes. The presence of HLA DR2 and HLA DR7 haplotypes in some young patients with progressive thymus-independent myasthenia gravis (M) led to the development of myasthenia gravis with thymoma (MT) in the elderly people. The pathogenic role also belongs to infection (СMV, EBV, HBV, HCV, HSV-1, HSV-2, HHV-6, mycoplasma) and food intolerance (IgE and IgG4) in the development and progression of myasthenia gravis. A four-fold prevalence of α7 subunit nicotinic acetylcholine receptors on the thymocyte mitochondria as an additional targets of autoimmune aggression in myasthenia gravis was determined. Specific antinuclear antibodies to centromere chromosome proteins were visualized in the elderly people with thymoma. Conclusion. The prognosis of the myasthenia gravis progression and the development of remission can be made using genomic (the presence of certain HLA-DR haplotypes) and molecular (ANA antibodies to centromere chromosome proteins, expression of CD20+, CD14+CD11c+, CD14+HLA-DR+) biomarkers, that can be used for the choice of treatment tactics. What this paper adds The change of complex biomarkers has been firstly studied for prognosis and choice of complex treatment tactics for young patients with progressive thymus-independent myasthenia gravis and for the elderly patients with thymus-dependent myasthenia gravis. In the presence of certain HLA-DR haplotypes, antinuclear antibodies to centromere chromosome proteins, an increasing expression of CD20+, CD14+CD11c+ and CD14+HLADR+ in some young patients with thymus-independent myasthenia gravis, analogically to biomarkers in thymus-dependent myasthenia gravis with thymoma, to perform a thymectomy is of high dangerous. potentialrisksof the procedure.

Molecular Biological and Clinical Understanding of the Pathophysiology and Treatments of Hyperuricemia and Its Association with Metabolic Syndrome, Cardiovascular Diseases and Chronic Kidney Disease.

Uric acid (UA) is synthesized mainly in the liver, intestines, and vascular endothelium as the end product of an exogenous purine from food and endogenously from damaged, dying, and dead cells. The kidney plays a dominant role in UA excretion, and the kidney excretes approximately 70% of daily produced UA; the remaining 30% of UA is excreted from the intestine. When UA production exceeds UA excretion, hyperuricemia occurs. Hyperuricemia is significantly associated with the development and severity of the metabolic syndrome. The increased urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) expression, and glycolytic disturbances due to insulin resistance may be associated with the development of hyperuricemia in metabolic syndrome. Hyperuricemia was previously thought to be simply the cause of gout and gouty arthritis. Further, the hyperuricemia observed in patients with renal diseases was considered to be caused by UA underexcretion due to renal failure, and was not considered as an aggressive treatment target. The evidences obtained by basic science suggests a pathogenic role of hyperuricemia in the development of chronic kidney disease (CKD) and cardiovascular diseases (CVD), by inducing inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and activation of the renin-angiotensin system. Further, clinical evidences suggest that hyperuricemia is associated with the development of CVD and CKD. Further, accumulated data suggested that the UA-lowering treatments slower the progression of such diseases.

Humour and (mock) aggression: Distinguishing cyberbullying from roasting

This paper postulates a distinction between two types of discursive aggression in the context of humour production. This theoretical argument is supported by a qualitative (meta)pragmatic analysis of posts on the RoastMe subreddit devoted to an online community's original humorous practice based on jocular insults. The study of emic (community members') and etic (outsiders') metapragmatic evaluations of the content on the subreddit yields divergent insider/outsider interpretations of the practice at hand; it also uncovers some ambivalence in the polysemous folk concepts of roasting and cyberbullying and the relationship between them. “Roasting” and “cyberbullying” are formally distinguished based on the intended form of aggression on which each relies. Also, the points of convergence between humour and aggression are surveyed. First, mock aggression underlies benevolent humour (typified by roasting proper); second, genuine aggression (exemplified by cyberbullying proper) may amuse individuals other than the target of discursive aggression.

Population pharmacokinetics of meropenem in critically ill infant patients

BackgroundPopulation pharmacokinetic analysis in critically ill infants remains a challenge for lack of information. ObjectivesTo determine the population pharmacokinetic parameters of meropenem and evaluate the covariates affecting population pharmacokinetic parameters. MethodsA prospective study was conducted on 35 patients. A total of 160 blood samples were collected and determined free of drug concentrations of meropenem. Population pharmacokinetic data were analyzed using NONMEM software. Internal validation methods, including bootstrapping and prediction-corrected visual predictive checks, were applied to evaluate the robustness and predictive power of the final model. ResultsA one-compartment model with first-order elimination showed the best fit to the data.The typical clearance (CL) values and volume of distribution (Vd) were 1.33 L/h and 2.27 L, respectively. Weight and creatinine clearance were influential covariates for CL, while weight was a significant covariate for Vd of meropenem. The model evaluation results suggested robustness and good predictability of the final model. The standard dosage regimens of meropenem achieved 40% f T>MIC but not enough if a more aggressive target of 80% f T>MIC at MIC value of ≥ 16 µg/mL is desired. ConclusionsThis population pharmacokinetic model could be used for suggesting individualized meropenem dosage regimens in critically ill infants.

Cape union mart: digital transformation and customer experience during a crisis

Learning outcomes The learning outcomes of this paper are as follows: to define the scope of digital customer experience, why it is important and how it can be used to create a competitive advantage, to evaluate the various challenges for traditional retail businesses that undertake a digital transformation strategy, to critically assess a chosen digital transformation strategy, to identify the key features of a successful digital transformation strategy and to develop a crisis communication strategy. Case overview/synopsis The Cape Union Mart Group is a typical apparel retail company faced with the challenge of improving the digital customer experience and accelerating digital transformation in the wake of the Covid-19 pandemic. Due to the pandemic, the demand for e-commerce increased dramatically. However, strict lockdown regulations forbade the delivery of clothing. When the lockdown was lifted, there was an order backlog of four weeks. To add to this challenge, the Group was in the midst of a technology update. They moved their entire information technology (IT) backbone to three clouds and, just a week before the lockdown, launched five new websites for its five different retail chains. The ultimate goal with the technology update was to give the company a competitive advantage by improving the customer experience. However, having to do this at an accelerated pace due to the pandemic posed a number of challenges. The case provides a vivid description of how the crisis unfolded and how Grant De Waal-Dubla, the executive of e-commerce and IT at the Group and his team responded to the challenges, together with the marketing team. Based on the success of e-commerce during the lockdown, the owners of the business then tasked Grant with new, aggressive growth targets. Whilst dealing with the aftermath of the lockdown, Grant’s main challenge is to develop a strategy to reach those targets. Complexity academic level The primary target audience for this case are postgraduate students enrolled on programmes such as Master of Business Administration or specialist masters in a business field such as marketing or strategy and also for Executive Education courses. Supplementary materials Teaching notes are available for educators only. Subject code CSS 11: Strategy.

Evaluation of relative performance of Indian states in PV resource utilization through MPI

Abstract To participate in the global fight against climate change, India has set an aggressive target of installing 100 GW of photovoltaic (PV) energy resources by 2022. However, only about 37% of this target is achieved till date, and, presently, the set target appears to be elusive. Hence it is crucial and the need of the hour to analyze the performance of different utilities to identify the regions that need a course correction. In the present work, the relative performance of the Indian states in realizing the national target of PV installed capacity is analyzed through the Data Envelopment Analysis (DEA) model. Time series analysis of the PV sector’s growth in different Indian states over the period 2017–2021 is quantified through the Malmquist productivity index (MPI). The applied methodology revealed that Rajasthan, which has the highest PV potential and second-highest PV installed capacity, is less productive than the small hilly states and union territories, which have meager PV potential. The result provides insight into the factors contributing to the inefficiencies in the development of the PV energy sector, which will help the policymakers take necessary corrective actions to improve the states’ productivity and thereby contribute more effectively to the national goal. The work may be extended to other regions of the world to strengthen the global effort to fight climate change.

Implication of ESC/EAS 2019 dyslipidemia guidelines for PCSK9 inhibition in patients with familial hypercholesterolemia: An analysis from the Hellas-FH registry

Background and Aims: The ESC/EAS 2019 guidelines for the management of dyslipidemia recommend aggressive LDL-C targets in patients with familial hypercholesterolemia (FH). Intensive hypolipidemic treatment with statin and ezetimibe is often insufficient to achieve these targets. For very-high-risk FH patients (that is, with atherosclerotic cardiovascular disease or with another major risk factor) who do not achieve their goal on a maximum tolerated dose of a statin and ezetimibe, the addition of a PCSK9 inhibitor (PCSK9i) is recommended.

Characterizing SOFC Stack Electrochemical Performance at Elevated Pressure

In this report, we present our work to characterize the electrochemical performance of solid-oxide fuel cell stacks under elevated-pressure operation. The effort is part of a five-year U.S. DoE ARPA-E INTEGRATE program to combine the high efficiency of solid-oxide fuel cells with the low-cost of reciprocating engines to demonstrate an 70%-efficient hybrid electric generator. Within this hybrid system, solid-oxide fuel cells (SOFCs) convert natural gas into electricity. Unconverted fuel leaving the SOFC stacks feeds a downstream reciprocating engine that drives an electric generator. In this architecture, the stacks are hydraulically placed upstream of the engine, necessitating stack operation at elevated pressures of 2-5 barg. SOFC stack performance at elevated pressure has witnessed limited study. The team at the Colorado School of Mines is characterizing SOFC stack performance at elevated pressure through design and commissioning of the pressurized stack electrochemical test stand shown in the figure. The facility is used to explore the performance of 5-kW SOFC stack test modules (Ceres Power, Ltd., Horsham, UK) at the unusual operating conditions presented by the hybrid system, including pressurized operation at high anode tail-gas recycle.A simulant of steam-reformed natural gas with anode tail-gas recycle is synthesized using mass flow controllers. A fuel processor will be incorporated into the stand at a later stage of the research program. Reactants flow through a preheat furnace and into a pressure vessel to reach the insulated solid-oxide fuel cell stack test module. The pressure within this vessel is matched to the operating pressure of the SOFC stack, minimizing pressure differentials between the internal flow channels of the stack and the surrounding environment. Following electrochemical conversion, exhaust gases exit the stack and the pressure vessel, and are cooled through a series of heat exchangers. Back-pressure regulators near the end of the flow stream regulate stack and vessel operating pressure.The stand has been used to explore the impacts of elevated pressure operation on the electrochemical performance of Ceres SteelCell stacks. Additional parameters being explored include fuel composition, anode recycle, and internal fuel reforming. In this talk, we will present our findings on the effects of these variables on stack performance, and their impact in achieving the aggressive performance targets of the SOFC-engine hybrid electric generator.A principal concern during performance testing at elevated pressures is minimizing pressure differentials across the anode and cathode gas-flow streams. Such differentials can bring substantial mechanical stress to the metal-supported membrane-electrode assemblies. Pressure differentials in this work are below +/- 25 mbar at 5 barg operating pressure, well below manufacturer’s specifications. The stacks show steady, stable performance over all conditions tested.In addition to exploring the electrochemical-performance impacts brought by pressurization and anode recycle, experiments explore the roles of methane internal reforming and cathode air flow on stack cooling. The endothermicity of methane steam reforming can bring meaningful reductions in cooling-air flow rate, raising system efficiency. The results of these studies and the trajectory of the research will be presented. Figure 1

Integrated assessment modeling reveals near-channel management as cost-effective to improve water quality in agricultural watersheds

Despite decades of policy that strives to reduce nutrient and sediment export from agricultural fields, surface water quality in intensively managed agricultural landscapes remains highly degraded. Recent analyses show that current conservation efforts are not sufficient to reverse widespread water degradation in Midwestern agricultural systems. Intensifying row crop agriculture and increasing climate pressure require a more integrated approach to water quality management that addresses diverse sources of nutrients and sediment and off-field mitigation actions. We used multiobjective optimization analysis and integrated three biophysical models to evaluate the cost-effectiveness of alternative portfolios of watershed management practices at achieving nitrate and suspended sediment reduction goals in an agricultural basin of the Upper Midwestern United States. Integrating watershed-scale models enabled the inclusion of near-channel management alongside more typical field management and thus directly the comparison of cost-effectiveness across portfolios. The optimization analysis revealed that fluvial wetlands (i.e., wide, slow-flowing, vegetated water bodies within the riverine corridor) are the single-most cost-effective management action to reduce both nitrate and sediment loads and will be essential for meeting moderate to aggressive water quality targets. Although highly cost-effective, wetland construction was costly compared to other practices, and it was not selected in portfolios at low investment levels. Wetland performance was sensitive to placement, emphasizing the importance of watershed scale planning to realize potential benefits of wetland restorations. We conclude that extensive interagency cooperation and coordination at a watershed scale is required to achieve substantial, economically viable improvements in water quality under intensive row crop agricultural production.