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Research methodology This case is based on primary archival research. The original reports from MSCI, Sustainalytics and S&P 500 formed the foundation of the case in addition to the 144-page Tesla’s 2021 Impact Report. Secondary sources were used to provide contextual information. All sources are cited as endnotes. Case overview/synopsis In June 2022, Tesla, Inc., the Austin, Texas-based electric car company faced a number of challenges that called into question its environmental, social and governance (ESG) credentials. Questioning the company’s corporate governance practices, SOC Capital, a watchdog organization publicly released a letter that it had sent to the United States Securities and Exchange Commission where it had demanded that the agency sanction the company for not replacing an independent director at its next stockholder meeting. The State of California’s Department of Fair Housing and Employment filed a lawsuit alleging various counts of discrimination at Tesla’s manufacturing facility in Fremont, California. S&P Global removed the company from its index of ESG companies. This action had negative consequences for the company’s stock price. Tesla’s board of directors, led by Robyn M. Denholm, had to address Tesla’s overall approach to ESG in light of these challenges. Complexity academic level The case is suitable for an upper-level undergraduate or an MBA course on strategy or strategic management.The issues in the case involve the stakeholder perspective, corporate governance and the purpose of a firm. Instructors face two choices here: using this case early in the course introduces the broader stakeholder perspective early on without addressing it as an afterthought at the very end of the course. The other choice is to use it at the end because most strategy textbooks cover these topics at the back end.

Complex networked systems can be modeled and represented as graphs, with nodes representing the agents and the links describing the dynamic coupling between them. The fundamental objective of network identification for dynamic systems is to identify causal influence pathways. However, dynamically related data-streams that originate from different sources are prone to corruption caused by asynchronous time-stamps, packet drops, and noise. In this article, we show that identifying causal structure using corrupt measurements results in the inference of spurious links. A necessary and sufficient condition that delineates the effects of corruption on a set of nodes is obtained. Our theory applies to nonlinear systems, and systems with feedback loops. Our results are obtained by the analysis of conditional directed information in dynamic Bayesian networks. We provide consistency results for the conditional directed information estimator that we use by showing almost-sure convergence.

A controlled pilot study was performed to evaluate implementation of a medication identification device intended to reduce errors in nursing homes. Naïve observation was used for data collection of medication errors on an intervention unit using the device and a control unit, along with field notes describing observation details. Ten staff were observed administering medications to 70 residents over the study time-frame. Of the 9,099 medication administrations observed ( n = 4,588 intervention; n = 4,511 control), 1,068 (12%) errors were identified. The intervention unit had fewer non-time errors versus the control unit, including dose ( n = 21 vs. n = 59; p < 0.01), drug ( n = 4 vs. n = 21; p n = 0 vs. n = 4; p < 0.01), and given without order ( n = 1 vs. n = 8; p < 0.01). However, time errors were higher on the intervention unit and were often due to late start and interruptions. Non-time errors were due to reliance on memory and nursing judgment. A combination of technology and staff dedicated solely to medication administration likely affected error rate differences. [ Journal of Gerontological Nursing, 48 (4), 5–11.]

Theoretical basis 1. Maria Jarlstrom, Essi Saru, and Sinikka Vanhala, “Sustainable Human Resource Management With Salience of Stakeholders: A Top Management Perspective,” Journal of Business Ethics, 152, (2008): 703–724. 2. Benjamin A. Neville, Simon J. Bell, and Gregory J., “Stakeholder Salience Revisited: Refining, Redefining, and Refueling an Underdeveloped Conceptual Tool,” Journal of Business Ethics, 102, (2011): 357–378. 3. Mick Marchington, Fang Lee Cooke, and Gail Hebson. “Human Resource Management Across Organizational Boundaries,” Sage Handbook of Human Resource Management, (2009): 460–477. Research methodology This secondary source case is based mainly on three documents: the 20-page report by a labor union, Unite Here, titled “One Job Should Be Enough: Inequality at Starbucks”; and two reports by former U.S. Attorney General Eric Holder Jr. and Covington & Burlington, LLP. Case overview/synopsis In February 2020, Unite Here, a labor union, released a damming report about employment practices at the airport Starbucks stores operated by licensee, HMSHost. Among other charges, the report identified several instances of racial and gender discrimination that HMSHost dismissed as a ploy by a union intent on organizing its employees. The adverse publicity, however, put Starbucks Corporation in the spotlight because of the company’s publicly stated commitment to workplace equality. The recently hired Nzinga Shaw, the company’s first-ever Global Chief Inclusion and Diversity Officer, had to address the issue at HMSHost lest it adversely affect Starbucks’ reputation as a progressive employer. Complexity academic level The case is best suited for a graduate or undergraduate course in human resource management or labor relations. As diversity is typically covered in the first third of such courses, the ideal placement of this case would be in the early part of the course. As Starbucks is a well-known name, and it is very likely that students have had their own experience with Starbucks, as either a customer or an employee, the case is likely to draw their interest. Supplementary materials Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Liver transplantation remains the only definitive treatment for advanced liver disease and liver failure. Current allocation schemes utilized for liver transplantation mandate a 'sickest first' approach, thus most liver transplants occur in patients with severe systemic illness. For intensive care providers who care for liver transplant recipients, a foundation of knowledge of technical considerations of orthotopic liver transplantation, basic management considerations, and common complications is essential. This review highlights the authors' approach to intensive care management of the postoperative liver transplant recipient with a review of common issues, which arise in this patient population.The number of centers offering liver transplantation continues to increase globally and the number of patients receiving liver transplantation also continues to increase. The number of patients with advanced liver disease far outpaces organ availability and, therefore, patients undergoing liver transplant are sicker at the time of transplant. Outcomes for liver transplant patients continue to improve owing to advancements in surgical technique, immunosuppression management, and intensive care management of liver disease both pretransplant and posttransplant.Given a global increase in liver transplantation, an increasing number of intensive care professionals are likely to care for this patient population. For these providers, a foundational knowledge of the common complications and key management considerations is essential.

Objectives The molecular adsorbent recirculating system removes water-soluble and albumin-bound toxins and may be beneficial for acute liver failure patients. We compared the rates of 21-day transplant-free survival in acute liver failure patients receiving molecular adsorbent recirculating system therapy and patients receiving standard medical therapy. Design Propensity score-matched retrospective cohort analysis. Setting Tertiary North American liver transplant centers. Patients Acute liver failure patients receiving molecular adsorbent recirculating system at three transplantation centers (n = 104; January 2009-2019) and controls from the U.S. Acute Liver Failure Study Group registry. Interventions Molecular adsorbent recirculating system treatment versus standard medical therapy (control). Measurements and main results One-hundred four molecular adsorbent recirculating system patients were propensity score-matched (4:1) to 416 controls. Using multivariable conditional logistic regression adjusting for acute liver failure etiology (acetaminophen: n = 248; vs nonacetaminophen: n = 272), age, vasopressor support, international normalized ratio, King's College Criteria, and propensity score (main model), molecular adsorbent recirculating system was significantly associated with increased 21-day transplant-free survival (odds ratio, 1.90; 95% CI, 1.07-3.39; p = 0.030). This association remained significant in several sensitivity analyses, including adjustment for acute liver failure etiology and propensity score alone ("model 2"; molecular adsorbent recirculating system odds ratio, 1.86; 95% CI, 1.05-3.31; p = 0.033), and further adjustment of the "main model" for mechanical ventilation, and grade 3/4 hepatic encephalopathy ("model 3"; molecular adsorbent recirculating system odds ratio, 1.91; 95% CI, 1.07-3.41; p = 0.029). In acetaminophen-acute liver failure (n = 51), molecular adsorbent recirculating system was associated with significant improvements (post vs pre) in mean arterial pressure (92.0 vs 78.0 mm Hg), creatinine (77.0 vs 128.2 µmol/L), lactate (2.3 vs 4.3 mmol/L), and ammonia (98.0 vs 136.0 µmol/L; p ≤ 0.002 for all). In nonacetaminophen acute liver failure (n = 53), molecular adsorbent recirculating system was associated with significant improvements in bilirubin (205.2 vs 251.4 µmol/L), creatinine (83.1 vs 133.5 µmol/L), and ammonia (111.5 vs 140.0 µmol/L; p ≤ 0.022 for all). Conclusions Treatment with molecular adsorbent recirculating system is associated with increased 21-day transplant-free survival in acute liver failure and improves biochemical variables and hemodynamics, particularly in acetaminophen-acute liver failure.

Transjugular intrahepatic portosystemic shunt (TIPS) is well established as a salvage therapy for refractory esophageal variceal hemorrhage (EVH). A more controversial issue is the upper limit of Model for End-Stage Liver Disease (MELD) scores at which this procedure can be performed safely. We present 2 cases of TIPS performed for EVH in patients with severely high MELD scores as a successful intervention for hemostatic and hemodynamic stabilization, and as a bridge to urgent liver transplantation. Both patients had endoscopically confirmed EVH with high blood product transfusion and vasopressor needs despite standard medical therapy. Each received narrow bore TIPS at MELD 42 and 44, respectively, with subsequent resolution of hemorrhage despite worsening synthetic liver function. Detrimental consequences of metabolic acidosis associated with minimal residual hepatic function were avoided via continuous renal replacement therapy and mechanical ventilation, with a goal to maintain cardiopulmonary stability and favorable acid base balance. Liver transplant followed TIPS 4 and 3 days, respectively, with both patients maintaining good functional status at discharge. Both cases suggest that in patients deemed otherwise appropriate for liver transplantation, a severely high MELD score alone should not preclude TIPS as salvage therapy for refractory EVH bleeds.

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BACKGROUND: Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility. METHODS: Thirty-five international experts from anesthesiology/intensive care, hepatology, and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement. RESULTS: The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty and persistent fever or 1 μg/kg per minute and a serum lactate level >9 mmol/L. CONCLUSIONS: Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented., SCOPUS: ar.j, info:eu-repo/semantics/published

Cirrhosis and chronic liver disease cause a myriad of systemic health problems mostly caused by the presence of portal hypertension. Esophageal varices are one result of portal hypertension. They can rupture and bleed, which can be catastrophic in already coagulopathic liver failure patients. We present a patient who presented with decompensated liver failure for transplant. He developed a severe and refractory gastrointestinal bleed and was put on an octreotide infusion to increase splanchnic flow and decrease portal pressures. He subsequently developed complete heart block. Understanding the mechanisms of octreotide is imperative due to its frequent use in medically complex patients

Hepatic hydrothorax (HH) remains a difficult-to-treat complication of cirrhosis. To define the mortality, length of stay (LOS), and risk of ACLF in patients admitted with HH. We utilized the North American Consortium for the Study of End-stage Liver Disease, a prospective cohort of 2868 non-electively hospitalized patients with cirrhosis from 14 tertiary care hepatology centers in North America. A total of 121 patients who required an inpatient thoracentesis (HH group) were compared to 736 patients with refractory ascites without HH, and to 1639 patients without these complications (Other). Patients with a TIPS before or during admission were excluded. There were no differences between the groups in age, gender, or liver disease etiology. Admission MELD (20.5, 21.6 vs. 18.7; p

Introduction Readmission and death in cirrhosis are common, expensive, and difficult to predict. Our aim was to evaluate the abilities of multiple artificial intelligence (AI) techniques to predict clinical outcomes based on variables collected at admission, during hospitalization, and at discharge. Methods We used the multicenter North American Consortium for the Study of End-Stage Liver Disease (NACSELD) cohort of cirrhotic inpatients who are followed up through 90-days postdischarge for readmission and death. We used statistical methods to select variables that are significant for readmission and death and trained 3 AI models, including logistic regression (LR), kernel support vector machine (SVM), and random forest classifiers (RFC), to predict readmission and death. We used the area under the receiver operating characteristic curve (AUC) from 10-fold crossvalidation for evaluation to compare sexes. Data were compared with model for end-stage liver disease (MELD) at discharge. Results We included 2,170 patients (57 ± 11 years, MELD 18 ± 7, 61% men, 79% White, and 8% Hispanic). The 30-day and 90-day readmission rates were 28% and 47%, respectively, and 13% died at 90 days. Prediction for 30-day readmission resulted in 0.60 AUC for all patients with RFC, 0.57 AUC with LR for women-only subpopulation, and 0.61 AUC with LR for men-only subpopulation. For 90-day readmission, the highest AUC was achieved with kernel SVM and RFC (AUC = 0.62). We observed higher predictive value when training models with only women (AUC = 0.68 LR) vs men (AUC = 0.62 kernel SVM). Prediction for death resulted in 0.67 AUC for all patients, 0.72 for women-only subpopulation, and 0.69 for men-only subpopulation, all with LR. MELD-Na model AUC was similar to those from the AI models. Discussion Despite using multiple AI techniques, it is difficult to predict 30- and 90-day readmissions and death in cirrhosis. AI model accuracies were equivalent to models generated using only MELD-Na scores. Additional biomarkers are needed to improve our predictive capability (See also the visual abstract at http://links.lww.com/AJG/B710).

Little is known about patients discharged to hospice following hospitalization for complications of cirrhosis. We sought to understand the current pattern of hospice utilization in patients with cirrhosis by evaluating the North American Consortium for the Study of End-stage Liver Disease (NACSELD) cohort. Patients with cirrhosis from 14 tertiary-care hepatology centers across North America non-electively hospitalized and prospectively enrolled were evaluated. Exclusion criteria included HIV infection, transplantation or non-hepatic malignancy. Random computer-based propensity score matching was undertaken in a 1:2 ratio based on admission MELD score ± 3 points. Totally, 2718 patients were enrolled, 5% (N = 132) were discharged to hospice, 6% (N = 171) died, and the rest were discharged alive. Patients discharged to hospice were older (60 vs. 57 years, p = 0.04), less likely to have had SBP (13% vs. 28%, p = 0.002) and be listed for liver transplantation (11% vs. 26%, p = 0.0007). Features, on multivariable modeling, associated with increased probability of discharge to hospice as opposed to being discharged alive: grade-3–4 hepatic encephalopathy, a higher Child–Turcotte–Pugh (CTP) score, and a higher discharge serum creatinine; however, a higher serum sodium, being listed for transplant and being prescribed rifaximin or a statin were protective from hospice discharge. Patients with more advanced liver disease, hepatic encephalopathy, renal dysfunction, and those not candidates for liver transplantation were more likely to be discharged to hospice. However, in this sick multinational cohort of cirrhotic inpatients, it seems that hospice is markedly underutilized (5%) since 25% of patients not discharged to hospice died within 6 months.

The prognosis of acute kidney disease (AKD), defined as a glomerular filtration rate of60 ml/min/1.73 mTo study the prevalence, predictive factors and clinical outcomes in hospitalized cirrhotic patients with AKD.The North American Consortium for the Study of End-Stage Liver Disease prospectively enrolled hospitalized decompensated cirrhotic patients. Patients were separated into those with normal renal function (controls or C), AKD or stage 1 AKI as their worst renal dysfunction per International Club of Ascites definition and compared. Parameters assessed included demographics, laboratory data, haemodynamics, renal and patient outcomes.1244 patients with cirrhosis and ascites (C: 704 or 57%; AKD: 176 or 14%; stage 1 AKI: 364 or 29%) with similar demographics were enrolled. AKD patients had similar baseline sCr but higher hospital admission in the previous 6 months, and higher peak sCr, compared to controls, with their peak sCr being lower than that in stage 1 AKI patients (all P .0001). The in-hospital and 30-day survival for AKD patients were intermediary between that for controls and stage 1 AKI patients (96% vs 91% vs 86%, P .0001). The strongest predictors for AKD development while in hospital were the presence of a second infection (OR: 2.44) and diabetes (OR: 1.53).Patients with AKD had intermediate outcomes between stage 1 AKI and controls. AKD patients, especially those with diabetes and a second infection, need careful monitoring and prompt treatment for AKD to prevent negative outcomes.

BACKGROUND AND AIMS: Acute kidney injury (AKI) has a poor prognosis in cirrhosis. Given the variability of creatinine, the prediction of AKI and dialysis by other markers is needed. The aim of this study is to determine the role of serum and urine metabolomics in the prediction of AKI and dialysis in an inpatient cirrhosis cohort. APPROACH AND RESULTS: Inpatients with cirrhosis from 11 North American Consortium of End-stage Liver Disease centers who provided admission serum/urine when they were AKI and dialysis-free were included. Analysis of covariance adjusted for demographics, infection, and cirrhosis severity was performed to identify metabolites that differed among patients (1) who developed AKI or not; (2) required dialysis or not; and/pr (3) within AKI subgroups who needed dialysis or not. We performed random forest and AUC analyses to identify specific metabolite(s) associated with outcomes. Logistic regression with clinical variables with/without metabolites was performed. A total of 602 patients gave serum (218 developed AKI, 80 needed dialysis) and 435 gave urine (164 developed AKI, 61 needed dialysis). For AKI prediction, clinical factor–adjusted AUC was 0.91 for serum and 0.88 for urine. Major metabolites such as uremic toxins (2,3-dihydroxy-5-methylthio-4-pentenoic acid [DMTPA], N2N2dimethylguanosine, uridine/pseudouridine) and tryptophan/tyrosine metabolites (kynunerate, 8-methoxykyunerate, quinolinate) were higher in patients who developed AKI. For dialysis prediction, clinical factor–adjusted AUC was 0.93 for serum and 0.91 for urine. Similar metabolites as AKI were altered here. For dialysis prediction in those with AKI, the AUC was 0.81 and 0.79 for serum/urine. Lower branched-chain amino-acid (BCAA) metabolites but higher cysteine, tryptophan, glutamate, and DMTPA were seen in patients with AKI needing dialysis. Serum/urine metabolites were additive to clinical variables for all outcomes. CONCLUSIONS: Specific admission urinary and serum metabolites were significantly additive to clinical variables to predict AKI development and dialysis initiation in inpatients with cirrhosis. These observations can potentially facilitate earlier initiation of renoprotective measures.

Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure. We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence. We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain. ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes.

Headquartered in the state of Maharashtra in India, Prabhat Dairy was one of the small, emerging private players in a growing market. India’s dairy market was dominated by farmer cooperatives who controlled both milk pricing and, to a large extent, its distribution. While the commodity side of the industry featured strong incumbents and low margins, the value-added milk market was both in high growth mode and rewarded strong players with sizeable margins. Prabhat had started in 1998 serving as an intermediary to players such as Mondelez, Abbott, Perfetti Van Mele, and Britannia but now wants to move into the consumer market. It faces significant challenges in this crossover and has to come up with the right strategy to address them.

Nosocomial infections (NIs) can be a major cause of morbidity and mortality in cirrhosis. This study aims to define the determinants of NI development and its impact on 30-day outcomes among hospitalized patients with cirrhosis.North American Consortium for the Study of End-Stage Liver Disease enrolled patients with cirrhosis who were admitted nonelectively. Admission variables and 30-day outcomes were compared between patients with and without NI. These were also compared based on whether there was an isolated admission infection, NI, or both. Models were created for NI development using admission variables and for 30-day mortality.The study included 2,864 patients; of which, 15% (n = 436) developed NI. When comparing NI vs no NI, 1,866 patients were found to be infection free, whereas 562 had admission infections only, 228 had only NI, and 208 had both infections. At admission, patients with NI were more likely to be infected and have advanced cirrhosis. NIs were associated with higher rates of acute-on-chronic liver failure, death, and transplant regardless of admission infections. Patients with NI had higher respiratory infection, urinary tract infection, Clostridium difficile infection, fungal infections, and infection with vancomycin-resistant enterococci compared with patients without NI. Risk factors for NIs were admission infections, model for end-stage liver disease (MELD)20, systemic inflammatory response syndrome criteria, proton pump inhibitor, rifaximin, and lactulose use, but the regression model (sensitivity, 0.67; specificity, 0.63) was not robust. Age, alcohol etiology, admission MELD score, lactulose use, acute-on-chronic liver failure, acute kidney injury, intensive care unit, and NI increased the risk of death, whereas rifaximin decreased the risk of death.NIs are prevalent in hospitalized patients with cirrhosis and are associated with poor outcomes. Although higher MELD scores and systemic inflammatory response syndrome are associated with NI, all hospitalized patients with cirrhosis require vigilance and preventive strategies.

Objective: Warfarin is the most commonly prescribed oral anticoagulant, although having a narrow therapeutic index and wide interindividual variability. The aim of this study was to replicate the utility of VKORC1 (−1639G>A) rs9923231 genotyping in predicting the mean daily dose and to evaluate its ability to categorize warfarin-treated patients to high-, intermediate-, or low-dose categories in the South Indian population. Materials and methods: A cohort of 222 warfarin-treated patients was genotyped using restriction fragment length polymorphism method. The influence of the rs9923231 polymorphism on the variations in the mean daily dose was compared using one-way analysis of variance and linear regression analysis. Discriminatory ability of the rs9923231 polymorphism to group the patients into ordered dose categories was assessed by estimating the proportional odds ratios using the ordered logit regression analysis. Results: The frequency of AA genotype and A allele in the study sample was found to be 1.8% and 9.23%, respectively, which was similar to reports from other South Indian populations. The mean daily dose required to achieve the optimum international normalized ratio was significantly lower in AA homozygous genotype carriers (3.99 ± 1.67 mg/day) and GA heterozygous (4.26 ± 1.57 mg/day) compared to the GG genotype carriers (5.51 ± 2.13 mg/day), p = 0.003. The A allele carriers (GA+AA genotypes) had a 3.23 higher odds of being grouped as a low-dose requiring category compared to non-carriers (95% CI 1.49–6.98, p = 0.003). Conclusions: These preliminary results strongly support the use of VKORC1 (−1639G>A) rs9923231 polymorphism for genetically guided initial warfarin dosing in South Indian patients with heart valve replacements. Keywords: VKORC1, Polymorphism, Warfarin, Pharmacogenetics, Regression

Background & Aims Acetaminophen (APAP)-induced acute liver failure (ALF) remains the most common cause of ALF in the Western world. Conventional prognostic models, utilising markers of liver injury and organ failure, lack sensitivity for mortality prediction. We previously identified a microRNA signature that is associated with successful regeneration post-auxiliary liver transplant and with recovery from APAP-ALF. Herein, we aimed to use this microRNA signature to develop outcome prediction models for APAP-ALF. Methods We undertook a nested, case-control study using serum samples from 194 patients with APAP-ALF enrolled in the US ALF Study Group registry (1998-2014) at early (day 1-2) and late (day 3-5) time-points. A microRNA qPCR panel of 22 microRNAs was utilised to assess microRNA expression at both time-points. Multiple logistic regression was used to develop models which were compared to conventional prognostic models using the DeLong method. Results Individual microRNAs confer limited prognostic value when utilised in isolation. However, incorporating them within microRNA-based outcome prediction models increases their clinical utility. Our early time-point model (AUC = 0.78, 95% CI 0.71–0.84) contained a microRNA signature associated with liver regeneration and our late time-point model (AUC = 0.83, 95% CI 0.76–0.89) contained a microRNA signature associated with cell-death. Both models were enhanced when combined with model for end-stage liver disease (MELD) score and vasopressor use and both outperformed the King’s College criteria. The early time-point model combined with clinical parameters outperformed the ALF Study Group prognostic index and the MELD score. Conclusions Our findings demonstrate that a regeneration-linked microRNA signature combined with readily available clinical parameters can outperform existing prognostic models for ALF in identifying patients with poor prognosis who may benefit from transplantation. Lay summary While acute liver failure can be reversible, some patients will die without a liver transplant. We show that blood test markers that measure the potential for liver recovery may help improve identification of patients unlikely to survive acute liver failure who may benefit from a liver transplant.

Supplemental Digital Content is available in the text., Background. The current surge of coronavirus 2019 (COVID-19) cases in certain parts of the country has burdened the healthcare system, limiting access to tertiary centers for many. As a result, COVID-19-positive Solid Organ Transplant (SOT) recipients are increasingly being managed by local healthcare providers. It is crucial for community providers to understand disease severity and know if COVID-19-impacted SOT recipients have a different clinical course compared with COVID-19-negative SOT recipients with a similar presentation. Methods. We conducted a retrospective analysis on SOT recipients suspected to have COVID-19 infection tested during March 14, 2020–April 30, 2020. Patients were followed from time of testing to May 31, 2020. Results. One hundred sixty SOT recipients underwent testing: 22 COVID-19 positive and 138 COVID-19 negative. COVID-19-positive patients were more likely to have rapid progression of symptoms (median 3 vs 6 d, P = 0.002), greater hospitalizations (78% vs 64%, P < 0.017), and need for intensive care unit care (45% vs 17%, P < 0.001) Severe COVID-19 infection was not observed in patients on Belatacept for immunosuppression (30% vs 87%,P = 0.001). COVID- 19 positive patients in the intensive care unit were more likely to have multifocal opacities on radiological imaging in comparison to those admitted to the medical floor (90% vs 11%). Survival probability was similar in both cohorts. Conclusion. COVID-19-infected SOT recipients have a propensity for rapid clinical decompensation. Local providers need to be work closely with transplant centers to appropriately triage and manage COVID-19 SOT recipients in the community.

Hepatic hydrothorax (HH) remains a difficult-to-treat complication of cirrhosis.To define the mortality, length of stay (LOS), and risk of ACLF in patients admitted with HH.We utilized the North American Consortium for the Study of End-stage Liver Disease, a prospective cohort of 2868 non-electively hospitalized patients with cirrhosis from 14 tertiary care hepatology centers in North America. A total of 121 patients who required an inpatient thoracentesis (HH group) were compared to 736 patients with refractory ascites without HH, and to 1639 patients without these complications (Other). Patients with a TIPS before or during admission were excluded.There were no differences between the groups in age, gender, or liver disease etiology. Admission MELD (20.5, 21.6 vs. 18.7; p 0.0001) was lower in HH than RA patients but lowest in other patients, respectively. In hospital, HH patients' rate of second infections and ICU transfer were the highest, and their LOS was the longest of all groups. Despite a similar mean discharge MELD compared to RA patients, the 90-day transplant rate was lower. Multivariable modeling showed patients with HH had an increased risk of ACLF (HR = 2.37 vs. RA, HR = 2.56 vs. Other; p = 0.01) even when controlling for MELD score, AKI, second infection, and history of prior 6-month hospitalization. Multivariable modeling also showed that HH increased the risk of inpatient mortality (HR = 2.22 vs. RA alone, HR = 2.31 vs. Other; p = 0.04).HH that required a therapeutic thoracentesis more than doubled the risk of ACLF and inpatient mortality among hospitalized patients with cirrhosis.

Complex networked systems can be modeled as graphs with nodes representing the agents and links describing the dynamic coupling between them. Previous work on network identification has shown that the network structure of linear time-invariant (LTI) systems can be reconstructed from the joint power spectrum of the data streams. These results assumed that data is perfectly measured. However, real-world data is subject to many corruptions, such as inaccurate time-stamps, noise, and data loss. We show that identifying the structure of linear time-invariant systems using corrupt measurements results in the inference of erroneous links. We provide an exact characterization and prove that such erroneous links are restricted to the neighborhood of the perturbed node. We extend the analysis of LTI systems to the case of Markov random fields with corrupt measurements. We show that data corruption in Markov random fields results in spurious probabilistic relationships in precisely the locations where spurious links arise in LTI systems., Submitted to IEEE TAC. Under review

Background & Aims Inpatients with cirrhosis have high rates of acute-on-chronic failure (ACLF) development and high mortality within 30 days of admission to the hospital. Better biomarkers are needed to predict these outcomes. We performed metabolomic analyses of serum samples from patients with cirrhosis at multiple centers to determine whether metabolite profiles might identify patients at high risk for ACLF and death. Methods We performed metabolomic analyses, using liquid chromatography, of serum samples collected at time of admission to 12 North American tertiary hepatology centers from 602 patients in the North American Consortium for the Study of End-Stage Liver Disease sites from 2015 through 2017 (mean age, 56 years; 61% men; mean model for end-stage liver disease score, 19.5). We performed analysis of covariance, adjusted for model for end-stage liver disease at time of hospital admission, serum levels of albumin and sodium, and white blood cell count, to identify metabolites that differed between patients who did vs did not develop ACLF and patients who did vs did not die during hospitalization and within 30 days. We performed random forest analysis to identify specific metabolite(s) that were associated with outcomes and area under the curve (AUC) analyses to analyze them in context of clinical parameters. We analyzed microbiomes of stool samples collected from 133 patients collected at the same time and examined associations with serum metabolites. Results Of the 602 patients analyzed, 88 developed ACLF (15%), 43 died in the hospital (7%), and 72 died within 30 days (12%). Increased levels of compounds of microbial origin (aromatic compounds, secondary or sulfated bile acids, and benzoate) and estrogen metabolites, as well as decreased levels of phospholipids, were associated with development of ACLF, inpatient, and 30-day mortality and were also associated with fecal microbiomes. Random forest analysis and logistic regression showed that levels of specific microbially produced metabolites identified patients who developed ACLF with an AUC of 0.84 (95% confidence interval [CI] 0.78–0.88; P = .001), patients who died while in the hospital with an AUC of 0.81 (95% CI 0.74–0.85; P = .002), and patients who died within 30 days with an AUC of 0.77 (95% CI 0.73–0.81; P = .02). The metabolites were significantly additive to clinical parameters for predicting these outcomes. Metabolites associated with outcomes were also correlated with microbiomes of stool samples. Conclusions In an analysis of serum metabolites and fecal microbiomes of patients hospitalized with cirrhosis at multiple centers, we associated metabolites of microbial origin and lipid moieties with development of ACLF and death as an inpatient or within 30 days, after controlling for clinical features.

Many complex engineering systems admit bidirectional and linear couplings between their agents. Blind and passive methods to identify such influence pathways/couplings from data are central to many applications. However, dynamically related data-streams originating at different sources are prone to corruption caused by asynchronous time-stamps of different streams, packet drops and noise. Such imperfect information may be present in the entire observation period, and hence not detected by change-detection algorithms that require an initial clean observation period. Prior work has shown that spurious links are inferred in the graph structure due to the corrupted data-streams, which prevents consistent learning. In this article, we provide a novel approach to detect the location of corrupt agents as well as present an algorithm to learn the structure of radial dynamical systems despite corrupted data streams. In particular, we show that our approach provably learns the true radial structure if the unknown corrupted nodes are at least three hops away from each other. Our theoretical results are further validated in test dynamical network., Comment: Under review in IEEE TCNS

Currently in most of the cases the material deposition or dispensing is done only on planar surfaces, in applications such as extrusion 3D printing and surface mount technology (SMT) electronics assembly solutions. In future, the dispensing will be carried out on arbitrary three dimensional objects, where the dispenser needs to know the exact shape and location of them. This drives the necessity of using vision based high degree of freedom (DoF) robotic manipulator dispensers, instead of existing hard-coded Computer Numerical Control (CNC) based limited DoF 3D dispensers. Given a 3D object to be dispensed on and a CAD model of it along with the dispensing path, this thesis aims to answer the following industrial problem: How to adapt the 3D dispensing path if the object is displaced from CAD model position? The most important requirement is high dispensing accuracy, in the order of 100 _m with respect to the ideal (CAD) dispensing path, to improve the dispensing quality. Moreover, maintaining an appropriate distance between the dispensing tip and the surface of the object is important for both the positioning accuracy and the volume precision of the deposit. In order to achieve high dispensing accuracy, robust volumetric scanning (3D reconstruction) of the object closely resembling the CAD model and robotic manipulator with high path tracking accuracy are required. However, the scope of this thesis is restricted only to 3D reconstruction and dispensing path adaptation based on the object’s pose displacement. The additional requirements are low overall tact time and low equipment cost. This thesis aims at three things: i) investigating different types of fiducial marker based camera 3D pose estimations using low cost consumer-grade RGBD camera ii) generating 3D reconstruction of the object for all the pose estimation types and iii) finding the object pose displacement from CAD model position. Checkerboard and ArUco markers are used as fiducial markers. Different types of pose estimation involving RGB only and RGB-D fused techniques are used to find the pose of the object. Truncated Signed Distance Function (TSDF) is used for surface reconstruction and Iterative Closest Point (ICP) is used for finding the pose alignment between the CAD and reconstruction. Tests are conducted for different object shapes in different positions. Then the reconstruction and the dispensing path adaptation accuracy are evaluated, along with the alignment tact time. Dispensering av vätskor är en viktig del av många industriella tillämpningar, som 3D-skrivare och ytmontering. I en majoritet av dessa tillämpningar idag sker dispenseringen på platta, två-dimensionella ytor (eller substrat). I framtiden kommer dispensering i ökad omfattning ske på godtyckliga tredimensionella objekt, varför positionen av dispenseringshuvudet relativt hela det tre-dimensionella substratet kommer att krävas. Behovet driver på möjligheten att använda vision-baserade, fem- eller sex-axliga robotmanipulatorer, istället för befintliga lösningar med hårdkodade rumsbeskrivningar av ett objekt som dispenseringshuvudet ska följa. Given en tre-dimensionell kropp, en CAD-beskrivning av densamme och en bana på kroppen som ska följas av ett dispenseringshuvud syftar denna avhandling till att svara på följande industriella problem: Hur anpassas dispenseringsbanan om kroppen förskjuts från CAD-modellens position? Det viktigaste kravet för tillämpningen är hög volymsnoggrannhet på den nedlagda volymen som kräver hög positioneringsnoggrannhet, ned till 100 um med avseende på den tänkta CAD-definierade dispenseringsbanan. Den hög positioneringsnoggrannheten på dispenseringshuvudet garanterar även god positioneringsnoggrannhet på den dispenserade vätskan på substratet. För att uppnå hög doseringsnoggrannhet krävs robust volymetrisk skanning (3D-rekonstruktion) av objektet som liknar CADmodellen och robotmanipulator med hög noggrannhet. Arbetet i denna avhandling är begränsad till den tre-dimensionella rekonstruktionen och justering av dispenseringsbanan baserat på en ändring av objektets position. Andra tillämpningsspecifikationer är låg total takttid och låg utrustningskostnad. Avhandling syftar till att: i) undersöka olika typer av markörbaserade 3Dpositioneringsuppskattningar med en billig RGBD konsumentkamera ii) generera en 3D-rekonstruktion av objektet för alla typer av poseuppskattningar och iii) hitta objektets positioneringsförskjutning från CAD-modellens. Schackbräda och ArUco-markörer används som fiducialmarkörer. Olika typer av poseuppskattningar som utnyttjar RGB or RGB-D-kombinerade tekniker används. Truncated Signed Distance Function (TSDF) används för ytrekonstruktion. Iterative Closest Point (ICP) används för att hitta pose-justering mellan CADbeskrivningen och rekonstruktionen. Tester utförs för olika objektformer i olika positioner och riktningar. Därefter utvärderas rekonstruktionen, noggrannheten i justeringen av dispenseringsbanan, samt takttiden.