Pacioli, Popes, and the Bottom Billion: A Timeless Perspective on Economic Development

In 1494 Luca Pacioli, Franciscan friar, published Summa de Arithmetica Geometria Proportioni et Proportionalita (The Summa). Simply put, The Summa was an early business textbook comprised of five sections; four of mathematics and one of bookkeeping (or accounting). A textbook written to support the economic development of the common person of 1500 Italy. Today developing nations still struggle with economic (often low) growth. Especially impacted are the bottom billion, those who are still largely impoverished. Consequently, a debate over foreign aid has emerged. This debate centers on methods rather than objectives and is often characterized by the contrasting approaches. The books of Sachs (The End of Poverty, 2005) and Easterly (The White Man’s Burden, 2006) serve as a classic contrast of solution perspectives. This paper suggests a significant contribution to the economic development (aid) solution in the 500-year-old work of Luca Pacioli with its focus on developing human capital. The problems faced by an evolving merchant-based economy in 16th century Italy are surprisingly similar to those of contemporary developing economies, including the socially positive impacts of business and education’s role therein. Pacioli lists the elements of business success as access to capital (financing, mathematical and accounting skills), ability to model business and make business decisions, and an appropriate accounting system (“Venetian” or double entry bookkeeping). This paper argues these fundamentals are as important today and they were 500 years ago and considers them in the context of today’s emerging economies. In addition, Pacioli’s work integrates well with both various economic development theories and Catholic Social Teaching

The American Corporation in the Twenty-first Century

Opportunistic Downsizing of Senior Workers: Exploring the Fiduciary/Contract Distinction to Enforce Implicit Employment Agreements lecture given by Marleen A. O\u27Connor, Professor of Law at Stetson College. The Motivational Implications of Debt Financing lecture given by George Triantis, Nicholas E. Chimicles Research Professor of Business Law and Regulation at the University of Virginia and the Director of the John M. Olin Program in Law and Economics. Political Backlash and the Corporation lecture given by Mark Roe, Professor of Law at Columbia University and Director of the Columbia Law School Sloan Project on Corporate Governance. Venture Capital and the Structure of Capital Markets: Banks versus Stock Markets lecture given by Ronald J. Gilson, Charles J. Meyers Professor of Law and Business at Stanford University and The Marc and Eva Stern Professor of Law and Business at Columbia University. The Shaping Force of Corporate Law in the New Economic Order lecture given by Jeffrey N. Gordon, Professor of Law and Co-director Center for Law and Economic Studies at Columbia University

Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.

OBJECTIVES: The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of BACKGROUND: Elevations in natriuretic peptide (NP) levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies of this strategy thus far have been mixed, and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF. METHODS: GUIDE-IT is a prospective, randomized, controlled, unblinded, multicenter clinical trial designed to randomize approximately 1,100 high-risk subjects with systolic HF (left ventricular ejection fraction ≤40%) to either usual care (optimized guideline-recommended therapy) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of CONCLUSIONS: The GUIDE-IT study is designed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinically relevant endpoints of mortality, hospitalization, quality of life, and medical resource use. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840)

Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ( guided therapy ) with inconsistent results. Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). Design, Settings, and Participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Interventions: Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. Main Outcomes and Measures: The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. Results: The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. Conclusions and Relevance: In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01685840

Inhibition of Fatty Acid Synthase Attenuates CD44-Associated Signaling and Reduces Metastasis in Colorectal Cancer

Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of CD44, a transmembrane protein associated with metastases in several cancers including CRC. In addition, inhibition of lipogenic enzymes and reduced expression of CD44 attenuated the activation of MET, Akt, FAK, and paxillin, which are known to regulate adhesion, migration, and invasion. These changes were consistent with an observed decrease in migration and adhesion of CRC cells in functional assays and with reorganization of actin cytoskeleton upon FASN inhibition. Despite the modest effect of FASN inhibition on tumor growth in xenografts, attenuation of lipogenesis completely abolished establishment of hepatic metastasis and formation of secondary metastasis. Together, our findings suggest that targeting de novo lipogenesis may be a potential treatment strategy for advanced CRC

Standards for plant synthetic biology: A common syntax for exchange of DNA parts

© 2015 New Phytologist Trust. Inventors in the field of mechanical and electronic engineering can access multitudes of components and, thanks to standardization, parts from different manufacturers can be used in combination with each other. The introduction of BioBrick standards for the assembly of characterized DNA sequences was a landmark in microbial engineering, shaping the field of synthetic biology. Here, we describe a standard for Type IIS restriction endonuclease-mediated assembly, defining a common syntax of 12 fusion sites to enable the facile assembly of eukaryotic transcriptional units. This standard has been developed and agreed by representatives and leaders of the international plant science and synthetic biology communities, including inventors, developers and adopters of Type IIS cloning methods. Our vision is of an extensive catalogue of standardized, characterized DNA parts that will accelerate plant bioengineering

Multiethnic Meta-Analysis Identifies Ancestry-Specific and Cross-Ancestry Loci for Pulmonary Function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci

Clinical Characteristics, Racial Inequities, and Outcomes in Patients with Breast Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Cohort Study

BACKGROUND: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. METHODS: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. RESULTS: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. CONCLUSIONS: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. FUNDING: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. CLINICAL TRIAL NUMBER: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701

Outcomes of Prehospital Chemical Sedation With Ketamine Versus Haloperidol and Benzodiazepine or Physical Restraint Only

OBJECTIVE: The goal of this study is to describe complications and outcomes of prehospital ketamine use for agitation as compared to other methods of physical or chemical restraint such as haloperidol plus benzodiazepine or physical restraint only. METHODS: We conducted a single-center retrospective review of patient encounters in which restraint was administered in the prehospital setting. At the beginning of our study window, only physical restraint was available to paramedics managing agitated patients but subsequently, haloperidol and benzodiazepines were introduced, followed by ketamine 2 years later. By comparing patients before and after each transition, we divided subjects into 3 cohorts based on restraint type: physical restraint, haloperidol plus benzodiazepine, and ketamine. Demographic data were collected, and outcome measures included intubation rate, need for additional physical or chemical restraint, emergency department (ED) length of stay, need for hospital admission, and employee injury. RESULTS: Of 214 subjects included in the study, 95 patients were administered ketamine, 68 received haloperidol and benzodiazepine, and 51 were physically restrained. Eleven of the patients (11.6%) who received ketamine were intubated. Compared to patients who received haloperidol plus benzodiazepine, patients who received ketamine were more likely to be intubated (odds ratio [OR] = 8.77, 95% confidence interval [CI], 1.10-69.68) and were more likely to require additional chemical restraint when compared to haloperidol/benzodiazepine or physical restraint only (OR =2.94, 95% CI, 1.49-5.80, and OR =2.15, 95% CI, 1.07-4.31, respectively). There were no differences between the 2 chemical sedation groups in terms of ED length of stay or hospital admission rate. CONCLUSIONS: This study demonstrates a lower intubation rate in patients administered ketamine than prior literature in association with a lower weight-based dosing regimen. Ketamine use was correlated with a higher frequency of intubation and a greater need for additional chemical restraint when compared with other restraint modalities, though exogenous factors such as provider preference may have impacted this result. There was no difference in ED length of stay or admission rate between the ketamine and haloperidol plus benzodiazepine groups. Further prospective study is needed to determine whether there is a subset of patients for whom ketamine would be beneficial compared to other therapies