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Purpose: Current endoscopy-based screening and surveillance programs have not been proven effective at decreasing esophageal adenocarcinoma (EAC) mortality, creating an unmet need for effective molecular tests for early detection of this highly lethal cancer. We conducted a genome-wide methylation screen to identify novel methylation markers that distinguish EAC and high-grade dysplasia (HGD) from normal squamous epithelium (SQ) or nondysplastic Barrett's esophagus (NDBE). Experimental Design: DNA methylation profiling of samples from SQ, NDBE, HGD, and EAC was performed using HM450 methylation arrays (Illumina) and reduced-representation bisulfate sequencing. Ultrasensitive methylation-specific droplet digital PCR and next-generation sequencing (NGS)-based bisulfite-sequencing assays were developed to detect the methylation level of candidate CpGs in independent esophageal biopsy and endoscopic brushing samples. Results: Five candidate methylation markers were significantly hypermethylated in HGD/EAC samples compared with SQ or NDBE (P < 0.01) in both esophageal biopsy and endoscopic brushing samples. In an independent set of brushing samples used to construct biomarker panels, a four-marker panel (model 1) demonstrated sensitivity of 85.0% and 90.8% for HGD and EACs respectively, with 84.2% and 97.9% specificity for NDBE and SQ respectively. In a validation set of brushing samples, the panel achieved sensitivity of 80% and 82.5% for HGD and EAC respectively, at specificity of 67.6% and 96.3% for NDBE and SQ samples. Conclusions: A novel DNA methylation marker panel differentiates HGD/EAC from SQ/NDBE. DNA-methylation–based molecular assays hold promise for the detection of HGD/EAC using esophageal brushing samples.

Purpose:Current endoscopy-based screening and surveillance programs have not been proven effective at decreasing esophageal adenocarcinoma (EAC) mortality, creating an unmet need for effective molecular tests for early detection of this highly lethal cancer. We conducted a genome-wide methylation screen to identify novel methylation markers that distinguish EAC and high-grade dysplasia (HGD) from normal squamous epithelium (SQ) or nondysplastic Barrett's esophagus (NDBE).Experimental Design:DNA methylation profiling of samples from SQ, NDBE, HGD, and EAC was performed using HM450 methylation arrays (Illumina) and reduced-representation bisulfate sequencing. Ultrasensitive methylation-specific droplet digital PCR and next-generation sequencing (NGS)-based bisulfite-sequencing assays were developed to detect the methylation level of candidate CpGs in independent esophageal biopsy and endoscopic brushing samples.Results:Five candidate methylation markers were significantly hypermethylated in HGD/EAC samples compared with SQ or NDBE (P < 0.01) in both esophageal biopsy and endoscopic brushing samples. In an independent set of brushing samples used to construct biomarker panels, a four-marker panel (model 1) demonstrated sensitivity of 85.0% and 90.8% for HGD and EACs respectively, with 84.2% and 97.9% specificity for NDBE and SQ respectively. In a validation set of brushing samples, the panel achieved sensitivity of 80% and 82.5% for HGD and EAC respectively, at specificity of 67.6% and 96.3% for NDBE and SQ samples.Conclusions:A novel DNA methylation marker panel differentiates HGD/EAC from SQ/NDBE. DNA-methylation–based molecular assays hold promise for the detection of HGD/EAC using esophageal brushing samples.

Supplementary Figure from Colorectal Cancer Is Associated with the Presence of Cancer Driver Mutations in Normal Colon

Supplementary Data from Novel DNA Methylation Biomarker Panel for Detection of Esophageal Adenocarcinoma and High-Grade Dysplasia

Supplementary Data from Colorectal Cancer Is Associated with the Presence of Cancer Driver Mutations in Normal Colon

Supplementary Figure from Novel DNA Methylation Biomarker Panel for Detection of Esophageal Adenocarcinoma and High-Grade Dysplasia

PurposeThe purpose of this paper is to measure the effect of superstar gig workers, defined as independent contractors who are the most successful in their field, on shareholder value. Gig workers comprise as much as 33% of the workforce and are projected to exceed 50% by 2028. Thus, understanding their impact on shareholder value is important.Design/methodology/approachThis paper uses OLS regression analysis. To establish causality regarding wealth effects, the sudden deaths of superstar gig workers are used. To facilitate the uncontaminated measurement of wealth effects, sudden deaths that coincide with a significant event on a [−3, 3] window about the death event are not used.FindingsThe sudden death of a superstar gig worker causes shareholder wealth to increase significantly by 0.35% or almost $1.5m. Rational and behavioral explanations are offered for this result.Research limitations/implicationsGeneralizability is limited because data on superstar gig workers in traditional corporations are unavailable. For this reason, this paper uses the only available data, namely, data on superstar wrestlers, who are contracted to perform in matches (i.e. “gigs”) in a lucrative promotion (e.g. World Wrestling Entertainment (WWE)). Future research could examine the effect of corporate gig workers on shareholder value if the data become available at some point.Originality/valueThis paper is the first to document the effects of any type of gig worker, whether superstar or regular, on shareholder value.

PurposeMuch evidence exists that rational investors factor rational information into their valuation of shares. This paper aims to examine whether sentimental investors do the same.Design/methodology/approachTo investigate this issue, the author measures sentimental investors’ reaction to the surprise player transactions of the Boston Celtics, which traded on the New York Stock Exchange for 18 years. The team’s shares were bought mainly as souvenirs by sports fans, whose largely unwavering support makes them perhaps the least likely investors to be influenced by rational information. Thus, if the team’s share price changes because of the arrival of rational information, evidence that sentimental traders price rational information into their valuation of a stock will exist.FindingsAn acquired player’s salary, education and firm-specific experience with the Boston Celtics cause higher returns. This result provides evidence that sentimental traders factor rational information into their valuations of shares. On a broader scale, the findings underscore the importance of rational information to the valuation process, as even sentimental investors price rational information into a stock that is held for sentimental reasons. Moreover, the results are consistent with the nudge theory, in that the arrival of rational information encourages (i.e. nudges) sentimental investors to price the rational information as a rational investor world.Originality/valueThis study is the first to show that sentimental traders also factor rational information into the valuation process – an idea that was likely assumed prior to this study, but was never substantiated.

In addressing end-of-life care in veterinary medicine, the role of the veterinary technician can have a profound impact on quality of life during the final days in a pet's life. The role of the veterinary technician in end-of-life care is multifaceted, as duties range from nursing care to social and emotional support for pet caregivers. Human hospice care is helpful as a a model to better understand the importance of palliative care in animals. The skills of the veterinary technician are well suited for caring for hospice and palliative care patients. This article demonstrates and reviews how a technician's expertise is used in end-of-life care including assistance in the euthanasia process.

Although somatic mutations in colorectal cancer are well characterized, little is known about the accumulation of cancer mutations in the normal colon before cancer. Here, we have developed and applied an ultrasensitive, single-molecule mutational test based on CRISPR-DS technology, which enables mutation detection at extremely low frequency ( Significance: This work suggests prevalent somatic evolution in the normal colon of patients with colorectal cancer, highlighting the potential of using ultrasensitive gene sequencing to predict disease risk.

I measure the effect of differences in labor-management complementarities (LMCs) on differences in production and efficiency when management is paid but labor is not paid. I find that differences in LMCs are positively associated with differences in production and efficiency. This result implies that relatively stronger LMCs are associated with relatively greater production and efficiency even in the absence of compensation for one factor of production.

This chapter covers the fundamentals of corporate bond markets. It begins by highlighting the size and importance of these markets, followed by a discussion of the major types of corporate bonds and the process of issuing bonds. Next, the chapter provides a discussion of important relationships between a bond’s price and market interest rates, including the key observation that bond prices move opposite market interest rates. The next topic focuses on duration and convexity, which are techniques to estimate the dollar and percent changes in bond prices for a given change in market interest rates, followed by a discussion of bond immunization, which is a technique used to protect the value of bond portfolios from adverse changes in market interest rates. The final topics covered concern yield curves, credit ratings, and the impact of the Dodd-Frank Wall Street Reform Act of 2010 on corporate bond markets.

Using data from the National Collegiate Athletic Association Men's Basketball Tournament, I examine the impact of travel on team production in a setting where one team is geographically closer than its opponent to a neutral site. I hypothesize and find that the closer team, or relative home team, has a relative home-court advantage that helps it to out-produce its opponent. When the relative home team travels a much shorter distance than its opponent to a neutral site, binary logistic and ordinary least squares regressions indicate a positive relationship between relative home-court advantage and, respectfully, winning and margin of victory. Copyright © 2015 John Wiley & Sons, Ltd.

I find evidence that shareholders prefer political connectedness to corporate social responsibility (CSR). Choosing political connectedness with President Trump over CSR causes shareholder value to increase by $345 million per firm, on average. However, choosing CSR over political connectedness with Trump causes shareholders to lose $570 million on average, and as much as $1.8 billion, per firm. These results reveal an asymmetric response to the choice between political connectedness and CSR and support the view that CSR is an agency problem. Spillover also exists, as rival firms typically incur wealth gains (losses) when main firms choose political connectedness (CSR).

U.S. News estimates that gig workers comprise one-third of the workforce. Moreover, by 2028, gig workers are projected to form the majority of the workforce. Thus, understanding their effect on shareholder value is important. Overall, I find that the typical gig worker erodes shareholder value by 0.35 percent, or almost $1.5 million. This result can be explained by the incentive of gig workers to hoard their human capital so as to increase their likelihood of receiving follow-on contracts. This result also suggests that hiring gig workers is an agency problem.

SYNOPSIS I examine Sarbanes-Oxley's (SOX) effect on capital structure. I find that SOX is associated with higher long-term debt ratios, as firms listed in the U.S. raise their long-term debt ratios by 2 to 3 percentage points. This finding is consistent with the idea that, although the reduction in information asymmetry associated with SOX could prompt managers to increase equity financing, debt is still safer and less costly than equity in the SOX era. Further analysis shows that the increase in debt occurs in the two quarters prior to SOX, suggesting that firms anticipate a higher cost of debt after SOX and acquire debt while it is relatively cheap. Also, firms that heavily (lightly) manage earnings prior to SOX use less (more) debt after SOX. This result is consistent with the view that firms that aggressively manage earnings before SOX reveal intrinsically weaker earnings after SOX, casting doubt on those firms' ability to repay debt and relegating those firms to issue equity for financing purposes. JEL Classifications: G32; G38. Data Availability: Data available upon request.

On the basis of the principles of management and leadership, our organization has worked over the years to formalize the orientation program for new nurse managers. This program meets the needs of new nurse managers and responds to today’s complex health care system needs. This article describes the components of a nurse manager orientation program for the novice nurse manager and methods for evaluating nurse manager effectiveness.

I use data from the Boston Celtics, which traded on the New York Stock Exchange from 1986 to 1998, to investigate the employee characteristics that move stock prices. Investors positively value top-level training when firms seek to hire inexperienced employees. For all added employees, most of whom are experienced, investors respond positively to expected complementarities with existing workers but do not respond to salary. Investors positively value the removal of an older, highly-paid worker but negatively value the removal of a long-tenured worker. These results suggest that a firm’s employee base affects its value.

This essay addresses the topic of women's professional development in the academy, noting the critical roles fulfilled by support networks. Research and personal narratives explore the diverse choices women make, the resistance they sometimes face, and the need to find validation for those choices. Recognizing the importance of women's achievement of tenure and publication, the authors also challenge the notion that those traditional measures of academic success are the only, or the best, way to assess women's professional development.

I examine comovement in the returns of firms added to the Standard and Poor’s (S&P) 500 Index and their downstream customers. I find that a firm’s announcement of inclusion into the S&P 500 is associated with lower value for its downstream customers. On average, when S&P announces the inclusion of a firm into the 500 Index, its customers experience cumulative abnormal returns of -0.8%. This result suggests that S&P 500 inclusion announcements contain information about the downstream customers of firms added to the Index. In addition, further results may suggest information leakage prior to inclusion announcements.

The Sarbanes-Oxley Act (SOX) is an exogenous shock to the information environment of firms listed in the U.S. Thus, firms might adjust their capital structures to reflect the new information environment. I examine SOX’s effect on capital structure. Since SOX applies only to firms listed in the U.S, the control group consists of Canadian firms listed in Canada. The test groups in this study are U.S. firms listed in the U.S. and Canadian firms cross-listed in the U.S. Relative to the control firms, SOX is associated with higher long-term debt ratios for U.S. firms listed in the U.S. but not for Canadian firms cross-listed in the U.S. Also, firms that heavily (modestly) manage pre-SOX earnings decrease (increase) their long-term debt ratios post-SOX.

Objectives: The emergency medicine (EM) job market is increasingly focused on incentive-based reimbursement, which is largely based on relative value units (RVUs) and is directly related to documentation of patient care. Previous studies have shown a need to improve resident education in documentation. The authors created a focused educational intervention on billing and documentation practices to meet this identified need. The hypothesis of this study was that this educational intervention would result in an increase in RVUs generated by EM resident physicians and the average amount billed per patient. Methods: The authors used a quasi-experimental study design. An educational intervention included a 1-hour lecture on documentation and billing, biweekly newsletters, and case-specific feedback from the billing department for EM resident physicians. RVUs and charges generated per patient were recorded for all second- and third-year resident physicians for a 3-month period prior to the educational intervention and for a 3-month period following the intervention. Pre- and postintervention data were compared using Student’s t-test and repeated-measures analysis of variance, as appropriate. Results: The evaluation and management (E/M) chart levels billed during each phase of the study were significantly different (p

Objective: The healthcare chart is becoming ever more complex, serving clinicians, patients, third party payers, regulators, and even medicolegal parties. The purpose of this study was to identify our emergency medicine (EM) resident and attending physicians’ current knowledge and attitudes about billing and documentation practices. We hypothesized that resident and attending physicians would identify billing and documentation as an area in which residents need further education. Methods: We gave a 15-question Likert survey to resident and attending physicians regarding charting practices, knowledge of billing and documentation, and opinions regarding need for further education. Results: We achieved a 100% response rate, with 47% (16/34) of resident physicians disagreeing or strongly disagreeing that they have adequate training in billing and documentation, while 91% (31/34) of residents and 95% (21/22) of attending physicians identified this skill as important to a resident’s future practice. Eighty-two percent (28/34) of resident physicians and 100% of attending physicians recommended further education for residents Conclusion: Residents in this academic EM department identified a need for further education in billing and documentation practices.

This paper provides a perspective on some of the major issues and challenges associated with developing a dedicated capability for placing 10 kg “nanosat” payloads into low earth orbit. By offering dedicated launches in place of secondary payload opportunities and/or converted surplus Soviet ballistic missile systems, it is anticipated that such a service could significantly expand the participation of the domestic academic and research communities in space operations. The observations and conclusions presented herein are derived from extensive personal interactions that have taken place during the initial phases of the development of such launch services. * AIAA Senior Member † AIAA Member