Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Differences in opioid prescribing in low back pain patients with and without depression: a cross-sectional study of a national sample from the United States

Abstract. Introduction:. Low back pain (LBP) is among the leading indications for the prescription of opioid analgesics in clinical practice. There is increasing evidence suggesting that these agents may have diminished efficacy in the treatment of LBP. Objectives:. We evaluated the relationship between depression, the probability of receiving an opioid prescription, and the amount of morphine equivalent amounts prescribed per year among patients with LBP using nationwide data. Methods:. A cross-sectional analysis was performed on existing data from the Medical Expenditure Panel Survey data set from the period 2004 to 2009. Demographic, medical condition, Patient Health Questionnaire-2 responses, and prescription drug information were obtained on 56,811,864 weighted person-years of data from individuals aged 18 to 65 with an ICD-9 code specific to LBP. Results:. Increases in PHQ-2 score, as well a positive screen for depression, were associated with an increased probability of being prescribed opioid therapy and more morphine equivalents per year. Conclusion:. Analysis of a nationwide sample of patients with LBP shows an association between depression and higher rates of opioid prescribing after controlling for several known cofounders. Clinicians prescribing opioids in LBP populations that rely on clinical trial results that exclude depressed patients may misjudge the risks and benefits of this class of therapy

Shareholder Votes and Proxy Advisors: Evidence from Say on Pay

ABSTRACT We investigate the economic role of proxy advisors (PAs) in the context of mandatory “say on pay” votes, a novel and complex item requiring significant firm‐specific analysis. PAs are more likely to issue an Against recommendation at firms with poor performance and higher levels of CEO pay and do not appear to follow a “one‐size‐fits‐all” approach. PAs’ recommendations are the key determinant of voting outcome but the sensitivity of shareholder votes to these recommendations varies with the institutional ownership structure, and the rationale behind the recommendation, suggesting that at least some shareholders do not blindly follow these recommendations. More than half of the firms respond to the adverse shareholder vote triggered by a negative recommendation by engaging with investors and making changes to their compensation plan. However, we find no market reaction to the announcement of such changes, even when material enough to result in a favorable recommendation and vote the following year. Our findings suggest that, rather than identifying and promoting superior compensation practices, PAs' key economic role is processing a substantial amount of executive pay information on behalf of institutional investors, hence reducing their cost of making informed voting decisions. Our findings contribute to the literature on shareholder voting and the related policy debate

Board of Directors' Responsiveness to Shareholders: Evidence from Shareholder Proposals

In recent years boards have become significantly more likely to implement non-binding, majority-vote (MV) shareholder proposals. Using a sample of 620 MV proposals between 1997 and 2004, we find that shareholder pressure (e.g., the voting outcome and the influence of the proponent) and the type of proposals are the main determinants of the implementation decision, while traditional governance indicators do not seem to affect the decision. We then examine the labor market consequences of the implementation decision for outside directors and find that directors implementing MV shareholder proposals experience a one-fifth reduction in the likelihood of losing their board seat as well as other directorships