Overdose deaths involving prescription opioids killed more than 17,000 Americans in 2017, marking a five-fold increase since 1999. High prescribing rates of opioid analgesics have been a substantial contributor to prescription opioid misuse, dependence, overdose and heroin use. There was recognition approximately ten years ago that opioid prescribing patterns were contributing to this startling increase in negative opioid-related outcomes, and federal actions, including Medicare reimbursement reform and regulatory actions, were initiated to restrict opioid prescribing. The current manuscript is a description (...) of those actions, the effect of those actions on opioid prescribing and related patient outcomes. We also describe our proposal of methods of expanding these efforts as an important piece to further reduce opioid-related misuse, dependence, and overdose death. (shrink)

Taking Isaac Newton at his own word, historians have long agreed that the decade of the 1660s, when Newton was a young man in his twenties, was the critical period in his scientific career. In the years 1665 and 1666, he has told us, he hit on the ideas of cosmic gravitation, the composition of white light, and the fluxional calculus. The elaboration of these basic ideas constituted his scientific achievement. Nevertheless, the decade of the 1660s has remained a virtual (...) blank in our knowledge of Newton. It need not remain so always. His papers contain a wealth of manuscripts from his undergraduate years and the period immediately following. The first volume of his mathematical papers, which will soon be published, will demonstrate how extensive the information on his early mathematical development is. The development of his non-mathematical studies, especially of what I shall call his scientific studies to distinguish them from the mathematical, can be followed as well—in his reading notes, in his notebooks, above all in the passage in his philosophical notebook labelled Quaestiones quaedam Philosophicae. In this passage we see emerging into consciousness for the first time the questions on which Newton's philosophy of nature was built. (shrink)

I wish, for the sake of the vivacity of any discussion which might ensue, that I could find myself more in disagreement with Dr. Brodbeck than I do. As a matter of fact, however, I find myself in substantial agreement with her on practically all of the points upon which she takes issue with Hayek. There are, to be sure a few questions of relatively minor import that I should like to ask Dr. Brodbeck, but in the main I have (...) confined my own discussion to an elaboration and supplementation of some of the points considered in her paper, and some related considerations raised in Hayek's book but which Dr. Brodbeck did not have the time, perhaps, to treat. (shrink)

How transcription factors achieve their in vivo specificities is a fundamental question in biology. For the Homeotic Complex (HOM/Hox) family of homeoproteins, specificity in vivo is likely to be in part determined by subtle differences in the DNA binding properties inherent in these proteins. Some of these differences in DNA binding are due to sequence differences in the N‐terminal arms of HOM/Hox homeodomains. Evidence also exists to suggest that cofactors can modify HOM/Hox function by cooperative DNA binding interactions. The Drosophila (...) homeoprotein extradenticle (exd) is likely to be one such cofactor. In HOM/Hox proteins, both the conserved ‘YPWM’ peptide motif and the homeodomain are important for interacting with exd. Although exd provides part of the answer as to how specificity is achieved, there may be additional cofactors and mechanisms that have yet to be identified. (shrink)

From the very day in 1686 when Edmond Halley placed Book I of the Principia before the Royal Society, Robert Hooke's claim to prior discovery has been associated with the law of universal gravitation. If the seventeenth century rejected Hooke's claim summarily, historians of science have not forgotten it, and a steady stream of articles continues the discussion. In our own day particularly, when some of the glitter has worn off, not from the scientific achievement, but from the character of (...) Newton, there has been a tendency vicariously to atone for the treatment Hooke received. The judgement Lohne cites with approval from Vavilov appears to summarize the current estimate of the issue—in the seventeenth century only Newton could have written the Principia; nevertheless Hooke first sketched out its programme. What with all the knocks he has received both alive and dead, one feels guilty in assuming the role of “debunker” at this late date. Apologetically draped in sackcloth then, head covered with ashes I venture softly to suggest that Hooke has received more than his due. There is no question here of justifying Newton's behaviour toward Hooke. Wholly lacking in generosity as it appears to me, Newton's behaviour neither deserves nor can receive justification. The question turns rather on Hooke's scientific theories. Granting always his lack of demonstrations, historians have been prone to interpret his words in the light of Newton's demonstrations. A close examination of Hooke's writings does not sustain the interpretation. Contrary to what is generally asserted, he did not hold a conception of universal gravitation. And if he announced the inverse square relation, he derived it from such a medley of confusion as will not allow his claim to priority. (shrink)

Conflicts of interest have been reduced to financial conflicts. The National Institutes of Health’s new rules for managing conflicts of interest in medical research, the first major change to the regulations in over 15 years, address only financial ties. Although several commentators urged that the regulations also cover non-financial interests, the Department of Health and Human Services declined to do so. Similarly, the Institute of Medicine’s influential 2009 Conflict of Interest Report focuses almost exclusively on financial conflicts. Institutional policies at (...) academic medical centers and guidance from professional bodies and medical journals also primarily emphasize financial ties. Even broadly worded rules are applied more readily to financial ties than non-financial interests, such as the regulations that restrict institutional review board members with conflicting interests from participating in protocol reviews. (shrink)

As a result of health care reform, medicine has entered a new era of comparative effectiveness. The Patient Protection and Affordable Care Act created the nation’s first comprehensive comparative effectiveness research program, investing in CER at record levels and establishing a new regulatory framework for oversight of the research. CER attracts considerable enthusiasm as a tool for reform because it compares competing interventions to determine which works best, supplying critical information for medical decision-making and health policy. In theory, better evidence (...) of how treatments fare relative to one another will translate to better medical care. According to some optimistic accounts, CER can lead to a “revolution” in clinical practice, has transformative power “to reshape major portions of the practice of medicine,” and represents a major “turning point” for the health care system. (shrink)

Isaac Newton was indisputably one of the greatest scientists in history. His achievements in mathematics and physics marked the culmination of the movement that brought modern science into being. Richard Westfall's biography captures in engaging detail both his private life and scientific career, presenting a complex picture of Newton the man, and as scientist, philosopher, theologian, alchemist, public figure, President of the Royal Society, and Warden of the Royal Mint. An abridged version of his magisterial study Never at Rest, (...) this concise biography makes Westfall's highly acclaimed portrait of Newton newly accessible to general readers. (shrink)

While it seems to be evident that the vision of the eternal return of the same is the solution to the riddle mentioned in "On the vision and the riddle," exactly what constitutes the riddle is anything but clear. Li ke all good riddles the solution demands a paradigm shift. Nietzsche's riddle is solved by a radical rethinking of the concept of time, from a straight line to a circle. I give a detailed account of how Nietzsche's riddle is formulated (...) in such a way tha t the eternal return of the same is the only possible solution. (shrink)