Overdiagnosis and overtreatment over time

Overdiagnosis and overtreatment are often thought of as relatively recent phenomena, influenced by a contemporary combination of technology, specialization, payment models, marketing, and supply-related demand. Yet a quick glance at the historical record reveals that physicians and medical manufacturers have been accused of iatrogenic excess for centuries, if not millennia. Medicine has long had therapeutic solutions that search for ever-increasing diagnostic problems. Whether the intervention at hand has been leeches and lancets, calomel and cathartics, aspirins and amphetamines, or statins and SSRIs, medical history is replete with skeptical critiques of diagnostic and therapeutic enthusiasm. The opportunity cost of this profusion shapes the other side of the coin: chronic persistence of underdiagnosis and undertreatment. Drawing from key controversies of the 19th and 20th centuries, we chart the enduring challenges of inter-related diagnostic and therapeutic excess. As the present critique of overdiagnosis and overtreatment seeks to mobilize resources from inside and outside of medicine to rein in these impulses, we provide an instructive historical context from which to act

Designing antibiotic cycling strategies by determining and understanding local adaptive landscapes

The evolution of antibiotic resistance among bacteria threatens our continued ability to treat infectious diseases. The need for sustainable strategies to cure bacterial infections has never been greater. So far, all attempts to restore susceptibility after resistance has arisen have been unsuccessful, including restrictions on prescribing [1] and antibiotic cycling [2,3]. Part of the problem may be that those efforts have implemented different classes of unrelated antibiotics, and relied on removal of resistance by random loss of resistance genes from bacterial populations (drift). Here, we show that alternating structurally similar antibiotics can restore susceptibility to antibiotics after resistance has evolved. We found that the resistance phenotypes conferred by variant alleles of the resistance gene encoding the TEM {\beta}-lactamase (blaTEM) varied greatly among 15 different {\beta}-lactam antibiotics. We captured those differences by characterizing complete adaptive landscapes for the resistance alleles blaTEM-50 and blaTEM-85, each of which differs from its ancestor blaTEM-1 by four mutations. We identified pathways through those landscapes where selection for increased resistance moved in a repeating cycle among a limited set of alleles as antibiotics were alternated. Our results showed that susceptibility to antibiotics can be sustainably renewed by cycling structurally similar antibiotics. We anticipate that these results may provide a conceptual framework for managing antibiotic resistance. This approach may also guide sustainable cycling of the drugs used to treat malaria and HIV

The Local Nanohertz Gravitational-Wave Landscape From Supermassive Black Hole Binaries

Supermassive black hole binaries (SMBHBs) in the 10 million to 10 billion $M_\odot$ range form in galaxy mergers, and live in galactic nuclei with large and poorly constrained concentrations of gas and stars. There are currently no observations of merging SMBHBs--- it is in fact possible that they stall at their final parsec of separation and never merge. While LIGO has detected high frequency GWs, SMBHBs emit GWs in the nanohertz to millihertz band. This is inaccessible to ground-based interferometers, but possible with Pulsar Timing Arrays (PTAs). Using data from local galaxies in the 2 Micron All-Sky Survey, together with galaxy merger rates from Illustris, we find that there are on average $91\pm7$ sources emitting GWs in the PTA band, and $7\pm2$ binaries which will never merge. Local unresolved SMBHBs can contribute to GW background anisotropy at a level of $\sim20\%$, and if the GW background can be successfully isolated, GWs from at least one local SMBHB can be detected in 10 years.Comment: submitted to Nature Astronomy (reformatted for arXiv

Avoiding Irrational NeuroLaw Exuberance: A Plea for Neuromodesty

In a 2002 editorial published in The Economist, the following warning was given: Genetics may yet threaten privacy, kill autonomy, make society homogeneous and gut the concept of human nature. But neuroscience could do all of these things first. The genome was fully sequenced in 2001, and there has not been one resulting major advance in therapeutic medicine since. Thus, even in its most natural applied domain-medicine-genetics has not had the far-reaching consequences that were envisioned. The same has been true for various other sciences that were predicted to revolutionize the law, including behavioral psychology, sociology, psychodynamic psychology, and others. This will also be true of neuroscience, which is simply the newest science on the block. Neuroscience is not going to do the terrible things The Economist fears, at least not for the foreseeable future. Neuroscience has many things to say but not nearly as much as people would hope, especially in relation to law. At most, in the near to intermediate term, neuroscience may make modest contributions to legal policy and case adjudication. Nonetheless, there has been irrational exuberance about the potential contribution of neuroscience, an issue I have addressed previously and referred to as Brain Overclaim Syndrome. I first consider the law\u27s motivation and the motivation of some advocates to turn to science to solve the very hard normative problems that law addresses. Part III discusses the law\u27s psychology and its concepts of the person and responsibility. The next Part considers the general relation of neuroscience to law, which I characterize as the issue of translation. Part V canvasses various distractions that have bedeviled clear thinking about the relation of scientific, causal accounts of behavior to responsibility. The following Part examines the limits of neurolaw and Part VII considers why neurolaw does not pose a genuinely radical challenge to the law\u27s concepts of the person and responsibility. Part VIII makes a case for cautious optimism about the contribution neuroscience may make to law in the near and intermediate term. A brief conclusion follows..

Psychometric Evaluation of a 13‐Point Measure of Students’ Overall Competence in Community‐Based Dental Education Programs

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153670/1/jddj0022033720168010tb06207x.pd

Assessing the effectiveness of business support services in England: evidence from a theory based evaluation

In England, publicly supported advisory services for small firms are organised primarily through the Business Link (BL) network. Based on the programme theory underlying this business support services we develop four propositions and test these empirically using data from a new survey of over 3,000 English small firms. Our empirical results provide a broad validation of the programme theory underlying BL assistance for small firms in England during 2003, and more limited support for its effectiveness. More specifically, we find strong support for the value of BL operators maintaining a high profile as a way of boosting take-up. We also find some support for the approach to market segmentation adopted by BL allowing more intensive assistance to be targeted on younger firms and those with limited liability status. In terms of the outcomes of BL support, and allowing for issues of sample selection, we find no significant effects on growth from ‘other’ assistance but do find positive and significant employment growth effects from intensive assistance. This provides partial support for the programme theory assertion that BL support will lead to improvements in business growth performance and stronger support for the proposition that there would be differential outcomes from intensive and other assistance. The positive employment growth outcomes identified here from intensive assistance, even allowing for sample selection, suggest something of an improvement in the effectiveness of the BL network since the late 1990s

Arene oxidation with malonoyl peroxides

Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic labeling, Hammett analysis, EPR investigations and reactivity profile studies is proposed

Development of quantum perspectives in modern physics

Introductory undergraduate courses in classical physics stress a perspective that can be characterized as realist; from this perspective, all physical properties of a classical system can be simultaneously specified and thus determined at all future times. Such a perspective can be problematic for introductory quantum physics students, who must develop new perspectives in order to properly interpret what it means to have knowledge of quantum systems. We document this evolution in student thinking in part through pre- and post-instruction evaluations using the Colorado Learning Attitudes about Science Survey. We further characterize variations in student epistemic and ontological commitments by examining responses to two essay questions, coupled with responses to supplemental quantum attitude statements. We find that, after instruction in modern physics, many students are still exhibiting a realist perspective in contexts where a quantum-mechanical perspective is needed. We further find that this effect can be significantly influenced by instruction, where we observe variations for courses with differing learning goals. We also note that students generally do not employ either a realist or a quantum perspective in a consistent manner.Comment: 18 pages, plus references; 3 figures; 9 tables. PACS: 01.40.Fk, 03.65._