Unblocking Blockbusters: Using Boolean Text-Mining to Optimise Clinical Trial Design and Timeline for Novel Anticancer Drugs

Two problems now threaten the future of anticancer drug development: (i) the information explosion has made research into new target-specific drugs more duplication-prone, and hence less cost-efficient; and (ii) high-throughput genomic technologies have failed to deliver the anticipated early windfall of novel first-in-class drugs. Here it is argued that the resulting crisis of blockbuster drug development may be remedied in part by innovative exploitation of informatic power. Using scenarios relating to oncology, it is shown that rapid data-mining of the scientific literature can refine therapeutic hypotheses and thus reduce empirical reliance on preclinical model development and early-phase clinical trials. Moreover, as personalised medicine evolves, this approach may inform biomarker-guided phase III trial strategies for noncytotoxic (antimetastatic) drugs that prolong patient survival without necessarily inducing tumor shrinkage. Though not replacing conventional gold standards, these findings suggest that this computational research approach could reduce costly ‘blue skies’ R&D investment and time to market for new biological drugs, thereby helping to reverse unsustainable drug price inflation

Debate, Implicit Race Bias and the 2008 Presidential Election: Much Ado About Nothing?

The election of Barack Obama marks a significant milestone for race relations in our nation—on this much our debaters agree. The meaning of this milestone for the future of race-based policies, such as affirmative action and antidiscrimination laws, is where they disagree. Dr. Gregory Parks and Professor Jeffrey Rachlinski argue that any announcement of the arrival of a “post-racial America” is premature, as the presidential campaign actually revealed an implicit racial bias present in “most white adult brains.” The stereotypical criticisms of Obama, explicit racial references by supporters of opposing candidates, and “deeply racially stratified voting” were, in fact, “reflection[s] of how contemporary racism works.” Modern racism, they maintain, “operates not as an absolute barrier, but as a kind of tax on members of racial minorities.” Accordingly, race-based policies “can hardly be said to be unnecessary in a world in which the enormous resources Obama had available are necessary to combat bias.” Professor Richard Epstein believes that in the face one of “America’s great racial achievements,” it’s “almost incredible” that Parks and Rachlinski focus on “a list of the worst racial episodes” of the campaign. In doing so, he argues, they ignore the widespread praise that Obama garnered from “people of all races”; neglect the “vicious treatment” of his opponents; and fail to “place the question of implicit racial bias in its larger social context”—ignoring implicit sexism and the explicit biases exhibited in the fights over gay marriage and immigration reform. Ultimately, in regards to race-based policies, Epstein believes that the debate is a “sideshow,” as “any private individual or firm can hire a person for good reason, bad reason, or no reason at all.” Rather than utilizing public force to end such practices, it is better that “they should just die on the vine because people have consciously decided not to do business with them.

Debate, Implicit Race Bias and the 2008 Presidential Election: Much Ado About Nothing?

The election of Barack Obama marks a significant milestone for race relations in our nation—on this much our debaters agree. The meaning of this milestone for the future of race-based policies, such as affirmative action and antidiscrimination laws, is where they disagree. Dr. Gregory Parks and Professor Jeffrey Rachlinski argue that any announcement of the arrival of a “post-racial America” is premature, as the presidential campaign actually revealed an implicit racial bias present in “most white adult brains.” The stereotypical criticisms of Obama, explicit racial references by supporters of opposing candidates, and “deeply racially stratified voting” were, in fact, “reflection[s] of how contemporary racism works.” Modern racism, they maintain, “operates not as an absolute barrier, but as a kind of tax on members of racial minorities.” Accordingly, race-based policies “can hardly be said to be unnecessary in a world in which the enormous resources Obama had available are necessary to combat bias.” Professor Richard Epstein believes that in the face one of “America’s great racial achievements,” it’s “almost incredible” that Parks and Rachlinski focus on “a list of the worst racial episodes” of the campaign. In doing so, he argues, they ignore the widespread praise that Obama garnered from “people of all races”; neglect the “vicious treatment” of his opponents; and fail to “place the question of implicit racial bias in its larger social context”—ignoring implicit sexism and the explicit biases exhibited in the fights over gay marriage and immigration reform. Ultimately, in regards to race-based policies, Epstein believes that the debate is a “sideshow,” as “any private individual or firm can hire a person for good reason, bad reason, or no reason at all.” Rather than utilizing public force to end such practices, it is better that “they should just die on the vine because people have consciously decided not to do business with them.

Electrocaloric devices based on thini-film heat switches

We describe a new approach to refrigeration and electrical generation that exploits the attractive properties of thin films of electrocaloric materials. Layers of electrocaloric material coupled with thin-film heat switches can work as either refrigerators or electrical generators, depending on the phasing of the applied voltages and heat switching. With heat switches based on thin layers of liquid crystals, the efficiency of these thin-film heat engines can be at least as high as that of current thermoelectric devices. Advanced heat switches would enable thin-film heat engines to outperform conventional vaporcompression devices

Adaptive evolution hotspots at the GC-extremes of the human genome: Evidence for two functionally distinct pathways of positive selection

We recently reported that the human genome is "splitting" into two gene subgroups characterised by polarised GC content (Tang et al, 2007), and that such evolutionary change may be accelerated by programmed genetic instability (Zhao et al, 2008). Here we extend this work by mapping the presence of two separate high-evolutionary-rate (Ka/Ks) hotspots in the human genome-one characterized by low GC content, high intron length, and low gene expression, and the other by high GC content, high exon number, and high gene expression. This finding suggests that at least two different mechanisms mediate adaptive genetic evolution in higher organisms: (1) intron lengthening and reduced repair in hypermethylated lowly-transcribed genes, and (2) duplication and/or insertion events affecting highly-transcribed genes, creating low-essentiality satellite daughter genes in nearby regions of active chromatin. Since the latter mechanism is expected to be far more efficient than the former in generating variant genes that increase fitnesss, these results also provide a potential explanation for the controversial value of sequence analysis in defining positively selected genes. Copyright © 2010 C. S. M. Tang and R. J. Epstein.Link_to_subscribed_fulltex

Response to Questions in the First White Paper, \u27Modernizing the Communications Act\u27

The House Energy and Commerce Committee has begun a process to review and update the Communications Act of 1934, last revised in any material way in 1996. As the Committee begins the review process, this paper responds to questions posed by the Committee that all relate, in fundamental ways, to the question: What should a modern Communications Act look like? The Response advocates a clean slate approach under which the regulatory silos that characterize the current statute would be eliminated, along with almost all of the ubiquitous \u27public interest\u27 delegation of authority found throughout the Communications Act. The replacement regime would have at its core a new competition-based standard that, except in limited circumstances, would require that the FCC\u27s regulatory activities be tied to findings of consumer harm resulting from lack of sufficient competition. The FCC\u27s authority to adopt broad anticipatory rules on an ex ante basis would be substantially circumscribed, and the agency would be required to rely more heavily than is presently the case on ex post adjudication of individual complaints alleging specific abuses of market power and consumer harm. Some aspects of the FCC\u27s current jurisdiction, such as privacy and data security regulation, might be transferred to the FTC in light of the FTC\u27s institutional competence in these areas

Development of a Qualified Clinical Data Registry for emergency medicine

The passage of the Medicare Access and CHIP Reauthorization Act (MACRA) in 2015 marked a fundamental transition in physician payment by the Centers for Medicare and Medicaid Services (CMS) from traditional fee-for service to value-based models. MACRA led to the creation of the CMS Quality Payment Program (QPP), which bases the value of physician care in large part on physician quality reporting. The QPP enabled a shift away from legacy CMS-stewarded quality measures that had limited applicability to individual specialties toward specialty-specific quality measures developed and stewarded by physician specialty societies using Qualified Clinical Data Registries (QCDRs). This article describes the development of the first nationally available emergency medicine QCDR as a means for emergency physicians to participate in the QPP, measure, and benchmark emergency physician quality