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"Howard, David"
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Pricing in the Market for Anticancer Drugs
In 2011, Bristol-Myers Squibb set the price of its newly approved melanoma drug ipilimumab—brand name Yervoy—at$120,000 for a course of therapy. The drug was associated with an incremental increase in life expectancy of four months. Drugs like ipilimumab have fueled the perception that the launch prices of new anticancer drugs and other drugs in the so-called “specialty” pharmaceutical market have been increasing over time and that increases are unrelated to the magnitude of the expected health benefits. In this paper, we discuss the unique features of the market for anticancer drugs and assess trends in the launch prices for 58 anticancer drugs approved between 1995 and 2013 in the United States. We restrict attention to anticancer drugs because the use of median survival time as a primary outcome measure provides a common, objective scale for quantifying the incremental benefit of new products. We find that the average launch price of anticancer drugs, adjusted for inflation and health benefits, increased by 10 percent annually—or an average of $ 8,500 per year—from 1995 to 2013. We argue that the institutional features of the market for anticancer drugs enable manufacturers to set the prices of new products at or slightly above the prices of existing therapies, giving rise to an upward trend in launch prices. Government-mandated price discounts for certain classes of buyers may have also contributed to launch price increases as firms sought to offset the growth in the discount segment by setting higher prices for the remainder of the market.
Journal Article
Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism
Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt)
1
; heritability estimated from twin studies ranges from 30 to 50%
2
, and SNP-based heritability ranges from 6 to 15%
3
–
6
. Increased neuroticism is associated with poorer mental and physical health
7
,
8
, translating to high economic burden
9
. Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci
3
,
4
. Here we report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at
P
< 0.00045 in an unrelated cohort (
N
= 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (
r
g
= 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD;
r
g
= 0.69, s.e. = 0.07) and subjective well-being (
r
g
= –0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of neuroticism and its association with MDD.
Analysis of 329,000 individuals in the UK Biobank identifies 116 loci associated with neuroticism. Genes implicated are enriched in neuronal differentiation pathways, and genetic correlations between neuroticism and other mental health traits are elucidated.
Journal Article
Television finales : from Howdy Doody to Girls
\"TV finales fascinate us because they bring universes to an end--in the case of long-running shows, very complicated universes--exposing in the process our cultural obsessions, our 'reading' practices, our imagined identities, our fascination with television. This volume brings together the work of 63 scholars in 71 essays, each essay discussing a different television finale\"-- Provided by publisher.
Book
From Bioinspiration to Computer Generation: Developments in Autonomous Soft Robot Design
The emerging field of soft robotics presents a new paradigm for robot design in which “precision through rigidity” is replaced by “cognition through compliance.” Lightweight and flexible, soft robots have vast potential to interact with fragile objects and navigate unstructured environments. Like octopuses and worms in nature, soft robots’ flexible bodies conform to hard objects and reconfigure for different tasks, delegating the burden of control from brain to body through embodied cognition. However, because of the lack of efficient modeling and simulation tools, soft robots are primarily designed by hand. Typically, hard components from rigid robots or living creatures are heuristically substituted for comparable soft ones. Autonomous design and manufacturing methodologies are urgently required to produce bespoke, high‐performing robots. Currently, design methodologies exist between simple but realistic parametric optimizations, and evolutionary algorithms which simulate morphology and control coevolution. To find high‐performing designs, novel high‐fidelity simulators and high‐throughput manufacturing and testing processes are required to explore the complex soft material, morphology and control landscape, blending simulation, and experimental data. This article reviews the state of the art in autonomous soft robotic design. Existing manual and automated designs are surveyed and future directions to automate soft robot design and manufacturing are presented. By using soft and functional materials to deform around objects and adapt to new environments, soft robotics has the potential to revolutionize material handling and terrain navigation. But in the absence of accurate modeling tools, they are still laboriously designed manually. This article reviews progress toward autonomous modeling, simulation, and design.
Journal Article
A sex-specific genome-wide association study of depression phenotypes in UK Biobank
There are marked sex differences in the prevalence, phenotypic presentation and treatment response for major depression. While genome-wide association studies (GWAS) adjust for sex differences, to date, no studies seek to identify sex-specific markers and pathways. In this study, we performed a sex-stratified genome-wide association analysis for broad depression with the UK Biobank total participants (
N
= 274,141), including only non-related participants, as well as with males (
N
= 127,867) and females (
N
= 146,274) separately. Bioinformatics analyses were performed to characterize common and sex-specific markers and associated processes/pathways. We identified 11 loci passing genome-level significance (
P
< 5 × 10
−8
) in females and one in males. In both males and females, genetic correlations were significant between the broad depression GWA and other psychopathologies; however, correlations with educational attainment and metabolic features including body fat, waist circumference, waist-to-hip ratio and triglycerides were significant only in females. Gene-based analysis showed 147 genes significantly associated with broad depression in the total sample, 64 in the females and 53 in the males. Gene-based analysis revealed “Regulation of Gene Expression” as a common biological process, but suggested sex-specific molecular mechanisms. Finally, sex-specific polygenic risk scores (PRSs) for broad depression outperformed total and the opposite sex PRSs in the prediction of broad major depressive disorder. These findings provide evidence for sex-dependent genetic pathways for clinical depression as well as for health conditions comorbid with depression.
Journal Article