Insurance and Incentives for Medical Innovation

This paper studies the interactions between health insurance and the incentives for innovation. Although we focus on pharmaceutical innovation, our discussion applies to other industries producing novel technologies for sale in markets with subsidized demand. Standard results in the growth and productivity literatures suggest that firms in many industries may possess inadequate incentives to innovate. Standard results in the health literature suggest that health insurance leads to the overutilization of health care. Our study of innovation in the pharmaceutical industry emphasizes the interaction of these incentives. Because of the large subsidies to demand from health insurance, limits on the lifetime of patents and possibly limits on monopoly pricing may be necessary to ensure that pharmaceutical companies do not possess excess incentives for innovation.

Binding-incompetent adenovirus facilitates molecular conjugate-mediated gene transfer by the receptor-mediated endocytosis pathway

Molecular conjugate vectors may be constructed that accomplish high efficiency gene transfer by the receptor-mediated endocytosis pathway. In order to mediate escape from lysosomal degradation, we have incorporated adenoviruses into the functional design of the conjugate. In doing so, however, we have introduced an additional ligand, which can bind to receptors on the cell surface, undermining the potential for cell specific targeting. To overcome this, we have treated the adenovirus with a monoclonal anti-fiber antibody, which renders the virus incapable of binding to its receptor. The result is a multi-functional molecular conjugate vector, which has preserved its binding specificity while at the same time being capable of preventing lysosomal degradation of endosome-internalized conjugate-DNA complexes. This finding indicates that adenoviral binding is not a prerequisite for adenoviral-mediated endosome disruption

The New Kaldor Facts: Ideas, Institutions, Population, and Human Capital

In 1961, Nicholas Kaldor used his list of six "stylized" facts both to summarize the patterns that economists had discovered in national income accounts and to shape the growth models that they were developing to explain them. Redoing this exercise today, nearly fifty years later, shows how much progress we have made. In contrast to Kaldor's facts, which revolved around a single state variable, physical capital, our six updated facts force consideration of four far more interesting variables: ideas, institutions, population, and human capital. Dynamic models have uncovered subtle interactions between these variables and generated important insights about such big questions as: Why has growth accelerated? Why are there gains from trade?

Pairing symmetry of the one-band Hubbard model in the paramagnetic weak-coupling limit: a numerical RPA study

We study the spin-fluctuation-mediated superconducting pairing gap in a weak-coupling approach to the Hubbard model for a two dimensional square lattice in the paramagnetic state. Performing a comprehensive theoretical study of the phase diagram as a function of filling, we find that the superconducting gap exhibits transitions from p-wave at very low electron fillings to d_{x^2-y^2}-wave symmetry close to half filling in agreement with previous reports. At intermediate filling levels, different gap symmetries appear as a consequence of the changes in the Fermi surface topology and the associated structure of the spin susceptibility. In particular, the vicinity of a van Hove singularity in the electronic structure close to the Fermi level has important consequences for the gap structure in favoring the otherwise sub-dominant triplet solution over the singlet d-wave solution. By solving the full gap equation, we find that the energetically favorable triplet solutions are chiral and break time reversal symmetry. Finally, we also calculate the detailed angular gap structure of the quasi-particle spectrum, and show how spin-fluctuation-mediated pairing leads to significant deviations from the first harmonics both in the singlet d_{x^2-y^2} gap as well as the chiral triplet gap solution.Comment: 11 pages 11 figure

Emotional Graphic Cigarette Warning Labels Reduce the Electrophysiological Brain Response to Smoking Cues

There is an ongoing public debate about the new graphic warning labels (GWLs) that the Food and Drug Administration (FDA) proposes to place on cigarette packs. Tobacco companies argued that the strongly emotional images FDA proposed to include in the GWLs encroached on their constitutional rights. The court ruled that FDA did not provide sufficient scientific evidence of compelling public interest in such encroachment. This study\u27s objectives were to examine the effects of the GWLs on the electrophysiological and behavioral correlates of smoking addiction and to determine whether labels rated higher on the emotional reaction (ER) scale are associated with greater effects. We studied 25 non-treatment-seeking smokers. Event-related potentials (ERPs) were recorded while participants viewed a random sequence of paired images, in which visual smoking (Cues) or non-smoking (non-Cues) images were preceded by GWLs or neutral images. Participants reported their cigarette craving after viewing each pair. Dependent variables were magnitude of P300 ERPs and self-reported cigarette craving in response to Cues. We found that subjective craving response to Cues was significantly reduced by preceding GWLs, whereas the P300 amplitude response to Cues was reduced only by preceding GWLs rated high on the ER scale. In conclusion, our study provides experimental neuroscience evidence that weighs in on the ongoing public and legal debate about how to balance the constitutional and public health aspects of the FDA-proposed GWLs. The high toll of smoking-related illness and death adds urgency to the debate and prompts consideration of our findings while longitudinal studies of GWLs are underway

Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues

Background: Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times.Results: in each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed sleep specific changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time.Conclusion: Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific molecular functions and that it has a ubiquitous role in reducing cellular metabolic stress in both brain and peripheral tissues. Finally, our data suggest a novel role for sleep in synchronizing transcription in peripheral tissues.Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health SciencesNational Institutes of HealthAmerican Sleep Medicine FoundationNational Heart Lung Blood InstituteUniv Penn, Perelman Sch Med, Div Sleep Med, Philadelphia, PA 19104 USAUniv Penn, Perelman Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USAChildrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USAUniversidade Federal de São Paulo UNIFESP, São Paulo, BrazilNIEHS, US Dept HHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USAUniversidade Federal de São Paulo UNIFESP, São Paulo, BrazilNational Institutes of Health: AG-17628National Heart Lung Blood Institute: HL090021: K12Web of Scienc

Effect of abdominal binding on cardiorespiratory function in paralympic athletes with cervical spinal cord injury

Spinal cord injury (SCI) causes a lesion-dependent impairment in cardiorespiratory function that may limit exercise capacity. The aims of this thesis were to describe cardiorespiratory function in highly-trained athletes with low-cervical SCI, and to investigate whether abdominal binding enhances cardiorespiratory function at rest and during exercise in this population. Using body plethysmography, bilateral phrenic nerve stimulation and transthoracic ultrasound, it was demonstrated that Paralympic athletes with cervical SCI exhibit a restrictive pulmonary defect, impaired diaphragm and expiratory muscle function, and low left ventricular mass and ejection fraction compared to able-bodied controls. Using the same methods, it was shown that abdominal binding improves resting cardiorespiratory function by reducing operating lung volumes, and increasing vital capacity, twitch transdiaphragmatic pressure, expiratory muscle strength and cardiac output. A further finding was a positive relationship between binder tightness and cardiorespiratory function. During a field-based assessment of fitness, abdominal binding reduced the time taken to complete an acceleration/deceleration test and increased the distance covered during a repeated maximal 4-min push test. During laboratory-based incremental wheelchair propulsion, abdominal binding altered breathing mechanics by reducing operating lung volumes and attenuating the rise in the pressure-time index of the diaphragm. Furthermore, abdominal binding increased peak oxygen uptake and reduced peak blood lactate concentration, despite no change in peak work rate. Peak oxygen uptake in the laboratory was related to the distance covered during the maximal 4-min push, suggesting that the improvement in field-based performance with binding was due to an improvement in aerobic capacity. In conclusion, this thesis demonstrates that abdominal binding significantly enhances cardiorespiratory function at rest, improves exercise performance in the field, and improves operating lung volumes, breathing mechanics and peak oxygen uptake during incremental treadmill exercise. Thus, abdominal binding provides a simple, easy-to-use tool that can be used to enhance cardiorespiratory function at rest and during exercise in highly-trained athletes with cervical SCI.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Linear Momentum Density in Quasistatic Electromagnetic Systems

We discuss a couple of simple quasistatic electromagnetic systems in which the density of electromagnetic linear momentum can be easily computed. The examples are also used to illustrate how the total electromagnetic linear momentum, which may also be calculated by using the vector potential, can be understood as a consequence of the violation of the action-reaction principle, because a non-null external force is required to maintain constant the mechanical linear momentum. We show how one can avoid the divergence in the interaction linear electromagnetic momentum of a system composed by an idealization often used in textbooks (an infinite straight current) and a point charge.Comment: 22 pages, 5 figures, to appear in Eur. J. Phy

Analysis of Collectivism and Egoism Phenomena within the Context of Social Welfare

Comparative benefits provided by the basic social strategies including collectivism and egoism are investigated within the framework of democratic decision-making. In particular, we study the mechanism of growing "snowball" of cooperation.Comment: 12 pages, 5 figures. Translated from Russian. Original Russian Text published in Problemy Upravleniya, 2008, No. 4, pp. 30-3