Personal Federal Tax Issues And The Affordable Care Act: Can Tax Penalties And Subsidized Premiums Provide Sufficient Incentives For Health Insurance Purchases

The Patient Protection and Affordable Care Act of 2010 (ACA) includes many changes to the U.S. Federal Tax Code.  The tax penalty imposed on individuals who choose to remain uninsured received extraordinary attention while the Supreme Court determined the constitutionality of the ACA.  Now, the more relevant question is what impact the penalty may have on individual behavior.   This paper presents information that suggests the tax penalty may provide insufficient incentive for many individuals to purchase insurance, even with premium tax credits to reduce the cost for households earning up to 400% of the federal poverty limit.  The ACA also reduces the tax benefit from themedical expense deduction by increasing the threshold amount from 7.5% of adjusted gross income to 10% of adjusted gross income.  This may increase the after-tax cost of purchasing health insurance, especially for healthier individuals whose medical expenses (excluding insurance premiums) are below the threshold amount, increasing the incentive to forego the purchase of health insurance and to pay the penalty instead.  An approach more consistent with the aims of the ACA is to eliminate the threshold amount but limit the deduction to lower-income taxpayers

Lifetime Earnings, Mortality, And Social Security Benefits: Implications For Reform

The Social Security system is facing significant financial challenges, but politicians, economists, and other experts cannot agree on appropriate solutions.  Raising taxes and/or cutting benefits are never popular proposals, and competing groups want to protect the poor while at the same time maintain fairness for the more wealthy.  Recent studies, such as Cristia (2007), Duggan et al. (2007), and Waldron (2007), have shown a strong correlation between lifetime earnings and mortality, suggesting that differences in life expectancy between the wealthy and the less wealthy may be getting larger, thus eroding the progressivity of the Social Security system.  Our results show that for a mortality difference of one or two years, benefit reductions in the range of 2.5% to 16% would be needed to maintain the current level of progressivity for a male living to age 80.  If the mortality difference grows to four or five years, the benefit reductions would need to be much greater, anywhere from approximately 14% to 31%.  A reduction in benefits based on lifetime earnings can improve the long-run viability of the Social Security system while maintaining its current level of progressivity

The Mre11 Nuclease is Critical for the Sensitivity of Cells to Chk1 Inhibition

The Chk1 kinase is required for the arrest of cell cycle progression when DNA is damaged, and for stabilizing stalled replication forks. As a consequence, many Chk1 inhibitors have been developed and tested for their potential to enhance DNA damage-induced tumor cell killing. However, inhibition of Chk1 alone, without any additional exogenous agent, can be cytotoxic. Understanding the underlying mechanisms of this sensitivity is critical for defining which patients might respond best to therapy with Chk1 inhibitors. We have investigated the mechanism of sensitivity in U2OS osteosarcoma cells. Upon incubation with the Chk1 inhibitor MK-8776, single-stranded DNA regions (ssDNA) and double-strand breaks (DSB) begin to appear within 6 h. These DSB have been attributed to the structure-specific DNA endonuclease, Mus81. The Mre11/Rad50/Nbs1 complex is known to be responsible for the resection of DSB to ssDNA. However, we show that inhibition of the Mre11 nuclease activity leads, not only to a decrease in the amount of ssDNA following Chk1 inhibition, but also inhibits the formation of DSB, suggesting that DSB are a consequence of ssDNA formation. These findings were corroborated by the discovery that Mre11-deficient ATLD1 cells are highly resistant to MK-8776 and form neither ssDNA nor DSB following treatment. However, once complimented with exogenous Mre11, the cells accumulate both ssDNA and DSB when incubated with MK-8776. Our findings suggest that Mre11 provides the link between aberrant activation of Cdc25A/Cdk2 and Mus81. The results highlight a novel role for Mre11 in the production of DSB and may help define which tumors are more sensitive to MK-8776 alone or in combination with DNA damaging agents

Acquired Cisplatin Resistance in Human Ovarian Cancer Cells is Associated with Enhanced Repair of Cisplatin-DNA Lesions and Reduced Drug Accumulation.

Studies were undertaken to investigate acquired resistance to cisplatin in human ovarian cancer cells. The cell lines A2780 and A2780/CP70 were studied to assess their respective characteristics of drug accumulation and efflux, cytosolic inactivation of drug, and DNA repair. All experiments were performed using 1-h drug exposures. The A2780/CP70 cell line was 13-fold more resistant to cisplatin than A2780 cells. When studied at their respective IC50 doses, drug accumulation rates were similar for the two cell lines. However, the resistant cell line was twofold more efficient at effluxing drug, which was associated with reduced total drug accumulation for equivalent micromolar drug exposures. At equivalent levels of total cellular drug accumulation, the two cell lines formed the same levels of cisplatin-DNA damage, suggesting that cytosolic inactivation of drug does not contribute to the differential in resistance between these cell lines. Resistant cells were also twofold more efficient at repairing cisplatin-DNA lesions in cellular DNA and in transfected plasmid DNA. We conclude that in these paired cell lines, alterations in drug uptake/efflux and in DNA repair are the major contributing factors to acquired resistance to cisplatin

Sensitization of Human Cancer Cells to Gemcitabine by the Chk1 Inhibitor MK-8776: Cell Cycle Perturbation and Impact of Administration Schedule in Vitro and in Vivo

Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence

Renormalization group and perfect operators for stochastic differential equations

We develop renormalization group methods for solving partial and stochastic differential equations on coarse meshes. Renormalization group transformations are used to calculate the precise effect of small scale dynamics on the dynamics at the mesh size. The fixed point of these transformations yields a perfect operator: an exact representation of physical observables on the mesh scale with minimal lattice artifacts. We apply the formalism to simple nonlinear models of critical dynamics, and show how the method leads to an improvement in the computational performance of Monte Carlo methods.Comment: 35 pages, 16 figure

[DL-1,2-bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II), a new compound for the therapy of ovarian cancer

The synthesis of diastereoisomeric [1,2-bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complexes, DL-3-PtCl2 and meso-3-PtCl2, and their evaluation on the hormone-independent, human MDA-MB231 breast cancer cell line, on the cisplatin-sensitive and -resistant L1210 leukemia cell line, on the cisplatin-resistant human NIH:OVCAR 3 ovarian cancer cell line, on the P-388 leukemia of the mouse and on the cisplatin-sensitive and -resistant Ehrlich ascites tumor of the mouse are described. On all tumor models DL-3-PtCl2 produces a marked inhibitory effect. The diastereoisomer meso-3-PtCl2 is less active and more toxic. It is striking that DL-3-PtCl2 leads to a pronounced inhibition of all cisplatin-resistant tumors. At non-toxic concentrations DL-3-PtCl2 produces cytocidal effects on the NIH:OV-CAR 3 cell line. Therefore DL-3-PtCl2 is of interest for further evaluation for the therapy of ovarian cancer

PEXO : a global modeling framework for nanosecond timing, microsecond astrometry, and μm/s radial velocities

54 pages, 2 tables, 19 figures, accepted for publication in ApJS, PEXO is available at https://github.com/phillippro/pexoThe ability to make independent detections of the signatures of exoplanets with complementary telescopes and instruments brings a new potential for robust identification of exoplanets and precision characterization. We introduce PEXO, a package for Precise EXOplanetology to facilitate the efficient modeling of timing, astrometry, and radial velocity data, which will benefit not only exoplanet science but also various astrophysical studies in general. PEXO is general enough to account for binary motion and stellar reflex motions induced by planetary companions and is precise enough to treat various relativistic effects both in the solar system and in the target system. We also model the post-Newtonian barycentric motion for future tests of general relativity in extrasolar systems. We benchmark PEXO with the pulsar timing package TEMPO2 and find that PEXO produces numerically similar results with timing precision of about 1 ns, space-based astrometry to a precision of 1{\mu}as, and radial velocity of 1 {\mu}m/s and improves on TEMPO2 for decade-long timing data of nearby targets, due to its consideration of third-order terms of Roemer delay. PEXO is able to avoid the bias introduced by decoupling the target system and the solar system and to account for the atmospheric effects which set a practical limit for ground-based radial velocities close to 1 cm/s. Considering the various caveats in barycentric correction and ancillary data required to realize cm/s modeling, we recommend the preservation of original observational data. The PEXO modeling package is available at GitHub (https://github.com/phillippro/pexo).Peer reviewe