Failure to Connect: The Massachusetts Plan for Individual Health Insurance

This is the published version

Measuring Disease-Free Survival and Cancer Relapse Using Medicare Claims From CALGB Breast Cancer Trial Participants (Companion to 9344)

To determine the accuracy with which Medicare claims data measure disease-free survival in elderly Medicare beneficiaries with cancer, we performed a criterion validation study. We merged gold-standard clinical trial data of 45 elderly patients with node-positive breast cancer who were treated on the Cancer and Leukemia Group B (CAL-GB) adjuvant breast trial 9344 with Centers for Medicare and Medicaid Services (CMS) data files and compared the results of a CMS-based algorithm with the CALGB disease-free survival information to determine sensitivity and specificity. For 5-year disease-free survival, the sensitivity of the CMS-based algorithm was 100% (95% confidence interval [CI] = 81% to 100%), the specificity was 97% (95% CI = 83% to 100%), and the area under the receiver operator curve was 97% (95% CI = 90% to 100%). For 2-year disease-free survival, the test characteristics were less favorable: sensitivity was 83% (95% CI = 36% to 100%), specificity was 95% (95% CI = 83% to 100%), and area under the receiver operator curve was 84% (95% CI = 66% to 100%)

National Federation of Independent Business v. Sebelius, 567 U.S. 519 (2012)

In National Federation of Independent Business v. Sebelius, decided in 2012, twenty-six states as well as private individuals and an organization of independent businesses challenged the constitutionality of two key components of the Affordable Care Act. The Court upheld the individual mandate but converted the Medicaid eligibility expansion from mandatory to optional for states. Elizabeth Weeks’ feminist rewrite breaks down the public law-private law distinction to get beyond the traditional view of health insurance as a commercial product providing individual financial protection against risk and instead to view it as effecting a risk pool premised on cross-subsidization of the health-care “haves” by the health-care “have-nots.” Weeks also rejects the original opinion’s dichotomy between “old” and “new” Medicaid as an artifice evidencing a fundamental discomfort with extending public assistance to able-bodied people who are judged capable of providing for themselves on the private market. In their commentary, Mary Ann Chirba and Alice Noble assess the original opinion and Weeks’ feminist rewrite in terms of their concrete effects on women’s lives

Packaged and Free Satellite Tobacco Mosaic Virus (STMV) RNA Genomes Adopt Distinct Conformational States

The RNA genomes of viruses likely undergo multiple functionally important conformational changes during their replication cycles, changes that are poorly understood at present. We used two complementary in-solution RNA structure probing strategies (SHAPE-MaP and RING-MaP) to examine the structure of the RNA genome of satellite tobacco mosaic virus inside authentic virions and in a capsid-free state. Both RNA states feature similar three-domain architectures in which each major replicative function-translation, capsid coding, and genome synthesis-fall into distinct domains. There are, however, large conformational differences between the in-virion and capsid-free states, primarily in one arm of the central T domain. These data support a model in which the packaged capsid-bound RNA is constrained in a local high-energy conformation by the native capsid shell. The removal of the viral capsid then allows the RNA genome to relax into a more thermodynamically stable conformation. The RNA architecture of the central T domain thus likely changes during capsid assembly and disassembly and may play a role in genome packaging

Everything But the Merits: Analyzing the Procedural Aspects of the Healthcare Litigation

The role of States as Litigants in the Mandate Litigation Panel featured E. Duncan Getchell, Jr., Solicitor General of Virginia; William F. Brockman, Acting Solicitor General of Maryland; and William P. Marshall, the William Rand Kenan, Jr. Distinguished Professor of Law at the University of North Carolina School of Law. The Defining the Scope and Legal Effect of the Challenges to the Individual Mandate Panel featured Edward A. Hartnett, Richard J. Hughes Professor at the Seton Hall University School of Law; Tobias A. Dorsey, Special Counsel for the United States Sentencing Commission (USSC); and Kevin C. Walsh, Assistant Professor of Law at the University of Richmond School of Law The Situating the Mandate Litigation in the Broader Regulatory and Political Landscape Panel featured Bradley W. Joondeph, Santa Clara University School of Law, Creator of the ACA litigation blog; A. Christopher Bryant, Professor of Law at the University of Cincinnati College of Law; and Elizabeth Weeks Leonard, Associate Professor of Law at the University of Georgia Law School

A Selective HDAC 1/2 Inhibitor Modulates Chromatin and Gene Expression in Brain and Alters Mouse Behavior in Two Mood-Related Tests

Psychiatric diseases, including schizophrenia, bipolar disorder and major depression, are projected to lead global disease burden within the next decade. Pharmacotherapy, the primary – albeit often ineffective – treatment method, has remained largely unchanged over the past 50 years, highlighting the need for novel target discovery and improved mechanism-based treatments. Here, we examined in wild type mice the impact of chronic, systemic treatment with Compound 60 (Cpd-60), a slow-binding, benzamide-based inhibitor of the class I histone deacetylase (HDAC) family members, HDAC1 and HDAC2, in mood-related behavioral assays responsive to clinically effective drugs. Cpd-60 treatment for one week was associated with attenuated locomotor activity following acute amphetamine challenge. Further, treated mice demonstrated decreased immobility in the forced swim test. These changes are consistent with established effects of clinical mood stabilizers and antidepressants, respectively. Whole-genome expression profiling of specific brain regions (prefrontal cortex, nucleus accumbens, hippocampus) from mice treated with Cpd-60 identified gene expression changes, including a small subset of transcripts that significantly overlapped those previously reported in lithium-treated mice. HDAC inhibition in brain was confirmed by increased histone acetylation both globally and, using chromatin immunoprecipitation, at the promoter regions of upregulated transcripts, a finding consistent with in vivo engagement of HDAC targets. In contrast, treatment with suberoylanilide hydroxamic acid (SAHA), a non-selective fast-binding, hydroxamic acid HDAC 1/2/3/6 inhibitor, was sufficient to increase histone acetylation in brain, but did not alter mood-related behaviors and had dissimilar transcriptional regulatory effects compared to Cpd-60. These results provide evidence that selective inhibition of HDAC1 and HDAC2 in brain may provide an epigenetic-based target for developing improved treatments for mood disorders and other brain disorders with altered chromatin-mediated neuroplasticity.Stanley Medical Research InstituteNational Institutes of Health (U.S.) (R01DA028301)National Institutes of Health (U.S.) (R01DA030321