Do Childhood Vaccines Have Non-Specific Effects on Mortality

A recent article by Kristensen et al. suggested that measles vaccine and bacille Calmette–Guérin (BCG) vaccine might\ud reduce mortality beyond what is expected simply from protection against measles and tuberculosis. Previous reviews of the potential effects of childhood vaccines on mortality have not considered methodological features of reviewed studies. Methodological considerations play an especially important role in observational assessments, in which selection factors for vaccination may be difficult to ascertain. We reviewed 782 English language articles on vaccines and childhood mortality and found only a few whose design met the criteria for methodological rigor. The data reviewed suggest that measles vaccine delivers its promised reduction in mortality, but there is insufficient evidence to suggest a mortality benefit above that caused by its effect on measles disease and its sequelae. Our review of the available data in the literature reinforces how difficult answering these considerations has been and how important study design will be in determining the effect of specific vaccines on all-cause mortality.\u

Gee Whiz, the Sky Is Falling!

I am reminded of Chicken Little’s famous mantra as I listen to some Supreme Court Justices’ reactions to the prospect of televising oral arguments. Their fears—such as Justice Kennedy’s warning that allowing cameras in the courtroom may change the Court’s dynamics—are, in my opinion, overblown. And some comments, most notably Justice Souter’s famous exclamation in a 1996 House subcommittee hearing that “the day you see a camera come into our courtroom, it’s going to roll over my dead body,” make it sound as if the Justices have forgotten that our nation’s court system belongs to the public, not merely the nine Justices who sit atop it. I write this essay in order to give my own perspective. Having served as a judge on the Sixth Circuit Court of Appeals for nearly twenty-eight years, I believe that I am in a unique position to understand the concerns raised by televising oral arguments. I can make this guarantee—televising the Supreme Court’s oral arguments will not produce the disastrous results predicted by some frightened Justices; rather, it will yield positive results. Most notably, it will increase the public’s knowledge of the appellate process

Gee Whiz, the Sky Is Falling!

I am reminded of Chicken Little’s famous mantra as I listen to some Supreme Court Justices’ reactions to the prospect of televising oral arguments. Their fears—such as Justice Kennedy’s warning that allowing cameras in the courtroom may change the Court’s dynamics—are, in my opinion, overblown. And some comments, most notably Justice Souter’s famous exclamation in a 1996 House subcommittee hearing that “the day you see a camera come into our courtroom, it’s going to roll over my dead body,” make it sound as if the Justices have forgotten that our nation’s court system belongs to the public, not merely the nine Justices who sit atop it. I write this essay in order to give my own perspective. Having served as a judge on the Sixth Circuit Court of Appeals for nearly twenty-eight years, I believe that I am in a unique position to understand the concerns raised by televising oral arguments. I can make this guarantee—televising the Supreme Court’s oral arguments will not produce the disastrous results predicted by some frightened Justices; rather, it will yield positive results. Most notably, it will increase the public’s knowledge of the appellate process

Biology of RANK, RANKL, and osteoprotegerin

The discovery of the receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin (OPG) system and its role in the regulation of bone resorption exemplifies how both serendipity and a logic-based approach can identify factors that regulate cell function. Before this discovery in the mid to late 1990s, it had long been recognized that osteoclast formation was regulated by factors expressed by osteoblast/stromal cells, but it had not been anticipated that members of the tumor necrosis factor superfamily of ligands and receptors would be involved or that the factors involved would have extensive functions beyond bone remodeling. RANKL/RANK signaling regulates the formation of multinucleated osteoclasts from their precursors as well as their activation and survival in normal bone remodeling and in a variety of pathologic conditions. OPG protects the skeleton from excessive bone resorption by binding to RANKL and preventing it from binding to its receptor, RANK. Thus, RANKL/OPG ratio is an important determinant of bone mass and skeletal integrity. Genetic studies in mice indicate that RANKL/RANK signaling is also required for lymph node formation and mammary gland lactational hyperplasia, and that OPG also protects arteries from medial calcification. Thus, these tumor necrosis factor superfamily members have important functions outside bone. Although our understanding of the mechanisms whereby they regulate osteoclast formation has advanced rapidly during the past 10 years, many questions remain about their roles in health and disease. Here we review our current understanding of the role of the RANKL/RANK/OPG system in bone and other tissues