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Gamma-glutamyltransferase (GGT) is a well-established serum marker for alcohol-related liver disease. However, GGT’s predictive utility applies well beyond liver disease: elevated GGT is linked to increased risk to a multitude of diseases and conditions, including cardiovascular disease, diabetes, metabolic syndrome (MetS), and all-cause mortality. The literature from multiple population groups worldwide consistently shows strong predictive power for GGT, even across different gender and ethnic categories. Here, we examine the relationship of GGT to other serum markers such as serum ferritin (SF) levels, and we suggest a link to exposure to environmental and endogenous toxins, resulting in oxidative and nitrosative stress. We observe a general upward trend in population levels of GGT over time, particularly in the US and Korea. Since the late 1970s, both GGT and incident MetS and its related disorders have risen in virtual lockstep. GGT is an early predictive marker for atherosclerosis, heart failure, arterial stiffness and plaque, gestational diabetes, and various liver diseases, including viral hepatitis, other infectious diseases, and several life-threatening cancers. We review literature both from the medical sciences and from life insurance industries demonstrating that serum GGT is a superior marker for future disease risk, when compared against multiple other known mortality risk factors., Quanta Computer (Firm)

Thesis (Ph.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 1998., Includes bibliographical references (leaves 219-232)., by Gerald C. Koenig., Ph.D.

Current Congressional Budget Office (CBO) budget scoring rules cheat taxpayers and warfighters by ignoring the high cost of not acquiring cost-effective upgrades to critical combat weapons. Treating paid-over-time procurements as if they are paid-up-front budget outlays necessarily perpetuates waste and inefficiency where we can least afford it: on the modern battlefield. As a result, the current acquisition process for such upgrades involves a simplistic, two-step process. First, determine if paying the entire cost up-front of an upgrade is less expensive than the net present value of paying for the upgrade over time. Once paying up-front is "discovered" to be the cheaper option (as nearly always occurs), the next step is to abandon the upgrade as soon as it fails to compete successfully for scarce procurement budget dollars. An extremely conscientious program official may repeat this process for a number of budget cycles. But in the end, the outcome is predictable. The game is just rigged that way. The problem is that these policies have real consequences that squander taxpayer dollars while degrading battlefield performance. Many of America's major combat weapons systems have engines that are so old and obsolete that modern upgrades would easily pay for themselves in fuel and maintenance savings while dramatically increasing combat range and battlefield reliability. The private sector is willing to give the DoD such upgrades at no up-front cost in exchange for annual "mortgage-like" payments that are never greater than verified savings in fuel and maintenance. How can we know this? Because the DoD has routinely used such "paid-from-savings" contracts for over a decade to upgrade infrastructure on military bases. Similar contracts are widely used by the DoD to acquire vast amounts of information technology and telecommunication assets., Presented at the Annual Acquisition Research Symposium (4th): Creating Synergy for Informed Change, Thursday sessions, held in Monterey, CA, on May 16-17, 2007. Published in the proceedings of the symposium, p366-375, 2007. Prepared in collaboration with Hannon Armstrong Advisory Services. Document includes briefing charts in addition to text. The original document contains color images.

Symposium Presentation

During pathologic vessel remodeling, vascular smooth muscle cells (VSMCs) embedded within the collagen-rich matrix of the artery wall mobilize uncharacterized proteolytic systems to infiltrate the subendothelial space and generate neointimal lesions. Although the VSMC-derived serine proteinases, plasminogen activator and plasminogen, the cysteine proteinases, cathepsins L, S, and K, and the matrix metalloproteinases MMP-2 and MMP-9 have each been linked to pathologic matrix-remodeling states in vitro and in vivo, the role that these or other proteinases play in allowing VSMCs to negotiate the three-dimensional (3-D) cross-linked extracellular matrix of the arterial wall remains undefined. Herein, we demonstrate that VSMCs proteolytically remodel and invade collagenous barriers independently of plasmin, cathepsins L, S, or K, MMP-2, or MMP-9. Instead, we identify the membrane-anchored matrix metalloproteinase, MT1-MMP, as the key pericellular collagenolysin that controls the ability of VSMCs to degrade and infiltrate 3-D barriers of interstitial collagen, including the arterial wall. Furthermore, genetic deletion of the proteinase affords mice with a protected status against neointimal hyperplasia and lumen narrowing in vivo. These studies suggest that therapeutic interventions designed to target MT1-MMP could prove beneficial in a range of human vascular disease states associated with the destructive remodeling of the vessel wall extracellular matrix.