Rate of change of carotid intima-media thickness with magnesium administration in Abcc6⁻/⁻ mice.

Pseudoxanthoma elasticum (PXE), caused by mutations in the ABCC6 gene, demonstrates progressive build-up of calcium phosphate and proteoglycans in the skin, eye, and arteries, and is associated to myocardial infarctions, stroke, blindness, and elevated carotid intima-media thickness (CIMT). Although CIMT reduction with magnesium (Mg) has been documented in a mouse model for PXE (Abcc6(-/-) ), it is not clear if Mg is effective in humans with PXE to reduce CIMT. To examine this, we calculated the rate of change of CIMT (washout) in 15- and 12-month-old Abcc6(-/-) mice fed standard rodent diet with or without Mg supplementation for 2 months. Using means in untreated 15- and 12-month-old Abcc6(-/-) mice (145 and 120 μm, respectively), the rate of change was 8.3 μm/month. Using means in treated 15- and 12-month-old Abcc6(-/-) mice (118 and 104.6 μm, respectively), the rate of change was 4.5 μm. Compared to normal progression of CIMT in humans without PXE, PXE has advanced atherosclerosis and possibly a higher CIMT rate of change. This experiment may portend, at least in PXE, the rationale for a 1-year oral Mg CIMT clinical trial and may be useful for application in other progressive mineralizing disorders like atherosclerosis

The Arrow of Time

Time is used throughout physical theories as a quantity that helps us understand how things change. It is also something that we experience in our day-to-day lives as an irreversible movement: the universe appears to “move” from some notion of a past to some notion of a future, with no way of moving in the opposite direction. Yet many of the fundamental physical laws do not seem to place any restrictions on, or give any preferences to, whether a system evolves “forwards” or “backwards” in time. How can we reconcile our observations and experiences of a definite arrow of time with the apparent time-direction-agnosticism of physical laws? To answer this, I will explore how time is conceptualized in various physics subfields and to what extent these conceptions have a preferred direction. I will then develop the thermodynamic law that gives rise to the observed arrow of time and analyze its relation to other physical laws

Healthy Volunteer Registries and Ethical Research Principles

The dual enrolling of phase I volunteers is a potential risk to subjects. It can also distort study results, threaten study validity, and possibly cause harm to future patients. Existing subject registries differ in structure, funding, and governance. Although the choice of the ideal system is driven by the scope of the risk and the funding mechanism, and is ultimately a value judgment of freedom versus paternalism, none of the registries significantly impinges on the tenets of ethically based research