Catalyzing the Critical Path Initiative: FDA's progress in drug development activities.

The US Food and Drug Administration (FDA) has directed considerable effort towards modernizing its regulatory processes over the past decade to address the challenges in the drug development sector. Through partnerships and input from stakeholders, multiple initiatives are under way, many projects have been launched, several have resulted in tangible results, and many are ongoing and under discussion. We are learning that collaborative efforts can better inform and leverage existing knowledge, that the challenges of data sharing and intellectual property can be overcome, and that there is wide interest in partnering to address key public health regulatory science issues. It is crucial that we continue to build on these initial efforts to facilitate drug development.

Comparison of the dependence of blood R2 and R2* on oxygen saturation at 1.5 and 4.7 Tesla.

Gradient-echo (GRE) blood oxygen level-dependent (BOLD) effects have both intra- and extravascular contributions. To better understand the intravascular contribution in quantitative terms, the spin-echo (SE) and GRE transverse relaxation rates, R(2) and R(2)(*), of isolated blood were measured as a function of oxygenation in a perfusion system. Over the normal oxygenation saturation range of blood between veins, capillaries, and arteries, the difference between these rates, R'(2) = R(2)(*) - R(2), ranged from 1.5 to 2.1 Hz at 1.5 T and from 26 to 36 Hz at 4.7 T. The blood data were used to calculate the expected intravascular BOLD effects for physiological oxygenation changes that are typical during visual activation. This modeling showed that intravascular DeltaR(2)(*) is caused mainly by R(2) relaxation changes, namely 85% and 78% at 1.5T and 4.7T, respectively. The simulations also show that at longer TEs (>70 ms), the intravascular contribution to the percentual BOLD change is smaller at high field than at low field, especially for GRE experiments. At shorter TE values, the opposite is the case. For pure parenchyma, the intravascular BOLD signal changes originate predominantly from venules for all TEs at low field and for short TEs at high field. At longer TEs at high field, the capillary contribution dominates. The possible influence of partial volume contributions with large vessels was also simulated, showing large (two- to threefold) increases in the total intravascular BOLD effect for both GRE and SE.

Measurement of tissue oxygen extraction ratios from venous blood T(2): increased precision and validation of principle.

It has recently been shown that parenchymal oxygen extraction ratios (OERs) can be quantified using the absolute T(2) of venous blood draining from this tissue (Oja et al., J Cereb Blood Flow Metab 1999;19:1289-1295). Here, a modified Carr-Purcell-Meiboom-Gill (CPMG) multiecho experiment was used to increase the efficiency and precision of this approach and to test the applicability of the two-compartment exchange model for spin-echo BOLD effects in pure venous blood. Relaxation measurements on bovine blood as a function of CPMG interecho spacing, oxygen saturation, and hematocrit provided the baseline relaxation and susceptibility shift parameters necessary to directly relate OER to T(2) of venous blood in vivo. Using an interecho spacing of 25 ms, the results on visual activation studies in eight volunteers showed T(2)(CPMG) values increasing from 128 +/- 9 ms to 174 +/- 18 ms upon activation, corresponding to local OER values of 0.38 +/- 0.04 and 0.18 +/- 0.05 during baseline activity and visual stimulation, respectively. These OER values are in good agreement with literature data on venous oxygenation and numbers determined previously using a single-echo approach, while the measured T(2)s are about 20-40 ms longer.

A neglected geometry for finding perspective.

A method for dividing quadrilateral spaces is described to assist artists with perspective illustrations. Linear perspective, key to realistic drawings, can be time-consuming to use, hampering illustrators who need to be efficient to compete in today's market. Using this method, art benefits in speed from an overlooked geometry based on right triangles. It also fascinates with versatility as it presumes to solve two ancient math riddles.

Foodservice Manager Certification-The NIFI Program.

A trend toward tightening sanitation regulations is spreading across the nation. Supported by an increasing number of health jurisdictions at all levels (city, county, and state) and by the industry's customers in every state, new regulations are becoming a way of life for every restaurateur. Courses at all degrees of technical specificity, length and cost have appeared, culminating in what has been called "cross-country chaos." The National Institute for the Food Service Industry (NIFI) course, "Applied Foodservice Sanitation," meets the FDA's recently-issued recommendations in every respect and is finding increased acceptance each day. It serves as the basis for the Illinois mandatory program and is accepted as one means of obtaining certification in the other two state mandatory programs (Florida and Washington, D.C.). Statewide voluntary programs are in full operation in Wisconsin, Michigan, Mssouri, and Massachusetts and have started in Hawaii. South Carolina, Southern California, and Pennsylvania. Pilot programs are underway in Indiana and Kentucky and have been approved for early implementation in the state of Washington. Approximately 7,000 foodservice managers and supervisors have been certified by NIFI, and more than 17,000 textbooks are in use. NIFI has been chosen by the Food and Drug Administration to develop a plan for implementing a uniform national foodservice sanitation training and certification program.