Pharmacokinetic comparison of sustained-release and standard buprenorphine in mice.

Effective pain medication is important for animal stewardship and valid research results. We compared the pharmacokinetic assessments of standard, immediate-release buprenorphine (Bup IR) and a sustained-release buprenorphine formulation (Bup SR Lab) in male C57BL/6J mice, a mouse strain commonly used in biomedical research. We postulated that the administration of Bup SR Lab would achieve a more persistent blood drug concentration (>1 ng/mL) compared with single-dose Bup IR. The study assumed a blood buprenorphine concentration of 1 ng/mL as the minimum that may result in adequate analgesia, as previously reported. The 7 experimental groups included Bup IR (0.03, 0.05, 0.1, and 2 mg/kg), Bup SR Lab (0.3 and 1.2 mg/ kg), and saline placebo (0.7 mL/100 g). Blood sampling occurred at 0.5, 1, 3, 6, 12, 24, 48, and 72 h for evaluation by using a forensic ELISA. Bup IR at 0.03 and 0.05 mg/kg and Bup SR Lab at 0.3 mg/kg failed to obtain maximal blood concentrations (Cmax) above 1 ng/mL. All other doses (0.1 and 2 mg/kg Bup IR and 1.2 mg/kg Bup SR Lab) reached a Cmax above 1 ng/mL within 3 h after injection. In addition, 1.2 mg/kg Bup SR Lab and 2 mg/kg Bup IR provided blood concentrations above 1 ng/mL for up to 12 h, and 0.1 mg/kg Bup IR achieved this criterion for as long as 3 h. In conclusion, Bup SR Lab at 1.2 mg/kg and Bup IR at 0.1 or 2.0 mg/kg achieve or surpass the published threshold for adequate analgesia in mice.

Cost cutting in health systems without compromising quality care.

Intermountain Healthcare is a high-performing health system and a recognized leader in quality improvement. We use a clinical integration strategy focused on eight clinical programs to support the practice of evidence-based care. Accelerated improvements that enhance patient safety, clinical excellence, and operational efficiency are tested and then spread across the system via care process models and program-specific board goals. While we have nearly 60 evidence-based care process models in place (in addition to multiple operational effectiveness initiatives), we provide three exemplars to illustrate cost savings and the relative impact on hospital/medical group versus payer benefit. These clinical best practices include very early lung recruitment (VE LR) for neonates with respiratory distress syndrome, guidelines for elective inductions in labor and delivery, and prevention of congestive heart failure (CHF) readmissions. Due to perverse incentives in the third party payment system--where healthcare providers are often paid to do more tests and treatments as opposed to providing clinical value--doing what's right for our patients commonly yields savings to our payers while negatively impacting the delivery system budget. In this article, we present a suggested strategy for negotiated capture of these savings.

The National Ignition Facility neutron imaging system.

The National Ignition Facility (NIF) is scheduled to begin deuterium-tritium (DT) shots possibly in the next several years. One of the important diagnostics in understanding capsule behavior and to guide changes in Hohlraum illumination, capsule design, and geometry will be neutron imaging of both the primary 14 MeV neutrons and the lower-energy downscattered neutrons in the 6-13 MeV range. The neutron imaging system (NIS) described here, which we are currently building for use on NIF, uses a precisely aligned set of apertures near the target to form the neutron images on a segmented scintillator. The images are recorded on a gated, intensified charge coupled device. Although the aperture set may be as close as 20 cm to the target, the imaging camera system will be located at a distance of 28 m from the target. At 28 m the camera system is outside the NIF building. Because of the distance and shielding, the imager will be able to obtain images with little background noise. The imager will be capable of imaging downscattered neutrons from failed capsules with yields Y(n)>10(14) neutrons. The shielding will also permit the NIS to function at neutron yields >10(18), which is in contrast to most other diagnostics that may not work at high neutron yields. The following describes the current NIF NIS design and compares the predicted performance with the NIF specifications that must be satisfied to generate images that can be interpreted to understand results of a particular shot. The current design, including the aperture, scintillator, camera system, and reconstruction methods, is briefly described. System modeling of the existing Omega NIS and comparison with the Omega data that guided the NIF design based on our Omega results is described. We will show NIS model calculations of the expected NIF images based on component evaluations at Omega. We will also compare the calculated NIF input images with those unfolded from the NIS images generated from our NIS numerical modeling code.

Direct visualization of cystic fibrosis transmembrane regulator mutations in the clinical laboratory setting.

BACKGROUND: The recommendation for population- based cystic fibrosis (CF) carrier screening by the American College of Medical Genetics for the 25 most prevalent mutations and 6 polymorphisms in the CF transmembrane regulatory gene has greatly increased clinical laboratory test volumes. We describe the development and technical validation of a DNA chip in a 96-well format to allow for high-throughput genotype analysis. METHODS: The CF Portrait chip contains an 8 x 8 array of capture probes and controls to detect all requisite alleles. Single-tube multiplex PCR with 15 biotin-labeled primer pairs was used to amplify sequences containing all single-nucleotide polymorphisms to be interrogated. Detection of a thin-film signal created by hybridization of multiplex PCR-amplified DNA to complementary capture probes was performed with an automated image analysis instrument, NucleoSight. Allele classification, data formatting, and uploading to a laboratory information system were fully automated. RESULTS: The described platform correctly classified all mutations and polymorphisms and can screen approximately 1300 patient samples in a 10-h shift. Final validation was performed by two separate 1000-sample comparisons with Roche CF Gold line probe strips and the Applera CF OLA, Ver 3.0. The CF Portrait Biochip made no errors during this validation, whereas the Applera assay made seven miscalls of the IVS-8 5T/7T/9T polymorphism CONCLUSIONS: The CF Portrait platform is an automated, high-throughput, DNA chip-based assay capable of accurately classifying all CF mutations in the recommended screening panel, including the IVS-8 5T/7T/9T polymorphism.