Liver-directed adeno-associated virus serotype 8 gene transfer rescues a lethal murine model of citrullinemia type 1.

Citrullinemia type 1 (CTLN1) is an autosomal recessive disorder of metabolism caused by a deficiency of argininosuccinate synthetase. Despite optimal management, CTLN1 patients still suffer from lethal metabolic instability and experience life-threatening episodes of acute hyperammonemia. A murine model of CTLN1 (fold/fold) that displays lethality within the first 21 days of life was used to determine the efficacy of adeno-associated viral (AAV) gene transfer as a potential therapy. An AAV serotype 8 (AAV8) vector was engineered to express the human ASS1 cDNA under the control of a liver-specific promoter (thyroxine-binding globulin, TBG), AAV8-TBG-hASS1, and delivered to 7-10 days old mice via intraperitoneal injection. Greater than 95% of the mice were rescued from lethality and survival was extended beyond 100 days after receiving a single dose of vector. AAV8-TBG-hASS1 treatment resulted in liver-specific expression of hASS1, increased ASS1 enzyme activity, reduction in plasma ammonia and citrulline concentrations and significant phenotypic improvement of the fold/fold growth and skin phenotypes. These experiments highlight a gene transfer approach using AAV8 vector for liver-targeted gene therapy that could serve as a treatment for CTLN1.

Analysis of gunshot residue test results in 112 suicides.

The results of gunshot residue (GSR) tests in 112 suicide cases investigated by the U.S. Army Criminal Investigation Command over a ten-year period are described. Only suicide cases in which there was certainty that the victim fired a weapon were examined in an effort to reduce ambiguous results. Previous case work research by Rudzitis indicated that positive GSR test results were encountered in suicides 62% of the time using various combinations of neutron activation analysis (NAA) and atomic absorption spectrophotometry (AAS). Threshold values of 0.2-micrograms antimony and 0.3-micrograms barium (0.2-micrograms antimony and 0.5-micrograms barium after 1985) used by the U.S. Army Criminal Investigation Laboratory resulted in positive GSR results in suicide cases 38% of the time. The effects of time, location of body, handling of the body, weapon type, caliber, and condition of the hands on GSR results are examined. Case studies involving suicides by unit armorers are discussed.

Prosthetic hip range of motion and impingement. The effects of head and neck geometry.

Two major design parameters to total hip arthroplasty which can be selected to optimize for anatomical variation are head diameter and neck length. By using a cadaveric pelvis mounted in a three-dimensional protractor, it was shown that increased head-neck diameter ratio results in increased range of motion, with decreased prosthetic impingement, and that increased neck-length results in increased range of motion, with increased prosthetic impingement. Head diameter has no range of motion effect in arcs characterized exclusively by bony impingement, and neck length has no range of motion effect in arcs characterized exclusively by prosthetic impingement. The surgeon is currently confronted with a variety of prostheses with different head-neck diameter ratios and neck lengths. When choosing the optimal prosthesis for a particular patient, the surgeon is often restricted by various anatomical constraints. While a large head diameter cannot always be chosen, an adequate range of motion without prosthetic impingement can still be achieved by ensuring that head-neck diameter ratio is optimum. A sufficient neck length to ensure adequate range of motion is desirable, but the neck should not be so long that neck-socket impingement is of concern. Optimum clinical range of motion, with minimal prosthetic impingement, may be achieved with a large head size and a medium neck length.

Why performance appraisals fail.

Our faith in the effectiveness of performance appraisal derives in part from its planned redundancy, in the interplay of employee, appraiser and reviewer. But this very safeguard, as Dr. McGuire points out, means that each party is trying too hard to satisfy the others' needs and expectations, both real and imagined.