Analysis of the safety and reliability of a hydrothermal ablation system: a multicenter, prospective postmarket study.

OBJECTIVE: To obtain information on practitioner experience in the use of the Genesys HydroThermAblator (HTA) System under normal clinical conditions through documentation of the system's acute safety features, in terms of burn rates, and its technical reliability. STUDY DESIGN: This was a prospective, observational, multicenter, postmarket interventional clinical trial with outcome measures of acute (within 21 days post-procedure) safety, serious adverse device effects, and technical malfunctions in a population of premenopausal women > or = 18 years of age. RESULTS: A total of 992 women (mean age, 41.7 +/- 6.8 years; range, 22-65 years) were enrolled in 18 clinical sites throughout the United States. The Genesys HTA System provided low burn rates in the intent-to-treat (n = 992 [0.4%] [95% CI 0.1-1.0%]) and evaluable (n = 931 [0.2%] [95% CI 0.1-0.8%]) subject populations. Only 1 burn was clinically significant and was defined as a serious adverse device effect (1/992 [0.10%] [95% CI 0.0-0.6%]). Fifty-three (5.1%) technical malfunctions occurred in 44 procedures, and 27 (27/44 [61.4%]) patients completed their procedures after 31 (31/ 53 [58.5%]) technical problems were addressed and resolved. CONCLUSION: The Genesys HTA System delivers a safe and reliable treatment option for premenopausal women with heavy menstrual bleeding.

Amputee locomotion: determining the inertial properties of running-specific prostheses.

OBJECTIVES: (1) To test the validity of a trifilar pendulum in estimating moments of inertia (MOIs) for running-specific prostheses (RSPs), (2) to measure inertial properties (mass, center of mass [CM] position, and MOIs) for 4 RSPs, (3) to verify the influence of the stiffness on the inertial properties of RSPs, and (4) to develop a predictive equation to estimate RSP CM positions. DESIGN: An aluminum block with known MOIs was used for verifying the accuracy of the trifilar pendulum MOI measurements. MOI errors were investigated by systematically misaligning the block and pendulum principal axes across a range of 1 to 10cm. Mass, CM position, and MOI were tested across 4 RSP designs with 3 stiffness categories each. SETTING: University biomechanics laboratory. SPECIMENS: Four different RSP designs and 3 stiffness categories per design were examined. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: MOI errors from known values and principal axis misalignments between RSPs and pendulum; mass, CM positions, and RSP principal axis MOIs; and predictive equation CM position errors. RESULTS: The trifilar pendulum estimated MOIs within -6.21×10(-5)kg/m(2) (≤1% error) for a block with known MOIs. Misalignments of 1 to 5cm between the RSPs' and pendulum's CM yielded errors from .00002 to .00113 kg/m(2) (0.3%-59.2%). Each RSP's inertial properties are presented. MOIs about any axis varied <.004kg/m(2) across stiffness categories; MOIs differed up to .013kg/m(2) between different designs. The predictive CM equation erred between .010 and .028m when using average input values across an RSP design. CONCLUSIONS: Trifilar pendulums can accurately measure RSP MOI. The RSP inertial properties differed slightly across stiffness categories within each design, but differed more substantially across different RSP designs. Using a predictive equation to estimate RSP CM positions can provide adequate data, but directly measuring CM positions is preferable.

Structure-based design of 7-azaindole-pyrrolidine amides as inhibitors of 11ß-hydroxysteroid dehydrogenase type I.

Indole-pyrrolidines were identified as inhibitors of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) by high-throughput screening. Optimisation of the initial hit through structure-based design led to 7-azaindole-derivatives, with the best analogues displaying single digit nanomolar IC(50) potency. The modeling hypotheses were confirmed by solving the X-ray co-crystal structure of one of the lead compounds. These compounds were selective against 11ß-hydroxysteroid dehydrogenase type 2 (selectivity ratio >200) and exhibited good inhibition of 11ß-HSD1 (IC(50)<1µM) in a cellular model (3T3L1 adipocytes).

Helically chiral polymers: a class of ligands for asymmetric catalysis.

Helically chiral polymers from achiral monomers containing N and P atoms have been shown to be ligands for transition metals such as Pd and Rh. The Rh complex of the phosphane-containing polyisocyanate p(18-co-17) was an active albeit hardly enantioselective catalyst in the asymmetric hydrogenation of the dehydro amino acid N-acetamidocinnamic acid (15% enantiomeric excess). The most active catalyst obtained until now was the Pd-complexed polymethacrylate Pd-p12, which catalyzes the allylic substitution reaction of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate even at -20 degrees C in quantitative yield, although again the enantioselectivity was unsatisfactory. The most successful application of a helically chiral polymer in asymmetric catalysis with respect to both reactivity and enantioselectivity is the polymethacrylate p(5-co-8). Its palladium complex catalyzes the above-mentioned reaction at 0 degrees C with quantitative yield and 60% enantiomeric excess.