Francisella tularensis is a highly infectious facultative intracellular pathogen that is considered a potential agent of bioterrorism. Four different F. tularensis subspecies have been identified and they appear to display different ecological and virulence characteristics as well as differences in geographical distribution. One simple explanation for the variation in ecological and virulence characteristics is that they are conferred by differences in genome content. To characterize genome content among stains isolated from United States, we have used a DNA microarray designed from a shotgun library of a reference strain. Polymorphisms distributed among polyphyletic sets of strains was the most common pattern of genome alteration observed, indicating that strain-specific genome variability is significant. Nonetheless, 13 different contiguous segments of the genome were found to be missing exclusively in each of the subsp. holarctica strains tested. All 13 are associated with repeat sequences or transposases that could promote insertion/deletion events. Comparison of the live vaccine strain to other holarctica strains also identified three regions that are absent exclusively in the live vaccine strain derived from holarctica.
Laser shock micro-forming is a non-thermal laser forming method that uses laser-induced shockwave to modify surface properties and to adjust shapes and geometry of work pieces. The magnitude and spatial distribution of the laser-induced shockwaves depend on the energy profiles of the laser beam focused on sample surfaces. In this paper, we present an adaptive optical technique to engineer spatial profiles of laser beams to control the shapes, sizes, and locations of the laser-induced shockwaves and the resulting forming features. Using a spatial light modulator, this adaptive laser beam forming tool was used to process free-standing MEMS structures in aluminum, which has led to highly uniform forming features. Shockwave simultaneously excited by multiple laser beams generated by the spatial light modulator and its effects on the micro-forming process were also studied. The results presented in this paper show that the adaptive optics laser beam forming is an effective and flexible method to generate shockwave with various shapes and sizes of wavefront and at multiple locations for laser processing at microscales.
progressed following initial treatment with SRS. The purpose of this project is to report the outcome of our repeat SRS series. Materials/Methods: A total of 6 patients were treated with repeat SRS at our institution between 1993 and 2019. We excluded patients with bilateral disease at presentation or neurofibromatosis. All patients were required to have undergone magnetic resonance (MR) planning for both SRS treatments. DVH analysis was performed on the tumor and critical structures. Toxicity was assessed per CTCAE grading. All SRS treatments were delivered with a Linac system using head frame immobilization with the dose prescribed to the 70% or 80% isodose covering the periphery of the visible tumor on MR scan. The prescribed dose was 12.5 Gy in all initial and repeat SRS treatments with the exception of one repeat treatment that was 10 Gy. The average GTV volume was larger during repeat treatment than initial treatment (3.8 cc vs 1.9 cc). In addition to being larger tumors, tumors during repeat treatment had higher average touching distance with the brainstem (15.0 mm vs 6.7 mm) and more brainstem compression (2.8 mm vs 0.3 mm). Results: Follow-up with MR scan following the second SRS treatment was a median 3.9 years (range, 0.9-8.7 years). A second SRS treatment resulted in a tumor control rate (lack of progression) of 83% (5/6). The one patient who progressed after repeat SRS subsequently underwent surgical resection and is alive. Actuarial rates at 10 years following repeat SRS were as follows: tumor control, 80%; absolute survival, 80%; and cause-specific survival, 100%. Of the patients with at least minimal hearing retention prior to initial SRS, none had ipsilateral hearing preservation after initial radiation treatment. Improvement in any pretreatment cranial nerve deficits was not seen. The only permanent grade 3 toxicity from repeat SRS was a single case of V2 deficit. No patient developed a stroke, malignant transformation, induced second tumor, or facial nerve deficit. Conclusion: Repeat single fraction SRS as delivered in our series is an excellent treatment option for vestibular schwannoma that has progressed following initial treatment with SRS.
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