Optically-guided frameless linac-based radiosurgery for brain metastases: clinical experience

The purpose of this study was to describe our clinical experience using optically-guided linear accelerator (linac)-based frameless stereotactic radiosurgery (SRS) for the treatment of brain metastases. Sixty-five patients (204 lesions) were treated between 2005 and 2008 with frameless SRS using an optically-guided bite-block system. Patients had a median of 2 lesions (range, 1–13). Prescription dose ranged from 14 to 22 Gy (median, 18 Gy) and was given in a single fraction. Clinical and radiographic evaluation occurred every 2–4 months following treatment. At a median follow-up of 6.2 months, actuarial survival at 12 months was 40% [95% confidence interval (CI), 28–52). Of 135 lesions that were evaluable for local control (LC), 119 lesions (88%) did not show evidence of progression. Actuarial 12 month LC was 76% (95% CI, 66–86). Tumors ≤2 cm in size had a better 12 month LC rate (81% vs. 36%, P = 0.017) than those >2 cm. Adverse events occurred in three patients (5%). Optically-guided linac-based frameless SRS can produce clinical outcomes that compare favorably to frame-based techniques. As this technique is convenient to use and allows for the uncomplicated delivery of hypofractionated radiotherapy, frameless SRS will likely have an increasingly important role in the management of brain metastases

Secular Evolution in Mira Variable Pulsations

Stellar evolution theory predicts that asymptotic giant branch stars undergo a series of short thermal pulses that significantly change their luminosity and mass on timescales of hundreds to thousands of years. Secular changes in these stars resulting from thermal pulses can be detected as measurable changes in period if the star is undergoing Mira pulsations. The American Association of Variable Star Observers (AAVSO) International Database currently contains visual data for over 1500 Mira variables. Light curves for these stars span nearly a century in some cases, making it possible to study the secular evolution of the pulsation behavior on these timescales. In this paper, we present the results of our study of period change in 547 Mira variables using data from the AAVSO. We find non-zero rates of period change, dlnP/dt, at the 2-sigma significance level in 57 of the 547 stars, at the 3-sigma level in 21 stars, and at the level of 6-sigma or greater in eight of the 547. The latter eight stars have been previously noted in the literature, and our derived rates of period changes largely agree with published values. The largest and most statistically significant dlnP/dt are consistent with the rates of period change expected during thermal pulses on the AGB. A number of other stars exhibit non-monotonic period changes on decades-long timescales, the cause of which is not yet known.Comment: 37 pages, with 9 figures and 1 table. The complete electronic version of Table 1 is available from the authors upon request. Accepted for publication in The Astronomical Journa

β-Lactam Resistance Response Triggered by Inactivation of a Nonessential Penicillin-Binding Protein

It has long been recognized that the modification of penicillin-binding proteins (PBPs) to reduce their affinity for β-lactams is an important mechanism (target modification) by which Gram-positive cocci acquire antibiotic resistance. Among Gram-negative rods (GNR), however, this mechanism has been considered unusual, and restricted to clinically irrelevant laboratory mutants for most species. Using as a model Pseudomonas aeruginosa, high up on the list of pathogens causing life-threatening infections in hospitalized patients worldwide, we show that PBPs may also play a major role in β-lactam resistance in GNR, but through a totally distinct mechanism. Through a detailed genetic investigation, including whole-genome analysis approaches, we demonstrate that high-level (clinical) β-lactam resistance in vitro, in vivo, and in the clinical setting is driven by the inactivation of the dacB-encoded nonessential PBP4, which behaves as a trap target for β-lactams. The inactivation of this PBP is shown to determine a highly efficient and complex β-lactam resistance response, triggering overproduction of the chromosomal β-lactamase AmpC and the specific activation of the CreBC (BlrAB) two-component regulator, which in turn plays a major role in resistance. These findings are a major step forward in our understanding of β-lactam resistance biology, and, more importantly, they open up new perspectives on potential antibiotic targets for the treatment of infectious diseases