Validation of rectal sparing throughout the course of proton therapy treatment in prostate cancer patients treated with SpaceOAR®.

The purpose of this study was to investigate the consistency of rectal sparing using multiple periodic quality assurance computerized tomography imaging scans (QACT) obtained during the course of proton therapy for patients with prostate cancer treated with a hydrogel spacer. Forty-one low- and intermediate-risk prostate cancer patients treated with image-guided proton therapy with rectal spacer hydrogel were analyzed. To assess the reproducibility of rectal sparing with the hydrogel spacer, three to four QACTs were performed for each patient on day 1 and during weeks 1, 3, and 5 of treatment. The treatment plan was calculated on the QACT and the rectum V90%, V75%, V65%, V50%, and V40% were evaluated. For the retrospective analysis, we evaluated each QACT and compared it to the corresponding treatment planning CT (TPCT), to determine the average change in rectum DVH points. We were also interested in how many patients exceeded an upper rectum V90% threshold on a QACT. Finally, we were interested in a correlation between rectum volume and V90%. On each QACT, if the rectum V90% exceeded the upper threshold of 6%, the attending physician was notified and the patient was typically prescribed additional stool softeners or laxatives and reminded of dietary compliance. In all cases of the rectum V90% exceeding the threshold, the patient had increased gas and/or stool, compared to the TPCT. On average, the rectum V90% calculated on the QACT was 0.81% higher than that calculated on the TPCT. The average increase in V75%, V65%, V50%, and V40% on the QACT was 1.38%, 1.59%, 1.87%, and 2.17%, respectively. The rectum V90% was within ± 1% of the treatment planning dose in 71.2% of the QACTs, and within ± 5% in 93.2% of the QACTs. The 6% threshold for rectum V90% was exceeded in 7 out of 144 QACTs (4.8%), identified in 5 of the 41 patients. We evaluated the average rectum V90% across all QACTs for each of these patients, and it was found that the rectum V90% never exceeded 6%. 53% of the QACTs had a rectum volume within 5 cm3 of the TPCT volume, 68% were within 10 cm3. We found that patients who exceeded the threshold on one or more QACTs had a lower TPCT rectal volume than the overall average. By extrapolating patient anatomy from three to four QACT scans, we have shown that the use of hydrogel in conjunction with our patient diet program and use of stool softeners is effective in achieving consistent rectal sparing in patients undergoing proton therapy.

Routine and timely sub-picoNewton force stability and precision for biological applications of atomic force microscopy.

Force drift is a significant, yet unresolved, problem in atomic force microscopy (AFM). We show that the primary source of force drift for a popular class of cantilevers is their gold coating, even though they are coated on both sides to minimize drift. Drift of the zero-force position of the cantilever was reduced from 900 nm for gold-coated cantilevers to 70 nm (N = 10; rms) for uncoated cantilevers over the first 2 h after wetting the tip; a majority of these uncoated cantilevers (60%) showed significantly less drift (12 nm, rms). Removing the gold also led to ∼10-fold reduction in reflected light, yet short-term (0.1-10 s) force precision improved. Moreover, improved force precision did not require extended settling; most of the cantilevers tested (9 out of 15) achieved sub-pN force precision (0.54 ± 0.02 pN) over a broad bandwidth (0.01-10 Hz) just 30 min after loading. Finally, this precision was maintained while stretching DNA. Hence, removing gold enables both routine and timely access to sub-pN force precision in liquid over extended periods (100 s). We expect that many current and future applications of AFM can immediately benefit from these improvements in force stability and precision.

A requirement for CARMA1 in TCR-induced NF-kappa B activation.

Stimulation of the T cell receptor (TCR) complex initiates multiple signaling cascades that lead to the activation of several transcription factors, including the NF-kappa B family members. Although various proximal signaling components of the TCR have been intensively studied, the distal components that mediate TCR-induced NF-kappa B activation remain largely unknown. Using a somatic mutagenesis approach, we cloned a CARMA1-deficient T cell line. Deficiency in CARMA1 (originally known as CARDII) resulted in selectively impaired activation of NF-kappa B induced by the TCR and a consequent defect in interleukin-2 (IL-2) production. Reconstitution of the CARMA1-deficient cells with CARMA1 fully rescued this signaling defect. Together, our results show that CARMA1 is an essential signaling component that mediates TCR-induced NF-kappa B activation.