Assessment of Knowledge-Based Planning for Prostate Intensity Modulated Proton Therapy

Purpose: To assess the performance of a proton-specific knowledge based planning (KBPP) model in creation of robustly optimized intensity-modulated proton therapy (IMPT) plans for treatment of patients with prostate cancer. Materials and Methods: Forty-five patients with localized prostate cancer, who had previously been treated with volumetric modulated arc therapy, were selected and replanned with robustly optimized IMPT. A KBPP model was generated from the results of 30 of the patients, and the remaining 15 patient results were used for validation. The KBPP model quality and accuracy were evaluated with the model-provided organ-at-risk regression plots and metrics. The KBPP quality was also assessed through comparison of expert and KBPP-generated IMPT plans for target coverage and organ-at-risk sparing. Results: The resulting R (2) (mean ± SD, 0.87 ± 0.07) between dosimetric and geometric features, as well as the χ(2) test (1.17 ± 0.07) between the original and estimated data, showed the model had good quality. All the KBPP plans were clinically acceptable. Compared with the expert plans, the KBPP plans had marginally higher dose-volume indices for the rectum V65Gy (0.8% ± 2.94%), but delivered a lower dose to the bladder (-1.06% ± 2.9% for bladder V65Gy). In addition, KBPP plans achieved lower hotspot (-0.67Gy ± 2.17Gy) and lower integral dose (-0.09Gy ± 0.3Gy) than the expert plans did. Moreover, the KBPP generated better plans that demonstrated slightly greater clinical target volume V95 (0.1% ± 0.68%) and lower homogeneity index (-1.13 ± 2.34). Conclusions: The results demonstrated that robustly optimized IMPT plans created by the KBPP model are of high quality and are comparable to expert plans. Furthermore, the KBPP model can generate more-robust and more-homogenous plans compared with those of expert plans. More studies need to be done for the validation of the proton KBPP model at more-complicated treatment sites

Validation of the cell cycle G2 delay assay in assessing ionizing radiation sensitivity and breast cancer risk

Genetic variations in cell cycle checkpoints and DNA repair genes are associated with prolonged cell cycle G2 delay following ionizing radiation (IR) treatment and breast cancer risk. However, different studies reported conflicting results examining the association between post-IR cell cycle delay and breast cancer risk utilizing four different parameters: cell cycle G2 delay index, %G2–M, G2/G0–G1, and (G2/G0–G1)/S. Therefore, we evaluated whether different parameters may influence study results using a data set from 118 breast cancer cases and 225 controls as well as lymphoblastoid and breast cancer cell lines with different genetic defects. Our results suggest that cell cycle G2 delay index may serve as the best parameter in assessing breast cancer risk, genetic regulation of IR-sensitivity, and mutations of ataxia telangiectasia mutated (ATM) and TP53. Cell cycle delay in 21 lymphoblastoid cell lines derived from BRCA1 mutation carriers was not different from that in controls. We also showed that IR-induced DNA-damage signaling, as measured by phosphorylation of H2AX on serine 139 (γ-H2AX) was inversely associated with cell cycle G2 delay index. In summary, the cellular responses to IR are extremely complex; mutations or genetic variations in DNA damage signaling, cell cycle checkpoints, and DNA repair contribute to cell cycle G2 delay and breast cancer risk. The cell cycle G2 delay assay characterized in this study may help identify subpopulations with elevated risk of breast cancer or susceptibility to adverse effects in normal tissue following radiotherapy

Decadal changes in summertime reactive oxidized nitrogen and surface ozone over the Southeast United States

Widespread efforts to abate ozone (O3) smog have significantly reduced emissions of nitrogen oxides (NOx) over the past 2 decades in the Southeast US, a place heavily influenced by both anthropogenic and biogenic emissions. How reactive nitrogen speciation responds to the reduction in NOx emissions in this region remains to be elucidated. Here we exploit aircraft measurements from ICARTT (July–August 2004), SENEX (June–July 2013), and SEAC4RS (August–September 2013) and long-term ground measurement networks alongside a global chemistry–climate model to examine decadal changes in summertime reactive oxidized nitrogen (RON) and ozone over the Southeast US. We show that our model can reproduce the mean vertical profiles of major RON species and the total (NOy) in both 2004 and 2013. Among the major RON species, nitric acid (HNO3) is dominant (∼ 42–45%), followed by NOx (31%), total peroxy nitrates (ΣPNs; 14%), and total alkyl nitrates (ΣANs; 9–12%) on a regional scale. We find that most RON species, including NOx, ΣPNs, and HNO3, decline proportionally with decreasing NOx emissions in this region, leading to a similar decline in NOy. This linear response might be in part due to the nearly constant summertime supply of biogenic VOC emissions in this region. Our model captures the observed relative change in RON and surface ozone from 2004 to 2013. Model sensitivity tests indicate that further reductions of NOxemissions will lead to a continued decline in surface ozone and less frequent high-ozone events

Thinking like a man? The cultures of science

Culture includes science and science includes culture, but conflicts between the two traditions persist, often seen as clashes between interpretation and knowledge. One way of highlighting this false polarity has been to explore the gendered symbolism of science. Feminism has contributed to science studies and the critical interrogation of knowledge, aware that practical knowledge and scientific understanding have never been synonymous. Persisting notions of an underlying unity to scientific endeavour have often impeded rather than fostered the useful application of knowledge. This has been particularly evident in the recent rise of molecular biology, with its delusory dream of the total conquest of disease. It is equally prominent in evolutionary psychology, with its renewed attempts to depict the fundamental basis of sex differences. Wars over science have continued to intensify over the last decade, even as our knowledge of the political, economic and ideological significance of science funding and research has become ever more apparent

Fast Beam Condition Monitor for CMS: performance and upgrade

The CMS beam and radiation monitoring subsystem BCM1F (Fast Beam Condition Monitor) consists of 8 individual diamond sensors situated around the beam pipe within the pixel detector volume, for the purpose of fast bunch-by-bunch monitoring of beam background and collision products. In addition, effort is ongoing to use BCM1F as an online luminosity monitor. BCM1F will be running whenever there is beam in LHC, and its data acquisition is independent from the data acquisition of the CMS detector, hence it delivers luminosity even when CMS is not taking data. A report is given on the performance of BCM1F during LHC run I, including results of the van der Meer scan and on-line luminosity monitoring done in 2012. In order to match the requirements due to higher luminosity and 25 ns bunch spacing, several changes to the system must be implemented during the upcoming shutdown, including upgraded electronics and precise gain monitoring. First results from Run II preparation are shown.Comment: 10 pages, 8 figures. To be published in NIM A as proceedings for the 9th Hiroshima Symposium on Semiconductor Tracking Detectors (2013

Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist

Relevance of collagen piezoelectricity to "Wolff's Law": A critical review

According to “Wolff's Law”, bone is deposited and reinforced at areas of greatest stress. From a clinical perspective, this “law” is supported by the strong association between bone density and physical activity. From a mechanistic standpoint, however, the law presents a challenge to scientists seeking to understand how osteocytes and osteoblasts sense the mechanical load. In the 1960s, collagen piezoelectricity was invoked as a potential mechanism by which osteocytes could detect areas of greater stress but piezoelectricity diminished in importance as more compelling mechanisms, such as streaming potential, were identified. In addition, accumulating evidence for the role of fluid-related shear stress in osteocyte's mechanosensory function has made piezoelectricity seemingly more obsolete in bone physiology. This review critically evaluates the role of collagen piezoelectricity (if any) in Wolff's Law—specifically, the evidence regarding its involvement in strain-generated potentials, existing alternate mechanisms, the present understanding of bone mechanosensation, and whether piezoelectricity serves an influential role within the context of this newly proposed mechanism. In addition to reviewing the literature, this review generates several hypotheses and proposes future research to fully address the relevance of piezoelectricity in bone physiology.National Center for Complementary and Alternative Medicine (U.S.) (grant K23-AT003238