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Standard of care for lower-grade glioma (LGG) is maximal safe resection and risk-adaptive adjuvant therapy. While patients who benefit the most from adjuvant chemotherapy have been elucidated in prospective randomized studies, comparable insights for adjuvant radiotherapy (RT) are lacking. We sought to identify and validate patterns of gene expression that are associated with differential outcomes among LGG patients treated by RT from two large genomics databases.Patients from The Cancer Genome Atlas (TCGA) with LGG (WHO grade II-III glioma) treated by surgery and adjuvant RT were randomized 1:1 to a discovery cohort or an internal validation cohort. Using the discovery cohort only, associations between tumor RNA-seq expression and progression-free survival (PFS) as well as overall survival (OS) were evaluated with adjustment for clinicopathologic covariates. A Genomic Risk Score (GRS) was then constructed from the expression levels of top genes also screened for involvement in glioma carcinogenesis. The prognostic value of GRS was further assessed in the internal validation cohort of TCGA and a second distinct database, compiled by the Chinese Glioma Genome Association (CGGA).From TCGA, 289 patients with LGG received adjuvant RT alone (38 grade II, 30 grade III) or chemoradiotherapy (CRT) (51 grade II, 170 grade III) between 2009 and 2015. From CGGA, 178 patients with LGG received adjuvant RT alone (40 grade II, 13 grade III) or CRT (41 grade II, 84 grade III) between 2004 and 2016. The genes comprising GRS are involved in MAP kinase activity, T cell chemotaxis, and cell cycle transition: MAP3K15, MAPK10, CCL3, CCL4, and ADAMTS1. High GRS, defined as having a GRS in the top third, was significantly associated with poorer outcomes independent of age, sex, glioma histology, WHO grade, IDH mutation, 1p/19q co-deletion, and chemotherapy status in the discovery cohort (PFS HR 1.61, 95% CI 1.10-2.36, P = 0.014; OS HR 2.74, 95% CI 1.68-4.47, P 0.001). These findings were replicated in the internal validation cohort (PFS HR 1.58, 95% CI 1.05-2.37, P = 0.027; OS HR 1.84, 95% CI 1.13-3.00, P = 0.015) and the CGGA external validation cohort (OS HR 1.72, 95% CI 1.27-2.34, P 0.001). Association between GRS and outcomes was observed only among patients who underwent RT, in both TCGA and CGGA.This study successfully identified an expression signature of five genes that stratified outcomes among LGG patients who received adjuvant RT, with two rounds of validation leveraging independent genomics databases. Expression levels of the highlighted genes were associated with PFS and OS only among patients whose treatment included RT, but not among those with omission of RT, suggesting that expression of these genes may be predictive of radiation treatment response. While additional prospective studies are warranted, interrogation of these genes may be considered in the multidisciplinary management of LGG.

Analyze the impact of implementing a structured reporting system for primary brain tumors, the Brain Tumor Reporting and Data System, on attitudes toward radiology reports at a single institution.Following Institutional Review Board approval, an initial 22 question, 5 point (1-worst to 5-best), survey was sent to faculty members, house staff members, and nonphysician providers at our institution who participate in the direct care of brain tumor patients. Results were used to develop a structured reporting strategy for brain tumors which was implemented across an entire neuroradiology section in a staged approach. Nine months following structured reporting implementation, a follow-up 27 question survey was sent to the same group of providers. Keyword search of radiology reports was used to assess usage of Brain Tumor Reporting and Data System over time.Fifty-three brain tumor care providers responded to the initial survey and 38 to the follow-up survey. After implementing BT-RADS, respondents reported improved attitudes across multiple areas including: report consistency (4.3 vs. 3.4; p0.001), report ambiguity (4.2 vs. 3.2, p0.001), radiologist/physician communication (4.5 vs. 3.8; p0.001), facilitation of patient management (4.2 vs. 3.6; p = 0.003), and confidence in reports (4.3 vs. 3.5; p0.001). Providers were more satisfied with the BT-RADS structured reporting system (4.3 vs. 3.7; p = 0.04). Use of the reporting template progressively increased with 81% of brain tumor reports dictated using the new template by 9 months.Implementing a structured template for brain tumor imaging improves perception of radiology reports among radiologists and referring providers involved in the care of brain tumor patients.

Nuclear instruments & methods in physics research / A 1027, 166220 (2022). doi:10.1016/j.nima.2021.166220, A three-cell 1.3 GHz, Normal Conducting (NC) buncher is designed for a possible future upgrade of the European X-ray Free Electron Laser (Eu-XFEL) to operate in a continuous-wave (CW)/ long pulse (LP) mode. The RF geometry of the buncher is optimized for high shunt impedance, large mode separation as well as multipacting free in the operation range. The nominal buncher voltage is 400 kV with an RF power dissipation of 14 kW, and its shunt impedance is ∼50% higher than existing CW bunchers. The RF power coupler cell is optimized for field symmetry to minimize coupler kick effect on beam dynamics. The thermal load due to RF power dissipation is analyzed using Multiphysics simulations in CSTMWS and a cooling scheme is designed., Published by North-Holland Publ. Co., Amsterdam

Purpose Radiation oncologists are frequently involved in providing palliative and supportive care (PSC) for patients with advanced cancers through delivery of palliative radiation. Whether they are confident in their ability to assess and initiate treatments for pain, nonpain, and psychosocial distress is unknown. The American Society for Radiation Oncology surveyed its practicing members in the United States on self-assessment of their primary PSC skills and access to continuing medical education on PSC. Methods We electronically surveyed 4093 practicing radiation oncologists in the United States. The survey consisted of 16-questions in 5 sections 1 : demographics, 2 PSC training, 3 domains of PSC, 4 perceived barriers as a radiation oncologist to initiate advanced care planning, and 5 discussion of prognosis. Results The survey was e-mailed to 4093 American Society for Radiation Oncology members, and 649 responses were received (response rate 16%). The majority (91%) of radiation oncologists surveyed believe PSC is an important competency for radiation oncologists. Most radiation oncologists reported that they are moderately confident in their ability to assess and manage pain and gastrointestinal symptoms, but less confident in their ability to manage anorexia, anxiety, and depression. Despite areas of decreased confidence, a large number (42%) of radiation oncologists do not receive any additional PSC education beyond their residency training. Lastly, a perceived fear of upsetting referring medical oncologists and lack of clinic time are concerns for radiation oncologists who may want to initiate goals of care/advance care planning discussions with patients and their families. Conclusion Radiation oncologists are more confident in their ability to assess and manage pain than in their ability to manage depression, anxiety, anorexia, and fatigue. There is a need for increasing continuing medical educational efforts in PSC for practicing radiation oncologists, and strengthening PSC training in residency programs.

This study evaluated the effects of different amounts (0, 2.5, 5, 10 g/kg) of dietary yeast extract (YE, including 102 g/kg nucleotides) on the milk composition, oxidative stress status, and performance of sows and their offspring. A total of 80 multiparous Large White sows (2-3 of parity) were allotted to 1 of the 4 dietary treatments (0, 2.5, 5, 10 g/kg YE, with 0 g/kg YE used as control (CON)) based on body weight at day 85 of gestation (n=20 per treatment), and the experiment lasted from day 85 of gestation to day 21 of lactation. The reproductive performance of sows and growth performance of piglets were measured. Blood samples were collected from sows and weaning piglets for measuring the level of oxidative stress parameters. The general composition and nucleotide concentrations of colostrum and milk were also measured. Results indicated that, with increasing YE amount in the diet, sows had a linear increase (P ≤ 0.05) in average daily feed intake (ADFI) during the first week of lactation, while a linear decrease (P ≤ 0.01) in body weight loss during lactation. Additionally, the 10 g/kg YE treatment tended to increase the number of weaned piglets per litter (P = 0.08). Furthermore, with increasing YE, the milk exhibited a linear increase (P

We report on growth of polycrystalline diamond (PCD) by chemical vapor deposition (CVD) in a microwave plasma reactor under high absorbed microwave power density (MWPD) and high pressures, in conditions more typical for single crystal diamond epitaxy. The growth rates as high as 30–36 μm/h have been achieved in CH4-H2 mixtures at pressure of 320 Torr and MWPD of ~700 W/cm3 even at relatively low (3%) CH4 concentration, using PCD substrates with diameter of 5–20 mm and different textures. The structure and quality of the produced PCD thick films were assessed with SEM, Raman and X-ray diffraction. The plasma shapes and spatial profiles of species (excited atomic hydrogen and C2 dimer) were characterized with spatially resolved optical emission spectroscopy (OES) at moderate and high MWPD. The maximum rotational gas temperature Tg significantly enhanced to 3700 K in the latter case (675 W/cm3) compared with Tg ≈ 3100 K for lower pressure and MWPD (100 Torr, 160 W/cm3), being in agreement with the obtained high growth rates at high pressures. Analysis of numerous literature data on PCD growth rate vs substrate size in MPCVD reactors reveals a clear trend of enhanced growth rate with diminishing of the substrate dimension, our findings further confirming this tendency indirectly related to a change in absorbed power density.

Cyclooxygenases (COXs) are crucial rate-limiting enzymes required for the biosynthesis of prostaglandins. COX-2 is an inducible isoform of this enzyme, which is believed to play important roles in the development of atherosclerotic vascular disease. We found that COX-2 expression rapidly increases in response to various signaling events, including activation of the platelet-derived growth factor (PDGF) pathway. Activation of PDGF receptor (PDGFR) in rat aortic vascular smooth muscle cells leads to c-Src-dependent stabilization of COX-2 mRNA requiring an AU-rich region within the 3'-untranslated region of this transcript. This regulation correlates with tyrosine phosphorylation of the RNA-associated protein, CUG-binding protein 2 (CUGBP2), which appears to enhance its interaction with COX-2 mRNA. Site-directed mutagenesis of putative tyrosine phosphorylation sites in CUGBP2 identified tyrosine 39 as a c-Src target, and a CUGBP2 with a mutated tyrosine 39 displayed an attenuated ability to bind COX-2 mRNA. We further show that silencing of CUGBP2 with specific small interference RNAs significantly reduces PDGF-dependent induction of COX-2 at both mRNA and protein levels. Furthermore, forced expression of CUGBP2 or constitutively active c-Src leads to stabilization of co-expressed COX-2 mRNA. Finally, in vitro RNA decay assay demonstrates that CUGBP2 is functionally required for the stabilization of COX-2 mRNA. Therefore, our data suggest that tyrosine phosphorylation of CUGBP2 is an important underlying mechanism for the ability of PDGFR/c-Src signaling to control the stability of COX-2 mRNA.

Objectives. To report the toxicity profile of patients treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) receiving doses of 82 Gy or more to portions of their prostate. Methods. Forty-four patients treated with radiation therapy for prostate cancer between June 1992 and August 1998 at the University of California, San Francisco received a maximal dose within the target volume (Dmax) of 82 Gy or more. Eighteen patients were boosted selectively to a limited portion of their prostate using IMRT, whereas 26 patients were treated with 3D-CRT and had unselected “hot spots” within their prostate. The Radiation Therapy Oncology Group (RTOG) acute and late toxicity scales were used to score gastrointestinal (GI) and genitourinary (GU) morbidity. Results. Median follow-up and Dmax were 23.1 months (range 10.0 to 84.7) and 84.5 Gy (range 82.0 to 96.7), respectively. Of the patients, 59.1% and 34.1% developed some level of acute GU and GI toxicity, respectively. One patient experienced grade 3 acute GI toxicity. No other grade 3 or greater acute toxicity was observed. The 2-year actuarial rates for freedom from late GI and GU morbidity were 77.1% (95% confidence interval [CI] 60.4% to 87.5%) and 79.5% (95% CI 62.7% to 89.3%), respectively. Although no grade 3 or greater late GU morbidity has been observed to date, 3 patients experienced grade 3 late GI morbidity. However, these cases involved rectal bleeding and were effectively managed with laser coagulation/fulguration. Conclusions. Doses of 82 Gy or more to a portion of the prostate gland can be tolerated with acceptable morbidity. This observation supports the continued investigation of IMRT as a means for improving disease control in prostate cancer.

In this paper, a three species thermomechanical constitutive model for Shape Memory Alloy (SMA) actuators, based on previous work by Boyd and Lagoudas (Proceedings of the 4th International Symposium on Plasticity and its Current Applications, Baltimore, MD, 19–23 July, 1993) is developed. The three species that contribute to the specific free energy of SMA are: self-accommodated martensite, detwinned martensite and austenite. The total martensitic volume fraction is decomposed into two parts: self-accommodated and detwinned martensite. The dissipation potentials, utilized for the evolution of the volume fractions of the two parts of martensite, are explicity given for 1-D. The concept of critical stress associated with detwinning of self-accommodated martensite, is introduced to incorporate the observed phenomenon during cooling of SMA actuators. The constitutive model described above is well suited for applications in active structures, because the maximum amount of the detwinned martensitic volume fraction is related to the current stress and temperature of the SMA actuator. This maximum amount of volume fraction can be reached during cooling in a constrained structural environment and is determined by the evolution of the internal variables. A prototype structural example, which is a flexible cantilever beam with an externally attached SMA actuator, is used to demonstrate the capability to predict the residual deformation and stress upon cooling.

The development of brain metastases from any primary cancer generally portends a very limited life expectancy. Without treatment, the median length of survival of patients with neurologic symptoms is about 1 month. 36 Although pharmacologic therapies aimed at reducing cerebral edema often improve symptoms, these interventions have little impact on patient survival. 24,46 The mainstay of treatment for patients with brain metastases has been fractionated radiation therapy since the first reports of its effectiveness. 11,13 In the early 1970s, the Radiation Therapy Oncology Group (RTOG) conducted randomized trials that helped define optimal dose fractionation schemes for whole-brain radiation therapy (WBRT). 4,5,31 Although WBRT can alleviate neurologic symptoms, its impact on survival remains modest: Median survival is typically 12 to 24 weeks 4,34,38 and may approach 30 weeks. 18 Other forms of therapy for patients with brain metastases include chemotherapy, which has not been shown to improve patient survival, 23,42 and surgery. The latter has been evaluated in clinical trials in highly selected patients with a single brain metastasis. In one randomized trial, Patchell et al 38 observed significantly improved median survival (40 weeks versus 15 weeks) and local control (18/25 patients versus 11/23 patients) with resection followed by WBRT as opposed to WBRT alone. In a similar randomized trial, Noordijk et al 37 observed a median survival of 10 months in patients treated with resection followed by WBRT versus 6 months in patients treated with WBRT alone. Although patients with multiple brain metastases usually do not have surgery for each separate gross tumor focus in the brain, Bindal et al 3 showed that survival in such surgically treated patients was similar to that of patients with a solitary brain metastasis that was surgically resected. Nonetheless, most patients are not good candidates for gross total resection, either because of tumor location in the brain or because of concomitant medical problems. In addition, patients with recurrent brain metastases who have failed previous WBRT may be ineligible for further fractionated radiation therapy. In all these patients, as well as in patients who may have undergone subtotal resection, radiosurgery has often been recommended, both because it is a noninvasive procedure that requires minimal hospitalization and because retrospective reports have shown improved survival and local control compared with historical results of conventional fractionated radiation therapy. 1,14,15,19,20,21,30,32,33,36 However, no randomized studies have sorted out the relative efficacy of WBRT, radiosurgery, and surgery or combinations of these therapies. The existing studies specifically involving melanoma brain metastases are listed in Table 1. Although the role of radiosurgery for melanoma brain metastases has not been defined, it may provide local control rates comparable to those of conventional surgery. This is supported by a small retrospective series by Samoza et al, 44 in which 23 patients with melanoma metastases to the brain were treated with WBRT and adjuvant Gamma Knife (Elekta Instruments S.A., Geneva, Switzerland) radiosurgery. They observed a median survival of 28 weeks after radiosurgery and a 97% local tumor control rate. In this article we review patients with single or multiple intracranial melanoma metastases treated at the University of California, San Francisco (UCSF), with Gamma Knife radiosurgery.

Quantum yields (Φλ) of hydrogen peroxide (HOOH) photoproduction are reported at 313, 334, and 366 nm for authentic cloud waters collected over a three-year period (1991–1993) at Whiteface Mountain, New York. Quantum yields of HOOH production (based on the total sample absorbance) in these cloud waters ranged up to 0.014. For each sample the HOOH quantum yield decreased with increasing wavelength: Φ313 > Φ334 > Φ366. Action spectra for HOOH photoproduction in these cloud waters indicate that light between 290 and 380 nm is primarily responsible for the aqueous-phase HOOH photoproduction in tropospheric water drops. Quantum yields at 334 and 366 nm were each highly correlated with quantum yields at 313 nm. The cloud water absorbances per centimeter at 334 and 313 nm were also highly correlated. This suggests that similar classes; of chromophores were responsible for the aqueous-phase HOOH photoformation in the cloud waters from different events over a three-year period. The chromophores have not been identified, thus absolute quantum yields for HOOH formation from specific chromophores in an authentic sample could not be calculated. Comparisons of wavelength-dependent relative quantum yields in a given authentic cloud water sample (assuming Fe(oxalate)2− was the primary source of HOOH) with those for Fe(oxalate)2− in well-defined aqueous systems indicate that photolysis of Fe(oxalate)2− was not the primary source of HOOH photoproduction in any of the nine authentic cloud water samples studied. Filtration (0.5 μm Teflon) caused only small differences (⩽15% increase) in rates of HOOH photoformation versus unfiltered controls. Filtration through a 0.05 μm polycarbonate membrane filter did not cause distinguishable differences in the ultraviolet-visible absorption spectra of a cloud water sample previously filtered with a 0.5 μm Teflon filter. These observations suggest that particles were neither the dominant source nor the dominant sink of the photoproduced HOOH. Freezing (up to 403 d) caused only minor changes in HOOH photoproduction rates (−9 to + 12%), and in the ultraviolet-visible absorbance spectra and pH values of the cloud water studied. These observations indicate that freeze-thaw cycles in clouds will have only minor influences on the aqueous-phase photoformation of HOOH.