Cochlea-sparing acoustic neuroma treatment with 4π radiation therapy.

PurposeThis study investigates whether 4π noncoplanar radiation therapy can spare the cochleae and consequently potentially improve hearing preservation in patients with acoustic neuroma who are treated with radiation therapy.Methods and materialsClinical radiation therapy plans for 30 patients with acoustic neuroma were included (14 stereotactic radiation surgery [SRS], 6 stereotactic radiation therapy [SRT], and 10 intensity modulated radiation therapy [IMRT]). The 4π plans were created for each patient with 20 optimal beams selected using a greedy column generation method and subsequently recalculated in Eclipse for comparison. Organ-at-risk (OAR) doses, homogeneity index, conformity, and tumor control probability (TCP) were compared. Normal tissue complication probability (NTCP) was calculated for sensorineural hearing loss (SNHL) at 3 and 5 years posttreatment. The dose for each plan was then escalated to achieve 99.5% TCP.Results4π significantly reduced the mean dose to both cochleae by 2.0 Gy (32%) for SRS, 3.2 Gy (29%) for SRT, and 10.0 Gy (32%) for IMRT. The maximum dose to both cochleae was also reduced with 4π by 1.6 Gy (20%), 2.2 Gy (15%), and 7.1 Gy (18%) for SRS, SRT, and IMRT plans, respectively. The reductions in mean/maximum brainstem dose with 4π were also statistically significant. Mean doses to other OARs were reduced by 19% to 56% on average. 4π plans had a similar CN and TCP, with a significantly higher average homogeneity index (0.93 vs 0.92) and significantly lower average NTCP for SNHL at both 3 years (30.8% vs 40.8%) and 5 years (43.3% vs 61.7%). An average dose escalation of approximately 116% of the prescription dose achieved 99.5% TCP, which resulted in 32.6% and 43.4% NTCP for SNHL at 3 years and 46.4% and 64.7% at 5 years for 4π and clinical plans, respectively.ConclusionsCompared with clinical planning methods, optimized 4π radiation therapy enables statistically significant sparing of the cochleae in acoustic neuroma treatment as well as lowering of other OAR doses, potentially reducing the risk of hearing loss

A Paleoethnobotanical Comparison of Mortuary and Village Langford Tradition Sites in Northern Illinois

Archaeologists working in northern Illinois have conducted research on Langford Tradition (ca AD 1100-1450) sites for more than a century. The last 40 years have seen increasing methodological sophistication providing for a relatively nuanced understanding of food technology and resource use. Paleoethnobotany has provided one way to observe the diversity of plant use among Langford site occupants. Using standard paleoethnobotanical practices, plant macroremain from the Robinson Reserve Site (11CK2) are analyzed. The results of the plant macroremain analysis are then compared to existing floral data from the Washington Irving Site (11K52). This research investigates whether site functionality is distinguishable between Langford tradition mortuary and village sites

Meanings and Strategies for Good Health: The Perspectives of Latina Immigrant Mothers in Rural Iowa

Presentation made at Latinos in the Heartland (12th : 2014 : St. Louis, Mo.) and published in the annual conference proceedingLimited research has examined the variety of strategies Latino immigrants, especially those living in rural communities, use to maintain or improve their health. This study identified Latina immigrant mothers? conceptualizations of good health and their strategies to maintain or improve their health. Data from 19 semi-structured interviews with Latina immigrant mothers living in a rural Midwestern community were coded and analyzed using qualitative methods. Results reveal that mothers define being healthy as the absence of illness (i.e., "not being sick") and interpreted health in terms of being physically, mentally, and emotionally well. Mothers identified four primary strategies they implement to maintain or improve their health a) eating healthy food, b) participating in moderate and vigorous physical activities, c) monitoring intake of unhealthy foods, and d) visiting the doctor for preventative care (e.g., checkups). Religious beliefs were also noted as sources of strength to tackle their emotional problems. Understanding how Latina immigrant mothers perceive "being healthy" and perceive the status of their own health, as well as being knowledgeable of the strategies they employ to maintain or improve their health, can assist researchers and practitioners interested in improving health outcomes among Latino immigrant families

Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas.

PurposeGlioblastoma (GBM) remains an incurable disease despite extensive treatment with surgical resection, irradiation, and temozolomide. In line with many other forms of aggressive cancers, GBM is currently under consideration as a target for immunotherapy. However, GBM tends to be nonimmunogenic and exhibits a microenvironment with few or no effector T cells, a relatively low nonsynonymous somatic mutational load, and a low predicted neoantigen burden. GBM also exploits a multitude of immunosuppressive strategies.Methods and materialsA number of immunotherapeutic approaches have been tested with disappointing results. A rationale exists to combine immunotherapy and radiation therapy, which can induce an immunogenic form of cell death with T-cell activation and tumor infiltration.ResultsVarious immunotherapy agents, including immune checkpoint modulators, transforming growth factor beta receptor inhibitors, and indoleamine-2,3-dioxygenase inhibitors, have been evaluated with irradiation in preclinical GBM models, with promising results, and are being further tested in clinical trials.ConclusionsThis review aims to present the basic rationale behind this emerging complementary therapeutic approach in GBM, appraise the current preclinical and clinical data, and discuss the future challenges in improving the antitumor immune response

Systematic Analysis of Clinical Outcomes Following Stereotactic Radiosurgery for Central Neurocytoma.

Central neurocytoma (CN) typically presents as an intraventricular mass causing obstructive hydrocephalus. The first line of treatment is surgical resection with adjuvant conventional radiotherapy. Stereotactic radiosurgery (SRS) was proposed as an alternative therapy for CN because of its lower risk profile. The objective of this systematic analysis is to assess the efficacy of SRS for CN. A systematic analysis for CN treated with SRS was conducted in PubMed. Baseline patient characteristics and outcomes data were extracted. Heterogeneity and publication bias were also assessed. Univariate and multivariate linear regressions were used to test for correlations to the primary outcome: local control (LC). The estimated cumulative rate of LC was 92.2% (95% confidence interval: 86.5-95.7%, p<0.001). Mean follow-up time was 62.4 months (range 3-149 months). Heterogeneity and publication bias were insignificant. The univariate linear regression models for both mean tumor volume and mean dose were significantly correlated with improved LC (p<0.001). Our data suggests that SRS may be an effective and safe therapy for CN. However, the rarity of CN still limits the efficacy of a quantitative analysis. Future multi-institutional, randomized trials of CN patients should be considered to further elucidate this therapy

Regulation of reactive oxygen species during plant immunity through phosphorylation and ubiquitination of RBOHD.

Production of reactive oxygen species (ROS) is critical for successful activation of immune responses against pathogen infection. The plant NADPH oxidase RBOHD is a primary player in ROS production during innate immunity. However, how RBOHD is negatively regulated remains elusive. Here we show that RBOHD is regulated by C-terminal phosphorylation and ubiquitination. Genetic and biochemical analyses reveal that the PBL13 receptor-like cytoplasmic kinase phosphorylates RBOHD's C-terminus and two phosphorylated residues (S862 and T912) affect RBOHD activity and stability, respectively. Using protein array technology, we identified an E3 ubiquitin ligase PIRE (PBL13 interacting RING domain E3 ligase) that interacts with both PBL13 and RBOHD. Mimicking phosphorylation of RBOHD (T912D) results in enhanced ubiquitination and decreased protein abundance. PIRE and PBL13 mutants display higher RBOHD protein accumulation, increased ROS production, and are more resistant to bacterial infection. Thus, our study reveals an intricate post-translational network that negatively regulates the abundance of a conserved NADPH oxidase

Expressing linear equality constraints in feedforward neural networks

We seek to impose linear, equality constraints in feedforward neural networks. As top layer predictors are usually nonlinear, this is a difficult task if we seek to deploy standard convex optimization methods and strong duality. To overcome this, we introduce a new saddle-point Lagrangian with auxiliary predictor variables on which constraints are imposed. Elimination of the auxiliary variables leads to a dual minimization problem on the Lagrange multipliers introduced to satisfy the linear constraints. This minimization problem is combined with the standard learning problem on the weight matrices. From this theoretical line of development, we obtain the surprising interpretation of Lagrange parameters as additional, penultimate layer hidden units with fixed weights stemming from the constraints. Consequently, standard minimization approaches can be used despite the inclusion of Lagrange parameters -- a very satisfying, albeit unexpected, discovery. Examples ranging from multi-label classification to constrained autoencoders are envisaged in the future