Evaluating and Improving 4D-CT Image Segmentation for Lung Cancer Radiotherapy

Lung cancer is a high-incidence disease with low survival despite surgical advances and concurrent chemo-radiotherapy strategies. Image-guided radiotherapy provides for treatment measures, however, significant challenges exist for imaging, treatment planning, and delivery of radiation due to the influence of respiratory motion. 4D-CT imaging is capable of improving image quality of thoracic target volumes influenced by respiratory motion. 4D-CT-based treatment planning strategies requires highly accurate anatomical segmentation of tumour volumes for radiotherapy treatment plan optimization. Variable segmentation of tumour volumes significantly contributes to uncertainty in radiotherapy planning due to a lack of knowledge regarding the exact shape of the lesion and difficulty in quantifying variability. As image-segmentation is one of the earliest tasks in the radiotherapy process, inherent geometric uncertainties affect subsequent stages, potentially jeopardizing patient outcomes. Thus, this work assesses and suggests strategies for mitigation of segmentation-related geometric uncertainties in 4D-CT-based lung cancer radiotherapy at pre- and post-treatment planning stages

SARA LEE FOODS TAKES FLIGHT: AN ECONOMIC IMPACT ANALYSIS OF A TURKEY PLANT CLOSURE

In 1998, the Sara Lee Corporation implemented a corporate strategy of deverticalization. Bil Mar Foods, Inc., a subsidiary of Sara Lee responsible for the processing of packaged meat products, followed the strategy by shutting down its turkey slaughter facility in Zeeland, Michigan. As a consequence, turkey growers in Michigan were left with no viable outlet for live bird slaughter and the potential end of live bird production in the region. This study analyzes the economic impact associated with the cessation of live bird slaughter at the Bil Mar Foods plant. The economic consequences may be as high as an $81 million loss in total industry output, a$29 million loss in income, and a total employment loss of nearly 800 jobs. Faced with these economic consequences, turkey growers in the region joined forces to form a valued-added cooperative.impact analysis, plant closure, turkey industry, Community/Rural/Urban Development, Livestock Production/Industries,

Model of surface instabilities induced by stress

We propose a model based on a Ginzburg-Landau approach to study a strain relief mechanism at a free interface of a non-hydrostatically stressed solid, commonly observed in thin-film growth. The evolving instability, known as the Grinfeld instability, is studied numerically in two and three dimensions. Inherent in the description is the proper treatment of nonlinearities. We find these nonlinearities can lead to competitive coarsening of interfacial structures, corresponding to different wavenumbers, as strain is relieved. We suggest ways to experimentally measure this coarsening.Comment: 4 pages (3 figures included

Static and Dry Friction due to Multiscale Surface Roughness

It is shown on the basis of scaling arguments that a disordered interface between two elastic solids will quite generally exhibit static and "dry friction" (i.e., kinetic friction which does not vanish as the sliding velocity approaches zero), because of Tomlinson model instabilities that occur for small length scale asperities. This provides a possible explanation for why static and "dry" friction are virtually always observed, and superlubricity almost never occurs

An in silico performance characterization of respiratory motion guided 4DCT for high-quality low-dose lung cancer imaging.

This work aims to characterize the performance of an improved 4DCT technique aiming to overcome irregular breathing-related image artifacts. To address this, we have developed respiratory motion guided (RMG) 4DCT, which uses real-time breathing motion analysis to prospectively gate scans based on detection of irregular breathing. This is the first investigation of RMG-4DCT using a real-time software prototype, testing the hypothesis that it can reduce breathing irregularities during imaging, reduce image oversampling and improve image quality compared to a 'conventional' 4DCT protocol without breathing guidance. RMG-4DCT scans were simulated based on 100+  hours of breathing motion acquired for 20 lung cancer patients. Scan performance was quantified in terms of the beam on time (a surrogate for imaging dose), total scan time and the breathing irregularity during imaging (via RMSE of the breathing motion during acquisition). A conventional 4DCT protocol was also implemented using the same software prototype for a direct comparator to the RMG-4DCT results. We investigated the impact of key RMG-4DCT parameters such as gating tolerance, gantry rotation time and the use of baseline drift correction. Using a representative set of algorithm parameters, RMG-4DCT achieved significant mean reductions in estimated imaging dose (-17.8%, p  <  0.001) and breathing RMSE during imaging (-12.6%, p  <  0.001) compared to conventional 4DCT. These improvements came with increased scan times, roughly doubled on average (104%, p  <  0.001). Image quality simulations were performed using the deformable digital XCAT phantom, with image quality quantified based on the normalized cross correlation (NCC) between axial slices. RMG-4DCT demonstrated qualitative image quality improvements for three out of 10 phase bins, however the improvement was not significant across all 10 phases (p  =  0.08) at a population level. In choosing RMG-4DCT scan parameters, the trade-off between gating sensitivity and scan time may be optimized, demonstrating potential for RMG-4DCT as a viable pathway to improve clinical 4DCT imaging

Naturalness and Higgs Decays in the MSSM with a Singlet

The simplest extension of the supersymmetric standard model - the addition of one singlet superfield - can have a profound impact on the Higgs and its decays. We perform a general operator analysis of this scenario, focusing on the phenomenologically distinct scenarios that can arise, and not restricting the scope to the narrow framework of the NMSSM. We reexamine decays to four b quarks and four tau's, finding that they are still generally viable, but at the edge of LEP limits. We find a broad set of Higgs decay modes, some new, including those with four gluon final states, as well as more general six and eight parton final states. We find the phenomenology of these scenarios is dramatically impacted by operators typically ignored, specifically those arising from D-terms in the hidden sector, and those arising from weak-scale colored fields. In addition to sensitivity of m_Z, there are potential tunings of other aspects of the spectrum. In spite of this, these models can be very natural, with light stops and a Higgs as light as 82 GeV. These scenarios motivate further analyses of LEP data as well as studies of the detection capabilities of future colliders to the new decay channels presented.Comment: 3 figures, 1 appendix; version to appear in JHEP; typos fixed and additional references and acknowledgements adde

Disorder and Sorption Preferences in a Highly Stable Fluoride- Containing Rare-Earth fcu-Type Metal−Organic Framework

Rare-earth (RE) metal−organic frameworks (MOFs) synthesized in the presence of fluorine-donating modulators or linkers are an important new subset of functional MOFs. However, the exact nature of the REaXb core of the molecular building block (MBB) of the MOF, where X is a μ2 or 3-bridging group, remains unclear. Investigation of one of the archetypal members of this family with the stable fcu framework topology, Y-fum-fcu-MOF (1), using a combination of experimental techniques, including high-field (20 T) solid-state nuclear magnetic resonance spectroscopy, has determined two sources of framework disorder involving the μ3-X face-capping group of the MBB and the fumarate (fum) linker. The core of the MBB of 1 is shown to contain a mixture of μ3-F− and (OH)− groups with preferential occupation at the crystallographically different facecapping sites that result in different internally lined framework tetrahedral cages. The fum linker is also found to display a disordered arrangement involving bridging− or chelating−bridging bis-bidentate modes over the fum linker positions without influencing the MBB orientation. This linker disorder will, upon activation, result in the creation of Y3+ ions with potentially one or two additional uncoordinated sites possessing differing degrees of Lewis acidity. Crystallographically determined host−guest relationships for simple sorbates demonstrate the favored sorption sites for N2, CO2, and CS2 molecules that reflect the chemical nature of both the framework and the sorbate species with the structural partitioning of the μ3-groups apparent in determining the favored sorption site of CS2. The two types of disorder found within 1 demonstrate the complexity of fluoride-containing RE-MOFs and highlight the possibility to tune this and other frameworks to contain different proportions and segregations of μ3-face-capping groups and degrees of linker disorder for specifically tailored applications.EPSRC and the University of Manchester for the award of a DTG PhD studentship (EPSRC EP/R513131/1) and funding the dual source Rigaku FR-X diffractometer (EPSRC EP/P001386/1)Henry Royce Institute, funded through EPSRC grants EP/R00661X/1, EP/P025021/1, and EP/P025498/1EPSRC and BBSRC (EP/T015063/1)University of WarwickBirmingham Science City Advanced Materials Projects 1 and 2 supported by Advantage West Midlands (AWM) and the European Regional Development Fund (ERDF

Comparative acute efficacy and tolerability of OROS and immediate release formulations of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder

<p>Abstract</p> <p>Background</p> <p>The main aim of this study was to compare the safety and efficacy of IR MPH administered three times daily to those of once daily OROS-MPH.</p> <p>Methods</p> <p>Subjects were outpatient adults satisfying full diagnostic criteria for DSM-IV ADHD between 19 and 60 years of age. Data from two independently conducted 6-week placebo controlled, randomized clinical trials of IR-MPH (tid) and of OROS-MPH were pooled to create three study groups: Placebo (N = 116), IR-MPH (tid) (N = 102) and OROS-MPH (N = 67).</p> <p>Results</p> <p>Eight-five percent (N = 99) of placebo treated subjects, 77% (N = 79) of the IR-MPH (tid) treated subjects, and 82% (N = 55) of the OROS-MPH treated subjects completed the 6-week trial. Total daily doses at endpoint were 80.9 ± 31.9 mg, 74.8 ± 26.2 mg, and 95.4 ± 26.3 mg in the OROS-MPH, IR-MPH (tid), and placebo groups, respectively. At endpoint, 66% (N = 44) of subjects receiving OROS-MPH and 70% (N = 71) of subjects receiving IR-MPH (tid) were considered responders compared with 31% (N = 36) on placebo.</p> <p>Conclusion</p> <p>Comparison of data from two similarly designed, large, randomized, placebo-controlled, trials, showed that equipotent daily doses of once daily OROS-MPH had similar efficacy to that of TID administered IR MPH.</p> <p>Trial Registration</p> <p>The trial of OROS-MPH was registered at clinicaltrials.gov, number NCT00181571.</p

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient\u27s progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. ©2017 AACR

The AEPEX CubeSat Mission: Quantifying Energetic Particle Precipitation through Bremsstrahlung X-Ray Imaging

Fundamental gaps exist in the understanding and observation of energetic particle precipitation (EPP),a solar-terrestrial coupling mechanism that is vital for climatelogical modeling of the atmosphere and magnetosphere. The Atmospheric Effects of Precipitation through Energetic X-rays (AEPEX) mission is a 6U CubeSat that will measure energetic electron spectra and X-ray images in order to quantify the spatial scales and amount of energy input into the atmosphere, and therefore lost from the magnetosphere, via EPP. AEPEX includes two instruments; AEPEX’s FIRE (Focused Investigations of Relativistic Electron) instrument (AFIRE), a TRL 9 electron detector previously flown on the FIREBIRD mission; and the Atmospheric X-ray Imaging Spectrometer (AXIS), an instrument being developed at CU Boulder that will take novel images and spectra of 50–300 keV X-ray photons. This work describes the AEPEX mission overview, the detailed design and operation of AXIS, and initial test and calibration results