Enhanced structure-function relationship in glaucoma with an anatomically and geometrically accurate neuroretinal rim measurement

yesPurpose: To evaluate the structure–function relationship between disc margin–based rim area (DM-RA) obtained with confocal scanning laser tomography (CSLT), Bruch's membrane opening–based horizontal rim width (BMO-HRW), minimum rim width (BMO-MRW), peripapillary retinal nerve fiber layer thickness (RNFLT) obtained with spectral-domain optical coherence tomography (SD-OCT), and visual field sensitivity. Methods: We examined 151 glaucoma patients with CSLT, SD-OCT, and standard automated perimetry on the same day. Optic nerve head (ONH) and RNFL with SD-OCT were acquired relative to a fixed coordinate system (acquired image frame [AIF]) and to the eye-specific fovea-BMO center (FoBMO) axis. Visual field locations were mapped to ONH and RNFL sectors with fixed Garway-Heath (VFGH) and patient-specific (VFPS) maps customized for various biometric parameters. Results: Globally and sectorally, the structure–function relationships between DM-RA and VFGH, BMO-HRWAIF and VFGH, and BMO-HRWFoBMO and VFPS were equally weak. The R2 for the relationship between DM-RA and VFGH ranged from 0.1% (inferonasal) to 11% (superotemporal) whereas that between BMO-HRWAIF and VFGH ranged from 0.1% (nasal) to 10% (superotemporal). Relatively stronger global and sectoral structure–function relationships with BMO-MRWAIF and with BMO-MRWFoBMO were obtained. The R2 between BMO-MRWAIF and VFGH ranged from 5% (nasal) to 30% (superotemporal), whereas that between BMO-MRWFoBMO and VFPS ranged from 5% (nasal) to 25% (inferotemporal). The structure–function relationship with RNFLT was not significantly different from that with BMO-MRW, regardless of image acquisition method. Conclusions: The structure–function relationship was enhanced with BMO-MRW compared with the other neuroretinal rim measurements, due mainly to its geometrically accurate properties

Non-standard embedding and five-branes in heterotic M-Theory

We construct vacua of M-theory on S^1/Z_2 associated with Calabi-Yau three-folds. These vacua are appropriate for compactification to N=1 supersymmetry theories in both four and five dimensions. We allow for general E_8 x E_8 gauge bundles and for the presence of five-branes. The five-branes span the four-dimensional uncompactified space and are wrapped on holomorphic curves in the Calabi-Yau space. Properties of these vacua, as well as of the resulting low-energy theories, are discussed. We find that the low-energy gauge group is enlarged by gauge fields that originate on the five-brane world-volumes. In addition, the five-branes increase the types of new E_8 x E_8 breaking patterns allowed by the non-standard embedding. Characteristic features of the low-energy theory, such as the threshold corrections to the gauge kinetic functions, are significantly modified due to the presence of the five-branes, as compared to the case of standard or non-standard embeddings without five-branes.Comment: 34 pages, Latex 2e with amsmath, typos removed, factors corrected, refs improve

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Neighborhood search approaches to non-coplanar beam orientation optimization for total marrow irradiation using IMRT

We consider the beam orientation optimization (BOO) problem for total marrow irradiation (TMI) treatment planning using intensity modulated radiation therapy (IMRT). Currently, IMRT is not widely used in TMI treatment delivery; furthermore, the effect of using non-coplanar beam orientations is not known. We propose and implement several variations of a single neighborhood search algorithm that solves the BOO problem effectively when gantry angles and couch translations are considered. Our work shows that the BOO problem for TMI cases can be solved in a clinically acceptable amount of time and leads to treatment plans that are more effective than the conventional approach to TMI.Total marrow irradiation Total body irradiation Intensity modulated radiation therapy Radiotherapy optimization Local search Beam orientation optimization