DACH1: its role as a classifier of long term good prognosis in luminal breast cancer

Background: Oestrogen receptor (ER) positive (luminal) tumours account for the largest proportion of females with breast cancer. Theirs is a heterogeneous disease presenting clinical challenges in managing their treatment. Three main biological luminal groups have been identified but clinically these can be distilled into two prognostic groups in which Luminal A are accorded good prognosis and Luminal B correlate with poor prognosis. Further biomarkers are needed to attain classification consensus. Machine learning approaches like Artificial Neural Networks (ANNs) have been used for classification and identification of biomarkers in breast cancer using high throughput data. In this study, we have used an artificial neural network (ANN) approach to identify DACH1 as a candidate luminal marker and its role in predicting clinical outcome in breast cancer is assessed. Materials and methods: A reiterative ANN approach incorporating a network inferencing algorithm was used to identify ER- associated biomarkers in a publically available cDNA microarray dataset. DACH1 was identified in having a strong influence on ER associated markers and a positive association with ER. Its clinical relevance in predicting breast cancer specific survival was investigated by statistically assessing protein expression levels after immunohistochemistry in a series of unselected breast cancers, formatted as a tissue microarray. Results: Strong nuclear DACH1 staining is more prevalent in tubular and lobular breast cancer. Its expression correlated with ER-alpha positive tumours expressing PgR, epithelial cytokeratins (CK)18/19 and 'luminal-like' markers of good prognosis including FOXA1 and RERG (p , 0.05). DACH1 is increased in patients showing longer cancer specific survival and disease free interval and reduced metastasis formation (p , 0.001). Nuclear DACH1 showed a negative association with markers of aggressive growth and poor prognosis. Conclusion: Nuclear DACH1 expression appears to be a Luminal A biomarker predictive of good prognosis, but is not independent of clinical stage, tumour size, NPI status or systemic therapy

A New H I Survey of Active Galaxies

We have conducted a new Arecibo survey for H I emission for 113 galaxies with broad-line (type 1) active galactic nuclei (AGNs) out to recession velocities as high as 35,000 km/s. The primary aim of the study is to obtain sensitive H I spectra for a well-defined, uniformly selected sample of active galaxies that have estimates of their black hole masses in order to investigate correlations between H I properties and the characteristics of the AGNs. H I emission was detected in 66 out of the 101 (65%) objects with spectra uncorrupted by radio frequency interference, among which 45 (68%) have line profiles with adequate signal-to-noise ratio and sufficiently reliable inclination corrections to yield robust deprojected rotational velocities. This paper presents the basic survey products, including an atlas of H I spectra, measurements of H I flux, line width, profile asymmetry, optical images, optical spectroscopic parameters, as well as a summary of a number of derived properties pertaining to the host galaxies. To enlarge our primary sample, we also assemble all previously published H I measurements of type 1 AGNs for which can can estimate black hole masses, which total an additional 53 objects. The final comprehensive compilation of 154 broad-line active galaxies, by far the largest sample ever studied, forms the basis of our companion paper, which uses the H I database to explore a number of properties of the AGN host galaxies.Comment: To appear in ApJS; 31 pages. Preprint will full-resolution figures can be downloaded from http://www.ociw.edu/~lho/preprints/ms1.pd

Preoperative and postoperative features of macular holes on en face imaging and optical coherence tomography angiography

AbstractPurposeTo characterize and quantify the pre- and postoperative foveal structural and functional patterns in full-thickness macular holes.MethodsSubjects presenting with a full-thickness macular hole that had pre- and postoperative imaging were included. En face optical coherence tomography (OCT) and OCT angiography (OCTA) was performed. Foveal avascular zone (FAZ) area, macular hole size, number and size of perifoveal cysts were measured.ResultsFive eyes from 5 patients were included in the study. The hole was closed in all eyes after the initial surgery. OCTA showed enlargement of the FAZ and delineation of the holes within the FAZ. Mean preoperative FAZ area was 0.41 ± 0.104 mm2. Visual acuity was improved and mean FAZ area was reduced to 0.27 ± 0.098 mm2 postoperatively (P < 0.05) with resolution of the macular hole and adjacent cystic areas. En face images of the middle retina showed a range of preoperative cystic patterns surrounding the hole. Smaller holes showed fewer but larger cystic areas and larger holes had more numerous but smaller cystic areas.Conclusions and ImportanceQuantitative evaluation of vascular and cystic changes following macular hole repair demonstrates the potential for recovery due to neuronal and vascular plasticity. Perifoveal microstructural patterns and their quantitative characteristics may serve as useful anatomic biomarkers for assessment of macular holes

Reducing malaria misdiagnosis: the importance of correctly interpreting Paracheck Pf® "faint test bands" in a low transmission area of Tanzania

Although malaria rapid diagnostic tests (RDTs) have been extensively evaluated since their introduction in the early 1990's, sensitivity and specificity vary widely limiting successful integration into clinical practice. This paper reviews specific issues surrounding RDT use in field settings and presents results of research investigating how to interpret "faint test bands" on ParaCheck Pf® in areas of low transmission in order to reduce malaria misdiagnosis.\ud A multi-phase cross-sectional study was conducted at a remote hospital in the northern Tanzanian highlands. Capillary blood samples were taken from consenting participants (n = 319) for blood smear and ParaCheck Pf® testing. Primary outcome variables were sensitivity, specificity and proportion misdiagnosed by ParaCheck Pf® and local microscopy. ParaCheck Pf® "faint bands" were classified as both true positives or true negatives during evaluation to determine appropriate clinical interpretation. Multivariate logistic regression adjusted for age and gender was conducted to determine odds of misdiagnosis for local microscopy and ParaCheck Pf®. Overall, 23.71% of all ParaCheck Pf® tests resulted in a "faint band" and 94.20% corresponded with true negatives. When ParaCheck Pf® "faint bands" were classified as positive, specificity was 75.5% (95% CI = 70.3%-80.6%) as compared to 98.9% (95% CI = 97.0%-99.8%) when classified as negative. The odds of misdiagnosis by local microscopy for those > 5 years as compared to those ≤ 5 years are 0.370 (95% CI = 0.1733-0.7915, p = 0.010). In contrast, even when ParaCheck Pf® faint bands are considered positive, the odds of misdiagnosis by ParaCheck Pf® for those > 5 years as compared to those ≤ 5 years are 0.837 (95% CI = 0.459-1.547, p = 0.5383). We provide compelling evidence that in areas of low transmission, "faint bands" should be considered a negative test when used to inform clinical decision-making. Correct interpretation of RDT test bands in a clinical setting plays a central role in successful malaria surveillance, appropriate patient management and most importantly reducing misdiagnosis

The Narrow-Line Regions of LINERs as Resolved with the Hubble Space Telescope

LINERs exist in the nuclei of a large fraction of luminous galaxies, but their connection with the AGN phenomenon has remained elusive. We present Hubble Space Telescope narrowband [O III]5007 and H-alpha+[N II] emission-line images of the central regions of 14 galaxies with LINER nuclei. The compact, ~1 arcsec-scale, unresolved emission that dominates the line flux in ground-based observations is mostly resolved by HST. The bulk of this emission comes from regions with sizes of tens to hundreds of parsecs that are resolved into knots, filaments, and diffuse gas whose morphology differs from galaxy to galaxy. Most of the galaxies do not show clear linear structures or ionization cones analogous to those often seen in Seyfert galaxies. An exception is NGC 1052, the prototypical LINER, in which we find a 3 arcsec-long (~ 250 pc) biconical structure that is oriented on the sky along the galaxy's radio jet axis. Seven of the galaxies have been shown in previously published HST images to have a bright compact ultraviolet nuclear source, while the other seven do not have a central UV source. Our images find evidence of dust in the nuclear regions of all 14 galaxies, with clear indications of nuclear obscuration in most of the "UV-dark" cases. The data suggest that the line-emitting gas in most LINERs is photoionized by a central source (which may be stellar, nonstellar, or a combination thereof) but that this source is often hidden from direct view. We find no obvious morphological differences between LINERs with detected weak broad H-alpha wings in their spectra and those with only narrow lines. Likewise, there is no clear morphological distinction between objects whose UV spectra are dominated by hot stars (e.g., NGC 4569) and those that are AGN-like (e.g., NGC 4579).Comment: Accepted for publication in the ApJ. 25 pages, 3 tables, 9 JPEG Figure

Personality and functional vision in older adults with age-related macular degeneration

Introduction: The purpose of the study was to determine whether personality traits influence self-reported functional vision in patients with age-related macular degeneration (AMD). Methods: This is a prospective cross-sectional analysis of baseline data from the Low Vision Depression Prevention Trial. Participants (N = 182) over age 65 with bilateral AMD, visual acuity worse than 20/70 in the better-seeing eye, and subthreshold depression were recruited from the Wills Eye Hospital retina practice. Assessments included visual acuity, contrast sensitivity, National Eye Institute Visual Function Questionnaire-25 plus Supplement (NEI VFQ-25) near and distance subscales, depression, and personality testing. Structural equation models were used to investigate the relationship of the NEI VFQ near activities and distance activities with the various demographic, clinical, and psychological predictors. Results: In the single-predictor model for near functional vision, visual acuity at logMAR ≤ 1 (estimate = -0.33 [95% confidence interval {CI} -0.46, -0.20]; p ≤ 0.001), neuroticism (estimate = -0.05 [95% CI -0.08, -0.01]; p = 0.01), and education (estimate = -0.08 [95% CI 0.01, 0.15]; p = 0.03) were statistically significant predictors. In the single-predictor model for distance functional vision, only visual acuity at logMAR ≤ 1 (estimate = -0.49 [95% CI -0.69, -0.29]; p ≤ 0.001) and neuroticism (estimate = -0.09 [95% CI -0.15, 0.02]; p = 0.008) were statistically significant predictors. Discussion: Self-reported functional vision depends on the severity of vision loss as well as the personality trait of neuroticism. Implications for practitioners: Assessment of personality traits, particularly neuroticism, may increase the precision of rating scales of functional vision and suggest new rehabilitative interventions to improve the functional vision and quality of life of patients with AMD © 2014 AFB, All Rights Reserved

Structure and dynamics of Rh surfaces

Lattice relaxations, surface phonon spectra, surface energies, and work functions are calculated for Rh(100) and Rh(110) surfaces using density-functional theory and the full-potential linearized augmented plane wave method. Both, the local-density approximation and the generalized gradient approximation to the exchange-correlation functional are considered. The force constants are obtained from the directly calculated atomic forces, and the temperature dependence of the surface relaxation is evaluated by minimizing the free energy of the system. The anharmonicity of the atomic vibrations is taken into account within the quasiharmonic approximation. The importance of contributions from different phonons to the surface relaxation is analyzed.Comment: 9 pages, 7 figures, scheduled to appear in Phys. Rev. B, Feb. 15 (1998). Other related publications can be found at http://www.rz-berlin.mpg.de/th/paper.htm

A targeted gene panel that covers coding, non-coding and short tandem repeat regions improves the diagnosis of patients with neurodegenerative diseases

Genetic testing for neurodegenerative diseases (NDs) is highly challenging because of genetic heterogeneity and overlapping manifestations. Targeted-gene panels (TGPs), coupled with next-generation sequencing (NGS), can facilitate the profiling of a large repertoire of ND-related genes. Due to the technical limitations inherent in NGS and TGPs, short tandem repeat (STR) variations are often ignored. However, STR expansions are known to cause such NDs as Huntington\u27s disease and spinocerebellar ataxias type 3 (SCA3). Here, we studied the clinical utility of a custom-made TGP that targets 199 NDs and 311 ND-associated genes on 118 undiagnosed patients. At least one known or likely pathogenic variation was found in 54 patients; 27 patients demonstrated clinical profiles that matched the variants; and 16 patients whose original diagnosis were refined. A high concordance of variant calling were observed when comparing the results from TGP and whole-exome sequencing of four patients. Our in-house STR detection algorithm has reached a specificity of 0.88 and a sensitivity of 0.82 in our SCA3 cohort. This study also uncovered a trove of novel and recurrent variants that may enrich the repertoire of ND-related genetic markers. We propose that a combined comprehensive TGPs-bioinformatics pipeline can improve the clinical diagnosis of NDs