The VLBA Imaging and Polarimetry Survey at 5 GHz

We present the first results of the VLBA Imaging and Polarimetry Survey (VIPS), a 5 GHz VLBI survey of 1,127 sources with flat radio spectra. Through automated data reduction and imaging routines, we have produced publicly available I, Q, and U images and have detected polarized flux density from 37% of the sources. We have also developed an algorithm to use each source's I image to automatically classify it as a point-like source, a core-jet, a compact symmetric object (CSO) candidate, or a complex source. The mean ratio of the polarized to total 5 GHz flux density for VIPS sources with detected polarized flux density ranges from 1% to 20% with a median value of about 5%. We have also found significant evidence that the directions of the jets in core-jet systems tend to be perpendicular to the electric vector position angles (EVPAs). The data is consistent with a scenario in which ~24% of the polarized core-jets have EVPAs that are anti-aligned with the directions of their jet components and which have a substantial amount of Faraday rotation. In addition to these initial results, plans for future follow-up observations are discussed.Comment: 36 pages, 3 tables, 13 figures; accepted for publication in Ap

Tensor electrical impedance myography identifies bulbardisease progression in amyotrophic lateral sclerosis

Objective Electrical impedance myography (EIM) is a promising biomarker for amyotrophic lateral sclerosis (ALS). A key issue is how best to utilise the complex high dimensional, multi-frequency data output by EIM to fully characterise the progression of disease. Methods Muscle volume conduction properties were obtained from EIM recordings of the tongue across three electrode configurations and 14 input frequencies (76 Hz–625 kHz). Analyses of individual frequencies, averaged EIM spectra and non-negative tensor factorisation were undertaken. Longitudinal data were collected from 28 patients and 17 healthy volunteers at 3-monthly intervals for a maximum of 9 months. EIM was evaluated against the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) bulbar sub-score, tongue strength and an overall bulbar disease burden score. Results Longitudinal changes to individual patient EIM spectra demonstrated complex shifts in the spectral shape. At a group level, a clear pattern emerged over time, characterised by an increase in centre frequency and general shift to the right of the spectral shape. Tensor factorisation reduced the spectral data from a total of 168 data points per participant per recording to a single value which captured the complexity of the longitudinal data and which we call tensor EIM (T-EIM). The absolute change in tensor EIM significantly increased within 3 months and continued to do so over the 9-month study duration. In a hypothetical clinical trial scenario tensor EIM required fewer participants (n = 64 at 50% treatment effect), than single frequency measures (n range 87–802) or ALSFRS-R bulbar subscore (n = 298). Conclusions Changes to tongue EIM spectra over time in ALS are complex. Tensor EIM captured and quantified disease progression and was more sensitive to changes than single frequency EIM measures and other biomarkers of bulbar disease. Significance Objective biomarkers for the assessment of bulbar disease in ALS are lacking. Tensor EIM enhances the biomarker potential of EIM data and can improve bulbar symptom monitoring in clinical trials

Tensor electrical impedance myography identifies clinically relevant features in amyotrophic lateral sclerosis

Objective. Electrical impedance myography (EIM) shows promise as an effective biomarker in amyotrophic lateral sclerosis (ALS). EIM applies multiple input frequencies to characterise muscle properties, often via multiple electrode configurations. Herein, we assess if non-negative tensor factorisation (NTF) can provide a framework for identifying clinically relevant features within a high dimensional EIM dataset. Approach. EIM data were recorded from the tongue of healthy and ALS diseased individuals. Resistivity and reactivity measurements were made for 14 frequencies, in three electrode configurations. This gives 84 (2 × 14 × 3) distinct data points per participant. NTF was applied to the dataset for dimensionality reduction, termed tensor EIM. Significance tests, symptom correlation and classification approaches were explored to compare NTF to using all raw data and feature selection. Main Results. Tensor EIM provides highly significant differentiation between healthy and ALS patients (p < 0.001, AUROC = 0.78). Similarly tensor EIM differentiates between mild and severe disease states (p < 0.001, AUROC = 0.75) and significantly correlates with symptoms (ρ = 0.7, p < 0.001). A trend of centre frequency shifting to the right was identified in diseased spectra, which is in line with the electrical changes expected following muscle atrophy. Significance. Tensor EIM provides clinically relevant metrics for identifying ALS-related muscle disease. This procedure has the advantage of using the whole spectral dataset, with reduced risk of overfitting. The process identifies spectral shapes specific to disease allowing for a deeper clinical interpretation

Multi-dimensional electrical impedance myography of the tongue as a potential biomarker for amyotrophic lateral sclerosis

Objective In amyotrophic lateral sclerosis (ALS) bulbar disease biomarkers are lacking. We evaluated a novel tongue electrical impedance myography (EIM) system, utilising both 2D and 3D electrode configurations for detection of tongue pathology. Methods Longitudinal multi-frequency phase angle spectra were recorded from 41 patients with ALS (baseline, 3 and 6 months) and 30 healthy volunteers (baseline and 6 months). ALS functional rating scale-revised (ALSFRS-R) data and quantitative tongue strength measurements were collected. EIM data were analysed for reliability (intra-class correlation coefficient; ICC) and differences between patients and volunteers ascertained using both univariate (Mann-Whitney U test) and multivariate techniques (feature selection and L2 norm). Results The device produced highly reliable data (pooled ICC: 0.836). Significant EIM differences were apparent between ALS patients and healthy volunteers (P<0.001). EIM data demonstrated a significant relationship to tongue strength and bulbar ALSFRS-R scores (P<0.015). The EIM recordings revealed a group level longitudinal change over 6 months and consistently identified patients in whom symptoms or tongue strength changed. Conclusions The novel EIM tongue system produces reliable data and can differentiate between healthy muscle and ALS-related disease. Significance Tongue EIM utilising multiple frequencies and electrode configurations has potential as a bulbar disease biomarker in ALS

Use of electrical impedance spectroscopy to detect malignant and potentially malignant oral lesions

The electrical properties of tissues depend on their architecture and cellular composition. We have previously shown that changes in electrical impedance can be used to differentiate between different degrees of cervical dysplasia and cancer of the cervix. In this proof-of-concept study, we aimed to determine whether electrical impedance spectroscopy (EIS) could distinguish between normal oral mucosa; benign, potentially malignant lesions (PML); and oral cancer. EIS data were collected from oral cancer (n=10), PML (n=27), and benign (n=10) lesions. EIS from lesions was compared with the EIS reading from the normal mucosa on the contralateral side of the mouth or with reference spectra from mucosal sites of control subjects (n=51). Healthy controls displayed significant differences in the EIS obtained from different oral sites. In addition, there were significant differences in the EIS of cancer and high-risk PML versus low-risk PML and controls. There was no significant difference between benign lesions and normal controls. Study subjects also deemed the EIS procedure considerably less painful and more convenient than the scalpel biopsy procedure. EIS shows promise at distinguishing among malignant, PML, and normal oral mucosa and has the potential to be developed into a clinical diagnostic tool

Marine diatoms grown in chemostats under silicate or ammonium limitation. III. Cellular chemical composition and morphology of Chaetoceros debilis, Skeletonema costatum , and Thalassiosira gravida

Three marine diatoms, Skeletonema costatum, Chaetoceros debilis , and Thalassiosira gravida were grown under no limitation and ammonium or silicate limitation or starvation. Changes in cell morphology were documented with photomicrographs of ammonium and silicate-limited and non-limited cells, and correlated with observed changes in chemical composition. Cultures grown under silicate starvation or limitation showed an increase in particulate carbon, nitrogen and phosporus and chlorophyll a per unit cell volume compared to non-limited cells; particulate silica per cell volume decreased. Si-starved cells were different from Si-limited cells in that the former contained more particulate carbon and silica per cell volume. The most sensitive indicator of silicate limitation or starvation was the ratio C:Si, being 3 to 5 times higher than the values for non-limited cells. The ratios Si:chlorophyll a and S:P were lower and N:Si was higher than non-limited cells by a factor of 2 to 3. The other ratios, C:N, C:P, C:chlorophyll a , N:chlorophyll a , P:chlorophyll a and N:P were considered not to be sensitive indicators of silicate limitation or starvation. Chlorophyll a , and particulate nitrogen per unit cell volume decreased under ammonium limitation and starvation. NH 4 -starved cells contained more chlorophyll a , carbon, nitrogen, silica, and phosphorus per cell volume than NH 4 -limited cells. N:Si was the most sensitive ratio to ammonium limitation or starvation, being 2 to 3 times lower than non-limited cells. Si:chlorophyll a , P:chlorophyll a and N:P were less sensitive, while the ratios C:N, C:chlorophyll a , N:chlorophyll a , C:Si, C:P and Si:P were the least sensitive. Limited cells had less of the limiting nutrient per unit cell volume than starved cells and more of the non-limiting nutrients (i.e., silica and phosphorus for NH 4 -limited cells). This suggests that nutrient-limited cells rather than nutrient-starved cells should be used along with non-limited cells to measure the full range of potential change in cellular chemical composition for one species under nutrient limitation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46631/1/227_2004_Article_BF00392568.pd

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Experimental Study of the Dynamic Response of a Ten-Story Reinforced Concrete Frame with a Tall First Story

This report documents the experimental work and presents the response data obtained in three earthquake simulation tests of a ten-story reinforced concrete frame. Changes in the dynamic properties of the test structure, such as apparent frequencies and equivalent damping, are discussed. Observed maximum lateral displacements are compared with those obtained from modal spectral analysis.National Science Foundation Research Grant ENV74-2296