Comparison of PAX-2, RCC antigen, and antiphosphorylated H2AX antibody (Γ-H2AX) in diagnosing metastatic renal cell carcinoma by fine-needle aspiration

Diagnosing metastatic renal cell carcinoma (RCC) by fine-needle aspiration (FNA) can be challenging. Existing antibodies supporting a diagnosis of RCC, including CD10 and RCC-Ma, have problems with specificity and interpretation. In this report, we evaluate the use of two newer immunostains, PAX-2 and Γ-H2AX, which to our knowledge have not been studied in FNA material, in the diagnosis of metastatic RCC and in comparison with RCC-Ma. 29 cases of metastatic RCC were identified as well as a TMA of an additional 30 RCC cases. In the case cohort, RCC-Ma in a membranous pattern of staining identified 15/27 (56%) metastatic RCC, although interpretation was made difficult in many cases due to focality of staining and non-specific cytoplasmic staining. PAX-2 stained 23/29 (79%) of tumors in a nuclear stain, most strongly. Gamma-H2AX stained 19/26 (73%) of metastatic RCC strongly in a nuclear stain. In the TMA, strong, diffuse nuclear staining with Γ-H2AX was present in 22/30 RCC (73%). If weak staining was also included as positive, 26/30 (87%) were positive. PAX-2 stained RCC TMA with a lower percentage at 56%, including weaker staining intensity. Both PAX-2 and Γ-H2AX demonstrated patchy staining of normal renal tubules, PAX-2 to a greater extent. Both PAX-2 and Γ-H2AX are sensitive markers for the diagnosis of metastatic RCC, with improved ease of interpretation when compared with RCC-Ma. A combination of all 3 markers identified 87% of cases, and failure to stain for both PAX-2 and Γ-H2AX suggests against, but does not disprove, a diagnosis of RCC. Diagn. Cytopathol. 2008; 36: 568–573. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60448/1/20839_ftp.pd

Epidemiology of Danish Aeromonas salmonicida subsp salmonicida in Fish Farms Using Whole Genome Sequencing

Furunculosis, a serious infection caused by the bacterium Aeromonas salmonicida subsp. salmonicida is common in sea-reared rainbow trout production in Denmark. Developing an effective control strategy requires knowledge of the epidemiology, as well as the genomic and virulent variability of the Danish A. salmonicida subsp. salmonicida isolates. To obtain this, the genomes of 101 A. salmonicida subsp. salmonicida, including 99 Danish isolates, one Scottish strain and the type strain NCIMB 1102, were sequenced using the Illumina HiSeq platform. Isolates were de novo assembled, examined for presence of plasmids, virulence and iron acquisition proteins, genomic islands, and antibiotic resistance genes. Single Nucleotide Polymorphisms were aligned and subjected to Bayesian temporal phylogenetic and maximum likelihood tree reconstruction using the published genome of A. salmonicida subsp. salmonicida A449 as reference. Bayesian temporal phylogenetic reconstruction suggests that four major introductions of A. salmonicida subsp. salmonicida into Denmark have occurred. The introductions correlate with the freshwater and subsequent seawater expansion of rainbow trout production. Initial transmission of the bacterium could have been from seawater to freshwater or vice versa, and most minor clades include a mixture of strains from different fresh- and seawater farms. Genomic variation of A. salmonicida subsp. salmonicida mostly appeared to be associated with their plasmids and plasmid encoded virulence factors. Nine A. salmonicida subsp. salmonicida isolates harbored worldwide known antibiotic resistance genes against several antibiotics and there is an indication that 33% of the isolates contained the genomic island AsaGEI1b. These findings not only support the usefulness of whole genome sequencing for genetic studies of homogeneous bacteria in general, but provide novel information about the Danish A. salmonicida subsp. salmonicida population, with implications for vaccine development in efforts to better protect Danish rainbow trout in the future

Impact of frame rate on automatic speech-text alignment for corpus-based phonetic studies

International audiencePhonetic segmentation is the basis for many phonetic and linguistic studies. As manual segmentation is a lengthy and tedious task, automatic procedures have been developed over the years. They rely on acoustic Hidden Markov Models. Many studies have been conducted, and refinements developed for corpus based speech synthesis, where the technology is mainly used in a speaker-dependent context and applied on good quality speech signals. In a different research direction, automatic speech-text alignment is also used for phonetic and linguistic studies on large speech corpora. In this case, speaker independent acoustic models are mandatory, and the speech quality may not be so good. The speech models rely on 10 ms shift between acoustic frames, and their topology leads to strong minimum duration constraints. This paper focuses on the acoustic analysis frame rate, and gives a first insight on the impact of the frame rate on corpus-based phonetic studies

Analysis of prosodic correlates of emotional speech data

International audienceThe study of expressive speech styles remains an important topic as to their parameters detection or prediction in speech processing. In this paper, we analyze prosodic correlates for six emotion styles (anger, disgust, joy, fear, surprise and sadness), using data uttered by two speakers. The analysis is focused on the way pronunciations and prosodic parameters are modified in emotional speech, compared to neutral style. The analysis concerns speech pronunciation modifications, presence of pauses in sentences, and local prosodic behavior, with an emphasis set on the analysis of the prosody over prosodic groups and breathing groups

Acoustical Frame Rate and Pronunciation Variant Statistics

International audienceSpeech technology enables computing statistics on word pronunciation variants as well as investigating various phonetic phenomena. This is achieved through a forced alignment of large amounts of speech signals with their possible pronunciations variants. Such alignments are usually performed using a 10 ms frame shift acoustical analysis. Therefore , the three emitting state structure of conventional acoustic hidden Markov models introduces a minimum duration constraint of 30 ms for each phone segment. This constraint is not critical at low speaking rates, but may introduce artefacts at high speaking rates. Thus, this paper investigates the impact of the acoustical frame rate on corpus-based phonetic statistics. Statistics on pronunciation variants obtained with a shorter frame shift (5 ms) are compared to the statistics resulting from the standard 10 ms frame shift. Statistics are computed on a large speech corpus of more than 3 million running words, and are analyzed with respect to the estimated local speaking rate. Results exhibit some discrepancies between the two sets of statistics, in particular for high speaking rates where the usual acoustic analysis frame shift of 10 ms leads to an underestimation of the frequency of the longest pronunciation variants

Markers associated with genomic instability, immunogenicity and immune therapy responsiveness in Metaplastic carcinoma of the breast : Expression of gamma H2AX, pRPA2, P53, PD-L1 and tumor infiltrating lymphocytes in 76 cases

Peer reviewe

APOBEC3 as a driver of genetic intratumor heterogeneity

Our recent study revealed that APOBEC3B is upregulated during the preinvasive stages of non-small cell lung cancer and breast cancer. In addition to its role in mediating single nucleotide variants, we propose that APOBEC3 promotes copy number intratumor heterogeneity prior to invasion, providing a substrate for cancer evolution