Speech intelligibility among modulated and spatially distributed noise sources

At a cocktail party, listeners are faced with multiple, spatially distributed interfering voices. The dominant interfering voice may change from moment to moment and, consequently, change in spatial location. The ability of the binaural system to deal with such a dynamic scene has not been systematically analyzed. Spatial release from masking (SRM) was measured in simple spatial scenes, simulated over headphones with a frontal speech source. For a single noise at 105°, , SRM was reduced if that noise modulated (10 Hz square wave, 50% duty cycle, 20 dB modulation depth), but, for two noises in symmetrical locations, SRM increased if the noises were modulated in alternation, suggesting that the binaural system can “switch” between exploiting different spatial configurations. Experiment 2 assessed the contributions of interaural time and level differences as a function of modulation rate (1–20 Hz). Scenes were created using the original head-related impulse responses and ones that had been manipulated to isolate each cue. SRM decreased steeply with modulation rate. The combined effects of interaural time and level differences were consistent with additive contributions. The results indicate that binaural sluggishness limits the contribution of binaural switching to speech understanding at a cocktail part

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Reproductive biology and biochemical composition of the brooding echinoid Amphipneustes lorioli on the Antarctic continental shelf

The bathyal West Antarctic Peninsula (WAP) shelf experiences intense seasonal variability in primary production, with summer phytoplankton blooms yielding intense pulse of phytodetritus to shelf sediments. Echinoderms form a conspicuous proportion of the deposit-feeding megabenthos on the shelf and of these Amphipneustes lorioli was the most abundant irregular echinoid. To explore the reproductive response of A. lorioli to this seasonal production cycle, A. Lorioli was sampled at one location on the WAP shelf during four separate cruises between March 2000 and March 2001. Reproductive patterns were determined by histological analyses of gonad tissue, and elemental (CHN) analyses were used to estimate the nutritional and energetic status of the body tissues. Histological analysis of the brooding echinoid A. lorioli suggested a quasi-continuous gametogenic pattern in both the ovaries and the testes. Biochemical analysis of the gonads and the gut tissues were consistent with a continuous gametogenic cycle, showing no significant changes in the biochemical composition of the tissues among seasons. Size-frequency distributions of the embryo and juvenile echinoids within the adults’ brood pouches revealed a synchronous recruitment of embryos and juveniles in specific cohorts between different adult specimens. Whilst this occurrence of different cohorts of the developing brood may be an adaptation to limited brood space, there may also be an external factor influencing the synchrony between adult individuals. Nonetheless, a continuous gametogenic cycle and the lack of seasonal variation in the biochemical composition of gonad and gut tissues suggest that this deposit-feeding irregular urchin is exploiting a persistent sediment food bank in WAP shelf sediments throughout much of the year

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Abstract: Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy