Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast ...cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10(-7)). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The spectral resolution of the binaural system was measured using a tone-detection task in a binaural analog of the notched-noise technique. Three listeners performed 2-interval, 2-alternative, ...forced choice tasks with a 500-ms out-of-phase signal within 500 ms of broadband masking noise consisting of an "outer" band of either interaurally uncorrelated or anticorrelated noise, and an "inner" band of interaurally correlated noise. Three signal frequencies were tested (250, 500, and 750 Hz), and the asymmetry of the filter was measured by keeping the signal at a constant frequency and moving the correlated noise band relative to the signal. Thresholds were taken for bandwidths of correlated noise ranging from 0 to 400 Hz. The equivalent rectangular bandwidth of the binaural filter was found to increase with signal frequency, and estimates tended to be larger than monaural bandwidths measured for the same listeners using equivalent techniques.
There is increasing recognition of the importance of blood-brain barrier (BBB) disruption in aging, dementia, stroke and multiple sclerosis in addition to more commonly-studied pathologies such as ...tumors. Dynamic contrast-enhanced MRI (DCE-MRI) is a method for studying BBB disruption in vivo. We review pathologies studied, scanning protocols and data analysis procedures to determine the range of available methods and their suitability to different pathologies. We systematically review the existing literature up to February 2014, seeking studies that assessed BBB integrity using T1-weighted DCE-MRI techniques in animals and humans in normal or abnormal brain tissues. The literature search provided 70 studies that were eligible for inclusion, involving 417 animals and 1564 human subjects in total. The pathologies most studied are intracranial neoplasms and acute ischemic strokes. There are large variations in the type of DCE-MRI sequence, the imaging protocols and the contrast agents used. Moreover, studies use a variety of different methods for data analysis, mainly based on model-free measurements and on the Patlak and Tofts models. Consequently, estimated K (Trans) values varied widely. In conclusion, DCE-MRI is shown to provide valuable information in a large variety of applications, ranging from common applications, such as grading of primary brain tumors, to more recent applications, such as assessment of subtle BBB dysfunction in Alzheimer's disease. Further research is required in order to establish consensus-based recommendations for data acquisition and analysis and, hence, improve inter-study comparability and promote wider use of DCE-MRI.
The "cocktail party problem" was studied using virtual stimuli whose spatial locations were generated using anechoic head-related impulse responses from the AUDIS database Blauert et al., J. Acoust. ...Soc. Am. 103, 3082 (1998). Speech reception thresholds (SRTs) were measured for Harvard IEEE sentences presented from the front in the presence of one, two, or three interfering sources. Four types of interferer were used: (1) other sentences spoken by the same talker, (2) time-reversed sentences of the same talker, (3) speech-spectrum shaped noise, and (4) speech-spectrum shaped noise, modulated by the temporal envelope of the sentences. Each interferer was matched to the spectrum of the target talker. Interferers were placed in several spatial configurations, either coincident with or separated from the target. Binaural advantage was derived by subtracting SRTs from listening with the "better monaural ear" from those for binaural listening. For a single interferer, there was a binaural advantage of 2-4 dB for all interferer types. For two or three interferers, the advantage was 2-4 dB for noise and speech-modulated noise, and 6-7 dB for speech and time-reversed speech. These data suggest that the benefit of binaural hearing for speech intelligibility is especially pronounced when there are multiple voiced interferers at different locations from the target, regardless of spatial configuration; measurements with fewer or with other types of interferers can underestimate this benefit.
Four experiments sought evidence that listeners can use coherent changes in the frequency or amplitude of harmonics to segregate
concurrent vowels. Segregation was not helped by giving the harmonics ...of competing vowels different patterns of frequency
or amplitude modulation. However, modulating the frequencies of the components of one vowel was beneficial when the other
vowel was not modulated, provided that both vowels were composed of components placed randomly in frequency. In addition,
staggering the onsets of the two vowels, so that the amplitude of one vowel increased abruptly while the amplitude of the
other was stationary, was also beneficial. Thus, the results demonstrate that listeners can group changing harmonics and can
segregate them from stationary harmonics, but cannot use coherence of change to separate two sets of changing harmonics.
Impaired cargo trafficking and the aggregation of intracellular macromolecules are key features of neurodegeneration, and a hallmark of aged as well as diseased retinal pigment epithelial (RPE) cells ...in the eye. Here, photoreceptor outer segments (POS), which are internalized daily by RPE cells, were modified by UV-irradiation to create oxidatively modified POS (OxPOS). Oxidative modification was quantified by a protein carbonyl content assay. Human ARPE-19 cells were synchronously pulsed with POS or OxPOS to study whether oxidatively modified cargos can recapitulate features of RPE pathology associated with blinding diseases. Confocal immunofluorescence microscopy analysis showed that OxPOS was trafficked to LAMP1, LAMP2 lysosomes and to LC3b autophagy vacuoles. Whilst POS were eventually degraded, OxPOS cargos were sequestered in late compartments. Co-localization of OxPOS was also associated with swollen autolysosomes. Ultrastructural analysis revealed the presence of electron-dense OxPOS aggregates in RPE cells, which appeared to be largely resistant to degradation. Measurement of cellular autofluorescence, using parameters used to assess fundus autofluorescence (FAF) in age-related macular disease (AMD) patients, revealed that OxPOS contributed significantly to a key feature of aged and diseased RPE. This in vitro cell model therefore represents a versatile tool to study disease pathways linked with RPE damage and sight-loss.
The distribution of the K±→π±π+π− decays in the Dalitz plot has been measured by the NA48/2 experiment at the CERN SPS with a sample of 4.71×108 fully reconstructed events. With the standard Particle ...Data Group parameterization the following values of the slope parameters were obtained: g=(−21.134±0.017)%, h=(1.848±0.040)%, k=(−0.463±0.014)%. The quality and statistical accuracy of the data have allowed an improvement in precision by more than an order of magnitude, and are such as to warrant a more elaborate theoretical treatment, including pion–pion rescattering, which is in preparation.
Bone-anchored hearing aids are a widely used method of treating conductive hearing loss, but the benefit of bilateral implantation is limited due to interaural cross-talk. The present study measured ...the phase and level of pure tones reaching each cochlea from a single, mastoid placed bone transducer on normal hearing participants. In principle, the technique could be used to implement a cross-talk cancellation system in those with bilateral bone conductors. The phase and level of probe tones over two insert earphones was adjusted until they canceled sound from a bone transducer (i.e., resulting in perceived silence). Testing was performed in 50-Hz steps between 0.25 and 8 kHz. Probe phase and level results were used to calculate inter-cochlear level and phase differences. The inter-cochlear phase differences of the bone-conducted sound were similar for all three participants showing a relatively linear increase between 4 and 8 kHz. The attenuation characteristics were highly variable over the frequency range as well as between participants. This variability was thought to be related to differences in skull dynamics across the ears. Repeated measurements of cancellation phase and level of the same frequency produced good consistency across sessions from the same participant.
This paper presents the Clarity Speech Corpus, a publicly available, forty speaker British English speech dataset. The corpus was created for the purpose of running listening tests to gauge speech ...intelligibility and quality in the Clarity Project, which has the goal of advancing speech signal processing by hearing aids through a series of challenges. The dataset is suitable for machine learning and other uses in speech and hearing technology, acoustics and psychoacoustics. The data comprises recordings of approximately 10,000 sentences drawn from the British National Corpus (BNC) with suitable length, words and grammatical construction for speech intelligibility testing. The collection process involved the selection of a subset of BNC sentences, the recording of these produced by 40 British English speakers, and the processing of these recordings to create individual sentence recordings with associated transcripts and metadata.
The use of various types of filtering facepiece class 3 (FFP3) mask have become commonplace since the Covid-19 outbreak. These have been evaluated in terms of efficacy regarding aerosol filtration ...but less emphasis has been placed on the acoustic effects of such masks and their consequences for clinical communication.
A microphone 65 cm from a sound-producing Head and Torso Simulator (wearing the masks) was used to measure attenuation via a tone sweep. Predicted impact on speech reception in noise was assessed by weighting the attenuations of cochlear excitation patterns by the frequency importance function of the Speech Intelligibility Index.
We evaluated acoustic attenuation properties of seven FFP3 masks and a Type IIR surgical mask (as a comparator).
The Type IIR mask had the smallest impact on SNR (2.6 dB with visor). Most FFP3s with an addition of a visor (if not already face covering) impacted SNR by approximately 6 dB. The 3 M 6000 was significantly worse (15.8 dB).
Mouth-and-nose covering FFP3s masks had similar effects on SNR (≈6.2 dB with visor). The Tecmen TM-H2 had several advantages over other masks evaluated. It was reusable, allowed lipreading clues and the attenuation was similar to other FFP3s.
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