Cortical tracking of formant modulations derived from silently presented lip movements and its decline with age

The integration of visual and auditory cues is crucial for successful processing of speech, especially under adverse conditions. Recent reports have shown that when participants watch muted videos of speakers, the phonological information about the acoustic speech envelope, which is associated with but independent from the speakers’ lip movements, is tracked by the visual cortex. However, the speech signal also carries richer acoustic details, for example, about the fundamental frequency and the resonant frequencies, whose visuophonological transformation could aid speech processing. Here, we investigated the neural basis of the visuo-phonological transformation processes of these more fine-grained acoustic details and assessed how they change as a function of age. We recorded whole-head magnetoencephalographic (MEG) data while the participants watched silent normal (i.e., natural) and reversed videos of a speaker and paid attention to their lip movements. We found that the visual cortex is able to track the unheard natural modulations of resonant frequencies (or formants) and the pitch (or fundamental frequency) linked to lip movements. Importantly, only the processing of natural unheard formants decreases significantly with age in the visual and also in the cingulate cortex. This is not the case for the processing of the unheard speech envelope, the fundamental frequency, or the purely visual information carried by lip movements. These results show that unheard spectral fine details (along with the unheard acoustic envelope) are transformed from a mere visual to a phonological representation. Aging affects especially the ability to derive spectral dynamics at formant frequencies. As listening in noisy environments should capitalize on the ability to track spectral fine details, our results provide a novel focus on compensatory processes in such challenging situations

Stirred, not shaken: genetic structure of the intermediate snail host Oncomelania hupensis robertsoni in an historically endemic schistosomiasis area

<p>Abstract</p> <p>Background</p> <p><it>Oncomelania hupensis robertsoni </it>is the sole intermediate host for <it>Schistosoma japonicum </it>in western China. Given the close co-evolutionary relationships between snail host and parasite, there is interest in understanding the distribution of distinct snail phylogroups as well as regional population structures. Therefore, this study focuses on these aspects in a re-emergent schistosomiasis area known to harbour representatives of two phylogroups - the Deyang-Mianyang area in Sichuan Province, China. Based on a combination of mitochondrial and nuclear DNA, the following questions were addressed: 1) the phylogeography of the two <it>O. h. robertsoni </it>phylogroups, 2) regional and local population structure in space and time, and 3) patterns of local dispersal under different isolation-by-distance scenarios.</p> <p>Results</p> <p>The phylogenetic analyses confirmed the existence of two distinct phylogroups within <it>O. h. robertsoni</it>. In the study area, phylogroups appear to be separated by a mountain range. Local specimens belonging to the respective phylogroups form monophyletic clades, indicating a high degree of lineage endemicity. Molecular clock estimations reveal that local lineages are at least 0.69-1.58 million years (My) old and phylogeographical analyses demonstrate that local, watershed and regional effects contribute to population structure. For example, Analyses of Molecular Variances (AMOVAs) show that medium-scale watersheds are well reflected in population structures and Mantel tests indicate isolation-by-distance effects along waterways.</p> <p>Conclusions</p> <p>The analyses revealed a deep, complex and hierarchical structure in <it>O. h. robertsoni</it>, likely reflecting a long and diverse evolutionary history. The findings have implications for understanding disease transmission. From a co-evolutionary standpoint, the divergence of the two phylogroups raises species level questions in <it>O. h. robertsoni </it>and also argues for future studies relative to the distinctness of the respective parasites. The endemicity of snail lineages at the regional level supports the concept of endemic schistosomiasis areas and calls for future geospatial analyses for a better understanding of respective boundaries. Finally, local snail dispersal mainly occurs along waterways and can be best described by using cost distance, thus potentially enabling a more precise modelling of snail, and therefore, parasite dispersal.</p

SWITCH : A randomised, sequential, open-label study to evaluate the efficacy and safety of Sorafenib-sunitinib versus Sunitinib-sorafenib in the treatment of metastatic renal cell cancer

Background Understanding how to sequence targeted therapies for metastatic renal cell carcinoma (mRCC) is important for maximisation of clinical benefit. Objectives To prospectively evaluate sequential use of the multikinase inhibitors sorafenib followed by sunitinib (So-Su) versus sunitinib followed by sorafenib (Su-So) in patients with mRCC. Design, setting, and participants The multicentre, randomised, open-label, phase 3 SWITCH study assessed So-Su versus Su-So in patients with mRCC without prior systemic therapy, and stratified by Memorial Sloan Kettering Cancer Center risk score (favourable or intermediate). Intervention Patients were randomised to sorafenib 400 mg twice daily followed, on progression or intolerable toxicity, by sunitinib 50 mg once daily (4 wk on, 2 wk off) (So-Su), or vice versa (Su-So). Outcome measurements and statistical analysis The primary endpoint was improvement in progression-free survival (PFS) with So-Su versus Su-So, assessed from randomisation to progression or death during second-line therapy. Secondary endpoints included overall survival (OS) and safety. Results and limitations In total, 365 patients were randomised (So-Su, n = 182; Su-So, n = 183). There was no significant difference in total PFS between So-Su and Su-So (median 12.5 vs 14.9 mo; hazard ratio [HR] 1.01; 90% confidence interval [CI] 0.81–1.27; p = 0.5 for superiority). OS was similar for So-Su and Su-So (median 31.5 and 30.2 mo; HR 1.00, 90% CI 0.77–1.30; p = 0.5 for superiority). More So-Su patients than Su-So patients reached protocol-defined second-line therapy (57% vs 42%). Overall, adverse event rates were generally similar between the treatment arms. The most frequent any-grade treatment-emergent first-line adverse events were diarrhoea (54%) and hand-foot skin reaction (39%) for sorafenib; and diarrhoea (40%) and fatigue (40%) for sunitinib. Conclusions Total PFS was not superior with So-Su versus Su-So. These results demonstrate that sorafenib followed by sunitinib and vice versa provide similar clinical benefit in mRCC

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements