Attention orienting effects of hesitations in speech: evidence from ERPs

Filled-pause disfluencies such as um and er affect listeners’ comprehension, possibly mediated by attentional mechanisms (J. E. Fox Tree, 2001). However, there is little direct evidence that hesitations affect attention. The current study used an coustic manipulation of continuous speech to induce event-related potential components associated with attention (mismatch negativity [MMN] and P300) during the comprehension of fluent and disfluent utterances. In fluent cases, infrequently occurring acoustically manipulated target words gave rise to typical MMN and P300 components when compared to nonmanipulated controls. In disfluent cases, where targets were preceded by natural sounding hesitations culminating in the filled pause er, an MMN (reflecting a detection of deviance) was still apparent for manipulated words, but there was little evidence of a subsequent P300. This suggests that attention was not reoriented to deviant words in disfluent cases. A subsequent recognition test showed that nonmanipulated words were more likely to be remembered if they had been preceded by a hesitation. Taken together, these results strongly implicate attention in an account of disfluency processing: Hesitations orient listeners’ attention, with consequences for the immediate processing and later representation of an utterance

Implementing a hybrid cognitive-behavioural therapy for pain-related insomnia in primary care : lessons learnt from a mixed-methods feasibility study

Objectives: To test the feasibility of implementing a brief but intensive hybrid cognitive behavioural therapy (Hybrid CBT) for pain-related insomnia. Design: Mixed-methods, with qualitative process evaluation on a two-arm randomised controlled feasibility trial. Setting: Primary care. Participants: Twenty-five adult patients with chronic pain and insomnia. Intervention: Hybrid CBT or self-help control intervention. Primary and secondary outcome measures: Primary outcomes measures were the Insomnia Severity Index and interference scale of the Brief Pain Inventory (BPI). Secondary outcomes measures were the present pain intensity rating from the BPI, Multidimensional Fatigue Inventory, Hospital Anxiety and Depression Scale and EQ-5D-5L. Results: Fourteen participants were randomised to receive Hybrid CBT, 11 to receive the self-help control treatment. Of the 14 in the Hybrid CBT group, 9 (64%) completed all four treatment sessions (4 discontinued due to poor health; 1 due to time constraints). Adherence to the self-help control treatment was not monitored. The total number of participants completing the 12-week and 24-week follow-ups were 12 (6 in each group; Hybrid CBT: 43%; self-help: 55%) and 10 (5 in each group; Hybrid CBT: 36%; self-help: 45%). Based on the data available, candidate outcome measures appeared to be sensitive to changes associated with interventions. Thematic analysis of pre-postintervention interview data revealed satisfaction with treatment content among those who completed the Hybrid CBT, whereas those in the self-help control treatment wanted more contact hours and therapist guidance. Other practical suggestions for improvement included shortening the duration of each treatment session, reducing the amount of assessment paperwork, and minimising the burden of sleep and pain monitoring. Conclusion: Important lessons were learnt with regard to the infrastructure required to achieve better patient adherence and retention. Based on the qualitative feedback provided by a subset of treatment completers, future trials should also consider lowering the intensity of treatment and streamlining the data collection procedure. Trial registration number: ISRCTN17294365

High-fidelity single-shot readout for a spin qubit via an enhanced latching mechanism

The readout of semiconductor spin qubits based on spin blockade is fast but suffers from a small charge signal. Previous work suggested large benefits from additional charge mapping processes, however uncertainties remain about the underlying mechanisms and achievable fidelity. In this work, we study the single-shot fidelity and limiting mechanisms for two variations of an enhanced latching readout. We achieve average single-shot readout fidelities > 99.3% and > 99.86% for the conventional and enhanced readout respectively, the latter being the highest to date for spin blockade. The signal amplitude is enhanced to a full one-electron signal while preserving the readout speed. Furthermore, layout constraints are relaxed because the charge sensor signal is no longer dependent on being aligned with the conventional (2, 0) - (1, 1) charge dipole. Silicon donor-quantum-dot qubits are used for this study, for which the dipole insensitivity substantially relaxes donor placement requirements. One of the readout variations also benefits from a parametric lifetime enhancement by replacing the spin-relaxation process with a charge-metastable one. This provides opportunities to further increase the fidelity. The relaxation mechanisms in the different regimes are investigated. This work demonstrates a readout that is fast, has one-electron signal and results in higher fidelity. It further predicts that going beyond 99.9% fidelity in a few microseconds of measurement time is within reach.Comment: Supplementary information is included with the pape

Aldehyde dehydrogenase 1A1 and gelsolin identified as novel invasion-modulating factors in conditioned medium of pancreatic cancer cells

Conditioned medium (CM) from clonal sub-populations of the pancreatic cancer cell line, MiaPaCa-2 with differing invasive abilities, were examined for their effect on in vitro invasion. Conditioned medium from Clone #3 (CM#3) strongly promoted invasion, while CM from Clone #8 (CM#8) inhibited invasion in vitro. 2D DIGE followed by MALDI-TOF MS analysis of CM#3 and CM#8 identified 41 proteins which were differentially regulated; 27 proteins were down-regulated and 14 proteins up-regulated in the invasion-promoting CM#3 when compared to CM#8. Western blotting analysis confirmed the down-regulated expression of gelsolin and the up-regulation of aldehyde dehydrogenase 1A1 in CM#3. Down-regulation of aldehyde dehydrogenase 1A1 in Clone #3 CM and gelsolin levels in Clone #8 CM by siRNA transfection revealed an important involvement of these proteins in promoting and inhibiting invasion in these pancreatic cancer cell lines

Cancer cell adaptation to hypoxia involves a HIF-GPRC5A-YAP axis

© 2018 The Authors. Published under the terms of the CC BY 4.0 license Hypoxia is a hallmark of solid tumours and a key physiological feature distinguishing cancer from normal tissue. However, a major challenge remains in identifying tractable molecular targets that hypoxic cancer cells depend on for survival. Here, we used SILAC-based proteomics to identify the orphan G protein-coupled receptor GPRC5A as a novel hypoxia-induced protein that functions to protect cancer cells from apoptosis during oxygen deprivation. Using genetic approaches invitro and invivo, we reveal HIFs as direct activators of GPRC5A transcription. Furthermore, we find that GPRC5A is upregulated in the colonic epithelium of patients with mesenteric ischaemia, and in colorectal cancers high GPRC5A correlates with hypoxia gene signatures and poor clinical outcomes. Mechanistically, we show that GPRC5A enables hypoxic cell survival by activating the Hippo pathway effector YAP and its anti-apoptotic target gene BCL2L1. Importantly, we show that the apoptosis induced by GPRC5A depletion in hypoxia can be rescued by constitutively active YAP. Our study identifies a novel HIF-GPRC5A-YAP axis as a critical mediator of the hypoxia-induced adaptive response and a potential target for cancer therapy

Measuring ocean surface velocities with the KuROS and KaRADOC airborne near-nadir Doppler radars: a multi-scale analysis in preparation of the SKIM mission, Submitted to Ocean SCience, July 2019

Surface currents are poorly known over most of the oceans. Satellite-borne Doppler Waves and Current Scatterom-eters (DWCS) can be used to fill this observation gap. The Sea surface KInematics Multiscale (SKIM) proposal, is the first satellite concept built on a DWCS design at near-nadir angles, and now one of the two candidates to become the 9th mission of the European Space Agency Earth Explorer program. As part of the detailed design and feasibility studies (phase A) funded by ESA, airborne measurements were carried out with both a Ku-Band and a Ka-Band Doppler radars looking at the sea surface at 5 near nadir-incidence in a real-aperture mode, i.e. in a geometry and mode similar to that of SKIM. The airborne radar KuROS was deployed to provide simultaneous measurements of the radar backscatter and Doppler velocity, in a side-looking configuration , with an horizontal resolution of about 5 to 10 m along the line of sight and integrated in the perpendicular direction over the real-aperture 3-dB footprint diameter (about 580 m). The KaRADOC system has a much narrower beam, with a circular footprint only 45 m in diameter. 10 The experiment took place in November 2018 off the French Atlantic coast, with sea states representative of the open ocean and a well known tide-dominated current regime. The data set is analyzed to explore the contribution of non-geophysical velocities to the measurement and how the geophysical part of the measured velocity combines wave-resolved and wave-averaged scales. We find that the measured Doppler velocity contains a characteristic wave phase speed, called here C 0 that is analogous to the Bragg phase speed of coastal High Frequency radars that use a grazing measurement geometry, with little 15 variations ∆ C associated to changes in sea state. The Ka-band measurements at an incidence of 12 • are 10% lower than the theoretical estimate C 0 2.4 m/s for typical oceanic conditions defined by a wind speed of 7 m/s and a significant wave height of 2 m. For Ku-band the measured data is 1 https://doi. 30% lower than the theoretical estimate 2.8 m/s. ∆ C is of the order of 0.2 m/s for a 1 m change in wave height, and cannot be confused with a 1 m/s change in tidal current. The actual measurement of the current velocity from an aircraft at 4 to 18 • incidence angle is, however, made difficult by uncertainties on the measurement geometry, which are much reduced in satellite measurements

Prioritizing cleft/craniofacial surgical care after the COVID-19 pandemic

Background: It is anticipated that in due course the burden of emergency care due to COVID-19 infected patients will reduce sufficiently to permit elective surgical procedures to recommence. Prioritizing cleft/craniofacial surgery in the already overloaded medical system will then become an issue. The European Cleft Palate Craniofacial Association, together with the European Cleft and Craniofacial Initiative for Equality in Care, performed a brief survey to capture a current snapshot during a rapidly evolving pandemic. Methods: A questionnaire was sent to the 2242 participants who attended 1 of 3 recent international cleft/craniofacial meetings. Results: The respondents indicated that children with Robin sequence who were not responding to nonsurgical options should be treated as emergency cases. Over 70% of the respondents indicated that palate repair should be performed before the age of 15 months, an additional 22% stating the same be performed by 18 months. Placement of middle ear tubes, primary cleft lip surgery, alveolar bone grafting, and velopharyngeal insufficiency surgery also need prioritization. Children with craniofacial conditions such as craniosynostosis and increased intracranial pressure need immediate care, whilst children with craniosynostosis and associated obstructive sleep apnea syndrome or proptosis need surgical care within 3 months of the typical timing. Craniosynostosis without signs of increased intracranial pressure needs correction before the age of 18 months. Conclusions: This survey indicates several areas of cleft and craniofacial conditions that need prioritization, but also certain areas where intervention is less urgent. We acknowledge that there will be differences in the post COVID-19 response according to circumstances and policies in individual countries