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Speech is perceived with both the ears and the eyes. Adding congruent visual speech improves the perception of a faint auditory speech stimulus, whereas adding incongruent visual speech can alter the perception of the utterance. The latter phenomenon is the case of the McGurk illusion, where an auditory stimulus such as e.g. “ba” dubbed onto a visual stimulus such as “ga” produces the illusion of hearing “da”. Bayesian models of multisensory perception suggest that both the enhancement and the illusion case can be described as a two-step process of binding (informed by prior knowledge) and fusion (informed by the information reliability of each sensory cue). However, there is to date no study which has accounted for how they each contribute to audiovisual speech perception. In this study, we expose subjects to both congruent and incongruent audiovisual speech, manipulating the binding and the fusion stages simultaneously. This is done by varying both temporal offset (binding) and auditory and visual signal-to-noise ratio (fusion). We fit two Bayesian models to the behavioural data and show that they can both account for the enhancement effect in congruent audiovisual speech, as well as the McGurk illusion. This modelling approach allows us to disentangle the effects of binding and fusion on behavioural responses. Moreover, we find that these models have greater predictive power than a forced fusion model. This study provides a systematic and quantitative approach to measuring audiovisual integration in the perception of the McGurk illusion as well as congruent audiovisual speech, which we hope will inform future work on audiovisual speech perception.

Light-based gamma entrainment using sensory stimuli (GENUS) shows considerable potential for the treatment of Alzheimer’s disease (AD) in both animal and human models. While the clinical efficacy of GENUS for AD is paramount, its effectiveness will eventually also rely on the barrier to treatment adherence imposed by the discomfort of gazing at luminance flickering (LF) light. Currently, there have been few attempts to improve the comfort of GENUS. Here we investigate if Invisible spectral flicker (ISF), a novel type of light-based 40 Hz GENUS for which the flicker is almost imperceptible, can be used as a more comfortable option. We found that whereas ISF, LF, and chromatic flicker (CF) all produce a 40 Hz steady-state visually evoked potential (SSVEP), ISF scores significantly better on measures of comfort and perceived flicker. We also demonstrate that, while there is a trend towards a lower SSVEP response, reducing the stimulation brightness has no significant effect on the 40 Hz SSVEP or perceived flicker, though it significantly improves comfort. Finally, there is a slight decrease in the 40 Hz SSVEP response when stimulating with ISF from increasingly peripheral angles. This may ease the discomfort of GENUS treatment by freeing patients from gazing directly at the light.

There is broad interest in discovering quantifiable physiological biomarkers for psychiatric disorders to aid diagnostic assessment. However, finding biomarkers for autism spectrum disorder (ASD) has proven particularly difficult, partly due to high heterogeneity. Here, we recorded five minutes eyes-closed rest electroencephalography (EEG) from 186 adults (51% with ASD and 49% without ASD) and investigated the potential of EEG biomarkers to classify ASD using three conventional machine learning models with two-layer cross-validation. Comprehensive characterization of spectral, temporal and spatial dimensions of source-modelled EEG resulted in 3443 biomarkers per recording. We found no significant group-mean or group-variance differences for any of the EEG features. Interestingly, we obtained validation accuracies above 80%; however, the best machine learning model merely distinguished ASD from the non-autistic comparison group with a mean balanced test accuracy of 56% on the entirely unseen test set. The large drop in model performance between validation and testing, stress the importance of rigorous model evaluation, and further highlights the high heterogeneity in ASD. Overall, the lack of significant differences and weak classification indicates that, at the group level, intellectually able adults with ASD show remarkably typical resting-state EEG.

Speech perception is influenced by vision through a process of audiovisual integration. This is demonstrated by the McGurk illusion where visual speech (for example /ga/) dubbed with incongruent auditory speech (such as /ba/) leads to a modified auditory percept (/da/). Recent studies have indicated that perception of the incongruent speech stimuli used in McGurk paradigms involves mechanisms of both general and audiovisual speech specific mismatch processing and that general mismatch processing modulates induced theta-band (4-8 Hz) oscillations. Here, we investigated whether the theta modulation merely reflects mismatch processing or, alternatively, audiovisual integration of speech. We used electroencephalographic recordings from two previously published studies using audiovisual sine-wave speech (SWS), a spectrally degraded speech signal sounding nonsensical to naïve perceivers but perceived as speech by informed subjects. Earlier studies have shown that informed, but not naïve subjects integrate SWS phonetically with visual speech. In an N1/P2 event-related potential paradigm, we found a significant difference in theta-band activity between informed and naïve perceivers of audiovisual speech, suggesting that audiovisual integration modulates induced theta-band oscillations. In a McGurk mismatch negativity paradigm (MMN) where infrequent McGurk stimuli were embedded in a sequence of frequent audio-visually congruent stimuli we found no difference between congruent and McGurk stimuli. The infrequent stimuli in this paradigm are violating both the general prediction of stimulus content, and that of audiovisual congruence. Hence, we found no support for the hypothesis that audiovisual mismatch modulates induced theta-band oscillations. We also did not find any effects of audiovisual integration in the MMN paradigm, possibly due to the experimental design.

Speech perception integrates auditory and visual information. This is evidenced by the McGurk illusion where seeing the talking face influences the auditory phonetic percept and by the audiovisual detection advantage where seeing the talking face influences the detectability of the acoustic speech signal. Here, we show that identification of phonetic content and detection can be dissociated as speech-specific and non-specific audiovisual integration effects. To this end, we employed synthetically modified stimuli, sine wave speech (SWS), which is an impoverished speech signal that only observers informed of its speech-like nature recognize as speech. While the McGurk illusion only occurred for informed observers, the audiovisual detection advantage occurred for naïve observers as well. This finding supports a multistage account of audiovisual integration of speech in which the many attributes of the audiovisual speech signal are integrated by separate integration processes.

Information processing in the sensory modalities is not segregated but interacts strongly. The exact nature of this interaction is not known and might differ for different multisensory phenomena. Here, we investigate two cases of categorical audiovisual perception: speech perception and the perception of rapid flashes and beeps.It is known that multisensory interactions in general depend on physical factors, such as information reliability and modality appropriateness, but it is not known how the effects occur. Here we parameterize the effect of information reliability for both our model phenomena. We also describe the effect of modality appropriateness as that of a factor that interacts with the effect of information reliability for counting rapid flashes and beeps.Less explored is whether multisensory perception depends on cognitive factors such as attention. Here we show that visual spatial attention and attentional set influence audiovisual speech perception. Whereas visual spatial attention affected unimodal perception prior to audiovisual integration, attentional set influenced the audiovisual integration stage. We also show a strong effect of intermodal attention on counting rapid flashes and beeps. Finally, we introduce a quantitative model, early maximum likelihood integration (MLI), of the interaction between counted flashes and counted beeps. We compare early MLI to the Fuzzy Logical Model of Perception (FLMP) which is a MLI model based on categorical percepts, and show that early MLI fits the data better using fewer parameters. Early MLI is also able to incorporate the effects of information reliability and intermodal attention in a more efficient way than the FLMP.

Quantum random number generators promise perfectly unpredictable random numbers. A popular approach to quantum random number generation is homodyne measurements of the vacuum state, the ground state of the electro-magnetic field. Here we experimentally implement such a quantum random number generator, and derive a security proof that considers quantum side-information instead of classical side-information only. Based on the assumptions of Gaussianity and stationarity of noise processes, our security analysis furthermore includes correlations between consecutive measurement outcomes due to finite detection bandwidth, as well as analog-to-digital converter imperfections. We characterize our experimental realization by bounding measured parameters of the stochastic model determining the min-entropy of the system’s measurement outcomes, and we demonstrate a real-time generation rate of 2.9 Gbit/s. Our generator follows a trusted, device-dependent, approach. By treating side-information quantum mechanically an important restriction on adversaries is removed, which usually was reserved to semi-device-independent and device-independent schemes. Security analyses for trusted quantum random number generators usually consider only classical side-information. Here, the authors fill this gap by fully characterising the experimental apparatus of a homodyne-based QRNG, assuming that the vacuum fluctuations and noise are stationary and Gaussian.

A quantum key distribution (QKD) system must fulfill the requirement of universal composability to ensure that any cryptographic application (using the QKD system) is also secure. Furthermore, the theoretical proof responsible for security analysis and key generation should cater to the number N of the distributed quantum states being finite in practice. Continuous-variable (CV) QKD based on coherent states, despite being a suitable candidate for integration in the telecom infrastructure, has so far been unable to demonstrate composability as existing proofs require a rather large N for successful key generation. Here we report a Gaussian-modulated coherent state CVQKD system that is able to overcome these challenges and can generate composable keys secure against collective attacks with N  ≈ 2 × 10 8 coherent states. With this advance, possible due to improvements to the security proof and a fast, yet low-noise and highly stable system operation, CVQKD implementations take a significant step towards their discrete-variable counterparts in practicality, performance, and security. Continuous-variable QKD protocols are usually easier to implement than discrete-variables ones, but their security analyses are less developed. Here, the authors propose and demonstrate in the lab a CVQKD protocol that can generate composable keys secure against collective attacks.

BACKGROUNDProteinuria is considered an unfavorable clinical condition that accelerates renal and cardiovascular disease. However, it is not clear whether all forms of proteinuria are damaging. Mutations in CUBN cause Imerslund-Gräsbeck syndrome (IGS), which is characterized by intestinal malabsorption of vitamin B12 and in some cases proteinuria. CUBN encodes for cubilin, an intestinal and proximal tubular uptake receptor containing 27 CUB domains for ligand binding.METHODSWe used next-generation sequencing for renal disease genes to genotype cohorts of patients with suspected hereditary renal disease and chronic proteinuria. CUBN variants were analyzed using bioinformatics, structural modeling, and epidemiological methods.RESULTSWe identified 39 patients, in whom biallelic pathogenic variants in the CUBN gene were associated with chronic isolated proteinuria and early childhood onset. Since the proteinuria in these patients had a high proportion of albuminuria, glomerular diseases such as steroid-resistant nephrotic syndrome or Alport syndrome were often the primary clinical diagnosis, motivating renal biopsies and the use of proteinuria-lowering treatments. However, renal function was normal in all cases. By contrast, we did not found any biallelic CUBN variants in proteinuric patients with reduced renal function or focal segmental glomerulosclerosis. Unlike the more N-terminal IGS mutations, 37 of the 41 proteinuria-associated CUBN variants led to modifications or truncations after the vitamin B12-binding domain. Finally, we show that 4 C-terminal CUBN variants are associated with albuminuria and slightly increased GFR in meta-analyses of large population-based cohorts.CONCLUSIONCollectively, our data suggest an important role for the C-terminal half of cubilin in renal albumin reabsorption. Albuminuria due to reduced cubilin function could be an unexpectedly common benign condition in humans that may not require any proteinuria-lowering treatment or renal biopsy.FUNDINGATIP-Avenir program, Fondation Bettencourt-Schueller (Liliane Bettencourt Chair of Developmental Biology), Agence Nationale de la Recherche (ANR) Investissements d'avenir program (ANR-10-IAHU-01) and NEPHROFLY (ANR-14-ACHN-0013, to MS), Steno Collaborative Grant 2018 (NNF18OC0052457, to TSA and MS), Heisenberg Professorship of the German Research Foundation (KO 3598/5-1, to AK), Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Centre (SFB) KIDGEM 1140 (project 246781735, to CB), and Federal Ministry of Education and Research (BMB) (01GM1515C, to CB).

Ultrasound-guided fine-needle aspiration biopsy (FNAB) is essential for evaluating thyroid nodules but often yields inadequate samples, leading to repeated procedures, increased discomfort, and higher costs. Previous non-randomized studies found promising results of spinal needles to improve diagnostic adequacy. Therefore, we conducted a multicenter randomized controlled trial to validate these findings. Between July 1st, 2021, and April 13th, 2023, patients with suspicious thyroid nodules were randomized to receive FNAB with either a 25G spinal needle or conventional needle. The primary outcome was the rate of adequate diagnostic cytology. Secondary outcomes included procedure-related pain, sensitivity and specificity of FNAB, and adverse events. A total of 359 patients (75.6% female), with a mean age of 59.7 years (range 23-94) were randomized. The rate of adequate diagnostic FNAB was 86.2% (156/181) for the spinal group compared to 84.8% (151/178) for the control group (OR 1.01; 95% CI: 0.95-1.08). The mean pain scale score was 4.0 (SD = 1.8) in the spinal group and 3.9 (SD = 2.0) in the control group (p = 0.40). No complications were observed in either group. We found a significantly better cytological adequacy rate of FNABs performed by physicians with more than four years of experience in the procedure (OR=1.07; 95% CI, 1.01-1.14). No significant improvement was found using spinal needles with a stylet compared to conventional needles. Given the significantly higher cost of spinal needles and comparable diagnostic outcomes, their routine use for thyroid FNAB is not recommended.