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Olivier Collignon Centre de Recherche Public de la Santé (CRP-Santé), Competences Centre for Methodology and Statistics (CCMS), Strassen, Luxembourg Abstract: Activity of rheumatoid arthritis (RA) can be evaluated using several scoring scales based on clinical features. The most widely used one is the Disease Activity Score involving 28 joint counts (DAS28) for which cut-offs were proposed to help physicians classify patients. However, inaccurate scoring can lead to inappropriate medical decisions. In this article some methodological issues in the design of such a score and its cut-offs are highlighted in order to further propose a strategy to overcome them. As long as the issues reviewed in this article are not addressed, results of studies based on standard disease activity scores such as DAS28 should be considered with caution. Keywords: DAS28, disease activity score, penalized logistic regression, clinical prediction, modeling

Background: Double-blind placebo-controlled food challenge (DBPCFC) is currently considered the gold standard for peanut allergy diagnosis. However, this procedure that requires the hospitalization of patients, mostly children, in specialized centers for oral exposure to allergens may cause severe reactions requiring emergency measures. Thus, a simpler and safer diagnosis procedure is needed. The aim of this study was to evaluate the diagnostic performance of a new set of in vitro blood tests for peanut allergy. Methods: The levels of IgE directed towards peanut extract and recombinant peanut allergens Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 7, and Ara h 8 were measured in 3 groups of patients enrolled at 2 independent centers: patients with proven peanut allergy (n = 166); pollen-sensitized subjects without peanut allergy (n = 61), and control subjects without allergic disease (n = 10). Results: Seventy-nine percent of the pollen-sensitized patients showed IgE binding to peanut, despite their tolerance to peanut. In contrast, combining the results of specific IgE to peanut extract and to recombinant Ara h 2 and Ara h 6 yielded a peanut allergy diagnosis with a 98% sensitivity and an 85% specificity at a positivity threshold of 0.10 kU/l. Use of a threshold of 0.23 kU/l for recombinant Ara h 2 increased specificity (96%) at the cost of sensitivity (93%). Conclusion: A simple blood test can be used to diagnose peanut allergy with a high level of precision. However, DBPCFC will remain useful for the few cases where immunological and clinical observations yield conflicting results. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Objective: Recombinant activated factor VII (rFVIIa), which is used off-label as an adjuvant therapy for uncontrolled and life-threatening bleeding, might also attenuate intractable bleeding related to macrovascular arterial lesions. Here we evaluated the efficacy of rFVIIa in sealing a large arterial wound in haemostatically competent rabbits.Methods: Sixty male New Zealand rabbits were randomly divided into vehicle control and 80 and 200 μg kg⁻¹ rFVIIa groups (n = 20 animals each). A standardized wound of the isolated right carotid artery was made in all rabbits with an 18-G catheter. Bleeding, which was limited by mild compression, was assessed every minute. At 5 min, an intravenous bolus of vehicle or human rFVIIa was given and the animals were further observed for 1 h. Efficacy was assessed from the bleeding duration and blood mass lost. Statistical significance was defined as P less than 0.05. All investigators were blinded to the treatment the animals received.Results: The bleeding duration and blood mass lost were significantly reduced in both rFVIIa dosage groups as compared with the vehicle control group. For the vehicle, 80 and 200 μg kg⁻¹ rFVIIa groups, the median bleeding durations were 56 min (range 7-60 min), 15 min (range 5-60 min) and 10 min (range 5-60 min), respectively; and the median blood mass losses were 22.5 g (range 1-58 g), 12 g (range 0-36 g) and 5 g (range 0-31 g), respectively. The prothrombin time was shorter in the rFVIIa groups. Visual inspection of the carotid artery and microscopic analysis of the liver and kidney revealed neither gross thrombi nor entrapped microthrombi in any rabbit.Conclusion: Recombinant FVIIa at 80 or 200 μg kg⁻¹ promoted the sealing of a large and slightly compressed arterial wound in rabbits. These results suggest a potential role for the drug in the management of massive bleeds due to an arterial lesion when surgical intervention is not immediately and readily available. Safety should remain a matter of concern. [ABSTRACT FROM AUTHOR]

Using a set of psychophysical tests, we compared the olfactory abilities of 8 persons who became blind early in life and 16 sighted persons in a control group who were matched for age, sex, and handedness. The results indicated that those who became blind early in life developed compensatory perceptual mechanisms in the olfactory domain that involve basic sensory processes, such as the detection of odors. [ABSTRACT FROM AUTHOR]

The animal brain is endowed with an innate sense of number allowing to intuitively perceive the approximate quantity of items in a scene, or "numerosity." This ability is not limited to items distributed in space, but also to events unfolding in time and to the average numerosity of dynamic scenes. How the brain computes and represents the average numerosity over time, however, remains unclear. Here, we investigate the mechanisms and EEG signature of the perception of average numerosity over time. To do so, we used stimuli composed of a variable number (3-12) of briefly presented dot arrays (50 msec each) and asked participants to judge the average numerosity of the sequence. We first show that the weight of different portions of the stimuli in determining the judgment depends on how many arrays are included in the sequence itself: the longer the sequence, the lower the weight of the latest arrays. Second, we show systematic adaptation effects across stimuli in consecutive trials. Importantly, the EEG results highlight two processing stages whereby the amplitude of occipital ERPs reflects the adaptation effect (∼300 msec after stimulus onset) and the accuracy and precision of average numerosity judgments (∼450-700 msec). These two stages are consistent with processes involved with the representation of perceived average numerosity and with perceptual decision-making, respectively. Overall, our findings provide new evidence showing how the visual system computes the average numerosity of dynamic visual stimuli, and support the existence of a dedicated, relatively low-level perceptual mechanism mediating this process., (© 2024 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

Philosophers and experimentalists have long debated whether bodily representation of emotion is grounded in our sensory experience. Indeed, we are used to observe emotional reactions expressed through the bodies of others, yet it is still unknown whether this observation influences how we experience affective states in our own bodies. To delve into this question, we developed a naturalistic haptic task and asked a group of early ( n = 20) and late ( n = 20) blind, as well as sighted individuals ( n = 20) to indicate where in the body they perceive changes associated with affective states. Our results show that visual experience shapes bodily representation of emotion. Blind and sighted individuals attribute different importance to body regions in relation to specific emotional states, as sighted people focus more on visceral sensations, while blind report as more relevant the mouth and the hand areas. We also observe differences in the coherence of bodily maps of specific emotions, such as aggressiveness, for which early and late blind are homogenous in reporting the mouth, while sighted subjects demonstrate a scattered pattern of activation across the body. Finally, our findings show that blind people rely on a different organization of affect, as only sighted categorize bodily maps of emotion through the valence and arousal dimensions. In summary, we demonstrate that sensory experience impacts the bodily representation of affect by modulating the relevance that different body parts have in emotional reactions, modifying the weights attributed to interoceptive and exteroceptive signals, and changing how emotions are conceptualized in the body. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

We do not have a veridical representation of our body in our mind. For instance, tactile distances of equal measure along the medial-lateral axis of our limbs are generally perceived as larger than those running along the proximal-distal axis. This anisotropy in tactile distances reflects distortions in body-shape representation, such that the body parts are perceived as wider than they are. While the origin of such anisotropy remains unknown, it has been suggested that visual experience could partially play a role in its manifestation. To causally test the role of visual experience on body shape representation, we investigated tactile distance perception in sighted and early blind individuals comparing medial-lateral and proximal-distal tactile distances of stimuli presented on the ventral and dorsal part of the forearm, wrist, and hand. Overestimation of distances in the medial-lateral over proximal-distal body axes were found in both sighted and blind people, but the magnitude of the anisotropy was significantly reduced in the forearms of blind people. We conclude that vision does not drive the emergence of tactile distance anisotropies, but visual experience can however modulate its expression on some specific body parts., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The ability to reliably discriminate vocal expressions of emotion is crucial to engage in successful social interactions. This process is arguably more crucial for blind individuals, since they cannot extract social information from faces and bodies, and therefore chiefly rely on voices to infer the emotional state of their interlocutors. Blind have demonstrated superior abilities in several aspects of auditory perception, but research on their ability to discriminate vocal features is still scarce and has provided unclear results. Here, we used a gating psychophysical paradigm to test whether early blind people would differ from individually matched sighted controls at the recognition of emotional expressions. Surprisingly, blind people showed lower performance than controls in discriminating specific vocal emotions. We presented segments of nonlinguistic emotional vocalizations of increasing duration (100-400 ms), portraying five basic emotions (fear, happy, sad, disgust, and angry), and we asked our participants for an explicit emotion categorization task. We then calculated sensitivity indices and confusion patterns of their performance. We observed better performance of the sighted group in the discrimination of angry and fearful expression, with no between-group differences for other emotions. This result supports the view that vision plays a calibrating role for specific threat-related emotions specifically. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Our ability to merge information from different senses into a unified percept is a crucial perceptual process for efficient interaction with our multisensory environment. Yet, the developmental process underlying how the brain implements multisensory integration (MSI) remains poorly known. This cross-sectional study aims to characterize the developmental patterns of audiovisual events in 131 individuals aged from 3 months to 30 years. Electroencephalography (EEG) was recorded during a passive task, including simple auditory, visual, and audiovisual stimuli. In addition to examining age-related variations in MSI responses, we investigated Event-Related Potentials (ERPs) linked with auditory and visual stimulation alone. This was done to depict the typical developmental trajectory of unisensory processing from infancy to adulthood within our sample and to contextualize the maturation effects of MSI in relation to unisensory development. Comparing the neural response to audiovisual stimuli to the sum of the unisensory responses revealed signs of MSI in the ERPs, more specifically between the P2 and N2 components (P2 effect). Furthermore, adult-like MSI responses emerge relatively late in the development, around 8 years old. The automatic integration of simple audiovisual stimuli is a long developmental process that emerges during childhood and continues to mature during adolescence with ERP latencies decreasing with age., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Recent studies have shown that during the typical resting-state, echo planar imaging (EPI) time series obtained from the eye orbit area correlate with brain regions associated with oculomotor control and lower-level visual cortex. Here, we asked whether congenitally blind (CB) shows similar patterns, suggesting a hard-wired constraint on connectivity. We find that orbital EPI signals in CB do correlate with activity in the motor cortex, but less so with activity in the visual cortex. However, the temporal patterns of this eye movement-related signal differed strongly between CB and sighted controls. Furthermore, in CB, a few participants showed uncoordinated orbital EPI signals between the two eyes, each correlated with activity in different brain networks. Our findings suggest a retained circuitry between motor cortex and eye movements in blind, but also a moderate reorganization due to the absence of visual input, and the inability of CB to control their eye movements or sense their positions., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Voices are the most relevant social sounds for humans and therefore have crucial adaptive value in development. Neuroimaging studies in adults have demonstrated the existence of regions in the superior temporal sulcus that respond preferentially to voices. Yet, whether voices represent a functionally specific category in the young infant's mind is largely unknown. We developed a highly sensitive paradigm relying on fast periodic auditory stimulation (FPAS) combined with scalp electroencephalography (EEG) to demonstrate that the infant brain implements a reliable preferential response to voices early in life. Twenty-three 4-month-old infants listened to sequences containing non-vocal sounds from different categories presented at 3.33 Hz, with highly heterogeneous vocal sounds appearing every third stimulus (1.11 Hz). We were able to isolate a voice-selective response over temporal regions, and individual voice-selective responses were found in most infants within only a few minutes of stimulation. This selective response was significantly reduced for the same frequency-scrambled sounds, indicating that voice selectivity is not simply driven by the envelope and the spectral content of the sounds. Such a robust selective response to voices as early as 4 months of age suggests that the infant brain is endowed with the ability to rapidly develop a functional selectivity to this socially relevant category of sounds., Competing Interests: Declaration of interests The authors declare no conflict of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Seamlessly extracting emotional information from voices is crucial for efficient interpersonal communication. However, it remains unclear how the brain categorizes vocal expressions of emotion beyond the processing of their acoustic features. In our study, we developed a new approach combining electroencephalographic recordings (EEG) in humans with a frequency-tagging paradigm to 'tag' automatic neural responses to specific categories of emotion expressions. Participants were presented with a periodic stream of heterogeneous non-verbal emotional vocalizations belonging to five emotion categories: anger, disgust, fear, happiness and sadness at 2.5 Hz (stimuli length of 350 ms with a 50 ms silent gap between stimuli). Importantly, unknown to the participant, a specific emotion category appeared at a target presentation rate of 0.83 Hz that would elicit an additional response in the EEG spectrum only if the brain discriminates the target emotion category from other emotion categories and generalizes across heterogeneous exemplars of the target emotion category. Stimuli were matched across emotion categories for harmonicity-to-noise ratio, spectral center of gravity and pitch. Additionally, participants were presented with a scrambled version of the stimuli with identical spectral content and periodicity but disrupted intelligibility. Both types of sequences had comparable envelopes and early auditory peripheral processing computed via the simulation of the cochlear response. We observed that in addition to the responses at the general presentation frequency (2.5 Hz) in both intact and scrambled sequences, a greater peak in the EEG spectrum at the target emotion presentation rate (0.83 Hz) and its harmonics emerged in the intact sequence in comparison to the scrambled sequence. The greater response at the target frequency in the intact sequence, together with our stimuli matching procedure, suggest that the categorical brain response elicited by a specific emotion is at least partially independent from the low-level acoustic features of the sounds. Moreover, responses at the fearful and happy vocalizations presentation rates elicited different topographies and different temporal dynamics, suggesting that different discrete emotions are represented differently in the brain. Our paradigm revealed the brain's ability to automatically categorize non-verbal vocal emotion expressions objectively (at a predefined frequency of interest), behavior-free, rapidly (in few minutes of recording time) and robustly (with a high signal-to-noise ratio), making it a useful tool to study vocal emotion processing and auditory categorization in general and in populations where behavioral assessments are more challenging., (© 2023. The Author(s).)

Background: Neurofilament lightchain has been proposed as a Phase 2 endpoint in clinical trials for multiple sclerosis. We evaluated via simulations the extent to which a positive Phase 2 trial would derisk a Phase 3 trial where the primary endpoint is time to confirmed clinical disability worsening., Methods: Using a prior distribution of the treatment effect on neurofilament lightchain and a model linking it with clinical disability worsening constructed using the FREEDOMS trial in RRMS patients, the probability of success of two randomized controlled Phase 2 and Phase 3 trials were computed for different scenarios., Results: The strength of the correlation between both treatment effects and the success criteria of the Phase 2 trial impact the ability of the Phase 2 to derisk Phase 3. Being more stringent with the success criteria in Phase 2 can increase the Phase 3 PoS by more than 20% after a positive Phase 2 study. Increasing the sample size of the Phase 2 has no substantial impact on the derisking., Conclusion: Under some assumptions a positive Phase 2 trial with neurofilament lightchain as primary endpoint can to a certain extent derisk a Phase 3 trial with clinical disability worsening as primary endpoint., Competing Interests: Declaration of Competing Interest OC is an employee and shareholder of GSK. The content of this article is reflective of the author's personal opinions and are not those of GSK., (Copyright © 2023. Published by Elsevier B.V.)