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CREBBP truncating mutations and deletions are responsible for the well-known Rubinstein-Taybi syndrome. Recently, a new, distinct CREBBP-linked syndrome has been described: missense mutations located at the 3' end of exon 30 and the 5' portion of exon 31 induce Menke-Hennekam syndrome. Patients with this syndrome present a recognizable facial dysmorphism, intellectual disability of variable severity, microcephaly, short stature, autism, epilepsy, visual and hearing impairments, feeding problems, upper airway infections, scoliosis, and/or kyphosis. To date, all diagnoses were made postnatally. Trio-whole exome sequencing (WES) was performed in a fetus showing increased nuchal translucency persistence and aorta abnormalities at 28 weeks of gestation (WG). WES revealed a CREBBP de novo missense mutation (c.5602C>T; p.Arg1868Trp) in exon 31, previously reported as the cause of Menke-Hennekam syndrome. Termination of pregnancy was performed at 32 WG. We further reviewed the prenatal signs of Menke-Hennekam syndrome already reported. Among the 35 patients reported and diagnosed postnatally up to this day, 15 presented recognizable prenatal signs, the most frequent being intra-uterine growth retardation, brain, and cardiovascular anomalies. Menke-Hennekam is a rare syndrome with unspecific, heterogeneous, and inconstant prenatal symptoms occurring most frequently with the c.5602C>T, p.(Arg1868Trp) mutation. Therefore, the prenatal diagnosis of Menke-Hennekam syndrome is only possible by molecular investigation. Moreover, this case report and review reinforce the importance of performing prenatal WES when unspecific signs are present on imaging.

The French Poison Centers database is a tool of choice for the analysis of poisoning cases requiring the administration of an antidote although not all uses are systematically reported. This national retrospective study aims to report trends of use of antidotes in France over a 7-year period from 2015 to 2021. A total of 25,289 cases of poisoning required the administration of an antidote, among which 46.7% were moderate to severe. While 77.1% of poisonings progressed toward recovery, the observed mortality rate was 1.7%. The 3 most frequently used antidotes according to data from Poison Centers were N-acetylcysteine (n = 13,555 [53.6%]), flumazenil (n = 3102 [12.3%]) and naloxone (n = 1740 [6.9%]) reflecting the most common types of poisoning involving acetaminophen, benzodiazepines, and opioids. The observed use of methylthioninium chloride, hydroxocobalamin, cyanocobalamin and DOAC reversal agents increased, both in terms of absolute numbers and proportions, revealing new behaviors leading to poisoning, such as nitrous oxide consumption. Conversely, the observed use of ethanol-based therapy, L-carnitine, and dantrolene decreased over time, reflecting both current medical practices and shifts in guidelines. This study provides a novel insight into the typology (circumstances, severity, development) of poisonings requiring an antidote, as well as the description of the causative agents.

Active sonar systems increasingly use frequencies below 1 kHz because, due to their low absorption coefficient, these frequencies enable detection ranges of several hundred kilometers. For maximum detection range and range resolution, they require acoustic projectors with high sensitivity, i.e. high peak acoustic power, and high bandwidth. In this research, the use of actively tunable transducers as high bandwidth-sensitivity product, low frequency projectors, is investigated. In low frequency active sonar, the most common signals used are frequency modulated (FM) pulses. The wider the frequency modulation range of the FM pulses, the better the range resolution. The first objective of this research was to establish the form of a tuning law that enables an actively tunable transducer to transmit FM pulses of frequency modulation bandwidth equal to their tunable range. Using numerical simulations of the transient velocity response of a hypothetical low frequency tunable transducer, and the Wigner time-frequency distribution to analyze input and output signals, this tuning law is shown to be tuning the resonance frequency to the instantaneous frequency of the FM pulse. The second objective of this research was to design a low frequency actively tunable transducer having a high effective bandwidth-sensitivity product. The proposed design is a trilaminar disk that exploits the change in flexural rigidity occurring in circular plates when subjected to in-plane loads. Two trilaminar disks are designed using finite element models. A PZT 5H-based disk and a PZT 8-based disk are predicted to have effective bandwidth-sensitivity products 188% and 133% higher, respectively, than those of typical non-tunable trilaminar disks made of the same materials. Prototype transducers made of both materials are built and tested. Experimental results show that PZT 5H experiences property changes under DC electric field and static stress, and is therefore unsuitable for quasi-static tuning applications. PZT 8 is stable and provides a linear, instantaneous, and reversible frequency change. However, due to domain clamping, the experimental bandwidth-sensitivity product is about 65% of the predicted value, or 50% higher than that of a non-tunable trilaminar disk made of the same material.

Low-tidal-volume ventilation with positive end-expiratory pressure is the standard of care in acute respiratory distress syndrome. In this trial, the use of protective ventilation during surgery, as compared with nonprotective ventilation, reduced postoperative complications. Worldwide, more than 230 million patients undergoing major surgery each year require general anesthesia and mechanical ventilation. 1 Postoperative pulmonary complications adversely affect clinical outcomes and health care utilization, 2 so prevention of these complications has become a measure of the quality of hospital care. 3 Previous, large cohort studies have shown that 20 to 30% of patients undergoing surgery with general anesthesia are at intermediate to high risk for postoperative pulmonary complications. 4 , 5 Mechanical ventilation with the use of high tidal volumes (10 to 15 ml per kilogram of predicted body weight) has traditionally been recommended to prevent hypoxemia and atelectasis in . . .

The success of human cooperation crucially depends on mechanisms enabling individuals to detect unreliability in their conspecifics. Yet, how such epistemic vigilance is achieved from naturalistic sensory inputs remains unclear. Here we show that listeners’ perceptions of the certainty and honesty of other speakers from their speech are based on a common prosodic signature. Using a data-driven method, we separately decode the prosodic features driving listeners’ perceptions of a speaker’s certainty and honesty across pitch, duration and loudness. We find that these two kinds of judgments rely on a common prosodic signature that is perceived independently from individuals’ conceptual knowledge and native language. Finally, we show that listeners extract this prosodic signature automatically, and that this impacts the way they memorize spoken words. These findings shed light on a unique auditory adaptation that enables human listeners to quickly detect and react to unreliability during linguistic interactions. It remains unclear whether and how listeners can infer speakers’ reliability from the sound of their voice. Here, the authors show that listeners from several languages rely on a common prosodic signature to infer whether speakers are lying or doubting.

In psychiatry, recent years have seen a change of focus from a clinician- to a patient-centered perspective that emphasizes quality of life as a treatment target. As a complex construct, quality of life is composed of multiple dimensions that interact with one-another (e.g. physical and psychological well-being, relationships, autonomy, self-esteem). Here, we used data from the REHABase cohort, which includes N = 2180 patients from 15 psychosocial rehabilitation centers in France, to explore networks of quality-of-life dimensions among six psychiatric disorders: schizophrenia, neurodevelopmental, bipolar, depressive, anxiety, and personality disorders. Stronger connections (edges) involved the Self-Esteem dimension, such as Self-Esteem–Physical Well-Being, Self-Esteem–Autonomy, Self-Esteem–Psychological Well-Being, and Self-Esteem–Resilience. Self-esteem was also consistently retrieved as the most central node (the dimension with the most connections within each network). Between-group tests did not reveal any differences regarding network structure, overall connectivity, edge-weights, and nodes’ centrality. Despite presenting with different symptom profiles, various psychiatric disorders may demonstrate similar inter-relationships among quality-of-life dimensions. In particular, self-esteem may have a crucial inter-connecting role in patients’ quality of life. Our findings could support treatment programmes that specifically target self-esteem to improve patients’ quality of life in a cost-effective way.

This article addresses the problem of derivative-free (single- or multi-objective) optimization subject to multiple inequality constraints. Both the objective and constraint functions are assumed to be smooth, non-linear and expensive to evaluate. As a consequence, the number of evaluations that can be used to carry out the optimization is very limited, as in complex industrial design optimization problems. The method we propose to overcome this difficulty has its roots in both the Bayesian and the multi-objective optimization literatures. More specifically, an extended domination rule is used to handle objectives and constraints in a unified way, and a corresponding expected hyper-volume improvement sampling criterion is proposed. This new criterion is naturally adapted to the search of a feasible point when none is available, and reduces to existing Bayesian sampling criteria—the classical Expected Improvement (EI) criterion and some of its constrained/multi-objective extensions—as soon as at least one feasible point is available. The calculation and optimization of the criterion are performed using Sequential Monte Carlo techniques. In particular, an algorithm similar to the subset simulation method, which is well known in the field of structural reliability, is used to estimate the criterion. The method, which we call BMOO (for Bayesian Multi-Objective Optimization), is compared to state-of-the-art algorithms for single- and multi-objective constrained optimization.

Human listeners excel at forming high-level social representations about each other, even from the briefest of utterances. In particular, pitch is widely recognized as the auditory dimension that conveys most of the information about a speaker’s traits, emotional states, and attitudes. While past research has primarily looked at the influence of mean pitch, almost nothing is known about how intonation patterns, i.e., finely tuned pitch trajectories around the mean, may determine social judgments in speech. Here, we introduce an experimental paradigm that combines state-of-the-art voice transformation algorithms with psychophysical reverse correlation and show that two of the most important dimensions of social judgments, a speaker’s perceived dominance and trust-worthiness, are driven by robust and distinguishing pitch trajectories in short utterances like the word “Hello,” which remained remarkably stable whether male or female listeners judged male or female speakers. These findings reveal a unique communicative adaptation that enables listeners to infer social traits regardless of speakers’ physical characteristics, such as sex and mean pitch. By characterizing how any given individual’s mental representations may differ from this generic code, the method introduced here opens avenues to explore dysprosody and social-cognitive deficits in disorders like autism spectrum and schizophrenia. In addition, once derived experimentally, these prototypes can be applied to novel utterances, thus providing a principled way to modulate personality impressions in arbitrary speech signals.

The aim of this review was to (1) characterize the time-course of markers of exercise-induced muscle damage (EIMD) based on the level of maximal voluntary contraction torque loss at 24-48h post-exercise (MVC.sub.loss24-48h ), (2) identify factors (e.g., exercise and population characteristics) affecting the level of MVC.sub.loss24-48h, and (3) evaluate the appropriateness of EIMD markers as indicators of MVC.sub.loss24-48h. Magnitude of change of each EIMD markers was normalized using the standardized mean differences method to compare the results from different studies. Time-course of EIMD markers were characterized according to three levels of MVC.sub.loss24-48h based on a clustering analysis of the 141 studies included. Association between MVC.sub.loss24-48h levels and participant's characteristics or exercise type/modalities were assessed. Meta-regressions were performed to investigate the associations between MVC.sub.loss24-48h and EIMD markers changes at 96h after exercise. Time-course of EIMD markers recovery differs between levels of MVC.sub.loss24-48h . Training status and exercise type/modality were associated with MVC.sub.loss24-48h level (p<0.05). MVC.sub.loss24-48h was correlated to changes in myoglobin concentration (<6h), jump height (24h) and range of motion (48h) (p<0.001). As the exercise could differently affect markers as function of the EIMD severity (i.e., MVC.sub.loss24-48h levels), different markers should be used as function of the timing of measurement. Mb concentration should be used during the first hours after the exercise (<6h), whereas jump height (24h) and range of motion (48h) could be used as surrogate for maximal voluntary contraction later. Moreover, training status and exercise type/modality could influence the magnitude of MVC.sub.loss24-48h.

The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa 1 – 3 . It has since spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of around 32 mutations in spike—located mostly in the N-terminal domain and the receptor-binding domain—that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development 4 , and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose. An isolate of the Omicron variant of SARS-COV-2 was completely or partially resistant to neutralization by all nine clinically approved monoclonal antibodies tested.