Resilience and Mental-Health Symptoms in ICU Healthcare Professionals Facing Repeated COVID-19 Waves.

Rationale: Psychological resilience (the ability to thrive in adversity) may protect against mental-health symptoms in healthcare professionals during coronavirus disease (COVID-19) waves. Objectives: To identify determinants of resilience in ICU staff members. Methods: In this cross-sectional survey in 21 French ICUs, staff members completed the 10-item Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Impact of Event Scale-Revised (for post-traumatic stress disorder [PTSD]). Factors independently associated with resilience were identified. Measurements and Main Results: The response rate was 73.1% (950 of 1,300). The median 10-item Connor-Davidson Resilience Scale score was 29 (interquartile range, 25-32). Symptoms of anxiety, depression, and PTSD were present in 61%, 39%, and 36% of staff members, respectively. Distress associated with the COVID-19 infodemic was correlated with symptoms of depression and PTSD. More resilient respondents less often had symptoms of anxiety, depression, and PTSD. Greater resilience was independently associated with male sex, having provided intensive care during the early waves, having managed more than 50 patients with COVID-19, and, compared with earlier waves, working longer hours, having greater motivation, and more often involving families in end-of-life decisions. Independent risk factors for lower resilience were having managed more than 10 patients who died of COVID-19, having felt frightened or isolated, and greater distress from the COVID-19 infodemic. Conclusions: This study identifies modifiable determinants of resilience among ICU staff members. Longitudinal studies are needed to determine whether prior resilience decreases the risk of mental ill health during subsequent challenges. Hospital and ICU managers, for whom preserving mental well-being among staff members is a key duty, should pay careful attention to resilience.

Multilevel development of cognitive abilities in an artificial neural network.

Several neuronal mechanisms have been proposed to account for the formation of cognitive abilities through postnatal interactions with the physical and sociocultural environment. Here, we introduce a three-level computational model of information processing and acquisition of cognitive abilities. We propose minimal architectural requirements to build these levels, and how the parameters affect their performance and relationships. The first sensorimotor level handles local nonconscious processing, here during a visual classification task. The second level or cognitive level globally integrates the information from multiple local processors via long-ranged connections and synthesizes it in a global, but still nonconscious, manner. The third and cognitively highest level handles the information globally and consciously. It is based on the global neuronal workspace (GNW) theory and is referred to as the conscious level. We use the trace and delay conditioning tasks to, respectively, challenge the second and third levels. Results first highlight the necessity of epigenesis through the selection and stabilization of synapses at both local and global scales to allow the network to solve the first two tasks. At the global scale, dopamine appears necessary to properly provide credit assignment despite the temporal delay between perception and reward. At the third level, the presence of interneurons becomes necessary to maintain a self-sustained representation within the GNW in the absence of sensory input. Finally, while balanced spontaneous intrinsic activity facilitates epigenesis at both local and global scales, the balanced excitatory/inhibitory ratio increases performance. We discuss the plausibility of the model in both neurodevelopmental and artificial intelligence terms.

Systematic detection of brain protein-coding genes under positive selection during primate evolution and their roles in cognition.

The human brain differs from that of other primates, but the genetic basis of these differences remains unclear. We investigated the evolutionary pressures acting on almost all human protein-coding genes (N = 11,667; 1:1 orthologs in primates) based on their divergence from those of early hominins, such as Neanderthals, and non-human primates. We confirm that genes encoding brain-related proteins are among the most strongly conserved protein-coding genes in the human genome. Combining our evolutionary pressure metrics for the protein-coding genome with recent data sets, we found that this conservation applied to genes functionally associated with the synapse and expressed in brain structures such as the prefrontal cortex and the cerebellum. Conversely, several genes presenting signatures commonly associated with positive selection appear as causing brain diseases or conditions, such as micro/macrocephaly, Joubert syndrome, dyslexia, and autism. Among those, a number of DNA damage response genes associated with microcephaly in humans such as BRCA1, NHEJ1, TOP3A, and RNF168 show strong signs of positive selection and might have played a role in human brain size expansion during primate evolution. We also showed that cerebellum granule neurons express a set of genes also presenting signatures of positive selection and that may have contributed to the emergence of fine motor skills and social cognition in humans. This resource is available online and can be used to estimate evolutionary constraints acting on a set of genes and to explore their relative contributions to human traits.

Typology of ICU-Healthcare Providers Who Delayed or Declined COVID-19 Vaccination.

OBJECTIVES: To assess COVID-19 vaccination rates in ICU-healthcare providers (HCPs) in France and to identify the typology of those who delayed or declined vaccination. DESIGN: Cross-sectional study. SETTING: Twenty-one ICUs in France. SUBJECTS: Members of the nursing and medical staff and other allied professionals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six hundred ninety-six of the 950 respondents (73.3%) had undergone a full vaccination schedule. Other HCPs either declined vaccination ( n = 112) or delayed vaccination until it became mandatory ( n = 142). Factors independently associated with full vaccination were age older than 50 years (odds ratio, 0.25 [95% CI, 0.12-0.51]), more than 5 years of ICU experience (0.66 [0.47-0.93]), increasing working time during the surge (0.94 [0.88-1.00]), and spending time with the family (0.92 [0.85-0.99]). Conversely, being a nurse (1.94 [1.25-2.99]) or a nurse assistant (2.77 [1.62-4.73]), and feeling not supported by hospital and ICU directors (1.49 [1.01-2.20]) was independently associated with not being vaccinated. CONCLUSIONS: These results are important to take into account to better implement vaccination strategies in HCPs for existing or future pandemics.

Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism.

Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals' adaptive skills naturally improve or remain stable, while others' decrease. To pave the way for 'precision-medicine' approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6-30 years), with two assessment time points separated by ~12-24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful "Increasers", "No-changers", and "Decreasers" in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup's neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences' potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes.

Processing of social and monetary rewards in autism spectrum disorders.

BACKGROUND: Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD. AIMS: Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. METHOD: Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.6 years of age) and 181 typically developing participants (7.6-30.8 years of age). RESULTS: Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD. CONCLUSIONS: Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Disorganized Communication and Social Dysfunction in Schizophrenia: Emerging Concepts and Methods.

PURPOSE OF REVIEW: In this review, we embrace the emerging field of second-person neuroscience to address disorganization in schizophrenia. We argue that the focus of interest for disorganization is the interpersonal space where shared mental processes ('social mind') occur based on the bio-behavioural synchrony between two (or more) interacting people. We lay out several bio-behavioural measures that can capture the component parts of this process. In particular, we highlight the real-time imaging technology of hyperscanning that enables multi-person analysis of naturalistic social interaction. We illustrate how these measures can be used in empirical studies by posing disorganization as a problem of interpersonal processing. RECENT FINDINGS: Traditionally, disorganized speech and behaviour have been studied as the product of hidden cognitive processes ('private mind'). A dysfunction in these processes was attributed to the brain afflicted by the illness ('brain-bound mechanisms'). But this approach has contributed to challenges in measuring and quantifying disorganization. Consequently, the single-brain focus has not provided satisfactory clarity or led to effective treatments for persistent social dysfunction in schizophrenia. Social dysfunction is a core feature of schizophrenia. This dysfunction arises from disorganized interpersonal interaction that typifies the social profile of affected individuals. We outline challenges in employing several emerging concepts and methods and how they can be addressed to investigate the mechanisms of social dysfunction in schizophrenia.

Sonometric assessment of cough predicts extubation failure: SonoWean-a proof-of-concept study.

BACKGROUND: Extubation failure is associated with increased mortality. Cough ineffectiveness may be associated with extubation failure, but its quantification for patients undergoing weaning from invasive mechanical ventilation (IMV) remains challenging. METHODS: Patients under IMV for more than 24 h completing a successful spontaneous T-tube breathing trial (SBT) were included. At the end of the SBT, we performed quantitative sonometric assessment of three successive coughing efforts using a sonometer. The mean of the 3-cough volume in decibels was named Sonoscore. RESULTS: During a 1-year period, 106 patients were included. Median age was 65 [51-75] years, mainly men (60%). Main reasons for IMV were acute respiratory failure (43%), coma (25%) and shock (17%). Median duration of IMV at enrollment was 4 [3-7] days. Extubation failure occurred in 15 (14%) patients. Baseline characteristics were similar between success and failure extubation groups, except percentage of simple weaning which was lower and MV duration which was longer in extubation failure patients. Sonoscore was significantly lower in patients who failed extubation (58 [52-64] vs. 75 [70-78] dB, P < 0.001). After adjustment on MV duration and comorbidities, Sonoscore remained associated with extubation failure. Sonoscore was predictive of extubation failure with an area under the ROC curve of 0.91 (IC95% [0.83-0.99], P < 0.001). A threshold of Sonoscore < 67.1 dB predicted extubation failure with a sensitivity of 0.93 IC95% [0.70-0.99] and a specificity of 0.82 IC95% [0.73-0.90]. CONCLUSION: Sonometric assessment of cough strength might be helpful to identify patients at risk of extubation failure in patients undergoing IMV.

Technologically-assisted communication attenuates inter-brain synchrony.

The transition to technologically-assisted communication has permeated all facets of human social life; yet, its impact on the social brain is still unknown and the effects may be particularly intense during periods of developmental transitions. Applying a two-brain perspective, the current preregistered study utilized hyperscanning EEG to measure brain-to-brain synchrony in 62 mother-child pairs at the transition to adolescence (child age; M = 12.26, range 10-14) during live face-to-face interaction versus technologically-assisted remote communication. The live interaction elicited 9 significant cross-brain links between densely inter-connected frontal and temporal areas in the beta range [14-30 Hz]. Mother's right frontal region connected with the child's right and left frontal, temporal, and central regions, suggesting its regulatory role in organizing the two-brain dynamics. In contrast, the remote interaction elicited only 1 significant cross-brain-cross-hemisphere link, attenuating the robust right-to-right-brain connectivity during live social moments that communicates socio-affective signals. Furthermore, while the level of social behavior was comparable between the two interactions, brain-behavior associations emerged only during the live exchange. Mother-child right temporal-temporal synchrony linked with moments of shared gaze and the degree of child engagement and empathic behavior correlated with right frontal-frontal synchrony. Our findings indicate that human co-presence is underpinned by specific neurobiological processes that should be studied in depth. Much further research is needed to tease apart whether the "Zoom fatigue" experienced during technological communication may stem, in part, from overload on more limited inter-brain connections and to address the potential cost of social technology for brain maturation, particularly among youth.

A neurodynamic model of inter-brain coupling in the gamma band.

The use of EEG to simultaneously record multiple brains (i.e., hyperscanning) during social interactions has led to the discovery of inter-brain coupling (IBC). IBC is defined as the neural synchronization between people and is considered to be a marker of social interaction. IBC has previously been observed across different frequency bands, including theta [4-7 Hz]. Given the proximity of this frequency range with behavioral rhythms, models have been able to combine IBC in theta with sensorimotor coordination patterns. Interestingly, empirical EEG-hyperscanning results also report the emergence of IBC in the gamma range [>30 Hz]. Gamma oscillations' fast and transient nature makes a direct link between gamma-IBC and other (much slower) interpersonal dynamics difficult, leaving gamma-IBC without a plausible model. However, at the intrabrain level, gamma activity is coupled with the dynamics of lower frequencies through cross-frequency coupling (CFC). This paper provides a biophysical explanation, through the simulation of neural data, for the emergence of gamma inter-brain coupling using a Kuramoto model of four oscillators divided into two separate (brain) units. By modulating both the degree of inter-brain coupling in the theta band (i.e., between-units coupling) and CFC (i.e., intraunit theta-gamma coupling), we provide a theoretical explanation of the observed gamma-IBC phenomenon in the EEG-hyperscanning literature.NEW & NOTEWORTHY The last years were marked by an increasing interest in multiple-brain recordings. However, the inter-brain coupling arising across interacting individuals also sparks debates about the underlying biological mechanisms. The inter-brain coupling in the gamma band [>30 Hz] was particularly criticized for lacking a theoretical framework. Here, by using biologically informed neural simulations with the Kuramoto model, we assess the role of intra- and inter-brain neural dynamics in the emergence of inter-brain synchrony in the gamma band.

Symptom network analysis of the sleep disorders diagnostic criteria based on the clinical text of the ICSD-3.

The third edition of the International Classification of Sleep Disorders (ICSD-3) is the authoritative clinical text for the diagnosis of sleep disorders. An important issue of sleep nosology is to better understand the relationship between symptoms found in conventional diagnostic manuals and to compare classifications. Nevertheless, to our knowledge, there is no specific exhaustive work on the general structure of the networks of symptoms of sleep disorders as described in diagnostic manuals. The general aim of the present study was to use symptom network analysis to explore the diagnostic criteria in the ICSD-3 manual. The ICSD-3 diagnostic criteria related to clinical manifestations were systematically identified, and the units of analysis (symptoms) were labelled from these clinical manifestation diagnostic criteria using three rules ("Conservation", "Splitting", "Lumping"). A total of 37 of the 43 main sleep disorders with 160 units of analysis from 114 clinical manifestations in the ICSD-3 were analysed. A symptom network representing all individual ICSD-3 criteria and connections between them was constructed graphically (network estimation), quantified with classical metrics (network inference with global and local measures) and tested for robustness. The global measure of the sleep symptoms network shows that it can be considered as a small world, suggesting a strong interconnection between symptoms in the ICSD-3. Local measures show the central role of three kinds of bridge sleep symptoms: daytime sleepiness, insomnia, and behaviour during sleep symptoms. Such a symptom network analysis of the ICSD-3 structure could provide a framework for better systematising and organising symptomatology in sleep medicine.

The meaning of significant mean group differences for biomarker discovery.

Over the past decade, biomarker discovery has become a key goal in psychiatry to aid in the more reliable diagnosis and prognosis of heterogeneous psychiatric conditions and the development of tailored therapies. Nevertheless, the prevailing statistical approach is still the mean group comparison between "cases" and "controls," which tends to ignore within-group variability. In this educational article, we used empirical data simulations to investigate how effect size, sample size, and the shape of distributions impact the interpretation of mean group differences for biomarker discovery. We then applied these statistical criteria to evaluate biomarker discovery in one area of psychiatric research-autism research. Across the most influential areas of autism research, effect size estimates ranged from small (d = 0.21, anatomical structure) to medium (d = 0.36 electrophysiology, d = 0.5, eye-tracking) to large (d = 1.1 theory of mind). We show that in normal distributions, this translates to approximately 45% to 63% of cases performing within 1 standard deviation (SD) of the typical range, i.e., they do not have a deficit/atypicality in a statistical sense. For a measure to have diagnostic utility as defined by 80% sensitivity and 80% specificity, Cohen's d of 1.66 is required, with still 40% of cases falling within 1 SD. However, in both normal and nonnormal distributions, 1 (skewness) or 2 (platykurtic, bimodal) biologically plausible subgroups may exist despite small or even nonsignificant mean group differences. This conclusion drastically contrasts the way mean group differences are frequently reported. Over 95% of studies omitted the "on average" when summarising their findings in their abstracts ("autistic people have deficits in X"), which can be misleading as it implies that the group-level difference applies to all individuals in that group. We outline practical approaches and steps for researchers to explore mean group comparisons for the discovery of stratification biomarkers.

Survival in Immunocompromised Patients Ultimately Requiring Invasive Mechanical Ventilation: A Pooled Individual Patient Data Analysis.

Rationale: Acute respiratory failure (ARF) is associated with high mortality in immunocompromised patients, particularly when invasive mechanical ventilation is needed. Therefore, noninvasive oxygenation/ventilation strategies have been developed to avoid intubation, with uncertain impact on mortality, especially when intubation is delayed. Objectives: We sought to report trends of survival over time in immunocompromised patients receiving invasive mechanical ventilation. The impact of delayed intubation after failure of noninvasive strategies was also assessed. Methods: Systematic review and meta-analysis using individual patient data of studies that focused on immunocompromised adult patients with ARF requiring invasive mechanical ventilation. Studies published in English were identified through PubMed, Web of Science, and Cochrane Central (2008-2018). Individual patient data were requested from corresponding authors for all identified studies. We used mixed-effect models to estimate the effect of delayed intubation on hospital mortality and described mortality rates over time. Measurements and Main Results: A total of 11,087 patients were included (24 studies, three controlled trials, and 21 cohorts), of whom 7,736 (74%) were intubated within 24 hours of ICU admission (early intubation). The crude mortality rate was 53.2%. Adjusted survivals improved over time (from 1995 to 2017, odds ratio [OR] for hospital mortality per year, 0.96 [0.95-0.97]). For each elapsed day between ICU admission and intubation, mortality was higher (OR, 1.38 [1.26-1.52]; P < 0.001). Early intubation was significantly associated with lower mortality (OR, 0.83 [0.72-0.96]), regardless of initial oxygenation strategy. These results persisted after propensity score analysis (matched OR associated with delayed intubation, 1.56 [1.44-1.70]). Conclusions: In immunocompromised intubated patients, survival has improved over time. Time between ICU admission and intubation is a strong predictor of mortality, suggesting a detrimental effect of late initial oxygenation failure.

Popular and Scientific Discourse on Autism: Representational Cross-Cultural Analysis of Epistemic Communities to Inform Policy and Practice.

BACKGROUND: Social media provide a window onto the circulation of ideas in everyday folk psychiatry, revealing the themes and issues discussed both by the public and by various scientific communities. OBJECTIVE: This study explores the trends in health information about autism spectrum disorder within popular and scientific communities through the systematic semantic exploration of big data gathered from Twitter and PubMed. METHODS: First, we performed a natural language processing by text-mining analysis and with unsupervised (machine learning) topic modeling on a sample of the last 10,000 tweets in English posted with the term #autism (January 2021). We built a network of words to visualize the main dimensions representing these data. Second, we performed precisely the same analysis with all the articles using the term "autism" in PubMed without time restriction. Lastly, we compared the results of the 2 databases. RESULTS: We retrieved 121,556 terms related to autism in 10,000 tweets and 5.7x109 terms in 57,121 biomedical scientific articles. The 4 main dimensions extracted from Twitter were as follows: integration and social support, understanding and mental health, child welfare, and daily challenges and difficulties. The 4 main dimensions extracted from PubMed were as follows: diagnostic and skills, research challenges, clinical and therapeutical challenges, and neuropsychology and behavior. CONCLUSIONS: This study provides the first systematic and rigorous comparison between 2 corpora of interests, in terms of lay representations and scientific research, regarding the significant increase in information available on autism spectrum disorder and of the difficulty to connect fragments of knowledge from the general population. The results suggest a clear distinction between the focus of topics used in the social media and that of scientific communities. This distinction highlights the importance of knowledge mobilization and exchange to better align research priorities with personal concerns and to address dimensions of well-being, adaptation, and resilience. Health care professionals and researchers can use these dimensions as a framework in their consultations to engage in discussions on issues that matter to beneficiaries and develop clinical approaches and research policies in line with these interests. Finally, our study can inform policy makers on the health and social needs and concerns of individuals with autism and their caregivers, especially to define health indicators based on important issues for beneficiaries.

Human attachments shape interbrain synchrony toward efficient performance of social goals.

The human brain has undergone massive expansion across primate evolution through life amidst multi-layered social attachments; within families, among friends, and between clan members and this enabled humans to coordinate their brains with those of others toward the execution of complex social goals.  We examined how human attachments facilitate efficient, resource-sensitive performance of social goals by balancing neural and behavioral synchrony. Using hyperscanning EEG, we collected neural data from male-female pairs in three groups (N=158, 79 pairs); long-term couples, best friends, and unfamiliar group members, during two ecologically-valid naturalistic tasks; motor coordination and empathy giving.  Across groups and tasks, neural synchrony was supported by behavior coordination and orchestrated multiple neural rhythms.  In the goal-directed motor task, interbrain synchrony implicated beta and gamma rhythms localized to sensorimotor areas. Couples showed the highest neural synchrony combined with greatest behavioral synchrony and such brain-behavior linkage resulted in speedy performance, conserving energy in the long run.  The socially-oriented empathy task triggered neural synchrony in widely-distributed sensorimotor and bilateral temporal regions, integrated alpha, beta, and gamma rhythms, and implicated brain-behavior complementarity; couples displayed the highest behavioral synchrony combined with lowest neural synchrony toward greatest felt support while strangers exhibited the opposite pattern.  Findings suggest that human attachments provide a familiar backdrop of temporal regularities, required for the brain's allostatic function, and interbrain and behavioral synchrony are sculpted by familiarity and closeness toward resource-sensitive performance of survival-related social goals, toiled by two.

Pattern of Brain Injury in Patients With Thrombotic Thrombocytopenic Purpura in the Precaplacizumab Era.

OBJECTIVES: To describe short- and long-term neurologic prognosis of patients with thrombotic thrombocytopenic purpura and to identify clusters associated with evolution. DESIGN: Prospective French cohort. SETTING: ICU in a reference center. PATIENTS: All consecutive patients with newly diagnosed thrombocytopenic purpura. INTERVENTION: Comprehensive clinical, biological, and radiological evaluation at admission. Neurocognitive recovery was assessed using Glasgow Outcome Scale (range 1-5, with 1 representing death and 5 representing no or minimal neurologic deficit). MEASUREMENTS AND MAIN RESULTS: Among the 130 newly diagnosed patients with thrombocytopenic purpura, 108 (83%; age 43 [30-52]; 73% women) presented with neurologic signs, including headaches (51%), limb weakness, paresthesia, and/or aphasia (49%), pyramidal syndrome (30%), decreased consciousness (20%), seizure (19%), cognitive impairment (34%), cerebellar syndrome (18%), and visual symptoms (20%). A hierarchical cluster analysis identified three distinct groups of patients. Cluster 1 included younger patients (37 [27-48], 41 [32-52], and 48 [35-54], in clusters 1, 2 and 3, respectively; p = 0.045), with a predominance of headaches (75%, 27%, and 36%; p < 0.0001). Cluster 2 patients had ataxic gait and cerebellar syndrome (77%, 0%, and 0%; p < 0.0001) and dizziness (50%, 0%, and 0%; p < 0.0001). Cluster 3 included patients with delirium (36%, 0%, and 9%; p < 0.0001), obtundation (58%, 0%, and 24%; p < 0.0001), and seizure (36%, 0%, and 14%; p < 0.0001). Acute kidney injury was 32%, 68%, and 77%, in clusters 1, 2, and 3, respectively (p < 0.0001). The three clusters did not differ for other biological or brain imaging. After a median follow-up of 34 months (12-71 mo), 100 patients (93%) were alive with full neurocognitive recovery (i.e., Glasgow Outcome Scale score 5) in 89 patients (89%). Patients from cluster 1 more frequently exhibited full recovery (Glasgow Outcome Scale score of 5) compared with clusters 2 and 3, (44 [98%], 13 [65%], and 21 [60%] at 3 mo; p < 0.0001), (44 [100%], 15 [68%], and 23 [69%] at 6 mo; p < 0.0001), and (40 [100%], 15 [79%], and 20 [57%] at 1 yr; p < 0.0001). CONCLUSIONS: Initial clinical neurologic evaluation in thrombocytopenic purpura patients distinguishes three groups of patients with different clinical and functional outcomes.

Learning Brain Dynamics With Coupled Low-Dimensional Nonlinear Oscillators and Deep Recurrent Networks.

Many natural systems, especially biological ones, exhibit complex multivariate nonlinear dynamical behaviors that can be hard to capture by linear autoregressive models. On the other hand, generic nonlinear models such as deep recurrent neural networks often require large amounts of training data, not always available in domains such as brain imaging; also, they often lack interpretability. Domain knowledge about the types of dynamics typically observed in such systems, such as a certain type of dynamical systems models, could complement purely data-driven techniques by providing a good prior. In this work, we consider a class of ordinary differential equation (ODE) models known as van der Pol (VDP) oscil lators and evaluate their ability to capture a low-dimensional representation of neural activity measured by different brain imaging modalities, such as calcium imaging (CaI) and fMRI, in different living organisms: larval zebrafish, rat, and human. We develop a novel and efficient approach to the nontrivial problem of parameters estimation for a network of coupled dynamical systems from multivariate data and demonstrate that the resulting VDP models are both accurate and interpretable, as VDP's coupling matrix reveals anatomically meaningful excitatory and inhibitory interactions across different brain subsystems. VDP outperforms linear autoregressive models (VAR) in terms of both the data fit accuracy and the quality of insight provided by the coupling matrices and often tends to generalize better to unseen data when predicting future brain activity, being comparable to and sometimes better than the recurrent neural networks (LSTMs). Finally, we demonstrate that our (generative) VDP model can also serve as a data-augmentation tool leading to marked improvements in predictive accuracy of recurrent neural networks. Thus, our work contributes to both basic and applied dimensions of neuroimaging: gaining scientific insights and improving brain-based predictive models, an area of potentially high practical importance in clinical diagnosis and neurotechnology.

Outcome of allogeneic hematopoietic stem cell transplant recipients admitted to the intensive care unit with a focus on haploidentical graft and sequential conditioning regimen: results of a retrospective study.

Haploidentical transplantation has extended the availability of allogeneic hematopoietic stem cell transplant (alloHCT) to almost all patients. Sequential conditioning regimens have been proposed for the treatment of hematological active disease. Whether these new transplantation procedures affect the prognosis of critically ill alloHCT recipients remains unknown. We evaluated this question in a retrospective study including consecutive alloHCT patients admitted to the intensive care unit of a tertiary academic center from 2010 to 2017. During the study period, 412 alloHCTs were performed and 110 (27%) patients-median age 55 (36-64) years-were admitted to ICU in a median time of 58.5 (14-245) days after alloHCT. Twenty-nine (26%) patients had received a haploidentical graft and 34 (31%) a sequential conditioning. Median SOFA score was 9 (6-11). Invasive mechanical ventilation (MV) was required in 61 (55%) patients. Fifty-six (51%) patients died in the hospital. Independent factors associated with in-hospital mortality were as follows: MV (OR=8.44 [95% CI 3.30-23.19], p<0.001), delta SOFA between day 3 and day 1 (OR=1.60 [95% CI 1.31-2.05], p<0.0001), and sequential conditioning (OR=3.7 [95% CI 1.14-12.92], p=0.033). Sequential conditioning was also independently associated with decreased overall survival (HR=1.86 [95% CI 1.05-3.31], p=0.03). Other independent factors associated with reduced overall survival were HCT-specific comorbidity index ≥2 (HR=1.76 [95% CI 1.10-2.84], p=0.02), acute GVHD grade ≥2 (HR=1.88 [95% CI 1.14-3.10], p=0.01), MV (HR=2.37 [95% CI 1.38-4.07, p=0.002), and vasopressors (HR=2.21 [95% CI 1.38-3.54], p=0.001). Haploidentical transplantation did not affect outcome. Larger multicenter studies are warranted to confirm these results.

Mass-spectrometry analysis of the human pineal proteome during night and day and in autism.

The human pineal gland regulates day-night dynamics of multiple physiological processes, especially through the secretion of melatonin. Using mass-spectrometry-based proteomics and dedicated analysis tools, we identify proteins in the human pineal gland and analyze systematically their variation throughout the day and compare these changes in the pineal proteome between control specimens and donors diagnosed with autism. Results reveal diverse regulated clusters of proteins with, among others, catabolic carbohydrate process and cytoplasmic membrane-bounded vesicle-related proteins differing between day and night and/or control versus autism pineal glands. These data show novel and unexpected processes happening in the human pineal gland during the day/night rhythm as well as specific differences between autism donor pineal glands and those from controls.

Acute cholangitis in intensive care units: clinical, biological, microbiological spectrum and risk factors for mortality: a multicenter study.

BACKGROUND: Little is known on the outcome and risk factors for mortality of patients admitted in Intensive Care units (ICUs) for Acute cholangitis (AC). METHODS: Retrospective multicenter study included adults admitted in eleven intensive care units for a proven AC from 2005 to 2018. Risk factors for in-hospital mortality were identified using multivariate analysis. RESULTS: Overall, 382 patients were included, in-hospital mortality was 29%. SOFA score at admission was 8 [5-11]. Biliary obstruction was mainly related to gallstone (53%) and cancer (22%). Median total bilirubin and PCT were respectively 83 µmol/L [50-147] and 19.1 µg/L [5.3-54.8]. Sixty-three percent of patients (n = 252) had positive blood culture, mainly Gram-negative bacilli (86%) and 14% produced extended spectrum beta lactamase bacteria. At ICU admission, persisting obstruction was frequent (79%) and biliary decompression was performed using therapeutic endoscopic retrograde cholangiopancreatography (76%) and percutaneous transhepatic biliary drainage (21%). Adjusted mortality significantly decreased overtime, adjusted OR for mortality per year was 0.72 [0.54-0.96] (p = 0.02). In a multivariate analysis, factors at admission associated with in-hospital mortality were: SOFA score (OR 1.14 [95% CI 1.05-1.24] by point, p = 0.001), lactate (OR 1.21 [95% CI 1.08-1.36], by 1 mmol/L, p < 0.001), total serum bilirubin (OR 1.26 [95% CI 1.12-1.41], by 50 µmol/L, p < 0.001), obstruction non-related to gallstones (p < 0.05) and AC complications (OR 2.74 [95% CI 1.45-5.17], p = 0.002). Time between ICU admission and biliary decompression > 48 h was associated with in-hospital mortality (adjusted OR 2.73 [95% CI 1.30-6.22], p = 0.02). CONCLUSIONS: In this large retrospective multicenter study, we found that AC-associated mortality significantly decreased overtime. Severity of organ failure, cause of obstruction and local complications of AC are risk factors for mortality, as well as delayed biliary drainage > 48 h.