Laboratoire Vision Action Cognition

BACKGROUND: The Surviving Sepsis Campaign recommends targeting a mean arterial pressure of at least 65 mm Hg during initial resuscitation of patients with septic shock. However, whether this blood-pressure target is more or less effective than a higher target is unknown. METHODS: In a multicenter, open-label trial, we randomly assigned 776 patients with septic shock to undergo resuscitation with a mean arterial pressure target of either 80 to 85 mm Hg (high-target group) or 65 to 70 mm Hg (low-target group). The primary end point was mortality at day 28. RESULTS: At 28 days, there was no significant between-group difference in mortality, with deaths reported in 142 of 388 patients in the high-target group (36.6%) and 132 of 388 patients in the low-target group (34.0%) (hazard ratio in the high-target group, 1.07; 95% confidence interval [CI], 0.84 to 1.38; P=0.57). There was also no significant difference in mortality at 90 days, with 170 deaths (43.8%) and 164 deaths (42.3%), respectively (hazard ratio, 1.04; 95% CI, 0.83 to 1.30; P=0.74). The occurrence of serious adverse events did not differ significantly between the two groups (74 events [19.1%] and 69 events [17.8%], respectively; P=0.64). However, the incidence of newly diagnosed atrial fibrillation was higher in the high-target group than in the low-target group. Among patients with chronic hypertension, those in the high-target group required less renal-replacement therapy than did those in the low-target group, but such therapy was not associated with a difference in mortality. CONCLUSIONS: Targeting a mean arterial pressure of 80 to 85 mm Hg, as compared with 65 to 70 mm Hg, in patients with septic shock undergoing resuscitation did not result in significant differences in mortality at either 28 or 90 days. (Funded by the French Ministry of Health; SEPSISPAM ClinicalTrials.gov number, NCT01149278.).

UNLABELLED: Histiocytic neoplasms are clonal, hematopoietic disorders characterized by an accumulation of abnormal, monocyte-derived dendritic cells or macrophages in Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (non-LCH), respectively. The discovery of BRAF(V600E) mutations in approximately 50% of these patients provided the first molecular therapeutic target in histiocytosis. However, recurrent driving mutations in the majority of patients with BRAF(V600E)-wild-type non-LCH are unknown, and recurrent cooperating mutations in non-MAP kinase pathways are undefined for the histiocytic neoplasms. Through combined whole-exome and transcriptome sequencing, we identified recurrent kinase fusions involving BRAF, ALK, and NTRK1, as well as recurrent, activating MAP2K1 and ARAF mutations in patients with BRAF(V600E)-wild-type non-LCH. In addition to MAP kinase pathway lesions, recurrently altered genes involving diverse cellular pathways were identified. Treatment of patients with MAP2K1- and ARAF-mutated non-LCH using MEK and RAF inhibitors, respectively, resulted in clinical efficacy, demonstrating the importance of detecting and targeting diverse kinase alterations in these disorders. SIGNIFICANCE: We provide the first description of kinase fusions in systemic histiocytic neoplasms and activating ARAF and MAP2K1 mutations in non-Langerhans histiocytic neoplasms. Refractory patients with MAP2K1- and ARAF-mutant histiocytoses had clinical responses to MEK inhibition and sorafenib, respectively, highlighting the importance of comprehensive genomic analysis of these disorders.

We report the synthesis of new aromatic biobased building-blocks from vanillin, for their promising use in polymer synthesis.

Early experience with faces of a given racial type facilitates visual recognition for this type of face relative to others. To assess whether this so-called other-race effect can be reversed by subsequent experience with new types of faces, we tested adults of Korean origin who were adopted by European Caucasian families when they were between the ages of 3 to 9. The adoptees performed a face recognition task with photographs of Caucasian and Asian faces. They performed exactly like a control group of French participants, identifying the Caucasian faces better than the Asiatic ones. In contrast, a control group of Koreans showed the reverse pattern. This result indicates that the face recognition system remains plastic enough during childhood to reverse the other-race effect.

BACKGROUND: People are better at recognizing faces of their own race than faces of another race. Such race specificity may be due to differential expertise in the two races. METHOD: In order to find out whether this other-race effect develops as early as face-recognition skills or whether it is a long-term effect of acquired expertise, we tested face recognition in 3-month-old Caucasian infants by conducting two experiments using Caucasian and Asiatic faces and a visual pair-comparison task. We hypothesized that if the other race effect develops together with face processing skills during the first months of life, the ability to recognize own-race faces will be greater than the ability to recognize other-race faces: 3-month-old Caucasian infants should be better at recognizing Caucasian faces than Asiatic faces. If, on the contrary, the other-race effect is the long-term result of acquired expertise, no difference between recognizing own- and other-race faces will be observed at that age. RESULTS: In Experiment 1, Caucasian infants were habituated to a single face. Recognition was assessed by a novelty preference paradigm. The infants' recognition performance was better for Caucasian than for Asiatic faces. In Experiment 2, Caucasian infants were familiarized with three individual faces. Recognition was demonstrated with both Caucasian and Asiatic faces. CONCLUSIONS: These results suggest that (i) the representation of face information by 3-month-olds may be race-experience-dependent (Experiment 1), and (ii) short-term familiarization with exemplars of another race group is sufficient to reduce the other-race effect and to extend the power of face processing (Experiment 2).

BACKGROUND AND OBJECTIVE: Low back pain (LBP) is one of the most common chronic pain conditions. This paper reviews the available literature on the role of neuropathic mechanisms in chronic LBP and discusses implications for its clinical management, with a particular focus on pharmacological treatments. DATABASES AND DATA TREATMENT: Literature searches were performed in PubMed, key pain congresses and ProQuest Dialog to identify published evidence on neuropathic back pain and its management. All titles were assessed for relevant literature. RESULTS: Chronic LBP comprises both nociceptive and neuropathic components, however, the neuropathic component appears under-recognized and undertreated. Neuropathic pain (NP) is challenging to manage. Many patients with chronic LBP have pain that is refractory to existing treatments. Typically, less than half of patients experience clinically meaningful analgesia with oral pharmacotherapies; these are also associated with risks of adverse effects. Paracetamol and NSAIDs, although widely used for LBP, are unlikely to ameliorate the neuropathic component and data on the use of NP medications such as antidepressants and gabapentin/pregabalin are limited. While there is an unmet need for improved treatment options, recent data have shown tapentadol to have efficacy in the neuropathic component of LBP, and studies suggest that the capsaicin 8% patch and lidocaine 5% medicated plaster, topical analgesics available for the treatment of peripheral NP, may be a valuable additional approach for the management of neuropathic LBP. CONCLUSIONS: Chronic LBP often has an under-recognized neuropathic component, which can be challenging to manage, and requires improved understanding and better diagnosis and treatment. WHAT DOES THIS REVIEW ADD?: Increased recognition and improved understanding of the neuropathic component of low back pain raises the potential for the development of mechanism-based therapies. Open and retrospective studies suggest that agents like tapentadol and topical analgesics - such as the capsaicin 8% patch and the lidocaine 5% medicated plaster - may be effective options for the treatment of neuropathic low back pain in defined patient groups.

AIMS: To assess physicians' adherence to guideline-recommended medications for the treatment of chronic heart failure (CHF) with reduced ejection fraction. METHODS AND RESULTS: QUALIFY is an international prospective observational longitudinal survey of 7092 CHF outpatients recruited 1-15 months after hospitalization for heart failure from September 2013 to December 2014 in 547 centres in 36 countries. We constructed a five-class guideline adherence score for angiotensin converting enzyme inhibitors (ACEIs), beta-blockers, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, and ivabradine. The adherence score was good in 67%, moderate in 25%, and poor in 8% of patients. Adherence was lower in women than men but there were differences in age (65.7 ± 12.5 years women vs. 62.2 ± 12.4 years men, P < 0.001) and the proportion of women at ≥50% target dose of beta-blockers was lower in those >67 years (median) (11% vs. 16.2%, P = 0.005). Geographic variations were observed with lower adherence scores in Central/Eastern European countries. The proportion of patients at target dose and ≥50% of target dose was low (27.9% and 63.3% for ACEIs, 14.8% and 51.8% for beta-blockers, 6.9% and 39.5% for ARBs, and 6.9% and 39.5% for ivabradine, respectively). It was also lower in patients most recently hospitalized (<6 vs. ≥6 months) except for beta-blockers. CONCLUSION: This international survey shows that adherence to guideline-recommended medications is relatively satisfactory but the dosage of recommended CHF medications is usually suboptimal. Action plans aimed at improving adherence to guidelines are required.

Striatal medium-sized spiny neurons (MSNs) integrate and convey information from the cerebral cortex to the output nuclei of the basal ganglia. Intracellular recordings from anesthetized animals show that MSNs undergo spontaneous transitions between hyperpolarized and depolarized states. State transitions, regarded as necessary for eliciting action potential firing in MSNs, are thought to control basal ganglia function by shaping striatal output. Here, we use an anesthetic-free rat preparation to show that the intracellular activity of MSNs is not stereotyped and depends critically on vigilance state. During slow-wave sleep, much as during anesthesia, MSNs displayed rhythmic step-like membrane potential shifts, correlated with cortical field potentials. However, wakefulness was associated with a completely different pattern of temporally disorganized depolarizing synaptic events of variable amplitude. Transitions from slow-wave sleep to wakefulness converted striatal discharge from a cyclic brisk firing to an irregular pattern of action potentials. These findings illuminate different capabilities of information processing in basal ganglia networks, suggesting in particular that a novel style of striatal computation is associated with the waking state.

Cocaine, already a significant drug problem in North and South America, has become a more prominent part of the European drug scene. Cocaine dependence has major somatic, psychological, psychiatric, socio-economic, and legal implications. No specific effective pharmacological treatment exists for cocaine dependence. Recent advances in neurobiology have identified various neuronal mechanisms implicated in cocaine addiction and suggested several promising pharmacological approaches. Data were obtained from Medline, EMBASE, and PsycINFO searches of English-language articles published between 1985 and June 2007 using the key words: cocaine, addiction, cocaine dependence, clinical trials, pharmacotherapy(ies) singly and in combination. Large well-controlled studies with appropriate statistical methods were preferred. Pharmacological agents such as GABA agents (topiramate, tiagabine, baclofen and vigabatrin) and agonist replacement agents (modafinil, disulfiram, methylphenidate) seem to be the most promising in treatment of cocaine dependence. The results from trials of first- and second-generation neuroleptics are largely negative. Aripiprazole, a partial dopaminergic agonist that may modulate the serotonergic system, shows some promise. Preliminary results of human studies with anti-cocaine vaccine, N-acetylcysteine, and ondansetron, are promising, as are several compounds in preclinical development. While no medication has received regulatory approval for the treatment of cocaine dependence, several medications marketed for other indications have shown efficacy in clinical trials. An anti-cocaine vaccine and several compounds in preclinical development have also shown promise. Findings from early clinical trials must be confirmed in larger, less selective patient populations.

Abstract This review of environmental psychology looks to the past, present, and future of this growing and important area of psychology. The environment, far from being a silent witness to human actions, is an integral part of the plot. The interdisciplinary origins and applied emphasis of environmental psychology have both conspired to prevent a straightforward and uncontentious definition of the discipline. Recent definitions adopt an inclusive, holistic, and transactional perspective on people‐environment relations. Various theories have been developed in environmental psychology: arousal theory, environmental load, adaptation level theory within a behaviorist and determinist paradigm; control, stress adaptation, behavioral elasticity, cognitive mapping, and environmental evaluation within an interactionist paradigm; and behavior settings, affordance theory, and theories of place, place identity, and place attachment within transactionalism. Environmental psychology deals with people's homes, the workplaces and leisure settings, the visual impact of buildings, the negative effects of cities, the restorative role of nature, and environmental attitudes and sustainable behavior. The issues at the forefront of the political and environmental agenda at the beginning of the twenty‐first century—human rights, well‐being and quality of life, globalization, and sustainability—need to be addressed and tackled by environmental psychologists in a way that incorporates both cross‐cultural and temporal dimensions.

Abstract Cross-presentation allows exogenous antigen presentation in association with major histocompatibility complex class I molecules, a process crucial for the priming of CD8 + T-cell responses against viruses and tumors. By contrast to conventional dendritic cells (cDC), which cross-present antigens in the steady state, plasmacytoid dendritic cells (pDC) acquire this ability only after stimulation by Toll-like receptor (TLR) ligands. The intracellular pathways accounting for this functional difference are still unknown. Here we show that the induction of cross-presentation by pDCs is regulated by mitochondria through a reactive oxygen species (ROS)-dependent mechanism, involving pH alkalization and antigen protection. The reduction of mitochondrial ROS production dramatically decreases the cross-presentation capacity of pDCs, leading to a strong reduction of their capacity to trigger CD8 + T-cell responses. Our results demonstrate the importance of mitochondrial metabolism in pDC biology, particularly for the induction of adaptive immune responses.

BACKGROUND: Rate control and rhythm control are accepted management strategies for atrial fibrillation (AF). OBJECTIVE: RealiseAF aimed to describe the success of either strategy and the impact of control on symptomatic status of patients with AF. METHODS: This international, observational, cross-sectional survey of patients with any history of AF in the previous year, recorded AF characteristics, management and frequency of control (defined as sinus rhythm or AF with resting heart rate ≤80 bpm). RESULTS: Overall, 9665 patients were evaluable for AF control, with 59.0% controlled (sinus rhythm 26.5%, AF ≤80 bpm 32.5%) and 41.0% uncontrolled. Symptom prevalence in the previous week was lower in controlled than uncontrolled AF (55.7% vs 68.4%; p<0.001) and similar for patients in sinus rhythm versus AF ≤80 bpm (54.8% vs 56.4%; p=0.23). At the visit, AF-related functional impairment (EHRA class >I) was seen in 67.4% of patients with controlled AF and 82.1% of patients with uncontrolled AF (p<0.001). Quality-of-life (QoL, measured using EQ-5D) was better for patients with controlled versus uncontrolled AF using the Visual Analogue Scale (mean (SD) score 67.1 (18.4) vs 63.2 (18.9); p<0.001), single index utility score (median 0.78 vs 0.73; p<0.001), or five dimensions of well-being (all p<0.001). Irrespective of AF control, cardiovascular events had led to hospitalisation in the past year in 28.1%. CONCLUSION: AF control is not optimal. Control appears to be associated with fewer symptoms and better QoL, but even patients with controlled AF have frequent symptoms, functional impairment, altered QoL and cardiovascular events. New treatments are needed to improve control and minimise the functional and QoL burden of AF.

Music perception and performance rely heavily on temporal processing: for instance, each event must be situated in time in relation to surrounding events, and events must be grouped together in order to overcome memory constraints. The temporal structure of music varies considerably from one culture to another, and so it has often been supposed that the specific implementation of perceptual and cognitive temporal processes will differ as a function of an individual's cultural exposure and experience. In this paper we examine the alternative position that some temporal processes may be universal, in the sense that they function in a similar manner irrespective of an individual's cultural exposure and experience. We first review rhythm perception and production studies carried out with adult musicians, adult nonmusicians, children, and infants in order to identify temporal processes that appear to function in a similar fashion irrespective of age, acculturation, and musical training. This review leads to the identification of five temporal processes that we submit as candidates for the status of "temporal universals." For each process, we select the simplest and most representative experimental paradigm that has been used to date. This leads to a research proposal for future intercultural studies that could test the universal nature of these processes.

Because of its ability of providing very high data transmission rates over distances up to several tens of meters, underwater wireless optical communication (UWOC) has attracted considerable interest during the past few years. The underwater channel is a challenging environment, especially because of its high attenuation. The difficulty of precise localization underwater also leads to unavoidable link misalignments that can have an important impact on the link availability and otherwise on the quality of signal transmission. In this paper, after a review of the recent research works on UWOC and the available commercialized systems, we present the performance study of a typical UWOC system under some simplifying assumptions for system modeling. We also address the open issues and the challenges that we are faced with in practice.

Six experiments explored Parisian French-learning infants' ability to segment bisyllabic words from fluent speech. The first goal was to assess whether bisyllabic word segmentation emerges later in infants acquiring European French compared to other languages. The second goal was to determine whether infants learning different dialects of the same language have partly different segmentation abilities, and whether segmenting a non-native dialect has a cost. Infants were tested on standard European or Canadian French stimuli, in the word-passage or passage-word order. Our study first establishes an early onset of segmentation abilities: Parisian infants segment bisyllabic words at age 0;8 in the passage-word order only (revealing a robust order of presentation effect). Second, it shows that there are differences in segmentation abilities across Parisian and Canadian French infants, and that there is a cost for cross-dialect segmentation for Parisian infants. We discuss the implications of these findings for understanding word segmentation processes.

The firing rates of neurons in primary visual cortex (V1) are suppressed by large stimuli, an effect known as surround suppression. In cats and monkeys, the strength of suppression is sensitive to orientation; responses to regions containing uniform orientations are more suppressed than those containing orientation contrast. This effect is thought to be important for scene segmentation, but the underlying neural mechanisms are poorly understood. We asked whether it is possible to study these mechanisms in the visual cortex of mice, because of recent advances in technology for studying the cortical circuitry in mice. It is unknown whether neurons in mouse V1 are sensitive to orientation contrast. We measured the orientation selectivity of surround suppression in the different layers of mouse V1. We found strong surround suppression in layer 4 and the superficial layers, part of which was orientation tuned: iso-oriented surrounds caused more suppression than cross-oriented surrounds. Surround suppression was delayed relative to the visual response and orientation-tuned suppression was delayed further, suggesting two separate suppressive mechanisms. Previous studies proposed that surround suppression depends on the activity of inhibitory somatostatin-positive interneurons in the superficial layers. To test the involvement of the superficial layers we topically applied lidocaine. Silencing of the superficial layers did not prevent orientation-tuned suppression in layer 4. These results show that neurons in mouse V1, which lacks orientation columns, show orientation-dependent surround suppression in layer 4 and the superficial layers and that surround suppression in layer 4 does not require contributions from neurons in the superficial layers.

ObjectiveEye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation.DesignMulticenter, double-masked, randomized, placebo-controlled phase III study.ParticipantsAnalysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 μg/day/eye) or placebo twice daily for 90 days and were followed up to day 180.Main Outcome MeasuresThe primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL.ResultsAlthough no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related.ConclusionsThis first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated. Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation. Multicenter, double-masked, randomized, placebo-controlled phase III study. Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 μg/day/eye) or placebo twice daily for 90 days and were followed up to day 180. The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL. Although no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related. This first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated.

The increase of chronic diseases worldwide impact quality of life, cause economic and medical costs, and make it necessary to look for strategies and solutions that allow people with chronic diseases (PwCDs) to lead an active working life. As part of the CHRODIS Plus Joint European Action project, a systematic review was conducted to identify studies of interventions that support the maintenance of work and return to work (RTW) among workers with chronic illnesses. These interventions should target employees with the following conditions: diabetes, cardiovascular diseases, metabolic vascular syndrome, respiratory diseases, musculoskeletal disorders, mental disorders, and neurological disorders. An extensive search was performed in PubMed, EMBASE, and PsycINFO for English language studies. Included in this review were 15 randomized controlled trials (RCT) for adult employees (aged 18+). We found that workplace-oriented and multidisciplinary programs are the most supportive to RTW and reducing the absence due to illness. In addition, cognitive behavioral therapies achieve positive results on RTW and sick leave. Finally, coaching is effective for the self-management of chronic disease and significantly improved perceptions of working capacity and fatigue.

Sensory substitution constitutes an interesting domain of study to consider the philosopher's classical question of distal attribution: how we can distinguish between a sensation and the perception of an object that causes this sensation. We tested the hypothesis that distal attribution consists of three distinct components: an object, a perceptual space, and a coupling between subjects' movements and stimulation. We equipped sixty participants with a visual-to-auditory substitution device, without any information about it. The device converts the video stream produced by a head-mounted camera into a sound stream. We investigated several experimental conditions: the existence or not of a correlation between movements and resulting stimulation, the direct or indirect manipulation of an object, and the presence of a background environment. Participants were asked to describe their impressions by rating their experiences in terms of seven possible "scenarios". These scenarios were carefully chosen to distinguish the degree to which the participants attributed their sensations to a distal cause. Participants rated the scenarios both before and after they were given the possibility to interrupt the stimulation with an obstacle. We were interested in several questions. Did participants extract laws of co-variation between their movements and resulting stimulation? Did they deduce the existence of a perceptual space originating from this coupling? Did they individuate objects that caused the sensations? Whatever the experimental conditions, participants were able to establish that there was a link between their movements and the resulting auditory stimulation. Detection of the existence of a coupling was more frequent than the inferences of distal space and object.

Surveillance systems for varicella in Europe are highly heterogeneous or completely absent. We estimated the varicella incidence based on seroprevalence data, as these data are largely available and not biased by under-reporting or underascertainment. We conducted a systematic literature search for varicella serological data in Europe prior to introduction of universal varicella immunization. Age-specific serological data were pooled by country and serological profiles estimated using the catalytic model with piecewise constant force of infection. From the estimated profiles, we derived the annual incidence of varicella infection (/100·000) for six age groups (<5, 5-9, 10-14, 15-19, 20-39 and 40-65 years). In total, 43 studies from 16 countries were identified. By the age of 15 years, over 90% of the population has been infected by varicella in all countries except for Greece (86·6%) and Italy (85·3%). Substantial variability across countries exists in the age-specific annual incidence of varicella primary infection among the <5 years old (from 7052 to 16 122 per 100 000) and 5-9 years old (from 3292 to 11 798 per 100 000). The apparent validity and robustness of our estimates highlight the importance of serological data for the characterization of varicella epidemiology, even in the absence of sampling or assay standardization.