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To study the frequency and types of strabismus in congenital aniridia, the presence of associated nystagmus, foveal hypoplasia, and congenital cataracts.Prospective, single-center cohort study.A review was conducted of 379 medical records of congenital aniridia patients who had a follow-up at the Necker-Enfants malades University Hospital between 2006 and 2022; the target age was between 12 months and 30 years. Ophthalmologic and orthoptic assessments according to age were performed. Strabismus was further analyzed according to the type of aniridia, foveal hypoplasia, and laterality of congenital cataract.Strabismus was diagnosed in 150 patients; 73 were included in the study (28 males [38%] and 45 females [62%]), with a mean age of 11.02 years. The mean follow-up was 24 months. Thirty-six (49.3%) presented with familial aniridia, and 37 (50.7%) presented with sporadic aniridia. Thirty-six (49.3%) were diagnosed with esotropia, 37 (50.7%) had exotropia. Nystagmus was detected in 70 patients (96%). Thirty-nine (53.4%) suffered from congenital cataract, 10 unilateral (25.7%) and 29 bilateral (74.3%). Foveal hypoplasia was found in 73 cases (100%); esotropia was predominant in all grades. PAX6 mutation was found in 56 patients (77%).Strabismus is one of the clinical signs of congenital aniridia. The laterality of congenital cataracts seems to affect the type of strabismus. The grade of foveal hypoplasia has little impact on strabismus but is prevalent for nystagmus. Foveal hypoplasia affects optical focus, which is essential for binocularity; this could explain the poor binocular adjustment leading to strabismus without exotropia or esotropia predominance.

IntroductionVernal keratoconjunctivitis (VKC) is a rare, severe allergic ocular disease, typically occurring in children and adolescents, that can have a significant impact on quality of life and lead to visual impairment. Long-term treatment may be necessary to tackle chronic inflammation and topical corticosteroid dependency must be minimised due to the risk of complications. There is a need for unified clinical guidance to aid the assessment, diagnosis and management of VKC across Europe. The aim of this expert panel (the EUR-VKC Group) was to provide clear guidance for primary care physicians and general ophthalmologists involved in the diagnosis and management of VKC.MethodsAn expert group of seven European ophthalmologists was convened and a modified nominal group technique used to develop key recommendations on VKC management. The recommendations were subject to up to two rounds of voting using a 5-point Likert scale to ascertain consensus and the strength of each recommendation. Consensus was set at a predetermined threshold of ≥ 75.0% of experts selecting ‘Strongly agree’ or ‘Agree’.ResultsA total of 47 recommendations were developed relating to the assessment of key of VKC, guidance on who and when to refer, as well as treatment-escalation pathways, long-term follow-up, and supportive care and education. All recommendations reached consensus after two rounds. The group emphasise how timely diagnosis and treatment initiation that is appropriate to disease severity are crucial to benefit patients with VKC. Patients with signs (‘red flags’) indicating severe VKC, or persistent mild-to-moderate VKC that is non-responsive following 2–4 weeks of treatment, should be referred to a sub-specialist.ConclusionThe EUR-VKC Group provides recommendations on the assessment, diagnosis, management, referral and follow-up of patients with VKC. It also provides a framework to facilitate collaboration between primary care physicians, general ophthalmologists and sub-specialists to improve the outcomes for patients with VKC. Introduction: Vernal keratoconjunctivitis (VKC) is a rare, severe allergic ocular disease, typically occurring in children and adolescents, that can have a significant impact on quality of life and lead to visual impairment. Long-term treatment may be necessary to tackle chronic inflammation and topical corticosteroid dependency must be minimised due to the risk of complications. There is a need for unified clinical guidance to aid the assessment, diagnosis and management of VKC across Europe. The aim of this expert panel (the EUR-VKC Group) was to provide clear guidance for primary care physicians and general ophthalmologists involved in the diagnosis and management of VKC. Methods: An expert group of seven European ophthalmologists was convened and a modified nominal group technique used to develop key recommendations on VKC management. The recommendations were subject to up to two rounds of voting using a 5-point Likert scale to ascertain consensus and the strength of each recommendation. Consensus was set at a predetermined threshold of ≥ 75.0% of experts selecting ‘Strongly agree’ or ‘Agree’. Results: A total of 47 recommendations were developed relating to the assessment of key of VKC, guidance on who and when to refer, as well as treatment-escalation pathways, long-term follow-up, and supportive care and education. All recommendations reached consensus after two rounds. The group emphasise how timely diagnosis and treatment initiation that is appropriate to disease severity are crucial to benefit patients with VKC. Patients with signs (‘red flags’) indicating severe VKC, or persistent mild-to-moderate VKC that is non-responsive following 2–4 weeks of treatment, should be referred to a sub-specialist. Conclusion: The EUR-VKC Group provides recommendations on the assessment, diagnosis, management, referral and follow-up of patients with VKC. It also provides a framework to facilitate collaboration between primary care physicians, general ophthalmologists and sub-specialists to improve the outcomes for patients with VKC.

Designing activity detection systems that can be successfully deployed in daily-living environments requires datasets that pose the challenges typical of real-world scenarios. In this paper, we introduce a new untrimmed daily-living dataset that features several real-world challenges: Toyota Smarthome Untrimmed (TSU). TSU contains a wide variety of activities performed in a spontaneous manner. The dataset contains dense annotations including elementary, composite activities and activities involving interactions with objects. We provide an analysis of the real-world challenges featured by our dataset, highlighting the open issues for detection algorithms. We show that current state-of-the-art methods fail to achieve satisfactory performance on the TSU dataset. Therefore, we propose a new baseline method for activity detection to tackle the novel challenges provided by our dataset. This method leverages one modality (i.e. optic flow) to generate the attention weights to guide another modality (i.e RGB) to better detect the activity boundaries. This is particularly beneficial to detect activities characterized by high temporal variance. We show that the method we propose outperforms state-of-the-art methods on TSU and on another popular challenging dataset, Charades., Toyota Smarthome Untrimmed dataset, project page: https://project.inria.fr/toyotasmarthome

Grass-dominated ecosystems cover ~40% of Earth's terrestrial surface, with tropical grasses accounting for ~20% of global net primary productivity. C3 (cool/temperate) and C4 (tropical and subtropical) grass distribution is driven primarily by temperature. In this work, we used phytolith assemblages collected from vegetation plots along an elevation and temperature gradient in the northern Andes (Colombia and Ecuador) to develop a paleothermometer for the region. To accomplish this, we created a transfer function based on the inverse relationship between mean annual temperature (MAT) and the phytolith-based climatic index (Ic), which is the proportion of C3 over C4 grass phytoliths (GSSCP). To evaluate how accurately the index reflects C4–C3 grass abundance in vegetation plots, we compared it with semiquantitative floristic estimates of C4–C3 grass abundance. To further evaluate the 1 − Ic index as a proxy for C4–C3 grass abundance, we compared it with corresponding δ13C values (an independent proxy for C4–C3 vegetation). Results indicate that (1) GSSCP assemblages correctly estimate C4–C3 grass abundance in vegetation plots; (2) the Ic index outperforms the δ13C record in estimating C4–C3 grass abundance, even in open-vegetation types; and (3) our Ic index–based model accurately predicts MAT. This new calibrated proxy will help improve paleotemperature reconstructions in the northern Andes since at least the emergence and spread of C4 grasses in the region during the late Miocene.

Droplet-based microfluidic platform for viscosity measurement over extended concentration range.

As an alpha emitter and chemical toxicant, uranium toxicity in living organisms is driven by its molecular interactions. It is therefore essential to identify main determinants of uranium affinity for proteins. Others and we showed that introducing a phosphoryl group in the coordination sphere of uranyl confers a strong affinity of proteins for uranyl. In this work, using calmodulin site 1 as a template, we modulate the structural organization of a metal-binding loop comprising carboxylate and/or carbonyl ligands and reach affinities for uranyl comparable to that provided by introducing a strong phosphoryl ligand. Shortening the metal binding loop of calmodulin site 1 from 12 to 10 amino acids in CaMΔ increases the uranyl-binding affinity by about 2 orders of magnitude to log

International audience; Muography uses muons contained in the natural cosmic rays to determine the density of rock volumes. The measurements consist of counting the muons emerging from the target to determine the screening effect produced by the rock. Since the larger the rock thickness, the smaller the number of muons able to cross, the time resolution that can be achieved by muography to monitor density changes is on the order of one or two weeks for kilometer-sized volcanoes. This limitation of the method can be reduced by joining muography with high time-resolution measurements like passive seismic monitoring. In the case of structural imaging, muography benefits from the fact that muon trajectories are linear, making the tomography problem simpler than for other geophysical techniques like electrical resistivity tomography. Experiments performed on La Soufrière of Guadeloupe volcano are described to show how muography can be used to contribute to structural imaging of a highly heterogeneous lava dome and to detect abrupt transient hydrothermal phenomena likely to produce dangerous explosive events.

The analysis of impacts of climatic events on socioeconomic systems is based on the collection of post-event data. However, this method rarely describes the processes and the decisions that generated the impacts. Yet, counting on thorough descriptions of those processes and decisions, although very time-consuming, takes on its full meaning when several climatic phenomena follow one another on complex economic systems. In the Mediterranean context, and moreover in the context of climate change, it is not uncommon for several climatic hazards to follow one another. For agricultural activities, whose harvests and thus added value are produced over several months, this implies that a production campaign can be affected by different events (e.g. frost, hail, drought, flooding, etc.), causing the strategy of the various actors involved to be readjusted. We propose to address the problem of the analysis of the succession of two climatic events for the estimation of the impacts on a complex economic system through the case study of a wine cooperative located in the department of Aude in the South-West of France which was affected during the 2021 production campaign by a frost in March and a flood in September at the time of the harvest. We are interested in three questions: (i) are there impacts resulting specifically from the succession of both climatic events?; (ii) are there impacts resulting from the organisational links between the winegrowers (individual level) and the wine-making cooperative (collective level)?; (iii) which indicators are relevant to highlight them? In our case study, the cooperative winery brings together 128 winegrowers representing 1100 ha and has three vinification sites. 65 winegrowers out of the 128 were impacted by at least one of the events. To analyse the impacts of both events on the cooperative, we carried out a questionnaire-type survey among the affected winegrowers. We obtained 57 responses to the preliminary questionnaire and 33 exhaustive interviews. Three interviews were also conducted with the managers in charge of the winery during this campaign. After an initial analysis of the results, we presented and discussed these results with the representatives and some of the winegrowers surveyed. The consolidation of the analyses is still in progress. However, this work already shows that there are cross-effects resulting from the succession of both events. For instance, our surveys enable us to discern the loss of quality or yield due to biophysical processes (e.g. frost, berries' rotting or bursting) from loss of quality due to organizational impacts at the winegrower level (e.g. inaccessibility of the plots at the time of harvesting due to flooding that aggravates the loss of quality). We also show that the succession of events generated specific impacts linked to collective readjustment decisions taken at the winery level. We will discuss the scope of this analysis and the interest of this approach to consider possible adaptations to be implemented.

Background The FLURESP project is a public health research funded by the European Commission, with the objective to design a methodological framework to assess the cost-effectiveness of existing public health measures against human influenza pandemics. A dataset has been specifically collected in the frame of the Italian health system. As most of interventions against human influenza are relavant against other respiratory diseases pandemics, potential interests in COVID-19 are discussed. Methods Ten public health measures against human influenza pandemics pandemic were selected to be also relevant to other respiratory virus pandemics such as COVID 19: individual (hand washing, using masks), border control (quarantine, fever screening, border closure), community infection (school closure, class dismissal, social distancing, limitation of public transport), reduction of secondary infections (implementation of antibiotic therapy guidelines), pneumococcal vaccination for at-risk people, development of Intensive Care Unit (ICU) capacity, implementation of life support equipments in ICU, screening interventions, vaccination programs targeting health professional and targeting general population. Results Using mortality reduction as effectiveness criteria, the most cost-effective strategies are “reduction of secondary infections” and “implementation of life support equipment in ICU”. The least cost-effective option whatever the level of pandemic events are screening interventions and mass vaccination. Conclusions A number of intervention strategies against human influenza pandemics appears relevant against every respiratory virus, including the COVID-19 event. Measures against pandemics should be considered according to their expected effectiveness but also their costs for the society because they impose substantial burden to the population, confirming the interest of considering cost-effectiveness of public health measures to enlighten decision making.

International audience; Purpose: To correlate the degree of foveal hypoplasia in congenital aniridia with visual acuity, iris phenotype, and PAX6 mutations.Design: Retrospective case series.Methods: 95 consecutive patients with high quality Spectral-domain optical coherence tomography (SD-OCT) records and available genotype were included in a single referral center. Iris hypoplasia was classified as complete, presence of iris root or remnants and mild atypical aniridia. SD-OCT images were assessed to classify foveal hypoplasia as Grade 1 to 4 and to determine mean thicknesses for retinal layers. For statistical analysis one eye for each patient have been used and one member of the same family has been included (n=76 eyes).Results: Most eyes (93.5%) showed variable degree of foveal hypoplasia. PAX6-positive patients presented higher degree of foveal hypoplasia than patients negative for PAX6 (p

Introduction While paramacular retinal atrophy (PRA) is known to be found in 48% of eyes of adults and 42% of eyes of children with homozygous SCD (SS-SCD), the aim of this study is to assess the association between PRA and red blood cell (RBC) deformability, hematological markers and brain imaging abnormalities in SS-SCD. Methods This study is a subset of DREAM2, a prospective observational study performed between August 2015 and August 2016. Children (5–17 years) with SS-SCD and no history of large vessel vasculopathy, were included. Ophthalmological characteristics including visual acuity, fundus examination, OCT of central and temporal retina (with several retinal thickness measurements) were explored in relation with RBC deformability (ektacytometry), hematological and biochemical (hemolysis parameters), and neurological (cerebral oxygenation estimated by Near Infrared Spectroscopy, brain magnetic resonance imaging) investigations. Results 17 children (5 boys; mean age: 13 years) with complete ophthalmological investigations were included in the analysis; 8 exhibited PRA. RBC deformability was found to be significantly lower in children with PRA for measurements made at 1.69 Pa (0.16 a.u ± 0.02 vs 0.21 a.u ± 0.03, p = 0.02) and above, as well as cerebral oxygenation (59.25% ± 9.9 vs 71.53% ± 4.9, p = 0.02). A significant positive correlation was found between temporal retinal thickness and hemoglobin level (ρ = 0.65, p = 0.007), hematocrit (ρ = 0.53, p = 0.04) and RBC deformability at 3 Pa (ρ = 0.75, p = 0.005) and above. Conclusions These results suggest that PRA could be an early marker of systemic severity and cerebral oxygenation in SCD. Whether it could help predicting cerebral vasculopathy requires further investigations.

Introduction Among non-syndromic, single-suture craniosynostoses, unicoronal craniosynostosis (UCS) presents the highest rate of ophthalmic manifestations requiring a visual follow-up, due to the high risk of amblyopia. After birth or during childhood, children with UCS have a high risk to present an aniso-astigmatism and a strabismus. The aim of this study was to characterize clinical ophthalmologic findings associated with UCS in a paediatric cohort. Methods This retrospective study included children admitted in our unit between 2015 and 2021, with isolated UCS treated in our institution and complete ophthalmological assessment comprising visual assessment, refractive status and oculomotor examination. Children with associated craniofacial disorders were excluded. Results A total of 28 children met the inclusion criteria. Median age was 62 [13-192] months with a large proportion of girls (86%) and 71% of right-sided UCS. The mean best corrected visual acuity was 0.07 (±0.13) LogMAR, including 10 (36%) children with an amblyopia or history of amblyopia. Astigmatism was significantly higher on the contralateral side of the UCS than on the ipsilateral side, with a refractive cylinder error of 0.97 (±1.06) vs 0.56 (±0.68) diopters, respectively (p = 0.03). Strabismus was observed in 20 patients (71%) with a main pattern of esotropia with a vertical component. A pseudo-superior oblique palsy was found in 13 children (65%) with a median cyclodeviation of 8.7° [-5,4°-20.6°]. Conclusion Children with UCS experience a high rate of various visual manifestations. This study highlights their need for a strict ophthalmological follow-up, in order to early diagnose and prevent visual complications.

Climatic changes in southern Europe during the Holocene are characterised by a strong spatial and temporal heterogeneity whose patterns are still poorly understood, notably the presence or not of a Holocene thermal maximum (HTM; 10,000–6,000 cal. BP). The reconstructed climatic patterns also differ according to the proxies used (e.g., pollen, chironomid) and the latitude of the data. Here, a multi-proxy approach combining pollen and lipid biomarkers (branched Glycerol Dialkyl Glycerol Tetraethers, brGDGTs) is applied to the Canroute sedimentological sequence to reconstruct the climatic variation over the last 15,000 years in southern Massif Central, France. This area is poorly documented in terms of vegetation and climate. To provide reliable climate reconstructions, we have (1) performed a multi-method comparison based on transfer functions applied to pollen (MAT, WA-PLS, BRT) and molecular biomarkers (brGDGTs), (2) investigated the role of modern databases/calibrations in climate reconstructions. Three different calibration databases were tested for pollen data: one global based on a Eurasian Pollen Database, and two regional databases corresponding to Mediterranean/Temperate Europe and Temperate Europe/Scandinavian databases respectively. Nine global calibrations were tested for lipid biomarkers including eight for soil and one for peat. The use of different modern databases highlights the importance of considering environmental and ecological constraints when using transfer functions on pollen sequences. Pollen and brGDGT-inferred climate trends are consistent, notably for the Lateglacial, the Early and Late Holocene. However, the reconstructions notably differ concerning the presence of a Holocene thermal maximum with the Modern Analogue Technique (MAT) pollen-based method but not apparent with the BRT pollen method nor brGDGT. The temperature reconstructions estimated from the two independent pollen and lipid proxies are then compared to regional published climate signals (chironomids, pollen, molecular biomarkers) to better derive global regional climatic patterns in South Europe. Altogether, our results from the Canroute sequence and those already available in southern Europe reveal that for the Lateglacial and Early Holocene, the regional climate trends are coherent between sites and proxies, supporting the reliability of their reconstructions despite some discrepancies. During the Holocene, the temperature signal of Canroute does not indicate the clear presence of a pronounced mid-Holocene thermal maximum, but rather stable and warmer temperature compared to Lateglacial ones and overall negative anomalies compared to modern annual temperatures.

Duchenne muscular dystrophy (DMD) is a severe and progressive myopathy leading to motor and cardiorespiratory impairment. We analyzed samples from patients with DMD and a preclinical rat model of severe DMD and determined that compromised repair capacity of muscle stem cells in DMD is associated with early and progressive muscle stem cell senescence. We also found that extraocular muscles (EOMs), which are spared by the disease in patients, contain muscle stem cells with long-lasting regenerative potential. Using single-cell transcriptomics analysis of muscles from a rat model of DMD, we identified the gene encoding thyroid-stimulating hormone receptor ( Tshr ) as highly expressed in EOM stem cells. Further, TSHR activity was involved in preventing senescence. Forskolin, which activates signaling downstream of TSHR, was found to reduce senescence of skeletal muscle stem cells, increase stem cell regenerative potential, and promote myogenesis, thereby improving muscle function in DMD rats. These findings indicate that stimulation of adenylyl cyclase leads to muscle repair in DMD, potentially providing a therapeutic approach for patients with the disease.

Ecosystem restoration is an important means to address global sustainability challenges. However, scientific and policy discourse often overlooks the social processes that influence the equity and effectiveness of restoration interventions. In the present article, we outline how social processes that are critical to restoration equity and effectiveness can be better incorporated in restoration science and policy. Drawing from existing case studies, we show how projects that align with local people's preferences and are implemented through inclusive governance are more likely to lead to improved social, ecological, and environmental outcomes. To underscore the importance of social considerations in restoration, we overlay existing global restoration priority maps, population, and the Human Development Index (HDI) to show that approximately 1.4 billion people, disproportionately belonging to groups with low HDI, live in areas identified by previous studies as being of high restoration priority. We conclude with five action points for science and policy to promote equity-centered restoration., Bioscience, 73 (2), ISSN:0006-3568, ISSN:1525-3244

BACKGROUND: Risdiplam is an oral small molecule approved for the treatment of patients with spinal muscular atrophy, with approval for use in patients with type 2 and type 3 spinal muscular atrophy granted on the basis of unpublished data. The drug modifies pre-mRNA splicing of the SMN2 gene to increase production of functional SMN. We aimed to investigate the safety and efficacy of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy. METHODS: In this phase 3, randomised, double-blind, placebo-controlled study, patients aged 2-25 years with confirmed 5q autosomal recessive type 2 or type 3 spinal muscular atrophy were recruited from 42 hospitals in 14 countries across Europe, North America, South America, and Asia. Participants were eligible if they were non-ambulant, could sit independently, and had a score of at least 2 in entry item A of the Revised Upper Limb Module. Patients were stratified by age and randomly assigned (2:1) to receive either daily oral risdiplam, at a dose of 5·00 mg (for individuals weighing =20 kg) or 0·25 mg/kg (for individuals weighing

Background Long-term and ongoing support in accordance with the changing needs of patients and their families is one of the main components of patient care, including therapeutic patient education (TPE). Objective To co-construct a TPE program for albinism with all those involved in the management of albinism patients. Methods Eight steps have been defined for the co-construction process: 1) identify all the relevant experts and invite them to participate in the construction of a TPE program to improve care for and support of patients with albinism, 2) review and analyse all publications regarding TPE for albinism, 3) conduct semi-structured interviews with the patients’ parents, 4) conduct brainstorming meetings with the participating experts for an exchange of experience and expertise, 5) elaborate the program's concrete content with the experts, 6) draw up a TPE skills checklist, 7) create TPE educational tools to facilitate learning, 8) review and summarize each step of the co-construction protocol. Results Co-construction of a TPE program for children, adolescents, and young adults with albinism, and their parents. Conclusion Strengths and advantages of the co-construction process include: i) highlighting of the experiential knowledge mentioned in the repository, ii) multiplicity of points of view and perspectives, iii) rapid improvement in TPE training both for the association and the patients, iv) awareness of the shift caregivers’ position with regards to TPE and recognition of the polysemy of their discourse. The TPE program for albinism has been authorized since 2018.

Aniridia is a panocular inherited rare eye disease linked to heterozygous mutations on the PAX6 gene, which fail to properly produce sufficient protein essential for normal eye development and function. Most of the patients suffer from aniridia-related keratopathy, a progressive opacification of the cornea. There is no effective treatment for this blinding disease. Here we screen for small compounds and identified Ritanserin, a serotonin 2A receptor antagonist, that can rescue PAX6 haploinsufficiency of mutant limbal cells, defective cell migration and PAX6-target gene expression. We further demonstrated that Ritanserin activates PAX6 production through the selective inactivation of the MEK/ERK signaling pathway. Our data strongly suggest that repurposing this therapeutic molecule could be effective in preventing or treating existing blindness by restoring corneal transparency.

Purpose: To evaluate whether retinopathy of prematurity (ROP) diagnosis was modified after the introduction of wide-field imaging for ROP screening compared to previously used binocular indirect ophthalmoscopy (BIO) in real-life conditions. Methods: Records of consecutive premature newborns screened for ROP in a level-3 reference center, over two 1-year periods, were retrospectively reviewed. Screening was performed by ophthalmologists using BIO in 2014, and digital wide-field retinal imaging (PanocamTM pro) in 2019. Systemic factors potentially influencing the occurrence of ROP were investigated using uni- and multivariable linear regression followed by stepwise forward regression. Results: Records of N=297 patients were analyzed (N=159 in 2014 and N=138 in 2019). The proportion of ROP diagnosed at any stage, over the total number of neonates screened, was significantly higher in 2019 (n=46/138, 33.1%) compared to 2014 (n=11/159, 6.9%) (pConclusions: After adjusting for many recognized systemic factors influencing the development of ROP, screening by wide-field digital retinal imaging was independently associated to higher ROP detection.

Background/Objectives Cyclosporine A cationic ophthalmic emulsion (CsA CE) was evaluated in paediatric and adolescent patients with vernal keratoconjunctivitis (VKC) in the NOVATIVE (NCT00328653) and VEKTIS (NCT01751126) trials. The similarity of these studies permitted pooled assessment of the effect of CsA CE on corneal damage as well as safety and tolerability. Subjects/Methods Pooled outcomes were assessed for the first 28 days of treatment. In NOVATIVE, 118 patients were randomised to 4 times daily (QID) CsA CE 0.05%, 0.1%, or vehicle eye drops. In VEKTIS, 169 patients were randomised to CsA CE 0.1% QID or twice daily (BID) or vehicle. For these analyses, treatment groups comprised: (1) pooled CsA CE 0.1% QID arms (high-dose; n = 96); (2) pooled CsA CE 0.05% QID arm from NOVATIVE and CsA CE 0.1% BID data from VEKTIS (low-dose; n = 93); and (3) pooled vehicle QID arms (vehicle; n = 98). Results Changes from baseline to day 28 (mean ± standard deviation) in corneal fluorescein staining (CFS) scores for CsA CE high-dose, low-dose, and vehicle groups were −1.6 ± 1.47 (95% CI: −0.9, −0.1; p = 0.0124 vs vehicle), −1.7 ± 1.39 (95% CI: −1.1, −0.3; p = 0.0015 vs vehicle), and −1.0 ± 1.55, respectively. Adverse events (AEs) of any type were reported in 37.5%, 34.4%, and 37.8% of the high-dose, low-dose, and vehicle groups, respectively. Most were mild or moderate in severity. Conclusions CsA CE significantly decreased corneal damage and was safe and well tolerated in patients with VKC. These data support CSA CE as a treatment option for the management of VKC.

Purpose Retinal vascular abnormalities (RVA) have been recently described in patients with neurofibromatosis type 1 (NF1) as vascular tortuosity, best visible on infrared imaging. This study assessed clinical RVA's characteristics in a large series of children with NF1. Methods This retrospective observational study was conducted in children (0 - 18 years old) with an NF1 diagnosis. Using near infrared imaging, RVAs were classified according to the nature of vessels involvement and their degree of tortuosity. Results Retinal imaging from 140 children, with a median age of 8.8 [1.5 - 18] years, were included; 52 (37.1%) patients (81 eyes) exhibited RVAs. These RVAs comprised 96% (50/52) of simple vascular tortuosity and 17% (9/52) of cork-screw pattern. Cork-screw pattern involved only small veins, while simple vascular tortuosity could affect both arteries and veins. No statistically significant age correlation was observed, but evolution of RVAs from simple vascular tortuosity to cork-screw pattern was observed in 5 cases. Conclusion Retinal vascular abnormalities occurred in 37.1% of children with NF1. These abnormalities may result from NF1 promoting localised tortuosity in both small arteries and veins, while only small second or tertiary order venules evolve to highly tortuous pattern.

Background Vernal keratoconjunctivitis (VKC) is a severe type of allergic conjunctivitis for which treatment strategies are still under debate. Objectives This study sought to conduct a systematic review and meta-analysis to evaluate the efficacy of medical treatments for VKC. Methods The PubMed, Cochrane Library, Embase, and ScienceDirect databases were searched to assess the efficacy of treatments for VKC. Random-effect meta-analyses on changes in clinical scores of symptoms and signs between baseline and after treatment, stratified on treatment classes, were computed. Meta-regressions were searched for potential influencing parameters. Results Included were 45 studies (27 randomized controlled trials and 18 prospective cohort studies), 1749 patients (78% were men; mean age, 11.2 years), and 12 different treatment classes. Mast cell stabilizers (MCSs; usually considered as first-line therapy), cyclosporine, and tacrolimus were the most studied drugs (in three-quarters of studies). Overall, all clinical scores improved. Total symptom and sign score decreased for MCSs (effect size, −3.19; 95% CI, –4.26 to −2.13), cyclosporine (effect size, −2.06; 95% CI, −2.72 to −1.40), and tacrolimus (effect size, −2.39; 95% CI, −3.36 to −1.43). No significant differences were shown depending on treatment classes, concentration, age, sex, baseline activity scores, and atopy. Sensitivity analyses demonstrated similar results. Conclusions This study confirms the efficacy of MCSs in the treatment of VKC. Efficacy of cyclosporine and tacrolimus did not differ, suggesting that tacrolimus is a good alternative to cyclosporine for severe cases of VKC. Further studies are needed to compare other drugs and their precise place in treatment strategy.

International audience; The recovery and identification of wood charcoals from soil not associated to archaeological excavation is called pedoanthracology. Researchers in this field use different sampling methods, and only one study, in a temperate context, has compared their efficiency so far. In this paper, we compare the efficiency of three sampling methods on charcoal concentration (> 4 mm) and on taxonomic representativeness in a tropical environment for the first time. These methods are pit sampling, auger sampling and opportunistic handpicking of charcoal on tree uprooted mounds or in the soil excavated during the digging of a pit. Our results suggest that the two digging methods (pit and auger) allow to recover similar charcoal concentrations whatever the site and the depth under consideration. But as expected, the charcoal concentration of a site depends on its history (e.g. type of activity). We also show that the estimation of the minimal sampling effort required to obtain taxonomically representative assemblages, in terms of number of charcoals and of auger samplings, varied greatly depending on the site and on the presence of overrepresented taxa. Finally, our results show that auger cores were often monospecific (34 %). Nevertheless, they allowed to recover different taxa from the pit method, with 18 to 21 % of the taxa exclusive to the first method and 30 to 40 % of the taxa exclusive to the second one in the sites under consideration. Charcoals from opportunistic handpicking also allowed to improve the taxonomic diversity of the whole assemblage of a site with 5 to 15 % of the taxa being exclusive to this method. The three methods are therefore complementary and we suggest to use the three of them to obtain the best taxonomic diversity in an anthracological assemblage and to overcome the specific biases of each method. With this study, we hope that we will help tropical (pedo)anthracologists to optimize charcoal sampling in anthropogenic sites were the sampling design cannot benefit from archaeological excavations.; La collecte et l'identification de charbons de bois de sol non associées à des fouilles archéologiques est appelée pédoanthracologie. Les chercheurs dans ce domaine utilisent différentes méthodes d'échantillonnage, et une seule étude, dans un contexte tempéré, a comparé leur efficacité jusqu'à présent. Dans cet article, nous comparons pour la première fois l'efficacité de trois méthodes d'échantillonnage sur la concentration en charbon de bois (> 4 mm) et sur la représentativité taxonomique dans un environnement tropical. Ces méthodes sont l'échantillonnage en fosse, l'échantillonnage à la tarière et le prélèvement manuel opportuniste de charbon de bois sur des monticules d'arbres déracinés ou dans le sol excavé lors du creusement d'une fosse. Nos résultats suggèrent que les deux méthodes de creusement (fosse et tarière) permettent de retrouver des concentrations de charbon de bois similaires quels que soient le site et la profondeur considérés. Mais comme prévu, la concentration en charbon de bois d'un site dépend de son histoire (ex. : type d'activité). Nous montrons également que l'estimation de l'effort d'échantillonnage minimal requis pour obtenir des assemblages taxonomiquement représentatifs, en termes de nombre de charbons de bois et de nombre de prélèvements à la tarière, varie fortement en fonction du site et de la présence de taxons surreprésentés. Enfin, nos résultats montrent que les tarières étaient souvent monospécifiques (34 %). Néanmoins, ils ont permis de récupérer des taxons différents de la méthode de la fosse, avec 18 à 21 % des taxons exclusifs à la première méthode et 30 à 40 % des taxons exclusifs à la seconde dans les sites considérés. Les charbons provenant d'une collecte manuelle opportuniste ont également permis d'améliorer la diversité taxonomique de l'ensemble de l'assemblage d'un site avec 5 à 15 % des taxons exclusifs à cette méthode. Les trois méthodes sont donc complémentaires et nous proposons de les utiliser toutes les trois pour obtenir la meilleure diversité taxonomique dans un assemblage anthracologique et pour surmonter les biais spécifiques de chaque méthode. Avec cette étude, nous espérons aider les (pédo)anthracologues tropicaux à optimiser l'échantillonnage des charbons de bois dans les sites anthropiques où le plan d'échantillonnage ne peut bénéficier des fouilles archéologiques.

Floods are the natural hazard that generates the most damage in the world, but many aspects of how this damage occurs are still poorly understood. Indeed, the impacts of floods can concern all types of stakes (dwellings, economic or agricultural activities, public infrastructures, networks, etc.), whether they are directly impacted by the flood or indirectly by the propagation of disturbances through society, or even in a temporal delay compared to the original event. Moreover, these impacts may differ according to the nature of the flood (e.g. overflow, runoff, salt water flooding). Finally, the impacts are the result of complex biophysical processes but also of protection, repair and adaptation actions implemented by affected people.Our objective is to highlight the diversity of flood impacts, including the issue of their persistence. To this end, we propose an original method that combines post-flood observation surveys with long-term monitoring of individuals exposed to floods. This methodology is implemented in the framework of the system of observations of the impacts of floods (so-ii, http://so-ii.org) in the Greater Montpellier area coordinated by our team. For the quantitative surveys, based on our past observation and modelling experiences, we have developed questionnaires that aim to collect the impacts of flooding, following an event, in an exhaustive and cumulative manner.These questionnaires were applied following a flood event that occurred on September 20th 2020 in the north of Montpellier. For long-term monitoring, we set up networks of impact observers (inhabitants and farmers for the moment), with whom we agreed to work over the long term (about fifteen years).With these groups, we have defined an observation protocol, combining individual interviews to better specify each person's situation (e.g. individual vulnerability, characteristics of buildings) with participatory workshops to discuss the results, orient future work, and pool each person's experiences. In this paper we present the intermediate results of this ongoing research. We also discuss the relevance and limitations of such an approach to improve the understanding and assessment of flood damage.

International audience; Primary cilia (PC) are important signaling hubs, and we here explored their role in colonic pathology. In the colon, PC are mostly present on fibroblasts, and exposure of mice to either chemically induced colitis-associated colon carcinogenesis (CAC) or dextran sodium sulfate (DSS)-induced acute colitis decreases PC numbers. We generated conditional knockout mice with reduced numbers of PC on colonic fibroblasts. These mice show increased susceptibility to CAC, as well as DSS-induced colitis. Secretome and immunohistochemical analyses of DSS-treated mice display an elevated production of the proinflammatory cytokine IL-6 in PC-deficient colons. An inflammatory environment diminishes PC presence in primary fibroblast cultures, which is triggered by IL-6 as identified by RNA-seq analysis together with blocking experiments. These findings suggest an activation loop between IL-6 production and PC loss. An analysis of PC presence on biopsies of patients with ulcerative colitis or colorectal cancer (CRC) reveals decreased numbers of PC on colonic fibroblasts in pathological compared with surrounding normal tissue. Taken together, we provide evidence that a decrease in colonic PC numbers promotes colitis and CRC.

Inherited epidermolysis bullosa (EB) is a group of genetic rare diseases associated with skin fragility, which leads to the formation of blisters, erosions, and scars on the skin and mucous membranes. Epidermolysis bullosa includes four main types and some several clinical subtypes including EB simplex, junctional EB, dystrophic EB, and Kindler's EB. Ocular involvement ranged from 51 to 68% in EB and can cause irreversible damages if not properly managed. Corneal erosions are the most common finding among series, including our cohort. We review here clinical and pathological features of ocular involvement in EB and the main keys for management, with a focus on recent innovative therapies.

International audience

Summary Study objective To study the performance of a pre-loaded Monoka stent in the management of congenital nasolacrimal duct obstruction (CNLDO). Study design Non-randomized study of consecutive cases. Materials and methods A preloaded classic Monoka silicone stent contained entirely inside its introducer (Lacrijet) was used to treat a consecutive series of subjects with CNLDO over an 11-month period (May 2019–March 2020). Only subjects with chronic symptomatic CNLDO were included. Subjects with intermittent tearing, canalicular pathology, trisomy 21, facial cleft, or history of lacrimal surgery were excluded. Intraoperative findings were recorded, including the degree and location of the nasolacrimal obstruction, successful metal to metal contact with the probe, any difficulties encountered by the Lacrijet device itself, procedure duration, tolerability of the fixation punctal plug, and finally, inspection of the stent after withdrawal of the inserter. Functional success was defined as disappearance of all symptoms of epiphora. Results A total of 45 preloaded Monoka Lacrijet stents (Lcj) were placed consecutively in 38 children. The mean age was 27.9 months (12–78 months). The mean procedural duration was 2.8 minutes (range: 1–10 min). The overall success with disappearance of all symptoms of epiphora was 88.8% (40/45). Surgery in cases of simple mucosal stenosis was successful in 92.2% (35/38) of cases, with a mean follow-up time of 7.9 months (range: 1 to 12 months). The duration of stent intubation was for this group was 32 days (range: 1–103). The surgical outcomes for the other 7 cases with more complex intraoperative findings are summarized in the publication. All withdrawn probes were intact. Conclusions The Lacrijet stent system is a simple and reliable pushed intubation device for CNLDO in appropriately selected cases where bony stenosis of the canal is minimal.