UV filters in everyday cosmetic products, a comparative study.

Today, UV filters are found as contaminants in a variety of biological fluids and environment, e.g. in vegetable crops and surface water. This is because UV filters are widely used in everyday products. In this context, we focused this study on cosmetic products, in order to assess the importance of this source of contamination. The study of 742 cosmetic products, excluding actual sunscreen products, but including hygiene, personal care and make-up products and perfumes revealed that the most common UV filters present are butyl methoxydibenzoylmethane (90 products or 12.1% of products tested), octyl methoxycinnamate (75 products or 10.1% of products tested), octocrylene (62 products or 8.3% of products tested), octyl salicylate (43 products or 5.8% of products tested) and titanium dioxide (33 products or 4.4% of products tested). Very few UV filters are found in the hygiene products (only in 12 shampoos/conditioners and in 2 shower gels) and deodorants and toothpastes are completely free of them. Conversely, make-up and perfumes are frequently formulated with at least one UV filter. Seventy-five of the two hundred and forty-four (or 30.7%) skincare products studied contained at least one UV filter. 49.1 of the makeup products studied and 74.3% of perfumes contained it.

Identifying interindividual variability of social perception and associated brain anatomical correlations in children with autism spectrum disorder using eye-tracking and diffusion tensor imaging MRI (DTI-MRI).

Even though deficits in social cognition constitute a core characteristic of autism spectrum disorders, a large heterogeneity exists regarding individual social performances and its neural basis remains poorly investigated. Here, we used eye-tracking to objectively measure interindividual variability in social perception and its correlation with white matter microstructure, measured with diffusion tensor imaging MRI, in 25 children with autism spectrum disorder (8.5 ± 3.8 years). Beyond confirming deficits in social perception in participants with autism spectrum disorder compared 24 typically developing controls (10.5 ± 2.9 years), results revealed a large interindividual variability of such behavior among individuals with autism spectrum disorder. Whole-brain analysis showed in both autism spectrum disorder and typically developing groups a positive correlation between number of fixations to the eyes and fractional anisotropy values mainly in right and left superior longitudinal tracts. In children with autism spectrum disorder a correlation was also observed in right and left inferior longitudinal tracts. Importantly, a significant interaction between group and number of fixations to the eyes was observed within the anterior portion of the right inferior longitudinal fasciculus, mainly in the right anterior temporal region. This additional correlation in a supplementary region suggests the existence of a compensatory brain mechanism, which may support enhanced performance in social perception among children with autism spectrum disorder.

Early-onset catatonia associated with SHANK3 mutations: looking at the autism spectrum through the prism of psychomotor phenomena.

Background: Individuals with Phelan-McDermid syndrome (PMS) present with a wide range of diagnoses: autism spectrum disorder, intellectual disability, or schizophrenia. Differences in the genetic background could explain these different neurodevelopmental trajectories. However, a more parsimonious hypothesis is to consider that they may be the same phenotypic entity. Catatonic disturbances occasionally reported from adolescence onwards in PMS prompts exploration of the hypothesis that this clinical entity may be an early-onset form of catatonia. The largest cohort of children with childhood catatonia was studied by the Wernicke-Kleist-Leonhard school (WKL school), which regards catatonia as a collection of qualitative abnormalities of psychomotricity that predominantly affecting involuntary motricity (reactive and expressive). The aim of this study was to investigate the presence of psychomotor signs in three young adults carrying a mutation or intragenic deletion of the SHANK3 gene through the prism of the WKL school conception of catatonia. Methods: This study was designed as an exploratory case study. Current and childhood psychomotor phenomena were investigated through semi-structured interviews with the parents, direct interaction with the participants, and the study of documents reporting observations of the participants at school or by other healthcare professionals. Results: The findings show catatonic manifestations from childhood that evolved into a chronic form, with possible phases of sub-acute exacerbations starting from adolescence. Conclusion: The presence of catatonic symptoms from childhood associated with autistic traits leads us to consider that this singular entity fundamentally related to SHANK3 mutations could be a form of early-onset catatonia. Further case studies are needed to confirm our observations.

Healico-a wound care assistant in your pocket.

Non-optimal wound management and late referral to specialised units negatively impacts patient prognosis and quality of life, as well as healthcare costs. Healico is a new mobile application (app), created in the wound care field, in response to the challenges and difficulties encountered by health professionals (HPs) who deal with patients with wounds on a daily basis. This article aims to describe how this new app was developed, how it works, as well as the real-life clinical benefits and evidence supporting its use. The Healico App assists nurses, physicians and other HPs by: supporting a holistic approach to patient management; facilitating wound assessment and documentation, irrespective of where care is provided (primary, specialised or hospital services, in either public or private institutions); and supporting consistent and safe clinical practice, as well as reducing variation in care. It also provides a fast, fluid and secure communication channel, and effective coordination between HPs, supporting early interventions. The app has also been shown to improve therapeutic adherence of patients by promoting inclusive dialogue with them.

Bayesian hierarchical models for the prediction of the driver flow and passenger waiting times in a stochastic carpooling service.

Carpooling is an integral component in smart carbon-neutral cities, in particular to facilitate home-work commuting. We study an innovative carpooling service which offers stochastic passenger-driver matching. Stochastic matching is when a passenger makes a carpooling request, and then waits for the first driver from a population of drivers who are already en route. Crucially a designated driver is not assigned as in a traditional carpooling service. For this new form of stochastic carpooling, we propose a two-stage Bayesian hierarchical model to predict the driver flow and the passenger waiting times. The first stage focuses on prediction of the aggregated daily driver flows, and the second stage processes these daily driver flow into hourly predictions of the passenger waiting times. We demonstrate, for an operational carpooling service, that the predictions from our Bayesian hierarchical model outperform the predictions from a frequentist model and a Bayesian non-hierarchical model. The inferences from our proposed model provide insights for the service operator in their evidence-based decision making.

Avant-propos.

Hard-to-heal wounds are a problem for both patients and caregivers. The biofi lm is one of the local factors of delayed healing. Wound hygiene carried out in 4 steps (cleansing, debridement, refashion - care of the edges, and dressing) constitutes the basis of proactive and curative anti-biofi lm strategies.

Alternatives to Gold Standard Diagnostic Tools for Distinguishing "Natural Kinds" on the Autism Spectrum.

Next-generation sequencing techniques have accelerated the discovery of rare mutations responsible for autism spectrum disorder (ASD) in genes involved in a large number of physiological processes, including the control of gene expression, chromatin remodeling, signaling pathways, synaptic scaffolding, neurotransmitter receptors, and lipid metabolism. Genetic diagnosis provides subjects with an explanation of the cause of their disorder. However, it does not, or at least does not yet, shed light on the psychopathological phenomena specific to the individual. It could be hypothesized that each physiological impact of a mutation corresponds to a specific psychopathological phenomenon of ASD, i.e., "a psychopathological natural kind". We discuss here the difficulties identifying this specificity of underlying psychopathology in individuals with ASD due to a rare mutation with a major effect. A comparison of Newson's pathological demand avoidance and Wing's Asperger's syndrome with Asperger's autistic psychopathy highlights different ways of approaching psychopathological descriptions and diagnosis, by focusing on either common or unusual features. Such a comparison calls into question the principles of clinical research recommended by Falret for characterizing "disease individuality" of ASD due to a rare mutation.

Interval debulking surgery after neoadjuvant chemotherapy in advanced ovarian cancer - retrospective study comparing surgery after 3 cycles or more of chemotherapy.

OBJECTIVE: To evaluate and compare overall survival and progression-free survival in two groups of patients with advanced ovarian cancer, managed by neoadjuvant chemotherapy (3 cycles or more) followed by interval debulking surgery. Secondary objectives regarded surgical morbidity and extent of cytoreduction. MATERIAL AND METHODS: We conducted a retrospective study, in a referral center, evaluating the management of patients diagnosed with advanced ovarian cancer (FIGO IIIC-IV) beneficiating of interval surgery after neoadjuvant chemotherapy. We compared two groups, one in which patients underwent 3 cycles of chemotherapy before surgery, and a second group in which patients underwent more than 3 cycles. RESULTS: 140 patients underwent interval surgery after neoadjuvant chemotherapy. Among these patients, 45 patients underwent 3 or less cycles (group 1) and 95 patients more than 3 cycles (group 2). There was no statistical difference for overall and progression free survival. The mean overall survival was 58,4 months for group 1 and 58,3 for group 2 (p.value = 0.56). The mean progression free survival was 30,5 months for group 1 and 23,8 months for group 2 (p.value = 0.17). More posterior pelvectomies were realized in group 1 compared to group 2 with a statistically significant difference (p=0,01). There was no difference regarding complete macroscopic difference during the surgery between the 2 groups (p=0,09). CONCLUSION: Debulking surgery is an invasive and heavy procedure and is not always possible in first line. Neoadjuvant chemotherapy followed by interval debulking surgery is an accepted alternative. The number of administered cycles is questionable, and does not seem to have a significant impact on overall survival and progression free survival. However, surgical morbidity is significantly reduced by increased cycles of chemotherapy.

[Medical oncological treatment of colorectal cancer in the elderly]. / Traitement oncologique médical du cancer colorectal chez la personne âgée.

Medical treatment with chemotherapy is discussed in several situations in the treatment of colon cancer. In the adjuvant setting, chemotherapy with 5FU±oxaliplatin for six months should be considered in the case of lymph node involvement. In the metastatic setting, several protocols exist. The choice of treatments should be based on the expected objectives in terms of response and survival gain, but also of tolerance and quality of life for the patient. A thorough oncogeriatric assessment helps to better define the therapeutic programme. The continuation of geriatric follow-up throughout the treatment process shows a benefit for the patient in terms of quality of life and tolerance of treatments.

An improved chronology for the Middle Stone Age at El Mnasra cave, Morocco.

North African coastal Middle Stone Age (MSA) sites are key to study the development and expansion of early H. sapiens. El Mnasra cave on the Atlantic coast of Morocco (Témara region) is a crucial site associated with MSA archaeological materials considered advanced cognitive hallmarks of behavioural innovation, such as numerous Nassariidae perforated shells, hematite pigments, bones industry and coastal resources exploitation. We provide new trapped-charges dates (OSL and combined US-ESR ages). Our Bayesian modelling strengthens the new lithostratigraphic interpretation of the cave stratigraphic units (US) and we propose an updated chronostratigraphic model for the Middle Stone Age archaeo-sequence of El Mnasra Cave. We confirm a human presence between 124-104 ka, earlier than what the previous OSL and US-ESR data showed. Our time range intervals allowed us to also extend the age of the MSA occupations considerably to the MIS 4/3 (~62-30 ka), marked by the disappearance of the Nassariidae perforated shells. Outstandingly, our model pushed back the age of the largest record of Nassariidae perforated shells and placed the age of their use by the Aterian groups at El Mnasra from the MIS 5d-5b (~115-94 ka).

Dating the landscape evolution around the Chauvet-Pont d'Arc cave.

The Chauvet cave (UNESCO World Heritage site, France) is located in the Ardèche Gorge, a unique physical and cultural landscape. Its setting within the gorge-overlooking a meander cutoff containing a natural arch called the Pont d'Arc-is also remarkable. Investigating possible associations between sites' physical and cultural settings, chronologies of human occupation, and access conditions has become a major theme in archeological research. The present study aims to reconstruct the landscape of the Pont d'Arc meander cutoff during the Upper Paleolithic, when humans were present in the Chauvet Cave. We used uranium-series and electron spin resonance analyses to date the formation of the Pont d'Arc natural arch in the Combe d'Arc meander cutoff, near the Chauvet Cave. Results show that the meander became totally cutoff between 108 and 138 ka (95%). Hence, the natural arch formed before the Upper Paleolithic and the first known human presence in the Chauvet Cave, dated to 37 ka cal BP. These results allowed us to reconstruct a key part of the landscape surrounding the Chauvet Cave when it was being used by Upper-Paleolithic societies.

Machine learning based white matter models with permeability: An experimental study in cuprizone treated in-vivo mouse model of axonal demyelination.

The intra-axonal water exchange time (τi), a parameter associated with axonal permeability, could be an important biomarker for understanding and treating demyelinating pathologies such as Multiple Sclerosis. Diffusion-Weighted MRI (DW-MRI) is sensitive to changes in permeability; however, the parameter has so far remained elusive due to the lack of general biophysical models that incorporate it. Machine learning based computational models can potentially be used to estimate such parameters. Recently, for the first time, a theoretical framework using a random forest (RF) regressor suggests that this is a promising new approach for permeability estimation. In this study, we adopt such an approach and for the first time experimentally investigate it for demyelinating pathologies through direct comparison with histology. We construct a computational model using Monte Carlo simulations and an RF regressor in order to learn a mapping between features derived from DW-MRI signals and ground truth microstructure parameters. We test our model in simulations, and find strong correlations between the predicted and ground truth parameters (intra-axonal volume fraction f: R2 =0.99, τi: R2 =0.84, intrinsic diffusivity d: R2 =0.99). We then apply the model in-vivo, on a controlled cuprizone (CPZ) mouse model of demyelination, comparing the results from two cohorts of mice, CPZ (N=8) and healthy age-matched wild-type (WT, N=8). We find that the RF model estimates sensible microstructure parameters for both groups, matching values found in literature. Furthermore, we perform histology for both groups using electron microscopy (EM), measuring the thickness of the myelin sheath as a surrogate for exchange time. Histology results show that our RF model estimates are very strongly correlated with the EM measurements (ρ = 0.98 for f, ρ = 0.82 for τi). Finally, we find a statistically significant decrease in τi in all three regions of the corpus callosum (splenium/genu/body) of the CPZ cohort (<τi>=310ms/330ms/350ms) compared to the WT group (<τi>=370ms/370ms/380ms). This is in line with our expectations that τi is lower in regions where the myelin sheath is damaged, as axonal membranes become more permeable. Overall, these results demonstrate, for the first time experimentally and in vivo, that a computational model learned from simulations can reliably estimate microstructure parameters, including the axonal permeability .

Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies.

BACKGROUND: Genome-edited donor-derived allogeneic anti-CD19 chimeric antigen receptor (CAR) T cells offer a novel form of CAR-T-cell product that is available for immediate clinical use, thereby broadening access and applicability. UCART19 is one such product investigated in children and adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Two multicentre phase 1 studies aimed to investigate the feasibility, safety, and antileukaemic activity of UCART19 in children and adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. METHODS: We enrolled paediatric or adult patients in two ongoing, multicentre, phase 1 clinical trials to evaluate the safety and antileukaemic activity of UCART19. All patients underwent lymphodepletion with fludarabine and cyclophosphamide with or without alemtuzumab, then children received UCART19 at 1·1-2·3 × 106 cells per kg and adults received UCART19 doses of 6 × 106 cells, 6-8 × 107 cells, or 1·8-2·4 × 108 cells in a dose-escalation study. The primary outcome measure was adverse events in the period between first infusion and data cutoff. These studies were registered at ClinicalTrials.gov, NCT02808442 and NCT02746952. FINDINGS: Between June 3, 2016, and Oct 23, 2018, seven children and 14 adults were enrolled in the two studies and received UCART19. Cytokine release syndrome was the most common adverse event and was observed in 19 patients (91%); three (14%) had grade 3-4 cytokine release syndrome. Other adverse events were grade 1 or 2 neurotoxicity in eight patients (38%), grade 1 acute skin graft-versus-host disease in two patients (10%), and grade 4 prolonged cytopenia in six patients (32%). Two treatment-related deaths occurred; one caused by neutropenic sepsis in a patient with concurrent cytokine release syndrome and one from pulmonary haemorrhage in a patient with persistent cytopenia. 14 (67%) of 21 patients had a complete response or complete response with incomplete haematological recovery 28 days after infusion. Patients not receiving alemtuzumab (n=4) showed no UCART19 expansion or antileukaemic activity. The median duration of response was 4·1 months with ten (71%) of 14 responders proceeding to a subsequent allogeneic stem-cell transplant. Progression-free survival at 6 months was 27%, and overall survival was 55%. INTERPRETATION: These two studies show, for the first time, the feasibility of using allogeneic, genome-edited CAR T cells to treat patients with aggressive leukaemia. UCART19 exhibited in-vivo expansion and antileukaemic activity with a manageable safety profile in heavily pretreated paediatric and adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. The results this study are an encouraging step forward for the field of allogeneic CAR T cells, and UCART19 offers the opportunity to treat patients with rapidly progressive disease and where autologous CAR-T-cell therapy is unavailable. FUNDING: Servier.

TEDIS, a Comprehensive Data Model for In-Depth Clinical Assessment of Patients Affected with Neuro-Developmental Disorders Including Autism.

TEDIS, an information system dedicated to patients affected with neuro-developmental disorders including autism, focuses on patient data generated during in-depth clinical assessment in nine expert centers in Ile-de-France region. Long term partnership involving methodologists and domain experts is necessary to support quality data production and analyses and to guarantee quality data and information governance in a domain characterized by frequent evolutions in clinical assessment instruments and in diagnostic criteria and classification.