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Climate Change and Materials Criticality challenges are driving urgent responses from global governments. These global responses drive policy to achieve sustainable, resilient, clean solutions with Advanced Materials (AdMats) for industrial supply chains and economic prosperity. The research landscape comprising industry, academe, and government identified a critical path to accelerate the Green Transition far beyond slow conventional research through Digital Technologies that harness Artificial Intelligence, Smart Automation and High Performance Computing through Materials Acceleration Platforms, MAPs. In this perspective, following the short paper, a broad overview about the challenges addressed, existing projects and building blocks of MAPs will be provided while concluding with a review of the remaining gaps and measures to overcome them., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Manganese (Mn) substitution is a widely explored strategy aimed at sustainably enhancing the energy density of iron (Fe)-based electrode materials by taking advantage of the higher redox potential of the former. However, excessive Mn content can lead to detrimental effects, offsetting the expected improvements. In experimental studies, triphylite NaFe 0.8 Mn 0.2 PO 4 has been identified as an optimal composition with enhanced electrochemical performance compared to that of its parent phase NaFePO 4 . Higher Mn contents result in a loss of capacity and increased voltage hysteresis. In this study, density functional theory (DFT) calculations were employed to investigate the phase stability upon desodiation of Mn-poor and -rich Na x Fe 1- y Mn y PO 4 compositions. Our findings reveal distinct stability behaviors in antagonistic systems Na x Fe 0.75 Mn 0.25 PO 4 and Na x Fe 0.25 Mn 0.75 PO 4 , where the presence of Na-vacancies and charge orderings appear to influence phase stability. In addition, the number of intermediate phases throughout the desodiation process is identified as a crucial factor in buffering the volume changes. This work sheds light on the superior electrochemical performance of lightly Mn-substituted phases and unveils a key parameter for designing future electrode materials with improved performance.

Operando synchrotron radiation-based techniques are a precious tool in battery research, as they enable the detection of metastable intermediates and ensure characterization under realistic cycling conditions. However, they do not come exempt of risks. The interaction between synchrotron radiation and samples, particularly within an active electrochemical cell, can induce relevant effects at the irradiated spot, potentially jeopardizing the experiment's reliability and biasing data interpretation. With the aim of contributing to this ongoing debate, a systematic investigation into these phenomena was carried out by conducting a root cause analysis of beam-induced effects during the operando characterization of two of the most commonly employed positive electrode materials in commercial Li-ion batteries: LiNi 0.33 Mn 0.33 Co 0.33 O 2 and LiFePO 4 . The study spans across diverse experimental conditions involving different cell types and absorption and scattering techniques and seeks to correlate beam effects with factors such as radiation energy, photon flux, exposure time, and other parameters associated with radiation dosage. Finally, it provides a comprehensive set of guidelines and recommendations for assessing and mitigating beam-induced effects that may affect the outcome of battery operando experiments., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Most marine organisms have a biphasic life cycle during which pelagic larvae transform into radically different juveniles. In vertebrates, the role of thyroid hormones (THs) in triggering this transition is well known, but how the morphological and physiological changes are integrated in a coherent way with the ecological transition remains poorly explored. To gain insight into this question, we performed an integrated analysis of metamorphosis of a marine teleost, the false clownfish (Amphiprion ocellaris). We show how THs coordinate a change in color vision as well as a major metabolic shift in energy production, highlighting how it orchestrates this transformation. By manipulating the activity of liver X regulator (LXR), a major regulator of metabolism, we also identify a tight link between metabolic changes and metamorphosis progression. Strikingly, we observed that these regulations are at play in the wild, explaining how hormones coordinate energy needs with available resources during the life cycle., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Fish development and acclimation to environmental conditions are strongly mediated by the hormonal endocrine system. In environments contaminated by anthropogenic stressors, hormonal pathway alterations can be detrimental for growth, survival, fitness, and at a larger scale for population maintenance. In the context of increasingly contaminated marine environments worldwide, numerous laboratory studies have confirmed the effect of one or a combination of pollutants on fish hormonal systems. However, this has not been confirmed in situ. In this review, we explore the body of knowledge related to the influence of anthropogenic stressors disrupting fish endocrine systems, recent advances (focusing on thyroid hormones and stress hormones such as cortisol), and potential research perspectives. Through this review, we highlight how harbours can be used as "in situ laboratories" given the variety of anthropogenic stressors (such as plastic, chemical, sound, light pollution, and invasive species) that can be simultaneously investigated in harbours over long periods of time., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aberrant expression of the transcription factor DUX4 from D4Z4 macrosatellite repeats on chromosome 4q35, and its transcriptome, associate with pathogenesis in facioscapulohumeral muscular dystrophy (FSHD). Forced DUX4 expression halts skeletal muscle cell proliferation and induces cell death. DUX4 binds DNA via two homeodomains that are identical in sequence to those of DUX4c (DUX4L9): a closely related transcriptional regulator encoded by a single, inverted, mutated D4Z4 unit located centromeric to the D4Z4 macrosatellite array on chromosome 4. However, the function and contribution of DUX4c to FSHD pathogenesis are unclear. To explore interplay between DUX4, DUX4c, and the DUX4-induced phenotype, we investigated whether DUX4c interferes with DUX4 function in human myogenesis. Constitutive expression of DUX4c rescued the DUX4-induced inhibition of proliferation and reduced cell death in human myoblasts. Functionally, DUX4 promotes nuclear translocation of β-CATENIN and increases canonical WNT signalling. Concomitant constitutive expression of DUX4c prevents β-CATENIN nuclear accumulation and the downstream transcriptional program. DUX4 reduces endogenous DUX4c levels, whereas constitutive expression of DUX4c robustly suppresses expression of DUX4 target genes, suggesting molecular antagonism. In line, DUX4 expression in FSHD myoblasts correlates with reduced DUX4c levels. Addressing the mechanism, we identified a subset of genes involved in the WNT/β-CATENIN pathway that are differentially regulated between DUX4 and DUX4c, whose expression pattern can separate muscle biopsies from severely affected FSHD patients from healthy. Finally, blockade of WNT/β-CATENIN signalling rescues viability of FSHD myoblasts. Together, our study highlights an antagonistic interplay whereby DUX4 alters cell viability via β-CATENIN signalling and DUX4c counteracts aspects of DUX4-mediated toxicity in human muscle cells, potentially acting as a gene modifier for FSHD severity. Importantly, direct DUX4 regulation of the WNT/β-CATENIN pathway informs future therapeutic interventions to ameliorate FSHD pathology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ganassi, Figeac, Reynaud, Ortuste Quiroga and Zammit.)

An operando dual-edge X-ray absorption spectroscopy on both transition-metal ordered and disordered LiNi 0.5 Mn 1.5 O 4 during electrochemical delithiation and lithiation was carried out. The large data set was analyzed via a chemometric approach to gain reliable insights into the redox activity and the local structural changes of Ni and Mn throughout the electrochemical charge and discharge reaction. Our findings confirm that redox activity relies predominantly on the Ni 2+/4+ redox couple involving a transient Ni 3+ phase. Interestingly, a reversible minority contribution of Mn 3+/4+ is also evinced in both LNMO materials. While the reaction steps and involved reactants of both ordered and disordered LNMO materials generally coincide, we highlight differences in terms of reaction dynamics as well as in local structural evolution induced by the TM ordering., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

This is a critical review of artificial intelligence/machine learning (AI/ML) methods applied to battery research. It aims at providing a comprehensive, authoritative, and critical, yet easily understandable, review of general interest to the battery community. It addresses the concepts, approaches, tools, outcomes, and challenges of using AI/ML as an accelerator for the design and optimization of the next generation of batteries─a current hot topic. It intends to create both accessibility of these tools to the chemistry and electrochemical energy sciences communities and completeness in terms of the different battery R&D aspects covered.

Purpose: This study aimed at evaluating the performance of Doppler-based resistive index (RI) and semi-quantitative evaluation of renal perfusion using color-Doppler (SQP) to predict de novo AKI in the subgroup of critically ill patients without AKI at admission., Methods: This study is an ancillary analysis of a prospective multicenter cohort study. Consecutive ICU patients requiring mechanical ventilation were included. Renal Doppler was performed at ICU admission. The diagnostic performance of RI and SQP to predict de novo AKI at day 3 was evaluated., Results: Among the 371 patients of the prospective cohort, 118 without AKI at study inclusion were included. Thirty-four patients (29%) developed an AKI. Neither RI (0.64 UI [0.57-0.70] vs 0.67 [0.62-0.70] in no AKI and de novo AKI group respectively, p = 0.177) nor SQP (2 [2, 3] vs 2 [1-3] in no AKI and de novo AKI group respectively, p = 0.061) were associated with AKI occurrence. Overall performance in predicting de novo AKI was null to poor with area under ROC curve of respectively 0.60 (95% CI 0.49-0.65) and 0.58 (95% CI 0.47-0.60) for RI and SQP. Similar results were obtained after adjustment for confounders., Conclusions: These results confirm the poor performance of Doppler-based indices in predicting renal prognosis of ICU patients., Competing Interests: Declaration of Competing Interest M.D. declare having received administrative support from his former institution (Saint-Etienne University Hospital) to conduct this study and having received research support from Astute Medical unrelated to the current study. Outside the scope of this study, MD declare having received grant from MSD, speaker fees from MSD, Astelas and Gilead-Kite and having attended an advisory board for Gilead-Kite. The other authors declare having no other conflict of interest related to this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study investigated the dynamic changes in the anaerobic metabolism end products (ethanol, acetaldehyde and ethyl acetate) of different apple cultivars during 84-days of regular air (RA) and controlled atmosphere (CA) storage after 0-, 3-, 7- and 14-days of anoxia. Increasing the length of exposure to anoxia increased the anaerobic metabolites concentrations (AMC) in all cultivars. Fruit could recover from anoxia, and the AMC dissipated after 84-days of storage under both storage systems when the duration of anoxia was <7-days. The rate of metabolite dissipation following 14-days of anoxia differed among cultivars and storage systems. The reduction in AMC was faster under CA than RA-storage for 'Golden Delicious' and 'Jonagold' fruit, while the opposite trend was observed for 'Kanzi'. These results indicate that storage under CA post anoxia maintains better fruit quality during 84-days of storage than RA and effectively reduces the AMC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Thick epitaxial BaTiO 3 films ranging from 120 nm to 1 μm were grown by off-axis RF magnetron sputtering on SrTiO 3 -templated silicon-on-insulator (SOI) substrates for use in electro-optic applications, where such large thicknesses are necessary. The films are of high quality, rivaling those grown by molecular beam epitaxy (MBE) in crystalline quality, but can be grown 10 times faster. Extraction of lattice parameters from geometric phase analysis of atomic-resolution scanning transmission electron microscopy images revealed how the in-plane and out-of-plane lattice spacings of sputtered BaTiO 3 changes as a function of layer position within a thick film. Our results indicate that compared to molecular beam epitaxy, sputtered films retain their out-of-plane polarization ( c -axis) orientation for larger thicknesses. We also find an unusual re-transition from in-plane polarization ( a -axis) to out-of-plane polarization ( c -axis), along with an anomalous lattice expansion, near the surface. We also studied a method of achieving 100% a -axis-oriented films using a two-step process involving amorphous growth and recrystallization of a seed layer followed by normal high temperature growth. While this method is successful in achieving full a -axis orientation even at low thicknesses, the resulting film has a large number of voids and misoriented grains. Electro-optic measurement using a transmission setup of a sputtered BTO film grown using the optimized conditions yields an effective Pockels coefficient as high as 183 pm/V. A Mach-Zehnder modulator fabricated on such films exhibits phase shifting with an equivalent Pockels coefficient of 157 pm/V. These results demonstrate that sputtered BTO thick films can be used for integrated electro-optic modulators for Si photonics.

Hydroxyurea (hydroxycarbamide) is an effective treatment for sickle cell anaemia (SCA), but clinical responses depend primarily upon the degree of fetal haemoglobin (HbF) induction and the heterogeneity of HbF expression across erythrocytes. The number and characteristics of HbF-containing cells (F-cells) are not assessed by traditional HbF measurements. Conventional hydroxyurea dosing (e.g. fixed doses or low starting doses with stepwise escalation) produces a moderate heterocellular HbF induction, but haemolysis and clinical complications continue. Robust, pancellular HbF induction is needed to minimise or fully inhibit polymerisation of sickle haemoglobin. We treated children with hydroxyurea using an individualised, pharmacokinetics-guided regimen starting at predicted maximum tolerated dose (MTD). We observed sustained HbF induction (mean >30%) for up to 6 years, which was not dependent on genetic determinants of HbF expression. Nearly 70% of patients had ≥80% F-cells (near-pancellular), and almost half had ≥90% F-cells (pancellular). The mean HbF/F-cell content was ~12 pg. Earlier age of initiation and better medication adherence were associated with high F-cell responses. In summary, early initiation of hydroxyurea using pharmacokinetics-guided starting doses at predicted MTD can achieve sustained near-pancellular or pancellular HbF expression and should be considered an achievable goal for children with SCA treated with hydroxyurea at optimal doses. Clinical trial registration number: NCT02286154 (clinicaltrials.gov)., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Determining how plasticity of developmental traits responds to environmental conditions is a challenge that must combine evolutionary sciences, ecology, and developmental biology. During metamorphosis, fish alter their morphology and color pattern according to environmental cues. We observed that juvenile clownfish ( Amphiprion percula ) modulate the developmental timing of their adult white bar formation during metamorphosis depending on the sea anemone species in which they are recruited. We observed an earlier formation of white bars when clownfish developed with Stichodactyla gigantea ( Sg ) than with Heteractis magnifica ( Hm ). As these bars, composed of iridophores, form during metamorphosis, we hypothesized that timing of their development may be thyroid hormone (TH) dependent. We treated clownfish larvae with TH and found that white bars developed earlier than in control fish. We further observed higher TH levels, associated with rapid white bar formation, in juveniles recruited in Sg than in Hm , explaining the faster white bar formation. Transcriptomic analysis of Sg recruits revealed higher expression of duox , a dual oxidase implicated in TH production as compared to Hm recruits. Finally, we showed that duox is an essential regulator of iridophore pattern timing in zebrafish. Taken together, our results suggest that TH controls the timing of adult color pattern formation and that shifts in duox expression and TH levels are associated with ecological differences resulting in divergent ontogenetic trajectories in color pattern development., Competing Interests: The authors declare no competing interest.

ERAP1 is a key aminopeptidase involved in peptide trimming before major histocompatibility complex (MHC) presentation. A single nucleotide polymorphism (SNP) in the ERAP1 gene can lead to impaired trimming activity and affect ERAP1 function. ERAP1 genetic variations have been linked to an increased susceptibility to cancer and autoimmune disease. Here, we report the discovery of novel ERAP1 inhibitors using a high throughput screening approach. Due to ERAP1 broad substrate specificity, the hit finding strategy included testing inhibitors with a range of biochemical assays. Based on the hit potency, selectivity, and in vitro absorption, distribution, metabolism, excretion, and toxicity, the benzofuran series was selected. Fifteen derivatives were designed and synthesized, the compound potency was improved to the nanomolar range, and the structure-activity relationship supported by modeling studies., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Lithium- and sodium-rich layered transition-metal oxides have recently been attracting significant interest because of their large capacity achieved by additional oxygen-redox reactions. However, layered transition-metal oxides exhibit structural degradation such as cation migration, layer exfoliation or cracks upon deep charge, which is a major obstacle to achieve higher energy-density batteries. Here we demonstrate a self-repairing phenomenon of stacking faults upon desodiation from an oxygen-redox layered oxide Na 2 RuO 3 , realizing much better reversibility of the electrode reaction. The phase transformations upon charging A 2 MO 3 (A: alkali metal) can be dominated by three-dimensional Coulombic attractive interactions driven by the existence of ordered alkali-metal vacancies, leading to counterintuitive self-repairing of stacking faults and progressive ordering upon charging. The cooperatively ordered vacancy in lithium-/sodium-rich layered transition-metal oxides is shown to play an essential role, not only in generating the electro-active nonbonding 2p orbital of neighbouring oxygen but also in stabilizing the phase transformation for highly reversible oxygen-redox reactions.

Introduction: Poor oral health in persons with schizophrenia is a major public health issue affecting 600,000 people in France. The aim of this article was to present the different stages in the development of a specific oral health educational program for persons with schizophrenia. It takes into account experimental knowledge of these persons and presents the results of the feasibility study., Patients and Method: The focus group method was applied to a group of health professionals and users to highlight an exploratory corpus in order to develop an oral health educational program. An expert group including persons with schizophrenia among others validated the fields and tools of this program. A feasibility study was then conducted in a control group of 7 persons with schizophrenia., Results: Altogether, 26 persons participated in this feasibility study. The main fields investigated by the expert group aimed to promote personal responsibility for one’s health, to improve access to the healthcare system and to promote the global management of health. The feasibility study showed the ability of this program to change persons with schizophrenia representations and knowledge of this health problem. Most educational tools were considered relevant., Conclusion: An oral health educational program was built as part of a caregiver-persons with schizophrenia partnership and showed its feasibility. A multicentric randomized trial is currently ongoing to assess the efficacy of this program with a high level of proof.

Purpose: The Doppler-based resistive index (RI) and semi-quantitative evaluation of renal perfusion using color Doppler (SQP) have shown promising results for predicting persistent acute kidney injury (AKI) in preliminary studies. This study aimed at evaluating the performance of RI and SQP to predict short-term renal prognosis in critically ill patients., Methods: Prospective multicenter cohort study including unselected critically ill patients. Renal Doppler was performed at admission to the intensive care unit. The diagnostic performance of RI and SQP to predict persistent AKI at day 3 was evaluated., Results: Overall, 371 patients were included, of whom 351 could be assessed for short-term renal recovery. Two thirds of the included patients had AKI (n = 233; 66.3%), of whom 136 had persistent AKI (58.4%). Doppler-based RI was higher and SQP lower in AKI patients and according to AKI recovery. Overall performance in predicting persistent AKI was however poor with area under ROC curve of respectively 0.58 (95% CI 0.52-0.64) and 0.59 (95% CI 0.54-0.65) for RI and SQP. Optimal cutoff was respectively 0.71 and 2 for RI and SQP. At optimal cutoff, sensitivity and specificity were 50% (95% CI 41-58%) and 68% (62-74%) for RI and 39% (32-45%) and 75% (66-82%) for SQP., Conclusion: Although statistically associated with AKI occurrence, RI and SQP perform poorly in predicting persistent AKI at day 3. Further studies are needed to adequately describe factors influencing Doppler-based assessment of renal perfusion and to delineate whether these indicators may be useful at the bedside. CLINICALTRIAL.GOV: NCT02355314.

The microstructural complexity of Li-rich cathode materials has so far hampered understanding the critical link between size, morphology and structural defects with both capacity and voltage fadings that this family of materials exhibits. Li2MnO3 is used here as a model material to extract reliable structure-property relationships that can be further exploited for the development of high-performing and long-lasting Li-rich oxides. A series of samples with microstructural variability have been prepared and thoroughly characterized using the FAULTS software, which allows quantification of planar defects and extraction of average crystallite sizes. Together with transmission electron microscopy (TEM) and density functional theory (DFT) results, the successful application of FAULTS analysis to Li2MnO3 has allowed rationalizing the synthesis conditions and identifying the individual impact of concurrent microstructural features on both voltage and capacity fadings, a necessary step for the development of high-capacity Li-ion cathode materials with enhanced cycle life.

Medication development for alcohol relapse prevention or reduction of consumption is highly challenging due to methodological issues of pharmacotherapy trials. Existing approved medications are only modestly effective with many patients failing to benefit from these therapies. Therefore, there is a pressing need for other effective treatments with a different mechanism of action, especially for patients with very high (VH) drinking risk levels (DRL) because this is the most severely affected population of alcohol use disorder patients. Life expectancy of alcohol-dependent patients with a VH DRL is reduced by 22 years compared with the general population and approximately 90 000 alcohol-dependent subjects with a VH DRL die prematurely each year in the EU (Rehm et al. ). A promising new medication for this population is sodium oxybate, a compound that acts on GABA B receptors and extrasynaptic GABA A receptors resulting in alcohol-mimetic effects. In this article, a European expert group of alcohol researchers and clinicians summarizes data (a) from published trials, (b) from two new-as yet unpublished-large clinical trials (GATE 2 (n = 314) and SMO032 (n = 496), (c) from post hoc subgroup analyses of patients with different WHO-defined DRLs and (d) from multiple meta-analyses. These data provide convergent evidence that sodium oxybate is effective especially in a subgroup of alcohol-dependent patients with VH DRLs. Depending on the study, abstinence rates are increased up to 34 percent compared with placebo with risk ratios up to 6.8 in favor of sodium oxybate treatment. These convergent data are supported by the clinical use of sodium oxybate in Austria and Italy for more than 25 years. Sodium oxybate is the sodium salt of γ-hydroxybutyric acid that is also used as a recreational (street) drug suggestive of abuse potential. However, a pharmacovigilance database of more than 260 000 alcohol-dependent patients treated with sodium oxybate reported very few adverse side effects and only few cases of abuse. We therefore conclude that sodium oxybate is an effective, well-tolerated and safe treatment for withdrawal and relapse prevention treatment, especially in alcohol-dependent patients with VH DRL., (© 2018 Society for the Study of Addiction.)

Introduction: Intrauterine device (IUD) is a reliable contraceptive method that is long term reversible, and well tolerated. Numerous studies prove its efficiency and report rare complications that are attributed to it. However, its use is limited due to fear that it can cause a pelvic inflammatory disease (PID). This is based on historical data on infections related to the "Dalkon Shield", which was removed from the market in 1974., Method: The analyzed articles were extracted from PUBMED database between 2000 and 2016. In total, 22 studies were retained. A meta-analysis was not possible due to the methodological diversity among the selected articles contributing to this narrative review of the literature., Results: After analysis, the following factors influence the risk of PID linked to IUDs: an advanced age and sexually transmitted infections., Conclusion: The risk of PID linked to IUDs is lower than 1%. This is explained by new models of IUD, better screening tests, more frequent follow-up of the patients and the improvement of care PID patients. In the light of our results, the threat of pelvic inflammatory disease should not hinder the use of IUDs., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Competing Interests: K. Chahraoui et M. Reynaud déclarent n’avoir aucun lien d’intérêts.

Competing Interests: K. Chahraoui et M. Reynaud déclarent n’avoir aucun lien d’intérêts.

Background: Chronic alcoholism and its related cognitive impairments are associated with increased social, relational, and professional deficits which have a variable overall impact on social integration. These impairments are known to have varying severities and have rarely been studied among healthy alcohol-dependent subjects with preserved psychosocial functioning. Thus, the objective of this study is to describe neuropsychological performance in this particular population., Method: Twenty-nine socially adjusted alcohol-dependent men, hospitalized for a first or second withdrawal and abstinent for 3 weeks minimum, were compared to 29 healthy non-alcoholic controls. All subjects underwent clinical and psychiatric examination, neuropsychological tests of memory (M), working memory (WM), and executive functions (EF). Comparisons were performed using Student's t -tests or Mann-Whitney U tests., Results: No group differences were found on the Self-Reported Social Adjustment Scale (SAS-SR) or in the Mini-Mental State Examination. Compared to controls, patients had greater episodic, spatial, and WM deficits as well as slightly altered executive functions. In contrast, their executive functions (spontaneous flexibility, criteria generation, rule maintenance, and inhibitory control) were relatively preserved., Conclusion: Our sample of socially and professionally integrated alcoholic patients shows fewer cognitive deficits than described in previous studies. Our results suggest that early on, alcohol-dependent subjects develop compensatory adaptation processes to preserve social function and adaptation. Minor cognitive impairments should be screened early in the disease to integrate cognitive interventions into the health-care plan to thus eventually prevent further socio-professional marginalization.

Aims: Alcohol dependence is a major public health issue with a need for new pharmacological treatments. The ALPADIR study assessed the efficacy and safety of baclofen at the target dose of 180 mg/day for the maintenance of abstinence and the reduction in alcohol consumption in alcohol-dependent patients., Methods: Three hundred and twenty adult patients (158 baclofen and 162 placebo) were randomized after alcohol detoxification. After a 7-week titration, the maintenance dose was provided for 17 weeks, then progressively decreased over 2 weeks before stopping., Results: The percentage of abstinent patients during 20 consecutive weeks (primary endpoint) was low (baclofen: 11.9%; placebo: 10.5%) and not significantly different between groups (OR 1.20; 95%CI: 0.58 to 2.50; P = 0.618). A reduction in alcohol consumption was observed from month 1 in both groups, but the difference of 10.9 g/day at month 6 between groups, in favour of baclofen, was not statistically significant (P = 0.095). In a subgroup of patients with high drinking risk level at baseline, the reduction was greater with a difference at month 6 of 15.6 g/day between groups in favour of baclofen (P = 0.089). The craving assessed with Obsessive-Compulsive Drinking Scale significantly decreased in the baclofen group (P = 0.017). No major safety concern was observed., Conclusions: This study did not demonstrate the superiority of baclofen in the maintenance of abstinence at the target dose of 180 mg/day. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen., Short Summary: Baclofen was assessed versus placebo for maintenance of abstinence and reduction in alcohol consumption in alcohol-dependent patients. This study did not demonstrate the superiority of baclofen in the maintenance of abstinence. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen., (© The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background and aims Gambling disorder-related illegal acts (GDRIA) are often crucial events for gamblers and/or their entourage. This study was designed to determine the predictive factors of GDRIA. Methods Participants were 372 gamblers reporting at least three DSM-IV-TR (American Psychiatric Association, 2000) criteria. They were assessed on the basis of sociodemographic characteristics, gambling-related characteristics, their personality profile, and psychiatric comorbidities. A multiple logistic regression was performed to identify the relevant predictors of GDRIA and their relative contribution to the prediction of the presence of GDRIA. Results Multivariate analysis revealed a higher South Oaks Gambling Scale score, comorbid addictive disorders, and a lower level of income as GDRIA predictors. Discussion and conclusion An original finding of this study was that the comorbid addictive disorder effect might be mediated by a disinhibiting effect of stimulant substances on GDRIA. Further studies are necessary to replicate these results, especially in a longitudinal design, and to explore specific therapeutic interventions.

The aim was to develop and validate an instrument to track online problem poker gamblers with player account-based gambling data (PABGD). We emailed an invitation to all active poker gamblers on the online gambling service provider Winamax. The 14,261 participants completed the Problem Gambling Severity Index (PGSI). PGSI served as a gold standard to track problem gamblers (i.e., PGSI ≥ 5). We used a stepwise logistic regression to build a predictive model of problem gambling with PABGD, and validated it. Of the sample 18% was composed of online poker problem gamblers. The risk factors of problem gambling included in the predictive model were being male, compulsive, younger than 28 years, making a total deposit > 0 euros, having a mean loss per gambling session > 1.7 euros, losing a total of > 45 euros in the last 30 days, having a total stake > 298 euros, having > 60 gambling sessions in the last 30 days, and multi-tabling. The tracking instrument had a sensitivity of 80%, and a specificity of 50%. The quality of the instrument was good. This study illustrates the feasibility of a method to develop and validate instruments to track online problem gamblers with PABGD only. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: The relationship between sleep disorders and Internet addiction has been little work. Given the importance of these disorders, we felt it appropriate to make a synthesis of available data and to establish causality or accountability between Internet addiction and the onset of sleep disorders., Methods: A literature review was then performed. We selected scientific articles in English and French, published between 1987 and 2016 by consulting the databases Medline, Embase, PsycINFO and Google Scholar. The words used alone or in combination are as follows: addiction, dependence, Internet, behavioral addiction, sleep., Results: A computer screen light inhibits melatonin secretion and acts as a real external desynchronizer circadian rhythm resulting in a withdrawal syndrome or syndrome sleep phase delay when the stress of social awakening is suppressed., Conclusion: We assume here that the specific treatment of addictive disorders have an influence on sleep disorders., (Copyright © 2016. Published by Elsevier Masson SAS.)

We report herein on the magnetic properties and structures of orthorhombic Li 2 M(SO 4 ) 2 (M = Co, Fe) and their oxidized phases Li x Fe(SO 4 ) 2 (x = 1, 1.5), which were previously studied as potential cathode materials for Li-ion batteries. The particular structure of these orthorhombic compounds (space group Pbca) consists of a three-dimensional network of isolated MO 6 octahedra enabling solely super-super-exchange interactions between transition metals. We studied the magnetic properties of these phases via temperature-dependent susceptibility measurements and applied neutron powder diffraction experiments to solve their magnetic structures. All compounds present an antiferromagnetic long-range ordering of the magnetic spins below their Néel temperature. Their magnetic structures are collinear and follow a spin sequence (+ + - - - - + +), with the time reversal associated with the inversion center, a characteristic necessary for a linear magneto-electric effect. We found that the orientation of the magnetic moments varies with the nature of M. While Li 2 Co(SO 4 ) 2 and Li 1 Fe(SO 4 ) 2 adopt the magnetic space group Pb'c'a', the magnetic space group for Li 2 Fe(SO 4 ) 2 and Li 1.5 Fe(SO 4 ) 2 is P112 1 '/a, which might hint for a possible monoclinic distortion of their nuclear structure. Moreover we compared the orthorhombic phases to their monoclinic counterparts as well as to the isostructural orthorhombic Li 2 Ni(SO 4 ) 2 compound. Finally, we show that this possible magneto-electric feature is driven by the topology of the magnetic interactions.

The cyclic imine toxin 20-methyl spirolide G (20-meSPX-G), produced by the toxigenic dinoflagellate Alexandrium ostenfeldii/Alexandrium peruvianum, has been previously reported to contaminate shellfish in various European coastal locations, as revealed by mouse toxicity bioassay. The aim of the present study was to determine its toxicological profile and its molecular target selectivity. 20-meSPX-G blocked nerve-evoked isometric contractions in isolated mouse neuromuscular preparations, while it had no action on contractions elicited by direct electrical stimulation, and reduced reversibly nerve-evoked compound muscle action potential amplitudes in anesthetized mice. Voltage-clamp recordings in Xenopus oocytes revealed that 20-meSPX-G potently inhibited currents evoked by ACh on Torpedo muscle-type and human α7 nicotinic acetylcholine receptors (nAChR), whereas lower potency was observed in human α4β2 nAChR. Competition-binding assays showed that 20-meSPX-G fully displaced [³H]epibatidine binding to HEK-293 cells expressing the human α3β2 (Ki = 0.040 nM), whereas a 90-fold lower affinity was detected in human α4β2 nAChR. The spirolide displaced [(125)I]α-bungarotoxin binding to Torpedo membranes (Ki = 0.028 nM) and in HEK-293 cells expressing chick chimeric α7-5HT₃ nAChR (Ki = 0.11 nM). In conclusion, this is the first study to demonstrate that 20-meSPX-G is a potent antagonist of nAChRs, and its subtype selectivity is discussed on the basis of molecular docking models., Competing Interests: The authors declare no conflict of interest.

Modafinil is a candidate compound for the treatment of cocaine addiction that binds to the dopamine transporter (DAT) in healthy humans, as observed by positron emission tomography (PET). This mechanism, analogous to that of cocaine, might mediate a putative therapeutic effect of modafinil on cocaine dependence, though the binding of modafinil to DAT has never been assessed in cocaine-dependent patients. We aimed at quantifying the DAT availability during a controlled treatment by modafinil, and its clinical and psychometric correlates in cocaine-dependent patients at the onset of abstinence initiation. Twenty-nine cocaine-dependent male patients were enrolled in a 3-month trial for cocaine abstinence. Modafinil was used in a randomized double-blind placebo-controlled design and was administered as follows: 400 mg/day for 26 days, then 300 mg/day for 30 days, and 200 mg/day for 31 days. Participants were examined twice during a 17-day hospitalization for their DAT availability using PET and [(11)C]-PE2I and for assessments of craving, depressive symptoms, working memory, and decision-making. Cocaine abstinence was further assessed during a 10-week outpatient follow-up period. Baseline [(11)C]-PE2I-binding potential covaried with risk taking and craving index in striatal and extrastriatal regions. A 65.6% decrease of binding potential was detected in patients receiving modafinil for 2 weeks, whereas placebo induced no significant change. During hospitalization, an equivalent improvement in clinical outcomes was observed in both treatment groups, and during the outpatient follow-up there were more therapeutic failures in the modafinil-treated group. Therefore, these results do not support the usefulness of modafinil to treat cocaine addiction.

The quest for new sustainable iron-based positive electrode materials for lithium-ion batteries recently led to the discovery of a new family of compounds with the general formula Li2M(SO4)2 with M = transition metal, which presents monoclinic and orthorhombic polymorphs. In terms of electrochemical performances, although both Li2Fe(SO4)2 polymorphs present a similar potential of ∼3.8 V vs. Li(+)/Li(0), the associated electrochemical processes drastically differ in terms of polarization and reaction redox mechanisms. We herein provide an explanation to account for such a behavior. While monoclinic Li2Fe(SO4)2 directly transforms into Li1.0Fe(SO4)2 upon oxidation, the orthorhombic counterpart forms a distinct intermediate Li1.5Fe(SO4)2 phase leading to a two-step delithiation process involving an unequal depopulation of the two Li sites pertaining to the structure as deduced by neutron powder diffraction experiments and confirmed by both density functional theory and Bond Valence Energy Landscape calculations. Moreover, to access band gap information, both polymorphs are studied by UV/Vis spectroscopy. Lastly, the possibility of transforming the monoclinic phase to the orthorhombic phase under pressure is explored.

Background: Internet-based interventions targeted at the most at-risk gamblers could reduce the treatment gap for addictive disorders. Currently, no clinical trial has included non-treatment-seeking patients who have been recruited directly in their gambling environment. This study was the first exclusively Internet-based randomized controlled trial among non-help-seeking problem gamblers with naturalistic recruitment in their gambling environment., Objective: The aim of this study was to assess the efficacy of three modalities of Internet-based psychotherapies with or without guidance, compared to a control condition, among problem gamblers who play online poker., Methods: All active poker gamblers on the Winamax website were systematically offered screening. All problem poker gamblers identified with a Problem Gambling Severity Index (PGSI) score of ≥ 5 were eligible to be included in the trial. Problem gamblers were randomized into four groups: (1) waiting list (control group), (2) personalized normalized feedback on their gambling status by email, (3) an email containing a self-help book to be downloaded with a Cognitive Behavioral Therapy (CBT) program without guidance, and (4) the same CBT program emailed weekly by a trained psychologist with personalized guidance. Efficacy was assessed based on the change in PGSI between baseline and 6 weeks (end of treatment) or 12 weeks (maintenance) and supported by player account-based gambling data automatically collected at the three time points., Results: All groups met high attrition rates (83%), but the group with guidance had a significantly higher dropout rate than the other three groups, including the control group. Although all groups showed some improvement, with a mean decrease of 1.35 on the PGSI, no significant difference in efficacy between the groups was observed. One-third of the problem gamblers fell below the problem gambling threshold at 6 weeks., Conclusions: Guidance could have aversively affected problem gamblers who had not sought help. Despite the lack of significant difference in efficacy between groups, this naturalistic trial provides a basis for the development of future Internet-based trials in individuals with gambling disorders. Comorbidities, natural course of illness, and intrinsic motivation seem to be critical issues to consider in future designs., Trial Registration: ANSM 2013-A00794-41.

Background: Alcohol consumption with its addictive potential may lead to physical and psychological dependence as well as systemic toxicity all of which have serious detrimental health outcomes in terms of morbimortality. Despite the harmful potential of alcohol use disorders, the disease is often not properly managed, especially in ambulatory care. Psychiatric and general practitioners in ambulatory care are first in line to detect and manage patients with excessive alcohol consumption. However, this is still often regarded as an acute medical condition and its management is generally considered only over the short-term. On the contrary, alcohol dependence has been defined as a primary chronic disease of the brain reward, motivation, memory and related circuitry, involving the signalling pathway of neurotransmitters such as dopamine, opioid peptides, and gamma-aminobutyric acid. Thus, it should be regarded in terms of long-term management as are other chronic diseases., Objective: To propose a standard pathway for the management of alcohol dependence in ambulatory care in terms of duration of treatment and follow-up., Methods: Given the lack of official recommendations from health authorities which may help ambulatory care physicians in long-term management of patients with alcohol dependence, we performed a review and analysis of the most recent literature regarding the long-term management of other chronic diseases (diabetes, bipolar disorders, and depression) drawing a parallel with alcohol dependence., Results: Alcohol dependence shares many characteristics with other chronic diseases, including a prolonged duration, intermittent acute and chronic exacerbations, and need for prolonged and often-lifelong care. In all cases, this requires sustained psychosocial changes from the patient. Patient motivation is also a major issue and should always be taken into consideration by psychiatric and general practitioners in ambulatory care. In chronic diseases, such as diabetes, bipolar disorders, or depression, psychosocial and motivational interventions have been effective to improve the patient's emotional functioning and to prevent or delay relapses. Such interventions help patients to accept their disease and to promote long-term therapeutic plans based on treatment adherence, behavioural changes, self-management and self-efficacy. The management of alcohol-dependence in ambulatory care should be addressed similarly. Therapeutic monitoring may be initiated to manage alcohol use disorders, including alcohol dependence, especially when the patient is unwilling or unready for alcohol withdrawal (i.e. using the strategy of reduction of alcohol consumption, which is considered a possible intermediate step toward abstinence)., Conclusion: Alcohol dependence needs long-term medical supervision, and the therapeutic success depends on the initiation of sustained monitoring at the time of diagnosis (initiating phase with several consultations over 2-4 weeks) with psychosocial and motivational interventions in order to address all the patient uncertainties, to involve him/her in a proactive disease management plan, and to insure adherence to treatment, behavioural changes and new lifestyle. A close monitoring (once a month during the first 6 months) during a consolidation phase is necessary. Finally, a regular monitoring should be maintained overtime after 6-12 months in order to insure that the patient maintains a minimal consumption during the first year, to consolidate the patient's motivation, to abstain in at risk situations, and to maintain a controlled consumption or abstinence., (Copyright © 2016. Published by Elsevier Masson SAS.)

Competing Interests: F. Deroche et P. Laure déclarent n’avoir aucun lien d’intérêts. A. Benyamina déclare avoir participé à des interventions ponctuelles pour l’entreprise Bristol-Myers-Squibb, Euthérapie, Lundbeck (essai clinique, conférences, colloques, actions de formations), Merck-Serono (conférences, colloques, actions de formations). Il déclare avoir été pris en charge, à l’occasion de déplacement pour congrès, par Lundbeck, Merck-Serono et Otsuka. M. Reynaud déclare avoir participé à des interventions ponctuelles pour l’entreprise D et A Pharma (essai clinique), Ethypharm (essai clinique), Lundbeck (essai clinique, conférences, colloques, actions de formations). Il déclare avoir été pris en charge, à l’occasion de déplacement pour congrès, par D et A Pharma, Ethypharm, Lundbeck. H. J. Aubin déclareavoir participé à des interventions ponctuelles pour les entreprises Bioprojet (essai clinique), D et A Pharma (essai clinique), Ethypharm (essai clinique), Lundbeck (essai clinique, conférences, colloques, actions de formations), Merck-Serono (conférences, colloques, actions de formations), Novartis (conférences, colloques, actions de formations), et Pfizer (essai clinique, conférences, colloques, actions de formations). Il déclare avoir été pris en charge, à l’occasion de déplacement pour congrès, par Bioprojet, D et A Pharma, Ethypharm, Lundbeck, Merck-Serono, Novartis, et Pfizer. L. Karila déclare avoir des liens durables et permanents avec l’entreprise GMsanté, participer ou avoir participé à des interventions ponctuelles pour Reckitt Benckiser, Bouchara, AstraZeneca, Lundbeck, Ethypharm, Janssen, Gilead, Sanofi, et avoir été pris en charge, à l’occasion de déplacements pour congrès, par Bouchara, Janssen-Cilag, Gilead.

Background and Objectives: Persistent smoking behaviours are associated with numerous motives, explaining the absence of a single treatment for quitting. One of these motives may include that of identification. The threat of losing their smoker's identity may represent a significant obstacle to lasting abstinence. The objective of this study is to design a specific identity questionnaire and examine correlations between the degree of smoking identity and persistent smoking., Methods: Patients attending a smoking cessation seminar completed the Modified Reasons for Smoking Scale, Barriers to smoking cessation checklist and our 6-item Smoker's Identity Scale (SIS) (n = 170 questionnaires)., Results: SIS showed good internal consistency, calculated by a Chronbach test (α = .785) with no redundant questions. There was a correlation between strong tobacco dependence (measured by the Fagerström questionnaire) and strong smoking identity (p = .0001). Strong identity was associated with less confidence in quitting at both 1 and 6 months (p = .037 and p = .002, respectively). We showed that identity represents an obstacle to quitting in 32% of our patients and is associated with decreased confidence in quitting., Conclusions and Scientific Significance: Our study shows that measuring identity in smokers who wish to make a quit attempt may help to identify specific obstacles to abstinence. This may also help in elaborating improved quitting strategies and patient management. Further research is necessary to confirm these results., (© American Academy of Addiction Psychiatry.)

Alcohol consumption patterns and recognition of health outcomes related to hazardous drinking vary widely internationally, raising the question whether these national differences are reflected in brain damage observed in alcoholism. This retrospective analysis assessed variability of alcoholism's effects on brain cerebrospinal fluid (CSF) and white matter volumes between France and the United States (U.S.). MRI data from two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) were acquired on 1.5T imaging systems in 287 controls, 165 uncomplicated alcoholics (ALC), and 26 alcoholics with Korsakoff's Syndrome (KS). All data were analyzed at the U.S. site using atlas-based parcellation. Results revealed graded CSF volume enlargement from ALC to KS and white matter volume deficits in KS only. In ALC from France but not the U.S., CSF and white matter volumes correlated with lifetime alcohol consumption, alcoholism duration, and length of sobriety. MRI highlighted CSF volume enlargement in both ALC and KS, serving as a basis for an ex vacuo process to explain correlated gray matter shrinkage. By contrast, MRI provided a sensitive in vivo biomarker of white matter volume shrinkage in KS only, suggesting a specific process sensitive to mechanisms contributing to Wernicke's encephalopathy, the precursor of KS. Identified structural brain abnormalities may provide biomarkers underlying alcoholism's heterogeneity in and among nations and suggest a substrate of gray matter tissue shrinkage. Proposed are hypotheses for national differences in interpreting whether the severity of sequelae observe a graded phenomenon or a continuum from uncomplicated alcoholism to alcoholism complicated by KS.

Pinnatoxins are macrocyclic imine phycotoxins associated with algal blooms and shellfish toxicity. Functional analysis of pinnatoxin A and pinnatoxin G by binding and voltage-clamp electrophysiology on membrane-embedded neuronal α7, α4β2, α3β2, and muscle-type α12βγδ nicotinic acetylcholine receptors (nAChRs) reveals high-affinity binding and potent antagonism for the α7 and α12βγδ subtypes. The toxins also bind to the nAChR surrogate, acetylcholine-binding protein (AChBP), with low Kd values reflecting slow dissociation. Crystal structures of pinnatoxin-AChBP complexes (1.9-2.2 Å resolution) show the multiple anchoring points of the hydrophobic portion, the cyclic imine, and the substituted bis-spiroketal and cyclohexene ring systems of the pinnatoxins that dictate tight binding between the opposing loops C and F at the receptor subunit interface, as observed for the 13-desmethyl-spirolide C and gymnodimine A congeners. Uniquely, however, the bulky bridged EF-ketal ring specific to the pinnatoxins extends radially from the interfacial-binding pocket to interact with the sequence-variable loop F and govern nAChR subtype selectivity and central neurotoxicity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

An acute substance induced psychotic disorder is a cause to raise with a state of agitation in an acute delusional clinical setting. Patients are most often seen in hospital emergency rooms. Rapid diagnosis must be made. An integrated therapeutic management should be considered. Both psychiatric and addiction problems must be taken into account.

Background: Doppler-based renal resistive index (RI) calculation may help in the early detection of acute kidney injury (AKI). Its feasibility and reproducibility by inexperienced operators remain unknown. The main objective of this study was to compare performances of junior and senior operators in assessing renal perfusion using both the semiquantitative color-Doppler scale and RI calculation., Methods: Prospective cohort study performed in 3 ICUs. Inexperienced juniors physicians attended a half-day course on renal perfusion assessment using RI calculation and color-Doppler (from 0, absence of renal perfusion; to 3, renal vessels identifiable in the entire field of view). Junior and senior operators used both methods in 69 mechanically ventilated patients, in blind fashion., Results: Failure to obtain RI occurred for a junior operator in a single patient. RI and color-Doppler semi-quantitative values obtained by operators were correlated (r²=0.64 and r²=0.61, respectively). Systematic bias across operators as assessed using Bland-Altman plots was negligible (-0.001 and -0.29, respectively), although precision was limited (95% confidence intervals, +0.105 to -0.107 and +0.98 to -1.04, respectively). RI calculation and semi-quantitative assessment performed well for diagnosing persistent AKI (area under the receiver-operating characteristic curve, 0.84 [95% confidence interval, 0.73-0.97] and 0.87 [0.77-0.97], respectively)., Conclusion: A brief course on renal Doppler allowed inexperienced operators to assess effectively renal perfusion with a good reliability when compared to senior operators. In addition, our results suggest the good diagnostic performance of both Doppler-based RI and semi-quantitative renal perfusion assessment in predicting short-term renal dysfunction reversibility.

Alcohol use disorders present a significant public health problem in France and the United States (U.S.), but whether the untoward effect of alcohol on the brain results in similar damage in both countries remains unknown. Accordingly, we conducted a retrospective collaborative investigation between two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) with T1-weighted, structural MRI data collected on a common imaging platform (1.5T, General Electric) on 288 normal controls (NC), 165 uncomplicated alcoholics (ALC), and 26 patients with alcoholic Korsakoff's syndrome (KS) diagnosed at all sites with a common interview instrument. Data from the two countries were pooled, then preprocessed and analyzed together at the U.S. site using atlas-based parcellation. National differences indicated that thalamic volumes were smaller in ALC in France than the U.S. despite similar alcohol consumption levels in both countries. By contrast, volumes of the hippocampus, amygdala, and cerebellar vermis were smaller in KS in the U.S. than France. Estimated amount of alcohol consumed over a lifetime, duration of alcoholism, and length of sobriety were significant predictors of selective regional brain volumes in France and in the U.S. The common analysis of MRI data enabled identification of discrepancies in brain volume deficits in France and the U.S. that may reflect fundamental differences in the consequences of alcoholism on brain structure between the two countries, possibly related to genetic or environmental differences., (Copyright © 2014 Wiley Periodicals, Inc.)

Li-ion batteries have enabled a revolution in the way portable consumer-electronics are powered and will play an important role as large-scale electrochemical storage applications like electric vehicles and grid-storage are developed. The ability to identify and design promising new positive insertion electrodes will be vital in continuing to push Li-ion technology to its fullest potential. Utilizing a combination of computational tools and structural analysis, we report new indicators which will facilitate the recognition of phases with the desired redox potential. Most importantly of these, we find there is a strong correlation between the presence of Li ions sitting in close-proximity to the redox center of polyanionic phases and the open circuit voltage in Fe-based cathodes. This common structural feature suggests that the bonding associated with Li may have a secondary inductive effect which increases the ionic character of Fe bonds beyond what is typically expected based purely on arguments of electronegativity associated with the polyanionic group. This correlation is supported by ab initio calculations which show the Bader charge increases (reflecting an increased ionicity) in a nearly linear fashion with the experimental cell potentials. These features are demonstrated to be consistent across a wide variety of compositions and structures and should help to facilitate the design of new, high-potential, and environmentally sustainable insertion electrodes.

The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action. Countries like the United States and Canada have modified their laws in order to make cannabinoid use legal in the medical context. It's also the case in France now, where a recent decree was issued, authorizing the prescription of medication containing "therapeutic cannabis" (decree no. 2013-473, June 5, 2013). Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis. However, longer-term studies are required to determine potential long-term adverse effects and risks of misuse and addiction.

Sexual addiction, which is also known as hypersexual disorder, has largely been ignored by psychiatrists, even though the condition causes serious psychosocial problems for many people. A lack of empirical evidence on sexual addiction is the result of the disease's complete absence from versions of the Diagnostic and Statistical Manual of Mental Disorders. However, people who were categorized as having a compulsive, impulsive, addictive sexual disorder or a hypersexual disorder reported having obsessive thoughts and behaviors as well as sexual fantasies. Existing prevalence rates of sexual addiction-related disorders range from 3% to 6%. Sexual addiction/ hypersexual disorder is used as an umbrella construct to encompass various types of problematic behaviors, including excessive masturbation, cybersex, pornography use, sexual behavior with consenting adults, telephone sex, strip club visitation, and other behaviors. The adverse consequences of sexual addiction are similar to the consequences of other addictive disorders. Addictive, somatic and psychiatric disorders coexist with sexual addiction. In recent years, research on sexual addiction has proliferated, and screening instruments have increasingly been developed to diagnose or quantify sexual addiction disorders. In our systematic review of the existing measures, 22 questionnaires were identified. As with other behavioral addictions, the appropriate treatment of sexual addiction should combine pharmacological and psychological approaches. Psychiatric and somatic comorbidities that frequently occur with sexual addiction should be integrated into the therapeutic process. Group-based treatments should also be attempted.

Cocaine has become a public health problem. Several studies have shown that cocaine addiction is associated with multiple cognitive damages, such as memory, inhibitory control, attention and executive functions. A French cohort of cocaine addicted patients was divided into two groups: CCU (Current cocaine users) and abstainers. Their cognitive abilities were compared to a control group and associations with clinical determinants were assessed. The CCU group and the abstainers had episodic memory, working memory and inhibitory control disabilities compared to the control group. Both the CCU and the abstainers group had the same cognitive abilities but their clinical determinants for these cognitive abilities differed. In the CCU group, exposure to cocaine seemed to have a negative impact on cognition especially inhibitory control, memory and impulsivity. In the abstainers group, craving and depression impeded cognition.

Cocaine remains the second most commonly used illicit drug worldwide after cannabis. Observed levels of cocaine use among countries considerably vary. An increased cocaine use is recorded in the general European population. Cocaine addiction is a worldwide public health problem, which has somatic, psychiatric, socio-economic and judicial complications. It is a multifactorial disorder variable in its clinical manifestations and heritable. Compared to the general population, there is a high prevalence of somatic and psychiatric disorders among cocaine-dependent patients. There are predictable dose-related effects of pharmacological action of cocaine and effects which are uncommon, unrelated to dose and occur randomly in this population. The number of patients entering drug treatment for primary cocaine use has been increasing in Europe for several years. However, there is no specific pharmacotherapy with established efficacy for the treatment of cocaine addiction, nor is any medication approved by regulatory authorities for such treatment. Recent controlled clinical studies and laboratory studies have highlighted some very promising medications. The perfect therapeutic platform for abstinence initiation and relapse prevention of cocaine addiction is a combination of pharmacological treatments and behavioral treatments. Targeting somatic and psychiatric comorbidity is another way to use pharmacological treatments in addictions., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Cannabis remains the most commonly used and trafficked illicit drug in the world. Its use is largely concentrated among young people (15- to 34-year-olds). There is a variety of cannabis use patterns, ranging from experimental use to dependent use. Men are more likely than women to report both early initiation and frequent use of cannabis. Due to the high prevalence of cannabis use, the impact of cannabis on public health may be significant. A range of acute and chronic health problems associated with cannabis use has been identified. Cannabis can frequently have negative effects in its users, which may be amplified by certain demographic and/or psychosocial factors. Acute adverse effects include hyperemesis syndrome, impaired coordination and performance, anxiety, suicidal ideations/tendencies, and psychotic symptoms. Acute cannabis consumption is also associated with an increased risk of motor vehicle crashes, especially fatal collisions. Evidence indicates that frequent and prolonged use of cannabis can be detrimental to both mental and physical health. Chronic effects of cannabis use include mood disorders, exacerbation of psychotic disorders in vulnerable people, cannabis use disorders, withdrawal syndrome, neurocognitive impairments, cardiovascular and respiratory and other diseases.

Background: Socially valorized, excessive indoor tanning can lead to dependence. This finding is based on the observations of many dermatologists, who report repeated failures in preventing their patients from visiting tanning cabins, despite the announcement of a diagnosis of malignant melanoma., Objective: The objective of this paper is to show that excessive indoor tanning can be included in the spectrum of addictive behavior. This review focuses on the clinical features, diagnosis, prevalence, etiology, treatment, prevention, and psychopathology of this disorder., Methods: A review of the medical literature was conducted using PubMed and Google Scholar and using the following key words alone or in combination: tanning, addiction, dependence, tanning bed, sun exposure, and solarium. We selected 41 English-language articles from 1974 to 2013., Results: Many excessive indoor tanners meet symptom criteria adapted from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) substance abuse and dependence criteria. Trial studies suggest that there may be a physiological basis, consisting of dependence on opioids, for excessive indoor tanning behaviors., Conclusion: Excessive indoor tanning can be included in the spectrum of addictive behaviors, although other models may be proposed. Further controlled studies must be performed, especially in neurobiology and imaging, to improve our understanding of tanning dependence.

Cannabis is the most widely used illicit substance, especially among young people. Cannabis use is extremely commonplace and frequently comorbid with psychiatric disorders that raise questions about the etiology. The use of cannabis is an aggravating factor of all psychiatric disorders. Psychiatric complications are related to the age of onset, duration of exposure and individual risk factors of the individual (mental and social health). The panic attack is the most common complication. The link with psychosis is narrow that leads to increased prevention for vulnerable populations. Cannabis is also an indicator of increased depressive vulnerability and an aggravating factor for bipolar disorder.