Radiological, histological and clinical side effects of incisor trimming in rabbits.

INTRODUCTION: Incisor malocclusion in rabbits (Oryctolagus cuniculus) is a common clinical problem seen in general practice. Given that the growth rate is about 2 mm per week, a lack of wear quickly leads to feeding difficulties and soft tissue injuries. Therefore, pathologically elongated incisors must be shortened every three to six weeks. The goal of this study was to assess the potential adverse effects on dental and periodontal tissues associated with the three most commonly used trimming methods: nail cutter, diamond-coated cutting disc and diamond burr. The left mandibular incisor of 28 healthy New Zealand rabbits was subjected to four trimmings with one of the three cutting methods. After the fattening period, the mandibles were collected and both mandibular incisors were investigated on dental radiographs, micro-computed tomography scans and histological sections. Dental and periodontal tissue changes were evaluated. This study allowed a more accurate statement of the potential short-term adverse effects of the three trimming methods. At the clinical level, the nail cutter caused the formation of an irregular occlusal surface with sharp edges. Both engine-drive methods allowed the attainment of a smooth surface but the disc was less accurate. Histological evaluation revealed that the primary modifications, including coronal fractures, periodontal ligament widening and inflammation, reparative osteodentine, paracementosis and biofilm accumulation, were found in the nail cutter group.

INTRODUCTION: La malocclusion des incisives chez le lapin (Oryctolagus cuniculus) est un problème clinique courant en médecine générale. Étant donné que le taux de croissance est d'environ 2 mm par semaine, un manque d'usure entraîne rapidement des difficultés d'alimentation et des lésions des tissus mous. Par conséquent, les incisives pathologiquement trop longues doivent être raccourcies toutes les trois à six semaines. L'objectif de cette étude était d'évaluer les effets négatifs potentiels sur les tissus dentaires et parodontaux associés aux trois méthodes de taille les plus couramment utilisées: le coupeongles, le disque de coupe diamanté et la fraise diamantée. L'incisive mandibulaire gauche de 28 lapins néo-zélandais en bonne santé a été soumise à quatre tailles avec l'une des trois méthodes de coupe. Après la période d'engraissement, les mandibules ont été prélevées et les deux incisives mandibulaires ont été examinées sur des radiographies dentaires, des examens micro-tomodensitométriques et des coupes histologiques. Les modifications des tissus dentaires et parodontaux ont été évaluées. Cette étude a permis de mieux cerner les effets indésirables potentiels à court terme des trois méthodes de coupe. Au niveau clinique, le coupe-ongles a entraîné la formation d'une surface occlusale irrégulière avec des bords tranchants. Les deux autres méthodes de taille permettent d'obtenir une surface lisse, mais le disque est moins précis. L'évaluation histologique a révélé que les modifications primaires, y compris les fractures coronaires, l'élargissement et l'inflammation du ligament parodontal, l'ostéodentine réparatrice, la paracémentose et l'accumulation de biofilm, ont été trouvées dans le groupe coupe-ongles.

Plakoglobin regulates adipocyte differentiation independently of the Wnt/ß-catenin signaling pathway.

The scaffold protein 14-3-3ζ is an established regulator of adipogenesis and postnatal adiposity. We and others have demonstrated the 14-3-3ζ interactome to be diverse and dynamic, and it can be examined to identify novel regulators of physiological processes, including adipogenesis. In the present study, we sought to determine if factors that influence adipogenesis during the development of obesity could be identified in the 14-3-3ζ interactome found in white adipose tissue of lean or obese TAP-tagged-14-3-3ζ overexpressing mice. Using mass spectrometry, differences in the abundance of novel, as well as established, adipogenic factors within the 14-3-3ζ interactome could be detected in adipose tissues. One novel candidate was revealed to be plakoglobin, the homolog of the known adipogenic inhibitor, ß-catenin, and herein, we report that plakoglobin is involved in adipocyte differentiation. Plakoglobin is expressed in murine 3T3-L1 cells and is primarily localized to the nucleus, where its abundance decreases during adipogenesis. Depletion of plakoglobin by siRNA inhibited adipogenesis and reduced PPARγ2 expression, and similarly, plakoglobin depletion in human adipose-derived stem cells also impaired adipogenesis and reduced lipid accumulation post-differentiation. Transcriptional assays indicated that plakoglobin does not participate in Wnt/ß-catenin signaling, as its depletion did not affect Wnt3a-mediated transcriptional activity. Taken together, our results establish plakoglobin as a novel regulator of adipogenesis in vitro and highlights the ability of using the 14-3-3ζ interactome to identify potential pro-obesogenic factors.

Incidence and predictors of metabolic syndrome onset in individuals with bipolar disorders: A longitudinal study from the FACE-BD cohort.

INTRODUCTION: Metabolic syndrome (MetS) is a cluster of components including abdominal obesity, hyperglycemia, hypertension, and dyslipidemia. MetS is highly prevalent in individuals with bipolar disorders (BD) with an estimated global rate of 32.6%. Longitudinal data on incident MetS in BD are scarce and based on small sample size. The objectives of this study were to estimate the incidence of MetS in a large longitudinal cohort of 1521 individuals with BD and to identify clinical and biological predictors of incident MetS. METHODS: Participants were recruited from the FondaMental Advanced Center of Expertise for Bipolar Disorder (FACE-BD) cohort and followed-up for 3 years. MetS was defined according to the International Diabetes Federation criteria. Individuals without MetS at baseline but with MetS during follow-up were considered as having incident MetS. A logistic regression model was performed to estimate the adjusted odds ratio and its corresponding 95% confidence interval (CI) for an association between each factor and incident MetS during follow-up. We applied inverse probability-of-censoring weighting method to minimize selection bias due to loss during follow-up. RESULTS: Among individuals without MetS at baseline (n = 1521), 19.3% developed MetS during follow-up. Multivariable analyses showed that incident MetS during follow-up was significantly associated with male sex (OR = 2.2, 95% CI = 1.7-3.0, p < 0.0001), older age (OR = 2.14, 95% CI = 1.40-3.25, p = 0.0004), presence of a mood recurrence during follow-up (OR = 1.91, 95% CI = 1.22-3.00, p = 0.0049), prolonged exposure to second-generation antipsychotics (OR = 1.56, 95% CI = 0.99, 2.45, p = 0.0534), smoking status at baseline (OR = 1.30, 95% CI = 1.00-1.68), lifetime alcohol use disorders (OR = 1.33, 95% CI = 0.98-1.79), and baseline sleep disturbances (OR = 1.04, 95% CI = 1.00-1.08), independently of the associations observed for baseline MetS components. CONCLUSION: We observed a high incidence of MetS during a 3 years follow-up (19.3%) in individuals with BD. Identification of predictive factors should help the development of early interventions to prevent or treat early MetS.

Animal movement on the hoof and on the cart and its implications for understanding exchange within the Indus Civilisation.

Movement of resources was essential to the survival and success of early complex societies. The sources and destinations of goods and the means of transportation - be it by boats, carts and/or foot - can often be inferred, but the logistics of these movements are inherently more difficult to ascertain. Here, we use strontium isotopic analysis to test hypotheses about the role of animal and animal-powered transport in medium and long-distance movement and exchange, using the Indus Civilization as a case study. Across the wide geographical spread of the Indus Civilisation, there is strong evidence for long-distance exchange of raw materials and finished objects and this process is presumed to involve boats and animal-driven transport, although there is little evidence as to the relative importance of each mode of movement. Strontium isotopic analysis of animal remains from four sites analysed for this study combined with results from nine other sites indicates limited long-distance animal movement between different geological zones within the Indus Civilisation. These findings suggest that individual animals primarily moved short- or medium-distances, though there are several significant exceptions seen in some pigs and cattle found at two large urban sites. We infer that long-distance transport of goods, be it raw materials, finished objects, other goods, or the animals themselves, could have occurred through the use of boats and waterways, by traction animals moving over long distances that did not end up in the archaeological record, and/or by different animals participating in many short to medium-distance movements.

Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment and self-reported side effects in the euthymic phase of bipolar disorders: Results from the FACE-BD cohort.

Bipolar disorders (BD) are characterized by cognitive impairment during the euthymic phase, to which treatments can contribute. The anticholinergic properties of medications, i.e., the ability of a treatment to inhibit cholinergic receptors, are associated with cognitive impairment in elderly patients and people with schizophrenia but this association has not been well characterized in individuals with remitted BD. Moreover, the validity of only one anticholinergic burden scale designed to assess the anticholinergic load of medications has been tested in BD. In a literature review, we identified 31 existing scales. We first measured the associations between 27 out of the 31 scales and objective cognitive impairment in bivariable regressions. We then adjusted the bivariable models with covariates: the scales significantly associated with cognitive impairment in bivariable and multiple logistic regressions were defined as having good concurrent validity to assess cognitive impairment. In a sample of 2,031 individuals with euthymic BD evaluated with a neuropsychological battery, two scales had good concurrent validity to assess cognitive impairment, whereas chlorpromazine equivalents, lorazepam equivalents, the number of antipsychotics, or the number of treatments had not. Finally, similar analyses with subjective anticholinergic side-effects as outcome variables reported 14 scales with good concurrent validity to assess self-reported peripheral anticholinergic side-effects and 13 to assess self-reported central anticholinergic side-effects. Thus, we identified valid scales to monitor the anticholinergic burden in BD, which may be useful in estimating iatrogenic cognitive impairment in studies investigating cognition in BD.

Impact of drug consumption rooms on non-fatal overdoses, abscesses and emergency department visits in people who inject drugs in France: results from the COSINUS cohort.

BACKGROUND: The effectiveness of drug consumption rooms (DCRs) for people who inject drugs (PWID) has been demonstrated for HIV and hepatitis C virus risk practices, and access to care for substance use disorders. However, data on other health-related complications are scarce. Using data from the French COSINUS cohort, we investigated the impact of DCR exposure on non-fatal overdoses, abscesses and emergency department (ED) visits, all in the previous 6 months. METHODS: COSINUS is a 12-month prospective cohort study of 665 PWID in France studying DCR effectiveness on health. We collected data from face-to-face interviews at enrolment, and at 6 and 12 months of follow-up. After adjusting for other correlates (P-value < 0.05), the impact of DCR exposure on each outcome was assessed using a two-step Heckman mixed-effects probit model, allowing us to adjust for potential non-randomization bias due to differences between DCR-exposed and DCR-unexposed participants, while taking into account the correlation between repeated measures. RESULTS: At enrolment, 21%, 6% and 38% of the 665 participants reported overdoses, abscesses and ED visits, respectively. Multivariable models found that DCR-exposed participants were less likely to report overdoses [adjusted coefficient (95% CI): -0.47 (-0.88; -0.07), P = 0.023], abscesses [-0.74 (-1.11; -0.37), P < 0.001] and ED visits [-0.74 (-1.27; -0.20), P = 0.007]. CONCLUSION: This is the first study to show the positive impact of DCR exposure on abscesses and ED visits, and confirms DCR effectiveness in reducing overdoses, when adjusting for potential non-randomization bias. Our findings strengthen the argument to expand DCR implementation to improve PWID injection environment and health.

Placenta-derived mesenchymal stromal cells as a treatment for refractory chronic gingivostomatitis in cats: eight cases (2018).

OBJECTIVES: The aim of this case series was to collect preliminary data on safety and efficacy of treating cats suffering from refractory feline chronic gingivostomatitis with a single intravenous therapy of cryopreserved placenta-derived mesenchymal stromal cells. MATERIALS AND METHODS: We planned the prospective inclusion of cats suffering from refractory chronic gingivostomatitis in three veterinary clinics. All cats received a single infusion of 10×106 cryopreserved cells. Follow-up evaluations were done at day 15 and at 2-, 3- and 6-months following infusion. Clinical disease severity was evaluated by dental specialists using a published stomatitis disease activity index scoring system coupled with an owners' assessment questionnaire. RESULTS: All eight cats attended all follow up visits. Cryopreserved ready-to-use placenta-derived cells administered systemically were safe and resulted in notable clinical improvement in all cats as reported by stomatitis disease activity index scoring and owner's survey. CLINICAL SIGNIFICANCE: Infusion of cryopreserved freshly thawed placenta-derived mesenchymal stromal cells appears to promote clinical and consequently behavioural benefits in cats with refractory chronic gingivostomatitis after having undergone full-mouth or premolar-molar tooth extraction. Future randomised studies are required to confirm safety and efficacy of this treatment.

[Drug Consumption Rooms : Opinion and willingness among people who inject drugs in Marseille, France]. / Salles de consommation à moindre risque : opinion et volonté d'utilisation des personnes injectrices de substances psychoactives à Marseille, France.

BACKGROUND: In France, people who inject drugs (PWID) are still one of the most at risk population for contracting hepatitis C virus (HCV). Drug consumption rooms (DCR) have shown their effectiveness on HCV risk behaviors abroad and in France, where they have been recently evaluated with the COSINUS study. In France, two DCRs opened in 2016, one in Paris and another in Strasbourg. The objective of this sub-analysis was to explore the willingness to use a DCR in PWID living in Marseille, where no DCR is opened. METHODS: The COSINUS study is a prospective multicenter cohort that included 665 PWID recruited in Bordeaux, Marseille, Paris and Strasbourg between 2016 and 2019. Investigators administered questionnaires face-to-face at regular intervals at baseline, 3 months, 6 months and 12 months. In Marseille, 199 PWID were recruited. A multivariable logistic regression model was performed to assess factors associated with willingness to use DCR among this population. RESULTS: Among 545 observations corresponding to 195 distinct participants selected for analyses, 57% declared they were willing to attend a DCR. The main reason given was "to consume more cleanly". Receiving allowances (OR = 2.38; 95% confidence interval (CI) (95% CI) = 1.17-4.81), not having health insurance (OR = 3.61; 95% CI = 1.49-8.75), injecting daily (OR = 1.97; 95% CI = 1.05-3.70) and in a public space (OR = 2.66; 95% CI = 1.29-5.47) were all positively associated with willingness to use a DCR. CONCLUSIONS: DCR are devices that target PWID exposed to high sanitary or social risks, i.e. people living in precarious conditions, who have to inject in public spaces, in deleterious sanitary environments and with rapid gestures in order not to be seen. These analyzes highlight that the people who most want to attend a DCR are aware of the harms associated with their practices and show a desire to seek protection from street-based drug scenes.

Key findings on bipolar disorders from the longitudinal FondaMental Advanced Center of Expertise-Bipolar Disorder (FACE-BD) cohort.

BACKGROUND: The FACE-BD cohort is an observational cohort of individuals with bipolar disorders (BD) who benefited from a systematic evaluation with evidence-based treatment recommendations and who were followed-up every year for 3 years in France. The objectives were to describe the lifetime course of BD, associated psychiatric and somatic comorbidities, and cognition profile. This cohort aims to identify clinical/biological signatures of outcomes, trajectories of functioning and transition between clinical stages. This article summarizes 10 years of findings of the FACE-BD cohort. METHOD & RESULTS: We included 4422 individuals, all having a baseline assessment, among which 61.2% had at least one follow-up visit at either one, two or three years. A subsample of 1200 individuals had at least one biological sample (serum, plasma, DNA). Assessments include family history of psychiatric disorders, psychiatric diagnosis, current mood symptoms, functioning, hospitalizations, suicidal attempts, physical health, routine blood tests, treatment history, psychological dimensions, medico-economic data and a cognitive assessment. Studies from this cohort illustrate that individuals with BD display multiple coexistent psychiatric associated conditions including sleep disturbances, anxiety disorders, substance use disorders and suicide attempts as well as a high prevalence of metabolic syndrome. During follow-up, we observed a 55% reduction of the number of days of hospitalization and a significant improvement in functioning. CONCLUSIONS: The FACE-BD cohort provides a strong research infrastructure for clinical research in BD and has a unique position among international cohorts because of its comprehensive clinical assessment and sustainable funding from the French Ministry of Health.

Influence of childhood maltreatment on prevalence, onset, and persistence of psychiatric comorbidities and suicide attempts in bipolar disorders.

BACKGROUND: Psychiatric comorbidities and suicide attempts are highly prevalent in Bipolar Disorders (BD). We examined the associations between childhood maltreatment, psychiatric comorbidities, and suicide attempts, in terms of lifetime prevalence, sequence of onset, and current symptoms. METHODS: We assessed 3,047 individuals with BD for suicide attempts, anxiety disorders, substance use disorders, and eating disorders. Participants completed a self-report for the assessment of childhood maltreatment. Associations between childhood maltreatment and characteristics of comorbidities (lifetime prevalence, current symptoms, and age at onset) were examined using logistic regressions and network analyses. RESULTS: Psychiatric comorbidities were frequent with a mean number per individual of 1.23 (SD = 1.4). Most comorbidities occurred prior to the onset of BD. Participants who reported higher levels of childhood maltreatment had more frequent and multiple comorbidities, which were also more currently active at inclusion. Childhood maltreatment did not decrease the age of onset of comorbidities, but was associated with a faster accumulation of comorbidities prior to the onset of BD. Logistic regression and network analyses showed that emotional abuse and sexual abuse might play a prominent role in the lifetime prevalence of psychiatric comorbidities and suicide attempts. CONCLUSIONS: Childhood maltreatment was associated with suicide attempts, and with frequent, multiple, and persistent psychiatric comorbidities that accumulated more rapidly prior to the onset of BD. Hence, childhood maltreatment should be systematically assessed in individuals with BD, in particular when the course of the disorder is characterized by a high comorbid profile or by a high suicidality.

B and δ11B biogeochemical cycle in a beech forest developed on a calcareous soil: Pools, fluxes, and forcing parameters.

Rock weathering and biological cycling hold the development and sustainability of continental ecosystems, yet the interdependence of macro- and micro-nutrients biogeochemical cycles and their implications for ecosystem functioning remains unclear, despite being of particular importance in the context of global changes. This study focuses on the stocks, fluxes and processes constituting the biogeochemical cycle of boron. Vegetation, soils and solutions were monitored for a full year in a temperate beech forest developed on calcareous soil. Despite an overwhelmingly large B pool in soils, this study points to limited influence of weathering emphasizing the importance of vegetation cycling on this site. The biological imprint on the B cycle is marked by (1) a strong 11B enrichment of solutions compared to the mineral source and (2) systematic correlations observed between B and other strongly recycled elements in all water samples. B isotopes are fractionated within the beech stand with higher values in leaves (23.5‰) and lower in fine roots (-11.7‰), suggesting that the light 10B isotope is preferentially assimilated during plant growth. B isotopic data are consistent with a Rayleigh-like behaviour during xylem transfer leading to an 11B enrichment in the higher parts of the trees, putting internal B transfer as the main driver of the large range of isotopic compositions between plant tissues. B apparent isotopic fractionations are observed in the annually produced biomass and total beech stand, albeit with different values: αxylem-biomass = 0.980 ± 0.009 and 0.990 ± 0.002, respectively, suggesting 11B transfer from old to new tissue. The developed model also points to an isotopic fractionation factor during B uptake much higher than previously evaluated (0.979 < αuptake < 0.994). Overall, this study demonstrates that B isotopes appear as a promising tracer of soil-plant interactions with particular emphasis on tree adaptation to B bioavailability in soil.

Reverse blood flow in cervicofacial veins after venous ligations: Potential implications in microsurgery.

INTRODUCTION: The consequences on the cervicofacial venous circulation of major cervicofacial vein ligations are poorly known. We aimed to highlight by using Doppler Ultrasound flow differences in the cervicofacial venous network in the case of unilateral or bilateral ligation of main venous collector trunks (external jugular vein [EJV] and internal jugular vein [IJV]) METHODS: A Doppler ultrasound was performed on 10 healthy volunteers, 8 patients with previous bilateral ligation of the EJV, 8 with a unilateral ligation of the EJV, and 8 with a unilateral ligation of the EJV and IJV, after modified radical neck dissection. The diameter, the flow direction and the peak systolic velocity (PSV) of the superficial temporal vein, the facial vein (FV) and the IJV were measured. RESULTS: Healthy patients had a similar right and left PSV for all the veins studied, with always antegrade flows. Patients with previous ligations had some significant right/left differences and retrograde flows. CONCLUSION: A redistribution of venous blood flow on the contralateral side of the face and neck seems to take place in the case of unilateral ligation of the EJV and/or IJV. Retrograde flows are sometimes observed in the case of previous ligation of the EJV and/or IJV and might compromise the success of venous microanastomoses.

Do DSM-5 substance use disorder criteria differ by user care settings? An item response theory analysis approach.

AIM: To examine differences in the psychometric characteristics of diagnostic criteria for Substance Use Disorders (SUD) between substance users in harm reduction settings (HR) and substance users seeking treatment (Tx). METHODS: Differential Item and Test Functioning (DIF & DTF) analysis were performed to examine differences in the difficulty of endorsement and in discrimination of the 11 diagnostic criteria and to test if the criteria set as a whole (the "test") functioned differently by care settings (Tx vs. HR) for alcohol, cocaine, cannabis, opiates and tobacco. To test uniform and nonuniform DIF, multiple indicator multiple cause (MIMIC) structural equation models were used. RESULTS: Regardless of the substance, the DSM-5 criteria "craving", "large amount", "time spent", "tolerance" and "activities given up" had similar functioning by care settings. Little evidence for DIF was found for other criteria. The criteria set as a whole did not function differently by care settings for alcohol, cocaine and tobacco. At the same trait severity, compared to HR, the Tx subgroup had a greater number of endorsed criteria for cannabis and a smaller number of endorsed criteria for opioids. CONCLUSION: The unidimensionality of the 11 DSM-5 criteria and applicability of all criteria and diagnosis was confirmed in this large sample of problematic substance users. While the majority of the criteria related to loss of control of substance use, functioned well in both care settings, the criteria related to consequences of substance use had several differential functioning.

Clinical predictors of recurrences in bipolar disorders type 1 and 2: A FACE-BD longitudinal study.

OBJECTIVE: To examine which characteristics predict the time to a first mood recurrence at three years in Bipolar Disorder type I (BD-I) and type II (BD-II). METHODS: Individuals with BD were followed up to 3 years. Turbull's extension of the Kaplan-Meier analysis for interval-censored data was used to estimate the cumulative probability of recurrence over time. Separate models were performed according to BD subtype to determine which baseline factors were predictive of recurrences and were adjusted for age, gender and educational level. RESULTS: We included 630 individuals with BD-I and 505 with BD-II. The first recurrence of any polarity occurred earlier in BD-II (p = 0.03). The first depressive recurrence occurred earlier in BD-II (p < 0.0001), whereas the first (hypo)manic recurrence occurred earlier in BD-I (p = 0.0003). In BD-I, the clinical variables that were associated to the time to a first mood recurrence were depressive symptoms, lifetime rapid cycling, global activation and the number of psychotropic medications at baseline. In BD-II, the time to a first recurrence was associated with a younger age at onset of BD and a higher number of lifetime mood episodes. The Areas Under the Curve for both models were moderate. CONCLUSION: Predictors of recurrences showed few specificities to BD-I or BD-II. The ability to predict recurrences in BD based on socio-demographic and clinical variables remained too moderate for a transfer in daily practice. This study highlights the need for further studies that would include other types of predictors, such as molecular, cognitive or neuro-imaging ones, to achieve an accurate level of prediction of recurrences in BD.

Robotic-assisted partial nephrectomy (RAPN) and standardization of outcome reporting: a prospective, observational study on reaching the "Trifecta and Pentafecta".

Partial nephrectomy (PN) for small renal masses is common, but outcomes are not reported in a standard manner. Traditionally, parameters such as 90-day mortality, blood loss, transfusion rates, length of stay, nephrometry scoring and complications are published but their collective impact on warm ischemia time (WIT) and post-surgery GFR is rarely determined. Thus, our aim was to assess if "Trifecta" and "Pentafecta" outcomes could be used as useful surgical outcome markers. A prospective database of 252 Robotic-Assisted PN (RAPN) cases (2008-2019) was analysed. "Pentafecta" was defined as achievement of "Trifecta" (negative surgical margin, no postoperative complications and WIT of < 25 min) plus over 90% estimated GFR preservation and no CKD stage upgrading at 1 year. Binary logistic regression analysis was conducted to predict factors which may prevent achieving a Trifecta/Pentafecta. Median tumour size was 3 cm and mean WIT was 15 min. Positive surgical margins (PSM) occurred in 2 cases. Overall, the intra-operative complication rate was 7%. One recurrence conferred 5-year cancer-free survival of 97%. Trifecta outcome was achieved in 169 (67%) and Pentafecta in 141 (56%) of cases. At logistic regression analysis, intraoperative blood loss was the only factor to affect Trifecta achievement (p = 0.018). Advanced patient age negatively impacted Pentafecta achievement (p = 0.010). The Trifecta and Pentafecta outcomes are easily applicable to PN data, and offer an internationally comparable PN outcome, quality measure. We recommend applying this standardization to national data collection to improve the quality of reporting and ease of interpretation of surgeon/centres' outcomes.

Saline groundwater in the Buffels River catchment, Namaqualand, South Africa: A new look at an old problem.

Namaqualand, South Africa, is a global biodiversity hotspot but local populations are affected by challenging economic conditions largely because of poor access to water. In this study groundwater types are characterised and sources of salts and salinisation processes are identified using hydrochemistry and δ18O, δ2H and 87Sr/86Sr data. Analysis of δ18O and δ2H data suggests that evaporation does not play a major role in salinisation of the groundwater. However, major ion chemistry and 87Sr/86Sr ratios indicate that salts present in the groundwater are linked to dry deposition of marine aerosols and ion-exchange reactions in soils in the alluvial aquifer systems. The hydrochemical variability of the groundwater in the basement aquifer system suggests that there are strong local controls linked to weathering processes in individual basement rock types. The region is also notable for the high density of heuweltjies, biophysical features associated with increased nutrient levels, associated with termite activity. Electromagnetic scanning as well as measurement of water-soluble soil electrical conductivity values on and off heuweltjies, show that heuweltjies are saline with salinity increasing with depth. The level of groundwater salinity correlates with the level of heuweltjie salinity. Precipitation records from the last 150 years provide support for the hypothesis that accumulated salts, and in particular, heuweltjie salts are flushed into the groundwater system during sporadic large volume precipitation events. Thus, heuweltjies and hence termite activity, could potentially represent a previously unrecognized contributor to groundwater salinisation across Namaqualand and in other parts of the world.

Natural Clinopyroxene Reference Materials for in situ Sr Isotopic Analysis via LA-MC-ICP-MS.

Clinopyroxene is a major host mineral for lithophile elements in the mantle lithosphere, and therefore, its origin is vital for constraints on mantle evolution and melt generation. In situ Sr isotopic measurement of clinopyroxene has been available since the recent development of laser ablation multicollector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) in the 2000s. Therefore, there is an increasing demand for natural clinopyroxene reference materials for Sr isotope microanalysis. In this contribution, we present six natural clinopyroxene reference materials from South Africa (JJG1424) and China (YY09-47, YY09-04, YY09-24, YY12-01, and YY12-02) for Sr isotope microanalysis. The Sr content of these clinopyroxenes ranges from 50 to 340 µg g-1, which covers most natural clinopyroxene compositions. Homogeneity of these potential reference materials were investigated and evaluated in detail over a 2-year period using 193-nm nanosecond and 257-nm femtosecond laser systems coupled to either a Neptune or Neptune Plus MC-ICP-MS. Additionally, the major and trace element of these clinopyroxenes were examined by electron probe microanalyzer (EPMA) as well as solution and laser ICP-MS. The in situ 87Sr/86Sr values obtained for the six natural clinopyroxene reference materials agree well with data obtained using the thermal ionization mass spectrometer (TIMS) method. The Sr isotopic stability and homogeneity of these clinopyroxenes make them potential reference materials for in situ Sr microanalysis to correct instrumental fractionation or as quality control materials for analytical sessions. The new Sr isotope data provided here might be beneficial for microbeam analysis in the geochemical community.

Evolution and characteristics of the use of valproate in women of childbearing age with bipolar disorder: Results from the FACE-BD cohort.

BACKGROUND: Valproate is associated with teratogenic and neurodevelopmental effects. Several agencies have restricted the conditions of its prescription in bipolar disorders (BD). We aimed to assess the evolution of valproate prescription and the clinical profile of BD women of childbearing age receiving valproate. METHODS: Based on a large national cohort, we included all BD women 16-50 years old. Sociodemographic, clinical and pharmacological data were recorded. Logistic regression analyses were used to describe variables associated with valproate prescription. RESULTS: Of the 1018 included women 16-50 years old, 26.9% were treated with valproate with a mean daily dosage of 968 mg. The prevalence of BD women using valproate was 32.6% before May 2015 and 17.3% after May 2015 (p<0.001), the date of French regulatory publication of restriction of valproate prescription. The multivariate analysis revealed that the inclusion period after May 2015 (OR=0.54, CI 95% 0.37-0.78, p=0.001), the age lower than 40 years (OR=0.65, CI 95% 0.43-0.98, p=0.040) and the number of lifetime mood episodes (OR=0.98, CI 95% 0.95-0.99, p=0.040) were the variables negatively associated with the use of valproate. LIMITATIONS: Study could be underpowered to determine a clinical profile associated with valproate prescription. CONCLUSIONS: The regulatory change in BD women of childbearing age had a significant impact on valproate prescription, even if the prescription rate remains high. Important efforts are needed to help clinicians and patients to improve quality of care in BD women of childbearing age.

Minimum clinically important differences for the Functioning Assessment Short Test and a battery of neuropsychological tests in bipolar disorders: results from the FACE-BD cohort.

AIMS: Establishing the minimum clinically important difference (MCID) in functioning and cognition is essential to the interpretation of the research and clinical work conducted in bipolar disorders (BD). The present study aimed to estimate the MCID for the Functioning Assessment Short Test (FAST) and a battery of neuropsychological tests in BD. METHODS: Anchor-based and distributive methods were used to estimate the MCID for the FAST and cognition using data from a large, multicentre, observational cohort of individuals with BD. The FAST and cognition were linked with the Clinical Global Impressions Scale-Severity (CGI-S) and Global Assessment of Functioning (GAF) using an equipercentile method. The magnitude of the standard error measurement (s.e.m.) provided another estimate of the MCID. RESULTS: In total, 570 participants were followed for 2 years. Cross-sectional CGI-S and GAF scores were linked to a threshold ⩽7 on the FAST for functional remission. The MCID for the FAST equalled 8- or 9-points change from baseline using the CGI-S and GAF. One s.e.m. on the FAST corresponded to 7.6-points change from baseline. Cognitive variables insufficiently correlated with anchor variables (all ρ <0.3). One s.e.m. for cognitive variables corresponded to a range of 0.45 to 0.93-s.d. change from baseline. CONCLUSIONS: These findings support the value of the estimated MCID for the FAST and cognition and may be a useful tool to evaluate cognitive and functional remediation effects and improve patient functional outcomes in BD. The CGI-S and GAF were inappropriate anchors for cognition. Further studies may use performance-based measures of functioning instead.