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Recent global market disruptions, including the COVID-19 crisis, inflation, and oil crises, have highlighted the need for industries to reduce dependence on petrochemicals. However, the coating industry remains reliant on petrochemicals due to a lack of knowledge about local and sustainable alternatives. This study explored the potential of wood extractives as precursors for producing high-quality wood coatings. Terpenes were modified through acrylation, and bio-based latexes were synthesized from these modified terpenes. Analysis showed that all tested latexes had conversion levels above 88.5%. The bio-based films were characterized, and their transparency, measured by ultraviolet-visible spectroscopy, exceeded 80%. The good incorporation of bio-based monomers in the latex films was confirmed by thermogravimetric analysis and pyrolysis-gas chromatography-mass spectrometry. Comparative analysis between bio-based and conventional latexes showed equivalent results in particle size, molecular weight, glass transition temperature, and minimum film formation temperature. However, bio-based films exhibited lower hardness. The study suggests that using monomers derived from wood extractives offers a viable alternative to petrochemicals, utilizing abundant forest residues. This approach could address raw material shortages and help make the coatings industry more sustainable by reducing its reliance on petrochemicals.

Abstact Background DRAGON was a phase 3, randomised, double-blind, placebo-controlled study which evaluated the efficacy and safety of erenumab in patients with chronic migraine (CM) from Asia not adequately represented in the global pivotal CM study. Methods DRAGON study was conducted across 9 Asian countries or regions including mainland China, India, the Republic of Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Patients (N = 557) with CM (aged 18–65 years) were randomised (1:1) to receive once-monthly subcutaneous erenumab 70 mg or matching placebo for 12 weeks. The primary endpoint was the change in monthly migraine days (MMD) from baseline to the last 4 weeks of the 12-week double-blind treatment phase (DBTP). Secondary endpoints included achievement of ≥ 50% reduction in MMD, change in monthly acute headache medication days, modified migraine disability assessment (mMIDAS), and safety. Study was powered for the primary endpoint of change from baseline in MMD. Results At baseline, the mean (SD) age was 41.7 (± 10.9) years, and 81.5% (n = 454) patients were women. The mean migraine duration was 18.0 (± 11.6) years, and the mean MMD was 19.2 (± 5.4). 97.8% (n = 545) randomised patients completed the DBTP. Overall, demographics and baseline characteristics were balanced between the erenumab and placebo groups except for a slightly higher proportion of women in the placebo group. At Week 12, the adjusted mean change from baseline in MMD was − 8.2 days for erenumab and − 6.6 days for placebo, with a statistically significant difference for erenumab versus placebo (adjusted mean difference vs placebo: − 1.57 [95%CI: − 2.83, − 0.30]; P = 0.015). A greater proportion of patients treated with erenumab achieved ≥ 50% reduction in MMD versus placebo (47.0% vs 36.7%, P = 0.014). At Week 12, greater reductions in monthly acute headache medication days (− 5.34 vs − 4.66) and mMIDAS scores (− 14.67 vs − 12.93) were observed in patients treated with erenumab versus placebo. Safety and tolerability profile of erenumab was comparable to placebo, except the incidence of constipation (8.6% for erenumab vs 3.2% for placebo). Conclusion DRAGON study demonstrated the efficacy and safety of erenumab 70 mg in patients with CM from Asia. No new safety signals were observed during the DBTP compared with the previous trials. Trial registration NCT03867201

Family is widely regarded as a cornerstone of student support. When family support exist as an essential form of social capital making, rupture of family ties places students in a disadvantageous position. This paper focuses on estranged students' accounts of their experiences of higher education, highlighting how capital dynamics shape their academic trajectories. Based on interviews with 21 estranged students, our research uncovers different dimensions of estranged students' struggles and successes as they move through academia. This paper explores the social imagination that surrounds the university student, or 'student experience', as resting upon family support. The authors propose that widening participation policies and practices need to be more attuned to the realities that mark estranged students' experiences, as they are not only impacted by the scarcity of either economic or social capital, but also by the instability of interrelated capitals that contribute to precarious and volatile experiences.

While investigation on family estrangement is growing within academic circles, research regarding the interconnection between experiences of estrangement and higher education (HE) is still limited. Sociological understandings of these issues are even scarcer, with policy interventions and practical guidance forming early interventions in HE. Set within the context of Scotland, this paper explores the experiences of HE students who are estranged from their family, and interrogates the ways students develop a sense of identity in the context of their academic lives. The paper applies Goffman's work on stigma and identity management in relation to Bourdieu's concept of capitals to cast a critical eye on the identity formation of estranged students. In doing so, we challenge normative assumptions of what it means to be a university student in contemporary society and urge institutions and policy makers to rethink the complexity of students' academic lives in more inclusive ways.

Variants in the UNC45A cochaperone have been recently associated with a syndrome combining diarrhea, cholestasis, deafness, and bone fragility. Yet the mechanism underlying intestinal failure in UNC45A deficiency remains unclear. Here, biallelic variants in UNC45A were identified by next-generation sequencing in 6 patients with congenital diarrhea. Corroborating in silico prediction, variants either abolished UNC45A expression or altered protein conformation. Myosin VB was identified by mass spectrometry as client of the UNC45A chaperone and was found misfolded in UNC45AKO Caco-2 cells. In keeping with impaired myosin VB function, UNC45AKO Caco-2 cells showed abnormal epithelial morphogenesis that was restored by full-length UNC45A, but not by mutant alleles. Patients and UNC45AKO 3D organoids displayed altered luminal development and microvillus inclusions, while 2D cultures revealed Rab11 and apical transporter mislocalization as well as sparse and disorganized microvilli. All those features resembled the subcellular abnormalities observed in duodenal biopsies from patients with microvillus inclusion disease. Finally, microvillus inclusions and shortened microvilli were evidenced in enterocytes from unc45a-deficient zebrafish. Taken together, our results provide evidence that UNC45A plays an essential role in epithelial morphogenesis through its cochaperone function of myosin VB and that UNC45A loss causes a variant of microvillus inclusion disease.

Recent global market disruptions, including the COVID-19 crisis, inflation, and oil crises, have highlighted the need for industries to reduce dependence on petrochemicals. However, the coating industry remains reliant on petrochemicals due to a lack of knowledge about local and sustainable alternatives. This study explored the potential of wood extractives as precursors for producing high-quality wood coatings. Terpenes were modified through acrylation, and bio-based latexes were synthesized from these modified terpenes. Analysis showed that all tested latexes had conversion levels above 88.5%. The bio-based films were characterized, and their transparency, measured by ultraviolet-visible spectroscopy, exceeded 80%. The good incorporation of bio-based monomers in the latex films was confirmed by thermogravimetric analysis and pyrolysis-gas chromatography-mass spectrometry. Comparative analysis between bio-based and conventional latexes showed equivalent results in particle size, molecular weight, glass transition temperature, and minimum film formation temperature. However, bio-based films exhibited lower hardness. The study suggests that using monomers derived from wood extractives offers a viable alternative to petrochemicals, utilizing abundant forest residues. This approach could address raw material shortages and help make the coatings industry more sustainable by reducing its reliance on petrochemicals. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls? SUMMARY ANSWER This study is the first to provide 24-h urinary gonadotropin assay data, using an electrochemiluminescent immunoassay (CMIA), and to report its usefulness as a tool for the diagnosis of CPP. WHAT IS KNOWN ALREADY Data about the GnRH test in the diagnosis of CPP are variable and there is no consensus regarding its interpretation. The measurement of FSH and LH in urines was previously reported to be an alternative biological tool. STUDY DESIGN, SIZE, DURATION This is a retrospective two-cohort study, involving a setting and a validation cohort. A total of 516 girls, included between October 2012 and July 2015, and 632 urinary collections were analyzed in the setting cohort. In the validation cohort, 39 girls were included between January 2021 and May 2023, and 49 urinary collections were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included girls who consulted for an investigation of disturbed growth rate or a clinical suspicion of puberty onset in different medical centres across France (setting cohort). Girls with a suspicion of precocious puberty onset were addressed at the expert centre of paediatric endocrinology of the Groupement Hospitalier Lyon Est (validation cohort). Pelvic ultrasonography was performed and enabled their classification according to clinical and morphologic changes criteria (prepubertal or pubertal groups). The parents collected 24-h urine samples (u24) according to standardized instructions. FSH and LH (urinary or plasmatic) were measured using a current and automated CMIA. MAIN RESULTS AND THE ROLE OF CHANCE The area under the ROC curves for CPP prediction was 0.709 for u24FSH (P  < 0.001), 0.767 for u24LH (P  < 0.001), and 0.753 for the u24LH/u24FSH ratio (P  < 0.001). We retained all possible combinations of the four thresholds in the validation cohort (u24FSH = 1.1 or 2.0 IU/24 h; u24LH = 0.035 or 0.08 IU/24 h). The combination of u24FSH > 1.1 IU/24 h and u24LH > 0.08 IU/24 h had a positive PV of 85.7% and a negative PV of 94.3%, a sensitivity of 85.7% and a specificity of 94.3%, for classifying prepubertal and pubertal girls in this cohort. LIMITATIONS, REASONS FOR CAUTION This is a retrospective study, in which a margin of error remains due to the inherent uncertainty regarding the clinical assessment of pubertal onset. It must be considered that the thresholds can only apply to the used reagents; measurements without extractions using other reagents are likely to show important heterogeneity. WIDER IMPLICATIONS OF THE FINDINGS The assay performed herein is a simple, non-invasive, and analytically robust technique meeting the criteria for an alternative to the GnRH test which could be used to supplement its lack of sensitivity. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was used. All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER In-house #23-5214 registered study. [ABSTRACT FROM AUTHOR]

Abstract Background Care goals are often implicit, although their identification is a key element of any prescription process. This study aimed to describe the clinical goals of drug prescriptions in general practice, their determinants and the agreement between physicians and patients. Methods This was a cross-sectional study conducted by 11 resident trainees acting as observers in 23 general practices. The residents recorded the indication and main physician’s goal for all drugs prescribed during five consultation days in each practice in December 2015, and the main patient’s goal for a sub-sample of consultations. We used an eight-category generic classification of prescription goals, including three specific (mortality, morbidity and cure), three non-specific (symptoms, quality of life, functioning) and two non-specified (other goal, no goal) categories. Analyses were based on a multivariable, multilevel model and on the kappa statistic applied to the sub-sample of consultations. Results The sample encompassed 2141 consultations and 5036 drugs. The main physicians’ goal of drug prescriptions was to relieve symptoms (43.3%). The other goals were to decrease the risk of morbidity (22.4%), to cure disease (11.7%), to improve quality of life (10.6%), to decrease the risk of mortality (8.5%) and to improve functioning (1.8%). The choice of a specific goal was more frequent in patients with the following characteristics: over 50 (OR [1.09;1.15]), of male gender (OR [1.09;1.39]), with full financial coverage for a long-term condition (OR [1.47;1.97]), known by the physician (OR [1.19;2.23]), or with a somatic health problem (OR [2.56;4.17]). Cohen’s kappa for drug prescription goals between the patients and the physicians was 0.26 (0.23–0.30). Conclusions Physicians’ goals are poorly shared with patients. It remains to be assessed whether it is possible to collect and discuss information on prescription goals on a daily basis.

To assess quality of care, groups of care units that cared for the same patients at various stages of end-stage renal disease, might be more appropriate than the centre level. These groups constitute “communities” that need to be delineated to evaluate their practices and outcomes. In this article, we describe the use of an agglomerative (Fast Greedy) and a divisive (Edge Betweenness) method to describe dialysis activities in France. The validation was based on the opinion of the field actors at the regional level of the REIN registry. At the end of 2018, ESRD care in France took place in 1,166 dialysis units. During 2016–2018, 32 965 transfers occurred between dialysis units. With the Edge Betweenness method, the 1,114 French dialysis units in metropolitan France were classified into 156 networks and with the Fast Greedy algorithm, 167 networks. Among the 32 965 transfers, 23 168 (70%) were defined in the same cluster by the Edge Betweenness algorithm and 26 016 (79%) in the same cluster by the Fast Greedy method. According to the Fast Greedy method, during the study period, 95% of patients received treatment in only one network. According to the opinion of the actors in the field, the Fast Greedy algorithm seemed to be the best method in the context of dialysis activity modelling. The Edge Betweenness classification was not retained because it seemed too sensitive to the volume of links between dialysis units.

BackgroundWorldwide, COVID-19 outbreaks in nursing homes have often been sudden and massive. The study investigated the role SARS-CoV-2 virus spread in nearby population plays in introducing the disease in nursing homes.Material and methodsThis was carried out through modelling the occurrences of first cases in each of 943 nursing homes of Auvergne-Rhône-Alpes French Region over the first epidemic wave (March-July, 2020). The cumulative probabilities of COVID-19 outbreak in the nursing homes and those of hospitalization for the disease in the population were modelled in each of the twelve Départements of the Region over period March-July 2020. This allowed estimating the duration of the active outbreak period, the dates and heights of the peaks of outbreak probabilities in nursing homes, and the dates and heights of the peaks of hospitalization probabilities in the population. Spearman coefficient estimated the correlation between the two peak series.ResultsThe cumulative proportion of nursing homes with COVID-19 outbreaks was 52% (490/943; range: 22-70% acc. Département). The active outbreak period in the nursing homes lasted 11 to 21 days (acc. Département) and ended before lockdown end. Spearman correlation between outbreak probability peaks in nursing homes and hospitalization probability peaks in the population (surrogate of the incidence peaks) was estimated at 0.71 (95% CI: [0.66; 0.78]).ConclusionThe modelling highlighted a strong correlation between the outbreak in nursing homes and the external pressure of the disease. It indicated that avoiding disease outbreaks in nursing homes requires a tight control of virus spread in the surrounding populations.

Summary: Background: Insufficient long-term data are available on antibody kinetics in survivors of Ebola virus disease (EVD). Likewise, few studies, with very small sample sizes, have investigated cross-reactions between Ebolavirus spp. In this study, we aimed to assess the humoral antibody response and its determinants in survivors of EVD and assess cross-reactivity of antibodies between diverse Ebolavirus spp. Methods: In this observational, prospective cohort study, we collected blood samples from patients from three recruitment sites in Guinea included in the Postebogui study, and we assessed IgG antibody binding to recombinant glycoprotein, nucleoprotein, and 40-kDa viral protein (VP40) of Zaire (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) Ebolaviruses. Participants from the PostEbogui study, from whom we had at least one blood sample that could be tested for the presence of antibodies, were eligible for this analysis. Patients in the PostEbogui study were assessed clinically at inclusion, 1 month and 3 months later, and subsequently every 6 months for up to 60 months after discharge from the Ebola treatment centre. We explored predictors of glycoprotein, nucleoprotein, and VP40 antibody concentrations through a linear mixed model. A logistic mixed model was done to estimate the probability of seropositivity and associated determinants. We assessed cross-reactivity by use of hierarchical cluster analysis. Findings: Of the 802 patients included in the Postebogui study, 687 were included in our analyses. 310 (45%) patients were men and 377 (55%) were women, with an overall median age at the time of the first blood sample of 27·3 years (IQR 19·5–38·2). We observed an overall significant decrease over time of EBOV antibodies, with antibodies against nucleoproteins decreasing more rapidly. At 60 months after discharge from the Ebola treatment centre, the probability of having antibodies against glycoproteins was 76·2% (95% CI 67·2–83·3), against nucleoproteins was 59·4% (46·3–71·3), and against VP40 was 60·9% (51·4–69·8). Persistence of EBOV RNA in semen was associated with higher concentrations of IgG antibodies against nucleoprotein EBOV antigens. Individually, we observed in some survivors an antibody wax-and-wane pattern. The proportion of cross-reactions was highest between glycoproteins from Kissidougou and Mayinga EBOV strains (94·5%, 95% CI 92·5–96·1), followed by EBOV VP40 and BDBV VP40 (88·3%, 85·7–90·6), and EBOV VP40 and SUDV VP40 (83·3%, 80·3–86·1). Interpretation: The probability for survivors of EVD to have antibodies against one or more EBOV antigens remained high, although approximately 25% of survivors had undetectable antibodies, which could have implications, such as a possible decreasing population immunity, for future Ebola outbreaks in the same region. Funding: Reacting–Institut National de la Santé et de la Recherche Médicale, Institut de Recherche pour le Developpement, and Montpellier Université d'Excellence.

Background: Intrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for couples with unexplained infertility. Individual participant data meta-analysis (IPD-MA) is the gold standard for evidence synthesis. Aim: To compare the effectiveness and safety of ovarian stimulation with gonadotrophin, Letrozole and clomiphene citrate (CC) and to explore treatment-covariate interactions for important baseline characteristics in women undergoing IUI. Method: We searched electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL). We included randomised controlled trials (RCTs) comparing IUI-OS with gonadotropins, Letrozole or CC among couples with unexplained infertility. We excluded dose comparing studies of the same drug. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. We used a one-stage approach using a random effects model. Results: Six RCTs (n= 2299) provided IPD. Gonadotropins increased the chance of a live birth compared to both CC (5 RCTs, 1946 women, RR 1.28, 95%CI 1.10 to 1.49, I2 = 25%, moderate-quality evidence) whereas there was insufficient evidence of a difference between Letrozole and CC (1 RCT, 599 women, RR 0.77 95%CI 0.58 to 1.03). Gonadotropins increased the risk of a multiple pregnancy compared to both CC (4 RCTs, 1696 women, RR 2.17, 95%CI 1.33 to 3.55, I2 = 69%, low-quality evidence) whereas there was insufficient evidence of a difference between Letrozole and CC (1 RCT, 599 women, RR 0.71, 95%CI 0.33 to 1.56). No strong evidence on the treatment-covariate interactions (female age, BMI or primary versus secondary infertility) was found. Conclusion: Gonadotropins increased the chance of a live birth compared to both CC and Letrozole but also increased the chance of a multiple pregnancy. Further RCTs comparing Letrozole and other interventions in couples with unexplained infertility are needed.

Variants in the UNC45A cochaperone have been recently associated with a syndrome combining diarrhea, cholestasis, deafness, and bone fragility. Yet the mechanism underlying intestinal failure in UNC45A deficiency remains unclear. Here, biallelic variants in UNC45A were identified by next-generation sequencing in 6 patients with congenital diarrhea. Corroborating in silico prediction, variants either abolished UNC45A expression or altered protein conformation. Myosin VB was identified by mass spectrometry as client of the UNC45A chaperone and was found misfolded in [UNC45A.sup.KO] Caco-2 cells. In keeping with impaired myosin VB function, [UNC45A.sup.KO] Caco-2 cells showed abnormal epithelial morphogenesis that was restored by full-length UNC45A, but not by mutant alleles. Patients and [UNC45A.sup.KO] 3D organoids displayed altered luminal development and microvillus inclusions, while 2D cultures revealed Rab11 and apical transporter mislocalization as well as sparse and disorganized microvilli. All those features resembled the subcellular abnormalities observed in duodenal biopsies from patients with microvillus inclusion disease. Finally, microvillus inclusions and shortened microvilli were evidenced in enterocytes from unc45a-deficient zebrafish. Taken together, our results provide evidence that UNC45A plays an essential role in epithelial morphogenesis through its cochaperone function of myosin VB and that UNC45A loss causes a variant of microvillus inclusion disease., Introduction Congenital diarrhea disorders (CDDs) are rare monogenic diseases characterized by chronic, life-threatening diarrhea starting early in life (1, 2). Depending on the mechanism, diarrhea can be the only symptom [...]

Although central venous catheter (CVC)-related thrombosis (CRT) is a severe complication of home parenteral nutrition (HPN), the amount and quality of data in the diagnosis and management of CRT remain low. We aimed to describe current practices regarding CVC management in French adult and pediatric HPN centers, with a focus on CVC obstruction and CRT. Current practices regarding CVC management in patients on HPN were collected by an online-based cross-sectional survey sent to expert physicians of French HPN centers. We compared these practices to published guidelines and searched for differences between pediatric and adult HPN centers’ practices. Finally, we examined the heterogeneity of practices in both pediatric and adult HPN centers. The survey was completed by 34 centers, including 21 pediatric and 13 adult centers. We found a considerable heterogeneity, especially in the responses of pediatric centers. On some points, the centers’ responses differed from the current guidelines. We also found significant differences between practices in adult and pediatric centers. We conclude that the management of CVC and CRT in patients on HPN is a serious and complex situation for which there is significant heterogeneity between HPN centers. These findings highlight the need for more well-designed clinical trials in this field.