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Abstract The East African Rift is one of Earth’s largest continental landforms. It is recognized as a critical region for understanding hominin evolution yet has also undergone important transformation through ongoing tectonic and volcanic activity. An understanding of the interplay of rift kinematics, magma genesis and geomorphic evolution requires firm geochronology but this has been lacking for much of the East African Rift. Here we present detailed stratigraphic observations and high-precision 40Ar/39Ar ages for major volcanic units in the Central Main Ethiopian Rift. Our new data identify a volumetrically major episode of explosive volcanism between circa 3.85–3.42 million years ago, after aproximately 5-million years-long quiescence. Four other pulses followed but with intensity and magnitude declining over time. We suggest that the observed temporal clustering and the pulsatory volcanic activity may have influenced environmental conditions in the area, with possible implications for hominin evolution.

Abstract Objective COASY, the gene encoding the bifunctional enzyme CoA synthase, which catalyzes the last two reactions of cellular de novo coenzyme A (CoA) biosynthesis, has been linked to two exceedingly rare autosomal recessive disorders, such as COASY protein‐associated neurodegeneration (CoPAN), a form of neurodegeneration with brain iron accumulation (NBIA), and pontocerebellar hypoplasia type 12 (PCH12). We aimed to expand the phenotypic spectrum and gain insights into the pathogenesis of COASY‐related disorders. Methods Patients were identified through targeted or exome sequencing. To unravel the molecular mechanisms of disease, RNA sequencing, bioenergetic analysis, and quantification of critical proteins were performed on fibroblasts. Results We identified five new individuals harboring novel COASY variants. While one case exhibited classical CoPAN features, the others displayed atypical symptoms such as deafness, language and autism spectrum disorders, brain atrophy, and microcephaly. All patients experienced epilepsy, highlighting its potential frequency in COASY‐related disorders. Fibroblast transcriptomic profiling unveiled dysregulated expression in genes associated with mitochondrial respiration, responses to oxidative stress, transmembrane transport, various cellular signaling pathways, and protein translation, modification, and trafficking. Bioenergetic analysis revealed impaired mitochondrial oxygen consumption in COASY fibroblasts. Despite comparable total CoA levels to control cells, the amounts of mitochondrial 4′‐phosphopantetheinylated proteins were significantly reduced in COASY patients. Interpretation These results not only extend the clinical phenotype associated with COASY variants but also suggest a continuum between CoPAN and PCH12. The intricate interplay of altered cellular processes and signaling pathways provides valuable insights for further research into the pathogenesis of COASY‐associated diseases.

Introduction: Prenatal ultrasound (US) anomalies are detected in around 5%–10% of pregnancies. In prenatal diagnosis, exome sequencing (ES) diagnostic yield ranges from 6% to 80% depending on the inclusion criteria. We describe the first French national multicenter pilot study aiming to implement ES in prenatal diagnosis following the detection of anomalies on US.Patients and methods: We prospectively performed prenatal trio-ES in 150 fetuses with at least two US anomalies or one US anomaly known to be frequently linked to a genetic disorder. Trio-ES was only performed if the results could influence pregnancy management. Chromosomal microarray (CMA) was performed before or in parallel.Results: A causal diagnosis was identified in 52/150 fetuses (34%) with a median time to diagnosis of 28 days, which rose to 56/150 fetuses (37%) after additional investigation. Sporadic occurrences were identified in 34/56 (60%) fetuses and unfavorable vital and/or neurodevelopmental prognosis was made in 13/56 (24%) fetuses. The overall diagnostic yield was 41% (37/89) with first-line trio-ES versus 31% (19/61) after normal CMA. Trio-ES and CMA were systematically concordant for identification of pathogenic CNV.Conclusion: Trio-ES provided a substantial prenatal diagnostic yield, similar to postnatal diagnosis with a median turnaround of approximately 1 month, supporting its routine implementation during the detection of prenatal US anomalies.

P4-ATPases comprise a family of lipid flippases that translocate lipids from the exoplasmic (or luminal) to the cytoplasmic leaflet of biological membranes. Of the 14 known human P4-ATPases, ATP8B2 is a phosphatidylcholine flippase at the plasma membrane, but its physiological function is not well understood. Although ATP8B2 could interact with both CDC50A and CDC50B, it required only the CDC50A interaction for its exit from the endoplasmic reticulum and subsequent transport to the plasma membrane. Three de novo monoallelic missense variations of ATP8B2 were found in patients with intellectual disability. None of these variations affected the interaction of ATP8B2 with CDC50A or its localization to the plasma membrane. However, variations of either of two amino acid residues, which are conserved in all P4-ATPases, significantly reduced the phosphatidylcholine flippase activity of ATP8B2. Furthermore, mutations in the corresponding residues of ATP8B1 and ATP11C were found to decrease their flippase activities toward phosphatidylcholine and phosphatidylserine, respectively. These results indicate that the conserved amino acid residues are crucial for the enzymatic activities of the P4-ATPases. [ABSTRACT FROM AUTHOR]

Abstract Neonicotinoids are insecticides widely used as seed treatments that appear to have multiple negative effects on birds at a diversity of biological scales. Adult birds exposed to a low dose of imidacloprid, one of the most commonly used neonicotinoids, presented reduced fat stores, delayed migration and potentially altered orientation. However, little is known on the effect of imidacloprid on birds growth rate despite studies that have documented disruptive effects of low imidacloprid doses on thyroid gland communication. We performed a $$2 \times 2$$ 2 × 2 factorial design experiment in Zebra finches, in which nestling birds were exposed to a very low dose (0.205 mg kg body $$\hbox {mass}^{-1}$$ mass - 1 ) of imidacloprid combined with food restriction during posthatch development. During the early developmental period, imidacloprid exposure resulted in an improvement of body condition index in treated nestlings relative to controls. Imidacloprid also led to compensatory growth in food restricted nestlings. This early life neonicotinoid exposure also carried over to adult age, with exposed birds showing higher lean mass and basal metabolic rate than controls at ages of 90–800 days. This study presents the first evidence that very low-dose neonicotinoid exposure during early life can permanently alter adult phenotype in birds.

Introduction Mental health care is considered to be one of the main sources of mental illness stigmatization. Detailed information about these stigmatization experiences is needed to reduce stigma in mental health practices. Objectives The study aimed i) to identify the most relevant stigmatizing situations in mental health care encountered by users and families, ii) to characterize the relative importance of these situations in terms of frequency, experienced stigmatization and suffering, and iii) to identify individual and contextual factors associated with these experiences. Methods In a focus group, users were asked to select the 15 most relevant stigmatization situations among those they elicited and those that were taken from the literature. An online survey was then conducted among users and family members to characterize these situations and identify predictors. Results A total of 235 participants were included: 59 participants with schizophrenia diagnosis, 96 with other psychiatric diagnoses and 80 family members. The results revealed 15 situations with different levels of frequency, stigmatization and suffering. Participants with a diagnosis of schizophrenia experienced more situations of stigmatization and with a higher frequency. Moreover, factors such as recovery-oriented practices and measures without consent were the best predictors of experienced stigmatization. Conclusions These original stigmatization situations could be targeted to reduce stigmatization and associated suffering in mental health practices. Results strongly suggest that recovery-oriented practice should be fostered to fight stigma in mental health care. Disclosure No significant relationships.

Introduction The consequences of schizophrenia stigma are numerous and highly damaging to individuals, their families, the health care system and society. Mental health professionals (MHP) are considered to be one of the main sources of schizophrenia stigmatization. Objectives The aim of the study was to identify individual and contextual factors associated with stigmatization in MHP in its three dimensions. Methods An online survey was conducted with specific measures of MHP stigmatization (stereotypes, prejudices and discrimination). Four categories of potential associated factors were also measured: sociodemographic information, contextual characteristics (e.g. work setting), individual characteristics (e.g. profession, recovery-oriented practices) and theoretical beliefs (e.g. biological beliefs, perceived similarities, continuum beliefs). Models of prediction were computed when applicable. Results Responses of 357 MHP were analysed. The main factors associated with stigmatization (stereotypes, prejudice) in MHP are of two types: i) individual beliefs (about mental illness: biological etiological beliefs, categorical beliefs; or about MHP themselves: professional utility beliefs, similarity beliefs) and ii) characteristics of practices (recovery oriented practice, work setting, profession). Conclusions These original results suggest new strategies for reducing stigma in mental health practices such as focusing on individual beliefs and fostering recovery-oriented practice and professional utility beliefs. Disclosure No significant relationships.

Introduction Mental health professionals are one of the major sources of stigma for persons with schizophrenia and their families. The stereotype of incompetence is central in this stigmatization, whereas valuing skills is a fundamental aspect of mental health care and recovery. Objectives The aim of this study is to identify the domains of competence stigmatized in schizophrenia by mental health professionals and the factors associated with this stigmatization. Methods An online survey was conducted with a specific measure of the stereotype of incompetence and these associated factors. Participants were to be mental health professionals who work or have worked with persons with schizophrenia. These participants were recruited through professional social networks. Results Responses of 164 participants were analyzed. The results reported four highly stigmatized skill domains: ability to relate well socially, ability to be effective in their work, ability to make decisions about their health, and ability to control their emotions. Intelligence was found to be less stigmatized than the other dimensions. Recovery beliefs, categorical beliefs, and perceived similarities were factors associated with the stereotype of incompetence. Conclusions Responses of 164 participants were analyzed. The results reported four highly stigmatized skill domains: ability to relate well socially, ability to be effective in their work, ability to make decisions about their health, and ability to control their emotions. Intelligence was found to be less stigmatized than the other dimensions. Recovery beliefs, categorical beliefs, and perceived similarities were factors associated with the stereotype of incompetence. Disclosure No significant relationships.

Introduction The consequences of schizophrenia stigma are numerous and highly damaging to individuals, their families, the health care system and society. Mental health professionals (MHP) are considered to be one of the main sources of stigmatization. Objectives To identify the characteristics of MHP stigma in schizophrenia in comparison with other psychiatric disorders, the specificities of MHP compared with other social groups, and associated factors. Methods Following PRISMA guidelines, we systematically searched multiple electronic databases for articles: (i) reporting original data published in English in peer-reviewed journals, (ii) reporting quantitative data with statistical analysis, (iii) assessing stigma in a broad sense, and (iv) including samples composed only of MHP. Results A total of 38 articles published from 1999 to 2019 and involving 10926 MHP fulfilled our inclusion criteria. Studies showed that schizophrenia is the most stigmatized mental illnesses in MHP, despite recent results suggesting that borderline personality disorder and substance abuse may be more stigmatized. In comparison with other social groups, MHP reported less dangerousness beliefs and more positive beliefs regarding pharmacological treatment. Nevertheless, results were less consistent regarding prognosis and desire for social distance. Age, education level, type of mental health profession, or length of practice were associated factors that showed inconsistent relations with stigma. Work setting and biological causal beliefs were more clearly associated with MHP stigma. Conclusions These findings provide strong support for the need to conduct specific research on schizophrenia stigma in MHP and the importance of controlling for several variables to identify predictors of stigma. Disclosure No significant relationships.

Recent identification of four additional polyaminopathies, including Bachmann–Bupp syndrome, have benefited from previous research on Snyder–Robinson syndrome in order to advance from research to treatment more quickly. As a result of the discovery of these conditions, the potential for treatment within this pathway, and for other possible unidentified polyaminopathies, the International Center for Polyamine Disorders (ICPD) was created to help promote understanding of these conditions, research opportunities, and appropriate care for families. This case study provides insights from two new patients diagnosed with Bachmann–Bupp syndrome, further expanding our understanding of this ultra-rare condition, as well as a general discussion about other known polyaminopathies. This work also presents considerations for collaborative research efforts across these conditions, along with others that are likely to be identified in time, and outlines the role that the ICPD hopes to fill as more patients with these polyaminopathies continue to be identified and diagnosed.

As a key domain of cognition, social cognition abilities are altered in a wide range of clinical groups. Accordingly, many clinical tests and theories of social cognition have been developed these last decades. Contrasting this abundant development from a research perspective, recent evidence suggests that social cognition remains rarely addressed from a clinial perspective. The aim of the present research was to characterize the current practices, representations, and needs linked to social cognition from the perspective of professional neuropsychologists and graduate students. A nationwide survey allowed us to determine the classical field conception of social cognition and its associated symptoms or notions. It also allowed us to quantify practice activities and the use of the different clinical tools available. This study revealed that neuropsychologists lack confidence regarding social cognition assessment and its rehabilitation, and that students are in demand for more knowledge and training. Suggestions of change in practices and dissemination of knowledge are discussed. Considering the importance of social cognition, an extension of initial and continuous training alongside an enrichment of interactions between researchers and clinicians were key recommendations to formulate, as well as the need for a consensual lexicon of current concepts. [ABSTRACT FROM AUTHOR]