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Diagnosis of glutaric aciduria type I based on neuroradiological findings: when neonatal screening fails
Get PDFBackground: Glutaric aciduria type I (GA-I) is an autosomal recessive disorder affecting the metabolism of lysine, hydroxylysine, and tryptophan. Patients present in the first age of life with an irreversible motor disorder, and neuroradiological imaging can suggest the presence of the condition. Biochemically, the disorder is characterized by elevated levels of glutaric and 3-hydroxy glutaric acid in the urine and glutarylcarnitine in the blood. This latter metabolite can be detected in dried blood spots, and the condition can therefore be included in some newborn screening programs. Case presentation: We present the case of a patient affected by GA-I that was undetected by newborn screening in whom the diagnosis was clinically oriented at the age of nine months by acute neurological symptoms, represented by persistent tonic seizures, and by neuroimaging showing bilateral signal alterations in the basal ganglia. Biochemical data, including glutarylcarnitine in dried blood spots and urinary excretion of glutaric acid, were normal in the acute phase and during follow-up. Molecular analysis confirmed a diagnosis of GA-I, showing a homozygous M405V variant of the GCDH gene, which is common in African populations and associated with a low-excretor phenotype characteristic of the disorder. Conclusions: In conclusion, although GA-I is included in neonatal screening programs, the biochemical markers in dried blood spots can be absent. Therefore, in patients of African origin, clinicians should maintain a high degree of vigilance in the presence of suggestive clinical and neuroradiological findings, even if biochemical parameters are normal
Loss of MTAP expression is not an accurate surrogate for CDKN2A homozygous deletions in peritoneal mesothelioma
No full textAims: Mesothelioma is a malignant neoplasm of the serosal membranes originating from mesothelial cells. Peritoneal mesothelioma is the second most common mesothelial neoplasm after pleural mesothelioma, accounting for approximately 6%–15% of cases. Due to its high morphological variability, often mimicking other lesions, mesothelioma remains a diagnostic challenge. CDKN2A homozygous deletion has been established as a highly accurate biomarker for differentiating mesothelioma from benign mesothelial proliferations. MTAP immunohistochemistry (IHC) has been proposed as a cheaper and more reproducible surrogate for CDKN2A homozygous deletion (HD) detected by FISH in pleural mesothelioma. The aim of our study was to evaluate the reliability of MTAP IHC as a surrogate marker for CDKN2A HD in peritoneal mesothelioma. Methods and results: Thirty-nine FFPE tissue samples of PeM were analysed for CDKN2A copy number status by FISH. MTAP IHC was performed using antibody clone 2G4, and cytoplasmic positivity was evaluated using two different cut-offs (1% and 30%). Agreement between IHC and FISH was assessed using Cohen's Kappa. A ROC curve analysis was performed to evaluate the overall diagnostic performance of MTAP IHC. McNemar's test was used to identify statistically significant discordance between the techniques, and a power analysis was conducted to confirm the adequacy of the sample size. Additionally, 14 benign peritoneal lesions were included as external controls and underwent both FISH and IHC. All control samples showed preserved MTAP expression and no CDKN2A deletion. CDKN2A HD was detected in 27/39 cases. MTAP loss was observed in 13 cases, while the remaining 26 cases showed variable levels of MTAP positivity (15%–100%; mean: 36.4%; median: 25%). Cohen's Kappa revealed a low, non-significant concordance between MTAP IHC and CDKN2A HD (cut-off 1%: Kappa = 0.091, P = 0.462; cut-off 30%: Kappa = 0.083, P = 0.326). ROC curve analysis (AUC = 0.569) confirmed the poor discriminatory performance of MTAP IHC. McNemar's test showed a statistically significant discordance between MTAP IHC and CDKN2A FISH results. Power analysis confirmed that the sample size (n = 39) was adequate. Conclusions: These findings may reflect biological and pathogenetic differences between pleural and peritoneal mesotheliomas. Larger, multicentric studies are needed to validate the diagnostic role of MTAP IHC in peritoneal mesothelioma
MULTIMODAL MEDIATION IN EAL TEACHER EDUCATION: Scaffolding meaning-making and interaction through picture books
No full textThis article explores the multimodal mediation strategies employed by student teachers during
picturebook read-aloud performances in English as an Additional Language (EAL). The data for the present study was gathered during a postgraduate course at the University of Udine (Italy). Using Multimodal Interaction Analysis as an analytical framework, the study focuses on two self-video recordings of student teachers' read-aloud performances and employs an innovative approach to data visualization and analysis through TMA software to generate graphs for the visual representations of modal configurations. The article discusses the co-deployment of various semiotic resources, including spoken language, gestures, facial expressions, gaze direction, orchestrated by student teachers to scaffold meaning-making and engage an imagined audience of children. The findings reveal the central role of spoken language and prosodic features in student teachers’ mediation strategies, these are complemented by the strategic use of visual modes in
specific sequences. The results emphasize the need for developing student teachers' multimodal awareness and reflective practices for picturebook mediation. The study highlights also the value of Multimodal Interaction Analysis as a tool for understanding and assessing multimodal practices and offering teacher educators insights into designing activities that promote effective multimodal mediation strategies
Modeling Cracks in Silicon-Heterojunction Photovoltaic Modules: A Real-World Case Study
No full textThis work investigates the impact of cracks on silicon heterojunction photovoltaic (PV) modules by analyzing their electrical and thermal behavior under low and high current conditions. The analysis was conducted on PV modules affected by a severe hailstorm, which produced hailstones up to 16 cm in diameter, far exceeding the standard test sizes (IEC 61215). A combination of electroluminescence (EL) and infrared (IR) thermography, along with dark and light current-voltage characterization, was employed to examine both hail and operator-induced cracks. The findings revealed that these cracks, which are latent damages not visible to the naked eye but only with EL and IR investigations, lead to localized temperature increase near open circuit voltage, and to a more uniform distributed temperature increase near short circuit conditions. A Simulink/Matlab model was developed to reproduce the thermal behavior of cracked cells in series with intact ones, to reproduce what happens in a real-world scenario. The results emphasize the importance of identifying latent defects in PV modules to ensure long-term reliability, safety, and efficiency, offering insights into their electrical and thermal behavior in low and high current regime
Aquatic Toxicity of Antibiotics Ciprofloxacin and Sulfamethoxazole: Significant Impact on Early Life Stages of Crustaceans, a Marine Diatom, and a Freshwater Plant
Get PDFThe occurrence of antibiotic residues in the environment is of concern not only because of their contribution to the spread of bacterial resistance, but also due to their possible toxicity to non-target organisms. In this study, the aquatic environmental toxicity of ciprofloxacin (CIP) and sulfamethoxazole (SMX) was assessed in the following model organisms: Daphnia magna and Artemia salina (embryonic and immobilisation test with a 10-d follow-up), Phaeodactylum tricornutum (algal growth inhibition test), and Spirodela polyrhiza (duckweed growth inhibition test). Results showed that among the two saltwater organisms, A. salina was insensitive to both antibiotics, whilst P. tricornutum responded only to SMX with an EC50 of 2.7 mg L−1. In freshwater species, D. magna embryos were more sensitive than juveniles to SMX (EC50 53.8 and 439.2 mg L−1, respectively), whereas the opposite trend was observed for CIP (EC50 95.9 and 15 mg L−1, respectively). S. polyrhiza confirmed the remarkable sensitivity of aquatic plants to fluoroquinolones, with EC50 values between 0.28 and 0.34 mg L−1 depending on the endpoint considered. Notably, this species was also more sensitive to SMX than expected, with EC50 values between 1.5 and 2.5 mg L−1, which are an order of magnitude lower than those typically obtained with Lemna spp. exposed to sulphonamides. Considering the high environmental input of these antibiotics from both human and veterinary treatments, adverse effects on aquatic plants cannot be excluded, potentially leading to ecosystem-level consequences
ADAPTING TO CHANGE: DEVELOPMENTAL, CLINICAL AND ECOLOGICAL PERSPECTIVES ON COGNITIVE CONTROL DYNAMICS
Get PDFThis doctoral thesis explores cognitive control (CC) as a domain-general, dimensional, and contextually driven construct, shedding light on its dynamic and adaptive nature. While traditionally viewed as a static ability, CC is reinterpreted here in terms of its dimensionalities, particularly its distinction between "hot" (emotionally charged) and "cold" (emotionally neutral) processes (Zelazo & Carlson, 2012), as well as its adaptive mechanisms within different environmental contexts. The Dual Mechanism of Control (DMC) model (Braver, 2012) is leveraged to conceptualize CC as operating through proactive and reactive modes, depending on task demands. This thesis further emphasizes the dynamic adaptability of CC, exploring its modulation through environmental regularities and learning mechanisms (learning-based CC; Abrahamse et al., 2016; Braem & Egner, 2018). Specifically, proportion congruency (PC) manipulations are employed to investigate how CC evolves in response to varying task difficulty and predictability.
The first major aim of this thesis was to trace the developmental trajectories of learning-based CC in typically developing children, examining how their cognitive strategies adapt to task regularities over time. This focus provides a foundation for understanding deviations in populations with atypical development, such as children with attention deficit/hyperactivity disorder (ADHD). In comparing these groups, the study highlights how learning-based CC may serve as a endophenotypic marker of atypical development, with implications for early diagnosis and intervention strategies.
In addition to developmental trajectories, this research investigates the impact of environmental factors on learning-based CC. The potential influence of digital content, which has been linked to short-term cognitive impairments (Kostyrka-Allchorne et al., 2017), is a key focus, as is the role of cognitively engaging content in mitigating these effects (Hirsh-Pasek et al., 2015). Additionally, this thesis examines the potential benefits of school-based yoga and mindfulness training. These practices, shown to enhance emotional regulation and cognitive function, are explored for their potential impact on learning-based CC.
Overall, this thesis contributes to the sparse literature on learning-based CC in children, providing a comprehensive exploration of how it adapts to various challenges and contexts. By investigating both typical and atypical developmental trajectories and considering the influence of modern environmental factors, this work offers new insights into the dynamic nature of CC and its implications for both education and intervention.
The main take-home message is that the development of CC is not only about the refinement of individual cognitive processes but also about the integration and coordination of these processes in complex, real-world situations. Embracing the complexity of reality, instead of minimizing it, can lead to more accurate insights into how CC operates in everyday life and how it varies across different developmental trajectories and neurodevelopmental disorders
Coordinated implementation of a conventional PCR assay to detect all Ebola and Marburg virus species in a European laboratory network
Get PDFBackground: Filoviruses, including Ebola and Marburg viruses, cause severe hemorrhagic fever in humans and primates. These viruses pose significant threats to public health, making rapid and sensitive detection critical for controlling outbreaks. We developed and validated a hemi-nested generic PanFilo assay to detect all Ebola virus species, Marburg viruses, and recently discovered bat filoviruses. This assay was deployed to 15 European laboratories and evaluated through testing of eight non-infectious samples. Objectives: Laboratories were asked to determine the detection limit of positive controls and test all samples using the assay provided. The deployed assay enables direct Nanopore sequencing of PCR products, by using tagged primers during the second round of PCR. Sequencing of the samples was carried out on a voluntary basis. Results: Multicenter validation revealed a 95 % limit of detection of 5309 RNA copies/μL for Ebola, 10,273 copies/μL for Marburg, and 2145 copies/μL for Mengla virus. In an implementation quality assessment, 93.3 % (84/90) of samples containing filovirus RNA were correctly identified and 100 % (30/30) of filovirus-negative samples were correctly identified. Thirteen laboratories sequenced PCR products, with nine identifying all positive samples correctly. Conclusion: The assay enables rapid and reliable detection of filoviruses, with sequencing capabilities for identifying both known and novel variants. This assay might be used for detection during the initial phase of an emerging filovirus outbreak, before a specific assay has been developed. However, our distribution across 15 laboratories revealed variability challenges due to reagents, human performance, and sequencing capacity, emphasizing the need for more training and standardization
