Safety Assessment Research Articles

Toxicity assessment of wastewater using a battery of bioassays in two textile wastewater treatment plants from a large industrial park in Guangxi, Southwest China.

Textile effluents are important sources of pollutants in aquatic environments. The textile industry in China has been relocating from developed to less developed regions, yet the potential environmental impact of textile effluents remains unclear. Here, we investigated the acute toxicity of wastewater collected from different processing units of two textile wastewater treatment plants (WWTPs) in a large industrial park in Guangxi province (Southwest China), using whole effluent toxicity testing. Moreover, we explored the relationships between the toxicity of wastewater and its characteristics, including physicochemical parameters, heavy metals, fluorescence intensity, and non-persistent and persistent organic pollutants. Untreated textile effluents were highly toxic to all test organisms, with toxic units reaching 42.9 for lux-modified bacteria, 14.0 for green algae, 10.1 for duckweed, and 17.3 for zebrafish embryos. Their toxicity was reduced significantly but not removed completely, following treatment processes that included coagulation, anaerobic-aerobic process, Fenton oxidation process, chlorine disinfection and wetland treatment systems. In the wetland effluent, both toxicity and physicochemical parameters met the textile effluent discharge standards in China and other countries. The toxicity of wastewater was associated with various characteristics, such as chemical oxygen demand (COD), fluorescence intensity related to fulvic acid-like materials, 4-nonylphenol, bisphenol A, bis(2-ethylhexyl) phthalate, perfluorobutane sulfonic acid, and acenaphthene. These results suggest the effectiveness of the investigated WWTPs in treating textile effluents concerning both physicochemical parameters and acute toxicity. The present study highlights the importance of integrating ecotoxicological data alongside chemical data to enhance the risk assessment and evaluation of the environmental safety of effluent discharges.

Post-marketing surveillance of encorafenib in combination with binimetinib in Japanese patients with BRAF-mutant melanoma.

A BRAF inhibitor, encorafenib, combined with a MEK inhibitor, binimetinib, was approved in Japan in early 2019 for the treatment of BRAF V600-mutant, unresectable malignant melanoma based on results of the global phase III trial, COLUMBUS, conducted in various countries including Japan. This post-marketing surveillance (PMS) assessed the combination in real-world clinical practice in Japan. We performed a prospective, multicentre, 12-month PMS of the safety and effectiveness of encorafenib plus binimetinib for radically unresectable, BRAF-mutant malignant melanoma in Japan. Among 174 survey forms collected from 85 centres between February 2019 and August 2020, 172 were included for safety and effectiveness analysis. Patients (male [52.3%], median age 62.0years) had Eastern Cooperative Oncology Group Performance Status 0 or 1 (91.8%) and comorbidities (55.2%). Respective encorafenib and binimetinib median dosages were 450mg/day and 90mg/day; median treatment duration, 24.1 and 24.2weeks, and discontinuation, 71.5% for each, primarily for disease progression (56.9%) and adverse drug reactions (ADRs, 38.2%). Safety assessment ADRs occurred in 99 patients (57.6%), including eye disorders (40.7%), hepatic dysfunction (20.3%), rhabdomyolysis (4.7%), haemorrhage (2.3%), palmar-plantar erythrodysaesthesia syndrome (1.7%), and hypertension (1.7%); 19.8% were grade ≥ 3, none were grade 5, most resolved with/without treatment modification. At 12months, the objective response rate was 48.8% (95% CI 41.2, 56.6; complete [19.2%], partial [29.7%]), overall survival was 40.1%. The safety and effectiveness of encorafenib plus binimetinib in Japanese patients with BRAF-mutant malignant melanoma were similar to data reported in COLUMBUS; no new safety concerns were identified.

A Survey Assessment of Psychological Safety in Colon and Rectal Surgery Residents and Comparison to General Surgery Residents.

Psychological safety (PS) is the shared belief that the team is safe for interpersonal risk-taking. Although some research has been conducted regarding PS in healthcare settings, there is minimal research in surgical training programs. Our objective was to study PS levels in colorectal surgery (CRS) residents. Our survey was adapted from Amy Edmonson's psychological safety scale and the Maslach Burnout Inventory for the surgical work environment. Questions regarding interactions with attending surgeons (AS) and program directors (PD) and regarding burnout were asked. Each question was scored on a 1-9 Likert Scale. Total PS scores for questions targeting AS or PD ranged from 3 (low) to 126 (high) and the overall PS score ranged from 6 (low) to 252 (high). Burnout scores ranged from 0 (low) to 32 (high). Descriptive statistics including medians and interquartile ranges (IQR) are used to present the data. The survey was distributed to CRS residents in-person at the 2023 Colorectal Career Course in November, 2023. Of the 87 CRS residents in attendance, 50 completed the survey (57%). CRS residents had overall high psychological safety overall (median score 228, IQR 198-247) with 92% of CRS residents having PS scores in the top third of the range. CRS residents had low burnout scores (median score 6, IQR 3-11) with 80% having burnout scores in the lowest third of the range. CRS residents generally have high PS levels and low burnout levels. This high level of PS could stem from the consistency of working with the same attendings, the shared interest in 1 subspecialty, and/or more frequent high-quality feedback. Further research to determine the mediators of high PS in surgical residency and CRS can be used to foster PS in other healthcare fields.

Predictive classification-based read-across for diverse functional vitiligo-linked chemical exposomes (ViCE): A new approach for the assessment of chemical safety for the vitiligo disease in humans.

We have explored a new approach using a similarity measure-based read-across derived hypothesis to address the precise risk assessment of vitiligo active chemicals. In this analysis, we initially developed a data set by combining vitiligo active compounds taken from the previous literature with non-vitiligo chemicals, which are non-skin sensitizers reported in another literature. Afterward, we performed the manual curation process to obtain a curated dataset. Furthermore, the optimum similarity measure was identified from a validation set using a pool of 47 descriptors from the analysis of the most discriminating features. The identified optimum similarity measure (i.e., Euclidean distance-based similarity along with seven close source compounds) has been utilized in the read-across derived similarity-based classification studies on close source congeners concerning target compounds. In this study, we identified the positive and negative contributing features toward the assessment of vitiligo potential as well, including the estimation of target chemicals with better accuracy. The applicability domain status of the reported compounds was also studied, and the outliers were identified. As there are no comparative studies in this regard to the best of our knowledge, we can further affirm that it is the first report on the in-silico identification of potential vitiligo-linked chemical exposomes (ViCE) based on the similarity measure of the read-across.

Safety assessment of selinexor: a real-world pharmacovigilance study

ABSTRACT Background Selinexor is approved for the treatment of relapsed or refractory multiple myeloma. However, a comprehensive understanding of adverse events associated with selinexor is lacking. Methods Clinical trials of selinexor in patients with multiple myeloma were reviewed. We investigated selinexor-related adverse events through data of the US Food and Drug Administration Adverse Event Reporting System (FAERS). The disproportionality analysis was conducted. Four algorithms were employed to evaluate the signals of adverse events. The adverse effects of selinexor combined with dexamethasone were compared with bortezomib and dexamethasone. Sensitivity analysis was performed to exclude consumer-reported adverse events. The onset of adverse reactions were calculated. Results A total of 1,698 reports related with selinexor from FAERS were identified. 6 significant system organ class and 42 significant preferred terms (PTs) were found. Unexpected significant adverse events including mania, acute kidney injury, orthostatic hypotension, and embolisms were identified. 14 PTs reported significant signals in treatment of selinexor combined dexamethasone compared with traditional treatment of bortezomib and dexamethasone. 45.2% of adverse events occurred within the first month of starting selinexor. Conclusions Comprehensive analyses of selinexor related adverse events are helpful for clinical detection of adverse events and timely intervention, advancing selinexor’s therapeutic progress in future treatment.

Safety assessment of rosuvastatin-fenofibrate combination in the treatment of hyperlipidemia based on FDA’s adverse event reporting system database

BackgroundWith the improvement of living standards, an increasing number of patients are presenting with mixed hyperlipidemia. In addition to cholesterol reduction, it is imperative to lower triglyceride levels. The combination of statin and fibrate for reducing lipid levels has commonly been applied in clinical therapy. However, the combination of drugs also increases the risk of adverse events (AEs). In this study, we analyzed the safety signals of rosuvastatin-fenofibrate combination by assessing the publicly available US Food and Drug Administration Adverse Event Reporting System (FAERS), so as to provide a reference for rational clinical use of rosuvastatin and fenofibrate, and reduce the occurrence of related AEs.MethodsReports to the FAERS from 1 January 2004 to 19 March 2020 were analyzed. The proportional report ratio (PRR), reporting odds ratio (ROR), and Bayesian Confidence Propagation Neural Network (BCPNN) analysis were used to extract data from FAERS for suspected signals referring to the combination of rosuvastatin and fenofibrate.ResultsA total of 68 safety signals were detected from the top 250 AEs in 3,587 reports, of which 28 signals were not included in the drug labels. All the detected AEs were associated with 12 System Organ Classes (SOC), such as gastrointestinal, musculoskeletal and connective tissue, general diseases, investigations and nervous system. The most frequent AEs were analyzed, and it was found that women generally have a higher susceptibility to experiencing AEs, including pain, nausea, fatigue, myalgia, diarrhea, dyspnea, headache, weakness, and dizziness.ConclusionClinicians should pay more attention to the AEs of gastrointestinal and muscular system during combination therapy, and it is recommended to strengthen pharmaceutical care during clinical application.

Assessing Hybridization-Dependent Off-Target Risk for Therapeutic Oligonucleotides: Updated Industry Recommendations.

Hybridization-dependent off-target (OffT) effects, occurring when oligonucleotides bind via Watson-Crick-Franklin hybridization to unintended RNA transcripts, remain a critical safety concern for oligonucleotide therapeutics (ONTs). Despite the importance of OffT assessment of clinical trial ONT candidates, formal guidelines are lacking, with only brief mentions in Japanese regulatory documents (2020) and US Food and Drug Administration (FDA) recommendations for hepatitis B virus treatments (2022). This article presents updated industry recommendations for assessing OffTs of ONTs, building upon the 2012 Oligonucleotide Safety Working Group (OSWG) recommendations and accounting for recent technological advancements. A new OSWG subcommittee, comprising industry experts in RNase H-dependent and steric blocking antisense oligonucleotides and small interfering RNAs, has developed a comprehensive framework for OffT assessment. The proposed workflow encompasses five key steps: (1) OffT identification through in silico complementarity prediction and transcriptomics analysis, (2) focus on cell types with relevant ONT activity, (3) in vitro verification and margin assessment, (4) risk assessment based on the OffT biological role, and (5) management of unavoidable OffTs. The authors provide detailed considerations for various ONT classes, emphasizing the importance of ONT-specific factors such as chemistry, delivery systems, and tissue distribution in OffT evaluation. The article also explores the potential of machine learning models to enhance OffT prediction and discusses strategies for experimental verification and risk assessment. These updated recommendations aim to improve the safety profile of ONTs entering clinical trials and to manage unavoidable OffTs. The authors hope that these recommendations will serve as a valuable resource for ONT development and for the forthcoming finalization of the FDA draft guidance and the International Council for Harmonization S13 guidance on Nonclinical Safety Assessment of Oligonucleotide-Based Therapeutics.

Insights for a Next Pandemic: An Assessment of Laboratory COVID-19 Safety

In January 2020, the WHO declared COVID-19 a global pandemic, underscoring the importance of safeguarding measures and mental health support for medical professionals due to its serious impact and widespread reach. This study aimed to assess knowledge gaps in safety guidelines and the use of personal protective equipment (PPE) among staff in medical laboratories, specifically all accredited laboratories actively engaged in COVID-19 testing in Jordan. Data were collected via a blinded, non-stratified electronic questionnaire, with one response submitted from each laboratory through a Google Form. The survey targeted laboratory personnel affiliated with the 40 accredited laboratories handling COVID-19 testing. A validated questionnaire consisting of 25 questions was used to evaluate the knowledge of these laboratories. The findings indicate that workers in certain laboratories exhibited deficiencies in their understanding of safety regulations, quality control, and the proper use of PPE when handling COVID-19 samples. Additionally, the study highlights the increasing impact of the COVID-19 pandemic on individuals’ mental health. The demanding laboratory work necessitated by the pandemic can have negative psychological effects on staff. These effects underscore the importance of implementing supportive mental health policies and resources to mitigate psychological impact and enhance the overall well-being of laboratory personnel. Addressing these knowledge gaps, improving safety protocols, and providing adequate mental health support are crucial steps in ensuring the safety and well-being of laboratory staff and enhancing the overall management of future pandemics.

Radiological safety assessment of monazite industry worker due to NORM inhalation.

Monazite is used as a raw material for the production of rare earth elements. The workers in the monazite industry are exposed to radiation from the raw material. Therefore, internal radiation dose should be assessed for radiological safety assessment of the workers. The objective of this study is to assess the internal radiation dose to workers of the monazite industry in Korea by means of measured particulate. Particulate properties, including size distribution, density, shape, and radioactivity concentration were analyzed. Then, the internal radiation dose coefficients were derived using the IMBA software. Work scenarios were derived by identifying the work time. Finally, internal radiation doses were calculated with the collected and calculated data. The internal radiation dose ranged from 7.48×10-3 to 3.25×10-1mSv y-1 with dose difference by orders of magnitude. It is highlighted why such data should be directly collected at sites to realistically assess radiation dose to workers.

Towards safer mines: Analyzing occupational health and safety perceptions and injury patterns in Serbian underground mining

Background Mining is a high-risk sector, particularly in underground environments, where workers face daily hazards. This research evaluates workplace safety perceptions in Serbian underground coal mines, ranking workers by education, age, and job role, while incorporating injury data to provide a comprehensive assessment of safety across different worker groups. Objective This study is aimed at analyses of the correlation between occupational health and safety (OHS) perceptions and the injury index across different worker groups, to identify improvement opportunities and propose targeted measures for enhancing OHS practices. Methods The PROMETHEE II method categorized workers based on production units, qualifications, and age, focusing on criteria like protective equipment, work conditions, risk awareness, management, work organization, and training. The entropy method provided objective weightings for these criteria, allowing for comparison with injury index rankings to establish priorities for improvement. Results Štavalj and Vrška Čuka ranked highest in OHS perception. Workers with MSc/Dr qualifications displayed heightened awareness of safety, while those aged 56 to 65 exhibited the best understanding of health and safety. Spearman rank correlation coefficients revealed a strong negative correlation (−0.796) for production units, a strong positive correlation (0.70) for qualifications, and a very strong positive correlation (0.90) for age concerning PROMETHEE II rankings and injury index indicators. Conclusions The disparities between worker perception rankings and injury index rankings suggest opportunities for targeted safety improvements and enhanced training protocols.

Efficacy and safety assessment of propranolol tablets vs. oral solution for infantile hemangioma: a retrospective study in China

BackgroundPropranolol for infantile hemangiomas (IHs) is effective and relatively safe. However, propranolol has different formulations and there is no consensus on the optimal formulation for IHs. The propranolol oral solution was not used in China until 2022.ObjectiveTo evaluate the efficacy and safety of propranolol tablets and an oral solution in infants with high-risk IH.MethodsA retrospective cohort study was conducted involving 234 consecutive patients with a clinical diagnosis of high-risk IH who were treated with propranolol between August 2018 and February 2023 (propranolol tablets, 168 patients; propranolol oral solution, 66 patients). All patients were assessed in the hospital at the initiation of treatment and in the outpatient setting during treatment. The Hemangioma Activity and Severity Index was used to monitor the clinical activity of the hemangioma after propranolol treatment.ResultsBased on the Hemangioma Activity and Severity Index, 66.52% and 69.15% improvement occurred in the propranolol tablet and oral solution groups, respectively. 23.21% of patients in the propranolol tablet group and 42.42% in the oral solution group achieved >75% score improvement (X2 = 8.557; P = 0.003). Adverse reactions occurred in 34 (20.24%) and 11 patients (16.67%) in the propranolol tablet and oral solution groups, respectively. The most common adverse reaction in the propranolol tablet group was liver function abnormalities due to mild elevation of liver enzymes (X2 = 4.09; P = 0.045).ConclusionBoth propranolol tablets and oral solution had positive efficacy in patients with high-risk IHs, but more patients in the propranolol oral solution group achieve >75% score improvement compared to the propranolol tablet group. No life-threatening adverse reactions occurred in either group but liver function abnormalities were more likely to occur in patients treated with propranolol tablets.

European Society of Toxicologic Pathology-Pathology 2.0 Mass Spectrometry Imaging Special Interest Group: Mass Spectrometry Imaging in Diagnostic and Toxicologic Pathology for Label-Free Detection of Molecules-From Basics to Practical Applications.

Mass Spectrometry Imaging (MSI) is a powerful tool to understand molecular pathophysiology and therapeutic and toxicity mechanisms, as well as for patient stratification and precision medicine. MSI, a label-free technique offering detailed spatial information on a large number of molecules in different tissues, encompasses various techniques including Matrix-Assisted Laser Desorption Ionization (MALDI), Desorption Electrospray Ionization (DESI), and Secondary Ion Mass Spectrometry (SIMS) that can be applied in diagnostic and toxicologic pathology. Given the utmost importance of high-quality samples, pathologists play a pivotal role in providing comprehensive pathobiology and histopathology knowledge, as well as information on tissue sampling, orientation, morphology, endogenous biomarkers, and pathogenesis, which are crucial for the correct interpretation of targeted experiments. This article introduces MSI and its fundamentals, and reports on case examples, determining the best suited technology to address research questions. High-level principles and characteristics of the most used modalities for spatial metabolomics, lipidomics and proteomics, sensitivity and specific requirements for sample procurement and preparation are discussed. MSI applications for projects focused on drug metabolism, nonclinical safety assessment, and pharmacokinetics/pharmacodynamics and various diagnostic pathology cases from nonclinical and clinical settings are showcased.

Discovery of a Novel Multitarget Analgesic Through an In Vivo-Guided Approach

Background: Pain is a complex condition influenced by peripheral, central, immune, and psychological factors. Multitarget approaches offer a more effective and safer alternative to single-target analgesics by enhancing efficacy, reducing side effects, and minimizing tolerance. This study aimed to identify a novel multitarget analgesic with improved pharmacological properties. Methods: An in vivo-guided screening approach was used to discover a new analgesic compound. Compound 29, derived from a novel scaffold inspired by opiranserin and vilazodone pharmacophores, was identified through analog screening in the formalin test. Its efficacy was further evaluated in the spinal nerve ligation (SNL) model of neuropathic pain. Mechanistic studies explored its interaction with neurotransmitter transporters and receptors, while pharmacokinetic and safety assessments were conducted to determine its stability, brain penetration, and potential toxicity. Results: Compound 29 demonstrated high potency in the formalin test, with an ED50 of 0.78 mg/kg in the second phase and a concentration-dependent effect in the first phase. In the SNL model, it produced dose-dependent analgesic effects, increasing withdrawal thresholds by 24% and 45% maximum possible effect (MPE) at 50 and 100 mg/kg, respectively. Mechanistic studies revealed strong triple uptake inhibition, particularly at dopamine (DAT) and serotonin (SERT) transporters, alongside high-affinity 5-HT2A receptor antagonism. Pharmacokinetic analysis indicated enhanced stability and blood–brain barrier permeability. In vitro studies confirmed its nontoxicity to HT-22 cells but revealed potential hERG inhibition and strong CYP3A4 inhibition. Conclusions: Compound 29 is a promising multitarget analgesic with potent efficacy and favorable pharmacokinetics. Ongoing optimization efforts aim to mitigate side effects and enhance its therapeutic profile for clinical application.

Unlocking the potential of l-α-glycerylphosphorylcholine in the food industry: From safety approvals to market prospects.

With the exacerbation of global population aging, age-related neurodegenerative disorders have been posing an increasing public health concern. l-α-Glycerylphosphorylcholine (l-α-GPC) has demonstrated significant therapeutic potential for mental health-related disorders and possesses promising market prospects. Recently, l-α-GPC has been successively approved as a new food resource in Canada (2023) and in China (2024). These policies pointed out the recognized safety and utility of l-α-GPC. The utilization of l-α-GPC in dietary supplements and health foods could be a convenient option for early intervention strategies to potentially delay or mitigate the progression of neurodegenerative disorders. Additionally, other unique nutritional benefits of l-α-GPC have been highlighted, further expanding its application in food industry. Encouraged by the policy incentives, there is likely to be a new upsurge in the research interest surrounding l-α-GPC. To fully capitalize on these emerging opportunities, we present a comprehensive review of l-α-GPC. The chemical properties, pharmacological characteristics, safety assessments, and preparation methods of l-α-GPC were summarized. A brief outlook on the future perspectives and unsolved challenges was also proposed.

Model-informed repurposing of eliglustat for treatment and prophylaxis of Shiga toxin-producing Escherichia coli hemolytic-uremic syndrome (STEC-HUS) in children.

Shiga toxin-producing Escherichia coli hemolytic-uremic syndrome (STEC-HUS) is a severe illness predominantly affecting young children, with limited treatment options beyond supportive care. Eliglustat, approved for Gaucher disease, shows potential in reducing Shiga toxin binding to target glomerular endothelial cells in vitro, prompting interest as a treatment for STEC-HUS. However, it remains unknown what dose is likely to be effective and safe for treatment of STEC-HUS in the pediatric population. We hypothesize that effective and safe levels of eliglustat can be reached in children. We identified pharmacokinetic targets of efficacy for treatment and prophylaxis of STEC-HUS based on a preclinical model and human cardiac safety data. Then, we developed oral and intravenous dosing regimens using population pharmacokinetic (popPK) simulations based on an existing model enriched to allow extrapolation to a simulated virtual pediatric population. These dosing regimens were then confirmed using a verified physiologically based pharmacokinetic (PBPK) model. We simulated, using popPK data, oral and intravenous dosing regimens resulting in adequate target exposure in > 90% of all patients, with minimal expected risk for cardiotoxicity. Confirmation of these dosing regimens with PBPK modeling resulted in very similar exposure, with lower interindividual variability and minimal toxicity potential. Based on pharmacokinetic modeling, we developed oral and intravenous eliglustat dosing regimens that are likely safe and effective for treatment of STEC-HUS and prophylaxis in case of outbreaks of STEC infections. Clinical evaluation of these dosing regimens in children suspected of or diagnosed with STEC-HUS is required and should include assessment of pharmacokinetics, efficacy, and safety (e.g., ECG monitoring).

QbD-Enabled Development of Quercetin Dihydrate-Loaded Nanostructured Lipid Carriers: In vitro Characterization, Safety and Efficacy Assessment in Androgenetic Alopecia Mice Model

QbD-Enabled Development of Quercetin Dihydrate-Loaded Nanostructured Lipid Carriers: In vitro Characterization, Safety and Efficacy Assessment in Androgenetic Alopecia Mice Model

Probiotic Characteristics and Whole Genome Analysis of Lactiplantibacillus plantarum PM8 from Giant Panda (Ailuropoda melanoleuca) Milk.

Milk is a rich source of probiotics, particularly lactic acid bacteria (LAB), which have been shown to promote gut health, support the immune system, enhance digestion, and prevent pathogen colonization. This study aimed to isolate and identify LAB strains from giant panda (Ailuropoda melanoleuca) milk, evaluate their probiotic properties, and analyze the genomic characteristics of a promising strain. Thirteen LAB strains were isolated from 12 samples of giant panda milk. Among all LAB strains, Lactiplantibacillus plantarum PM8 (PM8) demonstrated probiotic properties and safety features. It exhibited strong growth performance, high antipathogenic activity against four pathogens, and strong survival rates under simulated gastrointestinal conditions. PM8 also showed excellent adhesion capabilities to Caco-2 cells. Additionally, safety assessment revealed no hemolysin production and minimal antibiotic resistance, making it a promising candidate for probiotic applications. The genome of PM8 consists of 3,227,035 bp with a GC content of 44.60% and contains 3171 coding sequences, including 113 carbohydrate-active enzyme genes and genes related to exopolysaccharides synthesis, vitamin B biosynthesis, adhesion, antioxidant activity, and bile salt hydrolysis. Notably, it contains genes involved in nonribosomally synthesized secondary metabolite and bacteriocin production. The genomic safety analysis confirmed that PM8 lacks the capacity to transmit bacterial antimicrobial resistance and is non-pathogenic to both humans and animals. These findings suggest that PM8 holds considerable potential for enhancing gut health and supporting the development of safe probiotic products.

Methods for Analyzing Avionics Reliability Reflecting Atmospheric Radiation in the Preliminary Development Phase: An Integrated Failure Rate Analysis

Abstract: Advances in deep submicron semiconductor technology have increased the significance of studying soft errors caused by atmospheric radiation in avionics systems. Atmospheric radiation particles, such as protons and neutrons, can induce Single Event Upsets (SEUs) in sensitive electronic components, leading to system malfunctions and data corruption. Traditional reliability analysis based on older IC or LSI components may fail to account for radiation-induced effects. However, modern avionics systems equipped with state-of-the-art VLSI components are increasingly susceptible to Single Event Upsets (SEUs), potentially leading to underestimated failure rates in these advanced systems. This study introduces an integrated failure rate analysis that incorporates both the physics of failure rates resulting from aging and wear-out and soft error rates induced by atmospheric radiation. The proposed failure rate analysis of the reliability of avionics operating at altitudes of up to 18 km by combining the physics of failure rates with radiation-induced failure rates was derived using a semi-empirical SEU estimation method. Case studies using the Zynq 7000 board, sourced from AMD (San Jose, USA), confirmed that the integrated failure rate analysis provides more accurate reliability predictions compared to conventional analysis. This approach is expected to improve the accuracy of safety assessments during the preliminary development stages, leading to a shortened development timeline and enhanced design quality.

Assessment of Long-Term Safety and Efficacy of Purple Sweet Potato Color (PSPC) and Myo-Inositol (MI) Treatment for Motor Related and Behavioral Phenotypes in a Mouse Model of Classic Galactosemia.

Classic galactosemia (CG) is a rare inherited metabolic disease caused by mutations in the GALT gene encoding the enzyme galactose-1 phosphate uridylyltransferase in galactose metabolism. The condition develops as a potentially fatal illness during the newborn period, but its acute clinical manifestations can be alleviated through a galactose restricted diet. Nonetheless, such dietary intervention is inadequate in preventing significant long-term consequences, including neurological impairments, growth restriction, cognitive delays, and, for most females, primary ovarian insufficiency. At present, no effective therapy exists to stop the progression of these complications, highlighting the urgent need for new treatment approaches to be developed. Supplements have been used in the treatment of other inborn errors of metabolism; however, they are not typically included in the clinical therapeutic regimen for CG. Recently, our research team has demonstrated that two generally recognized as safe supplements (purple weet potato color, PSPC and myo-inositol, MI) have been effective in partially restoring functions in the ovaries of our GalT-KO mouse model. However, the toxicological profile of both PSPC and MI has not been determined. In this study, we investigated the acute (30 days) and chronic (180 days) oral toxicities of PSPC and MI both in WT control and GalT-KO mice. Furthermore, our study aims to evaluate the effectiveness of oral feeding of PSPC and MI in correcting motor-related and behavioral phenotypes in GalT-KO mice. The long-term treatment of MI at a lower dose demonstrated promising improvements in motor deficit and anxiety driven hyperactivity in the mutant mice.

Spatially Referenced Global River Flow Data for Aquatic Safety Assessment Exposure Models Developed from Publicly Available Global Data Sets

Spatially Referenced Global River Flow Data for Aquatic Safety Assessment Exposure Models Developed from Publicly Available Global Data Sets