A novel modelling paradigm for online diagnostics and prognostics for autonomous systems is presented. A model for the autonomous system being diagnosed is designed using a logic-based formalism. The ...model supports the run-time ability to verify that the autonomous system is safe and reliable for operation within a dynamic environment. The paradigm is based on the philosophy that there are different types of semantic relationships between the states of different parts of the system. A finite state automaton is devised for each sensed component and some of the non-sensed components. To capture the interdependencies of components within such a complex robotic platform, automatons were related to each other by semantic relationships. Modality was utilised by the formalism to abstract the relationships and to add measures for the possibility and uncertainty of the relationships. The complexity of the model was analysed to evaluate its scalability and applicability to other systems. The results demonstrate that the complexity is not linear and a computational time of 10 ms was required to achieve run-time diagnostics for 2200 KB of knowledge for complex system interdependences. The ability to detect and mitigate hardware related failures was demonstrated within a confined space autonomous operation. Our findings provide evidence of the applicability of our approach for the significant challenge of run-time safety compliance and reliability in autonomous systems.
Background
Glutaric aciduria type 1 is a rare neurometabolic disease with high morbidity.
Objective
To describe the MR imaging abnormalities in glutaric aciduria type 1 and to identify any ...association between the clinical and imaging features.
Materials and methods
MRI scans of 29 children (mean age: 16.9 months) with confirmed diagnosis of glutaric aciduria type 1 were retrospectively reviewed. Gray matter and white matter scores were calculated based on a previously published pattern-recognition approach of assessing leukoencephalopathies. Hippocampal formation and opercular topography were assessed in relation to the known embryological basis. MRI scores were correlated with morbidity score.
Results
The most consistent MRI abnormality was widened operculum with dilatation of the subarachnoid spaces surrounding underdeveloped frontotemporal lobes. Incomplete hippocampal inversion was also seen. The globus pallidus was the most frequently involved gray matter structure (86%). In addition to the central tegmental tract, white matter abnormalities preferentially involved the central and periventricular regions. The morbidity score correlated with the gray matter abnormality score (
P
= 0.004). Patients with dystonia had higher gray matter and morbidity scores.
Conclusion
Morbidity is significantly correlated with abnormality of gray matter, rather than white matter, whether secondary to acute encephalopathic crisis or insidious onset disease.
To reduce Operation and Maintenance (O&M) expenditure on offshore wind farms, wherein 80% of the cost relates to deploying personnel, the offshore wind sector looks to advances in Robotics and ...Artificial Intelligence (RAI) for solutions. Barriers to residential Beyond Visual Line of Sight (BVLOS) autonomy as a service, include operational challenges in run-time safety compliance, reliability and resilience, due to the complexities of dealing with known and unknown risk in dynamic environments. In this paper we incorporate a Symbiotic System Of Systems Approach (SSOSA) that uses a Symbiotic Digital Architecture (SDA) to provide a cyber physical orchestration of enabling technologies. Implementing a SSOSA enables Cooperation, Collaboration and Corroboration (C 3 ), as to address run-time verification of safety, reliability and resilience during autonomous missions. Our SDA provides a means to synchronize distributed digital models of the robot, environment and infrastructure. Through the coordinated bidirectional communication network of the SDA, the remote human operator has improved visibility and understanding of the mission profile. We evaluate our SSOSA in an asset inspection mission within a confined operating environment. Demonstrating the ability of our SSOSA to overcome safety, reliability and resilience challenges. The SDA supports lifecycle learning and co-evolution with knowledge sharing across the interconnected systems. Our results evaluate both sudden and gradual faults, as well as unknown events, that may jeopardize an autonomous mission. Using distributed and coordinated decision making, the SSOSA enhances the analysis of the mission status, which includes diagnostics of critical sub-systems within the resident robot. This evaluation demonstrates that the SSOSA provides enhanced run-time operational resilience and safety compliance to BVLOS autonomous missions. The SSOSA has the potential to be a highly transferable methodology to other mission scenarios and technologies, providing a pathway to implementing scalable autonomy as a service.
The UK has set plans to increase offshore wind capacity from 22GW to 154GW by 2030. With such tremendous growth, the sector is now looking to Robotics and Artificial Intelligence (RAI) in order to ...tackle lifecycle service barriers as to support sustainable and profitable offshore wind energy production. Today, RAI applications are predominately being used to support short term objectives in operation and maintenance. However, moving forward, RAI has the potential to play a critical role throughout the full lifecycle of offshore wind infrastructure, from surveying, planning, design, logistics, operational support, training and decommissioning. This paper presents one of the first systematic reviews of RAI for the offshore renewable energy sector. The state-of-the-art in RAI is analyzed with respect to offshore energy requirements, from both industry and academia, in terms of current and future requirements. Our review also includes a detailed evaluation of investment, regulation and skills development required to support the adoption of RAI. The key trends identified through a detailed analysis of patent and academic publication databases provide insights to barriers such as certification of autonomous platforms for safety compliance and reliability, the need for digital architectures for scalability in autonomous fleets, adaptive mission planning for resilient resident operations and optimization of human machine interaction for trusted partnerships between people and autonomous assistants. Our study concludes with identification of technological priorities and outlines their integration into a new ‘symbiotic digital architecture’ to deliver the future of offshore wind farm lifecycle management.
Isovaleric acidaemia (IVA) is an autosomal recessive inborn error of leucine metabolism. It is caused by a deficiency in the mitochondrial isovaleryl-CoA dehydrogenase (IVD) enzyme. In this study, we ...investigated eight patients with IVA. The patients' diagnoses were confirmed by urinary organic acid analysis and the blood C5-Carnitine value. A molecular genetic analysis of the IVD gene revealed nine different variants: five were missense variants (c.1193G > A; p. R398Q, c.1207T > A; p. Y403N, c.872C > T; p. A291V, c.749G > C; p. G250A, c.1136T > C; p.I379T), one was a frameshift variant (c.ins386 T; p. Y129fs), one was a splicing variant (c.465 + 2T > C), one was a polymorphism (c.732C > T; p. D244D), and one was an intronic benign variant (c.287 + 14T > C). Interestingly, all variants were in homozygous form, and four variants were novel (p. Y403N, p. Y129fs, p. A291V, p. G250A) and absent from 200 normal chromosomes. We performed protein modelling and dynamics analyses, pathogenicity and stability analyses, and a physiochemical properties analysis of the five missense variants (p.Y403N, R398Q, p.A291V, p.G250A, and p.I379T). Variants p.I379T and p.R398Q were found to be the most deleterious and destabilizing compared to variants p.A291V and p.Y403N. However, the four variants were predicted to be severe by the protein dynamic and in silico analysis, which was consistent with the patients' clinical phenotypes. The p.G250A variant was computationally predicted as mild, which was consistent with the severity of the clinical phenotype. This study reveals a potentially meaningful genotype-phenotype correlation for our patient cohort and highlights the development and use of this computational analysis for future assessments of genetic variants in the clinic.
Glutaric acidemia I (GAI) is an autosomal recessive metabolic disease caused by a deficiency of glutaryl-CoA dehydrogenase enzyme (GCDH). Patients with GAI are characterized by macrocephaly, acute ...encephalitis-like crises, dystonia and frontotemporal atrophy. In this study, we investigated 18 Egyptian patients that were diagnosed with GAI based on their clinical, neuroradiological, and biochemical profiles. Of the 18 patients, 16 had developmental delay and/or regression, dystonia was prominent in 75% of the cases, and three patients died. Molecular genetics analysis identified 14 different mutations in the
GCDH
gene in the 18 patients, of the 14 mutations, nine were missense, three were in the 3′-Untranslated Region (3′-UTR), one was nonsense, and one was a silent mutation. Four novel mutations were identified (c.148 T > A; p.Trp50Arg, c.158C > A; p.Pro53Gln, c.1284C > G; p.Ile428Met, and c.1189G > T; p.Glu397*) that were all absent in 300 normal chromosomes. The 3′-UTR mutation (c.*165A > G; rs8012), was the most frequent mutation observed (0.5; 18/36), followed by the most common mutation among Caucasian patients (p.Arg402Trp; rs121434369) with allele frequency of 0.36 (13/36), and the 3′-UTR mutation (c.*288G > T; rs9384, 0.22; 8/16). The p.Arg257Gln mutation was found with allele frequency of ~0.17 (6/36). The marked homozygosity observed in our patients is probably due to the high level of consanguinity that is observed in 100% of the cases. We used nine in silico prediction tools to predict the pathogenicity (SIFT, PhD-SNP, SNAP, Meta-SNP, PolyPhen2, and Align GVGD) and protein stability (I-Mutant2.0, Mupro, and istable) of the nine missense mutants. The mutant p.Arg402Trp was predicted to be most deleterious by all the six pathogenicity prediction tools and destabilizing by all the three-stability prediction tools, and highly conserved by the ConSurf server. Using the clinical, biochemical, family history of the 18 patients, and the in silico analysis of the missense mutations, our study showed a mix of conclusive and inconclusive genotype-phenotype correlations among our patient’s cohort and suggests the usefulness of using various sophisticated computational analysis to be utilized for future variant classifications in the genetic clinics.
Purpose
This paper aims to provide a systematic review of literature pertaining to how executive behavioral characteristics relate to financial reporting decisions.
Design/methodology/approach
The ...authors review 44 papers published between 2001 and 2021 in top journals that are nested in leading business, economic and accounting journals.
Findings
Through the systematic review, the authors provide a framework for the emergence of narcissism and how it relates to decision making and hence, firm performance. Additionally, this paper identifies different measures of measuring narcissism with their pros and cons and suggest that different measures lead to different outcomes in prior literature.
Originality/value
The study contributes to a growing stream of research on executives' attributes influence on decision making. The authors recommend that future research may focus more on the chief financial officer (CFO) role as the majority of literature in CEO based. Additionally, the authors suggest that different settings may moderate the outcomes, and the authors propose that future research may be conducted to show how the regulatory environment affects or moderates narcissism effect.
Tetrahydrobiopterin deficiency in newborns with atypical hyperphenylalaninemia requires rapid and accurate diagnosis and the ability to distinguish it from the classical type to prevent early ...irreversible neurological damage. The study aimed to evaluate neopterin and biopterin (products of tetrahydrobiopterin recycling pathway) and amino acid profiles (used in supplementation therapy) in patients with hyperphenylalaninemia after optimizing ultra-performance liquid chromatography coupled with tandem mass spectrometry to simultaneously measure neopterin, biopterin, and amino acids in dried blood spots. The study enrolled preselected infants with classic (
n
= 46), atypical (
n
= 14) hyperphenylalaninemia, and a control group (
n
= 50).
Result
Tandem mass spectrometry detected neo/biopterin in the blood with a sensitivity and specificity of 100%. The mean neo/biopterin levels were significantly lower in the atypical cases (4 ± 1 and 3 ± 1 nmol/L) than the classic (49 ± 13 and 50 ± 12 nmol/L) and control (15.2 and 15.3 nmol/L) groups and correlated with phenylalanine and phenylalanine to tyrosine ratio (
all P
< 0.05). The study compared classic and atypical hyperphenylalaninemia cases with the control group. Both classic and atypical cases exhibited decreased levels of arginine, valine, and leucine compared to controls. Classic cases showed increased levels of citrulline, ornithine, and methionine, while atypical cases showed increased citrulline levels only. Comparing atypical versus classic cases, atypical cases exhibited decreased levels of citrulline, ornithine, methionine, arginine, leucine, and valine (all
P
< 0.05). Correlation analysis revealed negative associations between ornithine and biopterin and between arginine and neopterin in classic PKU cases. These findings highlight distinct metabolic differences between classic and atypical PKU.
Conclusion
The optimized method detected neo/biopterin in the blood with accuracy and precision. The characteristic pattern of neo/biopterin in the blood makes it possible to differentiate between classic and atypical hyperphenylalaninemia with a sensitivity and specificity of 100%. The amino acid profile could add value when treatment with large neutral amino acids is considered.
The purpose of this study was to enhance understanding of lysosomal acid lipase deficiency (LALD) in infancy.
Investigators reviewed medical records of infants with LALD and summarized data for the ...overall population and for patients with and without early growth failure (GF). Kaplan–Meier survival analyses were conducted for the overall population and for treated and untreated patients.
Records for 35 patients, 26 with early GF, were analyzed. Prominent symptom manifestations included vomiting, diarrhea, and steatorrhea. Median age at death was 3.7 months; estimated probability of survival past age 12 months was 0.114 (95% confidence interval (CI): 0.009-0.220). Among patients with early GF, median age at death was 3.5 months; estimated probability of survival past age 12 months was 0.038 (95% CI: 0.000-0.112). Treated patients (hematopoietic stem cell transplant (HSCT), n = 9; HSCT and liver transplant, n = 1) in the overall population and the early GF subset survived longer than untreated patients, but survival was still poor (median age at death, 8.6 months).
These data confirm and expand earlier insights on the progression and course of LALD presenting in infancy. Despite variations in the nature, onset, and severity of clinical manifestations, and treatment attempts, clinical outcome was poor.
Glutaric acidemia type 1 (GA1) is an inherited metabolic autosomal recessive disorder that is caused by a deficiency in glutaryl-CoA dehydrogenase (GCDH). Untreated patients suffer primarily from ...severe striatal damage. More than 250 variants in the
GCDH
gene have been reported with a variable frequency among different ethnic groups. In this study, we aimed to characterize 89 Egyptian patients with GA1 and identify the variants in the 41 patients who were available for genotyping. All of our patients demonstrated clinical, neuroradiological, and biochemical characteristics that are consistent with a diagnosis of GA1. All patients presented with variable degrees of developmental delay ranging from mild to severe. Most of the 89 patients presented with acute onset type (71.9%), followed by insidious (19%) and asymptomatic (9%). A delay in diagnosis was inversely associated with macrocephaly. The prevalence rate ratio (PR) for macrocephaly that was associated with each 6-month delay was 0.95 (95%CI 0.91–0.99). However, high body weight was associated with a higher likelihood of having macrocephaly (PR 1.16, 95%CI 1.06–1.26 per 1 SD increment of Z score weight). However, body weight was inversely associated with the morbidity score. Consanguinity level was 64% among our patient’s cohort and was positively associated with the C5DC level (β (95%CI) 1.06 (0.12–1.99)). Forty-one patients were available for genotyping and were sequenced for the
GCDH
gene. We identified a total of 25 variants, of which the following six novel variants were identified: three missense variants, c.320G > T (p.Gly107Val), c.481C > T (p.Arg161Trp) and c.572 T > G (p.Met191Arg); two deletions, c.78delG (p.Ala27Argfs34) and c.1035delG (p.Gly346Alafs*11); and one indel, c.272_331del (p.Val91_Lys111delinsGlu). All of the novel variants were absent in the 300 normal chromosomes. The most common variant, c.*165A > G, was detected in 42 alleles, and the most commonly detected missense variant, c.1204C > T (p.Arg402Trp), was identified in 29 mutated alleles in 15/41 (34.2%) of patients. Our findings suggest that GA1 is not uncommon organic acidemia disease in Egypt; therefore, there is a need for supporting neonatal screening programs in Egypt.
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