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"Salgado, Duarte"
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A digital twins concept model for integrated maintenance: a case study for crane operation
The paper presents an Integrated Maintenance Decision Making Model (IMDMM) concept for cranes under operation especially into the container type terminals. The target is to improve cranes operational efficiency through minimizing the risk of the Gantry Cranes Inefficiency (GCI) results based on the implementation of the Digital Twins concept for maintenance purposes. The proposed model makes a joint transportation process and crane maintenance scheduling, relevant to assure more robust performances in stochastic environments, as well as to assess and optimize performances at different levels, from components and transport device to production systems (container terminal). The crane operation risk is estimated with a sequential Markov chain Monte Carlo simulation model and the optimization model behind of IMDMM is supported through the Particle Swarm Optimization algorithms because the objective function a non-linear stochastics problem with bounded constrains. The developed model allows the container terminal operators (management process) to obtain a maintenance schedule that minimizes the GCI (holistic indicator), as well as establishing the desired level of risk. The paper demonstrates the effectiveness of the proposed maintenance decision making concept model for cranes under operation using data from of a real container terminal (case study).
Journal Article
Selumetinib for plexiform neurofibromas in neurofibromatosis type 1: a single-institution experience
BackgroundPlexiform neurofibromas (PN) are the most frequent tumors associated with Neurofibromatosis type 1 (NF-1). PN can cause significant complications, including pain, functional impairment, and disfigurement. There is no efficient medical treatment and, surgical resection of large PN is frequently infeasible. Selumetinib (AZD6244/ARRY-142886) is a mitogen-activated protein kinase enzyme (MEK1/2) inhibitor and works by targeting the MAPK pathway. It is an investigational treatment option for inoperable symptomatic PN associated with NF-1. Herein, we describe a single institutional experience with selumetinib for inoperable PN in NF-1.MethodsCase series study of demographics, clinical, baseline characteristics, treatment effect, and follow-up of consecutive genetically confirmed NF1 patients with inoperable PN associated with significant or potential significant morbidity treated with selumetinib (April 2018 to April 2019).ResultsNineteen patients were treated with selumetinib. Predominant target locations were head and neck (31.6%, 6/19), chest (26.3%, 5/19) and pelvis (21%, 4/19) and the most important comorbidities were disfigurement (47.4%, 9/19) and pain (26.3%, 5/19). The mean follow-up time was 223 days (range 35–420 days). All but one had sustained clinical improvement, mainly in the first 60–90 days of treatment. In one patient, the treatment was suspended after 168 days (lack of clear benefit and left ventricular ejection fraction drop). There were no adverse effects leading to treatment suspension.ConclusionsIn the first observational study of selumetinib for NF-1 associated PN we showed that the drug was associated with clinical and radiological improvement. Our study also confirms the safety described in the clinical trials.
Journal Article
Maintenance Strategies Overlook for Devices Under Operation
An updated systematization of maintenance strategies based on selected transport device exploitation parameters, working in continuous process was presented. The presented framework provides guidelines of assessment methods and an evolution of the way-of-thinking and technological changes in the modern industry related with the maintenance strategies. The paper present also a holistic discussion about the maintenance strategies applicability on overhead operating cranes.
Journal Article
BRAF V600E mutation and 9p21: CDKN2A/B and MTAP co-deletions - Markers in the clinical stratification of pediatric gliomas
Background
Genetic alterations in pediatric primary brain tumors can be used as diagnostic and prognostic markers and are the basis for the development of new target therapies that, ideally, would be associated with lower mortality and morbidity. This study evaluates the incidence and interplay of the presence of
BRAF V600E
mutation and chromosomal 9p21 deletions in a series of 100 pediatric gliomas, aiming to determine the role of these alterations in recurrence and malignant transformation, and to verify if they could be used in the clinical set for stratifying patients for tailored therapies and surveillance.
Methods
Sanger sequencing was used for the assessment of
BRAF
mutations at exon 15 and
Fluorescent
In Situ
Hybridization (FISH)
with BAC: RP11–14192 for the detection of 9p21 alterations. Expression levels of the
CDKN2A
and
MTAP
by real-time PCR were evaluated in cases with 9p21 deletions. Statistical analysis of genetic and clinical data was performed using
Graph Pad Prism 5
and
SPSS Statistics 24
software.
Results
In our cohort it was observed that 7 /78 (8,9%) of the low-grade tumors recurred and 2 (2,6%) showed malignant transformation.
BRAF V600E
mutations were detected in 15 cases. No statistically significant correlations were found between the presence of
BRAF V600E
mutation and patient’s morphologic or clinical features. Deletions at 9p21 abrogating the
CDKN2A/B
and
MTAP
loci were rare in grade I gliomas (12.2%,
p
= 0.0178) but frequent in grade IV gliomas (62.5%,
p
= 0.0087). Moreover it was found that deletions at these loci were correlated with a shorter overall survival (
p
= 0.011) and a shorter progression-free survival (
p
= 0.016).
Conclusions
It was demonstrated that in these tumors
BRAF V600E
mutated and that
CDKN2A/B MTAP
co-deletions may be used for stratifying patients for a stricter surveillance. The Investigating and defining if glial tumors with
CDKN2A/B
and
MTAP
homozygous loss may be vulnerable to new forms of therapy, namely those affecting the methionine salvage pathway, was proven to be of importance.
Journal Article
Markov Chain Monte Carlo Simulation Model for Risk Assessment the Power Systems for Electromobility Use
A simulation model to evaluate risks in Power Systems including green energy sources to generate electricity for electro mobility use is presented in the paper. The model allows to calculate risk indicator that characterize the performance of the Power Systems. The model considers the additional risks of wind and solar variability in the Power Systems, through wind farms and PV farms, respectively. Also, in the recent years, the number of electric vehicles (EVs) on the road have been rapidly increasing. Charging this increasing number of EVs is expected to have an impact on the power grid especially if high charging powers and opportunistic charging are used. Multiple papers have observed that the charging stations are used by multiple users during the day. In a context where electric mobility is gaining increasing importance as a more sustainable solution for urban environments, this work presents the optimization of charging profiles of the potential users of these charging stations. We analyzed the charging profiles in a power grid with renewables sources of energy and we determine the optimal charging profiles for the power grid based on maximizing the energy delivered by renewable sources of energy.
Journal Article
Endocrine Health Problems Detected in 764 Patients Evaluated in a Late Effects Clinic
Background: Many pediatric cancer survivors have endocrine conditions. After treatment with alkylating agents, steroids, methotrexate, and radiation, several endocrine dysfunctions may appear. Surveillance for late effects is recommended by guidelines worldwide. Objective: The objective of this study was to describe the endocrine outcomes of 764 patients followed during a 20 years’ period in our out-patient clinic. Design: We retrospectively reviewed the medical records. Patients: The study included 764 patients whose oncological or hematological dangerous diseases appeared before they were 18 years old. Larger groups were constituted by leukemias, central nervous tumors, and lymphomas. Outcome Measures: The frequency and types of endocrine conditions were analyzed. Results: 1,091 endocrine conditions were observed in all groups. The most common types of endocrine conditions were problems with growth and the thyroid. We found puberty abnormalities and bone problems in third and fourth places of frequency. ACTH insufficiency was found in seventh place. Conclusion: Endocrine dysfunctions are very common in survivor populations. Endocrinologists should be aware of international guidelines and make an effort to optimize screening and treatment of endocrine effects of cancer therapy. The crucial period is the puberty with growth spurt failure and accelerated maturity both of which can bring future social and professional difficulties.
Journal Article
Palatal tremor in relation to brainstem tumour involvement
2013 Tetraparesis, worsening of the pre-existing cognitive impairment brain magnetic resonance: hypointense on T2-weighted a with T1 gadolinium-enhancing lesions in the dorsal midbrain tegmentum and periaqueductal area Negative extensive blood and CSF testing; normal EEG Corticotherapy Primary CNS lymphoma? *antineutrophilic cytoplasmic antibodies, antinuclear antibody, antiphospholipid antibodies, C-reactive protein, haemosedimentation rate, renal function, hepatic function, electrolites, lactate, pyruvate, arylsulfatase A, thyroid function, adrenal function, HIV, hepatitis B and C virus. **neurotropic virus, John Cunningham virus, immunophenotyping. ***Central nervous system.
Journal Article
Remission of pediatric diffuse intrinsic pontine glioma: Case report and review of the literature
Background: Diffuse midline glioma (DMG) is one of the most aggressive pediatric tumors. Approximately 60% of pediatric DMG patients die within the first year of diagnosis. Complete clinical and radiological remission of DMG is extremely rare. The objective of this study was to describe a case of remission of pediatric DMG and to compare with similar cases published so far. Results: DMG was diagnosed in a 2-year-old girl who presented with brainstem and increased intracranial pressure manifestations. Ventriculoperitoneal shunt and chemotherapy-based treatment were offered. From the diagnosis, in spite of progressive enlargement of the tumoral lesion, her clinical condition improved remarkably. After the end of chemotherapy, progressive and gradual imagiological improvements occurred. At the end of the 60th month of follow-up, she was asymptomatic with total remission. Six pediatric DMG cases, from birth to the age of 3, in whom remission occurred were found in the literature. Histology sample was available in two of them (fibrillary astrocytoma-WHO Grade II and anaplastic astrocytoma-WHO Grade III). None received chemotherapy or radiotherapy. Conclusion: Remission of pediatric DMG is extremely rare and reinforces the biological heterogeneity of the tumor. In the absence of reliable predictors of prognosis, offering the best supportive treatment, including neurosurgical interventions should be considered in similar cases.
Journal Article
The role of lupus susceptibility mhc haplotypes and interferon-alpha in gene regulation
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell dysregulation and type 1 interferon (IFN) activity. Variants in the major histocompatibility complex (MHC) region confer the greatest genetic risk for SLE; however, the underlying causes of association remain elusive. One mechanism by which causal variants may drive genetic associations at the MHC is through regulating gene expression in a context-specific manner. This project investigates the effect of (i) SLE-associated MHC haplotypes, and (ii) IFN-α stimulation on gene regulation in ex vivo B cells, in order to further our understanding of how these factors contribute to disease risk. Expression quantitative trait loci (eQTLs) were investigated for variants tagging six SLE-risk or -protective haplotypes: DRB1*03:01 (rs2187668), DRB1*15:01 (rs3135391), DPB1 (rs3117213, rs2071351, rs2071349), and MSH5 (rs409558). eQTL analyses were conducted using publicly-available data sets. Additionally, gene expression data were generated from resting and IFN-α-stimulated ex vivo B cells. Several cis-eQTLs were identified and replicated in the publicly-available data sets. A novel trans-eQTL was identified for DRB1*03:01 haplotypes in the exon array data set, in both resting and IFN-α-stimulated cells, involving down-regulation of BTN3A2 (P < 2.63 × 10-6). These results suggest a regulatory role for disease-associated MHC haplotypes, and implicate BTN3A2 as a novel candidate gene on the DRB1*03:01 haplotype. The global effect of IFN-α stimulation on the B cell transcriptome was also explored. Several SLE susceptibility genes outside canonical type 1 IFN signalling pathways were differentially expressed in response to IFN-α. The direction of effect of IFN-α on the expression of SLE candidate genes paralleled the known functional consequences of SLE-associated polymorphisms in those genes. This suggests a previously unrecognised role for SLE candidate genes following activation of the type 1 IFN pathway, and sheds light into the role of IFN-α in the aetiopathogenesis of SLE.
Dissertation