Implementation of a program for the analysis of the costs of equipments' maintenance until the end of their useful life

Companies face nowadays a very competitive environment and they have to be well managed to remain sustainable. For being sustainable the company needs either to increase its prices over time or has to reduce the amount of expenses. Reducing costs may be the best option once the global market is very competitive. This work results from the intention of a company (ME-Construction Company) to get a tool to support the decisions related to the equipment management. The aim is to create a model for the analysis of the costs resulting from using MEConstruction Company’s equipments. The studied case is real. This model is the Life Cycle Cost complemented by the Net Present Value and Equivalent Annual Cost. It is worked on a representative sample of the equipment of the company. The application of this model allows the manager to have the estimating tools which may support and justify his decisions in the company. During the equipment’s lifetime, he may have the right perception of the evolution of the expenses and income. The company should develop an equipment costing methodology as much effective as possible in order to consider the expenses that are not included in the equipment value and to consider the equipments which release less greenhouse gases contributing to reduce the global greenhouse effect

Survival of the fittest: tourism exposure and firm survival

In this article, a discrete-time hazard model to study firm survival in the Portuguese Tourism sector is estimated. This sector has experienced a remarkable performance over the last decades. Results show that when compared to other sectors, tourism firms are more likely to exit: (i) if they are young (less than 10 years of existence); and (ii) if they belong to the group of worse performers (i.e. belong to the lower tail of the firm distribution). Within tourism related sectors, firms with highest tourism exposure, such as travel agencies and hotels are always among the best performers in terms of survival. Moreover, despite of Tourism being one of the most volatile sectors in periods of high uncertainty, results show a higher survival resilience among established tourism associated firms.info:eu-repo/semantics/acceptedVersio

Huntington's disease clinical trials corner: April 2022

In this edition of the Huntington's Disease Clinical Trials Corner we expand on GENERATION HD1, PRECISION-HD1 and PRECISION-HD2, SELECT-HD, and VIBRANT-HD trials, and list all currently registered and ongoing clinical trials in Huntington's disease

Placebo response in chronic peripheral neuropathic pain trials: systematic review and meta-analysis

Objective: To estimate the magnitude of the placebo and nocebo responses in chronic peripheral neuropathic pain (CNP) and explore possible associations with trial characteristics. // Methods: We searched CENTRAL, MEDLINE, and Embase for randomized controlled trials (RCTs) from inception to May 2020. We included placebo-controlled RCTs of ≥8 weeks investigating first-line pharmacological interventions for CNP. Primary endpoints were the placebo response, the proportion of patients receiving placebo with pain intensity reduction (PIR) ≥30% from baseline, and the nocebo response, the proportion of patients receiving placebo experiencing adverse events (AEs). Screening, data extraction, and bias assessment (with the Cochrane risk of bias tool) were conducted by independent reviewers. We pooled data using a random-effects model. // Results: We included 50 trials, with a combined 5,693 participants allocated to placebo, conducted between 1998 and 2020. Overall, 38% of patients receiving placebo reported PIR≥30% (95% CI 34 to 42, I2=86%); 23% reported PIR≥50% (95% CI 20 to 26; I2=81%). 50% of patients receiving placebo reported AEs (95% CI 0.43 to 0.58; I2=97%); 2% reported serious AEs (95% CI 2 to 3; I2=58%). In patients receiving active interventions, the placebo response accounts for 75% of the treatment effect on PIR≥30%, and the nocebo response accounts for 75% of the AEs. Interpreted inversely, only 25% of responses and 25% of adverse events can be attributed to the intervention. Publication year positively correlated with PIR≥30% and negatively correlated with AEs. Female sex negatively correlated with AEs. // Conclusions: The placebo and nocebo responses in parallel-designed RCTs in CNP are substantial and should be considered in trial interpretation and in the design of future trials

Modeling and analysis of the ankle joint complex with muscles

[Excerpt] 1. INTRODUCTION The ankle joint complex of the human foot is composed of the talocrural and the talocalcaneal joints, and it is the focal point of this work. In general, plantarflexion and dorsiflexion are allowed by the talocrural joint, while the talocalcaneal joint permits inversion and eversion of the human foot. In this study, a spatial biomechanical multibody model of the ankle joint complex is presented, which extends the authors’ previous work [1] to incorporate the muscle behavior [2].[...]This work has been supported by Portuguese Foundation for Science and Technology, under the national support to R&D units grant, with the reference project UIDB/04436/2020 and UIDP/04436/2020, as well as through IDMEC, via the projects LAETA Base Funding (DOI: 10.54499/UIDB/50022/2020) and LAETA Programmatic Funding (DOI: 10.54499/UIDP/50022/2020). The first author expresses her gratitude to the Portuguese Foundation for Science and Technology through the PhD grant (DOI: 10.54499/2021.04840.BD)

Neurofilament Light Protein as a Potential Blood Biomarker for Huntington's Disease in Children

BACKGROUND: Juvenile-onset Huntington's disease (JOHD) is a rare and particularly devastating form of Huntington's disease (HD) for which clinical diagnosis is challenging and robust outcome measures are lacking. Neurofilament light protein (NfL) in plasma has emerged as a prognostic biomarker for adult-onset HD. METHODS: We performed a retrospective analysis of samples and data collected between 2009 and 2020 from the Kids-HD and Kids-JHD studies. Plasma samples from children and young adults with JOHD, premanifest HD (preHD) mutation carriers, and age-matched controls were used to quantify plasma NfL concentrations using ultrasensitive immunoassay. RESULTS: We report elevated plasma NfL concentrations in JOHD and premanifest HD mutation-carrying children. In pediatric HD mutation carriers who were within 20 years of their predicted onset and patients with JOHD, plasma NfL level was associated with caudate and putamen volumes. CONCLUSIONS: Quantifying plasma NfL concentration may assist clinical diagnosis and therapeutic trial design in the pediatric population. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society

Experimental and computacional analisys of the human gait with crutches

[Excerpt] 1. INTRODUCTION The use of mobility assistive devices, such as crutches, presentssignificant benefitsto disabled patients, as they not only promote independence, but also enable and enhance the participation in daily activities. However, the prolonged and repetitive use of such devices can be a source of secondary health problems, including shoulder and elbow tendinopathies [1]. The analysis of device-assisted gait based on biomechanical multibody systems has been increasing over the years, allowing for the estimation of biomechanical parameters, such as muscle or joint forces, which are difficult, if not impossible, to measure experimentally.[...]This work has been supported by Portuguese Foundation for Science and Technology, under the national support to R&D units grant, with the reference project UIDB/04436/2020 and UIDP/04436/2020, as well as through IDMEC, via the projects LAETA Base Funding (DOI:10.54499/UIDB/50022/2020) and LAETA Programmatic Funding (DOI: 10.54499/UIDP/50022/2020). The second author expresses her gratitude to the Portuguese Foundation for Science and Technology through the PhD grant (DOI: 10.54499/2021.04840.BD)

Longitudinal evaluation of proton magnetic resonance spectroscopy metabolites as biomarkers in Huntington’s disease

Proton Magnetic resonance spectroscopy (1H-MRS) is a non-invasive method of exploring cerebral metabolism. In Huntington’s disease, altered 1H-MRS-determined concentrations of several metabolites have been described; however, findings are often discrepant and longitudinal studies are lacking. 1H-MRS metabolites may represent a source of biomarkers, thus their relationship with established markers of disease progression require further exploration to assess prognostic value and elucidate pathways associated with neurodegeneration. In a prospective single-site controlled cohort study with standardised collection of CSF, blood, phenotypic and volumetric imaging data, we used 3T 1H-MRS in conjunction with the linear combination of model spectra method to quantify seven metabolites (total n-acetylaspartate, total creatine, total choline, myo-inositol, GABA, glutamate and glutathione) in the putamen of 59 participants at baseline (15 healthy controls, 15 premanifest and 29 manifest Huntington’s disease gene expansion carriers) and 48 participants at 2-year follow-up (12 healthy controls, 13 premanifest and 23 manifest Huntington’s disease gene expansion carriers). Intergroup differences in concentration and associations with CSF and plasma biomarkers; including neurofilament light chain and mutant Huntingtin, volumetric imaging markers; namely whole brain, caudate, grey matter and white matter volume, measures of disease progression and cognitive decline, were assessed cross-sectionally using generalized linear models and partial correlation. We report no significant groupwise differences in metabolite concentration at baseline but found total creatine and total n-acetylaspartate to be significantly reduced in manifest compared with premanifest participants at follow-up. Additionally, total creatine and myo-inositol displayed significant associations with reduced caudate volume across both time points in gene expansion carriers. Although relationships were observed between 1H-MRS metabolites and biofluid measures, these were not consistent across time points. To further assess prognostic value, we examined whether baseline 1H-MRS values, or rate of change, predicted subsequent change in established measures of disease progression. Several associations were found but were inconsistent across known indicators of disease progression. Finally, longitudinal mixed effects models revealed glutamine + glutamate to display a slow linear decrease over time in gene expansion carriers. Altogether, our findings show some evidence of reduced total n-acetylaspartate and total creatine as the disease progresses and cross-sectional associations between select metabolites, namely total creatine and myo-inositol, and markers of disease progression, potentially highlighting the proposed roles of neuroinflammation and metabolic dysfunction in disease pathogenesis. However, the absence of consistent group differences, inconsistency between baseline and follow-up, and lack of clear longitudinal change suggests that 1H-MRS metabolites have limited potential as Huntington’s disease biomarkers

Quinone oxidoreductase from Staphylococcus aureus

Funding Information: Helena Gaspar is acknowledged for the HPLC analyses and Bruno Victor for advice on modelling. F.M.S. and M.S.S. are recipients of fellowships by Fundação para a Ciência e a Tecnologia (PD/BD/128213/2016 and PD/BD/128202/2016, respectively, both within the scope of the PhD program Molecular Biosciences PD/00133/2012). A.B. is recipient of a fellowship by Fundação para a Ciência e a Tecnologia UI/BD/153052/2022. The work was funded by Fundação para a Ciência e a Tecnologia ( PTDC/BIA-BQM/2599/2021 to M.M.P). The project was further supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT , Portugal (to BioISI), by LISBOA-01-0145-FEDER-007660 cofunded by FEDER through COMPETE2020-POCI and by Fundação para a Ciência e a Tecnologia and by UIDB/04612/2020 and UIDP/04612/2020 research unit grants from FCT (to Mostmicro). The NMR spectrometers are part of the National NMR Network (PTNMR) and are supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). Funding Information: Helena Gaspar is acknowledged for the HPLC analyses and Bruno Victor for advice on modelling. F.M.S. and M.S.S. are recipients of fellowships by Fundação para a Ciência e a Tecnologia (PD/BD/128213/2016 and PD/BD/128202/2016, respectively, both within the scope of the PhD program Molecular Biosciences PD/00133/2012). A.B. is recipient of a fellowship by Fundação para a Ciência e a Tecnologia UI/BD/153052/2022. The work was funded by Fundação para a Ciência e a Tecnologia (PTDC/BIA-BQM/2599/2021 to M.M.P). The project was further supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT, Portugal (to BioISI), by LISBOA-01-0145-FEDER-007660 cofunded by FEDER through COMPETE2020-POCI and by Fundação para a Ciência e a Tecnologia and by UIDB/04612/2020 and UIDP/04612/2020 research unit grants from FCT (to Mostmicro). The NMR spectrometers are part of the National NMR Network (PTNMR) and are supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). Publisher Copyright: © 2022 The Author(s)Staphylococcus aureus is an opportunistic pathogen and one of the most frequent causes for community acquired and nosocomial bacterial infections. Even so, its energy metabolism is still under explored and its respiratory enzymes have been vastly overlooked. In this work, we unveil the dihydroorotate:quinone oxidoreductase (DHOQO) from S. aureus, the first example of a DHOQO from a Gram-positive organism. This protein was shown to be a FMN containing menaquinone reducing enzyme, presenting a Michaelis-Menten behaviour towards the two substrates, which was inhibited by Brequinar, Leflunomide, Lapachol, HQNO, Atovaquone and TFFA with different degrees of effectiveness. Deletion of the DHOQO coding gene (Δdhoqo) led to lower bacterial growth rates, and effected in cell morphology and metabolism, most importantly in the pyrimidine biosynthesis, here systematized for S. aureus MW2 for the first time. This work unveils the existence of a functional DHOQO in the respiratory chain of the pathogenic bacterium S. aureus, enlarging the understanding of its energy metabolism.publishersversionpublishe

Safety and Feasibility of Research Lumbar Puncture in Huntington’s Disease: The HDClarity Cohort and Bioresource

Background: Biomarkers are needed to monitor disease progression, target engagement and efficacy in Huntington’s disease (HD). Cerebrospinal fluid (CSF) is an ideal medium to research such biomarkers due to its proximity to the brain. Objective: To investigate the safety and feasibility of research lumbar punctures (LP) in HD. Methods: HDClarity is an ongoing international biofluid collection initiative built on the Enroll-HD platform, where clinical assessments are recorded. It aims to recruit 1,200 participants. Biosamples are collected following an overnight fast: blood via venipuncture and CSF via LP. Participants are healthy controls and HD gene expansion carriers across the disease spectrum. We report on monitored data from February 2016 to September 2019. Results: Of 448 participants screened, 398 underwent at least 1 sampling visit, of which 98.24% were successful (i.e., CSF was collected), amounting to 10,610 mL of CSF and 8,200 mL of plasma. In the total 572 sampling visits, adverse events were reported in 24.13%, and headaches of any kind and post-LP headaches in 14.86% and 12.24%, respectively. Frequencies were less in manifest HD; gender, age, body mass index and disease burden score were not associated with the occurrence of the events in gene expansion carriers. Headaches and back pain were the most frequent adverse events. Conclusion: HDClarity is the largest CSF collection initiative to support scientific research into HD and is now stablished as a leading resource for HD research. Our data confirm that research LP in HD are feasible and acceptable to the community, and have a manageable safety profile