Determination Of Moxidectin In Serum By Liquid Chromatography-tandem Mass Spectrometry And Its Application In Pharmacokinetic Study In Lambs

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The widespread use of moxidectin (MOX), a parasiticide used in the sheep breeding, has induced the parasite resistance in Brazilian farms. As a consequence, the farmers often increase the dose and frequency of drug utilization, and disregards safety of meat or milk. In order to establish adequate therapeutic treatment it is necessary to know the pharmacokinetics of the drug in the animal's body. Thus, high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed for the determination of MOX in serum lamb. Serum samples were treated with acetonitrile to precipitate proteins. A clean up by dispersive extraction in solid phase (SPE-d), using primary/secondary amine (PSA) and C18 sorbents, followed by freezing was performed. Method validation presented precision (coefficient of variation) and accuracy (recovery%) between 1.7-6.7 and 80.0-107.3%, respectively. The limit of quantification (LOQ) of the method was 2.0 ng mL(-1) and a linear response was obtained over a range of 2.0 to 100 ng mL(-1). This method was successfully applied to the determination of MOX in serum from suffolk lamb to evaluate the pharmacokinetic profile.282250256Coordination for the Improvement of Higher Level Education PersonnelNational Council for Scientific and Technological Development (CNPq), Brazil [305390/2013-9, 483839/2010-8]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

OECD principles on water governance in practice:an assessment of existing frameworks in Europe, Asia-Pacific, Africa and South America

Through the lens of the 12 OECD Principles on Water Governance, this article examines six water resources and water services frameworks in Europe, Asia-Pacific, Africa and South America to understand enhancing and constraining contextual factors. Qualitative and quantitative methods are used to analyze each framework against four criteria: alignment; implementation; on-ground results; and policy impact. Four main target areas are identified for improving water governance: policy coherence; financing; managing trade-offs; and ensuring integrity and transparency by all decision makers and stakeholders. Suggestions are presented to support practical implementation of the principles through better government action and stakeholder involvement.No Full Tex

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Advancing aircraft engine RUL predictions: an interpretable integrated approach of feature engineering and aggregated feature importance

Abstract In this study, we present a comprehensive approach for predicting the remaining useful life (RUL) of aircraft engines, incorporating advanced feature engineering, dimensionality reduction, feature selection techniques, and machine learning models. The process begins with a rolling time series window, followed by the extraction of a multitude of statistical features, and the application of principal component analysis for dimensionality reduction. We utilize a variety of feature selection methods, such as Genetic Algorithm, Recursive Feature Elimination, Least Absolute Shrinkage and Selection Operator Regression, and Feature Importances from a Random Forest model. As a significant contribution, we introduce the novel aggregated feature importances with cross-validation (AFICv) technique, which ranks features based on their mean importance. We establish a selection criterion that retains features with a cumulative mean sum equal to 70%, thereby reducing the complexity of machine learning models and enhancing their generalizability. Four machine learning regression models—Natural and Extreme Gradient Boosting, Random Forest, and Multi-Layer Perceptron—were employed to evaluate the effectiveness of the selected features. The performance of our proposed method is assessed by the evaluation metrics Root Mean Square Error (RMSE) and R2 Score, and also considered within-interval percentages and relative accuracy metrics. Importantly, a novel PCA interpretability was introduced to provide real-world context and enhance the utility of our findings for domain experts. Our results indicate that the proposed AFICv technique efficiently achieves competitive performance across the Commercial Modular Aero-Propulsion System Simulation (C-MAPSS) sub-datasets using a significantly smaller subset of features, thus contributing to a more effective and interpretable RUL prediction methodology for aircraft engines

Psychosocial impact of early onset dementia among caregivers

Introduction: There is growing recognition of early onset dementia (EOD) as a significant clinical and social problem because of its effects on physical and mental health of people with dementia (PWD) and their caregivers. Objective: To analyze the psychosocial impact of EOD in family caregivers. Methods: The study design was qualitative. Nine EOD caregivers (7 women) were recruited at a service for Alzheimer's disease and assessed using semi-structured interviews. Interpretative phenomenological analysis was used to analyze caregivers' reports. Results: Five themes emerged from the narratives: psychological and emotional impact; physical impact; financial and professional impact; social impact and need for support services. The majority of the caregivers of people with EOD perceived their emotional wellbeing as poor or extremely poor. Carers reported poor physical health, which tends to be longer-lasting than mental health problems. Two caregivers had to retire after the disclosure of the dementia diagnosis, and seven reduced their work loads because they had to look after PWD. Preserving the abilities of PWD is essential to maintain their self-esteem, dignity and sense of utility. For the caregivers, interventions and stimulating activities make PWD feel worthwhile and contribute to improving life. Conclusion: The caregivers of people with EOD assume the role of caregiver prematurely and need to balance this activity with other responsibilities. There is a need for more studies of EOD in order to improve understanding of the impact of this disease and to enable development of adequate services for PWD and their caregivers

Ocorrência de hepatites não-anão-B em unidade de hemodiálise

A monitorização mensal de alanina aminotransferase (ALT) sérica de pacientes em hemodiálise e os testes sorológicos para exclusões de infecções por vírus da hepatite A (HAV), vírus da hepatite B (HBV), citomegalovirus (CMV) e vírus Epstein-Barr (EBV), permitiu-nos identificar 11 casos de hepatites não-A, não-B em 111 indivíduos avaliados durante o período de 12 meses e acompanhados por 2 anos. Foram observados 3 padrões de atividade de ALT: elevação em pico monofásico em 2, bifásico ou polifásico em 6 e em platô em 3 pacientes. Individíduos com padrão monofásico exibiram os níveis mais elevados de ALT. Cinco pacientes apresentaram normalização bioquímica persistente 4,8 meses em média após o início da elevação aguda e seis evoluíram com ascensão crônica de ALT durante o período de estudo. A hepatite não-A, não-B foi, predominantemente, assintomática e anictérica, sempre antecedida por transfusões sangüíneas e com maior incidência nos seis primeiros meses de terapia dialítica dos pacientes.<br>Through monthly monitorization of alanine amino transferase (ALT) in hemodialysis patients and serological tests for exclusion of HA V (hepatitis A virus), HBV(hepatitis B virus), CMV (cytomegalovirus) and EBV (Epstein-Barr virus) infections, it was possible to identify 11 cases of non-A, non-B hepatitis among 111 individuals evaluated in a period of 12 months and followed-up for 2 years. Three patterns of ALT activity were observed: an elevation in monophasic peak in 2 patients, biphasic andpolyphasic in 6 patients and elevation in plateau in three others. Patients with the monophasic pattern showed the most elevated levels of ALT. Five patients showed biochemical normalization within approximately 4.8 months after the beginning of acute elevation and 6 evolved with chronic intermittent elevation during the period of study. Hepatitis non-A, non-B was predominantly asymptomatic and anicteric, always preceeded by blood tranfusions and with higher incidence in the 6 first months after hemodialysis

SHORT COMMUNICATION - In Situ Hybridization of Hepatitis C Virus RNA in Liver Cells of an Experimentally Infected Rhesus Macaque

The liver tissue of a rhesus macaque inoculated with hepatitis C virus (HCV) has been analyzed for the presence of HCV RNA using the technique of in situ hybridization, both at light and electron microscopy levels. The animal was inoculated by the intrasplenic route using a HCV infected autogenic hepatocyte transplant. The serum sample used to infect the hepatocyte cells was characterized by polymerase chain reaction technique and shown to be positive for HCV RNA, genotype 3 with 107 RNA copies/ml. In situ hybridization was performed using a complementary negative strand probe made with the specific primer. We were able to detect and localize viral RNA in altered membranes of the rough endoplasmic reticulum of infected liver cells, showing evidence of virus replication in vivo