Assessment of a novel Cu (II) complex as a potential anticancer agent

Widely used in cancer treatment, chemotherapy still faces hindering challenges, ranging from severe induced toxicity to drug resistance acquisition. As means to overcome these setbacks, newly synthetized compounds have recently come into play with the basis of improved pharmacokinetic/pharmacodynamic properties. With this mind-set, this project aimed towards the antiproliferative potential characterization of a group of metallic compounds. Additionally the incorporation of the compounds within a nanoformulation and within new combination strategies with commercial chemotherapeutic drugs was also envisaged. Cell viability assays presented copper (II) compound (K4) as the most promising, presenting an IC50 of 6.10 μM and 19.09 μM for HCT116 and A549 cell line respectively. Exposure in fibroblasts revealed a 9.18 μM IC50. Hoechst staining assays further revealed the compound’s predisposition to induce chromatin condensation and nuclear fragmentation in HCT116 upon exposure to K4 which was later demonstrated by flow cytometry and annexin V-FITC/propidium iodide double staining analysis (under 50 % cell death induction). The compound further revealed the ability to interact with major macromolecules such as DNA (Kb = 2.17x105 M-1), inducing structural brakes and retardation, and further affecting cell cycle progression revealing delay in S-phase. Moreover BSA interactions were also visible however not conclusive. Proteome profiling revealed overexpression of proteins involved in metabolic activity and underexpression of proteins involved in apoptosis thus corroborating Hoechst and apoptosis flow cytometry data. K4 nanoformulation suffered from several hindrances and was ill succeeded in part due to K4’s poor solubility in aqueous buffers. Other approaches were considered in this regard. Combined chemotherapy assays revealed high cytotoxicity for afatinib and lapatinib strategies. Lapatinib and K4 proteome profiling further revealed high apoptosis rates, high metabolic activity and activation of redundant proteins as part of compensatory mechanisms.

Versão portuguesa do CANE (Camberwell Assessment of Need for the Elderly) : desenvolvimento e dados preliminares

RESUMO - A avaliação de necessidades de cuidados é crucial no planeamento, monitorização e avaliação de serviços de psiquiatria e saúde mental, bem como na investigação e na clínica. Este princípio é obviamente aplicável aos serviços responsáveis por populações de pessoas mais velhas. O instrumento CANE — Camberwell Assessment of Need for the Elderly possibilita uma avaliação consistente das necessidades de utentes idosos, nomeadamente em situações de patologia neuropsiquiátrica. Procede-se a uma avaliação cruzada, entrevistando a pessoa em questão, o seu cuidador informal e o técnico responsável. Esta avaliação multidimensional abrange domínios da esfera biológica, psicológica e social, sendo aplicável na comunidade ou em internamento (regime parcial ou completo). A utilidade do CANE tem sido evidenciada em contextos clínicos, de investigação e de avaliação de serviços. Existem múltiplas traduções a nível internacional, a maioria das quais validada. Na área da epidemiologia psiquiátrica nem sempre estão disponíveis os dados relativos à qualidade das adaptações de instrumentos, pelo que se apresenta o processo de desenvolvimento da versão portuguesa (de acordo com as regras para validação transcultural, no processo de tradução-retroversão). A aplicabilidade da versão portuguesa foi satisfatória neste estudo-piloto, representando a primeira fase de um trabalho multicêntrico nacional. Nesta fase inicial, foram considerados casos de idosos com patologia neuropsiquiátrica (maioritariamente demência — 71,4%), em dois centros (Lisboa e Porto) (n = 21). A média de idades foi 73,9 (± 6,3) anos, sendo 76,2% do sexo feminino. A maioria vivia em casa, apresentava co-morbilidade somática e estava em contacto com um cuidador informal (em geral, familiares do sexo feminino). Os avaliadores identificaram necessidades, nem sempre cobertas, nas seguintes dimensões: cuidados com a casa, alimentação, actividades diárias, memória, saúde física, sofrimento psicológico, companhia e dinheiro/economias. Nem sempre a perspectiva de doentes, cuidadores, técnicos e avaliadores foi inteiramente coincidente. Estes resultados preliminares da aplicação da versão portuguesa do CANE são consistentes quanto à sua validade ecológica, facial e de conteúdo, estando em curso contributos adicionais para a validação efectiva numa amostra de maior dimensão.

Implementation of a probabilistic based framework for safety assessment of existing timber elements

The assessment of existing timber structures is often limited to information obtained from non or semi destructive testing, as mechanical testing is in many cases not possible due to its destructive nature. Therefore, the available data provides only an indirect measurement of the reference mechanical properties of timber elements, often obtained through empirical based correlations. Moreover, the data must result from the combination of different tests, as to provide a reliable source of information for a structural analysis. Even if general guidelines are available for each typology of testing, there is still a need for a global methodology allowing to combine information from different sources and infer upon that information in a decision process. In this scope, the present work presents the implementation of a probabilistic based framework for safety assessment of existing timber elements. This methodology combines information gathered in different scales and follows a probabilistic framework allowing for the structural assessment of existing timber elements with possibility of inference and updating of its mechanical properties, through Bayesian methods. The probabilistic based framework is based in four main steps: (i) scale of information; (ii) measurement data; (iii) probability assignment; and (iv) structural analysis. In this work, the proposed methodology is implemented in a case study. Data was obtained through a multi-scale experimental campaign made to old chestnut timber beams accounting correlations of non and semi-destructive tests with mechanical properties. Finally, different inference scenarios are discussed aiming at the characterization of the safety level of the elements.

Experimental and numerical approaches for structural assessment in new footbridge designs (SFRSCC–GFPR hybrid structure)

Within the civil engineering field, the use of the Finite Element Method has acquired a significant importance, since numerical simulations have been employed in a broad field, which encloses the design, analysis and prediction of the structural behaviour of constructions and infrastructures. Nevertheless, these mathematical simulations can only be useful if all the mechanical properties of the materials, boundary conditions and damages are properly modelled. Therefore, it is required not only experimental data (static and/or dynamic tests) to provide references parameters, but also robust calibration methods able to model damage or other special structural conditions. The present paper addresses the model calibration of a footbridge bridge tested with static loads and ambient vibrations. Damage assessment was also carried out based on a hybrid numerical procedure, which combines discrete damage functions with sets of piecewise linear damage functions. Results from the model calibration shows that the model reproduces with good accuracy the experimental behaviour of the bridge.

A bayesian approach for NDT data fusion: The Saint Torcato Church case study

This paper presents a methodology based on the Bayesian data fusion techniques applied to non-destructive and destructive tests for the structural assessment of historical constructions. The aim of the methodology is to reduce the uncertainties of the parameter estimation. The Young's modulus of granite stones was chosen as an example for the present paper. The methodology considers several levels of uncertainty since the parameters of interest are considered random variables with random moments. A new concept of Trust Factor was introduced to affect the uncertainty related to each test results, translated by their standard deviation, depending on the higher or lower reliability of each test to predict a certain parameter.

The economic assessment of health benefits of active transport

Purpose:This chapter addresses the economic assessment of health benefits of active transport and presents most recent valuation studies with an overview of progresses made towards the inclusion of health benefits in the cost-benefit analysis (CBA) of active transport. Methodology/approach: It is built upon the contracted study for the World Health Organization (WHO) on the economic appraisal of health benefits of walking and cycling investments at the city of Viana do Castelo, the former pilot study in Portugal for evaluating the health benefits of non-motorized transport using the WHO Health Economic Assessment Tool (HEAT). The relative risk values adopted in the HEAT for walking refer to adult population of the age group 20â 74 years and the assessment focus in on average physical activity/regular behaviour of groups of pedestrians and all-cause mortality health impacts. During the case study, it was developed and implemented a mobility survey which aimed to collect behavioural data before and after a street intervention in the historic centre. Findings: Most recent appraisal guidance of walking and cycling and health impact modelling studies reviewed confirm that further research is expected before a more comprehensive appraisal procedure can be adopted in Europe, able to integrate physical activity effects along with other health risks such as those related to road traffic injuries and exposure to air pollution. Social implications: The health benefits assessment of walking investments helped local decision-makers to progress towards sustainable mobility options in the city. Making the population aware of the potential health benefits of regular walking can encourage more people to uptake active transport as part of their daily activities. Originality/value: This study provides a useful review of the health benefits of active transport with a comprehensive analysis of valuation studies, presenting value-added information. It then reports a former assessment of the health effects of active transport in the Portuguese context (case study) using the state-of-the-art economic analysis tool (HEAT) of the World Health Organization which is believed to contribute to a paradigm shift in the transport policy and appraisal practice given the need of shaping future cities (and their citizens) for health through more investments in active transport.

Assessment of national parks affected by naturbanization processes in Southern Europe

This paper assesses land-use changes related to naturbanization processes on three biosphere reserves in Southern Europe. A comparative analysis has been done on the National Parks in Peneda-Ger^es in North Portugal, C_evennes in South France and Sierra Nevada in South Spain, using Corine Land Cover data from 1990 until 2006. Results indicate that the process of land-use intensification is taking place in the frame of naturbanization dynamics that could jeopardize the role of Protected Areas. Focusing on the trends faced by National Parks and their surrounding territories, the analysis demonstrates, both in quantitative and spatial terms, the intensification processes of land-use changes and how it is important to know them for coping with increasing threats. The article concludes that in the current context of increasing stresses, a broader focus on nature protection, encompassing the wider countryside, is needed if the initiatives for biodiversity protection are to be effective.

Rockburst laboratory tests database - Application of data mining techniques

Rockburst is characterized by a violent explosion of a block causing a sudden rupture in the rock and is quite common in deep tunnels. It is critical to understand the phenomenon of rockburst, focusing on the patterns of occurrence so these events can be avoided and/or managed saving costs and possibly lives. The failure mechanism of rockburst needs to be better understood. Laboratory experiments are undergoing at the Laboratory for Geomechanics and Deep Underground Engineering (SKLGDUE) of Beijing and the system is described. A large number of rockburst tests were performed and their information collected, stored in a database and analyzed. Data Mining (DM) techniques were applied to the database in order to develop predictive models for the rockburst maximum stress (σRB) and rockburst risk index (IRB) that need the results of such tests to be determined. With the developed models it is possible to predict these parameters with high accuracy levels using data from the rock mass and specific project.

Rapid assessment of fruit-color selection by birds using artificial fruits at local scale in Central Amazonia

Modeling clays have been used in several ecological experiments and have proved to be an important tool to variables control. The objective of our study was to determine if fruit color in isolated and grouped displays influences the fruit selection by birds in the field using artificial fruits. Data were collected in six plots distributed homogeneously in 3 km long trails with a minimum distance of 0.5 km. We used a paired experimental design to establish our experiments, so that all treatments were available to the local bird community in each plot. Overall, red was more pecked than brown and white. Isolated red and brown displays were significantly more pecked than others display. Even though our study was conducted in small spatial scales, artificial fruits appeared to be efficient in register fruit consumption attempts by bird. Although inconclusive about selective forces that sharp the dynamics of fruit color polymorphisms and choice by frugivorous birds, our findings corroborate recent studies wherein birds showed preferences by high- over low-contrast fruit signals.

Spatial-temporal modellization of the NO2 concentration data through geostatistical tools

The nitrogen dioxide is a primary pollutant, regarded for the estimation of the air quality index, whose excessive presence may cause significant environmental and health problems. In the current work, we suggest characterizing the evolution of NO2 levels, by using geostatisti- cal approaches that deal with both the space and time coordinates. To develop our proposal, a first exploratory analysis was carried out on daily values of the target variable, daily measured in Portugal from 2004 to 2012, which led to identify three influential covariates (type of site, environment and month of measurement). In a second step, appropriate geostatistical tools were applied to model the trend and the space-time variability, thus enabling us to use the kriging techniques for prediction, without requiring data from a dense monitoring network. This method- ology has valuable applications, as it can provide accurate assessment of the nitrogen dioxide concentrations at sites where either data have been lost or there is no monitoring station nearby.

Data quality in biofilm high-throughput routine analysis: intralaboratory protocol adaptation and experiment reproducibility

Biofilm research is growing more diverse and dependent on high-throughput technologies and the large-scale production of results aggravates data substantiation. In particular, it is often the case that experimental protocols are adapted to meet the needs of a particular laboratory and no statistical validation of the modified method is provided. This paper discusses the impact of intra-laboratory adaptation and non-rigorous documentation of experimental protocols on biofilm data interchange and validation. The case study is a non-standard, but widely used, workflow for Pseudomonas aeruginosa biofilm development, considering three analysis assays: the crystal violet (CV) assay for biomass quantification, the XTT assay for respiratory activity assessment, and the colony forming units (CFU) assay for determination of cell viability. The ruggedness of the protocol was assessed by introducing small changes in the biofilm growth conditions, which simulate minor protocol adaptations and non-rigorous protocol documentation. Results show that even minor variations in the biofilm growth conditions may affect the results considerably, and that the biofilm analysis assays lack repeatability. Intra-laboratory validation of non-standard protocols is found critical to ensure data quality and enable the comparison of results within and among laboratories.

Mercury and methylmercury concentration assessment in children's hair from Manaus, Amazonas state, Brazil

The present study evaluated Hg and MeHg content in hair samples of 201 children 2 to 7 years old, living in six neighborhoods of the city of Manaus, Amazonas State, Brazil. In general, the total Hg and MeHg median ranges in hair were similar (0.91 to 1.71 mg kg-1) except for the São Jose neighborhood, which was lower (0.16 mg kg-1). De spite the fact that the Manaus population consumes fish as part of the normal dietary intake, the Hg hair levels were below the level for an adult population not exposed to mercury (2.0 mg kg-1). These data were compared to demographic, socioeconomic information and eating habits of the families that took part in the study. The results were also compared to other published data from the Amazon region, other regions of Brazil and other countries. Future studies to set Hg and MeHg levels in hair of children in Brazil should take into account and assess the diversity of the country, mainly in terms of eating habits, socio-economic and cultural aspects.

Assessment of distinctive road runoff quality in coastal areas, based on a monitoring case study

High levels of marine salt deposition present in coastal areas have a relevant effect on road runoff characteristics. This study assesses this effect with the purpose of identifying the relationships between monitored water quality parameters and intrinsic site variables. To achieve this objective, an extensive monitoring program was conducted on a Portuguese coastal highway. The study included 30 rainfall events, in different weather, traffic, and salt deposition conditions. The evaluations of various water quality parameters were carried out in over 200 samples. In addition, the meteorological, hydrological, and traffic parameters were continuously measured. The salt deposition rates were determined by means of a wet candle device, which is an innovative feature of the monitoring program. The relation between road runoff pollutants and independent variables associated with weather, traffic, and salt deposition conditions was assessed. Significant correlations among pollutants were observed. A high salinity concentration and its influence on the road runoff were confirmed. Furthermore, the concentrations of the most relevant pollutants seemed to be very dependent on some meteorological variables, particularly the duration of the antecedent dry period prior to each rainfall event and the average wind speed.

An innovative framework for probabilistic-based structural assessment with an application to existing reinforced concrete structures

A novel framework for probabilistic-based structural assessment of existing structures, which combines model identification and reliability assessment procedures, considering in an objective way different sources of uncertainty, is presented in this paper. A short description of structural assessment applications, provided in literature, is initially given. Then, the developed model identification procedure, supported in a robust optimization algorithm, is presented. Special attention is given to both experimental and numerical errors, to be considered in this algorithm convergence criterion. An updated numerical model is obtained from this process. The reliability assessment procedure, which considers a probabilistic model for the structure in analysis, is then introduced, incorporating the results of the model identification procedure. The developed model is then updated, as new data is acquired, through a Bayesian inference algorithm, explicitly addressing statistical uncertainty. Finally, the developed framework is validated with a set of reinforced concrete beams, which were loaded up to failure in laboratory.

Assessment of the mechanical performance of recycled unbound materials for pavement subbase layers

The cyclic load triaxial test is a laboratory test that allows studying the mechanical behaviour of unbound granular materials used in base/subbase layers of road pavements. The resilient modulus and permanent strains are required as inputs in structural pavement design. This paper presents some results obtained for recycled materials (crushed concrete aggregate and blended crushed waste aggregate), with a view to promoting their use in pavement structures. Results relating to a reference material (limestone) are also presented, for comparison. All the test results discussed in this paper were obtained in variable cyclic radial pressure (VCP) tests. The tests performed (VCP) aim to study the influence of water content on the resilient modulus of recycled materials, as well as on the resistance to permanent deformation. Using the experimental data as a basis, further modelling work was carried out to establish the stresses developing in base/capping layers in typical Belgian road pavements. These numerical results allow to propose some simplifications of the stress paths applied in the testing procedures and to establish a new test protocol that also considers compaction during construction works. The results of this research work provide an excellent set of findings for the mechanical characterization of unbound base materials through the cyclic triaxial test, and contribute to a better understanding and correct application of recycled materials under geotechnical engineering background