Detection of outliers in multivariate data: a method based on clustering and robust estimators

Outlier identification is important in many applications of multivariate analysis. Either because there is some specific interest in finding anomalous observations or as a pre-processing task before the application of some multivariate method, in order to preserve the results from possible harmful effects of those observations. It is also of great interest in supervised classification (or discriminant analysis) if, when predicting group membership, one wants to have the possibility of labelling an observation as does not belong to any of the available groups. The identification of outliers in multivariate data is usually based on Mahalanobis distance. The use of robust estimates of the mean and the covariance matrix is advised in order to avoid the masking effect (Rousseeuw and Leroy, 1985; Rousseeuw and von Zomeren, 1990; Rocke and Woodruff, 1996; Becker and Gather, 1999). However, the performance of these rules is still highly dependent of multivariate normality of the bulk of the data. The aim of the method here described is to remove this dependence

Análise dos Alertas Sobre os Dispositivos Médicos Emitidos pela Agência Portuguesa do Medicamento: Delineando o Propósito de Novas Recomendações Regulatórias

Introduction: Medical devices are healthcare technologies with a significantly growing market worldwide. This study aims to analyze medical device alerts issued by the Portuguese Medicines Agency, INFARMED, I.P. during 2017, as well as to identify the respective regulatory actions and to suggest additional recommendations. Material and Methods: All alerts on medical device alerts publicly available in the website of INFARMED, I.P. were identified and analyzed, including actions taken. Additionally, reports on medical devices from the Portuguese national competent authorities were compared with reports from other European Union member states such as Germany. Results: A total of 32 safety alerts were identified: 18 (56%) related with devices without identified records of commercialization in Portugal, six (19%) related with devices voluntarily withdrawn from the market, such as counterfeit products, and eight (25%) categorized as ‘other’. In both Portugal and Germany, 0.28 and 4.53 reports of national competent authorities per million inhabitants were identified, respectively. Diverse regulatory actions were taken, such as six compulsory indications to not acquire or use devices. Discussion: Considering that the European Union is an open market where citizens should have equal access to medical devices, the Portuguese system of medical device safety alerts seems to be functioning normally. The identified safety alerts seemed relevant, with Portugal registering a proportionally slightly lower number of alerts when compared with higher sales volume markets, which may be explained by an underreporting of this type of problems. Further studies are needed to confirm these preliminary results, although the development of databases comprising data on patients using medical devices is recommended in order to generate automatic email and text message alerts. Conclusion: A limited number of safety alerts on medical devices was identified in Portugal, with few reported cases of counterfeit or falsified devices. The Portuguese Medicines Agency contributes to the citizens’ access to quality medical devices, by issuing safety alerts, recommendations and mandatory market withdrawals for unsuitable or unsafe medical devices.Fundação para a Ciência e a Tecnologia (FCT) project UID/DTP/04567/2016.info:eu-repo/semantics/publishedVersio

Climate change impact on the Portuguese exposure to aflatoxins

As alterações climáticas têm sido identificadas como um fator determinante para a segurança dos alimentos consumidos em todo o mundo. As micotoxinas, contaminantes alimentares produzidos por fungos, são habitualmente identificadas como um dos principais perigos neste contexto. As aflatoxinas assumem particular relevo, face à sua toxicidade aguda e crónica. A região do Mediterrâneo, incluindo Portugal, tem sido considerada uma região particularmente vulnerável às consequências das alterações climáticas. O presente estudo pretende estimar o impacto na saúde da exposição a aflatoxinas em Portugal e discutir a potencial influência das alterações climáticas no risco para a saúde associado a esta exposição. Para estimar o número de casos de carcinoma hepatocelular associados à exposição a aflatoxinas, foi determinada a fração atribuível da população. Para estimar o impacto da exposição a aflatoxinas na saúde dos Portugueses, a carga de doença foi determinada aplicando-se o conceito de anos de vida ajustados por incapacidade (DALY). É expectável que no futuro, em consequência das alterações climáticas, o número de DALYs bem como do número de casos de carcinoma hepatocelular aumente. A quantificação do impacto na saúde da exposição a aflatoxinas em cenário de alterações climáticas reveste-se de particular importância, em especial para o desenvolvimento de políticas e medidas preventivas que possam proteger a população.Climate change has been indicated as a driver for food safety issues worldwide, mainly due to the impact on the occurrence of food safety hazards at various stages of food chain. Mycotoxins, natural contaminants produced by fungi, are among the most important of such hazards. Aflatoxins, which have the highest acute and chronic toxicity of all mycotoxins, assume particular importance. Mediterranean region, including Portugal, was considered a climate change hotspot. The present study aims to estimate the health impact of aflatoxins exposure in Portugal and to discuss the potential influence of climate change on the health risk associated to this exposure. A population attributable fraction was determined to estimate the number of extra cases of hepatocellular carcinoma (HCC) associated to the Portuguese aflatoxin exposure, and the Disability Adjusted Life Years (DALYs) were derived to estimate the associated burden of disease. It is expected that in the future the number of DALYs and the associated cases of HCC due to aflatoxins exposure will increase due to climate change. The quantification of the health impact associated with exposure to aflatoxins in climate change scenarios presents particular importance, especially for the development of politics and preventive measures to protect human population.info:eu-repo/semantics/publishedVersio

An Insight into the Release Kinetics

The authors acknowledge the financial support from Fundação para a Ciência e a Tecnologia (FCT-MEC), Portugal, through the dedicated project (PTDC/EDM-EDM/30828/2017) (BeLive) Publisher Copyright: © 2023 by the authors.This work explores the unique features of magnetic-responsive hydrogels to obtain liposomal hydrogel delivery platforms capable of precise magnetically modulated drug release based on the mechanical responses of these hydrogels when exposed to an external magnetic field. Magnetic-responsive liposomal hydrogel delivery systems were prepared by encapsulation of 1,2-dipalmitoyl-sn-glycero-3-phosphocoline (DPPC) multilayered vesicles (MLVs) loaded with ferulic acid (FA), i.e., DPPC:FA liposomes, into gelatin hydrogel membranes containing dispersed iron oxide nanoparticles (MNPs), i.e., magnetic-responsive gelatin. The FA release mechanisms and kinetics from magnetic-responsive liposomal gelatin were studied and compared with those obtained with conventional drug delivery systems, e.g., free liposomal suspensions and hydrogel matrices, to access the effect of liposome entrapment and magnetic field on FA delivery. FA release from liposomal gelatin membranes was well described by the Korsmeyer–Peppas model, indicating that FA release occurred under a controlled diffusional regime, with or without magnetic stimulation. DPPC:FA liposomal gelatin systems provided smoother controlled FA release, relative to that obtained with the liposome suspensions and with the hydrogel platforms, suggesting the promising application of liposomal hydrogel systems in longer-term therapeutics. The magnetic field, with low intensity (0.08 T), was found to stimulate the FA release from magnetic-responsive liposomal gelatin systems, increasing the release rates while shifting the FA release to a quasi-Fickian mechanism. The magnetic-responsive liposomal hydrogels developed in this work offer the possibility to magnetically activate drug release from these liposomal platforms based on a non-thermal related delivery strategy, paving the way for the development of novel and more efficient applications of MLVs and liposomal delivery systems in biomedicine.publishersversionpublishe

Biology of the iberian chub (Squalius carolitertii) in an atlantic-type stream (river Lima basin-north Portugal). A preliminary approach

The iberian chub (Squalius carolitertii) is an endemic species whose biology is yet largely unknown and which is catalogued as being endangered. Therefore more information about its biology is essential to develop appropriate management strategies. The Estorâos River population has been studied from December 1995 to March 2002 through regular electro-fishing surveys. Additionally, a fish trap installed in the river from November 2001 to July 2002 allowed for the collection of information on population movements and reproduction. The results revealed some fluctuations in the density estimates, though the Squalius carolitertii population in the Estorâos River is quite low. Six age classes (0+ to 5+) were identified. Iberian chub growth is isometric and can reach a final length of 33.5 cm. Sexual dimorphism is evident, with males maturing earlier and at smaller sizes. An increase of the Iberian chub movements was detected from middle April onwards. These movements were related to the beginning of the reproductive period and were mainly correlated with the rise of water temperature. Our results indicate that the population characteristics do not differ substantially from those of other endemic chub populations in the Iberic peninsula.El bordallo (Squalius carolitertii) es una especie cuya biología es en gran parte desconocida y que está catalogada en peligro de extinción. El estudio de su biología es importante para la gestión de sus poblaciones y de su hábitat. La población del río Estorâos (Cuenca del río Límia) ha sido estudiada de Diciembre de 1995 a Marzo de 2002 mediante muestreos con pesca eléctrica. Un sistema de redes utilizado de Noviembre de 2001 a Julio de 2002 permitió la obtención de información sobre los movimientos y parámetros reproductivos de la población. Los datos indican fluctuaciones de la densidad, a pesar de la población presentar valores muy bajos. Seis clases de edad (0+ a 5+) han sido identificadas. El crecimiento de Squalius carolitertii es isométrico y puede llegar a una talla final de 33,5 cm. El dimorfismo sexual es evidente y los machos maduran más temprano y con tallas inferiores a de las hembras. Un creciente de movimientos del bordallo ha sido encontrado a mediados del mes de Abril, lo que está de acuerdo con la fecha del período reproductivo y también con el incremento de la temperatura del agua. Nuestros datos indican que esta población no es muy distinta de otras poblaciones de bordallos endémicos de la península Ibérica

Antioxidant activity of protein hydrolysates obtained from discarded Mediterranean fish species

In this study, five discarded species in the Mediterranean Sea, namely sardine, horse mackerel, axillary seabream, bogue and small-spotted catshark, were evaluated as raw material for obtaining fish protein hydrolysates exhibiting antioxidant activity. The DH of the hydrolysates ranged from 13.2 to 21.0%, with a protein content varying from 60.7 to 89.5%. The peptide profile of all hydrolysates was very similar, except for the hydrolysate of small-spotted catshark. Their lipid content was found to be between 4.6 and 25.3%. The highest DPPH scavenging activity was found for the hydrolysates of sardine and horse mackerel with EC50 values varying from 0.91 to 1.78 mg protein/mL. Sardine and small-spotted catshark hydrolysates exhibited the highest ferrous chelating activity with an EC50 value of 0.32 mg protein/mL. Moreover, sardine and bogue hydrolysates presented the highest reducing power. Finally, a total of six antioxidant peptides were theoretically identified within the structure of myosin and actin proteins from sardine and small-spotted catshark. The potential antioxidant activity exhibited by the hydrolysates suggests that it is feasible to obtain added-value products such as natural antioxidants from these discarded species.This work was supported by the Spanish National Plan I + D + i (projects CTQ2008-02978 and CTQ2011-23009) and by Santander Bank (grant for young researchers

Gellan gum-based hydrogels support the recreation of the dermal papilla microenvironment

The dermal papilla (DP), a specialized compartment within the hair follicle, regulates hair growth. However, human DP cells rapidly lose their inductivity in 2D-culture given the loss of positional and microenvironmental cues. Spheroids have been capable of recreating the 3D intercellular organization of DP cells, however, DP cell-matrix interactions are poorly represented. Considering the specific nature of the DP's extracellular matrix (ECM), we functionalized gellan gum (GG) with collagen IV-(HepIII) or fibronectin-(cRGDfC) derived peptide sequences to generate a 3D environment in which the phenotype and physiological functions of DP cells are restored. We further tuned the stiffness of the microenvironments by varying GG amount. Biomimetic peptides in stiffer hydrogels promoted the adhesion of DP cells, while each peptide and amount of polymer independently influenced the type and quantity of ECM proteins deposited. Furthermore, although peptides did not seem to have an influence, stiffer hydrogels improved the inductive capacity of DP cells after short term culture. Interestingly, independently of the peptide, these hydrogels supported the recapitulation of basic hair morphogenesis-like events when incorporated in an organotypic human skin in vitro model. Our work demonstrates that tailored GG hydrogels support the generation of a microenvironment in which both cell-ECM and cell-cell interactions positively influence DP cells towards the creation of an artificial DP.Authors would like to acknowledge the financial support from the Consolidator Grant “ECM_INK” (ERC-2016-COG-726061) and from FCT/MCTES (Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior) through the PD/59/2013, PD/BD/113800/2015 (Carla Abreu), PD/169/2013 (Manuela Lago) and IF/00945/2014 (Alexandra Marques) grants. The authors also appreciate the support given by the FSE/POCH (Fundo Social Europeu through the Programa Operacional do Capital Humano) under the scope of the NORTE-08-5369-FSE-000037 grant (Manuela Lago)