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    Valutazione dei fattori di rischio precoci di patologia cerebrale nel neonato prematuro: fattori perinatali e nuovi biomarkers su liquido amniotico e amnion

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    Background. La nascita pretermine si accompagna ad un aumentato rischio di sviluppare un danno neurologico, che può presentarsi con diversi quadri patologici, in relazione all’entità del danno e all’età gestazionale del neonato. L’identificazione precoce dei fattori di rischio di danno neurologico nella popolazione dei nati prematuri è di fondamentale importanza per migliorare l’assistenza al neonato sia durante il ricovero in Terapia Intensiva Neonatale, sia per guidare e personalizzare il follow-up post-dimissione. Mentre diversi studi hanno evidenziato un significativo ruolo dei fattori postnatali precoci sullo sviluppo di tali lesioni, il ruolo dell’ambiente intrauterino e della patologia placentare sullo sviluppo di tali lesioni non è ancora stato del tutto chiarito. L’analisi istologica placentare può fornire indicazioni preziose circa la possibile eziopatogenesi delle lesioni cerebrali neonatali e, nella sua componente fetale, rappresenta un ottimo tessuto di partenza per l’identificazione di nuovi biomarker. Metodi. Lo studio, che ha interessato 289 neonati pretermine < 32 settimane gestazionali ricoverati alla nascita presso la U.O. Terapia Intensiva Neonatale tra gennaio 2012 e ottobre 2017, ha valutato il ruolo di numerosi fattori di rischio perinatali sullo sviluppo di lesioni cerebrali della prematurità (emorragia intraventricolare, emorragia cerebellare, lesioni della sostanza bianca), diagnosticate mediante RM al termine di età corretta. È stata inoltre effettuata la ricerca di un’associazione tra tali lesioni e le caratteristiche istopatologiche placentari, rivalutate secondo la recente classificazione di Amsterdam. Inoltre, su un sottogruppo di tali soggetti è stata eseguita l’analisi proteomica con spettrometria di massa del liquido amniotico e dell’amnion prelevati alla nascita, analizzata tramite Weight Gene Co-expression Network Analysis (WGCNA). Per l’analisi statistica dei fattori di rischio è stata effettuata una analisi descrittiva dei dati mediante l’utilizzo del t test di Student per le variabili continue e il test χ2 o il Fisher's exact test per le variabili categoriche. È stata inoltre effettuata una analisi univariata dei fattori considerati e successivamente multivariata considerando unicamente le variabili statisticamente significative o borderline all’analisi univariata. Risultati. Lo studio ha evidenziato una significativa correlazione tra lesioni cerebrali e alcune caratteristiche perinatali, confermando le osservazioni di studi precedenti (presenza di emorragia cerebellare [OR: 8.14], ventilazione meccanica nelle prime 72 ore [OR: 2.67] e pervietà del dotto di Botallo trattata farmacologicamente [OR: 2.6]. Dopo correzione per l’età gestazionale, uno dei fattori di rischio indipendenti più importanti nel determinare il rischio neurologico, e nello specifico, di emorragia intraventricolare è risultata essere la corioamnionite coinvolgente il versante materno di stadio 1 [OR: 2.92] e stadio 3 [OR: 4], mentre non emersa alcuna correlazione tra reperti placentari e altre lesioni cerebrali. Dallo studio di proteomica è emerso un pattern di co-espressione proteica caratteristico in caso di corioamnionite interessante il versante fetale della placenta [ME brown: indice di Pearson 0.9; p < 0.05]. L’identificazione delle componenti proteiche presenti in tale pool potrebbe portare all’identificazione di uno o più nuovi marker di corioamnionite che dosato nel sangue neonatale, o possibilmente, in quello materno potrebbe essere utilizzato per guidare una precoce valutazione del rischio di lesione cerebrale nel neonato pretermine. Conclusioni. Dalla combinazione di entrambi gli studi emerge la evidente complessità del quadro di infiammazione della diade madre/feto che consta della corioamnionite istologica (solo di recente definita) e della meno oggettivabile, addirittura se non solo sospetta, corioamnionite clinica (febbre materna). Il fattore più importante per capire il coinvolgimento del futuro neonato, del suo essere più o meno “pre-condizionato” dallo stato materno, più o meno prono a sviluppare patologie neonatali, è la presenza di FIRS (Fetal Inflammatory Response Syndrome) che è verosimile debba prevedere l’infiammazione della membrana amniotica e presentare valori di proteomica significativamente alterati sul versante fetale a dimostrazione del coinvolgimento di questa componente. Rimane indiscutibile la multifattorialità delle lesioni cerebrali ed il preponderante ruolo dell’età gestazionale nella loro insorgenza. Tali osservazioni, insieme alla doverosa continua ricerca di biomarker plausibili come il nostro studio ha cercato di dimostrare, sottolineano l’importanza della ottimizzazione del timing del parto prematuro, nel quale il bilancio tra rischi di una nascita troppo pretermine ed i benefici dall’escludere il feto/neonato da un ambiente ostile, quale quello gravidico in corso di infiammazione, vanno ponderati con estrema accortezza.Background. Preterm birth is associated with an increased risk of brain injuries, which may present with a broad spectrum of clinical features, depending on the severity and the gestational age. The early identification of risk factors for neurological damage in the preterm population is important to improve the perinatal care and to guide the subsequent follow-up. While several studies have highlighted a significant role of early postnatal factors on the development of these lesions, the possible role of the intrauterine environment and the placental pathology has not yet been fully clarified. Placental histological analysis can provide valuable information on the etiopathogenesis of neonatal brain lesions and, in its fetal component, it represents an valuable tissue for the identification of new biomarkers. Methods. The study, which involved 289 preterm infants <32 gestational weeks admitted at birth at our Neonatal Intensive Care Unit between January 2012 and October 2017, evaluated the role of numerous perinatal risk factors on the development of brain lesions of prematurity (intraventricular haemorrhage, cerebellar haemorrhage, white matter lesions), diagnosed by MRI at corrected age. A research project was also carried out to find an association between these lesions and placental histopathological characteristics, re-evaluated according to the recent Amsterdam classification. Furthermore, proteomic analysis with mass spectrometry of the amniotic fluid and amnion was performed on a subgroup of these subjects, analyzed by Weight Gene Co-expression Network Analysis (WGCNA). For the statistical analysis of risk factors, a descriptive analysis of the data was carried out using the Student's t test for continuous variables and the χ2 test or Fisher's exact test for categorical variables. A univariate analysis of the factors considered and subsequently multivariate was also carried out considering only the statistically significant or borderline variables in the univariate analysis. Results. The study highlighted a significant correlation between brain lesions and some perinatal characteristics, confirming the observations of previous studies (presence of cerebellar hemorrhage [OR: 8.14], mechanical ventilation in the first 72 hours [OR: 2.67] and patency of the Botallo duct treated pharmacologically [OR: 2.6]. After correction for gestational age, one of the most important independent risk factors in determining the neurological risk, and specifically, of intraventricular hemorrhage, was stage 1 chorioamnionitis involving the maternal side [OR : 2.92] and stage 3 [OR: 4], while no correlation emerged between placental findings and other brain lesions. The proteomics study revealed a pattern of protein co-expression characteristic in case of chorioamnionitis involving the fetal side of the placenta [ ME brown: Pearson index 0.9; p <0.05] The identification of the protein components present in this pool could b lead to the identification of one or more new markers of chorioamnionitis which, when measured in neonatal blood, or possibly, in maternal blood, could be used to guide an early assessment of the risk of brain injury in the preterm infant. Conclusions. The hystopatogenesis of the inflammation of the mother / fetus dyad consisting of histological chorioamnionitis (only recently defined) and the less objectified, often only suspected, clinical chorioamnionitis (maternal fever) is complex. The most important factor to understand the involvement of the future newborn, of his being more or less "pre-conditioned" by the maternal state, more or less prone to developing neonatal brain complications, is the presence of FIRS (Fetal Inflammatory Response Syndrome) which shows significantly altered proteomic values on the fetal side. The multifactoriality of brain lesions and the preponderant role of gestational age in their onset remains indisputable. These observations, together with the necessary continuous search for plausible biomarkers as our study tried to demonstrate, underline the importance of optimizing the timing of premature birth, in which the balance between the risks of a preterm birth and the benefits of excluding the fetus / newborn from a hostile environment, such as that of pregnancy in the course of inflammation, must be weighed with extreme caution

    Ceramic membrane filtration of organic compounds: effect of concentration, pH, and mixtures interactions on fouling

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    A comparative assessment of iron oxide ceramic ultrafiltration membranes fouling by model organic compounds was performed. To characterize this fouling phenomenon, humic acid (HA), bovine serum albumin (BSA) and sodium alginate (SA) were used as models of humic substances, proteins and polysaccharides respectively. Clean and fouled iron oxide membranes surfaces were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The influence of concentration, foulant mixtures and pH on the fouling mechanism was investigated. Fouling was observed to depend first on foulant–membrane interactions, followed by a second step where membrane material plays a less important role. Membrane surface chemistry and solution pH were significant factors affecting irreversibility of the fouling layer. A strong dependence was observed in foulant concentration and solution pH. Foulant mixtures showed synergetic results, determined by foulant–foulant interactions.Fil: De Angelis, Laura. Instituto Tecnológico de Buenos Aires. Departamento de Ingeniería Química; ArgentinaFil: Fidalgo, María Marta. Instituto Tecnológico de Buenos Aires. Departamento de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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