22 research outputs found
Immunohistochemical Evaluation of the Expression of Specific Membrane Antigens in Patients with Pancreatic Ductal Adenocarcinoma
No full textPancreatic ductal adenocarcinoma (PDAC) is an increasing cause of cancer-related death, due to its biologic aggressiveness and the lack of effective treatments. The cell membrane plays a significant role in carcinogenesis, expressing components that mediate the interaction with the peritumoral environment. The aims of our study were to evaluate the expression of six membrane components (CA 19-9, mucin 1 and 4 (MUC1, MUC4), mesothelin (MSLN), Glypican-1 (GPC-1), and Annexin A10 (ANXA10)) on 50 surgical samples of patients with PDAC and correlate it with the oncologic outcomes. The expression was assessed using the histo-score (H-score), a quantitative method based on immunostaining, on tumoral and peritumoral tissues. CA 19-9 and MUC1 showed an intense expression on tumor cells and a lower expression on pancreatic acini and ducts. Moreover, a high intensity of CA 19-9 correlated with a worse prognosis. MUC4, MSLN, GPC-1, and ANXA10 were selectively expressed by PDAC cells and may be potential biomarkers of the disease.(1) Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. The lack of validated disease biomarkers makes timely diagnosis challenging in most cases. Cell membrane and surface proteins play a crucial role in several routes of oncogenesis. The aim of this study was to evaluate the expression of six membrane antigens on PDAC (CA 19-9, mucin 1 and 4 (MUC1, MUC4), mesothelin (MSLN), Annexin A10 (ANXA10), Glypican-1 (GPC-1)) and their correlation with oncologic outcomes. (2) Methods: Immunohistochemical staining for CA 19.9, MUC1, MUC4, MSLN, ANXA10, and GPC-1 of surgical samples of 50 consecutive patients with PDAC was performed. Antigen expression for tumor, ductal, and acinar tissues was classified according to the histo-score (H-score) by two pathologists. (3) Results: Recurrence rate was 47% and 18 patients (36%) deceased (median follow-up 21.5 months). Immunostaining for CA 19-9 and MUC1 showed a significantly higher expression in the neoplastic tissue compared to non-tumor ductal and acinar tissues (p < 0.001). MUC4, MSLN, ANXA10, and GPC-1 were selectively expressed in the neoplastic tissue (p < 0.001). A CA 19-9 H-score value >270 was independently associated with a worse overall survival (p = 0.05) and disease-free survival (p = 0.05). (4) Conclusions: CA 19-9 and MUC1 are highly expressed in PDAC cells. The histological expression of CA 19-9 may predict prognosis. MUC4, MSLN, ANXA10, and GPC-1 are selectively expressed by neoplastic tissue and may represent a potential histological biomarker of disease
Raphael and Pirro Ligorio — Historical and Philological Descriptions and Archaeological Studies of the Architecture of Ancient Rome in the 16th century
No full textThe difficulty of comprehending artistic terminology in the Renaissance was associated with
the activities of humanist philologists and scholarly antiquarians. Interest in antiquity was inherent in artists and architects. Around the archaeological work of Raphael, Ligorio, associations
of learned humanists were organized, which accompanied their archaeological research
with philological clarifications. The functions of archeology were combined with the need to
check the terms, with the help of a visual, graphically reconstructed monument, which, as a
rule, came down with losses. In this regard, scientists had to use their erudition and ingenuity
to display the ruined monument in its entirety. An example of such a field of activity is printed
graphics, which allows depicting monuments graphically and accompanying illustrations with
albums of antiquities, replicating images of individual works of art. Such was the direction
of the printing workshop of comrade Rafael Marcantonio Raimondi. A number of works by
Marcantonio, as well as engravings by Agostino Veneziano and Marco Dente, were made from
drawings by Raphael. Some of the drawings were related to Raphael’s archaeological interests,
such as the engraving of the Laocoön group (1519) by Marco Dente. Among philologists,
after the publication of P. Bembo’s treatise “Discourses in Prose on the Folk Language” (1525),
where in the second part of the treatise the author proposed to strictly follow the style of
Petrarch and Boccaccio, a controversy flared up about the literary language, as the humanists
held different points of view, to the term “volgare” (“folk”). Discussions on this topic were
reflected in the association of humanists “Accademia degli Sdegnati” (1541–1545), which was
joined by P. Ligorio, who, like Raphael, accompanied his studies with etymological clarifications,
graphic representations and archaeological maps
Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study)
No full textBackground: Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in severe COVID-19.
Methods: In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76).
Findings: Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% [95% CI 81-94] in arm A vs 85% [74-93], HR 1.07 [0.8-1.5] in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% [77-96] vs 79% [63-91], HR 1.55 [0.9-2.6]; log-rank p = 0.049) and in the strata with lymphocytes <870/mmc (90% [79-96]) vs (73% [55-89], HR 1.53 [0.9-2.7]; log-rank p = 0.058). Overall, 39/121 (32%) AEs were reported in arm A and 14/55 (23%) in B (p = 0.195), while serious AEs were 22/121 (18%) and 7/55 (11%), respectively (p = 0.244). There were no treatment-related deaths.
Interpretation: The efficacy of sarilumab in severe COVID-19 was not demonstrated both in the overall and in the stratified for severity analysis population. Exploratory analyses suggested that subsets of patients with lower CRP values or lower lymphocyte counts might have had benefit with sarilumab treatment, but this finding would require replication in other studies. The relatively low rate of concomitant corticosteroid use, could partially explain our results
Innovative method for damage identification and structural health monitoring based on vibration measurements
No full text[ITALIANO] Scopo della tesi è presentare una nuova metodologia, appartenente al campo dei Controlli Non Distruttivi, e basata su misure di vibrazioni, sviluppata dall’autore presso il Dipartimento di Progettazione Aeronautica dell’Università degli Studi di Napoli “Federico II”. Scopo della ricerca è stato sviluppare una tecnica di controllo non distruttivo che soddisfacesse la maggior parte dei requisiti necessari allo sviluppo di un sistema di Health Monitoring (monitoraggio dello stato di salute di una struttura), riducendo nel contempo la complessità sia dell’algoritmo di analisi dei dati sia della strumentazione necessaria per l’acquisizione degli stessi.
La tecnica proposta è basata sulla acquisizione e sul confronto delle Funzioni di Risposta in Frequenza (FRF) della struttura monitorata, prima e dopo che un qualsivoglia danno insorga. Per effetto di un danneggiamento strutturale si viene a modificare il comportamento dinamico della struttura in termini di massa, rigidezza e smorzamento, e, conseguentemente, si avrà una variazione delle Funzioni di Risposta in Frequenza relative alla struttura danneggiata rispetto a quelle ricavate dalla struttura integra. Il metodo è quindi in grado di rilevare l’insorgere di un danneggiamento (identificazione), localizzarne la posizione (individuazione), ed indicarne l’eventuale accrescimento e propagazione (quantificazione). Ai fini della valutazione quantitativa della variazione tra le Funzioni di Risposta in Frequenza della struttura integra e di quella danneggiata è stato definito un indice detto “del danno”, il quale fornisce direttamente la misura dell’eventuale presenza del danneggiamento strutturale.
La sopra citata metodologia è stata applicata su di un pannello reale di fusoliera di un MD11, su di un pannello realizzato in materiale composito di tipo aeronautico, e su di un velivolo ATR-72.
È stato sviluppato inoltre un algoritmo di Reti Neurali al fine di ottenere un metodo di apprendimento basato sulla ricognizione. Questa tecnica di apprendimento consente di addestrare la rete neurale rendendola in grado di riconoscere solo gli esempi “positivi”, scartando, di conseguenza, quelli “negativi”. Nell’ambito di un controllo non distruttivo di una struttura un esempio “positivo” rappresenta uno stato di “salute” del componente strutturale analizzato, e, ovviamente, un esempio “negativo” rappresenta uno stato “danneggiato” dello stesso. Sulla base di questo obiettivo le reti neurali sono state addestrate facendo uso delle stesse FRF, relative alle strutture “sane”, impiegate per la determinazione degli Indici del Danno.
Con riferimento al danno: corrosione, danneggiamento di rivetti di collegamento, cricche, impatti su strutture ed altre tipologie di danneggiamenti sono stati indotti sugli articoli di prova.
Relativamente al sistema di eccitazione e sensoristica, dispositivi magnetostrittivi sono stati impiegati quali attuatori, e piastrine piezoceramiche in qualità di attuatori e sensori. Inoltre è stato impiegato, per l’acquisizione delle FRF, anche un sistema di vibrometria laser a scansione. Queste tecniche consentiranno lo sviluppo di un sistema di Health Monitoring automatico in grado di identificare danni strutturali in tempo reale, aumentando l’affidabilità strutturale e riducendo i costi di manutenzione. / [ENGLISH] The purpose of the thesis is to present an innovative application within the Non Destructive Testing field based upon vibration measurements developed by the author at the Department of Aeronautical Engineering of the University of Naples “Federico II” (Italy). The aim of the research has been to develop a Non Destructive Test (NDT) which meets most of the mandatory requirements for effective health monitoring systems while, at the same time, reducing as much as possible the complexity of the data analysis algorithm and the experimental acquisition instrumentation.
This proposed new method is based upon the acquisition and comparison of the Frequency Response Functions (FRFs) of the monitored structure before and after a damage occurs. Structural damage modifies the dynamic behaviour of a structure affecting its mass, stiffness and damping and consequently the FRFs of a damaged structure, when compared with the FRFs of a sound structure, makes the identification, localization and quantification of structural damage possible.
The activities presented in this thesis focus mainly on a new FRFs processing technique based upon the determination of a representative “Damage Index” for identifying and analysing damage on real-scale aeronautical structural components, such as large-scale fuselage reinforced panels, on aeronautical composite panels and on a real ATR-72 aircraft.
Furthermore, a dedicated neural network algorithm has been elaborated aimed at obtaining a “recognition-based learning” method. This kind of learning methodology permits us to train the neural network in order to enable it to recognise only “positive” examples and consequently discarding “negative” ones. Within the structural NDT a “positive” example means a “healthy” state of the analysed structural component and, obviously, a “negative” example means a “damaged” or perturbed state. With this objective in mind the neural network has been trained to make use of the same FRFs of the healthy structure used in determining the Damage Index.
Regarding damage, corrosion, failure of linking rivets, simple cracks, impacts on structure and other kind of damage have been induced on the test articles.
From an architectural standpoint, magnetostrictive devices have been tested as actuators, and piezoceramic patches as actuators and sensors. Besides it has been used a laser-scanning vibrometer system to acquire the FRFs. These techniques promise to bring us a step forward in the implementation of an automatic “health monitoring” system which will be able to identify structural damage in real time thereby improving safety and reducing maintenance costs
The theory of eucharistic presence in the early Caroline divines, examined in its European theological setting
No full textThe question of Christ's presence in the eucharist was an issue
which caused great controversy in the Reformation period, and which
continued to evoke dispute during the seventeenth century. Various
interpretations of the Caroline divines' teaching on the eucharistic
presence have been offered, but often they seem either to indicate the
theological position of the writer rather than that of the theologians
considered, or to ignore the broader context of eucharistic doctrine.
The purpose of this study, therefore, was 1. to investigate the
theology of eucharistic presence in the thinking of several seventeenth-century
Anglican divines, and 2. to examine their teaching in relation
to the sixteenth-century Anglican heritage and the various continental
sacramental doctrines, Reformed, Lutheran, Roman Catholic and Eastern
Orthodox.
To accomplish this goal, eight theologians were chosen for examination:
Adrianus Saravia, Lancelot Andrewes, John Cosin, Richard
Montague, William Forbes, William Laud, Jeremy Taylor and Herbert
Thorndike. When available, nineteenth-century editions of their works
were used; otherwise, seventeenth-century texts were employed.
Similarly, modern editions of Roman, Orthodox, Lutheran and Reformed
writings were utilized when possible. Thy examination of eucharistic
teaching included seven major points: 1. the sacrament as mystery,
2. eucharistic change, 3. the relationship between Christ's body and
the bread, 4. eucharistic communion, 5. the nature of Christ's body in
the sacrament, 6. consecration, and 7. adoration in the eucharist.
This study has shown that there was great diversity in the
thinking of the Caroline divines (although they did not treat the
subject of eucharistic presence with equal detail or depth); no
unified understanding of sacramental presence was expressed. Reformed
ideas inherited from the previous century remained strong, but new
tendencies toward other understandings of the eucharist can be
discerned. The period, therefore, can be seen to represent a new
stage in the history of Anglican eucharistic doctrine
Diversidad y análisis biogegráfico del género Ulmeritoides TRAVER, 1959 (Ephemeroptera; Leptophlebiidae) en Colombia
No full textLa presente investigación devela patrones de distribución biogeográfica locales y generales, además de estimar la diversidad ecorregional del género Ulmeritoides en zonas del Dominio Pacífico y Boreal Brasileño, principalmente en el territorio colombiano, a partir de modelamientos de nicho y distribución potencial; dando como resultado modelos para la mayoría de especies descritas, entre los que se destacan los modelos de U. guanacaste, U. haarupi y U. acosa, por presentar mayor capacidad predictora; adicional, se identificaron tres morfoespecies diferentes a las especies reportadas para el país, las cuales, comparten características morfológicas con las reportada en Centro América, permitiendo definir a la población colectada en parte de la cuenca del Magdalena medio y bajo como posible especie nueva.Proyecto Semilla, Facultad de Ciencias, Universidad de los AndesMaestríaBiogeografíaTaxonomí
SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
No full textVariability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types. © 2021 The Author(s
Engendering agricultural research
No full textThis paper makes a case for gender equity in the agricultural R&D system. It reviews the evidence on exactly why it is important to pay attention to gender issues in agriculture and why it is necessary to recognize women�s distinct food-security roles throughout the entire value chain�for both food and nonfood crops, marketed and nonmarketed commodities. The authors examine whether women are factored into the work of research institutions, and whether research institutions effectively focus on women�s needs. In short, are these institutions conducting research by and for women? The paper�s conceptual framework demonstrates the need to integrate gender into setting agricultural priorities; conducting the research itself; designing, implementing, and adopting extension services; and evaluating their impacts. It concludes with recommendations regarding how to make these suggested changes.Agriculture, extension services, Gender equity, nonmarket commodities, Priority setting, R&D, value chains,
Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study)
No full textBackground Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in severe COVID-19.Methods In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76).Findings Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% [95% CI 81-94] in arm A vs 85% [74-93], HR 1.07 [0.8-1.5] in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% [77-96] vs 79% [63-91], HR 1.55 [0.9-2.6]; log-rank p = 0.049) and in the strata with lymphocytes <870/mmc (90% [79-96]) vs (73% [55-89], HR 1.53 [0.9-2.7]; log-rank p = 0.058). Overall, 39/121 (32%) AEs were reported in arm A and 14/55 (23%) in B (p = 0.195), while serious AEs were 22/121 (18%) and 7/55 (11%), respectively (p = 0.244). There were no treatment-related deaths.Interpretation The efficacy of sarilumab in severe COVID-19 was not demonstrated both in the overall and in the stratified for severity analysis population. Exploratory analyses suggested that subsets of patients with lower CRP values or lower lymphocyte counts might have had benefit with sarilumab treatment, but this finding would require replication in other studies. The relatively low rate of concomitant corticosteroid use, could partially explain our results.Funding This study was supported by INMI "Lazzaro Spallanzani" Ricerca Corrente Linea 1 on emerging and ree-merging infections, funded by Italian Ministry of Health.Copyright (c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
A review of empirical evidence on gender differences in nonland agricultural inputs, technology, and services in developing countries
No full textThis paper reviews existing microeconomic empirical literature on gender differences in use, access, and adoption of nonland agricultural inputs in developing countries. This review focuses on four key areas: (1) technological resources, (2) natural resources, (3) human resources, and (4) social and political capital. In general, there has been more empirical research on inorganic fertilizer, seed varieties, extension services, and group membership than on tools and mechanization, life-cycle effects, and political participation. Across input areas, generally men have higher input measures than women; however, this finding is often sensitive to the use of models that control for other background factors, as well as the type of gender indicator implemented in the analysis. We find few studies that meet our inclusion criteria outside Sub-Saharan Africa. Finally, future directions, opportunities, and recommendations for microeconomic gender analysis of nonland agricultural inputs are discussed.access to farm inputs, Agricultural inputs, Agriculture, assets, Developing countries, Gender, life-cycle effects, mechanization, Women,
