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We examined miRNA biomarkers for ALS extracted from extracellular vesicles in blood samples using a large and diverse patient and control population. Different blood collection and storage protocols by different investigators could impact repeatability of miRNA analysis. We tested the hypotheses that miRNA extracted from extracellular vesicles using immunoaffinity purification techniques are robust and repeatable across investigators, laboratories and in a broad ALS population.De-identified patient blood plasma samples obtained from the U.S. National ALS Biorepository were compared with plasma from non-ALS controls. Extracellular vesicles were extracted and isolated using L1CAM immunoaffinity purification. Total RNA was extracted, and miRNA quantified using qPCR following careful quality control measures. Gene fold expressions of eight miRNAs were compared using a Mann-Whitney two-tailed test.One hundred blinded, blood plasma samples were analyzed. Thirty-five men and 15 women with ALS were compared with controls consisting of 30 men and 20 women. None of the ALS patient cohort reported family members with ALS suggesting sporadic ALS. Five of the eight biomarkers previously published were found to significantly discriminate ALS patient samples from control samples.The methods used in this study provide a repeatable measure of miRNA biomarkers that statistically differentiate ALS patient samples from control samples. The broad inclusion criteria for both the ALS patient cohort and controls along with the collection of blood samples by different investigators suggest that these methods are robust and represent good candidates for further research and development aimed at clinical application.

Le 30 août 1481, Cristoforo Landino présentait à la population de Florence une édition de la Divine Comédie, imprimée dans la ville natale du poète. Ce n’était pas le premier tirage de l’oeuvre; mais cette première édition florentine se distinguait nettement des exemplaires précédents. Pour la ville de Florence, l’ouvrage remplissait une triple fonction : il témoignait de la maîtrise, voire de la suprématie, des Florentins dans le domaine de l’impression, il marquait le rapatriement symbolique du poète et de son oeuvre et soulignait les mérites du vernaculaire toscan comme langue littéraire. Cependant cette “ré-inscription” de l’oeuvre se heurtait à la longue histoire visuelle, textuelle et orale du poème : le vernaculaire de la Comédie avait engendré un grand nombre de légendes et de mythes qui liaient l’oeuvre à un public de lecteurs et d’auditeurs ignorants et illettrés. Pour faire de la Divine Comédie un poème savant et proprement florentin, les éditeurs avaient fait appel à toute une gamme de stratégies textuelles, visuelles et typographiques : les “Commenti” de Ficino et de Landino, un format in-folio propre aux livres savants, des caractères “humanistes” et dix-neuf illustrations dont la structure visuelle était connue de l’élite florentine. Raffinées structurellement et très détaillées, les images permettaient à chacun des lecteurs de reconstruire individuellement les épisodes du poème, d’une manière qui correspondait étroitement aux pratiques de lecture des humanistes et des élites toscans.

When the tomb of Cangrande della Scala (d. 1329), ruler of Verona, was opened in 1921, it was found to contain an array of silks from Central Asia. These textiles are a reminder of the important links between the Veneto and Eurasian trade around 1300 - l’eta di Marco Polo. With the rise of the interconnected Mongol states from the mid-thirteenth century, Venice became a gateway between Europe and the Asian world: people and ideas, as well as materials and objects of value, moved as both commodities and gifts. This essay explores some of the ways that Mongol Eurasia penetrated the collective imagination and material culture of the fourteenth-century Veneto. The goal is to think about the larger context and implications of these links, and Venice’s function within them. What emerges is less a fascination with the exotic than an inclination to absorb new images, stories, materials, and objects into the native cultural models.

African American (AA) women experience higher rates of maternal morbidity and mortality compared to US women of other racial/ ethnic groups. Cardiometabolic complications of pregnancy (including gestational diabetes, gestational hypertension, and preeclampsia) are leading contributors to maternal morbidity and mortality. Marked changes in circulating lipids are known to accompany cardiometabolic complications of pregnancy. Serum concentrations of docosahexaenoic acid (DHA) have been shown to be inversely correlated with risk for preeclampsia. DHA is a biosynthetic precursor of a class of specialized pro-resolving mediators (SPMs), resolvins, that have anti-inflammatory properties and are also associated with hypertensive disorders of pregnancy. We employed targeted lipidomics to characterize the distribution of DHA-containing phospholipids and SPMs in maternal serum collected in early and late pregnancy (8–14 weeks and 24–30 weeks gestation, respectively) to identify key lipids that are dysregulated during pregnancy in AA women who develop cardiometabolic complications. We identified a lipid signature in early pregnancy serum samples of AA women that is predictive of cardiometabolic complications of pregnancy with 74% accuracy. These are Resolvin D1, Resolvin E1, 2-AG, PGE2-glyerol ester, and 36:6 PC. These findings suggest that there are blood-based markers detectable in early pregnancy that can potentially identify persons at risk and tailor clinical interventions.

This issue of the Bulletin of the John Rylands Library has its origins in a 2016–19 teaching and research collaboration, Connecting Collections, driven by the extraordinary early modern European art and cultural collections of the Universities of Manchester andMelbourne and backed by an initiative of the vice-chancellors of the two institutions to enhance institutional links. The Connecting Collections project brought together a binational team of researchers, from early career to senior scholars, to support and promote original work on the collections of the two institutions and cities.

A Prayer Book owned by the Rothschilds, an Italian bronze casket by Antico, a lavishly illustrated Carnival chronicle from sixteenth-century Germany, an altarpiece by Pieter Brueghel the Younger - much of the artwork in this book, held by Australian collections, is essentially unknown beyond the continent. The authors of these essays showcase these extraordinary objects to their full potential, revealing a wide range of contemporary art and historical research. This collection of essays will surprise even specialists.

Part I:Matter 1. The matter of the medium: some tools for an art-theoretical interpretation of materials - Ann-Sophie Lehmann 2. The matter of ideas in the working of metals in early modern Europe - Pamela H. Smith 3. On the origins of European painting materials, real and imagined - Anne Dunlop 4. Gold coins and gold leaf in early Italian paintings - Irma Passeri Part II: Practices 5. The 'Genealogy of Jean le Blanc': accounting for the materiality of the medieval Eucharist - Aden Kumler 6. Lead white's mysteries - Spike Bucklow 7. Material distinctions: plaster, terracotta and wax in the Renaissance artist's workshop - Eckart Marchand 8. Rocks and reverence: Inka and Spanish perceptions of stonework in the early modern Andes - Carolyn Dean Part III: Cultural logics 9. Precious stones, material beings: performative materiality in fifteenth-century northern art - Brigitte Buettner 10. Carving life: the meaning of wood in early modern European sculpture - Christina Neilson 11. Arti povere, 1300-1650 - Michael Cole 12. Polish stone, Venetian glass, and red Hungarian marble: the materials of a Renaissance chapel in Jagiellonian Poland - Katie Jakobiec 13. Reveal or conceal: chopines and the display of material wealth in early modern Valencia and Venice - Elizabeth Semmelhack 14. Entanglements of body, text and stone: the crafting and connoisseurship of inkstones in eighteenth-century China - Dorothy Ko Index

Early meningococcal disease (MD) diagnosis is difficult. We assessed rapid molecular testing of respiratory specimens. We performed genotyping of respiratory swabs, blood, and cerebrospinal fluid from children with suspected disease and nasal swabs (NSs) from matched controls. Thirty-nine of 104 suspected cases had confirmed disease. Four controls were carriers. Throat swab ctrA and porA testing for detection of disease gave a sensitivity of 81% (17/21), specificity of 100% (44/44), positive predictive value (PPV) of 100% (17/17), negative predictive value (NPV) of 92% (44/48), and relative risk of 12. NS ctrA and porA testing gave a sensitivity of 51% (20/39), specificity of 95% (62/65), PPV of 87% (20/23), NPV of 77% (62/81), and relative risk of 4. Including only the 86 NSs taken within 48 h of presentation, the results were sensitivity of 60% (18/30), specificity of 96% (54/56), PPV of 90% (18/20), NPV of 82% (54/66), and relative risk of 5. Swab type agreement was excellent (kappa 0.80, P < 0.001). There was exact phylogenetic agreement from different specimen sites for individuals. Carried genosubtypes were P1.7 and P1.21-7. Prehospital rapid molecular testing of easily obtained respiratory specimens could accelerate diagnosis of MD.

In 1370, four years before he died, the poet Francesco Petrarca drew up his will. He began with various pious bequests, and then moved to gifts for friends and family. For Francesco il Vecchio da Carrara, the ruler of Padua, who had sheltered and supported Petrarch at his court, the poet left a Madonna by Giotto, calling Giotto ‘egregii’ and noting that although the icon's beauty was incomprehensible to the uneducated, masters of art were stupefied by it.1 Comments on the visual arts were unusual in the Trecento, and the bequest is famous as an early and rare instance of a great writer commenting on a great artist. Yet Petrarch then explained that he was leaving the panel so that the blessed Virgin would be well disposed to intervene for Carrara with her son Jesus Christ.2 If artistry and devotion seem to be linked in the poet's mind, the relation of the panel's surface beauty to its persuasive power is left unclear.

Summary Objectives To determine whether the nasopharyngitis prodrome of meningococcal disease is caused by the disease itself or respiratory viral coinfection. Methods Case control study of children with suspected meningococcal disease. Nasal swabs and a respiratory history were obtained from suspected cases and matched controls. Molecular testing for 12 respiratory viruses was used. Results 104 suspected cases and controls were recruited. Detection rates for respiratory viruses were 27% (28/104) for suspected cases and 29% (30/104) for controls. Rhinoviruses (43/58, 74%) and adenoviruses (14/58, 24%) occurred most frequently with 3 coinfections. 39 (38%) suspected cases were confirmed as meningococcal disease with a detection rate for respiratory viruses of 26% (10/39). No significant difference was found in the respiratory viral detection rate between this group and their controls, Odds ratio=1.0 (95% CI 0.3 to 3.3). Prodromal respiratory symptoms were significantly more likely for suspected cases (77/104, 74%) than controls (55/104, 53%), Odds ratio 2.8 (95% CI 1.4 to 6.0), but were equally common in confirmed (28/39, 72%) and unconfirmed cases (49/65, 75%), Odds ratio 0.8 (95% CI 0.3 to 2.3). Conclusions This study found no evidence that respiratory viral infections contribute to the prodrome of meningococcal disease. Rhinovirus and adenovirus detection by nasal swab is common in well and unwell children.

PINTURICCHIO E I PELLEGRINI: LA DEVOZIONE E IL PASSATO A SANTA MARIA DEL POPOLOQuesto studio esamina le cappelle dei Cardinali Domenico e Girolamo Basso della Rovere in Santa Maria del Popolo a Roma, chiesa ricostruita sotto il pontificato di Papa Sixtus IV della Rovere negli anni Settanta del XV secolo. Le cappelle datano rispettivamente all'inizio e alla metà degli anni Ottanta del XV secolo, e sono attribuite all'artista umbro Pinturicchio, uno dei favoriti dellacuriadella Rovere. Gli studi precedenti delle cappelle si sono prevalentemente occupati dell'abilità dell'artista nel realizzare architetture fittizie e dell'uso esteso di grottesche, ma non si sono mai soffermati a lungo sulle scene devozionali all'interno di esse. Questo articolo riconsidera l'opera dei della Rovere nella ricostruzione della chiesa, inclusa la sua importanza come luogo di pellegrinaggio, per sostenere che la distinzione moderna tra immagini votive e architetture fittizie mal rappresenta l'idea del Quattrocento di dipinti ‘classici’ innovativi, mentre potrebbero entrambe derivare da bisogni ben precisi della Chiesa.

Cet article veut contribuer a la comprehension de la masculinite du Moyen Age tardif. Il est centre sur une ressemblance non reconnue jusqu'alors de Francesco Casali, dans une fresque datee de 1371 qui se trouve dans l'eglise de Santa Maria delle Grazie, a Magione pres de Perouges. L'A. veut montrer que cette representation etait reliee a la guerre, la chevalerie et la piete chretienne et qu'une telle construction a participe aux idees contemporaines des sexes et de noblesse. Il discute des aspects de la fresque, puis du lien entre F. Casali et les Chevaliers de St. Jean de Jerusalem. Il termine en montrant que l'association dans la fresque de la masculinite, la guerre et la piete laique a participe a un modele social et devotionnel beaucoup plus vaste.

John T. Paoletti and Gary M. Radke, Art in Renaissance Italy A. Richard Turner, The Renaissance in Florence: The Birth of a New Art Hermann Voss (trans. Susanne Pelzel), Painting of the Late Renaissance in Rome and Florence I: From the High Renaissance to Mannerism 1520–1570 Evelyn Welch, Art and Society in Italy 1350–1500

In the castle of Sabbionara d'Avio north of Verona, there is a painted Chamber of Love. The God of Love at Sabbionara has an interesting place in the history of art. Love is a figure from a nightmare, taloned on a frenzied horse. Like Panofsky, the author wants to suggest that something can be seen to be shifting at Sabbionara, and that love lies at the heart of it. In the early Renaissance, however, both love and painting were becoming sources of anxiety for the elites who dwelt in rooms like Sabbionara's Chamber of Love, a room which seems to make these conflicts visible. This chapter briefly reviews the intertwined theories of love, vision, and perception in the period. It then moves to how both art and love were slowly being recast in these years, and concludes by returning to Sabbionara and the stresses that have marked it. Keywords:Chamber of Love; early Renaissance; Italian painting; Panofsky; Sabbionara d'Avio

A considerable amount of work has been published recently which seeks to document the history of the presence of people of South Asian and Caribbean origin in Britain. This welcome addition to the literature is marred only by the almost total silence about the Scottish dimension of this history. A task of historical recovery therefore remains, and this paper initiates that task by demonstrating not only that people of colonial origin have been resident in Scotland since the second half of the nineteenth century, but also that they have been the victims of racism and exclusionary practices.