Viscoelastic Properties of Rapid Prototyped Magnetic Nanocomposite Scaffolds for Osteochondral Tissue Regeneration

Poly(ϵ-caprolactone) and poly(ethylene glycol) based magnetic nanocomposite scaffolds were fabricated using fused deposition modeling and stereolithography approaches, and a hybrid scaffold was obtained by combining these additive manufacturing technologies. Viscoelastic properties in compression were investigated at 37 °C, spanning a range frequency of four decades. Results suggest that poly(ϵ-caprolactone) and poly(ethylene glycol) based scaffolds adequately reproduce viscoelastic properties of subchondral bone and articular cartilage tissues, respectively. By combining fused deposition modeling and stereolithography it is possible to manufacture a hybrid scaffold suitable for osteochondral tissue regeneration. Poly(ϵ-caprolactone) and poly(ethylene glycol) based magnetic nanocomposite scaffolds were fabricated using fused deposition modeling and stereolithography approaches, and a hybrid scaffold was obtained by combining these additive manufacturing technologies. Viscoelastic properties in compression were investigated at 37 °C, spanning a range frequency of four decades. Results suggest that poly(ϵ-caprolactone) and poly(ethylene glycol) based scaffolds adequately reproduce viscoelastic properties of subchondral bone and articular cartilage tissues, respectively. By combining fused deposition modeling and stereolithography it is possible to manufacture a hybrid scaffold suitable for osteochondral tissue regeneration

The Gas Pixel Detector as an X-ray photoelectric polarimeter with a large field of view

The Gas Pixel Detector (GPD) is a new generation device which, thanks to its 50 um pixels, is capable of imaging the photoelectrons tracks produced by photoelectric absorption in a gas. Since the direction of emission of the photoelectrons is strongly correlated with the direction of polarization of the absorbed photons, this device has been proposed as a polarimeter for the study of astrophysical sources, with a sensitivity far higher than the instruments flown to date. The GPD has been always regarded as a focal plane instrument and then it has been proposed to be included on the next generation space-borne missions together with a grazing incidence optics. Instead in this paper we explore the feasibility of a new kind of application of the GPD and of the photoelectric polarimeters in general, i.e. an instrument with a large field of view. By means of an analytical treatment and measurements, we verify if it is possible to preserve the sensitivity to the polarization for inclined beams, opening the way for the measurement of X-ray polarization for transient astrophysical sources. While severe systematic effects arise for inclination greater than about 20 degrees, methods and algorithms to control them are discussed.Comment: 11 pages, 8 figure

Novel C16orf57 mutations in patients with Poikiloderma with Neutropenia: bioinformatic analysis of the protein and predicted effects of all reported mutations

<p>Abstract</p> <p>Background</p> <p>Poikiloderma with Neutropenia (PN) is a rare autosomal recessive genodermatosis caused by <it>C16orf57 </it>mutations. To date 17 mutations have been identified in 31 PN patients.</p> <p>Results</p> <p>We characterize six PN patients expanding the clinical phenotype of the syndrome and the mutational repertoire of the gene. We detect the two novel <it>C16orf57 </it>mutations, c.232C>T and c.265+2T>G, as well as the already reported c.179delC, c.531delA and c.693+1G>T mutations. cDNA analysis evidences the presence of aberrant transcripts, and bioinformatic prediction of C16orf57 protein structure gauges the mutations effects on the folded protein chain.</p> <p>Computational analysis of the C16orf57 protein shows two conserved H-X-S/T-X tetrapeptide motifs marking the active site of a two-fold pseudosymmetric structure recalling the 2H phosphoesterase superfamily. Based on this model C16orf57 is likely a 2H-active site enzyme functioning in RNA processing, as a presumptive RNA ligase.</p> <p>According to bioinformatic prediction, all known <it>C16orf57 </it>mutations, including the novel mutations herein described, impair the protein structure by either removing one or both tetrapeptide motifs or by destroying the symmetry of the native folding.</p> <p>Finally, we analyse the geographical distribution of the recurrent mutations that depicts clusters featuring a founder effect.</p> <p>Conclusions</p> <p>In cohorts of patients clinically affected by genodermatoses with overlapping symptoms, the molecular screening of <it>C16orf57 </it>gene seems the proper way to address the correct diagnosis of PN, enabling the syndrome-specific oncosurveillance.</p> <p>The bioinformatic prediction of the C16orf57 protein structure denotes a very basic enzymatic function consistent with a housekeeping function. Detection of aberrant transcripts, also in cells from PN patients carrying early truncated mutations, suggests they might be translatable. Tissue-specific sensitivity to the lack of functionally correct protein accounts for the main cutaneous and haematological clinical signs of PN patients.</p

Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values

ABSTRACT Estimating epidemiological cutoff endpoints (ECVs/ECOFFS) may be hindered by the overlap of MICs for mutant and nonmutant strains (strains harboring or not harboring mutations, respectively). Posaconazole MIC distributions for the Aspergillus fumigatus species complex were collected from 26 laboratories (in Australia, Canada, Europe, India, South and North America, and Taiwan) and published studies. Distributions that fulfilled CLSI criteria were pooled and ECVs were estimated. The sensitivity of three ECV analytical techniques (the ECOFFinder, normalized resistance interpretation [NRI], derivatization methods) to the inclusion of MICs for mutants was examined for three susceptibility testing methods (the CLSI, EUCAST, and Etest methods). The totals of posaconazole MICs for nonmutant isolates (isolates with no known cyp51A mutations) and mutant A. fumigatus isolates were as follows: by the CLSI method, 2,223 and 274, respectively; by the EUCAST method, 556 and 52, respectively; and by Etest, 1,365 and 29, respectively. MICs for 381 isolates with unknown mutational status were also evaluated with the Sensititre YeastOne system (SYO). We observed an overlap in posaconazole MICs among nonmutants and cyp51A mutants. At the commonly chosen percentage of the modeled wild-type population (97.5%), almost all ECVs remained the same when the MICs for nonmutant and mutant distributions were merged: ECOFFinder ECVs, 0.5 μg/ml for the CLSI method and 0.25 μg/ml for the EUCAST method and Etest; NRI ECVs, 0.5 μg/ml for all three methods. However, the ECOFFinder ECV for 95% of the nonmutant population by the CLSI method was 0.25 μg/ml. The tentative ECOFFinder ECV with SYO was 0.06 μg/ml (data from 3/8 laboratories). Derivatization ECVs with or without mutant inclusion were either 0.25 μg/ml (CLSI, EUCAST, Etest) or 0.06 μg/ml (SYO). It appears that ECV analytical techniques may not be vulnerable to overlap between presumptive wild-type isolates and cyp51A mutants when up to 11.6% of the estimated wild-type population includes mutants. KEYWORDS Aspergillus fumigatus, CLSI ECVs, ECVs, EUCAST ECVs, Etest, SYO, cyp51A mutants, posaconazole, triazole resistance, wild typ

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Recupero e ampliamento del fabbricato B della Fondazione Mazzali - Mantova

Il consumo di territorio è a livelli ormai insostenibili per la nostra società, il disegno urbano mostra città sempre più diffuse dai limiti incontrollati e voraci di nuovo territorio: abbiamo bisogno di città più dense. L’impossibilità etica di utilizzare in modo consistente nuovi territori destinati al suolo agricolo, la necessità di contenere il consumo delle risorse disponibili (energia, acqua, suolo, ecc.), impone la sperimentazione di nuove pratiche di progetto della città sostenibili per le generazioni future. Le città sono sempre state il luogo della rigenerazione e del cambiamento, non solo della conservazione cosi come si fa oggi. Oggi non mancano i mezzi per coniugare estetica e tecnica ma da tempo siamo incapaci di generare una nuova modernità che ci rappresenti perché abbiamo separato la forma dalla sostanza. Generare una nuova modernità significa innovare, che corrisponde a un modo nuovo di fare le cose capace di produrre un cambiamento positivo. La metodologia dell’addizione volumetrica può divenire un concetto capace di coniugare l’efficienza delle scelte di densificazione e di retrofit urbano con l’efficacia delle scelte di ricomposizione architettonica e di espressione della modernità. Il progetto per la rigenerazione dell’edificio B (degli anni ’70) della Fondazione "Mons. Mazzali", storica struttura per anziani del centro storico di Mantova, è il risultato dell’efficienza di una struttura antisismica (passando dal 20% al 100% di adeguamento) ed energeticamente virtuoso (con il miglioramento del 68% dell’efficienza energetica) e dell’efficacia di una ricomposizione architettonica, che privilegia il rapporto con il lago e la città storica. La nuova facciata di ampliamento verso il lago, è trattata come un foglio di laterizio a vista staccato dalla facciata in un’alternanza di pieni e di vuoti a tutt’altezza che determinano le nuove aperture e lasciano libero l’ultimo piano. Una soletta in c.a. tra la nuova e la vecchia facciata unita alla struttura verticale, funziona come una grande trave in grado di assorbire le sollecitazioni orizzontali provenienti dal sisma. L'adeguamento sismico utilizza, inoltre, i due vani scala e ascensore come nuclei resistenti cui sono ancorati i pilastri della facciata interna tramite un sistema di controventature metalliche puntualmente collegate ai solai intermedi. Una struttura interamente a secco dell’ultimo piano (legno e acciaio), isolanti di origine naturale a elevato spessore, isolanti sottili termoriflettenti, vetrate a doppia camera, laterizi alveolati rettificati, pannelli radianti a soffitto con impianto di trigenerazione, sono le principali caratteristiche tecnologiche dell’intervento