Preclinical Evaluation of [18F]LCATD as a PET Tracer to Study Drug-Drug Interactions Caused by Inhibition of Hepatic Transporters

Acknowledgements: A.T. gratefully acknowledges SINAPSE (www.sinapse.ac.uk) and AstraZeneca (UK) for co-funding a studentship. P.S. and C.S.E. are employees of AstraZeneca Ltd., UK. This project has also received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 675417.Peer reviewedPublisher PD

Risk of COVID-19 in-hospital mortality in people living with HIV compared to general population according to age and CD4 strata: data from the ICONA network

OBJECTIVES: We aimed to study whether people living with HIV (PLWH) are at higher risk of in-hospital COVID-19 mortality compared to the general population (GenPop). METHODS: This was a retrospective study in 19 Italian centers (February 2020 to November 2022) including hospitalized PLWH and GenPop with SARS-CoV-2 infection. The main outcome was in-hospital mortality. Competing risk analyses by Fine-Gray regression model were used to estimate the association between in-hospital mortality and HIV status/age. RESULTS: A total of 7399 patients with COVID-19 were included, 239 (3.2%) PLWH, and 7160 (96.8%) GenPop. By day 40, in-hospital death occurred in 1283/7160 (17.9%) among GenPop and 34/239 (14.2%) among PLWH. After adjusting for potential confounders, compared to GenPop 350 (aSHR 1.11 [95% CI 0.41-2.99]). CONCLUSIONS: In PLWH aged <65 years a CD4 ≤350 rather than HIV itself seems the driver for the observed higher risk of in-hospital mortality. We cannot however rule out that HIV infection per se is the risk factor in those aged ≥65 years

A Quantitative Estimate of the Expected Shortening of the Median Isolation Period of Patients With COVID-19 After the Adoption of a Symptom-Based Strategy

A long period of isolation was observed in patients hospitalized for COVID-19 in Milan over March-September 2020 (45; IQR: 37–54 days). A significantly shorter period would have been observed by the application of May-WHO (22, IQR: 17–30 days, P &lt; 0.001) and October-Italian (26, IQR: 21–34 days, P &lt; 0.001) Guidelines. The adoption of the new symptom-based criteria is likely to lead to a significant reduction in the length of the isolation period with potential social, economic and psychological benefits, particularly in the younger population with mild/moderate disease and no comorbidities. In our opinion, the release from isolation after 21 days from symptoms onset, even without a PCR diagnostic test, in most cases seems the most adequate strategy that could balance precautions to prevent SARS CoV-2 transmission and unnecessary prolonged isolation or overuse of diagnostic testing

Inhibitors of apoptosis proteins (IAPs) expression and their prognostic significance in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Similarly to other tumor types, an imbalance between unrestrained cell proliferation and impaired apoptosis appears to be a major unfavorable feature of hepatocellular carcinoma (HCC). The members of IAP family are key regulators of apoptosis, cytokinesis and signal transduction. IAP survival action is antagonized by specific binding of Smac/DIABLO and XAF1. This study aimed to investigate the gene and protein expression pattern of IAP family members and their antagonists in a series of human HCCs and to assess their clinical significance.</p> <p>Methods</p> <p>Relative quantification of IAPs and their antagonist genes was assessed by quantitative Real Time RT-PCR (qPCR) in 80 patients who underwent surgical resection for HCC. The expression ratios of XIAP/XAF1 and of XIAP/Smac were also evaluated. Survivin, XIAP and XAF1 protein expression were investigated by immunohistochemistry. Correlations between mRNA levels, protein expression and clinicopathological features were assessed. Follow-up data were available for 69 HCC patients. The overall survival analysis was estimated according to the Kaplan-Meier method.</p> <p>Results</p> <p>Survivin and Livin/ML-IAP mRNAs were significantly over-expressed in cancer tissues compared to non-neoplastic counterparts. Although Survivin immunoreactivity did not correlate with qPCR data, a significant relation was found between higher Survivin mRNA level and tumor stage, tumor grade and vascular invasion.</p> <p>The mRNA ratio XIAP/XAF1 was significantly higher in HCCs than in cirrhotic tissues. Moreover, high XIAP/XAF1 ratio was an indicator of poor prognosis when overall survival was estimated and elevated XIAP immunoreactivity was significantly associated with shorter survival.</p> <p>Conclusion</p> <p>Our study demonstrates that alterations in the expression of IAP family members, including Survivin and Livin/ML-IAP, are frequent in HCCs. Of interest, we could determine that an imbalance in XIAP/XAF1 mRNA expression levels correlated to overall patient survival, and that high XIAP immunoreactivity was a poor prognostic factor.</p

Corporate Cultural Policies and Museums: a Critical Evaluation of the Role of the Industry in the Evolution of Fashion Curation in Italy

This thesis critically evaluates the role of the Italian fashion and textile industries in the evolution of fashion curation. Italy is rarely mentioned in publications on fashion curation in English, however through this research I demonstrate that a small number of exhibitions in Italy were influential in shaping curatorial approaches now employed internationally and that these approaches originated directly from the involvement of the industry. This study presents a history of Italian fashion curation, previously not available, combining the limited accounts in Italian literature with evidence gathered from exhibition catalogues, specialist publications, and conference proceedings. Starting with the 1996 Biennale di Firenze, industry associations have organised exhibitions intended not as scholarly tools to present research but as visual reflections on the culture of fashion, viewed as an expression of contemporaneity, whose past is used as a key to understand the present. The approach has since been employed by corporate institutions like the Fondazione Pitti Immagine Discovery in Florence. The account is instrumental in informing a nuanced understanding of corporate museums and enriches the debates on fashion curation by positioning Italy within existing international discourses. This study also examines the status of corporate heritage in Italy and evaluates the impact of corporate cultural policies. Since the 2000s, the industry has invested major resources in the development of corporate museums, which are becoming a vital communication tool for companies and a core component of their cultural production. To date, corporate museums have only been studied from marketing, organisational and architectural perspectives. Through a definitional analysis of these institutions, I integrate existing literature with museum theory and collecting studies and illustrate the theoretical observations with the analysis of two corporate museums, the Museo Salvatore Ferragamo in Florence and the Museo del Tessuto in Prato. I propose a new definition of a corporate museum that provides a critical model that may be applied to non-Italian and non-fashion corporate museums. This thesis makes an original contribution to the field of fashion curation by providing the first historical account of Italian fashion curation from the 1950s as well as access to and critical analysis of Italian literature. It also positions Italian curation in an international dimension, by engaging with English-language theory and drawing links with foreign practices and theories. Furthermore, it enriches the field of museum studies with a theoretical analysis of corporate museums, integrating the museological perspective to existing research in the field. Through this study I have demonstrated that an evaluation of corporate cultural policies and museums is critical to interpret fashion curation as a part of the fashion system in which both research and commercial aims can be achieved simultaneously, and that Italy is a particularly rich example given the role played by the industry in the evolution of fashion curation

Disappearance of Electrocardiographic Abnormalities Associated with the Arrhythmic Pattern of a Barlow Disease after Surgical Mitral Valve Repair

We describe the case of a 46-year old female with a Barlow’s disease (MVP) characterized by systolic curling of posterior left ventricular (LV) wall + significant mitral annular disjunction + complex ventricular arrhythmias + syncope + inverted T waves in inferolateral leads in whom a successful surgical mitral valve rapair determined the disappearance not only of the echocardiographic but also the electrocardiographic abnormalities (in particular the inferolateral T waves inversion on basal electrocardiogram and the complex basal arrhythmic pattern). This case demonstrates that electrocardiographic abnormalities may disappear after the surgical correction of the mechanical stretch imposed on the inferior LV free wall by the prolapsing mitral valve leaflets. Electrocardiographic changes remain an important and easy marker to recognize for the identification of a high-risk subgroup of MVP patients

Disappearance of electrocardiographic abnormalities associated with the arrhythmic pattern of a Barlow disease after surgical mitral valve repair

We describe the case of a 46-year old female with a Barlow’s disease (MVP) characterized by systolic curling of posterior left ventricular (LV) wall + significant mitral annular disjunction + complex ventricular arrhythmias + syncope + inverted T waves in inferolateral leads in whom a successful surgical mitral valve rapair determined the disappearance not only of the echocardiographic but also the electrocardiographic abnormalities (in particular the inferolateral T waves inversion on basal electrocardiogram and the complex basal arrhythmic pattern). This case demonstrates that electrocardiographic abnormalities may disappear after the surgical correction of the mechanical stretch imposed on the inferior LV free wall by the prolapsing mitral valve leaflets. Electrocardiographic changes remain an important and easy marker to recognize for the identification of a high-risk subgroup of MVP patients

Acausal equation-based and object-oriented modeling of heating systems: The College Thermal library

With the growing demand for adequate thermal comfort and increasingly sophisticated and interconnected energy systems, software tools able to easily and effectively study complex thermal systems need to be developed. Here, a novel acausal equation-based and object-oriented modeling (OOM) approach is used to model the seasonal performance of a residential heating system taken as a case study. To this end, a purpose-built library named College Thermal was developed using Modelica language in the Wolfram System Modeler simulation environment. In detail, dynamic simulations under varying operating conditions were performed to assess the ability of the system to ensure the design conditions, and to estimate the resulting energy consumption during the heating season. Then, the effect of key parameters of the thermal components on the overall energy performance of the system is analyzed. The developed OOM library, which is characterized by interoperability, modularity, and scalability features and thus could easily incorporate extensions/evolutions of the studied system, would be prospectively suitable for optimizing system layouts and testing control strategies in various thermal engineering applications

Large-deflection analysis of composite and FGM thin-walled beams under thermal pre-stresses

In some applications, working structures, such as rotor shafts, can be simultaneously exposed to mechanical and thermal loads. Moreover, due to extreme service conditions, mechanical loads may induce large deflections and rotations within the structure, so an accurate evaluation of the geometrically nonlinear behavior of the structure is mandatory for an ac- curate design of such components. Finally, the thermal condition causes pre-stresses that afflict the static nonlinear equilibrium path, so they need to be included within the analysis. The moderns techniques rely on three-dimensional (3D) Finite Element (FE) models for the numerical simulation of such structures (see [1]). Despite significant advances in computing power, complex three-dimensional (3D) Finite Element (FE) models still impose large computational costs, especially during the iterative design stage. For this reason, reduced refined models may be used to obtain solutions with lower computational efforts The proposed methodology for the structural analysis of components subjected to thermal pre-stressed and large-deflections was built in the framework of the Carrera Unified Formulation (CUF) ([2]). This methodology, according to which the 3D displacement field can be evaluated as an arbitrary expansion of the unknowns evaluated through the FE method, is extremely suitable for this analysis. In fact, every component or layer within the structure can have its own kinematic described independently from the others, without the need for any ad-hoc theory implementation. As a matter of fact, one can evaluate the influence of pre-stress, material properties, and geometric characteristics in a unified manner. Arch-type structures are analyzed, comparing obtained results with those provided from literature and experimental tests. The results establish and report graphs showing the effects of the reinforcements on the overall behavior of the components, with the aim of providing a reliable starting point for the future design of the structure in the civil engineering field. References: [1] M. Zhuo, L.H. Yang, and L. Yu. The steady-state thermal effect on rotor dynamics of a rod-fastened rotor-bearing system. In ASME International Mechanical EngineeringCongress and Exposition, Volume 46483, page V04BT04A014. American Society of Mechanical Engineers, 2014. [2] E. Carrera, M. Cinefra, M. Petrolo, and E. Zappino. Finite element analysis ofstructures through unified formulation. John Wiley Sons, 2014.</p