White paper on EUSO-SPB2 Adams, James H; Anchordoqui, Luis A; Apple, Jeffrey A ...
arXiv (Cornell University),
06/2017
Paper, Journal Article
Odprti dostop
EUSO-SPB2 is a second generation Extreme Universe Space Observatory (EUSO) on a Super-Pressure Balloon (SPB). This document describes the physics capabilities, the proposed technical design of the ...instruments, and the simulation and analysis software.
Point-of-care testing INR: an overview Barcellona, Doris; Fenu, Lara; Marongiu, Francesco
Clinical chemistry and laboratory medicine,
06/2017, Letnik:
55, Številka:
6
Journal Article
Recenzirano
Oral anticoagulant therapies with the anti-vitamin K drugs (AVK), warfarin, acenocoumarol and phenprocoumon, are employed in primary and secondary anti-thrombotic prophylaxis in patients with venous ...thromboembolism, atrial fibrillation and cardiac mechanical valves. However, a monitoring test such as the International Normalized Ratio (INR) is required. The periodic monitoring of this therapy entails discomfort for the patients. Telemedicine and telecare can provide significant aid in the management of this therapy allowing patients to perform the test at home or anywhere else with a portable device, i.e. point-of-care testing (POCT), and to send the result to a thrombosis (TC) via web. Patients can receive dose adjustment sent back by the TC. The effectiveness of this type of management is equal or superior to the traditional AVK monitoring in terms of hemorrhagic and thrombotic events. Analysis of the costs with a horizon of 10 years reveals that both self-testing and self-management are cost-effective. The aim of this overview is to describe the pros and cons of the use of POCT as an alternative in the monitoring of AVK. In particular, description of the POCT, decentralization, quality of the therapy, safety and costs will be examined.
4-anilino quinazolines have been identified as inhibitors of HCV replication. The target of this class of compounds was proposed to be the viral protein NS5A, although unequivocal proof has never ...been presented. A 4-anilino quinazoline moiety is often found in kinase inhibitors, leading us to formulate the hypothesis that the anti-HCV activity displayed by these compounds might be due to inhibition of a cellular kinase. Type III phosphatidylinositol 4-kinase α (PI4KIIIα) has recently been identified as a host factor for HCV replication. We therefore evaluated AL-9, a compound prototypical of the 4-anilino quinazoline class, on selected phosphatidylinositol kinases. AL-9 inhibited purified PI4KIIIα and, to a lesser extent, PI4KIIIβ. In Huh7.5 cells, PI4KIIIα is responsible for the phosphatidylinositol-4 phosphate (PI4P) pool present in the plasma membrane. Accordingly, we observed a gradual decrease of PI4P in the plasma membrane upon incubation with AL-9, indicating that this agent inhibits PI4KIIIα also in living cells. Conversely, AL-9 did not affect the level of PI4P in the Golgi membrane, suggesting that the PI4KIIIβ isoform was not significantly inhibited under our experimental conditions. Incubation of cells expressing HCV proteins with AL-9 induced abnormally large clusters of NS5A, a phenomenon previously observed upon silencing PI4KIIIα by RNA interference. In light of our findings, we propose that the antiviral effect of 4-anilino quinazoline compounds is mediated by the inhibition of PI4KIIIα and the consequent depletion of PI4P required for the HCV membranous web. In addition, we noted that HCV has a profound effect on cellular PI4P distribution, causing significant enrichment of PI4P in the HCV-membranous web and a concomitant depletion of PI4P in the plasma membrane. This observation implies that HCV--by recruiting PI4KIIIα in the RNA replication complex--hijacks PI4P metabolism, ultimately resulting in a markedly altered subcellular distribution of the PI4KIIIα product.
Abstract Prosthetic joint infections (PJIs) are becoming a growing public health concern in developed countries as more people undergo arthroplasty for bone fixation or joint replacement. Because a ...wide range of bacterial strains responsible for PJIs can produce biofilms on prosthetic implants and because the biofilm structure confers elevated bacterial resistance to antibiotic therapy, new drugs and therapies are needed to improve the clinical outcome of treatment of PJIs. Antimicrobial photodynamic therapy (APDT), a non-antibiotic broad-spectrum antimicrobial treatment, is also active against multidrug-resistant micro-organisms such as meticillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa . APDT uses a photosensitiser that targets bacterial cells following exposure to visible light. APDT with RLP068/Cl, a novel photosensitiser, was studied by confocal laser scanning microscopy (CLSM) to evaluate the disruption of MRSA and P. aeruginosa biofilms on prosthetic material. Quantitative CLSM studies showed a reduction in biofilm biomass (biofilm disruption) and a decrease in viable cell numbers, as determined by standard plate counting, in the S. aureus and P. aeruginosa biofilms exposed to APDT with the photosensitiser RLP068/Cl. APDT with RLP068/Cl may be a useful approach to the treatment of PJI-associated biofilms.
The definition of disease-specific prognostic scores plays a fundamental role in the treatment decision-making process in myelodysplastic syndrome (MDS), a group of myeloid disorders characterized by ...a heterogeneous clinical behavior.
We applied the recently published Revised International Prognostic Scoring System (IPSS-R) to 380 patients with MDS, registered in an Italian regional database, recruiting patients from the city of Rome (Gruppo Romano Mielodisplasie). Patients were selected based on the availability of IPSS-R prognostic factors, including complete peripheral-blood and bone marrow counts, informative cytogenetics, and follow-up data.
We validated the IPSS-R score as a significant predictor of overall survival (OS) and leukemia-free survival (LFS) in MDS (P < .001 for both). When comparing the prognostic value of the International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS), and IPSS-R, using the Cox regression model and the likelihood ratio test, a significantly higher predictive power for LFS and OS became evident for the IPSS-R, compared with the IPSS and WPSS (P < .001 for both). The multivariate analysis, including IPSS, WPSS, age, lactate dehydrogenase, ferritin concentration, Eastern Cooperative Oncology Group performance status, transfusion dependency, and type of therapy, confirmed the significant prognostic value of IPSS-R subgroups for LFS and OS. Treatment with lenalidomide and erythropoiesis-stimulating agents was shown to be an independent predictor of survival in the multivariate analysis.
Our data confirm that the IPSS-R is an excellent prognostic tool in MDS in the era of disease-modifying treatments. The early recognition of patients at high risk of progression to aggressive disease may optimize treatment timing in MDS.
Nowadays, research into personalization has been focusing on explainability and fairness. Several approaches proposed in recent works are able to explain individual recommendations in a post-hoc ...manner or by explanation paths. However, explainability techniques applied to unfairness in recommendation have been limited to finding user/item features mostly related to biased recommendations. In this paper, we devised a novel algorithm that leverages counterfactuality methods to discover user unfairness explanations in the form of user-item interactions. In our counterfactual framework, interactions are represented as edges in a bipartite graph, with users and items as nodes. Our bipartite graph explainer perturbs the topological structure to find an altered version that minimizes the disparity in utility between the protected and unprotected demographic groups. Experiments on four real-world graphs coming from various domains showed that our method can systematically explain user unfairness on three state-of-the-art GNN-based recommendation models. Moreover, an empirical evaluation of the perturbed network uncovered relevant patterns that justify the nature of the unfairness discovered by the generated explanations. The source code and the preprocessed data sets are available at https://github.com/jackmedda/RS-BGExplainer.
Background:
With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences.
Objectives:
To identify ...prognostic factors for early switch after first therapy choice.
Methods:
Newly diagnosed relapsing–remitting MS patients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models.
Results:
We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50; p = 0.009), natalizumab (HR = 0.13; p < 0.001), dimethyl-fumarate (HR = 0.60; p = 0.037), teriflunomide (HR = 0.21; p = 0.031) as compared to interferons. Younger age (HR = 0.96; p < 0.001), diagnosis delay (HR = 1.23; p = 0.021), higher baseline Expanded Disability Status Scale (HR = 1.17; p = 0.001), and spinal cord lesions (HR = 1.46; p = 0.001) were independently associated with higher inefficacy switch rates. We found lower switch for intolerance/safety with glatiramer acetate (HR = 0.61; p = 0.001), fingolimod (HR = 0.35; p = 0.002), and dimethyl-fumarate (HR = 0.57; p = 0.022) as compared to interferons, while it increased with natalizumab (HR = 1.43; p = 0.022). Comorbidities were associated with intolerance switch (HR = 1.28; p = 0.047).
Conclusion:
Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.
The tourism and hospitality sectors have become increasingly important in the last few years and the companies operating in this field are constantly challenged with providing new innovative ...services. At the same time, (big-) data has become the "new oil" of this century and Knowledge Graphs are emerging as the most natural way to collect, refine, and structure this heterogeneous information. In this paper, we present a methodology for semi-automatic generating a Tourism Knowledge Graph (TKG), which can be used for supporting a variety of intelligent services in this space, and a new ontology for modelling this domain, the Tourism Analytics Ontology (TAO). Our approach processes and integrates data from Booking.com, Airbnb, DBpedia, and GeoNames. Due to its modular structure, it can be easily extended to include new data sources or to apply new enrichment and refinement functions. We report a comprehensive evaluation of the functional, logical, and structural dimensions of TKG and TAO.
In recent years, transformer-based models have emerged as powerful tools for natural language processing tasks, demonstrating remarkable performance in several domains. However, they still present ...significant limitations. These shortcomings become more noticeable when dealing with highly specific and complex concepts, particularly within the scientific domain. For example, transformer models have particular difficulties when processing scientific articles due to the domain-specific terminologies and sophisticated ideas often encountered in scientific literature. To overcome these challenges and further enhance the effectiveness of transformers in specific fields, researchers have turned their attention to the concept of knowledge injection. Knowledge injection is the process of incorporating outside knowledge into transformer models to improve their performance on certain tasks. In this paper, we present a comprehensive study of knowledge injection strategies for transformers within the scientific domain. Specifically, we provide a detailed overview and comparative assessment of four primary methodologies, evaluating their efficacy in the task of classifying scientific articles. For this purpose, we constructed a new benchmark including both 24K labelled papers and a knowledge graph of 9.2K triples describing pertinent research topics. We also developed a full codebase to easily re-implement all knowledge injection strategies in different domains. A formal evaluation indicates that the majority of the proposed knowledge injection methodologies significantly outperform the baseline established by Bidirectional Encoder Representations from Transformers.
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