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Clinical outcomes of avelumab and pembrolizumab in advanced urothelial cancer: an observational multicenter retro-prospective study on patients undergoing treatment in clinical practice (AVePEm study)
No full textIntroduction and objectives: Patients (pts) with metastatic urothelial carcinoma (mUC) gain substantial benefit from immunotherapy exposure. If they do not experience disease progression after 4-6 cycles of first-line platinum-based chemotherapy (PBC), they may benefit from immunotherapy as maintenance treatment with Avelumab; otherwise, Pembrolizumab is an approved second-line therapy after disease progression on first-line chemotherapy. However, no clinical trial data currently demonstrate which treatment strategy offers superior survival outcomes. Patients and methods: This is a multicenter, observational, retro-prospective study involving pts with mUC who did not progress after 4-6 cycles of PBC: GroupA received Avelumab and GroupB Pembrolizumab. The primary endpoints were overall survival (OS) and progression-free survival (PFS), with neutrophil-to-lymphocyte ratio (NLR) ≥3 at the baseline of PBC and at the start of immunotherapy in predicting outcome, adverse events (AEs), subsequent therapies after the immunotherapy strategy, and costs associated with these treatments as secondary endpoints. Results: From August 2019 to October 2024, we identified 30 pts. Of those, 53% were in GroupA and 47% in GroupB. The mOS in GroupA was 27 mo and in GroupB 26 mo and the mPFS of immunotherapy was 7.5 mo and 5.5 mo. At the time of data analysis, 33% (n=10) of pts were alive and 27% (n=8) on treatment, with 38% (n=3) still receiving Avelumab, and 50% (n=4) and 12% (n=1) on subsequent therapies after Avelumab and Pembrolizumab, respectively. Approximately 55% of patients in both groups had a baseline neutrophil-to-lymphocyte ratio (NLR) ≥3 at the baseline of PBC. No statistically significant association was found between NLR, whether considered as a continuous or dichotomous variable, and overall survival or progression free survival. Both treatments were well tolerated, with Grade 3 AEs in 1 pt on Avelumab and 3 on Pembrolizumab, and no Grade 4 AEs reported. Conclusions: The two immunotherapy strategies showed no significant differences in OS and PFS. Of note, more pts were on Avelumab treatment at the data cut-off. AEs were similar in the two groups. Further investigation and follow-up are warranted to gain definitive conclusions on optimal mUC management in the era of immunotherapy and immunoconjugates
Weak Measurement of the Angular Goos-Hänchen Shift from a Monolayer MoS2 Immersed in a Dielectric Medium
No full textOptical beam shifts in two-dimensional crystals have been measured until now on samples deposited on some substrates. In these cases, the reflected beam is the linear superposition of the atomic crystal and the substrate contribution. By immersion of a monolayer MoS2 in polydimethylsiloxane, a transparent dielectric material, we can measure the light reflected from the two-dimensional material only. In conjunction with a weak measurement amplification scheme, this allows us to observe for the first time the role of the out-of-plane susceptibility on the angular Goos-Hänchen shift from a two-dimensional material
Remote sensing in the geomorphological and geoarchaeological study of alluvial plains
No full textIn the last two decades rising remote sensing technologies have dramatically changed geomorphological and geoarchaeological investigations. At the same time, an increasing quantity of stratigraphic and earth-surface processes studies have improved knowledge on the evolution of several alluvial plains. Despite the plethora of available data sets, the reconstruction of the landscape evolution in these environments remains challenging, due to the scarce visibility of landforms and the frequent superimposition between natural and anthropogenic processes. A key to shed light on the evolution of these surfaces lies on the signature of fluvial and human activities, which can be revealed through optical and topographic traces. An abundance of these features is present in the Venetian-Friulian Plain, located in North East Italy, which has been chosen as the main study area. With a multi-methodological and interdisciplinary approach, this thesis employs a broad range of remote sensing methods and techniques and integrates different data sets to analyse several case studies. Among the key results, high-resolution Digital Terrain Models (DTMs) derived from Light Detection And Ranging (LiDAR) surveys reveal the topographic surface preserved by old-growth lowland woods; and the integration with optical imagery allows to identify aeolian dunes and relict archaeological depressions. High-resolution oblique aerial photos and daily satellite images are combined to assess the evidence of optical archaeological traces from 2017 to 2023 in order to infer the correlation between visibility parameters. Finally, high-resolution aerial orthophotos are used as input data to train and test a deep learning model to automatically map fluvial palaeochannels. Overall, by considering various data sets, techniques and case studies, this thesis aims to assess how recent and innovative remotely sensed data and methods can be applied to the alluvial plains in order to advance the knowledge about their geomorphological and geoarchaeological evolution
Recoverable degradation of FAPbBr3 perovskite solar cells under reverse-bias: A combined electro-optical investigation
Get PDFReverse-bias stability in PV devices is critical to guarantee adequate reliability during sporadic shading instances or when deliberately applying reverse-bias in photodetection applications. Testing reverse-bias stability on PSCs is crucial in providing characterizing insights both into the current state and performance of such devices and also towards their iterative improvement. This paper describes reverse-bias stability testing of semi-transparent FAPbBr3 perovskite solar cells. Stability against reverse-bias was extensively evaluated through both reverse-bias step-stress (RBSS) tests and constant-bias stress (CBS) tests at different voltage bias intensities. During a series of 10 ks tests, cells were revealed to be stable when operated down to −1.5 V (corresponding to approximately 20 % of the breakdown voltage threshold), whereas at −3 V the observed degradation mainly consists in a decrease in open-circuit voltage (from ∼1.5 ÷ 1.6 V to as low as 0.3 V) and parallel resistance (..
What is more likely in orthorexia nervosa: perfectionism or OC symptoms? A bayesian method in clinical and non-clinical samples
Get PDFPurposeOrthorexia Nervosa (ON) exhibits specific features that may overlap with Obsessive-Compulsive Disorder (OCD), Perfectionism Striving (PS), and Perfectionism Concern (PC). While previous literature has shown predictiveness in different characteristics of ON, this study aimed to determine if PS, PC and OCD symptoms could predict ON dimensions in at-risk populations using Bayesian models.MethodThe study enrolled 622 individuals from three different at-risk populations: people who were following treatment for an Eating Disorder (Patients), people who were following a diet (Dieters) and University students with a degree in medicine or nursing (Students).ResultsUsing Bayesian probabilistic methods and considering group factors, the model was enhanced highlighting that ON characterised Patients, Dieters, and Students. The predictiveness of OC features, PS, and PC in different ON characteristics was confirmed in each group, and different patterns were observed in the three groups. Regarding problems related to ON, predictors were higher in Patients, followed by Dieters and Students. Posterior Predictive Distribution (PPD) showed that almost 50% of Patients incur ON-related problems. In ON knowledge, Patients and Dieters are very similar. When feelings related to ON were considered, Patients and Dieters showed different interactions.ConclusionClinicians should consider that one in two patients suffering from EDs might develop ON-related problems. People on a diet could show similar patterns of symptoms to patients in ON knowledge and feelings. Finally, our results confirm that perfectionism represents a risk factor for ON in each group considered
Genetic variability and population structure analysis of Protostrongylus oryctolagi (Nematoda: Protostrongylidae) in Lepus europaeus from Central and Northern Italy
Get PDFNematodes are abundant and ubiquitous animals which are poorly known at intraspecific level. This work represents the first attempt to fill the gap on basic knowledge of genetic variability and differentiation in Protostrongylus oryctolagi, a nematode parasite of lagomorphs. 68 cox1 sequences were obtained from brown hares collected in five locations in Northern and Central Italy, highlighting the presence of a high amount of genetic variation inside this species. The eleven haplotypes identified (Haplotype diversity equal to 0.702) were split into two lineages: lineage A (comprising six different haplotypes, A1-A6) and lineage B (B1-B5). The mean intra-lineage amount of genetic variation was 0.3%, whereas the inter-lineage percentage of variation was ten-fold higher (3%). These two lineages were non-randomly distributed in the investigated areas. Lineage A showed a preference for Central Italy (Tuscany) even if it was sporadically found also in northern territories (Emilia-Romagna), while B-haplotypes were present exclusively in Emilia-Romagna. The analysis of molecular variance identified two main barriers to gene flow: (i) a strong major one which separate samples of Central Italy (PIA and GR7) from the northern ones (RE1, RE3 and MO1; ΦST = 0.750, P = 0.00); (ii) a secondary faint barrier which separates Pianosa island from Grosseto (ΦST = 0.133, P = 0.00). Any difference was found among northern samples (ΦST = 0.009, P = 0.00). The observed data may be explained by several factors ranging from the parasite’s biology (presence of a narrow host spectrum), the final host’s behaviour (small home range), the natural dispersion of the host-parasite dyad occurred in past or the recent passive men-mediated migration. Finally, the presence of unconventional shortened amplicons revealed the presence of NUMTs (nuclear copy of mitochondrial genes) in the P. oryctolagi nuclear genome, suggesting caution when using DNA barcode as unique marker for the identification of species belonging to this genus
Who is Supporting Whom? Balanced and Unbalanced Support Perceptions Shaping Acceptance of Collaborative Robots
Get PDFHumans and industrial collaborative robots (cobots) form intricate relationships as they both possess agency, share spaces, and must coordinate effectively to work together. In initial interactions, much like human-team dynamics, the perceived contribution of each agent plays a crucial role in shaping the collaborative experience and the acceptance of cobots. Beyond unilateral support perceptions from or to the cobot-termed as Received Support (RS) and Given Support (GS)-Mutual Support (MS) embodies a balanced, reciprocal dynamic where humans view their contribution as equal to that of the cobot. Drawing from social knowledge in human teams and aligning with recent interpretations of human-robot interactions, we propose that perceiving MS can foster fluent, trusting, and harmonious collaboration, ultimately increasing cobot acceptance in work routines. In this observational study, 56 novices collaborated with the industrial cobot UR10e to assess support dynamics. We explored how perceptions of balanced (MS) or unbalanced support (RS and GS) impact task performance (i.e., task time), Cognitive Factors (COG-F), User Experience (UX-F), and Human-Robot Relationship Factors (HRR-F), ultimately influencing cobot acceptance. We also examined the influence of initial attitudes toward robots. The findings suggest that fostering perceptions of MS, rather than focusing solely on functionality or work relief (RS), can lead to smoother integration and greater acceptance of cobots, especially among novices, regardless of their initial attitudes toward robots
Model Checking of Optimal LTL and ASAP Properties
No full textModel checking has long been employed as a method for the formal verification of control systems, with a focus on ensuring correctness and safety. However, in practical scenarios (e.g., robotics, aviation and aerospace), simply verifying whether a control system satisfies a given property may not suffice. There is often the requisite to optimize system behavior with respect to certain criteria, such as response time. For instance, in verifying a reachability property, one may be interested in knowing if the controller reaches the goal as soon as possible (ASAP). Despite the simplicity of such requirement, its formalization has not yet been addressed in the literature and requires to reason about the strategy of the controller and the cost of the executions in closed-loop with the given environment. More in general, this paper proposes the formalization and verification of properties for controllers that must satisfy a temporal logic specification optimally, i.e., in the best way possible given the behavior on the plant to be controlled. This relies on and is parametrized by a quantitative semantics for temporal logic. We focus on linear-time temporal logic (LTL), for which various quantitative semantics have been defined. In order to characterize the fulfillment of LTL properties as soon as possible (ASAP), we introduce a new quantitative semantics related to the length of the shortest informative prefix. Finally, we focus on ASAP co-safety properties and reduce the optimal model checking to standard qualitative reactive synthesis. We provide a proof of concept demonstration of the reduction with nuXmv
The monitoring of gastrointestinal nematodes and anthelmintic resistance and its implementation in small ruminant farms of Northern Italy
No full textGastrointestinal nematodes (GIN) pose a significant challenge to the health and productivity of sheep and goats worldwide. Anthelmintic drugs have historically been the primary strategy for managing GIN infections, but this approach has led to the emergence and spread of anthelmintic resistance (AR), threatening the sustainability of small ruminant farming. This thesis addressed the growing concern of AR in small ruminant farms in Northern Italy, a region characterized by diverse farming practices. The project was organized around two main aims: i) improving AR monitoring by exploring practical solutions; ii) building knowledge on the status of AR in North-eastern Italy, where studies on GIN and AR are still lacking. Firstly, an in-depth review of the epidemiology and control of GIN infections in Italy was conducted to summarize the knowledge on the issue and to examine the existing control measures, pointing out their limitations and the gaps in current knowledge. Secondly, the research investigated the potential of using pooled faecal samples as a cost-effective alternative to individual analysis for both faecal egg counts (for GIN monitoring) and faecal egg count reduction tests (FECRT). The findings suggested that pooled sampling can reliably estimate GIN burden and treatment efficacy, though individual analyses remain strongly preferable for FECRT. The third part focused on promoting a genus-specific approach to FECRT, using coprocultures to differentiate between genera. By monitoring the response to treatment of each GIN genus, this study, carried out in two goat farms, enhanced the precision of AR diagnosis, improving the interpretation of FECRT results. The genusspecific approach was then applied in the fourth phase to assess the efficacy of anthelmintics in six sheep and six goat farms of North-Eastern Italy. This application provided insights into the current state of AR across different GIN genera, revealing high levels of treatment ineffectiveness, especially against Haemonchus contortus. Lastly, a novel real-time PCR assay was designed to quantify the relative presence of H. contortus eggs among the overall GIN egg population. This assay was tested during FECRT trials conducted in five sheep and five goat farms, demonstrating greater specificity in monitoring GIN infections. The real-time PCR assay showed strong potential for integration into routine AR monitoring, providing more accurate diagnoses and enabling better-targeted interventions. Overall, this thesis provides valuable contributions to the understanding and monitoring of AR in Northern Italy, with broader implications for optimizing diagnostic practices. By promoting practical methods for AR monitoring, this thesis lays the groundwork for more effective and sustainable management practices
