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Characterizing the Learning Curve of ION Robotic Bronchoscopy: A CUSUM-Based Analysis of Diagnostic Yield
No full textBACKGROUND: To characterize the procedural learning curve for shape-sensing ION robotic-assisted bronchoscopy (ION) at a single institution, based on diagnostic performance and procedure time. METHODS: A retrospective analysis was conducted on 147 pulmonary nodules sampled with the ION SYSTEM across 129 procedures. The diagnostic yield was defined as the proportion of samples that led to a definitive diagnosis of malignancy or non-neoplastic disease. Learning curve analyses included cumulative sum (CUSUM) control chart methods for diagnostic yield and procedure time. To minimize procedural variability, only single-target cases were used in procedural time analysis. Generalized linear mixed-effects models (GLMMs) were used to identify predictors of diagnostic success. RESULTS: Among the 147 nodules, 129 (87.8%) yielded a definitive diagnosis, comprising 108 malignant and 21 non-malignant. The diagnostic CUSUM analysis revealed a steady performance improvement, approaching a plateau after 45 cases had been processed. For the subset of single-nodule procedures, the median procedure time decreased from 60 to 35 minutes, with visual change-point stabilization evident by case 40. GLMM identified a significant inverse association between procedure duration and diagnostic success (OR: 0.997; 95% CI: 0.994-0.999; P=0.005). Nodule size <15 mm was not significantly associated with a lower diagnostic yield (OR: 0.971; 95% CI: 0.873-1.080; P=0.611). No significant complications occurred; minor self-limited bleeding was observed in 7% of cases. CONCLUSION: Implementing the ION system demonstrates a measurable learning curve, with significant improvements in diagnostic yield and procedural efficiency observed after 40 cases have been performed. These findings underscore the importance of structured training and performance monitoring during the initial phase of adoption
Overlapping Schwarz preconditioners for isogeometric discretizations of acoustic wave problems
No full textThe aim of this work is to construct and analyze two-level overlapping additive Schwarz (OAS) preconditioners for isogeometric discretizations of the acoustic wave equation with absorbing boundary conditions. Both Collocation and Galerkin isogeometric methods are employed for space discretization, while time advancing is performed by means of a Newmark implicit scheme. The linear systems to be solved at each time step are ill conditioned, especially in case of highly regular splines, thus their solution requires the use of effective preconditioners. Two-level OAS solvers consist of partitioning the domain into overlapping subdomains, solving independent local problems on each subdomain and an additional coarse problem associated with the subdomain mesh. Several two-dimensional numerical results validate our theoretical estimates, showing the scalability and quasi-optimality of the algorithms proposed. We also investigate numerically the robustness of the OAS preconditioners with respect to the spline polynomial degree, the spline regularity and the overlap parameter
Advancing Sustainability in Hydrocarbon Production: Breakthroughs in CO2 Hydrogenation with Iron-Based Catalysts and Comprehensive Life Cycle Assessment of Environmental Impacts
No full textThe need for carbon-neutral synthetic fuels drives research into CO2 hydrogenation via Fischer−Tropsch (FT) synthesis,wherecatalyst selectionaffectsconversionefficiencyand environmentalperformance.Thisstudyapplieslifecycleassessment to three hydrotalcite-derived catalysts (Fe30, Fe40, Co45), evaluatingCO2utilizationefficiency, energydemand, andenvironmental impacts under laboratory-scale FTconditions. TheCO2 utilizationfactor(CUF),definedas theratioofCO2consumedto emitted, reached167%forCo45 at 350 °C, indicatingnetCO2 consumptiondespiteburdens fromcobalt productionandcritical rawmaterialuse. Iron-basedcatalystsofferlowerproduction-related emissions but lowerCO2 conversion,withFe40performing least favorably. Scenario analysis highlights electricity supply effects: replacing fossil powerwithhydroor biomass electricity improvesCO2 sequestrationbut introduces land-use and ecotoxicity challenges. These findings expose limitations of extrapolating laboratory-scale LCA to industrial systems and support the developmentof carbon-negativeFTfuelsbyguidingcatalystdesign,processefficiency, andenergyintegration
Mentalization and Emotional-Cognitive Rigidity as predictors of esketamine's effects on Treatment-Resistant Depression: Findings from a prospective observational study
No full textIntroduction: Treatment-Resistant Depression (TRD) remains a major challenge in the management of Major Depressive Disorder (MDD). Esketamine, the S-enantiomer of ketamine and a glutamatergic modulator, has been approved by the FDA and EMA for TRD in 2019. Beyond its rapid antidepressant effects, esketamine may enhance neuroplasticity, facilitating the reconnection with emotional and cognitive processes, improving mentalization, social cognition and promoting resilience. Objective: This prospective multicenter observational study aimed to evaluate esketamine's therapeutic impact on depressive symptoms and explore whether psychological and clinical factors—including mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity—could predict treatment response, enabling a more personalized approach to TRD management. Methods: Thirty-six TRD patients treated with esketamine were assessed over a six-month follow-up period using psychometric measures of depression severity, suicidality, mentalization, social cognition, psychache, and cognitive-emotional rigidity. Results: A significant association emerged between mentalization deficits and depressive symptoms. Specifically, patients with poor baseline mentalization abilities exhibited higher Montgomery-Åsberg Depression Rating Scale (MADRS) scores both at baseline and throughout follow-up. In contrast, greater cognitive rigidity appeared to have a protective role, potentially mitigating negative thinking and providing emotional stability, which may enhance resilience to stressors. Conclusions: These findings highlight the importance of a personalized treatment approach in TRD. Esketamine may be particularly beneficial in reducing cognitive rigidity, improving mentalization, and breaking the cognitive inflexibility that contributes to sustained negative depressive thinking patterns. Further research is needed to refine patient stratification and optimize treatment strategies for individuals with TRD
From Cyberspace to Virtual Space: Media-Phenomenological Aspects of Immersive Digital Environments
No full textThe essay investigates the specific mode of spatial experience generated by virtual reality (VR) environments, through a phenomenological and mediarcheological approach. Unlike other digital media, VR transforms images into inhabitable environments, requiring a redefinition of the very concept of image and its relationship to spatiality. Starting from the genealogy of cyberspace and the conceptual pair deterritorialisation/reterritorialisation, the author analyses how VR technologies produce a specific form of spatial immersion, in which the user is positioned as the zero-point of the coordinate system of the digital scenario. Drawing on phenomenological descriptions of spatiality, particularly from Husserl’s theory, the study reconstructs the perceptual and kinesthetic structures underlying the constitution of virtual space. It is argued that while VR environments succeed in generating a sense of spatial presence, they struggle to evoke the contingent, open-ended quality of physical space — what could be called the worldliness or sense of world
Long-term predictors of assisted erectile function after high-flow priapism: patient profile matters more than embolization technique
No full textBackground High-flow priapism (HFP) is a rare urological condition, often secondary to genitoperineal trauma, resulting in arterio-cavernosal fistulas. Superselective arterial embolization is the preferred treatment when conservative management fails, but long-term data on erectile function (EF) outcomes remain limited. Aim To evaluate long-term EF outcomes in patients with HFP undergoing embolization and to identify predictors of EF impairment at follow-up. Methods Data from 41 patients with HFP admitted to six tertiary referral centers (2002- 2024) were analyzed. Diagnosis was confirmed using penile Doppler ultrasound, blood gas analysis, and selective pudendal arteriography. Embolization was performed using absorbable or non-absorbable agents. EF was evaluated pre- and post-embolization using the International Index of Erectile Function-5 (IIEF-5) and the Erection Hardness Score questionnaires. Logistic and linear regression models were used to assess predictors of EF at follow-up. Outcomes Primary outcome was long-term erectile function, including the need for pharmacological or device-assisted EF. Secondary outcomes included patient satisfaction and associations with clinical and procedural variables. Results Median (interquartile range) age was 35 (27-44) years, and the pre-embolization IIEF-5 was 25 (24-25). Non-absorbable embolic agents were used in 35 (85.4%) patients. Median follow-up was 44 (12-80) months. At follow-up, the median IIEF-5 score was 21 (18-24), with a median decrease of -4 (-6-1) points from baseline. Severe ED occurred in only 2.4% of patients; however, 46.3% had assisted EF (phosphodiesterase type 5 inhibitors, nutraceuticals, low-intensity shock wave therapy, or vacuum devices). Patients with assisted EF at follow up had higher baseline Charlson Comorbidity Index (CCI) and lower IIEF-5 scores than those with unassisted EF (all P < 0.03). Lower CCI, and higher baseline IIEF-emerged as predictors of IIEF-5 scores at follow-up, after accounting for age. Higher CCI was the only predictor of assisted EF at follow-up. No significant associations were found with embolization technique and EF. Clinical Implications Baseline EF and comorbidity burden may help identify patients at risk for EF worsening and assisted EF post-embolization. These findings can guide individualized counseling and follow-up strategies. Strengths & Limitations This is the largest real-life cohort evaluating EF after embolization for HFP, using validated questionnaires. Limitations include the retrospective design and potential recall bias. Conclusion Superselective embolization for HFP is highly effective with limited impact on EF at long term. Nonetheless, nearly half of patients required assisted EF at follow-up, with comorbidities and lower baseline EF as significant predictors. Long-term monitoring and individualized counseling are essential
Electric Field-Induced Destabilization and Surface Modulation of Aβ42 Fibrils in Molecular Simulations: Theoretical Implications for DC Stimulation in Alzheimer’s Disease
No full textThe amyloid-β peptide 42 (Aβ42) forms fibrillar aggregates that are a hallmark of Alzheimer’s disease. While recent pharmacologic therapeutic strategies targeting Aβ42 fibrils and oligomers have shown promising results, safer and more effective approaches are still needed. Non-invasive brain stimulation (NIBS) techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been increasingly explored as a possible complementary intervention, but the molecular mechanisms by which static electric fields could influence amyloid aggregation remain poorly understood. Here, we use atomistic molecular dynamics simulations to investigate the effects of static electric fields on Aβ42 fibrils. We examine the response of an ex vivo fibril structure, with reconstructed N-terminal regions, to increasing field strengths under different structural restraint conditions. Our results show that the electric field perturbs the disordered N-terminal “fuzzy coat,” altering its conformational dynamics and reducing its interactions with the fibril core. This reorganization modifies the surface properties of the fibril, potentially impairing secondary nucleation. Additionally, simulations with unrestrained fibril ends reveal increased fluctuations in core residues, particularly near the N-terminus, indicating a destabilizing effect that may hinder fibril elongation. While the field strengths used here exceed those typical of NIBS, our findings provide a molecular-level rationale for how electric fields could modulate fibril propagation and support further experimental investigations under physiologically relevant conditions
THE PERSISTENCE OF INDETERMINACY: CONTEMPORARY THEORIES AND KRIPKENSTEIN'S CHALLENGE TO REPRESENTATIONAL CONTENT
No full textThis thesis is concerned with the foundations of representational content. There is a familiar feature of words, sentences, beliefs, and perceptions: they are about, or mean, or represent something. The sentence “cats are cute” is about cats being cute, and my belief that cats are cute is also about cats being cute. Most things in the world are not about something else – they just are. In virtue of what, then, do words, sentences, beliefs, and perceptions represent the things they represent? In other words, in virtue of what do they have the contents that they do?
In Wittgenstein on Rules and Private Language (1982/1995), Saul Kripke argued that there is no fact of the matter about what we mean by our words. Though Kripke intended to target theories of meaning in the linguistic sense, his arguments ultimately challenge theories of mental content as well. The effects of Kripke’s argument have been devastating: Theories of content have struggled to avoid his sceptical paradox ever since. The aim of this work is to investigate and determine whether several contemporary approaches to meaning broadly understood meet the sceptical challenge Kripke set up nearly fifty years ago. These contemporary approaches include causal theories of reference, teleosemantic theories of mental content, and phenomenal intentionality theories. The result of my investigation is, unfortunately, negative. None of the contemporary approaches examined in this work successfully isolate what makes representations have the contents that they do
From Neanderthals to Homo sapiens: new palaeoecological and tephrocronological data from the MIS3 layers of Grotta-Riparo di Uluzzo C (Apulia, southern Italy)
No full textThe southern Italian Peninsula plays a crucial role as a biogeographical hotspot in Southern Europe, influenced significantly by the Mediterranean climate. This environment acted as a glacial refuge for diverse flora and fauna, humans included. This study employs pollen analysis on Mousterian and Uluzzian sediments from Grotta-Riparo di Uluzzo C in the Salento Peninsula (southern Italy) to reconstruct the vegetation landscapes encountered by the late Italian Neanderthals (thus far associated with the Mousterian) and early modern humans (linked to the Uluzzian) during the mid Marine Isotope Stage (MIS) 3. Our palynological analyses reveal a distinctive and diverse environment within the Mediterranean landscape. Tephrochronological and OSL constraints and paleoenvironmental variability consistently allow us to date the investigated interval between ~46.6 ka and 43.4 ka, encompassing the second part of the long Greenland interstadial 12 (GI-12) and the onset of the GI-11. Over these three millennia, the environment in the area of Uluzzo C is characterized by a rich flora mainly composed of evergreen elements. Additionally, heliophytes such as Amaranthaceae, Artemisia, and Poaceae are observed. The consistent presence of pollen taxa such as Juglans, and Pinus halepensis/pinea, among others, highlights the importance of this coastal area of Apulia for the long-term persistence of Mediterranean species during the Late Pleistocene. These taxa could be supported by a generally mild climate, as suggested by the occurrence of Olea, Myrtus, and Cistus. These diverse environments would undeniably have offered various opportunities for the survival of Neanderthals and early Upper Palaeolithic hominins, especially during the warm phases and, critically, the cold events of the Late Pleistocene. Our integrated approach underscores the importance of GrottaRiparo di Uluzzo C as a MIS 3 archive, contributing to the ongoing debate on the spatial extent of glacial refugia. Our data from Uluzzo C corroborate the previous idea that the climatic and environmental setting were not the main reason for Neanderthals' abandonment of Uluzzo Bay and potentially southern Italy around 45,000 years ago
