University of Lugano
  • Lugano, Ticino, Switzerland
Recent publications
The dual role of macrophages in the healing process depends on macrophage ability to polarize into phenotypes that can propagate inflammation or exert anti-inflammatory and tissue-remodeling functions. Controlling scaffold geometry has been proposed as a strategy to influence macrophage behavior and favor the positive host response to implants. Here, we fabricated Polycaprolactone (PCL) scaffolds by Melt Electrowriting (MEW) to investigate the ability of scaffold architecture to modulate macrophage polarization. Primary human macrophages unpolarized (M0) or polarized into M1, M2a, and M2c phenotypes were cultured on PCL films and MEW scaffolds with pore geometries (square, triangle, and rhombus grid) characterized by different angles. M0, M2a, and M2c macrophages wrapped along the fibers, while M1 macrophages formed clusters with rounded cells. Cell bridges were formed only for angles up to 90°. No relevant differences were found among PCL films and 3D scaffolds in terms of surface markers. CD206 and CD163 were highly expressed by M2a and M2c macrophages, with M2a macrophages presenting also high levels of CD86. M1 macrophages expressed moderate levels of all markers. The rhombus architecture promoted an increased release by M2a macrophages of IL10, IL13, and sCD163 compared to PCL films. The proangiogenic factor IL18 was also upregulated by the rhombus configuration in M0 and M2a macrophages compared to PCL films. The interesting findings obtained for the rhombus architecture represent a starting point for the design of scaffolds able to modulate macrophage phenotype, prompting investigations addressed to verify their ability to facilitate the healing process in vivo.
Laser Metal Deposition (LMD) is an additive manufacturing technology that attracts great interest from the industry, thanks to its potential to realize parts with complex geometries in one piece, and to repair damaged ones, while maintaining good mechanical properties. Nevertheless, the complexity of this process has limited its widespread adoption, since different part geometries, strategies and boundary conditions can yield very different results in terms of external shapes and inner flaws. Moreover, monitoring part quality during the process execution is very challenging, as direct measurements of both structural and geometrical properties are mostly impracticable. This work proposes an on-line monitoring and prediction approach for LMD that exploits coaxial melt pool images, together with process input data, to estimate the size of a track deposited by LMD. In particular, a novel deep learning architecture combines the output of a convolutional neural network (that takes melt pool images as inputs) with scalar variables (process and trajectory data). Various network architectures are evaluated, suggesting to use at least three convolutional layers. Furthermore, results imply a certain degree of invariance to the number and size of dense layers. The effectiveness of the proposed method is demonstrated basing on experiments performed on single tracks deposited by LMD using powders of Inconel 718, a relevant material for the aerospace and automotive sectors.
Time plays an integral role in understanding International Business (IB) phenomena, and so does qualitative inquiry. Despite this, time has received little attention in qualitative IB research. To rectify this, we engage in a qualitative content analysis of qualitative articles published from 1999 until 2020 in the Journal of World Business, Journal of International Business Studies, as well as the Academy of Management Journal, and Journal of Management Studies. Our findings suggest four temporal theorizing styles, namely temporal variation, temporal accumulation, temporal evolution, and temporal story. We add further granularity by distinguishing for each how time (i.e., snapshots, incremental, evolutionary, discursive), and context (detached context, descriptive context, contextual specificity, intertwined context), generate different theorizing outputs (variation, staged process, evolutionary process, (process) story). Our paper contributes by offering researchers a rich vocabulary and conceptual building blocks to engage with different temporal theorizing styles in qualitative IB research.
Background Groin pain is a very common injury in multidirectional sports such as soccer, ice hockey, rugby and Australian football. Long-standing adductor-related groin pain is a persistent clinical condition and a frequent complaint in athletes involved in sports that require multiplanar movement patterns (change of direction, high-speed sprinting and kicking). To date, the lack of rehabilitation guidelines and return-to-play criteria makes this clinical entity difficult to manage. The aim of the present Delphi was to suggest, based on opinion and practical experience of a panel of experts, potential criteria that could be taken into consideration by clinicians in the RTP decision-making process in athletes suffering from long-standing adductor-related groin pain. Methods Thirty two out of 40 experts participated to a 3-Round Delphi questionnaire. In round 1, open-ended and closed questions about 9 different sections (palpation, flexibility, strength, patient-reported outcome measures, imaging, intersegmental control, performance tests, sport-specific skills, training load) were proposed to investigate return to play evaluation criteria used by each expert. Responses were analysed and coded to produce round 2 questionnaire that investigated only the sections and the items that reached the cut-off value (≥ 70%). Round 3 questionnaire was based on sections and items that reached cut-off value in previous rounds and experts rated their agreement for return to play criteria with a 5-point Likert Scale. Descriptive statistics enabled interpretation of consensus. Results High participation rate (80%) and response rate across the 3 rounds (100%) were recorded. 6 sections reached positive consensus in round 1, 1 section reached negative consensus. In round 2 positive consensus was confirmed only for 3 sections and negative consensus for 1 section. In round 3, positive agreement was established for strength (3 items), performance tests (3 items) and sport-specific skills (2 items) sections. Negative consensus was confirmed for imaging section. Conclusion Experts agreed that strength, performance tests and sport-specific skills can be used to support RTP decision, while imaging cannot be used. These findings could be useful in assisting clinicians in the RTP decision making.
Background The biochemical hallmarks of transient pseudo-hypoaldosteronism associated with a pyelonephritis include hyponatremia, hyperkalemia, and acidosis. We tested if the kidney-urinary tract ultrasound helps in predicting the diagnosis of overt pseudo-hypoaldosteronism in infants with a pyelonephritis. Cases presentation Between 2013 and 2020, we managed 71 previously healthy infants 4 weeks to 24 months of age with a pyelonephritis (42 males and 29 females) and made the biochemical diagnosis of pseudo-hypoaldosteronism in 17 (24%). Infants with and without pseudo-hypoaldosteronism did not significantly differ with respect to the prevalence of kidney-urinary tract ultrasound abnormalities, graded by means of the UTD classification system of urinary tract abnormalities. Conclusions Kidney-urinary tract ultrasound is almost routinely obtained in children with a febrile urinary tract infection. Our experience does not support the hypothesis that ultrasound might be relevant for the diagnosis of overt transient pseudo-hypoaldosteronism in babies affected by a urinary tract infection. Our data confirm the assumption that negative studies may be important for advancing clinical practice.
Background We investigated to what extent tube voltage, scanner model, and reconstruction algorithm affect radiomic feature reproducibility in a single-institution retrospective database of computed tomography images of non-small-cell lung cancer patients. Methods This study was approved by the Institutional Review Board (UID 2412). Images of 103 patients were considered, being acquired on either among two scanners, at 100 or 120 kVp. For each patient, images were reconstructed with six iterative blending levels, and 1414 features were extracted from each reconstruction. At univariate analysis, Wilcoxon-Mann-Whitney test was applied to evaluate feature differences within scanners and voltages, whereas the impact of the reconstruction was established with the overall concordance correlation coefficient (OCCC). A multivariable mixed model was also applied to investigate the independent contribution of each acquisition/reconstruction parameter. Univariate and multivariable analyses were combined to analyse feature behaviour. Results Scanner model and voltage did not affect features significantly. The reconstruction blending level showed a significant impact at both univariate analysis (154/1414 features yielding an OCCC < 0.85) and multivariable analysis, with most features (1042/1414) revealing a systematic trend with the blending level (multiple comparisons adjusted p < 0.05). Reproducibility increased in association to image processing with smooth filters, nonetheless specific investigation in relation to clinical endpoints should be performed to ensure that textural information is not removed. Conclusions Combining univariate and multivariable models is allowed to identify features for which corrections may be applied to reduce the trend with the algorithm and increase reproducibility. Subsequent clustering may be applied to eliminate residual redundancy.
Introduction Patellar tendinopathy is one of the most common musculoskeletal problems associated with sport. While commonly perceived as a predominantly male problem, recent epidemiological studies revealed that it also affects a large number of sport-active women. The aim of this systematic review was to understand how the available treatments apply to women affected by patellar tendinopathy. Methods We analysed the available literature with a systematic review on three databases (PubMed, Cochrane, Web of Science) on February 2021, retrieving a total of 136 studies published from 1983. Results The overall scientific field offers an astonishingly low number of data on treatment results referring to only 78 women (2%) in the entire literature. Only 5% of the retrieved articles considered focusing only or mostly on men to be a limitation. Conclusions Women represent only a minority of patients studied for this topic. The few documented cases are further fragmented by being related to different treatments, thus basically offering no solid evidence for results and limitations of any therapeutic approach in women. This literature analysis showed a greater gender gap than what is recognized in science and general medicine; it showed a gender blindness in sports medicine when investigating a common problem like patellar tendinopathy.
Optimal power flow (OPF) problems are ubiquitous for daily power grid operations and planning. These optimal control problems are nonlinear, non-convex, and computationally demanding for large power networks especially for OPF problems defined over a large number of time periods, which are commonly intertemporally coupled due to constraints associated with energy storage devices. A robust interior point optimization library BELTISTOS is proposed, which allows fast and accurate solutions to single-period OPF problems and significantly accelerates the solution of multi-period OPF problems via the aid of structure-exploiting algorithms. Adhering to high reporting standards for replicable and reliable analysis, BELTISTOS is compared with interior point optimizers within the software package MATPOWER and evaluated using large scale power networks with up to 193,000 buses and problems spanning up to 4800 time periods.
Context The aim of this review is to describe the proportion of testicular germ cell tumours (tGCTs) with recurrence, and the timing and anatomical sites of relapse across different disease stages and after different treatment options. We summarise published follow-up protocols and discuss current and future developments to personalise follow-up for patients with tGCT. Evidence acquisition A systematic literature search was conducted and current guidelines and selected institutional follow-up protocols were reviewed. Evidence synthesis Of 302 publications, we screened 68 full texts and included 29 studies; 22 of these were retrospective and seven were prospective in nature, contributing data for 20 570 patients. The number of patients included per study ranged from 119 to 2483. We compared the guideline follow-up protocols of the European Society for Medical Oncology, European Association of Urology, National Comprehensive Cancer Network, and American Urological Association, as well as institutional follow-up protocols. The protocols differed in terms of the number, time points, and type of follow-up investigations. Conclusions Future research should assess how tGCT can be followed to ensure high adherence, define the role of miR-371a-3p microRNA during follow-up, and develop follow-up protocols after curative treatment in the metastatic setting. Patient summary In this review of follow-up protocols for men with testis cancer, we observed different recommendations and discuss future research areas to improve follow-up for these patients.
Objectives The objective of this systematic review was to assess associations between quantitative body composition measures extracted from imaging examinations and chemotherapy-related toxicity in pancreatic cancer patients. A secondary objective was to evaluate the different definitions of sarcopenia across included studies. Methods This systematic review was conducted according to the PRISMA statement. A comprehensive literature search of three electronic databases was performed by two authors. For each eligible article, information was collected concerning the clinical setting; basic study; population characteristics; technical; body composition features evaluated; CA 19.9 tumor marker levels; chemotherapy drugs administered; toxicities (hematologic, nausea/vomiting, diarrhea, neuropathy, reduction of number of cycles, overall toxicity); association of body composition values with toxicities. The overall quality of the included studies was critically evaluated. Results After the initial retrieval of 1137 articles, the systematic review included 12 articles (1/12 in the neo-adjuvant setting; 2/12 in the adjuvant setting; 3/12 in the metastatic setting; 2/12 in the unresectable setting; the other 4/12 included more than one clinical setting). The number of patients included ranged between 17 and 251; mean/median age ranged between 63 and 77 years; the percentage of sarcopenic patients ranged between 23 and 76%. The most frequent body composition parameter evaluated was skeletal muscle index (11/12). Chemotherapy regimens included gemcitabine (as monotherapy or in combination with other drugs); FOLFIRINOX and S-1. Among the trials including gemcitabine, 2/9 demonstrated an association with toxicity, whereas 7/9 did not; among those including FOLFIRINOX, one demonstrated associated toxicity whereas the others did not. Altogether, 4/12 papers demonstrated an association between the body composition values and the development of chemotherapy-related toxicities. Conclusions There is a wide variability of results about the association of body composition and chemotherapy-related toxicity in PC patients. Furthermore, cut-off values to define sarcopenia in PC patients are not yet uniformly defined. Systematic Review Registration , identifier CRD42022337753.
Smart contracts are tempting targets of attacks, since they often hold and manipulate significant financial assets, are immutable after deployment, and have publicly available source code, with assets estimated in the order of millions of US Dollars being lost in the past due to vulnerabilities. Formal verification is thus a necessity, but smart contracts challenge the existing highly efficient techniques routinely applied in the symbolic verification of software, due to specificities not present in general programming languages. A common feature of existing works in this area is the attempt to reuse off-the-shelf verification tools designed for general programming languages. This reuse can lead to inefficiency and potentially unsound results, since domain translation is required. In this paper we describe a carefully crafted approach that directly models the central aspects of smart contracts natively, going from the contract to its logical representation without intermediary steps. We use the expressive and highly automatable logic of constrained Horn clauses for modeling and we instantiate our approach to the Solidity language. A tool implementing our approach, called Solicitous, was developed and integrated into the SMTChecker module of the Solidity compiler solc. We evaluated our approach on an extensive benchmark set containing 22446 real-world smart contracts deployed on the Ethereum blockchain over a 27 months period. The results show that our approach is able to establish safety of significantly more contracts than comparable, publicly available verification tools, with an order of magnitude increase in the percentage of formally verified contracts.
Objectives To evaluate the combined contribution of brain and cervical cord damage in predicting 5-year clinical worsening in a multicentre cohort of definite multiple sclerosis (MS) patients. Methods Baseline 3.0T brain and cervical cord T2-weighted and three-dimensional T1-weighted MRI was acquired in 367 patients with MS (326 relapse-onset and 41 progressive-onset) and 179 healthy controls. Expanded Disability Status Scale (EDSS) score was obtained at baseline and after a median follow-up of 5.1 years (IQR=4.8–5.2). At follow-up, patients were classified as clinically stable/worsened according to EDSS changes. Generalised linear mixed models identified predictors of clinical worsening, evolution to secondary progressive (SP) MS and reaching EDSS=3.0, 4.0 and 6.0 milestones at 5 years. Results At follow-up, 120/367 (33%) patients with MS worsened clinically; 36/256 (14%) patients with relapsing–remitting evolved to SPMS. Baseline predictors of EDSS worsening were progressive-onset versus relapse-onset MS (standardised beta (β)=0.97), higher EDSS (β=0.41), higher cord lesion number (β=0.41), lower normalised cortical volume (β=−0.15) and lower cord area (β=−0.28) (C-index=0.81). Older age (β=0.86), higher EDSS (β=1.40) and cord lesion number (β=0.87) independently predicted SPMS conversion (C-index=0.91). Predictors of reaching EDSS=3.0 after 5 years were higher baseline EDSS (β=1.49), cord lesion number (β=1.02) and lower normalised cortical volume (β=−0.56) (C-index=0.88). Baseline age (β=0.30), higher EDSS (β=2.03), higher cord lesion number (β=0.66) and lower cord area (β=−0.41) predicted EDSS=4.0 (C-index=0.92). Finally, higher baseline EDSS (β=1.87) and cord lesion number (β=0.54) predicted EDSS=6.0 (C-index=0.91). Conclusions Spinal cord damage and, to a lesser extent, cortical volume loss helped predicting worse 5-year clinical outcomes in MS.
IntroductionCardiovascular disease is the leading cause of morbidity and mortality. Besides traditional cardiovascular risk factors, arterial stiffness is a recognized predictor of cardiovascular risk.Methods We investigated the relationship between traditional cardiovascular risk factors, sex, and aortic pulse wave velocity in subjects living in a countryside area of Southern Switzerland. For this aim, we performed a cross-sectional analysis of data from adult participants of the Swiss Longitudinal Cohort Study, which, initiated in 2015, follows health status and disease risk factors in a Swiss countryside cohort at least 6 years of age.ResultsA total of 387 people (205 women and 182 men) were included. Hyperlipidemia, overweight, and obesity were more common (p ≤ 0.001) and LDL-cholesterol, triglycerides, and hemoglobin A1c were higher (p < 0.03) in men than women. Systolic and diastolic brachial and aortic blood pressures were higher in men (p < 0.02), whereas aortic pulse wave velocity and aortic pulse pressure were higher in women (p < 0.05). The aortic pulse wave velocity was significantly higher in subjects with hypertension, hyperlipidemia, diabetes, and obesity, and significantly increased with age (p < 0.0001). Multiple linear regression analysis showed a significant correlation between pulse wave velocity and age, female sex, brachial systolic blood pressure, and heart rate (p < 0.005).Conclusion Also in a countryside area, the aortic pulse wave velocity is higher in subjects with hypertension, hyperlipidemia, diabetes and obesity, and significantly increases with age. Furthermore, with advancing age, aortic pulse wave velocity is higher in women than men.Trial identifier, NCT02282748.
The concrete used in floor slabs accounts for large greenhouse gas emissions in building construction. Solid slabs, often used today, consume much more concrete than ribbed slabs built by pioneer structural engineers like Hennebique, Arcangeli and Nervi. The first part of this paper analyses the evolution of slab systems over the last century and their carbon footprint, highlighting that ribbed slabs have been abandoned mainly for the sake of construction time and cost efficiency. However, highly material-efficient two-way ribbed slabs are essential to reduce the environmental impact of construction. Hence, the second part of this paper discusses how digital fabrication can help to tackle this challenge and presents four concrete floor systems built with digitally fabricated formwork. The digital fabrication technologies employed to produce these slab systems are digital cutting, binder-jetting, polymer extrusion and 3D concrete printing. The presented applications showcase a reduction in concrete use of approximately 50% compared to solid slabs. However, the digitally fabricated complex formworks produced were wasteful and/or labour-intensive. Further developments are required to make the digital processes sustainable and competitive by streamlining the production, using low carbon concrete mixes as well as reusing and recycling the formwork or structurally activating stay-in-place formwork.
Cette contribution porte sur des aspects séquentiels de l'évidentialité en interaction. A travers l'observation qualitative des données d'un corpus d'italien parlé, nous documentons des cas où la catégorisation de la source d'information - par exemple, perception directe, inférence, rumeur, discours d'autrui - par des moyens linguistiques se lie à la progression temporelle des tours et des séquences. L'émergence de l'évidentialité au niveau de la construction du tour de parole dans des incréments, des parenthèses et des autoréparations se corrèle avec des positions séquentielles à l'intérieur de paires de négociation de l'accord. Cette manifestation séquentielle de l'évidentialité permet aux participants d'atténuer ou de renforcer leur positionnement épistémique, de l'aligner à leur statut et de le justifier. Cela se passe dans le contexte d'un trouble dans la machinerie épistémique, touchant aux dimensions du savoir-en-interaction, notamment la primauté et la responsabilité.
The field of cardiac electrophysiology tries to abstract, describe and finally model the electrical characteristics of a heartbeat. With recent advances in cardiac electrophysiology, models have become more powerful and descriptive as ever. However, to advance to the field of inverse electrophysiological modeling, i.e. creating models from electrical measurements such as the ECG, the less investigated field of smoothness of the simulated ECGs w.r.t. model parameters need to be further explored. The present paper discusses smoothness in terms of the whole pipeline which describes how from physiological parameters, we arrive at the simulated ECG. Employing such a pipeline, we create a test-bench of a simplified idealized left ventricle model and demonstrate the most important factors for efficient inverse modeling through smooth cost functionals. Such knowledge will be important for designing and creating inverse models in future optimization and machine learning methods.
Introduction The aim of this systematic review and meta-analysis was to evaluate whether volar locking plate (VLP) fixation leads to better clinical and radiological outcomes than those of closed reduction and cast immobilization for the treatment of distal radius fractures (DRFs). Materials and methods A comprehensive literature search was performed in PubMed, Web of Science, and Cochrane databases up to January 2022. Inclusion criteria included randomized controlled trial (RCT) studies comparing VLP fixation with cast immobilization for DRFs. Investigated parameters were Patient-Rated Wrist Evaluation questionnaire, Disabilities of the Harm, Shoulder, and Hand score (DASH), range of motion (ROM), grip strength, quality of life (QoL), radiological outcome, and complication and reoperation rate, both at short- and mid-/long-term follow-up. Assessment of risk of bias and quality of evidence was performed with Downs and Black’s ‘Checklist for Measuring Quality’. Results A total of 12 RCTs (1368 patients) were included. No difference was found for ROM, grip strength, QoL, and reoperation, while the DASH at 3 months was statistically better in the VLP group ( P < 0.05). No clinical differences were confirmed at longer follow-up. From a radiological perspective, only radial inclination (4°) and ulnar variance (mean difference 1.1 mm) at >3 months reached statistical significance in favor of the VLP group (both P < 0.05). Fewer complications were found in the VLP group ( P < 0.05), but they did not result in different reintervention rates. Conclusions This meta-analysis showed that the surgical approach leads to a better clinical outcome in the first months, better fracture alignment, and lower complication rate. However, no differences in the clinical outcomes have been confirmed after 3 months. Overall, these findings suggest operative treatment for people with higher functional demand requiring a faster recovery, while they support the benefit of a more conservative approach in less demanding patients.
Modeling perception is critical for many applications and developments in computer graphics to optimize and evaluate content generation techniques. Most of the work to date has focused on central (foveal) vision. However, this is insufficient for novel wide-field-of-view display devices, such as virtual and augmented reality headsets. Furthermore, the perceptual models proposed for the fovea do not readily extend to the off-center, peripheral visual field, where human perception is drastically different. In this paper, we focus on modeling the temporal aspect of visual perception in the periphery. We present new psychophysical experiments that measure the sensitivity of human observers to different spatio-temporal stimuli across a wide field of view. We use the collected data to build a perceptual model for the visibility of temporal changes at different eccentricities in complex video content. Finally, we discuss, demonstrate, and evaluate several problems that can be addressed using our technique. First, we show how our model enables injecting new content into the periphery without distracting the viewer, and we discuss the link between the model and human attention. Second, we demonstrate how foveated rendering methods can be evaluated and optimized to limit the visibility of temporal aliasing.
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Serena Petrocchi
  • Institute of Communication and Health
Michael Bronstein
  • Faculty of Informatics
Rolf Krause
  • Institute of Computational Sciences / Center for Computational Medicine in Cardiology
Via G. Buffi 13, 6900, Lugano, Ticino, Switzerland