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Computational modelling of the interplay between genetic and epigenetic in tumour evolution
No full textCancer arises from complex interactions between genetic and epigenetic alterations that accumulate across cell populations over time. Copy number alterations (CNAs), DNA methylation changes, and clonal heterogeneity are fundamental drivers of tumour progression; understanding how these layers interact is key to decoding tumour evolution.
This thesis presents a comprehensive computational framework for the integrative analysis of tumour evolution through the joint modelling of genetic, epigenetic, and clonal variation using whole-genome sequencing data.
In the first part, we introduce a Bayesian approach for allele-specific copy number inference that leverages the native properties of long-read sequencing, including haplotype phasing and direct DNA methylation detection. The model jointly analyses read depth, B-allele frequency, and variant allele frequency to estimate tumour purity, ploidy, and allele-specific copy number states, while integrating haplotype-resolved methylation profiles. This formulation enables the identification of genomic regions where structural imbalance and methylation asymmetry co-occur, providing new insights into the interplay between genetic and epigenetic regulation. Benchmarking across simulated datasets spanning multiple sequencing depths and purity levels demonstrates comparable accuracy compared to existing short-read methods. Application to colorectal cancer organoids and preliminary analysis of 100-patient Genomics England cohort further reveals consistent relationships between CNAs and allele-specific methylation in key regulatory regions, supporting the hypothesis that copy number variation and methylation jointly shape gene regulation during tumour evolution.
The second part of the thesis introduces a population genetics-informed simulation framework designed to generate realistic synthetic tumour genomes and corresponding sequencing data for benchmarking and methodological development. The simulator models tumour evolution as a stochastic branching process, where each subclone acquires somatic point mutations, CNAs, and epigenetic alterations under user-defined evolutionary parameters such as mutation rate, selection strength, and clonal expansion dynamics. This approach captures the genetic heterogeneity observed in real tumours while maintaining explicit control over ground-truth evolutionary history. The framework includes a read-level sequencing simulator capable of producing both real whole genome sequencing data with customizable coverage, error rate, read length, and tumour purity, thereby allowing systematic evaluation of analytical tools under controlled conditions.
To ensure reproducibility and accessibility, the simulation platform is complemented by a standardized Nextflow pipeline, nf-core/tumourevo, which integrates modules for variant and driver annotation, copy number quality control, mutational signature analysis, and subclonal reconstruction. Benchmarking experiments demonstrate the framework’s capacity to reproduce realistic tumour evolutionary scenarios and to quantify the accuracy and limitations of existing inference methods.
Together, these contributions establish a unified framework that connects Bayesian modelling, evolutionary simulation, and long-read sequencing technologies. By jointly analysing copy number, methylation, and clonal structure, this work advances our capacity to interpret tumour evolution and provides a robust methodological foundation for integrating multi-layer molecular data in cancer genomics.Cancer arises from complex interactions between genetic and epigenetic alterations that accumulate across cell populations over time. Copy number alterations (CNAs), DNA methylation changes, and clonal heterogeneity are fundamental drivers of tumour progression; understanding how these layers interact is key to decoding tumour evolution.
This thesis presents a comprehensive computational framework for the integrative analysis of tumour evolution through the joint modelling of genetic, epigenetic, and clonal variation using whole-genome sequencing data.
In the first part, we introduce a Bayesian approach for allele-specific copy number inference that leverages the native properties of long-read sequencing, including haplotype phasing and direct DNA methylation detection. The model jointly analyses read depth, B-allele frequency, and variant allele frequency to estimate tumour purity, ploidy, and allele-specific copy number states, while integrating haplotype-resolved methylation profiles. This formulation enables the identification of genomic regions where structural imbalance and methylation asymmetry co-occur, providing new insights into the interplay between genetic and epigenetic regulation. Benchmarking across simulated datasets spanning multiple sequencing depths and purity levels demonstrates comparable accuracy compared to existing short-read methods. Application to colorectal cancer organoids and preliminary analysis of 100-patient Genomics England cohort further reveals consistent relationships between CNAs and allele-specific methylation in key regulatory regions, supporting the hypothesis that copy number variation and methylation jointly shape gene regulation during tumour evolution.
The second part of the thesis introduces a population genetics-informed simulation framework designed to generate realistic synthetic tumour genomes and corresponding sequencing data for benchmarking and methodological development. The simulator models tumour evolution as a stochastic branching process, where each subclone acquires somatic point mutations, CNAs, and epigenetic alterations under user-defined evolutionary parameters such as mutation rate, selection strength, and clonal expansion dynamics. This approach captures the genetic heterogeneity observed in real tumours while maintaining explicit control over ground-truth evolutionary history. The framework includes a read-level sequencing simulator capable of producing both real whole genome sequencing data with customizable coverage, error rate, read length, and tumour purity, thereby allowing systematic evaluation of analytical tools under controlled conditions.
To ensure reproducibility and accessibility, the simulation platform is complemented by a standardized Nextflow pipeline, nf-core/tumourevo, which integrates modules for variant and driver annotation, copy number quality control, mutational signature analysis, and subclonal reconstruction. Benchmarking experiments demonstrate the framework’s capacity to reproduce realistic tumour evolutionary scenarios and to quantify the accuracy and limitations of existing inference methods.
Together, these contributions establish a unified framework that connects Bayesian modelling, evolutionary simulation, and long-read sequencing technologies. By jointly analysing copy number, methylation, and clonal structure, this work advances our capacity to interpret tumour evolution and provides a robust methodological foundation for integrating multi-layer molecular data in cancer genomics
UTILIZZO DI NANOFIBRE DI POLICAPROLATTONE RIVESTITE DI COLLAGENE PER MIGLIORARE LA GUARIGIONE DI FERITE DIFFICILI
No full textQuesto studio sviluppa e valuta membrane nanofibrose di policaprolattone (PCL) rivestite con collagene e funzionalizzate con nanoparticelle d’argento (AgNPs) come medicazioni avanzate per ferite complesse. Le membrane sono state ottenute per elettrofilatura (PCL 12% p/v), attivate al plasma per aumentare l’idrofilia e successivamente rivestite tramite deposito controllato di collagene di Tipo I; le AgNP sono state sintetizzate con riduzione al citrato (Lee–Meisel) e applicate come strato antimicrobico. La caratterizzazione morfologica e superficiale (SEM, AFM, confocale) ha mostrato reti fibrose omogenee (≈350–600 nm) e coating uniformi senza alterazioni della nano‐architettura. Le proprietà fisico-meccaniche hanno indicato materiale conforme e non rigido, idoneo al movimento cutaneo; la gestione dei fluidi è risultata adeguata (WVTR nell’intervallo desiderabile). In vitro, i fibroblasti 3T3 hanno mostrato migliore adesione e incremento di segnale metabolico su PCL+collagene rispetto al PCL nudo (MTT, Alamar Blue on-disc), mentre le membrane con AgNPs hanno mantenuto citocompatibilità a breve termine. L’attività antimicrobica è stata quantificata mediante microdiluizione in brodo (MIC) contro Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853 ed Enterococcus faecium VRE (Ef-5), e mediante saggi di inibizione del biofilm su membrana, evidenziando riduzione della crescita planktonica e della biomassa aderente. La citotossicità è stata indagata con Alamar Blue in sospensione (contatto) e rilascio di LDH a 24–48 h, con valori elevati di vitalità e LDH basso-moderato, inferiori al controllo positivo, suggerendo una finestra operativa sicura ai carichi di AgNPs impiegati. Nel complesso, l’integrazione PCL/collagene/AgNPs fornisce un supporto meccanico conforme, segnali bioattivi pro-rigenerativi e un vantaggio antimicrobico misurabile, ponendo le basi per ulteriori studi ex vivo/in vivo verso applicazioni cliniche in wound care avanzato.This study develops and evaluates electrospun polycaprolactone (PCL) nanofiber membranes coated with collagen and functionalized with silver nanoparticles (AgNPs) as advanced dressings for complex wounds. Membranes were produced by electrospinning (12% w/v PCL), plasma-activated to increase hydrophilicity, then coated with Type I collagen; AgNPs were synthesized by citrate reduction (Lee–Meisel) and applied as the antimicrobial layer. Morphological and surface characterization (SEM, AFM, confocal) showed homogeneous fibrous networks (≈350–600 nm) and uniform coatings without nanoarchitectural changes. Physicomechanical testing indicated a compliant, non-rigid material suitable for cutaneous motion; fluid management was appropriate (WVTR within the desirable range). In vitro, 3T3 fibroblasts exhibited improved adhesion and higher metabolic signal on PCL+collagen versus bare PCL (MTT, on-disc Alamar Blue), while AgNPs-bearing membranes maintained short-term cytocompatibility. Antimicrobial activity was quantified by broth microdilution (MIC) against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, and VRE Enterococcus faecium Ef-5, and by on-membrane biofilm inhibition assays, demonstrating reduced planktonic growth and adherent biomass. Cytotoxicity was assessed using suspension Alamar Blue (contact exposure) and LDH release at 24–48 h, yielding high viability with low–moderate LDH, clearly below the positive control, consistent with a safe operating window at the applied AgNPs loading. Overall, the integrated PCL/collagen/AgNPs system provides compliant mechanical support, pro-regenerative bioactive cues, and a measurable antimicrobial advantage, establishing the basis for ex vivo/in vivo studies toward clinical wound-care applications
Enhancing Trustworthiness via Explanation Robustness and Aggregations
No full textQuesta Tesi si focalizza sulla affidabilità delle tecniche di Intelligenza Artificiale Spiegabile (in inglese, eXplainable Artificial Intelligence, XAI di seguito), con un focus sugli ambiti assicurativo e degli investimenti. Come prima direzione di ricerca, questo lavoro analizza il ruolo della robustezza delle spiegazioni al fine di aumentare l'affidabilità dei sistemi. La robustezza è, infatti, una proprietà essenziale sia dei sistemi di Intelligeza Artificiale (IA) che delle loro spiegazioni, ma talvolta risulta un aspetto trascurato. E' stato verificato come approcci di XAI molto popolari, ad esempio LIME e SHAP, siano molto instabili nonostante il loro vasto utilizzo in applicazioni reali ad alto rischio.
La seconda direzione di ricerca assume che una aggregazione di spiegazioni possa aumentare l'affidabilità. In particolare, assumendo che una delle singole spiegazioni possa fallire o risultare non robusta per uno specifico datapoint, una aggregazione di spiegazioni è in grado di tenere conto di questa vulnerabilità e proporre una singola spiegazione che riassuma molteplici punti di vista. E' importante sottolineare che i metodi di XAI sono soggetti al problema della discordanza (disagreement problem). Una aggregazione può quindi essere costruita per affrontare questi aspetti e aumentare l'affidabilità del sistema di IA.
Questi aspetti sono stati analizzati rispetto a un singolo modello e molteplici approcci XAI applicati ad esso, ma anche rispetto a spiegazioni derivanti da diversi modelli di apprendimento automatico. I risultati ottenuti dimostrano che la aggregazione di spiegazioni, così come la valutazione della robustezza, siano strumenti utili per lo sviluppo e l'utilizzo di soluzioni IA affidabili.This Thesis focuses on the trustworthiness of eXplainable Artificial Intelligence (XAI) approaches, with a focus on the fields of insurance and asset management. As a first research direction, this work investigates the role of explanation robustness to increase the system’s trustworthiness. Robustness is, in fact, an essential property of both Artificial Intelligence (AI) systems and their explanations, but may be overlooked at times. Popular XAI techniques such as LIME and SHAP have been proved to be highly unstable but are still widely used in high-risk real-world applications.
The second research direction posits that an aggregation of explanations may increase trustworthiness, providing a more conservative explanation. In particular, assuming that one of the individual explanations may fail or be non-robust for a single datapoint, an aggregation of explanation would be able to account for this and provide a single explanation that summarizes multiple points of view. Critically, XAI methods suffer from the disagreement problem, that is, may at times return explanations that disagree with one another. An aggregation can be constructed to deal with this aspect and increase the overall trustworthiness of the AI system.
These aspects have been investigated with respect to a single model and multiple XAI approaches applied to it, as well as with respect to explanations derived from different Machine Learning models. Results have shown that explanation aggregation as well as robustness evaluation are useful tools towards the development and deployment of trustworthy AI solutions
Complexity Assessments for Decidable Fragments of Set Theory. IV: A Quadratic Reduction from Constraints over Nested Sets to Boolean Formulae
No full textAs a contribution to automated set-theoretic inferencing, a translation is proposed of
conjunctions of literals of the forms x = y \z, x ̸= y \z, and z = {x}, where x, y, z stand
for variables ranging over the von Neumann universe of sets, into quantifier-free Boolean
formulae of a rather simple conjunctive normal form. The formulae in the target language
involve variables ranging over a Boolean ring of sets, along with a difference operator
and relators designating equality, non-disjointness, and inclusion. Moreover, the result
of each translation is a conjunction of literals of the forms x = y \z and x ̸= y \z and
of implications whose antecedents are isolated literals and whose consequents are either
inclusions (strict or non-strict) between variables, or equalities between variables. Besides
reflecting a simple and natural semantics, which ensures satisfiability preservation, the
proposed translation has quadratic algorithmic time complexity and bridges two languages,
both of which are known to have an NP-complete satisfiability problem
Spazio e potere nelle città lombarde del XIV secolo: le cittadelle viscontee
No full textLa ricerca indaga quali rapporti (anche di forza) legarono la forma materiale delle città lombarde e le strategie di affermazione del potere dei Visconti nell’Italia settentrionale del Trecento, quando il passaggio dalla frammentazione comunale allo stato regionale visconteo si manifestò, nel corso del secolo, attraverso la costruzione di fortificazioni urbane signorili. Soprattutto, la maggior parte delle realtà sottomesse vide la sistematica comparsa di una nuova struttura fortificata, la cittadella, con cui le comunità urbane si trovarono a convivere nel medio-lungo periodo. Trattandosi di grandi recinti fortificati, spesso collocati a ridosso della cinta muraria più esterna, che delimitavano con sbarramenti, ponti levatoi e torri delle aree pubbliche e private già esistenti, si è scelto di affrontare le implicazioni della diffusione e dell’utilizzo di tali fortezze attraverso una prospettiva che affiancasse alle problematiche politico-istituzionali una visione più prettamente ispirata allo studio della percezione e delle pratiche di fruizione dello spazio urbano, proponendo un approccio alternativo e integrativo all’interpretazione tradizionale che, già a partire da Machiavelli, ne ha visto il segno del rafforzamento dell’autorità principesca in chiave tirannica e oppressiva. In questo modo, la duplice analisi della forma urbis medievale e della documentazione scritta di età viscontea (XIV-XV secolo) ha cercato di decostruire l’idea di un’installazione rigida e astratta della dominazione dei Visconti nelle realtà sottomesse e di ricollocare le cittadelle nel loro contesto, in qualità di luoghi “vivi” all’interno della città, restituendo le concrete modifiche che interessarono la dimensione fisico-materiale e le pratiche di uso sociale degli spazi pubblici e privati a seguito della conquista dei signori di Milano e della costruzione dei quartieri fortificati. Ciò ha reso possibile riflettere, da un lato, sulle diverse finalità pratiche e ideologiche che spinsero i Visconti a servirsi di queste strutture a sostegno del proprio potere politico, le quali furono soggette a un’evidente modificazione morfologica nel corso del tempo. Dall’altro lato, lo studio dell’impiego militare delle cittadelle concretamente attestato, dei costi e dei tempi di realizzazione, così come degli interventi di manutenzione sostenuti dalle amministrazioni comunali, ha cercato di riempire e ripopolare i quartieri fortificati signorili, chiarendo le modalità di percezione di questi spazi “condivisi” e al tempo stesso “contesi” tra il potere signorile, le comunità urbane soggette, i soldati e i rappresentanti del governo visconteo a livello locale, soprattutto nei casi in cui la chiusura delle cittadelle interessava degli elementi essenziali per il controllo politico, religioso ed economico della città.The research investigates the relationships (including those of strength) that linked urban material forms to the political strategies of affirmation pursued by the Visconti family in 14th-century northern Italy, as the transition from municipal fragmentation to regional state manifested itself, over the course of the period, through the construction of seigneurial fortifications. Above all, most of the conquered centres saw the systematic appearance of a new fortified structure, the citadel, with which the urban communities were forced to live together in the medium-long term. Since these were large fortified enclosures, often located at the edges of the city walls, which surrounded existing areas with barriers, drawbridges and towers, the study choose to address the implications of the spread and use of such fortresses through a perspective that combines political and institutional problems with a vision more purely inspired by the study of the perception and practices of urban space use. The aim is to propose an alternative and complementary approach to the dominant interpretation which, starting from Machiavelli, sees these constructions as a sign of the strengthening of seigneurial authority in a tyrannical and oppressive key. In this way, the double analysis of the medieval forma urbis and of the written documentation from the Visconti age (14th-15th centuries) sought to deconstruct the idea of a rigid and abstract induction of seigneurial government in conquered realities to relocate citadels in their context, as “living” places within the city, by reporting the concrete changes that affected the material dimension of the city and social practices involving the use of public and private spaces after the conquest of the lords of Milan and the construction of the fortified enclosures. This made it possible to reflect, on the one hand, on the practical and ideological factors that led the Visconti family to employ different structural morphologies of fortified areas in support of their political power over time. On the other hand, the study of the documented military use of citadels, their costs and times of building, as well as maintenance interventions supported by communal administrations, has tried to fill and repopulate the fortresses with the intention of clarifying the ways of perception of these spaces “shared” and at the same time “disputed” between the seigneurial authority, the urban communities, the soldiers and the officers of the Visconti at a local level, especially when the closure of the citadels involved essential elements for the political, religious and economic control of the city
Martin Davis: obzor ego issledovanij po logike, informatike i filosofii
No full textMartin Davis (8 March 1928 – 1 January 2023) was a prominent logician and computer scientist. This article reviews his major contributions to logic, theoretical computer science, and philosophy, highlighting the connections between foundational theory and practical computation. It draws on his 1999 essay “From Logic to Computer Science and Back” and his 2016 autobiographical essay “My Life as a Logician”, reflecting on his research journey, key achievements, and the evolution of his interests over decades. The discussion emphasizes the lasting impact of his work on both logic and computer science
Heat stress alters the microenvironment of corals: oxygen depletion and oxidative damage in the gastrovascular cavity of two tropical species
No full textCurrent climate changes cause increasing stress to corals, which can disrupt host-symbiont relationships, leading to bleach-ing and mortality. While stress responses are well-documented at the coral colony and reef scales, less is known abouthow stress responses affect different compartments within the coral holobiont. Here, we investigated the impact of ther-mal stress on macro– and microscale compartments, including the endoderm-lined gastrovascular cavity (GVC) and theectoderm-lined external tissue surface, in two tropical corals, Caulastrea curvata and Galaxea fascicularis. We assessedthe coral physiological status via respirometry, variable chlorophyll fluorometry, O2 and H2O2 microsensor analyses, chlo-rophyll measurements, and oxidative stress biomarkers during a 14-day thermal stress exposure. Under heat stress, bothspecies showed a reduced O2 concentration in the GVC by up to 90% in the light, reaching hypoxic (< 50 μmol O2 L−1)to anoxic levels, while the O2 concentration in the external surface tissue of C. curvata decreased by 20%. Moreover, nochanges in the H2O2 dynamics of the coral’s external tissue surface were detected. Lipid peroxidation in the gastrodermisof both species increased significantly by 90–198% indicating oxidative damage, although antioxidant enzyme activity(SOD and CAT), chlorophyll content, and bulk metabolic rates (respiration and photosynthesis) remained stable. Our find-ings indicated that thermal stress could affect the microenvironment of corals, particularly in the GVC, without visiblebleaching or major disruptions in bulk physiology. This suggested the importance of microenvironmental metrics for theearly detection of coral physiological stress
Echoes of the earthquake: evidence-based suggestions for the management of psychological consequences of earthquakes
No full textExperiencing an earthquake can be a traumatic event, sometimes followed by another negative experience represented by post-earthquake temporary displacement. Both can have serious and lasting consequences on people’s wellbeing, quality of life, and life satisfaction even years after the traumatic event. These consequences can hinder the recovery of individuals and communities affected by an earthquake. After summarizing our previous investigations of psychological consequences in individuals who faced different experiences in terms of temporary displacement from their home after an earthquake, we provide a new empirical contribution on the predictors and correlates of autobiographical memory of post-traumatic stress disorder (PTSD) symptoms in individuals who had or had not been displaced from their homes after three Italian earthquakes (n = 340). We also examined the association between the PTSD memory measure and measures of wellbeing, quality of life, life satisfaction, and event-related health impairment. Being female, having lower individual resilience and stronger place attachment, having been or still being displaced from home, and having higher current risk awareness were associated with higher scores on the PTSD memory measure. Higher scores were also associated with lower current wellbeing, lower current and expected quality of life, lower life satisfaction during displacement, and more severe perceived health consequences. The results suggest that experiencing an earthquake followed by prolonged displacement hinders recovery from the negative psychological effects of the disaster. Overall, the reviewed research suggests the need for tailored interventions at the individual, social, and management levels to prevent and manage the negative psychological consequences of earthquakes at different stages of the disaster risk management cycle
Highlighting the bottom: light jet mistag efficiency calibration with ML-based b-tagging algorithms and b-quark forward-backward asymmetry measurement with the ATLAS Experiment
No full textThe Standard Model (SM) of particle physics has proven to be remarkably successful, with predictions tested to per-mille precision. Nonetheless, several open questions remain, such as the dominance of matter over antimatter, the existence of dark matter, non-zero neutrino masses, the hierarchy problem, and the strong CP problem.
Electroweak precision measurements are powerful tools to probe the SM and possible beyond-the-SM (BSM) effects. A persistent ~3σ tension exists between the two most precise determinations of sin^2 θW,eff, from the LEP measurement of the forward–backward asymmetry in b-quark production, Afb(b), and from the SLD measurement of A_l. Clarifying this discrepancy requires new experimental input.
This thesis presents preliminary studies, based on simulated events and on the LHC Run-2 and partial Run-3 dataset collected by ATLAS, aiming at a new experimental determination of Afb(b). The analysis explores methods for reconstructing the b-quark charge and building the asymmetry observable, with unfolding techniques used to evaluate statistical and systematic uncertainties.
An essential part of the work concerns jet flavour tagging, which is essential both for this measurement and for many other ATLAS analyses, including Higgs and top-quark physics. Recent improvements in b-jet tagging are highlighted, in particular the GN2 algorithm based on transformer architectures. Compared to the previous DL1d algorithm, GN2 achieves more than a factor of two improvement in rejecting light- and c-jets. The calibration of the b-tagging algorithms for Run-2 and Run-3 analyses, and in particular the strategies adopted to measure light-jet mistagging rates, are discussed. A further look into the next steps of the algorithm development is also shown.
Looking ahead, these developments set the stage for the HL-LHC era, where the increased luminosity and the upgraded ATLAS Inner Tracker (ITk) will provide unprecedented opportunities for precision measurements. The advances in flavour tagging and the methodology explored in this work will be key to fully exploiting the HL-LHC dataset, further refining electroweak precision tests and enhancing ATLAS sensitivity to new physics. Together, these studies demonstrate the potential of ATLAS to refine SM precision physics and to strengthen the tools needed for searches for new physics.The Standard Model (SM) of particle physics has proven to be remarkably successful, with predictions tested to per-mille precision. Nonetheless, several open questions remain, such as the dominance of matter over antimatter, the existence of dark matter, non-zero neutrino masses, the hierarchy problem, and the strong CP problem.
Electroweak precision measurements are powerful tools to probe the SM and possible beyond-the-SM (BSM) effects. A persistent ~3σ tension exists between the two most precise determinations of sin^2 θW,eff, from the LEP measurement of the forward–backward asymmetry in b-quark production, Afb(b), and from the SLD measurement of A_l. Clarifying this discrepancy requires new experimental input.
This thesis presents preliminary studies, based on simulated events and on the LHC Run-2 and partial Run-3 dataset collected by ATLAS, aiming at a new experimental determination of Afb(b). The analysis explores methods for reconstructing the b-quark charge and building the asymmetry observable, with unfolding techniques used to evaluate statistical and systematic uncertainties.
An essential part of the work concerns jet flavour tagging, which is essential both for this measurement and for many other ATLAS analyses, including Higgs and top-quark physics. Recent improvements in b-jet tagging are highlighted, in particular the GN2 algorithm based on transformer architectures. Compared to the previous DL1d algorithm, GN2 achieves more than a factor of two improvement in rejecting light- and c-jets. The calibration of the b-tagging algorithms for Run-2 and Run-3 analyses, and in particular the strategies adopted to measure light-jet mistagging rates, are discussed. A further look into the next steps of the algorithm development is also shown.
Looking ahead, these developments set the stage for the HL-LHC era, where the increased luminosity and the upgraded ATLAS Inner Tracker (ITk) will provide unprecedented opportunities for precision measurements. The advances in flavour tagging and the methodology explored in this work will be key to fully exploiting the HL-LHC dataset, further refining electroweak precision tests and enhancing ATLAS sensitivity to new physics. Together, these studies demonstrate the potential of ATLAS to refine SM precision physics and to strengthen the tools needed for searches for new physics
Heparin pretreatment in patients with ST-segment elevation myocardial infarction: A meta-analysis
No full textObjectives: To compare the prognostic impact of heparin pretreatment versus intraprocedural administration in patients with ST-segment elevation myocardial infarction. Background: There is a paucity of data regarding the best timing for heparin administration in STEMI. Methods: We systematically searched the literature for studies evaluating the comparative efficacy and safety of heparin pretreatment versus intraprocedural administration for the treatment of STEMI from 1980 to 2024. Random-effect meta-analysis was performed comparing clinical outcomes between the two groups. Results: 11 observational studies and 4 clinical trials with a total of 72,249 patients were included. The patients either received UFH at the time of diagnosis or during the pPCI. A pretreatment approach showed a significant decrease in death both at 30 days (OR = 0.68; 95 % CI 0.56–0.84) as well as at longer follow-up (Mean follow-up time 14.4 months; OR = 0.67; 95 % CI 0.48–0.94). Moreover, UFH pretreatment increased the rate of infarct related artery patency (IRA) (defined as TIMI 2–3) at first coronary angiography (OR = 1.54; 95 % CI 1.37–1.74), and did not show increase in major bleedings (OR 0.96, 95 % CI 0.74–1.24). Conclusion: A heparin pretreatment strategy at the time of diagnosis of STEMI is associated with increased patency of the infarct related artery and with a decreased risk of death without any safety concern regarding bleeding complications