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Jeremy Corbyn’s election to Labour Party leader represented an ideological challenge to the neoliberal consensus in British politics. It also signalled the start of an uncritical hostility from the British press (Cammaerts et al, 2020). There has been research on citizen-generated, digital content in favour of Corbyn (Dean, 2019; Mcloughlin and Southern, 2020) which includes a large visual element. However, there has been no research on the visual aspect of the negative coverage he received. In this thesis, I answer Dean’s (2019) call to take visuals more seriously in the study of British politics and consider how conditions offline influence those online, and vice versa. I adopt Chadwick’s (2017) notion of the hybrid media to move beyond the old vs new media binary, whilst recognising that news organisations still have a strong influence within the hybrid media (Chadwick et al., 2018; Chadwick and Vaccari, 2019). Focusing on the visual element of the coverage, I carry out multimodal discourse analysis of negative coverage across the hybrid media. I find that Corbyn was constructed as dangerous through a process of ‘Othering’. This ‘Otherness’ was articulated through its binary opposition to a ‘Britishness’ constructed via an (neo)imperial discursive repertoire. Analysing the visual dimension of this coverage reveals how power operated to position Corbyn within the ‘space of the possible’. Ultimately, this power ensured the dominance of a neoliberal dogma integral to Britain’s neo-imperial international presence and domestic relations of inequality. The power to (in)visibilise is the power to hide the past, construct the present and deny any number of possible futures, both domestically and internationally.

Plasma membrane (PM) H+-ATPases of the P-type family are highly conserved in yeast, other fungi, and plants. Their main role is to establish an H+ gradient driving active transport of small ions and metabolites across the PM and providing the main component of the PM potential. Furthermore, in both yeast and plant cells, conditions have been described under which active H+-ATPases promote activation of TORC1, the rapamycin-sensitive kinase complex controlling cell growth. Fungal and plant PM H+-ATPases are self-inhibited by their respective cytosolic carboxyterminal tails unless this domain is phosphorylated at specific residues. In the yeast H+-ATPase Pma1, neutralization of this autoinhibitory domain depends mostly on phosphorylation of the adjacent Ser911 and Thr912 residues, but the kinase(s) and phosphatase(s) controlling this tandem phosphorylation remain unknown. In this study, we show that S911-T912 phosphorylation in Pma1 is mediated by the largely redundant Ptk1 and Ptk2 kinase paralogs. Dephosphorylation of S911-T912, as occurs under glucose starvation, is dependent on the Glc7 PP1 phosphatase. Furthermore, proper S911-T912 phosphorylation in Pma1 is required for optimal TORC1 activation upon H+ influx coupled amino-acid uptake. We finally show that TORC1 controls S911-T912 phosphorylation in a manner suggesting that activated TORC1 promotes feedback inhibition of Pma1. Our results shed important new light on phosphoregulation of the yeast Pma1 H+- ATPase and on its interconnections with TORC1., SCOPUS: ar.j, info:eu-repo/semantics/published

The advent of time-domain astronomy has led to the discovery of a plethora of energetic transient phenomena showcasing a wide range of luminosities and durations, the latter spanning from a few seconds to a few months. While photons remain our primary observational tool, at high-energy they can interact with matter and radiation in their journey from the source to Earth, therefore carrying limited information about distant sources. Consequently, unraveling the mechanism powering transients solely through electromagnetic radiation can pose significant challenges, and the nature of most of these sources remains puzzling. Yet astrophysical transients also act as cosmic accelerators, producing cosmic rays and high-energy neutrinos, and they can emit gravitational waves. As each of these messengers carries unique information about their source, only by combining them can we gain a deep understanding of the most powerful phenomena occurring in the cosmos. Within the vibrant landscape of multi-messenger astronomy, the focus of this thesis is on high-energy neutrinos. Due to their feeble interaction with matter, neutrinos can travel large distances almost unhindered and therefore stand out as unique probes of the high-energy sky. This thesis endeavors to assess the potential of high-energy neutrinos to unravel the enigmatic nature of some transient phenomena. The first part of this thesis offers a broad overview of multi-messenger astronomy and its current status, followed by a discussion on particle acceleration and radiative processes in high-energy astrophysics. Next, relevant transient sources and their connection with high-energy neutrinos are outlined. Finally, the thesis provides an overview of the currently operating and forthcoming electromagnetic as well as high-energy neutrino telescopes. These introductory Chapters pave the road towards discussing the potential of combining multi-wavelength and high-energy neutrino data. The second and third pa

Plasma membrane H+-ATPases are highly conserved in yeast, other fungi and plants. Their main role is to establish the H+ gradient at the plasma membrane (PM) to maintain the cytosolic pH close to neutral values and fuel the uptake of nutrients through secondary active transport systems. In both plants and yeast, PM H+-ATPases have also been described to promote activation of TORC1, the rapamycin-sensitive kinase complex controlling cell growth. This for instance occurs in yeast upon H+ influx coupled to amino acid uptake. Fungal and plant PM H+-ATPases are self-inhibited by their carboxyterminal tails unless this domain is phosphorylated at specific residues. In the yeast PM H+-ATPase (Pma1), the self-inhibitory action of the carboxyterminal tail is neutralized when the adjacent S911 and T912 are phosphorylated, but the kinase(s) and phosphatase(s) controlling their phosphorylation remain unknown.In this thesis work, with the objective of understanding the molecular events taking place at Pma1`s level upon H+ influx and triggering the signaling cascade towards TORC1, we show that the largely redundant Ptk1 and Ptk2 kinases are responsible for phosphorylating S911-T912 at the carboxyterminal tail of Pma1. We also show that the carboxyterminal tail of Pma1 is not essential to initial TORC1 activation induced by H+-coupled amino acid uptake. However, if not properly phosphorylated by Ptk1 and Ptk2 kinases, the carboxyterminal tail of Pma1 can interfere with TORC1 activation. Additionally, we provide evidence that activated TORC1 exerts negative feedback control on Pma1 by reducing phosphorylation of its carboxyterminal tail.Overall, our results shed important new light on phosphoregulation of the yeast Pma1 H+-ATPase and on its interconnections with TORC1., Doctorat en Sciences, info:eu-repo/semantics/nonPublished

IMPACT: While both the academic literature and practice suggest that the use of accounting information is often not neutral, the factors behind a manipulative use of accounting information are under-researched—especially in the public sector context. This article is intended to stimulate the debate about ethical questions related to accounting information manipulation that are often neglected. The authors aim to increase awareness among politicians and public managers about the disputability, or even inappropriateness, of the accounting information they receive.

Whale migrations are poorly understood. Two competing hypotheses dominate the literature: 1. moving between feeding and breeding grounds increases population fitness, 2. migration is driven by dynamic environmental gradients, without consideration of fitness. Other hypotheses invoke communication and learned behaviors. In this article, their migration was investigated with a minimal individual-based model at the scale of the Global Ocean. Our aim is to test if global migration patterns can emerge from only the local, individual perception of environmental change. The humpback whale (Megaptera novaeangliae) meta-population is used as a case study. This species reproduces in 14 zones spread across tropical latitudes. From these breeding areas, humpback whales are observed to move to higher latitudes seasonally, where they feed, storing energy in their blubber, before returning to lower latitudes. For the model, we developed a simplified ethogram that conditions the individual activity. Then trajectories of 420 whales (30 per DPS) were simulated in two oceanic configurations. The first is a homogeneous ocean basin without landmasses and a constant depth of −1000 m. The second configuration used the actual Earth topography and coastlines. Results show that a global migration pattern can emerge from the movements of a set of individuals which perceive their environment only locally and without a pre-determined destination. This emerging property is the conjunction of individual behaviors and the bathymetric configuration of the Earth’s oceanic basins. Topographic constraints also maintain a limited connectivity between the 14 DPSs. An important consequence of invoking a local perception of environmental change is that the predicted routes are loxodromic and not orthodromic. In an ocean without landmasses, ecophysiological processes tended to over-estimate individual weights. With the actual ocean configuration, the excess weight gain was mitigated and also produced incre

The objective was to carry out a Systematic Literature Review (SLR), based on a central question: “Are anatomical pieces and histological slides used as a didactic resource in Teaching Snakes in Basic Education?”. For the SLR, the descriptors “Didactic Manual”, “Morphology of Snakes” and “Snakes” were used, totaling 17 journals; 5 congress annals and 2 symposiums related to the theme. As a result, a total of 33,135 works were identified and of these, 57 were selected since they agreed with the central question, and only 28 were classified as Included as they contained theoretical and practical content related to the central question. It is concluded that there are few works that address the theme Snakes, mainly listing theory to practice, and none of them mention Histology., Objetivou-se a realização de uma Revisão Sistemática da Literatura (RSL), baseando-se em uma questão central: “Utiliza-se peças anatômicas e lâminas histológicas como recurso didático no Ensino de Serpentes na Educação Básica?”. Para a RSL foram utilizados descritores “Manual Didático”, “Morfologia de Serpentes” e “Serpentes”, totalizando 17 periódicos; 5 anais de congressos e 2 simpósios relacionados com a temática. Como resultado, foram identificados ao todo 33.135 trabalhos e destes, 57 foram selecionados por apresentarem concordância com a questão central, e apenas 28 foram classificados como Incluídos por conter conteúdos teóricos e práticos relacionados a questão central. Conclui-se que são poucos os trabalhos que abordam a temática Serpentes, principalmente elencando a teoria à prática, e em nenhum deles foi encontrado menção a Histologia.

Whale migrations are poorly understood. Two competing hypotheses dominate the literature: 1. moving between feeding and breeding grounds increases population fitness, 2. migration is driven by dynamic environmental gradients, without consideration of fitness. Other hypotheses invoke communication and learned behaviors. In this article, their migration was investigated with a minimal individual-based model at the scale of the Global Ocean. Our aim is to test if global migration patterns can emerge from only the local, individual perception of environmental change. The humpback whale (Megaptera novaeangliae) meta-population is used as a case study. This species reproduces in 14 zones spread across tropical latitudes. From these breeding areas, humpback whales are observed to move to higher latitudes seasonally, where they feed, storing energy in their blubber, before returning to lower latitudes. For the model, we developed a simplified ethogram that conditions the individual activity. Then trajectories of 420 whales (30 per DPS) were simulated in two oceanic configurations. The first is a homogeneous ocean basin without landmasses and a constant depth of −1000 m. The second configuration used the actual Earth topography and coastlines. Results show that a global migration pattern can emerge from the movements of a set of individuals which perceive their environment only locally and without a pre-determined destination. This emerging property is the conjunction of individual behaviors and the bathymetric configuration of the Earth’s oceanic basins. Topographic constraints also maintain a limited connectivity between the 14 DPSs. An important consequence of invoking a local perception of environmental change is that the predicted routes are loxodromic and not orthodromic. In an ocean without landmasses, ecophysiological processes tended to over-estimate individual weights. With the actual ocean configuration, the excess weight gain was mitigated and also produced incre

Night sleep and parental bedtime practices have rarely been investigated in late talkers. This study aimed to explore: night sleep, parental bedtime practices, and their associations in late talkers as well as individual, socio-demographic, and socio-relational factors affecting them. Parents of 47 30-month-old late talkers, born low-risk preterm (n = 24) or full-term (n = 23), with an expressive vocabulary size ≤10th percentile measured by the MacArthur-Bates Communicative Development Inventory Words and Sentences, and normal cognitive abilities measured by the Bayley Scales, completed the Infant Sleep Questionnaire, the Parental Interactive Bedtime Behaviour Scale, and the Parenting Stress Index Short Form. Results showed slight settling difficulties, night wakings, and frequent co-sleeping in late talkers. Encouraging autonomy practices were frequently used by parents, rather than active physical comforting ones. Recurrent settling difficulties were reported by parents who often applied encouraging autonomy practices, whereas greater night waking problems and frequent co-sleeping were reported by parents who often left their child crying. Low-risk preterm birth and mother’s parenting stress predicted total sleep difficulties and night wakings; first-born, high maternal education level and mother’s parenting stress predicted settling difficulties; mother’s parenting stress was the only predictor for co-sleeping and leaving to cry. These findings have relevant implications for improving late talkers’ night sleep and their parents’ bedtime practices.

Purpose: This article investigates how Sustainable Development Goals (SDGs) can be integrated into the strategic planning and management processes of local governments (LGs). It draws from the classic strategic planning and control framework developed in management studies and elaborates some propositions for adapting, implementing and monitoring the SDGs at the city level. Design/methodology/approach: As a first step in the assessment of the ways the principles of sustainable development can be integrated into LG management, this research scrutinizes the incorporation of sustainability goals in the strategic plans of all medium-to-large capital cities of provinces in Italy, a context in which there has been a National Strategy for Sustainable Development (NSSD) since 2016. Findings: The focus on SDGs at the LG level in Italy is in its initial stage, and few capital cities have started to integrate sustainable development concerns into their comprehensive strategic plans. SDGs are used mainly as a reference framework in the strategic plans to demonstrate the contribution of LG strategies to global concerns on sustainable development. Practical implications: The paper offers insights for political leaders and public managers to rethink their strategic management systems, including the continuous process of evaluating and updating of strategic plans, in accordance with the multidimensional perspective of sustainability. To this end, the study has identified possible patterns of actions that public managers elsewhere will find useful. Originality/value: The managerial approach behind the proposed conceptual framework might contribute to effectively localize the SDGs in multilevel government settings and to integrate the concept of sustainability as a guiding principle into organizational routines.

Background: During the COVID-19 pandemic, many inflammatory bowel disease (IBD) centres had to reorganise their work, and multidisciplinary teams, including IBD nurses, have had to try to deliver services to patients as safely as possible. Aims: This survey aimed to assess the thoughts, opinions and feelings of IBD patients on biologics regarding the efforts of IBD nurses to organise care during the COVID-19 pandemic. Methods: An evaluation survey based on an anonymous questionnaire was distributed to IBD nurses in five Italian IBD centres, in parallel. Findings: Of 306 participants, 55.6% had Crohn’s disease and 44.4% had ulcerative colitis. Most (79.1%) were aware of the specialist IBD nurse role, and 75.8% could distinguish it from generalist nurses. Of patients, 99.7% felt IBD nurses were competent to care for their condition and 91.2% felt that IBD nurses could provide valid scientific information. Meanwhile, 81.4% had a good or excellent relationship with their IBD nurse. Patients reported that most nurses wore personal protective equipment (94.4%), promoted self-care (91.8%), asked about presence of fever or cough (84.3%), asked about patient health status (83.7%) and covered pandemic safety and social distancing rules (69.3%), but fewer spoke about patient mood (44.4%) or relevant benefits, rules and exemptions (26.8%). Most participants (77.8%) faced pandemic-related issues for infusions. Nearly all (97.4%) knew immunosuppressed people were vulnerable to COVID-19, but only 42.8% spoke to their nurse about it. Some 61.8% of patients were concerned about COVID-19, but only 39.2% raised this with the IBD nurse. However, many more patients spoke to a nurse about concerns regarding biologics (41.8%) and worsening IBD symptoms (46.4%) in the pandemic than the actual number experiencing these issues (13.7% and 4.3%, respectively). Conclusion: The results show that IBD patients appreciate the role of the specialist nurse in their care.

There is sufficient evidence on the negative consequences of cyberbullying victimisation depending on the coping styles. Social support seeking is among the most effective strategies for coping with cybervictimisation, but it is scarcely used. The robust Maximum Likelihood (ML) method was used to test the potential mediating role of individual (self-awareness, and responsible decision-making) and contextual variables (self-perceived parental and peer support) in the relationship between cybervictimisation and social support seeking in boys and girls. This cross-sectional study collected data from 1,276 Spanish secondary school students (51.2% boys, 48.8% girls) aged 11–18 (M = 13.88, SD = 1.42). Structural equation modelling (SEM) results pointed out responsible decision-making and self-perceived parental support as relevant mediating factors for girls. By contrast, the model was not significant for boys. These findings highlight the importance of both individual and contextual variables in helping adolescents cope with cyberaggressions, considering gender differences.

Internet usage is a salient developmental factor in adolescents’ lives. Although relevant correlates of Internet use have been documented earlier, there is a lack of information on lower socioeconomic status groups. This is important, as these adolescents have increased risk of negative online experiences. The current survey aimed to explore Internet use and parental involvement amongst adolescents from areas of socio-economic disadvantage in 30 urban schools across five European countries. A total of 2594 students participated, of whom 90% were 14–16 years. Virtually all adolescents of socioeconomic disadvantage had Internet access, with 88.5% reporting spending more than two hours per day online, often on apps such as Instagram, Snapchat, and YouTube. Almost one-third of adolescents did not talk with their parents about their Internet use and almost two-thirds indicated that their parents were only a little or not interested in their Internet use. A consistent finding across countries was that girls more often talked with their parents about their Internet use and more often reported that their parents were interested in their Internet use than boys. The results suggest that parents have an important task in explicitly showing interest in their adolescents’ Internet use, with special attention needed for boys.

There is sufficient evidence on the negative consequences of cyberbullying victimisation depending on the coping styles. Social support seeking is among the most effective strategies for coping with cybervictimisation, but it is scarcely used. The robust Maximum Likelihood (ML) method was used to test the potential mediating role of individual (self-awareness, and responsible decision-making) and contextual variables (self-perceived parental and peer support) in the relationship between cybervictimisation and social support seeking in boys and girls. This cross-sectional study collected data from 1,276 Spanish secondary school students (51.2% boys, 48.8% girls) aged 11–18 (M = 13.88, SD = 1.42). Structural equation modelling (SEM) results pointed out responsible decision-making and self-perceived parental support as relevant mediating factors for girls. By contrast, the model was not significant for boys. These findings highlight the importance of both individual and contextual variables in helping adolescents cope with cyberaggressions, considering gender differences.

There is sufficient evidence on the negative consequences of cyberbullying victimisation depending on the coping styles. Social support seeking is among the most effective strategies for coping with cybervictimisation, but it is scarcely used. The robust Maximum Likelihood (ML) method was used to test the potential mediating role of individual (self-awareness, and responsible decision-making) and contextual variables (self-perceived parental and peer support) in the relationship between cybervictimisation and social support seeking in boys and girls. This cross-sectional study collected data from 1,276 Spanish secondary school students (51.2% boys, 48.8% girls) aged 11–18 (M = 13.88, SD = 1.42). Structural equation modelling (SEM) results pointed out responsible decision-making and self-perceived parental support as relevant mediating factors for girls. By contrast, the model was not significant for boys. These findings highlight the importance of both individual and contextual variables in helping adolescents cope with cyberaggressions, considering gender differences.

Collapsing massive stars lead to a broad range of astrophysical transients, whose multi-wavelength emission is powered by a variety of processes including radioactive decay, activity of the central engine, and interaction of the outflows with a dense circumstellar medium. These transients are also candidate factories of neutrinos with energy up to hundreds of PeV. We review the energy released by such astrophysical objects across the electromagnetic wavebands as well as neutrinos, in order to outline a strategy to optimize multi-messenger follow-up programs. We find that, while a significant fraction of the explosion energy can be emitted in the infrared-optical-ultraviolet (UVOIR) band, the optical signal alone is not optimal for neutrino searches. Rather, the neutrino emission is strongly correlated with the one in the radio band, if a dense circumstellar medium surrounds the transient, and with X-rays tracking the activity of the central engine. Joint observations of transients in radio, X-rays, and neutrinos will crucially complement those in the UVOIR band, breaking degeneracies in the transient parameter space. Our findings call for heightened surveys in the radio and X-ray bands to warrant multi-messenger detections., Comment: 26 pages, including 7 figures and 2 appendices. Minor revisions, conclusions unchanged. Matches version accepted for publication in PRD

The integration of digital technology in school is a complex phenomenon that affects both teaching and peer relationships. Accordingly, the main aim of this dissertation was to investigate the implementation of distance education among Italian teachers during the COVID-19 pandemic and analyze peer relationships concerning cyberbullying and bullying. While the theoretical section provided an overview of the phenomena, four empirical studies were presented. The first one tested a moderated moderation model among 178 secondary teachers on the interactions among perceived usefulness, perceived ease of use of technology and online teaching self-efficacy. Findings showed that each variable significantly predicted the intention to use technology. In addition, a moderation effect of online teaching self-efficacy on perceived usefulness was found. The second study analyzed the differences in factors promoting the integration of digital technology among 357 teachers of different levels and subjects and their positive and negative experiences with distance education. Results revealed several differences in the function of the grade and subjects taught. Moreover, four main themes emerged from the content analysis. The third study investigated the dyadic perception of bullying and cyberbullying among 50 students using the eye-tracker. Findings showed that, despite differences among different kinds of bullying and cyberbullying, the victim and bully were the most observed roles. Finally, the last study tested two multiple mediation models among 563 students on the association between bullying, cyberbullying, and well-being, considering three different variables related to the school context (peer network, teacher support and school connectedness). The results highlighted the importance of peer networks and school connectedness in mediating the association between victimization, cybervictimzation and well-being. Taken together, the findings provided a rich overview of digital tech

A growing number of gamma-ray burst (GRB) afterglows is observed at very-high energies (VHE, $\gtrsim 100$ GeV). Yet, our understanding of the mechanism powering the VHE emission remains baffling. We make use of multi-wavelength observations of the afterglow of GRB 180720B, GRB 190114C, and GRB 221009A to investigate whether the bursts exhibiting VHE emission share common features. We assume the standard afterglow model and microphysical parameters consistent with a synchrotron self-Compton (SSC) scenario for the VHE radiation. By requiring that the blastwave should be transparent to $\gamma$-$\gamma$ pair production at the time of observation of the VHE photons and relying on typical prompt emission efficiencies and data in the radio, optical and X-ray bands, we infer for those bursts that the initial energy of the blastwave is $\tilde{E}_{k, \rm{iso}} \gtrsim \mathcal{O}(10^{54})$ erg and the circumburst density is $n_0 \lesssim \mathcal{O}(10^{-1})$ cm$^{-3}$ for a constant circumburst profile [or $A_\star \lesssim \mathcal{O}(10^{-1})$ cm$^{-1}$ for a wind scenario]. Our findings thus suggest that these VHE bursts might be hosted in low-density environments, if the SSC radiation is responsible for the VHE emission. While these trends are based on a small number of bursts, the Cherenkov Telescope Array has the potential to provide crucial insight in this context by detecting a larger sample of VHE GRBs. In addition, due to the very poor statistics, the non-observation of high-energy neutrinos cannot constrain the properties of these bursts efficiently, unless additional VHE GRBs should be detected at distances closer than $15$ Mpc when IceCube-Gen2 radio will be operational., Comment: 14 pages, including 3 figures and 3 appendices. Discussion expanded, main results unchanged. Matches version accepted for publication in MNRAS

This study aims to shed light on how external and internal variables affect the anticipatory and coping ability of local governments in the management of exogenous crises. The case is interpreted through the lens of organizational resilience theory through the analysis of the actions taken by the administrators of the Milan City Council to anticipate and counteract periods of crisis due to soaring bread and flour prices in the period 1860-1898.The analysis is based on archival research using minutes of the City Council meetings and by triangulating data with statistics and literature as secondary sources. Comparison is also carried out between actions taken by other municipalities in the period analysed and as a response to the current inflation crisis in Europe. Findings show how local government’s coping decisions in the short term may be in contrast with decisions aimed at maintaining the organization’s financial condition in the long run and have important consequences on the capacity to prevent future social crises. The City Council abolished the excise duty on bread only after the dramatic riots of 1898. Riots occurred in the years before were underestimated by city councilors as they only tried to develop a better knowledge of the external environment; the political vision and priorities substantially procrastinated the decision to abolish the duties but linked them to the future tax reform. These findings are in line with recent delays occurred in Europe for the set-up of a price cap on the gas market, despite the current socio-political context is profoundly different from that of the period under consideration. The study contributes to the literature on accounting by exploring the factors that influence the use of financial and non-financial information during social crises and affect organizational resilience. From a practitioner’s point of view, it highlights how the City of Milan developed an early system of regulatory cost accounting to support bread p

The GIMEMA phase II LLC1518 VERITAS trial investigated the efficacy and safety of frontline, fixed-duration venetoclax and rituximab (VenR) combination in young (≤65 years) and fit patients with chronic lymphocytic leukemia (CLL) and unmutated IGHV and/or TP53 disruption. Treatment consisted of the Ven ramp-up, six-monthly courses of the VenR combination, followed by six monthly courses of Ven single agent. A centralized assessment of measurable minimal residual disease (MRD) was performed on the peripheral blood (PB) and bone marrow (BM) by ASO-PCR at the end of treatment (EOT) and during the follow-up. The primary endpoint was the complete remission (CR) rate at the EOT. Seventy-five patients were enrolled; the median age was 54 years (range 38-65), 96% had unmutated IGHV, 9 (12%) had TP53 disruption, and 4% were IGHV mutated with TP53 disruption. The overall response rate (ORR) at the EOT was 94.7%, with a CR rate of 76%. An undetectable (u) MRD was recorded in 69.3% of patients in the PB and 58.7% in the BM. The 12-month MRD-free survival in the 52 patients with uMRD in the PB at the EOT was 73.1%. After a median follow-up of 20.8 months, no disease progressions were observed. Three patients have died, two due to Covid-19 and 1 to tumor lysis syndrome. The first report of the VERITAS study shows that frontline VenR was associated with a high rate of CRs and durable responses with uMRD in young patients with CLL and unfavorable genetic characteristics.

As a contribution to the ongoing effort toward high-frequency sound manipulation in composite materials, we use Inelastic X-ray Scattering to probe the phonon spectrum of ice, either in a pure form or with a sparse amount of nanoparticles embedded in it. The study aims at elucidating the ability of nanocolloids to condition the collective atomic vibrations of the surrounding environment. We observe that a nanoparticle concentration of about 1 % in volume is sufficient to visibly affect the phonon spectrum of the icy substrate, mainly canceling its optical modes and adding nanoparticle phonon excitations to it. We highlight this phenomenon thanks to the lineshape modeling based on a Bayesian inference, which enables us to capture the finest detail of the scattering signal. The results of this study can empower new routes toward the shaping of sound propagation in materials through the control of their structural heterogeneity.

Purpose: This article investigates how Sustainable Development Goals (SDGs) can be integrated into the strategic planning and management processes of local governments (LGs). It draws from the classic strategic planning and control framework developed in management studies and elaborates some propositions for adapting, implementing and monitoring the SDGs at the city level. Design/methodology/approach: As a first step in the assessment of the ways the principles of sustainable development can be integrated into LG management, this research scrutinizes the incorporation of sustainability goals in the strategic plans of all medium-to-large capital cities of provinces in Italy, a context in which there has been a National Strategy for Sustainable Development (NSSD) since 2016. Findings: The focus on SDGs at the LG level in Italy is in its initial stage, and few capital cities have started to integrate sustainable development concerns into their comprehensive strategic plans. SDGs are used mainly as a reference framework in the strategic plans to demonstrate the contribution of LG strategies to global concerns on sustainable development. Practical implications: The paper offers insights for political leaders and public managers to rethink their strategic management systems, including the continuous process of evaluating and updating of strategic plans, in accordance with the multidimensional perspective of sustainability. To this end, the study has identified possible patterns of actions that public managers elsewhere will find useful. Originality/value: The managerial approach behind the proposed conceptual framework might contribute to effectively localize the SDGs in multilevel government settings and to integrate the concept of sustainability as a guiding principle into organizational routines.

Early recognition of Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) cases could impact on the management and outcome of this subset of B-lineage ALL. In order to assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)driven trial, we screened 88 B-lineage ALL cases negative for major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the “BCR/ABL1-like predictor” - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission rate was significantly lower in Ph-like compared to non-Ph-like cases (74.1% vs. 91.5%, P=0.044); ii) at time point 2, decisional for transplant allocation, 52.9% of Ph-like cases versus 20% of non-Ph-like were MRD-positive (P=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at time point 2 (P=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs. 66.2%, P=0.005 and 45.5% vs. 72.3%, P=0.062, respectively). This study documents that Ph-like patients have a lower complete remission rate, event-free survival and disease-free survival, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies.

Minimal residual disease (MRD) is the most powerful prognostic factor in pediatric acute lymphoblastic leukemia (ALL). Real-time quantitative polymerase chain reaction (RQ-PCR) represents the gold standard for molecular MRD assessment and risk-based stratification of front-line treatment. In the protocols of the Italian Association of Pediatric Hematology and Oncology (AIEOP) and the Berlin-Frankfurth-Munschen (BFM) group AIEOP-BFM ALL2009 and ALL2017, B-lineage ALL patients with high RQ-PCR-MRD at day+33 and positive at day+78 are defined slow early responders (SERs). Based on results of the AIEOP-BFM ALL2000 study, these patients are treated as high-risk also when positive MRD signal at day +78 is below the lower limit of quantification of RQ-PCR ("positive not-quantifiable," POS-NQ). To assess whether droplet digital polymerase chain reaction (ddPCR) could improve patients' risk definition, we analyzed MRD in 209 pediatric B-lineage ALL cases classified by RQ-PCR as POS-NQ and/or negative (NEG) at days +33 and/or +78 in the AIEOP-BFM ALL2000 trial. ddPCR MRD analysis was performed on 45 samples collected at day +78 from SER patients, who had RQ-PCR MRD ≥ 5.0 * 10-4 at day+33 and POS-NQ at day+78 and were treated as medium risk (MR). The analysis identified 13 of 45 positive quantifiable cases. Most relapses occurred in this patients' subgroup, while ddPCR NEG or ddPCR-POS-NQ patients had a significantly better outcome (P < 0.001). Overall, in 112 MR cases and 52 standard-risk patients, MRD negativity and POS-NQ were confirmed by the ddPCR analysis except for a minority of cases, for whom no differences in outcome were registered. These data indicate that ddPCR is more accurate than RQ-PCR in the measurement of MRD, particularly in late follow-up time points, and may thus allow improving patients' stratification in ALL protocols.

This article proposes and discusses a managerial framework to provide guidance on implementing and monitoring the 17 sustainable development goals (SDGs) at the local government level. The integration of SDGs into city strategic plans will help city leaders and local politicians strengthen their planning and management processes and improve the communication of strategic goals.

Public-policy assumptions regarding sub-national governments' financial behavior are based on economic rationality. Therefore, to achieve fiscal stability at the macro level, central governments use fiscal rules both to constrain the behavior of local policymakers and to resolve deficit/debt biases. Using the Italian fiscal governance system as an illustrative example, this chapter considers both the tensions derived from achieving fiscal responsibility at the national level in a decentralized environment and the difficulties of maintaining adequate performance at the local government level. It is argued that the public management perspective can be helpful not only at the micro-level but also at the macro level in developing public policies to promote fiscal stability. It is suggested that public policy should adopt a more holistic approach toward fiscal responsibility in multi-level governance environments. Such an approach requires a deep understanding of the determinants of financial viability of public sector organizations.

Background: Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19. Methods: This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov, NCT04352556, and the prospective part of the study is ongoing. Findings: We enrolled 536 patients with a median follow-up of 20 days (IQR 10–34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77–2·34) in our whole study cohort and 3·72 (2·86–4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1–44·9). Older age (hazard ratio 1·03, 95% CI 1·01–1·05); progressive disease status (2·10, 1·41–3·12); diagnosis of

Partendo dall’esame di alcuni contributi di Francesco Parrillo, compresi in un arco temporale che va dal 1983 al 1999, sul tema delle PMI (anche nei suoi riflessi finanziari), l’articolo propone una attualizzazione di quella riflessione per interpretare la realtà del sistema produttivo italiano nella seconda decade del nuovo millennio. I temi emergenti sono legati alla vitalità delle medie imprese, alla nuova manifattura digitale, ad una maggiore attenzione per la diversificazione delle fonti di finanziamento. A fronte di questi spiragli, permangono alcuni nodi critici strutturali come le difficoltà della maggior parte delle imprese, segnate dalla ridotta dimensione, la loro sottocapitalizzazione, i modelli superati di governance, che, a livello macroeconomico, comportano bassi livelli di produttività. Al riguardo viene condotta un’analisi econometrica per testare l’ipotesi che una “soluzione” possa venire da reti d’impresa che collaborano su progetti mirati di innovazione (e/o internazionalizzazione)., Starting from an accurate selection of contributions written, in the 1983-1999 period, by Francesco Parrillo on SMEs (also in its financial implications), the paper proposes to contextualize its analysis in recent times, in order to interpret the modern nature of the Italian productive system. Emerging relevant topics arerelated to the dynamism of Medium-sized firms, the new digital manufacture, and to the diversification of funding sources. However, critical issues still remain, such as small dimension, undercapitalization, outdated governance, which imply low productivity levels. In this regard, we propose an econometric analysis to test the hypothesis that a “solution” can come from business networks with firms that collaborate on targeted innovation (and/or internationalization) projects.

Purpose: Studies on how accounting is involved in financial crises and austerity are limited. The context of austerity provides an interesting opportunity to explore the role of accounting in shaping governmental financial resilience, i.e. the capacity of governments to cope with shocks affecting their financial conditions. Design/methodology/approach: Based on a multiple case analysis of eight Italian municipalities, this paper explores how accounting contributes to the government capacities which are used to anticipate and respond to shocks affecting public finances. Findings: Municipalities cope with financial shocks differently; accounting can support self–regulation and can affect internally-led or externally-led adaptation. Different combinations of anticipatory and coping capacities lead to different responses to shocks. Practical implications: The findings can be useful for public managers, policymakers and oversight bodies for strengthening governmental financial resilience in the face of crises and austerity. Originality/value: The results provide evidence of the conditions, contexts, processes under which accounting becomes a medium which can support both anticipation of and coping with financial shocks, supporting cuts in some cases and resistance in the short run or driving long-term changes intended to maintain public services as much intact as possible. This highlights the existence of different patterns of governmental financial resilience and thus indicates ways of best preserving the service of the public interest.

Aims: To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). Methods and Results: We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7-32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3-70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7-6.6; P < 0.001]. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1-2.8; P = 0.009). Conclusion: Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.

Mounting evidence suggests that Luminous Fast Blue Optical Transients (LFBOTs) are powered by a compact object, launching an asymmetric and fast outflow responsible for the radiation observed in the ultraviolet, optical, infrared, radio, and X-ray bands. Proposed scenarios aiming to explain the electromagnetic emission include an inflated cocoon, surrounding a jet choked in the extended stellar envelope. In alternative, the observed radiation may arise from the disk formed by the delayed merger of a black hole with a Wolf-Rayet star. We explore the neutrino production in these scenarios, i.e. internal shocks in a choked jet and interaction between the outflow and the circumstellar medium (CSM). If observed on-axis, the choked jet provides the dominant contribution to the neutrino fluence. Intriguingly, the IceCube upper limit on the neutrino emission inferred from the closest LFBOT, AT2018cow, excludes a region of the parameter space otherwise allowed by electromagnetic observations. After correcting for the Eddington bias on the observation of cosmic neutrinos, we conclude that the emission from an on-axis choked jet and CSM interaction is compatible with the detection of two track-like neutrino events observed by the IceCube Neutrino Observatory in coincidence with AT2018cow, and otherwise considered to be of atmospheric origin. While the neutrino emission from LFBOTs does not constitute the bulk of the diffuse background of neutrinos observed by IceCube, detection prospects of nearby LFBOTs with IceCube and the upcoming IceCube-Gen2 are encouraging. Follow-up neutrino searches will be crucial for unravelling the mechanism powering this emergent transient class., Comment: 23 pages, including 9 figures and 1 appendix. Minor changes, matches version accepted for publication in ApJ

Mounting evidence suggests that the launching of collapsar jets is magnetically driven. Recent general relativistic magneto-hydrodynamic simulations of collapsars reveal that the jet is continuously loaded with baryons, owing to strong mixing with the cocoon. This results in a high photosphere at $\gtrsim 10^{12}$ cm. Consequently, collisionless internal shocks below the photosphere are disfavored, and the neutrino production in the deepest jet regions is prevented, in contrast to what has been assumed in the literature. We find that subphotospheric neutrino production could only take place in the presence of collisionless sub-shocks or magnetic reconnection. Efficient particle acceleration is not possible in the cocoon, at the cocoon-counter cocoon shock interface, or at the shock driven by the cocoon in the event of a jet halted in an extended envelope. These subphotospheric neutrinos have energy $E_\nu \lesssim 10^5$ GeV for initial jet magnetizations $\sigma_0=15$-$2000$. More than one neutrino and antineutrino event is expected to be observed in Hyper-Kamiokande and IceCube DeepCore for sources located at $z \lesssim \mathcal{O}(0.1)$. Because of their energy, these neutrinos do not contribute to the diffuse flux detected by the IceCube Neutrino Observatory. Our findings have implications on neutrino searches ranging from gamma-ray bursts to luminous fast blue optical transients., Comment: 28 pages, including 16 figures and 2 appendices. Minor changes in the text. Matches version published in PRD

Il presente articolo intende contribuire al dibattito sul PNRR e sulle riforme analizzando gli effetti prodotti dalla pandemia Covid-19 sui processi organizzativi della Pubblica Amministrazione (PA) alla luce del mutato scenario. Le analisi sono basate su quanto riportato da una comunità di circa trecento manager pubblici in momenti strutturati di confronto e co-produzione di conoscenza (Bartunek, 2007; Cepiku e 2010; Barretta et al., 2018). Grazie al coinvolgimento attivo in alcuni percorsi formativi di sviluppo manageriale, ai partecipanti è stato chiesto di analizzare e condividere le loro riflessioni circa gli effetti che la pandemia ha prodotto, con particolare riferimento al ruolo dello smart working. Gli ambiti di indagine hanno considerato da un lato i cambiamenti nei processi di misurazione e valutazione delle performance, dall’altro i cambiamenti nei processi di lavoro e dell’ambiente lavorativo.

The design of internal control functions in Italian governments has been strongly influenced by the legislation that has driven a fragmentation of control activities. Over the years, such an approach has prevented the development of a complete internal control and risk management system. Furthermore, the absence of a sound organizational model feeds the lack of structured processes of risk management and control, the lack of an integrated information system, and problems of coordination with the multi-layered system of external controls. This article proposes a framework for the re-design of the internal control system in governments within the perspective of fully integration of administrative processes, information, and risk management. This is done by utilizing the insights provided by the empirical verification of the three lines of defense model conducted at the regional government of Lombardy in Italy.