Treatment of young adults with colorectal cancer (CRC) represents an unmet clinical need, especially as diagnosis in this population might lead to the greatest loss of years of life. Since 1994, CRC ...incidence in individuals younger than 50 years has been increasing by 2% per year. The surge in CRC incidence in young adults is particularly alarming as the overall CRC frequency has been decreasing. Early‐onset CRC are characterized by a more advanced stage at diagnosis, poorer cell differentiation, higher prevalence of signet ring cell histology, and left colon‐sided location of the primary tumor. Among EO‐CRC, approximately 30% of patients are affected by tumors harboring mutations causing hereditary cancer predisposing syndromes, and 20% have familial CRC. Most notably, the remaining 50% of EO‐CRC patients have neither hereditary syndromes nor familial CRC, thus representing a formidable challenge for research. In this review article we summarize epidemiology, clinical and molecular features, heredity and outcome of treatments of EO‐CRC, and provide considerations for future perspectives.
The prevalence of hereditary syndromes, familial syndromes and neither hereditary or familial (‘terra incognita’) syndromes among early‐onset colorectal cancer in young individuals. Figures are derived from studies in the text.
A coalition of leftist political groups, civic movements, and grassroots organizations led by social activist Ada Colau won the Barcelona municipal elections of 2015 and is now governing the Catalan ...capital. The key to this success may well have been its critical positioning in relation to its tourism. Until recently considered a best practice in urban regeneration and a successful global destination, Barcelona has seen in the last 2 years a radical change in the public perception on tourism: from “manna from heaven” to serious issues that are affecting the quality of life of its citizens.This article looks into the factors that may have determined this political change, from the growth of tourism beyond what could be considered a critical threshold for an urban system, to the development of a critical discourse on tourism by the new coalition—attributed to its peculiar constituency and working methods—and the role of the media in airing this discursive shift. The article follows the thread of the “growth machine” theorizations and questions whether the increasing dimension of tourism in urban societies could be a driver for regime changes.
The article analyzes the evolution of the gap between the Centre-North and the South of Italy during the transition from the Fordist techno-economic paradigm to the learning economy paradigm, and the ...consequent impact on development policies. According to the discussed hypothesis, in order to support the South of Italy in overcoming the middle-income trap, it appears necessary to shift from convergence policies to innovation policies. The former, at least during a certain phase of the Extraordinary Intervention, triggered a catching-up dynamic in the southern economy. However, over time, the South gradually lost its push towards convergence, leading to a situation where it fell into the middle-income trap. The presence of multiple deficits, both in the national innovation system and in regional systems, significantly limits the development potential in the South area.
Our knowledge about the activity of Girolamo Rainaldi (1570-1655) in northernItaly, and particularly inMilan, has recently been enriched with data coming from previously unpublished documents. From ...those, we discover that the architect was active in theLombardcity for the long-running question of the conclusion of Duomo’s façade, for which a project dating to circa 1607 is preserved in the Ambrosiana Library. Now the discovery of a presentation drawing with a proposal for the façade of the same church, dated and signed in 1642, preserved in a private collection, allows a further contribution to the information on Rainaldi's activity in Milan where he claims to be at the time of execution of the drawing. In 1642 the bishop ofMilanwas Cardinal Cesare Monti, for whom, in the same year, Girolamo had presented a project for the transformation of a suburban building into the family residence. In the occasion of this design for the façade of the largest Lombardchurch, we appreciate how Girolamo is dealing with a pre-existing building. His "hybridizing" approach already expressed in the drawing for the same church of 1607 and in the well-known foglio with the proposal for the façade of the Basilica of San Petronio in Bologna from the 1620s, gets confirmed in the project discussed in this study, albeit less explicitly. At the same time, this study permits reaching some clarifications on Rainaldi's graphic corpus which confirm the attributions previously made by the author and resolves some historiographical issues on the architect's activity during his long career.
The prepandemic unbridled growth of tourism has triggered a significant debate regarding the future of cities; several authors suggest that neighbourhood change produced by tourism should be ...conceived as a form of gentrification. Yet research on population shifts—a fundamental dimension of gentrification—in such neighbourhoods is scarce. Our exploration of the Gòtic area in Barcelona, using quantitative and qualitative techniques, reveals a process of population restructuring characterised by a decrease of long‐term residents and inhabited dwellings, and the arrival of young and transnational gentrifiers that are increasingly mobile and form a transient population. We then use some insights from the mobilities literature to make sense of these results. In the gentrification of the Gòtic, the attractiveness of the area for visitors and for a wider palette of transnational dwellers feeds one another, resulting in an uneven negotiation whereby more wealthy and ‘footloose’ individuals gain access and control of space and housing over less mobile and more dependent populations.
•GUT microbiota alterations have a role in gastrointestinal carcinogenesis.•GUT microbiota modulates the activity and the toxicity of several chemotherapy agents.•The manipulation of GUT microbiota ...could improve the chemotherapy efficacy.•Toxicity from chemotherapy could be reduced through GUT microbiota manipulation.
Gut microbiota is involved in gastrointestinal carcinogenesis. Also, it modulates the activity, efficacy and toxicity of several chemotherapy agents, such as gemcitabine, cyclophosphamide, irinotecan, cisplatin and 5-Fluorouracil, and target therapy, such as tyrosine kinase inhibitors. More recently, accumulating data suggest that the composition of gut microbiota may also affect efficacy and toxicity of cancer immunotherapy. Therefore, the manipulation of gut microbiota through antibiotics, probiotics, prebiotics or fecal transplantation has been investigating with the aim to improve efficacy and mitigate toxicity of anticancer drugs.
The need for greener and cleaner aviation has accelerated the transition towards more electric systems on the More Electric Aircraft. One of the key challenges related to the increasing number of ...electrical devices onboard is the control of bidirectional power converters. In this work, stability analysis and control of a buck–boost converter for aeronautic applications are presented. Firstly, stability of the buck–boost converter in the Lyapunov sense is proven by resorting to input-to-state stability notions. Then, a novel control design based on second order sliding mode control and uniting control, aimed at overcoming the difficulties generated by the nonlinear input gain function of the system not being sign definite, is presented. Extensive and detailed simulations, designed to emulate one of the possible energy management policies onboard a More Electric Aircraft, confirm the correctness of the theoretical analysis both in buck and in boost mode.
•Uncommon mutations account for 10% of all EGFR mutations.•No specific studies have prospectively evaluated uncommon sensitizing mutations.•NGS gene panels have improved EGFR mutations detection ...accuracy.•Molecular Tumor Board is mandatory to optimize the treatment strategy for NSCLC.
Uncommon epidermal growth factor receptor (EGFR) mutations collectively account for 10% of EGFR mutations, harboring heterogeneous molecular alterations within exons 18–21 with clinically variable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced Non-Small Cell Lung Cancer (NSCLC) patients. In addition, with the introduction of different NGS gene approach an improvement of EGFR mutations detection was reported. Today, no specific studies have prospectively evaluated uncommon sensitizing mutations in detail and no firm standard of care has been established in the first-line setting. The aim of this comprehensive review is to critically consider the clinical role of uncommon EGFR mutations highlighting the results of several in vitro and in vivo studies, which singly evaluated the sensitivity of uncommon mutations to currently European of Medicines Agency (EMA)-approved EGFR TKIs in cell lines, xenograft models and humans, in order to obtain a practical guide for refining the clinical decision-making process.
In February 2021, the spread of a new variant of SARS-CoV-2 in the Lombardy Region, Italy caused concerns about school-aged children as a source of contagion, leading local authorities to adopt an ...extraordinary school closure measure. This generated a debate about the usefulness of such an intervention in light of the trade-off between its related benefits and costs (e.g. delays in educational attainment, impact on children and families' psycho-physical well-being). This article analyses the epidemiological impact of the school closure intervention in the Milan metropolitan area. Data from the Agency for Health Protection of the Metropolitan City of Milan allowed analysing the trend of contagion in different age classes before and after the intervention, adopting an interrupted times series design, providing a quasi-experimental counterfactual scenario. Segmented Poisson regression models of daily incident cases were performed separately for the 3-11-year-old, the 12-19-year-old, and the 20+-year-old age groups, examining the change in the contagion curves after the intervention, adjusting for time-varying confounders. Kaplan-Meier survival curves and Cox regression were used to assess the equality of survival curves in the three age groups before and after the intervention. Net of time-varying confounders, the intervention produced a daily reduction of the risk of contagion by 4% in those aged 3-11 and 12-19 (IRR = 0·96) and by 3% in those aged 20 or more (IRR = 0·97). More importantly, there were differences in the temporal order of contagion decrease between the age groups, with the epidemic curve lowering first in the school-aged children directly affected by the intervention, and only subsequently in the adult population, which presumably indirectly benefitted from the reduction of contagion among children. Though it was not possible to completely discern the effect of school closures from concurrent policy measures, a substantial decrease in the contagion curves was clearly detected after the intervention. The extent to which the slowdown of infections counterbalanced the social costs of the policy remains unclear.
We present protocols to generate arbitrary photonic graph states from quantum emitters that are in principle deterministic. We focus primarily on two-dimensional cluster states of arbitrary size due ...to their importance for measurement-based quantum computing. Our protocols for these and many other types of two-dimensional graph states require a linear array of emitters in which each emitter can be controllably pumped, rotated about certain axes, and entangled with its nearest neighbors. We show that an error on one emitter produces a localized region of errors in the resulting graph state, where the size of the region is determined by the coordination number of the graph. We describe how these protocols can be implemented for different types of emitters, including trapped ions, quantum dots, and nitrogen-vacancy centers in diamond.
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