Forced System with Vibro-impact Energy Sink: Chaotic Strongly Modulated Responses

AbstractThe paper treats forced response of primary linear oscillator with vibro-impact energy sink. This system exhibits some features of dynamics, which resemble forced systems with other types of nonlinear energy sinks, such as steady-state and strongly modulated responses. However, the differences are crucial: in the system with vibro-impact sink the strongly modulated response consists of randomly distributed periods of resonant and non-resonant motion. This salient feature allows us to identify this type of dynamic behavior as chaotic strongly modulated response (CSMR). It is demonstrated, that the CSMR exists due to special structure of a slow invariant manifold (SIM), which is derived with the help of a multiple-scale analysis of the system. In the considered system, this manifold has only one stable and one unstable branch. This feature defines new class of universality for the nonlinear energy sinks. In the system with the vibro-impact sink, such responses are observed even for very low level of the external forcing. This feature makes such system viable for possible energy harvesting applications

heavy ion effects from track structure to dna and chromosome damage

The use of carbon ions for the treatment of certain tumour types, especially radioresistant tumours, is becoming more frequent due to the carbon- ion dose localization and high relative biological effectiveness (RBE) in the Bragg peak region. Human beings can also be exposed to heavy ions in space, since galactic cosmic rays are a mixed field consisting of not only high-energy protons and He ions, but also heavier ions including iron. Due to their high linear energy transfer (LET), heavy ions have peculiar track structures, characterized by a high level of energy deposition clustering. Furthermore, high-energy ions produce energetic secondary electrons ('delta rays') which can give rise to energy depositions several micrometres away from the core of the primary particle track. Also in view of hadron therapy and space radiation applications, it is therefore important to characterize heavy-ion tracks from a physical and biophysical point of view. In this framework, herein we will discuss the main physical features of heavy-ion track structure, as well as heavy-ion-induced DNA double-strand breaks, which are regarded as one of the most important initial radiobiological lesions and chromosome aberrations, which are correlated both with cell death and with cell conversion to malignancy

Una procedura per la valutazione dei limiti di utilizzo di O-Ring sottoposti ad intensi fasci di neutroni

Si presenta una procedura per la previsione della durata di utilizzo di O-ring in materiale polimerico impiegati nei bersagli per la produzione di fasci di ioni radioattivi. Si sono dapprima condotte prove di tenuta a vuoto e analisi a elementi finiti di un O-ring di riferimento operante con diversi livelli di interferenza con la cava, identificando la precompressione limite per la tenuta e la corrispondente pressione di contatto con la cava. Si sono poi effettuate prove di trazione e di Compression Set su campioni di O-ring in EPDM, preventivamente sottoposti a diversi livelli di irraggiamento in campi misti di neutroni e gamma, analizzando l’effetto della dose assorbita sul comportamento meccanico del materiale e sulle corrispondenti proprietà resistenziali, e definendo opportune leggi costitutive. Si sono infine simulate le progressive modifiche di comportamento della guarnizione indotte dall’irraggiamento, prevedendone la durata in esercizio in termini di tenuta e di resistenza strutturale

Human equilibrative nucleoside transporter 1 and carcinoma of the ampulla of Vater: expression differences in tumour histotypes

The human equilibrative nucleoside transporter 1 (hENT1) is the major means by which gemcitabine enters human cells; recent evidence exists that hENT1 is expressed in carcinoma of the ampulla of Vater and that it should be considered as a molecular prognostic marker for patients with resected ampullary cancer. Aim of the present study is to evaluate the variations of hENT1 expression in ampullary carcinomas and to correlate such variations with histological subtypes and clinicopathological parameters. Forty-one ampullary carcinomas were histologically classified into intestinal, pancreaticobiliary and unusual types. hENT1 and Ki67 expression were evaluated by immunohistochemistry, and apoptotic cells were identified by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL) method. hENT1 overexpression was detected in 63.4% ampullary carcinomas. A significant difference in terms of hENT1 and Ki67 expression was found between intestinal vs. pancreaticobiliary types (P=0.03 and P=0.009 respectively). Moreover, a significant statistical positive correlation was found between apoptotic and proliferative Index (P=0.036), while no significant correlation was found between hENT1 and apoptosis. Our results on hENT1 expression suggest that classification of ampullary carcinoma by morphological subtypes may represent an additional tool in prospective clinical trials aimed at examining treatment efficacy; in addition, data obtained from Ki67 and TUNEL suggest a key role of hENT1 in tumour growth of ampullary carcinoma

Promyelocytic leukemia (PML) gene expression is a prognostic factor in ampullary cancer patients

BACKGROUND: Promyelocytic leukemia (PML) tumor suppressor gene plays a key role in acute PML pathogenesis but its involvement in pathogenesis and prognosis of solid cancers has not been defined yet. PATIENTS AND METHODS: In all, 62 ampullary adenocarcinoma patients who underwent curative surgery between 1996 and 2005 were included. Expression analysis of PML was carried out by immunohistochemical staining and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS: In 24 tumor specimens (38.7%), PML was classified as absent, in 16 (25.8%) as focally expressed and in 22 (35.5%) as diffusely expressed. By univariate analysis, DFS was significantly influenced by pathological T stage (P=0.03), lymph nodal involvement (P=0.002), and PML expression (P=0.001). DFS in patients without PML expression was 28.0 months versus 45.1 and 75.5 for patients with focal and diffuse expression, respectively. OS in the group of patients without PML expression, with focal expression, and with diffuse expression was 40, 48, and 77 months, respectively (P=0.002). By a multivariate analysis, PML expression was the strongest prognostic factor for DFS (P=0.003) and the only statically significant prognostic factor for OS (P=0.009). CONCLUSIONS: Our preliminary data suggest PML as a novel prognostic tool for ampullary cancer patients

Charged particle effects: Experimental and theoretical studies on the mechanisms underlying the induction of molecular and cellular damage and the modulation of intercellular signalling

In this paper we present the main outcomes of a wide collaborative effort (carried out within the INFN project “EPICA” and in part within the European projects “RISC-RAD” and “NOTE” and the ASI project MoMa-COUNT), both experimental and theoretical, devoted to the characterization and quantification of the induction of DNA-targeted and non-DNA-targeted molecular and cellular biological endpoints, following irradiation of human cells with different charged particles. The work was mainly aimed at reaching a better understanding of the mechanisms governing the physical and biophysical pathways leading from the initial energy deposition by radiation in matter to the induction of observable radiobiological damage, with particular focus on the role played by radiation quality. More specifically, we characterized the induction of DNA DSB within different fragment-size ranges outlining the effectiveness of high-LET radiation at inducing small fragments and thus clustered DNA breaks, which can evolve in terms of endpoints like chromosome aberrations (CAs). This was confirmed by the development and application of a model of CA induction based on the assumption that only clustered DNA breaks can lead to aberrations. Concerning non-DNA-targeted damage, we quantified the time-dependent induction of medium-mediated DNA damage in bystander cells and we characterized the time and dose dependence of cytokine concentration in the culture medium of sham-irradiated and irradiated cells, since medium-mediated bystander damage is thought to arise from molecular signalling between irradiated and unirradiated cells. The mechanisms governing such signalling were investigated developing a model and a MC code simulating cytokine release, diffusion and internalization, showing good agreement with experimental data. Non-DNA-targeted effects were further characterized by MRS investigation of the radiation effects on lipids and oxidative metabolism, which are particularly relevant also considering that they may be differently expressed in different tumors and in normal tissues

International comparisons of laboratory values from the 4CE collaborative to predict COVID-19 mortality

Given the growing number of prediction algorithms developed to predict COVID-19 mortality, we evaluated the transportability of a mortality prediction algorithm using a multi-national network of healthcare systems. We predicted COVID-19 mortality using baseline commonly measured laboratory values and standard demographic and clinical covariates across healthcare systems, countries, and continents. Specifically, we trained a Cox regression model with nine measured laboratory test values, standard demographics at admission, and comorbidity burden pre-admission. These models were compared at site, country, and continent level. Of the 39,969 hospitalized patients with COVID-19 (68.6% male), 5717 (14.3%) died. In the Cox model, age, albumin, AST, creatine, CRP, and white blood cell count are most predictive of mortality. The baseline covariates are more predictive of mortality during the early days of COVID-19 hospitalization. Models trained at healthcare systems with larger cohort size largely retain good transportability performance when porting to different sites. The combination of routine laboratory test values at admission along with basic demographic features can predict mortality in patients hospitalized with COVID-19. Importantly, this potentially deployable model differs from prior work by demonstrating not only consistent performance but also reliable transportability across healthcare systems in the US and Europe, highlighting the generalizability of this model and the overall approach

Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study

Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings: Advanced age (HR 2.77, 95%CI 2.53–3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03–4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55–5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14–1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37–0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17–1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20–1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45–1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80–13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10–1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32–1.67) and 365 days (RR 1.54, 95%CI 1.21–1.96) compared to COVID-19 patients with no AKI. Interpretation: COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery. Funding: Authors are supported by various funders, with full details stated in the acknowledgement section