Behavior of confined granular beds under cyclic thermal loading

We investigate the mechanical behavior of a confined granular packing of irregular polyhedral particles under repeated heating and cooling cycles by means of numerical simulations with the Non-Smooth Contact Dynamics method. Assuming a homogeneous temperature distribution as well as constant temperature rate, we study the effect of the container shape, and coefficients of thermal expansions on the pressure buildup at the confining walls and the density evolution. We observe that small changes in the opening angle of the confinement can lead to a drastic peak pressure reduction. Furthermore, the displacement fields over several thermal cycles are obtained and we discover the formation of convection cells inside the granular material having the shape of a torus. The root mean square of the vorticity is then calculated from the displacement fields and a quadratic dependency on the ratio of thermal expansion coefficients is established

New approaches to the objective diagnosis of alcohol abuses

Driving under the influence of alcohol is one of the most common risk factor of road accidents and it is one of the main causes of mortality. Since the detection of ethanol in the body is possible only for a relatively short time after intake, the assessment of a condition of alcohol intoxication/addiction has been and still is an issue in clinical and forensic toxicology. In recent years, however, the diagnosis of alcohol abuse has been revolutionized by the introduction of new specific biomarkers, among which EtG is one of the most promising. Ethyl glucuronide (EtG) is a minor alcohol metabolite, formed by conjugation of ethanol with activated glucuronic acid, and it has been proposed as a stable marker to detect and quantify alcohol consumption. The major advantage of EtG is an extended detection window after ethanol consumption. The aim of the present study was to evaluate the use of blood EtG as a potential marker in the occurrence of fatal and non-fatal alcohol-related traffic accidents. Moreover, the correlation between ethanol and EtG was studied to establish whether or not ethanol ingestion occurred at the time of the road accident. On these grounds, an analytical LC-MS/MS method for blood EtG has been validated. Subsequently, real blood samples of subjects involved in fatal and non-fatal road accidents have been analysed. Finally, the serum and blood concentration ratio has been evaluated to verify the EtG partitioning between the different portions of blood. Conclusions show a relevance of blood EtG for BAC interpretation

CE-MS in forensic sciences with focus on forensic toxicology

The present chapter reviews the literature on CE-MS applications in the main analytical fields of forensic science from the end of 1980s to current times. However, because of the number of papers and the variety of the subjects of potential forensic interest, no review can be comprehensive. Moreover, any ambition of completeness would be frustrated in the near future by the tide of publications of new research. Hence, the present work aims mainly at showing and discussing the different strategies adopted in the development and application of forensic CE-MS, with particular attention devoted to the peculiarities of this new technology

Development and preliminary use of CDT analysis on dried blood spot (DBS) in forensic and administrative contexts

BACKGROUND-AIM Carbohydrate Deficient Transferrin (CDT) defines two minor glycoforms of transferrin (asialo and disialo-tansferrin), characterized by a reduced glycosylation degree, whose serum concentration increases after chronic sustained alcohol intake (60-80 g per day for at least 10 days). The use of finger-prick and related dried blood spots (fpDBS) is an innovative tool for blood sample collection in clinical and forensic toxicology. The aim of this work was to develop a screening method for CDT analysis based on the use of fpDBS coupled with capillary electrophoresis. METHODS Capillary blood drops collected by finger-prick were placed on DBS cards and left to air dry. Each dried fpDBS disc was sliced and suspended in acid solution. After centrifugation the sample pH was adjusted by 120 mmol HCl to pH 3-4. After overnight incubation the sample pH was neutralized and an iron rich solution was added. The resulting sample was analyzed by a validated CE method. The CDT level was expressed as %CDT (%ratio of disialo-Tf on total transferrin). The blood samples were obtained from volunteers of the forensic toxicology laboratory and from subjects submitted to blood testing for mandatory toxicological investigations. The DBS were analyzed in parallel with the sera of each investigated subject, using HPLC and CE techniques. The %CDT cut-offs used for the study were 1.80% and 1.90% for CE and HPLC, respectively. RESULTS The observed fpDBS transferrin glycoform CE patterns were comparable with serum CE CDT patterns. Moreover, a statistical correlation was demonstrated of fpDBS CDT percentage levels with both HPLC and CE % CDT (p< 0.01). This correlation was confirmed also by Passing-Bablok tests and Bland Altman test. The cut off proposed for this %CDT screening method was 1.6% demonstrating a sensitivity and specificity of about 75% and 90%, respectively. These data were calculated comparing %CDT by fpDBS CE vs serum HPLC, the latter considered the reference method. CONCLUSIONS The results of the study, even if preliminary, showed that fpDBS procedure coupled with CE for CDT analysis could express a simplified and inexpensive tool designed for use in population screening

Interleukin-15 and soluble interleukin-15 receptor α in coronary artery disease patients: association with epicardial fat and indices of adipose tissue distribution.

Interleukin-15 (IL-15) is a pro-inflammatory cytokine which signals via a specific alpha receptor subunit (IL-15Rα). Increased IL-15 level has been observed in cardiovascular patients and IL-15 immunoreactivity has been detected at vulnerable atherosclerotic plaques. Due to the association between adipose tissue distribution, inflammation and coronary artery disease (CAD), we quantified IL-15 and IL-15Rα in CAD patients with different adiposity and adipose tissue distribution and we evaluated whether epicardial adipose tissue (EAT), a visceral fat depot surrounding and infiltrating myocardium, may be a source of both molecules. IL-15 and IL-15Rα proteins were quantified by enzyme-linked immunosorbent assays. Gene expression of IL-15 and IL-15Rα in EAT depots was evaluated by one colour microarray platform. EAT thickness was measured by echocardiography. Plasmatic IL-15 and IL-15Rα levels were higher in CAD than non-CAD patients. After classification according to adipose tissue distribution, IL-15 was higher in CAD patients with increased abdominal adiposity. Increased level of IL-15Rα was observed both in CAD and non-CAD patients with increased abdominal fat. EAT was a source of IL-15 and IL-15Rα and their expression was higher in CAD patients with increased EAT thickness. In conclusion, our data suggest that circulating levels of IL-15 and IL-15Rα seem to reflect visceral distribution of adipose tissue and that EAT may be a potential source of both IL-15 and IL-15Rα. Future studies on the relationship between IL-15, visceral fat and characteristics of atherosclerotic plaques could help to better understand the complex biology of this cytokine

DIRITTI E DOVERI

Analisi dei diritti e doveri fondamentali, con particolare riguardo all'analisi della giurisprudenza costituzionale e sovranazional

Radiomics approaches to predict PD-L1 and PFS in advanced non-small cell lung patients treated with immunotherapy: a multi-institutional study

Abstract With the increasing use of immune checkpoint inhibitors (ICIs), there is an urgent need to identify biomarkers to stratify responders and non-responders using programmed death-ligand (PD-L1) expression, and to predict patient-specific outcomes such as progression free survival (PFS). The current study is aimed to determine the feasibility of building imaging-based predictive biomarkers for PD-L1 and PFS through systematically evaluating a combination of several machine learning algorithms with different feature selection methods. A retrospective, multicenter study of 385 advanced NSCLC patients amenable to ICIs was undertaken in two academic centers. Radiomic features extracted from pretreatment CT scans were used to build predictive models for PD-L1 and PFS (short-term vs. long-term survivors). We first employed the LASSO methodology followed by five feature selection methods and seven machine learning approaches to build the predictors. From our analyses, we found several combinations of feature selection methods and machine learning algorithms to achieve a similar performance. Logistic regression with ReliefF feature selection (AUC = 0.64, 0.59 in discovery and validation cohorts) and SVM with Anova F-test feature selection (AUC = 0.64, 0.63 in discovery and validation datasets) were the best-performing models to predict PD-L1 and PFS. This study elucidates the application of suitable feature selection approaches and machine learning algorithms to predict clinical endpoints using radiomics features. Through this study, we identified a subset of algorithms that should be considered in future investigations for building robust and clinically relevant predictive models

Demographic and anthropometric characteristics of CABG and VR patients.

<p>ACEI: angiotensinogen-converting enzyme inhibitor; ARB: angiotensin receptor blockade; BMI: body mass index; CABG: coronary artery bypass grafting; CAD, coronary artery disease; EAT: epicardial adipose tissue; VR: valve replacement; WHR: waist to hip ratio. Data are expressed as mean ± SD (range) or number and %.</p

Influence of adiposity and EAT thickness on interleukin-15 plasma level.

<p>A) Interleukin-15 (IL-15) level in coronary artery bypass grafting surgery (CABG) and valve replacement (VR) patients classified, according to body mass index, in normal weight (NW) and overweight-obese (OB) groups. Data are mean ± SD; *p = 0.01. B) IL-15 level in CABG and VR patients classified, according to waist circumference cut off value of ≥102 cm. Data are mean ± SD; *p<0.05, °p<0.01. C) IL-15 level in CABG and VR patients classified according to waist-to-hip ratio (WHR) cut off value of ≥0.95. Data are mean ± SD; *p<0.05, °p = 0.01. D) IL-15 level in CABG and VR patients classified, according to the median echocardiographic epicardial adipose tissue (EAT) thickness value. Data are mean ± SD; °p = 0.01.</p

Influence of adiposity and EAT thickness on interleukin-15 receptor α plasma level.

<p>A) Interleukin-15 receptor α (IL-15Rα) level in coronary artery bypass grafting surgery (CABG) and valve replacement (VR) patients classified, according to body mass index, in normal weight (NW) and overweight-obese (OB) groups. Data are mean ± SD. *p<0.05, °p<0.001. B) IL-15Rα level in CABG and VR patients classified, according to waist circumference cut off value of ≥102 cm. Data are mean ± SD. *p<0.05, °p<0.01. C) IL-15Rα level in CABG and VR patients classified according to waist-to-hip ratio (WHR) cut off value of ≥0.95. Data are mean ± SD. *p<0.05. D) IL-15Rα level in CABG and VR patients classified according to the median echocardiographic epicardial adipose tissue (EAT) thickness value. Data are mean ± SD.</p