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Improvements in ischemic heart disease (IHD) management have been unbalanced between sexes, with coronary microvascular dysfunction considered the likely underlying reason. The Endocrine Vascular disease Approach (EVA) is an observational study (Clinicaltrial.gov NCT02737982) aiming to assess sex and gender interactions between coronary circulation, sexual hormones, and platelet function. Consecutive patients with IHD undergoing coronary angiography will be recruited: (1) to assess sex and gender differences in angiographic reperfusion indexes; (2) to evaluate the effects of estrogen/androgen on sex-related differences in myocardial ischemia; (3) to investigate the platelet biology differences between men and women with IHD; (4) to verify sex- and gender-driven interplay between response to percutaneous coronary intervention, platelets, sex hormones, and myocardial damage at baseline and its impact on 12-month outcomes. The integration of sex and gender in this translational project on IHD will contribute to the identification of new targets for further innovative clinical interventions.

Objective: Short chain fatty acids (SCFAs) derived from dietary fiber fermentation by gut microbiota have been identified as one of the mechanisms behind the association between habitual whole- grain intake and a lower risk of cardiometabolic diseases. The aims of the present work are: (1) to evaluate whether a whole-grain wheat-based diet may increase SCFAs concentration, and (2) to identify possible associations between SCFAs and metabolic changes observed after the nutritional intervention. Methods: Fifty-four subjects participated in the trial. They underwent a 12-wk dietary intervention based on whole-grain or refined cereal products. At baseline and after the intervention, glucose, insulin, triacylglycerol, inflammatory markers (hs-CRP, IL-1 ra, IL-6, and TNF-a), and SCFAs plasma concentrations were evaluated. Results: After the intervention, in the whole-grain group fasting plasma propionate concentrations were higher than at baseline, whereas a reduction was detected in the control group. The absolute changes (end of trial minus baseline) in fasting plasma propionate concentrations were signifi- cantly different between the two groups (P ¼ 0.048). The absolute changes of fasting propionate correlated with cereal fiber intake (r ¼ 0.358, P ¼ 0.023), but no significant correlations with clinical outcomes were found. However, postprandial insulin was significantly decreased in the group having the absolute changes of fasting propionate concentration above the median value (P ¼ 0.022 versus subjects with fasting propionate changes below the median value). Conclusions: A 12-wk whole-grain wheat-based diet increases fasting plasma propionate. This increase correlates with the cereal fiber intake and is associated with lower postprandial insulin concentrations.

Negli ultimi anni un notevole impulso allo sviluppo degli alimenti funzionali è stato dato dai risultati delle ricerche scientifiche che legano il consumo di alcuni alimenti o pattern alimentari ad un ridotto rischio di sviluppare le malattie cronico-degenerative. Tutto ciò ha contribuito a cambiare il significato di alimento che non è più, quindi, inteso solo come fonte di energia e veicolo di nutrienti essenziali per l'organismo, ma anche come strumento in grado di influenzare beneficamente alcune funzioni biologiche e/o il rischio di sviluppo di malattie. Il mercato offre diversi tipi di alimenti funzionali: convenzionali e modificati. I primi sono quelli che contengono naturalmente componenti con effetti benefici per la salute. Un esempio interessante è rappresentato dai cereali integrali le cui componenti (fibre, oligosaccaridi, minerali, vitamine e molecole antiossidanti) migliorano diverse funzioni biologiche riducendo il rischio di sviluppo del diabete tipo 2 (DM2). Gli alimenti modificati sono, invece, quelli resi funzionali attraverso processi tecnologici che arricchiscono o addizionano l'alimento di uno o più componenti con effetti benefici, rimuovono dall'alimento uno o più componenti con effetti negativi, sostituiscono un componente con un altro con effetti benefici o migliorano la biodisponibilità di alcune molecole. In particolare, nella prevenzione e terapia del DM2 tra gli alimenti funzionali di interesse possiamo annoverare quelli diretti al miglioramento dell'ambiente intestinale (prebiotici, probiotici e/o simbiotici); infatti, le più recenti evidenze scientifiche suggeriscono che l'alterazione della flora batterica intestinale è coinvolta sia nello sviluppo dell'obesità che della sindrome metabolica, importanti fattori di rischio per tale patologia. Un'altra categoria di alimenti funzionali, utili nel trattamento del DM2, è rappresentata dagli alimenti a basso indice glicemico il cui consumo migliora il controllo glicemico e la sensibilità insulinica nei pazienti diabetici ed aiuta a prevenire lo sviluppo della malattia nella popolazione generale. Infine, particolarmente interessanti risultano gli alimenti funzionali con proprietà ipocolesterolemizzante, che contribuiscono a ridurre notevolmente il rischio cardiovascolare che nel paziente diabetico è maggiore rispetto alla popolazione generale. A fronte di un buon numero di alimenti funzionali presenti sul mercato, ad oggi solo pochi di essi hanno ottenuto il conferimento di un "Health Claim" per l'assenza di evidenze scientifiche sufficienti basate su studi d'intervento sull'uomo. D'altra parte, gli alimenti funzionali rappresentano anche una sfida per l'industria alimentare che è chiamata ad implementare e/o sviluppare tecnologie innovative utili per la creazione di nuovi alimenti che, oltre ad avere proprietà salutistiche esaltate, abbiano anche proprietà organolettiche migliori così da poter essere consumati nella dieta abituale.

The literature on the impact of dietary carbohydrates in the regulation of blood glucose levels and other metabolic abnormalities in diabetic patients over the last 3 years is reviewed. We try to differentiate the metabolic effects due to the amount of carbohydrates from those due to their different types. The review comprises a part dealing with the effects of diets having low or high carbohydrate content on body weight reduction, and a part in which the amount and the quality of carbohydrates are discussed in relation to isoenergetic diets. Overall, the data accumulated in the period considered seem to confirm that the decrease in energy intake is more important than the qualitative composition of the diet to reduce body weight, but that both the amount and the quality of carbohydrates are important in modulating blood glucose levels and other cardiovascular risk factors in both the fasting and the postprandial phases in diabetic individuals.

Low frequency transport measurements are performed on GdSr$_2$RuCu$_2$O$_8$ pellets. The observed current-voltage curves are qualitatively explained in the framework of a simple phenomenological model accounting for coexistence of ferromagnetism and superconductivity in the sample. A Curie temperature $T_{cM}$=133 K and a superconducting critical temperature $T_{cS}$=18 K, with an onset temperature $T_{cO}$=33 K, are extracted from the analysis of the current-voltage curves., 5 pages, 7 figures

Flucytosine (5-fluorocytosine, 5-FC) is a fluorinated analogue of cytosine currently approved for the systemic treatment of fungal infections, which has recently demonstrated a very promising antivirulence activity against the bacterial pathogen Pseudomonas aeruginosa. In this work, we propose novel inhalable hyaluronic acid (HA)/mannitol composite dry powders for repositioning 5-FC in the local treatment of lung infections, including those affecting cystic fibrosis (CF) patients. Different dry powders were produced in one-step by spray-drying. Powder composition and process conditions were selected after in depth formulation studies aimed at selecting the 5-FC/HA/mannitol formulation with convenient aerosolization properties and drug release profile in simulated lung fluids. The optimized 5-FC/HA/mannitol powder for inhalation (HyaMan_FC#3) was effectively delivered from different breath-activated dry powder inhalers (DPI) already available to CF patients. Nevertheless, the aerodynamic assessment of fine particles suggested that the developed formulation well fit with a low-resistance DPI. HyaMan_FC#3 inhibited the growth of the fungus Candida albicans and the production of the virulence factor pyoverdine by P. aeruginosa at 5-FC concentrations that did not affect the viability of both wild type (16HBE14o-) and CF (CFBE41o-) human bronchial epithelial cells. Finally, pharmacokinetics of HyaMan_FC#3 inhalation powder and 5-FC solution after intratracheal administration in rats were compared. In vivo results clearly demonstrated that, when formulated as dry powder, 5-FC levels in both bronchoalveolar lavage fluid and lung tissue were significantly higher and sustained over time as compared to those obtained with the 5-FC solution. Of note, when the same 5-FC amount was administered intravenously, no significant drug amount was found in the lung at each time point from the injection. To realize a 5-FC lung concentration similar to that obtained by using HyaMan_FC#3, a 6-fold higher dose of 5-FC should be administered intravenously. Taken together, our data demonstrate the feasibility to deliver 5-FC by the pulmonary route likely avoiding/reducing the well-known side effects associated to the high systemic 5-FC doses currently used in humans. Furthermore, our results highlight that an appropriate formulation design can improve the persistence of the drug at lungs, where microorganisms causing severe infections are located.

Inhaled siRNA therapy has a unique potential for treatment of severe lung diseases, such as cystic fibrosis (CF). Nevertheless, a drug delivery system tackling lung barriers is mandatory to enhance gene silencing efficacy in the airway epithelium. We recently demonstrated that lipid-polymer hybrid nanoparticles (hNPs), comprising a poly(lactic-co-glycolic) acid (PLGA) core and a lipid shell of dipalmitoyl phosphatidylcholine (DPPC), may assist the transport of the nucleic acid cargo through mucus-covered human airway epithelium. To study in depth the potential of hNPs for siRNA delivery to the lungs and to investigate the hypothesized benefit of PEGylation, here, an siRNA pool against the nuclear factor-kappa B (siNF kappa B) was encapsulated inside hNPs, endowed with a non-PEGylated (DPPC) or a PEGylated (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) or DSPE-PEG) lipid shell. Resulting hNPs were tested for their stability profiles and transport properties in artificial CF mucus, mucus collected from CF cells, and sputum samples from a heterogeneous and representative set of CF patients. Initial information on hNP properties governing their interaction with airway mucus was acquired by small-angle X-ray scattering (SAXS) studies in artificial and cellular CF mucus. The diffusion profiles of hNPs through CF sputa suggested a crucial role of lung colonization of the corresponding donor patient, affecting the mucin type and content of the sample. Noteworthy, PEGylation did not boost mucus penetration in complex and sticky samples, such as CF sputa from patients with polymicrobial colonization. In parallel, in vitro cell uptake studies performed on mucus-lined Calu-3 cells grown at the air-liquid interface (ALI) confirmed the improved ability of non-PEGylated hNPs to overcome mucus and cellular lung barriers. Furthermore, effective in vitro NF kappa B gene silencing was achieved in LPS-stimulated 16HBE14o-cells. Overall, the results highlight the potential of non-PEGylated hNPs as carriers for pulmonary delivery of siRNA for local treatment of CF lung disease. Furthermore, this study provides a detailed understanding of how distinct models may provide different information on nanoparticle interaction with the mucus barrier.

Interest has arisen on the anti-inflammatory action of dietary components, including long-chain n-3 fatty acids (LCn3) and polyphenols (PP). The aim of this study was to evaluate the effects of diets rich in PP and oily fish (high-LCn3 diets) on markers of subclinical inflammation and growth factors in people at high cardiometabolic risk. Individuals with high waist circumference and one more component of metabolic syndrome were randomized to one of the following isoenergetic diets: low LCn3&amp, PP, high LCn3, high PP, high LCn3&amp, PP. Before and after 8 weeks, fasting and postprandial plasma concentrations of hs-CRP and fasting serum concentrations of IL-1β, IL-4, IL-6, IL-10, IL-17, INF-γ, TNF-α, FGF, VEGF, PDGF-ββ, G-CSF, and GM-CSF were determined. An oily fish diet reduced fasting plasma hs-CRP (1.28 ± 12.0, −12.5 ± 6.9, 22.5 ± 33.6, −12.2 ± 11.9, 8-week percent change, Mean ± SEM, low LCn3&amp, PP group, respectively), postprandial 6h-AUC hs-CRP (4.6 ± 16.3, −18.2 ± 7.2, 26.9 ± 35.1, −11.5 ± 11.8, 8-week percent change) and fasting IL-6 (20.8 ± 18.7, −2.44 ± 12.4, 28.1 ± 17.4, −9.6 ± 10.2), IL-17 (2.40 ± 4.9, −13.3 ± 4.9, 3.8 ± 4.43, −11.5 ± 4.7), and VEGF (−5.7 ± 5.8, −5.6 ± 7.5, 3.5 ± 5.8, −11.1 ± 5.5) (8-week percent change, p &lt, 0.05 for LCn3 effect for all, no significant effect for PP, 2-factor ANOVA). An oily fish diet improved subclinical inflammation, while no significant effect was observed for dietary polyphenols.

Background Plasma trimethylamine N-oxide (TMAO) has drawn much attention as a marker of several chronic diseases. Data on the relation between diet and TMAO are discordant and few human intervention studies have assessed causality for this association. Objectives We aimed to evaluate the effects on plasma TMAO of diets based on foods rich in polyphenols (PP) and/or long-chain n-3 fatty acids (LCn3) or whole-grain cereals (WGCs), in individuals at high cardiometabolic risk. Methods An ancillary study was performed within 2 randomized controlled trials, aimed at evaluating the medium-term effects on cardiometabolic risk factors of diets naturally rich in PP and/or LCn3 (Etherpaths Project) or WGCs (HealthGrain Project). Results In the Etherpaths study (n = 78), the changes in TMAO (8-wk minus baseline) were statistically significant for the diets rich in LCn3 (+1.15 ± 11.58 μmol/L) (P = 0.007), whereas they were not for the diets rich in PP (-0.14 ± 9.66 μmol/L) (P = 0.905) or their interaction (P = 0.655) (2-factor ANOVA). In the HealthGrain Study (n = 48), the TMAO change (12-wk minus baseline) in the WGC group (+0.94 ± 3.58 μmol/L) was significantly different from that in the Refined Cereal group (-1.29 ± 3.09 μmol/L) (P = 0.037). Considering the pooled baseline data of the participants in the 2 studies, TMAO concentrations directly correlated with LCn3, EPA (20:5n-3), and protein intake, but not SFAs, fiber, MUFAs, and PP intake. Among food groups, TMAO directly correlated with the intake of fish, vegetables, and whole-grain products, but not meat, processed meat, and dairy products. Conclusions Diets rich in LCn3 of marine origin or WGCs significantly increased plasma TMAO concentration. These changes mirrored the direct associations between TMAO concentrations and intakes of fish and WGCs, suggesting that TMAO reflects intakes of these healthy foods and, therefore, it is not a universally valid biomarker of cardiometabolic risk independent of the background diet.These trials were registered at clinicaltrials.gov as NCT01154478 and NCT00945854.

Aims: Gut microbiota significantly impacts human health and is influenced by dietary changes. We evaluated the effects of diets naturally rich in polyphenols (PP) and/or long-chain n-3 polyunsaturated fatty acids (LCn3) on microbiota composition in an ancillary analysis of a randomized controlled trial in individuals at high cardiometabolic risk. Methods: Seventy-eight individuals with high waist circumference and at least one additional component of the metabolic syndrome were randomized to an isoenergetic 8-week diet: (a) low LCn3 and PP; (b) high LCn3; (c) high PP; or (d) high LCn3 and PP. Microbiota analysis was performed on feces collected before and after the intervention. DGGE analysis of the predominant bacteria, Eubacterium rectale and Blautia coccoides group (Lachnospiraceae, EREC), Clostridium leptum (Ruminococcaceae, CLEPT), Bacteroides spp., Bifidobacteria, and Lactobacillus group was performed. A quantitative real-time PCR was performed for the same group, additionally including Atopobium cluster (Coriobatteriaceae). Before and after the intervention, participants underwent a 75 g OGTT and a high-fat test meal to evaluate glucose and lipid response. Results: Adherence to the four diets was optimal. PP significantly increased microbial diversity (p = 0.006) and CLEPT (p = 0.015), while it reduced EREC (p = 0.044). LCn3 significantly increased the numbers of Bifidobacteria (p = 0.041). Changes in CLEPT numbers correlated with changes in early insulin secretion (r = 0.263, p = 0.030). Changes in Atopobium numbers correlated with postprandial triglycerides in plasma (r = 0.266, p = 0.026) and large VLDL (r = 0.313, p = 0.009), and cholesterol in large VLDL (r = 0.319, p = 0.008). Conclusions: Diets naturally rich in PP or LCn3 influenced gut microbiota composition in individuals at high cardiometabolic risk. These modifications were associated with changes in glucose/lipid metabolism.

C109 is a potent but poorly soluble FtsZ inhibitor displaying promising activity against Burkholderia cenocepacia, a high-risk pathogen for cystic fibrosis (CF) sufferers. To harness C109 for inhalation, we developed nanocrystal-embedded dry powders for inhalation suspension consisting in C109 nanocrystals stabilized with D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) embedded in hydroxypropyl-beta-cyclodextrin (CD). The powders could be safely re-dispersed in water for in vitro aerosolization. Owing to the presence of a PEG shell, the rod shape and the peculiar aspect ratio, C109 nanocrystals were able to diffuse through artificial CF mucus. The promising technological features were completed by encouraging in vitro/in vivo effects. The formulations displayed no toxicity towards human bronchial epithelial cells and were active against planktonic and sessile B. cenocepacia strains. The efficacy of C109 nanosuspensions in combination with piperacillin was confirmed in a Galleria mellonella infection model, strengthening their potential for combined therapy of B. cenocepacia lung infections.

Dietary (poly)phenol intake has been associated with a lower risk of cardiovascular mortality and new events. However, no conclusive data can be drawn from clinical trials evaluating the effects of (poly)phenols on cardiovascular risk factors. In addition, the mechanisms of action behind the beneficial association of (poly)phenol intake with cardiovascular health are not completely understood. Therefore, this perspective aimed to highlight the main methodological limitations that might explain the conflicting results obtained so far. In addition, novel insights on local and systemic effects of (poly)phenols were discussed. Finally, some critical issues to take into consideration in future studies were reported. This more comprehensive approach could represent a strategy to deeply understand the effects of (poly)phenols on human health.

Adults with central adiposity and other features of the metabolic syndrome have a markedly elevated risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD). A Mediterranean-style healthy eating pattern (MED-HEP) and consumption of foods with a lower glycemic index (GI) are potential dietary approaches to curb the T2D and CVD epidemic. However, experimental evidence of the effectiveness of MED-HEP and of the contribution of GI towards improving indices of glucose homeostasis, especially among non-diabetic people, are lacking. Therefore, we developed the MedGI-Carb trial, a multi-center (Italy, Sweden, and United States) intervention in adults with at least two components of the metabolic syndrome (elevated waist circumference + one other component) that aims to improve markers of glucose homeostasis through dietary modification. All participants were randomized to consume an isocaloric high- or low-GI MED-HEP for 12 weeks. We hypothesized that indexes of insulinemia (primary outcome: postprandial insulin and glucose after standardized breakfast and lunch; secondary outcomes: fasting plasma glucose and insulin, HbA1c, 24-h continuous glucose monitoring) would be improved more with the low-GI versus the high-GI MED-HEP. Additionally, we hypothesized that consumption of a MED-HEP would improve other markers of cardiometabolic health and well-being (fasting blood pressure, fasting lipid profile, sleep quality, satiety, global metabolic alterations in the plasma metabolome, changes in the gut microbiota, subjective health and well-being), with no difference between groups. Collectively, the design of MEDGI-Carb allows several different research questions to be explored. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03410719.

Plasma lipoprotein composition, especially in the postprandial state, could be relevant for cardiovascular risk and could be influenced by eating habits. This study evaluated the effects of a polyphenol-rich diet on postprandial lipoprotein composition in individuals at high cardiometabolic risk. Seventy-eight individuals with high waist circumference and at least another component of the metabolic syndrome were randomized to either a high-polyphenol (HighP) or low-polyphenol (LowP) diet. Before and after the 8-week intervention, chylomicrons, VLDL1, VLDL2, IDL, LDL, HDL particles, and their lipid concentrations were determined over a 6-h high-fat test meal with high or low-polyphenol content, according to the diet assigned. VLDL1 postprandial areas under the curve (AUCs) were lower for cholesterol (Chol) (1.48 ± 0.98 vs. 1.91 ± 1.13 mmol/L × 6 h, M ± SD, p = 0.014) and triglycerides (Tg) (4.70 ± 2.70 vs. 6.02 ± 3.07 mmol/L × 6 h, p = 0.005) after the HighP than after the LowP diet, with no changes in Chol/Tg ratio. IDL Chol AUCs were higher after the HighP than after the LowP diet (1.29 ± 0.77 vs. 1.01 ± 0.51 mmol/L × 6 h, p = 0.037). LDL Tg AUCs were higher after the HighP than after the LowP diet (1.15 ± 0.33 vs. 1.02 ± 0.35 mmol/L × 6 h, p

The emergence of pan-resistant strains in nosocomial settings underscores the urgent need of novel therapies targeting vital bacterial functions. Bacterial iron metabolism is a fascinating target for new antimicrobials. Iron mimetic metal Ga(III) has been repurposed as an antimicrobial drug, in pre-clinical studies and recent clinical studies have raised the possibility of using Ga(III) for the treatment of P. aeruginosa pulmonary infection. Ga(III) has been approved by FDA for the treatment of cancer, autoimmune and bone resorption disorders. However, some critical issues affect the therapeutic schedule of Ga(III), principally the intra-venous (i.v.) administration, and the nephrotoxicity caused by prolonged administration. Ga(III) aerosolization could represent a viable alternative for treatment of lung infections, since delivery of antimicrobial agents to the airways maximizes drug concentration at the site of infection, improves the therapeutic efficacy, and alleviates systemic toxic effects. We demonstrate the advantage of inhaled vs i.v. administered Ga(III), in terms of bio-distribution and lung acute toxicity, by using a rat model. In vivo results support the use of Ga(III) for inhalation since intra-tracheal Ga(III) delivery improved its persistence in the lung, while the i.v. administration caused rapid clearance and did not allow to attain a significant Ga(III) concentration in this organ. Moreover, local and systemic acute toxicity following intra-tracheal administration was not observed, since no significant signs of inflammation were found. At this stage of evidence, the direct administration of Ga(III) to the lung appears feasible and safe, boosting the development of Ga(III)-based drugs for inhalation therapy.

Additive manufacturing (AM) maturity allows diffusion of this technology in conventional production environments. In the decision to adopt a new technology, production costs are one of the most important factors to analyse, even if they are not developed enough yet. In the last decade, several cost models for AM have been proposed, but each of them focuses on a specific aspect of the process, lacking the ability to consider the effective costs associated with AM, i.e. regarding AM as part of a more general production context. The aim of this study is to develop a cost model that evaluates process costs of AM for relevant technologies such as stereolithography, selective laser sintering and electron beam melting when integrated in a general production process. The integration of AM on the shop floor is proved by the introduction of an index such as the Overall Equipment Effectiveness (OEE) index, which allows this evaluation to be more connected to real production system issues. At the end of the paper, an experiment to compare the results of the proposed model with those of previous studies is reported and it is put in evidence how this model overcomes the previous problem of estimation.

Background & aims: Dietary polyphenols have beneficial effects on glucose/lipid metabolism in subjects at high risk to develop type 2 diabetes; however, the underlying mechanisms are not clear. We aimed to evaluate: 1) the acute effects of the consumption of a drink rich in polyphenols from red grape pomace (RGPD) on glucose/insulin and triglyceride responses to a standard meal in healthy individuals, and, 2) the relationship between plasma levels of phenolic metabolites and metabolic parameters. Methods: Twelve healthy men, aged 20-40 years participated in a randomized, controlled study according to a cross-over design. After a 3-day low-polyphenol diet, all participants consumed, on two different days and separated by a one week interval, after an overnight fast, a drink rich in polyphenols (1.562 g gallic acid equivalents (GAE)) or a control drink (CD, no polyphenols), followed after 3 h by a standard meal (960 kcal, 18% protein, 30% fat, 52% CHO). Blood samples were taken at fasting, 3 h after the drink, over 5 h after the standard meal and at fasting on the next day to measure plasma concentrations of glucose, insulin, triglyceride and phenolic metabolites. Results: Glycemic and triglyceride post-meal responses were similar after both the RGPD and the control drink. In contrast, postprandial insulin incremental area (iAUC0-5h) was 31% lower (p < 0.05), insulin secretion index was 18% lower (p < 0.016) and insulin sensitivity (SI) index was 36% higher (p = 0.037) after the RGPD compared to CD. Among phenolic metabolites, gallic acid correlated inversely with the insulin response (r = -0.604; p = 0.032) and positively with the SI index (r = 0.588, p = 0.037). Conclusions: RGPD consumption acutely reduced postprandial insulin levels and improved insulin sensitivity. This effect could be likely related to the increase in gallic acid levels. This drink, added to usual diet, could contribute to increase the daily intake of polyphenols, with potential health benefits. Clinicaltrials.gov identifier: NCT02865278

From the past decades, increasing attention has been paid to the quality level of technological and mechanical properties achieved by the Additive Manufacturing (AM); these two elements have achieved a good performance, and it is possible to compare this with the results achieved by traditional technology. Therefore, the AM maturity is high enough to let industries adopt this technology in a more general production framework as the mechanical manufacturing industrial one is. Since the technological and mechanical properties are also beneficial for the materials produced with AM, the primary objective of this paper is to focus more on managerial facets, such as the cost control of a production environment, where these new technologies are present. This paper aims to analyse the existing literature about the cost models developed specifically for AM from an operations management point of view and discusses the strengths and weaknesses of all models.

This paper examines user behavior during multimodal human-computer interaction (HCI). It discusses how pointing, natural language, and graphical layout should be integrated to enhance the usability of multimodal systems. Two experiments were run to study simulated systems capable of understanding written natural language and mouse-supported pointing gestures. Results allowed to: (a) develop a taxonomy of communication acts aimed at identifying targets; (b) determine the conditions under which specific referent identification strategies are likely to be produced; (c) suggest guidelines for designing effective multimodal interfaces; (d) show that performance is strongly influenced by interface graphical layout and by user expertise. Our study confirms the value of simulation as a tool for building HCI models and supports the basic idea that linguistic, visual, and motor cues can be integrated to favor effective multimodal communication.