Beyond the Implicit/Explicit Dichotomy: The Pragmatics of Plausible Deniability

In everyday conversation, messages are often communicated indirectly, implicitly. Why do we seem to communicate so inefficiently? How speakers choose to express a message (modulating confidence, using less explicit formulations) has been proposed to impact how committed they will appear to be to its content. This commitment can be assessed in terms of accountability – is the speaker held accountable for what they communicated? – and deniability – can the speaker plausibly deny they intended to communicate it? We investigated two factors that may influence commitment to implicitly conveyed messages. In a preregistered online study, we tested the hypothesis that the degree of meaning strength (strongly or weakly communicated) and the level of meaning used by the speaker (an enrichment or a conversational implicature) modulate accountability and plausible deniability. Our results show that both meaning strength and level of meaning influence speaker accountability and plausible deniability. Participants perceived enrichments to be harder to deny than conversational implicatures, and strongly implied content as more difficult to deny than weakly implied content. Furthermore, participants held the speaker more accountable to content conveyed via an enrichment than to content conveyed via an implicature. These results corroborate previously found differences between levels of meaning (enrichment vs. implicature). They also highlight the largely understudied role of meaning strength as a cue to speaker commitment in communication

The design of CO2-based working fluids for high-temperature heat source power cycles

The application of CO2power cycles is advantageous to exploit high-temperature sources (500-800°C) in the case of available low-temperature heat sinks (15-25°C). However, their efficiency is strongly reduced for higher heat sink temperatures. At these temperatures, due to the low-critical temperature of CO2(about 31°C), CO2is in fact compressed in the supercritical vapor phase rather than in the liquid phase, thus increasing energetic demand for compression. One of the solutions envisaged to overcome this problem is the addition of one or more chemicals that allow having a mixture with a higher critical temperature than the one of pure CO2. This preserve the working fluid compression in its liquid phase, even in the case of heat sinks with temperatures greater than 25°C. This research shows that the addition to CO2of a properly selected chemical component enables to increase the critical temperature up to 45°C with relevant improvements of cycle efficiency with respect to pure-CO2power cycles. In particular, it summarizes the most relevant criteria to be accounted for when selecting CO2-additives. Moreover, the paper warns of the thermodynamic effects deriving from adding to CO2a second characterized by a much more high critical temperature, such as the occurrence of infinite-pressure critical points and multiple-phase liquid-liquid and vapor-liquid critical points. Finally, the paper analyses the thermodynamic properties of a high-critical temperature CO2-based mixture, suitable for these applications, that presents multiple phase critical points. In this regard, it is specified that the paper also aims at filling a knowledge gap in the study of thermodynamic properties of mixtures presenting how do enthalpy and specific volume change in response to pressure variations in the event of liquid-liquid and vapour-liquid critical points. Finally, we present the comparison between performances of power cycles which use, as working fluid, either pure CO2or the novel designed higher temperature CO2-based mixture

Bioengineering a cryogel-derived bioartificial liver using particle image velocimetry defined fluid dynamics

Bioartificial Liver (BAL) devices are extracorporeal systems designed to support or recover hepatic function in patients with liver failure. The design of an effective BAL remains an open challenge since it requires a complex co-optimisation of cell colonisation, biomaterial scaffold and BAL fluid dynamics. Building on previous evidence of suitability as a blood perfusion device for detoxification, the current study investigated the use of RGD-containing p(HEMA)-alginate cryogels as BAL scaffolds. Cryogels were modified with alginate to reduce protein fouling and functionalised with an RGD-containing peptide to increase hepatocyte adhesion. A novel approach for characterisation of the internal flow through the porous matrix was developed by employing Particle Image Velocimetry (PIV) to visualise flow inside cryogels. Based on PIV results, which showed the laminar nature of flow inside cryogel pores, a multi-layered bioreactor composed of spaced cryogel discs was designed to improve blood/hepatocyte mass exchange. The stacked bioreactor showed a significantly higher production of albumin and urea compared to the column version, with improved cell colonisation and proliferation over time. The cell-free cryogel-based device was tested for safety in a bile-duct ligation model of liver cirrhosis. Thus, a stacked bioreactor prototype was developed based on a surface-engineered cryogel design with optimised fluid dynamics for BAL use

Changes in body composition in early breast cancer patients treated with aromatase inhibitors

Purpose The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs).Methods This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors.Results A significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean -3.1%, 95% CI -3.9; -2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from-1.3% to -3.9%, respectively.Conclusion Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients

Chromosome 19p13.3 deletion in a child with Peutz-Jeghers syndrome, congenital heart defect, high myopia, learning difficulties and dysmorphic features: Clinical and molecular characterization of a new contiguous gene syndrome

The Peutz-Jeghers syndrome (PJS) is an autosomal-dominant hamartomatous polyposis syndrome characterized by mucocutaneous pigmentation, gastrointestinal polyps and the increased risk of multiple cancers. The causative point mutation in the STK11 gene of most patients accounts for about 30% of the cases of partial and complete gene deletion. This is a report on a girl with PJS features, learning difficulties, dysmorphic features and cardiac malformation, bearing a de novo 1.1 Mb deletion at 19p13.3. This deletion encompasses at least 47 genes, including STK11. This is the first report on 19p13.3 deletion associated with a PJS phenotype, as well as other atypical manifestations, thereby implying a new contiguous gene syndrome

A real-life study of daratumumab-bortezomib-dexamethasone (D-VD) in lenalidomide exposed/refractory multiple myeloma patients: a report from the Triveneto Myeloma Working Group

Treatment of lenalidomide refractory (Len-R) multiple myeloma (MM) patients still represents an unmet clinical need. In the last years, daratumumab-bortezomib-dexamethasone (D-VD) combination was extensively used in this setting, even though only a small fraction of Len-R patients was included in the pivotal trial. This real-life study aimed to evaluate the efficacy and safety of the D-VD regimen in a cohort that exclusively enrolled Len exposed or refractory MM patients. The study cohort included 57 patients affected by relapsed/refractory MM. All patients were previously exposed to Len, with 77.2% being refractory. The overall response rate (ORR) was 79.6% with 43% of cases obtaining at least a very good partial response (VGPR). The D-VD regimen showed a favorable safety profile, with low frequency of grade 3–4 adverse events, except for thrombocytopenia observed in 21.4% of patients. With a median follow-up of 13 months, median progression-free survival (PFS) was 17 months. No significant PFS differences were observed according to age, ISS, LDH levels, type of relapse, and high-risk FISH. Len exposed patients displayed a PFS advantage as compared to Len refractory patients (29 vs 16 months, p = 0.2876). Similarly, patients treated after Len maintenance showed a better outcome as compared to patients who had received a full-dose Len treatment (23 vs 13 months, p = 0.1728). In conclusion, our real-world data on D-VD combination showed remarkable efficacy in Len-R patients, placing this regimen as one of the standards of care to be properly taken into account in this MM setting