Stability and determinants of the public debt-to-GDP ratio: an Input Output – Stock Flow Consistent approach

The paper develops a dynamic Input Output - Stock Flow consistent model based on the Supermultiplier approach. This framework integrates the dimension of output determination with the system of relative prices. Through this model, we define the determinants of the public debt-to-GDP ratio and the conditions for its stability. The main results of the research show that: i) Given the interest rate, the saving rate, the tax rate, the industrial profit rate and the coefficients of production there exist a steady-state value of the public debt-to-GDP ratio ingrained in the economic system. This result calls into question the idea of imposing budgetary rules with threshold levels independently from the very specific features of each economic system; ii) Expansions in the level of public expenditure have a permanent effect on the public debt-to-GDP ratio only in the presence of the accelerator effect, that is, through an induced increase in the share of private indebtedness on GDP and aggregate debt. Because of the accelerator channel, the public debt-to-GDP ratio depends on the capital intensity of the aggregate production process and, thus, on the system of relative prices. With this respect, the capital intensity determines the elasticity of private indebtedness with respect to one-point change in public spending; iii) Conversely to the neoclassical argument, the relationship between the interest rate and public debt-to-GDP ratio goes from the first to the second. In particular, changes in the interest rate modify the public debt-to-GDP ratio through both variations in the quantitative and value dimension. Such variations have a puzzling effect on the steady-state value of the public debt-to-GDP ratio. For instance, the reverse capital deepening implies that an increase in the interest rate produces a decrease in the public debt-to-GDP ratio. Finally, we point out that, in contrast to the standard argument proposed by mainstream macroeconomics, the condition of fiscal balance jointly a positive differential between the growth rate of output and the interest rate has no relevance for the stability conditions of the public debt-to-GDP ratio. In this regard, we develop a taxonomy of the growth regimes depicted by the model deriving such conditions in each scenario. The necessary condition of stability is the absence of budgetary constraints, it becomes sufficient when one of the following is respected: the growth rate of primary public expenditure is higher than zero, the interest rate is higher than zero or the propensity to consume out of wealth is non-zero

Intrahepatic cholangiocarcinoma: review and update

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that could develop at any level from the biliary tree. CCA is currently classified into intrahepatic (iCCA), perihilar and distal on the basis of its anatomical location. Of note, these three CCA subtypes have common features but also important inter-tumor and intra-tumor differences that can affect the pathogenesis and outcome. A unique feature of iCCA is that it recognizes as origin tissues, the hepatic parenchyma or large intrahepatic and extrahepatic bile ducts, which are furnished by two distinct stem cell niches, the canals of Hering and the peribiliary glands, respectively. The complexity of iCCA pathogenesis highlights the need of a multidisciplinary, translational and systemic approach to this malignancy. This review will focus on the advances of iCCA epidemiology, histo-morphology, risk factors, molecular pathogenesis, revealing the existence of multiple subsets of iCCA

Spesa pubblica, moltiplicatori fiscali e sostenibilità del debito pubblico

In questo lavoro si quantificano gli effetti della spesa pubblica e delle sue componenti, ossia i consumi e gli investimenti pubblici, sul livello del prodotto interno lordo e sul rapporto debito pubblico/PIL. Applicando un modello econometrico basato sul Local-Projection ad un panel di 14 Paesi OCSE, i risultati mostrano che i moltiplicatori della spesa pubblica totale sono positivi e intorno all’unità e i moltiplicatori degli investimenti pubblici sono più alti di quelli dei consumi. Quando si analizzano gli effetti delle politiche fiscali espansive sulla sostenibilità del debito pubblico, si osserva che tutti gli stimoli fiscali conducono ad una riduzione del rapporto debito/PIL, ma gli investimenti pubblici sono lo strumento più efficace per promuovere la sostenibilità del debito pubblic

In vitro effects of fluticasone propionate on IL-13 production by mitogen-stimulated lymphocytes.

BACKGROUND: Corticosteroid administration produces multiple immunomodulatory effects, including down-regulation of cytokine production by CD4 T lymphocytes. Fluticasone propionate (FP) (Glaxo Smith&Kline, Greenford, UK), a highly lipophilic topical corticosteroid, has been shown to be safe and effective in the treatment of asthma and of both seasonal and perennial rhinitis. AIMS: To gain insight into the mechanisms of FP therapeutic effects, we evaluated interleukin (IL)-13 (a type 2 cytokine that seemingly plays a pivotal role in allergic mechanisms) production by mitogen-stimulated peripheral blood mononuclear cells (MNC) in vitro, treated or not with FP. METHODS: MNC from 10 healthy subjects and 10 asthmatic atopic patients with Parietaria allergy were stimulated v/v with phytohaemagglutinin (PHA) (50 gamma/ml) or with complete medium alone as a control. Culture supernatants, in vitro treated or not with 10(-7) or 10(-8) M FP, were collected after 48 or 72 h incubation. IL-13 production was assessed by enzyme-linked immunosorbent assay. In random selected samples, after 4 or 24 h of cell cultures, RNA was extracted and IL-4 and IL-5 reverse transcriptase-polymerase chain reaction (RT-PCR) products analyzed. RESULTS: At 48 h, there were no differences in IL-13 concentration in PHA-stimulated cultures between healthy subjects and asthmatic patients (93.6 +/- 18.9 versus 111.0 +/- 25.1 pg/ml). At 72 h, similar results were obtained (63.9 +/- 3.0 versus 73.3 +/- 2.5 pg/ml, respectively). At this time, however, IL-13 concentrations were significantly decreased versus 48 h both in asthmatics (p < 0.001) and in controls (p < 0.001). Treatment with 10(-7) M FP significantly reduced IL-13 production in healthy subjects and asthmatic patients both at 48 h (93.6 +/- 18.9 versus 50.50 +/- 10.6 pg/ml, p < 0.001, and 111.0 +/- 25.1 versus 59.3 +/- 13.6 pg/ml, p < 0.001, respectively) and at 72 h (63.9 +/- 9.6 versus 35.5 +/- 4.4 pg/ml, p < 0.001, and 73.3 +/- 8.0 versus 40.7 +/- 4.5 pg/ml, p < 0.001, respectively). Similar results were obtained with 10(-8) M FP at 48 and 72 h. Accordingly, evaluation of RT-PCR products from selected cell samples showed a FP dosage-dependent inhibition of IL-4 and IL-5 mRNA production both for healthy subjects and asthmatic patients. CONCLUSIONS: FP in vitro impairs IL-13 production by PHA-stimulated MNC from asthmatic and control subjects. This strengthens previous suggestions that IL-13 inhibition by steroids may, at least in part, account for their therapeutic effects

Preliminary Assessment of Two Simultaneous and Proportional Myocontrol Methods for 3-DoFs Prostheses Using Incremental Learning

Despite progressive developments over the last decades, current upper limb prostheses still lack a suitable control able to fully restore the functionalities of the lost arm. Traditional control approaches for prostheses fail when simultaneously actuating multiple Degrees of Freedom (DoFs), thus limiting their usability in daily-life scenarios. Machine learning, on the one hand, offers a solution to this issue through a promising approach for decoding user intentions but fails when input signals change. Incremental learning, on the other hand, reduces sources of error by quickly updating the model on new data rather than training the control model from scratch. In this study, we present an initial evaluation of a position and a velocity control strategy for simultaneous and proportional control over 3-DoFs based on incremental learning. The proposed controls are tested using a virtual Hannes prosthesis on two healthy participants. The performances are evaluated over eight sessions by performing the Target Achievement Control test and administering SUS and NASA-TLX questionnaires. Overall, this preliminary study demonstrates that both control strategies are promising approaches for prosthetic control, offering the potential to improve the usability of prostheses for individuals with limb loss. Further research extended to a wider population of both healthy subjects and amputees will be essential to thoroughly assess these control paradigms

Simulated microgravity promotes the formation of tridimensional cultures and stimulates pluripotency and a glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells

Many pivotal biological cell processes are affected by gravity. The aim of our study was to evaluate biological and functional effects, differentiation potential and exo-metabolome profile of simulated microgravity (SMG) on human hepatic cell line (HepG2) and human biliary tree stem/progenitor cells (hBTSCs). Both hBTSCs and HepG2 were cultured in a weightless and protected environment SGM produced by the Rotary Cell Culture System (Synthecon) and control condition in normal gravity (NG). Self-replication and differentiation toward mature cells were determined by culturing hBTSCs in Kubota's Medium (KM) and in hormonally defined medium (HDM) tailored for hepatocyte differentiation. The effects on the expression and cell exo-metabolome profiles of SMG versus NG cultures were analyzed. SMG promotes tridimensional (3D) cultures of hBTSCs and HepG2. Significative increase of stemness gene expression (p < 0.05) has been observed in hBTSCs cultured in SMG when compared to NG condition. At the same time, the expression of hepatocyte lineage markers in hBTSCs differentiated by HDM was significantly lower (p < 0.05) in SMG compared to NG, demonstrating an impaired capability of hBTSCs to differentiate in vitro toward mature hepatocytes when cultured in SMG condition. Furthermore, in HepG2 cells the SMG caused a lower (p < 0.05 vs controls) transcription of CYP3A4, a marker of late-stage (i.e. Zone 3) hepatocytes. Exo-metabolome NMR-analysis showed that both cell cultures consumed a higher amount of glucose and lower glutamate in SMG respect to NG (p < 0.05). Moreover, hBTSCs media cultures resulted richer of released fermentation (lactate, acetate) and ketogenesis products (B-hydroxybutyrate) in SGM (p < 0.05) than NG. While, HepG2 cells showed higher consumption of amino acids and release of ketoacids (3-Methyl-2-oxovalerate, 2-oxo-4-methyl-valerate) and formiate with respect to normogravity condition (p < 0.05). Based on our results, SMG could be helpful for developing hBTSCs-derived liver devices. In conclusion, SMG favored the formation of hBTSCs and HepG2 3D cultures and the maintenance of stemness contrasting cell differentiation; these effects being associated with stimulation of glycolytic metabolism. Interestingly, the impact of SMG on stem cell biology should be taken into consideration for workers involved in space medicine programs

Update on gingival overgrowth by cyclosporine A in renal transplants

Severe gingival overgrowth is one of the most frequent side effects in renal transplant patients associated with assumption of cyclosporine A. Several associations with age, sex, dosage, duration of therapy or interval since transplantation have been hypothesized. The introduction of alternative immunosuppressant drugs have been suggested to permit better long-term transplant outcomes and a decrease in incidence of gingival overgrowth. The aim of the present paper is to summarize current knowledge regarding aetiology, pathogenesis and management of gingival overgrowth induced by Cyclosporine A

Bevacizumab plus XELOX as first-line treatment of metastatic colorectal cancer: The OBELIX study

AIM: To confirm the efficacy and safety of bevacizumab/XELOX combination for the treatment of locally advanced or metastatic colorectal cancer (CRC) in Italy. METHODS: This multicentric, prospective, open-label study included patients with CRC previously untreated with chemotherapy. Patients were administered bevacizumab in combination with XELOX. The primary efficacy end-point was progression-free survival (PFS). Secondary end-points included time to overall response (TOR), duration of response (DOR), time to treatment failure (TTF) and overall survival (OS). The incidence and type of adverse events AEs and severe AEs were evaluated. Also, the mutational status of BRAF and KRAS was assessed by high resolution melting and direct sequencing, and quality of life (QoL) was measured by the EuroQoL EQ-5D questionnaire at baseline and at the last visit. RESULTS: The intention-to-treat population included 197 patients (mean age: 62.3 ± 9.9 years, 56.4% males). At baseline, 16/34 evaluable subjects (47.1%) harbored a KRAS and/or a BRAF mutation; the mean QoL index was 80.2 ± 14.3. First-line therapy was given for 223.7 ± 175.9 d, and after a mean follow-up of 387.7 ± 238.8 d all patients discontinued from the study mainly for disease progression (PD, 45.4%) and AEs (25.4%). Median PFS was 9.7 mo (95%CI: 8.4-10.5) and the median values for secondary end-points were: TOR = 3.9 mo (95%CI: 2.6-4.7), DOR = 8.5 mo (95%CI: 7.3-10.3), TTF = 6.7 mo (95%CI: 6.0-7.7) and OS = 23.2 mo (95%CI: 20.1-27.2). Patients carrying at least one lesion had a lower overall response rate (66.7% vs 88.9%) and a lower probability of achieving complete or partial response than those without mutations, but the difference in relative risk was not statistically significant (P = 0.2). Mean EQ-5D-3L raw index score significantly decreased to 74.9 ± 19.1 at the last visit (signed-rank test, P = 0.0076), but in general the evaluation on QoL perceived by patients was good. CONCLUSION: The efficacy of bevacizumab in combination with XELOX in terms of PFS in patients with aCRC or mCRC in Italy was confirmed, with acceptable toxicity

Soil Biocementation via Enzyme Induced Carbonate Precipitation (eicp) Method Employing Soybeans as a Source of Cheap Enzyme

In this work, the soil improvement technique via Enzyme Induced Carbonate Precipitation (EICP) was investigated by employing, as an alternative to expensive pure enzymes, enzymes extracted from agro-food wastes (tomato, apple, and soybean) such that the process is economically viable and fully embraces the concept of the circular economy. The feasibility of the process was evaluated by monitoring calcium carbonate precipitation in a sand sample. The effect of selected operative parameters was investigated during the injection into different grain size sand samples. The optimal operating conditions in terms of sand grain size, temperature, Urea/Calcium concentration were found. Results demonstrated the effectiveness of this alternative solution for EICP method in term of acquired material strength and the possibility to operate sand consolidation through an economically sustainable process

Thrombosis in Autoimmune Diseases: A Role for Immunosuppressive Treatments?

Autoimmune diseases are not infrequently associated with arterial or venous thrombotic events. Chronic inflammation and immune system impairment are considered the main pathogenetic mechanisms. Some of the drugs used in the treatment of such diseases have been associated with an increased risk of thrombosis. On the contrary, their anti-inflammatory and immune modulator activity could correct some mechanisms leading to thrombosis. In this review, recent evidence available on this topic is examined. There is a lack of adequate studies, but available evidence suggests that glucocorticoids and high-dose immunoglobulins are associated with an increased incidence of venous thromboembolism. Although available data do not allow drawing definite conclusions and more data are needed from future studies and registries, physicians should be aware of these associations