Public Debt Management in Brazil

This paper derives the optimal composition of the Brazilian public debt by looking at the relative impact of the risk and cost of alternative debt instruments on the probability of missing the stabilization target. This allows to price risk against the expected cost of debt service and thus to find the optimal combination along the trade off between cost and risk minimization. The optimal debt structure is a function of the expected return differentials between debt instruments, of the conditional variance of debt returns and of their covariances with output growth, inflation, exchange-rate depreciation and the Selic rate. We estimate the relevant covariances by: i) exploiting the daily survey of expectations; ii) simulating a small structural model of the Brazilian economy under different shocks; iii) estimating the unanticipated components of the relevant variables with forecasting regressions. The empirical evidence strongly supports the funding strategy of Brazilian Treasury in 2003 of relying heavily on fixed-rate LTN bonds. It also supports its recent decision to revitalize the market for price-indexed bonds with the new NTN-B program of IPCA indexation. Though decreasing, the exposure to exchange rate risk appears too large suggesting that more efforts should be made to reduce funding in foreign currencies.

Immune contexture monitoring in solid tumors focusing on Head and Neck Cancer

Forti evidenze dimostrano una stretta interazione tra il sistema immunitario e lo sviluppo biologico e la progressione clinica dei tumori solidi. L'effetto che il microambiente immunitario del tumore può avere sul comportamento clinico della malattia è indicato come "immunecontexture". Nonostante ciò, l'attuale gestione clinica dei pazienti affetti da cancro non tiene conto di alcuna caratteristica immunologica né per la stadiazione né per le scelte terapeutiche. Il tumore della testa e del collo (HNSCC) rappresenta il 7° tumore più comune al mondo ed è caratterizzato da una prognosi relativamente sfavorevole e dall'effetto negativo dei trattamenti sulla qualità della vita dei pazienti. Oltre alla chirurgia e alla radioterapia, sono disponibili pochi trattamenti sistemici, rappresentati principalmente dalla chemioterapia a base di platino-derivati o dal cetuximab. L'immunoterapia è una nuova strategia terapeutica ancora limitata al setting palliativo (malattia ricorrente non resecabile o metastatica). La ricerca di nuovi biomarcatori o possibili nuovi meccanismi target è molto rilevante quindi nel contesto clinico dell'HNSCC. In questa tesi ci si concentrerà sullo studio di tre possibili popolazioni immunitarie pro-tumorali studiate nell'HNSCC: i neutrofili tumore-associati (TAN), le cellule B intratumorali con fenotipo immunosoppressivo e i T-reg CD8+. Particolare attenzione è data all'applicazione di moderne tecniche biostatistiche e bioinformatiche per riassumere informazioni complesse derivate da variabili cliniche e immunologiche multiparametriche e per validare risultati derivati ​​in situ, attraverso dati di espressione genica derivati da dataset pubblici. Infine, la seconda parte della tesi prenderà in considerazione progetti di ricerca clinica rilevanti, volti a migliorare l'oncologia di precisione nell'HNSCC, sviluppando modelli predittivi di sopravvivenza, confrontando procedure oncologiche alternative, validando nuovi classificatori o testando l'uso di nuovi protocolli clinici come l'uso dell'immunonutrizione.Strong evidences demonstrate a close interplay between the immune system and the biological development and clinical progression of solid tumors. The effect that the tumor immune microenvironment can have on the clinical behavior of the disease is referred as the immuno contexture. Nevertheless, the current clinical management of patients affected by cancer does not take into account any immunological features either for the staging or for the treatment choices. Head and Neck Cancer (HNSCC) represents the 7th most common cancer worldwide and it is characterized by a relatively poor prognosis and detrimental effect of treatments on the quality of life of patients. Beyond surgery and radiotherapy, few systemic treatments are available, mainly represented by platinum-based chemotherapy or cetuximab. Immunotherapy is a new therapeutical strategy still limited to the palliative setting (recurrent not resectable or metastatic disease). The search for new biomarkers or possible new targetable mechanisms is meaningful especially in the clinical setting of HNSCC. In this thesis a focus will be given on the study of three possible pro-tumoral immune populations studied in HNSCC: the tumor associated neutrophils (TAN), intratumoral B-cells with a immunosuppressive phenotype and the CD8+ T-regs. Biostatistical and bioinformatical techniques are applied to summarize complex information derived from multiparametric clinical and immunological variables and to validate in-situ derived findings through gene expression data of public available datasets. Lastly, the second part of the thesis will take into account relevant clinical research projects, aimed at improving the precision oncology in HNSCC developing survival prediction models, comparing alternative oncological procedures, validating new classifiers or testing the use of novel clinical protocols as the use of immunnutrition

How is the Debt Managed? Learning from Fiscal Stabilizations

This paper provides evidence on the behavior of public debt managers during fiscal stabilizations. Such episodes provide valuable information on the way debt instruments are chosen because they allow to overcome the problem that policymakers' expectations of interest rates are generally not observable. We find that governments increase the share of fixed-rate long-term debt denominated in the domestic currency the higher is the conditional volatility of short-term interest rates, the lower are long-term interest rates, and the stronger is the fall in long-term rates that follows the announcement of the stabilization program. By contrast, conventional measures of the relative cost of issuing long-term debt, such as the long-short interest-rate spread, are not significant. This evidence suggests that debt managers tend to prefer long to short maturity debt because they are concerned about the risk of refinancing at higher than expected interest rates. However, when long-term rates are high relative to their expectations, they issue short maturity debt to minimize borrowing costs.This paper provides evidence on the behavior of public debt managers during fiscal stabilizations. Such episodes provide valuable information on the way debt instruments are chosen because they allow to overcome the problem that policymakers' expectations of interest rates are generally not observable. We find that governments increase the share of fixed-rate long-term debt denominated in the domestic currency the higher is the conditional volatility of short-term interest rates, the lower are long-term interest rates, and the stronger is the fall in long-term rates that follows the announcement of the stabilization program. By contrast, conventional measures of the relative cost of issuing long-term debt, such as the long-short interest-rate spread, are not significant. This evidence suggests that debt managers tend to prefer long to short maturity debt because they are concerned about the risk of refinancing at higher than expected interest rates. However, when long-term rates are high relative to their expectations, they issue short maturity debt to minimize borrowing costs.Non-Refereed Working Papers / of national relevance onl

Managing the Public Debt in Fiscal Stabilizations: the Evidence

This paper provides evidence on the behavior of public debt managers during fiscal stabilizations in OECD countries over the last two decades. We find that debt maturity tends to lengthen the more credible is the program, the lower is the long-term interest rate and the higher is the volatility of short-term interest rates. We show that this debt issuing strategy is consistent with optimal debt management if information bewteen the government and private investors is asymmetric, as it is usually the case at the outset of a stabilization attempt when private investors may lack full confidence in the announced budget cuts.This paper provides evidence on the behavior of public debt managers during fiscal stabilizations in OECD countries over the last two decades. We find that debt maturity tends to lengthen the more credible is the program, the lower is the long-term interest rate and the higher is the volatility of short-term interest rates. We show that this debt issuing strategy is consistent with optimal debt management if information bewteen the government and private investors is asymmetric, as it is usually the case at the outset of a stabilization attempt when private investors may lack full confidence in the announced budget cuts.Non-Refereed Working Papers / of national relevance onl

COVID-19 pandemic: a mobility-dependent SEIR model with undetected cases in Italy, Europe and US

OBJECTIVES: to describe the first wave of the COVID-19 pandemic with a focus on undetected cases and to evaluate different post-lockdown scenarios. DESIGN: the study introduces a SEIR compartmental model, taking into account the region-specific fraction of undetected cases, the effects of mobility restrictions, and the personal protective measures adopted, such as wearing a mask and washing hands frequently. SETTING AND PARTICIPANTS: the model is experimentally validated with data of all the Italian regions, some European countries, and the US. MAIN OUTCOME MEASURES: the accuracy of the model results is measured through the mean absolute percentage error (MAPE) and Lewis criteria; fitting parameters are in good agreement with previous literature. RESULTS: the epidemic curves for different countries and the amount of undetected and asymptomatic cases are estimated, which are likely to represent the main source of infections in the near future. The model is applied to the Hubei case study, which is the first place to relax mobility restrictions. Results show different possible scenarios. Mobility and the adoption of personal protective measures greatly influence the dynamics of the infection, determining either a huge and rapid secondary epidemic peak or a more delayed and manageable one. CONCLUSIONS: mathematical models can provide useful insights for healthcare decision makers to determine the best strategy in case of future outbreaks.Comment: 8 pages, 1 Table, 3 Figures, Supplementary Method

Functional outcomes after transoral CO2 laser treatment for posterior glottic stenosis: a bicentric case series

Purpose The aim of this study is to evaluate functional outcomes in terms of decannulation rate and quality of life of patients affected by PGS (Grades I-IV) treated only by transoral CO2 laser microsurgery (TOLMS) in two tertiary centers. Methods An observational retrospective study was carried out, enrolling 22 patients affected by PGS who were treated by a transoral approach at two tertiary referral centers. Surgical treatment included TOLMS with tailored laser resection of the scar tissue combined with posterior cordotomy, resurfacing of the raw area with mucosal microflap, or placement of a Montgomery T-tube or Keel stent. All patients were evaluated and staged preoperatively and postoperatively, at least 6 months after the surgery. Functional outcomes were objectively evaluated by the Airway-Dysphonia-Voice-Swallowing (ADVS) staging system, Voice Handicap Index-30 (VHI-30), and Eating Assessment Tool-10 (EAT-10) questionnaires. Results Quality of life significantly improved as measured by the VHI-30 questionnaire with a median variation of - 31.0 (p = 0.003), the EAT-10 with a median variation of - 4.0 (p = 0.042), and the ADVS with a median variation of - 3.5 (p < 0.001). No significant changes were observed in swallowing scores. We were able to decannulate 7 of 9 patients (almost 80%) with previous tracheotomy. Conclusion In conclusion, even if there is still no general agreement on an exact therapeutic algorithm to treat PGS, our results confirm that transoral surgery, in terms of scar tissue removal, combined in selected patients with posterior cordotomy and pedicled local flaps and/or placement of stents, represents a safe and effective surgical approach even for more severe PGS

Managing the Public Debt in Fiscal Stabilizations: The Evidence

This paper provides evidence on the behavior of public debt managers during fiscal" stabilizations in OECD countries over the last two decades. We find that debt maturity tends to" lengthen the more credible the program, the lower the long-term interest rate and the higher the" volatility of short-term interest rates. We show that this debt issuing strategy is consistent with" optimal debt management if information between the government and private investors is" asymmetric, as is usually the case at the outset of a stabilization attempt when private investors" may lack full confidence in the announced budget cuts.

Treatment of primary epiglottis collapse in OSA in adults with glossoepiglottopexy: a 5-year experience

Objective. To review our 5-year experience with a modified version of glossoepiglottopexy for treatment of obstructive sleep apnoea syndrome (OSA) in two hospitals.Methods. A retrospective analysis was carried out on a cohort of adult patients affected by OSA suffering from primary collapse of the epiglottis who underwent a modified glossoepiglottopexy. All patients underwent drug-induced sleep endoscopy, polysomnographic and swallowing evaluation, and assessment with the Epworth Sleepiness Scale (ESS).Results. Forty-nine patients were retrospectively evaluated. Both the apnoea-hypopnoea index (AHI) (median AHI(post)-AHI(pre) = -22.4 events/h; p < 0.001) and oxygen desaturation index (ODI) showed a significant postoperative decrease (median ODIpost-ODIpre = -18 events/h; p < 0.001), as did hypoxaemia index (median T-90% post - T-90% pre = 5%; p < 0.001). The ESS questionnaire revealed a significant decrease in postoperative scores (median ESSpost-ESSpre =- 9; p < 0.001). None of the patients developed postoperative dysphagia.Conclusions. Our 5-year experience demonstrates that modified glossoepiglottopexy is a safe and reliable surgical technique for treatment of primary epiglottic collapse in OSA patients

Metavariables resuming host immune features and nodal involvement are associated with oncological outcomes in oral cavity squamous cell carcinoma

Oral cavity squamous cell carcinoma (OSCC) is a common head and neck cancer characterized by a poor prognosis associated with locoregional or distant failure. Among the predictors of prognosis, a dense infiltration of adaptive immune cells is protective and associated with improved clinical outcomes. However, few tools are available to integrate immune contexture variables into clinical settings. By using digital microscopy analysis of a large retrospective OSCC cohort (n = 182), we explored the clinical significance of tumor-infiltrating CD

Impaired activation of plasmacytoid dendritic cells via toll-like receptor 7/9 and STING is mediated by melanoma-derived immunosuppressive cytokines and metabolic drift

IntroductionPlasmacytoid dendritic cells (pDCs) infiltrate a large set of human cancers. Interferon alpha (IFN-α) produced by pDCs induces growth arrest and apoptosis in tumor cells and modulates innate and adaptive immune cells involved in anti-cancer immunity. Moreover, effector molecules exert tumor cell killing. However, the activation state and clinical relevance of pDCs infiltration in cancer is still largely controversial. In Primary Cutaneous Melanoma (PCM), pDCs density decreases over disease progression and collapses in metastatic melanoma (MM). Moreover, the residual circulating pDC compartment is defective in IFN-α production.MethodsThe activation of tumor-associated pDCs was evaluated by in silico and microscopic analysis. The expression of human myxovirus resistant protein 1 (MxA), as surrogate of IFN-α production, and proximity ligation assay (PLA) to test dsDNA-cGAS activation were performed on human melanoma biopsies. Moreover, IFN-α and CXCL10 production by in vitro stimulated (i.e. with R848, CpG-A, ADU-S100) pDCs exposed to melanoma cell lines supernatants (SN-mel) was tested by intracellular flow cytometry and ELISA. We also performed a bulk RNA-sequencing on SN-mel-exposed pDCs, resting or stimulated with R848. Glycolytic rate assay was performed on SN-mel-exposed pDCs using the Seahorse XFe24 Extracellular Flux Analyzer.ResultsBased on a set of microscopic, functional and in silico analyses, we demonstrated that the melanoma milieu directly impairs IFN-α and CXCL10 production by pDCs via TLR-7/9 and cGAS-STING signaling pathways. Melanoma-derived immunosuppressive cytokines and a metabolic drift represent relevant mechanisms enforcing pDC-mediated melanoma escape.DiscussionThese findings propose a new window of intervention for novel immunotherapy approaches to amplify the antitumor innate immune response in cutaneous melanoma (CM)