Detecting and Predicting Forecast Breakdowns

We propose a theoretical framework for assessing whether a forecast model estimated over one period can provide good forecasts over a subsequent period. We formalize this idea by defining a forecast breakdown as a situation in which the out-of-sample performance of the model, judged by some loss function, is significantly worse than its in-sample performance. Our framework, which is valid under general conditions, can be used not only to detect past forecast breakdowns but also to predict future ones. We show that main causes of forecast breakdowns are instabilities in the data generating process and relate the properties of our forecast breakdown test to those of existing structural break tests. The main differences are that our test is robust to the presence of unstable regressors and that it has greater power than previous tests to capture systematic forecast errors caused by recurring breaks that are ignored by the forecast model. As a by-product, we show that our results can be applied to forecast rationality tests and provide the appropriate asymptotic variance estimator that corrects the size distortions of previous forecast rationality tests. The empirical application finds evidence of a forecast breakdown in the Phillipsí curve forecasts of U.S. inflation, and links it to inflation volatility and to changes in the monetary policy reaction function of the Fed.

Forecast Comparisons in Unstable Environments

We propose new methods for comparing the relative out-of-sample forecasting performance of two competing models in the presence of possible instabilities. The main idea is to develop a measure of the relative ìlocal forecasting performanceî for the two models, and to investigate its stability over time by means of statistical tests. We propose two tests (the ìFluctuation testî and the test against a ìOne-time Reversalî) that analyze the evolution of the modelsí relative performance over historical samples. In contrast to previous approaches to forecast comparison, which are based on measures of ìglobal performanceî, we focus on the entire time path of the modelsí relative performance, which may contain useful information that is lost when looking for the model that forecasts best on average. We apply our tests to the analysis of the time variation in the out-of-sample forecasting performance of monetary models of exchange rate determination relative to the random walk.Predictive Ability Testing, Instability, Structural Change, Forecast Evaluation

Model Comparisons in Unstable Environments

The goal of this paper is to develop formal techniques for analyzing the relative in-sample performance of two competing, misspeci?ed models in the presence of possible data instability. The central idea of our methodology is to propose a measure of the models? local relative performance: the "local Kullback-Leibler Information Criterion" (KLIC), which measures the relative distance of the two models? (misspeci?ed) likelihoods from the true likelihood at a particular point in time. We discuss estimation and inference about the local relative KLIC; in particular, we propose statistical tests to investigate its stability over time. Compared to previous approaches to model selection, which are based on measures of "global performance", our focus is on the entire time path of the models? relative performance, which may contain useful information that is lost when looking for a globally best model. The empirical application provides insights into the time variation in the performance of a representative DSGE model of the European economy relative to that of VARs. implement IRFMEs.Model Selection Tests, Misspeci?cation, Structural Change, Kullback-Leibler Information Criterion

Shaping Copper Nanocatalysts to Steer Selectivity in the Electrochemical CO2 Reduction Reaction

The carbon-neutral production of fuels and chemical feedstocks is one of the grand challenges for our society to solve. The electrochemical conversion of CO2 is emerging as a promising technology contributing to this goal. Despite the huge amount of progress made over the past decade, selectivity still remains a challenge. This Account presents an overview of recent progress in the design of selective catalysts by exploiting the structural sensitivity of the electrochemical CO2 reduction reaction (CO2RR). In particular, it shows that the accurate and precise control of the shape and size of Cu nanocatalysts is instrumental in understanding and in discovering the structure-selectivity relationships governing the reduction of CO2 to valuable hydrocarbons, such as methane and ethylene. It further illustrates the use of faceted Cu nanocatalysts to interrogate catalytic pathways and to increase selectivity toward oxygenates, such as ethanol, in the framework of tandem schemes. The last part of the Account highlights the role of well-defined nanocatalysts in identifying reconstruction mechanisms which might occur during operation. An outlook for the emerging paradigms which will empower the design of novel catalysts for CO2RR concludes the Account

Extra-telomeric functions of telomerase in the pathogenesis of Epstein-Barr virus-driven B-cell malignancies and potential therapeutic implications

Abstract The Epstein-Barr virus (EBV) is a ubiquitous human \u3b3-herpesvirus causally linked to a broad spectrum of both lymphoid and epithelial malignancies. In order to maintain its persistence in host cells and promote tumorigenesis, EBV must restrict its lytic cycle, which would ultimately lead to cell death, selectively express latent viral proteins, and establish an unlimited proliferative potential. The latter step depends on the maintenance of telomere length provided by telomerase. The viral oncoprotein LMP-1 activates TERT, the catalytic component of telomerase. In addition to its canonical role in stabilizing telomeres, TERT may promote EBV-driven tumorigenesis through extra-telomeric functions. TERT contributes toward preserving EBV latency; in fact, through the NOTCH2/BATF pathway, TERT negatively affects the expression of BZLF1, the master regulator of the EBV lytic cycle. In contrast, TERT inhibition triggers a complete EBV lytic cycle, leading to the death of EBV-infected cells. Interestingly, short-term TERT inhibition causes cell cycle arrest and apoptosis, partly by inducing telomere-independent activation of the ATM/ATR/TP53 pathway. Importantly, TERT inhibition also sensitizes EBV-positive tumor cells to antiviral therapy and enhances the pro-apoptotic effects of chemotherapeutic agents. We provide here an overview on how the extra-telomeric functions of TERT contribute to EBV-driven tumorigenesis. We also discuss the potential therapeutic approach of TERT inhibition in EBV-driven malignancies

Host factors and early treatments to restrict paediatric HIV infection and early disease progression

open6noA body of evidence indicates that a threshold level of the virus is required to establish systemic and persistent HIV infection in the host and that this level depends on virus-host interactions. Mother-to-child transmission (MTCT) of HIV is the main source of paediatric HIV infection and occurs when the host's immune system is still developing. Thus, innate resistance and immunity, rather than adaptive immune response, may be the main drivers in restricting the establishment of HIV reservoirs and the long-lived persistence of HIV infection in infants. Genetic variations in HIV co-receptors and their ligands, as well as in Toll-like receptors and defensins, key elements of innate immunity, have been demonstrated to influence the risk of perinatal HIV infection and disease progression in HIV-infected infants. Early treatments with combined antiretroviral therapy (cART) restrict paediatric infection by reducing the level of the transmitted/infecting virus to below the threshold required for the onset of immune response to the virus and also significantly reduce HIV reservoirs. However, despite long periods with no signs and symptoms of HIV infection, all early cART-treated children who later discontinued cART had a rebound of HIV, except for one case in whom a period of viral remission occurred. Which parameters predict viral remission or viral rebound after cART discontinuation? Could early cART prevent rather than just reduce the establishment of viral reservoirs? And, if so, how? Answers to these questions are also important in order to optimise the use of early cART in infants at high risk of HIV infection.openGianesin, Ketty; Petrara, Raffaella; Freguja, Riccardo; Zanchetta, Marisa; Giaquinto, Carlo; DE ROSSI, AnitaGianesin, Ketty; Petrara, Raffaella; Freguja, Riccardo; Zanchetta, Marisa; Giaquinto, Carlo; DE ROSSI, Anit

Accelerated aging in perinatally HIV-infected children: clinical manifestations and pathogenetic mechanisms

BACKGROUND: Premature aging and related diseases have been documented in HIV-infected adults. Data are now emerging also regarding accelerated aging process in HIV-infected children. METHODS: A narrative review was performed searching studies on PubMed published in English language in 2004-2017, using appropriate key words, including "aging", "children", "HIV", "AIDS", "immunosenescence", "pathogenesis", "clinical conditions". RESULTS: Premature immunosenescence phenotype of B and T cells in HIV-infected children is mediated through immune system activation and chronic inflammation. Ongoing inflammation processes have been documented by increased levels of pathogen-associated molecular patterns (PAMPS), increased mitochondrial damage, higher levels of pro-inflammatory cytokines, and a positive correlation between sCD14 levels and percentages of activated CD8+ cells. Other reported features of premature aging include cellular replicative senescence, linked to an accelerated telomeres shortening. Finally, acceleration of age-associated methylation pattern and other epigenetic modifications have been described in HIV-infected children. All these features may favor the clinical manifestations related to premature aging. Lipid and bone metabolism, cancers, cardiovascular, renal, and neurological systems should be carefully monitored, particularly in children with detectable viremia and/or with CD4/CD8 ratio inversion. CONCLUSION: Aging processes in children with HIV infection impact their quality and length of life. Further studies regarding the mechanisms involved in premature aging are needed to search for potential targets of treatment

Influence of dietary conjugated linoleic acid (CLA) and L-Lysine on heavy pigs performances and meat quality

Conjugated linoleic acid (CLA) refers to a group of positional and geometric fatty acid isomers derived from linoleic acid. Dietary CLA supplementation has been shown to increase feed efficiency and may reduce body fat content in swine as recently reviewed by Corino et al., (2005). There was only one research conducted in heavy pig in which the authors did not observed any significant effect of dietary CLA on growth performances and lean tissue (Corino et al., 2003)

Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon

Background and aims Increased levels of chemokine interferon-gamma (IFN-γ)-inducible protein-10 (CXCL10), soluble CD163 (sCD163) and soluble CD14 (sCD14) have been reported in HCV infection. The aim of this study was to compare, sCD163 and sCD14 levels in HCV-infected patients undergoing direct acting antiviral (DAA)-containing regimens with or without interferon (IFN). Methods sCD163, sCD14 and CXCL10 were longitudinally measured by ELISA in 159 plasma samples from 25 HCV-infected patients undergoing IFN-based treatment plus telaprevir or boceprevir and 28 HCV infected subjects treated with DAA IFN-free regimens. Twenty-five healthy donors (HD) were included as controls. Results At baseline CXCL10, sCD163 and sCD14 levels were higher in HCV-infected patients than in HD. CXCL10 and sCD163 levels were significantly decreased in responder (R) patients who achieved sustained virological response (SVR), with both IFN-based and IFN-free regimens, while they were persistently elevated in non-responders (NR) patients who stopped IFN-based treatments because of failure or adverse events. Conversely, sCD14 levels were apparently unchanged during therapy, but at the end of treatment the levels reached normal ranges. Comparing the two regimens, the extent of CXCL10 reduction was more pronounced in patients undergoing DAA IFN-free therapies, whereas sCD163 and sCD14 reduction was similar in the two groups. Interestingly, only in IFN-based regimens baseline sCD163 levels were significantly higher in NR than in R patients, while in the IFN-free treatment group also patients with highsCD163 plasma levels obtained SVR. At the end of therapy, even if the biomarkers were largely decreased, their levels remained significantly higher compared to HD. Only in the early fibrosis stages, sCD163 values tended to normalize. Conclusions These results indicate that IFN-free regimens including newer DAA induce an early and marked decrease in circulating inflammatory biomarkers. However, the full normalization of biomarkers was not obtained, especially in patients with advanced fibrosis, thus underlying the need for a treatment in the early stages of HCV infection

Biohydrogen production from food waste: Influence of the inoculum-to-substrate ratio

In this study, the influence of the inoculum-to-substrate ratio (ISR) on dark fermentative hydrogen production from food waste (FW) was evaluated. ISR values ranging from 0.05 to 0.25 g VSinoculum/g VSsubstrate were investigated by performing batch tests at T = 39 °C and pH = 6.5, the latter being the optimal value identified based on a previous study. The ISR was found to affect the fermentation process, clearly showing that an adequate ISR is essential in order to optimise the process kinetics and the H2 yield. An ISR of 0.14 proved to optimum, leading to a maximum H2 yield of 88.8 L H2/kg VSFW and a maximum production rate of 10.8 L H2/kg VSFW∙h. The analysis of the fermentation products indicated that the observed highest H2 production mostly derived from the typical acetate/butyrate-type fermentation