Refining reproduction number estimates to account for unobserved generations of infection in emerging epidemics

Background: Estimating the transmissibility of infectious diseases is key to inform situational awareness and for response planning. Several methods tend to overestimate the basic (R0) and effective (Rt) reproduction numbers during the initial phases of an epidemic. The reasons driving the observed bias are unknown. In this work we explore the impact of incomplete observations and underreporting of the first generations of infections during the initial epidemic phase. Methods: We propose a debiasing procedure which utilises a linear exponential growth model to infer unobserved initial generations of infections and apply it to EpiEstim. We assess the performance of our adjustment using simulated data, considering different levels of transmissibility and reporting rates. We also apply the proposed correction to SARS-CoV-2 incidence data reported in Italy, Sweden, the United Kingdom and the United States of America. Results: In all simulation scenarios, our adjustment outperforms the original EpiEstim method. The proposed correction reduces the systematic bias and the quantification of uncertainty is more precise, as better coverage of the true R0 values is achieved with tighter credible intervals. When applied to real world data, the proposed adjustment produces basic reproduction number estimates which closely match the estimates obtained in other studies while making use of a minimal amount of data. Conclusions: The proposed adjustment refines the reproduction number estimates obtained with the current EpiEstim implementation by producing improved, more precise estimates earlier than with the original method. This has relevant public health implications

HIV-Reverse Transcriptase Inhibition: Inclusion of Ligand-Induced Fit by Cross-Docking Studies

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) have, in addition to the nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), a definitive role in the treatment of HIV-1 infections. Since the appearance of HEPT and TIBO, more than 30 structurally different classes of compounds have been reported as NNRTIs, which are specific inhibitors of HIV-1 replication, targeting the HIV-1 reverse transcriptase (RT). Nevirapine and delavirdine are the first formally licensed for clinical use, and others have been licensed afterward, while several are in preclinical or clinical development. The NNRTIs interact with a specific site of HIV-1 RT (nonnucleoside binding site, NNBS) that is close to, but distinct from, the NRTI binding site. In this work we report the application of the Autodock program assessing its usability through reproduction of 41 NNRTI experimental bound conformations. Moreover, cross-docking experiments on the wild-type and mutated RT forms were conducted to take into account the enzyme flexibility as a valuable tool for structure-based drug design (SBDD) studies and to gain insight on the mode of action of new anti-HIV agents active against both wild-type and resistant strains

Evaluation of Major Minerals and Trace Elements in Wild and Domesticated Edible Herbs Traditionally Used in the Mediterranean Area

The human diet is characterized by the intake of major minerals (Na, K, Ca, Mg, P, N) and trace elements (Zn, Mn, Se, Cu, Fe, Co, I, Cr, F, Pb, Cd) for their key role in many metabolic functions. Nowadays, the research of sources able to improve their intake is in continuous evolution, especially in the undeveloped countries. In this sense, wild edible herbs, commonly used since ancient times, can represent a good alternative to improve the daily human intake of minerals. In this study, four wild edible species, Rumex acetosa, Picris hieracioides, Cichorium intybus, and Plantago coronopus, were analyzed for their content in Na, K, Ca, Mg, Cu, Mn, Fe, and Zn and, besides, three domestications (named “soilless,” pot, and open field) were evaluated in the analyzed species in the prospective of their commercialization as valuable sources of minerals in the human diet. Nitrate and oxalate contents were also evaluated, given their negative impact on human health. Results unveil that open field domestication allowed the plants to maintain the content of major minerals similar to those measured in wild plants, especially in C. intybus and P. hieracioides. The trace elements Cu, Mn, Fe, and Zn were not recorded at high content irrespectively to the wild collection or domestications. Finally, plants grown in the open field also accounted for a high oxalate and nitrate content, especially in R. acetosa. Further researches should be aimed at decreasing the oxalate and nitrate content in the domesticated species and to promote the commercialization of the domesticated species

Fluorescence spectroscopy of normal and follicular cancer samples from human thyroid

An autofluorescence analysis has been performed on healthy as well as tumour thyroid tissue samples to distinguish follicular cancer from normal thyroid. Complete spectra and synchronous spectra have been recordered from properly stored samples. Fluorescence bands located at 350 nm and 400 nm has been observed in the analysed cancer samples

Protective role of dehydroascorbate in rat liver ischemia-reperfusion injury

BACKGROUND: Oxidative stress plays an important role in liver ischemia/reperfusion (I/R) injury. Thus, enhancing the liver antioxidant capacity could be a promising therapeutic strategy. Ascorbate (AA) is considered the perfect antioxidant, but its therapeutic efficacy is greatly limited by its slow achievement of high intracellular levels. This might be circumvented by administering dehydroascorbate (DHA), which presents a several-fold greater uptake than AA, and undergoes rapid intracellular reduction to AA. Thus, our aim was to assess the protective role of DHA in liver I/R injury. MATERIALS AND METHODS: Wistar rats (200-300 g bw) were pretreated iv with different doses of AA or DHA 20 min before liver ischemia, followed by 6 h reperfusion. Liver damage was assessed by biochemical and morphological indices. RESULTS: DHA pretreatment induced a rapid increase in liver ascorbate levels, significantly higher than findings for AA, without any significant reduction in glutathione levels. Liver damage during I/R in controls showed significant increases in serum transaminases and hepatic thiobarbituric acid reactive substances with alterations of liver morphology. DHA administration induced a clear, significant protection against I/R injury, whereas liver damage was only moderately prevented by AA. CONCLUSIONS: DHA might represent a simple, effective therapeutic option to prevent liver damage associated with ischemia/reperfusion

Operations and maintenance for multipurpose offshore platforms using statistical weather window analysis

With increasing offshore-related commerce, the choice of appropriate operations and maintenance activities must take into consideration safety, costs and performance targets. Stochastic weather conditions at each site of interest presents uncertain situations. We present an optimized decision making procedure that seeks to maximize monetary benefits while minimizing safety risks. Our proposed approach outlines and illustrates application of such a policy by incorporating traditional weather window analysis using a Markov Decision Process approach. In particular, the approach is applied in case study involving the operation of a multipurpose platform at an offshore Scotland site

Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study

Direct-acting antiviral agents (DAAs) are extremely effective in eradicating hepatitis C virus (HCV) in chronically infected patients. However, the protective role of the sustained virologic response (SVR) achieved by second- and third-generation DAAs against the onset of hepatocellular carcinoma (HCC) and mortality is less well established