Pharmacoeconomic Analysis of Treatment Regimens for Coronavirus Infection Coronavirus Disease-19

BACKGROUND: In March 2020, the coronavirus disease (COVID-19) infection was assigned the status of a pandemic. As of the beginning of 2021, the Russian Federation ranks fourth in terms of the prevalence of coronavirus infection. Over the period from March 2020 to February 2021, more than 84,000 fatal cases of the disease were recorded in Russia. AIM: However, at the moment, there are no medications with proven effectiveness and safety against the novel coronavirus infection. In this regard, the purpose of our study was to conduct a pharmacoeconomic analysis of medications for etiotropic therapy of all forms of COVID-19 recommended by the Ministry of Health of the Russian Federation (clinical guidelines, version 10 dated February 8, 2021) to identify the best treatment option. MATERIALS AND METHODS: In the course of the study, the “cost of illness” was determined for all forms of the disease in an outpatient and inpatient setting. The authors took into account the direct medical costs of medication therapy and diagnostic and treatment procedures. In terms of direct non-medical costs, they calculated the cost of a bed-day excluding medication treatment, and indirect costs included payments for temporary disability sheets. Costs for medications were calculated based on the active ingredient (AI) and the packages for treatment on an outpatient basis and in the case of the hospital setting based on the AI only. The cost of medical and diagnostic procedures was determined based on the Tariff Agreement for 2020 dated December 30, 2019. Next, a cost-effectiveness analysis was performed. Effectiveness criteria were selected based on published clinical trial results for the medications in question. Then, they performed a calculation of the cost-effectiveness coefficients and an incremental analysis. RESULTS: Thus, in the course of the analysis of the cost of illness, the most economically profitable treatment regimens were the ones with hydroxychloroquine both for outpatient treatment (13,150.31 rubles: Mild form, 22,326.44 rubles: Moderate form excluding antibiotic therapy, and 21,513.76 rubles: Moderate form, taking into account antibacterial therapy) and for inpatient treatment (34,441.53 rubles). CONCLUSION: As a result of the cost-effectiveness analysis, the use of favipiravir can be considered optimal (comparative effectiveness research = 17,607.14 rubles), and for the mild form, the optimal medication is umifenovir, since during the incremental analysis, it was found that for therapy with favipiravir, 100 people would need an additional allocation of 96.291 rubles, which, given the form of the disease, is not entirely appropriate.

Improving the Four-Dimensional Incremental Analysis Update (4DIAU) with the HWRF 4DEnVar Data Assimilation System for Rapidly Evolving Hurricane Prediction

Short-term spin-up for strong storms is a known difficulty for the operational Hurricane Weather Research and Forecasting (HWRF) model after assimilating high-resolution inner-core observations. Our previous study associated this short-term intensity prediction issue with the incompatibility between the HWRF model and the data assimilation (DA) analysis. While improving physics and resolution of the model was found helpful, this study focuses on further improving the intensity predictions through the four-dimensional incremental analysis update (4DIAU).In the traditional 4DIAU, increments are pre-determined by subtracting background forecasts from analyses. Such pre-determined increments implicitly require linear evolution assumption during the update, which are hardly valid for rapid-evolving hurricanes. To confirm the hypothesis, a corresponding 4D analysis nudging (4DAN) method which uses online increments is first compared with the 4DIAU in an oscillation model. Then, variants of 4DIAU are proposed to improve its application for nonlinear systems. Next, 4DIAU, 4DAN and their proposed improvements are implemented into the HWRF 4DEnVar DA system and are investigated with hurricane Patricia (2015).Results from both oscillation model and HWRF model show that: 1. the pre-determined increments in 4DIAU can be detrimental when there are discrepancies between the updated and background forecasts during a nonlinear evolution. 2. 4DAN can improve the performance of incremental update upon 4DIAU, but its improvements are limited by the over-filtering. 3. Relocating initial background before the incremental update can improve the corresponding traditional methods. 4. the feature-relative 4DIAU method improves the incremental update the most and produces the best track and intensity predictions for Patricia among all experiments.

Something Old, Something New, Something Borrowed, Something Taboo: Interaction and Creativity in Humour

In this paper we treat humorous situations as a series of events underpinned by topoi, principles of reasoning recognised within a socio-cultural community. We claim that humorous effect in jokes and other discourse is often created by the juxtaposition of topoi evoked. A prerequisite for this is that there is a shift where the interpreter of the discourse updates their information state with regard to a second topos being evoked. This view of humour is consistent with an incremental analysis of dialogue, and we therefore argue that interaction is central both for humour creation and interpretation. We point out some different ways in which topoi are juxtaposed in humorous dialogues as well as in jokes published in social media or in joke books, and take jokes from the coronavirus pandemic as an example because this makes lots of new topoi available and therefore offers the opportunity of creating novel jokes based on the juxtaposition of the new and existing topoi. We explore how the mechanisms of inference in dialogue can be applied to humour through the four elements from our title: old (existing), new (not previously existing), borrowed (associated with a different situation) and taboo (inappropriate in the context).

Expletive Negation

This chapter provides the state-of-the-art around expletive negation (EN), by discussing: (i) the relationship between EN and negative concord; (ii) EN as a real negation; (iii) EN as a special formative linked to an additional evaluative/expressive layer in the semantics of language. Moreover, the chapter offers a potentially unifying analysis of EN in comparative, exclamative, and temporal clauses: EN as an operator of implicature denial. This approach derives the fact that EN is logically and compositionally independent from what is said from the fact that EN shifts the semantics of negation to the layer of implicated meaning. Some of the interpretive effects normally linked to the expressive/evaluative analysis of EN can be arguably derived as side-effects of this semantic analysis. The proposal advanced here has a number of implications regarding the relationship among morpho-syntax, pragmatic enrichment, and the non-incremental analysis of negation in theories of negation processing.

Validation of Annulus Formation in Golden Shiner Otoliths

Golden Shiner Notemigonus crysoleucas is found in many lakes and ponds across the southeastern United States. Though it is a common species, otolith age validation methods have not been published. The objective of this study was to confirm annulus formation in lapillar otoliths of Golden Shiners collected monthly from September 2015 through August 2016 in Lake Jackson, Florida (Leon County). We collected at least 12 individuals each month of similar length (168–249 mm; presumably of the same cohort) to document annulus formation throughout the year. We sacrificed a total of 177 individuals from the 2013 year class, and we used their lapillar otoliths for marginal incremental analysis to calculate an index of completion and validate annulus formation. The monthly index of completion was highest from January through March and lowest in May and June, indicating that annuli were deposited once per year and confirming that lapillar otoliths are a valid age estimation structure for Golden Shiners.