In-hospital electrical muscle stimulation for patients early after heart failure decompensation: results from a prospective randomised controlled pilot trial.

BACKGROUND Electrical muscle stimulation (EMS) is being evaluated as a possible alternative to exercise training to improve functional capacity in severely deconditioned patients with heart failure (HF). However, there is insufficient data on delayed effects of EMS starting early after decompensation. The aim of this study was to determine the impact of a short inpatient EMS intervention in severely deconditioned patients with HF on functional capacity and quality of life (QoL) over a follow-up period of 1 month. METHODS This is a prospective randomised sham-controlled pilot study. 45 patients hospitalised for decompensated systolic HF (58% men, mean age 66.4±10.2 years) were randomised to EMS (n=22) or sham stimulation (n=23) of lower limbs starting within 3 days after admission. The intervention included 7-10 sessions lasting from 30 to 90 min. The 6-minute walking test distance (6-MWTD), Duke Activity Status Index (DASI) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were evaluated at baseline, discharge and after 1 month. RESULTS All patients completed the programme with good EMS tolerance. 37 patients were included in the final analysis. At discharge, 6-MWTD improved from 206,1±61,3 to 299.5±91 m, DASI from 12.1±5.6 to 18.3±7.2 and MLHFQ from 55.6±8.5 to 34.2±9 with EMS compared with smaller improvements in the sham group (p<0.05 for all). One month after discharge, improvements in the EMS group remained significant for MLHFQ (p=0.004) and DASI (p=0.042) and statistically non-significant for 6-MWTD compared with the sham group. CONCLUSIONS Short-term in-hospital EMS leads to improvements in functional capacity and QoL in selected patients early after HF decompensation that are retained over 1 month after discharge and therefore may serve as initial intervention to improve physical capacity or as a bridge to further conventional exercise training. Larger studies are required to evaluate individual responses to an early initiation of EMS in decompensated HF as well as long-term effects

Enhancement of the expression of HCV core gene does not enhance core-specific immune response in DNA immunization: advantages of the heterologous DNA prime, protein boost immunization regimen

BACKGROUND: Hepatitis C core protein is an attractive target for HCV vaccine aimed to exterminate HCV infected cells. However, although highly immunogenic in natural infection, core appears to have low immunogenicity in experimental settings. We aimed to design an HCV vaccine prototype based on core, and devise immunization regimens that would lead to potent anti-core immune responses which circumvent the immunogenicity limitations earlier observed. METHODS: Plasmids encoding core with no translation initiation signal (pCMVcore); with Kozak sequence (pCMVcoreKozak); and with HCV IRES (pCMVcoreIRES) were designed and expressed in a variety of eukaryotic cells. Polyproteins corresponding to HCV 1b amino acids (aa) 1–98 and 1–173 were expressed in E. coli. C57BL/6 mice were immunized with four 25-μg doses of pCMVcoreKozak, or pCMV (I). BALB/c mice were immunized with 100 μg of either pCMVcore, or pCMVcoreKozak, or pCMVcoreIRES, or empty pCMV (II). Lastly, BALB/c mice were immunized with 20 μg of core aa 1–98 in prime and boost, or with 100 μg of pCMVcoreKozak in prime and 20 μg of core aa 1–98 in boost (III). Antibody response, [(3)H]-T-incorporation, and cytokine secretion by core/core peptide-stimulated splenocytes were assessed after each immunization. RESULTS: Plasmids differed in core-expression capacity: mouse fibroblasts transfected with pCMVcore, pCMVcoreIRES and pCMVcoreKozak expressed 0.22 ± 0.18, 0.83 ± 0.5, and 13 ± 5 ng core per cell, respectively. Single immunization with highly expressing pCMVcoreKozak induced specific IFN-γ and IL-2, and weak antibody response. Single immunization with plasmids directing low levels of core expression induced similar levels of cytokines, strong T-cell proliferation (pCMVcoreIRES), and antibodies in titer 10(3)(pCMVcore). Boosting with pCMVcoreKozak induced low antibody response, core-specific T-cell proliferation and IFN-γ secretion that subsided after the 3rd plasmid injection. The latter also led to a decrease in specific IL-2 secretion. The best was the heterologous pCMVcoreKozak prime/protein boost regimen that generated mixed Th1/Th2-cellular response with core-specific antibodies in titer ≥ 3 × 10(3). CONCLUSION: Thus, administration of highly expressed HCV core gene, as one large dose or repeated injections of smaller doses, may suppress core-specific immune response. Instead, the latter is induced by a heterologous DNA prime/protein boost regimen that circumvents the negative effects of intracellular core expression

A representation theorem for guilt aversion

Guilt aversion has been shown to play an important role in economic decision-making. In this paper, we take an axiomatic approach to guilt by deducing a utility representation from a list of easily interpretable assumptions on an agent's preferences. It turns out that our logarithmic representation can mitigate the problem of multiplicity of equilibria to which psychological games are prone. We apply the model in three well-known games and show that its predictions are consistent with experimental observations

Busulfan/Fludarabine- or Treosulfan/Fludarabine-Based Conditioning Regimen for Patients with Wiskott-Aldrich Syndrome – an EBMT Inborn Errors Working Party and Scetide Study

Introduction Excellent survival rates have been reported after allogeneic haematopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome (WAS) patients. Recipient age >5 years in MUD HSCT as well as MMFD as donor were negative predictors for outcome. However, the vast majority of HSCTs in previously published studies were performed with (oral) busulfan/cyclophosphamide-based conditioning and in the early 2000 years or before. Objectives To compare OS and EFS after HSCT with either busulfan/fludarabine (BuFlu) ± thiotepa (TT) or treosulfan/fludarabine (TreoFlu) ± TT as recommended for primary immunodeficiencies since 2005 by the inborn errors working party (IEWP) of EBMT and ESID. Methods We performed a retrospective analysis via the EBMT and SCETIDE registries of WAS patients transplanted between 20006 and 2016 with these two regimens. At the time of this interim analysis, 174 patients were included, 92 (53%) with BuFlu±TT and 82 (47%) with TreoFlu±TT conditioning, with a median age of 1.6 years (0.2-30) at HSCT and a median follow-up of 32.9 months (1.5-128.9). Donors were MSD in 30, other MRD in 5, MUD (9/10 or 10/10) in 105, MMUD ( Results Two year overall survival (OS) of the entire cohort was 88.6% (95% c.i. 83.5%-93.6%). There was no significant difference in OS between BuFlu±TT or TreoFlu±TT conditioning (2-year OS 88.1% vs. 89.5%; p=0.7). Patients aged >5 years had a worse OS as compared to those 5 years or younger at HSCT (74.9% vs. 90.8%; p=0.005). The type of donor had no influence on OS: 96.4% for MSD/MFD, 86.8% for MUD/MMUD and 87.7% for MMFD (p=0.4). The rate of complete (≥90%) donor chimerism at last follow-up or before a secondary procedure (if a patient had one) was 41/42 (98%) in the BuFlu±TT group and 21/35 (60%) in the TreoFlu±TT group (p=0.0001). Twenty-six patients required a second procedure: stem cell boost in 4, donor lymphocyte infusion in 9, 2nd HSCT in 15 and splenectomy in 1. The 2-year cumulative incidence (CI) of second procedures was higher at 33.9% in the TreoFlu±TT versus 12.8% in the BuFlu±TT group (p=0.017), and 2-year EFS (events: second procedure or death) was 61.4% in the TreoFlu±TT and 75.0% in the BuFlu±TT group (p=0.2). Grade II-IV acute GVHD had the same incidence in both groups (24.4% vs. 26.3%; p=0.849) and chronic GVHD of any grade was borderline more frequent in the TreoFlu±TT group (17.2% vs 6.7%; p=0.054). Conclusion HSCT with either BuFlu±TT or TreoFlu±TT conditioning reliably cures almost 90% of patients with WAS regardless of donor type. Age >5 years at HSCT remains a negative risk factor. More patients were mixed chimeras and required second procedures after TreoFlu±TT than after BuFlu±TT conditioning. These data confirm the feasibility and efficacy of the regimens currently recommended by the IEWP

Three Essays in Game Theory

This thesis applies game theoretic methods to problems of individual choice and business strategy. It consists of three self-contained chapters. Chapters 2 and 3 explore strategic interaction between agents who are concerned about the social consequences of their actions, while Chapter 4 considers information use by firms who can spy on their competitors. By investigating these diverse topics, the thesis shows how Game Theory can be used to explain and predict outcomes in a variety of real-life scenarios of economic interest. Chapter 2 explores the effect of “other-regarding” preferences on the outcomes of repeated social interactions, modelled as a Prisoner’s Dilemma game. The models of inequality aversion and guilt aversion are identified as compatible with the existing laboratory evidence on the game, and a novel experiment is run to test them against each other. The experiment provided support for the inequality aversion model, which shows that fairness is an important consideration in repeated social interaction. Chapter 3 develops a formal theory of moral choice by proving a representation theorem for guilt-averse preferences. In the chapter, an axiomatic approach is used to deduce a utility function which explains how people trade off material and moral incentives. A novel logarithmic utility is proposed, which is grounded in realistic psychological assumptions and accounts well for the existing body of laboratory evidence. Chapter 4 investigates the welfare consequences of industrial espionage by modelling it as an information acquisition game played by duopolists. In the model, firms can acquire information about unobservable demand either by conducting market research, or by spying on their competitors. The chapter shows how the two information sources affect price and quantity decisions taken by firms. It also shows that aggregate profit and social welfare grow with the precision of the intelligence technology in most environments

A difficulty in characterising mixed Nash equilibria in a strategic market game

We analyse the conditions for a strategy profile to be an equilibrium in a specific buy and sell strategic market game, with two goods, using best responses of a player against random bids from the opponents. The difficulty in characterising mixed Nash equilbria is that the expected utility is not quasiconcave in strategies. We still prove that any mixed strategy Nash equilibrium profile in which every player faces only two random bids is trivial, that is, is a convex combination of some pure strategy Nash equilibria; moreover, we show that the outcome (the price and the allocations) is deterministic in such an equilibrium

Problems of learning Russian as a foreign language in a distance format at the pre-university stage

In the 2020/2021 academic year, due to objective circumstances caused by the COVID-19 pandemic, Russian universities were forced to organize the admission of foreign citizens to preparatory departments exclusively in a distance format. This academic year turned out to be experimental and opened up many opportunities for both students and teachers. At the same time, taking into account the accumulated training experience, it can be concluded that when using an exclusively distance learning format, both advantages and significant disadvantages were identified, which, in turn, became a prerequisite for conducting the study. The purpose of this article is to identify and analyze in detail the main disadvantages of teaching types of speech activities in the online format and using remote learning platforms. The authors, as practicing teachers of Russian as a foreign language, directly faced all the problems considered in the article, and they observed the same difficulties among their colleagues. In this regard, the main methods for carrying out the work were methods characteristic of empirical research, first of all, observation, classification of results and generalization. The novelty of the research lies in the fact that for the first time an attempt was made to analyze the problems related to different areas of the organization and functioning of educational activities that arise in the distance learning process at the pre-university stage. This determines both theoretical and practical significance of the work carried out. As a result, the authors managed to summarize and systematize the disparate difficulties, which in the future may become the basis for finding systemic solutions to the identified problems

Environmental Surveillance for Poliovirus and Other Enteroviruses: Long-Term Experience in Moscow, Russian Federation, 2004–2017

Polio and enterovirus surveillance may include a number of approaches, including incidence-based observation, a sentinel physician system, environmental monitoring and acute flaccid paralysis (AFP) surveillance. The relative value of these methods is widely debated. Here we summarized the results of 14 years of environmental surveillance at four sewage treatment plants of various capacities in Moscow, Russia. A total of 5450 samples were screened, yielding 1089 (20.0%) positive samples. There were 1168 viruses isolated including types 1&#8722;3 polioviruses (43%) and 29 different types of non-polio enteroviruses (51%). Despite using the same methodology, a significant variation in detection rates was observed between the treatment plants and within the same facility over time. The number of poliovirus isolates obtained from sewage was roughly 60 times higher than from AFP surveillance over the same time frame. All except one poliovirus isolate were Sabin-like polioviruses. The one isolate was vaccine-derived poliovirus type 2 with 17.6% difference from the corresponding Sabin strain, suggesting long-term circulation outside the scope of the surveillance. For some non-polio enterovirus types (e.g., Echovirus 6) there was a good correlation between detection in sewage and incidence of clinical cases in a given year, while other types (e.g., Echovirus 30) could cause large outbreaks and be almost absent in sewage samples. Therefore, sewage monitoring can be an important part of enterovirus surveillance, but cannot substitute other approaches