Project description:Influenza is still a frequent seasonal infection of the upper respiratory tract, which may have deadly consequences, especially for the elderly. This is in spite of the availability of vaccines suggested for persons above 65 years of age. Two types of conventional influenza vaccines are currently licensed for use-live attenuated and inactivated vaccines. Depending on local regulatory requirements, live attenuated vaccines are produced by the reverse genetics technique or by classical reassortment in embryonated chicken eggs. Sometimes, the efficiency of classical reassortment is complicated by certain properties of the wild-type parent virus. Cases of low efficacy of vaccines have been noted, which, among other reasons, may be associated with suboptimal properties of the wild-type parent virus that are not considered when recommendations for influenza vaccine composition are made. Unfortunately, knowledge surrounding the roles of properties of the circulating influenza virus and its impact on the efficacy of the reassortment process, vaccination efficiency, the infectivity of the vaccine candidates, etc., is now scattered in different publications. This review summarizes the main features of the influenza virus that may dramatically affect different aspects of the preparation of egg-derived live attenuated vaccine candidates and their effectiveness. The author expresses her personal view, which may not coincide with the opinion of other experts in the field of influenza vaccines.
Project description:Vanishing white matter (VWM) is a leukodystrophy caused by recessive variants in the genes EIF2B1-EIF2B5. It is characterized by chronic neurologic deterioration with superimposed stress-provoked episodes of rapid decline. Disease onset spans from the antenatal period through senescence. Age at onset predicts disease evolution for patients with early onset, whereas disease evolution is unpredictable for later onset; patients with infantile and early childhood onset consistently have severe disease with rapid neurologic decline and often early death, whereas patients with later onset have highly variable disease. VWM is rare, but likely underdiagnosed, particularly in adults. Apart from measures to prevent stressors that could provoke acute deteriorations, only symptomatic care is currently offered. With increased insight into VWM disease mechanisms, opportunities for treatment have emerged. EIF2B1-EIF2B5 encode the 5-subunit eukaryotic initiation factor 2B complex, which is essential for translation of mRNAs into proteins and is a principal regulator of the integrated stress response (ISR). ISR deregulation is central to VWM pathology. Targeting components of the ISR has proven beneficial in mutant VWM mouse models, and several drugs are now in clinical development. However, clinical trials in VWM pose considerable challenges: low numbers of known patients with VWM, unpredictable disease course for patients with onset after early childhood, absence of intermediate biomarkers, and novel first-in-human molecular targets. Given these challenges and considering the critical need to offer therapies, we have formulated recommendations for enhanced diagnosis, drug trial setup, and patient selection, based on our expert evaluation of molecular, laboratory, and clinical data.
Project description:Through what mechanism do interest groups shape public opinion on concrete policies? In this article, three hypotheses are proposed that distinguish between the effect of the arguments conveyed by interest groups and the effect of interest groups as source cues. Two survey experiments on the proposed Transatlantic Trade and Investment Partnership (TIPP) and the 2015 Paris Agreement on climate change allow the testing of these hypotheses. The resulting evidence from several countries shows that, with respect to interest groups' attempts at shaping public opinion, arguments matter more than their sources. This is so even when accounting for people's trust in the interest groups that serve as source cues and for people's level of information about a policy. The finding that interest groups affect public opinion via arguments rather than as source cues has implications for the literature on elite influence on public opinion and the normative evaluation of interest group activities.
Project description:An empirically founded and widely established driving force in opinion dynamics is homophily i.e. the tendency of "birds of a feather" to "flock together". The closer our opinions are the more likely it is that we will interact and converge. Models using these assumptions are called bounded confidence models (BCM) as they assume a tolerance threshold after which interaction is unlikely. They are known to produce one or more clusters, depending on the size of the bound, with more than one cluster being possible only in the deterministic case. Introducing noise, as is likely to happen in a stochastic world, causes BCM to produce consensus which leaves us with the open problem of explaining the emergence and sustainance of opinion clusters and polarisation. We investigate the role of heterogeneous priors in opinion formation, introduce the concept of opinion copulas, argue that it is well supported by findings in Social Psychology and use it to show that the stochastic BCM does indeed produce opinion clustering without the need for extra assumptions.
Project description:The presence of bilateral pulmonary nodules in lung cancer usually means distant metastases (M1a). We present an extraordinary example that challenges to look beyond this classification, and illustrates the potential benefits of a multidisciplinary re-evaluation in such a case.
Project description:We propose two analytical relationships between affinity and opinion change. The first one focuses on value homophily, while the second one incorporates affinity in opinion dynamics. Three analytical test models are derived based on these relationships: the value homophily model, the temporal evolution of opinion summation, and the evolution of opinion difference between two individuals. We test these models using data from a previous experiment, and the results demonstrate their validity.
Project description:Research into cyber-conflict, public opinion, and international security is burgeoning, yet the field suffers from an absence of conceptual agreement about key terms. For instance, every time a cyberattack takes place, a public debate erupts as to whether it constitutes cyberterrorism. This debate bears significant consequences, seeing as the ascription of a "terrorism" label enables the application of heavy-handed counterterrorism powers and heightens the level of perceived threat among the public. In light of widespread conceptual disagreement in cyberspace, we assert that public opinion plays a heightened role in understanding the nature of cyber threats. We construct a typological framework to illuminate the attributes that drive the public classification of an attack as cyberterrorism, which we test through a ratings-based conjoint experiment in the United States, the United Kingdom, and Israel (N = 21,238 observations). We find that the public (1) refrains from labeling attacks by unknown actors or hacker collectives as cyberterrorism; and (2) classifies attacks that disseminate sensitive data as terrorism to a greater extent even than physically explosive attacks. Importantly, the uniform public perspectives across the three countries challenge a foundational tenet of public opinion and international relations scholarship that divided views among elites on foreign policy matters will be reflected by a divided public. This study concludes by providing a definitive conceptual baseline to support future research on the topic.
Project description:In many Western societies there are rising concerns about increasing polarization in public debate. However, statistics on private attitudes paint a different picture: the average attitudes in societies are more moderate and remain rather stable over time. The present paper presents an agent-based model of how such discrepancies between public opinion and private attitudes develop at the scale of micro-societies. Based on social psychological theorizing, the model distinguishes between two types of agents: a) those seeking to gain or maintain a good reputation and status, and b) those seeking to promote group harmony by reaching consensus. We characterized these different types of agents by different decision rules for either voicing their opinion or remaining silent, based on the behavior of their proximal network. Results of the model simulations show that even when the private attitudes of the agents are held constant, publicly expressed opinions can oscillate and (depending on the reputational concerns of individual actors) situations can occur in which minorities as well as majorities are silenced. We conclude that the macro-level consequences of micro-level decisions to either voice an opinion or remain silent provide a foundation for better understanding how public opinions are shaped. Moreover, we discuss the conditions under which public opinion could be considered a good representation of private attitudes in a society.