In this paper we examine three forms of regret in relation to the UK’s hugely significant referendum on EU membership that was held in June 2016. They are: (i) whether ‘leave’ voters at the ...referendum subsequently regretted their choice (in the light of the result), (ii) whether non-voters regretted their decisions to abstain (essentially supporting ‘remain’) and (iii) whether individuals were more likely to indicate that it is everyone’s duty to vote following the referendum. We find evidence in favor of all three types of regret. In particular, leave voters and non-voters were significantly more likely to indicate that they would vote to remain given a chance to do so again; moreover, the probability of an individual stating that it was everyone’s duty to vote in a general election increased significantly in 2017 (compared to 2015). The implications of the findings are discussed in the context of the referendum’s outcome.
It is recognised that expressive preferences may play a major role in determining voting decisions because the low probability of being decisive in elections undermines standard instrumental ...reasoning. Expressive and instrumental preferences may deviate and in electoral settings it is more important to make policies expressively appealing. But policies are even more attractive if they can be made both expressively and instrumentally appealing. This paper studies education policy in England and proposes that the argument for increased state spending in school education is expressively appealing as it appears equitable, but the allocation of students to schools by catchment area is also instrumentally appealing to middle-class families. Allocation to schools by lottery may be expressively but not instrumentally appealing. Cutting education spending and dividing the proceeds between a tax cut to the affluent and a cash transfer to the poor may be instrumentally but not expressively appealing. The effort to provide instrumentally appealing policies with sufficient ethical content to satisfy expressive preferences may lead to inefficiency and distract attention from more serious ethical problems related to the policies.
•Policies that are instrumentally and expressively appealing are politically popular•But such policies are potentially inefficient and inequitable•Generous state funding of education is expressively appealing•Catchment areas are instrumentally appealing•More efficient or equitable policies are not politically popular
This paper provides a rationale for group support for political violence which does not provide a material benefit. Rabin's (1993) theory of fairness is adopted to demonstrate that although group ...violence may not be a Nash equilibrium it may be a fairness equilibrium in a game containing psychological payoffs. For this to happen the material stakes must be perceived as low and psychological payoffs are expressive. Although the material stakes are actually high, members of each group may choose expressively to support the use of violence because the probability of being decisive is low. The paper also considers the possibility of peace emerging as a fairness equilibrium. This can only happen if each group perceives the other as making some sacrifice in choosing peace.
This paper extends the political agency approach to an environment in which voting is categorised into informed and instrumental, informed and ‘expressive’, and uninformed due to ‘rational ...irrationality’. Politicians may be “good”, “bad”, or “populist”. Initially the existence of only good and populist politicians is assumed: the incentives for good politicians to pool with or separate from populists are investigated and the implications for voter welfare are explored. Then the consequences of the inclusion of bad politicians are considered. The paper makes three main contributions. First, I provide a rational choice analysis of populism as populism is commonly understood. Second, I locate a potential role for government as a persuasive provider of information regarding the quality of policy. Third, when bad politicians are added to the analysis, it is shown that a little potential corruption can improve voter welfare.
► The paper provides a rational choice analysis of populism. ► Populism may be provided because voting is expressive and/or rationally irrational. ► Government may instead work to provide information regarding the quality of policy. ► It is shown that a little potential corruption can improve voter welfare.
Adeno-associated viruses (AAVs) have recently emerged as the leading vector for retinal gene therapy. However, AAV vectors that are capable of achieving clinically relevant levels of transgene ...expression and widespread retinal transduction are still an unmet need. Using rationally designed AAV2-based capsid variants, we investigate the role of capsid hydrophilicity and hydrophobicity as it relates to retinal transduction. We show that hydrophilic, single-amino-acid mutations (V387R, W502H, E530K, L583R) in AAV2 negatively impact retinal transduction when heparan sulfate proteoglycan (HSPG) binding remains intact. Conversely, addition of hydrophobic point mutations to an HSPG binding-deficient capsid (AAV2ΔHS) leads to increased retinal transduction in both mouse and macaque. Our top performing vector, AAV2(4pMut)ΔHS, achieved robust rod and cone photoreceptor (PR) transduction in macaque, especially in the fovea, and demonstrates the ability to spread laterally beyond the borders of the subretinal injection (SRI) bleb. This study both evaluates biophysical properties of AAV capsids that influence retinal transduction and assesses the transduction and tropism of a novel capsid variant in a clinically relevant animal model. IMPORTANCE Rationally guided engineering of AAV capsids aims to create new generations of vectors with enhanced potential for human gene therapy. By applying rational design principles to AAV2-based capsids, we evaluated the influence of hydrophilic and hydrophobic amino acid mutations on retinal transduction as it relates to vector administration route. Through this approach, we identified a largely deleterious relationship between hydrophilic amino acid mutations and canonical HSPG binding by AAV2-based capsids. Conversely, the inclusion of hydrophobic amino acid substitutions on an HSPG binding-deficient capsid (AAV2ΔHS) generated a vector capable of robust rod and cone photoreceptor (PR) transduction. This vector AAV2(4pMut)ΔHS also demonstrates a remarkable ability to spread laterally beyond the initial subretinal injection (SRI) bleb, making it an ideal candidate for the treatment of retinal diseases that require a large area of transduction.
The majority of inherited retinal diseases (IRDs) are caused by mutations in genes expressed in photoreceptors (PRs). The ideal vector to address these conditions is one that transduces PRs in large ...areas of retina with the smallest volume/lowest titer possible, and efficiently transduces foveal cones, the cells responsible for acute, daylight vision that are often the only remaining area of functional retina in IRDs. The purpose of our study was to evaluate the retinal tropism and potency of a novel capsid, AAV44.9, and rationally designed derivatives thereof. We found that AAV44.9 and AAV44.9(E531D) transduced retinas of subretinally injected (SRI) mice with higher efficiency than did benchmark AAV5- and AAV8-based vectors. In macaques, highly efficient cone and rod transduction was observed following submacular and peripheral SRI. AAV44.9- and AAV44.9(E531D)-mediated GFP fluorescence extended laterally well beyond SRI bleb margins. Notably, extrafoveal injection (i.e., fovea not detached during surgery) led to transduction of up to 98% of foveal cones. AAV44.9(E531D) efficiently transduced parafoveal and perifoveal cones, whereas AAV44.9 did not. AAV44.9(E531D) was also capable of restoring retinal function to a mouse model of IRD. These novel capsids will be useful for addressing IRDs that would benefit from an expansive treatment area.
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This study describes novel AAV vectors that are highly potent and promote gene expression well outside the margins of subretinal injection blebs. They transduce 98% of foveal cone photoreceptors without the need to surgically detach this precious retinal region. These vectors will be useful for treating diseases where the central retina is the target or those that require an expansive treatment area.
A growing literature has focused attention on ‘expressive’ rather than ‘instrumental’ behaviour in political settings, particularly voting. A common criticism of the expressive idea is that it is ad ...hoc and lacks both predictive and normative bite. No clear definition of expressive behaviour has gained wide acceptance yet, and no detailed understanding of the range of foundations of specific expressive motivations has emerged. This article provides a foundational discussion and definition of expressive behaviour accounting for a range of factors. The content of expressive choice – distinguishing between identity-based, moral and social cases – is discussed and related to the specific theories of expressive choice in the literature. There is also a discussion of the normative and institutional implications of expressive behaviour.
A method for sampling and electrophoretic analysis of aqueous plugs segmented in a stream of immiscible oil is described. In the method, an aqueous buffer and oil stream flow parallel to each other ...to form a stable virtual wall in a microfabricated K-shaped fluidic element. As aqueous sample plugs in the oil stream make contact with the virtual wall, coalescence occurs and sample is electrokinetically transferred to the aqueous stream. Using this virtual wall, two methods of injection for channel electrophoresis were developed. In the first, discrete sample zones flow past the inlet of an electrophoresis channel and a portion is injected by electroosmotic flow, termed the “discrete injector”. With this approach at least 800 plugs could be injected without interruption from a continuous segmented stream with 5.1% RSD in peak area. This method generated up to 1,050 theoretical plates, although analysis of the injector suggested that improvements may be possible. In a second method, aqueous plugs are sampled in a way that allows them to form a continuous stream that is directed to a microfluidic cross-style injector, termed the “desegmenting injector”. This method does not analyze each individual plug but instead allows periodic sampling of a high-frequency stream of plugs. Using this system at least 1000 injections could be performed sequentially with 5.8% RSD in peak area and 53,500 theoretical plates. This method was demonstrated to be useful for monitoring concentration changes from a sampling device with 10 s temporal resolution. Aqueous plugs in segmented flows have been applied to many different chemical manipulations including synthesis, assays, sampling processing and sampling. Nearly all such studies have used optical methods to analyze plug contents. This method offers a new way to analyze such samples and should enable new applications of segmented flow systems.
This paper reviews four economic theories of leadership selection in conflict settings. The 'credibility rationale', argues that hawks may actually be necessary to initiate peace agreements. The ...'bargaining rationale' predicts that while doves are more likely to secure peace, post-conflict hawks may be rationally selected. The 'social psychological rationale' captures the idea of a competition over which group can form the strongest identity. Dove selection can be predicted during conflict, but hawk selection post-conflict. Finally, the 'expressive rationale' predicts that regardless of the underlying nature of the game the large group nature of decision-making in rendering individual decision makers non-decisive in determining the outcome of elections may cause them to make choices based primarily on emotions. Finally, the paper analyses the extent to which the theories can throw light on Northern Ireland electoral history over the last 25 years.
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