The neural career of sensory-motor metaphors

Abstract The role of sensory-motor systems in conceptual understanding has been controversial. It has been proposed than many abstract concepts are understood metaphorically through concrete sensorymotor domains such as actions. Using fMRI, we compared neural responses to literal action (Lit; The daughter grasped the flowers), metaphoric action (Met; The public grasped the idea), and abstract (Abs; The public understood the idea) sentences of varying familiarity. Both Lit and Met sentences activated the left anterior inferior partial lobule (aIPL), an area involved in action planning, with Met sentences also activating a homologous area in the right hemisphere, relative to Abs sentences. Both Met and Abs sentences activated left superior temporal regions associated with abstract language. Importantly, activation in primary motor and biological motion perception regions was inversely correlated with Lit and Met familiarity. These results support the view that the understanding of metaphoric action retains a link to sensory-motor systems involved in action performance. However, the involvement of sensory-motor systems in metaphor understanding changes through a gradual abstraction process whereby relatively detailed simulations are used for understanding unfamiliar metaphors, and these simulations become less detailed and involve only secondary motor regions as familiarity increases. Consistent with these data, we propose that aIPL serves as an interface between sensory-motor and conceptual systems and plays an important role in both domains. The similarity of abstract and metaphoric sentences in the activation of left superior temporal regions suggests that action metaphor understanding is not completely based on sensory-motor simulations, but relies also on abstract lexical-semantic codes

Multiple treatment interruptions and protecting HIV-specific CD4 T cells enable durable CD8 T cell response and viral control

Human Immunodeficiency Virus (HIV) remains a global health challenge, and novel approaches to improve HIV control are significantly important. The cell and gene therapy product AGT103-T was previously evaluated (NCT04561258) for safety, immunogenicity, and persistence in seven patients for up to 180 days post infusion. In this study, we sought to investigate the impact of AGT103-T treatment upon analytical treatment interruptions (ATIs). Six patients previously infused with AGT103-T were enrolled into an ATI study (NCT05540964), wherein they suspended their antiretroviral therapy (ART) until their viral load reached 100,000 copies/mL in two successive visits, or their CD4 count was reduced to below 300 cells/μL. During the ATI, all patients experienced viral rebound followed by a notable expansion in HIV specific immune responses. The participants demonstrated up to a five-fold increase in total CD8 counts over baseline approximately 1–2 weeks followed by the peak viremia. This coincided with a rise in HIV-specific CD8 T cells, which was attributed to the increase in antigen availability and memory recall. Thus, the protocol was amended to include a second ATI with the first ATI serving as an “auto-vaccination.” Four patients participated in a second ATI. During the second ATI, the Gag-specific CD8 T cells were either maintained or rose in response to viral rebound and the peak viremia was substantially decreased. The patients reached a viral set point ranging from 7,000 copies/mL to 25,000 copies/mL. Upon resuming ART, all participants achieved viral control more rapidly than during the first ATI, with CD4 counts remaining within 10% of baseline measurements and without any serious adverse events or evidence of drug resistance. In summary, the rise in CD8 counts and the viral suppression observed in 100% of the study participants are novel observations demonstrating that AGT103-T gene therapy when combined with multiple ATIs, is a safe and effective approach for achieving viral control, with viral setpoints consistently below 25,000 copies/mL and relatively stable CD4 T cell counts. We conclude that HIV cure-oriented cell and gene therapy trials should include ATI and may benefit from designs that include multiple ATIs when induction of CD8 T cells is required to establish viral control

The financialization of mass wealth, banking crises and politics over the long run

The co-evolution of democratic politics and mass, financialized wealth has destabilized highly integrated financial systems and the socio-political underpinnings of neoliberal policy norms at domestic and global levels. Over the long run, it has increased the political pressure on governments to undertake bailouts during major banking crises and, by raising voters’ attentiveness to wealth losses and distributional inequities, has sharply raised the bar for government performance. The result has been more costly bailouts, greater political instability and the sustained politicization of wealth cleavages in crisis aftermaths. We underline the crucial importance and modernity of this phenomenon by showing how the high concentration of wealth in pre-1914 Britain and America among elites was associated with limited crisis interventions and surprisingly tranquil political aftermaths. By contrast, the 2007–2009 crises in both countries epitomise the political dilemmas facing elected governments in a new world of mass financialized wealth and the impact on political polarization and democratic politics. We show that these dilemmas were embryonic in the interwar period and highlight how the evolutionary forces shaping policy and political outcomes reveal the importance of time, context and the effects of long cycles in the world economy and global politics

Entrepreneurial Orientation, Distinctive Marketing Competencies And Organizational Performance

This study examined the entrepreneurial orientation (EO) of 599 independent businesspeople and compared those with high, medium and low EO along a series of distinctive marketing competency and organizational performance measures. EO is measured using a new multi-item scale that is based on an integrative definition of entrepreneurship. Results indicate that EO is positively and significantly related to distinctive marketing competencies and organizational performance. Demographic profiles of the high, medium and low EO groups are also developed and provide additional insights

Marketing Program Planning, Process Benefits, And Store Performance: An Initial Study Among Small Retail Firms

Despite the importance of thinking strategically when adapting to environmental change, independent retail firms often find that day-to-day operational demands inhibit their ability to participate in the marketing planning process. Further, the marketing and retailing literature provides few insights to retailers interested in better understanding how to plan most effectively. Past research has emphasized the formal aspects of planning and the empirical evidence is mixed regarding the relationship between planning and performance. This study develops new measures of both marketing program planning (MPP) and the intermediate process benefits that result from planning. We then assess their impact on performance using data collected from independent computer store retailers. Results indicate 1) the planning dimension strategic clarity is significantly related to the process benefits market knowledge and marketing program effectiveness, 2) process benefits mediate the relationship between planning and performance, and 3) process benefits are positively related to financial performance. © 1999 New York University

Marketing Strategy Development Styles, Implementation Capability, And Firm Performance: Investigating The Curvilinear Impact Of Multiple Strategy-Making Styles

There is growing interest in the process by which marketing strategy is developed. This article reports on a study in which we investigate the performance implications of using multiple organizational approaches to the development of marketing strategy. Specifically, we test a model in which implementation capability mediates the relationship between number of marketing strategy development (MSD) styles used and firm performance. Based on data collected from manufacturers, the results indicate that: (1) the relationship between the number of MSD styles used and implementation capability is curvilinear (an inverse U-shaped relationship), (2) implementation capability positively impacts firm performance, and (3) implementation capability mediates the relationship between number of MSD styles used and firm performance