Semantics and pragmatics in a modular mind

This dissertation asks how we should understand the distinction between semantic and pragmatic aspects of linguistic understanding within the framework of mentalism, on which the study of language is a branch of psychology. In particular, I assess a proposal on which the distinction between semantics and pragmatics is ultimately grounded in the modularity or encapsulation of semantic processes. While pragmatic processes involved in understanding the communicative intentions of a speaker are non-modular and highly inferential, semantic processes involved in understanding the meaning of an expression are modular and encapsulated from top-down influences of general cognition. The encapsulation hypothesis for semantics is attractive, since it would allow the semantics-pragmatics distinction to cut a natural joint in the communicating mind. However, as I argue, the case in favor of the modularity hypothesis for semantics is not particularly strong. Many of the arguments offered in its support are unsuccessful. I therefore carefully assess the relevant experimental record, in rapport with parallel debates about modular processing in other domains, such as vision. I point to several observations that raise a challenge for the encapsulation hypothesis for semantics; and I recommend consideration of alternative notions of modularity. However, I also demonstrate some principled strategies that proponents of the encapsulation hypothesis might deploy in order to meet the empirical challenge that I raise. I conclude that the available data neither falsify nor support the modularity hypothesis for semantics, and accordingly I develop several strategies that might be pursued in future work. It has also been argued that the encapsulation of semantic processing would entail (or otherwise strongly recommend) a particular approach to word meaning. However, in rapport with the literature on polysemy—a phenomenon whereby a single word can be used to express several related concepts, but not due to generality—I show that such arguments are largely unsuccessful. Again, I develop strategies that might be used, going forward, to adjudicate among the options regarding word meaning within a mentalistic linguistics

Accelarated immune ageing is associated with COVID-19 disease severity

Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease

Additional file 2: of The Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial: update to the study protocol and detailed statistical analysis plan (SAP)

Health-related quality of life (HRQoL) questionnaires. The HRQoL questionnaires to be used in the PEDOCELL trial are to be found in Additional File 2. The EQ-5D-5L, the SF-12 and the Extremity Soft Tissue Infection (ESTI) score will be used to measure HRQoL outcomes in patients enrolled to the PEDOCELL trial at each follow-up visit. (DOCX 86 kb