Fictional reference as simulation

According to a widespread view, the author of a fiction makes pretend assertions, which themselves rest on ancillary acts of pretend reference. Fictional discourse is thus asymmetrically dependent upon ‘serious’ (non-fictional) discourse: fictional reference and fictional assertion alike are parasitic on genuine reference and genuine assertion, which they mimic. Recently, however, several authors have criticized the pretence approach. According to the alternative, two-stage model they argue for, fiction and non-fiction are on a par (rather than one being asymmetrically dependent upon the other). This chapter shows how this debate connects with the current controversy about the force/content distinction. A sustained defence of the pretence approach is provided, and the approach is shown to extend to the parafictional uses of fictional names.

Recursion and the Definition of Universal Prosodic Categories

It is widely agreed that prosodic constituents should mirror syntactic constituents (unless high-ranking prosodic constraints interfere). Because recursion is a feature of syntactic representations, one expects recursion in prosodic representations as well. However, it is of current controversy what kinds of syntactic representation motivate prosodic recursion. In this paper, the use of Phonological Phrase recursion is reviewed in several case studies, chosen because prosodic recursion mostly does not reflect syntactic recursion as defined in current syntactic theory. We provide reanalyses that do not appeal to prosodic recursion (unless syntactically motivated), showing that Phonological Phrase recursion is not necessary to capture the relevant generalizations. The more restrictive use of prosodic recursion we argue for has the following conceptual advantages. It allows for more consistent cross-linguistic generalizations about the syntax–prosody mapping so that prosodic representations more closely reflect syntactic ones. It allows the fundamental syntactic distinctions between clause (and other phases) and phrase to be reflected in the prosodic representation, and it allows cross-linguistic generalizations to be made about the prosodic domain of intonational processes, such as downstep and continuation rise.

Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( p < 0.001 ). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Biologia Futura: is ADAM 17 the reason for COVID-19 susceptibility in hyperglycemic and diabetic patients?

COVID-19 is a disease-causing current pandemic. It prevails in patients with pre-existing conditions such as diabetes and hypertension. Renin–angiotensin system was identified as a center of COVID-19 pathophysiology. There is a current controversy concerning the usage of ACE inhibitors and AR blockers in patients with COVID-19. Multiple clinical trials are on the way to determine the effect of RAS blockers in patients with COVID-19. ACE2 receptor is thought to be the point of entry utilized by a coronavirus. However, other factors have been identified which potentially facilitate SARS-CoV-2 entry into the cell. ADAM17 could facilitate viral entry in hyperglycemic and diabetic patients. Insulin is an ADAM17 inhibitor. Heme oxygenase (HO)-1 level is reduced in diabetic patients, contributing to the worst outcome for patients with poor glycemic control. The combined therapy of glycemic control and antioxidant response to oxidative stress could be explored in patients with COVID-19.

Part IV Vitiation, 13 Duress

A coerced agreement can be set aside, in accordance with a Common Law doctrine of duress which has acquired generality during the last fifty years (although it remains customary to divide the topic into three sectors, duress as to person, duress as to goods, and economic duress, that is the threat to break a contract). The four elements of duress are: (i) pressure or a threat; (ii) which is (a) unlawful or (b) illegitimate (despite being lawful); (iii) objectively there was enough pressure so that the coerced party’s submission was not an instance of undue fragility; and instead the coerced party had no real or practical choice other than to submit; and (iv) the coerced party was in fact induced by the duress to enter the contract or agree to its variation or termination. The current controversy is when a threat to do something which is lawful can be characterized as ‘illegitimate’.

Short- and long-term outcomes of aortic root-sparing repair and replacement in acute type A aortic dissection repair

Acute type A aortic dissection is a surgical emergency with a high mortality rate if left untreated. Management of the aortic root in this setting constitutes an intricate decision-making framework, further complicated by the emergent nature of the dissection. There exists much controversy regarding pursuit of the aggressive aortic root replacement versus a conservative root-sparing repair, alongside considerations for valve-sparing root replacement. In this review, we critically appraise the current controversy in the literature considering the fate of the aortic root, discussing the aforementioned root interventions for which provides better outcomes for mortality and risk of re-intervention. Literature search was performed using electronic database through PubMed, Google scholar, and Embase focussing on studies reporting outcomes and re-intervention rates for these approaches. Limited by the heterogeneity in surgical strategy, with most studies being single-centred retrospective experiences, further fuel this ongoing debate. The literature reveals rather contrasting results whilst comparing root-sparing repair, versus the extensive root replacement; whilst some studies report no statistically significant difference, others show one superior over the other. There is greater consensus when considering risk of re-operation, with studies showing higher rates of re-operation in root-sparing group compared to replacement; however, many others show no statistically significant difference. In conclusion, the conflicting outcomes reported in the literature, with their inherent limitations, results in the current inability to reach a definitive answer. There remains support in the current literature for both approaches with much of the decision-making being surgeon-bound with many significant influencing factors on a case-by-case basis.

Peritoneal Tuberculosis during Infliximab Treatment in a Patient with Ulcerative Colitis Despite a Negative Quantiferon Test

Infliximab is an IgG1 antitumor necrosis factor monoclonal antibody that is commonly used to treat inflammatory bowel disease (IBD) and other autoimmune disorders. However, it is known to increase the risk of reactivation of latent tuberculosis (LTBI) due to its capability to disrupt TB granulomas. We describe a case of extrapulmonary TB in a patient with ulcerative colitis who was treated with Infliximab after a negative Quantiferon Test. In addition, we report briefly on the current controversy about the appropriateness, interval, and methods for the repeated screening of latent TB in IBD patients that are treated with antitumor necrosis factor alpha (TNF-α) antibodies.