Lessons from the English auxiliary system

The English auxiliary system exhibits many lexical exceptions and subregularities, and considerable dialectal variation, all of which are frequently omitted from generative analyses and discussions. This paper presents a detailed, movement-free account of the English Auxiliary System within Sign-Based Construction Grammar (Sag 2010, Michaelis 2011, Boas & Sag 2012) that utilizes techniques of lexicalist and construction-based analysis. The resulting conception of linguistic knowledge involves constraints that license hierarchical structures directly (as in context-free grammar), rather than by appeal to mappings over such structures. This allows English auxiliaries to be modeled as a class of verbs whose behavior is governed by general and class-specific constraints. Central to this account is a novel use of the feature aux, which is set both constructionally and lexically, allowing for a complex interplay between various grammatical constraints that captures a wide range of exceptional patterns, most notably the vexing distribution of unstressed do, and the fact that Ellipsis can interact with other aspects of the analysis to produce the feeding and blocking relations that are needed to generate the complex facts of EAS. The present approach, superior both descriptively and theoretically to existing transformational approaches, also serves to undermine views of the biology of language and acquisition such as Berwick et al. (2011), which are centered on mappings that manipulate hierarchical phrase structures in a structure-dependent fashion

Prioritizing persons deprived of liberty in global guidelines for tuberculosis preventive treatment

In this Policy Forum piece, Aditya Narayan and colleagues discuss the challenges and opportunities for tuberculosis preventive treatment in carceral settings

Prioritizing persons deprived of liberty in global guidelines for tuberculosis preventive treatment

Persons deprived of liberty (PDLs) are disproportionately impacted by tuberculosis, with high incidence rates and often limited access to diagnostics, treatment, and preventive measures. The World Health Organization (WHO) expanded its recommendations for tuberculosis preventive treatment (TPT) to many high-risk populations, but their guidance does not include PDL, and most low- and middle-income countries do not routinely provide edforthoseusedthroughoutthetext TPT in prisons. :Pleaseverifythatallentriesarecorrectlyabbreviated: Recent studies demonstrate high acceptability and completion rates of short-course TPT regimens in jails and prisons; costs of these regimens have been markedly reduced through international agreements, making this an opportune for further expanding their use. We argue that PDL should be a priority group for TPT in national guidelines and discuss implementation considerations and resource needs for TPT programs in carceral facilities. Scaling access to TPT for PDL is important for reducing disease and transmission in this population; it is also critical to advancing an equitable response to tuberculosis

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

Lifestyles and the risk of depression in the “Seguimiento Universidad de Navarra” cohort

Background: Lifestyles are involved in the pathogenesis of depression and many of these factors can be modified for the potential prevention of depression. Our aim was to assess the association between a healthy-lifestyle score, that includes some less-studied lifestyle indicators, and the risk of depression. Methods: We followed 14,908 participants initially free of any history of depression in the “Seguimiento Universidad de Navarra” (SUN) cohort. Information was collected biennially from 1999 to December 2016. We calculated a healthy-lifestyle score (0–10 points), previously associated with cardioprotection, by giving one point to each of the following components: never smoking, physical activity (> 20 METs-h/ week), Mediterranean diet adherence ( 4 points), healthy body mass index ( 22 kg/m2 ), moderate alcohol consumption (women 0.1–5 g/d; men 0.1–10 g/d of ethanol), avoidance of binge drinking (never more than 5 alcoholic drinks in a row), low television exposure ( 2 h/d), short afternoon nap ( 30 min/ day), time spent with friends (>1 h/d) and working at least 40 h/week. Results: During a median follow-up of 10.4 years, we observed 774 new cases of major depression among participants initially free of depression. The highest category (8–10 factors) showed a significant inverse association with a 32% relative risk reduction for depression compared to the lowest category (0–3 factors) (multivariable-adjusted hazard ratio: 0.68; 95% CI:0.49-0.95) (p for trend = 0.010). Conclusions: Adopting a healthy-lifestyle was associated with a lower risk of incident depression in the SUN cohort. This index, including ten simple healthy lifestyle habits, may be useful for a more integrative approach to depression prevention

Use of non-steroidal anti-inflammatory drugs, aspirin and the risk of depression: The "Seguimiento Universidad de Navarra (SUN)" cohort.

Background: The potential effect of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) to prevent depression remains largely unknown, in spite of the implication of inflammation in depression. This study aimed to investigate whether the habitual intake of aspirin and other NSAIDs was prospectively associated with a reduction in the observed incidence of depression. Methods: A dynamic cohort including 22,564 Spanish university graduates (mean age: 37 years) initially free of depression was followed during an average of 8.7 years. Exposure to NSAIDs was assessed with specific repeated questionnaires throughout follow-up, starting in the 2-year follow-up questionnaire. Incident cases of depression were defined as either a new validated medical diagnosis of depression or reporting the initiation of habitual use of antidepressants. Results: We identified 772 incident cases of depression. Regular intake of aspirin and other NSAIDs was not associated with depression risk. Only in secondary sensitivity analyses using a definition of the outcome with higher specificity (a validated medical diagnosis of depression), an inverse association of aspirin with depression was found [HR (95%CI): 0.20 (0.04–0.87)]. However, these results were non-significant after adjustment for multiple testing. Limitations: A possible underestimation of incident depression and a limited ability to detect all possible residual confounding. Conclusions: Regular use of NSAIDs was not associated with the incidence of depression. Further longitudinal controlled studies are necessary to clarify a potential role of aspirin use in depression risk