They Be Taggin, Don\u27t They?: The Acquisition of Invariant Be

Does African-American English (AAE) have a separate grammar from Standard American English (SAE)? AAE has a number of distinctive features, several of which have been discussed extensively in the sociolinguistic literature: the variable use of third-person singular -s; the absence of plura -s; the variable use of copula; and others. (See Labov, 1966, 1969a, b, and Fasold, 1972 for discussion.) Perhaps the most distinctive feature of AAE is habitual or invariant be

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A Revised Protocol for Culture of Airway Epithelial Cells as a Diagnostic Tool for Primary Ciliary Dyskinesia

Air–liquid interface (ALI) culture of nasal epithelial cells is a valuable tool in the diagnosis and research of primary ciliary dyskinesia (PCD). Ex vivo samples often display secondary dyskinesia from cell damage during sampling, infection or inflammation confounding PCD diagnostic results. ALI culture enables regeneration of healthy cilia facilitating differentiation of primary from secondary ciliary dyskinesia. We describe a revised ALI culture method adopted from April 2018 across three collaborating PCD diagnostic sites, including current University Hospital Southampton COVID-19 risk mitigation measures, and present results. Two hundred and forty nasal epithelial cell samples were seeded for ALI culture and 199 (82.9%) were ciliated. Fifty-four of 83 (63.9%) ex vivo samples which were originally equivocal or insufficient provided diagnostic information following in vitro culture. Surplus basal epithelial cells from 181 nasal brushing samples were frozen in liquid nitrogen; 39 samples were ALI-cultured after cryostorage and all ciliated. The ciliary beat patterns of ex vivo samples (by high-speed video microscopy) were recapitulated, scanning electron microscopy demonstrated excellent ciliation, and cilia could be immuno-fluorescently labelled (anti-alpha-tubulin and anti-RSPH4a) in representative cases that were ALI-cultured after cryostorage. In summary, our ALI culture protocol provides high ciliation rates across three centres, minimising patient recall for repeat brushing biopsies and improving diagnostic certainty. Cryostorage of surplus diagnostic samples was successful, facilitating PCD research

'Preventing the pain' when working with family and sexual violence in primary care

Primary care professionals (PCPs) are increasingly being expected to identify and respond to family and sexual violence as the chronic nature and severity of the long-term health impacts are increasingly recognized. This discussion paper reports the authors’ expert opinion from their experiences running international workshops to prevent trauma among those who work and research sexual violence. It describes the burnout and secondary traumatic stress literature which provides the evidence supporting their work. Implications for practicing basic training in response to trauma and ongoing education are a key area for responding to family violence and preventing professional stress. A professional culture that supports and values caring well for those who have experienced family violence as well as “caring for the carer” is needed. Working in teams and having more support systems in place are likely to protect PCPs from secondary traumatic stress and burnout. Undergraduate and postgraduate training of PCPs to develop trauma knowledge and the skills to ask about and respond to family violence safely are essential. In addition, the healthcare system, workplace, and the individual practitioner support structures need to be in place to enable PCPs to provide safe and effective long-term care and access to other appropriate services for those who have experienced family violence

Seasonal variation in success and ciliation of airway epithelial cells cultured at air-liquid interface; patients samples referred for primary ciliary dyskinesia testing

Background: Air-liquid interface (ALI) culture is used to differentiate primary airway epithelial cells for cilia studies and can diagnostically confirm or excludes primary ciliary dyskinesia (PCD). This technique is capricious, time-consuming and expensive with variable success.Aims: To evaluate ALI-culture ciliation and culture failure in PCD diagnostic samples.Methods: Nasal epithelial cells from PCD referrals were cultured submerged before ALI-culture at p2 by established methods. 202 consecutive cultures (October 2013-December 2014; 27 PCD positive) were evaluated for outcome including seasonal variation.Results: 88 (43.6%; 16 PCD positive) ALI-cultures ciliated. Of 202 cultures, 72 (35.6%) were diagnostically re-analysed, 52 (25.7%) were terminated or used for research (if PCD definitely excluded by prior diagnostics) and 78 (38.6%) failed. Of 78 failed cultures: 11 failed submerged at p0 (4 non-viable, 2 fungal and 5 bacterial infections) and 67 failed at ALI (1 non-viable, 1 fungal and 2 bacterial infections, 56 unciliated and 7 no data). Seasonal variation was observed: in June-August (n=50) ciliation increased to 62.1% and culture failure decreased to 25.5%; by contrast in December-February (n=37) ciliation decreased to 25% and culture failure increased to 47.5%.Conclusion: ALI-culture complements PCD diagnostics and in vitro cilia studies. In specialist hands 44% ALI-cultures ciliate. Culture failure due to non-viable cells or bacterial or fungal infection was <5%. 28% p2 ALI-cultures failed to ciliate; winter months were suboptimal, likely associated with peaks in viral respiratory illness

Diagnosis of primary ciliary dyskinesia: potential options for resource-limited countries

Primary ciliary dyskinesia is a genetic disease of ciliary function leading to chronic upper and lower respiratory tract symptoms. The diagnosis is frequently overlooked because the symptoms are nonspecific and the knowledge about the disease in the primary care setting is poor. Additionally, none of the available tests is accurate enough to be used in isolation. These tests are expensive, and need sophisticated equipment and expertise to analyse and interpret results; diagnosis is therefore only available at highly specialised centres. The diagnosis is particularly challenging in countries with limited resources due to the lack of such costly equipment and expertise. In this review, we discuss the importance of early and accurate diagnosis especially for countries where the disease is clinically prevalent but diagnostic tests are lacking. We review the diagnostic tests available in specialised centres (nasal nitric oxide, high-speed video microscopy, transmission electron microscopy, immunofluorescence and genetics). We then consider modifications that might be considered in less well-resourced countries whilst maintaining acceptable accuracy