PHONOLOGYCAL VARIATION AND CHANGE IN CONTEMPORARY ENGLISH: EVIDENCE FROM NEWCASTLE UPON TYNE AND DERBY

This paper gives an overview of the principal findings of a recent project carried out on phonological variation and change in contemporary urban dialects, using quantitative sociolinguistic methods, instrumental phonetic, and phonological analysis. Conversational and word-list data were sistematically collected from 32 Tyneside and 32 Derby speakers, each sample being stratified to include equal numbers of men and woman, two age-groups and two social class groups. This sample design allowed us to assesss the impact of age, class, and gender on patterns of language variation and change as well as the geographical domains of specific changers. The principal results are described and their theoretical implications are phonetics.Este trabajo ofrece un resumen de un proyecto de investigación centrado en la variación y el cambio fonológico en inglés oral contemporáneo. Se han estudiado tendencias de variación y cambio fonológico en distintos dialécticos urbanos del inglés contemporáneo aplicando métodos de sociolingüistica cuantitativa, de fonética acústica e instrumental y de análisis fonológico. Los datos proceden de 32 informantes de Tyneside y 32 de Derby, cada uno de estos dos grupos incluía el mismo número de hombres y mujeres y distinguía dos grupos de edades y dos clases sociales. Los datos se obtuvieron, en ambos casos, a partir de la lectura de listas de palabras o de conversaciones con los informantes. Esta muestra nos ha permitido evaluar la influencia que factores como la edad, la clase social y el sexo en las distintas tendencias de variación y cambio lingüístico que se analizan, además de ofrecernos información sobre los ámbitos geográficos de algunos cambios concretos. Tanto los resultados de este proyecto, como sus implicaciones teóricas se describen en el artículo

Three steps forward for predictability : Consideration of methodological robustness, indexical and prosodic factors, and replication in the laboratory

There is now abundant evidence that phonetic forms are shaped by probabilistic effects reflecting predictability or informativity. We outline a number of challenges for such work, where theoretical claims are often based on small differences in acoustic measurements, or interpretations of small statistical effect sizes. We outline caveats about the methods and assumptions encountered in many studies of predictability effects, particularly regarding corpus-based approaches. We consider the wide range of factors that influence patterns of variability in phonetic forms, taking a broad perspective on what is meant by “the message” in order to show that predictability effects need to be considered alongside many others, including indexical and prosodic factors. We suggest a number of ways forward to extend our understanding of the form-predictability relationship.Full Tex

Resilience of English vowel perception across regional accent variation

In two categorization experiments using phonotactically legal nonce words, we tested Australian English listeners’ perception of all vowels in their own accent as well as in four less familiar regional varieties of English which differ in how their vowel realizations diverge from Australian English: London, Yorkshire, Newcastle (UK), and New Zealand. Results of Experiment 1 indicated that amongst the vowel differences described in sociophonetic studies and attested in our stimulus materials, only a small subset caused greater perceptual difficulty for Australian listeners than for the corresponding Australian English vowels. We discuss this perceptual tolerance for vowel variation in terms of how perceptual assimilation of phonetic details into abstract vowel categories may contribute to recognizing words across variable pronunciations. Experiment 2 determined whether short-term multi-talker exposure would facilitate accent adaptation, particularly for those vowels that proved more difficult to categorize in Experiment 1. For each accent separately, participants listened to a pre-test passage in the nonce word accent but told by novel talkers before completing the same task as in Experiment 1. In contrast to previous studies showing rapid adaptation to talker-specific variation, our listeners’ subsequent vowel assimilations were largely unaffected by exposure to other talkers’ accent-specific variation

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19

OBJECTIVE: To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications. RESEARCH DESIGN AND METHODS: In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors. RESULTS: Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication. CONCLUSIONS: Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19

ObjectiveTo investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications.Research design and methodsIn this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors.ResultsCardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age ConclusionsIncreased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes

Using imaging to combat a pandemic:rationale for developing the UK National COVID-19 Chest Imaging Database

No abstract available

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Cohort Profile: Post-hospitalisation COVID-19 study (PHOSP-COVID)

PHOSP-COVID is a national UK multi-centre cohort study of patients who were hospitalised for COVID-19 and subsequently discharged.PHOSP-COVID was established to investigate the medium- and long-term sequelae of severe COVID-19 requiring hospitalisation, understand the underlying mechanisms of these sequelae, evaluate the medium- and long-term effects of COVID-19 treatments, and to serve as a platform to enable future studies, including clinical trials.Data collected covered a wide range of physical measures, biological samples, and Patient Reported Outcome Measures (PROMs).Participants could join the cohort either in Tier 1 only with remote data collection using hospital records, a PROMs app and postal saliva sample for DNA, or in Tier 2 where they were invited to attend two specific research visits for further data collection and biological research sampling. These research visits occurred at five (range 2-7) months and 12 (range 10-14) months post-discharge. Participants could also participate in specific nested studies (Tier 3) at selected sites.All participants were asked to consent to further follow-up for 25 years via linkage to their electronic healthcare records and to be re-contacted for further research.In total, 7935 participants were recruited from 83 UK sites: 5238 to Tier 1 and 2697 to Tier 2, between August 2020 and March 2022.Cohort data are held in a Trusted Research Environment and samples stored in a central biobank. Data and samples can be accessed upon request and subject to approvals

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification