Rhythm and Vowel Quality in Accents of English

In a sample of 27 speakers of Scottish Standard English two notoriously variable consonantal features are investigated: the contrast of /m/ and /w/ and non-prevocalic /r/, the latter both in terms of its presence or absence and the phonetic form it takes, if present. The pattern of realisation of non-prevocalic /r/ largely confirms previously reported findings. But there are a number of surprising results regarding the merger of /m/ and /w/ and the loss of non-prevocalic /r/: While the former is more likely to happen in younger speakers and females, the latter seems more likely in older speakers and males. This is suggestive of change in progress leading to a loss of the /m/ - /w/ contrast, while the variation found in non-prevocalic /r/ follows an almost inverse sociolinguistic pattern that does not suggest any such change and is additionally largely explicable in language-internal terms. One phenomenon requiring further investigation is the curious effect direct contact with Southern English accents seems to have on non-prevocalic /r/: innovation on the structural level (i.e. loss) and conservatism on the realisational level (i.e. increased incidence of [r] and [r]) appear to be conditioned by the same sociolinguistic factors

Integrated care and optimal management of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) may occur as an idiopathic process or as a component of a variety of diseases, including connective tissue diseases, congenital heart disease, and exposure to appetite suppressants or infectious agents such as HIV. Untreated, it is a potentially devastating disease; however, diagnosis can be difficult due to the non-specific nature of symptoms during the early stages, and the fact that patients often present to a range of different medical specialties. The past decade has seen remarkable improvements in our understanding of the pathology associated with the condition and the development of PAH-specific therapies with the ability to alter the natural history of the disease. This article reviews the evidence for screening and diagnosis of susceptible patient groups and discusses treatment selection and recommendations based on data available from randomized controlled trials. In addition, due to the complexity of the diagnostic evaluation required and the treatment options available, this review mandates for a multidisciplinary approach to the management of PAH. We discuss the roles and organizational structure of a specialized PAH center in Perth, Western Australia to highlight these issues

Ejection fraction and mortality: A nationwide register-based cohort study of 499 153 women and men

Aims: We investigated the sex-based risk of mortality across the spectrum of left ventricular ejection fraction (LVEF) in a large cohort of patients in Australia. Methods and results: Quantified levels of LVEF from 237 046 women (48.1%) and 256 109 men undergoing first-time, routine echocardiography (2000–2019) were linked to 119 232 deaths (median 5.6 years of follow-up). Overall, 17.6% of men vs. 8.3% of women had an LVEF P\u3c 0.001] in women and 1.21 (95% CI 1.05–1.39; P = 0.008) in men. In women, an LVEF of 60.0–64.9% was also associated with a HR 1.33 (95% CI 1.16–1.52; P\u3c 0.001) for cardiovascular-related mortality. These associations were most striking in women and men aged Conclusions: Among patients investigated for suspected or established cardiovascular disease, we found clinically relevant sex-based differences in the distribution and mortality associated with an LVE

Prevalence of pulmonary hypertension in mitral regurgitation and its influence on outcomes

Objective: Pulmonary hypertension (PHT) commonly coexists with significant mitral regurgitation (MR), but its prevalence and prognostic importance have not been well characterised. In a large cohort of adults with moderate or greater MR, we aimed to describe the prevalence and severity of PHT and assess its influence on outcomes. Methods: In this retrospective study, we analysed the National Echocardiography Database of Australia (data from 2000 to 2019). Adults with an estimated right ventricular systolic pressure (eRVSP), left ventricular ejection fraction >50% and with moderate or greater MR were included (n=9683). These subjects were then categorised according to their eRVSP. The relationship between PHT severity and mortality outcomes was evaluated (median follow-up of 3.2 years, IQR 1.3–6.2 years). Results: Subjects were aged 76±12 years, and 62.6% (6038) were women. Overall, 959 (9.9%) had no PHT, and 2952 (30.5%), 3167 (32.7%), 1588 (16.4%) and 1017 (10.5%) patients had borderline, mild, moderate and severe PHT, respectively. A ‘typical left heart disease’ phenotype was identified with worsening PHT, showing rising E:e′, right and left atrial sizes increasing progressively, from no PHT to severe PHT (p<0.0001, for all). With increasing PHT severity, 1- and 5-year actuarial mortality increased from 8.5% and 33.0% to 39.7% and 79.8%, respectively (p<0.0001). Similarly, adjusted survival analysis showed the risk of long-term mortality progressively increased with higher eRVSP levels (adjusted HR 1.20–2.86, borderline to severe PHT, p<0.0001 for all). A mortality inflection was apparent at an eRVSP level >34.00 mm Hg (HR 1.27, CI 1.00–1.36). Conclusions: In this large study, we report on the importance of PHT in patients with MR. Mortality increases as PHT becomes more severe from an eRVSP of 34 mm Hg onwards

Prevalence and outcomes of low‐gradient severe aortic stenosis—from the National Echo Database of Australia

Background: The prevalence and outcomes of the different subtypes of severe low‐gradient aortic stenosis (AS) in routine clinical cardiology practice have not been well characterized. Methods and Results: Data were derived from the National Echocardiography Database of Australia. Of 192 060 adults (aged 62.8±17.8 [mean±SD] years) with native aortic valve profiling between 2000 and 2019, 12 013 (6.3%) had severe AS. Of these, 5601 patients (47%) had high‐gradient and 6412 patients (53%) had low‐gradient severe AS. The stroke volume index was documented in 2741 (42.7%) patients with low gradient; 1750 patients (64%) with low flow, low gradient (LFLG); and 991 patients with normal flow, low gradient. Of the patients with LFLG, 1570 (89.7%) had left ventricular ejection fraction recorded; 959 (61%) had paradoxical LFLG (preserved left ventricular ejection fraction), and 611 (39%) had classical LFLG (reduced left ventricular ejection fraction). All‐cause and cardiovascular‐related mortality were assessed in the 8162 patients with classifiable severe AS subtype during a mean±SD follow‐up of 88±45 months. Actual 1‐year and 5‐year all‐cause mortality rates varied across these groups and were 15.8% and 49.2% among patients with high‐gradient severe AS, 11.6% and 53.6% in patients with normal‐flow, low‐gradient severe AS, 16.9% and 58.8% in patients with paradoxical LFLG severe AS, and 30.5% and 72.9% in patients with classical LFLG severe AS. Compared with patients with high‐gradient severe AS, the 5‐year age‐adjusted and sex‐adjusted mortality risk hazard ratios were 0.94 (95% CI, 0.85–1.03) in patients with normal‐flow, low‐gradient severe AS; 1.01 (95% CI, 0.92–1.12) in patients with paradoxical LFLG severe AS; and 1.65 (95% CI, 1.48–1.84) in patients with classical LFLG severe AS. Conclusions: Approximately half of those patients with echocardiographic features of severe AS in routine clinical practice have low‐gradient hemodynamics, which is associated with long‐term mortality comparable with or worse than high‐gradient severe AS. The poorest survival was associated with classical LFLG severe AS

Enhanced detection of severe aortic stenosis via artificial intelligence: a clinical cohort study

Objective We developed an artificial intelligence decision support algorithm (AI-DSA) that uses routine echocardiographic measurements to identify severe aortic stenosis (AS) phenotypes associated with high mortality.Methods 631 824 individuals with 1.08 million echocardiograms were randomly spilt into two groups. Data from 442 276 individuals (70%) entered a Mixture Density Network (MDN) model to train an AI-DSA to predict an aortic valve area <1 cm2, excluding all left ventricular outflow tract velocity or dimension measurements and then using the remainder of echocardiographic measurement data. The optimal probability threshold for severe AS detection was identified at the f1 score probability of 0.235. An automated feature also ensured detection of guideline-defined severe AS. The AI-DSA’s performance was independently evaluated in 184 301 (30%) individuals.Results The area under receiver operating characteristic curve for the AI-DSA to detect severe AS was 0.986 (95% CI 0.985 to 0.987) with 4622/88 199 (5.2%) individuals (79.0±11.9 years, 52.4% women) categorised as ‘high-probability’ severe AS. Of these, 3566 (77.2%) met guideline-defined severe AS. Compared with the AI-derived low-probability AS group (19.2% mortality), the age-adjusted and sex-adjusted OR for actual 5-year mortality was 2.41 (95% CI 2.13 to 2.73) in the high probability AS group (67.9% mortality)—5-year mortality being slightly higher in those with guideline-defined severe AS (69.1% vs 64.4%; age-adjusted and sex-adjusted OR 1.26 (95% CI 1.04 to 1.53), p=0.021).Conclusions An AI-DSA can identify the echocardiographic measurement characteristics of AS associated with poor survival (with not all cases guideline defined). Deployment of this tool in routine clinical practice could improve expedited identification of severe AS cases and more timely referral for therapy

An evaluation of Admedus' tissue engineering process-treated (ADAPT) bovine pericardium patch (CardioCel) for the repair of cardiac and vascular defects

Tissue engineers have been seeking the ‘Holy Grail’ solution to calcification and cytotoxicity of implanted tissue for decades. Tissues with all of the desired qualities for surgical repair of congenital heart disease (CHD) are lacking. An anti-calcification tissue engineering process (ADAPT® TEP) has been developed and applied to bovine pericardium (BP) tissue (CardioCel®, AdmedusRegen Pty Ltd, Perth, WA, Australia) to eliminate cytotoxicity, improve resistance to acute and chronic inflammation, reduce calcification and facilitate controlled tissue remodeling. Clinical data in pediatric patients, and additional pre-market authorized prescriber data demonstrate that CardioCel performs extremely well in the short term and is safe and effective for a range of congenital heart deformations. These data are supported by animal studies which have shown no more than normal physiologic levels of calcification, with good durability, biocompatibility and controlled healing

Markers of elevated left ventricular filling pressure are associated with increased mortality in nonsevere aortic stenosis

Background: Echocardiographic measures of elevated left ventricular filling pressures are associated with an adverse prognosis. The aim of this study was to determine the relationship between acute (ratio of early transmitral flow to mitral annular velocities; E/e’) and chronic (indexed left atrial volume; LAVI) markers of left ventricular filling pressure (LVFP) and mortality in patients with non-severe aortic stenosis (AS), within the National Echo Database of Australia cohort. We hypothesised that they would reflect the early haemodynamic consequences of AS and be associated with increased mortality in this setting. Methods: The first record for patients 18 years or over showing hemodynamically significant but non-severe (mild or moderate) AS (mean pressure gradient ≥10 to \u3c40mmHg and AVA\u3e1cm2) was analysed. Baseline demographics and echocardiographic variables were compared to patients without AS (mean pressure gradient \u3c10mmHg). Mortality linkage data were available for all patients. Results: Of 78,886 patients with aortic valve mean pressure gradient \u3c40mmHg and AVA\u3e1cm2, 13,768 (17%) were identified with non-severe AS (aortic valve mean pressure gradient 10-40mmHg), of which 57% were male (mean age 73 ±13.4 years) with a median follow-up of 3.4 years (interquartile range: 1.7-6.1 years). In unadjusted models, non-severe AS and a LAVI\u3e34ml/m2 [Hazard Ratio (HR)=2.29 (95% CI 2.03-2.58)], an E/e’\u3e14 [HR=2.27 (95% CI 2.08-2.49)], a left ventricular ejection fraction (LVEF) \u3c50% [HR 2.82 (95% CI 2.50-3.19)], and a tricuspid regurgitation (TR) peak velocity\u3e280cm/s [HR=2.54 (95% CI 2.30-2.80)] were associated with increased mortality hazard. The effect remained independent when combined in a multi-variable model. Conclusions: Indices of elevated LVFP are independently associated with death in non-severe AS. Risk stratification models incorporating these variables may identify patients at risk of complications, warranting closer surveillance and possibly earlier intervention

Adverse prognostic impact of even mild or moderate tricuspid regurgitation: insights from the National Echocardiography Database of Australia

Background: The prevalence and prognostic impact of tricuspid regurgitation (TR) remains incompletely characterized. Methods: The distribution of TR severity was analyzed in 439,558 adults (mean age 62.1 ±17.8 years, 51.5% men) being investigated for heart disease, from 2000-2019, by 25 centers contributing to the National Echocardiography Database of Australia. Survival status and cause of death were ascertained, in all adults, from the National Death Index of Australia. The relationship between TR severity and mortality was examined. Results: Of those studied, 311,604 (70.9%) had no/trivial TR; 94,172 (21.4%) mild TR; 26,056 (5.9%) moderate TR; and 7,726 (1.8%) severe TR. During a median 4.1 years (interquartile range 2.2-7.0 years) follow up, 109,004 died (49% from cardiovascular causes). Moderate or greater TR was associated with older age and female sex (p<0.001). Individuals with moderate and severe TR had a 2.0- to 3.2-fold increased risk of all-cause long-term mortality after adjustment for age and sex, compared to those with no/trivial TR (p<0.001 for both comparisons). Even those with mild TR had a significantly increased risk for mortality (HR 1.29, 95% CI 1.27-1.31). In fully adjusted models, including for RV systolic pressure, atrial fibrillation and significant left-heart disease, there remained a 1.24 to 2.65-fold increased risk of mortality with mild (HR 1.24, 95% CI 1.23-1.26), moderate (HR 1.72, 95% CI 1.68-1.75) or severe TR (HR 2.65, 95% CI 2.57-2.73), compared to those with no/trivial TR (p<0.001 for all). Conclusions: TR is a common condition in adults referred for echocardiography. Moreover, even in the presence of other cardiac disease, increasing grades of TR are independently associated with increasing risks of CV and all-cause mortality. Furthermore, we show that even mild TR is independently associated with a significant increase in mortality