Identification of cardiac MRI thresholds for risk stratification in pulmonary arterial hypertension

Rationale: Pulmonary arterial hypertension (PAH) is a life-shortening condition. The European Society of Cardiology and European Respiratory Society and the REVEAL (North American Registry to Evaluate Early and Long-Term PAH Disease Management) risk score calculator (REVEAL 2.0) identify thresholds to predict 1-year mortality. Objectives: This study evaluates whether cardiac magnetic resonance imaging (MRI) thresholds can be identified and used to aid risk stratification and facilitate decision-making. Methods: Consecutive patients with PAH (n = 438) undergoing cardiac MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Center) MRI database. Thresholds were identified from a discovery cohort and evaluated in a test cohort. Measurements and Main Results: A percentage-predicted right ventricular end-systolic volume index threshold of 227% or a left ventricular end-diastolic volume index of 58 ml/m2 identified patients at low (10%) risk of 1-year mortality. These metrics respectively identified 63% and 34% of patients as low risk. Right ventricular ejection fraction >54%, 37–54%, and <37% identified 21%, 43%, and 36% of patients at low, intermediate, and high risk, respectively, of 1-year mortality. At follow-up cardiac MRI, patients who improved to or were maintained in a low-risk group had a 1-year mortality <5%. Percentage-predicted right ventricular end-systolic volume index independently predicted outcome and, when used in conjunction with the REVEAL 2.0 risk score calculator or a modified French Pulmonary Hypertension Registry approach, improved risk stratification for 1-year mortality. Conclusions: Cardiac MRI can be used to risk stratify patients with PAH using a threshold approach. Percentage-predicted right ventricular end-systolic volume index can identify a high percentage of patients at low-risk of 1-year mortality and, when used in conjunction with current risk stratification approaches, can improve risk stratification. This study supports further evaluation of cardiac MRI in risk stratification in PAH

Express: The incremental shuttle walk test predicts mortality in non-group 1 pulmonary hypertension: results from the ASPIRE Registry.

Pulmonary hypertension (PH) is classified into 5 groups based on disease etiology but there is only limited information on the prognostic value of exercise testing in non-Group 1 PH. In Group 1 PH the incremental shuttle walking test (ISWT) distance has been shown to correlate with pulmonary hemodynamics and predict survival without a ceiling-effect. This study assessed the ISWT in non-group 1 PH. Data were retrieved from the ASPIRE registry (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) for consecutive patients diagnosed with PH. Patients were required to have been systematically assessed as Group 2-5 PH and to have a baseline ISWT within 3 months of cardiac catheterization. Patients were stratified according to incremental shuttle walk test distance (ISWD) and ISWT distance percent predicted (ISWD%pred). 479 patients with non-Group 1 PH were identified. ISWD and ISWD%pred correlated significantly with symptoms and hemodynamic severity. ISWD and ISWD%pred predicted survival with no ceiling-effect. The test was prognostic in Groups 2, 3 and 4. ISWD and ISWD%pred and change in ISWD and ISWD%pred at 1 year were all significant predictors of outcome. In patients with non-Group 1 PH the Incremental Shuttle Walk Test is a simple non-invasive test that is easy to perform, is predictive of survival at baseline and follow-up, reflects change and can be used in the assessment of PH of any etiology

Incremental Shuttle Walking Test Distance and Autonomic Dysfunction Predict Survival in Pulmonary Arterial Hypertension

Background To ensure effective monitoring of pulmonary arterial hypertension (PAH), a simple, reliable assessment of exercise capacity applicable over a range of disease severity is needed. The aim of this study was to assess the ability of the incremental shuttle walk test (ISWT) to correlate with disease severity, measure sensitivity to change, and predict survival in PAH. Methods We enrolled 418 treatment-naïve patients with PAH with baseline ISWT within 3 months of cardiac catheterization. Clinical validity and prognostic value of ISWT distance were assessed at baseline and 1 year. Results ISWT distance was found to correlate at baseline with World Health Organization functional class, Borg score, and hemodynamics without a ceiling effect (all p 18 beats/min, highest SBP, change in SBP, and 3-minute SBP ratio) were significant predictors of survival (all p < 0.05). Conclusions In patients with PAH, the ISWT is simple to perform, allows assessment of maximal exercise capacity, is sensitive to treatment effect, predicts outcome, and has no ceiling effect. Also, measures of autonomic function made post-exercise predict survival in PAH

Search for the glueball candidates f0(1500) and fJ(1710) in gamma gamma collisions

Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f0(1500) and fJ(1710) via their decay to pi+pi-. No signal is observed and upper limits to the product of gamma gamma width and pi+pi- branching ratio of the f0(1500) and the fJ(1710) have been measured to be Gamma_(gamma gamma -> f0(1500)). BR(f0(1500)->pi+pi-) < 0.31 keV and Gamma_(gamma gamma -> fJ(1710)). BR(fJ(1710)->pi+pi-) < 0.55 keV at 95% confidence level.Comment: 10 pages, 3 figure

Search for supersymmetry with a dominant R-parity violating LQDbar couplings in e+e- collisions at centre-of-mass energies of 130GeV to 172 GeV

A search for pair-production of supersymmetric particles under the assumption that R-parity is violated via a dominant LQDbar coupling has been performed using the data collected by ALEPH at centre-of-mass energies of 130-172 GeV. The observed candidate events in the data are in agreement with the Standard Model expectation. This result is translated into lower limits on the masses of charginos, neutralinos, sleptons, sneutrinos and squarks. For instance, for m_0=500 GeV/c^2 and tan(beta)=sqrt(2) charginos with masses smaller than 81 GeV/c^2 and neutralinos with masses smaller than 29 GeV/c^2 are excluded at the 95% confidence level for any generation structure of the LQDbar coupling.Comment: 32 pages, 30 figure

Maximal exercise testing using the incremental shuttle walking test can be used to risk stratify patients with pulmonary arterial hypertension

Rationale: Exercise capacity predicts mortality in pulmonary arterial hypertension but limited data exist on the routine use of maximal exercise testing. Objectives: This study evaluates a simple to perform maximal test, the incremental shuttle walking test, and its utility in risk stratification in pulmonary arterial hypertension (PAH). Methods: Consecutive patients with pulmonary hypertension were identified from the ASPIRE registry (2001-2018). Thresholds for levels of risk were identified at baseline, tested at follow-up and incorporation into current risk stratification approaches assessed. Results: Of 4524 treatment-naïve patients with pulmonary hypertension who underwent maximal exercise testing 1,847 patients had PAH. A step-wise reduction in one-year-mortality was seen between levels 1 (≤30m; 32% mortality) and 7 (340-420m; 1% mortality) with no mortality for levels 8-12 (≥430m) in idiopathic and connective tissue disease related PAH. Thresholds derived at baseline of ≤180m (>10%; high-risk), 190-330m (5-10%; intermediate-risk) and ≥340m (<5%; low-risk of one-year mortality) were applied at follow-up and also accurately identified levels of risk. Thresholds were incorporated into the REVEAL 2.0 risk score calculator and French low-risk approach to risk stratification and distinct categories of risk remained. Conclusion: We have demonstrated that maximal exercise testing in PAH stratifies mortality-risk at baseline and follow-up. This study highlights the potential value of the incremental shuttle walking test as an alternative to the 6-minute-walk-test, combining some of the advantages of maximal exercise testing whilst maintaining the simplicity of a simple to perform field test

Shop stewards’ leadership, left-wing activism and collective workplace union organisation

Providing an account of the dynamic interrelationship between shop steward leadership and membership interaction, Ralph Darlington focuses particular attention on the much-neglected crucial role that left-wing political activists can play in shaping the nature of collective workplace relations

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes

Search for Bs0B^{0}_{s} oscillations using inclusive lepton events

A search for Bs oscillations is performed using a sample of semileptonic b-hadron decays collected by the ALEPH experiment during 1991-1995. Compared to previous inclusive lepton analyses, the prop er time resolution and b-flavour mistag rate are significantly improved. Additional sensitivity to Bs mixing is obtained by identifying subsamples of events having a Bs purity which is higher than the average for the whole data sample. Unbinned maximum likelihood amplitude fits are performed to derive a lower limit of Dms>9.5 ps-1 at 95% CL. Combining with the ALEPH Ds based analyses yields Dms>9.6 ps-1 at 95% CL.A search for B0s oscillations is performed using a sample of semileptonic b-hadron decays collected by the ALEPH experiment during 1991-1995. Compared to previous inclusive lepton analyses, the proper time resolution and b-flavour mistag rate are significantly improved. Additional sensitivity to B0s mixing is obtained by identifying subsamples of events having a B0s purity which is higher than the average for the whole data sample. Unbinned maximum likelihood amplitude fits are performed to derive a lower limit of Deltam_s>9.5ps^-1 at 95% CL. Combining with the ALEPH D-s based analyses yields Deltam_s>9.6ps^-1 at 95% CL