53 research outputs found
Validation of the DECAF score to predict hospital mortality in acute exacerbations of COPD
Background
Hospitalisation due to acute
exacerbations of COPD (AECOPD) is common, and
subsequent mortality high. The DECAF score was derived
for accurate prediction of mortality and risk strati
fi
cation
to inform patient care. We aimed to validate the DECAF
score, internally and externally, and to compare its
performance to other predictive tools.
Methods
The study took place in the two hospitals
within the derivation study (internal validation) and in
four additional hospitals (external validation) between
January 2012 and May 2014. Consecutive admissions
were identi
fi
ed by screening admissions and searching
coding records. Admission clinical data, including DECAF
indices, and mortality were recorded. The prognostic
value of DECAF and other scores were assessed by the
area under the receiver operator characteristic (AUROC)
curve.
Results
In the internal and external validation cohorts,
880 and 845 patients were recruited. Mean age was
73.1 (SD 10.3) years, 54.3% were female, and mean
(SD) FEV
1
45.5 (18.3) per cent predicted. Overall
mortality was 7.7%. The DECAF AUROC curve for
inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in
the internal cohort and 0.82 (95% CI 0.77 to 0.87) in
the external cohort, and was superior to other
prognostic scores for inhospital or 30-day mortality.
Conclusions
DECAF is a robust predictor of mortality,
using indices routinely available on admission. Its
generalisability is supported by consistent strong
performance; it can identify low-risk patients (DECAF
0
–
1) potentially suitable for Hospital at Home or early
supported discharge services, and high-risk patients
(DECAF 3
–
6) for escalation planning or appropriate early
palliation.
Trial registration number
UKCRN ID 14214
Antiferromagnetic interlayer exchange coupled Co₆₈B₃₂/Ir/Pt multilayers
Synthetic antiferromagnetic structures can exhibit the advantages of high velocity similarly to antiferromagnets with the additional benefit of being imaged and read-out through techniques applied to ferromagnets. Here, we explore the potential and limits of synthetic antiferromagnets to uncover ways to harness their valuable properties for applications. Two synthetic antiferromagnetic systems have been engineered and systematically investigated to provide an informed basis for creating devices with maximum potential for data storage, logic devices, and skyrmion racetrack memories. The two systems considered are (system 1) CoB/Ir/Pt of N repetitions with Ir inducing the negative coupling between the ferromagnetic layers and (system 2) two ferromagnetically coupled multilayers of CoB/Ir/Pt, coupled together antiferromagnetically with an Ir layer. From the hysteresis, it is found that system 1 shows stable antiferromagnetic interlayer exchange coupling between each magnetic layer up to N = 7. Using Kerr imaging, the two ferromagnetic multilayers in system 2 are shown to undergo separate maze-like switches during hysteresis. Both systems are also studied as a function of temperature and show different behaviors. Micromagnetic simulations predict that in both systems the skyrmion Hall angle is suppressed with the skyrmion velocity five times higher in system 1 than system 2
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
Discovery of distinct immune phenotypes using machine learning in pulmonary arterial hypertension
RATIONALE: Accumulating evidence implicates inflammation in pulmonary arterial hypertension (PAH) and therapies targeting immunity are under investigation, though it remains unknown if distinct immune phenotypes exist. OBJECTIVE: Identify PAH immune phenotypes based on unsupervised analysis of blood proteomic profiles. METHODS AND RESULTS: In a prospective observational study of Group 1 PAH patients evaluated at Stanford University (discovery cohort, n=281) and University of Sheffield (validation cohort, n=104) between 2008-2014, we measured a circulating proteomic panel of 48 cytokines, chemokines, and factors using multiplex immunoassay. Unsupervised machine learning (consensus clustering) was applied in both cohorts independently to classify patients into proteomic immune clusters, without guidance from clinical features. To identify central proteins in each cluster, we performed partial correlation network analysis. Clinical characteristics and outcomes were subsequently compared across clusters. Four PAH clusters with distinct proteomic immune profiles were identified in the discovery cohort. Cluster 2 (n=109) had low cytokine levels similar to controls. Other clusters had unique sets of upregulated proteins central to immune networks- cluster 1 (n=58)(TRAIL, CCL5, CCL7, CCL4, MIF), cluster 3 (n=77)(IL-12, IL-17, IL-10, IL-7, VEGF), and cluster 4 (n=37)(IL-8, IL-4, PDGF-β, IL-6, CCL11). Demographics, PAH etiologies, comorbidities, and medications were similar across clusters. Non-invasive and hemodynamic surrogates of clinical risk identified cluster 1 as high-risk and cluster 3 as low-risk groups. Five-year transplant-free survival rates were unfavorable for cluster 1 (47.6%, CI 35.4-64.1%) and favorable for cluster 3 (82.4%, CI 72.0-94.3%)(across-cluster p<0.001). Findings were replicated in the validation cohort, where machine learning classified four immune clusters with comparable proteomic, clinical, and prognostic features. CONCLUSIONS: Blood cytokine profiles distinguish PAH immune phenotypes with differing clinical risk that are independent of World Health Organization Group 1 subtypes. These phenotypes could inform mechanistic studies of disease pathobiology and provide a framework to examine patient responses to emerging therapies targeting immunity
Irish cardiac society - Proceedings of annual general meeting held 20th & 21st November 1992 in Dublin Castle
Target and distractor processing and the influence of load on the allocation of attention to task-irrelevant threat
This study investigated the characteristics of two distinct mechanisms of attention – stimulus enhancement and stimulus suppression – using an event-related potential (ERP) approach. Across three experiments, participants viewed sparse visual search arrays containing one target and one distractor. The main results of Experiments 1 and 2 revealed that whereas neural signals for stimuli that are not inherently salient could be directly suppressed without prior attentional enhancement, this was not the case for stimuli with motivational relevance (human faces). Experiment 3 showed that as task difficulty increased, so did the need for suppression of distractor stimuli. It also showed the preferential attentional enhancement of angry over neutral distractor faces, but only under conditions of high task difficulty, suggesting that the effects of distractor valence on attention are greatest when there are fewer available resources for distractor processing. The implications of these findings are considered in relation to contemporary theories of attention
Understanding the genetic complexity of puberty timing across the allele frequency spectrum
Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease
Accounting for heterogeneous variance components in multiple breed evaluations of beef traits in black and white cattle
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