Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are ...applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL
Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29-0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33-0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.
To improve the performance and signal integrity for printed circuit board designs, considering differential pairs in the escape routing is an important issue. Previous works use two-stage approaches, ...meeting points determining followed by differential pairs connecting, to generate a routing solution. However, existing approaches may produce either non-length-matching solutions or longer length-matching solutions. In this Letter, the authors propose an escape routing model with one-stage optimisation to simultaneously determine median points and route length-matching paths for all differential pairs. Experimental results show that their approach can significantly reduce maximum and average differential-pair skews with 100% length-matching results.
Layout migration is a fast methodology to generate the required layout for given circuits with different device attributes or different technology. By keeping the original layout topology, the ...previous design experience can help to keep the circuit performance. However, routing preservation is often not mentioned in previous layout migration techniques, which requires a complete rerouting to break the original style. Pan et al. (2015) proposed a topological slicing tree and a constrained delaunay triangulation (CDT) model to keep the routing style during migration. However, this approach may incur some missing nets after migration, which still requires tedious manual works to fix those nets. In this article, we propose a sequence pair (SP)-based placement migration methodology and a novel Cartesian detection line (CDL) model to preserve the routing styles in original layouts. By using the proposed approach, the routability information and routing behaviors can be preserved during layout migration. In order to prevent from missing nets, several refinement techniques are also proposed to fix unreasonable routing nets due to block displacement. In the experiments, the missing nets after migration can be reduced to almost zero with the proposed CDL model, which greatly reduces the extra design efforts.
Pulse oximetry is widely used in the clinical setting. The purpose of this validation study was to investigate the level of agreement between oxygen saturations measured by pulse oximeter (SpO
) and ...arterial blood gas (SaO
) in a range of oximeters in clinical use in Australia and New Zealand.
Paired SpO
and SaO
measurements were collected from 400 patients in one Australian and two New Zealand hospitals. The ages of the patients ranged from 18 to 95 years. Bias and limits of agreement were estimated. Sensitivity and specificity for detecting hypoxaemia, defined as SaO
< 90%, were also estimated.
The majority of participants were recruited from the Outpatient, Ward or High Dependency Unit setting. Bias, oximeter-measured minus arterial blood gas-measured oxygen saturation, was - 1.2%, with limits of agreement - 4.4 to 2.0%. SpO
was at least 4% lower than SaO
for 10 (2.5%) of the participants and SpO
was at least 4% higher than the SaO
in 3 (0.8%) of the participants. None of the participants with a SpO
≥ 92% were hypoxaemic, defined as SaO
< 90%. There were no clinically significant differences in oximetry accuracy in relation to clinical characteristics or oximeter brand.
In the majority of the participants, pulse oximetry was an accurate method to assess SaO
and had good performance in detecting hypoxaemia. However, in a small proportion of participants, differences between SaO
and SpO
could have clinical relevance in terms of patient monitoring and management. A SpO
≥ 92% indicates that hypoxaemia, defined as a SaO
< 90%, is not present.
Australian and New Zealand Clinical Trials Registry (ACTRN12614001257651). Date of registration: 2/12/2014.
As devices continue to shrink, the parameter shift due to process variation and aging effects has an increasing impact on the circuit yield and reliability. However, predicting how long a circuit can ...maintain its design yield above the design specification is difficult because the design yield changes during the aging process. Moreover, performing Monte Carlo (MC) simulation iteratively during aging analysis is infeasible. Therefore, most existing approaches ignore the continuity during simulations to obtain high speed, which may result in accumulation of extrapolation errors with time. In this paper, an incremental simulation technique is proposed for lifetime yield analysis to improve the simulation speed while maintaining the analysis accuracy. Because aging is often a gradual process, the proposed incremental technique is effective for reducing the simulation time. For yield analysis with degraded performance, this incremental technique also reduces the simulation time because each sample is the same circuit with small parameter changes in the MC analysis. When the proposed dynamic aging sampling technique is employed, 50× speedup can be obtained with almost no decline accuracy, which considerably improves the efficiency of lifetime yield analysis.
A Tree-Topology Multiplexer for Multiphase Clock System Lu, Hungwen; Su, Chauchin; Liu, Chien-Nan Jimmy
IEEE transactions on circuits and systems. I, Regular papers,
2009-Jan., 2009-01-00, 20090101, Letnik:
56, Številka:
1
Journal Article
Recenzirano
Odprti dostop
This paper proposes a tree-topology multiplexer (MUX) that employs a multiphase low-frequency clock rather than a high-frequency clock. Analysis and simulation results show that the proposed design ...can achieve higher bandwidth and be less sensitive to process variations than the conventional single-stage MUX. In order to verify the feasibility, this proposed design is integrated with a multiphase phase-locked loop and a low-voltage differential signaling driver in a 0.18- mum CMOS technology. Measured results indicate that the proposed design can operate up to 7 gigabits/s under 0.3-UI jitter limitation.
As design complexity is increased exponentially, electronic design automation (EDA) tools are essential to reduce design efforts. However, the analog layout design has still been done manually for ...decades because it is a sensitive and error-prone task. Tool-generated layouts are still not well-accepted by analog designers due to the performance loss under non-ideal effects. Most previous works focus on adding more layout constraints on the analog placement. Routing the nets is thus considered as a trivial step that can be done by typical digital routing methodology, which is to use vias to connect every horizontal and vertical lines. Those extra vias will significantly increase the wire loads and degrade the circuit performance. Therefore, in this article, a wire load oriented analog routing methodology is proposed to reduce the number of layer changing of each routing net. Wire load is considered in the optimization goal as well as the wire length to keep the circuit performance after layout, while the analog layout constraints like symmetry and length matching are still satisfied during routing. As shown in the experimental results, this approach significantly reduces the wire load and performance loss after layout with little overhead on wire length.
A 52-year-old man presented with palpitations and dyspnea. Extensive bilateral pulmonary emboli (PEs) were identified on computed tomography pulmonary angiogram. Transthoracic echocardiography ...demonstrated a mobile bi-atrial thrombus straddling the interatrial septum. Consensus decision of a multidisciplinary pulmonary embolus response team was made for emergency thrombectomy of the pulmonary and intra-cardiac clot. Intraoperatively, a patent foramen ovale was identified and repaired. He had an excellent outcome and was discharged home on oral anticoagulation. In this unique case of a bi-atrial thrombus and sub-massive PEs, we demonstrate the utility of dedicated pulmonary embolus response teams in providing rapid and individualized management decisions for complex PE patients.
Un homme de 52 ans s’est présenté avec des palpitations et une dyspnée. Des embolies pulmonaires (EP) bilatérales étendues ont été identifiées sur l'angiographie pulmonaire par tomodensitométrie. L'échocardiographie transthoracique a mis en évidence un thrombus mobile biauriculaire à cheval sur le septum interauriculaire. Une équipe multidisciplinaire spécialisée dans la réponse à l'embolie pulmonaire a décidé par consensus de procéder à une thrombectomie d'urgence du caillot pulmonaire et intracardiaque. En peropératoire, un foramen ovale a été identifié et réparé. Le patient a reçu un excellent pronostic et a été renvoyé chez lui sous anticoagulation orale. À travers ce cas inhabituel de thrombus biauriculaire et d'EP limitée, nous démontrons l'utilité d'équipes spécialisées dans la réponse aux embolies pulmonaires pour des décisions rapides et individualisées de prise en charge des patients souffrant d'EP complexes.
Simulation-based functional validation is still one of the primary approaches for verifying designs described in hardware description languages. Traditional code coverage metrics do not address the ...observability issue and may overestimate the extent of functional validation. Observability-based code coverage metric (OCCOM) is the first code coverage metric considering the essential observability issue. However, tags can only be observed or unobserved, providing only two levels of measurement (i.e., 1 and 0). Errors with lower opportunities to be observed may still be judged as observable, thus misleading the verification results. Therefore, instead of extending tag coverage, we develop a probabilistic observability measure and its efficient computation algorithm. Besides being used as a new OCCOM, our new measure can point out hard-to-observe points for inserting assertions to prevent bugs from hiding behind these points. Experimental results show that the detection of the injected errors and the degree of our observability measure are strongly related. The results also show that our fine-grained observability measure is less likely to overestimate the extent of validation with reasonable computation time.
Flexible electronics are a possible alternative for portable consumer applications and have many advantages. However, the circuit design for flexible electronics is still challenging, especially for ...sensitive analog circuits. Due to the different properties of flexible thin-film transistors (TFTs), conventional CMOS design techniques cannot be used directly on flexible electronics. Significant parameter variations and degradation effects of flexible TFTs further increase difficulties for circuit designers. In this paper, a reliability-aware circuit sizing approach is proposed for the analog circuits with flexible TFTs. The process variation, bending, and degradation effects of flexible TFTs in the optimization flow are considered simultaneously. Instead of optimizing the fresh yield and lifetime yield separately, a unified optimization approach is proposed to consider the two yield issues simultaneously. As shown in the experimental results, the proposed approach can further improve the lifetime yield and significantly reduce the design overhead with a fast computation time.
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