Long-term (>10 years) prognostic value of dobutamine stress echocardiography in a high-risk cohort

The prognostic value of dobutamine stress echocardiography (DSE) at >10-year follow-up is unknown. The aim of this study was to assess the very long-term prognostic value of DSE in a high-risk cohort of patients with known or suspected coronary artery disease. This prospective, single-center study included 3,381 patients who underwent DSE from January 1990 to January 2003. Two-dimensional echocardiographic images were acquired at rest, during dobutamine stress, and during recovery. Follow-up events were collected and included overall mortality, cardiac death, nonfatal myocardial infarction, and revascularization. The incremental value of DSE in the prediction of selected end points was evaluated using multivariate Cox proportional hazard analysis. During a mean follow-up of 13 ± 3.2 years (range 7.3 to 20.5 years), there were 1,725 deaths (51%), of which 1,128 (33%) were attributed to cardiac causes. Patients with an abnormal DSE had a higher mortality rate (44% vs 35% at 15-year follow-up, p <0.001) than those with a normal DSE. When comparing echocardiographic variables at rest to variables at maximum dose dobutamine, the chi-square of the test improved from 842 to 870 (p <0.0001) and from 684 to 740 (p <0.0001) for all-cause mortality and cardiac death, respectively. DSE provided incremental value in predicting all-cause mortality, cardiac death, and hard cardiac events. There seems, however, to be a "warranty period" of approximately 7 years, when the survival curves of a normal and abnormal DSE no longer diverge

Applying Market Shaping Approaches to Increase Access to Assistive Technology: Summary of the Wheelchair Product Narrative

To accelerate access to assistive technology (AT), we need to leverage the capabilities and resources of the public, private, and non-profit sectors to harness innovation and break down barriers to access. Market shaping interventions can play a role in enhancing market efficiencies, coordinating and incentivizing the number of stakeholders involved in demand and supply-side activities. Across health sectors, market shaping has demonstrated its potential to enhance national governments’ or donors’ value-for-money, diversify the supply base, and increase reliability – ultimately increasing product and service delivery access for end users. These market shaping successes in other health areas have led practitioners to hypothesize that market shaping could also be applied to assistive technology markets. ATscale, the Global Partnership for AT, aims to mobilise global stakeholders to shape markets in line with a unified strategy. To inform this strategy, it is critical to identify specific interventions required to shape markets and overcome barriers. The first product undergoing analysis by ATscale is wheelchairs. The market for appropriate wheelchairs in low-and middle income countries (LMICs) is highly fragmented and characterized by limited government interest, investment, and a low willingness-to-pay. Moreover, the market is dominated by cheaper, low quality wheelchairs which fail to meet the needs of end-users. Non-profit organizations have attempted to fill the need for context-appropriate wheelchairs, but market uptake is limited. These initial findings led ATscale to believe that market shaping could support increased access to appropriate wheelchairs. This paper outlines what market shaping is, and how it can be applied to assistive technology at large -- using the aforementioned wheelchair product narrative as an illustrative case study and presents the proposed market shaping strategy for wheelchairs. ATscale will develop a framework to evaluate short-term interventions identified to achieve a healthy market and increase access. This paper provides an opportunity to obtain feedback from interested stakeholders on the market shaping strategy for wheelchairs, as well as the product narrative process to be undertaken for other priority AT

USTOPIA REQUIREMENTS THOUGHTS ON A USER-FRIENDLY SYSTEM FOR TRANSFORMATION OF PROGRAMS IN ABSTRACTO

Transformational programming is a program development method which is usually applied using 'pen and paper'. Since this requires a lot of clerical work (copying expressions, con- sistent substitution) which is tiresome and prone to error, some form of machine support is desirable. In this paper a number of systems are described that have already been built to this aim. Some of their shortcomings and limitations are identified. Based on experience with program transformation and transformation systems, a long list of features is given that would be useful in an 'utopian' transformation system. This list is presented using an orthogonal division of the problem area. A number of problems with the realisation of some aspects of our 'utopian' system are identified, and some areas for further research are indicated

Coordination Dynamics meets Active Inference and Artificial Intelligence (CD + AI2):A multi-pronged approach to understanding the dynamics of brain and the emergence of conscious agency

How do humans discover their ability to act on the world? By tethering a baby’s foot to a mobile (Fig. 1a) and measuring the motion of both in 3D, we explore how babies begin to make sense of their coordinative relationship with the world and realize their ability to make things happen (N= 16; mean age = 100.33 days). Machine and deep learning classification architectures (e.g., CapsNet) indicate that functionally connecting infants to a mobile via a tether influences the baby movement most where it matters, namely at the point of infant∼world connection (Table 1). Using dynamics as a guide, we have developed tools to identify the moment an infant switches from spontaneous to intentional action (Fig. 1b). Preliminary coordination dynamics analysis and active inference generative modeling indicate that moments of stillness hold important epistemic value for young infants discovering their ability to change the world around them (Fig. 1c). Finally, a model of slow~fast brain coordination dynamics based on a 3D extension of the Jirsa-Kelso Excitator successfully simulated the evolution of tethered foot activity as infants transition from spontaneous to ordered action. By tuning a small number of parameters, this model captures patterns of emergent goal-directed action (Fig. 1d). Meshing concepts, methods and tools of Active Inference, Artificial Intelligence and Coordination Dynamics at multiple levels of description, the CD + AI2 program of research aims to identify key control parameters that shift the infant system from spontaneous to intentional behavior. The potent combination of mathematical modeling and quantitative analysis along with empirical study allow us to express the emergence of agency in quantifiable, lawful terms

Coordination Dynamics meets Active Inference and Artificial Intelligence (CD + AI2):A multi-pronged approach to understanding the dynamics of brain and the emergence of conscious agency

How do humans discover their ability to act on the world? By tethering a baby’s foot to a mobile (Fig. 1a) and measuring the motion of both in 3D, we explore how babies begin to make sense of their coordinative relationship with the world and realize their ability to make things happen (N= 16; mean age = 100.33 days). Machine and deep learning classification architectures (e.g., CapsNet) indicate that functionally connecting infants to a mobile via a tether influences the baby movement most where it matters, namely at the point of infant∼world connection (Table 1). Using dynamics as a guide, we have developed tools to identify the moment an infant switches from spontaneous to intentional action (Fig. 1b). Preliminary coordination dynamics analysis and active inference generative modeling indicate that moments of stillness hold important epistemic value for young infants discovering their ability to change the world around them (Fig. 1c). Finally, a model of slow~fast brain coordination dynamics based on a 3D extension of the Jirsa-Kelso Excitator successfully simulated the evolution of tethered foot activity as infants transition from spontaneous to ordered action. By tuning a small number of parameters, this model captures patterns of emergent goal-directed action (Fig. 1d). Meshing concepts, methods and tools of Active Inference, Artificial Intelligence and Coordination Dynamics at multiple levels of description, the CD + AI2 program of research aims to identify key control parameters that shift the infant system from spontaneous to intentional behavior. The potent combination of mathematical modeling and quantitative analysis along with empirical study allow us to express the emergence of agency in quantifiable, lawful terms

Formalising the Continuous/Discrete Modeling Step

Formally capturing the transition from a continuous model to a discrete model is investigated using model based refinement techniques. A very simple model for stopping (eg. of a train) is developed in both the continuous and discrete domains. The difference between the two is quantified using generic results from ODE theory, and these estimates can be compared with the exact solutions. Such results do not fit well into a conventional model based refinement framework; however they can be accommodated into a model based retrenchment. The retrenchment is described, and the way it can interface to refinement development on both the continuous and discrete sides is outlined. The approach is compared to what can be achieved using hybrid systems techniques.Comment: In Proceedings Refine 2011, arXiv:1106.348

Small Vessel Ischemic Disease of the Brain and Brain Metastases in Lung Cancer Patients

Brain metastases occur commonly in patients with lung cancer. Small vessel ischemic disease is frequently found when imaging the brain to detect metastases. We aimed to determine if the presence of small vessel ischemic disease (SVID) of the brain is protective against the development of brain metastases in lung cancer patients.A retrospective cohort of 523 patients with biopsy confirmed lung cancer who had received magnetic resonance imaging of the brain as part of their standard initial staging evaluation was reviewed. Information collected included demographics, comorbidities, details of the lung cancer, and the presence of SVID of the brain. A portion of the cohort had the degree of SVID graded. The primary outcome measure was the portion of study subjects with and without SVID of the brain who had evidence of brain metastases at the time of initial staging of their lung cancer.109 patients (20.8%) had evidence of brain metastases at presentation and 345 (66.0%) had evidence of SVID. 13.9% of those with SVID and 34.3% of those without SVID presented with brain metastases (p<0.0001). In a model including age, diabetes mellitus, hypertension, hyperlipidemia, and tobacco use, SVID of the brain was found to be the only protective factor against the development of brain metastases, with an OR of 0.31 (0.20, 0.48; p<0.001). The grade of SVID was higher in those without brain metastases.These findings suggest that vascular changes in the brain are protective against the development of brain metastases in lung cancer patients

Sonication of heart valves detects more bacteria in infective endocarditis

Optimal antimicrobial treatment of infective endocarditis requires identification and susceptibility patterns of pathogens. Sonication of explanted heart valves could increase the identification and culture of pathogens, as shown in prosthetic joint and pacemaker/ICD infections. We tested 26 explanted heart valves from 20 patients with active definite endocarditis for added diagnostic value of sonication to the standard microbiological workup in a prospective diagnostic proof of concept study. Two sonication protocols (broth enrichment vs. centrifugation) were compared in an additional 35 negative control valves for contamination rates. We selected sonication/centrifugation based on acceptable false positive rates (11.4%; 4/35). Sonication/enrichment yielded many false positive results in negative controls (28.6%; 10/35), mainly Propionibacterium acnes (next-generation sequencing excluded technical problems). Compared to direct culture only, adding sonication/centrifugation (including molecular testing) significantly increased the diagnostic yield from 6/26 to 17/26 valves (p = 0.003). Most importantly, culture positives almost doubled (from 6 to 10), providing unique quantitative information about antimicrobial susceptibility. Even if direct molecular testing was added to the standard workup, sonication/centrifugation provided additional diagnostic information in a significant number of valves (8/26; 31%; p = 0.013). We concluded that sonication/centrifugation added relevant diagnostic information in the workup of heart valves with infective endocarditis, with acceptable contamination rates

Refinement-based verification of sequential implementations of Stateflow charts

Simulink/Stateflow charts are widely used in industry for the specification of control systems, which are often safety-critical. This suggests a need for a formal treatment of such models. In previous work, we have proposed a technique for automatic generation of formal models of Stateflow blocks to support refinement-based reasoning. In this article, we present a refinement strategy that supports the verification of automatically generated sequential C implementations of Stateflow charts. In particular, we discuss how this strategy can be specialised to take advantage of architectural features in order to allow a higher level of automation.Comment: In Proceedings Refine 2011, arXiv:1106.348