Caveat Anicula! Beware of the Quiet Little Old Ladies : Demographics, Pharmacotherapy, Survival and Readmissions in a 10 Year Cohort of Heart Failure Patients with Preserved Systolic Function

Objective--To determine whether heart failure with preserved systolic function (HFPSF) has different natural history from left ventricular systolic dysfunction (LVSD). Design and setting--A retrospective analysis of 10 years of data (for patients admitted between 1 July 1994 and 30 June 2004, and with a study census date of 30 June 2005) routinely collected as part of clinical practice in a large tertiary referral hospital.Main outcome measures-- Sociodemographic characteristics, diagnostic features, comorbid conditions, pharmacotherapies, readmission rates and survival.Results--Of the 2961 patients admitted with chronic heart failure, 753 had echocardiograms available for this analysis. Of these, 189 (25%) had normal left ventricular size and systolic function. In comparison to patients with LVSD, those with HFPSF were more often female (62.4% v 38.5%; P = 0.001), had less social support, and were more likely to live in nursing homes (17.9% v 7.6%; P < 0.001), and had a greater prevalence of renal impairment (86.7% v 6.2%; P = 0.004), anaemia (34.3% v 6.3%; P = 0.013) and atrial fibrillation (51.3% v 47.1%; P = 0.008), but significantly less ischaemic heart disease (53.4% v 81.2%; P = 0.001). Patients with HFPSF were less likely to be prescribed an angiotensin-converting enzyme inhibitor (61.9% v 72.5%; P = 0.008); carvedilol was used more frequently in LVSD (1.5% v 8.8%; P < 0.001). Readmission rates were higher in the HFPSF group (median, 2 v 1.5 admissions; P = 0.032), particularly for malignancy (4.2% v 1.8%; P < 0.001) and anaemia (3.9% v 2.3%; P < 0.001). Both groups had the same poor survival rate (P = 0.912). Conclusions--Patients with HFPSF were predominantly older women with less social support and higher readmission rates for associated comorbid illnesses. We therefore propose that reduced survival in HFPSF may relate more to comorbid conditions than suboptimal cardiac management.

Which components of heart failure programs are effective? A meta-analysis of the outcomes of structured telephone support or telemonitoring as the primary component of heart failure management in 9,560 patients (Abridged Cochrane Review)

Aims--Telemonitoring (TM) and structured telephone support (STS) have the potential to deliver specialised management to more patients with chronic heart failure (CHF), but their efficacy is still to be proven. Objectives To review randomised controlled trials (RCTs) of TM or STS on all- cause mortality and all-cause and CHF-related hospitalisations in patients with CHF, as a non-invasive remote model of specialised disease-management intervention.--Methods and Results--Data sources:We searched 15 electronic databases and hand-searched bibliographies of relevant studies, systematic reviews, and meeting abstracts. Two reviewers independently extracted all data. Study eligibility and participants: We included any randomised controlled trials (RCT) comparing TM or STS to usual care of patients with CHF. Studies that included intensified management with additional home or clinic visits were excluded. Synthesis: Primary outcomes (mortality and hospitalisations) were analysed; secondary outcomes (cost, length of stay, quality of life) were tabulated.--Results: Thirty RCTs of STS and TM were identified (25 peer-reviewed publications (n=8,323) and five abstracts (n=1,482)). Of the 25 peer-reviewed studies, 11 evaluated TM (2,710 participants), 16 evaluated STS (5,613 participants) and two tested both interventions. TM reduced all-cause mortality (risk ratio (RR 0•66 [95% CI 0•54-0•81], p<0•0001) and STS showed similar trends (RR 0•88 [95% CI 0•76-1•01], p=0•08). Both TM (RR 0•79 [95% CI 0•67-0•94], p=0•008) and STS (RR 0•77 [95% CI 0•68-0•87], p<0•0001) reduced CHF-related hospitalisations. Both interventions improved quality of life, reduced costs, and were acceptable to patients. Improvements in prescribing, patient-knowledge and self-care, and functional class were observed.--Conclusion: TM and STS both appear effective interventions to improve outcomes in patients with CHF.

The probability archive : from essence to uncertainty in the growth of knowledge

From a ‘cultural science’ perspective, this paper traces one aspect of a more general shift, from the realist representational regime of modernity to the productive DIY systems of the internet era. It argues that collecting and archiving is transformed by this change. Modern museums – and also broadcast television – were based on determinist or ‘essence’ theory; while internet archives like YouTube (and the internet as an archive) are based on ‘probability’ theory. The paper goes through the differences between modernist ‘essence’ and postmodern ‘probability’; starting from the obvious difference that in a museum each object is selected by experts for its intrinsic properties, while on the internet you don’t know what you will find. The status of individual objects is uncertain, although the productivity of the overall archive is unlimited. The paper links these differences with changes in contemporary culture – from a Newtonian to a quantum universe, progress to risk, institutional structure to evolutionary change, objectivity to uncertainty, identity to performance. Borrowing some of its methodology from science fiction, the paper uses examples from museums and online archives, ranging from the oldest stone tool in the world to the latest tribute vid on the net.

Ryanodine receptor phosphorylation in human heart failure

Heart failure is a complex disorder, characterized by activation of the sympathetic nervous system, leading to dysregulated Ca2+ homeostasis in cardiac myocytes and tissue remodeling. In a variety of diseases, cardiac malfunction is associated with aberrant fluxes of Ca2+ across both the surface membrane and the internal Ca2+ store, the sarcoplasmic reticulum (SR). One prominent hypothesis residues is that in heart failure, the activity of the ryanodine receptor (RyR2) Ca2+ release channel in the SR is increased due to excess phosphorylation and that this contributes to excess SR Ca2+ leak in diastole, reduced SR Ca2+ load and decreased contractility (Huke & Bers, 2008). There is controversy over which serine residues in RyR2 are hyperphosphorylated in animal models of heart failure and whether this is via the CaMKII or the PKA-linked signaling pathway. S2808, S2814 and S2030 in RyR2 have been variously claimed to be hyperphosphorylated. Our aim was to examine the degree of phosphorylation of these residues in RyR2 from failing human hearts. The use of human tissue was approved by the Human Research Ethics Committee, The Prince Charles Hospital, EC28114. Left ventricular tissue samples were obtained from an explanted heart of a patient with endstage heart failure (Emery Dreifuss Muscular Dystrophy with cardiomyopathy) and non-failing tissue was from a patient with cystic fibrosis undergoing heart-lung transplantation with no history of heart disease. SR vesicles were prepared as described by Laver et al. (1995) and examined with SDS-Page and Western Blot. Transferred proteins were probed with antibodies to detect total protein phosphorylation, phosphorylation of RyR2 serine residues S2808, S2814, S2030 and for the key proteins calsequestrin, triadin, junctin and FKBP12.6. To avoid membrane stripping artifact, each membrane was exposed to one phosphorylation-specific antibody and signal densities quantified using Bio-Rad Quantity One software. We found no distinguishable difference between failing and healthy hearts in the protein expression levels of RyR2, triadin, junctin or calsequestrin. We found an expected upregulation of total RyR2 phosphorylation in the failing heart sample, compared to a matched amount of RyR2 (quantified using densiometry) in healthy heart. Probing with antibodies detecting only the phosphorylated form of the specific RyR2 residues showed that the increase in total RyR2 phosphorylation in the failing heart was due to hyperphosphorylation of S2808 and S2814. We found that S2030 phosphorylation levels were unchanged in human heart failure. Interestingly, we found that S2030 has a basal level of phosphorylation in the healthy human heart, different from the absence of basal phosphorylation recently reported in rodent heart (Huke & Bers, 2008). Finally, preliminary results indicate that less FKBP 12.6 is associated with RyR2 in the failing heart, possibly as a consequence of PKA activation. In conclusion, residues S2808 and S2814 are hyperphosphorylated in human heart failure, presumably due to upregulation of the CaMKII and/or PKA signaling pathway as a result of chronic activation of the sympathetic nervous system. Such changes in RyR2 phosphorylation are believed to contribute to the leaky RyR2 phenotype associated with heart failure, which increases the incidence of arrhythmia and contributes to the severely impaired contractile performance of the failing heart. Huke S & Bers DM. (2008). Ryanodine receptor phosphorylation at serine 2030, 2808 and 2814 in rat cardiomyocytes. Biochemical and Biophysical Research Communications 376, 80-85. Laver DR, Roden LD, Ahern GP, Eager KR, Junankar PR & Dulhunty AF. (1995). Cytoplasmic Ca2+ inhibits the ryanodine receptor from cardiac muscle. Journal of Membrane Biology 147, 7-22. Proceedings

Efficient control of an autonomous underwater vehicle while accounting for thruster failure

This paper is concerned with the design and implementation of control strategies onto a test-bed vehicle with six degrees-of-freedom. We design our trajectories to be efficient in time and in power consumption. Moreover, we also consider cases when actuator failure can arise and discuss alternate control strategies in this situation. Our calculations are supplemented by experimental results.

Noise robust voice activity detection using normal probability testing and time-domain histogram analysis

This paper presents a method of voice activity detection (VAD) suitable for high noise scenarios, based on the fusion of two complementary systems. The first system uses a proposed non-Gaussianity score (NGS) feature based on normal probability testing. The second system employs a histogram distance score (HDS) feature that detects changes in the signal through conducting a template-based similarity measure between adjacent frames. The decision outputs by the two systems are then merged using an open-by-reconstruction fusion stage. Accuracy of the proposed method was compared to several baseline VAD methods on a database created using real recordings of a variety of high-noise environments.

Flight testing of an augmented separation management system providing separation protection during failure of the central communication network

Future air traffic management concepts often involve the proposal of automated separation management algorithms that replaces human air traffic controllers. This paper proposes a new type of automated separation management algorithm (based on the satisficing approach) that utilizes inter-aircraft communication and a track file manager (or bank of Kalman filters) that is capable of resolving conflicts during periods of communication failure. The proposed separation management algorithm is tested in a range of flight scenarios involving during periods of communication failure, in both simulation and flight test (flight tests were conducted as part of the Smart Skies project). The intention of the conducted flight tests was to investigate the benefits of using inter-aircraft communication to provide an extra layer of safety protection in support air traffic management during periods of failure of the communication network. These benefits were confirmed.

Reliability analysis and economic equipment replacement appraisal for substation and sub-transmission systems with explicit inclusion of non-repairable failures

The modern society has come to expect the electrical energy on demand, while many of the facilities in power systems are aging beyond repair and maintenance. The risk of failure is increasing with the aging equipments and can pose serious consequences for continuity of electricity supply. As the equipments used in high voltage power networks are very expensive, economically it may not be feasible to purchase and store spares in a warehouse for extended periods of time. On the other hand, there is normally a significant time before receiving equipment once it is ordered. This situation has created a considerable interest in the evaluation and application of probability methods for aging plant and provisions of spares in bulk supply networks, and can be of particular importance for substations. Quantitative adequacy assessment of substation and sub-transmission power systems is generally done using a contingency enumeration approach which includes the evaluation of contingencies, classification of the contingencies based on selected failure criteria. The problem is very complex because of the need to include detailed modelling and operation of substation and sub-transmission equipment using network flow evaluation and to consider multiple levels of component failures. In this thesis a new model associated with aging equipment is developed to combine the standard tools of random failures, as well as specific model for aging failures. This technique is applied in this thesis to include and examine the impact of aging equipments on system reliability of bulk supply loads and consumers in distribution network for defined range of planning years. The power system risk indices depend on many factors such as the actual physical network configuration and operation, aging conditions of the equipment, and the relevant constraints. The impact and importance of equipment reliability on power system risk indices in a network with aging facilities contains valuable information for utilities to better understand network performance and the weak links in the system. In this thesis, algorithms are developed to measure the contribution of individual equipment to the power system risk indices, as part of the novel risk analysis tool. A new cost worth approach was developed in this thesis that can make an early decision in planning for replacement activities concerning non-repairable aging components, in order to maintain a system reliability performance which economically is acceptable. The concepts, techniques and procedures developed in this thesis are illustrated numerically using published test systems. It is believed that the methods and approaches presented, substantially improve the accuracy of risk predictions by explicit consideration of the effect of equipment entering a period of increased risk of a non-repairable failure.

A probability-based approach for assessing the relationship between crash accidents and pavement properties

Skid resistance is a condition parameter characterising the contribution that a road makes to the friction between a road surface and a vehicle tyre. Studies of traffic crash histories around the world have consistently found that a disproportionate number of crashes occur where the road surface has a low level of surface friction and/or surface texture, particularly when the road surface is wet. Various research results have been published over many years and have tried to quantify the influence of skid resistance on accident occurrence and to characterise a correlation between skid resistance and accident frequency. Most of the research studies used simple statistical correlation methods in analysing skid resistance and crash data.----- ------ Preliminary findings of a systematic and extensive literature search conclude that there is rarely a single causation factor in a crash. Findings from research projects do affirm various levels of correlation between skid resistance and accident occurrence. Studies indicate that the level of skid resistance at critical places such as intersections, curves, roundabouts, ramps and approaches to pedestrian crossings needs to be well maintained.----- ----- Management of risk is an integral aspect of the Queensland Department of Main Roads (QDMR) strategy for managing its infrastructure assets. The risk-based approach has been used in many areas of infrastructure engineering. However, very limited information is reported on using risk-based approach to mitigate crash rates related to road surface. Low skid resistance and surface texture may increase the risk of traffic crashes.----- ----- The objectives of this paper are to explore current issues of skid resistance in relation to crashes, to provide a framework of probability-based approach to be adopted by QDMR in assessing the relationship between crash accidents and pavement properties, and to explain why the probability-based approach is a suitable tool for QDMR in order to reduce accident rates due to skid resistance.

Identifying relationship between skid resistance, road characteristics and crashes using probability-based risk approach

Road accidents are of great concerns for road and transport departments around world, which cause tremendous loss and dangers for public. Reducing accident rates and crash severity are imperative goals that governments, road and transport authorities, and researchers are aimed to achieve. In Australia, road crash trauma costs the nation A$ 15 billion annually. Five people are killed, and 550 are injured every day. Each fatality costs the taxpayer A$1.7 million. Serious injury cases can cost the taxpayer many times the cost of a fatality. Crashes are in general uncontrolled events and are dependent on a number of interrelated factors such as driver behaviour, traffic conditions, travel speed, road geometry and condition, and vehicle characteristics (e.g. tyre type pressure and condition, and suspension type and condition). Skid resistance is considered one of the most important surface characteristics as it has a direct impact on traffic safety. Attempts have been made worldwide to study the relationship between skid resistance and road crashes. Most of these studies used the statistical regression and correlation methods in analysing the relationships between skid resistance and road crashes. The outcomes from these studies provided mix results and not conclusive. The objective of this paper is to present a probability-based method of an ongoing study in identifying the relationship between skid resistance and road crashes. Historical skid resistance and crash data of a road network located in the tropical east coast of Queensland were analysed using the probability-based method. Analysis methodology and results of the relationships between skid resistance, road characteristics and crashes are presented.

Tailoring Consumer Resources to Enhance Self-Care in Chronic Heart Failure

Background Chronic heart failure (CHF) is associated with high hospitalisation and mortality rates and debilitating symptoms. In an effort to reduce hospitalisations and improve symptoms individuals must be supported in managing their condition. Patients who can effectively self-manage their symptoms through lifestyle modification and adherence to complex medication regimens will experience less hospitalisations and other adverse events. Aim The purpose of this paper is to explain how providing evidence-based information, using patient education resources, can support self-care. Discussion Self-care relates to the activities that individuals engage in relation to health seeking behaviours. Supporting self-care practices through tailored and relevant information can provide patients with resources and advice on strategies to manage their condition. Evidence-based approaches to improve adherence to self-care practices in patients with heart failure are not often reported. Low health literacy can result in poor understanding of the information about CHF and is related to adverse health outcomes. Also a lack of knowledge can lead to non-adherence with self-care practices such as following fluid restriction, low sodium diet and daily weighing routines. However these issues need to be addressed to improve self-management skills. Outcome Recently the Heart Foundation CHF consumer resource was updated based on evidence-based national clinical guidelines. The aim of this resource is to help consumers improve understanding of the disease, reduce uncertainty and anxiety about what to do when symptoms appear, encourage discussions with local doctors, and build confidence in self-care management. Conclusion Evidence-based CHF patient education resources promote self-care practices and early detection of symptom change that may reduce hospitalisations and improve the quality of life for people with CHF.

Probability distributed time delays: integrating spatial effects into temporal models

Background In order to provide insights into the complex biochemical processes inside a cell, modelling approaches must find a balance between achieving an adequate representation of the physical phenomena and keeping the associated computational cost within reasonable limits. This issue is particularly stressed when spatial inhomogeneities have a significant effect on system's behaviour. In such cases, a spatially-resolved stochastic method can better portray the biological reality, but the corresponding computer simulations can in turn be prohibitively expensive. Results We present a method that incorporates spatial information by means of tailored, probability distributed time-delays. These distributions can be directly obtained by single in silico or a suitable set of in vitro experiments and are subsequently fed into a delay stochastic simulation algorithm (DSSA), achieving a good compromise between computational costs and a much more accurate representation of spatial processes such as molecular diffusion and translocation between cell compartments. Additionally, we present a novel alternative approach based on delay differential equations (DDE) that can be used in scenarios of high molecular concentrations and low noise propagation. Conclusions Our proposed methodologies accurately capture and incorporate certain spatial processes into temporal stochastic and deterministic simulations, increasing their accuracy at low computational costs. This is of particular importance given that time spans of cellular processes are generally larger (possibly by several orders of magnitude) than those achievable by current spatially-resolved stochastic simulators. Hence, our methodology allows users to explore cellular scenarios under the effects of diffusion and stochasticity in time spans that were, until now, simply unfeasible. Our methodologies are supported by theoretical considerations on the different modelling regimes, i.e. spatial vs. delay-temporal, as indicated by the corresponding Master Equations and presented elsewhere.