Passive control of a biventricular assist device with compliant inflow cannulae

Rotary ventricular assist device (VAD) support of the cardiovascular system is susceptible to suction events due to the limited preload sensitivity of these devices. This may be of particular concern with rotary biventricular support (BiVAD) where the native, flow-balancing Starling response is diminished in both ventricles. The reliability of sensor and sensor-less based control systems which aim to control VAD flow based on preload have limitations and thus an alternative solution is desired. This study introduces a compliant inflow cannula (CIC) which could improve the preload sensitivity of a rotary VAD by passively altering VAD flow depending on preload. To evaluate the design, both the CIC and a standard rigid inflow cannula were inserted into a mock circulation loop to enable biventricular heart failure support using configurations of atrial and ventricular inflow, and arterial outflow cannulation. A range of left (LVAD) and right VAD (RVAD) rotational speeds were tested as well as step changes in systemic/pulmonary vascular resistance to alter relative preloads, with resulting flow rates recorded. Simulated suction events were observed, particularly at higher VAD speeds, during support with the rigid inflow cannula, while the CIC prevented suction events under all circumstances. The compliant section passively restricted its internal diameter as preload was reduced, which increased the VAD circuit resistance and thus reduced VAD flow. Therefore, a compliant inflow cannula could potentially be used as a passive control system to prevent suction events in rotary left, right and biventricular support.

No right to live? Malaysia’s Islam and implications for its sexual minority storytellers

This paper discusses the fast emerging challenges for Malay and Muslim sexual minority storytellers in the face of an aggressive state-sponsored Islamisation of a constitutionally secular Malaysia. I examine the case of Azwan Ismail, a gay Malay and Muslim Malaysian who took part in the local ‘It Gets Better’ Project, initiated in December 2010 by Seksualiti Merdeka (an annual sexuality rights festival) and who suffered an onslaught of hostile comments from fellow Malay Muslims. In this paper, I ask how a message aimed at discouraging suicidal tendencies among sexual minority teenagers can go so wrong. In discussing the contradictions between Azwan’s constructions of self and the expectations others have of him, I highlight the challenges for Azwan’s existential self. For storytellers who are vulnerable if visible, the inevitable sharing of a personal story with unintended and hostile audiences when placed online, can have significant repercussions. The purist Sunni Islam agenda in Malaysia not only rejects the human rights of the sexual minority in Malaysia but has influenced and is often a leading hostile voice in both regional and international blocs. This self-righteous and supremacist political Islam fosters a more disabling environment for vulnerable, minority communities and their human rights. It creates a harsher reality for the sexual minority that manifests in State-endorsed discrimination, compulsory counselling, forced rehabilitation and their criminalisation. It places the right of the sexual minority to live within such a community in doubt. I draw on existing literature on how personal stories have historically been used to advance human rights. Included too, is the signifance and implications of the work by social psychologists in explaining this loss of credibility of personal stories. I then advance an analytical framework that will allow storytelling as a very individual form of witnessing to reclaim and regain its ‘truth to power’.

Positive reappraisal improves heart rate variability during stressful work

Recent developments in wearable ECG technology have seen renewed interest in the use of Heart Rate Variability (HRV) feedback for stress management. Yet, little is know about the efficacy of such interventions. Positive reappraisal is an emotion regulation strategy that involves changing the way a situation is construed to decrease emotional impact. We sought to test the effectiveness of an intervention that used feedback on HRV data to prompt positive reappraisal during a stressful work task. Participants (N=122) completed two 20-minute trials of an inbox activity. In-between the first and the second trial participants were assigned to the waitlist control condition, a positive reappraisal via psycho-education condition, or a positive reappraisal via HRV feedback condition. Results revealed that using HRV data to frame a positive reappraisal message is more effective than using psycho-education (or no intervention)–especially for increasing positive mood and reducing arousal.

Phase II clinical trial of first or second-line treatment with bortezomib in patients with malignant pleural mesothelioma

Based on promising preclinical efficacy of bortezomib in mesothelioma, a single-arm phase II trial (Ireland Cooperative Oncology Research Group 05-10 study), with Simon's two-stage design, was undertaken to assess efficacy of bortezomib monotherapy in the first-line (poor performance status) and second-line settings. The Bcl-2 homology domain 3-only protein Noxa has been implicated as a key inducer of apoptosis by bortezomib. Thus, in a biomarker research substudy, we hypothesized that deficiency in Noxa expression might correlate with resistance. In the second-line setting, 23 patients were enrolled. Partial response was confirmed in one patient (4.8%) who received four cycles of bortezomib. One patient had stable disease; however, progression occurred in the majority of patients within the first two cycles. Median progression-free survival and overall survival were 2.1 and 5.8 months, respectively. In the first-line setting, ten patients were accrued, and there was no evidence of objective response. In the tumor analysis, expression of Noxa was seen in all biopsies. Bortezomib monotherapy exhibits insufficient activity to warrant further investigation in unselected patients with mesothelioma. © 2012 by the International Association for the Study of Lung.

Histone deacetylase inhibitors target diabetes via chromatin remodeling or as chemical chaperones?

Globally, obesity and diabetes (particularly type 2 diabetes) represents a major challenge to world health. Despite decades of intense research efforts, the genetic basis involved in diabetes pathogenesis & conditions associated with obesity are still poorly understood. Recent advances have led to exciting new developments implicating epigenetics as an important mechanism underpinning diabetes and obesity related disease. One epigenetic mechanism known as the "histone code" describes the idea that specific patterns of post-translational modifications to histones act like a molecular "code" recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as lysine acetyltransferases or KATs and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. Some of the known inhibitors of HDACs (HDACi) have also been shown to act as "chemical chaperones" to alleviate diabetic symptoms. In this review, we discuss the available evidence concerning the roles of HDACs in regulating chaperone function and how this may have implications in the management of diabetes. © 2009 Bentham Science Publishers Ltd.

Safety and efficacy of the combination of trastuzumab with docetaxel for HER2-positive women with advanced breast cancer : a review of the existing clinical trials and results of the expanded access programme in the UK

Trastuzumab is a humanised monoclonal antibody against the extracellular domain of HER2 (human epidermal growth factor receptor-2) that is overexpressed in about 25% of human breast cancers. It has shown clinical benefit in HER2-positive breast cancer cases when used alone or in combination with chemotherapy. Trastuzumab increases the response rate to chemotherapy and prolongs survival when used in combination with taxanes. In this article, we review the clinical trials where trastuzumab has been administered together with docetaxel, and we present the results of the trastuzumab expanded access programme (EAP) in the UK. Combination of trastuzumab with docetaxel results in similar response rates and time-to-progression with the trastuzumab/paclitaxel combinations. The toxicity of the combination and the risk of heart failure are low. The clinical data for the docetaxel/trastuzumab combination indicate a favourable profile from both the efficacy and the safety point of view and confirm the feasibility and safety of trastuzumab administration both as monotherapy and in combination with docetaxel. © 2004 Blackwell Publishing Ltd.

Effective technologies for noninvasive remote monitoring in heart failure

Background Trials of new technologies to remotely monitor for signs and symptoms of worsening heart failure are continually emerging. The extent to which technological differences impact the effectiveness of non-invasive remote monitoring for heart failure management is unknown. Objective To examine the effect of specific technology used for non-invasive remote monitoring of people with heart failure on all-cause mortality and heart failure-related hospitalisations. Methods A sub-analysis of a large systematic review and meta-analysis was conducted. Studies were stratified according to the specific type of technology used and separate meta-analyses were performed. Four different types of non-invasive remote monitoring technologies were identified including structured telephone calls, videophone, interactive voice response devices and telemonitoring. Results Only structured telephone calls and telemonitoring were effective in reducing the risk of all-cause mortality (RR 0.87; 95% CI=0.75-1.01; p=0.06 and 0.62; 95% CI=0.50-0.77; p<0.0001) and heart failure-related hospitalisations (RR 0.77; 95% CI=0.68-0.87; p<0.001) and 0.75; 95% CI=0.63-0.91; p=0.003). More research data is required for videophone and interactive voice response technologies. Conclusions This sub-analysis identified that only two of the four specific technologies used for non-invasive remote monitoring in heart failure improved outcomes. When results of studies that involved these disparate technologies were combined in previous meta-analyses, significant improvements in outcomes were identified. As such, this study has highlighted implications for future meta-analyses of randomised controlled trials focused on evaluating the effectiveness of remote monitoring in heart failure.

The effectiveness of non-pharmacological interventions in improving psychological outcomes for heart transplant recipients : a systematic review

Background Post-heart transplant psychological distress may both directly hinder physiological health as well as indirectly impact on clinical outcomes by increasing unhealthy behaviours, such as immunosuppression non-adherence. Reducing psychological distress for heart transplant recipients is therefore vitally important, in order to improve patients’ overall health and well-being but also clinical outcomes, such as morbidity and mortality. Evidence from other populations suggests that non-pharmacological interventions may be an effective strategy. Aim To appraise the efficacy of non-pharmacological interventions on psychological outcomes after heart transplant. Method A systematic review was conducted using the Joanna Briggs Institute methodology. Experimental and quasi-experimental studies that involved any non-pharmacological intervention for heart transplant recipients were included, provided that data on psychological outcomes were reported. Multiple electronic databases were searched for published and unpublished studies and reference lists of retrieved studies were scrutinized for further primary research. Data were extracted using a standardised data extraction tool. Included studies were assessed by two independent reviewers using standardised critical appraisal instruments. Results Three studies fulfilled the inclusion and exclusion criteria, which involved only 125 heart transplant recipients. Two studies reported on exercise programs. One study reported a web-based psychosocial intervention. While psychological outcomes significantly improved from baseline to follow-up for the recipients who received the interventions, between-group comparisons were not reported. The methodological quality of the studies was judged to be poor. Conclusions Further research is required, as we found there is insufficient evidence available to draw conclusions for or against the use of non-pharmacological interventions after heart transplant.

Design of physiological control and magnetic levitation systems for a total artificial heart

Total Artificial Hearts are mechanical pumps which can be used to replace the failing natural heart. This novel study developed a means of controlling a new design of pump to reproduce physiological flow bringing closer the realisation of a practical artificial heart. Using a mathematical model of the device, an optimisation algorithm was used to determine the best configuration for the magnetic levitation system of the pump. The prototype device was constructed and tested in a mock circulation loop. A physiological controller was designed to replicate the Frank-Starling like balancing behaviour of the natural heart. The device and controller provided sufficient support for a human patient while also demonstrating good response to various physiological conditions and events. This novel work brings the design of a practical artificial heart closer to realisation.

Creating efficiencies in teaching : where are the right resources when you need them?

Early career engineering academics are encouraged to join and contribute to established research groups at the leading edge of their discipline. This is often facilitated by various staff development and support programs. Given that academics are often appointed primarily on the basis of their research skills and outputs, such an approach is justified and is likely to result in advancing the individual academic’s career. It also enhances their capacity to attract competitive research funding, while contributing to the overall research performance of their institution, with further potential for an increased share of government funding. In contrast, there is much less clarity of direction or availability of support mechanisms for those academics in their role as teachers. Following a general induction to teaching and learning at their institution, they would commonly think about preparing some lecture materials, whether for delivery in a face-to-face or on-line modality. Typically they would look for new references and textbooks to act as a guide for preparing the content. They would probably find out how the course has been taught before, and what laboratory facilities and experiments have been used. In all of these and other related tasks, the majority of newly appointed academics are guided strongly by their own experiences as students, rather than any firm knowledge of pedagogical principles. At a time of increased demands on academics’ time, and high expectations of performance and productivity in both research and teaching, it is essential to examine possible actions to support academics in enhancing their teaching performance in effective and efficient ways. Many resources have been produced over the years in engineering schools around the world, with very high intellectual and monetary costs. In Australia, the last few years have seen a surge in the number of ALTC/OLT projects and fellowships addressing a range of engineering education issues and providing many resources. There are concerns however regarding the extent to which these resources are being effectively utilised. Why are academics still re-inventing the wheel and creating their own version of teaching resources and pedagogical practice? Why do they spend so much of their precious time in such an inefficient way? A symposium examining the above issues was conducted at the AAEE2012 conference, and some pointers to possible responses to the above questions were obtained. These are explored in this paper and supplemented by the responses to a survey of a group of engineering education leaders on some of the aspects of these research questions. The outcomes of the workshop and survey results have been analysed in view of the literature and the ALTC/OLT sponsored learning and teaching projects and resources. Other factors are discussed, including how such resources can be found, how their quality might be evaluated, and how assessment may be appropriately incorporated, again using readily available resources. This study found a strong resonance between resources reuse with work on technology acceptance (Davis, 1989), suggesting that technology adoption models could be used to encourage resource sharing. Efficient use of outstanding learning materials is an enabling approach. The paper provides some insights on the factors affecting the re-use of available resources, and makes some recommendations and suggestions on how the issue of resources re-use might be incorporated in the process of applying and completing engineering education projects.

Online belongings : female fan experiences in online soccer forums

Introduction: The Paradox at the Heart of Online Interaction

Nicklinson v Ministry of Justice [2012] 304 (QB) : further UK developments regarding a person's right to choose when and how to die : assisted termination of life

UK High Court decision - application for declarations legitimising third party assistance in voluntary termination of life - facts - moral, social and ethical issues - analysis.

A randomized controlled trial of self-management programme improves health-related outcomes of older people with heart failure

Aims This paper is a report on the effectiveness of a self-management programme based on the self-efficacy construct, in older people with heart failure. Background Heart failure is a major health problem worldwide, with high mortality and morbidity, making it a leading cause of hospitalization. Heart failure is associated with a complex set of symptoms that arise from problems in fluid and sodium retention. Hence, managing salt and fluid intake is important and can be enhanced by improving patients' self-efficacy in changing their behaviour. Design Randomized controlled trial. Methods Heart failure patients attending cardiac clinics in northern Taiwan from October 2006–May 2007 were randomly assigned to two groups: control (n = 46) and intervention (n = 47). The intervention group received a 12-week self-management programme that emphasized self-monitoring of salt/fluid intake and heart failure-related symptoms. Data were collected at baseline as well as 4 and 12 weeks later. Data analysis to test the hypotheses used repeated-measures anova models. Results Participants who received the intervention programme had significantly better self-efficacy for salt and fluid control, self-management behaviour and their heart failure-related symptoms were significantly lower than participants in the control group. However, the two groups did not differ significantly in health service use. Conclusion The self-management programme improved self-efficacy for salt and fluid control, self-management behaviours, and decreased heart failure-related symptoms in older Taiwanese outpatients with heart failure. Nursing interventions to improve health-related outcomes for patients with heart failure should emphasize self-efficacy in the self-management of their disease.

The effect of a supervised exercise training programme on sleep quality in recently discharged heart failure patients

Background Sleep disturbances, including insomnia and sleep-disordered breathing, are a common complaint in people with heart failure and impair well-being. Exercise training (ET) improves quality of life in stable heart failure patients. ET also improves sleep quality in healthy older patients, but there are no previous intervention studies in heart failure patients. Aim The aim of this study was to examine the impact of ET on sleep quality in patients recently discharged from hospital with heart failure. Methods This was a sub-study of a multisite randomised controlled trial. Participants with a heart failure hospitalisation were randomised within six weeks of discharge to a 12-week disease management programme including exercise advice (n=52) or to the same programme with twice weekly structured ET (n=54). ET consisted of two one-hour supervised aerobic and resistance training sessions, prescribed and advanced by an exercise specialist. The primary outcome was change in Pittsburgh Sleep Quality Index (PSQI) between randomisation and week 12. Results At randomisation, 45% of participants reported poor sleep (PSQI≥5). PSQI global score improved significantly more in the ET group than the control group (–1.5±3.7 vs 0.4±3.8, p=0.03). Improved sleep quality correlated with improved exercise capacity and reduced depressive symptoms, but not with changes in body mass index or resting heart rate. Conclusion Twelve weeks of twice-weekly supervised ET improved sleep quality in patients recently discharged from hospital with heart failure.

Phosphodiesterase PDE3, but not PDE4, reduces β1- and β2-adrenoceptor-mediated inotropic and lusitropic effects in failing ventricle from metoprolol-treated patients

Background and purpose Phosphodiesterases PDE3 and/or PDE4 control ventricular effects of catecholamines in several species but their relative effects in failing human ventricle are unknown. We investigated whether the PDE3-selective inhibitor cilostamide (0.3-1μM) or PDE4 inhibitor rolipram (1-10μM) modified the positive inotropic and lusitropic effects of catecholamines in human failing myocardium. Experimental approach Right and left ventricular trabeculae from freshly explanted hearts of 5 non-β-blocker-treated and 15 metoprolol-treated patients with terminal heart failure were paced to contract at 1Hz. The effects of (-)-noradrenaline, mediated through β1-adrenoceptors (β2-adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β2-adrenoceptors (β1-adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of PDE inhibitors. Catecholamine potencies were estimated from –logEC50s. Key results Cilostamide did not significantly potentiate the inotropic effects of the catecholamines in non-β-blocker-treated patients. Cilostamide caused greater potentiation (P=0.037) of the positive inotropic effects of (-)-adrenaline (0.78±0.12 log units) than (-)-noradrenaline (0.47±0.12 log units) in metoprolol-treated patients. Lusitropic effects of the catecholamines were also potentiated by cilostamide. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline on right and left ventricular trabeculae from metoprolol-treated patients. Conclusions and implications Metoprolol induces a control by PDE3 of ventricular effects mediated through both β1- and β2-adrenoceptors, thereby further reducing sympathetic cardiostimulation in patients with terminal heart failure. Concurrent therapy with a PDE3 blocker and metoprolol could conceivably facilitate cardiostimulation evoked by adrenaline through β2-adrenoceptors. PDE4 does not appear to reduce inotropic and lusitropic effects of catecholamines in failing human ventricle.