Towards scalable end-to-end QoS provision for VoIP applications

The growth of the Internet and the development of its new applications have increased the demand for providing a certain level of resource assurance and service support. The concept of ensuring quality of service (QoS) has been introduced in order to provide the support and assurance for these services. Different QoS mechanisms, such as integrated services (IntServ) and differentiated services (DiffServ), have been developed and introduced to provide different levels of QoS provision. However, IntServ can suffer from scalability issues that make it infeasible for large-scale network implementations. On the other hand, the aggregated-based per-flow technique of DiffServ does not provide such an end-to-end QoS guarantee. Recently, the IETF have proposed a new QoS architecture that implements IntServ over DiffServ in order to provide an end-to-end QoS for scalable networks. Hence, it became possible to provide and support a certain level of QoS for some delay sensitive and bandwidth-demanding applications such as voice over Internet Protocol (VoIP). With regard to VoIP applications, delay, jitter and packet loss are crucial issues that have to be taken into consideration for any VoIP system design and such parameters need a distinct level of QoS support

Panel on future challenges in modeling methodology

This panel paper presents the views of six researchers and practitioners of simulation modeling. Collectively we attempt to address a range of key future challenges to modeling methodology. It is hoped that the views of this paper, and the presentations made by the panelists at the 2004 Winter Simulation Conference will raise awareness and stimulate further discussion on the future of modeling methodology in areas such as modeling problems in business applications, human factors and geographically dispersed networks; rapid model development and maintenance; legacy modeling approaches; markup languages; virtual interactive process design and simulation; standards; and Grid computing

Disease management interventions for heart failure.

BACKGROUND: Despite advances in treatment, the increasing and ageing population makes heart failure an important cause of morbidity and death worldwide. It is associated with high healthcare costs, partly driven by frequent hospital readmissions. Disease management interventions may help to manage people with heart failure in a more proactive, preventative way than drug therapy alone. This is the second update of a review published in 2005 and updated in 2012. OBJECTIVES: To compare the effects of different disease management interventions for heart failure (which are not purely educational in focus), with usual care, in terms of death, hospital readmissions, quality of life and cost-related outcomes. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL for this review update on 9 January 2018 and two clinical trials registries on 4 July 2018. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least six months' follow-up, comparing disease management interventions to usual care for adults who had been admitted to hospital at least once with a diagnosis of heart failure. There were three main types of intervention: case management; clinic-based interventions; multidisciplinary interventions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Outcomes of interest were mortality due to heart failure, mortality due to any cause, hospital readmission for heart failure, hospital readmission for any cause, adverse effects, quality of life, costs and cost-effectiveness. MAIN RESULTS: We found 22 new RCTs, so now include 47 RCTs (10,869 participants). Twenty-eight were case management interventions, seven were clinic-based models, nine were multidisciplinary interventions, and three could not be categorised as any of these. The included studies were predominantly in an older population, with most studies reporting a mean age of between 67 and 80 years. Seven RCTs were in upper-middle-income countries, the rest were in high-income countries.Only two multidisciplinary-intervention RCTs reported mortality due to heart failure. Pooled analysis gave a risk ratio (RR) of 0.46 (95% confidence interval (CI) 0.23 to 0.95), but the very low-quality evidence means we are uncertain of the effect on mortality due to heart failure. Based on this limited evidence, the number needed to treat for an additional beneficial outcome (NNTB) is 12 (95% CI 9 to 126).Twenty-six case management RCTs reported all-cause mortality, with low-quality evidence indicating that these may reduce all-cause mortality (RR 0.78, 95% CI 0.68 to 0.90; NNTB 25, 95% CI 17 to 54). We pooled all seven clinic-based studies, with low-quality evidence suggesting they may make little to no difference to all-cause mortality. Pooled analysis of eight multidisciplinary studies gave moderate-quality evidence that these probably reduce all-cause mortality (RR 0.67, 95% CI 0.54 to 0.83; NNTB 17, 95% CI 12 to 32).We pooled data on heart failure readmissions from 12 case management studies. Moderate-quality evidence suggests that they probably reduce heart failure readmissions (RR 0.64, 95% CI 0.53 to 0.78; NNTB 8, 95% CI 6 to 13). We were able to pool only two clinic-based studies, and the moderate-quality evidence suggested that there is probably little or no difference in heart failure readmissions between clinic-based interventions and usual care (RR 1.01, 95% CI 0.87 to 1.18). Pooled analysis of five multidisciplinary interventions gave low-quality evidence that these may reduce the risk of heart failure readmissions (RR 0.68, 95% CI 0.50 to 0.92; NNTB 11, 95% CI 7 to 44).Meta-analysis of 14 RCTs gave moderate-quality evidence that case management probably slightly reduces all-cause readmissions (RR 0.92, 95% CI 0.83 to 1.01); a decrease from 491 to 451 in 1000 people (95% CI 407 to 495). Pooling four clinic-based RCTs gave low-quality and somewhat heterogeneous evidence that these may result in little or no difference in all-cause readmissions (RR 0.90, 95% CI 0.72 to 1.12). Low-quality evidence from five RCTs indicated that multidisciplinary interventions may slightly reduce all-cause readmissions (RR 0.85, 95% CI 0.71 to 1.01); a decrease from 450 to 383 in 1000 people (95% CI 320 to 455).Neither case management nor clinic-based intervention RCTs reported adverse effects. Two multidisciplinary interventions reported that no adverse events occurred. GRADE assessment of moderate quality suggested that there may be little or no difference in adverse effects between multidisciplinary interventions and usual care.Quality of life was generally poorly reported, with high attrition. Low-quality evidence means we are uncertain about the effect of case management and multidisciplinary interventions on quality of life. Four clinic-based studies reported quality of life but we could not pool them due to differences in reporting. Low-quality evidence indicates that clinic-based interventions may result in little or no difference in quality of life.Four case management programmes had cost-effectiveness analyses, and seven reported cost data. Low-quality evidence indicates that these may reduce costs and may be cost-effective. Two clinic-based studies reported cost savings. Low-quality evidence indicates that clinic-based interventions may reduce costs slightly. Low-quality data from one multidisciplinary intervention suggested this may be cost-effective from a societal perspective but less so from a health-services perspective. AUTHORS' CONCLUSIONS: We found limited evidence for the effect of disease management programmes on mortality due to heart failure, with few studies reporting this outcome. Case management may reduce all-cause mortality, and multidisciplinary interventions probably also reduce all-cause mortality, but clinic-based interventions had little or no effect on all-cause mortality. Readmissions due to heart failure or any cause were probably reduced by case-management interventions. Clinic-based interventions probably make little or no difference to heart failure readmissions and may result in little or no difference in readmissions for any cause. Multidisciplinary interventions may reduce the risk of readmission for heart failure or for any cause. There was a lack of evidence for adverse effects, and conclusions on quality of life remain uncertain due to poor-quality data. Variations in study location and time of occurrence hamper attempts to review costs and cost-effectiveness.The potential to improve quality of life is an important consideration but remains poorly reported. Improved reporting in future trials would strengthen the evidence for this patient-relevant outcome

Impact of high-cost drugs for individual patient use

To document and describe the individual patient use (IPU) scheme at St Vincent's Hospital, Sydney in terms of submissions and approvals and assess the financial impact of the scheme on the hospital drug expenditure. Method: All submissions for IPU approvals received between January 1997 and December 2001 were reviewed. Submissions were collected on a calendar year basis. Data collection and analysis included identification of approved medication and indication, off- label or approved indication, prescriber, ward, outcome of therapy, person deciding the approval, approval date duration and expiry, amount of medication dispensed and the cost of therapy. The annual cost and proportion of overall drug expenditure for each approval was calculated. Results: The number of approvals had a trend to increase each year. 67.1% of the IPU approvals were for off-label indications. Requested feedback on clinical outcomes was provided only in 18% of cases. The drug acquisition cost of the IPU scheme more than doubled in the period between 1999 and 2001. Similarly the proportion of the drug expenditure on IPU drugs increased significantly (p<0.001) from 1.6% in 1999 to 3.6% in 2001. Conclusion: The results indicated that the number of approvals and submissions for IPU had a tendency to increase. The financial impact of the IPU scheme increased over the years reviewed

A Bootstrap Stationarity Test for Predictive Regression Invalidity

We examine how the familiar spurious regression problem can manifest itself in the context of recently proposed predictability tests. For these tests to provide asymptotically valid inference, account has to be taken of the degree of persistence of the putative predictors. Failure to do so can lead to spurious over-rejections of the no predictability null hypothesis. A number of methods have been developed to achieve this. However, these approaches all make an underlying assumption that any predictability in the variable of interest is purely attributable to the predictors under test, rather than to any unobserved persistent latent variables, themselves uncorrelated with the predictors being tested. We show that where this assumption is violated, something that could very plausibly happen in practice, sizeable (spurious) rejections of the null can occur in cases where the variables under test are not valid predictors. In response, we propose a screening test for predictive regression invalidity based on a stationarity testing approach. In order to allow for an unknown degree of persistence in the putative predictors, and for both conditional and unconditional heteroskedasticity in the data, we implement our proposed test using a fixed regressor wild bootstrap procedure. We establish the asymptotic validity of this bootstrap test, which entails establishing a conditional invariance principle along with its bootstrap counterpart, both of which appear to be new to the literature and are likely to have important applications beyond the present context. We also show how our bootstrap test can be used, in conjunction with extant predictability tests, to deliver a two-step feasible procedure. Monte Carlo simulations suggest that our proposed bootstrap methods work well in finite samples. An illustration employing U.S. stock returns data demonstrates the practical usefulness of our procedures

Sue Jane Taylor (Art Forum)

Scottish artist Sue Jane Taylor works in sculpture, drawing and print. She has worked on industrial sites such as North Sea Oil and most recently in Queenstown, where she worked with local mining companies to develop her ideas about labour and its place within the natural world

Protocol for an HTA report: Does therapeutic writing help people with long-term conditions? Systematic review, realist synthesis and economic modelling

This article is made available through the Brunel Open Access Publishing Fund. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/Introduction: Long-term medical conditions (LTCs) cause reduced health-related quality of life and considerable health service expenditure. Writing therapy has potential to improve physical and mental health in people with LTCs, but its effectiveness is not established. This project aims to establish the clinical and cost-effectiveness of therapeutic writing in LTCs by systematic review and economic evaluation, and to evaluate context and mechanisms by which it might work, through realist synthesis. Methods: Included are any comparative study of therapeutic writing compared with no writing, waiting list, attention control or placebo writing in patients with any diagnosed LTCs that report at least one of the following: relevant clinical outcomes; quality of life; health service use; psychological, behavioural or social functioning; adherence or adverse events. Searches will be conducted in the main medical databases including MEDLINE, EMBASE, PsycINFO, The Cochrane Library and Science Citation Index. For the realist review, further purposive and iterative searches through snowballing techniques will be undertaken. Inclusions, data extraction and quality assessment will be in duplicate with disagreements resolved through discussion. Quality assessment will include using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data synthesis will be narrative and tabular with meta-analysis where appropriate. De novo economic modelling will be attempted in one clinical area if sufficient evidence is available and performed according to the National Institute for Health and Care Excellence (NICE) reference case.National Institute for Health Research Health Technology Assessment (NIHR HTA) Programm

Disruption of SorCS2 reveals differences in the regulation of stereociliary bundle formation between hair cell types in the inner ear

Behavioural anomalies suggesting an inner ear disorder were observed in a colony of transgenic mice. Affected animals were profoundly deaf. Severe hair bundle defects were identified in all outer and inner hair cells (OHC, IHC) in the cochlea and in hair cells of vestibular macular organs, but hair cells in cristae were essentially unaffected. Evidence suggested the disorder was likely due to gene disruption by a randomly inserted transgene construct. Whole-genome sequencing identified interruption of the SorCS2 (Sortilin-related VPS-10 domain containing protein) locus. Real-time-qPCR demonstrated disrupted expression of SorCS2 RNA in cochlear tissue from affected mice and this was confirmed bySorCS2 immuno-labelling. In all affected hair cells, stereocilia were shorter than normal, but abnormalities of bundle morphology and organisation differed between hair cell types. Bundles on OHC were grossly misshapen with significantly fewer stereocilia than normal. However, stereocilia were organised in rows of increasing height. Bundles on IHC contained significantly more stereocilia than normal with some longer stereocilia towards the centre, or with minimal height differentials. In early postnatal mice, kinocilia (primary cilia) of IHC and of OHC were initially located towards the lateral edge of the hair cell surface but often became surrounded by stereocilia as bundle shape and apical surface contour changed. In macular organs the kinocilium was positioned in the centre of the cell surface throughout maturation. There was disruption of the signalling pathway controlling intrinsic hair cell apical asymmetry. LGN and Gαi3 were largely absent, and atypical Protein Kinase C (aPKC) lost its asymmetric distribution. The results suggest that SorCS2 plays a role upstream of the intrinsic polarity pathway and that there are differences between hair cell types in the deployment of the machinery that generates a precisely organised hair bundle

Average acceleration and intensity gradient of primary school children and associations with indicators of health and wellbeing

Average acceleration (AvAcc) and intensity gradient (IG) have been proposed as standardised metrics describing physical activity (PA) volume and intensity, respectively. We examined hypothesised between-group PA differences in AvAcc and IG, and their associations with health and wellbeing indicators in children. ActiGraph GT9X wrist accelerometers were worn for 24-h·d−1 over seven days by 145 children aged 9-10. Raw accelerations were averaged per 5-s epoch to represent AvAcc over 24-h. IG represented the relationship between log values for intensity and time. Moderate-to-vigorous PA (MVPA) was estimated using youth cutpoints. BMI z-scores, waist-to-height ratio (WHtR), peak oxygen uptake (VO2peak), Metabolic Syndrome risk (MetS score), and wellbeing were assessed cross-sectionally, and 8-weeks later. Hypothesised between-group differences were consistently observed for IG only (p<.001). AvAcc was strongly correlated with MVPA (r=0.96), while moderate correlations were observed between IG and MVPA (r=0.50) and AvAcc (r=0.54). IG was significantly associated with health indicators, independent of AvAcc (p<.001). AvAcc was associated with wellbeing, independent of IG (p<.05). IG was significantly associated with WHtR (p<.01) and MetS score (p<.05) at 8-weeks follow-up. IG is sensitive as a gauge of PA intensity that is independent of total PA volume, and which relates to important health indicators in children