Meta-analysis: a unifying meta-likelihood approach framing unobserved heterogeneity, study covariates, publication bias, and study quality

OBJECTIVES: This contribution provides a unifying concept for meta-analysis integrating the handling of unobserved heterogeneity, study covariates, publication bias and study quality. It is important to consider these issues simultaneously to avoid the occurrence of artifacts, and a method for doing so is suggested here. METHODS: The approach is based upon the meta-likelihood in combination with a general linear nonparametric mixed model, which lays the ground for all inferential conclusions suggested here. RESULTS: The concept is illustrated at hand of a meta-analysis investigating the relationship of hormone replacement therapy and breast cancer. The phenomenon of interest has been investigated in many studies for a considerable time and different results were reported. In 1992 a meta-analysis by Sillero-Arenas et al. concluded a small, but significant overall effect of 1.06 on the relative risk scale. Using the meta-likelihood approach it is demonstrated here that this meta-analysis is due to considerable unobserved heterogeneity. Furthermore, it is shown that new methods are available to model this heterogeneity successfully. It is argued further to include available study covariates to explain this heterogeneity in the meta-analysis at hand. CONCLUSIONS: The topic of HRT and breast cancer has again very recently become an issue of public debate, when results of a large trial investigating the health effects of hormone replacement therapy were published indicating an increased risk for breast cancer (risk ratio of 1.26). Using an adequate regression model in the previously published meta-analysis an adjusted estimate of effect of 1.14 can be given which is considerably higher than the one published in the meta-analysis of Sillero-Arenas et al. In summary, it is hoped that the method suggested here contributes further to a good meta-analytic practice in public health and clinical disciplines.

Revisiting Youden's index as a useful measure of the misclassification error in meta-analysis of diagnostic studies

The paper considers meta-analysis of diagnostic studies that use a continuous Score for classification of study participants into healthy, or diseased groups. Classification is often done on the basis of a threshold or cut-off value, which might vary between Studies. Consequently, conventional meta-analysis methodology focusing solely on separate analysis of sensitivity and specificity might he confounded by a potentially unknown variation of the cut-off Value. To cope with this phenomena it is suggested to use, instead an overall estimate of the misclassification error previously suggested and used as Youden's index and; furthermore, it is argued that this index is less prone to between-study variation of cut-off values. A simple Mantel-Haenszel estimator as a summary measure of the overall misclassification error is suggested, which adjusts for a potential study effect. The measure of the misclassification error based on Youden's index is advantageous in that it easily allows an extension to a likelihood approach, which is then able to cope with unobserved heterogeneity via a nonparametric mixture model. All methods are illustrated at hand of an example on a diagnostic meta-analysis on duplex doppler ultrasound, with angiography as the standard for stroke prevention.

A comparison of three different models for estimating relative risk in meta-analysis of clinical trials under unobserved heterogeneity

We focus on the comparison of three statistical models used to estimate the treatment effect in metaanalysis when individually pooled data are available. The models are two conventional models, namely a multi-level and a model based upon an approximate likelihood, and a newly developed model, the profile likelihood model which might be viewed as an extension of the Mantel-Haenszel approach. To exemplify these methods, we use results from a meta-analysis of 22 trials to prevent respiratory tract infections. We show that by using the multi-level approach, in the case of baseline heterogeneity, the number of clusters or components is considerably over-estimated. The approximate and profile likelihood method showed nearly the same pattern for the treatment effect distribution. To provide more evidence two simulation studies are accomplished. The profile likelihood can be considered as a clear alternative to the approximate likelihood model. In the case of strong baseline heterogeneity, the profile likelihood method shows superior behaviour when compared with the multi-level model. Copyright (C) 2006 John Wiley & Sons, Ltd.

Strategies to prevent falls and fractures in hospitals and care homes and effect of cognitive impairment: systematic review and meta-analyses

OBJECTIVES: To evaluate the evidence for strategies to prevent falls or fractures in residents in care homes and hospital inpatients and to investigate the effect of dementia and cognitive impairment. DESIGN: Systematic review and meta-analyses of studies grouped by intervention and setting (hospital or care home). Meta-regression to investigate the effects of dementia and of study quality and design. DATA SOURCES: Medline, CINAHL, Embase, PsychInfo, Cochrane Database, Clinical Trials Register, and hand searching of references from reviews and guidelines to January 2005. RESULTS: 1207 references were identified, including 115 systematic reviews, expert reviews, or guidelines. Of the 92 full papers inspected, 43 were included. Meta-analysis for multifaceted interventions in hospital (13 studies) showed a rate ratio of 0.82 (95% confidence interval 0.68 to 0.997) for falls but no significant effect on the number of fallers or fractures. For hip protectors in care homes (11 studies) the rate ratio for hip fractures was 0.67 (0.46 to 0.98), but there was no significant effect on falls and not enough studies on fallers. For all other interventions (multifaceted interventions in care homes; removal of physical restraints in either setting; fall alarm devices in either setting; exercise in care homes; calcium/vitamin D in care homes; changes in the physical environment in either setting; medication review in hospital) meta-analysis was either unsuitable because of insufficient studies or showed no significant effect on falls, fallers, or fractures, despite strongly positive results in some individual studies. Meta-regression showed no significant association between effect size and prevalence of dementia or cognitive impairment. CONCLUSION: There is some evidence that multifaceted interventions in hospital reduce the number of falls and that use of hip protectors in care homes prevents hip fractures. There is insufficient evidence, however, for the effectiveness of other single interventions in hospitals or care homes or multifaceted interventions in care homes.

Alkene-arene meta photocycloadditions with a four-carbon-atom tether: efficient approach toward the polycyclic ring systems of aphidicolin and stemodinone

At the end of its tether! The fusion of a six-membered ring onto the four-carbon-atom tether of substrate 1 provides an efficient approach toward the polycyclic ring systems of the natural products aphidicolin and stemodinone. The reaction represents a unique example of a preference for product formation from an endo exciplex in an intramolecular system (exo:endo 2:3=1.0:1.2).

From alpha-cedrene to crinipellin B and onward: 25 years of the alkene-arene meta-photocycloaddition reaction in natural product synthesis

Wender and Howbert's remarkable synthesis of alpha-cedrene in 1981 brought the attention of the synthetic community to the alkene - arene meta-photocycloaddition reaction. Here we review the natural product syntheses that have been achieved, over the last 25 years, utilising this strategic level reaction.

Design of a turn-linker-turn foldamer by incorporating meta-amino benzoic acid in the middle of a helix forming hexapeptide sequence: A helix breaking approach

Single crystal X-ray diffraction studies reveal that the incorporation of meta-amino benzoic acid in the middle of a helix forming hexapeptide sequence such as in peptide I Boc-Ile(1)-Aib(2)-Val(3)-m-ABA(4)-Ile(5)-Aib(6)-Leu(7)-OMe (Aib: alpha-amino isobutyric acid: m-ABA: meta-amino benzoic acid) breaks the helix propagation to produce a turn-linker-turn (T-L-T) foldamer in the solid state. In the crystalline state two conformational isomers of peptide I self-assemble in antiparallel fashion through intermolecular hydrogen bonds and aromatic pi-pi interactions to form a molecular duplex. The duplexes are further interconnected through intermolecular hydrogen bonds to form a layer of peptides. The layers are stacked one on top of the other through van der Waals interactions to form hydrophilic channels filled with solvent methanol. (C) 2009 Elsevier B.V. All rights reserved.

Economic models and algorithms for distributed systems

Distributed computing paradigms for sharing resources such as Clouds, Grids, Peer-to-Peer systems, or voluntary computing are becoming increasingly popular. While there are some success stories such as PlanetLab, OneLab, BOINC, BitTorrent, and SETI@home, a widespread use of these technologies for business applications has not yet been achieved. In a business environment, mechanisms are needed to provide incentives to potential users for participating in such networks. These mechanisms may range from simple non-monetary access rights, monetary payments to specific policies for sharing. Although a few models for a framework have been discussed (in the general area of a "Grid Economy"), none of these models has yet been realised in practice. This book attempts to fill this gap by discussing the reasons for such limited take-up and exploring incentive mechanisms for resource sharing in distributed systems. The purpose of this book is to identify research challenges in successfully using and deploying resource sharing strategies in open-source and commercial distributed systems.

Parallel and distributed computing with Java

The Java language first came to public attention in 1995. Within a year, it was being speculated that Java may be a good language for parallel and distributed computing. Its core features, including being objected oriented and platform independence, as well as having built-in network support and threads, has encouraged this view. Today, Java is being used in almost every type of computer-based system, ranging from sensor networks to high performance computing platforms, and from enterprise applications through to complex research-based.simulations. In this paper the key features that make Java a good language for parallel and distributed computing are first discussed. Two Java-based middleware systems, namely MPJ Express, an MPI-like Java messaging system, and Tycho, a wide-area asynchronous messaging framework with an integrated virtual registry are then discussed. The paper concludes by highlighting the advantages of using Java as middleware to support distributed applications.

Semantic organization to enhance active learning based on distributed multimedia educational resources

In order to organize distributed educational resources efficiently, to provide active learners an integrated, extendible and cohesive interface to share the dynamically growing multimedia learning materials on the Internet, this paper proposes a generic resource organization model with semantic structures to improve expressiveness, scalability and cohesiveness. We developed an active learning system with semantic support for learners to access and navigate through efficient and flexible manner. We learning resources in an efficient and flexible manner. We provide facilities for instructors to manipulate the structured educational resources via a convenient visual interface. We also developed a resource discovering and gathering engine based on complex semantic associations for several specific topics.

A flexible monitoring and notification system for distributed resources

Resource monitoring in distributed systems is required to understand the 'health' of the overall system and to help identify particular problems, such as dysfunctional hardware, a faulty, system or application software. Desirable characteristics for monitoring systems are the ability to connect to any number of different types of monitoring agents and to provide different views of the system, based on a client's particular preferences. This paper outlines and discusses the ongoing activities within the GridRM wide-area resource-monitoring project.

Linear hashtable motion estimation algorithm for distributed video processing

This paper presents a parallel Linear Hashtable Motion Estimation Algorithm (LHMEA). Most parallel video compression algorithms focus on Group of Picture (GOP). Based on LHMEA we proposed earlier [1][2], we developed a parallel motion estimation algorithm focus inside of frame. We divide each reference frames into equally sized regions. These regions are going to be processed in parallel to increase the encoding speed significantly. The theory and practice speed up of parallel LHMEA according to the number of PCs in the cluster are compared and discussed. Motion Vectors (MV) are generated from the first-pass LHMEA and used as predictors for second-pass Hexagonal Search (HEXBS) motion estimation, which only searches a small number of Macroblocks (MBs). We evaluated distributed parallel implementation of LHMEA of TPA for real time video compression.

Impact of transmission errors in enhanced relay-enabled distributed coordination function

This paper analyzes the performance of Enhanced relay-enabled Distributed Coordination Function (ErDCF) for wireless ad hoc networks under transmission errors. The idea of ErDCF is to use high data rate nodes to work as relays for the low data rate nodes. ErDCF achieves higher throughput and reduces energy consumption compared to IEEE 802.11 Distributed Coordination Function (DCF) in an ideal channel environment. However, there is a possibility that this expected gain may decrease in the presence of transmission errors. In this work, we modify the saturation throughput model of ErDCF to accurately reflect the impact of transmission errors under different rate combinations. It turns out that the throughput gain of ErDCF can still be maintained under reasonable link quality and distance.

Performance evaluation of enhanced relay-enabled distributed coordination function

In this paper we evaluate the performance of our earlier proposed enhanced relay-enabled distributed coordination function (ErDCF) for wireless ad hoc networks. The idea of ErDCF is to use high data rate nodes to work as relays for the low data rate nodes. ErDCF achieves higher throughput and reduced energy consumption compared to IEEE 802.11 distributed coordination function (DCF). This is a result of. 1) using relay which helps to increase the throughput and lower overall blocking time of nodes due to faster dual-hop transmission, 2) using dynamic preamble (i.e. using short preamble for the relay transmission) which further increases the throughput and lower overall blocking time and also by 3) reducing unnecessary overhearing (by other nodes not involved in transmission). We evaluate the throughput and energy performance of the ErDCF with different rate combinations. ErDCF (11,11) (ie. R1=R2=11 Mbps) yields a throughput improvement of 92.9% (at the packet length of 1000 bytes) and an energy saving of 72.2% at 50 nodes.