Showing papers by "University of Birmingham published in 2006"

Meta-DiSc: a software for meta-analysis of test accuracy data

Abstract: Systematic reviews and meta-analyses of test accuracy studies are increasingly being recognised as central in guiding clinical practice. However, there is currently no dedicated and comprehensive software for meta-analysis of diagnostic data. In this article, we present Meta-DiSc, a Windows-based, user-friendly, freely available (for academic use) software that we have developed, piloted, and validated to perform diagnostic meta-analysis. Meta-DiSc a) allows exploration of heterogeneity, with a variety of statistics including chi-square, I-squared and Spearman correlation tests, b) implements meta-regression techniques to explore the relationships between study characteristics and accuracy estimates, c) performs statistical pooling of sensitivities, specificities, likelihood ratios and diagnostic odds ratios using fixed and random effects models, both overall and in subgroups and d) produces high quality figures, including forest plots and summary receiver operating characteristic curves that can be exported for use in manuscripts for publication. All computational algorithms have been validated through comparison with different statistical tools and published meta-analyses. Meta-DiSc has a Graphical User Interface with roll-down menus, dialog boxes, and online help facilities. Meta-DiSc is a comprehensive and dedicated test accuracy meta-analysis software. It has already been used and cited in several meta-analyses published in high-ranking journals. The software is publicly available at http://www.hrc.es/investigacion/metadisc_en.htm .

Multidrug-resistance efflux pumps ? not just for resistance

Abstract: It is well established that multidrug-resistance efflux pumps encoded by bacteria can confer clinically relevant resistance to antibiotics. It is now understood that these efflux pumps also have a physiological role(s). They can confer resistance to natural substances produced by the host, including bile, hormones and host-defence molecules. In addition, some efflux pumps of the resistance nodulation division (RND) family have been shown to have a role in the colonization and the persistence of bacteria in the host. Here, I present the accumulating evidence that multidrug-resistance efflux pumps have roles in bacterial pathogenicity and propose that these pumps therefore have greater clinical relevance than is usually attributed to them.

The perindopril in elderly people with chronic heart failure (PEP-CHF) study

Abstract: Aims Many patients who receive a diagnosis of heart failure have neither a low left ventricular (LV) ejection fraction nor valve disease. Few substantial randomized controlled trials have been conducted in this population, none has focussed on patients with evidence of diastolic dysfunction and none has shown clear benefit on symptoms, morbidity, or mortality. Methods and results This was a randomized double-blind trial, comparing placebo with perindopril, 4 mg/ day in patients aged � 70 years with a diagnosis of heart failure, treated with diuretics and an echocardiogram suggesting diastolic dysfunction and excluding substantial LV systolic dysfunction or valve disease. The primary endpoint was a composite of all-cause mortality and unplanned heart failure related hospitalization with a minimum follow-up of 1 year. A total of 850 patients were randomized. Their mean age was 76 (SD 5) years and 55% were women. Median follow-up was 2.1 (IQR 1.5–2.8) years. Enrolment and event rates were lower than anticipated, reducing the power of the study to show a difference in the primary endpoint to 35%. Many patients withdrew from perindopril (28%) and placebo (26%) after 1 year and started taking open-label ACE-inhibitors. Overall, 107 patients assigned to placebo and 100 assigned to perindopril reached the primary endpoint (HR 0.919: 95% CI 0.700–1.208; P ¼ 0.545). By 1 year, reductions in the primary outcome (HR 0.692: 95% CI 0.474–1.010; P ¼ 0.055) and hospitalization for heart failure (HR 0.628: 95% CI 0.408–0.966; P ¼ 0.033) were observed and functional class (P , 0.030) and 6-min corridor walk distance (P ¼ 0.011) had improved in those assigned to perindopril. Conclusion Uncertainty remains about the effects of perindopril on long-term morbidity and mortality in this clinical setting since this study had insufficient power for its primary endpoint. However, improved symptoms and exercise capacity and fewer hospitalizations for heart failure in the first year were observed on perindopril, during which most patients were on assigned therapy, suggesting that it may be of benefit in this patient population.

A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling

Abstract: Lysine methylation of histones is recognized as an important component of an epigenetic indexing system demarcating transcriptionally active and inactive chromatin domains. Trimethylation of histone H3 lysine 4 (H3K4me3) marks transcription start sites of virtually all active genes. Recently, we reported that the WD40-repeat protein WDR5 is important for global levels of H3K4me3 and control of HOX gene expression. Here we show that a plant homeodomain (PHD) finger of nucleosome remodelling factor (NURF), an ISWI-containing ATP-dependent chromatin-remodelling complex, mediates a direct preferential association with H3K4me3 tails. Depletion of H3K4me3 causes partial release of the NURF subunit, BPTF (bromodomain and PHD finger transcription factor), from chromatin and defective recruitment of the associated ATPase, SNF2L (also known as ISWI and SMARCA1), to the HOXC8 promoter. Loss of BPTF in Xenopus embryos mimics WDR5 loss-of-function phenotypes, and compromises spatial control of Hox gene expression. These results strongly suggest that WDR5 and NURF function in a common biological pathway in vivo, and that NURF-mediated ATP-dependent chromatin remodelling is directly coupled to H3K4 trimethylation to maintain Hox gene expression patterns during development. We also identify a previously unknown function for the PHD finger as a highly specialized methyl-lysine-binding domain.

Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria

Abstract: Efflux pump genes and proteins are present in both antibiotic-susceptible and antibiotic-resistant bacteria. Pumps may be specific for one substrate or may transport a range of structurally dissimilar compounds (including antibiotics of multiple classes); such pumps can be associated with multiple drug (antibiotic) resistance (MDR). However, the clinical relevance of efflux-mediated resistance is species, drug, and infection dependent. This review focuses on chromosomally encoded pumps in bacteria that cause infections in humans. Recent structural data provide valuable insights into the mechanisms of drug transport. MDR efflux pumps contribute to antibiotic resistance in bacteria in several ways: (i) inherent resistance to an entire class of agents, (ii) inherent resistance to specific agents, and (iii) resistance conferred by overexpression of an efflux pump. Enhanced efflux can be mediated by mutations in (i) the local repressor gene, (ii) a global regulatory gene, (iii) the promoter region of the transporter gene, or (iv) insertion elements upstream of the transporter gene. Some data suggest that resistance nodulation division systems are important in pathogenicity and/or survival in a particular ecological niche. Inhibitors of various efflux pump systems have been described; typically these are plant alkaloids, but as yet no product has been marketed.

Resolution of inflammation: state of the art, definitions and terms.

Abstract: A recent focus meeting on Controlling Acute Inflammation was held in London, April 27-28, 2006, organized by D.W. Gilroy and S.D. Brain for the British Pharmacology Society. We concluded at the meeting that a consensus report was needed that addresses the rapid progress in this emerging field and details how the specific study of resolution of acute inflammation provides leads for novel anti-inflammatory therapeutics, as well as defines the terms and key components of interest in the resolution process within tissues as appreciated today. The inflammatory response protects the body against infection and injury but can itself become dysregulated with deleterious consequences to the host. It is now evident that endogenous biochemical pathways activated during defense reactions can counter-regulate inflammation and promote resolution. Hence, resolution is an active rather than a passive process, as once believed, which now promises novel approaches for the treatment of inflammation-associated diseases based on endogenous agonists of resolution.

Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells

Abstract: Normal intestinal mucosa contains abundant immunoglobulin A (IgA)-secreting cells, which are generated from B cells in gut-associated lymphoid tissues (GALT). We show that dendritic cells (DC) from GALT induce T cell-independent expression of IgA and gut-homing receptors on B cells. GALT-DC-derived retinoic acid (RA) alone conferred gut tropism but could not promote IgA secretion. However, RA potently synergized with GALT-DC-derived interleukin-6 (IL-6) or IL-5 to induce IgA secretion. Consequently, mice deficient in the RA precursor vitamin A lacked IgA-secreting cells in the small intestine. Thus, GALT-DC shape mucosal immunity by modulating B cell migration and effector activity through synergistically acting mediators.

The Internationalization of Chinese Firms: A Case for Theoretical Extension?

Abstract: This paper examines the patterns of, and motives for, internationalization by prominent market-seeking Chinese firms. Case studies of these firms indicate that they are seeking technological and brand assets to create a competitive position in international markets. While mainstream theory tends to assume that firms internationalize to exploit competitive advantages, Chinese firms are generally making such investments in order to address competitive disadvantages. They are engaging in 'inward' internationalization by means of original equipment manufacture (OEM) and joint venture partnerships, and 'outward' internationalization by means of acquisition and organic expansion abroad. Each of these routes offers certain benefits coupled with its own challenges or risks. The paper concludes that the Chinese case offers an opportunity to extend present theorizing in four primary areas concerning the latecomer perspective and catch-up strategies, institutional analysis with reference to the role of government, the relations between entrepreneurs and institutions, and the liability of foreignness.

Mortality in systemic lupus erythematosus.

Abstract: Objective. To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. Methods. Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for-all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. Results. The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration < 1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. Conclusion. Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished. (Less)

Post-translational modifications in the context of therapeutic proteins

Abstract: The majority of protein-based biopharmaceuticals approved or in clinical trials bear some form of post-translational modification (PTM), which can profoundly affect protein properties relevant to their therapeutic application. Whereas glycosylation represents the most common modification, additional PTMs, including carboxylation, hydroxylation, sulfation and amidation, are characteristic of some products. The relationship between structure and function is understood for many PTMs but remains incomplete for others, particularly in the case of complex PTMs, such as glycosylation. A better understanding of such structural-functional relationships will facilitate the development of second-generation products displaying a PTM profile engineered to optimize therapeutic usefulness.

Guidelines for Systematic Review in Conservation and Environmental Management

Abstract: An increasing number of applied disciplines are utilizing evidence-based frameworks to review and disseminate the effectiveness of management and policy interventions. The rationale is that increased accessibility of the best available evidence will provide a more efficient and less biased platform for decision making. We argue that there are significant benefits for conservation in using such a framework, but the scientific community needs to undertake and disseminate more systematic reviews before the full benefit can be realized. We devised a set of guidelines for undertaking formalized systematic review, based on a health services model. The guideline stages include planning and conducting a review, including protocol formation, search strategy, data inclusion, data extraction, and analysis. Review dissemination is addressed in terms of current developments and future plans for a Web-based open-access library. By the use of case studies we highlight critical modifications to guidelines for protocol formulation, data-quality assessment, data extraction, and data synthesis for conservation and environmental management. Ecological data presented significant but soluble challenges for the systematic review process, particularly in terms of the quantity, accessibility, and diverse quality of available data. In the field of conservation and environmental management there needs to be further engagement of scientists and practitioners to develop and take ownership of an evidence-based framework.

The stepped wedge trial design: a systematic review

Abstract: Stepped wedge randomised trial designs involve sequential roll-out of an intervention to participants (individuals or clusters) over a number of time periods. By the end of the study, all participants will have received the intervention, although the order in which participants receive the intervention is determined at random. The design is particularly relevant where it is predicted that the intervention will do more good than harm (making a parallel design, in which certain participants do not receive the intervention unethical) and/or where, for logistical, practical or financial reasons, it is impossible to deliver the intervention simultaneously to all participants. Stepped wedge designs offer a number of opportunities for data analysis, particularly for modelling the effect of time on the effectiveness of an intervention. This paper presents a review of 12 studies (or protocols) that use (or plan to use) a stepped wedge design. One aim of the review is to highlight the potential for the stepped wedge design, given its infrequent use to date. Comprehensive literature review of studies or protocols using a stepped wedge design. Data were extracted from the studies in three categories for subsequent consideration: study information (epidemiology, intervention, number of participants), reasons for using a stepped wedge design and methods of data analysis. The 12 studies included in this review describe evaluations of a wide range of interventions, across different diseases in different settings. However the stepped wedge design appears to have found a niche for evaluating interventions in developing countries, specifically those concerned with HIV. There were few consistent motivations for employing a stepped wedge design or methods of data analysis across studies. The methodological descriptions of stepped wedge studies, including methods of randomisation, sample size calculations and methods of analysis, are not always complete. While the stepped wedge design offers a number of opportunities for use in future evaluations, a more consistent approach to reporting and data analysis is required.

Idiopathic intracranial hypertension

Abstract: Idiopathic intracranial hypertension is common in obese women and can lead to significant visual impairment. First described more than 100 years ago, the cause of the disorder remains unknown. Despite a multitude of proposed links, the aetiology has never been established. Impairment of cerebrospinal-fluid reabsorption is the most likely underlying pathophysiological cause of the raised pressure, but this notion has yet to be proven. Cerebral venous sinus abnormalities associated with the disorder need further exploration. Although the major symptoms of headache and visual disturbance are well documented, most data for disease outcome have been from small retrospective case series. No randomised controlled trials of treatment have been done and the management is controversial. The importance of weight loss needs clarification, the role of diuretics is uncertain, and which surgical intervention is the most effective and safe is unknown. Prospective trials to examine these issues are urgently needed.

The design of simulation studies in medical statistics

Abstract: Simulation studies use computer intensive procedures to assess the performance of a variety of statistical methods in relation to a known truth. Such evaluation cannot be achieved with studies of real data alone. Designing high-quality simulations that reflect the complex situations seen in practice, such as in prognostic factors studies, is not a simple process. Unfortunately, very few published simulation studies provide sufficient details to allow readers to understand fully all the processes required to design a simulation study. When planning a simulation study, it is recommended that a detailed protocol be produced, giving full details of how the study will be performed, analysed and reported. This paper details the important considerations necessary when designing any simulation study, including defining specific objectives of the study, determining the procedures for generating the data sets and the number of simulations to perform. A checklist highlighting the important considerations when designing a simulation study is provided. A small review of the literature identifies the current practices within published simulation studies.

ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis

Abstract: We recently identified angiogenin (ANG) as a candidate susceptibility gene for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by adult-onset loss of motor neurons. We now report the finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS. Our findings provide further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration.

Escherichia coli K-12: a cooperatively developed annotation snapshot—2005

Abstract: The goal of this group project has been to coordinate and bring up-to-date information on all genes of Escherichia coli K-12. Annotation of the genome of an organism entails identification of genes, the boundaries of genes in terms of precise start and end sites, and description of the gene products. Known and predicted functions were assigned to each gene product on the basis of experimental evidence or sequence analysis. Since both kinds of evidence are constantly expanding, no annotation is complete at any moment in time. This is a snapshot analysis based on the most recent genome sequences of two E.coli K-12 bacteria. An accurate and up-to-date description of E.coli K-12 genes is of particular importance to the scientific community because experimentally determined properties of its gene products provide fundamental information for annotation of innumerable genes of other organisms. Availability of the complete genome sequence of two K-12 strains allows comparison of their genotypes and mutant status of alleles.

Synthesis, structure and properties of metal nanoclusters.

Abstract: Metal nanoclusters have physical properties differing significantly from their bulk counterparts. Metallic properties such as delocalization of electrons in bulk metals which imbue them with high electrical and thermal conductivity, light reflectivity and mechanical ductility may be wholly or partially absent in metal nanoclusters, while new properties develop. We review modern synthetic methods used to form metal nanoclusters. The focus of this critical review is solution based chemical synthesis methods which produce fully dispersed clusters. Control of cluster size and surface chemistry using inverse micelles is emphasized. Two classes of metals are discussed, transition metals such as Au and Pt, and base metals such as Co, Fe and Ni. The optical and catalytic properties of the former are discussed and the magnetic properties of the latter are given as examples of unexpected new size-dependent properties of nanoclusters. We show how classical surface science methods of characterization augmented by chemical analysis methods such as liquid chromatography can be used to provide feedback for improvements in synthetic protocols. Characterization of metal clusters by their optical, catalytic, or magnetic behavior also provides insights leading to improvements in synthetic methods. The collective physical properties of closely interacting clusters are reviewed followed by speculation on future technical applications of clusters. (125 references).

Human Factors Methods: A Practical Guide for Engineering and Design

Abstract: This second edition of Human Factors Methods: A Practical Guide for Engineering and Design now presents 107 design and evaluation methods as well as numerous refinements to those that featured in the original. The book has been carefully designed to act as an ergonomics methods manual, aiding both students and practitioners. The eleven sections represent the different categories of ergonomics methods and techniques that can be used in the evaluation and design process. Offering a 'how-to' text on a substantial range of ergonomics methods that can be used in the design and evaluation of products and systems, it is a comprehensive point of reference for all these methods. An overview of the methods is presented in chapter one, with a methods matrix showing which can be used in conjunction. The following chapters detail the methods showing how to apply them in practice. Flowcharts, procedures and examples cover the requirements of a diverse audience and varied applications of the methods. The final chapter, a new addition, illustrates the EAST method, which integrates several well-known methods into a teamwork analysis approach.

Moving towards acceleration for estimates of activity-specific metabolic rate in free-living animals: the case of the cormorant

Abstract: 1 Time and energy are key currencies in animal ecology, and judicious management of these is a primary focus for natural selection At present, however, there are only two main methods for estimation of rate of energy expenditure in the field, heart rate and doubly labelled water, both of which have been used with success; but both also have their limitations 2 The deployment of data loggers that measure acceleration is emerging as a powerful tool for quantifying the behaviour of free-living animals Given that animal movement requires the use of energy, the accelerometry technique potentially has application in the quantification of rate of energy expenditure during activity 3 In the present study, we test the hypothesis that acceleration can serve as a proxy for rate of energy expenditure in free-living animals We measured rate of energy expenditure as rates of O2 consumption (VO2) and CO2 production (VCO2) in great cormorants (Phalacrocorax carbo) at rest and during pedestrian exercise VO2 and VCO2 were then related to overall dynamic body acceleration (ODBA) measured with an externally attached three-axis accelerometer 4 Both VO2 and VCO2 were significantly positively associated with ODBA in great cormorants This suggests that accelerometric measurements of ODBA can be used to estimate VO2 and VCO2 and, with some additional assumptions regarding metabolic substrate use and the energy equivalence of O2 and CO2, that ODBA can be used to estimate the activity specific rate of energy expenditure of free-living cormorants 5 To verify that the approach identifies expected trends in from situations with variable power requirements, we measured ODBA in free-living imperial cormorants (Phalacrocorax atriceps) during foraging trips We compared ODBA during return and outward foraging flights, when birds are expected to be laden and not laden with captured fish, respectively We also examined changes in ODBA during the descent phase of diving, when power requirements are predicted to decrease with depth due to changes in buoyancy associated with compression of plumage and respiratory air 6 In free-living imperial cormorants, ODBA, and hence estimated VO2, was higher during the return flight of a foraging bout, and decreased with depth during the descent phase of a dive, supporting the use of accelerometry for the determination of activity-specific rate of energy expenditure

Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial extension phase].

Abstract: Aims The CArdiac REsynchronization-Heart Failure study randomized patients with left ventricular ejection fraction � 35%, markers of cardiac dyssynchrony, and persistent moderate or severe symptoms of heart failure despite pharmacological therapy, to implantation of a cardiac resynchronization therapy (CRT) device or not. The main study observed substantial benefits on morbidity and mortality during a mean follow-up of 29.4 months [median 29.6, interquartile range (IQR) 23.6–34.6]. Prior to study closure, an extension phase lasting a further 8 months (allowing time for data analysis and presentation) was declared during which cross-over was discouraged. Methods and results This was an extension of the already reported open-label randomized trial described above. The primary outcome of the extension phase was all-cause mortality from the time of randomization to completion of the extension phase. The secondary outcome was mode of death. The mean follow-up was 37.4 months (median 37.6, IQR 31.5–42.5, range 26.1–52.6 months). There were 154 deaths (38.1%) in 404 patients assigned to medical therapy and 101 deaths (24.7%) in 409 patients assigned to CRT (hazard ratio 0.60, 95% CI 0.47–0.77, P , 0.0001) without evidence of heterogeneity in pre-specified subgroups. A reduction in the risk of death due to heart failure (64 vs. 38 deaths; hazard ratio 0.55, 95% CI 0.37–0.82, P ¼ 0.003) and sudden death was observed (55 vs. 32; hazard ratio 0.54, 95% CI 0.35–0.84, P ¼ 0.005). Conclusion The benefits of CRT observed in the main trial persist or increase with longer follow-up. Reduction in mortality was due to fewer deaths both from worsening heart failure and from sudden death.

ALICE: Physics Performance Report, Volume II

Abstract: ALICE is a general-purpose heavy-ion experiment designed to study the physics of strongly interacting matter and the quark–gluon plasma in nucleus–nucleus collisions at the LHC. It currently involves more than 900 physicists and senior engineers, from both the nuclear and high-energy physics sectors, from over 90 institutions in about 30 countries.The ALICE detector is designed to cope with the highest particle multiplicities above those anticipated for Pb–Pb collisions (dNch/dy up to 8000) and it will be operational at the start-up of the LHC. In addition to heavy systems, the ALICE Collaboration will study collisions of lower-mass ions, which are a means of varying the energy density, and protons (both pp and pA), which primarily provide reference data for the nucleus–nucleus collisions. In addition, the pp data will allow for a number of genuine pp physics studies.The detailed design of the different detector systems has been laid down in a number of Technical Design Reports issued between mid-1998 and the end of 2004. The experiment is currently under construction and will be ready for data taking with both proton and heavy-ion beams at the start-up of the LHC.Since the comprehensive information on detector and physics performance was last published in the ALICE Technical Proposal in 1996, the detector, as well as simulation, reconstruction and analysis software have undergone significant development. The Physics Performance Report (PPR) provides an updated and comprehensive summary of the performance of the various ALICE subsystems, including updates to the Technical Design Reports, as appropriate.The PPR is divided into two volumes. Volume I, published in 2004 (CERN/LHCC 2003-049, ALICE Collaboration 2004 J. Phys. G: Nucl. Part. Phys. 30 1517–1763), contains in four chapters a short theoretical overview and an extensive reference list concerning the physics topics of interest to ALICE, the experimental conditions at the LHC, a short summary and update of the subsystem designs, and a description of the offline framework and Monte Carlo event generators.The present volume, Volume II, contains the majority of the information relevant to the physics performance in proton–proton, proton–nucleus, and nucleus–nucleus collisions. Following an introductory overview, Chapter 5 describes the combined detector performance and the event reconstruction procedures, based on detailed simulations of the individual subsystems. Chapter 6 describes the analysis and physics reach for a representative sample of physics observables, from global event characteristics to hard processes.

Consumer–resource body-size relationships in natural food webs

Abstract: It has been suggested that differences in body size between consumer and resource species may have important implications for interaction strengths, population dynamics, and eventually food web structure, function, and evolution. Still, the general distribution of consumer-'resource body-size ratios in real ecosystems, and whether they vary systematically among habitats or broad taxonomic groups, is poorly understood. Using a unique global database on consumer and resource body sizes, we show that the mean body-size ratios of aquatic herbivorous and detritivorous consumers are several orders of magnitude larger than those of carnivorous predators. Carnivorous predator-prey body-size ratios vary across different habitats and predator and prey types (invertebrates, ectotherm, and endotherm vertebrates). Predator-prey body-size ratios are on average significantly higher (1) in freshwater habitats than in marine or terrestrial habitats, (2) for vertebrate than for invertebrate predators, and (3) for invertebrate than for ectotherm vertebrate prey. If recent studies that relate body-size ratios to interaction strengths are general, our results suggest that mean consumer-resource interaction strengths may vary systematically across different habitat categories and consumer types.

Reinventing grounded theory: some questions about theory, ground and discovery

Abstract: Grounded theory's popularity persists after three decades of broad-ranging critique. In this article three problematic notions are discussed—‘theory,’ ‘ground’ and ‘discovery’—which linger in the continuing use and development of grounded theory procedures. It is argued that far from providing the epistemic security promised by grounded theory, these notions—embodied in continuing reinventions of grounded theory—constrain and distort qualitative inquiry, and that what is contrived is not in fact theory in any meaningful sense, that ‘ground’ is a misnomer when talking about interpretation and that what ultimately materializes following grounded theory procedures is less like discovery and more akin to invention. The procedures admittedly provide signposts for qualitative inquirers, but educational researchers should be wary, for the significance of interpretation, narrative and reflection can be undermined in the procedures of grounded theory.

WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity.

Abstract: Health care planning for chronic pelvic pain (CPP), an important cause of morbidity amongst women is hampered due to lack of clear collated summaries of its basic epidemiological data. We systematically reviewed worldwide literature on the prevalence of different types of CPP to assess the geographical distribution of data, and to explore sources of variation in its estimates. We identified data available from Medline (1966 to 2004), Embase (1980 to 2004), PsycINFO (1887 to 2003), LILACS (1982 to 2004), Science Citation index, CINAHL (January 1980 to 2004) and hand searching of reference lists. Two reviewers extracted data independently, using a piloted form, on participants' characteristics, study quality and rates of CPP. We considered a study to be of high quality (valid) if had at least three of the following features: prospective design, validated measurement tool, adequate sampling method, sample size estimation and response rate >80%. We performed both univariate and multivariate meta-regression analysis to explore heterogeneity of results across studies. There were 178 studies (459975 participants) in 148 articles. Of these, 106 studies were (124259 participants) on dysmenorrhoea, 54 (35973 participants) on dyspareunia and 18 (301756 participants) on noncyclical pain. There were only 19/95 (20%) less developed and 1/45 (2.2%) least developed countries with relevant data in contrast to 22/43 (51.2%) developed countries. Meta-regression analysis showed that rates of pain varied according to study quality features. There were 40 (22.5%) high quality studies with representative samples. Amongst them, the rate of dysmenorrhoea was 16.8 to 81%, that of dyspareunia was 8 to 21.8%, and that for noncyclical pain was 2.1 to 24%. There were few valid population based estimates of disease burden due to CPP from less developed countries. The variation in rates of CPP worldwide was due to variable study quality. Where valid data were available, a high disease burden of all types of pelvic pain was found.

Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development.

Abstract: Autotaxin (ATX), or nucleotide pyrophosphatase-phosphodiesterase 2, is a secreted lysophospholipase D that promotes cell migration, metastasis, and angiogenesis. ATX generates lysophosphatidic acid (LPA), a lipid mitogen and motility factor that acts on several G protein-coupled receptors. Here we report that ATX-deficient mice die at embryonic day 9.5 (E9.5) with profound vascular defects in yolk sac and embryo resembling the Galpha13 knockout phenotype. Furthermore, at E8.5, ATX-deficient embryos showed allantois malformation, neural tube defects, and asymmetric headfolds. The onset of these abnormalities coincided with increased expression of ATX and LPA receptors in normal embryos. ATX heterozygous mice appear healthy but show half-normal ATX activity and plasma LPA levels. Our results reveal a critical role for ATX in vascular development, indicate that ATX is the major LPA-producing enzyme in vivo, and suggest that the vascular defects in ATX-deficient embryos may be explained by loss of LPA signaling through Galpha13.