Showing papers by "University of Bath published in 2010"

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Genome Sequence of the Pea Aphid Acyrthosiphon pisum

Abstract: Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.

Evolution of MRSA During Hospital Transmission and Intercontinental Spread

Abstract: Current methods for differentiating isolates of predominant lineages of pathogenic bacteria often do not provide sufficient resolution to define precise relationships. Here, we describe a high-throughput genomics approach that provides a high-resolution view of the epidemiology and microevolution of a dominant strain of methicillin-resistant Staphylococcus aureus (MRSA). This approach reveals the global geographic structure within the lineage, its intercontinental transmission through four decades, and the potential to trace person-to-person transmission within a hospital environment. The ability to interrogate and resolve bacterial populations is applicable to a range of infectious diseases, as well as microbial ecology.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Abstract: Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Abstract: Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.

Oxide-ion and proton conducting electrolyte materials for clean energy applications: structural and mechanistic features

Abstract: This critical review presents an overview of the various classes of oxide materials exhibiting fast oxide-ion or proton conductivity for use as solid electrolytes in clean energy applications such as solid oxide fuel cells. Emphasis is placed on the relationship between structural and mechanistic features of the crystalline materials and their ion conduction properties. After describing well-established classes such as fluorite- and perovskite-based oxides, new materials and structure-types are presented. These include a variety of molybdate, gallate, apatite silicate/germanate and niobate systems, many of which contain flexible structural networks, and exhibit different defect properties and transport mechanisms to the conventional materials. It is concluded that the rich chemistry of these important systems provides diverse possibilities for developing superior ionic conductors for use as solid electrolytes in fuel cells and related applications. In most cases, a greater atomic-level understanding of the structures, defects and conduction mechanisms is achieved through a combination of experimental and computational techniques (217 references).

Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci

Abstract: To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P < 10(-800)), we found association with SNPs in two gene deserts at 2p15 (rs10865331; combined P = 1.9 x 10(-19)) and 21q22 (rs2242944; P = 8.3 x 10(-20)), as well as in the genes ANTXR2 (rs4333130; P = 9.3 x 10(-8)) and IL1R2 (rs2310173; P = 4.8 x 10(-7)). We also replicated previously reported associations at IL23R (rs11209026; P = 9.1 x 10(-14)) and ERAP1 (rs27434; P = 5.3 x 10(-12)). This study reports four genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility.

Corporate Social Responsibility in Western Europe: An Institutional Mirror or Substitute?

Abstract: In spite of extensive research on corporate social responsibility (CSR) and its link with economic and social performance, few studies have investigated the institutional determinants of CSR. This article draws upon neo-institutional theory and comparative institutional analysis to compare the influence of different institutional environments on CSR policies of European firms. On the basis of a dataset of European firms, we find that firms from the more liberal market economies of the Anglo-Saxon countries score higher on most dimensions of CSR than firms in the more coordinated market economies (CMEs) in Continental Europe. This result lends support to the view of voluntary CSR practices in liberal economies as being a substitute for institutionalized forms of stakeholder participation. Meanwhile, CSR tends not to mirror more institutionalized forms of stakeholder coordination. Instead, in CMEs, CSR often takes on more implicit forms. Our analysis also shows that national institutional and sectoral-level factors have an asymmetric effect – strongly influencing the likelihood of firms adopting ‘minimum standards’ of CSR, but having little influence on the adoption of ‘best practices’.

Statistical inference for noisy nonlinear ecological dynamic systems

Abstract: Many ecological systems have chaotic or near-chaotic dynamics. In such cases, it is difficult to test whether the data fit particular models, because the noise makes statistical comparison with the model impossible. Simon Wood has now devised a statistical method for making such inferences, based on extracting phase-insensitive summary statistics from the raw data and comparing to data that are simulated from the model. The method is demonstrated by an application to a well-known problem: the nature of the cycles in John Nicholson's classic ecological experiments on population size in the sheep blowfly Lucilia cuprina. Many ecological systems have chaotic or near-chaotic dynamics. In such cases, it has proved difficult to test whether data fit particular models that might explain the dynamics, because the noise in the data make statistical comparison with the model impossible. This author has devised a statistical method for making such inferences, based on extracting phase-insensitive summary statistics from the raw data and comparing with data simulated using the model. Chaotic ecological dynamic systems defy conventional statistical analysis. Systems with near-chaotic dynamics are little better. Such systems are almost invariably driven by endogenous dynamic processes plus demographic and environmental process noise, and are only observable with error. Their sensitivity to history means that minute changes in the driving noise realization, or the system parameters, will cause drastic changes in the system trajectory1. This sensitivity is inherited and amplified by the joint probability density of the observable data and the process noise, rendering it useless as the basis for obtaining measures of statistical fit. Because the joint density is the basis for the fit measures used by all conventional statistical methods2, this is a major theoretical shortcoming. The inability to make well-founded statistical inferences about biological dynamic models in the chaotic and near-chaotic regimes, other than on an ad hoc basis, leaves dynamic theory without the methods of quantitative validation that are essential tools in the rest of biological science. Here I show that this impasse can be resolved in a simple and general manner, using a method that requires only the ability to simulate the observed data on a system from the dynamic model about which inferences are required. The raw data series are reduced to phase-insensitive summary statistics, quantifying local dynamic structure and the distribution of observations. Simulation is used to obtain the mean and the covariance matrix of the statistics, given model parameters, allowing the construction of a ‘synthetic likelihood’ that assesses model fit. This likelihood can be explored using a straightforward Markov chain Monte Carlo sampler, but one further post-processing step returns pure likelihood-based inference. I apply the method to establish the dynamic nature of the fluctuations in Nicholson’s classic blowfly experiments3,4,5.

The Give and Take of Alcohol Activation

Abstract: Alcohols are relatively common starting materials for chemical reactions, even though they are quite unreactive. For example, reactions that would substitute another functional group (a nucleophile) for OH often fail because the hydroxide group (HO−) is difficult to displace—it is a poor leaving group. Alcohols are usually activated by turning the hydroxide into a better leaving group, either by protonating the alcohol or by converting it into a sulfonate or halide. However, both of these activation methods have some disadvantages ( 1 ). The acidic environment required for protonating the alcohol also protonates and deactivates the incoming nucleophile, especially amines. Conversion of the alcohol into a sulfonate or halide can lead to toxicity problems; many alkyl halides and alkyl sulfonates are mutagenic.

The automatic component of habit in health behavior: habit as cue-contingent automaticity.

Abstract: Objective: Habit might be usefully characterized as a form of automaticity that involves the association of a cue and a response. Three studies examined habitual automaticity in regard to different aspects of the cue-response relationship characteristic of unhealthy and healthy habits. Design, Main Outcome Measures, and Results: In each study, habitual automaticity was assessed by the Self-Report Habit Index (SRHI). In Study 1 SRHI scores correlated with attentional bias to smoking cues in a Stroop task. Study 2 examined the ability of a habit cue to elicit an unwanted habit response. In a prospective field study, habitual automaticity in relation to smoking when drinking alcohol in a licensed public house (pub) predicted the likelihood of cigarette-related action slips 2 months later after smoking in pubs had become illegal. In Study 3 experimental group participants formed an implementation intention to floss in response to a specified situational cue. Habitual automaticity of dental flossing was rapidly enhanced compared to controls. Conclusion: The studies provided three different demonstrations of the importance of cues in the automatic operation of habits. Habitual automaticity assessed by the SRHI captured aspects of a habit that go beyond mere frequency or consistency of the behavior.

The international labour organisation

Abstract: The International Labour Organization (ILO) has reached a venerable old age, celebrating its ninetieth birthday in 2009. It was established in the wake of the First World War by the Treaty of Versa...

A review of novel techniques for heavy oil and bitumen extraction and upgrading

Abstract: With World oil demand increasing in the face of limited supplies, increasing attention is turning towards non-conventional oil sources as a means to relieve the pressure exerted on conventional stocks. However, non-conventional oils are hard to extract, process and transport. Several technologies are already at work with differing levels of success, recovery ranging from as low as 5% through to more than 70%. This paper reviews the range of Enhanced Oil Recovery techniques, broadly classified into either thermal or non-thermal methods, and their applicability to the extraction of heavy oils and bitumens. Advantages and disadvantages are presented in terms of their recovery factors, requirements, limitations and economics. The potential benefits of additional downhole catalytic upgrading of heavy oils are also explored.

Randomized controlled trials of psychological therapies for management of chronic pain in children and adolescents: an updated meta-analytic review.

Abstract: The purpose of this meta-analytic review was to quantify the effects of psychological therapies for the management of chronic pain in youth. Specifically, in this review we updated previous systematic reviews of randomized controlled trials by including new trials, and by adding disability and emotional functioning to pain as treatment outcomes. Electronic searches of the Cochrane Register of Randomised Controlled Trials, MEDLINE, PsycLIT, EMBASE, and the Social Sciences Citation Index were conducted from inception through August 2008. Methodological quality of the studies was assessed, and data extracted on the three primary outcomes of interest. Twenty-five trials including 1247 young people met inclusion criteria and were included in the meta-analysis. Meta-analytic findings demonstrated a large positive effect of psychological intervention on pain reduction at immediate post-treatment and follow-up in youth with headache, abdominal pain, and fibromyalgia. Small and non-significant effects were found for improvements in disability and emotional functioning, although there were limited data on these outcomes available in the included studies. Omnibus cognitive–behavioral therapy, relaxation therapy, and biofeedback all produced significant and positive effects on pain reduction. Studies directly comparing the effects of self-administered versus therapist-administered interventions found similar effects on pain reduction. Psychological therapies result in improvement in pain relief across several different pain conditions in children. Future trials are needed that incorporate non-pain outcome domains, that focus significant therapeutic content on reductions in disability, and that include extended follow-up to better understand maintenance of treatment effects.

Privacy, trust, and self-disclosure online

Abstract: Despite increased concern about the privacy threat posed by new technology and the Internet, there is relatively little evidence that people's privacy concerns translate to privacy-enhancing behaviors while online. In Study 1, measures of privacy concern are collected, followed 6 weeks later by a request for intrusive personal information alongside measures of trust in the requestor and perceived privacy related to the specific request (n = 759). Participants' dispositional privacy concerns, as well as their level of trust in the requestor and perceived privacy during the interaction, predicted whether they acceded to the request for personal information, although the impact of perceived privacy was mediated by trust. In Study 2, privacy and trust were experimentally manipulated and disclosure measured (n = 180). The results indicated that privacy and trust at a situational level interact such that high trust compensates for low privacy, and vice versa. Implications for understanding the links between privacy attitudes, trust, design, and actual behavior are discussed.

Pharmacologically active compounds in the environment and their chirality

Abstract: Pharmacologically active compounds including both legally used pharmaceuticals and illicit drugs are potent environmental contaminants. Extensive research has been undertaken over the recent years to understand their environmental fate and toxicity. The one very important phenomenon that has been overlooked by environmental researchers studying the fate of pharmacologically active compounds in the environment is their chirality. Chiral drugs can exist in the form of enantiomers, which have similar physicochemical properties but differ in their biological properties such as distribution, metabolism and excretion, as these processes (due to stereospecific interactions of enantiomers with biological systems) usually favour one enantiomer over the other. Additionally, due to different pharmacological activity, enantiomers of chiral drugs can differ in toxicity. Furthermore, degradation of chiral drugs during wastewater treatment and in the environment can be stereoselective and can lead to chiral products of varied toxicity. The distribution of different enantiomers of the same chiral drug in the aquatic environment and biota can also be stereoselective. Biological processes can lead to stereoselective enrichment or depletion of the enantiomeric composition of chiral drugs. As a result the very same drug might reveal different activity and toxicity and this will depend on its origin and exposure to several factors governing its fate in the environment. In this critical review a discussion of the importance of chirality of pharmacologically active compounds in the environmental context is undertaken and suggestions for directions in further research are made. Several groups of chiral drugs of major environmental relevance are discussed and their pharmacological action and disposition in the body is also outlined as it is a key factor in developing a full understanding of their environmental occurrence, fate and toxicity. This review will be of interest to environmental scientists, especially those interested in issues associated with environmental contamination with pharmacologically active compounds and chiral pollutants. As the review will outline current state of knowledge on chiral drugs, it will be of value to anyone interested in the phenomenon of chirality, chiral drugs, their stereoselective disposition in the body and environmental fate (212 references).

Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis.

Abstract: Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10⁻¹⁷). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10⁻³). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10⁻²⁰, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.

Colloquium : Looking at a soliton through the prism of optical supercontinuum

Abstract: A traditional view on solitons in optical fibers as robust particlelike structures suited for information transmission has been significantly altered and broadened over the past decade when solitons have been found to play the major role in generation of octave broad supercontinuum spectra in photonic crystal and other types of optical fibers. This remarkable spectral broadening is achieved through complex processes of dispersive radiation being scattered from, emitted, and transformed by solitons. Thus solitons have emerged as the major players in nonlinear frequency conversion in optical fibers. Unexpected analogies of these processes have been found with dynamics of ultracold atoms and ocean waves. This Colloquium focuses on recent understanding and new insights into physics of soliton-radiation interaction and supercontinuum generation.

The influence of a hot environment on parental cooperation of a ground-nesting shorebird, the Kentish plover Charadrius alexandrinus

Abstract: Parental care often increases offspring survival, but is costly to the parents. A trade-off between the cost and benefit of care is expected, so that when care provisioning by both parents is essential for the success of young, for instance in extremely cold or hot environments, the parents should rear their young together. We investigated the latter hypothesis in a ground nesting shorebird, the Kentish plover Charadrius alexandrinus in an extremely hot environment, the Arabian Desert. Midday ground temperature was often above 50°C in our study site in Abu Dhabi (United Arab Emirates), thus leaving the eggs unattended even for a few minute risks overheating and death of embryos. Through the use of video surveillance systems we recorded incubation routines of male and female Kentish plovers at 28 nests over a full day (24 h). We show that ambient temperature had a significant influence on incubation behaviour of both sexes, and the relationships are often non-linear. Coordinated incubation between parents was particularly strong in midday with incubation shared approximately equally between the male and the female. The enhanced biparental incubation was due to males increasing their nest attendance with ambient temperature. Our results suggest biparental care is essential during incubation in the Kentish plover in extremely hot environments. Shared incubation may also help the parents to cope with heat stress themselves: they can relieve each other frequently from incubation duties. We suggest that once the eggs have hatched the risks associated with hot temperature are reduced: the chicks become mobile, and they gradually develop thermoregulation. When biparental care of young is no longer essential one parent may desert the family. The relaxed demand of the offspring may contribute to the diverse breeding systems exhibited by many shorebirds.

Interacting phenotypes and the evolutionary process. III. Social evolution.

Abstract: Interactions among conspecifics influence social evolution through two distinct but intimately related paths. First, they provide the opportunity for indirect genetic effects (IGEs), where genes expressed in one individual influence the expression of traits in others. Second, interactions can generate social selection when traits expressed in one individual influence the fitness of others. Here, we present a quantitative genetic model of multivariate trait evolution that integrates the effects of both IGEs and social selection, which have previously been modeled independently. We show that social selection affects evolutionary change whenever the breeding value of one individual covaries with the phenotype of its social partners. This covariance can be created by both relatedness and IGEs, which are shown to have parallel roles in determining evolutionary response. We show that social selection is central to the estimation of inclusive fitness and derive a version of Hamilton's rule showing the symmetrical effects of relatedness and IGEs on the evolution of altruism. We illustrate the utility of our approach using altruism, greenbeards, aggression, and weapons as examples. Our model provides a general predictive equation for the evolution of social phenotypes that encompasses specific cases such as kin selection and reciprocity. The parameters can be measured empirically, and we emphasize the importance of considering both IGEs and social selection, in addition to relatedness, when testing hypotheses about social evolution.

Bringing the Tiger Back from the Brink—The Six Percent Solution

Abstract: The Tiger Summit, to be hosted by Prime Minister Vladimir Putin in Russia in November 2010—the Chinese Year of the Tiger and the International Year of Biodiversity—promises to be the most significant meeting ever held to discuss the fate of a single non-human species. The Summit will culminate efforts by the Global Tiger Initiative (GTI), launched in 2008 by Robert Zoellick, World Bank President. Leaders of 13 tiger range states, supported by international donors and conservationists attending the summit, are being asked to commit to substantive measures to prevent the unthinkable: extinction of the world's last wild tiger populations. Wild tiger numbers are at an historic low. There is no evidence of breeding populations of tigers in Cambodia, China, Vietnam, and DPR Korea. Current approaches to tiger conservation are not slowing the decline in tiger numbers [1]–[3], which has continued unabated over the last two decades. While the scale of the challenge is enormous, we submit that the complexity of effective implementation is not: commitments should shift to focus on protecting tigers at spatially well-defined priority sites, supported by proven best practices of law enforcement, wildlife management, and scientific monitoring. Conflict with local people needs to be mitigated. We argue that such a shift in emphasis would reverse the decline of wild tigers and do so in a rapid and cost-efficient manner.

"Evidence" in chronic pain--establishing best practice in the reporting of systematic reviews.

Abstract: ‘‘Evidence” in chronic pain – establishing best practice in the reporting of systematic reviews R. Andrew Moore *, Christopher Eccleston , Sheena Derry , Phillip Wiffen , Rae F. Bell , Sebastian Straube , Henry McQuay , for the ACTINPAIN writing group of the IASP Special Interest Group (SIG) on Systematic Reviews in Pain Relief and the Cochrane Pain, Palliative and Supportive Care Systematic Review Group editors

Synthetic applications of rhodium catalysed conjugate addition

Abstract: The rhodium catalysed conjugate addition of organometallics to activated alkenes is a powerful synthetic tool for establishing new carbon–carbon bonds often with high stereoselectivity. The introduction of a practical, efficient method for introducing functionalised aryl and alkenyl fragments with predictable stereocontrol has caught the attention of synthetic chemists and emerging examples are growing in number and complexity. In this tutorial review, we document notable advances in the application of rhodium catalysed conjugate addition processes within the context of synthesis of complex molecules and intermediates in drug discovery. The chosen examples illustrate important issues regarding scope, selectivity and reactivity that will help guide the selection of appropriate donor and acceptor to achieve the desired carbon–carbon bond construction when planning new synthetic routes.

The impact of non-traditional activities on the estimation of bank efficiency: International evidence

Abstract: This paper investigates the relevance of non-traditional activities in the estimation of bank efficiency levels using a sample of 752 publicly quoted commercial banks from 87 countries around the world, allowing comparison of the impact of such activities under different levels of economic development, geographical regions and other country characteristics. We estimate both cost and profit efficiency of banks using a traditional function that considers loans and other earnings assets as the only outputs, and two additional functions to account for non-traditional activities, one with off-balance sheet (OBS) items and the other with non-interest income as an additional output. Controlling for cross-country differences in regulatory and environmental conditions, we find that, on average, cost efficiency increases irrespective of whether we use OBS or non-interest income, although the results for profit efficiency are mixed. Our results also reveal that while the inclusion of non-traditional outputs does not alter the directional impact of environmental variables on bank inefficiency, regulations that restrict bank activities and enhance monitoring and supervision provisions improve both cost and profit efficiency. © 2010 Elsevier B.V.