Showing papers by "University of Birmingham published in 2009"
University of Ottawa1, Mario Negri Institute for Pharmacological Research2, University of Modena and Reggio Emilia3, Ottawa Hospital Research Institute4, University of Oxford5, University of Freiburg6, Veterans Health Administration7, Johnson & Johnson8, Johnson & Johnson Pharmaceutical Research and Development9, University of Birmingham10, McMaster University11, Johns Hopkins University12, University of Bern13, University of Copenhagen14, Medical Research Council15, GlaxoSmithKline16, University of California, San Francisco17, FHI 36018, Cochrane Collaboration19
TL;DR: Provide a structured summary including, as applicable, background, objectives, data sources, study eligibility criteria, participants, interventions, study appraisal and synthesis methods, results, limitations, conclusions and implications of key findings, systematic review registration number 2.
Abstract: Provide a structured summary including, as applicable, background, objectives, data sources, study eligibility criteria, participants, interventions, study appraisal and synthesis methods, results, limitations, conclusions and implications of key findings, systematic review registration number 2 Structured summary
3,655 citations
TL;DR: For example, this article found that exposure to multiple types and repeated episodes of maltreatment is associated with increased risks of severe maltreatment and psychological consequences, which has longlasting effects on mental health, drug and alcohol misuse (especially in girls), risky sexual behaviour, obesity, and criminal behaviour.
3,034 citations
B. I. Abelev1, Madan M. Aggarwal2, Zubayer Ahammed3, A. V. Alakhverdyants4 +345 more•Institutions (49)
1,696 citations
Christopher Newton-Cheh1, Christopher Newton-Cheh2, Toby Johnson3, Toby Johnson4 +359 more•Institutions (64)
TL;DR: In this paper, the association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2(P = 1 × 10-23), FGF5 (P=1 × 10 -21), SH2B3(P= 3 × 10−18), MTHFR(MTHFR), c10orf107(P), ZNF652(ZNF652), PLCD3 (P,P = 5 × 10 −9),
Abstract: Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
1,205 citations
TL;DR: In this paper, the production of mesons containing strange quarks (KS, φ) and both singly and doubly strange baryons (,, and − + +) are measured at mid-rapidity in pp collisions at √ s = 0.9 TeV with the ALICE experiment at the LHC.
1,176 citations
TL;DR: It is found that substantial risks are found but no evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease.
Abstract: level was 1.6 μmol per liter (95% CI, −8.4 to 5.2 [0.02 mg per deciliter; 95% CI, −0.10 to 0.06]) lower in the revascularization group than in the medical-therapy group. There was no significant between-group difference in systolic blood pressure; the decrease in diastolic blood pressure was smaller in the revascularization group than in the medical-therapy group. The two study groups had similar rates of renal events (hazard ratio in the revascularization group, 0.97; 95% CI, 0.67 to 1.40; P = 0.88), major cardiovascular events (hazard ratio, 0.94; 95% CI, 0.75 to 1.19; P = 0.61), and death (hazard ratio, 0.90; 95% CI, 0.69 to 1.18; P = 0.46). Serious complications associated with revascularization occurred in 23 patients, including 2 deaths and 3 amputations of toes or limbs. Conclusions We found substantial risks but no evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease. (Current Controlled Trials number, ISRCTN59586944.)
948 citations
TL;DR: In this paper, the authors describe the contents and the construction of the EU KLEMS Growth and Productivity Accounts, which contains industry-level measures of output, inputs and productivity for 25 European countries, Japan and the US for the period from 1970 onwards.
Abstract: This article describes the contents and the construction of the EU KLEMS Growth and Productivity Accounts. This database contains industry-level measures of output, inputs and productivity for 25 European countries, Japan and the US for the period from 1970 onwards. The article considers the methodology employed in constructing the database and shows how it can be useful in comparing productivity trends. Although growth accounts are the organising principle, it is argued that the database is useful for a wider range of applications. We give some guidance to prudent use and indicate possible extensions.
923 citations
Columbia University1, University of Miami2, University of North Carolina at Chapel Hill3, SUNY Downstate Medical Center4, University College London5, Cambridge University Hospitals NHS Foundation Trust6, University of California, San Francisco7, University of California, Los Angeles8, University of Alabama at Birmingham9, Rio de Janeiro State University10, University of Guadalajara11, University of Düsseldorf12, New York University13, University of Barcelona14, Shanghai Jiao Tong University15, University of Lisbon16, Stellenbosch University17, Guy's and St Thomas' NHS Foundation Trust18, Oregon Health & Science University19, University of Padua20, University of Leeds21, North Shore-LIJ Health System22, Northwestern University23, Medical University of South Carolina24, University of Birmingham25, Sun Yat-sen University26, Lille University of Science and Technology27, Charité28, Rutgers University29, Federal University of São Paulo30, University of Debrecen31, Imperial College London32, Emory University33, University of Liège34, University of Pittsburgh35, University of Paris36, University of the Witwatersrand37, California State University, Long Beach38, Royal Melbourne Hospital39, University of Texas Southwestern Medical Center40, Autonomous University of Barcelona41, Pennsylvania State University42, Johns Hopkins University43, University of Szeged44, Duke University45, University of Colorado Denver46, Harvard University47, University of Cape Town48, University of Malaya49, Peking Union Medical College50
TL;DR: Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
Abstract: Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
909 citations
Book•
04 Mar 2009TL;DR: Part I (General) Entries include: central issues in translation theory (e.g., equivalence, translatability) terms which have a specific meaning in translation studies (i.e., imitation, paraphrase) various approaches to translation (e., e.g. linguistic perspective, interpretive approach) types of translation and interpreting (e,g. literary translation, dubbing, and signed language interpreting) Part II (History and Traditions) Entrants include Russian, French, Arabic, Japanese, Chinese and Finnish, and regions including Brazil, Canada and India
Abstract: Part I (General) Entries include: central issues in translation theory (e.g. equivalence, translatability) terms which have a specific meaning in translation studies (e.g.imitation, paraphrase) various approaches to translation (e.g. linguistic perspective, interpretive approach) types of translation and interpreting (e.g. literary translation, dubbing, and signed language interpreting) Part II (History and Traditions) Entries include Russian, French, Arabic, Japanese, Chinese and Finnish, and regions including Brazil, Canada and India.
902 citations
Queen Mary University of London1, Pompeu Fabra University2, Spanish National Research Council3, University of Würzburg4, University of Leeds5, Helmholtz Centre for Environmental Research - UFZ6, University of Birmingham7, Temuco Catholic University8, Alfred Wegener Institute for Polar and Marine Research9, University of York10, Aarhus University11, Imperial College London12, University of Sheffield13
TL;DR: A number of 'dead ends' and 'fruitful avenues' are suggested for future research into ecological networks by suggesting a new catalogue of evermore complete, taxonomically resolved, and quantitative data.
Abstract: Summary 1. A fundamental goal of ecological network research is to understand how the complexity observed in nature can persist and how this affects ecosystem functioning. This is essential for us to be able to predict, and eventually mitigate, the consequences of increasing environmental perturbations such as habitat loss, climate change, and invasions of exotic species. 2. Ecological networks can be subdivided into three broad types: ‘traditional’ food webs, mutualistic networks and host‐parasitoid networks. There is a recent trend towards cross-comparisons among network types and also to take a more mechanistic, as opposed to phenomenological, perspective. For example, analysis of network configurations, such as compartments, allows us to explore the role of co-evolution in structuring mutualistic networks and host‐parasitoid networks, and of body size in food webs. 3. Research into ecological networks has recently undergone a renaissance, leading to the production of a new catalogue of evermore complete, taxonomically resolved, and quantitative data. Novel topological patterns have been unearthed and it is increasingly evident that it is the distribution of interaction strengths and the configuration of complexity, rather than just its magnitude, that governs network stability and structure. 4. Another significant advance is the growing recognition of the importance of individual traits and behaviour: interactions, after all, occur between individuals. The new generation of high-quality networks is now enabling us to move away from describing networks based on species-averaged data and to start exploring patterns based on individuals. Such refinements will enable us to address more general ecological questions relating to foraging theory and the recent metabolic theory of ecology. 5. We conclude by suggesting a number of ‘dead ends’ and ‘fruitful avenues’ for future research into ecological networks.
867 citations
TL;DR: It is concluded that the sensitive detection of contamination events in recycled water systems may be achieved by monitoring Peak T and/or Peak C fluorescence.
TL;DR: It is proposed that the success of infants and nonhuman animals on some belief reasoning tasks may be best explained by a cognitively efficient but inflexible capacity for tracking belief-like states in humans.
Abstract: The lack of consensus on how to characterize humans' capacity for belief reasoning has been brought into sharp focus by recent research. Children fail critical tests of belief reasoning before 3 to 4 years of age (H. Wellman, D. Cross, & J. Watson, 2001; H. Wimmer & J. Perner, 1983), yet infants apparently pass false-belief tasks at 13 or 15 months (K. H. Onishi & R. Baillargeon, 2005; L. Surian, S. Caldi, & D. Sperber, 2007). Nonhuman animals also fail critical tests of belief reasoning but can show very complex social behavior (e.g., J. Call & A Tomasello, 2005). Fluent social interaction in adult humans implies efficient processing of beliefs, yet direct tests suggest that belief reasoning is cognitively demanding, even for adults (e.g., I. A. Apperly, D. Samson, & G. W. Humphreys, 2009). The authors interpret these findings by drawing an analogy with the domain of number cognition, where similarly contrasting results have been observed. They propose that the success of infants and nonhuman animals on some belief reasoning tasks may be best explained by a cognitively efficient but inflexible capacity for tracking belief-like states. In humans, this capacity persists in parallel with a later-developing, more flexible but more cognitively demanding theory-of-mind abilities.
TL;DR: In this article, the authors measured the charged-particle spectra at the BNL Relativistic Heavy Ion Collider (RHIC) time projection chamber and reported the average transverse momenta, total particle production, particle yield ratios, strangeness, and baryon production rates as a function of collision system and centrality.
Abstract: Identified charged-particle spectra of pi(+/-), K(+/-), p, and (p) over bar at midrapidity (vertical bar y vertical bar < 0.1) measured by the dE/dx method in the STAR (solenoidal tracker at the BNL Relativistic Heavy Ion Collider) time projection chamber are reported for pp and d + Au collisions at root s(NN) = 200 GeV and for Au + Au collisions at 62.4, 130, and 200 GeV. Average transverse momenta, total particle production, particle yield ratios, strangeness, and baryon production rates are investigated as a function of the collision system and centrality. The transverse momentum spectra are found to be flatter for heavy particles than for light particles in all collision systems; the effect is more prominent for more central collisions. The extracted average transverse momentum of each particle species follows a trend determined by the total charged-particle multiplicity density. The Bjorken energy density estimate is at least several GeV/fm(3) for a formation time less than 1 fm/c. A significantly larger net-baryon density and a stronger increase of the net-baryon density with centrality are found in Au + Au collisions at 62.4 GeV than at the two higher energies. Antibaryon production relative to total particle multiplicity is found to be constant over centrality, but increases with the collision energy. Strangeness production relative to total particle multiplicity is similar at the three measured RHIC energies. Relative strangeness production increases quickly with centrality in peripheral Au + Au collisions, to a value about 50% above the pp value, and remains rather constant in more central collisions. Bulk freeze-out properties are extracted from thermal equilibrium model and hydrodynamics-motivated blast-wave model fits to the data. Resonance decays are found to have little effect on the extracted kinetic freeze-out parameters because of the transverse momentum range of our measurements. The extracted chemical freeze-out temperature is constant, independent of collision system or centrality; its value is close to the predicted phase-transition temperature, suggesting that chemical freeze-out happens in the vicinity of hadronization and the chemical freeze-out temperature is universal despite the vastly different initial conditions in the collision systems. The extracted kinetic freeze-out temperature, while similar to the chemical freeze-out temperature in pp, d + Au, and peripheral Au + Au collisions, drops significantly with centrality in Au + Au collisions, whereas the extracted transverse radial flow velocity increases rapidly with centrality. There appears to be a prolonged period of particle elastic scatterings from chemical to kinetic freeze-out in central Au + Au collisions. The bulk properties extracted at chemical and kinetic freeze-out are observed to evolve smoothly over the measured energy range, collision systems, and collision centralities.
TL;DR: Current knowledge of methods and avenues for their exploitation in the clinic are summarized, which allow the production of rMAbs bearing pre-selected oligosaccharides — glycoforms — to provide maximum efficacy for a given disease indication.
Abstract: To date, more than 20 recombinant immunoglobulin G (IgG) antibody therapeutics are licensed for the treatment of various diseases The mechanism of action of recombinant monoclonal antibodies (rMAbs) has been extensively investigated and several distinct pathways have been defined; selective activation of specific pathways may optimize clinical outcomes for different diseases, such as cancer and chronic inflammation Human IgG is a glycoprotein with oligosaccharides attached at a single site These are essential to the mode of action of rMAbs, and the antibody efficacy can vary depending on the particular oligosaccharide that is attached Methods are now becoming available that allow the production of rMAbs bearing pre-selected oligosaccharides - glycoforms - to provide maximum efficacy for a given disease indication This Review summarizes current knowledge of these methods and avenues for their exploitation in the clinic
TL;DR: Some of the new mechanisms and recent trends in the global spread of multidrug resistant (MDR) bacteria are reviewed, with the emergence of community-associated methicillin-resistant Staphylococcus aureus blurring the distinction between hospital and community strains.
Abstract: Antibiotic resistance is now a linked global problem. Dispersion of successful clones of multidrug resistant (MDR) bacteria is common, often via the movement of people. Local evolution of MDR bacteria is also important under the pressure of excessive antibiotic use, with horizontal gene transfer providing the means by which genes such as bla(CTX-M) spread amongst different bacterial species and strains. Beta-lactamase production is a common resistance mechanism in Gram-negative bacteria, and the rapid dissemination of novel genes reflects their evolution under the selective pressure of antibiotic usage. Many Enterobacteriaceae now carry broad-spectrum beta-lactamases such as CTX-M, with particular genotypes associated with different geographical regions. The spread of these enzymes has compromised the clinical utility of a number of beta-lactam classes and with the spread of genes such as bla(KPC), carbapenems may be increasingly compromised in the future. High-level fluoroquinolone resistance (mainly caused by gyrA mutations) has also been shown to be associated with CTX-M and CMY-type enzymes, commonly due to co-carriage on conjugative plasmids of the gene for the aminoglycoside-inactivating enzyme AAC-6(1)-Ib-cr and qnr genes (which confer low-level resistance), allowing the easy selection of gyrA mutants in the host strain. Resistance in Gram-positive bacteria is also widely distributed and increasing, with the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) blurring the distinction between hospital and community strains. Antibiotic use and environmental factors all have a role in the emergence and spread of resistance. This article reviews some of the new mechanisms and recent trends in the global spread of MDR bacteria.
TL;DR: Solubility and interactions with SRHA indicate that there was a specific nanoparticle effect which could not be explained by the effect of dissolved Ag, and this impact on Pseudomonas fluorescens is investigated.
Abstract: Silver nanoparticles (Ag NPs) are widely used as antibacterial agents. This antibacterial property carries with it a potential environmental risk once these NPs are discharged into the environment. This study investigated the impact on Pseudomonas fluorescens over a 24 h exposure of well characterized Ag NPs at pH values of 6−9, in the presence and absence of Suwannee River humic acids (SRHA). Ag NPs were characterized by size, aggregation, morphology, dissolution, and surface properties under all conditions. Solubility was low (less than 2%) for all Ag NP concentrations (2−2000 ppb) and under all conditions was less than 40 ppb (0.38 μM). SRHA caused a partial disaggregation of Ag NP aggregates by nanoscale film formation, with individual NPs stabilized by charge and entropically driven steric effects. Dissolved Ag reduced bacterial growth entirely at 2000 ppb (19 μM) under all conditions and adversely affected growth at 200 ppb (1.9 μM) under some conditions, indicating some toxicity. The Ag NPs showed ...
TL;DR: It is reported that the ubiquitin ligase RNF168 is mutated in the RIDDLE syndrome, a recently discovered immunodeficiency and radiosensitivity disorder and their loss is the likely cause of the cellular and developmental phenotypes associated with RIDdLE syndrome.
The Royal Marsden NHS Foundation Trust1, University of Birmingham2, National Health Service3, Australian National University4, University of Leicester5, Guy's Hospital6, University of Warwick7, University of Liverpool8, British Geological Survey9, University Hospitals Bristol NHS Foundation Trust10, St James's University Hospital11, Staffordshire University12, University Hospitals Birmingham NHS Foundation Trust13, University of Southampton14, Medical University of Vienna15, University Hospital of Basel16, Royal Liverpool University Hospital17
TL;DR: GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer and the meta-analysis of published studies showed a significant survival benefit in favor of GEM- CAP.
Abstract: Purpose Both gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP).
Patients and Methods Patients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status ≤ 2 were recruited. Patients were randomly assigned to GEM or GEM-CAP. The primary outcome measure was survival. Meta-analysis of published studies was also conducted.
Results Between May 2002 and January 2005, 533 patients were randomly assigned to GEM (n = 266) and GEM-CAP (n = 267) arms. GEM-CAP significantly improved objective response rate (19.1% v 12.4%; P = .034) and progression-free survival (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .004) and was associated with a trend toward improved OS (HR, 0.86; 95% CI, 0.72 to 1.02; P = .08) compared with GEM alone. This trend for OS benefit for GEM-CAP was consistent across different prognostic subgroups according to baseline stratification factors (stage and performance status) and remained after adjusting for these stratification factors (P = .077). Moreover, the meta-analysis of two additional studies involving 935 patients showed a significant survival benefit in favor of GEM-CAP (HR, 0.86; 95% CI, 0.75 to 0.98; P = .02) with no intertrial heterogeneity.
Conclusion On the basis of our trial and the meta-analysis, GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.
TL;DR: This review provides a comprehensive and current overview of environmental metabolomics research, and critically evaluates the contribution that metabolomics has made to the environmental sciences, and highlights and discusses recommendations to advance the understanding of the environment, ecology and evolution using a metabolomics approach.
Abstract: Environmental metabolomics is the application of metabolomics to characterise the interactions of organisms with their environment. This approach has many advantages for studying organism–environment interactions and for assessing organism function and health at the molecular level. As such, metabolomics is finding an increasing number of applications in the environmental sciences, ranging from understanding organismal responses to abiotic pressures, to investigating the responses of organisms to other biota. These interactions can be studied from individuals to populations, which can be related to the traditional fields of ecophysiology and ecology, and from instantaneous effects to those over evolutionary time scales, the latter enabling studies of genetic adaptation. This review provides a comprehensive and current overview of environmental metabolomics research. We begin with an overview of metabolomic studies into the effects of abiotic pressures on organisms. In the field of ecophysiology, studies on the metabolic responses to temperature, water, food availability, light and circadian rhythms, atmospheric gases and season are reviewed. A section on ecotoxicogenomics discusses research in aquatic and terrestrial ecotoxicology, assessing organismal responses to anthropogenic pollutants in both the laboratory and field. We then discuss environmental metabolomic studies of diseases and biotic–biotic interactions, in particular herbivory. Finally, we critically evaluate the contribution that metabolomics has made to the environmental sciences, and highlight and discuss recommendations to advance our understanding of the environment, ecology and evolution using a metabolomics approach.
TL;DR: The results suggest that 1,25(OH)2D3 and IL-2 have direct synergistic effects on activated T cells, acting as potent anti-inflammatory agents and physiologic inducers of adaptive regulatory T cells.
Abstract: The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has potent immunomodulatory properties that have promoted its potential use in the prevention and treatment of infectious disease and autoimmune conditions. A variety of immune cells, including macrophages, dendritic cells, and activated T cells express the intracellular vitamin D receptor and are responsive to 1,25(OH)(2)D(3.) Despite this, how 1,25(OH)(2)D(3) regulates adaptive immunity remains unclear and may involve both direct and indirect effects on the proliferation and function of T cells. To further clarify this issue, we have assessed the effects of 1,25(OH)(2)D(3) on human CD4(+)CD25(-) T cells. We observed that stimulation of CD4(+)CD25(-) T cells in the presence of 1,25(OH)(2)D(3) inhibited production of proinflammatory cytokines including IFN- gamma, IL-17, and IL-21 but did not substantially affect T cell division. In contrast to its inhibitory effects on inflammatory cytokines, 1,25(OH)(2)D(3) stimulated expression of high levels of CTLA-4 as well as FoxP3, the latter requiring the presence of IL-2. T cells treated with 1,25(OH)(2)D(3) could suppress proliferation of normally responsive T cells, indicating that they possessed characteristics of adaptive regulatory T cells. Our results suggest that 1,25(OH)(2)D(3) and IL-2 have direct synergistic effects on activated T cells, acting as potent anti-inflammatory agents and physiologic inducers of adaptive regulatory T cells.
TL;DR: The proposed simple guidelines for combining estimates after MI may lead to a wider and more appropriate use of MI in future prognostic modelling studies.
Abstract: multiple imputation (mi) provides an effective approach to handle missing covariate data within prognostic modelling studies, as it can properly account for the missing data uncertainty. the multiply imputed datasets are each analysed using standard prognostic modelling techniques to obtain the estimates of interest. the estimates from each imputed dataset are then combined into one overall estimate and variance, incorporating both the within and between imputation variability. rubin's rules for combining these multiply imputed estimates are based on asymptotic theory. the resulting combined estimates may be more accurate if the posterior distribution of the population parameter of interest is better approximated by the normal distribution. however, the normality assumption may not be appropriate for all the parameters of interest when analysing prognostic modelling studies, such as predicted survival probabilities and model performance measures. guidelines for combining the estimates of interest when analysing prognostic modelling studies are provided. a literature review is performed to identify current practice for combining such estimates in prognostic modelling studies. methods for combining all reported estimates after mi were not well reported in the current literature. rubin's rules without applying any transformations were the standard approach used, when any method was stated. the proposed simple guidelines for combining estimates after mi may lead to a wider and more appropriate use of mi in future prognostic modelling studies.
deCODE genetics1, Radboud University Nijmegen Medical Centre2, University of Iceland3, University of Turin4, Karolinska Institutet5, German Cancer Research Center6, St James's University Hospital7, University of Brescia8, Katholieke Universiteit Leuven9, Maastricht University10, University of Birmingham11, University of Zaragoza12, Northwestern University13, Radboud University Nijmegen14, University of Gothenburg15, Imperial College London16
TL;DR: It is found that rs401681[C] on chromosome 5p15 satisfied the threshold for genome-wide significance and seems to confer protection against cutaneous melanoma, and investigation of the region led to rs2736098[A], which showed stronger association with some cancer types, but neither variant could fully account for the association of the other.
Abstract: The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.
Karolinska Institutet1, University of Pittsburgh2, Queen Mary University of London3, University of Exeter4, University of Texas Health Science Center at Houston5, University of St Andrews6, University of California, San Diego7, Aarhus University8, University of Warwick9, University of California, Santa Barbara10, University of Birmingham11, Yeshiva University12, University of Düsseldorf13, Louisiana State University in Shreveport14, Wake Forest University15, University of Vienna16, University of Alabama at Birmingham17, Emory University18, University of Glasgow19, Cleveland Clinic20, Uppsala University21, Russian Academy of Sciences22, University of Oklahoma23, National Institutes of Health24, University of Tokushima25, Utrecht University26, Ohio State University27
TL;DR: The latest advances in the understanding of the biochemistry, physiology and therapeutics of nitrate, nitrite and NO were discussed during a recent 2-day meeting at the Nobel Forum, Karolinska Institutet in Stockholm.
Abstract: Inorganic nitrate and nitrite from endogenous or dietary sources are metabolized in vivo to nitric oxide (NO) and other bioactive nitrogen oxides. The nitrate-nitrite-NO pathway is emerging as an important mediator of blood flow regulation, cell signaling, energetics and tissue responses to hypoxia. The latest advances in our understanding of the biochemistry, physiology and therapeutics of nitrate, nitrite and NO were discussed during a recent 2-day meeting at the Nobel Forum, Karolinska Institutet in Stockholm.
TL;DR: This review evaluates the results of three randomised controlled trials, which analysed the effectiveness and safety of male circumcision for preventing acquisition of HIV in heterosexual men, and formulated a comprehensive and exhaustive search strategy to identify all relevant studies.
Abstract: Background The findings from observational studies reviews and meta- analyses supported by biological theories that circumcised men appear less likely to acquire human immunodeficiency virus (HIV) has contributed to the recent ground swell of support for considering male circumcision as a strategy for preventing sexually acquired infection. We sought to elucidate and appraise the global evidence from published and unpublished studies that circumcision can be used as an intervention to prevent HIV infection. Objectives 1) To assess the evidence of an interventional effect of male circumcision for preventing acquisition of HIV-1 and HIV-2 by men through heterosexual intercourse; 2) To examine the feasibility and value of performing individual person data (IPD) meta-analysis. Search strategy We searched online for published and unpublished studies in The Cochrane Library (issue 2 2002) MEDLINE (April 2002) EMBASE (February 2002) and AIDSLINE (August 2001). We also searched databases listing conference abstracts scanned reference lists of articles and contacted authors of included studies. Selection criteria We searched for randomized and quasi- randomized controlled trials of male circumcisions or in their absence observational studies that compare acquisition rates of HIV-1 and HIV-2 infection in circumcised and uncircumcised heterosexual men. Data collection and analysis Independent reviewers selected studies assessed study quality and extracted data. We stratified studies based on study design and on whether they included participants from the general population or high-risk groups (such as patients treated for sexually transmitted infections). We expressed findings as crude and adjusted odds ratios (OR) together with their 95% confidence intervals (CI) and conducted a sensitivity analysis to explore the effect of adjustment on study results. We investigated whether the method of circumcision ascertainment influenced study outcomes. Main results We identified no completed randomized controlled trials. Three randomized controlled trials are currently underway or commencing shortly. We found 35 observational studies: 16 conducted in the general population and 19 in high-risk populations. It seems unlikely that potential confounding factors were completely accounted for in any of the included studies. In particular important risk factors such as religion and sexual practices were not adequately accounted for in many of the included studies. General population study results: The single cohort study (N = 5516) showed a significant difference in HIV transmission rates between circumcised and uncircumcised men [OR = 0.58; 95% CI: 0.36 to 0.96]. Results for the 14 cross-sectional studies were inconsistent with point estimates for unadjusted odds ratios varying between 0.28 and 1.73. Six studies had statistically significant results four in the direction of benefit and two in the direction of harm. The test for heterogeneity between the cross-sectional studies was highly significant (chi-square = 77.59; df = 13; P-value < 0.00001). Nine studies reported adjusted odds ratios with eight in the direction of benefit ranging from 0.26 to 0.80. Use of adjusted results tended to show stronger evidence of an association although they remained heterogeneous (chi-square = 75.2; df = 13; P-value < 0.00001). Only one case-control study was found (N = 51) which had a non-significant result [OR = 1.90; 95% CI: 0.50 to 7.20]. High- risk group study results: The four cohort studies identified found a protective effect from circumcision with point estimates for unadjusted odds ratios varying from 0.10 to 0.39. Two of these studies had statistically significant results. Two studies reported adjusted odds ratios both protective with one being significant. The chi-square test for between-study heterogeneity was not significant (chi-square = 5.21; df = 3; P-value = 0.16). All eleven cross- sectional studies reporting unadjusted results found benefit from circumcision eight of which had statistically significant results. Estimates of effect varied from an unadjusted odds ratio of 0.10 to 0.66. Between-study heterogeneity was significant with the chi-square = 29.77; df = 10; P-value = 0.0009. Four of these studies reported adjusted odds ratios ranging from 0.20 to 0.59 and all were significant. One additional cross-sectional study only reported an adjusted odds ratio ranging from 0.20 to 0.59 and all were significant. All three case- control studies found a protective effect of circumcision on HIV status two being statistically significant. Point estimates varied from unadjusted odds ratios of 0.37 to 0.88. One reported an adjusted odds ratio showing a significant protective effect. Adverse effects: No studies reported on the adverse effects of circumcision. In most studies circumcision had taken place during childhood or adolescence before the studies commenced. Authors conclusions We found insufficient evidence to support an interventional effect of male circumcision on HIV acquisition in heterosexual men. The results from existing observational studies show a strong epidemiological association between male circumcision and prevention of HIV especially among high-risk groups. However observational studies are inherently limited by confounding which is unlikely to be fully adjusted for. In the light of forthcoming results from RCTs the value of IPD analysis of the included studies is doubtful. The results of these trials will need to be carefully considered before circumcision is implemented as a public health intervention for prevention of sexually transmitted HIV. (authors)
TL;DR: The results suggest that the improvement in exercise performance that is observed when carbohydrate is present in the mouth may be due to the activation of brain regions believed to be involved in reward and motor control.
Abstract: Exercise studies have suggested that the presence of carbohydrate in the human mouth activates regions of the brain that can enhance exercise performance but direct evidence of such a mechanism is limited. The first aim of the present study was to observe how rinsing the mouth with solutions containing glucose and maltodextrin, disguised with artificial sweetener, would affect exercise performance. The second aim was to use functional magnetic resonance imaging (fMRI) to identify the brain regions activated by these substances. In Study 1A, eight endurance-trained cyclists ( 60.8 ± 4.1 ml kg−1 min−1) completed a cycle time trial (total work = 914 ± 29 kJ) significantly faster when rinsing their mouths with a 6.4% glucose solution compared with a placebo containing saccharin (60.4 ± 3.7 and 61.6 ± 3.8 min, respectively, P= 0.007). The corresponding fMRI study (Study 1B) revealed that oral exposure to glucose activated reward-related brain regions, including the anterior cingulate cortex and striatum, which were unresponsive to saccharin. In Study 2A, eight endurance-trained cyclists ( 57.8 ± 3.2 ml kg−1 min−1) tested the effect of rinsing with a 6.4% maltodextrin solution on exercise performance, showing it to significantly reduce the time to complete the cycle time trial (total work = 837 ± 68 kJ) compared to an artificially sweetened placebo (62.6 ± 4.7 and 64.6 ± 4.9 min, respectively, P= 0.012). The second neuroimaging study (Study 2B) compared the cortical response to oral maltodextrin and glucose, revealing a similar pattern of brain activation in response to the two carbohydrate solutions, including areas of the insula/frontal operculum, orbitofrontal cortex and striatum. The results suggest that the improvement in exercise performance that is observed when carbohydrate is present in the mouth may be due to the activation of brain regions believed to be involved in reward and motor control. The findings also suggest that there may be a class of so far unidentified oral receptors that respond to carbohydrate independently of those for sweetness.
TL;DR: It is argued that ‘propagule pressure’, a key term in invasion biology, has been attributed at least three distinct definitions, with the result that the distinct importance of these different concepts has been at best diluted, and at worst lost.
Abstract: Aim We argue that ‘propagule pressure’, a key term in invasion biology, has been attributed at least three distinct definitions (with usage of a related term causing additional confusion). All of the definitions refer to fundamental concepts within the invasion process, with the result that the distinct importance of these different concepts has been at best diluted, and at worst lost.
Location Global.
Methods We reviewed pertinent literature on propagule pressure to resolve confusion about different uses of the term ‘propagule pressure’ and we introduced a new term for one variant, colonization pressure. We conducted a computer simulation whereby the introduction of species is represented as a simple sampling process to elucidate the relationship between propagule and colonization pressure.
Results We defined colonization pressure as the number of species introduced or released to a single location, some of which will go on to establish a self-sustaining population and some of which will not. We subsequently argued that colonization pressure should serve as a null hypothesis for understanding temporal or spatial differences in exotic species richness, as the more species that are introduced, the more we should expect to establish. Finally, using a simple simulation, we showed that propagule pressure is related to colonization pressure, but in a non-linear manner.
Main conclusion We suggest that the nature of the relationship between propagule pressure and colonization pressure, as well as the efficacy of various proxy measures of each, require more detailed exploration if invasion ecology is to continue to develop into a more predictive science.
TL;DR: The formation of small aggregates of about 170 nm and surface coating of several nanometers of SRHA on iron oxide NPs confirm the role of NOM in the disaggregation process and indicate that NPs might mimic the behavior of natural colloids.
TL;DR: Genome analysis of other epidemic ST313 isolates from Malawi and Kenya provided evidence for microevolution and clonal replacement in the field, including evidence of genome degradation, including pseudogene formation and chromosomal deletions, when compared with other S. Typhimurium genome sequences.
Abstract: Whereas most nontyphoidal Salmonella (NTS) are associated with gastroenteritis, there has been a dramatic increase in reports of NTS-associated invasive disease in sub-Saharan Africa. Salmonella enterica serovar Typhimurium isolates are responsible for a significant proportion of the reported invasive NTS in this region. Multilocus sequence analysis of invasive S. Typhimurium from Malawi and Kenya identified a dominant type, designated ST313, which currently is rarely reported outside of Africa. Whole-genome sequencing of a multiple drug resistant (MDR) ST313 NTS isolate, D23580, identified a distinct prophage repertoire and a composite genetic element encoding MDR genes located on a virulence-associated plasmid. Further, there was evidence of genome degradation, including pseudogene formation and chromosomal deletions, when compared with other S. Typhimurium genome sequences. Some of this genome degradation involved genes previously implicated in virulence of S. Typhimurium or genes for which the orthologs in S. Typhi are either pseudogenes or are absent. Genome analysis of other epidemic ST313 isolates from Malawi and Kenya provided evidence for microevolution and clonal replacement in the field.
TL;DR: In this article, the adsorption behavior of natural zeolite (clinoptilolite) has been studied in order to determine its applicability in treating acid mine drainage.
TL;DR: Otley et al. as mentioned in this paper present a review of management control, focusing on the following emerging themes; decision making for strategic control; performance management for strategic controlling; control models for performance management and measurement; management control and new forms of organisation; control and risk; culture and control; and practice and theory.
Abstract: This review starts from the lines of enquiry suggested by Otley et al. [Otley, D.T., Broadbent, J.M., Berry, A.J., 1995. Research in management control: an overview of its development. British Journal of Management 6, S31–S34] and develops these themes in the light of more recently published research. Hence this review is structured around the following emerging themes; Decision making for Strategic Control; Performance Management for Strategic Control; Control Models for Performance Management and Measurement; Management Control and New Forms of Organisation; Control and Risk; Culture and Control; and Practice and Theory. Whilst research has been evident in all of these areas, relatively little attention has been paid to information and communication technologies and its impact upon control system design and capability, nor did we find much literature on control and gender, or on control and sustainability. Further there has been relatively little research on control and risk or upon control and culture. The limitations of overarching frameworks are noted and we conclude that it seems essential to place more emphasis on research which attends to the relationship of control practices and theory which will require more embedded and collaborative research processes.