Showing papers by "University of Southampton published in 2009"
Cardiff University1, Medical Research Council2, University of Bristol3, National Institute for Health Research4, King's College5, Trinity College, Dublin6, University of Cambridge7, University of Nottingham8, Queen's University Belfast9, University of Southampton10, University of Manchester11, John Radcliffe Hospital12, UCL Institute of Neurology13, University of Bonn14, University of Hamburg15, Charité16, University of Erlangen-Nuremberg17, University of Duisburg-Essen18, Ludwig Maximilian University of Munich19, Heidelberg University20, University College Dublin21, University of Freiburg22, Washington University in St. Louis23, Brigham Young University24, University of Antwerp25, University College London26, Wellcome Trust Sanger Institute27, King's College London28, Aristotle University of Thessaloniki29, National Institutes of Health30, Mayo Clinic31
TL;DR: A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.
Abstract: We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 10-157) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 10-9) and 5' to the PICALM gene (rs3851179, P = 1.9 10-8). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 10-10, odds ratio = 0.86; rs3851179, P = 1.3 10-9, odds ratio = 0.86).
2,956 citations
TL;DR: The present state of the art of constructing surrogate models and their use in optimization strategies is reviewed and extensive use of pictorial examples are made to give guidance as to each method's strengths and weaknesses.
1,919 citations
TL;DR: In this article, the authors present an assessment of 33 deltas chosen to represent the world's Deltas and find that in the past decade, 85% of them experienced severe flooding, resulting in the temporary submergence of 260,000 km2.
Abstract: Many of the world's deltas are densely populated and intensively farmed. An assessment of recent publications indicates that the majority of these deltas have been subject to intense flooding over the past decade, and that this threat will grow as global sea-level rises and as the deltas subside. Many of the world's largest deltas are densely populated and heavily farmed. Yet many of their inhabitants are becoming increasingly vulnerable to flooding and conversions of their land to open ocean. The vulnerability is a result of sediment compaction from the removal of oil, gas and water from the delta's underlying sediments, the trapping of sediment in reservoirs upstream and floodplain engineering in combination with rising global sea level. Here we present an assessment of 33 deltas chosen to represent the world's deltas. We find that in the past decade, 85% of the deltas experienced severe flooding, resulting in the temporary submergence of 260,000 km2. We conservatively estimate that the delta surface area vulnerable to flooding could increase by 50% under the current projected values for sea-level rise in the twenty-first century. This figure could increase if the capture of sediment upstream persists and continues to prevent the growth and buffering of the deltas.
1,825 citations
TL;DR: A wealth of data now demonstrate that the microglia have very diverse effector functions, in line with macrophage populations in other organs, and the term activatedmicroglia needs to be qualified to reflect the distinct and very different states of activation-associated effector function in different disease states.
Abstract: Microglia, the macrophages of the central nervous system parenchyma, have in the normal healthy brain a distinct phenotype induced by molecules expressed on or secreted by adjacent neurons and astrocytes, and this phenotype is maintained in part by virtue of the blood-brain barrier's exclusion of serum components. Microglia are continually active, their processes palpating and surveying their local microenvironment. The microglia rapidly change their phenotype in response to any disturbance of nervous system homeostasis and are commonly referred to as activated on the basis of the changes in their morphology or expression of cell surface antigens. A wealth of data now demonstrate that the microglia have very diverse effector functions, in line with macrophage populations in other organs. The term activated microglia needs to be qualified to reflect the distinct and very different states of activation-associated effector functions in different disease states. Manipulating the effector functions of microglia has the potential to modify the outcome of diverse neurological diseases.
1,611 citations
TL;DR: This review defines the DMN concept with regard to its neuro-anatomy, its functional organisation through low frequency neuronal oscillations, its relation to other recently discovered low frequency resting state networks, and the cognitive functions it is thought to serve, and introduces methodological and analytical issues and challenges.
1,515 citations
TL;DR: This 2007 global P. falciparum malaria endemicity map is the first of a series with which it will be possible to monitor and evaluate the progress of this intervention process, and shows significant opportunities for malaria control in Africa and for malaria elimination elsewhere.
Abstract: Transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations. Maps of transmission intensity are necessary to identify populations at different levels of risk and to evaluate objectively options for disease control. To remain relevant operationally, such maps must be updated frequently. Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010. This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (Pf EIR) and the basic reproductive number (PfR). Annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (Pf PR) surveys were used in a model-based geostatistical (MBG) prediction to create a continuous contemporary surface of malaria endemicity within these limits. A suite of transmission models were developed that link Pf PR to Pf EIR and PfR and these were fitted to field data. These models were combined with the Pf PR map to create new global predictions of Pf EIR and PfR. All output maps included measured uncertainty. An estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively. The majority of the endemic world was predicted with a median Pf EIR of less than one and a median PfRc of less than two. Values of either metric exceeding 10 were almost exclusive to Africa. The uncertainty described in both Pf EIR and PfR was substantial in regions of intense transmission. The year 2010 has a particular significance as an evaluation milestone for malaria global health policy. The maps presented here contribute to a rational basis for control and elimination decisions and can serve as a baseline assessment as the global health community looks ahead to the next series of milestones targeted at 2015.
1,161 citations
Wellcome Trust Sanger Institute1, Broad Institute2, J. Craig Venter Institute3, University of Texas Health Science Center at San Antonio4, University of York5, University of Maryland, College Park6, University of California, San Francisco7, Oswaldo Cruz Foundation8, University of Texas at San Antonio9, Universidade Federal de Minas Gerais10, University College Cork11, Iowa State University12, University of São Paulo13, University of Pittsburgh14, Kyoto University15, University of Southampton16, Natural History Museum17, Lille University of Science and Technology18, John Innes Centre19, Leiden University20, University of Göttingen21, University of Maryland, Baltimore22, Illinois State University23, Rush University Medical Center24, University at Buffalo25
TL;DR: Analysis of the 363 megabase nuclear genome of the blood fluke, the first sequenced flatworm, and a representative of the Lophotrochozoa offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and theDevelopment of tissues into organs.
Abstract: Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.
997 citations
TL;DR: Bariatric surgery was a more effective intervention for weight loss than non-surgical options and there was higher remission of Type 2 diabetes than in non-Surgical groups.
Abstract: Objectives: to assess the clinical effectiveness and cost-effectiveness of bariatric surgery for obesity. Data sources: seventeen electronic databases were searched [MEDLINE; EMBASE; PreMedline In-Process & Other Non-Indexed Citations; The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, DARE, NHS EED and HTA databases; Web of Knowledge Science Citation Index (SCI); Web of Knowledge ISI Proceedings; PsycInfo; CRD databases; BIOSIS; and databases listing ongoing clinical trials] from inception to August 2008. Bibliographies of related papers were assessed and experts were contacted to identify additional published and unpublished references Review methods: two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text using a standard form. Interventions investigated were open and laparoscopic bariatric surgical procedures in widespread current use compared with one another and with non-surgical interventions. Population comprised adult patients with body mass index (BMI) ? 30 and young obese people. Main outcomes were at least one of the following after at least 12 months follow-up: measures of weight change; quality of life (QoL); perioperative and postoperative mortality and morbidity; change in obesity-related comorbidities; cost-effectiveness. Studies eligible for inclusion in the systematic review for comparisons of Surgery versus Surgery were RCTs. For comparisons of Surgery versus Non-surgical procedures eligible studies were RCTs, controlled clinical trials and prospective cohort studies (with a control cohort). Studies eligible for inclusion in the systematic review of cost-effectiveness were full cost-effectiveness analyses, cost-utility analyses, cost-benefit analyses and cost-consequence analyses. One reviewer performed data extraction, which was checked by two reviewers independently. Two reviewers independently applied quality assessment criteria and differences in opinion were resolved at each stage. Studies were synthesised through a narrative review with full tabulation of the results of all included studies. In the economic model the analysis was developed for three patient populations, those with BMI ? 40; BMI ? 30 and Results: a total of 5386 references were identified of which 26 were included in the clinical effectiveness review: three randomised controlled trials (RCTs) and three cohort studies compared surgery with non-surgical interventions and 20 RCTs compared different surgical procedures. Bariatric surgery was a more effective intervention for weight loss than non-surgical options. In one large cohort study weight loss was still apparent 10 years after surgery, whereas patients receiving conventional treatment had gained weight. Some measures of QoL improved after surgery, but not others. After surgery statistically fewer people had metabolic syndrome and there was higher remission of Type 2 diabetes than in non-surgical groups. In one large cohort study the incidence of three out of six comorbidities assessed 10 years after surgery was significantly reduced compared with conventional therapy. Gastric bypass (GBP) was more effective for weight loss than vertical banded gastroplasty (VBG) and adjustable gastric banding (AGB). Laparoscopic isolated sleeve gastrectomy (LISG) was more effective than AGB in one study. GBP and banded GBP led to similar weight loss and results for GBP versus LISG and VBG versus AGB were equivocal. All comparisons of open versus laparoscopic surgeries found similar weight losses in each group. Comorbidities after surgery improved in all groups, but with no significant differences between different surgical interventions. Adverse event reporting varied; mortality ranged from none to 10%. Adverse events from conventional therapy included intolerance to medication, acute cholecystitis and gastrointestinal problems. Major adverse events following surgery, some necessitating reoperation, included anastomosis leakage, pneumonia, pulmonary embolism, band slippage and band erosion. Bariatric surgery was cost-effective in comparison to non-surgical treatment in the reviewed published estimates of cost-effectiveness. However, these estimates are likely to be unreliable and not generalisable because of methodological shortcomings and the modelling assumptions made. Therefore a new economic model was developed. Surgical management was more costly than non-surgical management in each of the three patient populations analysed, but gave improved outcomes. For morbid obesity, incremental cost-effectiveness ratios (ICERs) (base case) ranged between £2000 and £4000 per QALY gained. They remained within the range regarded as cost-effective from an NHS decision-making perspective when assumptions for deterministic sensitivity analysis were changed. For BMI ? 30 and Conclusions: bariatric surgery appears to be a clinically effective and cost-effective intervention for moderately to severely obese people compared with non-surgical interventions. Uncertainties remain and further research is required to provide detailed data on patient QoL; impact of surgeon experience on outcome; late complications leading to reoperation; duration of comorbidity remission; resource use. Good-quality RCTs will provide evidence on bariatric surgery for young people and for adults with class I or class II obesity. New research must report on the resolution and/or development of comorbidities such as Type 2 diabetes and hypertension so that the potential benefits of early intervention can be assessed.
977 citations
TL;DR: Both acute and chronic systemic inflammation, associated with increases in serum tumor necrosis factor α, is associated with an increase in cognitive decline in Alzheimer disease.
Abstract: Background: Acute and chronic systemic inflammation are characterized by the systemic production of the proinflammatory cytokine tumor necrosis factor α (TNF-α) that plays a role in immune to brain communication. Previous preclinical research shows that acute systemic inflammation contributes to an exacerbation of neurodegeneration by activation of primed microglial cells. Objective: To determine whether acute episodes of systemic inflammation associated with increased TNF-α would be associated with long-term cognitive decline in a prospective cohort study of subjects with Alzheimer disease. Methods: Three hundred community-dwelling subjects with mild to severe Alzheimer disease were cognitively assessed, and a blood sample was taken for systemic inflammatory markers. Each subject’s main caregiver was interviewed to assess the presence of incident systemic inflammatory events. Assessments of both patient and caregiver were repeated at 2, 4, and 6 months. Results: Acute systemic inflammatory events, found in around half of all subjects, were associated with an increase in the serum levels of proinflammatory cytokine TNF-α and a 2-fold increase in the rate of cognitive decline over a 6-month period. High baseline levels of TNF-α were associated with a 4-fold increase in the rate of cognitive decline. Subjects who had low levels of serum TNF-α throughout the study showed no cognitive decline over the 6-month period. Conclusions: Both acute and chronic systemic inflammation, associated with increases in serum tumor necrosis factor α, is associated with an increase in cognitive decline in Alzheimer disease.
932 citations
TL;DR: The prevalence of radiographically defined vertebral deformity, as a marker of vertebral osteoporosis, in different regions and populations within Europe was determined using a cross‐sectional population‐based survey.
Abstract: Our aim was to determine the prevalence of radiographically defined vertebral deformity, as a marker of vertebral osteoporosis, in different regions and populations within Europe. We used a cross-sectional population-based survey. Population-based sampling frames were obtained from 36 centers in 19 European countries. Stratified random sampling was used to recruit 15,570 males and females aged 50-79 years. Lateral spinal radiographs were taken according to a standardized protocol, and all X-rays were evaluated centrally. Vertebral deformity was morphometrically defined according to the published methods of McCloskey and Eastell. Based on the McCloskey method, the mean center prevalence of all deformities was 12% in females (range 6-21%) and 12% in males (range 8-20%). The prevalence increased with age in both sexes though the gradient was steeper in females. There was substantial geographical variation, with the highest rates in Scandinavian countries. Radiographically defined vertebral deformity is a common disorder and equally frequent in males and females. Using standardized methodology, there is important variation in occurrence across Europe, which might suggest clues to pathogenesis.
923 citations
TL;DR: Observations show that patients are at increased risk for premature death for many years after a fragility-related hip fracture and highlight the need to identify those patients who are candidates for interventions to reduce their risk.
Abstract: This systematic literature review has shown that patients experiencing hip fracture after low-impact trauma are at considerable excess risk for death compared with nonhip fracture/community control populations. The increased mortality risk may persist for several years thereafter, highlighting the need for interventions to reduce this risk.Patients experiencing hip fracture after low-impact trauma are at considerable risk for subsequent osteoporotic fractures and premature death. We conducted a systematic review of the literature to identify all studies that reported unadjusted and excess mortality rates for hip fracture. Although a lack of consistent study design precluded any formal meta-analysis or pooled analysis of the data, we have shown that hip fracture is associated with excess mortality (over and above mortality rates in nonhip fracture/community control populations) during the first year after fracture ranging from 8.4% to 36%. In the identified studies, individuals experienced an increased relative risk for mortality following hip fracture that was at least double that for the age-matched control population, became less pronounced with advancing age, was higher among men than women regardless of age, was highest in the days and weeks following the index fracture, and remained elevated for months and perhaps even years following the index fracture. These observations show that patients are at increased risk for premature death for many years after a fragility-related hip fracture and highlight the need to identify those patients who are candidates for interventions to reduce their risk.
TL;DR: In this article, the authors investigate the regularity of cluster pressure profiles with REXCESS, a representative sample of 33 local clusters observed with XMM-Newton, and derive an average profile from observations scaled by mass and z according to the standard self-similar model, and find that the dispersion about the mean is remarkably low beyond 0.2R_500, but increases towards the centre.
Abstract: (abridged) We investigate the regularity of cluster pressure profiles with REXCESS, a representative sample of 33 local clusters observed with XMM-Newton. The sample spans a mass range of 10^14 M_sun
TL;DR: In this paper, the authors present an accounting for uncertainty in DEMs from repeat topographic surveys: improved sediment budgets, which can be used to improve the quality of topographic data.
Abstract: Wheaton, J. M., Brasington, J., Darby, S. E., Sear, D. A. (2010). Accounting for uncertainty in DEMs from repeat topographic surveys: improved sediment budgets. Earth Surface Processes and Landforms, 35, (2), 136-156.
TL;DR: This critical review includes advances in anion complexation in the year 2007 and covers anion receptors that employ amides and thioamides, pyrroles and indoles, ureas and thioureas, guanidinium, ammonium, and imidazolium groups and receptors containing hydroxyl groups.
Abstract: This critical review includes advances in anion complexation in the year 2007. The review covers anion receptors that employ amides and thioamides, pyrroles and indoles, ureas and thioureas, guanidinium, ammonium, and imidazolium groups and receptors containing hydroxyl groups. In addition, receptors containing metal ions or Lewis acids are discussed along with anion–π interactions and the membrane transport of anionic species by synthetic transporters and channels (204 references).
TL;DR: The results show that maintenance of the ovarian phenotype is an active process throughout life and might have important medical implications for the understanding and treatment of some disorders of sexual development in children and premature menopause in women.
TL;DR: It is found that the formation of CO is enhanced with elevated temperature and residence time, while slight change is observed for the yield of CO(2).
Book•
02 Jul 2009TL;DR: In this paper, the authors draw together evidence from a variety of democratic innovations from around the world, including participatory budgeting in Brazil, Citizens’ Assemblies on Electoral Reform in Canada, direct legislation in California and Switzerland and emerging experiments in e-democracy.
Abstract: Can we design institutions that increase and deepen citizen participation in the political decision making process? At a time when there is growing disillusionment with the institutions of advanced industrial democracies, there is also increasing interest in new ways of involving citizens in the political decisions that affect their lives. This book draws together evidence from a variety of democratic innovations from around the world, including participatory budgeting in Brazil, Citizens’ Assemblies on Electoral Reform in Canada, direct legislation in California and Switzerland and emerging experiments in e-democracy. The book offers a rare systematic analysis of this diverse range of democratic innovations, drawing lessons for the future development of both democratic theory and practice.
TL;DR: The European Psychiatric Association (EPA) supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC) published a statement with the aim of improving the care of patients suffering from severe mental illness as mentioned in this paper.
TL;DR: In this article, femtosecond optical frequency plasmon pulses can propagate along a metal-dielectric waveguide and can be modulated on the femto-cond timescale by direct ultrafast optical excitation of the metal, thereby offering unprecedented terahertz modulation bandwidth.
Abstract: Surface plasmon polaritons, propagating bound oscillations of electrons and light at a metal surface, have great potential as information carriers for next-generation, highly integrated nanophotonic devices [1,2]. Since the term 'active plasmonics' was coined in 2004 [3], a number of techniques for controlling the propagation of guided surface plasmon polariton signals have been demonstrated [4-7]. However, with sub-microsecond or nanosecond response times at best, these techniques are likely to be too slow for future applications in such fields as data transport and processing. Here we report that femtosecond optical frequency plasmon pulses can propagate along a metal-dielectric waveguide and that they can be modulated on the femtosecond timescale by direct ultrafast optical excitation of the metal, thereby offering unprecedented terahertz modulation bandwidth - a speed at least five orders of magnitude faster than existing technologies.
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: In this paper, a negative index of refraction due to three-dimensional chirality is demonstrated for bilayered metamaterial based on pairs of mutually twisted planar metal patterns in parallel planes, which also shows negative electric and magnetic responses and exceptionally strong optical activity and circular dichroism.
Abstract: Recently it has been predicted that materials with exceptionally strong optical activity may also possess a negative refractive index, allowing the realization of superlenses for super-resolution imaging and data storage applications. Here we demonstrate experimentally and numerically that a chirality-induced negative index of refraction is possible. A negative index of refraction due to three-dimensional chirality is demonstrated for a bilayered metamaterial based on pairs of mutually twisted planar metal patterns in parallel planes, which also shows negative electric and magnetic responses and exceptionally strong optical activity and circular dichroism. Multilayered forms of the metamaterial are found to be suitable for use as ultrathin polarization rotators and circular polarizers for practical applications.
Cecilia M. Lindgren1, Iris M. Heid2, Joshua C. Randall1, Claudia Lamina3 +152 more•Institutions (36)
TL;DR: By focusing on anthropometric measures of central obesity and fat distribution, a meta-analysis of 16 genome-wide association studies informative for adult waist circumference and waist–hip ratio identified three loci implicated in the regulation of human adiposity.
Abstract: To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
TL;DR: The authors define self-enhancement and self-protection as interests that individuals have in advancing one or more self-domains or defending against negative self-views, and discuss the role of these motivational constructs in scientific explanations, argue for their importance in maintaining psychological and physical well-being, and consider conditions in which they are likely to operate.
Abstract: We define self-enhancement and self-protection as interests that individuals have in advancing one or more self-domains or defending against negative self-views. We review ways in which people pursue self-enhancement and self-protection, discuss the role of these motivational constructs in scientific explanations, argue for their importance in maintaining psychological and physical well-being, and consider the conditions in which they are likely to operate. At various points, we address the perennial “cognition–motivation” debate. We argue that, despite the conceptual and practical difficulties that attend this distinction, the pervasiveness of the self-enhancement and self-protection motives makes it impossible and imprudent to ignore them in explaining self-related findings and theories.
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TL;DR: The limited evidence suggests that weight loss following gastric bypass is greater than vertical banded gastroplasty or adjustable gastric banding, but similar to isolated sleeve gastrectomy and banded Gastric bypass, which is more effective than conventional management.
Abstract: Obesity is associated with many health problems and a higher risk of death. Bariatric (weight loss) surgery for obesity is usually only considered when all other treatments have failed. People who are eligible for surgery have a body mass index (BMI) greater than 40 or greater than 35 with related conditions such as type 2 diabetes. Recently, it has been suggested that people with a lower BMI may benefit from surgery.
A number of different bariatric procedures are available, and these can be carried out through open (traditional) surgery or laparoscopic (keyhole) surgery. It is not clear which procedures are the most effective in reducing weight or have the least complications. The review aimed to compare these bariatric procedures with each other and with conventional treatment (such as drugs, diet and exercise).
The review found that surgery results in greater weight loss than conventional treatment in people with BMI greater than 30 as well as those with more severe obesity. Surgery also leads to some improvements in quality of life and obesity related diseases such as hypertension and diabetes. However, complications (for example pulmonary embolism), side-effects (for example heartburn) and some deaths may occur. Although several different surgical procedures are available, not all have been compared with each other. Gastric bypass had greater weight loss than vertical banded gastroplasty or adjustable gastric banding, but similar to isolated sleeve gastrectomy and banded gastric bypass. Isolated sleeve gastrectomy appears to result in greater weight loss than adjustable gastric banding. The evidence comparing vertical banded gastroplasty with adjustable gastric banding was not clear. Complications may occur with any bariatric procedure, but information from the included trials did not allow us to reach any conclusions about the safety of these procedures compared with each other.
TL;DR: The evidence that environmental influences during mammalian development lead to stable changes in the epigenome that alter the individual's susceptibility to chronic metabolic and cardiovascular disease is reviewed, and the clinical implications are discussed.
Abstract: Cellular commitment to a specific lineage is controlled by differential silencing of genes, which in turn depends on epigenetic processes such as DNA methylation and histone modification. During early embryogenesis, the mammalian genome is 'wiped clean' of most epigenetic modifications, which are progressively re-established during embryonic development. Thus, the epigenome of each mature cellular lineage carries the record of its developmental history. The subsequent trajectory and pattern of development are also responsive to environmental influences, and such plasticity is likely to have an epigenetic basis. epigenetic marks may be transmitted across generations, either directly by persisting through meiosis or indirectly through replication in the next generation of the conditions in which the epigenetic change occurred. Developmental plasticity evolved to match an organism to its environment, and a mismatch between the phenotypic outcome of adaptive plasticity and the current environment increases the risk of metabolic and cardiovascular disease. These considerations point to epigenetic processes as a key mechanism that underpins the developmental origins of chronic noncommunicable disease. Here, we review the evidence that environmental influences during mammalian development lead to stable changes in the epigenome that alter the individual's susceptibility to chronic metabolic and cardiovascular disease, and discuss the clinical implications.
TL;DR: The combination of spectral and timing data on 1H 0707-495 provides strong evidence that the authors are witnessing emission from matter within a gravitational radius, or a fraction of a light minute, from the event horizon of a rapidly spinning, massive black hole.
Abstract: The emission line arising from a transition of an electron from the iron K shell to the ground state (the K line) is prominent in the reflection spectrum of the hard X-ray continuum irradiating dense accreting matter around a black hole. The corresponding iron L-line emission should be detectable when iron abundance is high. That's the theory, and now broad iron L-line emission has been observed, together with the broad K line in the narrow-line Seyfert galaxy 1H0707. There is a reverberation lag of about 30 s between the direct X-ray continuum and its reflection from matter falling into the hole, a timescale comparable to the light-crossing time of the innermost radii around a supermassive black hole. This discovery opens a window on events close to the black hole event horizon in these objects. Emission arising from a transition of an electron from the iron K shell to the ground state (the K line) is prominent in the reflection spectrum created by the hard X-ray continuum irradiating the dense accreting matter around a black hole. Here the presence of both iron K and L emission is reported in the spectrum of the active galaxy 1H 0707-495. There is a 'reverberation lag' with a timescale comparable to the light-crossing time of the innermost radii around a supermassive black hole. Since the 1995 discovery of the broad iron K-line emission from the Seyfert galaxy MCG–6-30-15 (ref. 1), broad iron K lines have been found in emission from several other Seyfert galaxies2, from accreting stellar-mass black holes3 and even from accreting neutron stars4. The iron K line is prominent in the reflection spectrum5,6 created by the hard-X-ray continuum irradiating dense accreting matter. Relativistic distortion7 of the line makes it sensitive to the strong gravity and spin of the black hole8. The accompanying iron L-line emission should be detectable when the iron abundance is high. Here we report the presence of both iron K and iron L emission in the spectrum of the narrow-line Seyfert 1 galaxy9 1H 0707-495. The bright iron L emission has enabled us to detect a reverberation lag of about 30 s between the direct X-ray continuum and its reflection from matter falling into the black hole. The observed reverberation timescale is comparable to the light-crossing time of the innermost radii around a supermassive black hole. The combination of spectral and timing data on 1H 0707-495 provides strong evidence that we are witnessing emission from matter within a gravitational radius, or a fraction of a light minute, from the event horizon of a rapidly spinning, massive black hole.
TL;DR: Using the Panzar and Rosse H-statistic as a measure of competition in 45 countries, the authors found that more competitive banking systems are less prone to experience a systemic crisis and exhibit increased time to crisis.
Abstract: Using the Panzar and Rosse H-statistic as a measure of competition in 45 countries, we find that more competitive banking systems are less prone to experience a systemic crisis and exhibit increased time to crisis. This result holds even when we control for banking system concentration, which is associated with higher probability of a crisis and shorter time to crisis. Our results indicate that competition and concentration capture different characteristics of banking systems, meaning that concentration is an inappropriate proxy for competition. The findings suggest that policies promoting competition among banks, if well executed, have the potential to improve systemic stability.
TL;DR: A brief overview of the key developments in the CORDIC algorithms and architectures along with their potential and upcoming applications is presented.
Abstract: Year 2009 marks the completion of 50 years of the invention of CORDIC (coordinate rotation digital computer) by Jack E. Volder. The beauty of CORDIC lies in the fact that by simple shift-add operations, it can perform several computing tasks such as the calculation of trigonometric, hyperbolic and logarithmic functions, real and complex multiplications, division, square-root, solution of linear systems, eigenvalue estimation, singular value decomposition, QR factorization and many others. As a consequence, CORDIC has been utilized for applications in diverse areas such as signal and image processing, communication systems, robotics and 3-D graphics apart from general scientific and technical computation. In this article, we present a brief overview of the key developments in the CORDIC algorithms and architectures along with their potential and upcoming applications.
TL;DR: Investigating whether the motivational salience of food cues differs between obese and normal-weight subjects in a manner consistent with altered reward system function in obesity found food cue incentive salience is elevated equally in normal- Weight and obese individuals during fasting.
Abstract: The major aim of this study was to investigate whether the motivational salience of food cues (as reflected by their attention-grabbing properties) differs between obese and normal-weight subjects in a manner consistent with altered reward system function in obesity. A total of 18 obese and 18 normal-weight, otherwise healthy, adult women between the ages of 18 and 35 participated in an eye-tracking paradigm in combination with a visual probe task. Eye movements and reaction time to food and non-food images were recorded during both fasted and fed conditions in a counterbalanced design. Eating behavior and hunger level were assessed by self-report measures. Obese individuals had higher scores than normal-weight individuals on self-report measures of responsiveness to external food cues and vulnerability to disruptions in control of eating behavior. Both obese and normal-weight individuals demonstrated increased gaze duration for food compared to non-food images in the fasted condition. In the fed condition, however, despite reduced hunger in both groups, obese individuals maintained the increased attention to food images, whereas normal-weight individuals had similar gaze duration for food and non-food images. Additionally, obese individuals had preferential orienting toward food images at the onset of each image. Obese and normal-weight individuals did not differ in reaction time measures in the fasted or fed condition. Food cue incentive salience is elevated equally in normal-weight and obese individuals during fasting. Obese individuals retain incentive salience for food cues despite feeding and decreased self-report of hunger. Sensitization to food cues in the environment and their dysregulation in obese individuals may play a role in the development and/or maintenance of obesity.
TL;DR: The classical phenomenon of optical activity can be observed in artificial planar media which exhibit neither 3D nor 2D chirality in the form of strong circular dichroism and birefringence indistinguishable from those of chiral three-dimensional media.
Abstract: We report that the classical phenomenon of optical activity, which is traditionally associated with chirality (helicity) of organic molecules, proteins, and inorganic structures, can be observed in artificial planar media which exhibit neither 3D nor 2D chirality. We observe the effect in the microwave and optical parts of the spectrum at oblique incidence to regular arrays of nonchiral subwavelength metamolecules in the form of strong circular dichroism and birefringence indistinguishable from those of chiral three-dimensional media.