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Showing papers by "University of Melbourne published in 2010"


Journal ArticleDOI
TL;DR: The International League Against Epilepsy (ILAE) Commission on Classification and Terminology has revised concepts, terminology, and approaches for classifying seizures and forms of epilepsy.
Abstract: The International League Against Epilepsy (ILAE) Commission on Classification and Terminology has revised concepts, terminology, and approaches for classifying seizures and forms of epilepsy. Generalized and focal are redefined for seizures as occurring in and rapidly engaging bilaterally distributed networks (generalized) and within networks limited to one hemisphere and either discretely localized or more widely distributed (focal). Classification of generalized seizures is simplified. No natural classification for focal seizures exists; focal seizures should be described according to their manifestations (e. g., dyscognitive, focal motor). The concepts of generalized and focal do not apply to electroclinical syndromes. Genetic, structural-metabolic, and unknown represent modified concepts to replace idiopathic, symptomatic, and cryptogenic. Not all epilepsies are recognized as electroclinical syndromes. Organization of forms of epilepsy is first by specificity: electroclinical syndromes, nonsyndromic epilepsies with structural-metabolic causes, and epilepsies of unknown cause. Further organization within these divisions can be accomplished in a flexible manner depending on purpose. Natural classes (e. g., specific underlying cause, age at onset, associated seizure type), or pragmatic groupings (e. g., epileptic encephalopathies, self-limited electroclinical syndromes) may serve as the basis for organizing knowledge about recognized forms of epilepsy and facilitate identification of new forms.

3,775 citations


Journal ArticleDOI
TL;DR: Evidence is provided that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.
Abstract: SNPs discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method with simulations based on the observed genotype data. We show that 45% of variance can be explained by considering all SNPs simultaneously. Thus, most of the heritability is not missing but has not previously been detected because the individual effects are too small to pass stringent significance tests. We provide evidence that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.

3,759 citations


Journal ArticleDOI
Koji Nakamura1, K. Hagiwara, Ken Ichi Hikasa2, Hitoshi Murayama1  +180 moreInstitutions (92)
TL;DR: In this article, a biennial review summarizes much of particle physics using data from previous editions, plus 2158 new measurements from 551 papers, they list, evaluate and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons.
Abstract: This biennial Review summarizes much of particle physics. Using data from previous editions, plus 2158 new measurements from 551 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. Among the 108 reviews are many that are new or heavily revised including those on neutrino mass, mixing, and oscillations, QCD, top quark, CKM quark-mixing matrix, V-ud & V-us, V-cb & V-ub, fragmentation functions, particle detectors for accelerator and non-accelerator physics, magnetic monopoles, cosmological parameters, and big bang cosmology.

2,788 citations


Journal ArticleDOI
TL;DR: This work presents an integrative 2-level MSEM mathematical framework that subsumes new and existing multilevel mediation approaches as special cases and uses several applied examples to illustrate the flexibility of this framework.
Abstract: Several methods for testing mediation hypotheses with 2-level nested data have been proposed by researchers using a multilevel modeling (MLM) paradigm. However, these MLM approaches do not accommodate mediation pathways with Level-2 outcomes and may produce conflated estimates of between- and within-level components of indirect effects. Moreover, these methods have each appeared in isolation, so a unified framework that integrates the existing methods, as well as new multilevel mediation models, is lacking. Here we show that a multilevel structural equation modeling (MSEM) paradigm can overcome these 2 limitations of mediation analysis with MLM. We present an integrative 2-level MSEM mathematical framework that subsumes new and existing multilevel mediation approaches as special cases. We use several applied examples and accompanying software code to illustrate the flexibility of this framework and to show that different substantive conclusions can be drawn using MSEM versus MLM.

2,595 citations


Journal ArticleDOI
TL;DR: The network-based statistic (NBS) is introduced for the first time and its power is evaluated with the use of receiver operating characteristic (ROC) curves to demonstrate its utility with application to a real case-control study involving a group of people with schizophrenia for which resting-state functional MRI data were acquired.

2,042 citations


Journal ArticleDOI
Thomas J. Hudson1, Thomas J. Hudson2, Warwick Anderson3, Axel Aretz4  +270 moreInstitutions (92)
15 Apr 2010
TL;DR: Systematic studies of more than 25,000 cancer genomes will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
Abstract: The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

2,041 citations


Journal ArticleDOI
TL;DR: Modelling approaches are explored that aim to minimize extrapolation errors and assess predictions against prior biological knowledge to promote methods appropriate to range‐shifting species.
Abstract: Summary 1. Species are shifting their ranges at an unprecedented rate through human transportation and environmental change. Correlative species distribution models (SDMs) are frequently applied for predicting potential future distributions of range-shifting species, despite these models’ assumptions that species are at equilibrium with the environments used to train (fit) the models, and that the training data are representative of conditions to which the models are predicted. Here we explore modelling approaches that aim to minimize extrapolation errors and assess predictions against prior biological knowledge. Our aim was to promote methods appropriate to range-shifting species. 2. We use an invasive species, the cane toad in Australia, as an example, predicting potential distributions under both current and climate change scenarios. We use four SDM methods, and trial weighting schemes and choice of background samples appropriate for species in a state of spread. We also test two methods for including information from a mechanistic model. Throughout, we explore graphical techniques for understanding model behaviour and reliability, including the extent of extrapolation. 3. Predictions varied with modelling method and data treatment, particularly with regard to the use and treatment of absence data. Models that performed similarly under current climatic conditions deviated widely when transferred to a novel climatic scenario. 4. The results highlight problems with using SDMs for extrapolation, and demonstrate the need for methods and tools to understand models and predictions. We have made progress in this direction and have implemented exploratory techniques as new options in the free modelling software, MaxEnt. Our results also show that deliberately controlling the fit of models and integrating information from mechanistic models can enhance the reliability of correlative predictions of species in non-equilibrium and novel settings. 5.Implications. The biodiversity of many regions in the world is experiencing novel threats created by species invasions and climate change. Predictions of future species distributions are required for management, but there are acknowledged problems with many current methods, and relatively few advances in techniques for understanding or overcoming these. The methods presented in this manuscript and made accessible in MaxEnt provide a forward step.

2,013 citations



Journal ArticleDOI
TL;DR: In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality and the hazard ratios for the men were similar.
Abstract: BACKGROUND A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. METHODS We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). RESULTS The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. CONCLUSIONS In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.

1,874 citations


Journal ArticleDOI
29 Apr 2010-Nature
TL;DR: It is shown that the Arctic warming is strongest at the surface during most of the year and is primarily consistent with reductions in sea ice cover, and suggests that strong positive ice–temperature feedbacks have emerged in the Arctic, increasing the chances of further rapid warming and sea ice loss.
Abstract: The rise in Arctic near-surface air temperatures has been almost twice as large as the global average in recent decades-a feature known as 'Arctic amplification'. Increased concentrations of atmospheric greenhouse gases have driven Arctic and global average warming; however, the underlying causes of Arctic amplification remain uncertain. The roles of reductions in snow and sea ice cover and changes in atmospheric and oceanic circulation, cloud cover and water vapour are still matters of debate. A better understanding of the processes responsible for the recent amplified warming is essential for assessing the likelihood, and impacts, of future rapid Arctic warming and sea ice loss. Here we show that the Arctic warming is strongest at the surface during most of the year and is primarily consistent with reductions in sea ice cover. Changes in cloud cover, in contrast, have not contributed strongly to recent warming. Increases in atmospheric water vapour content, partly in response to reduced sea ice cover, may have enhanced warming in the lower part of the atmosphere during summer and early autumn. We conclude that diminishing sea ice has had a leading role in recent Arctic temperature amplification. The findings reinforce suggestions that strong positive ice-temperature feedbacks have emerged in the Arctic, increasing the chances of further rapid warming and sea ice loss, and will probably affect polar ecosystems, ice-sheet mass balance and human activities in the Arctic.

1,842 citations


Journal ArticleDOI
TL;DR: An organized study of information theoretic measures for clustering comparison, including several existing popular measures in the literature, as well as some newly proposed ones, and advocates the normalized information distance (NID) as a general measure of choice.
Abstract: Information theoretic measures form a fundamental class of measures for comparing clusterings, and have recently received increasing interest. Nevertheless, a number of questions concerning their properties and inter-relationships remain unresolved. In this paper, we perform an organized study of information theoretic measures for clustering comparison, including several existing popular measures in the literature, as well as some newly proposed ones. We discuss and prove their important properties, such as the metric property and the normalization property. We then highlight to the clustering community the importance of correcting information theoretic measures for chance, especially when the data size is small compared to the number of clusters present therein. Of the available information theoretic based measures, we advocate the normalized information distance (NID) as a general measure of choice, for it possesses concurrently several important properties, such as being both a metric and a normalized measure, admitting an exact analytical adjusted-for-chance form, and using the nominal [0,1] range better than other normalized variants.

Journal ArticleDOI
TL;DR: RCC appears to be more common in patients with obesity, end-stage renal failure, acquired renal cystic disease and tuber-ous sclerosis, and severalautosomal dominant syndromes are described, each with a dis-tinct genetic basis and phenotype.

Journal ArticleDOI
Hana Lango Allen1, Karol Estrada2, Guillaume Lettre3, Sonja I. Berndt4  +341 moreInstitutions (90)
14 Oct 2010-Nature
TL;DR: It is shown that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait, and indicates that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Book
25 Feb 2010
TL;DR: This book describes recent advances in alcohol research which have direct relevance for the development of effective alcohol policies at the local, national and international levels.
Abstract: From a public health perspective, alcohol is a major contributor to morbidity and mortality. This book describes recent advances in alcohol research which have direct relevance for the development of effective alcohol policies at the local, national and international levels. The central purpose of the book is to empower those responsible for public health and social welfare.

Journal ArticleDOI
TL;DR: These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas.
Abstract: Background Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described. Methods We sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas. Results ARID1A mutations were seen in 55 of 119 ovarian clear-cell carcinomas (46%), 10 of 33 endometrioid carcinomas (30%), and none of the 76 high-grade serous ovarian carcinomas. Seventeen carcinomas had two somatic mutations each. Loss of the BAF250a protein correlated strongly with the ovarian c...

Journal ArticleDOI
TL;DR: There is substantial information on low back pain prevalence and estimates of the point prevalence range from 1.0% to 58.1% (mean: 18.1%; median: 15.0%), and 1 year prevalence from 0.8% to 82.5% ( mean: 38.1; median: 37.4%).
Abstract: Low back pain is an extremely common problem that most people experience at some point in their life. While substantial heterogeneity exists among low back pain epidemiological studies limiting the ability to compare and pool data, estimates of the 1 year incidence of a first-ever episode of low back pain range between 6.3% and 15.4%, while estimates of the 1 year incidence of any episode of low back pain range between 1.5% and 36%. In health facility- or clinic-based studies, episode remission at 1 year ranges from 54% to 90%; however, most studies do not indicate whether the episode was continuous between the baseline and follow-up time point(s). Most people who experience activity-limiting low back pain go on to have recurrent episodes. Estimates of recurrence at 1 year range from 24% to 80%. Given the variation in definitions of remission and recurrence, further population-based research is needed to assess the daily patterns of low back pain episodes over 1 year and longer. There is substantial information on low back pain prevalence and estimates of the point prevalence range from 1.0% to 58.1% (mean: 18.1%; median: 15.0%), and 1 year prevalence from 0.8% to 82.5% (mean: 38.1%; median: 37.4%). Due to the heterogeneity of the data, mean estimates need to be interpreted with caution. Many environmental and personal factors influence the onset and course of low back pain. Studies have found the incidence of low back pain is highest in the third decade, and overall prevalence increases with age until the 60-65 year age group and then gradually declines. Other commonly reported risk factors include low educational status, stress, anxiety, depression, job dissatisfaction, low levels of social support in the workplace and whole-body vibration. Low back pain has an enormous impact on individuals, families, communities, governments and businesses throughout the world. The Global Burden of Disease 2005 Study (GBD 2005) is currently making estimates of the global burden of low back pain in relation to impairment and activity limitation. Results will be available in 2011. Further research is needed to help us understand more about the broader outcomes and impacts from low back pain.

01 Jan 2010
TL;DR: In this paper, the authors describe recent advances in alcohol research which have direct relevance for the development of effective alcohol policies at the local, national and international levels, and the central purpose of the book is to empower those responsible for public health and social welfare.
Abstract: From a public health perspective, alcohol is a major contributor to morbidity and mortality. This book describes recent advances in alcohol research which have direct relevance for the development of effective alcohol policies at the local, national and international levels. The central purpose of the book is to empower those responsible for public health and social welfare.

Journal ArticleDOI
TL;DR: The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria, however, the results were potentially confounded by the treatment of G DM.
Abstract: In the accompanying comment letter (1), Weinert summarizes published data from the Brazilian Gestational Diabetes Study (2) and comments on applying International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommendations (3) for the diagnosis of gestational diabetes mellitus (GDM) to that cohort. The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria. However, the results were potentially confounded by the treatment of GDM. It did find that women with GDM were at increased risk for some …

Journal ArticleDOI
12 May 2010-JAMA
TL;DR: Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.
Abstract: Context Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor. Objective To determine whether a single annual dose of 500 000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture. Design, Setting, and Participants A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008. Intervention 500 000 IU of cholecalciferol or placebo. Main Outcome Measures Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels. Results Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing. Conclusion Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures. Trial Registration anzctr.org.au Identifier: ACTRN12605000658617; isrctn.org Identifier: ISRCTN83409867

Journal ArticleDOI
TL;DR: In this paper, the influence of pro-environmental self-identity on consistency across a range of behaviours was found to be a significant behavioural determinant over and above theory of planned behaviour variables for carbon offsetting behaviour.

Journal ArticleDOI
TL;DR: Assessing the behavior, structure and topological attributes of whole-brain anatomical networks over a wide range of nodal scales, a variety of grey-matter parcellations as well as different diffusion-MRI acquisition protocols indicates that any comparison of network parameters across studies must be made with reference to the spatial scale of the nodal parcellation.

Journal ArticleDOI
TL;DR: H. Bart van der Worp and colleagues discuss the controversies and possibilities of translating the results of animal experiments into human clinical trials and the prospects of doing so in the coming years.
Abstract: H. Bart van der Worp and colleagues discuss the controversies and possibilities of translating the results of animal experiments into human clinical trials.

Journal ArticleDOI
TL;DR: Paul Pharoah and colleagues evaluate the prognostic significance of immunohistochemical subtype classification in more than 10,000 breast cancer cases with early disease, and examines the influence of a patient's survival time on the prediction of future survival.
Abstract: Background: Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate mortality for patients with the major subtypes of breast cancer as classified using five immunohistochemical markers, to investigate patterns of mortality over time, and to test for heterogeneity by subtype. Methods and Findings: We pooled data from more than 10,000 cases of invasive breast cancer from 12 studies that had collected information on hormone receptor status, human epidermal growth factor receptor-2 (HER2) status, and at least one basal marker (cytokeratin [CK]5/6 or epidermal growth factor receptor [EGFR]) together with survival time data. Tumours were classified as luminal and nonluminal tumours according to hormone receptor expression. These two groups were further subdivided according to expression of HER2, and finally, the luminal and nonluminal HER2-negative tumours were categorised according to expression of basal markers. Changes in mortality rates over time differed by subtype. In women with luminal HER2-negative subtypes, mortality rates were constant over time, whereas mortality rates associated with the luminal HER2-positive and nonluminal subtypes tended to peak within 5 y of diagnosis and then decline over time. In the first 5 y after diagnosis the nonluminal tumours were associated with a poorer prognosis, but over longer follow-up times the prognosis was poorer in the luminal subtypes, with the worst prognosis at 15 y being in the luminal HER2-positive tumours. Basal marker expression distinguished the HER2-negative luminal and nonluminal tumours into different subtypes. These patterns were independent of any systemic adjuvant therapy. Conclusions: The six subtypes of breast cancer defined by expression of five markers show distinct behaviours with important differences in short term and long term prognosis. Application of these markers in the clinical setting could have the potential to improve the targeting of adjuvant chemotherapy to those most likely to benefit. The different patterns of mortality over time also suggest important biological differences between the subtypes that may result in differences in response to specific therapies, and that stratification of breast cancers by clinically relevant subtypes in clinical trials is urgently required. Please see later in the article for the Editors’ Summary.

Book ChapterDOI
21 May 2010
TL;DR: The results demonstrate that federated Cloud computing model has immense potential as it offers significant performance gains as regards to response time and cost saving under dynamic workload scenarios.
Abstract: Cloud computing providers have setup several data centers at different geographical locations over the Internet in order to optimally serve needs of their customers around the world However, existing systems do not support mechanisms and policies for dynamically coordinating load distribution among different Cloud-based data centers in order to determine optimal location for hosting application services to achieve reasonable QoS levels Further, the Cloud computing providers are unable to predict geographic distribution of users consuming their services, hence the load coordination must happen automatically, and distribution of services must change in response to changes in the load To counter this problem, we advocate creation of federated Cloud computing environment (InterCloud) that facilitates just-in-time, opportunistic, and scalable provisioning of application services, consistently achieving QoS targets under variable workload, resource and network conditions The overall goal is to create a computing environment that supports dynamic expansion or contraction of capabilities (VMs, services, storage, and database) for handling sudden variations in service demands. This paper presents vision, challenges, and architectural elements of InterCloud for utility-oriented federation of Cloud computing environments The proposed InterCloud environment supports scaling of applications across multiple vendor clouds We have validated our approach by conducting a set of rigorous performance evaluation study using the CloudSim toolkit The results demonstrate that federated Cloud computing model has immense potential as it offers significant performance gains as regards to response time and cost saving under dynamic workload scenarios.

Journal ArticleDOI
TL;DR: Findings indicate that alcohol impacts many disease outcomes causally, both chronic and acute, and injuries, and a pattern of heavy episodic drinking increases risk for some disease and all injury outcomes.
Abstract: Aims As part of a larger study to estimate the global burden of disease and injury attributable to alcohol: to evaluate the evidence for a causal impact of average volume of alcohol consumption and pattern of drinking on diseases and injuries; to quantify relationships identified as causal based on published meta-analyses; to separate the impact on mortality versus morbidity where possible; and to assess the impact of the quality of alcohol on burden of disease. Methods Systematic literature reviews were used to identify alcohol-related diseases, birth complications and injuries using standard epidemiological criteria to determine causality. The extent of the risk relations was taken from meta-analyses. Results Evidence of a causal impact of average volume of alcohol consumption was found for the following major diseases: tuberculosis, mouth, nasopharynx, other pharynx and oropharynx cancer, oesophageal cancer, colon and rectum cancer, liver cancer, female breast cancer, diabetes mellitus, alcohol use disorders, unipolar depressive disorders, epilepsy, hypertensive heart disease, ischaemic heart disease (IHD), ischaemic and haemorrhagic stroke, conduction disorders and other dysrhythmias, lower respiratory infections (pneumonia), cirrhosis of the liver, preterm birth complications and fetal alcohol syndrome. Dose-response relationships could be quantified for all disease categories except for depressive disorders, with the relative risk increasing with increased level of alcohol consumption for most diseases. Both average volume and drinking pattern were linked causally to IHD, fetal alcohol syndrome and unintentional and intentional injuries. For IHD, ischaemic stroke and diabetes mellitus beneficial effects were observed for patterns of light to moderate drinking without heavy drinking occasions (as defined by 60+ g pure alcohol per day). For several disease and injury categories, the effects were stronger on mortality compared to morbidity. There was insufficient evidence to establish whether quality of alcohol had a major impact on disease burden. Conclusions Overall, these findings indicate that alcohol impacts many disease outcomes causally, both chronic and acute, and injuries. In addition, a pattern of heavy episodic drinking increases risk for some disease and all injury outcomes. Future studies need to address a number of methodological issues, especially the differential role of average volume versus drinking pattern, in order to obtain more accurate risk estimates and to understand more clearly the nature of alcohol-disease relationships.

Journal ArticleDOI
04 Feb 2010-Leukemia
TL;DR: Although the emphasis is on γ-radiation-induced γH2AX foci, the effects of other genotoxic insults including exposure to ultraviolet rays, oxidative stress and chemical agents are also discussed.
Abstract: Phosphorylation of the Ser-139 residue of the histone variant H2AX, forming gammaH2AX, is an early cellular response to the induction of DNA double-strand breaks. Detection of this phosphorylation event has emerged as a highly specific and sensitive molecular marker for monitoring DNA damage initiation and resolution. Further, analysis of gammaH2AX foci has numerous other applications including, but not limited to, cancer and aging research. Quantitation of gammaH2AX foci has also been applied as a useful tool for the evaluation of the efficacy of various developmental drugs, particularly, radiation modifying compounds. This review focuses on the current status of gammaH2AX as a marker of DNA damage and repair in the context of ionizing radiation. Although the emphasis is on gamma-radiation-induced gammaH2AX foci, the effects of other genotoxic insults including exposure to ultraviolet rays, oxidative stress and chemical agents are also discussed.

Journal ArticleDOI
J. Abadie1, B. P. Abbott1, R. Abbott1, M. R. Abernathy2  +719 moreInstitutions (79)
TL;DR: In this paper, Kalogera et al. presented an up-to-date summary of the rates for all types of compact binary coalescence sources detectable by the initial and advanced versions of the ground-based gravitational-wave detectors LIGO and Virgo.
Abstract: We present an up-to-date, comprehensive summary of the rates for all types of compact binary coalescence sources detectable by the initial and advanced versions of the ground-based gravitational-wave detectors LIGO and Virgo. Astrophysical estimates for compact-binary coalescence rates depend on a number of assumptions and unknown model parameters and are still uncertain. The most confident among these estimates are the rate predictions for coalescing binary neutron stars which are based on extrapolations from observed binary pulsars in our galaxy. These yield a likely coalescence rate of 100 Myr−1 per Milky Way Equivalent Galaxy (MWEG), although the rate could plausibly range from 1 Myr−1 MWEG−1 to 1000 Myr−1 MWEG−1 (Kalogera et al 2004 Astrophys. J. 601 L179; Kalogera et al 2004 Astrophys. J. 614 L137 (erratum)). We convert coalescence rates into detection rates based on data from the LIGO S5 and Virgo VSR2 science runs and projected sensitivities for our advanced detectors. Using the detector sensitivities derived from these data, we find a likely detection rate of 0.02 per year for Initial LIGO–Virgo interferometers, with a plausible range between 2 × 10−4 and 0.2 per year. The likely binary neutron–star detection rate for the Advanced LIGO–Virgo network increases to 40 events per year, with a range between 0.4 and 400 per year.

Journal ArticleDOI
TL;DR: In this paper, the intention-behaviour gap of ethically-minded consumers is investigated, and a holistic conceptual model is proposed to bridge the intention gap of the consumer behavior gap.
Abstract: Despite their ethical intentions, ethically minded consumers rarely purchase ethical products (Auger and Devinney: 2007, Journal of Business Ethics 76, 361–383). This intentions–behaviour gap is important to researchers and industry, yet poorly understood (Belk et al.: 2005, Consumption, Markets and Culture 8(3), 275–289). In order to push the understanding of ethical consumption forward, we draw on what is known about the intention–behaviour gap from the social psychology and consumer behaviour literatures and apply these insights to ethical consumerism. We bring together three separate insights – implementation intentions (Gollwitzer: 1999, American Psychologist 54(7), 493–503), actual behavioural control (ABC) (Ajzen and Madden: 1986, Journal of Experimental Social Psychology 22, 453–474; Sheeran et al.: 2003, Journal of Social Psychology, 42, 393–410) and situational context (SC) (Belk: 1975, Journal of Consumer Research 2, 157–164) – to construct an integrated, holistic conceptual model of the intention–behaviour gap of ethically minded consumers. This holistic conceptual model addresses significant limitations within the ethical consumerism literature, and moves the understanding of ethical consumer behaviour forward. Further, the operationalisation of this model offers insight and strategic direction for marketing managers attempting to bridge the intention–behaviour gap of the ethically minded consumer.

Journal ArticleDOI
TL;DR: The largest validation study of the 2- and 9-question Patient Health Questionnaires (PHQ-2 and PHQ-9) in primary care settings is reported, reporting good sensitivity but poor specificity in detecting major depression.
Abstract: PURPOSE Although screening for unipolar depression is controversial, it is potentially an efficient way to find undetected cases and improve diagnostic acumen. Using a reference standard, we aimed to validate the 2- and 9-question Patient Health Questionnaires (PHQ-2 and PHQ-9) in primary care settings. The PHQ-2 comprises the first 2 questions of the PHQ-9. METHODS Consecutive adult patients attending Auckland family practices completed the PHQ-9, after which they completed the Composite International Diagnostic Interview (CIDI) depression reference standard. Sensitivities and specificities for PHQ-2 and PHQ-9 were analyzed. RESULTS There were 2,642 patients who completed both the PHQ-9 and the CIDI. Sensitivity and specificity of the PHQ-2 for diagnosing major depression were 86% and 78%, respectively, with a score of 2 or higher and 61% and 92% with a score 3 or higher; for the PHQ-9, they were 74% and 91%, respectively, with a score of 10 or higher. For the PHQ-2 a score of 2 or higher detected more cases of depression than a score of 3 or higher. For the PHQ-9 a score of 10 or higher detected more cases of major depression than the PHQ determination of major depression originally described by Spitzer et al in 1999. CONCLUSIONS We report the largest validation study of the PHQ-2 and PHQ-9, compared with a reference standard interview, undertaken in an exclusively primary care population. The PHQ-2 score or 2 or higher had good sensitivity but poor specificity in detecting major depression. Using a PHQ-2 threshold score of 2 or higher rather than 3 or higher resulted in more depressed patients being correctly identified. A PHQ-9 score of 10 or higher appears to detect more depressed patients than the originally described PHQ-9 scoring for major depression.

Journal ArticleDOI
TL;DR: It is suggested that the WBB could provide the average clinician with a standing balance assessment tool suitable for the clinical setting, given that it is portable, widely available and a fraction of the cost of a FP.