Snapshot Provisioning of Cloud Application Stacks to Face Traffic Surges

Traffic surges, like the Slashdot effect, occur when a web application is overloaded by a huge number of requests, potentially leading to unavailability. Unfortunately, such traffic variations are generally totally unplanned, of great amplitude, within a very short period, and a variable delay to return to a normal regime. In this report, we introduce PeakForecast as an elastic middleware solution to detect and absorb a traffic surge. In particular, PeakForecast can, from a trace of queries received in the last seconds, minutes or hours, to detect if the underlying system is facing a traffic surge or not, and then estimate the future traffic using a forecast model with an acceptable precision, thereby calculating the number of resources required to absorb the remaining traffic to come. We validate our solution by experimental results demonstrating that it can provide instantaneous elasticity of resources for traffic surges observed on the Japanese version of Wikipedia during the Fukushima Daiichi nuclear disaster in March 2011.Les pics de trafic, tels que l'effet Slashdot, apparaissent lorsqu'une application web doit faire face un nombre important de requêtes qui peut potentiellement entraîner une mise hors service de l'application. Malheureusement, de telles variations de traffic sont en général totalement imprévues et d'une grande amplitude, arrivent pendant une très courte période de temps et le retour à un régime normal prend un délai variable. Dans ce rapport, nous présentons PeakForecast qui est une solution intergicielle élastique pour détecter et absorber les pics de trafic. En particulier, PeakForecast peut, à partir des traces de requêtes reçues dans les dernières secondes, minutes ou heures, détecter si le système sous-jacent fait face ou non à un pic de trafic, estimer le trafic futur en utilisant un modèle de prédiction suffisamment précis, et calculer le nombre de ressources nécessaires à l'absorption du trafic restant à venir. Nous validons notre solution avec des résultats expérimentaux qui démontrent qu'elle fournit une élasticité instantanée des ressources pour des pics de trafic qui ont été observés sur la version japonaise de Wikipedia lors de l'accident nucléaire de Fukushima Daiichi en mars 2011

Familial factors in early deaths: Twins followed 30 years to ages 51–61 in 1978

Subjects in the National Academy of Sciences-National Research Council Twin Registry of 31,848 male twin veterans were followed for mortality from 1 January 1946, or from the date of entry into military service if that was later, to 31 December 1978. During this time 3,573 deaths occurred among them, 837 due to trauma and 2,712 due to disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47612/1/439_2004_Article_BF00278852.pd

Association of Researcher Characteristics with Views on Return of Incidental Findings from Genomic Research

Whole exome/ genome sequencing (WES/WGS) is now commonly used in research and is increasingly used in clinical care to identify the genetic basis of rare and unknown diseases. The management of incidental findings (IFs) generated through these analyses is debated within the research community. To examine how views regarding genomic research IFs are associated with researcher characteristics and experiences, we surveyed genetic professionals and assessed the effect of professional background and experience on their opinions. Researchers who did not have clinical training, provide clinical care to research participants, or have prior experience returning research results were in general more inclined to offer return of IFs than their colleagues with these characteristics. Understanding this will be important to fully appreciate the impact that policies on return of genetic IFs could have on participants, researchers, and genomic research

Effectiveness of smoking cessation therapies: a systematic review and meta-analysis

BACKGROUND: Smoking remains the leading preventable cause of premature deaths. Several pharmacological interventions now exist to aid smokers in cessation. These include Nicotine Replacement Therapy [NRT], bupropion, and varenicline. We aimed to assess their relative efficacy in smoking cessation by conducting a systematic review and meta-analysis. METHODS: We searched 10 electronic medical databases (inception to Sept. 2006) and bibliographies of published reviews. We selected randomized controlled trials [RCTs] evaluating interventions for smoking cessation at 1 year, through chemical confirmation. Our primary endpoint was smoking cessation at 1 year. Secondary endpoints included short-term smoking cessation (~3 months) and adverse events. We conducted random-effects meta-analysis and meta-regression. We compared treatment effects across interventions using head-to-head trials and when these did not exist, we calculated indirect comparisons. RESULTS: We identified 70 trials of NRT versus control at 1 year, Odds Ratio [OR] 1.71, 95% Confidence Interval [CI], 1.55–1.88, P =< 0.0001). This was consistent when examining all placebo-controlled trials (49 RCTs, OR 1.78, 95% CI, 1.60–1.99), NRT gum (OR 1.60, 95% CI, 1.37–1.86) or patch (OR 1.63, 95% CI, 1.41–1.89). NRT also reduced smoking at 3 months (OR 1.98, 95% CI, 1.77–2.21). Bupropion trials were superior to controls at 1 year (12 RCTs, OR1.56, 95% CI, 1.10–2.21, P = 0.01) and at 3 months (OR 2.13, 95% CI, 1.72–2.64). Two RCTs evaluated the superiority of bupropion versus NRT at 1 year (OR 1.14, 95% CI, 0.20–6.42). Varenicline was superior to placebo at 1 year (4 RCTs, OR 2.96, 95% CI, 2.12–4.12, P =< 0.0001) and also at approximately 3 months (OR 3.75, 95% CI, 2.65–5.30). Three RCTs evaluated the effectiveness of varenicline versus bupropion at 1 year (OR 1.58, 95% CI, 1.22–2.05) and at approximately 3 months (OR 1.61, 95% CI, 1.16–2.21). Using indirect comparisons, varenicline was superior to NRT when compared to placebo controls (OR 1.66, 95% CI 1.17–2.36, P = 0.004) or to all controls at 1 year (OR 1.73, 95% CI 1.22–2.45, P = 0.001). This was also the case for 3-month data. Adverse events were not systematically different across studies. CONCLUSION: NRT, bupropion and varenicline all provide therapeutic effects in assisting with smoking cessation. Direct and indirect comparisons identify a hierarchy of effectiveness

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk