User-Centric Quality of Service Provisioning in IP Networks

The Internet has become the preferred transport medium for almost every type of communication, continuing to grow, both in terms of the number of users and delivered services. Efforts have been made to ensure that time sensitive applications receive sufficient resources and subsequently receive an acceptable Quality of Service (QoS). However, typical Internet users no longer use a single service at a given point in time, as they are instead engaged in a multimedia-rich experience, comprising of many different concurrent services. Given the scalability problems raised by the diversity of the users and traffic, in conjunction with their increasing expectations, the task of QoS provisioning can no longer be approached from the perspective of providing priority to specific traffic types over coexisting services; either through explicit resource reservation, or traffic classification using static policies, as is the case with the current approach to QoS provisioning, Differentiated Services (Diffserv). This current use of static resource allocation and traffic shaping methods reveals a distinct lack of synergy between current QoS practices and user activities, thus highlighting a need for a QoS solution reflecting the user services. The aim of this thesis is to investigate and propose a novel QoS architecture, which considers the activities of the user and manages resources from a user-centric perspective. The research begins with a comprehensive examination of existing QoS technologies and mechanisms, arguing that current QoS practises are too static in their configuration and typically give priority to specific individual services rather than considering the user experience. The analysis also reveals the potential threat that unresponsive application traffic presents to coexisting Internet services and QoS efforts, and introduces the requirement for a balance between application QoS and fairness. This thesis proposes a novel architecture, the Congestion Aware Packet Scheduler (CAPS), which manages and controls traffic at the point of service aggregation, in order to optimise the overall QoS of the user experience. The CAPS architecture, in contrast to traditional QoS alternatives, places no predetermined precedence on a specific traffic; instead, it adapts QoS policies to each individual’s Internet traffic profile and dynamically controls the ratio of user services to maintain an optimised QoS experience. The rationale behind this approach was to enable a QoS optimised experience to each Internet user and not just those using preferred services. Furthermore, unresponsive bandwidth intensive applications, such as Peer-to-Peer, are managed fairly while minimising their impact on coexisting services. The CAPS architecture has been validated through extensive simulations with the topologies used replicating the complexity and scale of real-network ISP infrastructures. The results show that for a number of different user-traffic profiles, the proposed approach achieves an improved aggregate QoS for each user when compared with Best effort Internet, Traditional Diffserv and Weighted-RED configurations. Furthermore, the results demonstrate that the proposed architecture not only provides an optimised QoS to the user, irrespective of their traffic profile, but through the avoidance of static resource allocation, can adapt with the Internet user as their use of services change.France Teleco

DNA methylotype analysis in colorectal cancer

The methylation status of a gene promoter is considered to be an important mechanism for the development of many tumors, including colorectal cancer. Recent studies have shown that specific patterns of DNA methylation across multiple CpG loci in some human tumors are more informative than the detection of one single CpG locus in tumor genomes. In the present study, multiple CpG methylations of three genes (CDKN2A, DPYD and MLH1) were detected in DNA samples from patients with colorectal cancer using Pyrosequencing(®) technology. The bisulfite-converted DNA was amplified with a nested PCR and five or six CpG loci of each gene were assessed to determine DNA methylotype. Our data showed that 10/49 (20.4%), 6/48 (12.5%) and 14/49 (28.6%) of tumors were methylated with a DNA methylation level >0.2 in CDKN2A, DPYD and MLH1, respectively. Our study indicated a similar DNA methylation level across the multiple CpG loci for all three genes in the methylated tumor DNA samples, demonstrating a dichotomous trait in DNA methylation. The tumor DNA samples had unique DNA methylation patterns, which were high-degree and multiple-site methylation, but the normal DNA samples had no or a low-degree and dispersed single-site methylation. In addition, an inverse correlation in those methylated tumors was observed between DNA methylation and RNA expression for MLH1 (R(S)=−0.62, P=0.003), but not for CDKN2A and DPYD. In conclusion, distinctive DNA methylotypes exist in colorectal cancer and may depict a distinct biology in apparently homogeneous tumors

RAPID : research on automated plankton identification

Author Posting. © Oceanography Society, 2007. This article is posted here by permission of Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 20, 2 (2007): 172-187.When Victor Hensen deployed the first true plankton1 net in 1887, he and his colleagues were attempting to answer three fundamental questions: What planktonic organisms are present in the ocean? How many of each type are present? How does the plankton’s composition change over time? Although answering these questions has remained a central goal of oceanographers, the sophisticated tools available to enumerate planktonic organisms today offer capabilities that Hensen probably could never have imagined.This material is based upon work supported by the National Science Foundation under Grants OCE-0325018, OCE-0324937, OCE-0325167 and OCE-9423471, and the European Union under grants Q5CR-2002-71699, MAS3-ct98-0188, and MAS2-ct92-0015

Clinical effectiveness of vaginal pessary self-management vs clinic-based care for pelvic organ prolapse (TOPSY): a randomised controlled superiority trial

Background: Prolapse affects 30–40% of women. Those using a pessary for prolapse usually receive care as an outpatient. This trial determined effectiveness and cost-effectiveness of pessary self-management (SM) vs clinic-based care (CBC) in relation to condition-specific quality of life (QoL). Methods: Parallel-group, superiority randomised controlled trial, recruiting from 16 May 2018 to 7 February 2020, with follow-up to 17 September 2021. Women attending pessary clinics, ≥18 years, using a pessary (except Shelf, Gellhorn or Cube), with pessary retained ≥2 weeks were eligible. Limited manual dexterity; cognitive deficit; pregnancy; or requirement for non-English teaching were exclusions. SM group received a 30-min teaching session; information leaflet; 2-week follow-up call; and telephone support. CBC group received usual routine appointments. The primary clinical outcome was pelvic floor-specific QoL (PFIQ-7), and incremental net monetary benefit for cost-effectiveness, 18 months post-randomisation. Group allocation was by remote web-based application, minimised on age, user type (new/existing) and centre. Participants, intervention deliverers, researchers and the statistician were not blinded. The primary analysis was intention-to-treat based. Trial registration: https://doi.org/10.1186/ISRCTN62510577. Findings: The requisite 340 women were randomised (169 SM, 171 CBC) across 21 centres. There was not a statistically significant difference between groups in PFIQ-7 at 18 months (mean SM 32.3 vs CBC 32.5, adjusted mean difference SM-CBC −0.03, 95% CI −9.32 to 9.25). SM was less costly than CBC. The incremental net benefit of SM was £564 (SE £581, 95% CI −£576 to £1704). A lower percentage of pessary complications was reported in the SM group (mean SM 16.7% vs CBC 22.0%, adjusted mean difference −3.83%, 95% CI –6.86% to −0.81%). There was no meaningful difference in general self-efficacy. Self-managing women were more confident in self-management activities. There were no reported suspected unexpected serious adverse reactions, and 31 unrelated serious adverse events (17 SM, 14 CBC). Interpretation: Pessary self-management is cost-effective, does not improve or worsen QoL compared to CBC, and has a lower complication rate.</p

The Atacama Cosmology Telescope: Sunyaev Zel'dovich Selected Galaxy Clusters at 148 GHz in the 2008 Survey

We report on twenty-three clusters detected blindly as Sunyaev-Zel'dovich (SZ) decrements in a 148 GHz, 455 square-degree map of the southern sky made with data from the Atacama Cosmology Telescope 2008 observing season. All SZ detections announced in this work have confirmed optical counterparts. Ten of the clusters are new discoveries. One newly discovered cluster, ACT-CL J0102-4915, with a redshift of 0.75 (photometric), has an SZ decrement comparable to the most massive systems at lower redshifts. Simulations of the cluster recovery method reproduce the sample purity measured by optical follow-up. In particular, for clusters detected with a signal-to-noise ratio greater than six, simulations are consistent with optical follow-up that demonstrated this subsample is 100% pure. The simulations further imply that the total sample is 80% complete for clusters with mass in excess of 6x10^14 solar masses referenced to the cluster volume characterized by five hundred times the critical density. The Compton y -- X-ray luminosity mass comparison for the eleven best detected clusters visually agrees with both self-similar and non-adiabatic, simulation-derived scaling laws.Comment: 13 pages, 7 figures, Accepted for publication in Ap

Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10$^{−35}$ and <10$^{−8}$ respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10$^{−6}$). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10$^{−20}$) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

Peer reviewe

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Summary Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.Peer reviewe

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD

Peer reviewe