Dependence of Variational Perturbation Expansions on Strong-Coupling Behavior. Inapplicability of delta-Expansion to Field Theory

We show that in applications of variational theory to quantum field theory it is essential to account for the correct Wegner exponent omega governing the approach to the strong-coupling, or scaling limit. Otherwise the procedure either does not converge at all or to the wrong limit. This invalidates all papers applying the so-called delta-expansion to quantum field theory.Comment: Author Information under http://www.physik.fu-berlin.de/~kleinert/institution.html . Latest update of paper (including all PS fonts) at http://www.physik.fu-berlin.de/~kleinert/34

Confinement in Covariant Gauges

We examine the weak coupling limit of Euclidean SU(n) gauge theory in covariant gauges. Following an earlier suggestion, an equivariant BRST-construction is used to define the continuum theory on a finite torus. The equivariant gauge fixing introduces constant ghost fields as moduli of the model. We study the parameter- and moduli- space perturbatively. For $n_f \leq n$ quark flavors, the moduli flow to a non-trivial fixed point in certain critical covariant gauges and the one-loop effective potential indicates that the global SU(n) color symmetry of the gauge fixed model is spontaneously broken to $U(1)^{n-1}$. Ward identities and renormalization group arguments imply that the longitudinal gauge boson propagator at long range is dominated by $n(n-1)$ Goldstone bosons in these critical covariant gauges. In the large $n$ limit, we derive a nonlinear integral equation for the expectation value of large Wilson loops assuming that the exchange of Goldstone bosons dominates the interaction at long range in critical covariant gauges. We find numerically that the expectation value of large circular Wilson loops decreases exponentially with the enclosed area in the absence of dynamical fermions. The gauge invariance of this mechanism for confinement in critical covariant gauges is discussed.Comment: 45 pages, Latex, uses psfig.sty and epsfig.sty to include postscript-figure

Improving Oral Hygiene Skills by Computer-Based Training: A Randomized Controlled Comparison of the Modified Bass and the Fones Techniques

Background: Gingivitis and other plaque-associated diseases have a high prevalence in western communities even though the majority of adults report daily oral hygiene. This indicates a lack of oral hygiene skills. Currently, there is no clear evidence as to which brushing technique would bring about the best oral hygiene skills. While the modified Bass technique is often recommended by dentists and in textbooks, the Fones technique is often recommended in patient brochures. Still, standardized comparisons of the effectiveness of teaching these techniques are lacking. Methodology/Principal Findings: In a final sample of n=56 students, this multidisciplinary, randomized, examiner-blinded, controlled study compared the effects of parallel and standardized interactive computer presentations teaching either the Fones or the modified Bass technique. A control group was taught the basics of tooth brushing alone. Oral hygiene skills (remaining plaque after thorough oral hygiene) and gingivitis were assessed at baseline and 6, 12, and 28 weeks after the intervention. We found a significant group×time interaction for gingivitis (F(4/102)=3.267; p=0.016; e=0.957; ?2=0.114) and a significant main effect of group for oral hygiene skills (F(2/51)=7.088; p=0.002; ?2=0.218). Fones was superior to Bass; Bass did not differ from the control group. Group differences were most prominent after 6 and 12 weeks. Conclusions/Significance: The present trial indicates an advantage of teaching the Fones as compared to the modified Bass technique with respect to oral hygiene skills and gingivitis. Future studies are needed to analyze whether the disadvantage of teaching the Bass technique observed here is restricted to the teaching method employed. Trial Registration: German Clinical Trials Register http://www.drks.de/DRKS0000348

Genetic differentiation among host-associated Alebra leafhoppers (Hemiptera: Cicadellidae)

The limited importance ascribed to sympatric speciation pro cesses via host race formation is partially due to the few cases of host races that have been reported among host populations. This work sheds light on the taxonomy of Alebra leafhoppers and examines the possible existence of host races among host-associated populations. The species of this genus show varying degrees of host association with deciduous trees and shrubs and, frequently, host popu lations of uncertain taxonomic status coexist and occasion ally become pests. Allozyme electrophoresis of 21 Greek populations including sympatric, local and geographically distant samples collected on 13 different plant species, show that they represent at least five species: A. albostriella Falle´n, A. viridis (Rey) (sensu Gillham), A. wahlbergi Bo Keywords: host races; leafhoppers; sympatric speciation; sibling species; allozymes; Alebra Introduction Sympatric speciation is a controversial subject in evol utionary biology (see Mayr, 1963; Futuyma and Mayer, 1980; Paterson, 1981; Via, 2001). One of the reasons for this controversy is that sympatric speciation seems to be an extremely rare phenomenon occurring only in very few groups of taxa, represented chiefly by phytophagous insects (Tauber and Tauber, 1977; Menken, 1981; Wood, 1993; Emelianov et al, 1995; Via, 1999; Finchak et al, 2000; Craig et al, 2001). The limited number of reported cases among organisms with sexual reproduction can be at least partially attributed to the fact that taxa undergoing sympatric speciation events must fulfill very restrictive biological and ecological requirements. Most sympatric speciation models demand that there is intraspecific genetic variation in traits that differentially affect the fitness of individuals that colonise new habitats or hosts (Dieckman and Doebeli, 1999; Hawthorne and Via, 2001 but see Higashi et al, 1999 and Takimoto et al, 2000). They assume that selection acting on these traits can prevent genetic exchange between populations (Bush, 1975; Tauber and Tauber, 1977; Diehl and Bush, 1989). In phytophagous insects, this means that host pref erences must be genetically determined and mating should occur on the host (Bush, 1975; Diehl and Bush, Correspondence: D Aguin-Pombo, Department of Biology, University of Madeira, Campus Universitario da Penteada, 9000 Funchal, Madeira, Portugal. E-mail: aguin uma.pt Received 12 December 2000; accepted 13 December 2001 heman and two new species. Of these, one is associated to Quercus frainetto and other is specific to Crataegus spp. Significant genetic differences among sympatric and local host populations were found only in A. albostriella, between populations on Turkey oak, beech and common alder. It is suggested that the last two of these host populations may represent different host races. The results show that both the host plant and geographical distance affect the patterns of differentiation in the genus. The formation of some spec ies seems to have been the result of allopatric speciation events while, for others, their origin can be equally explained either by sympatric or allopatric speciation.info:eu-repo/semantics/publishedVersio

PEDIA: prioritization of exome data by image analysis

Purpose Phenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists. Methods Here, we introduce an approach driven by artificial intelligence that uses portrait photographs for the interpretation of clinical exome data. We measured the value added by computer-assisted image analysis to the diagnostic yield on a cohort consisting of 679 individuals with 105 different monogenic disorders. For each case in the cohort we compiled frontal photos, clinical features, and the disease-causing variants, and simulated multiple exomes of different ethnic backgrounds. Results The additional use of similarity scores from computer-assisted analysis of frontal photos improved the top 1 accuracy rate by more than 20–89% and the top 10 accuracy rate by more than 5–99% for the disease-causing gene. Conclusion Image analysis by deep-learning algorithms can be used to quantify the phenotypic similarity (PP4 criterion of the American College of Medical Genetics and Genomics guidelines) and to advance the performance of bioinformatics pipelines for exome analysis

Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8(+) tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non–small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit. Cytotoxic chemotherapy–induced subclonal neoantigens, contributing to an increased mutational load, were enriched in certain poor responders. These data suggest that neoantigen heterogeneity may influence immune surveillance and support therapeutic developments targeting clonal neoantigens

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies