Gravitons in One-Loop Quantum Cosmology: Correspondence Between Covariant and Non-Covariant Formalisms

The discrepancy between the results of covariant and non-covariant one-loop calculations for higher-spin fields in quantum cosmology is analyzed. A detailed mode-by-mode study of perturbative quantum gravity about a flat Euclidean background bounded by two concentric 3-spheres, including non-physical degrees of freedom and ghost modes, leads to one-loop amplitudes in agreement with the covariant Schwinger-DeWitt method. This calculation provides the generalization of a previous analysis of fermionic fields and electromagnetic fields at one-loop about flat Euclidean backgrounds admitting a well-defined 3+1 decomposition.Comment: 29 pages, latex, recently appearing in Physical Review D, volume 50, pages 6329-6337, November 1994. The authors apologize for the delay in circulating the paper, due to technical problems now fixe

Relativistic Gauge Conditions in Quantum Cosmology

This paper studies the quantization of the electromagnetic field on a flat Euclidean background with boundaries. One-loop scaling factors are evaluated for the one-boundary and two-boundary backgrounds. The mode-by-mode analysis of Faddeev-Popov quantum amplitudes is performed by using zeta-function regularization, and is compared with the space-time covariant evaluation of the same amplitudes. It is shown that a particular gauge condition exists for which the corresponding operator matrix acting on gauge modes is in diagonal form from the beginning. Moreover, various relativistic gauge conditions are studied in detail, to investigate the gauge invariance of the perturbative quantum theory.Comment: 26 pages, plain TeX, no figure

Gauge Theories on a 2+2 Anisotropic Lattice

The implementation of gauge theories on a four-dimensional anisotropic lattice with two distinct lattice spacings is discussed, with special attention to the case where two axes are finely and two axes are coarsely discretized. Feynman rules for the Wilson gauge action are derived and the renormalizability of the theory and the recovery of the continuum limit are analyzed. The calculation of the gluon propagator and the restoration of Lorentz invariance in on-shell states is presented to one-loop order in lattice perturbation theory for $SU(N_c)$ on both 2+2 and 3+1 lattices.Comment: 27 pages, uses feynmf. Font compatibility adjuste

Quantum Field Theory of three flavor neutrino mixing and oscillations with CP violation

We study in detail the Quantum Field Theory of mixing among three generations of Dirac fermions (neutrinos). We construct the Hilbert space for the flavor fields and determine the generators of the mixing transformations. By use of these generators, we recover all the known parameterizations of the three-flavor mixing matrix and we find a number of new ones. The algebra of the currents associated with the mixing transformations is shown to be a deformed $su(3)$ algebra, when CP violating phases are present. We then derive the exact oscillation formulas, exhibiting new features with respect to the usual ones. CP and T violation are also discussed.Comment: 15 pages, 7 figures, RevTeX, revised versio

A European spectrum of pharmacogenomic biomarkers: Implications for clinical pharmacogenomics

Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes. Our data show significant interpopulation pharmacogenomic biomarker allele frequency differences, particularly in 7 clinically actionable pharmacogenomic biomarkers in 7 European populations, affecting drug efficacy and/or toxicity of 51 medication treatment modalities. These data also reflect on the differences observed in the prevalence of high-risk genotypes in these populations, as far as common markers in the CYP2C9, CYP2C19, CYP3A5, VKORC1, SLCO1B1 and TPMT pharmacogenes are concerned. Also, our data demonstrate notable differences in predicted genotype-based warfarin dosing among these populations. Our findings can be exploited not only to develop guidelines for medical prioritization, but most importantly to facilitate integration of pharmacogenomics and to support pre-emptive pharmacogenomic testing. This may subsequently contribute towards significant cost-savings in the overall healthcare expenditure in the participating countries, where pharmacogenomics implementation proves to be cost-effective

SANI-Severe Asthma Network in Italy: a way forward to monitor severe asthma

Even if severe asthma (SA) accounts for 5-10% of all cases of the disease, it is currently a crucial unmet need, owing its difficult clinical management and its high social costs. For this reason several networks, focused on SA have been organized in some countries, in order to select these patients, to recognize their clinical features, to evaluate their adherence, to classify their biological/clinical phenotypes, to identify their eligibility to the new biologic therapies and to quantify the costs of the disease. Aim of the present paper is to describe the ongoing Italian Severe Asthma Network (SANI). Up today 49 centres have been selected, widespread on the national territory. Sharing the same diagnostic protocol, data regarding patients with SA will be collected and processed in a web platform. After their recruitment, SA patients will be followed in the long term in order to investigate the natural history of the disease. Besides clinical data, the cost/benefit evaluation of the new biologics will be verified as well as the search of peculiar biomarker(s) of the disease

Survival improvement over time of 960 s-AML patients included in 13 EORTC-GIMEMA-HOVON trials

We report the outcomes of secondary acute myeloid leukemia (s-AML) patients included in one of 13 European Organisation for Research and Treatment of Cancer (EORTC) collaborative AML trials using intensive remission-induction chemotherapy. Among 8858 patients treated between May 1986 and January 2008, 960 were identified as having s-AML, either after MDS (cohort A; n = 508), occurring after primary solid tumors or hematologic malignancies other than MDS (cohort B; n = 361), or after non-malignant conditions or with a history of toxic exposure (cohort C; n = 91). Median age was 64 years, 60 years and 61 years in cohort A, B and C, respectively. Among patients ≤60 years and classified in the cohorts A or B (n = 367), the 5-year overall survival (OS) rate was 28%. There was a systematic improvement in the 5-year OS rate over three time periods (p 60 years of age (n = 502), the OS was dismal, and there was no improvement over time

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase