432 research outputs found

    Motion in Quantum Gravity

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    We tackle the question of motion in Quantum Gravity: what does motion mean at the Planck scale? Although we are still far from a complete answer we consider here a toy model in which the problem can be formulated and resolved precisely. The setting of the toy model is three dimensional Euclidean gravity. Before studying the model in detail, we argue that Loop Quantum Gravity may provide a very useful approach when discussing the question of motion in Quantum Gravity.Comment: 30 pages, to appear in the book "Mass and Motion in General Relativity", proceedings of the C.N.R.S. School in Orleans, France, eds. L. Blanchet, A. Spallicci and B. Whitin

    A Closed-Form Solution of the Multi-Period Portfolio Choice Problem for a Quadratic Utility Function

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    In the present paper, we derive a closed-form solution of the multi-period portfolio choice problem for a quadratic utility function with and without a riskless asset. All results are derived under weak conditions on the asset returns. No assumption on the correlation structure between different time points is needed and no assumption on the distribution is imposed. All expressions are presented in terms of the conditional mean vectors and the conditional covariance matrices. If the multivariate process of the asset returns is independent it is shown that in the case without a riskless asset the solution is presented as a sequence of optimal portfolio weights obtained by solving the single-period Markowitz optimization problem. The process dynamics are included only in the shape parameter of the utility function. If a riskless asset is present then the multi-period optimal portfolio weights are proportional to the single-period solutions multiplied by time-varying constants which are depending on the process dynamics. Remarkably, in the case of a portfolio selection with the tangency portfolio the multi-period solution coincides with the sequence of the simple-period solutions. Finally, we compare the suggested strategies with existing multi-period portfolio allocation methods for real data.Comment: 38 pages, 9 figures, 3 tables, changes: VAR(1)-CCC-GARCH(1,1) process dynamics and the analysis of increasing horizon are included in the simulation study, under revision in Annals of Operations Researc

    Hepatitis C infection: eligibility for antiviral therapies

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    peer reviewedBackground Current treatments of chronic hepatitis C virus (HCV) are effective, but expensive and susceptible to induce significant side effects. Objectives To evaluate the proportion of HCV patients who are eligible for a treatment. Methods In a database comprising 1726 viraemic HCV patients, the files of 299 patients who presented to the same hepatologist for an initial appointment between 1996 and 2003 were reviewed. Results Patients' characteristics were age 43.1 +/- 15.6 years, 53% male and 92% Caucasian. The main risk factors were transfusion (43%) and drug use (22%). Genotypes were mostly genotype 1 (66%), genotype 3 (12%) and genotype 2 (10%). These characteristics were not different from those of the whole series of 1726 patients. A total of 176 patients (59%) were not treated, the reasons for non-treatment being medical contraindications (34%), non-compliance (25%) and normal transaminases (24%). In addition, 17% of patients declined therapy despite being considered as eligible, mainly due to fear of adverse events. Medical contraindications were psychiatric (27%), age (22%), end-stage liver disease (15%), willingness for pregnancy (13%), cardiac contraindication (7%) and others (16%). Only 123 patients (41%) were treated. A sustained viral response was observed in 41%. The treatment was interrupted in 16% for adverse events. Conclusions The majority of HCV patients are not eligible for treatment. This implies that, with current therapies, only 17% of patients referred for chronic HCV become sustained responders. Some modifications of guidelines could extend the rate of treatment (patients with normal transaminases), but an important barrier remains the patients' and the doctors' fear of adverse events

    Recurrent rare copy number variants increase risk for esotropia

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    Purpose: To determine whether rare copy number variants (CNVs) increase risk for comitant esotropia. Methods: CNVs were identified in 1614 Caucasian individuals with comitant esotropia and 3922 Caucasian controls from Illumina SNP genotyping using two Hidden Markov model (HMM) algorithms, PennCNV and QuantiSNP, which call CNVs based on logR ratio and B allele frequency. Deletions and duplications greater than 10 kb were included. Common CNVs were excluded. Association testing was performed with 1 million permutations in PLINK. Significant CNVs were confirmed with digital droplet polymerase chain reaction (ddPCR). Whole genome sequencing was performed to determine insertion location and breakpoints. Results: Esotropia patients have similar rates and proportions of CNVs compared with controls but greater total length and average size of both deletions and duplications. Three recurrent rare duplications significantly (P = 1 × 10-6) increase the risk of esotropia: chromosome 2p11.2 (hg19, 2:87428677-87965359), spanning one long noncoding RNA (lncRNA) and two microRNAs (OR 14.16; 95% confidence interval [CI] 5.4-38.1); chromosome 4p15.2 (hg19, 4:25554332-25577184), spanning one lncRNA (OR 11.1; 95% CI 4.6-25.2); chromosome 10q11.22 (hg19, 10:47049547-47703870) spanning seven protein-coding genes, one lncRNA, and four pseudogenes (OR 8.96; 95% CI 5.4-14.9). Overall, 114 cases (7%) and only 28 controls (0.7%) had one of the three rare duplications. No case nor control had more than one of these three duplications. Conclusions: Rare CNVs are a source of genetic variation that contribute to the genetic risk for comitant esotropia, which is likely polygenic. Future research into the functional consequences of these recurrent duplications may shed light on the pathophysiology of esotropia

    Estrogenic microenvironment generated by organochlorine residues in adipose mammary tissue modulates biomarker expression in ERα-positive breast carcinomas

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    INTRODUCTION: Breast cancer is the most frequent malignant disease in women. Exposure to estrogens throughout a woman's life is a risk factor for the development of breast cancer. Organochlorine compounds (OCCs), such as pesticides and polychlorinated biphenyls, are persistent lipophilic chemicals identified as endocrine disruptors, mainly with estrogenic effects. To test the hypothesis that the amount and quality of organochlorine residues in adipose tissue adjacent to breast carcinoma affect the biological behavior of the tumor, we studied biomarker expression in breast carcinoma and the OCC body burden in patients from an urban area adjacent to Paraná fluvial system, Argentina. METHODS: The studied patients were 55 women who had undergone excision biopsies of a breast lesion diagnosed as invasive breast carcinoma. Analysis of OCC residues in breast adipose tissue was conducted by electron-capture gas–liquid chromatography. Estrogen receptor alpha (ERα), progesterone receptor (PR) and proliferative activity (Ki-67) levels were measured in paraffin-embedded biopsies of breast tumors by immunohistochemistry. RESULTS: All patients had high levels of organochlorine pesticides in their breast adipose tissue. The most frequently detected compounds were p,p'-dichlorodiphenyldichloroethylene, hexachlorobenzene and β-hexachlorocyclohexane. When the whole sample was analyzed, no correlation between ERα or PR expression and OCC levels were found. In the subgroup of ERα-positive breast carcinoma patients, however, there was a positive correlation between PR expression (an estrogen-induced protein) in the neoplastic cells and OCC levels in adipose tissue surrounding the tumor. More significantly, all the ERα-positive breast carcinomas from postmenopausal women exhibited high proliferation when organochlorine levels in the surrounding adipose tissue reached levels higher than 2600 ppb. No associations were found between the organochlorine body burden and any other marker of tumor aggressiveness, such as node involvement or tumor size. CONCLUSION: The present results support the hypothesis that organochlorine residues in adipose tissue adjacent to breast carcinoma generate an estrogenic microenvironment that may influence the biological behavior of the tumor through ERα activation and ERα-dependent proliferation. These findings may have therapeutic implications, since interference between organochlorine compounds and hormonal therapy could be expected to occur

    The effect of maternal common mental disorders on infant undernutrition in Butajira, Ethiopia:The P-MaMiE study

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    BackgroundAlthough maternal common mental disorder (CMD) appears to be a risk factor for infant undernutrition in South Asian countries, the position in sub-Saharan Africa (SSA) is unclearMethodsA population-based cohort of 1065 women, in the third trimester of pregnancy, was identified from the demographic surveillance site (DSS) in Butajira, to investigate the effect of maternal CMD on infant undernutrition in a predominantly rural Ethiopian population. Participants were interviewed at recruitment and at two months post-partum. Maternal CMD was measured using the locally validated Self-Reported Questionnaire (score of ≥ six indicating high levels of CMD). Infant anthropometry was recorded at six and twelve months of age.ResultThe prevalence of CMD was 12% during pregnancy and 5% at the two month postnatal time-point. In bivariate analysis antenatal CMD which had resolved after delivery predicted underweight at twelve months (OR = 1.71; 95% CI: 1.05, 2.50). There were no other statistically significant differences in the prevalence of underweight or stunted infants in mothers with high levels of CMD compared to those with low levels. The associations between CMD and infant nutritional status were not significant after adjusting for pre-specified potential confounders.ConclusionOur negative finding adds to the inconsistent picture emerging from SSA. The association between CMD and infant undernutrition might be modified by study methodology as well as degree of shared parenting among family members, making it difficult to extrapolate across low- and middle-income countries
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