52 research outputs found

    Lorentz breaking Effective Field Theory and observational tests

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    Analogue models of gravity have provided an experimentally realizable test field for our ideas on quantum field theory in curved spacetimes but they have also inspired the investigation of possible departures from exact Lorentz invariance at microscopic scales. In this role they have joined, and sometime anticipated, several quantum gravity models characterized by Lorentz breaking phenomenology. A crucial difference between these speculations and other ones associated to quantum gravity scenarios, is the possibility to carry out observational and experimental tests which have nowadays led to a broad range of constraints on departures from Lorentz invariance. We shall review here the effective field theory approach to Lorentz breaking in the matter sector, present the constraints provided by the available observations and finally discuss the implications of the persisting uncertainty on the composition of the ultra high energy cosmic rays for the constraints on the higher order, analogue gravity inspired, Lorentz violations.Comment: 47 pages, 4 figures. Lecture Notes for the IX SIGRAV School on "Analogue Gravity", Como (Italy), May 2011. V.3. Typo corrected, references adde

    GWAS for Systemic Sclerosis Identifies Multiple Risk Loci and Highlights Fibrotic and Vasculopathy Pathways

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    Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.Funding: This work was supported by Spanish Ministry of Economy and Competitiveness (grant ref. SAF2015-66761-P), Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucía (P12-BIO-1395), Ministerio de Educación, Cultura y Deporte through the program FPU, Juan de la Cierva fellowship (FJCI-2015-24028), Red de Investigación en Inflamación y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013), and Scleroderma Research Foundation and NIH P50-HG007735 (to H.Y.C.). H.Y.C. is an Investigator of the Howard Hughes Medical Institute. PopGen 2.0 is supported by a grant from the German Ministry for Education and Research (01EY1103). M.D.M and S.A. are supported by grant DoD W81XWH-18-1-0423 and DoD W81XWH-16-1-0296, respectively

    Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project

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    Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14, 391 patients, 8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%, p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most

    Quantificação de fatores de crescimento na pele de equinos tratada com plasma rico em plaquetas

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    O plasma rico em plaquetas (PRP) é um produto derivado da centrifugação do sangue total, sendo rico em fatores bioativos, como os de crescimento. Apesar da ampla utilização em processos cicatriciais, há controvérsia sobre a eficácia da terapia na cicatrização cutânea. O objetivo desse estudo foi quantificar e comparar a concentração dos fatores TGF-β1 e PDGF-BB no PRP, plasma sanguíneo e pele, durante diferentes fases do processo de cicatrização da pele tratada ou não com PRP. Foram utilizados sete equinos machos castrados, mestiços, hígidos, com idade entre 16 e 17 (16,14±0,63) anos. Três lesões em formato quadrangular (6,25cm²) foram produzidas cirurgicamente nas regiões glúteas direita e esquerda de todos os animais. Doze horas após indução das feridas, 0,5mL do PRP foi administrado em cada uma das quatro extremidades das feridas de uma das regiões glúteas (Grupo tratado = GT), escolhida aleatoriamente. A região contralateral foi utilizada como controle (GC). As feridas foram submetidas à limpeza diária com água Milli Q, e amostras foram obtidas mediante biópsias realizadas com Punch de 6mm. Foram obtidas seis biópsias de pele, sendo a primeira realizada logo após a produção da ferida (T0), e as demais com 1 (T1) 2 (T2) 7 (T3) e 14 (T4) dias após a indução da lesão. A sexta biópsia (T5) foi obtida após completo fechamento da pele, que ocorreu aproximadamente aos 37 dias (36,85±7,45, GC; 38,85±6,46, GT). Também foram obtidas amostras de sangue com EDTA em todos os tempos mencionados. A quantificação dos fatores de crescimento TGF-β1 e PDGF-BB na pele, PRP e plasma sanguíneo foi realizada pela técnica ELISA. Os dados foram analisados estatisticamente pelo teste t, correlação de Pearson e regressão, utilizando nível de significância de 5%. Não houve diferença entre os grupos, nos valores dos dois fatores de crescimento mensurados na pele, nos diferentes tempos. Também não houve correlação entre a quantidade dos fatores de crescimento presentes na pele e no plasma. Por outro lado, correlação positiva foi observada entre PRP e pele no grupo tratado, para os fatores de crescimento TGF-β1 (r=0,31) e PDGF-BB (r=0,38), bem como entre ambos os fatores de crescimento presentes no PRP (r=0,81). Considerando as concentrações dos fatores de crescimento no T0, os maiores valores cutâneos (p<0,05) do TGF-β1, em ambos os grupos, ocorreram nos tempos T3 e T5. Valores mais elevados (p<0,05) do PDGF-BB ocorreram no T4 (GT) e T5 (GC). No plasma não houve alteração nas concentrações desses fatores em relação ao T0, o que sugere que o PRP não acarreta efeito sistêmico, quando os procedimentos adotados na presente pesquisa são utilizados. A administração local de PRP no volume estudado, 12 h após indução cirúrgica de ferida cutânea na região glútea de equinos não ocasiona maiores concentrações dos fatores de crescimento TGF-β1 e PDGF-BB no plasma sanguíneo e pele, durante o processo de cicatrização
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