Colorectal cancer in inflammatory bowel disease: Results of the 3rd ECCO pathogenesis scientific workshop (I)

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Nonlinear optics and saturation behavior of quantum dot samples under continuous wave driving

The nonlinear optical response of self-assembled quantum dots is relevant to the application of quantum dot based devices in nonlinear optics, all-optical switching, slow light and self-organization. Theoretical investigations are based on numerical simulations of a spatially and spectrally resolved rate equation model, which takes into account the strong coupling of the quantum dots to the carrier reservoir created by the wetting layer states. The complex dielectric susceptibility of the ground state is obtained. The saturation is shown to follow a behavior in between the one for a dominantly homogeneously and inhomogeneously broadened medium. Approaches to extract the nonlinear refractive index change by fringe shifts in a cavity or self-lensing are discussed. Experimental work on saturation characteristic of InGa/GaAs quantum dots close to the telecommunication O-band (1.24-1.28 mm) and of InAlAs/GaAlAs quantum dots at 780 nm is described and the first demonstration of the cw saturation of absorption in room temperature quantum dot samples is discussed in detail

Two truncating variants in FANCC and breast cancer risk

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95% CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.Peer reviewe

Insights into the high-energy γ-ray emission of Markarian 501 from extensive multifrequency observations in the Fermi era

We report on the γ-ray activity of the blazar Mrk 501 during the first 480 days of Fermi operation. We find that the average Large Area Telescope (LAT) γ-ray spectrum of Mrk 501 can be well described by a single power-law function with a photon index of 1.78 ± 0.03. While we observe relatively mild flux variations with the Fermi-LAT (within less than a factor of two), we detect remarkable spectral variability where the hardest observed spectral index within the LAT energy range is 1.52 ± 0.14, and the softest one is 2.51 ± 0.20. These unexpected spectral changes do not correlate with the measured flux variations above 0.3 GeV. In this paper, we also present the first results from the 4.5 month long multifrequency campaign (2009 March 15-August 1) on Mrk 501, which included the Very Long Baseline Array (VLBA), Swift, RXTE, MAGIC, and VERITAS, the F-GAMMA, GASP-WEBT, and other collaborations and instruments which provided excellent temporal and energy coverage of the source throughout the entire campaign. The extensive radio to TeV data set from this campaign provides us with the most detailed spectral energy distribution yet collected for this source during its relatively low activity. The average spectral energy distribution of Mrk 501 is well described by the standard one-zone synchrotron self-Compton (SSC) model. In the framework of this model, we find that the dominant emission region is characterized by a size ≲0.1 pc (comparable within a factor of few to the size of the partially resolved VLBA core at 15-43 GHz), and that the total jet power (≃1044 erg s-1) constitutes only a small fraction (∼10-3) of the Eddington luminosity. The energy distribution of the freshly accelerated radiating electrons required to fit the time-averaged data has a broken power-law form in the energy range 0.3 GeV-10 TeV, with spectral indices 2.2 and 2.7 below and above the break energy of 20 GeV. We argue that such a form is consistent with a scenario in which the bulk of the energy dissipation within the dominant emission zone of Mrk 501 is due to relativistic, proton-mediated shocks. We find that the ultrarelativistic electrons and mildly relativistic protons within the blazar zone, if comparable in number, are in approximate energy equipartition, with their energy dominating the jet magnetic field energy by about two orders of magnitude. © 2011. The American Astronomical Society

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)

Unsupervised analysis of small animal dynamic Cerenkov luminescence imaging.

Clustering analysis (CA) and principal component analysis (PCA) were applied to dynamic Cerenkov luminescence images (dCLI). In order to investigate the performances of the proposed approaches, two distinct dynamic data sets obtained by injecting mice with (32)P-ATP and (18)F-FDG were acquired using the IVIS 200 optical imager. The k-means clustering algorithm has been applied to dCLI and was implemented using interactive data language 8.1. We show that cluster analysis allows us to obtain good agreement between the clustered and the corresponding emission regions like the bladder, the liver, and the tumor. We also show a good correspondence between the time activity curves of the different regions obtained by using CA and manual region of interest analysis on dCLIT and PCA images. We conclude that CA provides an automatic unsupervised method for the analysis of preclinical dynamic Cerenkov luminescence image data

Quantum dots excitation using pure beta minus radioisotopes emitting Cerenkov radiation.

Cerenkov radiation imaging has been recently introduced as a new pre-clinical imaging tool to investigate many pathologies in vivo. It is well known that Cerenkov radiation is more intense at shorter wavelength than at longer wavelength in the visible range and, thus, in order to improve the detectability in biological tissues a shift towards the red and near infrared emission is needed. The use of Quantum Dot (QD) nanoparticles as Stokes shifters has been previously suggested, but the interaction mechanism with Cerenkov radiation was not fully investigated. Our experimental results showed a good agreement with the inverse squared law and, thus, we conclude that the excitation of QDs with a beta emitter is quite similar to the fluorescence by unbound excitation from the luminescence mechanis

Optimizing in vivo small animal Cerenkov luminescence imaging.

In vivo Cerenkov luminescence imaging is a rapidly growing molecular imaging research field based on the detection of Cerenkov radiation induced by beta particles when traveling though biological tissues. We investigated theoretically the possibility of enhancing the number of the detected Cerenkov photons in the near infrared (NIR) region of the spectrum. The analysis is based on applying a photon propagation diffusion model to Cerenkov photons in the tissue. Results show that despite the smaller number of Cerenkov photons in the NIR region, the fraction exiting the tissues is greater than in the visible range, and thus, a charge-coupled device detector optimized for the NIR range will allow to obtain a higher signal. The comparison was performed considering Cerenkov point sources located at different depths inside the animal. We concluded that the improvement can be up to 35% and is more significant when the Cerenkov source to be imaged is located deeper inside the animal