Proposal for an Integrated Raman-free Correlated Photon Source

We propose a dual-pump third-order nonlinear scheme for producing pairs of correlated photons that is less susceptible to Raman noise than typical spontaneous four wave mixing methods (SFWM). Beginning with the full multimode Hamiltonian we derive a general expression for the joint spectral amplitude, from which the probability of producing a pair of photons can be calculated. As an example, we demonstrate that a probability of 0.028 pairs per pulse can be achieved in an appropriately designed fused silica microfiber. As compared with single pump SFWM in standard fiber, we calculate that our process shows significant suppression of the spontaneous Raman scattering and an improvement in the signal to noise ratio.Comment: 7 pages, 3 figures (two containing 2 subfigures

Impact of organised programs on colorectal cancer screening

<p>Abstract</p> <p>Purpose</p> <p>Colorectal cancer (CRC) screening has been shown to decrease CRC mortality. Organised mass screening programs are being implemented in France. Its perception in the general population and by general practitioners is not well known.</p> <p>Methods</p> <p>Two nationwide observational telephone surveys were conducted in early 2005. First among a representative sample of subjects living in France and aged between 50 and 74 years that covered both geographical departments with and without implemented screening services. Second among General Practionners (Gps). Descriptive and multiple logistic regression was carried out.</p> <p>Results</p> <p>Twenty-five percent of the persons(N = 1509) reported having undergone at least one CRC screening, 18% of the 600 interviewed GPs reported recommending a screening test for CRC systematically to their patients aged 50–74 years. The odds ratio (OR) of having undergone a screening test using FOBT was 3.91 (95% CI: 2.49–6.16) for those living in organised departments (referent group living in departments without organised screening), almost twice as high as impact educational level (OR = 2.03; 95% CI: 1.19–3.47).</p> <p>Conclusion</p> <p>CRC screening is improved in geographical departments where it is organised by health authorities. In France, an organised screening programs decrease inequalities for CRC screening.</p

Inhibition of Chondrosarcoma Growth by mTOR Inhibitor in an In Vivo Syngeneic Rat Model

BACKGROUND: Chondrosarcomas are the second most frequent primary malignant type of bone tumor. No effective systemic treatment has been identified in advanced or adjuvant phases for chondrosarcoma. The aim of the present study was to determine the antitumor effects of doxorubicin and everolimus, an mTOR inhibitor on chondrosarcoma progression. METHODS AND FINDINGS: Doxorubin and/or everolimus were tested in vivo as single agent or in combination in the rat orthotopic Schwarm chondrosarcoma model, in macroscopic phase, as well as with microscopic residual disease. Response to everolimus and/or doxorubicin was evaluated using chondrosarcoma volume evolution (MRI). Histological response was evaluated with % of tumor necrosis, tumor proliferation index, metabolism quantification analysis between the treated and control groups. Statistical analyses were performed using chi square, Fishers exact test. Doxorubicin single agent has no effect of tumor growth as compared to no treatment; conversely, everolimus single agent significantly inhibited tumor progression in macroscopic tumors with no synergistic additive effect with doxorubicin. Everolimus inhibited chondrosarcoma proliferation as evaluated by Ki67 expression did not induce the apoptosis of tumor cells; everolimus reduced Glut1 and 4EBP1 expression. Importantly when given in rats with microscopic residual diseases, in a pseudo neoadjuvant setting, following R1 resection of the implanted tumor, everolimus significantly delayed or prevented tumor recurrence. CONCLUSIONS: MTOR inhibitor everolimus blocks cell proliferation, Glut1 expression and HIF1a expression, and prevents in vivo chondrosarcoma tumor progression in both macroscopic and in adjuvant phase post R1 resection. Taken together, our preclinical data indicate that mTOR inhibitor may be effective as a single agent in treating chondrosarcoma patients. A clinical trial evaluating mTOr inhibitor as neo-adjuvant and adjuvant therapy in chondrosarcoma patients is being constructed

Distant agricultural landscapes

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. The final publication is available at Springer via http://dx.doi.org/10.1007/s11625-014-0278-0This paper examines the relationship between the development of the dominant industrial food system and its associated global economic drivers and the environmental sustainability of agricultural landscapes. It makes the case that the growth of the global industrial food system has encouraged increasingly complex forms of “distance” that separate food both geographically and mentally from the landscapes on which it was produced. This separation between food and its originating landscape poses challenges for the ability of more localized agricultural sustainability initiatives to address some of the broader problems in the global food system. In particular, distance enables certain powerful actors to externalize ecological and social costs, which in turn makes it difficult to link specific global actors to particular biophysical and social impacts felt on local agricultural landscapes. Feedback mechanisms that normally would provide pressure for improved agricultural sustainability are weak because there is a lack of clarity regarding responsibility for outcomes. The paper provides a brief illustration of these dynamics with a closer look at increased financialization in the food system. It shows that new forms of distancing are encouraged by the growing significance of financial markets in global agrifood value chains. This dynamic has a substantial impact on food system outcomes and ultimately complicates efforts to scale up small-scale local agricultural models that are more sustainable.The Trudeau Foundation || Social Sciences and Humanities Research Council of Canad

Functional Characterization of Human Cancer-Derived TRKB Mutations

Cancer originates from cells that have acquired mutations in genes critical for controlling cell proliferation, survival and differentiation. Often, tumors continue to depend on these so-called driver mutations, providing the rationale for targeted anticancer therapies. To date, large-scale sequencing analyses have revealed hundreds of mutations in human tumors. However, without their functional validation it remains unclear which mutations correspond to driver, or rather bystander, mutations and, therefore, whether the mutated gene represents a target for therapeutic intervention. In human colorectal tumors, the neurotrophic receptor TRKB has been found mutated on two different sites in its kinase domain (TRKBT695I and TRKBD751N). Another site, in the extracellular part of TRKB, is mutated in a human lung adenocarcinoma cell line (TRKBL138F). Lastly, our own analysis has identified one additional TRKB point mutation proximal to the kinase domain (TRKBP507L) in a human melanoma cell line. The functional consequences of all these point mutations, however, have so far remained elusive. Previously, we have shown that TRKB is a potent suppressor of anoikis and that TRKB-expressing cells form highly invasive and metastatic tumors in nude mice. To assess the functional consequences of these four TRKB mutations, we determined their potential to suppress anoikis and to form tumors in nude mice. Unexpectedly, both colon cancer-derived mutants, TRKBT695I and TRKBD751N, displayed reduced activity compared to that of wild-type TRKB. Consistently, upon stimulation with the TRKB ligand BDNF, these mutants were impaired in activating TRKB and its downstream effectors AKT and ERK. The two mutants derived from human tumor cell lines (TRKBL138F and TRKBP507L) were functionally indistinguishable from wild-type TRKB in both in-vitro and in-vivo assays. In conclusion, we fail to detect any gain-of-function of four cancer-derived TRKB point mutations

SELNET clinical practice guidelines for bone sarcoma

Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context

Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study

Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC = 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.Peer reviewe

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease