Carcinoma-associated pancreatic fibroblasts (CAFs) are the major type of cells in the stroma of pancreatic ductal adenocarcinomas and besides their pathological release of extracellular matrix ...proteins, they are also perceived as key contributors to immune evasion. Despite the known relevance of tumor infiltrating lymphocytes in cancers, the interactions between T-cells and CAFs remain largely unexplored. Here, we found that CAFs isolated from tumors of pancreatic cancer patients undergoing surgical resection (
= 15) expressed higher levels of the PD-1 ligands PD-L1 and PD-L2 compared to primary skin fibroblasts from healthy donors. CAFs strongly inhibited T-cell proliferation in a contact-independent fashion. Blocking the activity of prostaglandin E
(PGE
) by indomethacin partially restored the proliferative capacity of both CD4
and CD8
T-cells. After stimulation, the proportion of proliferating T-cells expressing HLA-DR and the proportion of memory T-cells were decreased when CAFs were present compared to T-cells proliferating in the absence of CAFs. Interestingly, CAFs promoted the expression of TIM-3, PD-1, CTLA-4 and LAG-3 in proliferating T-cells. Immunohistochemistry stainings further showed that T-cells residing within the desmoplastic stromal compartment express PD-1, indicating a role for CAFs on co-inhibitory marker expression also
. We further found that PGE
promoted the expression of PD-1 and TIM-3 on T-cells. Functional assays showed that proliferating T-cells expressing immune checkpoints produced less IFN-γ, TNF-α, and CD107a after restimulation when CAFs had been present. Thus, this indicates that CAFs induce expression of immune checkpoints on CD4
and CD8
T-cells, which contribute to a diminished immune function.
Objective Telangiectasias of the lower legs are intradermal dilatations of the subpapillary venous plexus, but their pathophysiology and risk factors are still largely unknown. The purpose of this ...review is to summarize the current knowledge on the pathophysiology and risk factors for telangiectasias. Methods A systematic review of the literature indexed in Medline completed with textbooks and European phlebology journals from the French, Swiss, and German phlebology societies was performed. Results A multitude of risk factors and several pathophysiological hypotheses, such as reflux, arterio-venous micro-shunts, parietal, and connective tissue abnormalities, are described in the literature. The different hypotheses are discussed and put in a clinical perspective, in particular their therapeutic implications for phlebologists. Conclusion In conclusion, pathophysiology and risk factors of telangiectasias are still largely unknown, and a better understanding could improve treatment results and reduce recurrence.
The echinococcoses are chronic, parasitic diseases that are acquired after ingestion of infective taeniid tapeworm eggs from certain species of the genus Echinococcus. Cystic echinococcosis (CE) ...occurs worldwide, whereas, alveolar echinococcosis (AE) is restricted to the northern hemisphere, and neotropical echinococcosis (NE) has only been identified in Central and South America. Clinical manifestations and disease courses vary profoundly for the different species of Echinococcus. CE presents as small to large cysts, and has commonly been referred to as 'hydatid disease', or 'hydatidosis'. A structured stage-specific approach to CE management, based on the World Health Organization (WHO) ultrasound classification of liver cysts, is now recommended. Management options include percutaneous sterilization techniques, surgery, drug treatment, a 'watch-and-wait' approach or combinations thereof. In contrast, clinical manifestations associated with AE resemble those of a 'malignant', silently-progressing liver disease, with local tissue infiltration and metastases. Structured care is important for AE management and includes WHO staging, drug therapy and long-term follow-up for at least a decade. NE presents as polycystic or unicystic disease. Clinical characteristics resemble those of AE, and management needs to be structured accordingly. However, to date, only a few hundreds of cases have been reported in the literature. The echinococcoses are often expensive and complicated to treat, and prospective clinical studies are needed to better inform case management decisions.
We investigate collective effects in plasmonic oligomers of different symmetries using second-harmonic generation (SHG) microscopy with cylindrical vector beams (CVBs). The oligomers consist of gold ...nanorods that have a longitudinal plasmon resonance close to the fundamental wavelength that is used for SHG excitation and whose long axes are arranged locally such that they follow the distribution of the transverse component of the electric field of radially or azimuthally polarized CVBs in the focal plane. We observe that SHG from such rotationally symmetric oligomers is strongly modified by the interplay between the polarization properties of the CVB and interparticle coupling. We find that the oligomers with radially oriented nanorods exhibit small coupling effects. In contrast, we find that the oligomers with azimuthally oriented nanorods exhibit large coupling effects that lead to silencing of SHG from the whole structure. Our experimental results are in very good agreement with numerical calculations based on the boundary element method. The work describes a new route for studying coupling effects in complex arrangements of nano-objects and thereby for tailoring the efficiency of nonlinear optical effects in such structures.
Sclerotherapy is the targeted chemical ablation of varicose veins by intravenous injection of a liquid or foamed sclerosing drug. The treated veins may be intradermal, subcutaneous, and/or ...transfascial as well as superficial and deep in venous malformations. The aim of this guideline is to give evidence-based recommendations for liquid and foam sclerotherapy.
This guideline was drafted on behalf of 23 European Phlebological Societies during a Guideline Conference on 7-10 May 2012 in Mainz. The conference was organized by the German Society of Phlebology. These guidelines review the present state of knowledge as reflected in published medical literature. The regulatory situation of sclerosant drugs differs from country to country but this has not been considered in this document. The recommendations of this guideline are graded according to the American College of Chest Physicians Task Force recommendations on Grading Strength of Recommendations and Quality of Evidence in Clinical Guidelines.
This guideline focuses on the two sclerosing drugs which are licensed in the majority of the European countries, polidocanol and sodium tetradecyl sulphate. Other sclerosants are not discussed in detail. The guideline gives recommendations concerning indications, contraindications, side-effects, concentrations, volumes, technique and efficacy of liquid and foam sclerotherapy of varicose veins and venous malformations.
Image registration is a vital step in the processing of multispectral imagery. The accuracy to which imagery collected at multiple wavelengths can be aligned directly affects the resolution of the ...spectral end products. Automated registration of the multispectral imagery can often be unreliable, particularly between visible and infrared imagery, due to the significant differences in scene reflectance at different wavelengths. This is further complicated by the thermal features that exist at longer wavelengths. We develop new mathematical and computational models for robust image registration. In particular, we develop a frequency-domain model for the mutual-information surface around the optimal parameters and use it to develop a robust gradient ascent algorithm. For a robust performance, we require that the algorithm be initialized close to the optimal registration parameters. As a measure of how close we need to be, we propose the use of the correlation length and provide an efficient algorithm for estimating it. We measure the performance of the proposed algorithm over hundreds of random initializations to demonstrate its robustness on real data. We find that the algorithm should be expected to converge, as long as the registration parameters are initialized to be within the correlation-length distance from the optimum
Spectrographs for astrophotonics Blind, N; Le Coarer, E; Kern, P ...
Optics express,
2017-Oct-30, 2017-10-30, 20171030, Volume:
25, Issue:
22
Journal Article
Peer reviewed
Open access
The next generation of extremely large telescopes (ELT), with diameters up to 39 meters, is planned to begin operation in the next decade and promises new challenges in the development of instruments ...since the instrument size increases in proportion to the telescope diameter D, and the cost as D
or faster. The growing field of astrophotonics (the use of photonic technologies in astronomy) could solve this problem by allowing mass production of fully integrated and robust instruments combining various optical functions, with the potential to reduce the size, complexity and cost of instruments. Astrophotonics allows for a broad range of new optical functions, with applications ranging from sky background filtering, high spatial and spectral resolution imaging and spectroscopy. In this paper, we want to provide astronomers with valuable keys to understand how photonics solutions can be implemented (or not) according to the foreseen applications. The paper introduces first key concepts linked to the characteristics of photonics technologies, placed in the framework of astronomy and spectroscopy. We then describe a series of merit criteria that help us determine the potential of a given micro-spectrograph technology for astronomy applications, and then take an inventory of the recent developments in integrated micro-spectrographs with potential for astronomy. We finally compare their performance, to finally draw a map of typical science requirements and pin the identified integrated technologies on it. We finally emphasize the necessary developments that must support micro-spectrograph in the coming years.
This study compared the critical swimming speed (U
) and endurance performance of three Australian freshwater fish species in different swim-test apparatus. Estimates of U
measured in a large ...recirculating flume were greater for all species compared with estimates from a smaller model of the same recirculating flume. Large differences were also observed for estimates of endurance swimming performance between these recirculating flumes and a free-surface swim tunnel. Differences in estimates of performance may be attributable to variation in flow conditions within different types of swim chambers. Variation in estimates of swimming performance between different types of flumes complicates the application of laboratory-based measures to the design of fish passage infrastructure.
The present study was conducted in the isolated desert town of Oranjemund in the far south of Namibia. It is an extremely arid region where no livestock husbandry is practiced and only animals ...adapted to the desert can be found. However, in and around the city, artificial irrigation maintains lush green patches of grass that attract wild animals, in particular oryx antelopes (
). In 2015 four oryx antelopes were euthanised due to poor conditions and a post-mortem examination was conducted. Two were found positive for cystic echinococcosis and 16 cysts were collected for molecular analyses. In addition, faecal samples from black-backed jackals (n=5) and domestic dogs (n=9), which were regularly observed to feed on oryx carcasses, were collected and taeniid eggs isolated. Parasite species identification of the cysts and eggs was done by amplifying and sequencing the mitochondrial
gene. Both oryx antelopes were found infected with
and one co-infected with
G6/7. Both
species were able to develop fertile cysts in oryx, making oryx antelopes competent hosts for these parasites. Therefore, the analysis of faecal samples was of high interest and although the numbers were quite small, taeniid eggs were found in three out of five faecal samples of jackals and in all nine dog samples. However, species determination was only successful with two jackal and one dog sample. All three were positive for
G6/7. The absence of
may be due to the low number of faecal samples examined. In our small study, we discovered a rather unique lifecycle of
spp. between jackals and domestic dogs as definitive hosts and oryx antelopes as intermediate hosts. Here, the presence of
G6/7 is of particular concern, as it is the second most important causative agent of CE in humans.
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