Replacing the Transfusion of 1-2 Units of Blood with Plasma Expanders that Increase Oxygen Delivery Capacity: Evidence from Experimental Studies.

At least a third of the blood supply in the world is used to transfuse 1-2 units of packed red blood cells for each intervention and most clinical trials of blood substitutes have been carried out at this level of oxygen carrying capacity (OCC) restoration. However, the increase of oxygenation achieved is marginal or none at all for molecular hemoglobin (Hb) products, due to their lingering vasoactivity. This has provided the impetus for the development of "oxygen therapeutics" using Hb-based molecules that have high oxygen affinity and target delivery of oxygen to anoxic areas. However it is still unclear how these oxygen carriers counteract or mitigate the functional effects of anemia due to obstruction, vasoconstriction and under-perfusion. Indeed, they are administered as a low dosage/low volume therapeutic Hb (subsequently further diluted in the circulatory pool) and hence induce extremely small OCC changes. Hyperviscous plasma expanders provide an alternative to oxygen therapeutics by increasing the oxygen delivery capacity (ODC); in anemia they induce supra-perfusion and increase tissue perfusion (flow) by as much as 50%. Polyethylene glycol conjugate albumin (PEG-Alb) accomplishes this by enhancing the shear thinning behavior of diluted blood, which increases microvascular endothelial shear stress, causes vasodilation and lowering peripheral vascular resistance thus facilitating cardiac function. Induction of supra-perfusion takes advantage of the fact that ODC is the product of OCC and blood flow and hence can be maintained by increasing either or both. Animal studies suggest that this approach may save a considerable fraction of the blood supply. It has an additional benefit of enhancing tissue clearance of toxic metabolites

Galileo, the European GNSS program, and LAGEOS

With the ASI-INFN project “ETRUSCO-2 (Extra Terrestrial Ranging to Unified Satellite COnstellations-2)” we have the opportunity to continue and enhance the work already done with the former ETRUSCO INFN experiment. With ETRUSCO (2005-2010) the SCF LAB (Satellite/lunar laser ranging Characterization Facility LABoratory) team developed a new industry-standard test for laser retroreflectors characterization (the SCF-Test). This test is an integrated and concurrent thermal and optical measurement in accurately laboratory-simulated space environment. In the same period we had the opportunity to test several flight models of retroreflectors from NASA, ESA and ASI. Doing this we examined the detailed thermal behavior and the optical performance of LAGEOS (Laser GEOdynamics Satellites) cube corner retroreflectors and many others being used on the Global Navigation Satellite System (GNSS) constellations currently in orbit, mainly GPS, GLONASS and GIOVE-A/GIOVE-B (Galileo In Orbit Validation Element) satellites, which deploy old-generation aluminium back-coated reflectors; we also SCFTested for ESA prototype new-generation uncoated reflectors for the Galileo IOV (In-Orbit Validation) satellites, which is the most important result presented here. ETRUSCO-2 inherits all this work and a new lab with doubled instrumentation (cryostat, sun simulator, optical bench) inside a new, dedicated 85m2 class 10000 (or better) clean room. This new project aims at a new revision of the SCF-Test expressly conceived to dynamically simulate the actual GNSS typical orbital environment, a new, reliable Key Performance Indicator for the future GNSS retroreflectors payload. Following up on this and using LAGEOS as a reference standard target in terms of optical performances, the SCF LAB research team led by S. Dell’Agnello is designing, building and testing a new generation of GNSS retroreflectors array (GRA) for the new European GNSS constellation Galileo

MOONLIGHT: A NEW LUNAR LASER RANGING RETROREFLECTOR AND THE LUNAR GEODETIC PRECESSION

Since the 1970s Lunar Laser Ranging (LLR) to the Apollo Cube Corner Retroreflector (CCR) arrays (developed by the University of Maryland, UMD) supplied almost all significant tests of General Relativity (Alley et al., 1970; Chang et al., 1971; Bender et al.,1973): possible changes in the gravitational constant, gravitational self-energy, weak equivalence principle, geodetic precession, inverse-square force-law. The LNF group, in fact, has just completed a new measurement of the lunar geodetic precession with Apollo array, with accuracy of 9 × 10−3, comparable to the best measurement to date. LLR has also provided significant information on the composition and origin of the moon. This is the only Apollo experiment still in operation. In the 1970s Apollo LLR arrays contributed a negligible fraction of the ranging error budget. Since the ranging capabilities of ground stations improved by more than two orders of magnitude, now, because of the lunar librations, Apollo CCR arrays dominate the error budget. With the project MoonLIGHT (Moon Laser Instrumentation for General relativity High-accuracy Tests), in 2006 INFN-LNF joined UMD in the development and test of a new-generation LLR payload made by a single, large CCR (100mm diameter) unaffected by the effect of librations. With MoonLIGHT CCRs the accuracy of the measurement of the lunar geodetic precession can be improved up to a factor 100 compared to Apollo arrays. From a technological point of view, INFN-LNF built and is operating a new experimental apparatus (Satellite/lunar laser ranging Characterization Facility, SCF) and created a new industry-standard test procedure (SCF-Test) to characterize and model the detailed thermal behavior and the optical performance of CCRs in accurately laboratory-simulated space conditions, for industrial and scientific applications. Our key experimental innovation is the concurrent measurement and modeling of the optical Far Field Diffraction Pattern (FFDP) and the temperature distribution of retroreflector payloads under thermal conditions produced with a close-match solar simulator. The apparatus includes infrared cameras for non-invasive thermometry, thermal control and real-time payload movement to simulate satellite orientation on orbit with respect to solar illumination and laser interrogation beams. These capabilities provide: unique pre-launch performance validation of the space segment of LLR/SLR (Satellite Laser Ranging); retroreflector design optimization to maximize ranging efficiency and signal-to-noise conditions in daylight. Results of the SCF-Test of our CCR payload will be presented. Negotiations are underway to propose our payload and SCF-Test services for precision gravity and lunar science measurements with next robotic lunar landing missions. In particular, a scientific collaboration agreement was signed on Jan. 30, 2012, by D. Currie, S. Dell'Agnello and the Japanese PI team of the LLR instrument of the proposed SELENE-2 mission by JAXA (Registered with INFN Protocol n. 0000242-03/Feb/2012). The agreement foresees that, under no exchange of funds, the Japanese single, large, hollow LLR reflector will be SCF-Tested and that MoonLIGHT will be considered as backup instrument

MOONLIGHT: A NEW LUNAR LASER RANGING RETROREFLECTOR AND THE LUNAR GEODETIC PRECESSION

Since the 1970s Lunar Laser Ranging (LLR) to the Apollo Cube Corner Retroreflector (CCR) arrays (developed by the University of Maryland, UMD) supplied almost all significant tests of General Relativity (Alley et al., 1970; Chang et al., 1971; Bender et al.,1973): possible changes in the gravitational constant, gravitational self-energy, weak equivalence principle, geodetic precession, inverse-square force-law. The LNF group, in fact, has just completed a new measurement of the lunar geodetic precession with Apollo array, with accuracy of 9 × 10−3, comparable to the best measurement to date. LLR has also provided significant information on the composition and origin of the moon. This is the only Apollo experiment still in operation. In the 1970s Apollo LLR arrays contributed a negligible fraction of the ranging error budget. Since the ranging capabilities of ground stations improved by more than two orders of magnitude, now, because of the lunar librations, Apollo CCR arrays dominate the error budget. With the project MoonLIGHT (Moon Laser Instrumentation for General relativity High-accuracy Tests), in 2006 INFN-LNF joined UMD in the development and test of a new-generation LLR payload made by a single, large CCR (100mm diameter) unaffected by the effect of librations. With MoonLIGHT CCRs the accuracy of the measurement of the lunar geodetic precession can be improved up to a factor 100 compared to Apollo arrays. From a technological point of view, INFN-LNF built and is operating a new experimental apparatus (Satellite/lunar laser ranging Characterization Facility, SCF) and created a new industry-standard test procedure (SCF-Test) to characterize and model the detailed thermal behavior and the optical performance of CCRs in accurately laboratory-simulated space conditions, for industrial and scientific applications. Our key experimental innovation is the concurrent measurement and modeling of the optical Far Field Diffraction Pattern (FFDP) and the temperature distribution of retroreflector payloads under thermal conditions produced with a close-match solar simulator. The apparatus includes infrared cameras for non-invasive thermometry, thermal control and real-time payload movement to simulate satellite orientation on orbit with respect to solar illumination and laser interrogation beams. These capabilities provide: unique pre-launch performance validation of the space segment of LLR/SLR (Satellite Laser Ranging); retroreflector design optimization to maximize ranging efficiency and signal-to-noise conditions in daylight. Results of the SCF-Test of our CCR payload will be presented. Negotiations are underway to propose our payload and SCF-Test services for precision gravity and lunar science measurements with next robotic lunar landing missions. In particular, a scientific collaboration agreement was signed on Jan. 30, 2012, by D. Currie, S. Dell’Agnello and the Japanese PI team of the LLR instrument of the proposed SELENE-2 mission by JAXA (Registered with INFN Protocol n. 0000242-03/Feb/2012). The agreement foresees that, under no exchange of funds, the Japanese single, large, hollow LLR reflector will be SCF-Tested and that MoonLIGHT will be considered as backup instrument

Fundamental physics and absolute positioning metrology with the MAGIA lunar orbiter

MAGIA is a mission approved by the Italian Space Agency (ASI) for Phase A study. Using a single large-diameter laser retroreflector, a large laser retroreflector array and an atomic clock onboard MAGIA we propose to perform several fundamental physics and absolute positioning metrology experiments: VESPUCCI, an improved test of the gravitational redshift in the Earth–Moon system predicted by General Relativity; MoonLIGHT-P, a precursor test of a second generation Lunar Laser Ranging (LLR) payload for precision gravity and lunar science measurements under development for NASA, ASI and robotic missions of the proposed International Lunar Network (ILN); Selenocenter (the center of mass of the Moon), the determination of the position of the Moon center of mass with respect to the International Terrestrial Reference Frame/System (ITRF/ITRS); this will be compared to the one from Apollo and Lunokhod retroreflectors on the surface; MapRef, the absolute referencing of MAGIA's lunar altimetry, gravity and geochemical maps with respect to the ITRF/ITRS. The absolute positioning of MAGIA will be achieved thanks to: (1) the laboratory characterization of the retroreflector performance at INFN-LNF; (2) the precision tracking by the International Laser Ranging Service (ILRS), which gives two fundamental contributions to the ITRF/ITRS, i.e. the metrological definition of the geocenter (the Earth center of mass) and of the scale of length; (3) the radio science and accelerometer payloads; (4) support by the ASI Space Geodesy Center in Matera, Italy. Future ILN geodetic nodes equipped with MoonLIGHT and the Apollo/Lunokhod retroreflectors will become the first realization of the International Moon Reference Frame (IMRF), the lunar analog of the ITRF

Stochasticity of flow through microcirculation as a regulator of oxygen delivery

<p>Abstract</p> <p>Objective</p> <p>Observations of microcirculation reveal that the blood flow is subject to interruptions and resumptions. Accepting that blood randomly stops and resumes, one can show that the randomness could be a powerful means to match oxygen delivery with oxygen demand.</p> <p>Method</p> <p>The ability of the randomness to regulate oxygen delivery is based on two suppositions: (a) the probability for flow to stop does not depend on the time of uninterrupted flow, thus the number of interruptions of flow follows a Poisson distribution; (b) the probability to resume the flow does not depend on the time for flow being interrupted; meaning that time spent by erythrocytes at rest follows an exponential distribution. Thus the distribution of the time to pass an organ is a compound Poisson distribution. The Laplace transform of the given distribution gives the fraction of oxygen that passes the organ.</p> <p>Result</p> <p>Oxygen delivery to the tissues directly depends on characteristics of the irregularity of the flow through microcirculation.</p> <p>Conclusion</p> <p>By variation of vasomotion activity it is possible to change delivery of oxygen to a tissue by up to 8 times.</p

Orthogonal polarisation spectral imaging as a new tool for the assessment of antivascular tumour treatment in vivo: a validation study

Tumour angiogenesis plays a key role in tumour growth, formation of metastasis, detection and treatment of malignant tumours. Recent investigations provided increasing evidence that quantitative analysis of tumour angiogenesis is an indispensable prerequisite for developing novel treatment strategies such as anti-angiogenic and antivascular treatment options. Therefore, it was our aim to establish and validate a new and versatile imaging technique, that is orthogonal polarisation spectral™ imaging, allowing for non-invasive quantitative imaging of tumour angiogenesis in vivo. Experiments were performed in amelanotic melanoma A-MEL 3 implanted in a transparent dorsal skinfold chamber of the hamster. Starting at day 0 after tumour cell implantation, animals were treated daily with the anti-angiogenic compound SU5416 (25 mg kg bw−1) or vehicle (control) only. Functional vessel density, diameter of microvessels and red blood cell velocity were visualised by both orthogonal polarisation spectral™ imaging and fluorescence microscopy and analysed using a digital image system. The morphological and functional properties of the tumour microvasculature could be clearly identified by orthogonal polarisation spectral™ imaging. Data for functional vessel density correlated excellently with data obtained by fluroescence microscopy (y=0.99x+0.48, r2=0.97, RS=0.98, precision: 8.22 cm−1 and bias: −0.32 cm−1). Correlation parameters for diameter of microvessels and red blood cell velocity were similar (r2=0.97, RS=0.99 and r2=0.93, RS=0.94 for diameter of microvessels and red blood cell velocity, respectively). Treatment with SU5416 reduced tumour angiogenesis. At day 3 and 6 after tumour cell implantation, respectively, functional vessel density was 4.8±2.1 and 87.2±10.2 cm−1 compared to values of control animals of 66.6±10.1 and 147.4±13.2 cm−1, respectively. In addition to the inhibition of tumour angiogenesis, tumour growth and the development of metastasis was strongly reduced in SU5416 treated animals. This new approach enables non-invasive, repeated and quantitative assessment of tumour vascular network and the effects of antiangiogenic treatment on tumour vasculature in vivo. Thus, quantification of tumour angiogenesis can be used to more accurately classify and monitor tumour biologic characteristics, and to explore aggressiveness of tumours

Quantitative estimation of tissue blood flow rate

The rate of blood flow through a tissue (F) is a critical parameter for assessing the functional efficiency of a blood vessel network following angiogenesis. This chapter aims to provide the principles behind the estimation of F, how F relates to other commonly used measures of tissue perfusion, and a practical approach for estimating F in laboratory animals, using small readily diffusible and metabolically inert radio-tracers. The methods described require relatively nonspecialized equipment. However, the analytical descriptions apply equally to complementary techniques involving more sophisticated noninvasive imaging. Two techniques are described for the quantitative estimation of F based on measuring the rate of tissue uptake following intravenous administration of radioactive iodo-antipyrine (or other suitable tracer). The Tissue Equilibration Technique is the classical approach and the Indicator Fractionation Technique, which is simpler to perform, is a practical alternative in many cases. The experimental procedures and analytical methods for both techniques are given, as well as guidelines for choosing the most appropriate method

Next-generation laser retroreflectors for GNSS, solar system exploration, geodesy, gravitational physics and earth observation

The SCF_Lab (Satellite/lunar/gnss laser ranging and altimetry Characterization Facility Laboratory) of INFNLNF is designed to cover virtually LRAs (Laser Retroreflector Arrays) of CCRs (Cube Corner Retroreflectors) for missions in the whole solar system, with a modular organization of its instrumentation, two redundant SCF (SCF_Lab Characterization Facilities), and an evolutionary measurement approach, including customization and potentially upgrade on-demand. See http://www.lnf.infn.it/esperimenti/etrusco/ for a general description