147 research outputs found

    Safety and Feasibility of High-pressure Transvenous Limb Perfusion With 0.9% Saline in Human Muscular Dystrophy

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    We evaluated safety and feasibility of the transvenous limb perfusion gene delivery method in muscular dystrophy. A dose escalation study of single limb perfusion with 0.9% saline starting with 5% of limb volume was carried out in adults with muscular dystrophies under intravenous analgesia/anesthesia. Cardiac, vascular, renal, muscle, and nerve functions were monitored. A tourniquet was placed above the knee with inflated pressure of 310 mm Hg. Infusion was carried out with a clinically approved infuser via an intravenous catheter inserted in the saphenous vein with a goal infusion rate of 80 ml/minute. Infusion volume was escalated stepwise to 20% limb volume in seven subjects. No subject complained of any post procedure pain other than due to needle punctures. Safety warning boundaries were exceeded only for transient depression of limb tissue oximetry and transient elevation of muscle compartment pressures; these were not associated with nerve, muscle, or vascular damage. Muscle magnetic resonant imaging (MRI) demonstrated fluid accumulation in muscles of the perfused lower extremity. High-pressure retrograde transvenous limb perfusion with saline up to 20% of limb volume at above infusion parameters is safe and feasible in adult human muscular dystrophy. This study will serve as a basis for future gene transfer clinical trials

    The Effect of Heat Generation in the Railroad Bearing Thermoplastic Elastomer Suspension Element on the Thermal Behavior of Railroad Bearing Assembly

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    DTRT13-G-UTC59The main purpose of this study is to investigate the effect of heat generation in the railroad thermoplastic elastomer suspension element to develop an experimentally informed and validated finite element thermal model which can be used to attain temperature distribution maps of railroad bearing assemblies under a variety of normal and abnormal service conditions. Among other things, these maps will be useful for sensor data interpretation and identifying ideal locations for sensor placement for continuous temperature tracking of railroad bearings (e.g. IONX motes). Specifically, the main objectives of this project are: (1) to explore and quantify the heat generation in the railroad bearing elastomer suspension element with different material systems and under different loads, frequencies, and temperature scenarios; and (2) to determine the effect of this heat generation on the thermal behavior of railroad bearing assembly under different operation conditions. To this end, the contribution of the elastomer pad to the system energy balance was modeled using data from dynamic mechanical analysis (DMA) of common materials in use for that part. DMA provides a full characterization of the elastic deformation (energy storage) and viscous dissipation (energy dissipation) behavior of the material as a function of load, frequency, and temperature. In parallel, CAD models of the railroad bearing assembly were developed using SOLIDWORKS\u2122 commercial software to be used in constructing finite element models utilizing the ALGOR\u2122 commercial software. The finite element (FE) model was used to conduct thermal finite element analyses using some of the expected operational boundary conditions and loads including the heat generation in the elastomer suspension system. The FE models were then validated with physical laboratory experiments. Finally, based on the simulations and experimental results, bearing assembly recommendations are suggested to further ensure the safe operation of railroad bearings

    Tourmaline Reference Materials for the In Situ Analysis of Oxygen and Lithium Isotope Ratio Compositions

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    Three tourmaline reference materials sourced from the Harvard Mineralogical and Geological Museum (schorl 112566, dravite 108796 and elbaite 98144), which are already widely used for the calibration of in situ boron isotope measurements, are characterised here for their oxygen and lithium isotope compositions. Homogeneity tests by secondary ion mass spectrometry (SIMS) showed that at sub‐nanogram test portion masses their 18O/16O and 7Li/6Li isotope ratios are constant within ± 0.27‰ and ± 2.2‰ (1s), respectively. The lithium mass fractions of the three materials vary over three orders of magnitude. SIMS homogeneity tests showed variations in 7Li/28Si between 8% and 14% (1s), which provides a measure of the heterogeneity of the Li contents in these three materials. Here we provide recommended values for δ18O, Δ’17O and δ7Li for the three Harvard tourmaline reference materials based on results from bulk mineral analyses from multiple, independent laboratories using laser‐ and stepwise fluorination gas mass spectrometry (for O), and solution multi‐collector inductively coupled plasma‐mass spectroscopy (for Li). These bulk data also allow us to assess the degree of inter‐laboratory data that might be present in such datasets. This work also re‐evaluates the major element chemical composition of the materials by electron probe microanalysis and investigates the presence of a chemical matrix effect on SIMS instrumental mass fractionation with regards to δ18O determinations, which was found to be < 1.6‰ between these three materials. The final table presented here provides a summary of the isotope ratio values that we have determined for these three materials. Depending on their starting mass either 128 or 256 splits have been produced of each material, assuring their availability for many years into the future

    High-Pressure Transvenous Perfusion of the Upper Extremity in Human Muscular Dystrophy: A Safety Study with 0.9% Saline

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    We evaluated safety and feasibility of high-pressure transvenous limb perfusion in an upper extremity of adult patients with muscular dystrophy, after completing a similar study in a lower extremity. A dose escalation study of single-limb perfusion with 0.9% saline was carried out in nine adults with muscular dystrophies under intravenous analgesia. Our study demonstrates that it is feasible and definitely safe to perform high-pressure transvenous perfusion with 0.9% saline up to 35% of limb volume in the upper extremities of young adults with muscular dystrophy. Perfusion at 40% limb volume is associated with short-lived physiological changes in peripheral nerves without clinical correlates in one subject. This study provides the basis for a phase 1/2 clinical trial using pressurized transvenous delivery into upper limbs of nonambulatory patients with Duchenne muscular dystrophy. Furthermore, our results are applicable to other conditions such as limb girdle muscular dystrophy as a method for delivering regional macromolecular therapeutics in high dose to skeletal muscles of the upper extremity

    The faint young Sun problem

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    For more than four decades, scientists have been trying to find an answer to one of the most fundamental questions in paleoclimatology, the `faint young Sun problem'. For the early Earth, models of stellar evolution predict a solar energy input to the climate system which is about 25% lower than today. This would result in a completely frozen world over the first two billion years in the history of our planet, if all other parameters controlling Earth's climate had been the same. Yet there is ample evidence for the presence of liquid surface water and even life in the Archean (3.8 to 2.5 billion years before present), so some effect (or effects) must have been compensating for the faint young Sun. A wide range of possible solutions have been suggested and explored during the last four decades, with most studies focusing on higher concentrations of atmospheric greenhouse gases like carbon dioxide, methane or ammonia. All of these solutions present considerable difficulties, however, so the faint young Sun problem cannot be regarded as solved. Here I review research on the subject, including the latest suggestions for solutions of the faint young Sun problem and recent geochemical constraints on the composition of Earth's early atmosphere. Furthermore, I will outline the most promising directions for future research. In particular I would argue that both improved geochemical constraints on the state of the Archean climate system and numerical experiments with state-of-the-art climate models are required to finally assess what kept the oceans on the Archean Earth from freezing over completely.Comment: 32 pages, 8 figures. Invited review paper accepted for publication in Reviews of Geophysic

    A multilevel intervention to promote colorectal cancer screening among community health center patients: results of a pilot study

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    <p>Abstract</p> <p>Background</p> <p>Colorectal cancer screening rates are low among poor and disadvantaged patients. Patient navigation has been shown to increase breast and cervical cancer screening rates, but few studies have looked at the potential of patient navigation to increase colorectal cancer screening rates.</p> <p>Methods</p> <p>The objective was to determine the feasibility and effectiveness of a patient navigator-based intervention to increase colorectal cancer screening rates in community health centers. Patients at the intervention health center who had not been screened for colorectal cancer and were designated as "appropriate for outreach" by their primary care providers received a letter from their provider about the need to be screened and a brochure about colorectal cancer screening. Patient navigators then called patients to discuss screening and to assist patients in obtaining screening. Patients at a demographically similar control health center received usual care.</p> <p>Results</p> <p>Thirty-one percent of intervention patients were screened at six months, versus nine percent of control patients (p < .001).</p> <p>Conclusion</p> <p>A patient navigator-based intervention, in combination with a letter from the patient's primary care provider, was associated with an increased rate of colorectal cancer screening at one health center as compared to a demographically similar control health center. Our study adds to an emerging literature supporting the use of patient navigators to increase colorectal cancer screening in diverse populations served by urban health centers.</p

    Extrinsic Rewards and Intrinsic Motives: Standard and Behavioral Approaches to Agency and Labor Markets

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    Microbial sulfate reduction and metal attenuation in pH 4 acid mine water

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    Sediments recovered from the flooded mine workings of the Penn Mine, a Cu-Zn mine abandoned since the early 1960s, were cultured for anaerobic bacteria over a range of pH (4.0 to 7.5). The molecular biology of sediments and cultures was studied to determine whether sulfate-reducing bacteria (SRB) were active in moderately acidic conditions present in the underground mine workings. Here we document multiple, independent analyses and show evidence that sulfate reduction and associated metal attenuation are occurring in the pH-4 mine environment. Water-chemistry analyses of the mine water reveal: (1) preferential complexation and precipitation by H2S of Cu and Cd, relative to Zn; (2) stable isotope ratios of 34S/32S and 18O/16O in dissolved SO4 that are 2–3 ‰ heavier in the mine water, relative to those in surface waters; (3) reduction/oxidation conditions and dissolved gas concentrations consistent with conditions to support anaerobic processes such as sulfate reduction. Scanning electron microscope (SEM) analyses of sediment show 1.5-micrometer, spherical ZnS precipitates. Phospholipid fatty acid (PLFA) and denaturing gradient gel electrophoresis (DGGE) analyses of Penn Mine sediment show a high biomass level with a moderately diverse community structure composed primarily of iron- and sulfate-reducing bacteria. Cultures of sediment from the mine produced dissolved sulfide at pH values near 7 and near 4, forming precipitates of either iron sulfide or elemental sulfur. DGGE coupled with sequence and phylogenetic analysis of 16S rDNA gene segments showed populations of Desulfosporosinus and Desulfitobacterium in Penn Mine sediment and laboratory cultures
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