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OBJECTIVES/GOALS: The detection of liver fibrotic changes at an early and reversible stage is essential to prevent its progression to end-stage cirrhosis and hepatocellular carcinoma. Liver biopsy, which is the current gold standard for fibrosis assessment, is accompanied by several complications due to its invasive nature in addition to sampling errors and reader variability. In this study, we evaluate the use of quantitative parameters extracted from hybrid ultrasound and photoacoustic imaging to detect and monitor fibrotic changes in a DEN rat model. METHODS/STUDY POPULATION: Liver fibrotic changes were induced in 34 Wistar male rats by oral administration of Diethylnitrosamine (DEN) for 12 weeks. 22 rats were imaged with B-mode ultrasound at 3 different time points (baseline, 10 weeks and 13 weeks) for monitoring liver texture changes. Texture features studied included tissue echointensity (liver brightness normalized to kidney brightness) and tissue heterogeneity. 12 rats were imaged with photoacoustic imaging at 4 time points (baseline, 5 wks, 10 wks, and 13 wks) to look at changes in tissue oxygenation. Hemoglobin oxygen saturation (sO2A) and hemoglobin concentration (HbT) in the right and left lobes of the liver were measured. 8 rats were used as controls. Liver tissue samples were obtained following 13 weeks from DEN start time for METAVIR histopathology staging of fibrosis. RESULTS/ANTICIPATED RESULTS: Texture features studied showed an increase with time in DEN rats. Normalized echointensity increased from 0.28 ± 0.06 at baseline to 0.46 ± 0.10 at 10 weeks (p < 0.0005) and 0.53 ± 0.15 at 13 weeks in DEN rats (p < 0.0005). In the control rats, echointensity remained at an average of 0.25 ± 0.05 (p = 0.31). Tissue heterogeneity increased over time in the DEN-exposed rats from a baseline of 208.7 ± 58.3 to 344.6 ± 52.9 at 10 weeks (p < 0.0005) and 376.8 ± 54.9 at 13 weeks (p = 0.06) however it stayed constant at 225.7 ± 37.6 in control rats (p = 0.58). The quantitative analyses of the photoacoustic signals showed that blood oxygen saturation significantly increased with time. At 5 weeks sO2AvT increased by 53.83 % (± 0.25), and HbT by 35.31 % (± 0.07). Following 10 weeks of DEN; sO2AvT by 92.04 % (± 0.29), and HbT by 55.24 % (± 0.1). All increases were significant p < 0.05. In the 13th week, however, the values of all of these parameters were lower than those in the 10th week, however, the decrease was statistically insignificant. DISCUSSION/SIGNIFICANCE OF IMPACT: Quantitative features from B-mode ultrasound and photoacoustic imaging consistently increased over time corresponding to hepatic damage, inflammation and fibrosis progressed. The use of this hybrid imaging method in clinical practice can help meet the significant need for noninvasive assessment of liver fibrosis.
OBJECTIVES/SPECIFIC AIMS: Preliminary animal studies showed that low-intensity ultrasound (US) coincident with intravascularly administered microbubbles locally disrupts tumor vasculature. This study translates the novel therapy of antivascular ultrasound (AVUS) into an autochthonous model of hepatocellular carcinoma (HCC). The differential effects produced by AVUS at low and high doses are evaluated. METHODS/STUDY POPULATION: HCC was induced in 12 Wistar rats by ingestion of 0.01% diethylnitrosamine in drinking water for 12 weeks. Rats received AVUS treatment at low and high doses. Low dose group (n=6) received 1 W/cm2 US for 1 minute with 0.2 mL microbubbles injected IV. High dose group (n=6) received 2 W/cm2 for 2 minute with 0.7 mL microbubbles IV. Perfusion was measured before and after AVUS with contrast-enhanced ultrasound (CE-US) and power Doppler (PD-US). Peak enhancement (PE) and perfusion index (PI) were measured from each US mode. Histology after sacrifice or natural death was compared to pre/post US. Analysis of H&E and trichrome sections was evaluated for percent area of hemorrhage and findings of tissue injury and repair including inflammation, necrosis, and fibrosis. RESULTS/ANTICIPATED RESULTS: After high dose AVUS, PE, and PI of CE-US decreased from baseline by an average of 33.3% and 29.7%, respectively. Histology showed extensive tissue injury (hemorrhage, necrosis, fibrosis) in 58% of tumor cross-sectional area. Conversely, low dose AVUS increased PE and PI of CE-US by an average of 39.3% and 67.8%, respectively. Histology showed smaller areas of microhemorrhage Versus large pools of hemorrhage (only 17% area). PD-US changes were similar to CE-US. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, the opposing effects of AVUS observed at 2 doses allows for multiple roles in tumor therapy. Enhanced perfusion at a low dose may improve drug delivery or radiation therapy. Whereas, vascular disruption at high doses of AVUS may allow noninvasive ischemic therapy. Furthermore, AVUS is ripe for translation given the use its component parts clinically: low-intensity long-tone burst for physiotherapy and microbubbles as an US contrast agent. Thus, AVUS should be evaluated for translation of its differential effects into noninvasive therapies for HCC and other tumors.
Although there is extensive evidence that problematic alcohol use is associated with smaller hippocampal volume, the typical cross-sectional study design cannot determine whether hippocampal deviations reflect pre-existing liability toward problematic alcohol use or instead reflect an alcohol exposure-related effect. We used the co-twin control study design, which capitalizes upon differences within a twin pair in levels of drinking, to differentiate pre-existing liability from an effect of alcohol exposure.
The sample included 100 female twins, prospectively assessed from ages 11 to 24. Problematic alcohol use was assessed dimensionally and included indicators of quantity, frequency, and density of alcohol use and intoxication. Hippocampal volume was assessed using magnetic resonance imaging.
Problematic alcohol use (proximal and cumulative) was associated with significantly smaller left and right hippocampal volume. Follow-up co-twin control analyses that partitioned individual-level alcohol effects into pre-existing, familial liability and non-shared alcohol exposure-related effects indicated that this association reflected alcohol exposure. Greater alcohol using twins had smaller hippocampal volume relative to lesser alcohol using co-twins, beyond effects of their shared genetic and environmental liability toward problematic alcohol use. Results held accounting for recent alcohol use, other substance use, externalizing and internalizing psychopathology, personality traits, trauma exposure, and menstrual phase.
The association between problematic alcohol use and smaller hippocampal volume likely reflects an alcohol exposure-related effect. Differentiating pre-existing brain deviations that confer risk for problematic alcohol use from those that reflect effects of alcohol on the brain will inform etiological models of addiction and further prevention and intervention efforts.
Balancing of macronutrient intake has only recently been demonstrated in predators. In particular, the ability to regulate carbohydrate intake is little studied in obligate carnivores, as carbohydrate is present at very low concentrations in prey animal tissue. In the present study, we determined whether American mink (Neovison vison) would compensate for dietary nutritional imbalances by foraging for complementary macronutrients (protein, lipid and carbohydrate) when subsequently given a dietary choice. We used three food pairings, within which two macronutrients differed relative to each other (high v. low concentration), while the third was kept at a constant level. The mink were first restricted to a single nutritionally imbalanced food for 7 d and then given a free choice to feed from the same food or a nutritionally complementary food for three consecutive days. When restricted to nutritionally imbalanced foods, the mink were willing to overingest protein only to a certain level (‘ceiling’). When subsequently given a choice, the mink compensated for the period of nutritional imbalance by selecting the nutritionally complementary food in the food choice pairing. Notably, this rebalancing occurred for all the three macronutrients, including carbohydrate, which is particularly interesting as carbohydrate is not a major macronutrient for obligate carnivores in nature. However, there was also a ceiling to carbohydrate intake, as has been demonstrated previously in domestic cats. The results of the present study show that mink regulate their intake of all the three macronutrients within limits imposed by ceilings on protein and carbohydrate intake and that they will compensate for a period of nutritional imbalance by subsequently selecting nutritionally complementary foods.
Archaeobotanical analysis remains one of the least-utilized strategies for investigating the lifeways of African diasporic peoples despite the fact that the field of African diaspora archaeology has grown exponentially over the last 30 years. We consider the botanical remains from the Rich Neck Slave Quarter site as constituting a significant line of evidence for illuminating the nature of plant use among enslaved Afro-Virginians. As a result of the ambitious flotation program undertaken during the excavation of the Rich Neck site, the botanical assemblage provides evidence allowing for interpretations of the role of plants in enslaved subsistence and potential medicinal practices. Our research illustrates that Afro-Virginians actively participated in the creation of cultural practices related to plant use, and strategically shifted their production activities in response to both internal and external factors that influenced their lives within the context of plantation slavery.
Spherical aberration corrected Atomic Number Contrast Scanning Electron Microscopy (Z-STEM) has recently demonstrated an amazing ability to not only obtain sub-angstrom levels of detail but also yield chemical information at that level as well. With an optimal probe size of 0.8 Å, extremely detailed images of CdSe nanocrystals were obtained showing the lattice structure and surface morphology. As an example of the usefulness of this technique, a sample of CdSe nanocrystals prepared using trioctylphosphine oxide (TOPO) as the surfactant was compared to a sample of CdSe prepared using a mixture of TOPO and hexadecylamine (HDA) as the surfactant. The TOPO/HDA nanocrystals exhibit a narrower size distribution and several orders of magnitude greater fluorescence compared to that of the TOPO only nanocrystals. Interestingly, the Z-STEM images show a striking difference in nanocrystal morphology as the result of the addition of HDA to the reaction mixture. This result suggests surface morphology can be tuned through judicious choice of surfactant. A second example of Z- STEM imaging involves the characterization of CdSe/ZnS core/shell nanocrystals. The mass contrast afforded by Z-STEM can easily distinguish between core and shell.
The paper describes the initial results from renewed investigations at Niah Cave in Sarawak on the island of Borneo, famous for the discovery in 1958 of the c. 40,000–year old ‘Deep Skull’. The archaeological sequences from the West Mouth and the other entrances of the cave complex investigated by Tom and Barbara Harrisson and other researchers have potential implications for three major debates regarding the prehistory of south-east Asia: the timing of initial settlement by anatomically modern humans; the means by which they subsisted in the late Pleistocene and early Holocene; and the timing, nature, and causation of the transition from foraging to farming. The new project is informing on all three debates. The critical importance of the Niah stratigraphies was commonly identified – including by Tom Harrisson himself – as because the site provided a continuous sequence of occupation over the past 40,000 years. The present project indicates that Niah was first used at least 45,000 years ago, and probably earlier; that the subsequent Pleistocene and Holocene occupations were highly variable in intensity and character; and that in some periods, perhaps of significant duration, the caves may have been more or less abandoned. The cultural sequence that is emerging from the new investigations may be more typical of cave use in tropical rainforests in south-east Asia than the Harrisson model.
Sound and pressure wave propagation in a granular material is of interest not only for its intrinsic and practical value, but also because it provides a non-intrusive means of probing the state of a granular material. By examining wave speeds and attenuation, insight can be gained into the nature of the contacts between the particles. In the present paper, wave speeds and attenuation rates are first examined for a static granular bed for a variety of system parameters including particle size, composition and the overburden of the material above the measuring transducers. Agitation of the bed is then introduced by shaking the material vertically. This causes the bed to transition from a static granular state to a vibrofluidized state. The dilation of the bed allows for relative particle motion and this has a significant effect on the measured wave speeds and attenuation. Further, the fluid-like characteristics of the agitated bed distort the force-chain framework through which the waves are thought to travel. The consequences of bed consolidation, a natural result of shaking, are also examined.
The aim of this research is to determine whether people in the UK associate genetically modified food (GM food) with the ‘mad cow’ disease (or BSE) issue, and explain any such association in terms of analogical reasoning. Further, to test whether a lack of perceived ‘control over exposure’ to GM food accounts for the heightened vulnerability it is typically associated with. Two consecutive questionnaires were administered in various regions of the UK. The first asked 200 participants to indicate whether they regarded GM food as a health risk, and to spontaneously identify issues similar to GM food. The second asked a further 200 to rate the similarity between GM food and BSE, Salmonella, and food irradiation, and to give personal and general risk ratings for consuming GM food, and tolerance ratings for its availability and availability if ‘always clearly labelled’. The results indicate GM food is overwhelmingly identified as a health risk, and that BSE is widely held to be analogous with GM food. However, BSE was rated as less similar to GM food than food irradiation. The widespread identification of BSE as an analogue is explained in terms of it representing a ‘worst-case scenario’. The risk ratings are consistent with the heightened sense of vulnerability associated with GM food; the tolerance ratings are greater for the availability of GM food if ‘always clearly labelled’, indicating a perceived lack of control over exposure to GM food accounts, in part, for GM food risk perceptions. However, the results also indicate that, in terms of practical risk management, labelling may only be effective with respect to a younger age group.
Nuclear magnetic resonance (NMR) is a non-intrusive method that can characterize not only the particulate density but also velocity and velocity fluctuation parameters. A survey of all the known NMR measurements of granular flow will be followed by a brief description of NMR as it applies to granular flow. Two new experiments, both involving flows in partially filled rotating horizontal cylinders, will be described. First, the effect of a stationary blade to suppress the azimuthal velocity of particles being brought up and deposited into the flowing layer on flow-velocity profiles will be studied. Suppressing the azimuthal velocity reduces the deviation of the velocity profile from a quadratic dependence on the height above the rigid layer. Second, a new NMR scheme will be presented that yields spatial distributions of collisional correlation times for macroscopic particles undergoing granular flow. It is based on Pulsed-Gradient Spin-Echo strategy that is commonly used to measure molecular diffusion in liquids. The scheme will be demonstrated with an example from shear flow in a partially-filled horizontal cylinder. Spatially resolved collisional correlation times and velocity fluctuation intensities are derived from the measurements and have values of ∼1 ms and ∼10-3 m2/s2 respectively, at the center of the free surface for 2 mm particles in a 70 mm diameter cylinder rotating at 2.36 rad/s.
On-farm implementation of IWM includes the biological and economic rationalization of weed management decisions. This, in turn, requires the ability to predict how weed populations and pressures will change with farm management options such as tillage method. We have developed a set of algorithms that simulate seedling emergence of mixed populations of green and redroot pigweed on the basis of the ecophysiological responses of seed germination and shoot elongation to temperature and, for germination, to moisture. The algorithms were calibrated using field data from 1993 and evaluated with data from two locations in 1994 and 1995. Over both sites and years, for four tillage systems, cumulative emergence was predicted with an overall root mean square error of 1.7%. Overprediction in one year was attributed to moisture shortage. Errors were greater for moldboard plowed plots than for those no-tilled. This decreased ability to predict emergence with increased tillage (soil disturbance) suggests that the algorithms should be modified to account for increased heterogeneity in weed seed distribution and soil moisture within disturbed soil. The algorithms, which were explicitly designed for incorporation within a crop growth model (e.g., CROPSIM), could become a useful part of a decision support system to rationalize weed management. Importantly, they could help predict changes in weed populations as farm management is adjusted, thereby reducing economic and environmental risk in agroecosystems.
Supposed Upper Proterozoic strata in the southwest Taoudeni Basin, Guinea and Senegal, and from the Mauritanide fold belt, Mauritania, have yielded mostly poorly preserved small skeletal fossils of metazoan and protistan origin. Problematic, but possible echinoderm material and spicules of the heteractinid sponge Eiffelia dominate the Taoudeni Basin assemblage. The age of the material is not certain but the paleontologic data suggest an Early Cambrian age for the stratigraphically lowest faunas, and a Middle Cambrian age is possible for the stratigraphically highest collections.