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This is a copy of the slides presented at the meeting but not formally written up for the volume.
The field of nanomedicine is quickly evolving in response to achievements in genomics, proteomics, molecular biology, bioengineering, and the imaging sciences. New approaches to entrenched medical problems are being studied using a cadre of “nanotools”, one example of which is perfluorocarbon nanoparticles.Perfluorocarbon nanoparticles represent a platform technology with nominal sizes around 250nm, which can be modified to home to thrombi and the neovasculature in vivo after intravenous injection. They can be noninvasively imaged with ultrasound, magnetic resonance (MR, 1H and 19F), or SPECT/CT. In rabbit models, perfluorocarbon nanoparticles have been demonstrated to deliver drug payloads targeted to vascular tissues for anti-angiogenic and anti-restenotic applications and to noninvasively confirm and quantify delivery as well as to follow response to treatment. In canine studies these agents have been demonstrated to target and enhance the MR and ultrasound contrast of intravascular thrombi, and using ex vivo human carotid endarterectomy sections, these results have been extrapolated to human disease where the potential for sensitive detection of microthrombi in the fissures of ruptured plaques is clearly demonstrated. The development of emerging nanotechnology platforms, such as the perfluorocarbon nanoparticles, permits translation of immunohistology techniques from fixed tissue on a slide to live tissue in an animal. These new agents allow biochemical and physiological changes to be studied dynamically in vivo and permit the quest for site-directed therapy to be realized.
Electroconvulsive therapy (ECT) is a fast-acting intervention for major depressive disorder. Previous studies indicated neurotrophic effects following ECT that might contribute to changes in white matter brain structure. We investigated the influence of ECT in a non-randomized prospective study focusing on white matter changes over time.
Twenty-nine severely depressed patients receiving ECT in addition to inpatient treatment, 69 severely depressed patients with inpatient treatment (NON-ECT) and 52 healthy controls (HC) took part in a non-randomized prospective study. Participants were scanned twice, approximately 6 weeks apart, using diffusion tensor imaging, applying tract-based spatial statistics. Additional correlational analyses were conducted in the ECT subsample to investigate the effects of seizure duration and therapeutic response.
Mean diffusivity (MD) increased after ECT in the right hemisphere, which was an ECT-group-specific effect. Seizure duration was associated with decreased fractional anisotropy (FA) following ECT. Longitudinal changes in ECT were not associated with therapy response. However, within the ECT group only, baseline FA was positively and MD negatively associated with post-ECT symptomatology.
Our data suggest that ECT changes white matter integrity, possibly reflecting increased permeability of the blood–brain barrier, resulting in disturbed communication of fibers. Further, baseline diffusion metrics were associated with therapy response. Coherent fiber structure could be a prerequisite for a generalized seizure and inhibitory brain signaling necessary to successfully inhibit increased seizure activity.
Analyzing audiovisual communication is challenging because its content is highly symbolic and less rule-governed than verbal material. But audiovisual messages are important to understand: they amplify, enrich, and complicate the meaning of textual information. We describe a fully-reproducible approach to analyzing video content using minimally—but systematically—trained online workers. By aggregating the work of multiple coders, we achieve reliability, validity, and costs that equal those of traditional, intensively trained research assistants, with much greater speed, transparency, and replicability. We argue that measurement strategies relying on the “wisdom of the crowd” provide unique advantages for researchers analyzing complex and intricate audiovisual political content.
We present a workflow to track icebergs in proglacial fjords using oblique time-lapse photos and the Lucas-Kanade optical flow algorithm. We employ the workflow at LeConte Bay, Alaska, where we ran five time-lapse cameras between April 2016 and September 2017, capturing more than 400 000 photos at frame rates of 0.5–4.0 min−1. Hourly to daily average velocity fields in map coordinates illustrate dynamic currents in the bay, with dominant downfjord velocities (exceeding 0.5 m s−1 intermittently) and several eddies. Comparisons with simultaneous Acoustic Doppler Current Profiler (ADCP) measurements yield best agreement for the uppermost ADCP levels (~ 12 m and above), in line with prevalent small icebergs that trace near-surface currents. Tracking results from multiple cameras compare favorably, although cameras with lower frame rates (0.5 min−1) tend to underestimate high flow speeds. Tests to determine requisite temporal and spatial image resolution confirm the importance of high image frame rates, while spatial resolution is of secondary importance. Application of our procedure to other fjords will be successful if iceberg concentrations are high enough and if the camera frame rates are sufficiently rapid (at least 1 min−1 for conditions similar to LeConte Bay).
The advantages of using the full trace as input for search/match rather than the traditional list of d/I values are emphasized. These advantages stem from the availability and the logical employment of the whole information of the diffractogram.
The two key features which enable successful identification of minor phases are discussed: (1) the reliable discrimination between background and weak lines and (2) by regarding the actual full widths of major lines as regions where weak lines can, potentially, he obscured.
The user friendliness of the. package will be presented: the graphical user interface, the high level of interactivity, and the speed of the search/match - now less than 8 seconds for searching the current whole ICDD database of 61,993 reference patterns when using an i486/66-based PC.
Microdiffraction is defined as the x-ray diffraction analysis performed on small samples or small areas of large samples. Since smallness is a relative term, micro diffraction is considered the technique of choice when samples are too small for the optics and precision of conventional instrumentation.
None of the many studies on Montaigne appears to have pursued in a consequential manner the attitudes which the author of the Essais assumes towards his own work in the course of his twentyone years of literary production. For the most part, Montaigne's allusions to his book have been related to the moment when he made them (as facilitated by Pierre Villey's fine work on the chronology of the various chapters), or to whatever major theme the commentator has been developing. The aim of this essay is to assemble in chronological order Montaigne's observations concerning his book in order not only to compare one phase with another, but also to demonstrate the progressive manner in which the book becomes an integral, organic function of the essayist's introspective odyssey.
Although measles incidence has reached historic lows in many parts of the world, the disease still causes substantial morbidity globally. Even where control programs have succeeded in driving measles locally extinct, unless vaccination coverage is maintained at extremely high levels, susceptible numbers may increase sufficiently to spark large outbreaks. Human mobility will drive potentially infectious contacts and interact with the landscape of susceptibility to determine the pattern of measles outbreaks. These interactions have proved difficult to characterise empirically. We explore the degree to which new sources of data combined with existing public health data can be used to evaluate the landscape of immunity and the role of spatial movement for measles introductions by retrospectively evaluating our ability to predict measles outbreaks in vaccinated populations. Using inferred spatial patterns of accumulation of susceptible individuals and travel data, we predicted the timing of epidemics in each district of Pakistan during a large measles outbreak in 2012–2013 with over 30 000 reported cases. We combined these data with mobility data extracted from over 40 million mobile phone subscribers during the same time frame in the country to quantify the role of connectivity in the spread of measles. We investigate how different approaches could contribute to targeting vaccination efforts to reach districts before outbreaks started. While some prediction was possible, accuracy was low and we discuss key uncertainties linked to existing data streams that impede such inference and detail what data might be necessary to robustly infer timing of epidemics.
OBJECTIVES/SPECIFIC AIMS: The aims of this study are (1) to develop and characterize a novel nonhuman primate model of pneumococcal pneumonia that mimics human disease; and (2) determine whether Streptococcus pneumoniae can: (a) translocate to the heart, (b) cause adverse cardiac events, (c) induce cardiomyocyte death, and (d) lead to scar formation during severe pneumonia in baboons. METHODS/STUDY POPULATION: Six adult baboons (Papio cynocephalus) were surgically tethered to a monitoring system to continuously assess their heart rate, temperature, and electrocardiogram (ECG). A baseline transthoracic echocardiogram, 12-lead ECG, serum troponin-I levels, brain natriuretic peptide, and heart-type fatty acid binding protein (HFABP) levels were obtained before infection and at the end of the experiment to determine cardiovascular damage during pneumococcal pneumonia. Animals were challenged with 108 colony-forming units of S. pneumoniae in the right middle lobe using flexible bronchoscopy. Three baboons were rescued with ampicillin therapy (80 mg/kg/d) after the development of pneumonia. Cardiac damage was confirmed by examination of tissue sections using immunohistochemistry as well as electron and fluorescence microscopy. Western-blots and tissue staining were used to determine the presence of necroptosis (RIP3 and pMLKL) and apoptosis (Caspase-3) in the cardiac tissue. Cytokine and chemokine levels in the heart tissue were determined using Luminex technology. RESULTS/ANTICIPATED RESULTS: Four males (57%) and three (43%) females were challenged. The median age of all baboons was 11 (IQR, 10-19) years old, which corresponds to a middle-aged human. Infected baboons consistently developed severe pneumonia. All animals developed systemic inflammatory response syndrome with tachycardia, tachypnea, fever, and leukocytosis. Infection was characterized by initial leukocytosis followed by severe leukopenia on day 3 postinoculation. Non-specific ischemic alterations by ECG (ST segment and T-wave flattering) and in the premortem echocardiogram were observed. The median (IQR) levels of troponin I and HFABP at the end of the experiment were 3550 ng/mL (1717–5383) and 916.9 ng/mL (520.8–1323), respectively. Severe cardiomyopathy was observed using TEM and H&E stains in animals with severe pneumonia. Necroptosis was detected in cardiomyocytes of infected animals by the presence of pMLKL and RIP3 in cardiac tissues. Signs of cardiac remodeling indicated by disorganized collagen deposition was present in rescued animals but not in the other animals. DISCUSSION/SIGNIFICANCE OF IMPACT: We confirmed that baboons experience cardiac injury during severe pneumococcal pneumonia that is characterized by myocardial invasion, activation of necroptosis, and tissue remodeling in animals rescued by antimicrobial therapy. Cardiac damage by invading pneumococci may explain why adverse cardiac events that occur during and after pneumococcal pneumonia in adult human patients.
Rubella virus infection typically presents as a mild illness in children; however, infection during pregnancy may cause the birth of an infant with congenital rubella syndrome (CRS). As of February 2017, India began introducing rubella-containing vaccine (RCV) into the public-sector childhood vaccination programme. Low-level RCV coverage among children over several years can result in an increase in CRS incidence by increasing the average age of infection without sufficiently reducing rubella incidence. We evaluated the impact of RCV introduction on CRS incidence across India's heterogeneous demographic and epidemiological contexts. We used a deterministic age-structured model that reflects Indian states’ rural and urban area-specific demography and vaccination coverage levels to simulate rubella dynamics and estimate CRS incidence with and without RCV introduction to the public sector. Our analysis suggests that current low-level private-sector vaccination has already slightly increased the burden of CRS in India. We additionally found that the effect of public-sector RCV introduction depends on the basic reproductive number, R0, of rubella. If R0 is five, a value empirically estimated from an array of settings, CRS incidence post-RCV introduction will likely decrease. However, if R0 is seven or nine, some states may experience short-term or annual increases in CRS, even if a long-term total reduction in cases (30 years) is expected. Investment in population-based serological surveys and India's fever/rash surveillance system will be key to monitoring the success of the vaccination programme.
In glacial environments particle-size analysis of moraines provides insights into clast origin, transport history, depositional mechanism and processes of reworking. Traditional methods for grain-size classification are labour-intensive, physically intrusive and are limited to patch-scale (1 m2) observation. We develop emerging, high-resolution ground- and unmanned aerial vehicle-based ‘Structure-from-Motion’ (UAV-SfM) photogrammetry to recover grain-size information across a moraine surface in the Heritage Range, Antarctica. SfM data products were benchmarked against equivalent datasets acquired using terrestrial laser scanning, and were found to be accurate to within 1.7 and 50 mm for patch- and site-scale modelling, respectively. Grain-size distributions were obtained through digital grain classification, or ‘photo-sieving’, of patch-scale SfM orthoimagery. Photo-sieved distributions were accurate to <2 mm compared to control distributions derived from dry-sieving. A relationship between patch-scale median grain size and the standard deviation of local surface elevations was applied to a site-scale UAV-SfM model to facilitate upscaling and the production of a spatially continuous map of the median grain size across a 0.3 km2 area of moraine. This highly automated workflow for site-scale sedimentological characterization eliminates much of the subjectivity associated with traditional methods and forms a sound basis for subsequent glaciological process interpretation and analysis.
The spatial structure of smooth- and rough-wall boundary layers is examined spectrally at approximately matched friction Reynolds number (
). For each wall condition, temporal and true spatial descriptions of the same flow are available from hot-wire anemometry and high-spatial-range particle image velocimetry, respectively. The results show that over the resolved flow domain, which is limited to a streamwise length of twice the boundary layer thickness, true spatial spectra of smooth-wall streamwise and wall-normal velocity fluctuations agree, to within experimental uncertainty, with those obtained from time series using Taylor’s frozen turbulence hypothesis (Proc. R. Soc. Lond. A, vol. 164, 1938, pp. 476–490). The same applies for the streamwise velocity spectra on rough walls. For the wall-normal velocity spectra, however, clear differences are observed between the true spatial and temporally convected spectra. For the rough-wall spectra, a correction is derived to enable accurate prediction of wall-normal velocity length scales from measurements of their time scales, and the implications of this correction are considered. Potential violations to Taylor’s hypothesis in flows above perturbed walls may help to explain conflicting conclusions in the literature regarding the effect of near-wall modifications on outer-region flow. In this regard, all true spatial and corrected spectra presented here indicate structural similarity in the outer region of smooth- and rough-wall flows, providing evidence for Townsend’s wall-similarity hypothesis (The Structure of Turbulent Shear Flow, vol. 1, 1956).
This paper examines the racial ecology of lead exposure as a form of environmental inequity, one with both historical and contemporary significance. Drawing on comprehensive data from over one million blood tests administered to Chicago children from 1995-2013 and matched to over 2300 geographic block groups, we address two major questions: (1) What is the nature of the relationship between neighborhood-level racial composition and variability in children’s elevated lead prevalence levels? And (2) what is the nature of the relationship between neighborhood-level racial composition and rates of change in children’s prevalence levels over time within neighborhoods? We further assess an array of structural explanations for observed racial disparities, including socioeconomic status, type and age of housing, proximity to freeways and smelting plants, and systematic observations of housing decay and neighborhood disorder. Overall, our theoretical framework posits lead toxicity as a major environmental pathway through which racial segregation has contributed to the legacy of Black disadvantage in the United States. Our findings support this hypothesis and show alarming racial disparities in toxic exposure, even after accounting for possible structural explanations. At the same time, however, our longitudinal results show the power of public health policies to reduce racial inequities.
The carbon star IRC +10 216 is a long-period Asymptotic Giant Branch (AGB) star suffering from strong stellar winds (several 10-5 M⊙/yr; Loup et al. 1993) which have led to an almost complete obscuration of the star by dust. Due to the high mass-loss rate, long period of P = 649 d (Le Bertre 1992), and carbon-rich chemistry of the dust-shell, IRC +10 216 is obviously in a very advanced stage of its AGB evolution. High-resolution near-infrared imaging of IRC +10 216 has revealed that on sub-arcsecond scales (100 mas) its dust shell is clumpy, bipolar, and changing on a time scale of only ~1 yr (Weigelt et al. 1997, 1998, Haniff & Buscher 1998, Osterbart et al. 2000, Tuthill et al. 2000). Since most dust shells around AGB stars are known to be spherically symmetric, whereas most proto-planetary nebulae (PPN) show an axisymmetric geometry (Olofsson 1996), it appears likely that IRC +10 216 has already entered the transition phase to the PPN stage. This suggests that the break of the dust-shell symmetry between the AGB and post-AGB phase already takes place at the end of the AGB evolution.
The prototypical dust-enshrouded carbon Mira IRC +10216 is known to exhibit intrinsic changes on a time scale of the order of only a few years as revealed, e.g., by CO infrared line profiles (Winters et al. 2000a), its infrared light curves, and by high spatial resolution monitoring in the infrared (Osterbart et al. 2000; Tuthill et al. 2000). In particular, the infrared light curves indicate a possible periodicity on a ≈ 20 yr time scale, i.e. that a recurrent phenomenon might lead to the observed variations. Such multi-periodicity time scales of several (≈ 10) stellar pulsation periods are predicted by consistent hydrodynamical models which include a proper treatment of dust formation (e.g. Winters et al. 2000b). In these models discrete dust layers form in time intervals which are several times longer than the typical pulsation period of an AGB star (Fleischer, Gauger, & Sedlmayr 1995; Höfner, Feuchtinger, & Dorfi 1995).
We review dynamical models of circumstellar dust shells around long-period variables which include time-dependent hydrodynamics and a detailed treatment of dust formation, growth and evaporation. Important effects caused by the complex interaction between the dynamics of the pulsating atmosphere and the dust complex which only can be revealed in the dynamical approach are summarized. Special emphasis is given to the treatment of the dust and gas opacity.
We present dynamical models of circumstellar dust shells around long-period variables which include time-dependent hydrodynamics and a detailed treatment of dust formation, growth and evaporation. Important effects due to the complex interaction between the dynamics of the pulsating atmosphere and the dust complex are demonstrated.
The problem of dust formation in the circumstellar envelopes of Asymptotic Giant Branch stars is reviewed. Special emphasis is put on the consistent modelling of the dust-forming circumstellar shell, where due to a strong coupling the dust formation process governs the dynamical behavior of the object.