Assessing disease severity of diabetic retinopathy using novel graphical interpretation of flicker electroretinogram

Purpose: To assess the clinical value of reporting full-field electroretinogram (eg, flicker ERG) findings graphically to determine the severity of diabetic retinopathy (DR) within an office-based setting. Methods: Patients with type 2 diabetes mellitus were included and classified into varying degrees of DR based on presence and severity. Flicker ERG responses were recorded and compared between groups. Results: Between the varying disease stages, significant differences in the mean magnitude and phase values were found. There was also a significant difference between the proportions of the magnitude and phase color-coded frequencies between groups of severity and threat to vision. Conclusion: Magnitude and phase parameters of the flicker ERG test may be used to stage disease severity in patients with ongoing DR and determine risk of worsening. With utilization of these values organized into a visual diagram, interpretation of the recording may be more efficient and facilitate appropriate management of DR within the primary care setting

Detection of p75NTR trimers: Implications for receptor stoichiometry and activation

The p75 neurotrophin receptor (p75NTR) is a multifunctional receptor that participates in many critical processes in the nervous system, ranging from apoptosis to synaptic plasticity and morphological events. It is a member of the tumor necrosis factor receptor (TNFR) superfamily, whose members undergo trimeric oligomerization. Interestingly, p75NTR interacts with dimeric ligands (i.e., proneurotro-phins or mature neurotrophins), but several of the intracellular adaptors that mediate p75NTR signaling are trimeric (i.e., TNFR-associated factor 6 or TRAF6). Consequently, the active receptor signaling unit remains uncertain. To identify the functional receptor complex, we evaluated its oligomerization in vitro and in mice brain tissues using a combination of biochemical techniques. We found that the most abundant homotypic arrangement for p75NTR is a trimer and that monomers and trimers coexist at the cell surface. Interestingly, trimers are not required for ligand-independent or ligand-dependent p75NTR activation in a growth cone retraction functional assay. However, monomers are capable of inducing acute morphological effects in neurons. We propose that p75NTR activation is regulated by its oligomerization status and its levels of expression. These results indicate that the oligomeric state of p75NTR confers differential responses and offers an explanation for the diverse and contradictory actions of this receptor in the nervous system.Fil: Anastasia Gonzalez, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Cornell University; Estados UnidosFil: Barker, Phillip A.. McGill University; CanadáFil: Chao, Moses V.. University Of New York. School Of Medicine; Estados UnidosFil: Hempstead, Barbara L.. Cornell University; Estados Unido

Shrinking the lymphatic filariasis map of Ethiopia: reassessing the population at risk through nationwide mapping

BACKGROUND Mapping of lymphatic filariasis (LF) is essential for the delineation of endemic implementation units and determining the population at risk that will be targeted for mass drug administration (MDA). Prior to the current study, only 116 of the 832 woredas (districts) in Ethiopia had been mapped for LF. The aim of this study was to perform a nationwide mapping exercise to determine the number of people that should be targeted for MDA in 2016 when national coverage was anticipated. METHODOLOGY/PRINCIPAL FINDING A two-stage cluster purposive sampling was used to conduct a community-based cross-sectional survey for an integrated mapping of LF and podoconiosis, in seven regional states and two city administrations. Two communities in each woreda were purposely selected using the World Health Organization (WHO) mapping strategy for LF based on sampling 100 individuals per community and two purposely selected communities per woreda. Overall, 130 166 people were examined in 1315 communities in 658 woredas. In total, 140 people were found to be positive for circulating LF antigen by immunochromatographic card test (ICT) in 89 communities. Based on WHO guidelines, 75 of the 658 woredas surveyed in the nine regions were found to be endemic for LF with a 2016 projected population of 9 267 410 residing in areas of active disease transmission. Combining these results with other data it is estimated that 11 580 010 people in 112 woredas will be exposed to infection in 2016. CONCLUSIONS We have conducted nationwide mapping of LF in Ethiopia and demonstrated that the number of people living in LF endemic areas is 60% lower than current estimates. We also showed that integrated mapping of multiple NTDs is feasible and cost effective and if properly planned, can be quickly achieved at national scale

Feasibility Study of a Small Animal PET Insert Based on a Single LYSO Monolithic Tube

[EN] There are drawbacks with using a Positron Emission Tomography (PET) scanner design employing the traditional arrangement of multiple detectors in an array format. Typically PET systems are constructed with many regular gaps between the detector modules in a ring or box configuration, with additional axial gaps between the rings. Although this has been significantly reduced with the use of the compact high granularity SiPM photodetector technology, such a scanner design leads to a decrease in the number of annihilation photons that are detected causing lower scanner sensitivity. Moreover, the ability to precisely determine the line of response (LOR) along which the positron annihilated is diminished closer to the detector edges because the spatial resolution there is degraded due to edge effects. This happens for both monolithic based designs, caused by the truncation of the scintillation light distribution, but also for detector blocks that use crystal arrays with a number of elements that are larger than the number of photosensors and, therefore, make use of the light sharing principle. In this report we present a design for a small-animal PET scanner based on a single monolithic annulus-like scintillator that can be used as a PET insert in high-field Magnetic Resonance systems. We provide real data showing the performance improvement when edge-less modules are used. We also describe the specific proposed design for a rodent scanner that employs facetted outside faces in a single LYSO tube. In a further step, in order to support and prove the proposed edgeless geometry, simulations of that scanner have been performed and lately reconstructed showing the advantages of the design.This project was funded in part by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 695536). It has also been supported by the Spanish Ministerio de Economia, Industria y Competitividad under Grant TEC2016-79884-C2-1-R and through PROSPET (DTS15/00152) funded by the Ministerio de Economia y Competitividad. AR is a postdoctoral fellow of the FWO (project 12T7118N). The University of Virginia School of Medicine has provided seed funding for this project.González Martínez, AJ.; Berr, SS.; Cañizares-Ledo, G.; Gonzalez-Montoro, A.; Orero Palomares, A.; Correcher Salvador, C.; Rezaei, A.... (2018). Feasibility Study of a Small Animal PET Insert Based on a Single LYSO Monolithic Tube. Frontiers in Medicine. 5:1-8. https://doi.org/10.3389/fmed.2018.00328S185Kuntner, C., & Stout, D. (2014). Quantitative preclinical PET imaging: opportunities and challenges. Frontiers in Physics, 2. doi:10.3389/fphy.2014.00012Judenhofer, M. S., & Cherry, S. R. (2013). Applications for Preclinical PET/MRI. Seminars in Nuclear Medicine, 43(1), 19-29. doi:10.1053/j.semnuclmed.2012.08.004España, S., Marcinkowski, R., Keereman, V., Vandenberghe, S., & Van Holen, R. (2014). DigiPET: sub-millimeter spatial resolution small-animal PET imaging using thin monolithic scintillators. Physics in Medicine and Biology, 59(13), 3405-3420. doi:10.1088/0031-9155/59/13/3405Yang, Y., Bec, J., Zhou, J., Zhang, M., Judenhofer, M. S., Bai, X., … Cherry, S. R. (2016). A Prototype High-Resolution Small-Animal PET Scanner Dedicated to Mouse Brain Imaging. Journal of Nuclear Medicine, 57(7), 1130-1135. doi:10.2967/jnumed.115.165886Yamamoto, S., Watabe, H., Kanai, Y., Watabe, T., Kato, K., & Hatazawa, J. (2013). Development of an ultrahigh resolution Si-PM based PET system for small animals. Physics in Medicine and Biology, 58(21), 7875-7888. doi:10.1088/0031-9155/58/21/7875Yang, Y., James, S. S., Wu, Y., Du, H., Qi, J., Farrell, R., … Cherry, S. R. (2010). Tapered LSO arrays for small animal PET. Physics in Medicine and Biology, 56(1), 139-153. doi:10.1088/0031-9155/56/1/009Godinez, F., Gong, K., Zhou, J., Judenhofer, M. S., Chaudhari, A. J., & Badawi, R. D. (2018). Development of an Ultra High Resolution PET Scanner for Imaging Rodent Paws: PawPET. IEEE Transactions on Radiation and Plasma Medical Sciences, 2(1), 7-16. doi:10.1109/trpms.2017.2765486Gonzalez, A. J., Aguilar, A., Conde, P., Hernandez, L., Moliner, L., Vidal, L. F., … Benlloch, J. M. (2016). A PET Design Based on SiPM and Monolithic LYSO Crystals: Performance Evaluation. IEEE Transactions on Nuclear Science, 63(5), 2471-2477. doi:10.1109/tns.2016.2522179Moses, W. W. (2011). Fundamental limits of spatial resolution in PET. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 648, S236-S240. doi:10.1016/j.nima.2010.11.092Jones, T., & Townsend, D. (2017). History and future technical innovation in positron emission tomography. Journal of Medical Imaging, 4(1), 011013. doi:10.1117/1.jmi.4.1.011013Lewellen, T. K. (2008). Recent developments in PET detector technology. Physics in Medicine and Biology, 53(17), R287-R317. doi:10.1088/0031-9155/53/17/r01Lee, J. S. (2010). Technical Advances in Current PET and Hybrid Imaging Systems. The Open Nuclear Medicine Journal, 2(1), 192-208. doi:10.2174/1876388x01002010192Ren, S., Yang, Y., & Cherry, S. R. (2014). Effects of reflector and crystal surface on the performance of a depth-encoding PET detector with dual-ended readout. Medical Physics, 41(7), 072503. doi:10.1118/1.4881097Benlloch, J. M., González, A. J., Pani, R., Preziosi, E., Jackson, C., Murphy, J., … Schwaiger, M. (2018). The MINDVIEW project: First results. European Psychiatry, 50, 21-27. doi:10.1016/j.eurpsy.2018.01.002Gonzalez-Montoro, A., Benlloch, J. M., Gonzalez, A. J., Aguilar, A., Canizares, G., Conde, P., … Sanchez, F. (2017). Performance Study of a Large Monolithic LYSO PET Detector With Accurate Photon DOI Using Retroreflector Layers. IEEE Transactions on Radiation and Plasma Medical Sciences, 1(3), 229-237. doi:10.1109/trpms.2017.2692819Moliner, L., González, A. J., Soriano, A., Sánchez, F., Correcher, C., Orero, A., … Benlloch, J. M. (2012). Design and evaluation of the MAMMI dedicated breast PET. Medical Physics, 39(9), 5393-5404. doi:10.1118/1.4742850Morrocchi, M., Ambrosi, G., Bisogni, M. G., Bosi, F., Boretto, M., Cerello, P., … Del Guerra, A. (2017). Depth of interaction determination in monolithic scintillator with double side SiPM readout. EJNMMI Physics, 4(1). doi:10.1186/s40658-017-0180-9Xie, S., Zhao, Z., Yang, M., Weng, F., Huang, Q., Xu, J., & Peng, Q. (2017). LOR-PET: a novel PET camera constructed with a monolithic scintillator ring. 2017 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC). doi:10.1109/nssmic.2017.8532627Stolin, A. V., Martone, P. F., Jaliparthi, G., & Raylman, R. R. (2017). Preclinical positron emission tomography scanner based on a monolithic annulus of scintillator: initial design study. Journal of Medical Imaging, 4(1), 011007. doi:10.1117/1.jmi.4.1.011007Gonzalez, A. J., Aguilar, A., Conde, P., Gonzalez-Montoro, A., Sanchez, S., Moliner, L., … Benlloch, J. M. (2016). Pilot tests of a PET insert based on monolithic crystals in a 7T MR. 2016 IEEE Nuclear Science Symposium, Medical Imaging Conference and Room-Temperature Semiconductor Detector Workshop (NSS/MIC/RTSD). doi:10.1109/nssmic.2016.8069496Jan, S., Santin, G., Strul, D., Staelens, S., Assié, K., Autret, D., … Bloomfield, P. M. (2004). GATE: a simulation toolkit for PET and SPECT. Physics in Medicine and Biology, 49(19), 4543-4561. doi:10.1088/0031-9155/49/19/007Strulab, D., Santin, G., Lazaro, D., Breton, V., & Morel, C. (2003). GATE (geant4 application for tomographic emission): a PET/SPECT general-purpose simulation platform. Nuclear Physics B - Proceedings Supplements, 125, 75-79. doi:10.1016/s0920-5632(03)90969-8Pani, R., Gonzalez, A. J., Bettiol, M., Fabbri, A., Cinti, M. N., Preziosi, E., … Majewski, S. (2015). Preliminary evaluation of a monolithic detector module for integrated PET/MRI scanner with high spatial resolution. Journal of Instrumentation, 10(06), C06006-C06006. doi:10.1088/1748-0221/10/06/c06006Iida, H., Kanno, I., Miura, S., Murakami, M., Takahashi, K., & Uemura, K. (1986). A Simulation Study of a Method to Reduce Positron Annihilation Spread Distributions Using a Strong Magnetic Field in Positron Emission Tomography. IEEE Transactions on Nuclear Science, 33(1), 597-600. doi:10.1109/tns.1986.433717

Vehicle Signal Analysis Using Artificial Neural Networks for a Bridge Weigh-in-Motion System

This paper describes the procedures for development of signal analysis algorithms using artificial neural networks for Bridge Weigh-in-Motion (B-WIM) systems. Through the analysis procedure, the extraction of information concerning heavy traffic vehicles such as weight, speed, and number of axles from the time domain strain data of the B-WIM system was attempted. As one of the several possible pattern recognition techniques, an Artificial Neural Network (ANN) was employed since it could effectively include dynamic effects and bridge-vehicle interactions. A number of vehicle traveling experiments with sufficient load cases were executed on two different types of bridges, a simply supported pre-stressed concrete girder bridge and a cable-stayed bridge. Different types of WIM systems such as high-speed WIM or low-speed WIM were also utilized during the experiments for cross-checking and to validate the performance of the developed algorithms

Regulatory mechanisms mediated by peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in skin cancer

Considerable progress has been made during the past twenty years towards elucidating the role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in skin cancer. In 1999, the original notion that PPARβ/δ was involved with epithelial cell function was postulated based on a correlation between PPARβ/δ expression and the induction of mRNAs encoding proteins that mediate terminal differentiation in keratinocytes. Subsequent studies definitively revealed that PPARβ/δ could induce terminal differentiation and inhibit proliferation of keratinocytes. Molecular mechanisms have since been discovered to explain how this nuclear receptor can be targeted for preventing and treating skin cancer. This includes the regulation of terminal differentiation, mitotic signaling, endoplasmic reticulum stress, and cellular senescence. Interestingly, the effects of activating PPARβ/δ can preferentially target keratinocytes with genetic mutations associated with skin cancer. This review provides the history and current understanding of how PPARβ/δ can be targeted for both non-melanoma skin cancer and melanoma, and postulates how future approaches that modulate PPARβ/δ signaling may be developed for the prevention and treatment of these diseases

Prison Gerrymandering Report 2021

The purpose of the redistricting process should be to create districts that accurately reflect the communities they represent and to distribute political power across those communities. But counting incarcerated individuals at the facility where they are incarcerated, rather than their home addresses, artificially bolsters the political power of certain communities on the backs of individuals who are not truly part of those communities, while simultaneously reducing the political voices of their home communities. In Texas, there are dramatic implications, with a handful of rural regions gaining a disproportionate share of the political power over other rural regions and diminishing the true population count in certain urban areas. This under-representation only exacerbates existing problems with Census undercounts and socio economic disparities which have a root in racial discrimination. It also deviates from how Texas law treats incarcerated populations in every other context, creating a conflict with the Texas constitution that needs to be addressed.Traditionally, the United States Census Bureau has counted incarcerated individuals at the facility where they are housed, but the Bureau has made clear that this historical practice has persisted only for administrative reasons, not for legal or policy ones. Recently, the Census Bureau has evolved in its treatment of incarcerated populations, and, for the first time, will make it practical for states on tight timelines to assign incarcerated individuals to their home communities. Many states across the nation are taking advantage of this opportunity to correct for the distortions created by prison gerrymandering. In order to more accurately reflect the state's population, Texas legislators should take advantage of the Census Bureau's new tools and work with state agencies to identify those prisoners who, rightfully, should be counted at an address in their permanent community

Application of a recombinase polymerase amplification (RPA) assay and pilot field testing for Giardia duodenalis at Lake Albert, Uganda.

BACKGROUND: Giardia duodenalis is a gastrointestinal protozoan causing 184 million cases of giardiasis worldwide annually. Detection is by microscopy or coproantigen assays, although sensitivity is often compromised by intermittent shedding of cysts or trophozoites, or operator expertise. Therefore, for enhanced surveillance field-applicable, point-of-care (POC), molecular assays are needed. Our aims were to: (i) optimise the recombinase polymerase amplification (RPA) assay for the isothermal amplification of the G. duodenalis β-giardin gene from trophozoites and cysts, using published primer and probes; and (ii) perform a pilot field validation of RPA at a field station in a resource-poor setting, on DNA extracted from stool samples from schoolchildren in villages around Lake Albert, Uganda. Results were compared to an established laboratory small subunit ribosomal RNA (SSU rDNA) qPCR assay with additional testing using a qPCR targeting the triose phosphate isomerase (tpi) DNA regions that can distinguish G. duodenalis of two different assemblages (A and B), which are human-specific. RESULTS: Initial optimisation resulted in the successful amplification of predicted RPA products from G. duodenalis-purified gDNA, producing a double-labelled amplicon detected using lateral flow strips. In the field setting, of 129 stool samples, 49 (37.9%) were positive using the Giardia/Cryptosporidium QuikChek coproantigen test; however, the RPA assay when conducted in the field was positive for a single stool sample. Subsequent molecular screening in the laboratory on a subset (n = 73) of the samples demonstrated better results with 21 (28.8%) RPA positive. The SSU rDNA qPCR assay resulted in 30/129 (23.3%) positive samples; 18 out of 73 (24.7%) were assemblage typed (9 assemblage A; 5 assemblage B; and 4 mixed A+B). Compared with the SSU rDNA qPCR, QuikChek was more sensitive than RPA (85.7 vs 61.9%), but with similar specificities (80.8 vs 84.6%). In comparison to QuikChek, RPA had 46.4% sensitivity and 82.2% specificity. CONCLUSIONS: To the best of our knowledge, this is the first in-field and comparative laboratory validation of RPA for giardiasis in low resource settings. Further refinement and technology transfer, specifically in relation to stool sample preparation, will be needed to implement this assay in the field, which could assist better detection of asymptomatic Giardia infections

Influence of Lithophysae Geometry and Distribution on Mechanical Properties of Topopah Spring Tuff

The current Site Recommendation study for the proposed high level nuclear waste repository at Yucca Mountain locates the repository emplacement drifts approximately 81% within the lower lithophysal unit of the Topopah Springs Formation (Tptpll), 4% within the upper lithophysal unit of the Topopah Springs Formation (Tptpul), and roughly 15% within the middle, non-lithophysal unit (Tptpmn) of the same formation. A major geomechanical issue facing the Yucca Mountain Project is to understand the thermomechanical behavior of lithophysal tuff, which comprises roughly 85% of the repository host rock

A novel framework to study the effect of tree architectural traits on stemflow yield and its consequences for soil-water dynamics

International audienceA novel experimental approach and numerical framework are proposed to study the effect of tree architectural traits on stemflow yield and its effects on soil-water dynamics. The framework includes a data mining workflowemploying information from two experimental steps: (i) evaluation of the effect of tree aboveground architecture on stemflow yield and (ii) quantification of specific parameters for soil-water dynamics with and withoutstemflow. We studied double-funnelling (stemflow and root-induced preferential flow) under three sycamore (Acer pseudoplatanus L.) trees growing on a slope in Scotland during the summer season and measured architecturaltraits. Stemflow yield ranged from 1.3 to 3.8% of the incident rainfall, with funnelling ratios of between 2.2 ± 2.1 and 5.2 ± 3.9. Double-funnelling to a depth of up to 400 mm beneath the soil surface occurred as matrix flow and was significantly and positively correlated with the vertical root distribution. Soil-water dynamics were distinctly different with and without stemflow. Our framework revealed that the number of tree branches, their insertion angle, leaf number, and stem basal diameter influenced stemflow yield within rainfall thresholds of 1.1 and 3.5 mm d-1. The framework also showed that stemflow yield had a negative impact on soil matric suction, while air temperature was the most influential covariate affecting soil-water dynamics, likely due to its strong correlation to evapotranspiration during the summer season. In spite of the study limitations, such as small sample size and differences between individuals, we show that the proposed framework and experimental approach can contribute to our knowledge of how stemflow generated aboveground triggers major responses in soil-water dynamics belowgroun