Mapping Of Transmission Research Articles

High-throughput volumetric mapping of synaptic transmission.

Volumetric imaging of synaptic transmission in vivo requires high spatial and high temporal resolution. Shaping the wavefront of two-photon fluorescence excitation light, we developed Bessel-droplet foci for high-contrast and high-resolution volumetric imaging of synapses. Applying our method to imaging glutamate release, we demonstrated high-throughput mapping of excitatory inputs at >1,000 synapses per volume and >500 dendritic spines per neuron in vivo and unveiled previously unseen features of functional synaptic organization in the mouse primary visual cortex.

Single-molecule photoelectron tunnelling spectroscopy.

Experimental mapping of transmission is essential for understanding and controlling charge transport through molecular devices and materials. Here we developed a single-molecule photoelectron tunnelling spectroscopy approach for mapping transmission beyond the HOMO-LUMO gap of the single diketopyrrolopyrrole molecule junction using an ultrafast-laser combined scanning tunnelling microscope-based break junction set-up at room temperature. Two resonant transport channels of ultrafast photocurrent are found by our photoelectron tunnelling spectroscopy, ranging from 1.31 eV to 1.77 eV, consistent with the LUMO + 1 and LUMO + 2 in the transmission spectrum obtained by density functional theory calculations. Moreover, we observed the modulation of resonant peaks by varying bias voltages, which demonstrates the ability to quantitatively characterize the effect of the electric field on frontier molecular orbitals. Our single-molecule photoelectron tunnelling spectroscopy offers an avenue that allows us to explore the nature of energy-dependent charge transport through single-molecule junctions.

Detailed mapping of Bifidobacterium strain transmission from mother to infant via a dual culture-based and metagenomic approach

A significant proportion of the infant gut microbiome is considered to be acquired from the mother during and after birth. Thus begins a lifelong and dynamic relationship with microbes that has an enduring impact on host health. Based on a cohort of 135 mother-infant (F = 72, M = 63) dyads (MicrobeMom: ISRCTN53023014), we investigated the phenomenon of microbial strain transfer, with a particular emphasis on the use of a combined metagenomic-culture-based approach to determine the frequency of strain transfer involving members of the genus Bifidobacterium, including species/strains present at low relative abundance. From the isolation and genome sequencing of over 449 bifidobacterial strains, we validate and augment metagenomics-based evidence to reveal strain transfer in almost 50% of dyads. Factors important in strain transfer include vaginal birth, spontaneous rupture of amniotic membranes, and avoidance of intrapartum antibiotics. Importantly, we reveal that several transfer events are uniquely detected employing either cultivation or metagenomic sequencing, highlighting the requirement for a dual approach to obtain an in-depth insight into this transfer process.

Morbidity hotspot surveillance: A novel approach to detect lymphatic filariasis transmission in non-endemic areas of the Tillabéry region of Niger

The Niger Lymphatic Filariasis (LF) Programme is making good progress towards the elimination goal and scaling up morbidity management and disability prevention (MMDP) activities. Clinical case mapping and the increased availability of services has prompted patients to come forward in both endemic and non-endemic districts. The latter included Filingué, Baleyara and Abala districts of the Tillabéry region, and in 2019, 315 patients were found during a follow-up active case finding activity, suggesting it may have low transmission.The aim of this study was to assess the endemicity status in areas reporting clinical cases, ‘morbidity hotspots’, in three non-endemic districts of the Tillabéry region. A cross-sectional survey was conducted in 12 villages in June 2021. Filarial antigen was detected using the rapid Filariasis Test Strip (FTS) diagnostic, and information obtained on gender, age, residency length, bed net ownership and usage, and presence of hydrocoele and/or lymphoedema. Data were summarised and mapped using QGIS software.A total of 4058 participants between 5 and 105 years old were surveyed, with 29 (0.7%) participants found to be FTS positive. Baleyara district had significantly higher FTS positive rates than the other districts. No significant differences were found by gender (male 0.8%; female 0.6%), age group (<26 years 0.7%; ≥26 years 0. 7%), and residency length (<5 years 0.7%; ≥5 years 0.7%). Three villages reported no infections; seven villages <1%, one village 1.1% and one village 4.1%, which was on the border of an endemic district. Bed net ownership (99.2%) and usage (92.6%) was very high and there was no significant difference between FTS infection rates.The results indicate that there are low levels of transmission in populations, including children, living in districts previously classified as non-endemic. This has implications for the Niger LF programme in terms of delivering targeted mass drug administration (MDA) in transmission hotspots, and MMDP services, including hydrocoele surgery to patients. The use of morbidity data may be a practical proxy to trigger mapping of ongoing transmission in low endemic areas. Continued efforts to study morbidity hotspots, post-validation transmission, cross-border and cross-district endemicity are needed to meet the WHO NTD 2030 roadmap targets.

Optical Mie Scattering by DNA-Assembled Three-Dimensional Gold Nanoparticle Superlattice Crystals

Programmable assemblies of gold nanoparticles engineered with DNA have intriguing optical properties such as Coulomb-interaction-driven strong coupling, polaritonic response in the visible range, and ultralow dispersion dielectric response in the infrared spectral range. In this work, we demonstrate the optical Mie resonances of individual microcrystals of DNA–gold nanoparticle superlattices. Broadband hyperspectral mapping of both transmission and dark-field scattering reveal a polarization-insensitive optical response with distinct spectral features in the visible and near-infrared ranges. Experimental observations are supported by numerical simulations of the microcrystals under a resonant effective medium approximation in the regime of capacitively coupled nanoparticles. The study identifies a universal characteristic optical response which is defined by a band of multipolar Mie resonances, which only weakly depend on the crystal size and light polarization. The use of gold superlattice microcrystals as scattering materials is of interest for fields such as complex nanophotonics, thermoplasmonics, photocatalysis, sensing, and nonlinear optics.

Risk mapping and estimation of COVID-19 transmission in South Sulawesi, Indonesia by a self-identification survey.

The rapid transmission rate of coronavirus disease 2019 (COVID-19) is multi-factorial but primarily due to population mobility and aggregation. This research aimed at estimating the rate based on risk mapping and investigation of geospatial distribution. It was divided into different phases that included data collection through a self-identification form available online; data validation of the data collected; application of spatial statistics; comparison with official numbers of positive COVID-19; and mapping of the results. The results show that self-identification based on procurement of independent personal data online had an accuracy of 89%.

Imaging in vivo acetylcholine release in the peripheral nervous system with a fluorescent nanosensor

The ability to monitor the release of neurotransmitters during synaptic transmission would significantly impact the diagnosis and treatment of neurological diseases. Here, we present a DNA-based enzymatic nanosensor for quantitative detection of acetylcholine (ACh) in the peripheral nervous system of living mice. ACh nanosensors consist of DNA as a scaffold, acetylcholinesterase as a recognition component, pH-sensitive fluorophores as signal generators, and α-bungarotoxin as a targeting moiety. We demonstrate the utility of the nanosensors in the submandibular ganglia of living mice to sensitively detect ACh ranging from 0.228 to 358 μM. In addition, the sensor response upon electrical stimulation of the efferent nerve is dose dependent, reversible, and we observe a reduction of ∼76% in sensor signal upon pharmacological inhibition of ACh release. Equipped with an advanced imaging processing tool, we further spatially resolve ACh signal propagation on the tissue level. Our platform enables sensitive measurement and mapping of ACh transmission in the peripheral nervous system.

Predictive Risk Mapping for Schistosomiasis in Parts of Borgu Local Government Area (LGA) of Niger State, Nigeria.

This study constructed predictive risk mapping of schistosomiasis infection and transmission using environmental and proximity risk factors. Environmental risk factors were derived from satellite imageries. Proximity risk factors and parasitological results were derived from fieldwork. The geographic coordinates of the settlement layer were used to extract the underlying cell values of the rasterized data layers using spatial collocation method. The results suggest all the risk factors are likely to increase the odds of schistosomiasis infection, with the LST (Exp(β) =39.760) and NDVI (Exp(β) = 1.030E+068) as the most important predictors. This study suggests an urgent need to conduct parasitological tests in other communities in high-risk zone in order to develop an inclusive and comprehensive treatment campaigns to reach the unreached and leave no community behind in schistosomiasis containment.

High-resolution mapping of tuberculosis transmission: Whole genome sequencing and phylogenetic modelling of a cohort from Valencia Region, Spain

BackgroundWhole genome sequencing provides better delineation of transmission clusters in Mycobacterium tuberculosis than traditional methods. However, its ability to reveal individual transmission links within clusters is limited. Here, we used a 2-step approach based on Bayesian transmission reconstruction to (1) identify likely index and missing cases, (2) determine risk factors associated with transmitters, and (3) estimate when transmission happened.Methods and findingsWe developed our transmission reconstruction method using genomic and epidemiological data from a population-based study from Valencia Region, Spain. Tuberculosis (TB) incidence during the study period was 8.4 cases per 100,000 people. While the study is ongoing, the sampling frame for this work includes notified TB cases between 1 January 2014 and 31 December 2016. We identified a total of 21 transmission clusters that fulfilled the criteria for analysis. These contained a total of 117 individuals diagnosed with active TB (109 with epidemiological data). Demographic characteristics of the study population were as follows: 80/109 (73%) individuals were Spanish-born, 76/109 (70%) individuals were men, and the mean age was 42.51 years (SD 18.46). We found that 66/109 (61%) TB patients were sputum positive at diagnosis, and 10/109 (9%) were HIV positive. We used the data to reveal individual transmission links, and to identify index cases, missing cases, likely transmitters, and associated transmission risk factors. Our Bayesian inference approach suggests that at least 60% of index cases are likely misidentified by local public health. Our data also suggest that factors associated with likely transmitters are different to those of simply being in a transmission cluster, highlighting the importance of differentiating between these 2 phenomena. Our data suggest that type 2 diabetes mellitus is a risk factor associated with being a transmitter (odds ratio 0.19 [95% CI 0.02–1.10], p < 0.003). Finally, we used the most likely timing for transmission events to study when TB transmission occurred; we identified that 5/14 (35.7%) cases likely transmitted TB well before symptom onset, and these were largely sputum negative at diagnosis. Limited within-cluster diversity does not allow us to extrapolate our findings to the whole TB population in Valencia Region.ConclusionsIn this study, we found that index cases are often misidentified, with downstream consequences for epidemiological investigations because likely transmitters can be missed. Our findings regarding inferred transmission timing suggest that TB transmission can occur before patient symptom onset, suggesting also that TB transmits during sub-clinical disease. This result has direct implications for diagnosing TB and reducing transmission. Overall, we show that a transition to individual-based genomic epidemiology will likely close some of the knowledge gaps in TB transmission and may redirect efforts towards cost-effective contact investigations for improved TB control.

Wide-Area All-Optical Neurophysiology in Acute Brain Slices.

Optical tools for simultaneous perturbation and measurement of neural activity open the possibility of mapping neural function over wide areas of brain tissue. However, spectral overlap of actuators and reporters presents a challenge for their simultaneous use, and optical scattering and out-of-focus fluorescence in tissue degrade resolution. To minimize optical crosstalk, we combined an optimized variant (eTsChR) of the most blue-shifted channelrhodopsin reported to-date with a nuclear-localized red-shifted Ca2+ indicator, H2B-jRGECO1a. To perform wide-area optically sectioned imaging in tissue, we designed a structured illumination technique that uses Hadamard matrices to encode spatial information. By combining these molecular and optical approaches we made wide-area functional maps in acute brain slices from mice of both sexes. The maps spanned cortex and striatum and probed the effects of antiepileptic drugs on neural excitability and the effects of AMPA and NMDA receptor blockers on functional connectivity. Together, these tools provide a powerful capability for wide-area mapping of neuronal excitability and functional connectivity in acute brain slices.SIGNIFICANCE STATEMENT A new technique for simultaneous optogenetic stimulation and calcium imaging across wide areas of brain slice enables high-throughput mapping of neuronal excitability and synaptic transmission.

English

Schistosomiasis, an environmentally-mediated disease, contracted by swimming or wading in freshwater bodies harbouring the snail intermediate hosts of the genus Schistosoma consisting of five human species: S. haematobium S. mansoni, S. japonicum, S. intercalatum and S. mekongi. Transmission is on the increase with consequent adverse effects on children’s health and school attendance. There is a dearth of information in mapping and prediction of the disease transmission and distribution in the study area. This study made use of Geographic Information System and Remote Sensing (GIS/RS) in mapping and prediction of the disease in some affected areas of the state. There was a high prevalence of urinary schistosomiasis in the study communities. There is considerable interest in the literature on disease mapping to interpolate the occurrence, risk and probability from prevalence disease data. There is the need for continuous mapping using GIS/RS, and develop further risk model maps for the whole state using this approach to further understand the spatial pattern of urinary schistosomiasis in Nigeria. SPM is based on the number of interventions. The higher the number of interventions is the lower the prevalence of infection. This study will serve as a reliable baseline data for intervention planning in the State. Key words: Urinary schistosomiasis, remote sensing and geographical information system, Kriging interpolation, mapping, predictive risk models and simple proportion model.

Surveillance to Track Progress Toward Polio Eradication - Worldwide, 2016-2017.

Global efforts to eradicate polio began in 1988, and four of the six World Health Organization (WHO) regions currently have achieved poliofree certification. Within the remaining two regions with endemic poliomyelitis (African and Eastern Mediterranean), Afghanistan, Nigeria, and Pakistan have never interrupted transmission of wild poliovirus (WPV). The primary means of detecting poliovirus transmission is surveillance for acute flaccid paralysis (AFP) among children aged <15 years, combined with collection and testing of stool specimens for detection of WPV and vaccine-derived polioviruses (VDPVs)* in WHO-accredited laboratories within the Global Polio Laboratory Network (GPLN) (1,2). AFP surveillance is supplemented by environmental surveillance for polioviruses in sewage from selected locations. Genomic sequencing of isolated polioviruses enables the mapping of transmission by time and place, assessment of potential gaps in surveillance, and identification of the emergence of VDPVs (3). This report presents poliovirus surveillance data from 2016-2017, with particular focus on six countries in the Eastern Mediterranean Region (EMR) and 20 countries in the African Region (AFR) that reported WPV or circulating VDPVs (cVDPVs) during 2011-2017. Included in the 20 AFR countries are the three most affected by the 2014-2015 Ebola virus disease (Ebola) outbreak (Guinea, Liberia, and Sierra Leone), even though only one (Guinea) reported WPV or cVDPVs during the surveillance period. During 2017, a total of 14 (70%) of the 20 AFR countries and five (83%) of the six EMR countries met both surveillance quality indicators at the national level; however, provincial-level variation was seen. Surveillance strengthening activities are needed in specific countries of these regions to provide evidence supporting ultimate certification of the interruption of poliovirus circulation.

Geospatial Suitability Mapping of Climate-based Disease Transmission using Fuzzy Logic for Central India

Geographic Information System (GIS) today supports health and disease mapping in diverse ways. Present study divulges geographic dimensions of malaria disease in Madhya Pradesh and Chhattisgarh states located in Central India. Chhattisgarh is second and Madhya Pradesh is the third most malarious states after Odisha in India. In the present study, an attempt is made to map climate-based malaria transmission suitability using fuzzy logic for Central India. Temperature and relative humidity were selected as the two indicators for malaria transmission suitability analysis. District wise meteorological data for 2008 was used for the present study. Monthly temperature and relative humidity interpolation maps were generated using ‘Natural Neighbor’ interpolation algorithm. For both the indicators trapezoidal membership function was selected. Arc GIS software and its FUZZY tool were used to generate ‘climate suitability map’ for malaria transmission depicting the spatial distribution of Transmission Window length (in months) across the region. The findings illustrate that most districts of Chattisgarh and very few districts of Madhya Pradesh have transmission window open for more than 10 months and are identified as ‘High Endemic Regions’. Compared to Chhattisgarh, Madhya Pradesh experiences more numbers of least suitable months i.e. February, March, April and May. The study aims to benefit judicious decision making for efficient intervention implementation.

Energy-resolved neutron tomography of an unconventional cultured pearl at a pulsed spallation source using a microchannel plate camera

A non-destructive neutron analysis technique performed at the IMAT beamline of the STFC (Science and Technology Facility Council), UK, is presented. In this experiment, neutrons of different energy have been exploited to obtain a tomographic reconstruction of a biomineralic sample, more specifically a cultured pearl, by using a time-resolving pixel camera, the MicroChannel Plate (MCP) detector, utilizing an array of 2×2 Timepix readout chips. The MCP camera is capable of energy-resolved two-dimensional mapping of neutron transmission with a spatial resolution of ~55μm. By using a Simultaneous Iterative Reconstruction Technique (SIRT), virtual sections of the internal part of the sample have been created, thus revealing several features inside its bulk. The crystallographic phase map via Bragg edge analysis, showing a phase fraction distribution on the entire specimen, has been generated as well. Finally, 3D volume rendering of the pearl is presented.

Brain-wide Mapping of Endogenous Serotonergic Transmission via Chemogenetic fMRI

Serotonin-producing neurons profusely innervate brain regions via long-range projections. However, itremains unclear whether and how endogenous serotonergic transmission specifically influences regional or global functional activity. We combined designed receptors exclusively activated by designeddrugs (DREADD)-based chemogenetics and functional magnetic resonance imaging (fMRI), an approach weterm "chemo-fMRI," to causally probe the brain-wide substrates modulated by endogenous serotonergic activity. We describe the generation of a conditional knockin mouse line that, crossed with serotonin-specific Cre-recombinase mice, allowed us to remotely stimulate serotonergic neurons during fMRI scans. We show that endogenous stimulation of serotonin-producing neurons does not affect global brain activity but results in region-specific activation of a set of primary target regions encompassing corticohippocampal and ventrostriatal areas. By contrast, pharmacological boosting of serotonin levels produced widespread fMRI deactivation, plausibly reflecting the mixed contribution ofcentral and perivascular constrictive effects. Our results identify the primary functional targets of endogenous serotonergic stimulation and establish causation between activation of serotonergic neurons and regional fMRI signals.

Identifying Likely Transmission Pathways within a 10-Year Community Outbreak of Tuberculosis by High-Depth Whole Genome Sequencing.

BackgroundImproved tuberculosis control and the need to contain the spread of drug-resistant strains provide a strong rationale for exploring tuberculosis transmission dynamics at the population level. Whole-genome sequencing provides optimal strain resolution, facilitating detailed mapping of potential transmission pathways.MethodsWe sequenced 22 isolates from a Mycobacterium tuberculosis cluster in New South Wales, Australia, identified during routine 24-locus mycobacterial interspersed repetitive unit typing. Following high-depth paired-end sequencing using the Illumina HiSeq 2000 platform, two independent pipelines were employed for analysis, both employing read mapping onto reference genomes as well as de novo assembly, to control biases in variant detection. In addition to single-nucleotide polymorphisms, the analyses also sought to identify insertions, deletions and structural variants.ResultsIsolates were highly similar, with a distance of 13 variants between the most distant members of the cluster. The most sensitive analysis classified the 22 isolates into 18 groups. Four of the isolates did not appear to share a recent common ancestor with the largest clade; another four isolates had an uncertain ancestral relationship with the largest clade.ConclusionWhole genome sequencing, with analysis of single-nucleotide polymorphisms, insertions, deletions, structural variants and subpopulations, enabled the highest possible level of discrimination between cluster members, clarifying likely transmission pathways and exposing the complexity of strain origin. The analysis provides a basis for targeted public health intervention and enhanced classification of future isolates linked to the cluster.

Elimination of tropical disease through surveillance and response.

Surveillance and response represent the final crucial steps in achieving effective control and particularly elimination of communicable diseases as recognized in the area of neglected tropical diseases (NTDs), applied in increasing numbers in endemic countries with ongoing control and elimination programmers. More and more national NTD elimination initiatives are scheduled based on the innovative and effective One world-One health perspective to detect pockets of transmission and disease reintroduction. Resource-constrained countries, which carry the heaviest NTD burdens, face various challenges how to strengthen the health system as well as developing effective and novel tools for surveillance and response tailored to local settings. Surveillance-response approaches take place in two different stages corralling the basic components of the surveillance-response system for NTD elimination. Six different research priorities have been identified:1)dynamic mapping of transmission, 2) near real-time capture of population dynamics, 3) modelling based on a minimum essential database/dataset, 4) implementation of mobile health (m-health) and sensitive diagnostics, 5) design of effective response packages tailored to different transmission settings and levels, and 6) validation of approaches and responses packages.

Refining the global spatial limits of dengue virus transmission by evidence-based consensus.

BackgroundDengue is a growing problem both in its geographical spread and in its intensity, and yet current global distribution remains highly uncertain. Challenges in diagnosis and diagnostic methods as well as highly variable national health systems mean no single data source can reliably estimate the distribution of this disease. As such, there is a lack of agreement on national dengue status among international health organisations. Here we bring together all available information on dengue occurrence using a novel approach to produce an evidence consensus map of the disease range that highlights nations with an uncertain dengue status.Methods/Principal FindingsA baseline methodology was used to assess a range of evidence for each country. In regions where dengue status was uncertain, additional evidence types were included to either clarify dengue status or confirm that it is unknown at this time. An algorithm was developed that assesses evidence quality and consistency, giving each country an evidence consensus score. Using this approach, we were able to generate a contemporary global map of national-level dengue status that assigns a relative measure of certainty and identifies gaps in the available evidence.ConclusionThe map produced here provides a list of 128 countries for which there is good evidence of dengue occurrence, including 36 countries that have previously been classified as dengue-free by the World Health Organization and/or the US Centers for Disease Control. It also identifies disease surveillance needs, which we list in full. The disease extents and limits determined here using evidence consensus, marks the beginning of a five-year study to advance the mapping of dengue virus transmission and disease risk. Completion of this first step has allowed us to produce a preliminary estimate of population at risk with an upper bound of 3.97 billion people. This figure will be refined in future work.

Transmission Bragg edge spectroscopy measurements at ORNL Spallation Neutron Source

Results of neutron transmission Bragg edge spectroscopic experiments performed at the SNAP beamline of the Spallation Neutron Source are presented. A high resolution neutron counting detector with a neutron sensitive microchannel plate and Timepix ASIC readout is capable of energy resolved two dimensional mapping of neutron transmission with spatial accuracy of ∼55 μm, limited by the readout pixel size, and energy resolution limited by the duration of the initial neutron pulse. A two dimensional map of the Fe 110 Bragg edge position was obtained for a bent steel screw sample. Although the neutron pulse duration corresponded to ∼30 mÅ energy resolution for 15.3 m flight path, the accuracy of the Bragg edge position in our measurements was improved by analytical fitting to a few mÅ level. A two dimensional strain map was calculated from measured Bragg edge values with an accuracy of ∼few hundreds μistrain for 300s of data acquisition time.

Whole Body Vibration: Mapping Of Transmission With High Speed Motion Analysis

Whole body vibration (WBV) is used for its potential benefits in flexibility training and musculoskeletal strengthening. While bone-pin accelerometers have been used, vibration characteristics typically are assessed using skin mounted accelerometers which require corrections to the signal to minimize the effects of local skin-accelerometer resonance. Recent advances in camera technology allow measurement of small, low-mass skin mounted marker positions to a small fraction of a mm at sufficiently high sampling frequency to characterize local vibration. PURPOSE: Evaluate the capability of a motion analysis system to measure local vibrations over bony landmarks during WBV. METHODS: In this pilot study, two subjects experienced WBV while standing on a Freemotion iTonic machine which was set to vibrate under four conditions: low and high frequency (28 and 42 Hz) with low and high amplitude (about 1.5 and 3 mm displacement). Small (9 mm diameter) reflective markers were mounted on the vibration plate and on bony landmarks (lateral malleolus, tibial tuberosity, ASIS, sternum and forehead). Marker positions were measured using six Vicon T-20 cameras operating at 500 Hz. Each condition involved about 10 seconds of vibration exposure from which 40 consecutive cycles were extracted and analyzed. Mean (±SD) of vertical vibration amplitude was determined for each condition and subject. During measurement, knees were extended and feet were flat on the plate. RESULTS: Motion at the ankle closely matched the plate vibration however attenuation occurred at other points. Tibial vibration was about 0.8 mm and 1.0 - 1.5 mm under low and high amplitude conditions. ASIS and sternum vibrations ranged between 0.2 to 0.6 mm. At the head, high frequency vibrations had amplitude of about 0.7 mm while low frequency was transmitted more strongly (1.9 ± 0.4 mm for the high amplitude condition). CONCLUSIONS: High speed motion analysis has sufficient spatial precision to easily detect vibration of sub mm amplitude. When used with small, low-mass markers over bony landmarks, vibration transmission can be mapped across the body without the challenges associated with skin or bone mounted accelerometers.