1,579 results on '"M Reuter"'
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2. Automated detection of regions with persistently enhanced methane concentrations using Sentinel-5 Precursor satellite data
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S. Vanselow, O. Schneising, M. Buchwitz, M. Reuter, H. Bovensmann, H. Boesch, and J. P. Burrows
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Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Methane (CH4) is an important anthropogenic greenhouse gas, and its rising concentration in the atmosphere contributes significantly to global warming. A comparatively small number of highly emitting persistent methane sources are responsible for a large share of global methane emissions. The identification and quantification of these sources, which often show large uncertainties regarding their emissions or locations, are important to support mitigating climate change. Daily global column-averaged dry air mole fractions of atmospheric methane (XCH4) are retrieved from radiance measurements of the TROPOspheric Monitoring Instrument (TROPOMI) on board on the Sentinel-5 Precursor (S5P) satellite with a moderately high spatial resolution, enabling the detection and quantification of localized methane sources. We developed a fully automated algorithm to detect regions with persistent methane enhancement and to quantify their emissions using a monthly TROPOMI XCH4 dataset from the years 2018–2021. We detect 217 potential persistent source regions (PPSRs), which account for approximately 20 % of the total bottom-up emissions. By comparing the PPSRs in a spatial analysis with anthropogenic and natural emission databases, we conclude that 7.8 % of the detected source regions are dominated by coal, 7.8 % by oil and gas, 30.4 % by other anthropogenic sources like landfills or agriculture, 7.3 % by wetlands, and 46.5 % by unknown sources. Many of the identified PPSRs are in well-known source regions, like the Permian Basin in the USA, which is a large production area for oil and gas; the Bowen Basin coal mining area in Australia; or the Pantanal Wetlands in Brazil. We perform a detailed analysis of the PPSRs with the 10 highest emission estimates, including the Sudd Wetland in South Sudan, an oil- and gas-dominated area on the west coast in Turkmenistan, and one of the largest coal production areas in the world, the Kuznetsk Basin in Russia. The calculated emission estimates of these source regions are in agreement within the uncertainties in results from other studies but are in most of the cases higher than the emissions reported by emission databases. We demonstrate that our algorithm is able to automatically detect and quantify persistent localized methane sources of different source type and shape, including larger-scale enhancements such as wetlands or extensive oil- and gas-production basins.
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- 2024
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3. Towards a sector-specific CO∕CO2 emission ratio: satellite-based observations of CO release from steel production in Germany
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O. Schneising, M. Buchwitz, M. Reuter, M. Weimer, H. Bovensmann, J. P. Burrows, and H. Bösch
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Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Global crude steel production is expected to continue to increase in the coming decades to meet the demands of the growing world population. Currently, the dominant steelmaking technology worldwide is the conventional highly CO2-intensive blast furnace–basic oxygen furnace production route (also known as the Linz–Donawitz process), which uses iron ore as raw material and coke as a reducing agent. As a result, large quantities of special gases that are rich in carbon monoxide (CO) are by-products of the various stages of the steelmaking process. Given the challenges associated with satellite-based estimates of carbon dioxide (CO2) emissions at the scale of emitting installations due to significant background levels, co-emitted CO may serve as a valuable indicator of the carbon footprint of steel plants. We show that regional CO release from steel production sites can be monitored from space using 5 years of measurements (2018–2022) from the TROPOspheric Monitoring Instrument (TROPOMI) on board the Sentinel-5 Precursor satellite, benefiting from its relatively high spatial resolution and daily global coverage. We analyse all German steel plants with blast furnaces and basic oxygen furnaces and obtain associated CO emissions in the range of 50–400 kt yr−1 per site. A comparison with the respective CO2 emissions on the level of emitting installations available from emissions trading data of the European Union Emissions Trading System yields a linear relationship with a sector-specific CO/CO2 emission ratio for the analysed steelworks of 3.24 % [2.73–3.89; 1σ], suggesting the feasibility of using CO as a proxy for CO2 emissions from comparable steel production sites. An evaluation at other steel production sites indicates that the derived CO/CO2 emission ratio is also representative of other highly optimised state-of-the-art Linz–Donawitz steelworks outside Germany and that the emission ratio is potentially valuable for estimating sector-specific CO2 emissions from remotely sensed CO emissions, provided that the underlying CO emission estimate is not affected by other sources.
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- 2024
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4. Greenhouse gas retrievals for the CO2M mission using the FOCAL method: first performance estimates
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S. Noël, M. Buchwitz, M. Hilker, M. Reuter, M. Weimer, H. Bovensmann, J. P. Burrows, H. Bösch, and R. Lang
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Environmental engineering ,TA170-171 ,Earthwork. Foundations ,TA715-787 - Abstract
The Anthropogenic Carbon Dioxide Monitoring (CO2M) mission is a constellation of satellites currently planned to be launched in 2026. CO2M is planned to be a core component of a Monitoring and Verification Support (MVS) service capacity under development as part of the Copernicus Atmosphere Monitoring Service (CAMS). The CO2M radiance measurements will be used to retrieve column-averaged dry-air mole fractions of atmospheric carbon dioxide (XCO2), methane (XCH4) and total columns of nitrogen dioxide (NO2). Using appropriate inverse modelling, the atmospheric greenhouse gas (GHG) observations will be used to derive United Nations Framework Convention on Climate Change (UNFCCC) COP 21 Paris Agreement relevant information on GHG sources and sinks. This challenging application requires highly accurate XCO2 and XCH4 retrievals. Three different retrieval algorithms to derive XCO2 and XCH4 are currently under development for the operational processing system at EUMETSAT. One of these algorithms uses the heritage of the FOCAL (Fast atmOspheric traCe gAs retrievaL) method, which has already successfully been applied to measurements from other satellites. Here, we show recent results generated using the CO2M version of FOCAL, called FOCAL-CO2M. To assess the quality of the FOCAL-CO2M retrievals, a large set of representative simulated radiance spectra has been generated using the radiative transfer model SCIATRAN. These simulations consider the planned viewing geometry of the CO2 instrument and corresponding geophysical scene data (including different types of aerosols and varying surface properties), which were taken from model data for the year 2015. We consider instrument noise and systematic errors caused by the retrieval method but have not considered additional error sources due to, for example, instrumental issues, spectroscopy or meteorology. On the other hand, we have also not taken advantage in this study of CO2M's MAP (multi-angle polarimeter) instrument, which will provide additional information on aerosols and cirrus clouds. By application of the FOCAL retrieval to these simulated data, confidence is gained that the FOCAL method is able to fulfil the challenging requirements for systematic errors for the CO2M mission (spatio-temporal bias ≤ 0.5 ppm for XCO2 and ≤ 5 ppb for XCH4).
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- 2024
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5. A method for estimating localized CO2 emissions from co-located satellite XCO2 and NO2 images
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B. Fuentes Andrade, M. Buchwitz, M. Reuter, H. Bovensmann, A. Richter, H. Boesch, and J. P. Burrows
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Environmental engineering ,TA170-171 ,Earthwork. Foundations ,TA715-787 - Abstract
Carbon dioxide (CO2) is the most important anthropogenic greenhouse gas. Its atmospheric concentration has increased by almost 50 % since the beginning of the industrial era, causing climate change. Fossil fuel combustion is responsible for most of the atmospheric CO2 increase, which originates to a large extent from localized sources such as power stations. Independent estimates of the emissions from these sources are key to tracking the effectiveness of implemented climate policies to mitigate climate change. We developed an automatic procedure to quantify CO2 emissions from localized sources based on a cross-sectional mass-balance approach and applied it to infer CO2 emissions from the Bełchatów Power Station (Poland) using atmospheric observations from the Orbiting Carbon Observatory 3 (OCO-3) in its snapshot area map (SAM) mode. As a result of the challenge of identifying CO2 emission plumes from satellite data with adequate accuracy, we located and constrained the shape of emission plumes using TROPOspheric Monitoring Instrument (TROPOMI) NO2 column densities. We automatically analysed all available OCO-3 overpasses over the Bełchatów Power Station from July 2019 to November 2022 and found a total of nine that were suitable for the estimation of CO2 emissions using our method. The mean uncertainty in the obtained estimates was 5.8 Mt CO2 yr−1 (22.0 %), mainly driven by the dispersion of the cross-sectional fluxes downwind of the source, e.g. due to turbulence. This dispersion uncertainty was characterized using a semivariogram, made possible by the OCO-3 imaging capability over a target region in SAM mode, which provides observations containing plume information up to several tens of kilometres downwind of the source. A bottom-up emission estimate was computed based on the hourly power-plant-generated power and emission factors to validate the satellite-based estimates. We found that the two independent estimates agree within their 1σ uncertainty in eight out of nine analysed overpasses and have a high Pearson's correlation coefficient of 0.92. Our results confirm the potential to monitor large localized CO2 emission sources from space-based observations and the usefulness of NO2 estimates for plume detection. They also illustrate the potential to improve CO2 monitoring capabilities with the planned Copernicus Anthropogenic CO2 Monitoring (CO2M) satellite constellation, which will provide simultaneously retrieved XCO2 and NO2 maps.
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- 2024
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6. Multilingual Query-by-Example Keyword Spotting with Metric Learning and Phoneme-to-Embedding Mapping.
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Paul M. Reuter, Christian Rollwage, and Bernd T. Meyer
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- 2023
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7. Technical note: The CAMS greenhouse gas reanalysis from 2003 to 2020
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A. Agustí-Panareda, J. Barré, S. Massart, A. Inness, I. Aben, M. Ades, B. C. Baier, G. Balsamo, T. Borsdorff, N. Bousserez, S. Boussetta, M. Buchwitz, L. Cantarello, C. Crevoisier, R. Engelen, H. Eskes, J. Flemming, S. Garrigues, O. Hasekamp, V. Huijnen, L. Jones, Z. Kipling, B. Langerock, J. McNorton, N. Meilhac, S. Noël, M. Parrington, V.-H. Peuch, M. Ramonet, M. Razinger, M. Reuter, R. Ribas, M. Suttie, C. Sweeney, J. Tarniewicz, and L. Wu
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Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
The Copernicus Atmosphere Monitoring Service (CAMS) has recently produced a greenhouse gas reanalysis (version egg4) that covers almost 2 decades from 2003 to 2020 and which will be extended in the future. This reanalysis dataset includes carbon dioxide (CO2) and methane (CH4). The reanalysis procedure combines model data with satellite data into a globally complete and consistent dataset using the European Centre for Medium-Range Weather Forecasts' Integrated Forecasting System (IFS). This dataset has been carefully evaluated against independent observations to ensure validity and to point out deficiencies to the user. The greenhouse gas reanalysis can be used to examine the impact of atmospheric greenhouse gas concentrations on climate change (such as global and regional climate radiative forcing), assess intercontinental transport, and serve as boundary conditions for regional simulations, among other applications and scientific uses. The caveats associated with changes in assimilated observations and fixed underlying emissions are highlighted, as is their impact on the estimation of trends and annual growth rates of these long-lived greenhouse gases.
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- 2023
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8. Advances in retrieving XCH4 and XCO from Sentinel-5 Precursor: improvements in the scientific TROPOMI/WFMD algorithm
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O. Schneising, M. Buchwitz, J. Hachmeister, S. Vanselow, M. Reuter, M. Buschmann, H. Bovensmann, and J. P. Burrows
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Environmental engineering ,TA170-171 ,Earthwork. Foundations ,TA715-787 - Abstract
The TROPOspheric Monitoring Instrument (TROPOMI) on board the Sentinel-5 Precursor satellite enables the accurate determination of atmospheric methane (CH4) and carbon monoxide (CO) abundances at high spatial resolution and global daily sampling. Due to its wide swath and sampling, the global distribution of both gases can be determined in unprecedented detail. The scientific retrieval algorithm Weighting Function Modified Differential Optical Absorption Spectroscopy (WFMD) has proven valuable in simultaneously retrieving the atmospheric column-averaged dry-air mole fractions XCH4 and XCO from TROPOMI's radiance measurements in the shortwave infrared (SWIR) spectral range. Here we present recent improvements of the algorithm which have been incorporated into the current version (v1.8) of the TROPOMI/WFMD product. This includes processing adjustments such as increasing the polynomial degree to 3 in the fitting procedure to better account for possible spectral albedo variations within the fitting window and updating the digital elevation model to minimise topography-related biases. In the post-processing, the machine-learning-based quality filter has been refined using additional data when training the random forest classifier to further reduce scenes with residual cloudiness that are incorrectly classified as good. In particular, the cloud filtering over the Arctic ocean is considerably improved. Furthermore, the machine learning calibration, addressing systematic errors due to simplifications in the forward model or instrumental issues, has been optimised. By including an additional feature associated with the fitted polynomial when training the corresponding random forest regressor, spectral albedo variations are better accounted for. To remove vertical stripes in the XCH4 and XCO data, an efficient orbit-wise destriping filter based on combined wavelet–Fourier filtering has been implemented, while optimally preserving the original spatial trace gas features. The temporal coverage of the data records has been extended to the end of April 2022, covering a total length of 4.5 years since the start of the mission, and will be further extended in the future. Validation with the ground-based Total Carbon Column Observing Network (TCCON) demonstrates that the implemented improvements reduce the pseudo-noise component of the products, resulting in an improved random error. The XCH4 and XCO products have similar spatial coverage from year to year including high latitudes and the oceans. The analysis of annual growth rates reveals accelerated growth of atmospheric methane during the covered period, in line with observations at marine surface sites of the Global Monitoring Division of NOAA's Earth System Research Laboratory, which reported consecutive annual record increases over the past 2 years of 2020 and 2021.
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- 2023
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9. Calcification response of reef corals to seasonal upwelling in the northern Arabian Sea (Masirah Island, Oman)
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P. M. Spreter, M. Reuter, R. Mertz-Kraus, O. Taylor, and T. C. Brachert
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Ecology ,QH540-549.5 ,Life ,QH501-531 ,Geology ,QE1-996.5 - Abstract
Tropical shallow-water reefs are the most diverse ecosystems in the ocean. Their persistence rests upon adequate calcification rates of the reef building biota, such as reef corals. Coral calcification is favoured in oligotrophic environments with high seawater saturation states of aragonite (Ωsw), which leads to an increased vulnerability to anthropogenic ocean acidification and eutrophication. Here we present Porites calcification records from the northern Arabian Sea upwelling zone and investigate the coral calcification response to low Ωsw and high nutrient concentrations due to seasonal upwelling. The calcification rate was determined from the product of skeletal extension rate and bulk density. Skeletal Ba/Ca and Li/Mg proxy data were used to identify skeletal portions that calcified during upwelling and non-upwelling seasons, respectively, and to reconstruct growth temperatures. With regard to sub-annual calcification patterns, our results demonstrate compromised calcification rates during the upwelling season. This is due to declining extension rates, which we attribute to light dimming caused by high primary production. Interestingly, seasonal variations in skeletal density show no relationship with temporally low Ωsw during upwelling. This suggests relatively constant, year-round saturation states of aragonite at the site of calcification (Ωcf) independent of external variability in Ωsw. Although upwelling does not affect seasonal density variability, exceptionally low mean annual density implies permanent Ωcf adjustment to the lowest sub-annual Ωsw (e.g. upwelling). In the Arabian Sea upwelling zone, the mean annual calcification rate is similar to Porites from non-upwelling regions because low skeletal density is compensated by high extension growth. Variable responses of reef coral extension to nutrients, which either exacerbate or compensate negative effects of diminished skeletal density associated with ocean acidification, may therefore be critical to the maintenance of adequate carbonate accumulation rates in coral reefs under global change.
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- 2022
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10. Retrieval of greenhouse gases from GOSAT and GOSAT-2 using the FOCAL algorithm
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S. Noël, M. Reuter, M. Buchwitz, J. Borchardt, M. Hilker, O. Schneising, H. Bovensmann, J. P. Burrows, A. Di Noia, R. J. Parker, H. Suto, Y. Yoshida, M. Buschmann, N. M. Deutscher, D. G. Feist, D. W. T. Griffith, F. Hase, R. Kivi, C. Liu, I. Morino, J. Notholt, Y.-S. Oh, H. Ohyama, C. Petri, D. F. Pollard, M. Rettinger, C. Roehl, C. Rousogenous, M. K. Sha, K. Shiomi, K. Strong, R. Sussmann, Y. Té, V. A. Velazco, M. Vrekoussis, and T. Warneke
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Environmental engineering ,TA170-171 ,Earthwork. Foundations ,TA715-787 - Abstract
We show new results from an updated version of the Fast atmOspheric traCe gAs retrievaL (FOCAL) retrieval method applied to measurements of the Greenhouse gases Observing SATellite (GOSAT) and its successor GOSAT-2. FOCAL was originally developed for estimating the total column carbon dioxide mixing ratio (XCO2) from spectral measurements made by the Orbiting Carbon Observatory-2 (OCO-2). However, depending on the available spectral windows, FOCAL also successfully retrieves total column amounts for other atmospheric species and their uncertainties within one single retrieval. The main focus of the current paper is on methane (XCH4; full-physics and proxy product), water vapour (XH2O) and the relative ratio of semi-heavy water (HDO) to water vapour (δD). Due to the extended spectral range of GOSAT-2, it is also possible to derive information on carbon monoxide (XCO) and nitrous oxide (XN2O) for which we also show first results. We also present an update on XCO2 from both instruments. For XCO2, the new FOCAL retrieval (v3.0) significantly increases the number of valid data compared with the previous FOCAL retrieval version (v1) by 50 % for GOSAT and about a factor of 2 for GOSAT-2 due to relaxed pre-screening and improved post-processing. All v3.0 FOCAL data products show reasonable spatial distribution and temporal variations. Comparisons with the Total Carbon Column Observing Network (TCCON) result in station-to-station biases which are generally in line with the reported TCCON uncertainties. With this updated version of the GOSAT-2 FOCAL data, we provide a first total column average XN2O product. Global XN2O maps show a gradient from the tropics to higher latitudes on the order of 15 ppb, which can be explained by variations in tropopause height. The new GOSAT-2 XN2O product compares well with TCCON. Its station-to-station variability is lower than 2 ppb, which is about the magnitude of the typical N2O variations close to the surface. However, both GOSAT-2 and TCCON measurements show that the seasonal variations in the total column average XN2O are on the order of 8 ppb peak-to-peak, which can be easily resolved by the GOSAT-2 FOCAL data. Noting that only few XN2O measurements from satellites exist so far, the GOSAT-2 FOCAL product will be a valuable contribution in this context.
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- 2022
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11. Investigation of spaceborne trace gas products over St Petersburg and Yekaterinburg, Russia, by using COllaborative Column Carbon Observing Network (COCCON) observations
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C. Alberti, Q. Tu, F. Hase, M. V. Makarova, K. Gribanov, S. C. Foka, V. Zakharov, T. Blumenstock, M. Buchwitz, C. Diekmann, B. Ertl, M. M. Frey, H. Kh. Imhasin, D. V. Ionov, F. Khosrawi, S. I. Osipov, M. Reuter, M. Schneider, and T. Warneke
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Environmental engineering ,TA170-171 ,Earthwork. Foundations ,TA715-787 - Abstract
This work employs ground- and space-based observations, together with model data, to study columnar abundances of atmospheric trace gases (XH2O, XCO2, XCH4 and XCO) in two high-latitude Russian cities, St. Petersburg and Yekaterinburg. Two portable COllaborative Column Carbon Observing Network (COCCON) spectrometers were used for continuous measurements at these locations during 2019 and 2020. Additionally, a subset of data of special interest (a strong gradient in XCH4 and XCO was detected) collected in the framework of a mobile city campaign performed in 2019 using both instruments is investigated. All studied satellite products (TROPOMI, OCO-2, GOSAT, MUSICA IASI) show generally good agreement with COCCON observations. Satellite and ground-based observations at high latitudes are much sparser than at low or mid latitudes, which makes direct coincident comparisons between remote-sensing observations more difficult. Therefore, a method of scaling continuous Copernicus Atmosphere Monitoring Service (CAMS) model data to the ground-based observations is developed and used for creating virtual COCCON observations. These adjusted CAMS data are then used for satellite validation, showing good agreement in both Peterhof and Yekaterinburg. The gradients between the two study sites (ΔXgas) are similar between CAMS and CAMS-COCCON datasets, indicating that the model gradients are in agreement with the gradients observed by COCCON. This is further supported by a few simultaneous COCCON and satellite ΔXgas measurements, which also agree with the model gradient. With respect to the city campaign observations recorded in St Petersburg, the downwind COCCON station measured obvious enhancements for both XCH4 (10.6 ppb) and XCO (9.5 ppb), which is nicely reflected by TROPOMI observations, which detect city-scale gradients of the order 9.4 ppb for XCH4 and 12.5 ppb for XCO.
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- 2022
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12. XCO2 retrieval for GOSAT and GOSAT-2 based on the FOCAL algorithm
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S. Noël, M. Reuter, M. Buchwitz, J. Borchardt, M. Hilker, H. Bovensmann, J. P. Burrows, A. Di Noia, H. Suto, Y. Yoshida, M. Buschmann, N. M. Deutscher, D. G. Feist, D. W. T. Griffith, F. Hase, R. Kivi, I. Morino, J. Notholt, H. Ohyama, C. Petri, J. R. Podolske, D. F. Pollard, M. K. Sha, K. Shiomi, R. Sussmann, Y. Té, V. A. Velazco, and T. Warneke
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Environmental engineering ,TA170-171 ,Earthwork. Foundations ,TA715-787 - Abstract
Since 2009, the Greenhouse gases Observing SATellite (GOSAT) has performed radiance measurements in the near-infrared (NIR) and shortwave infrared (SWIR) spectral region. From February 2019 onward, data from GOSAT-2 have also been available. We present the first results from the application of the Fast atmOspheric traCe gAs retrievaL (FOCAL) algorithm to derive column-averaged dry-air mole fractions of carbon dioxide (XCO2) from GOSAT and GOSAT-2 radiances and their validation. FOCAL was initially developed for OCO-2 XCO2 retrievals and allows simultaneous retrievals of several gases over both land and ocean. Because FOCAL is accurate and numerically very fast, it is currently being considered as a candidate algorithm for the forthcoming European anthropogenic CO2 Monitoring (CO2M) mission to be launched in 2025. We present the adaptation of FOCAL to GOSAT and discuss the changes made and GOSAT specific additions. This particularly includes modifications in pre-processing (e.g. cloud detection) and post-processing (bias correction and filtering). A feature of the new application of FOCAL to GOSAT and GOSAT-2 is the independent use of both S- and P-polarisation spectra in the retrieval. This is not possible for OCO-2, which measures only one polarisation direction. Additionally, we make use of GOSAT's wider spectral coverage compared to OCO-2 and derive not only XCO2, water vapour (H2O), and solar-induced fluorescence (SIF) but also methane (XCH4), with the potential for further atmospheric constituents and parameters like semi-heavy water vapour (HDO). In the case of GOSAT-2, the retrieval of nitrous oxide (XN2O) and carbon monoxide (CO) may also be possible. Here, we concentrate on the new FOCAL XCO2 data products. We describe the generation of the products as well as applied filtering and bias correction procedures. GOSAT-FOCAL XCO2 data have been produced for the time interval 2009 to 2019. Comparisons with other independent GOSAT data sets reveal agreement of long-term temporal variations within about 1 ppm over 1 decade; differences in seasonal variations of about 0.5 ppm are observed. Furthermore, we obtain a station-to-station bias of the new GOSAT-FOCAL product to the ground-based Total Carbon Column Observing Network (TCCON) of 0.56 ppm with a mean scatter of 1.89 ppm. The GOSAT-2-FOCAL XCO2 product is generated in a similar way as the GOSAT-FOCAL product, but with adapted settings. All GOSAT-2 data until the end of 2019 have been processed. Because of this limited time interval, the GOSAT-2 results are considered to be preliminary only, but first comparisons show that these data compare well with the GOSAT-FOCAL results and also TCCON.
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- 2021
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13. Can a regional-scale reduction of atmospheric CO2 during the COVID-19 pandemic be detected from space? A case study for East China using satellite XCO2 retrievals
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M. Buchwitz, M. Reuter, S. Noël, K. Bramstedt, O. Schneising, M. Hilker, B. Fuentes Andrade, H. Bovensmann, J. P. Burrows, A. Di Noia, H. Boesch, L. Wu, J. Landgraf, I. Aben, C. Retscher, C. W. O'Dell, and D. Crisp
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Environmental engineering ,TA170-171 ,Earthwork. Foundations ,TA715-787 - Abstract
The COVID-19 pandemic resulted in reduced anthropogenic carbon dioxide (CO2) emissions during 2020 in large parts of the world. To investigate whether a regional-scale reduction of anthropogenic CO2 emissions during the COVID-19 pandemic can be detected using space-based observations of atmospheric CO2, we have analysed a small ensemble of OCO-2 and GOSAT satellite retrievals of column-averaged dry-air mole fractions of CO2, i.e. XCO2. We focus on East China and use a simple data-driven analysis method. We present estimates of the relative change of East China monthly emissions in 2020 relative to previous periods, limiting the analysis to October-to-May periods to minimize the impact of biogenic CO2 fluxes. The ensemble mean indicates an emission reduction by approximately 10 % ± 10 % in March and April 2020. However, our results show considerable month-to-month variability and significant differences across the ensemble of satellite data products analysed. For example, OCO-2 suggests a much smaller reduction (∼ 1 %–2 % ± 2 %). This indicates that it is challenging to reliably detect and to accurately quantify the emission reduction with current satellite data sets. There are several reasons for this, including the sparseness of the satellite data but also the weak signal; the expected regional XCO2 reduction is only on the order of 0.1–0.2 ppm. Inferring COVID-19-related information on regional-scale CO2 emissions using current satellite XCO2 retrievals likely requires, if at all possible, a more sophisticated analysis method including detailed transport modelling and considering a priori information on anthropogenic and natural CO2 surface fluxes.
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- 2021
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14. Development of a small unmanned aircraft system to derive CO2 emissions of anthropogenic point sources
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M. Reuter, H. Bovensmann, M. Buchwitz, J. Borchardt, S. Krautwurst, K. Gerilowski, M. Lindauer, D. Kubistin, and J. P. Burrows
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Environmental engineering ,TA170-171 ,Earthwork. Foundations ,TA715-787 - Abstract
A reduction of the anthropogenic emissions of CO2 (carbon dioxide) is necessary to stop or slow down man-made climate change. To verify mitigation strategies, a global monitoring system such as the envisaged European Copernicus anthropogenic CO2 monitoring mission (CO2M) is required. Those satellite data are going to be complemented and validated with airborne measurements. Unmanned aerial vehicle (UAV)-based measurements can provide a cost-effective way to contribute to these activities. Here, we present the development of an sUAS (small unmanned aircraft system) to quantify the CO2 emissions of a nearby point source from its downwind mass flux without the need for any ancillary data. Specifically, CO2 is measured by an NDIR (non-dispersive infrared) detector, and the wind speed and direction are measured with a 2-D ultrasonic acoustic resonance anemometer. By means of laboratory measurements and an in-flight validation at the ICOS (Integrated Carbon Observation System) atmospheric station Steinkimmen (STE) near Bremen, Germany, we estimate that the individual CO2 measurements have a precision of 3 ppm and that CO2 enhancements can be determined with an accuracy of 1.3 % or 0.9 ppm, whichever is larger. We introduce an anemometer calibration method to minimize the effect of rotor downwash on the wind measurements. This method derives the fit parameters of a linear calibration model accounting for scaling, rotation, and a potential constant bias. For this purpose, it analyzes wind measurements taken while following a suitable flight pattern and assuming stationary wind conditions. From the calibration and validation experiments, we estimate the single measurement precision of the horizontal wind speed to be 0.40 m s−1 and the accuracy to be 0.33 m s−1. By means of two flights downwind of the ExxonMobil natural gas processing facility in Großenkneten about 40 km west of Bremen, Germany, we demonstrate how the measurements of elevated CO2 concentrations can be used to infer mass fluxes of atmospheric CO2 related to the emissions of the facility.
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- 2021
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15. Spatially resolved evaluation of Earth system models with satellite column-averaged CO2
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B. K. Gier, M. Buchwitz, M. Reuter, P. M. Cox, P. Friedlingstein, and V. Eyring
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Ecology ,QH540-549.5 ,Life ,QH501-531 ,Geology ,QE1-996.5 - Abstract
Earth system models (ESMs) participating in the Coupled Model Intercomparison Project Phase 5 (CMIP5) showed large uncertainties in simulating atmospheric CO2 concentrations. We utilize the Earth System Model Evaluation Tool (ESMValTool) to evaluate emission-driven CMIP5 and CMIP6 simulations with satellite data of column-average CO2 mole fractions (XCO2). XCO2 time series show a large spread among the model ensembles both in CMIP5 and CMIP6. Compared to the satellite observations, the models have a bias of +25 to −20 ppmv in CMIP5 and +20 to −15 ppmv in CMIP6, with the multi-model mean biases at +10 and +2 ppmv, respectively. The derived mean atmospheric XCO2 growth rate (GR) of 2.0 ppmv yr−1 is overestimated by 0.4 ppmv yr−1 in CMIP5 and 0.3 ppmv yr−1 in CMIP6 for the multi-model mean, with a good reproduction of the interannual variability. All models capture the expected increase of the seasonal cycle amplitude (SCA) with increasing latitude, but most models underestimate the SCA. Any SCA derived from data with missing values can only be considered an “effective” SCA, as the missing values could occur at the peaks or troughs. The satellite data are a combined data product covering the period 2003–2014 based on the Scanning Imaging Absorption Spectrometer for Atmospheric Chartography (SCIAMACHY)/Envisat (2003–2012) and Thermal And Near infrared Sensor for carbon Observation Fourier transform spectrometer/Greenhouse Gases Observing Satellite (TANSO-FTS/GOSAT) (2009–2014) instruments. While the combined satellite product shows a strong negative trend of decreasing effective SCA with increasing XCO2 in the northern midlatitudes, both CMIP ensembles instead show a non-significant positive trend in the multi-model mean. The negative trend is reproduced by the models when sampling them as the observations, attributing it to sampling characteristics. Applying a mask of the mean data coverage of each satellite to the models, the effective SCA is higher for the SCIAMACHY/Envisat mask than when using the TANSO-FTS/GOSAT mask. This induces an artificial negative trend when using observational sampling over the full period, as SCIAMACHY/Envisat covers the early period until 2012, with TANSO-FTS/GOSAT measurements starting in 2009. Overall, the CMIP6 ensemble shows better agreement with the satellite data than the CMIP5 ensemble in all considered quantities (XCO2, GR, SCA and trend in SCA). This study shows that the availability of column-integral CO2 from satellite provides a promising new way to evaluate the performance of Earth system models on a global scale, complementing existing studies that are based on in situ measurements from single ground-based stations.
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- 2020
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16. PMIF v1.0: assessing the potential of satellite observations to constrain CO2 emissions from large cities and point sources over the globe using synthetic data
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Y. Wang, G. Broquet, F.-M. Bréon, F. Lespinas, M. Buchwitz, M. Reuter, Y. Meijer, A. Loescher, G. Janssens-Maenhout, B. Zheng, and P. Ciais
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Geology ,QE1-996.5 - Abstract
This study assesses the potential of satellite imagery of vertically integrated columns of dry-air mole fractions of CO2 (XCO2) to constrain the emissions from cities and power plants (called emission clumps) over the whole globe during 1 year. The imagery is simulated for one imager of the Copernicus mission on Anthropogenic Carbon Dioxide Monitoring (CO2M) planned by the European Space Agency and the European Commission. The width of the swath of the CO2M instruments is about 300 km and the ground horizontal resolution is about 2 km resolution. A Plume Monitoring Inversion Framework (PMIF) is developed, relying on a Gaussian plume model to simulate the XCO2 plumes of each emission clump and on a combination of overlapping assimilation windows to solve for the inversion problem. The inversion solves for the 3 h mean emissions (during 08:30–11:30 local time) before satellite overpasses and for the mean emissions during other hours of the day (over the aggregation between 00:00–08:30 and 11:30–00:00) for each clump and for the 366 d of the year. Our analysis focuses on the derivation of the uncertainty in the inversion estimates (the “posterior uncertainty”) of the clump emissions. A comparison of the results obtained with PMIF and those from a previous study using a complex 3-D Eulerian transport model for a single city (Paris) shows that the PMIF system provides the correct order of magnitude for the uncertainty reduction of emission estimates (i.e., the relative difference between the prior and posterior uncertainties). Beyond the one city or few large cities studied by previous studies, our results provide, for the first time, the global statistics of the uncertainty reduction of emissions for the full range of global clumps (differing in emission rate and spread, and distance from other major clumps) and meteorological conditions. We show that only the clumps with an annual emission budget higher than 2 MtC yr−1 can potentially have their emissions between 08:30 and 11:30 constrained with a posterior uncertainty smaller than 20 % for more than 10 times within 1 year (ignoring the potential to cross or extrapolate information between 08:30–11:30 time windows on different days). The PMIF inversion results are also aggregated in time to investigate the potential of CO2M observations to constrain daily and annual emissions, relying on the extrapolation of information obtained for 08:30–11:30 time windows during days when clouds and aerosols do not mask the plumes, based on various assumptions regarding the temporal auto-correlations of the uncertainties in the emission estimates that are used as a prior knowledge in the Bayesian framework of PMIF. We show that the posterior uncertainties of daily and annual emissions are highly dependent on these temporal auto-correlations, stressing the need for systematic assessment of the sources of uncertainty in the spatiotemporally resolved emission inventories used as prior estimates in the inversions. We highlight the difficulty in constraining the total budget of CO2 emissions from all the cities and power plants within a country or over the globe with satellite XCO2 measurements only, and calls for integrated inversion systems that exploit multiple types of measurements.
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- 2020
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17. Severe Californian wildfires in November 2018 observed from space: the carbon monoxide perspective
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O. Schneising, M. Buchwitz, M. Reuter, H. Bovensmann, and J. P. Burrows
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Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Due to proceeding climate change, some regions such as California face rising weather extremes with dry periods becoming warmer and drier, entailing the risk that wildfires and associated air pollution episodes will continue to increase. November 2018 turned into one of the most severe wildfire episodes on record in California, with two particularly destructive wildfires spreading concurrently through the north and the south of the state. Both fires ignited at the wildland–urban interface, causing many civilian fatalities and forcing the total evacuation of several cities and communities. Here we demonstrate that the inherent carbon monoxide (CO) emissions of the wildfires and subsequent transport can be observed from space by analysing radiance measurements of the TROPOspheric Monitoring Instrument (TROPOMI) onboard the Sentinel-5 Precursor satellite in the shortwave infrared spectral range. From the determined CO distribution we assess the corresponding air quality burden in major Californian cities caused by the fires and discuss the associated uncertainties. As a result of the prevailing wind conditions, the largest CO load during the first days of the fires is found in Sacramento and San Francisco, with city area averages reaching boundary layer concentration anomalies of about 2.5 mg CO m−3. Even the most polluted city scenes likely comply with the national ambient air quality standards (10 mg CO m−3 with 8 h averaging time). This finding based on dense daily recurrent satellite monitoring is consistent with isolated ground-based air quality measurements.
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- 2020
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18. Ensemble-based satellite-derived carbon dioxide and methane column-averaged dry-air mole fraction data sets (2003–2018) for carbon and climate applications
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M. Reuter, M. Buchwitz, O. Schneising, S. Noël, H. Bovensmann, J. P. Burrows, H. Boesch, A. Di Noia, J. Anand, R. J. Parker, P. Somkuti, L. Wu, O. P. Hasekamp, I. Aben, A. Kuze, H. Suto, K. Shiomi, Y. Yoshida, I. Morino, D. Crisp, C. W. O'Dell, J. Notholt, C. Petri, T. Warneke, V. A. Velazco, N. M. Deutscher, D. W. T. Griffith, R. Kivi, D. F. Pollard, F. Hase, R. Sussmann, Y. V. Té, K. Strong, S. Roche, M. K. Sha, M. De Mazière, D. G. Feist, L. T. Iraci, C. M. Roehl, C. Retscher, and D. Schepers
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Environmental engineering ,TA170-171 ,Earthwork. Foundations ,TA715-787 - Abstract
Satellite retrievals of column-averaged dry-air mole fractions of carbon dioxide (CO2) and methane (CH4), denoted XCO2 and XCH4, respectively, have been used in recent years to obtain information on natural and anthropogenic sources and sinks and for other applications such as comparisons with climate models. Here we present new data sets based on merging several individual satellite data products in order to generate consistent long-term climate data records (CDRs) of these two Essential Climate Variables (ECVs). These ECV CDRs, which cover the time period 2003–2018, have been generated using an ensemble of data products from the satellite sensors SCIAMACHY/ENVISAT and TANSO-FTS/GOSAT and (for XCO2) for the first time also including data from the Orbiting Carbon Observatory 2 (OCO-2) satellite. Two types of products have been generated: (i) Level 2 (L2) products generated with the latest version of the ensemble median algorithm (EMMA) and (ii) Level 3 (L3) products obtained by gridding the corresponding L2 EMMA products to obtain a monthly 5∘×5∘ data product in Obs4MIPs (Observations for Model Intercomparisons Project) format. The L2 products consist of daily NetCDF (Network Common Data Form) files, which contain in addition to the main parameters, i.e., XCO2 or XCH4, corresponding uncertainty estimates for random and potential systematic uncertainties and the averaging kernel for each single (quality-filtered) satellite observation. We describe the algorithms used to generate these data products and present quality assessment results based on comparisons with Total Carbon Column Observing Network (TCCON) ground-based retrievals. We found that the XCO2 Level 2 data set at the TCCON validation sites can be characterized by the following figures of merit (the corresponding values for the Level 3 product are listed in brackets) – single-observation random error (1σ): 1.29 ppm (monthly: 1.18 ppm); global bias: 0.20 ppm (0.18 ppm); and spatiotemporal bias or relative accuracy (1σ): 0.66 ppm (0.70 ppm). The corresponding values for the XCH4 products are single-observation random error (1σ): 17.4 ppb (monthly: 8.7 ppb); global bias: −2.0 ppb (−2.9 ppb); and spatiotemporal bias (1σ): 5.0 ppb (4.9 ppb). It has also been found that the data products exhibit very good long-term stability as no significant long-term bias trend has been identified. The new data sets have also been used to derive annual XCO2 and XCH4 growth rates, which are in reasonable to good agreement with growth rates from the National Oceanic and Atmospheric Administration (NOAA) based on marine surface observations. The presented ECV data sets are available (from early 2020 onwards) via the Climate Data Store (CDS, https://cds.climate.copernicus.eu/, last access: 10 January 2020) of the Copernicus Climate Change Service (C3S, https://climate.copernicus.eu/, last access: 10 January 2020).
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- 2020
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19. Economic benefits of load volume scanning of underground mining trucks
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P. Knights and M. Reuter
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General Earth and Planetary Sciences ,General Environmental Science - Published
- 2023
20. Patient experiences with clinical confirmatory genetic testing after using direct-to-consumer raw DNA and third-party genetic interpretation services
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Tiffany T Nguyen Dolphyn, Kelly E Ormond, Scott M Weissman, Helen J Kim, and Chloe M Reuter
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Behavioral Neuroscience ,Applied Psychology - Abstract
The availability of raw DNA and genetic interpretation tools allow individuals to access genetic health risk information, where analytical false-positives exist. Little is known about the experience of individuals who receive pathogenic or likely pathogenic variant(s) through raw DNA interpretation and follow-up with clinical confirmatory genetic testing. This qualitative study set out to describe the experiences of individuals who pursued clinical confirmatory genetic testing, including their perception of the process. Participants were recruited from social media and eligible if they discovered a potential pathogenic or likely pathogenic variant in a raw DNA interpretation report, completed clinical confirmatory genetic testing in the U.S., and provided documentation of those results. Individuals participated in semi-structured interviews, which were transcribed and inductively coded to identify themes. Of the 12 participants, 3 received clinical genetic testing results that confirmed pathogenic or likely pathogenic variants noted in raw DNA interpretation reports (confirmation positive), and 9 were not confirmed. Nearly all (n = 11) participants described emotional distress and information-seeking behavior as a coping mechanism after discovering a pathogenic or likely pathogenic variant in raw DNA interpretation. When pursuing confirmatory genetic testing, many (n = 9) faced challenges with finding knowledgeable healthcare providers and obtaining insurance coverage. Despite reporting concerns over raw DNA interpretation and a desire for more safeguards, almost all (n = 10) participants stated interest in using the service again. Overall, participants' experiences reveal they find personal utility in raw DNA interpretation results and provide insight into opportunities for patient and provider education.The availability of raw DNA data and online genetic interpretation tools allow individuals to access genetic health risk information, where false-positive results exist. Little is known about the experience of individuals who discover disease-causing variant(s) through raw DNA interpretation and follow-up with medical-grade confirmatory genetic testing. This qualitative study describes the experiences of individuals who pursued medical-grade confirmatory genetic testing in the U.S. after they discovered a potential disease-causing variant in a raw DNA interpretation report. Individuals participated in semi-structured interviews, which were transcribed and inductively coded to identify themes. Of the 12 participants, 3 received medical-grade genetic testing results that confirmed disease-causing variants noted in raw DNA interpretation reports, and 9 were not confirmed. Nearly all participants described emotional distress and information-seeking behavior after discovering a disease-causing variant in raw DNA interpretation. When pursuing confirmatory genetic testing, many faced challenges with finding knowledgeable healthcare providers and obtaining insurance coverage. Despite reporting concerns over raw DNA interpretation and a desire for more safeguards, almost all participants stated interest in using the service again. Overall, participants’ experiences reveal they find personal utility in raw DNA interpretation results and provide insight into opportunities for patient and provider education.
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- 2022
21. Proactive Variant Effect Mapping Aids Diagnosis in Pediatric Cardiac Arrest
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Brendan J. Floyd, Jochen Weile, Prince J. Kannankeril, Andrew M. Glazer, Chloe M. Reuter, Calum A. MacRae, Euan A. Ashley, Dan M. Roden, Frederick P. Roth, and Victoria N. Parikh
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General Medicine - Published
- 2023
22. What is a mammalian omnivore? Insights into terrestrial mammalian diet diversity, body mass and evolution
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Dana M. Reuter, Samantha S. B. Hopkins, and Samantha A. Price
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General Immunology and Microbiology ,General Medicine ,General Agricultural and Biological Sciences ,General Biochemistry, Genetics and Molecular Biology ,General Environmental Science - Abstract
Mammalian omnivores are a broad group of species that are often treated uniformly in ecological studies. Here, we incorporate omnivorous dietary differences to investigate previously found mammalian macroevolutionary and macroecological trends. We investigate the frequency with which vertebrate prey, invertebrate prey, fibrous plant material and non-fibrous plant material co-occur in the diets of terrestrial mammals. We quantify the body size distributions and phylogenetic signal of different omnivorous diets and use multistate reversible jump Markov chain Monte Carlo methods to assess the transition rates between diets on the mammalian phylogenetic tree. We find omnivores that consume all four food types are relatively rare, as most omnivores consume only invertebrate prey and non-fibrous plants. In addition, omnivores that only consume invertebrate prey, many of which are from Rodentia, are on average smaller than omnivores that incorporate vertebrate prey. Our transition models have high rates from invertivorous omnivory to herbivory, and from vertivory to prey mixing and ultimately invertivory. We suggest prey type is an important aspect of omnivore macroevolution and macroecology, as it is correlated with body mass, evolutionary history and diet-related evolutionary transition rates. Future work should avoid lumping omnivores into one category given the ecological variety of omnivore diets and their strong evolutionary influence.
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- 2023
23. On selfdual spin-connections and asymptotic safety
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U. Harst and M. Reuter
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Physics ,QC1-999 - Abstract
We explore Euclidean quantum gravity using the tetrad field together with a selfdual or anti-selfdual spin-connection as the basic field variables. Setting up a functional renormalization group (RG) equation of a new type which is particularly suitable for the corresponding theory space we determine the non-perturbative RG flow within a two-parameter truncation suggested by the Holst action. We find that the (anti-)selfdual theory is likely to be asymptotically safe. The existing evidence for its non-perturbative renormalizability is comparable to that of Einstein–Cartan gravity without the selfduality condition.
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- 2016
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24. Correlations Between Mechanical and Index Properties of Sandstone from the Central Salt Range
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M. Reuter, M. Krach, U. Kießling, and J. Veksler
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Metals and Alloys ,Geotechnical Engineering and Engineering Geology - Published
- 2022
25. Acoustic Noise in Coal Seam as an Indicator of Geodynamic Behavior in Longwall
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M. Reuter, M. Krach, U. Kießling, and J. Veksler
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Geology ,Geotechnical Engineering and Engineering Geology - Published
- 2022
26. Heterozygous loss-of-function variants significantly expand the phenotypes associated with loss of GDF11
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Thomas A. Ravenscroft, Jennifer B. Phillips, Elizabeth Fieg, Sameer S. Bajikar, Judy Peirce, Jeremy Wegner, Alia A. Luna, Eric J. Fox, Yi-Lin Yan, Jill A. Rosenfeld, Jonathan Zirin, Oguz Kanca, Maria T. Acosta, Margaret Adam, David R. Adams, Pankaj B. Agrawal, Mercedes E. Alejandro, Justin Alvey, Laura Amendola, Ashley Andrews, Euan A. Ashley, Mahshid S. Azamian, Carlos A. Bacino, Guney Bademci, Eva Baker, Ashok Balasubramanya, Dustin Baldridge, Jim Bale, Michael Bamshad, Deborah Barbouth, Pinar Bayrak-Toydemir, Anita Beck, Alan H. Beggs, Edward Behrens, Gill Bejerano, Jimmy Bennet, Beverly Berg-Rood, Jonathan A. Bernstein, Gerard T. Berry, Anna Bican, Stephanie Bivona, Elizabeth Blue, John Bohnsack, Carsten Bonnenmann, Devon Bonner, Lorenzo Botto, Brenna Boyd, Lauren C. Briere, Elly Brokamp, Gabrielle Brown, Elizabeth A. Burke, Lindsay C. Burrage, Manish J. Butte, Peter Byers, William E. Byrd, John Carey, Olveen Carrasquillo, Ta Chen Peter Chang, Sirisak Chanprasert, Hsiao-Tuan Chao, Gary D. Clark, Terra R. Coakley, Laurel A. Cobban, Joy D. Cogan, Matthew Coggins, F. Sessions Cole, Heather A. Colley, Cynthia M. Cooper, Heidi Cope, William J. Craigen, Andrew B. Crouse, Michael Cunningham, Precilla D’Souza, Hongzheng Dai, Surendra Dasari, Joie Davis, Jyoti G. Dayal, Matthew Deardorff, Esteban C. Dell’Angelica, Shweta U. Dhar, Katrina Dipple, Daniel Doherty, Naghmeh Dorrani, Argenia L. Doss, Emilie D. Douine, David D. Draper, Laura Duncan, Dawn Earl, David J. Eckstein, Lisa T. Emrick, Christine M. Eng, Cecilia Esteves, Marni Falk, Liliana Fernandez, Carlos Ferreira, Elizabeth L. Fieg, Laurie C. Findley, Paul G. Fisher, Brent L. Fogel, Irman Forghani, Laure Fresard, William A. Gahl, Ian Glass, Bernadette Gochuico, Rena A. Godfrey, Katie Golden-Grant, Alica M. Goldman, Madison P. Goldrich, David B. Goldstein, Alana Grajewski, Catherine A. Groden, Irma Gutierrez, Sihoun Hahn, Rizwan Hamid, Neil A. Hanchard, Kelly Hassey, Nichole Hayes, Frances High, Anne Hing, Fuki M. Hisama, Ingrid A. Holm, Jason Hom, Martha Horike-Pyne, Alden Huang, Yong Huang, Laryssa Huryn, Rosario Isasi, Fariha Jamal, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Lefkothea Karaviti, Jennifer Kennedy, Dana Kiley, Isaac S. Kohane, Jennefer N. Kohler, Deborah Krakow, Donna M. Krasnewich, Elijah Kravets, Susan Korrick, Mary Koziura, Joel B. Krier, Seema R. Lalani, Byron Lam, Christina Lam, Grace L. LaMoure, Brendan C. Lanpher, Ian R. Lanza, Lea Latham, Kimberly LeBlanc, Brendan H. Lee, Hane Lee, Roy Levitt, Richard A. Lewis, Sharyn A. Lincoln, Pengfei Liu, Xue Zhong Liu, Nicola Longo, Sandra K. Loo, Joseph Loscalzo, Richard L. Maas, John MacDowall, Ellen F. Macnamara, Calum A. MacRae, Valerie V. Maduro, Marta M. Majcherska, Bryan C. Mak, May Christine V. Malicdan, Laura A. Mamounas, Teri A. Manolio, Rong Mao, Kenneth Maravilla, Thomas C. Markello, Ronit Marom, Gabor Marth, Beth A. Martin, Martin G. Martin, Julian A. Martínez-Agosto, Shruti Marwaha, Jacob McCauley, Allyn McConkie-Rosell, Colleen E. McCormack, Alexa T. McCray, Elisabeth McGee, Heather Mefford, J. Lawrence Merritt, Matthew Might, Ghayda Mirzaa, Eva Morava, Paolo Moretti, Paolo M. Moretti, Deborah Mosbrook-Davis, John J. Mulvihill, David R. Murdock, Anna Nagy, Mariko Nakano-Okuno, Avi Nath, Stan F. Nelson, John H. Newman, Sarah K. Nicholas, Deborah Nickerson, Shirley Nieves-Rodriguez, Donna Novacic, Devin Oglesbee, James P. Orengo, Laura Pace, Stephen Pak, J. Carl Pallais, Christina GS. Palmer, Jeanette C. Papp, Neil H. Parker, John A. Phillips, Jennifer E. Posey, Lorraine Potocki, Bradley Power, Barbara N. Pusey, Aaron Quinlan, Wendy Raskind, Archana N. Raja, Deepak A. Rao, Genecee Renteria, Chloe M. Reuter, Lynette Rives, Amy K. Robertson, Lance H. Rodan, Natalie Rosenwasser, Francis Rossignol, Maura Ruzhnikov, Ralph Sacco, Jacinda B. Sampson, Susan L. Samson, Mario Saporta, C. Ron Scott, Judy Schaechter, Timothy Schedl, Kelly Schoch, Daryl A. Scott, Vandana Shashi, Jimann Shin, Rebecca Signer, Edwin K. Silverman, Janet S. Sinsheimer, Kathy Sisco, Edward C. Smith, Kevin S. Smith, Emily Solem, Lilianna Solnica-Krezel, Ben Solomon, Rebecca C. Spillmann, Joan M. Stoler, Jennifer A. Sullivan, Kathleen Sullivan, Angela Sun, Shirley Sutton, David A. Sweetser, Virginia Sybert, Holly K. Tabor, Amelia L.M. Tan, Queenie K.-G. Tan, Mustafa Tekin, Fred Telischi, Willa Thorson, Audrey Thurm, Cynthia J. Tifft, Camilo Toro, Alyssa A. Tran, Brianna M. Tucker, Tiina K. Urv, Adeline Vanderver, Matt Velinder, Dave Viskochil, Tiphanie P. Vogel, Colleen E. Wahl, Stephanie Wallace, Nicole M. Walley, Chris A. Walsh, Melissa Walker, Jennifer Wambach, Jijun Wan, Lee-kai Wang, Michael F. Wangler, Patricia A. Ward, Daniel Wegner, Mark Wener, Tara Wenger, Katherine Wesseling Perry, Monte Westerfield, Matthew T. Wheeler, Jordan Whitlock, Lynne A. Wolfe, Jeremy D. Woods, Shinya Yamamoto, John Yang, Muhammad Yousef, Diane B. Zastrow, Wadih Zein, Chunli Zhao, Stephan Zuchner, Paul J. Benke, Eric S. Cameron, Vincent Strehlow, Konrad Platzer, Rami Abou Jamra, Chiara Klöckner, Matthew Osmond, Thomas Licata, Samantha Rojas, David Dyment, Josephine S.C. Chong, Sharyn Lincoln, John H. Postlethwait, Joel Krier, and Hugo J. Bellen
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0301 basic medicine ,Craniofacial abnormality ,Mutation, Missense ,030105 genetics & heredity ,Biology ,Article ,Frameshift mutation ,Craniofacial Abnormalities ,03 medical and health sciences ,medicine ,Animals ,Humans ,Missense mutation ,Craniofacial ,Allele ,Zebrafish ,Genetics (clinical) ,Loss function ,Genetics ,medicine.disease ,biology.organism_classification ,Phenotype ,Spine ,Growth Differentiation Factors ,030104 developmental biology ,Bone Morphogenetic Proteins - Abstract
Purpose Growth differentiation factor 11 (GDF11) is a key signaling protein required for proper development of many organ systems. Only one prior study has associated an inherited GDF11 variant with a dominant human disease in a family with variable craniofacial and vertebral abnormalities. Here, we expand the phenotypic spectrum associated with GDF11 variants and document the nature of the variants. Methods We present a cohort of six probands with de novo and inherited nonsense/frameshift (4/6 patients) and missense (2/6) variants in GDF11. We generated gdf11 mutant zebrafish to model loss of gdf11 phenotypes and used an overexpression screen in Drosophila to test variant functionality. Results Patients with variants in GDF11 presented with craniofacial (5/6) , vertebral (5/6), neurological (6/6), visual (4/6), cardiac (3/6), auditory (3/6) and connective tissue abnormalities (3/6). gdf11 mutant zebrafish show craniofacial abnormalities and body segmentation defects that match some patient phenotypes. Expression of the patients’ variants in the fly showed that one nonsense variant in GDF11 is a severe loss-of-function (LOF) alleles whereas the missense variants in our cohort are partial LOF variants. Conclusion GDF11 is needed for human development, particularly neuronal development, and LOF GDF11 alleles can affect the development of numerous organs and tissues.
- Published
- 2021
27. Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients
- Author
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Philipp Ivanyi, Christoph W. M. Reuter, Arnold Ganser, Stefan Brunotte, Paula Kappler, and Michael A. Morgan
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Science ,Urology ,Antineoplastic Agents ,Docetaxel ,Article ,Targeted therapy ,Prostate cancer ,Limit of Detection ,Soft tissue metastasis ,medicine ,Clinical endpoint ,Humans ,Testosterone ,Neoplasm Metastasis ,Aged ,Cancer ,Multidisciplinary ,Free testosterone ,Proportional hazards model ,business.industry ,Prostatic Neoplasms ,Prostate-Specific Antigen ,medicine.disease ,Prognosis ,Medicine ,business ,medicine.drug - Abstract
To date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and its impact on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed below the detection limit during docetaxel treatment (FT: from 0.32 pg/mL to
- Published
- 2021
28. Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain
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Felix Marbach, Georgi Stoyanov, Florian Erger, Constantine A. Stratakis, Nikolaos Settas, Edra London, Jill A. Rosenfeld, Erin Torti, Chad Haldeman-Englert, Evgenia Sklirou, Elena Kessler, Sophia Ceulemans, Stanley F. Nelson, Julian A. Martinez-Agosto, Christina G.S. Palmer, Rebecca H. Signer, Maria T. Acosta, Margaret Adam, David R. Adams, Pankaj B. Agrawal, Mercedes E. Alejandro, Justin Alvey, Laura Amendola, Ashley Andrews, Euan A. Ashley, Mahshid S. Azamian, Carlos A. Bacino, Guney Bademci, Eva Baker, Ashok Balasubramanyam, Dustin Baldridge, Jim Bale, Michael Bamshad, Deborah Barbouth, Pinar Bayrak-Toydemir, Anita Beck, Alan H. Beggs, Edward Behrens, Gill Bejerano, Jimmy Bennett, Beverly Berg-Rood, Jonathan A. Bernstein, Gerard T. Berry, Anna Bican, Stephanie Bivona, Elizabeth Blue, John Bohnsack, Carsten Bonnenmann, Devon Bonner, Lorenzo Botto, Brenna Boyd, Lauren C. Briere, Elly Brokamp, Gabrielle Brown, Elizabeth A. Burke, Lindsay C. Burrage, Manish J. Butte, Peter Byers, William E. Byrd, John Carey, Olveen Carrasquillo, Ta Chen Peter Chang, Sirisak Chanprasert, Hsiao-Tuan Chao, Gary D. Clark, Terra R. Coakley, Laurel A. Cobban, Joy D. Cogan, Matthew Coggins, F. Sessions Cole, Heather A. Colley, Cynthia M. Cooper, Heidi Cope, William J. Craigen, Andrew B. Crouse, Michael Cunningham, Precilla D’Souza, Hongzheng Dai, Surendra Dasari, Joie Davis, Jyoti G. Daya, Matthew Deardorff, Esteban C. Dell’Angelica, Shweta U. Dhar, Katrina Dipple, Daniel Doherty, Naghmeh Dorrani, Argenia L. Doss, Emilie D. Douine, David D. Draper, Laura Duncan, Dawn Earl, David J. Eckstein, Lisa T. Emrick, Christine M. Eng, Cecilia Esteves, Marni Falk, Liliana Fernandez, Carlos Ferreira, Elizabeth L. Fieg, Laurie C. Findley, Paul G. Fisher, Brent L. Fogel, Irman Forghani, Laure Fresard, William A. Gahl, Ian Glass, Bernadette Gochuico, Rena A. Godfrey, Katie Golden-Grant, Alica M. Goldman, Madison P. Goldrich, David B. Goldstein, Alana Grajewski, Catherine A. Groden, Irma Gutierrez, Sihoun Hahn, Rizwan Hamid, Neil A. Hanchard, Kelly Hassey, Nichole Hayes, Frances High, Anne Hing, Fuki M. Hisama, Ingrid A. Holm, Jason Hom, Martha Horike-Pyne, Alden Huang, Yong Huang, Laryssa Huryn, Rosario Isasi, Fariha Jamal, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Lefkothea Karaviti, Jennifer Kennedy, Dana Kiley, Isaac S. Kohane, Jennefer N. Kohler, Susan Korrick, Mary Kozuira, Deborah Krakow, Donna M. Krasnewich, Elijah Kravets, Joel B. Krier, Grace L. LaMoure, Seema R. Lalani, Byron Lam, Christina Lam, Brendan C. Lanpher, Ian R. Lanza, Lea Latham, Kimberly LeBlanc, Brendan H. Lee, Hane Lee, Roy Levitt, Richard A. Lewis, Sharyn A. Lincoln, Pengfei Liu, Xue Zhong Liu, Nicola Longo, Sandra K. Loo, Joseph Loscalzo, Richard L. Maas, John MacDowall, Calum A. MacRae, Ellen F. Macnamara, Valerie V. Maduro, Marta M. Majcherska, Bryan C. Mak, May Christine V. Malicdan, Laura A. Mamounas, Teri A. Manolio, Rong Mao, Kenneth Maravilla, Thomas C. Markello, Ronit Marom, Gabor Marth, Beth A. Martin, Martin G. Martin, Shruti Marwaha, Jacob McCauley, Allyn McConkie-Rosell, Colleen E. McCormack, Alexa T. McCray, Elisabeth McGee, Heather Mefford, J. Lawrence Merritt, Matthew Might, Ghayda Mirzaa, Eva Morava, Paolo M. Moretti, Paolo Moretti, Deborah Mosbrook-Davis, John J. Mulvihill, David R. Murdock, Anna Nagy, Mariko Nakano-Okuno, Avi Nath, John H. Newman, Sarah K. Nicholas, Deborah Nickerson, Shirley Nieves-Rodriguez, Donna Novacic, Devin Oglesbee, James P. Orengo, Laura Pace, Stephen Pak, J. Carl Pallais, Jeanette C. Papp, Neil H. Parker, John A. Phillips, Jennifer E. Posey, Lorraine Potocki, Bradley Power, Barbara N. Pusey, Aaron Quinlan, Archana N. Raja, Deepak A. Rao, Wendy Raskind, Genecee Renteria, Chloe M. Reuter, Lynette Rives, Amy K. Robertson, Lance H. Rodan, Natalie Rosenwasser, Francis Rossignol, Maura Ruzhnikov, Ralph Sacco, Jacinda B. Sampson, Susan L. Samson, Mario Saporta, Judy Schaechter, Timothy Schedl, Kelly Schoch, C. Ron Scott, Daryl A. Scott, Vandana Shashi, Jimann Shin, Edwin K. Silverman, Janet S. Sinsheimer, Kathy Sisco, Edward C. Smith, Kevin S. Smith, Emily Solem, Lilianna Solnica-Krezel, null Ben Solomon, Rebecca C. Spillmann, Joan M. Stoler, Jennifer A. Sullivan, Kathleen Sullivan, Angela Sun, Shirley Sutton, David A. Sweetser, Virginia Sybert, Holly K. Tabor, Amelia L.M. Tan, Queenie K.-G. Tan, Mustafa Tekin, Fred Telischi, Willa Thorson, Audrey Thurm, Cynthia J. Tifft, Camilo Toro, Alyssa A. Tran, Brianna M. Tucker, Tiina K. Urv, Adeline Vanderver, Matt Velinder, Dave Viskochil, Tiphanie P. Vogel, Colleen E. Wahl, Melissa Walker, Stephanie Wallace, Nicole M. Walley, Chris A. Walsh, Jennifer Wambach, Jijun Wan, Lee-kai Wang, Michael F. Wangler, Patricia A. Ward, Daniel Wegner, Mark Wener, Tara Wenger, Katherine Wesseling Perry, Monte Westerfield, Matthew T. Wheeler, Jordan Whitlock, Lynne A. Wolfe, Jeremy D. Woods, Shinya Yamamoto, John Yang, Muhammad Yousef, Diane B. Zastrow, Wadih Zein, Chunli Zhao, Stephan Zuchner, Marisa V. Andrews, Dorothy K. Grange, Rebecca Willaert, Richard Person, Aida Telegrafi, Aaron Sievers, Magdalena Laugsch, Susanne Theiß, YuZhu Cheng, Olivier Lichtarge, Panagiotis Katsonis, Amber Stocco, and Christian P. Schaaf
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0301 basic medicine ,Apraxias ,Autism Spectrum Disorder ,Pain ,Biology ,Apraxia ,Article ,03 medical and health sciences ,0302 clinical medicine ,Neurodevelopmental disorder ,Pregnancy ,Intellectual Disability ,Intellectual disability ,medicine ,Humans ,Missense mutation ,Global developmental delay ,Genetics (clinical) ,Genetics ,medicine.disease ,Phenotype ,Human genetics ,030104 developmental biology ,Neurodevelopmental Disorders ,Autism spectrum disorder ,Cyclic AMP-Dependent Protein Kinase RIbeta Subunit ,Female ,030217 neurology & neurosurgery - Abstract
Purpose We characterize the clinical and molecular phenotypes of six unrelated individuals with intellectual disability and autism spectrum disorder who carry heterozygous missense variants of the PRKAR1B gene, which encodes the R1β subunit of the cyclic AMP-dependent protein kinase A (PKA). Methods Variants of PRKAR1B were identified by single- or trio-exome analysis. We contacted the families and physicians of the six individuals to collect phenotypic information, performed in vitro analyses of the identified PRKAR1B-variants, and investigated PRKAR1B expression during embryonic development. Results Recent studies of large patient cohorts with neurodevelopmental disorders found significant enrichment of de novo missense variants in PRKAR1B. In our cohort, de novo origin of the PRKAR1B variants could be confirmed in five of six individuals, and four carried the same heterozygous de novo variant c.1003C>T (p.Arg335Trp; NM_001164760). Global developmental delay, autism spectrum disorder, and apraxia/dyspraxia have been reported in all six, and reduced pain sensitivity was found in three individuals carrying the c.1003C>T variant. PRKAR1B expression in the brain was demonstrated during human embryonal development. Additionally, in vitro analyses revealed altered basal PKA activity in cells transfected with variant-harboring PRKAR1B expression constructs. Conclusion Our study provides strong evidence for a PRKAR1B-related neurodevelopmental disorder.
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- 2021
29. Low-current Spin Transfer Torque MRAM.
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Guohan Hu, J. J. Nowak, G. Lauer, J. H. Lee, J. Z. Sun, J. Harms, Anthony J. Annunziata, S. Brown, W. Chen, Y. H. Kim, N. Marchack, S. Murthy, Chandrasekharan Kothandaraman, Eugene J. O'Sullivan, J. H. Park, M. Reuter, R. P. Robertazzi, Philip Louis Trouilloud, Y. Zhu, and Daniel Christopher Worledge
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- 2017
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30. Consistent satellite XCO2 retrievals from SCIAMACHY and GOSAT using the BESD algorithm
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J. Heymann, M. Reuter, M. Hilker, M. Buchwitz, O. Schneising, H. Bovensmann, J. P. Burrows, A. Kuze, H. Suto, N. M. Deutscher, M. K. Dubey, D. W. T. Griffith, F. Hase, S. Kawakami, R. Kivi, I. Morino, C. Petri, C. Roehl, M. Schneider, V. Sherlock, R. Sussmann, V. A. Velazco, T. Warneke, and D. Wunch
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Environmental engineering ,TA170-171 ,Earthwork. Foundations ,TA715-787 - Abstract
Consistent and accurate long-term data sets of global atmospheric concentrations of carbon dioxide (CO2) are required for carbon cycle and climate-related research. However, global data sets based on satellite observations may suffer from inconsistencies originating from the use of products derived from different satellites as needed to cover a long enough time period. One reason for inconsistencies can be the use of different retrieval algorithms. We address this potential issue by applying the same algorithm, the Bremen Optimal Estimation DOAS (BESD) algorithm, to different satellite instruments, SCIAMACHY on-board ENVISAT (March 2002–April 2012) and TANSO-FTS on-board GOSAT (launched in January 2009), to retrieve XCO2, the column-averaged dry-air mole fraction of CO2. BESD has been initially developed for SCIAMACHY XCO2 retrievals. Here, we present the first detailed assessment of the new GOSAT BESD XCO2 product. GOSAT BESD XCO2 is a product generated and delivered to the MACC project for assimilation into ECMWF's Integrated Forecasting System. We describe the modifications of the BESD algorithm needed in order to retrieve XCO2 from GOSAT and present detailed comparisons with ground-based observations of XCO2 from the Total Carbon Column Observing Network (TCCON). We discuss detailed comparison results between all three XCO2 data sets (SCIAMACHY, GOSAT and TCCON). The comparison results demonstrate the good consistency between SCIAMACHY and GOSAT XCO2. For example, we found a mean difference for daily averages of −0.60 ± 1.56 ppm (mean difference ± standard deviation) for GOSAT–SCIAMACHY (linear correlation coefficient r=0.82), −0.34 ± 1.37 ppm (r = 0.86) for GOSAT–TCCON and 0.10 ± 1.79 ppm (r = 0.75) for SCIAMACHY–TCCON. The remaining differences between GOSAT and SCIAMACHY are likely due to non-perfect collocation (± 2 h, 10° x 10° around TCCON sites), i.e. the observed air masses are not exactly identical but likely also due to a still non-perfect BESD retrieval algorithm, which will be continuously improved in the future. Our overarching goal is to generate a satellite-derived XCO2 data set appropriate for climate and carbon cycle research covering the longest possible time period. We therefore also plan to extend the existing SCIAMACHY and GOSAT data set discussed here by also using data from other missions (e.g. OCO-2, GOSAT-2, CarbonSat) in the future.
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- 2015
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31. The greenhouse gas project of ESA’s climate change initiative (GHG-CCI): overview, achievements and future plans
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M. Buchwitz, M. Reuter, O. Schneising, H. Boesch, I. Aben, M. Alexe, R. Armante, P. Bergamaschi, H. Bovensmann, D. Brunner, B. Buchmann, J. P. Burrows, A. Butz, F. Chevallier, A. Chédin, C. D. Crevoisier, S. Gonzi, M. De Mazière, E. De Wachter, R. Detmers, B. Dils, C. Frankenberg, P. Hahne, O. P. Hasekamp, W. Hewson, J. Heymann, S. Houweling, M. Hilker, T. Kaminski, G. Kuhlmann, A. Laeng, T. T. v. Leeuwen, G. Lichtenberg, J. Marshall, S. Noël, J. Notholt, P. Palmer, R. Parker, M. Scholze, G. P. Stiller, T. Warneke, and C. Zehner
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Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Applied optics. Photonics ,TA1501-1820 - Abstract
The GHG-CCI project (http://www.esa-ghg-cci.org/) is one of several projects of the European Space Agency’s (ESA) Climate Change Initiative (CCI). The goal of the CCI is to generate and deliver data sets of various satellite-derived Essential Climate Variables (ECVs) in line with GCOS (Global Climate Observing System) requirements. The “ECV Greenhouse Gases” (ECV GHG) is the global distribution of important climate relevant gases – namely atmospheric CO2 and CH4 - with a quality sufficient to obtain information on regional CO2 and CH4 sources and sinks. The main goal of GHG-CCI is to generate long-term highly accurate and precise time series of global near-surface-sensitive satellite observations of CO2 and CH4, i.e., XCO2 and XCH4, starting with the launch of ESA’s ENVISAT satellite. These products are currently retrieved from SCIAMACHY/ENVISAT (2002-2012) and TANSO-FTS/GOSAT (2009-today) nadir mode observations in the near-infrared/shortwave-infrared spectral region. In addition, other sensors (e.g., IASI and MIPAS) and viewing modes (e.g., SCIAMACHY solar occultation) are also considered and in the future also data from other satellites. The GHG-CCI data products and related documentation are freely available via the GHG-CCI website and yearly updates are foreseen. Here we present an overview about the latest data set (Climate Research Data Package No. 2 (CRDP#2)) and summarize key findings from using satellite CO2 and CH4 retrievals to improve our understanding of the natural and anthropogenic sources and sinks of these important atmospheric greenhouse gases. We also shortly mention ongoing activities related to validation and initial user assessment of CRDP#2 and future plans.
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- 2015
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32. Increase in Mental Disorders During the COVID-19 Pandemic - Role of Occupational & Financial Strains
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N Dragano, M Reuter, A Peters, B Schmidt, B Bohn, and K Berger
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Public Health, Environmental and Occupational Health - Abstract
Background Numerous studies reported an increase in mental disorders during the COVID-19 pandemic, but the specific causes for this increase are unclear. We therefore investigate whether pandemic-related occupational and financial changes (e.g., reduced working hours, working from home, financial losses) were associated with increased symptoms of depression and anxiety compared with the situation before the pandemic. Methods We analyzed data from the German National Cohort Study (NAKO). Between May and November 2020, 161,849 participants answered questions on their mental state and social circumstances. Responses were compared with data from the baseline survey before the pandemic (2014-2019). Linear fixed-effects models were used to determine whether individual changes in the symptoms of depression (PHQ-9) or anxiety (GAD-7) were associated with occupational/financial changes (controlling for covariates). Results A pronounced increase in symptoms was observed among those who became unemployed during the pandemic (+ 1.16 points on the depression scale, 95% confidence interval [0.91; 1.41], range 0-27). Increases were also seen for reduced working hours without short-term working allowance, increased working hours, working from home, insecurity regarding employment, and financial strain. The deterioration in mental health was largely statistically explained by the occupational and financial changes investigated in the model. Conclusions Depressive symptoms and anxiety disorders increased in the study population during the first year of the COVID-19 pandemic and occupational and financial difficulties were an essential contributory factor. These strains should be taken into account both in the care of individual patients and in the planning of targeted prevention measures. Results suggest that welfare state benefits such as short-time allowance in times of crises may reduce mental load in affected populations.
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- 2022
33. A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder
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Suma P. Shankar, Kristin Grimsrud, Louise Lanoue, Alena Egense, Brandon Willis, Johanna Hörberg, Lama AlAbdi, Klaus Mayer, Koray Ütkür, Kristin G. Monaghan, Joel Krier, Joan Stoler, Maha Alnemer, Prabhu R. Shankar, Raffael Schaffrath, Fowzan S. Alkuraya, Ulrich Brinkmann, Leif A. Eriksson, Kent Lloyd, Katherine A. Rauen, Maria T. Acosta, Margaret Adam, David R. Adams, Justin Alvey, Laura Amendola, Ashley Andrews, Euan A. Ashley, Mahshid S. Azamian, Carlos A. Bacino, Guney Bademci, Ashok Balasubramanyam, Dustin Baldridge, Jim Bale, Michael Bamshad, Deborah Barbouth, Pinar Bayrak-Toydemir, Anita Beck, Alan H. Beggs, Edward Behrens, Gill Bejerano, Jimmy Bennet, Beverly Berg-Rood, Jonathan A. Bernstein, Gerard T. Berry, Anna Bican, Stephanie Bivona, Elizabeth Blue, John Bohnsack, Devon Bonner, Lorenzo Botto, Brenna Boyd, Lauren C. Briere, Elly Brokamp, Gabrielle Brown, Elizabeth A. Burke, Lindsay C. Burrage, Manish J. Butte, Peter Byers, William E. Byrd, John Carey, Olveen Carrasquillo, Thomas Cassini, Ta Chen Peter Chang, Sirisak Chanprasert, Hsiao-Tuan Chao, Gary D. Clark, Terra R. Coakley, Laurel A. Cobban, Joy D. Cogan, Matthew Coggins, F. Sessions Cole, Heather A. Colley, Cynthia M. Cooper, Heidi Cope, William J. Craigen, Andrew B. Crouse, Michael Cunningham, Precilla D'Souza, Hongzheng Dai, Surendra Dasari, Joie Davis, Jyoti G. Dayal, Matthew Deardorff, Esteban C. Dell'Angelica, Katrina Dipple, Daniel Doherty, Naghmeh Dorrani, Argenia L. Doss, Emilie D. Douine, Laura Duncan, Dawn Earl, David J. Eckstein, Lisa T. Emrick, Christine M. Eng, Cecilia Esteves, Marni Falk, Liliana Fernandez, Elizabeth L. Fieg, Paul G. Fisher, Brent L. Fogel, Irman Forghani, William A. Gahl, Ian Glass, Bernadette Gochuico, Rena A. Godfrey, Katie Golden-Grant, Madison P. Goldrich, Alana Grajewski, Irma Gutierrez, Don Hadley, Sihoun Hahn, Rizwan Hamid, Kelly Hassey, Nichole Hayes, Frances High, Anne Hing, Fuki M. Hisama, Ingrid A. Holm, Jason Hom, Martha Horike-Pyne, Alden Huang, Yong Huang, Wendy Introne, Rosario Isasi, Kosuke Izumi, Fariha Jamal, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Orpa Jean-Marie, Vaidehi Jobanputra, Lefkothea Karaviti, Jennifer Kennedy, Shamika Ketkar, Dana Kiley, Gonench Kilich, Shilpa N. Kobren, Isaac S. Kohane, Jennefer N. Kohler, Deborah Krakow, Donna M. Krasnewich, Elijah Kravets, Susan Korrick, Mary Koziura, Seema R. Lalani, Byron Lam, Christina Lam, Grace L. LaMoure, Brendan C. Lanpher, Ian R. Lanza, Kimberly LeBlanc, Brendan H. Lee, Roy Levitt, Richard A. Lewis, Pengfei Liu, Xue Zhong Liu, Nicola Longo, Sandra K. Loo, Joseph Loscalzo, Richard L. Maas, Ellen F. Macnamara, Calum A. MacRae, Valerie V. Maduro, Bryan C. Mak, May Christine V. Malicdan, Laura A. Mamounas, Teri A. Manolio, Rong Mao, Kenneth Maravilla, Ronit Marom, Gabor Marth, Beth A. Martin, Martin G. Martin, Julian A. Martínez-Agosto, Shruti Marwaha, Jacob McCauley, Allyn McConkie-Rosell, Alexa T. McCray, Elisabeth McGee, Heather Mefford, J. Lawrence Merritt, Matthew Might, Ghayda Mirzaa, Eva Morava, Paolo M. Moretti, Mariko Nakano-Okuno, Stan F. Nelson, John H. Newman, Sarah K. Nicholas, Deborah Nickerson, Shirley Nieves-Rodriguez, Donna Novacic, Devin Oglesbee, James P. Orengo, Laura Pace, Stephen Pak, J. Carl Pallais, Christina G.S. Palmer, Jeanette C. Papp, Neil H. Parker, John A. Phillips, Jennifer E. Posey, Lorraine Potocki, Barbara N. Pusey, Aaron Quinlan, Wendy Raskind, Archana N. Raja, Deepak A. Rao, Anna Raper, Genecee Renteria, Chloe M. Reuter, Lynette Rives, Amy K. Robertson, Lance H. Rodan, Jill A. Rosenfeld, Natalie Rosenwasser, Francis Rossignol, Maura Ruzhnikov, Ralph Sacco, Jacinda B. Sampson, Mario Saporta, C. Ron Scott, Judy Schaechter, Timothy Schedl, Kelly Schoch, Daryl A. Scott, Vandana Shashi, Jimann Shin, Edwin K. Silverman, Janet S. Sinsheimer, Kathy Sisco, Edward C. Smith, Kevin S. Smith, Emily Solem, Lilianna Solnica-Krezel, Ben Solomon, Rebecca C. Spillmann, Joan M. Stoler, Jennifer A. Sullivan, Kathleen Sullivan, Angela Sun, Shirley Sutton, David A. Sweetser, Virginia Sybert, Holly K. Tabor, Amelia L.M. Tan, K.-G. Queenie, Tan, Mustafa Tekin, Fred Telischi, Willa Thorson, Cynthia J. Tifft, Camilo Toro, Alyssa A. Tran, Brianna M. Tucker, Tiina K. Urv, Adeline Vanderver, Matt Velinder, Dave Viskochil, Tiphanie P. Vogel, Colleen E. Wahl, Stephanie Wallace, Nicole M. Walley, Melissa Walker, Jennifer Wambach, Jijun Wan, Lee-kai Wang, Michael F. Wangler, Patricia A. Ward, Daniel Wegner, Monika Weisz-Hubshman, Mark Wener, Tara Wenger, Katherine Wesseling Perry, Monte Westerfield, Matthew T. Wheeler, Jordan Whitlock, Lynne A. Wolfe, Kim Worley, Changrui Xiao, Shinya Yamamoto, John Yang, Diane B. Zastrow, Zhe Zhang, Chunli Zhao, Stephan Zuchner, Hugo Bellen, and Rachel Mahoney
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Adenosine Diphosphate ,Mice, Inbred C57BL ,Mice ,Saccharomyces cerevisiae Proteins ,Neurodevelopmental Disorders ,Animals ,Humans ,Histidine ,Methyltransferases ,Saccharomyces cerevisiae ,Syndrome ,Genetics (clinical) ,Article - Abstract
Diphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs).Molecular testing was performed using exome or genome sequencing. A targeted Dph5 knockin mouse (C57BL/6Ncrl-Dph5DPH5 variants p.His260Arg (homozygous), p.Asn110Ser and p.Arg207Ter (heterozygous), and p.Asn174LysfsTer10 (homozygous) were identified in 3 unrelated families with distinct overlapping craniofacial features, profound NDDs, multisystem abnormalities, and miscarriages. Dph5 p.His260Arg homozygous knockin was embryonically lethal with only 1 subviable mouse exhibiting impaired growth, craniofacial dysmorphology, and multisystem dysfunction recapitulating the human phenotype. Adenosine diphosphate-ribosylation assays showed absent to decreased function in DPH5-knockout human and yeast cells. In silico modeling of the variants showed altered DPH5 structure and disruption of its interaction with eEF2.We provide strong clinical, biochemical, and functional evidence for DPH5 as a novel cause of embryonic lethality or profound NDDs with multisystem involvement and expand diphthamide-deficiency syndromes and ribosomopathies.
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- 2022
34. Socioeconomic position and self-rated health among adolescents: the mediating role of the family
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P Rattay, M Blume, J Spallek, S Hoffmann, L Sander, R Herr, M Herke, M Reuter, A Novelli, and C Hövener
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Public Health, Environmental and Occupational Health - Abstract
Background Although health inequalities in adolescence are well documented, the underlying mechanisms remain unclear. Few studies have examined the role of the family in explaining adolescents’ health inequalities. The study aimed to explore whether the association between socioeconomic position and self-rated health (SRH) was mediated by familial determinants. Methods Using data from wave 2 of the KiGGS study (1,838 female and 1,718 male 11- to 17-year-olds), linear regression analyses were conducted to decompose the total effects of parents’ education, occupation, income, socioeconomic position index, and adolescents’ subjective social status on SRH into direct effects and indirect effects through familial determinants (family cohesion, parenting styles, parental well-being, stress, obesity, smoking and sporting activity). Results A significant total effect of all socioeconomic position indicators on SRH was found, except for income in male adolescents. In female adolescents, more than 70% of the total effects of each socioeconomic position indicator were explained by familial mediators, whereas no significant direct effects remained. The most important mediator was parental well-being, followed by family cohesion, parental smoking and sporting activity. In male adolescents, the associations of parental education, the socioeconomic position index and subjective social status with SRH were also mediated by familial determinants (family cohesion, parental smoking and obesity). However, a significant direct effect of subjective social status remained. Conclusions The family appears to play an important role in explaining health inequalities, particularly in female adolescents. Reducing health inequalities in adolescence requires policy interventions, community-based strategies, as well as programs to improve parenting and family functioning.
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- 2022
35. The impact of the school-to-work transition on self-rated health & subjective well-being in Germany
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M Reuter, M Herke, M Richter, K Diehl, S Hoffmann, CR Pischke, and N Dragano
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Public Health, Environmental and Occupational Health - Abstract
Background During the school-to-work transition (STWT), young people enter different states as vocational training, university or unemployment that may have immediate or long-term effects on health. Since research has not paid much attention to this, we investigate the development of self-rated health (SRH) and subjective well-being (SWB) during the STWT. Methods We used data from Starting Cohort 4 of the German National Educational Panel Study (NEPS), a nationally representative cohort of 11,098 ninth graders (50.5% girls) followed over nine years. Linear panel regression analysis with fixed-effects (FE) was used to explore intra-individual changes in SRH and SWB when moving between different STWT states (school, prevocational program, vocational training, university, employment, unemployment, inactivity). FE impact functions were used to compare trajectories of SRH and SWB by states reached after school-leave. Time-varying control variables were age, household composition, and residential area. Results School-leave was linked to increases in SRH and SWB, whereas no impact was found for job entry after vocational training or university. Upward transitions (e.g. from a prevocational program to vocational training, from vocational training to university or from unemployment to employment) increased SRH or SWB, while downward transitions (e.g. from vocational training or employment to unemployment) were related to decreases. Over the years after school-leave, we found a decline in SRH and SWB, which was faster in case of transitions to unemployment or prevocational programs directly after school. Conclusions Findings suggest that a smooth STWT is key for good health in youth and adulthood. Health and labour market intervention programs should focus on the time after school-leave, especially on those who are not able to find an academic or vocational training position.
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- 2022
36. Whole-genome RNA sequencing identifies distinct transcriptomic profiles in impingement cartilage between patients with femoroacetabular impingement and hip osteoarthritis
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Benjamin D. Kuhns, John M. Reuter, Victoria L. Hansen, Gillian L. Soles, Jennifer H. Jonason, Cheryl L. Ackert‐Bicknell, Chia‐Lung Wu, and Brian D. Giordano
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Orthopedics and Sports Medicine ,Article - Abstract
Femoroacetabular impingement (FAI) has a strong clinical association with the development of hip osteoarthritis (OA); however, the pathobiological mechanisms underlying the transition from focal impingement to global joint degeneration remain poorly understood. The purpose of this study is to use whole-genome RNA sequencing to identify and subsequently validate differentially expressed genes (DEGs) in femoral head articular cartilage samples from patients with FAI and hip OA secondary to FAI. Thirty-seven patients were included in the study with whole-genome RNA sequencing performed on 10 gender-matched patients in the FAI and OA cohorts and the remaining specimens were used for validation analyses. We identified a total of 3531 DEGs between the FAI and OA cohorts with multiple targets for genes implicated in canonical OA pathways. Quantitative reverse transcription-polymerase chain reaction validation confirmed increased expression of FGF18 and WNT16 in the FAI samples, while there was increased expression of MMP13 and ADAMTS4 in the OA samples. Expression levels of FGF18 and WNT16 were also higher in FAI samples with mild cartilage damage compared to FAI samples with severe cartilage damage or OA cartilage. Our study further expands the knowledge regarding distinct genetic reprogramming in the cartilage between FAI and hip OA patients. We independently validated the results of the sequencing analysis and found increased expression of anabolic markers in patients with FAI and minimal histologic cartilage damage, suggesting that anabolic signaling may be increased in early FAI with a transition to catabolic and inflammatory gene expression as FAI progresses towards more severe hip OA. Clinical significance:Cam-type FAI has a strong clinical association with hip OA; however, the cellular pathophysiology of disease progression remains poorly understood. Several previous studies have demonstrated increased expression of inflammatory markers in FAI cartilage samples, suggesting the involvement of these inflammatory pathways in the disease progression. Our study further expands the knowledge regarding distinct genetic reprogramming in the cartilage between FAI and hip OA patients. In addition to differences in inflammatory gene expression, we also identified differential expression in multiple pathways involved in hip OA progression.
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- 2022
37. Wie wirkt sich die sozioökonomische Komposition der Schule auf Ungleichheiten im subjektiven Wohlbefinden von Schülerinnen und Schülern in Deutschland aus?
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M Herke, M Reuter, A Mayer, J Spallek, P Rattay, I Moor, and M Richter
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- 2022
38. Die Rolle der sozio-ökonomischen Position und des institutionellen Betreuungsumfeldes für die Gesundheit von Kindergartenkindern
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R Herr, A Mayer, E Wiedemann, K Diehl, F De Bock, M Blume, S Hoffmann, M Herke, M Reuter, I Iashchenko, and S Schneider
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- 2022
39. Der Einfluss des Übergangs von der Schule in den Beruf auf die Gesundheit und das Wohlbefinden junger Menschen in Deutschland
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M Reuter, M Herke, M Richter, K Diehl, S Hoffmann, CR Pischke, and N Dragano
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- 2022
40. Increases in health problems during the first pandemic wave – An analysis of occupational differences based on the German National Cohort (NAKO)
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M Rigó, N Dragano, M Formazin, F Liebers, U Latza, and M Reuter
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- 2022
41. Regional disparities in SARS-CoV-2 infections by labour market indicators: a spatial panel analysis using nationwide German notification data
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M Wahrendorf, M Reuter, J Hoebel, B Wachtler, A Hoehmann, and N Dragano
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- 2022
42. Outcome of immuncheckpoint inhibitor therapy in adrenocortical carcinoma - A multicenter retrospective study
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H, Remde, primary, L, Schmidt-Pennington, additional, M, Reuter, additional, L, Landwehr, additional, M, Jensen, additional, H, Lahner, additional, K, Laubner, additional, J, Schreiner, additional, J, Bojunga, additional, S, Kircher, additional, A, Pohrt, additional, M., V. Teleanu, additional, D, Hubschmann, additional, A, Stenzinger, additional, H, Glimm, additional, S, Frohling, additional, M, Fassnacht, additional, K, Mai, additional, and M., Kroiss, additional
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- 2022
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43. Satellite-inferred European carbon sink larger than expected
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M. Reuter, M. Buchwitz, M. Hilker, J. Heymann, O. Schneising, D. Pillai, H. Bovensmann, J. P. Burrows, H. Bösch, R. Parker, A. Butz, O. Hasekamp, C. W. O'Dell, Y. Yoshida, C. Gerbig, T. Nehrkorn, N. M. Deutscher, T. Warneke, J. Notholt, F. Hase, R. Kivi, R. Sussmann, T. Machida, H. Matsueda, and Y. Sawa
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Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Current knowledge about the European terrestrial biospheric carbon sink, from the Atlantic to the Urals, relies upon bottom-up inventory and surface flux inverse model estimates (e.g. 0.27±0.16 GtC a−1 for 2000–2005 (Schulze et al., 2009), 0.17±0.44 GtC a−1 for 2001–2007 (Peters et al., 2010), 0.45±0.40 GtC a−1 for 2010 (Chevallier et al., 2014), 0.40±0.42 GtC a−1 for 2001–2004 (Peylin et al., 2013)). Inverse models assimilate in situ CO2 atmospheric concentrations measured by surface-based air sampling networks. The intrinsic sparseness of these networks is one reason for the relatively large flux uncertainties (Peters et al., 2010; Bruhwiler et al., 2011). Satellite-based CO2 measurements have the potential to reduce these uncertainties (Miller et al., 2007; Chevallier et al., 2007). Global inversion experiments using independent models and independent GOSAT satellite data products consistently derived a considerably larger European sink (1.0–1.3 GtC a−1 for 09/2009–08/2010 (Basu et al., 2013), 1.2–1.8 GtC a−1 in 2010 (Chevallier et al., 2014)). However, these results have been considered unrealistic due to potential retrieval biases and/or transport errors (Chevallier et al., 2014) or have not been discussed at all (Basu et al., 2013; Takagi et al., 2014). Our analysis comprises a regional inversion approach using STILT (Gerbig et al., 2003; Lin et al., 2003) short-range (days) particle dispersion modelling, rendering it insensitive to large-scale retrieval biases and less sensitive to long-range transport errors. We show that the satellite-derived European terrestrial carbon sink is indeed much larger (1.02±0.30 GtC a−1 in 2010) than previously expected. This is qualitatively consistent among an ensemble of five different inversion set-ups and five independent satellite retrievals (BESD (Reuter et al., 2011) 2003–2010, ACOS (O’Dell et al., 2012) 2010, UoL-FP (Cogan et al., 2012) 2010, RemoTeC (Butz et al., 2011) 2010, and NIES (Yoshida et al., 2013) 2010) using data from two different instruments (SCIAMACHY (Bovensmann et al., 1999) and GOSAT (Kuze et al., 2009)). The difference to in situ based inversions (Peylin et al., 2013), whilst large with respect to the mean reported European carbon sink (0.4 GtC a−1 for 2001–2004), is similar in magnitude to the reported uncertainty (0.42 GtC a−1). The highest gain in information is obtained during the growing season when satellite observation conditions are advantageous, a priori uncertainties are largest, and the surface sink maximises; during the dormant season, the results are dominated by the a priori. Our results provide evidence that the current understanding of the European carbon sink has to be revisited.
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- 2014
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44. Impact of sarcopenia in advanced and metastatic soft tissue sarcoma
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Christoph W. M. Reuter, Hendrik Eggers, Dennis Strassmann, Katharina Stange, Bennet Hensen, Patrick Zardo, Mohamed Omar, Hans Christiansen, Arnold Ganser, Florian Länger, Viktor Grünwald, Frank Wacker, and Philipp Ivanyi
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Sarcopenia ,Survival ,Medizin ,Soft Tissue Neoplasms ,Body composition ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,Internal medicine ,medicine ,Clinical endpoint ,Overall survival ,Humans ,Progression-free survival ,Retrospective Studies ,Soft tissue sarcoma ,Skeletal muscle index ,Smi ,Medical treatment ,business.industry ,Proportional hazards model ,Neoplasms, Second Primary ,Sarcoma ,Hematology ,General Medicine ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Surgery ,Original Article ,business - Abstract
Introduction Advanced or metastatic soft tissue sarcoma (a/mSTS) is associated with a dismal prognosis. Patient counseling on treatment aggressiveness is pivotal to avoid over- or undertreatment. Recently, evaluation of body composition markers like the skeletal muscle index (SMI) became focus of interest in a variety of cancers. This study focuses on the prognostic impact of SMI in a/mSTS, retrospectively. Methods 181 a/mSTS patients were identified, 89 were eligible due to prespecified criteria for SMI assessment. Baseline CT-Scans were analyzed using an institutional software solution. Sarcopenia defining cut-off values for the SMI were established by optimal fitting method. Primary end point was overall survival (OS) and secondary endpoints were progression free survival (PFS), disease control rate (DCR), overall response rate (ORR). Descriptive statistics as well as Kaplan Meier- and Cox regression analyses were administered. Results 28/89 a/mSTS patients showed sarcopenia. Sarcopenic patients were significantly older, generally tended to receive less multimodal therapies (62 vs. 57 years, P = 0.025; respectively median 2.5 vs. 4, P = 0.132) and showed a significantly lower median OS (4 months [95%CI 1.9–6.0] vs. 16 months [95%CI 8.8–23.2], Log-rank P = 0.002). Sarcopenia was identified as independent prognostic parameter of impaired OS (HR 2.40 [95%-CI 1.4–4.0], P P = 0.032). Conclusion This study identifies sarcopenia as a prognostic parameter in a/mSTS. Further on, the data suggest that sarcopenia shows a trend of being associated with first line therapy response. SMI is a promising prognostic parameter, which needs further validation.
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- 2021
45. Commonalities across computational workflows for uncovering explanatory variants in undiagnosed cases
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Shilpa Nadimpalli Kobren, Dustin Baldridge, Matt Velinder, Joel B. Krier, Kimberly LeBlanc, Cecilia Esteves, Barbara N. Pusey, Stephan Züchner, Elizabeth Blue, Hane Lee, Alden Huang, Lisa Bastarache, Anna Bican, Joy Cogan, Shruti Marwaha, Anna Alkelai, David R. Murdock, Pengfei Liu, Daniel J. Wegner, Alexander J. Paul, Maria T. Acosta, Margaret Adam, David R. Adams, Pankaj B. Agrawal, Mercedes E. Alejandro, Justin Alvey, Laura Amendola, Ashley Andrews, Euan A. Ashley, Mahshid S. Azamian, Carlos A. Bacino, Guney Bademci, Eva Baker, Ashok Balasubramanyam, Jim Bale, Michael Bamshad, Deborah Barbouth, Pinar Bayrak-Toydemir, Anita Beck, Alan H. Beggs, Edward Behrens, Gill Bejerano, Jimmy Bennett, Beverly Berg-Rood, Jonathan A. Bernstein, Gerard T. Berry, Stephanie Bivona, John Bohnsack, Carsten Bonnenmann, Devon Bonner, Lorenzo Botto, Brenna Boyd, Lauren C. Briere, Elly Brokamp, Gabrielle Brown, Elizabeth A. Burke, Lindsay C. Burrage, Manish J. Butte, Peter Byers, William E. Byrd, John Carey, Olveen Carrasquillo, Ta Chen Peter Chang, Sirisak Chanprasert, Hsiao-Tuan Chao, Gary D. Clark, Terra R. Coakley, Laurel A. Cobban, Joy D. Cogan, Matthew Coggins, F. Sessions Cole, Heather A. Colley, Cynthia M. Cooper, Heidi Cope, William J. Craigen, Andrew B. Crouse, Michael Cunningham, Precilla D’Souza, Hongzheng Dai, Surendra Dasari, Joie Davis, Jyoti G. Daya, Matthew Deardorff, Esteban C. Dell’Angelica, Shweta U. Dhar, Katrina Dipple, Daniel Doherty, Naghmeh Dorrani, Argenia L. Doss, Emilie D. Douine, David D. Draper, Laura Duncan, Dawn Earl, David J. Eckstein, Lisa T. Emrick, Christine M. Eng, Marni Falk, Liliana Fernandez, Carlos Ferreira, Elizabeth L. Fieg, Laurie C. Findley, Paul G. Fisher, Brent L. Fogel, Irman Forghani, Laure Fresard, William A. Gahl, Ian Glass, Bernadette Gochuico, Rena A. Godfrey, Katie Golden-Grant, Alica M. Goldman, Madison P. Goldrich, David B. Goldstein, Alana Grajewski, Catherine A. Groden, Irma Gutierrez, Sihoun Hahn, Rizwan Hamid, Neil A. Hanchard, Kelly Hassey, Nichole Hayes, Frances High, Anne Hing, Fuki M. Hisama, Ingrid A. Holm, Jason Hom, Martha Horike-Pyne, Yong Huang, Laryssa Huryn, Rosario Isasi, Fariha Jamal, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Lefkothea Karaviti, Jennifer Kennedy, Dana Kiley, Isaac S. Kohane, Jennefer N. Kohler, Susan Korrick, Mary Kozuira, Deborah Krakow, Donna M. Krasnewich, Elijah Kravets, Grace L. LaMoure, Seema R. Lalani, Byron Lam, Christina Lam, Brendan C. Lanpher, Ian R. Lanza, Lea Latham, Brendan H. Lee, Roy Levitt, Richard A. Lewis, Sharyn A. Lincoln, Xue Zhong Liu, Nicola Longo, Sandra K. Loo, Joseph Loscalzo, Richard L. Maas, John MacDowall, Calum A. MacRae, Ellen F. Macnamara, Valerie V. Maduro, Marta M. Majcherska, Bryan C. Mak, May Christine V. Malicdan, Laura A. Mamounas, Teri A. Manolio, Rong Mao, Kenneth Maravilla, Thomas C. Markello, Ronit Marom, Gabor Marth, Beth A. Martin, Martin G. Martin, Julian A. Martinez-Agosto, Jacob McCauley, Allyn McConkie-Rosell, Colleen E. McCormack, Alexa T. McCray, Elisabeth McGee, Heather Mefford, J. Lawrence Merritt, Matthew Might, Ghayda Mirzaa, Eva Morava, Paolo M. Moretti, Paolo Moretti, Deborah Mosbrook-Davis, John J. Mulvihill, Anna Nagy, Mariko Nakano-Okuno, Avi Nath, Stanley F. Nelson, John H. Newman, Sarah K. Nicholas, Deborah Nickerson, Shirley Nieves-Rodriguez, Donna Novacic, Devin Oglesbee, James P. Orengo, Laura Pace, Stephen Pak, J. Carl Pallais, Christina G.S. Palmer, Jeanette C. Papp, Neil H. Parker, John A. Phillips, Jennifer E. Posey, Lorraine Potocki, Bradley Power, Aaron Quinlan, Archana N. Raja, Deepak A. Rao, Wendy Raskind, Genecee Renteria, Chloe M. Reuter, Lynette Rives, Amy K. Robertson, Lance H. Rodan, Jill A. Rosenfeld, Natalie Rosenwasser, Francis Rossignol, Maura Ruzhnikov, Ralph Sacco, Jacinda B. Sampson, Susan L. Samson, Mario Saporta, Judy Schaechter, Timothy Schedl, Kelly Schoch, C. Ron Scott, Daryl A. Scott, Vandana Shashi, Jimann Shin, Rebecca H. Signer, Edwin K. Silverman, Janet S. Sinsheimer, Kathy Sisco, Edward C. Smith, Kevin S. Smith, Emily Solem, Lilianna Solnica-Krezel, null Ben Solomon, Rebecca C. Spillmann, Joan M. Stoler, Jennifer A. Sullivan, Kathleen Sullivan, Angela Sun, Shirley Sutton, David A. Sweetser, Virginia Sybert, Holly K. Tabor, Amelia L.M. Tan, Queenie K.-G. Tan, Mustafa Tekin, Fred Telischi, Willa Thorson, Audrey Thurm, Cynthia J. Tifft, Camilo Toro, Alyssa A. Tran, Brianna M. Tucker, Tiina K. Urv, Adeline Vanderver, Dave Viskochil, Tiphanie P. Vogel, Colleen E. Wahl, Melissa Walker, Stephanie Wallace, Nicole M. Walley, Chris A. Walsh, Jennifer Wambach, Jijun Wan, Lee-kai Wang, Michael F. Wangler, Patricia A. Ward, Daniel Wegner, Mark Wener, Tara Wenger, Katherine Wesseling Perry, Monte Westerfield, Matthew T. Wheeler, Jordan Whitlock, Lynne A. Wolfe, Jeremy D. Woods, Shinya Yamamoto, John Yang, Muhammad Yousef, Diane B. Zastrow, Wadih Zein, Chunli Zhao, Stephan Zuchner, and Shamil R. Sunyaev
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Prioritization ,Genome ,medicine.diagnostic_test ,Genomic sequencing ,Multimodal data ,Computational Biology ,Structural variant ,Genomics ,Undiagnosed Diseases ,Data science ,Shruti ,Article ,Workflow ,Biomedical data ,medicine ,Humans ,Genetic Testing ,Psychology ,Software ,Genetics (clinical) ,Genetic testing - Abstract
Author(s): Kobren, Shilpa Nadimpalli; Baldridge, Dustin; Velinder, Matt; Krier, Joel B; LeBlanc, Kimberly; Esteves, Cecilia; Pusey, Barbara N; Zuchner, Stephan; Blue, Elizabeth; Lee, Hane; Huang, Alden; Bastarache, Lisa; Bican, Anna; Cogan, Joy; Marwaha, Shruti; Alkelai, Anna; Murdock, David R; Liu, Pengfei; Wegner, Daniel J; Paul, Alexander J; Undiagnosed Diseases Network; Sunyaev, Shamil R; Kohane, Isaac S | Abstract: PurposeGenomic sequencing has become an increasingly powerful and relevant tool to be leveraged for the discovery of genetic aberrations underlying rare, Mendelian conditions. Although the computational tools incorporated into diagnostic workflows for this task are continually evolving and improving, we nevertheless sought to investigate commonalities across sequencing processing workflows to reveal consensus and standard practice tools and highlight exploratory analyses where technical and theoretical method improvements would be most impactful.MethodsWe collected details regarding the computational approaches used by a genetic testing laboratory and 11 clinical research sites in the United States participating in the Undiagnosed Diseases Network via meetings with bioinformaticians, online survey forms, and analyses of internal protocols.ResultsWe found that tools for processing genomic sequencing data can be grouped into four distinct categories. Whereas well-established practices exist for initial variant calling and quality control steps, there is substantial divergence across sites in later stages for variant prioritization and multimodal data integration, demonstrating a diversity of approaches for solving the most mysterious undiagnosed cases.ConclusionThe largest differences across diagnostic workflows suggest that advances in structural variant detection, noncoding variant interpretation, and integration of additional biomedical data may be especially promising for solving chronically undiagnosed cases.
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- 2021
46. Clinical efficacy and safety of intravenous ferric carboxymaltose treatment for restless legs symptoms and low serum ferritin in children with autism spectrum disorder
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Lourdes M. DelRosso, Lilith M. Reuter-Yuill, Yeilim Cho, Raffaele Ferri, Maria P. Mogavero, and Daniel L. Picchietti
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Male ,Treatment Outcome ,Autism Spectrum Disorder ,Child, Preschool ,Iron ,Restless Legs Syndrome ,Ferritins ,Humans ,Female ,General Medicine ,Child ,Ferric Compounds ,Retrospective Studies - Abstract
Restless legs syndrome (RLS) may be underdiagnosed in children with autism spectrum disorder (ASD) due to difficulty expressing the symptoms in their own words. In addition, administration of oral iron may be particularly difficult in children with ASD.This was a retrospective, open-label case series of children with ASD, restless legs (RL) symptoms, and serum ferritin30 μg/L, who either had failed or did not tolerate oral iron, and were subsequently treated with intravenous (IV) ferric carboxymaltose (FCM). Patients received a single dose of IV FCM, 15 mg/kg up to a maximum dose of 750 mg. Data collected pre- and eight weeks post-infusion included presenting symptoms, serum ferritin, iron profile, and Clinical Global Impression Scale (CGI-Severity pre- and CGI-Improvement post-infusion). Adverse effects were assessed.Nineteen children, 4-11 years old (12 male, median age 6, interquartile range (IQR 4-11) were included. A definite RLS diagnosis was identified in 6 verbal children (31.6%). RL symptoms (designated probable RLS) in the 13 other children met all RLS diagnostic criteria except "improvement of symptoms with movement," which was not definitively determined. Baseline median values were: ferritin 10 μg/L (IQR 10-16), iron 66.5 μg/dL (IQR 57-96), TIBC 382 μg/dL (IQR 360-411) and transferrin saturation 19% (IQR 14-28). Median CGI-S was 4 (moderate symptoms) (IQR 3-4). At eight weeks after IV FCM, all measures were improved. Median ferritin was 68 μg/L (IQR 62.5-109, p 0.00045). Median CGI-I was 1 (very much improved) (IQR 1-2). All children meeting definite RLS criteria improved. Three children in the probable RLS group did not improve. Children meeting the full RLS criteria had lower baseline ferritin levels than those with a probable diagnosis (9 μg/L, IQR 9-10 vs. 13 μg/L, IQR 10-16, Mann-Whitney test p 0.045). Adverse effects included lightheadedness, gastrointestinal discomfort, fever, and headache among others.The majority of children (84.2%) with ASD, restless legs symptoms, and serum ferritin30 μg/L had clinical improvement and significantly better serum iron parameters after a single IV FCM infusion. Although larger, randomized trials are needed, IV FCM appears to be a promising treatment for this subset of children with ASD.
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- 2022
47. Whole-Genome RNA Sequencing of Femoral Head Impingement Cartilage Identifies FGF18 As A Biomarker in Hip Osteoarthritis Progression
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Benjamin D. Kuhns, John M. Reuter, Victoria L. Hansen, Gillian Soles, Jennifer H. Jonason, Cheryl Ackert-Bicknell, Chia-Lung Wu, and Brian D. Giordano
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IntroductionThe natural history of Femoroacetabular Impingement (FAI) has been clinically associated with the development of hip osteoarthritis (OA); however, the pathobiological mechanisms underlying the transition from focal impingement to global joint degeneration remain unclear. The goal of the study was to investigate differences in transcriptomic profiles of the cartilage from FAI and hip OA patients using whole-genome RNA sequencing.MethodsThirty-seven patients were included in the study with 20 diagnosed with FAI undergoing arthroscopic treatment and 15 diagnosed with hip OA undergoing total hip arthroplasty (THA). Cartilage samples were obtained intraoperatively over the femoral head-neck junction for both FAI and OA cohorts. Whole-genome RNA sequencing was performed on 10 gender-matched patients in the FAI and OA cohorts with the remaining samples used for histopathologic analysis using the Osteoarthritis Research Society International (OARSI) grading system and qRT-PCR validation. Target validation was further confirmed with immunohistochemical staining for FGF18 on FAI and OA cartilage samples.ResultsWe identified a total of 3,531 Differentially Expressed Genes (DEGs) between the FAI and OA cohorts with multiple targets for genes implicated in canonical OA pathways. qRT-PCR validation confirmed increased expression of FGF18 and WNT16 in the FAI samples, while there was increased expression of MMP13 and ADAMTS4 in the OA samples. Expression levels of FGF18 and WNT16 were also higher in FAI samples with mild cartilage damage (OARSI grades 1-2) compared to FAI samples with severe cartilage damage or OA cartilage (OARSI grade 4-6). Immunohistochemical evaluation identified increased FGF18 staining in OARSI grade 1-2 FAI samples compared to OARSI grade 5-6 FAI and OA samples.ConclusionsRNA sequencing of cartilage of FAI and hip OA patients identified a negative association of FGF18 expression levels with cartilage damage severity, suggesting that FGF18 may be used as a marker for hip OA progression. Future evaluation of FGF18 signaling as well as other markers in early OA may yield further insight into disease prevention and treatment.
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- 2022
48. A Murine Model of Abductor Insufficiency Accelerates the Development of Hip Osteoarthritis
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Michael B. Geary, Caitlin A. Orner, Helen Shammas, John M. Reuter, Alayna E. Loiselle, Chia-Lung Wu, and Brian D. Giordano
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Osteoarthritis (OA) of the hip is a common and debilitating painful joint disease. A growing body of evidence suggests that there may be an association between periarticular myotendinous pathology and the development of hip OA. Thus, we hypothesized that a murine model of hip OA could be achieved through selective injury of the abductor complex around the hip. C57BL6/J mice were randomized to sham surgery or abductor injury, in which the myotendinous insertion at the third trochanter and greater trochanter were surgically detached. Mice were allowed free, active movement until sacrifice at either 3 weeks or 20 weeks post-injury. Histologic analyses and immunohistochemical staining (IHC) of the femoral head articular cartilage were performed, along with μCT analysis to assess subchondral bone remodeling. We observed that mice receiving abductor injury exhibited significant OA severity with loss of Type II Collagen staining compared to sham control mice at 20 weeks post-surgery, comparable MMPI13 expression was observed between injury and sham groups. No significant differences in subchondral bone were found on μCT after 20 weeks following injury. Our study suggests a link between abductor dysfunction and the development of hip OA, which are common pathomorphologies encountered in routine orthopaedic clinical practice. Further, this novel animal model may provide a valuable tool for future investigations into the pathogenesis and treatment of hip OA.
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- 2022
49. Questions and Controversies in the Clinical Application of Tyrosine Kinase Inhibitors to Treat Patients with Radioiodine-Refractory Differentiated Thyroid Carcinoma: Expert Perspectives
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Klemens Scheidhauer, Andreas K. Buck, Michael C. Kreissl, Christoph W. M. Reuter, Andreas Darr, Ingo Brink, Ina Binse, Ute König, Christine Dierks, Christine Koch, Markus Luster, Matthias Schott, Holger S. Willenberg, Frederik A. Verburg, Holger Amthauer, Andreas Zielke, and Radiology & Nuclear Medicine
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Oncology ,Sorafenib ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Medizin ,Psychological intervention ,030209 endocrinology & metabolism ,Subgroup analysis ,Antineoplastic Agents ,Review ,lenvatinib ,Biochemistry ,second-line therapy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,multi-kinase inhibitors ,SDG 3 - Good Health and Well-being ,treatment initiation and discontinuation ,Internal medicine ,medicine ,Humans ,Dosing ,Thyroid Neoplasms ,Protein Kinase Inhibitors ,Response rate (survey) ,Performance status ,Dose-Response Relationship, Drug ,business.industry ,Phenylurea Compounds ,Biochemistry (medical) ,General Medicine ,Protein-Tyrosine Kinases ,dosing ,3. Good health ,chemistry ,Tolerability ,030220 oncology & carcinogenesis ,Quinolines ,business ,Lenvatinib ,medicine.drug - Abstract
Notwithstanding regulatory approval of lenvatinib and sorafenib to treat radioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC), important questions and controversies persist regarding this use of these tyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiary referral centers convened to identify and explore such issues; this paper summarizes their discussions. One challenge is determining when to start TKI therapy. Decision-making should be shared between patients and multidisciplinary caregivers, and should consider tumor size/burden, growth rate, and site(s), the key drivers of RAI-R DTC morbidity and mortality, along with current and projected tumor-related symptomatology, co-morbidities, and performance status. Another question involves choice of first-line TKIs. Currently, lenvatinib is generally preferred, due to greater increase in progression-free survival versus placebo treatment and higher response rate in its pivotal trial versus that of sorafenib; additionally, in those studies, lenvatinib but not sorafenib showed overall survival benefit in subgroup analysis. Whether recommended maximum or lower TKI starting doses better balance anti-tumor effects versus tolerability is also unresolved. Exploratory analyses of lenvatinib pivotal study data suggest dose-response effects, possibly favoring higher dosing; however, results are awaited of a prospective comparison of lenvatinib starting regimens. Some controversy surrounds determination of net therapeutic benefit, the key criterion for continuing TKI therapy: if tolerability is acceptable, overall disease control may justify further treatment despite limited but manageable progression. Future research should assess potential guideposts for starting TKIs; fine-tune dosing strategies and further characterize antitumor efficacy; and evaluate interventions to prevent and/or treat TKI toxicity, particularly palmar-plantar erythrodysesthesia and fatigue.
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- 2021
50. Clinical sites of the Undiagnosed Diseases Network: unique contributions to genomic medicine and science
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Kelly Schoch, Cecilia Esteves, Anna Bican, Rebecca Spillmann, Heidi Cope, Allyn McConkie-Rosell, Nicole Walley, Liliana Fernandez, Jennefer N. Kohler, Devon Bonner, Chloe Reuter, Nicholas Stong, John J. Mulvihill, Donna Novacic, Lynne Wolfe, Ayat Abdelbaki, Camilo Toro, Cyndi Tifft, May Malicdan, William Gahl, Pengfei Liu, John Newman, David B. Goldstein, Jason Hom, Jacinda Sampson, Matthew T. Wheeler, Mercedes E. Alejandro, Mahshid S. Azamian, Carlos A. Bacino, Ashok Balasubramanyam, Lindsay C. Burrage, Hsiao-Tuan Chao, Gary D. Clark, William J. Craigen, Hongzheng Dai, Shweta U. Dhar, Lisa T. Emrick, Alica M. Goldman, Neil A. Hanchard, Fariha Jamal, Lefkothea Karaviti, Seema R. Lalani, Brendan H. Lee, Richard A. Lewis, Ronit Marom, Paolo M. Moretti, David R. Murdock, Sarah K. Nicholas, James P. Orengo, Jennifer E. Posey, Lorraine Potocki, Jill A. Rosenfeld, Susan L. Samson, Daryl A. Scott, Alyssa A. Tran, Tiphanie P. Vogel, Michael F. Wangler, Shinya Yamamoto, Christine M. Eng, Patricia A. Ward, Edward Behrens, Matthew Deardorff, Marni Falk, Kelly Hassey, Kathleen Sullivan, Adeline Vanderver, Vandana Shashi, Edward C. Smith, Rebecca C. Spillmann, Jennifer A. Sullivan, Queenie K.-G. Tan, Nicole M. Walley, Pankaj B. Agrawal, Alan H. Beggs, Gerard T. Berry, Lauren C. Briere, Laurel A. Cobban, Matthew Coggins, Cynthia M. Cooper, Elizabeth L. Fieg, Frances High, Ingrid A. Holm, Susan Korrick, Joel B. Krier, Sharyn A. Lincoln, Joseph Loscalzo, Richard L. Maas, Calum A. MacRae, J.Carl Pallais, Deepak A. Rao, Lance H. Rodan, Edwin K. Silverman, Joan M. Stoler, David A. Sweetser, Melissa Walker, Chris A. Walsh, Emily G. Kelley, Isaac S. Kohane, Kimberly LeBlanc, Alexa T. McCray, Anna Nagy, Surendra Dasari, Brendan C. Lanpher, Ian R. Lanza, Eva Morava, Devin Oglesbee, Guney Bademci, Deborah Barbouth, Stephanie Bivona, Olveen Carrasquillo, Ta Chen Peter Chang, Irman Forghani, Alana Grajewski, Rosario Isasi, Byron Lam, Roy Levitt, Xue Zhong Liu, Jacob McCauley, Ralph Sacco, Mario Saporta, Judy Schaechter, Mustafa Tekin, Fred Telischi, Willa Thorson, Stephan Zuchner, Heather A. Colley, Jyoti G. Dayal, David J. Eckstein, Laurie C. Findley, Donna M. Krasnewich, Laura A. Mamounas, Teri A. Manolio, Grace L. LaMoure, Madison P. Goldrich, Tiina K. Urv, Argenia L. Doss, Maria T. Acosta, Carsten Bonnenmann, Precilla D’Souza, David D. Draper, Carlos Ferreira, Rena A. Godfrey, Catherine A. Groden, Ellen F. Macnamara, Valerie V. Maduro, Thomas C. Markello, Avi Nath, Barbara N. Pusey, Colleen E. Wahl, Eva Baker, Elizabeth A. Burke, David R. Adams, William A. Gahl, May Christine V. Malicdan, Cynthia J. Tifft, Lynne A. Wolfe, John Yang, Bradley Power, Bernadette Gochuico, Laryssa Huryn, Lea Latham, Joie Davis, Deborah Mosbrook-Davis, Francis Rossignol, Ben Solomon, John MacDowall, Audrey Thurm, Wadih Zein, Muhammad Yousef, Margaret Adam, Laura Amendola, Michael Bamshad, Anita Beck, Jimmy Bennett, Beverly Berg-Rood, Elizabeth Blue, Brenna Boyd, Peter Byers, Sirisak Chanprasert, Michael Cunningham, Katrina Dipple, Daniel Doherty, Dawn Earl, Ian Glass, Katie Golden-Grant, Sihoun Hahn, Anne Hing, Fuki M. Hisama, Martha Horike-Pyne, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Christina Lam, Kenneth Maravilla, Heather Mefford, J.Lawrence Merritt, Ghayda Mirzaa, Deborah Nickerson, Wendy Raskind, Natalie Rosenwasser, C.Ron Scott, Angela Sun, Virginia Sybert, Stephanie Wallace, Mark Wener, Tara Wenger, Euan A. Ashley, Gill Bejerano, Jonathan A. Bernstein, Terra R. Coakley, Paul G. Fisher, Laure Fresard, Yong Huang, Elijah Kravets, Marta M. Majcherska, Beth A. Martin, Shruti Marwaha, Colleen E. McCormack, Archana N. Raja, Chloe M. Reuter, Maura Ruzhnikov, Jacinda B. Sampson, Kevin S. Smith, Shirley Sutton, Holly K. Tabor, Brianna M. Tucker, Diane B. Zastrow, Chunli Zhao, William E. Byrd, Andrew B. Crouse, Matthew Might, Mariko Nakano-Okuno, Jordan Whitlock, Gabrielle Brown, Manish J. Butte, Esteban C. Dell’Angelica, Naghmeh Dorrani, Emilie D. Douine, Brent L. Fogel, Irma Gutierrez, Alden Huang, Deborah Krakow, Hane Lee, Sandra K. Loo, Bryan C. Mak, Martin G. Martin, Julian A. Martínez-Agosto, Elisabeth McGee, Stanley F. Nelson, Shirley Nieves-Rodriguez, Christina G.S. Palmer, Jeanette C. Papp, Neil H. Parker, Genecee Renteria, Rebecca H. Signer, Janet S. Sinsheimer, Jijun Wan, Lee-kai Wang, Katherine Wesseling Perry, Jeremy D. Woods, Justin Alvey, Ashley Andrews, Jim Bale, John Bohnsack, Lorenzo Botto, John Carey, Laura Pace, Nicola Longo, Gabor Marth, Paolo Moretti, Aaron Quinlan, Matt Velinder, Dave Viskochil, Pinar Bayrak-Toydemir, Rong Mao, Monte Westerfield, Elly Brokamp, Laura Duncan, Rizwan Hamid, Jennifer Kennedy, Mary Kozuira, John H. Newman, John A. Phillips, Lynette Rives, Amy K. Robertson, Emily Solem, Joy D. Cogan, F. Sessions Cole, Nichole Hayes, Dana Kiley, Kathy Sisco, Jennifer Wambach, Daniel Wegner, Dustin Baldridge, Stephen Pak, Timothy Schedl, Jimann Shin, Lilianna Solnica-Krezel, and Joy Cogan
- Subjects
Exome sequencing ,0301 basic medicine ,Computational biology ,030105 genetics & heredity ,Genome sequencing ,Article ,DNA sequencing ,Retrospective data ,03 medical and health sciences ,Rare Diseases ,Animals ,Humans ,Genomic medicine ,Medicine ,Medical diagnosis ,Exome ,Genetics (clinical) ,Retrospective Studies ,Disease gene ,business.industry ,Genomics ,030104 developmental biology ,Phenotyping ,New disease ,Undiagnosed diseases ,Ultra-rare diseases ,business - Abstract
Purpose The NIH Undiagnosed Diseases Network (UDN) evaluates participants with disorders that have defied diagnosis, applying personalized clinical and genomic evaluations and innovative research. The clinical sites of the UDN are essential to advancing the UDN mission; this study assesses their contributions relative to standard clinical practices. Methods We analyzed retrospective data from four UDN clinical sites, from July 2015 to September 2019, for diagnoses, new disease gene discoveries and the underlying investigative methods. Results Of 791 evaluated individuals, 231 received 240 diagnoses and 17 new disease-gene associations were recognized. Straightforward diagnoses on UDN exome and genome sequencing occurred in 35% (84/240). We considered these tractable in standard clinical practice, although genome sequencing is not yet widely available clinically. The majority (156/240, 65%) required additional UDN-driven investigations, including 90 diagnoses that occurred after prior nondiagnostic exome sequencing and 45 diagnoses (19%) that were nongenetic. The UDN-driven investigations included complementary/supplementary phenotyping, innovative analyses of genomic variants, and collaborative science for functional assays and animal modeling. Conclusion Investigations driven by the clinical sites identified diagnostic and research paradigms that surpass standard diagnostic processes. The new diagnoses, disease gene discoveries, and delineation of novel disorders represent a model for genomic medicine and science.
- Published
- 2021
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