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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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4. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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- Fullman, N., et al.
(författare)
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Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016
- 2018
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 391:10136, s. 2236-2271
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Tidskriftsartikel (refereegranskat)abstract
- Background A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97.1 (95% UI 95.8-98.1) in Iceland, followed by 96.6 (94.9-97.9) in Norway and 96.1 (94.5-97.3) in the Netherlands, to values as low as 18.6 (13.1-24.4) in the Central African Republic, 19.0 (14.3-23.7) in Somalia, and 23.4 (20.2-26.8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91.5 (89.1-936) in Beijing to 48.0 (43.4-53.2) in Tibet (a 43.5-point difference), while India saw a 30.8-point disparity, from 64.8 (59.6-68.8) in Goa to 34.0 (30.3-38.1) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4.8-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20.9-point to 17.0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17.2-point to 20.4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle-SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view and subsequent provision of quality health care for all populations. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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11. |
- Krone-Martins, A., et al.
(författare)
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Gaia Focused Product Release: A catalogue of sources around quasars to search for strongly lensed quasars
- 2024
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 685
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Tidskriftsartikel (refereegranskat)abstract
- Context. Strongly lensed quasars are fundamental sources for cosmology. The Gaia space mission covers the entire sky with the unprecedented resolution of 0.18âà € ³ in the optical, making it an ideal instrument to search for gravitational lenses down to the limiting magnitude of 21. Nevertheless, the previous Gaia Data Releases are known to be incomplete for small angular separations such as those expected for most lenses.Aims. We present the Data Processing and Analysis Consortium GravLens pipeline, which was built to analyse all Gaia detections around quasars and to cluster them into sources, thus producing a catalogue of secondary sources around each quasar. We analysed the resulting catalogue to produce scores that indicate source configurations that are compatible with strongly lensed quasars.Methods. GravLens uses the DBSCAN unsupervised clustering algorithm to detect sources around quasars. The resulting catalogue of multiplets is then analysed with several methods to identify potential gravitational lenses. We developed and applied an outlier scoring method, a comparison between the average BP and RP spectra of the components, and we also used an extremely randomised tree algorithm. These methods produce scores to identify the most probable configurations and to establish a list of lens candidates.Results. We analysed the environment of 3 760 032 quasars. A total of 4 760 920 sources, including the quasars, were found within 6âà € ³ of the quasar positions. This list is given in the Gaia archive. In 87% of cases, the quasar remains a single source, and in 501 385 cases neighbouring sources were detected. We propose a list of 381 lensed candidates, of which we identified 49 as the most promising ones. Beyond these candidates, the associate tables in this Focused Product Release allow the entire community to explore the unique Gaia data for strong lensing studies further.
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12. |
- Panuzzo, P., et al.
(författare)
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Discovery of a dormant 33 solar-mass black hole in pre-release Gaia astrometry
- 2024
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 686
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Tidskriftsartikel (refereegranskat)abstract
- Context. Gravitational waves from black-hole (BH) merging events have revealed a population of extra-galactic BHs residing in short-period binaries with masses that are higher than expected based on most stellar evolution models-And also higher than known stellar-origin black holes in our Galaxy. It has been proposed that those high-mass BHs are the remnants of massive metal-poor stars.Aims. Gaia astrometry is expected to uncover many Galactic wide-binary systems containing dormant BHs, which may not have been detected before. The study of this population will provide new information on the BH-mass distribution in binaries and shed light on their formation mechanisms and progenitors.Methods. As part of the validation efforts in preparation for the fourth Gaia data release (DR4), we analysed the preliminary astrometric binary solutions, obtained by the Gaia Non-Single Star pipeline, to verify their significance and to minimise false-detection rates in high-mass-function orbital solutions.Results. The astrometric binary solution of one source, Gaia BH3, implies the presence of a 32.70a ±a 0.82aM- BH in a binary system with a period of 11.6 yr. Gaia radial velocities independently validate the astrometric orbit. Broad-band photometric and spectroscopic data show that the visible component is an old, very metal-poor giant of the Galactic halo, at a distance of 590 pc.Conclusions. The BH in the Gaia BH3 system is more massive than any other Galactic stellar-origin BH known thus far. The low metallicity of the star companion supports the scenario that metal-poor massive stars are progenitors of the high-mass BHs detected by gravitational-wave telescopes. The Galactic orbit of the system and its metallicity indicate that it might belong to the Sequoia halo substructure. Alternatively, and more plausibly, it could belong to the ED-2 stream, which likely originated from a globular cluster that had been disrupted by the Milky Way.
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13. |
- Weingrill, K., et al.
(författare)
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Gaia Focused Product Release: Sources from Service Interface Function image analysis: Half a million new sources in omega Centauri
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 680
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Tidskriftsartikel (refereegranskat)abstract
- Context. Gaia's readout window strategy is challenged by very dense fields in the sky. Therefore, in addition to standard Gaia observations, full Sky Mapper (SM) images were recorded for nine selected regions in the sky. A new software pipeline exploits these Service Interface Function (SIF) images of crowded fields (CFs), making use of the availability of the full two-dimensional (2D) information. This new pipeline produced half a million additional Gaia sources in the region of the omega Centauri (ω Cen) cluster, which are published with this Focused Product Release. We discuss the dedicated SIF CF data reduction pipeline, validate its data products, and introduce their Gaia archive table.Aims. Our aim is to improve the completeness of the Gaia source inventory in a very dense region in the sky, ω Cen.Methods. An adapted version of Gaia's Source Detection and Image Parameter Determination software located sources in the 2D SIF CF images. These source detections were clustered and assigned to new SIF CF or existing Gaia sources by Gaia s cross-match software. For the new sources, astrometry was calculated using the Astrometric Global Iterative Solution software, and photometry was obtained in the Gaia DR3 reference system. We validated the results by comparing them to the public Gaia DR3 catalogue and external Hubble Space Telescope data.Results. With this Focused Product Release, 526 587 new sources have been added to the Gaia catalogue in ω Cen. Apart from positions and brightnesses, the additional catalogue contains parallaxes and proper motions, but no meaningful colour information. While SIF CF source parameters generally have a lower precision than nominal Gaia sources, in the cluster centre they increase the depth of the combined catalogue by three magnitudes and improve the source density by a factor of ten.Conclusions. This first SIF CF data publication already adds great value to the Gaia catalogue. It demonstrates what to expect for the fourth Gaia catalogue, which will contain additional sources for all nine SIF CF regions.
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14. |
- David, P., et al.
(författare)
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Gaia Focused Product Release: Asteroid orbital solution : Properties and assessment
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 680
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Tidskriftsartikel (refereegranskat)abstract
- Context. We report the exploitation of a sample of Solar System observations based on data from the third Gaia Data Release (Gaia DR3) of nearly 157 000 asteroids. It extends the epoch astrometric solution over the time coverage planned for the Gaia DR4, which is not expected before the end of 2025. This data set covers more than one full orbital period for the vast majority of these asteroids. The orbital solutions are derived from the Gaia data alone over a relatively short arc compared to the observation history of many of these asteroids.Aims. The work aims to produce orbital elements for a large set of asteroids based on 66 months of accurate astrometry provided by Gaia and to assess the accuracy of these orbital solutions with a comparison to the best available orbits derived from independent observations. A second validation is performed with accurate occultation timings.Methods. We processed the raw astrometric measurements of Gaia to obtain astrometric positions of moving objects with 1D sub-mas accuracy at the bright end. For each asteroid that we matched to the data, an orbit fitting was attempted in the form of the best fit of the initial conditions at the median epoch. The force model included Newtonian and relativistic accelerations to derive the observation equations, which were solved with a linear least-squares fit.Results. Orbits are provided in the form of state vectors in the International Celestial Reference Frame for 156 764 asteroids, including near-Earth objects, main-belt asteroids, and Trojans. For the asteroids with the best observations, the (formal) relative uncertainty σa/a is better than 10-10. Results are compared to orbits available from the Jet Propulsion Laboratory and MPC. Their orbits are based on much longer data arcs, but from positions of lower quality. The relative differences in semi-major axes have a mean of 5 × 10-10 and a scatter of 5 × 10-9
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15. |
- Schultheis, M., et al.
(författare)
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Gaia Focused Product Release: Spatial distribution of two diffuse interstellar bands
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 680
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse interstellar bands (DIBs) are absorption features seen in optical and infrared spectra of stars and extragalactic objects that are probably caused by large and complex molecules in the galactic interstellar medium (ISM). Here we investigate the Galactic distribution and properties of two DIBs identified in almost six million stellar spectra collected by the Gaia Radial Velocity Spectrometer. These measurements constitute a part of the Gaia Focused Product Release to be made public between the Gaia DR3 and DR4 data releases. In order to isolate the DIB signal from the stellar features in each individual spectrum, we identified a set of 160 000 spectra at high Galactic latitudes (|b| ≥ 65) covering a range of stellar parameters which we consider to be the DIB-free reference sample. Matching each target spectrum to its closest reference spectra in stellar parameter space allowed us to remove the stellar spectrum empirically, without reference to stellar models, leaving a set of six million ISM spectra. Using the star's parallax and sky coordinates, we then allocated each ISM spectrum to a voxel (VOlume piXEL) on a contiguous three-dimensional grid with an angular size of 1.8 (level 5 HEALPix) and 29 unequally sized distance bins. Identifying the two DIBs at 862.1 nm (λ862.1) and 864.8 nm (λ864.8) in the stacked spectra, we modelled their shapes and report the depth, central wavelength, width, and equivalent width (EW) for each, along with confidence bounds on these measurements. We then explored the properties and distributions of these quantities and compared them with similar measurements from other surveys. Our main results are as follows: (1) the strength and spatial distribution of the DIB λ862.1 are very consistent with what was found in Gaia DR3, but for this work we attained a higher signal-to-noise ratio in the stacked spectra to larger distances, which allowed us to trace DIBs in the outer spiral arm and beyond the Scutum-Centaurus spiral arm; (2) we produced an all-sky map below ±65 of Galactic latitude to ∼4000 pc of both DIB features and their correlations; (3) we detected the signals of DIB λ862.1 inside the Local Bubble (≲200 pc); and (4) there is a reasonable correlation with the dust reddening found from stellar absorption and EWs of both DIBs with a correlation coefficient of 0.90 for λ862.1 and 0.77 for λ864.8.
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16. |
- Trabucchi, M., et al.
(författare)
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Gaia Focused Product Release: Radial velocity time series of long-period variables
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 680
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Tidskriftsartikel (refereegranskat)abstract
- Context. The third Gaia Data Release (DR3) provided photometric time series of more than 2 million long-period variable (LPV) candidates. Anticipating the publication of full radial-velocity data planned with Data Release 4, this Focused Product Release (FPR) provides radial-velocity time series for a selection of LPV candidates with high-quality observations.Aims. We describe the production and content of the Gaia catalog of LPV radial-velocity time series, and the methods used to compute the variability parameters published as part of the Gaia FPR.Methods. Starting from the DR3 catalog of LPV candidates, we applied several filters to construct a sample of sources with high-quality radial-velocity measurements. We modeled their radial-velocity and photometric time series to derive their periods and amplitudes, and further refined the sample by requiring compatibility between the radial-velocity period and at least one of the G, GBP, or GRP photometric periods.Results. The catalog includes radial-velocity time series and variability parameters for 9614 sources in the magnitude range 6 ≲ G/mag ≲ 14, including a flagged top-quality subsample of 6093 stars whose radial-velocity periods are fully compatible with the values derived from the G, GBP, and GRP photometric time series. The radial-velocity time series contain a mean of 24 measurements per source taken unevenly over a duration of about three years. We identify the great majority of the sources (88%) as genuine LPV candidates, with about half of them showing a pulsation period and the other half displaying a long secondary period. The remaining 12% of the catalog consists of candidate ellipsoidal binaries. Quality checks against radial velocities available in the literature show excellent agreement. We provide some illustrative examples and cautionary remarks.Conclusions. The publication of radial-velocity time series for almost ten thousand LPV candidates constitutes, by far, the largest such database available to date in the literature. The availability of simultaneous photometric measurements gives a unique added value to the Gaia catalog.
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18. |
- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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19. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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20. |
- Naghavi, Mohsen, et al.
(författare)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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21. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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22. |
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23. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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24. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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25. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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27. |
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29. |
- Rebbeck, Timothy R., et al.
(författare)
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Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
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30. |
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31. |
- Dahmen, J., et al.
(författare)
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Osteochondral Lesions of the Tibial Plafond and Ankle Instability With Ankle Cartilage Lesions: Proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle
- 2022
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Ingår i: Foot & Ankle International. - : SAGE Publications. - 1071-1007 .- 1944-7876. ; 43:3, s. 448-452
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Tidskriftsartikel (refereegranskat)abstract
- Background: An international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to present the consensus statements on osteochondral lesions of the tibial plafond (OLTP) and on ankle instability with ankle cartilage lesions developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three experts in cartilage repair of the ankle were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within 4 working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held. Results: A total of 11 statements on OLTP reached consensus. Four achieved unanimous support and 7 reached strong consensus (greater than 75% agreement). A total of 8 statements on ankle instability with ankle cartilage lesions reached consensus during the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. One achieved unanimous support, and seven reached strong consensus (greater than 75% agreement). Conclusions: These consensus statements may assist clinicians in the management of these difficult clinical pathologies.
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32. |
- Lewin, Harris A., et al.
(författare)
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The Earth BioGenome Project 2020 : Starting the clock
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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33. |
- Smol, T., et al.
(författare)
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MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype
- 2018
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Ingår i: Neurogenetics. - : SPRINGER. - 1364-6745 .- 1364-6753. ; 19:2, s. 93-103
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Tidskriftsartikel (refereegranskat)abstract
- Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Here we report 36 patients with MED13L molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15-17 and 25-31. We found that patients carrying missense mutations had more frequently epilepsy and showed a more severe phenotype. This study ascertains missense variations in MED13L as a cause for MED13L-related intellectual disability and improves the clinical delineation of the condition.
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35. |
- Armstrong, Janet L., et al.
(författare)
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Interannual and Spatial Feeding Patterns of Hatchery and Wild Juvenile Pink Salmon in the Gulf of Alaska in Years of Low and High Survival
- 2008
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Ingår i: Transactions of the American Fisheries Society 2008; 137: 1299-1316.
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Tidskriftsartikel (refereegranskat)abstract
- To improve understanding of the mechanisms affecting growth and survival, we evaluated the summer diets and feeding patterns (prey composition, energy density, and stomach fullness) of hatchery and wild juvenile pink salmon Oncorhynchus gorbuscha in Prince William Sound (PWS) and the northern coastal Gulf of Alaska (CGOA). Our study (19992004) included 2 years of low (3%), mid (5%), and high (89%) survival of PWS hatchery pink salmon. Because variations in diet should affect growth and ultimately survival, we expected that the variations in diet, growth, and survival would be correlated. During August in the CGOA, pteropod-dominated diets and higher gut fullness corresponded to high survival (59%), and copepod-dominated diets and lower gut fullness corresponded to low survival (3%). Within years, no significant differences were found in diet composition or gut fullness between hatchery and wild fish or among the four PWS hatchery stocks. Diets varied by water mass (habitat) as juveniles moved from PWS to more saline habitats in the CGOA. In July, when juveniles were most abundant in PWS, their diets were dominated by pteropods and hyperiid amphipods. The diets of fish that moved to inner-shelf (i.e., the least-saline) habitat in the CGOA in July were dominated by larvaceans in low-survival years and pteropods in high-survival years. Diet quality was higher in CGOA habitats than in PWS in July. In August, fish moved to the more productive, more saline water masses in the CGOA, where large copepods and pteropods were dominant prey and diet quality was better than in PWS. Our results indicate that spatial variation in the diets of juvenile pink salmon in July and the timing of migration to the CGOA play a critical role in marine growth and survival
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37. |
- Karlsson, Johan, et al.
(författare)
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Engineered nanoparticles for systemic siRNA delivery to malignant brain tumours.
- 2019
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 11:42, s. 20045-20057
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Tidskriftsartikel (refereegranskat)abstract
- Improved delivery materials are needed to enable siRNA transport across biological barriers, including the blood-brain barrier (BBB), to treat diseases like brain cancer. We engineered bioreducible nanoparticles for systemic siRNA delivery to patient-derived glioblastoma cells in an orthotopic mouse tumor model. We first utilized a newly developed biomimetic in vitro model to evaluate and optimize the performance of the engineered bioreducible nanoparticles at crossing the brain microvascular endothelium. We performed transmission electron microscopy imaging which indicated that the engineered nanoparticles are able to cross the BBB endothelium via a vesicular mechanism. The nanoparticle formulation engineered to best cross the BBB model in vitro led to safe delivery across the BBB to the brain in vivo. The nanoparticles were internalized by human brain cancer cells, released siRNA to the cytosol via environmentally-triggered degradation, and gene silencing was obtained both in vitro and in vivo. This study opens new frontiers for the in vitro evaluation and engineering of nanomedicines for delivery to the brain, and reports a systemically administered biodegradable nanocarrier for oligonucleotide delivery to treat glioma.
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38. |
- Micah, Angela E., et al.
(författare)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Forskningsöversikt (refereegranskat)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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39. |
- Puruleia, A., et al.
(författare)
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Rediscovery of the lost skink Proscelotes aenea and implications for conservation
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity loss is recognized as a grand challenge of the twenty-first century but ascertaining when a species is "lost" can be incredibly difficult-since the absence of evidence is not evidence of absence. This may be a relatively easy task for large and conspicuous animals, but extremely difficult for those living hidden lives or at low population sizes. We showcase this challenge by focusing on Africa's montane skink, Proscelotes aenea (Barbour & Loveridge 1928). In this study, we embarked on a year-long intensive survey to find this fossorial species in Lumbo, Northern Mozambique, the only remaining location where it may still occur but was recorded for the last time over 100 years ago. We located the species already after 20 days of intensive and targeted searching by five members of our team. The finding allowed us to describe, for the first time, details on the biology and ecology of the species, alongside photos and videos of live specimens (including a pregnant female), and to sequence DNA from the species, which we used to infer the phylogenetic placement. Our combined 12S and 16S phylogenetic analysis weakly suggest that the genus Proscelotes may not be monophyletic and therefore requires further phylogenetic work and potentially taxonomic revision. We also gathered evidence of a possible decrease in population abundance and, based on the species' ecology, we identified urbanization as a potential key threat, which could lead to the local or global extirpation of the species. We call for urgent conservation actions that help protect the future of the montane skink, and additional surveys to map its full distribution. As countries now work towards implementing the goals and targets of the Kunming-Montreal Global Biodiversity Framework, our study demonstrates the need for proper investments in biodiversity inventories and monitoring in order to halt species extinctions by 2030.
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40. |
- Bertz, L, et al.
(författare)
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Are there differences of inflammatory bio-markers between diabetic and non-diabetic patients with critical limb ischemia?
- 2006
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Ingår i: International Angiology. - 1827-1839. ; 25:4, s. 370-377
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Tidskriftsartikel (refereegranskat)abstract
- Aim. This observational study was undertaken in order to analyse whether any differences could be detected between diabetic and non-diabetic patients with critical limb ischemia (CLI) concerning the inflammatory response. Methods. A total number of 259 consecutive patients with CLI were treated between October 2001 and January 2003. Results. Among the 259 patients, 135 (52%) had diabetes, previously known in 123, and detected during hospitalization in 12. The diabetic patients more often showed gangrene (P < 0.05) and infra-inguinal atherosclerosis (84% vs 67%, P=0.001). The patients with diabetes showed a better lipid profile (total cholesterol 4.6 vs 5 mmol/L, P=0.006 and lower LDL-cholesterol (2.7 vs 3.1 mmol/L, P=0.010) despite the same frequency of statin treatment. They showed a higher creatinine (149 vs 117 pmol/L, P=0.0003) than the nondiabetic patients. Of the inflammatory markers, C-reactive protein (CRP) was equally elevated in both groups. Tumor necrosis factor-a (TNF-a) was increased among the diabetic patients (2.6 vs 1.8 pg/mL, P < 0.05), and this difference was most evident in those with gangrene. Neopterin was also higher among the diabetic patients (31 vs 21 mmol/L, P < 0.01), but CD40L was not different between groups. Conclusions. Diabetes mellitus was very common in CLI patients, and more often combined with renal impairment and infra-inguinal atherosclerosis. The inflammatory markers TNF-alpha and neopterin were elevated in patients with diabetes as compared to non-diabetic patients, but this difference cannot explain why CLI is 10 times more frequent in diabetic patients.
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41. |
- Biswas, Dhruva, et al.
(författare)
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A clonal expression biomarker associates with lung cancer mortality
- 2019
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:10, s. 1540-1548
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Tidskriftsartikel (refereegranskat)abstract
- An aim of molecular biomarkers is to stratify patients with cancer into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumor stage(1). Transcriptomic intratumor heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types(2-6). Here, we analyze multi-region whole-exome and RNA sequencing data for 156 tumor regions from 48 patients enrolled in the TRACERx study to explore and control for RNA-ITH in non-small cell lung cancer. We find that chromosomal instability is a major driver of RNA-ITH, and existing prognostic gene expression signatures are vulnerable to tumor sampling bias. To address this, we identify genes expressed homogeneously within individual tumors that encode expression modules of cancer cell proliferation and are often driven by DNA copy-number gains selected early in tumor evolution. Clonal transcriptomic biomarkers overcome tumor sampling bias, associate with survival independent of clinicopathological risk factors, and may provide a general strategy to refine biomarker design across cancer types.
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43. |
- Ebrahimi-Fakhari, Darius, et al.
(författare)
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Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
- 2020
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Ingår i: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
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Tidskriftsartikel (refereegranskat)abstract
- Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
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44. |
- Ejskjaer, N., et al.
(författare)
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A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis
- 2013
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 25:2, s. e140-e150
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Tidskriftsartikel (refereegranskat)abstract
- Background Gastroparesis causes significant morbidity and treatment options are limited. TZP-102 a novel, macrocyclic, selective, oral ghrelin receptor agonist, was evaluated in a randomized, double-blind, placebo-controlled trial in patients with diabetic gastroparesis. Methods A total of 92 outpatients were randomized to once-daily administrations of 10-mg (n=22), 20-mg (n=21), 40-mg (n=23) TZP-102 or placebo (n=26). The primary endpoint was the change from baseline in gastric half-emptying time (T1/2) utilizing 13C-breath test methodology and secondary endpoints included symptom improvement using patient-reported gastroparesis symptom scores (PAGI-SYM questionnaire) and patient and physician overall treatment evaluations (OTE). Key Results Gastric T1/2 changes were not statistically significant between TZP-102 and placebo after 28days of treatment at any dose. Clinical improvements (-1.0 to -1.4 point mean decrease in symptom severity) occurred in the Gastroparesis Cardinal Symptom Index (GCSI) component of the PAGI-SYM, which was significant vs placebo for all TZP-102 doses combined. Improvements became evident after 1week of treatment. Significantly, more patients given TZP-102 (any dose) had a 50% reduction in baseline GCSI score (28.8%vs 7.7% placebo). Safety profiles were similar across groups. All TZP-102 doses were well-tolerated with no adverse cardiac, weight, or glucose control outcomes. Conclusions & Inferences TZP-102 for 28days, at doses of 10-40mg once daily, was well-tolerated and resulted in a reduction in symptoms of gastroparesis. The lack of correlation between symptom improvement and gastric emptying change is consistent with previous studies in diabetic gastroparesis, and emphasizes the value of patient-defined outcomes in determining therapeutic benefit.
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46. |
- El Jamal, Ghada, et al.
(författare)
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Mixed H2O/H2plasma-induced redox reactions of thin uranium oxide films under UHV conditions
- 2021
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 50:36, s. 12583-12591
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Tidskriftsartikel (refereegranskat)abstract
- X-ray photoelectron spectroscopy (XPS) has been used to study the effect of mixed H2O/H2gas plasma on the surfaces of UO2, U2O5and UO3thin films at 400 °C. The experiments were performedin situunder ultra-high vacuum conditions. Deconvolution of the U4f7/2peaks into U(iv), U(v) and U(vi) components revealed the surface composition of the films after 10 min plasma exposure as a function of H2concentration in the feed gas of the plasma. Some selected films (unexposed and exposed) were also analysed using grazing-incidence X-ray diffraction (GIXRD). The XPS results show that U(v) is formed as a major product upon 10 minutes exposure of UO3by a mixed H2O/H2plasma in a fairly wide H2concentration range. When starting with U(v) (U2O5), rather high H2concentrations are needed to reduce U(v) to U(iv) in 10 minutes. In the plasma induced oxidation of UO2, U(v) is never observed as a major product after 10 minutes and it would seem that once U(v) is formed in the oxidation of UO2it is rapidly oxidized further to U(vi). The grazing incidence X-ray diffraction analysis shows that there is a considerable impact of the plasma and heating conditions on the crystal structure of the films in line with the change of the oxidation state. This structural difference is proposed to be the main kinetic barrier for plasma induced transfer between U(iv) and U(v) in both directions.
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47. |
- Murawski, Christopher D., et al.
(författare)
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Terminology for osteochondral lesions of the ankle: proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle
- 2022
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Ingår i: JOURNAL OF ISAKOS JOINT DISORDERS & ORTHOPAEDIC SPORTS MEDICINE. - : Elsevier BV. - 2059-7754 .- 2059-7762. ; 7:2, s. 62-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: The evidence supporting best practice guidelines in the field of cartilage repair of the ankle is based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on "terminology for osteochondral lesions of the ankle" developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three international experts in cartilage repair of the ankle representing 20 countries were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within four working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed, and the available evidence for each state-ment was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterised as follows: consensus, 51%-74%; strong consensus, 75%-99%; unanimous, 100%. Results: A total of 11 statements on terminology and classification reached consensus during the 2019 Interna-tional Consensus Meeting on Cartilage Repair of the Ankle. Definitions are provided for osseous, chondral and osteochondral lesions, as well as bone marrow stimulation and injury chronicity, among others. An osteochondral lesion of the talus can be abbreviated as OLT. Conclusions: This international consensus derived from leaders in the field will assist clinicians with the appro-priate terminology for osteochondral lesions of the ankle.
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48. |
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