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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- Forouzanfar, Mohammad H, et al.
(författare)
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Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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| 8. |
- 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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| 10. |
- Vos, Theo, et al.
(författare)
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Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 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. ; 386:9995, s. 743-800
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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