| 1. |
- 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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| 2. |
- Aquila, Andrew, et al.
(författare)
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Time-resolved protein nanocrystallography using an X-ray free-electron laser
- 2012
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Ingår i: Optics Express. - 1094-4087. ; 20:3, s. 2706-2716
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the use of an X-ray free electron laser synchronized with an optical pump laser to obtain X-ray diffraction snapshots from the photoactivated states of large membrane protein complexes in the form of nanocrystals flowing in a liquid jet. Light-induced changes of Photosystem I-Ferredoxin co-crystals were observed at time delays of 5 to 10 µs after excitation. The result correlates with the microsecond kinetics of electron transfer from Photosystem I to ferredoxin. The undocking process that follows the electron transfer leads to large rearrangements in the crystals that will terminally lead to the disintegration of the crystals. We describe the experimental setup and obtain the first time-resolved femtosecond serial X-ray crystallography results from an irreversible photo-chemical reaction at the Linac Coherent Light Source. This technique opens the door to time-resolved structural studies of reaction dynamics in biological systems.
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| 3. |
- Bajt, Sasa, et al.
(författare)
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Camera for coherent diffractive imaging and holography with a soft-x-ray free-electron laser
- 2008
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Ingår i: Applied Optics. - 1559-128X .- 2155-3165. ; 47:10, s. 1673-1683
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Tidskriftsartikel (refereegranskat)abstract
- We describe a camera to record coherent scattering patterns with a soft-x-ray free-electron laser (FEL). The camera consists of a laterally graded multilayer mirror, which reflects the diffraction pattern onto a CCD detector. The mirror acts as a bandpass filter for both the wavelength and the angle, which isolates the desired scattering pattern from nonsample scattering or incoherent emission from the sample. The mirror also solves the particular problem of the extreme intensity of the FEL pulses, which are focused to greater than 10(14) W/cm2. The strong undiffracted pulse passes through a hole in the mirror and propagates onto a beam dump at a distance behind the instrument rather than interacting with a beam stop placed near the CCD. The camera concept is extendable for the full range of the fundamental wavelength of the free electron laser in Hamburg (FLASH) FEL (i.e., between 6 and 60 nm) and into the water window. We have fabricated and tested various multilayer mirrors for wavelengths of 32, 16, 13.5, and 4.5 nm. At the shorter wavelengths mirror roughness must be minimized to reduce scattering from the mirror. We have recorded over 30,000 diffraction patterns at the FLASH FEL with no observable mirror damage or degradation of performance.
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| 4. |
- Barty, Anton, et al.
(författare)
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Ultrafast single-shot diffraction imaging of nanoscale dynamics
- 2008
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Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 2:7, s. 415-419
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Tidskriftsartikel (refereegranskat)abstract
- The transient nanoscale dynamics of materials on femtosecond to picosecond timescales is of great interest in the study of condensed phase dynamics such as crack formation, phase separation and nucleation, and rapid fluctuations in the liquid state or in biologically relevant environments. The ability to take images in a single shot is the key to studying non-repetitive behaviour mechanisms, a capability that is of great importance in many of these problems. Using coherent diffraction imaging with femtosecond X-ray free-electron-laser pulses we capture time-series snapshots of a solid as it evolves on the ultrafast timescale. Artificial structures imprinted on a Si3N4 window are excited with an optical laser and undergo laser ablation, which is imaged with a spatial resolution of 50 nm and a temporal resolution of 10 ps. By using the shortest available free-electron-laser wavelengths(1) and proven synchronization methods(2) this technique could be extended to spatial resolutions of a few nanometres and temporal resolutions of a few tens of femtoseconds. This experiment opens the door to a new regime of time-resolved experiments in mesoscopic dynamics.
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| 5. |
- Bogan, Michael J., et al.
(författare)
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Aerosol Imaging with a Soft X-Ray Free Electron Laser
- 2010
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 0278-6826 .- 1521-7388. ; 44:3, s. I-VI
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Tidskriftsartikel (refereegranskat)abstract
- Lasers have long played a critical role in the advancement of aerosol science. A new regime of ultrafast laser technology has recently be realized, the world's first soft x-ray free electron laser. The Free electron LASer in Hamburg, FLASH, user facility produces a steady source of 10 femtosecond pulses of 7–32 nm x-rays with 1012 photons per pulse. The high brightness, short wavelength, and high repetition rate (> 500 pulses per second) of this laser offers unique capabilities for aerosol characterization. Here we use FLASH to perform the highest resolution imaging of single PM2.5 aerosol particles in flight to date. We resolve to 35 nm the morphology of fibrous and aggregated spherical carbonaceous nanoparticles that existed for less than two milliseconds in vacuum. Our result opens the possibility for high spatial- and time-resolved single particle aerosol dynamics studies, filling a critical technological need in aerosol science.
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| 6. |
- Bogan, Michael J, et al.
(författare)
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Single particle X-ray diffractive imaging
- 2008
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Ingår i: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 8:1, s. 310-6
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Tidskriftsartikel (refereegranskat)abstract
- In nanotechnology, strategies for the creation and manipulation of nanoparticles in the gas phase are critically important for surface modification and substrate-free characterization. Recent coherent diffractive imaging with intense femtosecond X-ray pulses has verified the capability of single-shot imaging of nanoscale objects at suboptical resolutions beyond the radiation-induced damage threshold. By intercepting electrospray-generated particles with a single 15 femtosecond soft-X-ray pulse, we demonstrate diffractive imaging of a nanoscale specimen in free flight for the first time, an important step toward imaging uncrystallized biomolecules.
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| 7. |
- Chapman, Henry N., et al.
(författare)
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Femtosecond diffractive imaging with a soft-X-ray free-electron laser
- 2006
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Ingår i: Nature Physics. - : Springer Science and Business Media LLC. - 1745-2473 .- 1745-2481. ; 2:12, s. 839-843
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Tidskriftsartikel (refereegranskat)abstract
- Theory predicts(1-4) that, with an ultrashort and extremely bright coherent X-ray pulse, a single diffraction pattern may be recorded from a large macromolecule, a virus or a cell before the sample explodes and turns into a plasma. Here we report the first experimental demonstration of this principle using the FLASH soft-X-ray free-electron laser. An intense 25 fs, 4 x 10(13) W cm(-2) pulse, containing 10(12) photons at 32 nm wavelength, produced a coherent diffraction pattern from a nanostructured non-periodic object, before destroying it at 60,000 K. A novel X-ray camera assured single-photon detection sensitivity by filtering out parasitic scattering and plasma radiation. The reconstructed image, obtained directly from the coherent pattern by phase retrieval through oversampling(5-9), shows no measurable damage, and is reconstructed at the diffraction-limited resolution. A three-dimensional data set may be assembled from such images when copies of a reproducible sample are exposed to the beam one by one(10).
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| 8. |
- Chapman, Henry N, et al.
(författare)
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Femtosecond time-delay X-ray holography
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 448:7154, s. 676-679
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Tidskriftsartikel (refereegranskat)abstract
- Extremely intense and ultrafast X-ray pulses from free-electron lasers offer unique opportunities to study fundamental aspects of complex transient phenomena in materials. Ultrafast time-resolved methods usually require highly synchronized pulses to initiate a transition and then probe it after a precisely defined time delay. In the X-ray regime, these methods are challenging because they require complex optical systems and diagnostics. Here we propose and apply a simple holographic measurement scheme, inspired by Newton's 'dusty mirror' experiment1, to monitor the X-ray-induced explosion of microscopic objects. The sample is placed near an X-ray mirror; after the pulse traverses the sample, triggering the reaction, it is reflected back onto the sample by the mirror to probe this reaction. The delay is encoded in the resulting diffraction pattern to an accuracy of one femtosecond, and the structural change is holographically recorded with high resolution. We apply the technique to monitor the dynamics of polystyrene spheres in intense free-electron-laser pulses, and observe an explosion occurring well after the initial pulse. Our results support the notion that X-ray flash imaging2, 3 can be used to achieve high resolution, beyond radiation damage limits for biological samples4. With upcoming ultrafast X-ray sources we will be able to explore the three-dimensional dynamics of materials at the timescale of atomic motion.
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| 9. |
- Chapman, Henry N, et al.
(författare)
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Femtosecond X-ray protein nanocrystallography.
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 470:7332, s. 73-7
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Tidskriftsartikel (refereegranskat)abstract
- X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (∼200nm to 2μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.
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| 10. |
- Ekeberg, Tomas, et al.
(författare)
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Single-shot diffraction data from the Mimivirus particle using an X-ray free-electron laser
- 2016
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Free-electron lasers (FEL) hold the potential to revolutionize structural biology by producing X-ray pules short enough to outrun radiation damage, thus allowing imaging of biological samples without the limitation from radiation damage. Thus, a major part of the scientific case for the first FELs was three-dimensional (3D) reconstruction of non-crystalline biological objects. In a recent publication we demonstrated the first 3D reconstruction of a biological object from an X-ray FEL using this technique. The sample was the giant Mimivirus, which is one of the largest known viruses with a diameter of 450 nm. Here we present the dataset used for this successful reconstruction. Data-analysis methods for single-particle imaging at FELs are undergoing heavy development but data collection relies on very limited time available through a highly competitive proposal process. This dataset provides experimental data to the entire community and could boost algorithm development and provide a benchmark dataset for new algorithms.
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