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| 4. |
- Kinyoki, DK, et al.
(författare)
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Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
- 2020
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
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Tidskriftsartikel (refereegranskat)abstract
- A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
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| 7. |
- Frank, TD, et al.
(författare)
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Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017
- 2019
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Ingår i: The lancet. HIV. - 2352-3018. ; 6:12, s. E831-E859
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Tidskriftsartikel (refereegranskat)
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| 8. |
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| 10. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 11. |
- Ge, R, et al.
(författare)
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Normative Modeling of Brain Morphometry Across the Lifespan Using CentileBrain: Algorithm Benchmarking and Model Optimization
- 2023
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Normative modeling is a statistical approach to quantify the degree to which a particular individual-level measure deviates from the pattern observed in a normative reference population. When applied to human brain morphometric measures it has the potential to inform about the significance of normative deviations for health and disease. Normative models can be implemented using a variety of algorithms that have not been systematically appraised. Methods: To address this gap, eight algorithms were compared in terms of performance and computational efficiency using brain regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) collated from 87 international MRI datasets. Performance was assessed with the mean absolute error (MAE) and computational efficiency was inferred from central processing unit (CPU) time. The algorithms evaluated were Ordinary Least Squares Regression (OLSR), Bayesian Linear Regression (BLR), Generalized Additive Models for Location, Scale, and Shape (GAMLSS), Parametric Lambda, Mu, Sigma (LMS), Gaussian Process Regression (GPR), Warped Bayesian Linear Regression (WBLG), Hierarchical Bayesian Regression (HBR), and Multivariable Fractional Polynomial Regression (MFPR). Model optimization involved testing nine covariate combinations pertaining to acquisition features, parcellation software versions, and global neuroimaging measures (i.e., total intracranial volume, mean cortical thickness, and mean cortical surface area). Findings: Statistical comparisons across models at PFDR<0.05 indicated that the MFPR-derived sex- and region-specific models with nonlinear polynomials for age and linear effects of global measures had superior predictive accuracy; the range of the MAE of the models of regional subcortical volumes was 70-520 mm3 and the corresponding ranges for regional cortical thickness and regional cortical surface area were 0.09-0.26 mm and 24-560 mm2, respectively. The MFPR-derived models were also computationally more efficient with a CPU time below one second compared to a range of 2 seconds to 60 minutes for the other algorithms. The performance of all sex- and region-specific MFPR models plateaued at sample sizes exceeding 3,000 and showed comparable MAEs across distinct 10-year age-bins covering the human lifespan. Interpretation: These results provide an empirically benchmarked framework for normative modeling of brain morphometry that is useful for interpreting prior literature and supporting future study designs. The model and tools described here are freely available through CentileBrain (https://centilebrain.org/), a user-friendly web platform.
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| 12. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 14. |
- Barty, A., et al.
(författare)
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Self-terminating diffraction gates femtosecond X-ray nanocrystallography measurements
- 2012
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Ingår i: Nature Photonics. - 1749-4885 .- 1749-4893. ; 6:1, s. 35-40
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Tidskriftsartikel (refereegranskat)abstract
- X-ray free-electron lasers have enabled new approaches to the structural determination of protein crystals that are too small or radiation-sensitive for conventional analysis1. For sufficiently short pulses, diffraction is collected before significant changes occur to the sample, and it has been predicted that pulses as short as 10 fs may be required to acquire atomic-resolution structural information1, 2, 3, 4. Here, we describe a mechanism unique to ultrafast, ultra-intense X-ray experiments that allows structural information to be collected from crystalline samples using high radiation doses without the requirement for the pulse to terminate before the onset of sample damage. Instead, the diffracted X-rays are gated by a rapid loss of crystalline periodicity, producing apparent pulse lengths significantly shorter than the duration of the incident pulse. The shortest apparent pulse lengths occur at the highest resolution, and our measurements indicate that current X-ray free-electron laser technology5 should enable structural determination from submicrometre protein crystals with atomic resolution.
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| 16. |
- Gomez, L. F., et al.
(författare)
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Shapes and vorticities of superfluid helium nanodroplets
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6199, s. 906-909
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Tidskriftsartikel (refereegranskat)abstract
- Helium nanodroplets are considered ideal model systems to explore quantum hydrodynamics in self-contained, isolated superfluids. However, exploring the dynamic properties of individual droplets is experimentally challenging. In this work, we used single-shot femtosecond x-ray coherent diffractive imaging to investigate the rotation of single, isolated superfluid helium-4 droplets containing ~108 to 1011 atoms. The formation of quantum vortex lattices inside the droplets is confirmed by observing characteristic Bragg patterns from xenon clusters trapped in the vortex cores. The vortex densities are up to five orders of magnitude larger than those observed in bulk liquid helium. The droplets exhibit large centrifugal deformations but retain axially symmetric shapes at angular velocities well beyond the stability range of viscous classical droplets.
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| 17. |
- Li, M, et al.
(författare)
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Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.
- 2014
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 19:4
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P=6.32 × 10−5, odds ratio (OR)=1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P<0.005) and the prefrontal cortex (P<1.0 × 10−6). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations.
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| 18. |
- Martin, A. V., et al.
(författare)
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Femtosecond dark-field imaging with an X-ray free electron laser
- 2012
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Ingår i: Optics Express. - 1094-4087. ; 20:12, s. 13501-13512
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of femtosecond diffractive imaging with X-ray lasers has enabled pioneering structural studies of isolated particles, such as viruses, at nanometer length scales. However, the issue of missing low frequency data significantly limits the potential of X-ray lasers to reveal sub-nanometer details of micrometer-sized samples. We have developed a new technique of dark-field coherent diffractive imaging to simultaneously overcome the missing data issue and enable us to harness the unique contrast mechanisms available in dark-field microscopy. Images of airborne particulate matter (soot) up to two microns in length were obtained using single-shot diffraction patterns obtained at the Linac Coherent Light Source, four times the size of objects previously imaged in similar experiments. This technique opens the door to femtosecond diffractive imaging of a wide range of micrometer-sized materials that exhibit irreproducible complexity down to the nanoscale, including airborne particulate matter, small cells, bacteria and gold-labeled biological samples.
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| 19. |
- Martin, A. V., et al.
(författare)
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Noise-robust coherent diffractive imaging with a single diffraction pattern
- 2012
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Ingår i: Optics Express. - 1094-4087. ; 20:15, s. 16650-16661
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Tidskriftsartikel (refereegranskat)abstract
- The resolution of single-shot coherent diffractive imaging at X-ray free-electron laser facilities is limited by the low signal-to-noise level of diffraction data at high scattering angles. The iterative reconstruction methods, which phase a continuous diffraction pattern to produce an image, must be able to extract information from these weak signals to obtain the best quality images. Here we show how to modify iterative reconstruction methods to improve tolerance to noise. The method is demonstrated with the hybrid input-output method on both simulated data and single-shot diffraction patterns taken at the Linac Coherent Light Source. (C) 2012 Optical Society of America
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| 20. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 21. |
- Allum, F., et al.
(författare)
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A localized view on molecular dissociation via electron-ion partial covariance
- 2022
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Ingår i: Communications Chemistry. - : Springer Science and Business Media LLC. - 2399-3669. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Inner-shell photoelectron spectroscopy provides an element-specific probe of molecular structure, as core-electron binding energies are sensitive to the chemical environment. Short-wavelength femtosecond light sources, such as Free-Electron Lasers (FELs), even enable time-resolved site-specific investigations of molecular photochemistry. Here, we study the ultraviolet photodissociation of the prototypical chiral molecule 1-iodo-2-methylbutane, probed by extreme-ultraviolet (XUV) pulses from the Free-electron LASer in Hamburg (FLASH) through the ultrafast evolution of the iodine 4d binding energy. Methodologically, we employ electron-ion partial covariance imaging as a technique to isolate otherwise elusive features in a two-dimensional photoelectron spectrum arising from different photofragmentation pathways. The experimental and theoretical results for the time-resolved electron spectra of the 4d(3/2) and 4d(5/2) atomic and molecular levels that are disentangled by this method provide a key step towards studying structural and chemical changes from a specific spectator site. Coincidence experiments at free-electron lasers enable time resolved site-specific investigations of molecular photochemistry at high signal rates, but isolating individual dissociation processes still poses a considerable technical challenge. Here, the authors use electron-ion partial covariance imaging to isolate otherwise elusive chemical shifts in UV-induced photofragmentation pathways of the prototypical chiral molecule 1-iodo-2-methylbutane.
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| 22. |
- Chang, H., et al.
(författare)
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The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:2, s. 400-412
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Tidskriftsartikel (refereegranskat)abstract
- Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.
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| 23. |
- Duane Loh, N., et al.
(författare)
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Profiling structured beams using injected aerosols
- 2012
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Ingår i: Proceedings of SPIE. - : SPIE. - 9780819492210 ; , s. 850403-
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Konferensbidrag (refereegranskat)abstract
- Profiling structured beams produced by X-ray free-electron lasers (FELs) is crucial to both maximizing signal intensity for weakly scattering targets and interpreting their scattering patterns. Earlier ablative imprint studies describe how to infer the X-ray beam profile from the damage that an attenuated beam inflicts on a substrate. However, the beams in-situ profile is not directly accessible with imprint studies because the damage profile could be different from the actual beam profile. On the other hand, although a Shack-Hartmann sensor is capable of in-situ profiling, its lenses may be quickly damaged at the intense focus of hard X-ray FEL beams. We describe a new approach that probes the in-situ morphology of the intense FEL focus. By studying the translations in diffraction patterns from an ensemble of randomly injected sub-micron latex spheres, we were able to determine the non-Gaussian nature of the intense FEL beam at the Linac Coherent Light Source (SLAC National Laboratory) near the FEL focus. We discuss an experimental application of such a beam-profiling technique, and the limitations we need to overcome before it can be widely applied.
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| 24. |
- Düsterer, S, et al.
(författare)
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Two-color XUV+NIR femtosecond photoionization of neon in the near-threshold region
- 2019
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Results of angle-resolved electron spectroscopy of near-threshold photoionization of Ne atoms by combined femtosecond extreme ultraviolet and near infrared fields are presented. The dressed-electron spectra show an energetic distribution into so-called sidebands, being separated by the photon energy of the dressing laser. Surprisingly, for the low kinetic energy (few eV) sidebands, the photoelectron energy varies as a function of the emission angle. Such behavior has not yet been observed in sideband creation and has not been predicted in commonly used theoretical descriptions such as strong field approximation and soft photon approach. Describing the photoionization with a time-dependent Schrödinger equation allows a qualitative description of the observed effect, as well as the prediction of fine structure in the sideband distribution.
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| 25. |
- Fukuzawa, H., et al.
(författare)
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Deep Inner-Shell Multiphoton Ionization by Intense X-Ray Free-Electron Laser Pulses
- 2013
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 110:17
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated multiphoton multiple ionization dynamics of xenon atoms using a new x-ray free-electron laser facility, SPring-8 Angstrom Compact free electron LAser (SACLA) in Japan, and identified that Xen+ with n up to 26 is produced at a photon energy of 5.5 keV. The observed high charge states (n >= 24) are produced via five-photon absorption, evidencing the occurrence of multiphoton absorption involving deep inner shells. A newly developed theoretical model, which shows good agreement with the experiment, elucidates the complex pathways of sequential electronic decay cascades accessible in heavy atoms. The present study of heavy-atom ionization dynamics in high-intensity hard-x-ray pulses makes a step forward towards molecular structure determination with x-ray free-electron lasers. DOI: 10.1103/PhysRevLett.110.173005
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