| 1. |
- Aad, G, et al.
(author)
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- 2015
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swepub:Mat__t
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| 2. |
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| 3. |
- Clark, DW, et al.
(author)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Journal article (peer-reviewed)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 4. |
- Cossarizza, A., et al.
(author)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
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Journal article (peer-reviewed)abstract
- These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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| 5. |
- Abgrall, N., et al.
(author)
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The large enriched germanium experiment for neutrinoless double beta decay (LEGEND)
- 2017
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In: AIP Conference Proceedings. - : Author(s). - 1551-7616 .- 0094-243X. ; 1894
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Conference paper (peer-reviewed)abstract
- The observation of neutrinoless double-beta decay (0νββ) would show that lepton number is violated, reveal that neu-trinos are Majorana particles, and provide information on neutrino mass. A discovery-capable experiment covering the inverted ordering region, with effective Majorana neutrino masses of 15 - 50 meV, will require a tonne-scale experiment with excellent energy resolution and extremely low backgrounds, at the level of ∼0.1 count /(FWHM·t·yr) in the region of the signal. The current generation 76Ge experiments GERDA and the Majorana Demonstrator, utilizing high purity Germanium detectors with an intrinsic energy resolution of 0.12%, have achieved the lowest backgrounds by over an order of magnitude in the 0νββ signal region of all 0νββ experiments. Building on this success, the LEGEND collaboration has been formed to pursue a tonne-scale 76Ge experiment. The collaboration aims to develop a phased 0νββ experimental program with discovery potential at a half-life approaching or at 1028 years, using existing resources as appropriate to expedite physics results.
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| 6. |
- Liu, Y., et al.
(author)
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Recent enhancement of central Pacific El Nino variability relative to last eight centuries
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- The far-reaching impacts of central Pacific El Nino events on global climate differ appreciably from those associated with eastern Pacific El Nino events. Central Pacific El Nino events may become more frequent in coming decades as atmospheric greenhouse gas concentrations rise, but the instrumental record of central Pacific sea-surface temperatures is too short to detect potential trends. Here we present an annually resolved reconstruction of NINO4 sea-surface temperature, located in the central equatorial Pacific, based on oxygen isotopic time series from Taiwan tree cellulose that span from 1190 AD to 2007 AD. Our reconstruction indicates that relatively warm Nino4 sea-surface temperature values over the late twentieth century are accompanied by higher levels of interannual variability than observed in other intervals of the 818-year-long reconstruction. Our results imply that anthropogenic greenhouse forcing may be driving an increase in central Pacific El Nino-Southern Oscillation variability and/or its hydrological impacts, consistent with recent modelling studies.
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| 7. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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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| 8. |
- Sun, S., et al.
(author)
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Inhibition of the Activation and Recruitment of Microglia-Like Cells Protects Against Neomycin-Induced Ototoxicity
- 2015
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In: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 51:1, s. 252-267
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Journal article (peer-reviewed)abstract
- One of the most unfortunate side effects of aminoglycoside (AG) antibiotics such as neomycin is that they target sensory hair cells (HCs) and can cause permanent hearing impairment. We have observed HC loss and microglia-like cell (MLC) activation in the inner ear (cochlea) following neomycin administration. We focused on CX3CL1, a membrane-bound glycoprotein expressed on neurons and endothelial cells, as a way to understand how the MLCs are activated and the role these cells play in HC loss. CX3CL1 is the exclusive ligand for CX3CR1, which is a chemokine receptor expressed on the surface of macrophages and MLCs. In vitro experiments showed that the expression levels of CX3CL1 and CX3CR1 increased in the cochlea upon neomycin treatment, and CX3CL1 was expressed on HCs, while CX3CR1 was expressed on MLCs. When cultured with 1 mu g/mL exogenous CX3CL1, MLCs were activated by CX3CL1, and the cytokine level was increased in the cochleae leading to apoptosis in the HCs. In CX3CR1 knockout mice, a significantly greater number of cochlear HCs survived than in wild-type mice when the cochlear explants were cultured with neomycin in vitro. Furthermore, inhibiting the activation of MLCs with minocycline reduced the neomycin-induced HC loss and improved the hearing function in neomycin-treated mice in vivo. Our results demonstrate that CX3CL1-induced MLC activation plays an important role in the induction of HC death and provide evidence for CX3CL1 and CX3CR1 as promising new therapeutic targets for the prevention of hearing loss.
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| 9. |
- Barnett, R., et al.
(author)
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Euclid preparation V. Predicted yield of redshift 7 < z < 9 quasars from the wide survey
- 2019
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 631
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Journal article (peer-reviewed)abstract
- We provide predictions of the yield of 7 < z < 9 quasars from the Euclid wide survey, updating the calculation presented in the Euclid Red Book in several ways. We account for revisions to the Euclid near-infrared filter wavelengths; we adopt steeper rates of decline of the quasar luminosity function (QLF; Phi) with redshift, Phi proportional to 10(k(z-6)), k = 0:72, and a further steeper rate of decline, k = 0:92; we use better models of the contaminating populations (MLT dwarfs and compact early-type galaxies); and we make use of an improved Bayesian selection method, compared to the colour cuts used for the Red Book calculation, allowing the identification of fainter quasars, down to J(AB) similar to 23. Quasars at z > 8 may be selected from Euclid OYJH photometry alone, but selection over the redshift interval 7 < z < 8 is greatly improved by the addition of z-band data from, e.g., Pan-STARRS and LSST. We calculate predicted quasar yields for the assumed values of the rate of decline of the QLF beyond z = 6. If the decline of the QLF accelerates beyond z = 6, with k = 0.92, Euclid should nevertheless find over 100 quasars with 7.0 < z < 7.5, and similar to 25 quasars beyond the current record of z = 7.5, including similar to 8 beyond z = 8.0. The first Euclid quasars at z > 7.5 should be found in the DR1 data release, expected in 2024. It will be possible to determine the bright-end slope of the QLF, 7 < z < 8, M-1450 < 25, using 8m class telescopes to confirm candidates, but follow-up with JWST or E-ELT will be required to measure the faint-end slope. Contamination of the candidate lists is predicted to be modest even at J(AB) similar to 23. The precision with which k can be determined over 7 < z < 8 depends on the value of k, but assuming k = 0.72 it can be measured to a 1 sigma uncertainty of 0.07.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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| 14. |
- Ayeni, O. R., et al.
(author)
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Clinical and Radiographic Criteria Define "Acceptable" Surgical Correction of Hip Femoroacetabular Impingement Syndrome as Well as Postoperative Complications: An International Modified Delphi Study
- 2023
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In: Arthroscopy-the Journal of Arthroscopic and Related Surgery. - : Elsevier BV. - 0749-8063. ; 39:5, s. 1198-1210
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Journal article (peer-reviewed)abstract
- Objectives: To develop recommendations for clinical and radiographic criteria to help define the "acceptable" surgical correction of femoroacetabular impingement syndrome (FAIS) and identify/define complications postoperatively. Methods: A 3-phase modified Delphi study was conducted involving a case-based survey; a Likert/multiple choice-based survey concerning radiographic and physical examination characteristics to help define FAIS correction, as well as the prevalence and definition of potential postoperative complications; and 2 consensus meetings. Results: Of the 75 experts invited, 54 completed the Phase I survey, 50 completed the Phase II survey (72% and 67% response rate), and 50 participated in the Phase III consensus meetings. For both typical and atypical (complex) cases, there was consensus that fluoroscopy with multiple views and dynamic hip assessment should be used intraoperatively (96% and 100%, respectively). For typical FAIS cases, the Expert Panel agreed that Dunn lateral and anteroposterior radiographs were the most important radiographs to evaluate the hip postoperatively (88%, consensus). When asked about evaluating the correction of cam impingement postoperatively, 87% voted that they use subjective evaluation of the "sphericity" of the femoral head. In the case of focal and global pincer-type FAIS, there was consensus that the reduction or elimination of the crossover sign (84%) and lateral center-edge angle (91%) were important to inform the extent of the FAIS correction. There was consensus for recommending further investigation at 6 months postoperatively if hip pain had increased/plateaued (92% agreed); that additional investigation and treatment should occur between 6 and 12 months (90% agreed); and that a reoperation may be recommended at 12 months or later following this investigation period (89% agreed). Conclusions: This consensus project identified the importance of using fluoroscopy and dynamic hip assessment intraoperatively; Dunn lateral and anteroposterior view radiographs postoperatively; evaluating the "sphericity" of the femoral head for cam-type correction and the use of dynamic hip assessment; reducing/eliminating the crossover sign for focal pincertype FAIS; evaluating the lateral center-edge angle for global pincer-type FAIS; and avoiding overcorrection of pincer-type FAIS. In cases in which postoperative hip pain increased/plateaued, further investigation and treatment is warranted between 6 and 12 months, and a reoperation may be recommended at a minimum of 12 months depending on the cause of the hip pain. Clinical Relevance: Hip arthroscopy surgeons have yet to reach a firm agreement on what constitutes an "acceptable" or "good" surgery radiographically and how they can achieve desired clinical outcomes. Although this was a comprehensive effort, more study is needed to determine therapeutic thresholds that can be universally applied.
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| 15. |
- Chang, Chiao-Nien, et al.
(author)
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The Design, Structure–Activity, and Kinetic Studies of 3-Benzyl-5-oxa-1,2,3,4-Tetrahydro-2H-chromeno-(3,4-c)pyridin-8-yl Sulfamates as Steroid Sulfatase Inhibitors
- 2022
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In: Bioorganic chemistry. - : Elsevier BV. - 0045-2068.
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Journal article (peer-reviewed)abstract
- Steroid sulfatase inhibitors block the local production of estrogenic steroids and are attractive agents for the treatment of estrogen-dependent cancers. Inspiration of coumarin-based inhibitors, we synthesized thirty-two 5-oxa-1,2,3,4-tetrahydro-2H-chromeno-(3,4-c)pyridin-8-yl sulfamates, focusing on the substitution derivatives on the adjacent phenyl ring and evaluated their abilities to block STS from human placenta and MCF-7 cells. SAR analysis revealed that the incorporation of chlorine at either meta and/or para position of the adjacent phenyl ring of the tricyclic skeleton enhanced STS inhibition. Di-substitutions at the adjacent phenyl ring were superior to mono and tri-substitutions. Further kinetic analysis of these compounds revealed that chloride-bearing compounds, such as 19m, 19v, and 19w, had KI of 0.02 to 0.11 nM and kinact/KI ratios of 8.8-17.5 nM-1min-1, a parameter indicated for the efficiency of irreversible inhibition. We also used the docking model to illustrate the difference in STS inhibitory potency of compounds. Finally, the safety and anti-cancer activity of selected compounds 19m, 19v, and 19w were also studied, showing the results of low cytotoxicity on NHDF cell line and being more potent than irosustat on ZR-75-1 cell, which was a hormone-dependent cancer cell line with high STS expression.
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| 16. |
- Chiu, Pei-Fang, et al.
(author)
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Design, structure–activity relationships, and enzyme kinetic studies of tricyclic and tetracyclic coumarin–based sulfamates as steroid sulfatase inhibitors
- 2023
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In: Bioorganic chemistry. - : Elsevier BV. - 0045-2068. ; 138, s. 106581-106581
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Journal article (peer-reviewed)abstract
- Inhibition of steroid sulfatase (STS) decreases estrogen production and thus, suppresses tumor proliferation. Inspired by irosustat, the first STS inhibitor in clinical trials, we explored twenty-one tricyclic and tetra-heterocyclic coumarin–based derivatives. Their STS enzyme kinetic parameters, docking models, and cytotoxicity toward breast cancer and normal cells were evaluated. Tricyclic derivative 9e and tetracyclic derivative 10c were the most promising irreversible inhibitors developed in this study, with KI of 0.05 and 0.4 nM, and kinact/KI ratios of 28.6 and 19.1 nM−1min−1 on human placenta STS, respectively.
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| 17. |
- Contarini, S., et al.
(author)
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Euclid : cosmological forecasts from the void size function
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 667
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Journal article (peer-reviewed)abstract
- The Euclid mission - with its spectroscopic galaxy survey covering a sky area over 15 000 deg(2) in the redshift range 0.9 < z < 1.8 - will provide a sample of tens of thousands of cosmic voids. This paper thoroughly explores for the first time the constraining power of the void size function on the properties of dark energy (DE) from a survey mock catalogue, the official Euclid Flagship simulation. We identified voids in the Flagship light-cone, which closely matches the features of the upcoming Euclid spectroscopic data set. We modelled the void size function considering a state-of-the art methodology: we relied on the volume-conserving (Vdn) model, a modification of the popular Sheth & van de Weygaert model for void number counts, extended by means of a linear function of the large-scale galaxy bias. We found an excellent agreement between model predictions and measured mock void number counts. We computed updated forecasts for the Euclid mission on DE from the void size function and provided reliable void number estimates to serve as a basis for further forecasts of cosmological applications using voids. We analysed two different cosmological models for DE: the first described by a constant DE equation of state parameter, w, and the second by a dynamic equation of state with coefficients w(0) and w(a). We forecast 1 sigma errors on w lower than 10% and we estimated an expected figure of merit (FoM) for the dynamical DE scenario FoM(w0,wa) = 17 when considering only the neutrino mass as additional free parameter of the model. The analysis is based on conservative assumptions to ensure full robustness, and is a pathfinder for future enhancements of the technique. Our results showcase the impressive constraining power of the void size function from the Euclid spectroscopic sample, both as a stand-alone probe, and to be combined with other Euclid cosmological probes.
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| 18. |
- Gong, S., et al.
(author)
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Orientation effect on heat transfer coefficient of a downward surface for flow boiling in a rectangular channel under low flow rate
- 2020
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In: International Journal of Heat and Mass Transfer. - : Elsevier. - 0017-9310 .- 1879-2189. ; 153
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Journal article (peer-reviewed)abstract
- Natural convection boiling in channel with Arc-Shaped will be encountered in the IVR-ERVC (In-Vessel Retention measure by External Reactor Vessel Cooling) system in nuclear power plant under severe accident. The flow and heat transfer characters in this situation is simulated by flow boiling of deionized water in an inclined rectangular channel under low flow rates. This paper aims to separate various parameters (such as orientation, mass flow rate and inlet quality, etc.) to investigate their individual effects on heat transfer coefficient (HTC) in a rectangular channel with cross section of 17 mm × 10 mm. By using a preheater at the inlet of the rectangular channel, the inlet quality could be controlled and the two-phase flow situation could be observed before the fluids entering into the main heater region on one side of the channel wall in downstream. Thus the characteristics of HTC on the main heater could be investigated at different flow patterns. The channel orientations vary from 15 to 90°, the mass flow rates vary from 110 to 288 kg/(m2s) and the qualities vary from 0.003 to 0.036, respectively. Experimental results show that the mass flow rate and quality effects on the HTC are very weak in this study. However, the orientation angle effect on HTC shows an transition region within 45°~60°, while it slowly changes when the orientation angle is smaller than 45° and bigger than 60°. Such tendency could be well formulated by the error function. Compared with different empirical formulas of saturated boiling HTC, it is found that the Liu & Winterton correlation can well predict the experimental HTC results in 90° orientation channel. Based on such correlation and coupled with the error function, a new model was developed by considering the orientation effect, which has an error of ±15% comparing with the experimental data.
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| 19. |
- Hamaus, N., et al.
(author)
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Euclid : Forecasts from redshift-space distortions and the Alcock-Paczynski test with cosmic voids
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
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Journal article (peer-reviewed)abstract
- Euclid is poised to survey galaxies across a cosmological volume of unprecedented size, providing observations of more than a billion objects distributed over a third of the full sky. Approximately 20 million of these galaxies will have their spectroscopy available, allowing us to map the three-dimensional large-scale structure of the Universe in great detail. This paper investigates prospects for the detection of cosmic voids therein and the unique benefit they provide for cosmological studies. In particular, we study the imprints of dynamic (redshift-space) and geometric (Alcock-Paczynski) distortions of average void shapes and their constraining power on the growth of structure and cosmological distance ratios. To this end, we made use of the Flagship mock catalog, a state-of-the-art simulation of the data expected to be observed with Euclid. We arranged the data into four adjacent redshift bins, each of which contains about 11000 voids and we estimated the stacked void-galaxy cross-correlation function in every bin. Fitting a linear-theory model to the data, we obtained constraints on f/b and DMH, where f is the linear growth rate of density fluctuations, b the galaxy bias, D-M the comoving angular diameter distance, and H the Hubble rate. In addition, we marginalized over two nuisance parameters included in our model to account for unknown systematic effects in the analysis. With this approach, Euclid will be able to reach a relative precision of about 4% on measurements of f/b and 0.5% on DMH in each redshift bin. Better modeling or calibration of the nuisance parameters may further increase this precision to 1% and 0.4%, respectively. Our results show that the exploitation of cosmic voids in Euclid will provide competitive constraints on cosmology even as a stand-alone probe. For example, the equation-of-state parameter, w, for dark energy will be measured with a precision of about 10%, consistent with previous more approximate forecasts.
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| 20. |
- Jing, YK, et al.
(author)
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SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism
- 2021
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In: Signal transduction and targeted therapy. - : Springer Science and Business Media LLC. - 2059-3635. ; 6:1, s. 345-
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Journal article (peer-reviewed)abstract
- The SARS-CoV-2 infection causes severe immune disruption. However, it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients. In our study, we have characterized the immune phenotype of B cells from 15 recovered COVID-19 patients, and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation, but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation. However, the percentage of unswitched memory B cells was decreased in recovered patients but not changed in healthy controls upon BCR stimulation. Interestingly, we found that CD19 expression was significantly reduced in almost all the B-cell subsets in recovered patients. Moreover, the BCR signaling and early B-cell response were disrupted upon BCR stimulation. Mechanistically, we found that the reduced CD19 expression was caused by the dysregulation of cell metabolism. In conclusion, we found that SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism, which may provide a new intervention target to cure COVID-19.
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| 21. |
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| 22. |
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| 23. |
- Liu, Z. L., et al.
(author)
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Solar-blind 4.55 eV band gap Mg0.55Zn0.45O components fabricated using quasi-homo buffers
- 2009
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In: Journal of Crystal Growth. - : Elsevier BV. - 0022-0248 .- 1873-5002. ; 311:18, s. 4356-4359
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Journal article (peer-reviewed)abstract
- A route for synthesizing high Mg content single-phase wurtzite MgZnO films having band gaps in the solar-blind region is demonstrated by employing molecular beam epitaxy on Al2O3 substrates. Importantly, a low Mg content "quasi-homo" buffer, Mg0.17Zn0.83O, was applied to accommodate a host of structural discrepancies and therefore, avoiding phase separation in a high Mg content film, Mg0.55Zn0.45O, as proved by X-ray diffraction. The Mg fraction in the overgrown single-phase epilayer, Mg0.55Zn0.45O, was confirmed by Rutherford backscattering spectrometry.
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| 24. |
- Lozano, Rafael, et al.
(author)
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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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In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Journal article (peer-reviewed)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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| 25. |
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| 26. |
- Peeters, LM, et al.
(author)
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COVID-19 in people with multiple sclerosis: A global data sharing initiative
- 2020
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 26:10, s. 1157-1162
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Journal article (peer-reviewed)abstract
- We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. Objectives: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible. Methods: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale. Results: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process. Conclusions: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS.
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| 27. |
- Pöntinen, M., et al.
(author)
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Euclid: Identification of asteroid streaks in simulated images using deep learning
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 679
-
Journal article (peer-reviewed)abstract
- The material composition of asteroids is an essential piece of knowledge in the quest to understand the formation and evolution of the Solar System. Visual to near-infrared spectra or multiband photometry is required to constrain the material composition of asteroids, but we currently have such data, especially in the near-infrared wavelengths, for only a limited number of asteroids. This is a significant limitation considering the complex orbital structures of the asteroid populations. Up to 150 000 asteroids will be visible in the images of the upcoming ESA Euclid space telescope, and the instruments of Euclid will offer multiband visual to near-infrared photometry and slitless near-infrared spectra of these objects. Most of the asteroids will appear as streaks in the images. Due to the large number of images and asteroids, automated detection methods are needed. A non-machine-learning approach based on the Streak Det software was previously tested, but the results were not optimal for short and/or faint streaks. We set out to improve the capability to detect asteroid streaks in Euclid images by using deep learning. We built, trained, and tested a three-step machine-learning pipeline with simulated Euclid images. First, a convolutional neural network (CNN) detected streaks and their coordinates in full images, aiming to maximize the completeness (recall) of detections. Then, a recurrent neural network (RNN) merged snippets of long streaks detected in several parts by the CNN. Lastly, gradient-boosted trees (XGBoost) linked detected streaks between different Euclid exposures to reduce the number of false positives and improve the purity (precision) of the sample. The deep-learning pipeline surpasses the completeness and reaches a similar level of purity of a non-machine-learning pipeline based on the StreakDet software. Additionally, the deep-learning pipeline can detect asteroids 0.25–0.5 magnitudes fainter than StreakDet. The deep-learning pipeline could result in a 50% increase in the number of detected asteroids compared to the StreakDet software. There is still scope for further refinement, particularly in improving the accuracy of streak coordinates and enhancing the completeness of the final stage of the pipeline, which involves linking detections across multiple exposures.
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| 28. |
- Razavi-Shearer, Devin M., et al.
(author)
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Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories
- 2024
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In: JOURNAL OF HEPATOLOGY. - 0168-8278 .- 1600-0641. ; 80:2, s. 232-242
-
Journal article (peer-reviewed)abstract
- Background & Aims: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. Methods: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. Results: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. Conclusions: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened.
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| 29. |
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| 30. |
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| 31. |
- Zhan, Y., et al.
(author)
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Materials capability and device performance in flexible electronics for the Internet of Things
- 2014
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In: Journal of Materials Chemistry C. - : Royal Society of Chemistry (RSC). - 2050-7534. ; 2:7, s. 1220-1232
-
Journal article (peer-reviewed)abstract
- The Internet of Things (IoT) has a broad vision of connecting every single object in the world to form one network. Flexible electronic devices, including RFIDs, sensors, memory devices, displays and power sources, are considered to be the technological basis of the IoT. The development of flexible electronic devices has been extremely rapid in the last decade. Many novel applications have been demonstrated, showing a strong potential impact on human life. In this review, we will summarize the recent progress in the research of flexible electronic devices and related flexible material within the framework of the IoT.
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| 32. |
- Zhang, Yingyang, et al.
(author)
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Prescription Patterns of Antidementia and Psychotropic Drugs in People Living With Dementia : Findings From the Clinical Pathway Study of Alzheimer's Disease in China
- 2022
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In: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 23:6, s. 1073-
-
Journal article (peer-reviewed)abstract
- Objectives: Evidence about prescribing patterns of dementia medication in China is lacking. This study aimed to examine prescribing rates of antidementia and psychotropic drugs and factors associated with drug prescription for dementia in China.Design: A multicenter observational study.Setting and Participants: This study employed cross-sectional data from the Clinical Pathway for Alzheimer's Disease in China study that was conducted in 28 memory clinics at tertiary hospitals across 14 provinces between 2012 and 2013. Patients aged ≥45 years with a diagnosis of dementia were included.Methods: Antidementia and psychotropic drugs were classified according to the Anatomical Therapeutic Chemical codes. Odds ratios (ORs) of putative factors associated with prescription patterns were estimated using logistic regressions.Results: A total of 751 respondents were included in this study, 77.8% of whom were prescribed antidementia drugs, and 33.0% were prescribed at least 1 psychotropic drug. The concomitant prescription rate of antidementia and psychotropic drugs was 24.1%. Frontotemporal dementia [OR 9.92 (99.17% CI 3.08-42.70)], severe dementia [4.25 (1.88-9.79)], and apathy [1.94 (1.18-3.20)] were significantly associated with an elevated likelihood of memantine prescription. Psychotic symptoms [1.84 (1.02-3.35)], agitation [1.91 (1.08-3.40)], and depressive symptoms [2.10 (1.12-3.94)] were significantly associated with the coprescription of antidementia and psychotropic agents.Conclusions and Implications: The prescribing rate of antidementia drugs in the study sample was higher, whereas the rate of coprescription of psychotropic and antidementia drugs was lower than reported in Western studies. Dementia prescription practice was generally consistent with clinical guidelines in memory clinics in China, whereas the prescription of antidementia and psychotropic medication mainly depended on patients’ clinical symptoms.
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| 33. |
- Zhu, Y. -C, et al.
(author)
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Experimental Study of Critical Heat Flux on a Graphite Film
- 2020
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In: Kung Cheng Je Wu Li Hsueh Pao/Journal of Engineering Thermophysics. - : Science Press. - 0253-231X. ; 41:3, s. 643-647
-
Journal article (peer-reviewed)abstract
- Saturated pool boiling experiment with heater surfaces of smooth graphite films was conducted under atmospheric pressure, and the deionized water was used as working fluid. The test results showed that the graphite film began to expand and fracture in some parts of the surface as the heat flux reached 1.83 MW/m2. Then the expanded area enlarged and the resistance of the graphite film rapidly increased with the increase of the heat flux, until the whole film was expanded and the surface was ruptured uniformly under a heat flux of 2.40 MW/m2, while the resistance increased slowly during this process. Ultimately, the graphite film was burned out at a heat flux of 3.17 MW/m2. Consequently, the critical heat flux of the graphite film could be enhanced by an adaptively expanding processing with an enhancement ratio of 73%. The visualization results through a high-speed camera showed that compared with the smooth surface, the quantity of nucleation was greater, the bubble departure diameter was smaller, and the bubble departure frequency was higher on an expanded graphite surface under the same heat flux condition.
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| 34. |
- Abazajian, Kevork, et al.
(author)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
-
Journal article (peer-reviewed)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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| 35. |
- Ade, Peter, et al.
(author)
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The Simons Observatory : science goals and forecasts
- 2019
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In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
-
Journal article (peer-reviewed)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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| 36. |
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| 37. |
- Alchahin, AM, et al.
(author)
-
A transcriptional metastatic signature predicts survival in clear cell renal cell carcinoma
- 2022
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 5747-
-
Journal article (peer-reviewed)abstract
- Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer in adults. When ccRCC is localized to the kidney, surgical resection or ablation of the tumor is often curative. However, in the metastatic setting, ccRCC remains a highly lethal disease. Here we use fresh patient samples that include treatment-naive primary tumor tissue, matched adjacent normal kidney tissue, as well as tumor samples collected from patients with bone metastases. Single-cell transcriptomic analysis of tumor cells from the primary tumors reveals a distinct transcriptional signature that is predictive of metastatic potential and patient survival. Analysis of supporting stromal cells within the tumor environment demonstrates vascular remodeling within the endothelial cells. An in silico cell-to-cell interaction analysis highlights the CXCL9/CXCL10-CXCR3 axis and the CD70-CD27 axis as potential therapeutic targets. Our findings provide biological insights into the interplay between tumor cells and the ccRCC microenvironment.
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| 38. |
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| 39. |
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| 40. |
- Fang, Aoqi, et al.
(author)
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High Color Conversion Efficiency Realized in Graphene-Connected Nanorod Micro-LEDs Using Hybrid Ag Nanoparticles and Quantum Dots
- 2024
-
In: Advanced Optical Materials. - 2195-1071. ; 12:19
-
Journal article (peer-reviewed)abstract
- In this paper, a uniform nanorod (NR) array is etched onto the surface of Micro-Light-Emitting-Diodes (µLEDs) and mix Ag nanoparticles (NPs) with QDs to fill the gaps between the nanorods. Simultaneously, the study utilizes graphene to connect individual nanorods and enhance current spreading. The nanorod array's structure significantly reduces the distance between the QDs and the quantum well (QW), reducing energy loss from the excitation light source through a non-radiative energy transfer (NRET) mechanism. Additionally, the Ag NPs function as localized surface plasmons (LSPs), further enhancing the CCE of QDs via the absorption resonance. In this study, the effects of two types of Ag NPs are compared with different absorption resonance peaks on device performance. The results demonstrate that Ag NPs with absorption resonance peaks matching the emission wavelength of QDs play a more crucial role in the system. This configuration achieves a CCE of 77.78% for µLEDs with nanorod arrays, operating at a current of 10 mA. Compared to the conventional µLED structure with QDs only on the surface, the proposed method improves the CCE of µLEDs by an impressive 86.5%. This outcome underscores the significant contribution of the NR structure and LSPs in enhancing the CCE of QD-µLEDs.
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| 41. |
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| 42. |
- Gong, S., et al.
(author)
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An investigation on dynamic thickness of a boiling liquid film
- 2015
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In: International Journal of Heat and Mass Transfer. - : Elsevier BV. - 0017-9310 .- 1879-2189. ; 90, s. 636-644
-
Journal article (peer-reviewed)abstract
- Motivated by understanding the micro-hydrodynamics of boiling heat transfer and the mechanism of critical heat flux (CHF) occurrence, the present study is to investigate the boiling phenomenon in a liquid film whose dynamic thickness is recorded by a confocal optical sensor with the measurement accuracy of micrometres, while the bubble dynamics of the boiling in the film is visualized by a high-speed photography. This paper is focused on a statistical analysis of the measured thickness signals for the boiling condition ranging from low heat flux to high heat flux (near or at CHF). The dynamic thickness of liquid film appears oscillating with peak values, resulting from the liquid film movements due to nucleation of bubble(s) and its growth and rupture. The statistical analysis in a certain period indicates there emerge three distinct liquid film thickness ranges: 0-50 μm, 50-500 μm and 500-2500 μm, seemingly corresponding to the microlayer, macrolayer and bulk layer. With increasing heat flux to a specific extent, the bulk layer disappears, and then the macrolayer gradually decreases to ∼105 μm, beyond which the liquid film may lose its integrity and CHF occurs at 1.563 MW/m2.
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| 43. |
- Gu, H., et al.
(author)
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Investigation on contact angle measurement methods and wettability transition of porous surfaces
- 2016
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In: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 292, s. 72-77
-
Journal article (peer-reviewed)abstract
- Various solid surfaces (e.g., smooth titanium surface, smooth aluminum surface, polished copper surfaces, polished silver surfaces and porous copper surfaces) were prepared to quantify the reliability of half-angle algorithm and axisymmetric drop shape analysis (ADSA) algorithm for calculating contact angles. Besides, the effects of surface conditions on contact angle values were also investigated. The experimental results of 10 repeated tests for each surface show that both algorithms have good accuracy for an acute contact angle, while the ADSA algorithm is better than the half-angle algorithm for an obtuse contact angle. Furthermore, with the decrease of surface roughness, the contact angle increases but the standard deviation of contact angles by 10 repeated tests decreases. In addition, the porous layer on copper surface by electrochemical deposition shows a super hydrophilic property, but it could change to be super hydrophobic after exposed in ambient air for 24 h. Interestingly, the surface wettability reverses to be super hydrophilic again after it is immersed in water, and the inorganic contamination is the reason of formal change from the super hydrophilic status to the super hydrophobic status.
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| 44. |
- Hirz, T, et al.
(author)
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Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses
- 2023
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 663-
-
Journal article (peer-reviewed)abstract
- The treatment of low-risk primary prostate cancer entails active surveillance only, while high-risk disease requires multimodal treatment including surgery, radiation therapy, and hormonal therapy. Recurrence and development of metastatic disease remains a clinical problem, without a clear understanding of what drives immune escape and tumor progression. Here, we comprehensively describe the tumor microenvironment of localized prostate cancer in comparison with adjacent normal samples and healthy controls. Single-cell RNA sequencing and high-resolution spatial transcriptomic analyses reveal tumor context dependent changes in gene expression. Our data indicate that an immune suppressive tumor microenvironment associates with suppressive myeloid populations and exhausted T-cells, in addition to high stromal angiogenic activity. We infer cell-to-cell relationships from high throughput ligand-receptor interaction measurements within undissociated tissue sections. Our work thus provides a highly detailed and comprehensive resource of the prostate tumor microenvironment as well as tumor-stromal cell interactions.
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| 45. |
- Hirz, T, et al.
(author)
-
Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses
- 2023
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 663-
-
Journal article (peer-reviewed)abstract
- The treatment of low-risk primary prostate cancer entails active surveillance only, while high-risk disease requires multimodal treatment including surgery, radiation therapy, and hormonal therapy. Recurrence and development of metastatic disease remains a clinical problem, without a clear understanding of what drives immune escape and tumor progression. Here, we comprehensively describe the tumor microenvironment of localized prostate cancer in comparison with adjacent normal samples and healthy controls. Single-cell RNA sequencing and high-resolution spatial transcriptomic analyses reveal tumor context dependent changes in gene expression. Our data indicate that an immune suppressive tumor microenvironment associates with suppressive myeloid populations and exhausted T-cells, in addition to high stromal angiogenic activity. We infer cell-to-cell relationships from high throughput ligand-receptor interaction measurements within undissociated tissue sections. Our work thus provides a highly detailed and comprehensive resource of the prostate tumor microenvironment as well as tumor-stromal cell interactions.
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| 46. |
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| 47. |
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| 48. |
- Joshi, Peter K, et al.
(author)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
-
Journal article (peer-reviewed)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 49. |
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| 50. |
- Liang, H. L., et al.
(author)
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Growth of single-phase Mg0.3Zn0.7O films suitable for solar-blind optical devices on RS-MgO substrates
- 2012
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In: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 520:6, s. 1705-1708
-
Journal article (peer-reviewed)abstract
- Single-phase rock-salt Mg0.3Zn0.7O film was fabricated on MgO (100) substrate by radio-frequency plasma assisted molecular beam epitaxy. A smooth surface was observed by in-situ reflection high-energy electron diffraction and ex-situ atomic force microscopy. X-ray diffraction characterization demonstrated a high-quality single-phase structure with highly (200) orientation and cube-on-cube epitaxial relationship. Zn fraction in the single-phase rock-salt Mg0.3Zn0.7O film was determined by Rutherford backscattering spectrometry. Optical property of the film was investigated by reflectance spectroscopy, which indicated a solar-blind band gap of 255.5 nm. The reason why Zn solubility limit is greatly enhanced in non-polar (100) film compared with (111) polar epilayer is tentatively discussed in this work, suggesting MgO (100) is more suitable for the synthesis of single-phase rock-salt MgZnO with high Zn content towards solar-blind opto-device applications.
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