| 1. |
- Namkoong, H, et al.
(author)
-
DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
-
Journal article (peer-reviewed)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
|
|
| 2. |
|
|
| 3. |
- Wang, QBS, et al.
(author)
-
The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
-
Journal article (peer-reviewed)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
|
|
| 4. |
- Abe, K., et al.
(author)
-
Neutron tagging following atmospheric neutrino events in a water Cherenkov detector
- 2022
-
In: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 17:10
-
Journal article (peer-reviewed)abstract
- We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218 +/- 9 mu s.
|
|
| 5. |
|
|
| 6. |
- Tanaka, Y. K., et al.
(author)
-
Search for eta '-mesic nuclei using (p,d) reaction with FRS/Super-FRS at GSI/FAIR
- 2020
-
In: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1643
-
Journal article (peer-reviewed)abstract
- We plan a semi-exclusive measurement of the C-12(p,dp) reaction to search for eta'-mesic nuclei, aiming at investigating in-medium properties of the eta'-meson. We employ a 2.5 GeV proton beam impinging on a carbon target to produce eta'-mesic C-11 nuclei via the C-12(p,d)eta'circle times C-11 reaction. Using coincidence measurements of the forward going deuterons, important for missing-mass spectroscopy, and decay protons emitted from the eta'-mesic nuclei for event selection will provide a high experimental sensitivity to observe eta'-mesic nuclei. We will perform the measurements by combining the WASA detector system with the fragment separator FRS at GSI and also with the Super-FRS at FAIR in the future. The plan of the experiments and the present status are reported.
|
|
| 7. |
|
|
| 8. |
- Alfaray, R. I., et al.
(author)
-
Global Antimicrobial Resistance Gene Study of Helicobacter pylori: Comparison of Detection Tools, ARG and Efflux Pump Gene Analysis, Worldwide Epidemiological Distribution, and Information Related to the Antimicrobial-Resistant Phenotype
- 2023
-
In: Antibiotics-Basel. - 2079-6382. ; 12:7
-
Journal article (peer-reviewed)abstract
- We conducted a global-scale study to identify H. pylori antimicrobial-resistant genes (ARG), address their global distribution, and understand their effect on the antimicrobial resistance (AMR) phenotypes of the clinical isolates. We identified ARG using several well-known tools against extensive bacterial ARG databases, then analyzed their correlation with clinical antibiogram data from dozens of patients across countries. This revealed that combining multiple tools and databases, followed by manual selection of ARG from the annotation results, produces more conclusive results than using a single tool or database alone. After curation, the results showed that H. pylori has 42 ARG against 11 different antibiotic classes (16 genes related to single antibiotic class resistance and 26 genes related to multidrug resistance). Further analysis revealed that H. pylori naturally harbors ARG in the core genome, called the 'Set of ARG commonly found in the Core Genome of H. pylori (ARG-CORE)', while ARG-ACC-the ARG in the accessory genome-are exclusive to particular strains. In addition, we detected 29 genes of potential efflux pump-related AMR that were mostly categorized as ARG-CORE. The ARG distribution appears to be almost similar either by geographical or H. pylori populations perspective; however, some ARG had a unique distribution since they tend to be found only in a particular region or population. Finally, we demonstrated that the presence of ARG may not directly correlate with the sensitive/resistance phenotype of clinical patient isolates but may influence the minimum inhibitory concentration phenotype.
|
|
| 9. |
|
|
| 10. |
- Kang, JS, et al.
(author)
-
Risk prediction for malignant intraductal papillary mucinous neoplasm of the pancreas: logistic regression versus machine learning
- 2020
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 20140-
-
Journal article (peer-reviewed)abstract
- Most models for predicting malignant pancreatic intraductal papillary mucinous neoplasms were developed based on logistic regression (LR) analysis. Our study aimed to develop risk prediction models using machine learning (ML) and LR techniques and compare their performances. This was a multinational, multi-institutional, retrospective study. Clinical variables including age, sex, main duct diameter, cyst size, mural nodule, and tumour location were factors considered for model development (MD). After the division into a MD set and a test set (2:1), the best ML and LR models were developed by training with the MD set using a tenfold cross validation. The test area under the receiver operating curves (AUCs) of the two models were calculated using an independent test set. A total of 3,708 patients were included. The stacked ensemble algorithm in the ML model and variable combinations containing all variables in the LR model were the most chosen during 200 repetitions. After 200 repetitions, the mean AUCs of the ML and LR models were comparable (0.725 vs. 0.725). The performances of the ML and LR models were comparable. The LR model was more practical than ML counterpart, because of its convenience in clinical use and simple interpretability.
|
|
| 11. |
|
|
| 12. |
- Sakatani, N., et al.
(author)
-
Anomalously porous boulders on (162173) Ryugu as primordial materials from its parent body
- 2021
-
In: Nature Astronomy. - : Springer Nature. - 2397-3366. ; 5:8, s. 766-774
-
Journal article (peer-reviewed)abstract
- Planetesimals—the initial stage of the planetary formation process—are considered to be initially very porous aggregates of dusts1,2, and subsequent thermal and compaction processes reduce their porosity3. The Hayabusa2 spacecraft found that boulders on the surface of asteroid (162173) Ryugu have an average porosity of 30–50% (refs. 4,5,6), higher than meteorites but lower than cometary nuclei7, which are considered to be remnants of the original planetesimals8. Here, using high-resolution thermal and optical imaging of Ryugu’s surface, we discovered, on the floor of fresh small craters (<20 m in diameter), boulders with reflectance (~0.015) lower than the Ryugu average6 and porosity >70%, which is as high as in cometary bodies. The artificial crater formed by Hayabusa2’s impact experiment9 is similar to these craters in size but does not have such high-porosity boulders. Thus, we argue that the observed high porosity is intrinsic and not created by subsequent impact comminution and/or cracking. We propose that these boulders are the least processed material on Ryugu and represent remnants of porous planetesimals that did not undergo a high degree of heating and compaction3. Our multi-instrumental analysis suggests that fragments of the highly porous boulders are mixed within the surface regolith globally, implying that they might be captured within collected samples by touch-down operations10,11.
|
|
| 13. |
- Amano, T., et al.
(author)
-
Observational Evidence for Stochastic Shock Drift Acceleration of Electrons at the Earth's Bow Shock
- 2020
-
In: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 124:6
-
Journal article (peer-reviewed)abstract
- The first-order Fermi acceleration of electrons requires an injection of electrons into a mildly relativistic energy range. However, the mechanism of injection has remained a puzzle both in theory and observation. We present direct evidence for a novel stochastic shock drift acceleration theory for the injection obtained with Magnetospheric Multiscale observations at the Earth's bow shock. The theoretical model can explain electron acceleration to mildly relativistic energies at high-speed astrophysical shocks, which may provide a solution to the long-standing issue of electron injection.
|
|
| 14. |
- Bulla, Mattia, et al.
(author)
-
Polarized kilonovae from black hole-neutron star mergers
- 2021
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 501:2, s. 1891-1899
-
Journal article (peer-reviewed)abstract
- We predict linear polarization for a radioactively powered kilonova following the merger of a black hole and a neutron star. Specifically, we perform 3D Monte Carlo radiative transfer simulations for two different models, both featuring a lanthanide-rich dynamical ejecta component from numerical-relativity simulations while only one including an additional lanthanide-free disc-wind component. We calculate polarization spectra for nine different orientations at 1.5, 2.5, and 3.5 d after the merger and in the 0.1-2 mu m wavelength range. We find that both models are polarized at a detectable level 1.5 d after the merger while show negligible levels thereafter. The polarization spectra of the two models are significantly different. The model lacking a disc wind shows no polarization in the optical, while a signal increasing at longer wavelengths and reaching similar to 1-6 per cent at 2 mu m depending on the orientation. The model with a disc-wind component, instead, features a characteristic 'double-peak' polarization spectrum with one peak in the optical and the other in the infrared. Polarimetric observations of future events will shed light on the debated neutron richness of the disc-wind component. The detection of optical polarization would unambiguously reveal the presence of a lanthanide-free disc-wind component, while polarization increasing from zero in the optical to a peak in the infrared would suggest a lanthanide-rich composition for the whole ejecta. Future polarimetric campaigns should prioritize observations in the first similar to 48 h and in the 0.5-2 mu m range, where polarization is strongest, but also explore shorter wavelengths/later times where no signal is expected from the kilonova and the interstellar polarization can be safely estimated.
|
|
| 15. |
- Marriott, R. J., et al.
(author)
-
Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: The UK Biobank prospective cohort study
- 2022
-
In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:10, s. 1907-18
-
Journal article (peer-reviewed)abstract
- Introduction: The association of testosterone concentrations with dementia risk remains uncertain. We examined associations of serum testosterone and sex hormone–binding globulin (SHBG) with incidence of dementia and Alzheimer's disease. Methods: Serum total testosterone and SHBG were measured by immunoassay. The incidence of dementia and Alzheimer's disease (AD) was recorded. Cox proportional hazards regression was adjusted for age and other variables. Results: In 159,411 community-dwelling men (median age 61, followed for 7 years), 826 developed dementia, including 288 from AD. Lower total testosterone was associated with a higher incidence of dementia (overall trend: P=.001, lowest vs highest quintile: hazard ratio [HR]=1.43, 95% confidence interval [CI]=1.13-1.81), and AD (P=.017, HR=1.80, CI=1.21-2.66). Lower SHBG was associated with a lower incidence of dementia (P<.001, HR=0.66, CI=0.51-0.85) and AD (P=.012, HR=0.53, CI=0.34-0.84). Discussion: Lower total testosterone and higher SHBG are independently associated with incident dementia and AD in older men. Additional research is needed to determine causality. © 2021 the Alzheimer's Association
|
|
| 16. |
|
|
| 17. |
- Sekiguchi, M, et al.
(author)
-
Integrated multiomics analysis of hepatoblastoma unravels its heterogeneity and provides novel druggable targets
- 2020
-
In: NPJ precision oncology. - : Springer Science and Business Media LLC. - 2397-768X. ; 4:1, s. 20-
-
Journal article (peer-reviewed)abstract
- Although hepatoblastoma is the most common pediatric liver cancer, its genetic heterogeneity and therapeutic targets are not well elucidated. Therefore, we conducted a multiomics analysis, including mutatome, DNA methylome, and transcriptome analyses, of 59 hepatoblastoma samples. Based on DNA methylation patterns, hepatoblastoma was classified into three clusters exhibiting remarkable correlation with clinical, histological, and genetic features. Cluster F was largely composed of cases with fetal histology and good outcomes, whereas clusters E1 and E2 corresponded primarily to embryonal/combined histology and poor outcomes. E1 and E2, albeit distinguishable by different patient age distributions, were genetically characterized by hypermethylation of the HNF4A/CEBPA-binding regions, fetal liver-like expression patterns, upregulation of the cell cycle pathway, and overexpression of NQO1 and ODC1. Inhibition of NQO1 and ODC1 in hepatoblastoma cells induced chemosensitization and growth suppression, respectively. Our results provide a comprehensive description of the molecular basis of hepatoblastoma and rational therapeutic strategies for high-risk cases.
|
|
| 18. |
- Thorell, Kaisa, 1983, et al.
(author)
-
The Helicobacter pylori Genome Project: insights into H. pylori population structure from analysis of a worldwide collection of complete genomes
- 2023
-
In: Nature Communications. - 2041-1723. ; 14:1
-
Journal article (peer-reviewed)abstract
- Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics.
|
|
| 19. |
- Yeap, B. B., et al.
(author)
-
Androgens in men study (AIMS): Protocol for meta-analyses of individual participant data investigating associations of androgens with health outcomes in men
- 2020
-
In: BMJ Open. - : BMJ. - 2044-6055. ; 10:5
-
Journal article (peer-reviewed)abstract
- Introduction This study aims to clarify the role(s) of endogenous sex hormones to influence health outcomes in men, specifically to define the associations of plasma testosterone with incidence of cardiovascular events, cancer, dementia and mortality risk, and to identify factors predicting testosterone concentrations. Data will be accrued from at least three Australian, two European and four North American population-based cohorts involving approximately 20 000 men. Methods and analysis Eligible studies include prospective cohort studies with baseline testosterone concentrations measured using mass spectrometry and 5 years of follow-up data on incident cardiovascular events, mortality, cancer diagnoses or deaths, new-onset dementia or decline in cognitive function recorded. Data for men, who were not taking androgens or drugs suppressing testosterone production, metabolism or action; and had no prior orchidectomy, are eligible. Systematic literature searches were conducted from 14 June 2019 to 31 December 2019, with no date range set for searches. Aggregate level data will be sought where individual participant data (IPD) are not available. One-stage IPD random-effects meta-analyses will be performed, using linear mixed models, generalised linear mixed models and either stratified or frailty-augmented Cox regression models. Heterogeneity in estimates from different studies will be quantified and bias investigated using funnel plots. Effect size estimates will be presented in forest plots and non-negligible heterogeneity and bias investigated using subgroup or meta-regression analyses. Ethics and dissemination Ethics approvals obtained for each of the participating cohorts state that participants have consented to have their data collected and used for research purposes. The Androgens In Men Study has been assessed as exempt from ethics review by the Human Ethics office at the University of Western Australia (file reference number RA/4/20/5014). Each of the component studies had obtained ethics approvals; please refer to respective component studies for details. Research findings will be disseminated to the scientific and broader community via the publication of four research articles, with each involving a separate set of IPD meta-analyses (articles will investigate different, distinct outcomes), at scientific conferences and meetings of relevant professional societies. Collaborating cohort studies will disseminate findings to study participants and local communities. PROSPERO registration number CRD42019139668. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
|
|
| 20. |
- Aoyagi, M., et al.
(author)
-
Systematic effects on a Compton polarimeter at the focus of an X-ray mirror
- 2024
-
In: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 158
-
Journal article (peer-reviewed)abstract
- XL-Calibur is a balloon-borne Compton polarimeter for X-rays in the ∼15–80 keV range. Using an X-ray mirror with a 12 m focal length for collecting photons onto a beryllium scattering rod surrounded by CZT detectors, a minimum-detectable polarization as low as ∼3% is expected during a 24-hour on-target observation of a 1 Crab source at 45° elevation. Systematic effects alter the reconstructed polarization as the mirror focal spot moves across the beryllium scatterer, due to pointing offsets, mechanical misalignment or deformation of the carbon-fiber truss supporting the mirror and the polarimeter. Unaddressed, this can give rise to a spurious polarization signal for an unpolarized flux, or a change in reconstructed polarization fraction and angle for a polarized flux. Using bench-marked Monte-Carlo simulations and an accurate mirror point-spread function characterized at synchrotron beam-lines, systematic effects are quantified, and mitigation strategies discussed. By recalculating the scattering site for a shifted beam, systematic errors can be reduced from several tens of percent to the few-percent level for any shift within the scattering element. The treatment of these systematic effects will be important for any polarimetric instrument where a focused X-ray beam is impinging on a scattering element surrounded by counting detectors.
|
|
| 21. |
|
|
| 22. |
- Hilbert-Carius, Peter, et al.
(author)
-
Successfully REBOA performance: does medical specialty matter? International data from the ABOTrauma Registry
- 2020
-
In: World Journal of Emergency Surgery. - : Springer Science and Business Media LLC. - 1749-7922. ; 15:1
-
Journal article (peer-reviewed)abstract
- © 2020, The Author(s). Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive procedure being increasingly utilized to prevent patients with non-compressible torso hemorrhage from exsanguination. The increased use of REBOA is giving rise to discussion about “Who is and who should be performing it?” Methods: Data from the international ABO (aortic balloon occlusion) Trauma Registry from between November 2014 and April 2020 were analyzed concerning the question: By who, how, and where is REBOA being performed? The registry collects retrospective and prospective data concerning use of REBOA in trauma patients. Results: During the study period, 259 patients had been recorded in the registry, 72.5% (n = 188) were males with a median (range) age of 46 (10-96) years. REBOA was performed in the ER in 50.5%, in the OR in 41.5%, and in the angiography suite in 8% of patients. In 54% of the patients REBOA was performed by surgeons (trauma surgeons 28%, vascular surgeons 22%, general surgeons 4%) and in 46% of the patients by non-surgeons (emergency physicians 31%, radiologists 9.5%, anesthetists 5.5%). Common femoral artery (CFA) access was achieved by use of external anatomic landmarks and palpation alone in 119 patients (51%), by cutdown in 57 patients (24%), using ultrasound in 49 patients (21%), and by fluoroscopy in 9 patients (4%). Significant differences between surgeons and non-surgeons were found regarding patient’s age, injury severity, access methods, place where REBOA was performed, location patients were taken to from the emergency room, and mortality. Conclusion: A substantial number of both surgical and non-surgical medical disciplines are successfully performing REBOA to an almost equal extent. Surgical cutdown is used less frequently as access to the CFA compared with reports in older literature and puncture by use of external anatomic landmarks and palpation alone is used with a high rate of success. Instead of discussing “Who should be performing REBOA?” future research should focus on “Which patient benefits most from REBOA?”
|
|
| 23. |
- Hirano, T., et al.
(author)
-
An Earth-sized Planet around an M5 Dwarf Star at 22 pc
- 2023
-
In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 165:3
-
Journal article (peer-reviewed)abstract
- We report on the discovery of an Earth-sized transiting planet (R p = 1.015 ± 0.051 R ⊕) in a P = 4.02 day orbit around K2-415 (EPIC 211414619), an M5V star at 22 pc. The planet candidate was first identified by analyzing the light-curve data obtained by the K2 mission, and it is here shown to exist in the most recent data from TESS. Combining the light curves with the data secured by our follow-up observations, including high-resolution imaging and near-infrared spectroscopy with IRD, we rule out false-positive scenarios, finding a low false-positive probability of 2 × 10−4. Based on IRD’s radial velocities of K2-415, which were sparsely taken over three years, we obtain a planet mass of 3.0 ± 2.7 M ⊕ (M p < 7.5 M ⊕ at 95% confidence) for K2-415b. Being one of the lowest-mass stars (≈0.16 M ⊙) known to host an Earth-sized transiting planet, K2-415 will be an interesting target for further follow-up observations, including additional radial velocity monitoring and transit spectroscopy.
|
|
| 24. |
- Ivanics, Tommy, et al.
(author)
-
Impact of the acuity circle model for liver allocation on multivisceral transplant candidates
- 2022
-
In: American Journal of Transplantation. - : John Wiley & Sons. - 1600-6135 .- 1600-6143. ; 22:2, s. 464-473
-
Journal article (peer-reviewed)abstract
- Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018–2020) and post-AC (2020–2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96–74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15–0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.
|
|
| 25. |
- Iyer, Nirmal, et al.
(author)
-
The design and performance of the XL-Calibur anticoincidence shield
- 2023
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 1048
-
Journal article (peer-reviewed)abstract
- The XL-Calibur balloon-borne hard X-ray polarimetry mission comprises a Compton-scattering polarimeter placed at the focal point of an X-ray mirror. The polarimeter is housed within a BGO anticoincidence shield, which is needed to mitigate the considerable background radiation present at the observation altitude of -40 km. This paper details the design, construction and testing of the anticoincidence shield, as well as the performance measured during the week-long maiden flight from Esrange Space Centre to the Canadian Northwest Territories in July 2022. The in-flight performance of the shield followed design expectations, with a veto threshold <100 keV and a measured background rate of -0.5 Hz (20-40 keV). This is compatible with the scientific goals of the mission, where %-level minimum detectable polarisation is sought for a Hz-level source rate.
|
|
| 26. |
- Jelenkovic, A, et al.
(author)
-
Genetic and environmental influences on human height from infancy through adulthood at different levels of parental education
- 2020
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 7974-
-
Journal article (peer-reviewed)abstract
- Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.
|
|
| 27. |
- Matsumoto, D, et al.
(author)
-
Heritability and Environmental Correlation of Phase Angle with Anthropometric Measurements: A Twin Study
- 2020
-
In: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 17:21
-
Journal article (peer-reviewed)abstract
- Bioelectrical impedance analysis (BIA)-derived phase angle (PhA) is a valuable parameter to assess physical health. However, the genetic and environmental aspects of PhA are not yet well understood. The present study aimed to estimate the heritability of PhA and investigate the relationships between PhA and anthropometric measurements. PhA and skeletal muscle mass index (SMI) were examined using multi-frequency BIA in 168 Japanese twin volunteers (54 males and 114 females; mean age = 61.0 ± 16.5 years). We estimated the narrow-sense heritability of these parameters and the genetic and environmental relationships between them using a genetic twin modeling. For the PhA, 51% (95% confidence interval: 0.33, 0.64) of the variance was explained by additive genetic effects, and 49% (95% confidence interval: 0.36, 0.67) was explained by unique environmental effects. The heritability of PhA was lower than the height, body weight, and body mass index. PhA shared almost no genetic variation with anthropometric measurements and SMI but shared an environmental variation (14%) with SMI. These findings suggest that the genes affecting PhA are different than those affecting anthropometric measurements and SMI. The correlation between PhA and SMI is caused by common environmental factors.
|
|
| 28. |
- Nguyen, Thanh N, et al.
(author)
-
Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
-
In: Neurology. - 1526-632X. ; 100:4
-
Journal article (peer-reviewed)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
|
|
| 29. |
- Schijven, Dick, et al.
(author)
-
Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
- 2023
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
-
Journal article (peer-reviewed)abstract
- Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
|
|
| 30. |
|
|
