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Life Stress and Dementia Risk in Adults with Down Syndrome
Get PDFDown syndrome (DS) is the most common genetic cause of intellectual disability, resulting from a triplication of chromosome 21. Individuals with DS are at a higher risk of developing Alzheimer’s Disease (AD) compared to the general population. Previously, exposure to stress has been suggested as a risk factor for dementia and AD in the general population. However, the role of life stress in the timing of AD in DS is underinvestigated. Using the Alzheimer Biomarkers Consortium - Down Syndrome (ABC-DS) dataset, we analyzed the association between baseline life stressors, and later cognitive decline and dementia at 16 or 32-month follow-up. We found that a higher baseline sum of stress events was associated with greater risk of conversion from baseline stable cognition to mild cognitive impairment (MCI) or dementia at follow up, even when controlling for age, sex, premorbid level of intellectual disability, site, clinical latency between assessments, and the presence of anxiety or depression (odds ratio = 1.53, p = 0.021). Additionally, the death of a loved one at baseline, when rated as having a negative or complex impact, was associated with a decline of more than 6 points on the Block Design test (p = 0.009), compared to those without this experience. These results suggest that life stressors may predict cognitive decline and dementia in adults with DS, highlighting a potential target for treatment or intervention. Results also suggest that there may be similar risk factors for AD in adults with DS as those found in the general population
Asymmetric modular pulse synthesizer as a high-fidelity solution for transcranial magnetic stimulation with practically any pulse shape.
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A model-independent measurement of the CKM angle γ in the decays B±→ [K+K−π+π−]Dh± and B±→ [π+π−π+π−]Dh± (h = K, π)
Get PDFA model-independent determination of the CKM angle γ is presented, using the B± → [K+K−π+π−]Dh± and B± → [π+π−π+π−]Dh± decays, with h = K, π. This measurement is the first phase-space binned study of these decay modes, and uses a sample of proton-proton collision data collected by the LHCb experiment, corresponding to an integrated luminosity of 9 fb−1. The phase-space bins are optimised for sensitivity to γ, and in each bin external inputs from the BESIII experiment are used to constrain the charm strong-phase parameters. The result of this binned analysis is γ=53.9−8.9+9.5°, where the uncertainty includes both statistical and systematic contributions. Furthermore, when combining with existing phase-space integrated measurements of the same decay modes, a value of γ=52.6−6.4+8.5° is obtained, which is one of the most precise determinations of γ to date
Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.
Get PDFIMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world
Towards Trustworthy Highway Infrastructure Digital Twins: A Regional Graph-Based Method for Section-Level Pavement Data Quality Assessment
No full textDigital twins (DTs) are rapidly gaining attention as a powerful tool for intelligent highway infrastructure management. By integrating real-time sensing, modeling, and data-driven analytics, DTs enable transport agencies to monitor pavement performance and make informed maintenance decisions. However, data quality remains a critical trustworthiness concern, particularly as automated pavement condition surveys increasingly replace manual inspections. This study presents a regional graph-based method for assessing the quality of pavement condition data at the section level. Specifically, the method consists of two key steps: first, a region-based clustering approach using DBSCAN is applied to group neighboring road sections with similar deterioration patterns into homogeneous clusters. Then, a Graph-Mamba Attention Network (GMAN) is introduced to evaluate the reliability of each condition data point within these clusters by capturing spatial and temporal dependencies in the data. The method was evaluated using real-world characteristic skid coefficient (CSC) data from the UK’s Strategic Road Network (SRN), supported by TRL Software’s iROADS digital twin platform. Results showed that the proposed method consistently outperformed existing methods in identifying abnormal data points (38.8% and 7.1% increase in accuracy and recall, respectively), demonstrating its potential to improve the effectiveness and trustworthiness of pavement data quality management within highway DTs
Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019.
Get PDFBACKGROUND: Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. METHODS: We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (U5MR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. FINDINGS: Global U5MR decreased from 71·2 deaths per 1000 livebirths (95% uncertainty interval [UI] 68·3-74·0) in 2000 to 37·1 (33·2-41·7) in 2019 while global NMR correspondingly declined more slowly from 28·0 deaths per 1000 live births (26·8-29·5) in 2000 to 17·9 (16·3-19·8) in 2019. In 2019, 136 (67%) of 204 countries had a U5MR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030, 154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9·65 million (95% UI 9·05-10·30) in 2000 and 5·05 million (4·27-6·02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3·76 million [95% UI 3·53-4·02]) in 2000 to 48% (2·42 million; 2·06-2·86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0·80 (95% UI 0·71-0·86) deaths per 1000 livebirths and U5MR to 1·44 (95% UI 1·27-1·58) deaths per 1000 livebirths, and in 2019, there were as many as 1·87 million (95% UI 1·35-2·58; 37% [95% UI 32-43]) of 5·05 million more deaths of children younger than 5 years than the survival potential frontier. INTERPRETATION: Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve U5MR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. FUNDING: Bill & Melinda Gates Foundation
JWST Spectroscopy of GRB 250702B: An Extremely Rare and Exceptionally Energetic Burst in a Dusty, Massive Galaxy at z = 1.036
Get PDFWe present follow-up observations of the day-long, repeating gamma-ray burst (GRB) GRB 250702B with the Near Infrared Spectrograph on board the James Webb Space Telescope. Through the identification of narrow hydrogen emission lines at a consistent redshift of z = 1.036 ± 0.004, we calibrate the distance scale, and therefore the energetics, of this unique extragalactic transient. At this distance, the resulting γ-ray energy release is at least Eγ,iso = 2.2 × 1054 erg. We find no evidence for ongoing transient emission at the GRB position and exclude any accompanying supernova (SN) with a luminosity comparable to the Type Ic broad-line SN 2023lcr, though we are unable to rule out a fainter SN counterpart owing to high extinction. The inferred rate of such events, assuming at most one in the lifetime of Fermi, suggests that such bursts are very rare, with volumetric rates over 1000 times lower than normal high-luminosity long GRBs and >105 times lower than core-collapse SNe, when corrected for beaming. Furthermore, we find that the host galaxy is unique among GRB host galaxies and extremely rare in the general galaxy population, being extremely large and dusty and with high stellar mass. The identification of such an exotic GRB in such an unusual galaxy raises the possibility that the environment was important in the progenitor channel creating GRB 250702B
Porous GaN: Anion-Specific Electrochemical Etching Mechanisms and Morphological Control
Get PDFPorous GaN has emerged as a promising material for enhancing the performance of optoelectronic devices and broadening the range of possible GaN applications. However, the electrochemical etching (ECE) process used to create porosity remains poorly understood, particularly regarding the impact of the chemical environment on pore morphology. Here, the controlled ECE of n-type GaN is systematically investigated across a range of etchant chemicals and pH values. It is shown that the identity, speciation, and relative concentrations of anionic species play dominant roles in dictating porous morphology. Through deliberate manipulation of anion compositions within an etchant solution, for example, by adjusting initial polyprotic acid concentration and/or addition of a conjugate salt, porous morphology and surface structure can be controlled and tuned effectively. Further, ECE-generated current oscillations, previously interpreted as evidence for an oxidation–dissolution ECE mechanism, are shown to correlate with the presence of dynamic anion equilibria, providing an additional mechanistic interpretation of n-type GaN ECE. This furthered understanding enables more tailored and application-specific control over porous structure, offering opportunities for optimized, bespoke GaN-based porous architectures
Frozen elephant trunk: Approach and innovations from the UK's leading centre.
Get PDFThe frozen elephant trunk (FET) procedure has emerged as a transformative approach for complex aortic arch pathology, addressing limitations of conventional elephant trunk procedures, including the need for second-stage operations with interval mortality, inability to expand the true lumen in dissections and lack of distal anastomotic support.Our experience with over 200 procedures demonstrates FET technique evolution and refinement, achieving 13.8% overall mortality. Presenting pathologies were diverse, predominantly aneurysmal disease and acute or chronic dissections. Most utilised Thoraflex Hybrid, though the Jotec E-vita prosthesis has been increasingly used recently. Critical technical advancements include bilateral axillary artery cannulation, which has dramatically reduced neurological complications, including paraplegia and recurrent laryngeal nerve injury, compared to historical series. It also made the procedure technically less complex and more reproducible. In selected cases, we have also adopted a beating heart strategy to reduce the cardiac ischaemic time once the proximal aortic repair has been completed. The beating heart strategy demonstrated a tendency for reduced post-operative adrenaline requirements without compromising outcomes.Frozen elephant trunk demands advanced perfusion strategies, proactive spinal cord protection and meticulous surgical technique but reduces the need for future open repair, facilitating endovascular interventions. Our experience demonstrates that FET represents a paradigm shift toward comprehensive single-stage treatment of complex aortic arch pathology with acceptable outcomes when performed in high-volume centres by experienced multidisciplinary teams