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OBJECTIVES: The occurrence of cognitive deficits after subarachnoid hemorrhage (SAH) is highly possible, leading to vascular dementia. We performed a novel longitudinal genome-wide association study (GWAS) to identify genetic modifications associated with cognitive impairment following SAH in a long-term prospective cohort study. MATERIALS AND METHODS: This GWAS involved 153 patients with SAH sharing 5,971,372 markers after high-throughput imputation. Genome-wide Cox proportional hazard regression testing was performed to estimate the hazard ratio (HR) and 95% confidence interval (CI). Subsequently, a weighted polygenetic risk score (wPRS) was determined, based on GWAS-driven loci and risk stratification. RESULTS: Cognitive impairment was observed in 65 patients (42.5%) during a mean follow-up of 37.7 ± 12.4 months. Five genome-wide signals, including rs138753053 (PDCD6IP-LOC101928135, HR = 28.33, p = 3.4 × 10-8), rs56823384 (LINC00499, HR = 12.47, p = 2.8 × 10-9), rs145397166 (CASC15, HR = 11.16, p = 1.7 × 10-8), rs10503670 (LPL-SLC18A1, HR = 2.88, p = 4.0 × 10-8), and rs76507772 (IRS2, HR = 5.99, p = 3.5 × 10-8), were significantly associated with cognitive impairment following SAH. In addition, the well-constructed wPRS containing five markers showed nominal ability to predict cognitive impairment (AUROC = 0.745, 95% CI: 0.667-0.824). Tertile stratification showed a higher effectiveness in predicting cognitive impairment, especially in those with haptoglobin 2-1 (HR = 44.59, 95% CI: 8.61-231.08). CONCLUSIONS: Our study revealed novel susceptible loci for cognitive impairment, longitudinally measured in patients with SAH. The clinical utility of these loci will be evaluated in further follow-up studies.
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OBJECT: We aimed to investigate the association of Haptoglobin (Hp) phenotypes with perihematomal edema (PHE) and neurological outcomes after intracerebral hemorrhage (ICH). METHODS: This prospective multicenter study enrolled patients that suffered ICH from March 2017 to February 2020. Hp phenotypes were determined using Western blotting; relative α1 intensity was calculated in patients with Hp2-1. A multivariable logistic regression analysis was then conducted to identify risk factors for increased relative PHE at 96 h and 3-month poor outcomes. RESULTS: In total, 120 patients were ultimately enrolled: Hp1-1 (n = 15, 12.5%); Hp2-1 (n = 51, 42.5%); and Hp2-2 (n = 54, 45.0%). Hp phenotype was significantly associated with PHE (p = 0.028). With Hp1-1 as a reference value, Hp2-2 significantly increased the likelihood of increased rPHE (OR = 6.294, 95% CI: 1.283-30.881), while Hp2-1 did not (OR = 2.843, 95% CI: 0.566-14.284). Poor outcomes were found to be closely associated with hematoma volume at admission (OR = 1.057, 95% CI: 1.015-1.101) and surgical treatment (OR = 5.340, 95% CI: 1.665-17.122) but not Hp phenotypes (p = 0.190). Further, a high level of relative α1 intensity was identified to be significantly associated with decreased rPHE (OR = 0.020, 95% CI: 0.001-0.358). However, the relative α1 intensity was not associated with poor outcomes (OR = 0.057, 95% CI: 0.001-11.790). CONCLUSIONS: ICH patients with Hp2-2 exhibited a higher likelihood of increased rPHE than those with Hp1-1. Higher relative α1 intensities were identified to be closely associated with rPHE in patients with Hp2-1.
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OBJECTIVE: The influence of moderate-to-severe traumatic brain injury (TBI) on acute pulmonary injury is well established, but the association between acute pulmonary injury and mild TBI has not been well studied. Here, we evaluated the histological changes and fluctuations in inflammatory markers in the lungs to determine whether an acute pulmonary inflammatory response occurred after mild TBI. METHODS: Mouse models of mild TBI (n=24) were induced via open-head injuries using a stereotaxic impactor. The brain and lungs were examined 6, 24, and 72 hours after injury and compared to sham-operated controls (n=24). Fluoro-Jade B staining and Astra blue and hematoxylin staining were performed to assess cerebral neuronal degeneration and pulmonary histological architecture. Quantitative real-time polymerase chain reaction analysis was done to measure inflammatory cytokines. RESULTS: Increased neuronal degeneration and the mRNA expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-ß were observed after mild TBI. The IL-6, TNF-α, and TGF-ß levels in mice with mild TBI were significantly different compared to those of sham-operated mice 24 hours after injury, and this was more pronounced at 72 hours. Mild TBI induced acute pulmonary interstitial edema with cell infiltration and alveolar morphological changes. In particular, a significant infiltration of mast cells was observed. Among the inflammatory cytokines, TNF-α was significantly increased in the lungs at 6 hours, but there was no significant difference 24 and 72 hours after injury. CONCLUSION: Mild TBI induced acute pulmonary interstitial inflammation and alveolar structural changes, which are likely to worsen the patient's prognosis.
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Background: To assess the association of haptoglobin (Hp) phenotype with neurological and cognitive outcomes in a large cohort of patients with subarachnoid hemorrhage (SAH). Methods: This prospective multicenter study enrolled patients with aneurysmal SAH between May 2015 and September 2020. The Hp phenotype was confirmed via Western blots. The relative intensities of α1 in individuals carrying Hp2-1 were compared with those of albumin. Multivariable logistic and Cox proportional-hazard regression analyses were used to identify the risk factors for 6-month and long-term outcomes, respectively. Results: A total of 336 patients including the phenotypes Hp1-1 (n = 31, 9.2%), Hp2-1 (n = 126, 37.5%), and Hp2-2 (n = 179, 53.3%) were analyzed. The Hp phenotype was closely associated with 6-month outcome (p = 0.001) and cognitive function (p = 0.013), and long-term outcome (p = 0.002) and cognitive function (p < 0.001). Compared with Hp1-1 as the reference value, Hp2-2 significantly increased the risk of 6-month poor outcome (OR: 7.868, 95% CI: 1.764-35.093) and cognitive impairment (OR: 8.056, 95% CI: 1.020-63.616), and long-term poor outcome (HR: 5.802, 95% CI: 1.795-18.754) and cognitive impairment (HR: 7.434, 95% CI: 2.264-24.409). Long-term cognitive impairment based on the Hp phenotype was significantly higher in patients under 65 years of age (p < 0.001) and female gender (p < 0.001). A lower relative α1/albumin intensity (OR: 0.010, 95% CI: 0.000-0.522) was associated with poor outcome at 6 months but not cognitive impairment in patients with SAH expressing Hp2-1. Conclusion: Hp2-2 increased the risk of poor neurological outcomes and cognitive impairment compared with Hp1-1. For Hp2-1, higher relative α1 intensities were related to 6-month favorable outcomes.
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Background: Copeptin has been reported as a predictive biomarker for the prognosis after traumatic brain injury (TBI). However, most of them were in patients with severe TBI and limited value in predicting outcomes in patients with moderate TBI defined as Glasgow Coma Scale (GCS) score from 9 to 12. We aimed to investigate the predictive value of copeptin in assessing the neurologic outcome following moderate TBI. Methods: Patients were prospectively enrolled between May 2017 and November 2020. We consecutively measured plasma copeptin within 24 h after trauma, days 3, 5, and 7 using ELISA. The primary outcome was to correlate plasma copeptin levels with poor neurologic outcome at 6 months after moderate TBI. The secondary outcome was to compare the prognostic accuracy of copeptin and C-reactive protein (CRP) in assessing the outcome of patient. Results: A total of 70 patients were included for the final analysis. The results showed that 29 patients (41.4%) experienced a poor neurologic outcome at 6 months. Multivariable logistic regression analysis revealed that increased copeptin (odds ration [OR] = 1.020, 95% CI: 1.005-1.036), GCS score of 9 or 10 (OR = 4.507, 95% CI: 1.266-16.047), and significant abnormal findings on CT (OR = 4.770; 95% CI: 1.133-20.076) were independent risk factors for poor outcomes. Consecutive plasma copeptin levels were significantly different according to outcomes (p < 0.001). Copeptin on day 7 exhibited better prognostic performance than CRP with an area under receiver operating characteristic curve (AUROC) difference of 0.179 (95% CI: 0.032-0.325) in predicting 6-month poor outcomes. Conclusion: Plasma copeptin level can be a useful marker in predicting 6-month outcomes in patients with moderate TBI.
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Group III-nitride semiconductor-based ultraviolet (UV) light emitting diodes have been suggested as a substitute for conventional arc-lamps such as mercury, xenon and deuterium arc-lamps, since they are compact, efficient and have a long lifetime. However, in previously reported studies, group III-nitride UV light emitting diodes did not show a broad UV spectrum range as conventional arc-lamps, which restricts their application in fields such as medical therapy and UV spectrophotometry. Here, we propose GaN quantum dots (QDs) grown on different facets of hexagonal truncated pyramid structures formed on a conventional (0001) sapphire substrate. A hexagonal truncated GaN pyramid structure includes {101Ì1} semipolar facets as well as a (0001) polar facet, which have intrinsically different piezoelectric fields and growth rates of GaN QDs. Consequently, we successfully demonstrated a plateau-like broadband UV spectrum ranging from â¼400 nm (UV-A) to â¼270 nm (UV-C) from the GaN QDs. In addition, at the top-edge of the truncated pyramid structure, a strain was locally suppressed compared to the center of the truncated pyramid structure. As a result, various emission wavelengths in the UV range were achieved from the GaN QDs grown on the sidewall, top-edge and top-center of hexagonal truncated pyramid structures, which ultimately provide a broadband UV spectrum with high efficiency.
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The influence of thermal annealing on the properties of germanium grown on silicon (Ge-on-Si) has been investigated. Depth dependencies of strain and photoluminescence (PL) were compared for as-grown and annealed Ge-on-Si samples to investigate how intermixing affects the optical properties of Ge-on-Si. The tensile strain on thermally annealed Ge-on-Si increases at the deeper region, while the PL wavelength becomes shorter. This unexpected blue-shift is attributed to Si interdiffusion at the interface, which is confirmed by energy dispersive X-ray spectroscopy and micro-Raman experiments. Not only Γ- and L-valley emissions but also Δ2-valley related emission could be found from the PL spectra, showing a possibility of carrier escape from Γ valley. Temperature-dependent PL analysis reveals that the thermal activation energy of Γ-valley emission increases at the proximity of the Ge/Si interface. By comparing the PL peak energies and their activation energies, both SiGe intermixing and shallow defect levels are found to be responsible for the activation energy increase and consequent efficiency reduction at the Ge/Si interface. These results provide an in-depth understanding of the influence of strain and Si intermixing on the direct-bandgap optical transition in thermally annealed Ge-on-Si.
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The development of future 3D-printed electronics relies on the access to highly conductive inexpensive materials that are printable at low temperatures (<100 â¦C). The implementation of available materials for these applications are, however, still limited by issues related to cost and printing quality. Here, we report on the simple hydrothermal growth of novel nanocomposites that are well suited for conductive printing applications. The nanocomposites comprise highly Al-doped ZnO nanorods grown on graphene nanoplatelets (GNPs). The ZnO nanorods play the two major roles of (i) preventing GNPs from agglomerating and (ii) promoting electrical conduction paths between the graphene platelets. The effect of two different ZnO-nanorod morphologies with varying Al-doping concentration on the nanocomposite conductivity and the graphene dispersity are investigated. Time-dependent absorption, photoluminescence and photoconductivity measurements show that growth in high pH solutions promotes a better graphene dispersity, higher doping levels and enhanced bonding between the graphene and the ZnO nanorods. Growth in low pH solutions yields samples characterized by a higher conductivity and a reduced number of surface defects. These samples also exhibit a large persistent photoconductivity attributed to an effective charge separation and transfer from the nanorods to the graphene platelets. Our findings can be used to tailor the conductivity of novel printable composites, or for fabrication of large volumes of inexpensive porous conjugated graphene-semiconductor composites.
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Warm and natural white light (i.e., with a correlated colour temperature <5000 K) with good colour rendition (i.e., a colour rendering index >75) is in demand as an indoor lighting source of comfortable interior lighting and mood lighting. However, for warm white light, phosphor-converted white light-emitting diodes (WLEDs) require a red phosphor instead of a commercial yellow phosphor (YAG:Ce3+), and suffer from limitations such as unavoidable energy conversion losses, degraded phosphors and high manufacturing costs. Phosphor-free WLEDs based on three-dimensional (3D) indium gallium nitride (InGaN)/gallium nitride (GaN) structures are promising alternatives. Here, we propose a new concept for highly efficient phosphor-free warm WLEDs using 3D core-shell InGaN/GaN dodecagonal ring structures, fabricated by selective area growth and the KOH wet etching method. Electrically driven, phosphor-free warm WLEDs were successfully demonstrated with a low correlated colour temperature (4500 K) and high colour rendering index (Ra = 81). From our findings, we believe that WLEDs based on dodecagonal ring structures become a platform enabling a high-efficiency warm white light-emitting source without the use of phosphors.
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Control of the growth front in three-dimensional (3D) hexagonal GaN core structures is crucial for increased performance of light-emitting diodes (LEDs), and other photonic devices. This is due to the fact that InGaN layers formed on different growth facets in 3D structures exhibit various band gaps which originate from differences in the indium-incorporation efficiency, internal polarization, and growth rate. Here, a-plane {[Formula: see text] } facets, which are rarely formed in hexagonal pyramid based growth, are intentionally fabricated using mask patterns and adjustment of the core growth conditions. Moreover, the growth area covered by these facets is modified by changing the growth time. The origin of the formation of a-plane {[Formula: see text]} facets is also discussed. Furthermore, due to a growth condition transition from a 3D core structure to an InGaN multi-quantum well, a growth front transformation (i.e., a transformation of a-plane {[Formula: see text]} facets to semi-polar {[Formula: see text]} facets) is directly observed. Based on our understanding and control of this novel growth mechanism, we can achieve efficient broadband LEDs or photovoltaic cells.
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White light-emitting diodes (LEDs) are becoming an alternative general light source, with huge energy savings compared to conventional lighting. However, white LEDs using phosphor(s) suffer from unavoidable Stokes energy converting losses, higher manufacturing cost, and reduced thermal stability. Here, we demonstrate electrically driven, phosphor-free, white LEDs based on three-dimensional gallium nitride structures with double concentric truncated hexagonal pyramids. The electroluminescence spectra are stable with varying current. The origin of the emission wavelength is studied by cathodoluminescence and high-angle annular dark field scanning transmission electron microscopy experiments. Spatial variation of the carrier injection efficiency is also investigated by a comparative analysis between spatially resolved photoluminescence and electroluminescence.
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We report on the fabrication of novel InGaN nanowires (NWs) with improved crystalline quality and high radiative efficiency for applications as nanoscale visible light emitters. Pristine InGaN NWs grown under a uniform In/Ga molar flow ratio (UIF) exhibited multi-peak white-like emission and a high density of dislocation-like defects. A phase separation and broad emission with non-uniform luminescent clusters were also observed for a single UIF NW investigated by spatially resolved cathodoluminescence. Hence, we proposed a simple approach based on engineering the axial In content by increasing the In/Ga molar flow ratio at the end of NW growth. This new approach yielded samples with a high luminescence intensity, a narrow emission spectrum, and enhanced crystalline quality. Using time-resolved photoluminescence spectroscopy, the UIF NWs exhibited a long radiative recombination time (τr) and low internal quantum efficiency (IQE) due to strong exciton localization and carrier trapping in defect states. In contrast, NWs with engineered In content demonstrated three times higher IQE and a much shorter τr due to mitigated In fluctuation and improved crystal quality.
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We fabricated 8-in. Si nanocone (NC) arrays using a nanoimprint technique and investigated their optical characteristics. The NC arrays exhibited remarkable antireflection effects; the optical reflectance was less than 10% in the visible wavelength range. The photoluminescence intensity of the NC arrays was an order of magnitude larger than that of a planar wafer. Optical simulations and analyses suggested that the Mie resonance reduced effective refractive index, and multiple scattering in the NCs enabled the drastic decrease in reflection. PACS: 88.40.H-; 88.40.jp; 81.07.Gf.