Summary
Background
Non‐alcoholic fatty liver disease (NAFLD) affects 15–40% of the general population. Some patients have non‐alcoholic steatohepatitis (NASH) and progressive fibrosis, and would be ...candidates for monitoring and treatment.
Aim
To review current literature on the use of non‐invasive tests to assess the severity of NAFLD.
Methods
Systematic literature searching identified studies evaluating non‐invasive tests of NASH and fibrosis using liver biopsy as the reference standard. Meta‐analysis was performed for areas with adequate number of publications.
Results
Serum tests and physical measurements like transient elastography (TE) have high negative predictive value (NPV) in excluding advanced fibrosis in NAFLD patients. The NAFLD fibrosis score comprises of six routine clinical parameters and has been endorsed by current American guidelines as a screening test to exclude low‐risk individuals. The pooled sensitivities and specificities for TE to diagnose F ≥ 2, F ≥ 3 and F4 disease were 79% and 75%, 85% and 85%, and 92% and 92% respectively. Liver stiffness measurement often fails in obese patients, but the success rate can be improved with the use of the XL probe. A number of biomarkers have been developed for the diagnosis of NASH, but few were independently validated. Serum/plasma cytokeratin‐18 fragments have been most extensively evaluated and have a pooled sensitivity of 66% and specificity of 82% in diagnosing NASH.
Conclusions
Current non‐invasive tests are accurate in excluding advanced fibrosis in NAFLD patients, and may be used for initial assessment. Further development and evaluation of NASH biomarkers are needed.
Fluorescence-guided surgery has emerged as a powerful tool to detect, localize and resect tumors in the operative setting. Our laboratory has pioneered a novel way to administer an FDA-approved ...near-infrared (NIR) contrast agent to help surgeons with this task. This technique, coined Second Window ICG, exploits the natural permeability of tumor vasculature and its poor clearance to deliver high doses of indocyanine green (ICG) to tumors. This technique differs substantially from established ICG video angiography techniques that visualize ICG within minutes of injection. We hypothesized that Second Window ICG can provide NIR optical contrast with good signal characteristics in intracranial brain tumors over a longer period of time than previously appreciated with ICG video angiography alone. We tested this hypothesis in an intracranial mouse glioblastoma model, and corroborated this in a human clinical trial.
Intracranial tumors were established in 20 mice using the U251-Luc-GFP cell line. Successful grafts were confirmed with bioluminescence. Intravenous tail vein injections of 5.0 mg/kg (high dose) or 2.5 mg/kg (low dose) ICG were performed. The Perkin Elmer IVIS Spectrum (closed field) was used to visualize NIR fluorescence signal at seven delayed time points following ICG injection. NIR signals were quantified using LivingImage software. Based on the success of our results, human subjects were recruited to a clinical trial and intravenously injected with high dose 5.0 mg/kg. Imaging was performed with the VisionSense Iridium (open field) during surgery one day after ICG injection.
In the murine model, the NIR signal-to-background ratio (SBR) in gliomas peaks at one hour after infusion, then plateaus and remains strong and stable for at least 48 hours. Higher dose 5.0 mg/kg improves NIR signal as compared to lower dose at 2.5 mg/kg (SBR = 3.5 vs. 2.8; P = 0.0624). Although early (≤ 6 hrs) visualization of the Second Window ICG accumulation in gliomas is stronger than late (≥24 hrs) visualization (SBR = 3.94 vs. 2.32; p<0.05) there appears to be a long plateau period of stable ICG NIR signal accumulation within tumors in the murine model. We call this long plateau period the "Second Window" of ICG. In glioblastoma patients, the delayed visualization of intratumoral NIR signal was strong (SBR 7.50 ± 0.74), without any significant difference within the 19 to 30 hour visualization window (R2 = 0.019).
The Second Window ICG technique allows neurosurgeons to deliver NIR optical contrast agent to human glioblastoma patients, thus providing real-time tumor identification in the operating room. This nonspecific tumor accumulation of ICG within the tumor provides strong signal to background contrast, and is not significantly time dependent between 6 hours to 48 hours, providing a broad plateau for stable visualization. This finding suggests that optimal imaging of the "Second Window of ICG" may be within this plateau period, thus providing signal uniformity across subjects.
To evaluate the effectiveness of whole-genome array comparative genomic hybridization (aCGH) in prenatal diagnosis in Hong Kong.
Array CGH was performed on 220 samples recruited prospectively as the ...first-tier test study. In addition 150 prenatal samples with abnormal fetal ultrasound findings found to have normal karyotypes were analyzed as a 'further-test' study using NimbleGen CGX-135K oligonucleotide arrays.
Array CGH findings were concordant with conventional cytogenetic results with the exception of one case of triploidy. It was found in the first-tier test study that aCGH detected 20% (44/220) clinically significant copy number variants (CNV), of which 21 were common aneuploidies and 23 had other chromosomal imbalances. There were 3.2% (7/220) samples with CNVs detected by aCGH but not by conventional cytogenetics. In the 'further-test' study, the additional diagnostic yield of detecting chromosome imbalance was 6% (9/150). The overall detection for CNVs of unclear clinical significance was 2.7% (10/370) with 0.9% found to be de novo. Eleven loci of common CNVs were found in the local population.
Whole-genome aCGH offered a higher resolution diagnostic capacity than conventional karyotyping for prenatal diagnosis either as a first-tier test or as a 'further-test' for pregnancies with fetal ultrasound anomalies. We propose replacing conventional cytogenetics with aCGH for all pregnancies undergoing invasive diagnostic procedures after excluding common aneuploidies and triploidies by quantitative fluorescent PCR. Conventional cytogenetics can be reserved for visualization of clinically significant CNVs.
Summary
A better understanding of the features of subsequent fractures after distal radius fracture (DRF) is important for the prevention of further osteoporotic fractures. This study found that the ...cumulative incidence of subsequent osteoporotic fractures in South Korea increased over time and that the mortality rates of subsequent DRFs were lower than those of first-time DRFs.
Introduction
We examined the incidence of osteoporotic fractures following distal radius fractures (DRFs) and the mortality rate after subsequent DRFs using claims data from the Korea National Health Insurance (KNHI) Service.
Methods
We identified records for 41,417 patients with first-time DRFs in 2012. The occurrence of osteoporotic fractures of the spine, hip, wrist, and humerus at least 6 months after the index DRF was tracked through 2016. All fractures were identified by specific diagnosis and procedure codes. One-year mortality rates and standardized mortality ratios (SMRs) for initial and subsequent DRFs were calculated for all patients.
Results
The 4-year cumulative incidence of all subsequent osteoporotic fractures was 14.74% (6105/41,417; 9.47% in men, 15.9% in women). The number of associated subsequent fractures was 2850 for the spine (46.68%), 2271 for the wrist (37.2%), 708 for the hip (11.6%), and 276 for the humerus (4.52%). The cumulative mortality rate 1 year after the first-time and subsequent DRF was 1.47% and 0.71%, respectively, and the overall SMR was 1.48 (95% CI: 1.37–1.61) and 0.71 (95% CI: 0.42−1.21), respectively.
Conclusion
The cumulative incidence of osteoporotic fractures following DRFs increased over the study period and was higher among women. The cumulative mortality rates and SMRs of subsequent DRFs were lower than those of first-time DRFs at the 1-year follow-up. Given the increasing incidence rate of DRFs, the incidence of subsequent osteoporotic fractures may also increase.
The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown.
To investigate the risk of osteoporotic fracture with dabigatran vs warfarin ...in patients with NVAF.
Retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through 2014 and prescribed dabigatran or warfarin were matched by propensity score at a 1:2 ratio with follow-up until July 31, 2016.
Dabigatran or warfarin use during the study period.
Risk of osteoporotic hip fracture and vertebral fracture was compared between dabigatran and warfarin users using Poisson regression. The corresponding incidence rate ratio (IRR) and absolute risk difference (ARD) with 95% CIs were calculated.
Among 51 496 patients newly diagnosed with NVAF, 8152 new users of dabigatran (n = 3268) and warfarin (n = 4884) were matched by propensity score (50% women; mean SD age, 74 11 years). Osteoporotic fracture developed in 104 (1.3%) patients during follow-up (32 dabigatran users 1.0%; 72 warfarin users 1.5%). Results of Poisson regression analysis showed that dabigatran use was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (0.7 vs 1.1 per 100 person-years; ARD per 100 person-years, -0.68 95% CI, -0.38 to -0.86; IRR, 0.38 95% CI, 0.22 to 0.66). The association with lower risk was statistically significant in patients with a history of falls, fractures, or both (dabigatran vs warfarin, 1.6 vs 3.6 per 100 person-years; ARD per 100 person-years, -3.15 95% CI, -2.40 to -3.45; IRR, 0.12 95% CI, 0.04 to 0.33), but not in those without a history (0.6 vs 0.7 per 100 person-years; ARD per 100 person-years, -0.04 95% CI, 0.67 to -0.39; IRR, 0.95 95% CI, 0.45 to 1.96) (P value for interaction, <.001).
Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture. Additional study, perhaps including randomized clinical trials, may be warranted to further understand the relationship between use of dabigatran vs warfarin and risk of fracture.
A memory cell consisting of a Pt/VO2/Pt switch element and a Pt/NiO/Pt memory element connected in series. By applying a voltage higher than Vth of 0.6 V, the switch element reaches the on state and ...the cell can be accessed. Since reset and set voltages are higher than Vth, information can be written by simply applying an appropriate voltage to a selected cell. By applying a voltage lower than Vth to the other cells, we can keep the other cells in the off state and prevent interference between the selected cell and the others.
A key mechanism for atmospheric secondary organic aerosol (SOA) formation occurs when oxidation products of volatile organic compounds condense onto pre-existing particles. Here, we examine effects ...of aerosol liquid water (ALW) on relative SOA yield and composition from α-pinene ozonolysis and the photooxidation of toluene and acetylene by OH. Reactions were conducted in a room-temperature flow tube under low-NO x conditions in the presence of equivalent loadings of deliquesced (∼20 μg m–3 ALW) or effloresced (∼0.2 μg m–3 ALW) ammonium sulfate seeds at exactly the same relative humidity (RH = 70%) and state of wall conditioning. We found 13% and 19% enhancements in relative SOA yield for the α-pinene and toluene systems, respectively, when seeds were deliquesced rather than effloresced. The relative yield doubled in the acetylene system, and this enhancement was partially reversible upon drying the prepared SOA, which reduced the yield by 40% within a time scale of seconds. We attribute the high relative yield of acetylene SOA on deliquesced seeds to aqueous partitioning and particle-phase reactions of the photooxidation product glyoxal. The observed range of relative yields for α-pinene, toluene, and acetylene SOA on deliquesced and effloresced seeds suggests that ALW plays a complicated, system-dependent role in SOA formation.
Atmospheric brown carbon (BrC) is a collective term for light absorbing organic compounds in the atmosphere. While the identification of BrC and its formation mechanisms is currently a central effort ...in the community, little is known about the atmospheric removal processes of aerosol BrC. As a result, we report on a series of laboratory studies of photochemical processing of BrC in the aqueous phase, by direct photolysis and OH oxidation. Solutions of ammonium sulfate mixed with glyoxal (GLYAS) or methylglyoxal (MGAS) are used as surrogates for a class of secondary BrC mediated by imine intermediates. Three nitrophenol species, namely 4-nitrophenol, 5-nitroguaiacol and 4-nitrocatechol, were investigated as a class of water-soluble BrC originating from biomass burning. Photochemical processing induced significant changes in the absorptive properties of BrC. The imine-mediated BrC solutions exhibited rapid photo-bleaching with both direct photolysis and OH oxidation, with atmospheric half-lives of minutes to a few hours. The nitrophenol species exhibited photo-enhancement in the visible range during direct photolysis and the onset of OH oxidation, but rapid photo-bleaching was induced by further OH exposure on an atmospheric timescale of an hour or less. To illustrate the atmospheric relevance of this work, we also performed direct photolysis experiments on water-soluble organic carbon extracted from biofuel combustion samples and observed rapid changes in the optical properties of these samples as well. Overall, these experiments indicate that atmospheric models need to incorporate representations of atmospheric processing of BrC species to accurately model their radiative impacts.
Summary
The effects of diabetes medications on risk of fracture were investigated using the South Korea nationwide claims database. We demonstrated that the use of dipeptidyl peptidase-4 inhibitor ...could be associated with decreased risk of fracture. Thiazolidinedione use was associated with about 60 % increased risk of fracture in real clinical practice.
Introduction
The effects of diabetes medication on fracture have important clinical health consequences, since most diabetes patients are at high risk of fracture. We aimed to investigate the effect of diabetes medication on fracture risk.
Methods
The nationwide medical claim database in South Korea was investigated. Among 2,886,555 subjects with antidiabetes prescriptions, 207,558 subjects aged 50 years and older, who initiated diabetes medication from 2008 to 2011, were analyzed. The subjects were classified based on diabetes medication classes: non-user (insufficient exposure), metformin (MET), sulfonylurea (SU), alpha-glucosidase inhibitor (AGI), MET + SU, MET + thiazolidinedione (TZD), MET + dipeptidyl peptidase-4 inhibitor (DPP4-I), and SU + TZD.
Results
A total of 5996 fractures were observed. The fracture rate varied significantly across type of diabetes medications, with MET + DPP4-I combination group having the lowest rate and SU + TZD combination group having the highest rate. Compared to non-users, MET + DPP4-I inhibitor combination group had significantly reduced composite fracture risk (hazard ratio (HR) = 0.83,
P
= 0.025) and significantly reduced vertebral fracture risk (HR = 0.73,
P
= 0.013) in the unadjusted analysis. Compared to MET + SU users, MET + DPP4-I users showed a trend of lower non-vertebral fracture risk (HR = 0.82,
P
= 0.086) after adjusting for all confounding variables. Patients using TZD had significantly increased risk of fracture (HR = 1.59,
P
< 0.001) compared with patients not using TZDs adjusting for all confounding variables.
Conclusions
The results of this nationwide study showed a trend that DPP4 inhibitor might have a protective effect on bone metabolism compared with SU, when added to MET. Clinicians should take these results into consideration when prescribing diabetes medication, especially in elderly patients or those at high risk or fracture.
We perform full 3D topology optimization (in which "every voxel" of the unit cell is a degree of freedom) of photonic-crystal structures in order to find optimal omnidirectional band gaps for various ...symmetry groups, including fcc (including diamond), bcc, and simple-cubic lattices. Even without imposing the constraints of any fabrication process, the resulting optimal gaps are only slightly larger than previous hand designs, suggesting that current photonic crystals are nearly optimal in this respect. However, optimization can discover new structures, e.g. a new fcc structure with the same symmetry but slightly larger gap than the well known inverse opal, which may offer new degrees of freedom to future fabrication technologies. Furthermore, our band-gap optimization is an illustration of a computational approach to 3D dispersion engineering which is applicable to many other problems in optics, based on a novel semidefinite-program formulation for nonconvex eigenvalue optimization combined with other techniques such as a simple approach to impose symmetry constraints. We also demonstrate a technique for robust topology optimization, in which some uncertainty is included in each voxel and we optimize the worst-case gap, and we show that the resulting band gaps have increased robustness to systematic fabrication errors.
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