We prospectively investigated the diagnostic accuracy of contrast-free 3-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) with volume rendering (VR) at 3.0 T to detect ...intracranial aneurysms in a large cohort of patients.
We conducted a prospective clinical study including 411 patients with suspected aneurysms and other cerebral vascular diseases who were referred for contrast-free 3D-TOF-MRA at 3.0 T prior to digital subtraction angiography (DSA). 2D-DSA and VR-DSA were regarded as the gold standard. Forty-two patients were excluded. Accuracy, sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) as measures to detect or rule out intracranial aneurysms were determined by patient-, aneurysm-, vessel-, and aneurysm size-based evaluations.
In all 369 patients investigated, VR-DSA revealed 307 aneurysms in 246 patients (66.7%) and no aneurysm in 123 patients. The patient-based evaluation by VR 3D-TOF-MRA at 3.0 T yielded an accuracy of 97.6%, a sensitivity of 99.2%, specificity of 94.4%, PPV of 97.2%, and NPV of 98.3% in the detection of intracranial aneurysms. The aneurysm-based evaluation yielded an accuracy of 98.3%, sensitivity of 99.3%, specificity of 96.9%, PPV of 97.8%, and NPV of 99.1%. The vessel-based evaluation yielded accuracy of 98.8%, sensitivity of 99.2%, specificity of 98.5%, PPV of 97.5%, and NPV of 99.6%. The evaluation based on aneurysm sizes yielded similar results.
VR 3D-TOF-MRA at 3.0 T accurately identified the presence of intracranial aneurysms. High PPV and NPV indicated that VR 3D-TOF-MRA at 3.0 T may replace DSA as a contrast-free, noninvasive, and non-radiation-based modality for the diagnosis and screening of intracranial aneurysms.
•Optimal design of simple SSALTs for one-shot devices under Weibull distributions is discussed.•The optimal design can maintain the simulated standard deviation at the nominal level of standard ...error.•The optimal design is quite robust although mis-specification of planning values exists.•An application in grease-based magnetorheological fluids is presented to illustrate the optimal design.
One-shot devices, such as rockets, airbags of automobiles, and electro-explosive devices, can be used only once and will be extensively destroyed. The actual lifetimes of the devices cannot be observed, no matter whether the outcomes are successful or not. Step-stress accelerated life tests, which are useful for shortening the lifetimes of devices and quickly collecting lifetime data in a limited time, are widely adopted in engineering reliability studies. However, optimal designs of step-stress accelerated life tests for one-shot devices have not been well studied. This paper provides a procedure of determining optimal designs of simple step-stress accelerated life tests for one-shot devices by minimizing the asymptotic variance of the maximum likelihood estimate of reliability at normal operating conditions under Weibull distributions, with respect to inspection times and sample allocations. Comprehensive simulation studies are carried out to study the optimal designs under Weibull distributions with various hazard rates, showing that the optimal designs can maintain the simulated standard deviations at the nominal level of standard error. Besides, sensitivity analysis is conducted to evaluate the robustness of determined designs when mis-specification on planning values of model parameters exists. Finally, an application in grease-based magnetorheological fluids is presented to illustrate the optimal designs.
Summary
Women with chronic hepatitis B should maintain nucleotide analogue treatment to prevent disease progression during pregnancy. The aim of this study was to prospectively evaluate the efficacy ...and safety of telbivudine used throughout pregnancy for preventing hepatitis B virus (HBV) mother‐to‐child transmission (MTCT). From January 2012 to June 2014, women who were receiving telbivudine therapy and became pregnant were enrolled in group A at 28 weeks of gestation. Pregnant women with an HBV DNA level >106 IU/mL were enrolled in either group B (telbivudine started at 28 weeks of gestation) or group C (control group without treatment). MTCT was defined as infants who were positive for serum hepatitis B surface antigen at 7 months after birth. There were 41, 179 and 177 pregnant women (397 infants) enrolled in groups A, B and C, respectively. The HBV DNA load at 28 weeks of gestation and delivery was 1.50 ± 0.62 vs 1.45 ± 0.61, 8.05 ± 0.37 vs 4.24 ± 0.89 and 7.94 ± 0.62 vs 7.86 ± 0.73 log10 IU/mL in groups A, B and C, respectively. The rate of MTCT in group C was 4.60%, which was significantly higher than the rates in groups A and B (0% and 0.6%, respectively) (P = .043). The difference between group A and group B was not significant. The rates of neonatal congenital abnormalities were 2.4%, 0.6% and 2.3% in groups A, B and C, respectively, and there were no significant differences (P = .140). Telbivudine used throughout pregnancy may be safe and effective for mothers and infants, but it may not enhance the efficacy of an HBV MTCT block compared with treatment starting at 28 weeks of gestation (NCT02253485).
Cryptococcus neoformans is generally considered to be an opportunistic fungal pathogen because of its tendency to infect immunocompromised individuals, particularly those infected with HIV. However, ...this view has been challenged by the recent discovery of specialized interactions between the fungus and its mammalian hosts, and by the emergence of the related species Cryptococcus gattii as a primary pathogen of immunocompetent populations. In this Review, we highlight features of cryptococcal pathogens that reveal their adaptation to the mammalian environment. These features include not only remarkably sophisticated interactions with phagocytic cells to promote intracellular survival, dissemination to the central nervous system and escape, but also surprising morphological and genomic adaptations such as the formation of polyploid giant cells in the lung.
Aim
The aim was to evaluate the association of neoadjuvant therapy with increases in the incidence of anastomotic leakage (AL) after middle and low rectal anterior resection.
Method
The electronic ...databases of PubMed, Web of Science, Scopus and Ovid were searched between 1980 and 2015. The random effects model was used to model the pooled data to determine the odds ratio with 95% confidence interval. Heterogeneity was evaluated using the Q test and I2 statistics. Subgroup, sensitivity and meta‐regression analysis was conducted to explore heterogeneity.
Results
Neoadjuvant therapy was not shown to increase the incidence of postoperative AL as demonstrated by an OR of 1.16 95% CI 0.99–1.36; P = 0.07 (random effects model). The subgroup analysis of neoadjuvant radiotherapy using the random effects model suggested that it did not increase the rate of postoperative AL (OR = 1.24, 95% CI 0.97–1.58; P = 0.08). The subgroup analysis of neoadjuvant chemoradiotherapy indicated that the rate of postoperative AL again did not increase with an OR = 1.06 95% CI 0.86–1.30; P = 0.59 (random effects model). The interval to surgery after neoadjuvant therapy and preoperative radiotherapy (short or long course) was not associated with an increased incidence of postoperative AL.
Conclusion
Neoadjuvant therapy does not appear to increase the incidence of postoperative AL after anterior resection for mid and low rectal cancer. In addition, neither the interval to surgery after neoadjuvant therapy nor the radiotherapy regimen increases the rate of postoperative AL.
Aims/hypothesis
Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Despite recent advances, our understanding of its pathophysiology ...remains incomplete. The aim of this study was to provide deeper insight into the complex network of molecular and cellular changes that underlie diabetic retinopathy by systematically mapping the transcriptional changes that occur in the different cellular compartments of the degenerating diabetic mouse retina.
Methods
Single-cell RNA sequencing was performed on retinal tissue from 12-week-old wild-type and Akimba (
Ins2
Akita
×
Vegfa
+/
–
) mice, which are known to replicate features of clinical diabetic retinopathy. This resulted in transcriptome data for 9474 retinal cells, which could be annotated to eight distinct retinal cell types. Using STRING analysis, we studied differentially expressed gene networks in neuronal, glial and immune cell compartments to create a comprehensive view on the pathological changes that occur in the Akimba retina. Using subclustering analysis, we further characterised macroglial and inflammatory cell subpopulations. Prominent findings were confirmed at the protein level using immunohistochemistry, western blotting and ELISA.
Results
At 12 weeks, the Akimba retina was found to display degeneration of rod photoreceptors and presence of inflammatory cells, identified by subclustering analysis as monocyte, macrophage and microglial populations. Analysis of differentially expressed genes in the rod, cone, bipolar cell and macroglial compartments indicated changes in cell metabolism and ribosomal gene expression, gliosis, activation of immune system pathways and redox and metal ion dyshomeostasis. Experiments at the protein level supported a metabolic shift from glycolysis to oxidative phosphorylation (glyceraldehyde 3-phosphate dehydrogenase), activation of microglia/macrophages (isolectin-B4), metal ion and oxidative stress response (metallothionein and haem oxygenase-1) and reactive macroglia (glial fibrillary acidic protein and S100) in the Akimba retina, compared with wild-type mice. Our single-cell approach also indicates macroglial subpopulations with distinct fibrotic, inflammatory and gliotic profiles.
Conclusions/interpretation
Our study identifies molecular pathways underlying inflammatory, metabolic and oxidative stress-mediated changes in the Akimba mouse model of diabetic retinopathy and distinguishes distinct functional subtypes of inflammatory and macroglial cells.
Data availability
RNA-seq data have been deposited in the ArrayExpress database at EMBL-EBI (
www.ebi.ac.uk/arrayexpress
) under accession number E-MTAB-9061.
Graphical abstract
The exclusive process e+e−→ΛΛ¯, with Λ→pπ− and Λ¯→p¯π+, has been studied at s=2.396 GeV for measurement of the timelike Λ electric and magnetic form factors, GE and GM. A data sample, corresponding ...to an integrated luminosity of 66.9 pb−1, was collected with the BESIII detector for this purpose. A multidimensional analysis with a complete decomposition of the spin structure of the reaction enables a determination of the modulus of the ratio R=|GE/GM| and, for the first time for any baryon, the relative phase ΔΦ=ΦE−ΦM. The resulting values are R=0.96±0.14(stat)±0.02(syst) and ΔΦ=37°±12°(stat)±6°(syst), respectively. These are obtained using the recently established and most precise value of the asymmetry parameter αΛ=0.750±0.010 measured by BESIII. In addition, the cross section is measured with unprecedented precision to be σ=118.7±5.3(stat)±5.1(syst) pb, which corresponds to an effective form factor of |G|=0.123±0.003(stat)±0.003(syst). The contribution from two-photon exchange is found to be negligible. Our result enables the first complete determination of baryon timelike electromagnetic form factors.
The complicated structure of the neutron cannot be calculated using first-principles calculations due to the large colour charge of quarks and the self-interaction of gluons. Its simplest structure ...observables are the electromagnetic form factors1, which probe our understanding of the strong interaction. Until now, a small amount of data has been available for the determination of the neutron structure from the time-like kinematical range. Here we present measurements of the Born cross section of electron–positron annihilation reactions into a neutron and anti-neutron pair, and determine the neutron’s effective form factor. The data were recorded with the BESIII experiment at centre-of-mass energies between 2.00 and 3.08 GeV using an integrated luminosity of 647.9 pb−1. Our results improve the statistics on the neutron form factor by more than a factor of 60 over previous measurements, demonstrating that the neutron form factor data from annihilation in the time-like regime is on par with that from electron scattering experiments. The effective form factor of the neutron shows a periodic behaviour, similar to earlier observations of the proton form factor. Future works—both theoretical and experimental—will help illuminate the origin of this oscillation of the electromagnetic structure observables of the nucleon.Form factors encode the structure of nucleons. Measurements from electron–positron annihilation at BESIII reveal an oscillating behaviour of the neutron electromagnetic form factor, and clarify a long-standing photon–nucleon interaction puzzle.
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