Detection and characterization of individual nano-scale particles, virions, and pathogens are of paramount importance to human health, homeland security, diagnostic and environmental monitoring 1 .There is a strong demand for high-resolution, portable, and cost-effective systems to make label-free detection and measurement of individual nanoparticles, molecules, and viruses 2-6 . Here, we report an easily accessible, real-time and label-free detection method with single nanoparticle resolution that surpasses detection limit of existing micro-and nano-photonic devices. This is achieved by using an ultra-narrow linewidth whispering gallery microlaser, whose lasing line undergoes frequency splitting upon the binding of individual nano-objects. We demonstrate detection of polystyrene and gold nanoparticles as small as 15 nm and 10 nm in radius, respectively, and Influenza A virions by monitoring changes in self-heterodyning beat note of the split lasing modes. Experiments are performed in both air and aqueous environment. The built-in self-heterodyne interferometric method achieved in a microlaser provides a self-reference scheme with extraordinary sensitivity 7,8 , and paves the way for detection and spectroscopy of nano-scale objects using micro-and nano-lasers.Most of the biological agents and synthetic particles of interest have low polarizability due to their small size and low refractive index contrast with the surrounding medium, leading to weak light-particle interactions which make their label-free optical detection at single particle resolution difficult. Micro-and nano-photonic resonant devices have emerged as highly sensitive platforms for detection of individual virions and nanoparticles due to the significantly enhanced light-matter interactions originating from the high ratio of their quality-factor (Q) to mode volume (V) 7,9-15 . For example, detection of single Influenza virions and polystyrene nanospheres as small as 30 nm in radius have been demonstrated in whispering gallery mode (WGM) microspheres using reactive shift 12 and in microtoroids using mode splitting technique 7 , respectively. In both techniques, wavelength of a tunable laser is scanned to obtain the transmission spectrum of a resonant mode from which specific information, either the resonance shift and/or the mode splitting, is extracted to detect and measure nanoparticles. The ultimate detection limit strongly relies on Q/V which not only determines the light-matter interaction strength but also sets the smallest resolvable changes in the WGM spectrum 16 . Higher Q, limited by material absorption, implies narrower resonance linewidth and better resolution.Here we report the first microlaser-based detection scheme with single particle resolution surpassing the detection capabilities of existing micro-and nano-photonic devices. The ultimate detection limit is set by the laser linewidth, which can be as narrow as a few Hertz for a WGM microlaser, and is certainly much narrower than the resonance linewidth of any passive resonators 17 ...
Recently, deep-learning-based approaches have been proposed for the classification of neuroimaging data related to Alzheimer’s disease (AD), and significant progress has been made. However, end-to-end learning that is capable of maximizing the impact of deep learning has yet to receive much attention due to the endemic challenge of neuroimaging caused by the scarcity of data. Thus, this study presents an approach meant to encourage the end-to-end learning of a volumetric convolutional neural network (CNN) model for four binary classification tasks (AD vs. normal control (NC), progressive mild cognitive impairment (pMCI) vs. NC, stable mild cognitive impairment (sMCI) vs. NC and pMCI vs. sMCI) based on magnetic resonance imaging (MRI) and visualizes its outcomes in terms of the decision of the CNNs without any human intervention. In the proposed approach, we use convolutional autoencoder (CAE)-based unsupervised learning for the AD vs. NC classification task, and supervised transfer learning is applied to solve the pMCI vs. sMCI classification task. To detect the most important biomarkers related to AD and pMCI, a gradient-based visualization method that approximates the spatial influence of the CNN model’s decision was applied. To validate the contributions of this study, we conducted experiments on the ADNI database, and the results demonstrated that the proposed approach achieved the accuracies of 86.60% and 73.95% for the AD and pMCI classification tasks respectively, outperforming other network models. In the visualization results, the temporal and parietal lobes were identified as key regions for classification.
After the ARM, a sufficient level of PEEP is required as an antiderecruitment strategy. Pulmonary ARDS and extrapulmonary ARDS may be different pathophysiologic entities. An effective ARM may obviate the need for the prone position in ARDS at least in terms of oxygenation.
A cobalt(III)-salen complex (3) with an axial substituent on the diamine backbone has been synthesized. Crystal structure reveals that the axial substituent (p-nitrophenyl group) is positioned in close proximity to the metal binding site. The stereoselectivity of the cobalt complex for binding amino alcohols increases with increasing steric bulk of the amino alcohol from alaninol (2.9) to valinol (6.2) and t-leucinol (36.0).
IMPORTANCEThe burden of injury and costs of wrist fractures are substantial. Surgical treatment became popular without strong supporting evidence.OBJECTIVE To assess whether current surgical treatment for displaced distal radius fractures provided better patient-reported wrist pain and function than nonsurgical treatment in patients 60 years and older. DESIGN, SETTING, AND PARTICIPANTSIn this multicenter randomized clinical trial and parallel observational study, 300 eligible patients were screened from 19 centers in Australia and New Zealand from December 1, 2016, until December 31, 2018. A total of 166 participants were randomized to surgical or nonsurgical treatment and followed up at 3 and 12 months by blinded assessors. Those 134 individuals who declined randomization were included in a parallel observational cohort with the same treatment options and follow-up. The primary analysis was intention to treat; sensitivity analyses included as-treated and per-protocol analyses. INTERVENTION Surgical treatment was open reduction and internal fixation using a volar-locking plate (VLP). Nonsurgical treatment was closed reduction and cast immobilization (CR).MAIN OUTCOMES AND MEASURES The primary outcome was the Patient-Rated Wrist Evaluation score at 12 months. Secondary outcomes were Disabilities of Arm, Shoulder, and Hand questionnaire score, health-related quality of life, pain, major complications, patient-reported treatment success, bother with appearance, and therapy use. RESULTS In the 300 study participants (mean [SD] age, 71.2 [7.5] years; 269 [90%] female; 166 [81 VLP and 85 CR] in the randomized clinical trial sample and 134 [32 VLP and 102 CR] in the observational sample), no clinically important between-group difference in 12-month Patient-Rated Wrist Evaluation scores (mean [SD] score of 19.8 [21.1] for VLP and 21.5 [24.3] for CR; mean difference, 1.7 points; 95% CI −5.4 to 8.8) was observed. No clinically important differences were found in quality of life, wrist pain, or bother at 3 and 12 months. No significant difference was found in total complications between groups (12 of 84 [14%] for the CR group vs 6 of 80 [8%] for the VLP group; risk ratio [RR], 0.53; 95% CI, 0.21-1.33). Patient-reported treatment success favored the VLP group at 12 months (very successful or successful: 70 [89%] vs 57 [70%]; RR, 1.26; 95% CI, 1.07-1.48; P = .005). There was greater use of postoperative physical therapy in the VLP group (56 [72%] vs 44 [54%]; RR, 1.32; 95% CI, 1.04-1.69; P = 0.02).CONCLUSIONS AND RELEVANCE This randomized clinical trial found no between-group differences in improvement in wrist pain or function at 12 months from VLP fixation over CR for displaced distal radius fractures in older people.
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