Sodium-Glucose Cotransporter-2 Inhibitor-Related Diabetic Ketoacidosis: Accuracy Verification of Operational Definition

Background@#The most important aspect of a retrospective cohort study is the operational definition (OP) of the disease. We developed a detailed OP for the detection of sodiumglucose cotransporter-2 inhibitors (SGLT2i) related to diabetic ketoacidosis (DKA). The OP was systemically verified and analyzed. @*Methods@#All patients prescribed SGLT2i at four university hospitals were enrolled in this experiment. A DKA diagnostic algorithm was created and distributed to each hospital;subsequently, the number of SGLT2i-related DKAs was confirmed. Then, the algorithm functionality was verified through manual chart reviews by an endocrinologist using the same OP. @*Results@#A total of 8,958 patients were initially prescribed SGLT2i. According to the algorithm, 0.18% (16/8,958) were confirmed to have SGLT2i-related DKA. However, based on manual chart reviews of these 16 cases, there was only one case of SGLT2i-related DKA (positive predictive value = 6.3%). Even after repeatedly narrowing the diagnosis range of the algorithm, the effect of a positive predictive value was insignificant (6.3–10.0%, P > 0.999). @*Conclusion@#Owing to the nature of electronic medical record data, we could not create an algorithm that clearly differentiates SGLT2i-related DKA despite repeated attempts. In all retrospective studies, a portion of the samples should be randomly selected to confirm the accuracy of the OP through chart review. In retrospective cohort studies in which chart review is not possible, it will be difficult to guarantee the reliability of the results.

Informative sensor selection and learning for prediction of lower limb kinematics using generative stochastic neural networks.

We propose a novel approach of selecting useful input sensors as well as learning a mathematical model for predicting lower limb joint kinematics. We applied a feature selection method based on the mutual information called the variational information maximization, which has been reported as the state-of-the-art work among information based feature selection methods. The main difficulty in applying the method is estimating reliable probability density of input and output data, especially when the data are high dimensional and real-valued. We addressed this problem by applying a generative stochastic neural network called the restricted Boltzmann machine, through which we could perform sampling based probability estimation. The mutual informations between inputs and outputs are evaluated in each backward sensor elimination step, and the least informative sensor is removed with its network connections. The entire network is fine-tuned by maximizing conditional likelihood in each step. Experimental results are shown for 4 healthy subjects walking with various speeds, recording 64 sensor measurements including electromyogram, acceleration, and foot-pressure sensors attached on both lower limbs for predicting hip and knee joint angles. For test set of walking with arbitrary speed, our results show that our suggested method can select informative sensors while maintaining a good prediction accuracy.

A review of low-intensity focused ultrasound for neuromodulation

The ability of ultrasound to be focused into a small region of interest through the intact skull within the brain has led researchers to investigate its potential therapeutic uses for functional neurosurgery and tumor ablation. Studies have used high-intensity focused ultrasound to ablate tissue in localised brain regions for movement disorders and chronic pain while sparing the overlying and surrounding tissue. More recently, low-intensity focused ultrasound (LIFU) that induces reversible biological effects has been emerged as an alternative neuromodulation modality due to its bi-modal (i.e. excitation and suppression) capability with exquisite spatial specificity and depth penetration. Many compelling evidences of LIFU-mediated neuromodulatory effects including behavioral responses, electrophysiological recordings and functional imaging data have been found in the last decades. LIFU, therefore, has the enormous potential to improve the clinical outcomes as well as to replace the currently available neuromodulation techniques such as deep brain stimulation (DBS), transcranial magnetic stimulation and transcranial current stimulation. In this paper, we aim to provide a summary of pioneering studies in the field of ultrasonic neuromodulation including its underlying mechanisms that were published in the last 60 years. In closing, some of potential clinical applications of ultrasonic brain stimulation will be discussed.

Detecting voluntary gait intention of chronic stroke patients towards top-down gait rehabilitation using EEG.

One of the recent trends in gait rehabilitation is to incorporate bio-signals, such as electromyography (EMG) or electroencephalography (EEG), for facilitating neuroplasticity, i.e. top-down approach. In this study, we investigated decoding stroke patients' gait intention through a wireless EEG system. To overcome patient-specific EEG patterns due to impaired cerebral cortices, common spatial patterns (CSP) was employed. We demonstrated that CSP filter can be used to maximize the EEG signal variance-ratio of gait and standing conditions. Finally, linear discriminant analysis (LDA) classification was conducted, whereby the average accuracy of 73.2% and the average delay of 0.13 s were achieved for 3 chronic stroke patients. Additionally, we also found out that the inverse CSP matrix topography of stroke patients' EEG showed good agreement with the patients' paretic side.

Development and Accuracy Test of a Robot-arm Type Image-guided Surgery System for Percutaneous Screw Fixation of the Sacro-iliac Joint

PURPOSE: To develop a robot-arm type image-guided surgery system for percuatneous screw fixation of the sacro-iliac joint and to evaluate its accuracy. MATERIALS AND METHODS: We have developed an image-guided surgery system using a three-dimensional digitizer (Microscribe 3-D G2, Immersion, USA) and a personal computer. The registration error and target localization error at fiducial registration were measured 30 times for each using a phantom made with plastic pelvic bone model (Sawbones, USA). Sixteen 6.5 mm cannulated screws were inserted into four plastic bone models, and the accuracy was evaluated. RESULTS: The target localization error was 1.46+/-0.47 mm while the registration error was 0.73+/-0.23 mm. All of the 16 screws were inserted well across the sacro-iliac joint, and there was neither cortical breach nor collision between screws or washers. CONCLUSION: The accuracy of the developed system was similar to that of optical tracker-based navigation systems, and its helpfulness and usefulness was proven with simulation surgery using plastic bone models.

Enhanced expression of constitutive and inducible forms of nitric oxide synthase in autoimmune encephalomyelitis

To elucidate the role of nitric oxide synthase (NOS) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), we analyzed the expression of constitutive neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) in the spinal cords of rats with EAE. We further examined the structural interaction between apoptotic cells and spinal cord cells including neurons and astrocytes, which are potent cell types of nitric oxide (NO) production in the brain. Western blot analysis showed that three forms of NOS significantly increased in the spinal cords of rats at the peak stage of EAE, while small amounts of these enzymes were identified in the spinal cords of rats without EAE. Immunohistochemical study showed that the expression of either nNOS or eNOS increased in the brain cells including neurons and astrocytes during the peak and recovery stages of EAE, while the expression of iNOS was found mainly in the inflammatory macrophages in the perivascular EAE lesions. Double labeling showed that apoptotic cells had intimate contacts with either neurons or astrocytes, which are major cell types to express nNOS and eNOS constitutively. Our results suggest that the three NOS may play an important role in the recovery of EAE.