Image_1_Development of a wireless ultrasonic brain stimulation system for concurrent bilateral neuromodulation in freely moving rodents.pdf

Bilateral brain stimulation is an important modality used to investigate brain circuits and treat neurological conditions. Recently, low-intensity pulsed ultrasound (LIPUS) received significant attention as a novel non-invasive neurostimulation technique with high spatial specificity. Despite the growing interest, the typical ultrasound brain stimulation study, especially for small animals, is limited to a single target of sonication. The constraint is associated with the complexity and the cost of the hardware system required to achieve multi-regional sonication. This work presented the development of a low-cost LIPUS system with a pair of single-element ultrasound transducers to address the above problem. The system was built with a multicore processor with an RF amplifier circuit. In addition, LIPUS device was incorporated with a wireless module (bluetooth low energy) and powered by a single 3.7 V battery. As a result, we achieved an ultrasound transmission with a central frequency of 380 kHz and a peak-to-peak pressure of 480 kPa from each ultrasound transducer. The developed system was further applied to anesthetized rats to investigate the difference between uni- and bilateral stimulation. A significant difference in cortical power density extracted from electroencephalogram signals was observed between uni- and bilateral LIPUS stimulation. The developed device provides an affordable solution to investigate the effects of LIPUS on functional interhemispheric connection.</p

Table1_Introduction of managed entry agreements in Korea: Problem, policy, and politics.docx

Objectives: This study aimed to understand Managed Entry Agreements (MEAs) in Korea through the framework of three streams of the policy window model and its practical management and impact on pricing and reimbursement scheme.Methods: An extensive literature review based on Kingdon’s model was conducted. We also performed descriptive analyses of MEA implementation using data on medicines listed in Korea and compared its MEA scheme with four different countries.Results: As per problem streams, patients with rare disease or cancers have considerable difficulties in affording their medicines and this has challenged the drug benefit system and raised an issue of patient’s access. Policy streams highlighted that MEAs were introduced as a benefit enhancement plan for four major diseases since January 2014. MEAs have also been strengthened as a bypass mechanism to expand the insurance coverage especially for new premium-priced medicines under Moon Care (Listing all non-listed services). In descriptive analysis of MEAs, a total of 48 medicines were contracted as MEAs from January 2014 to December 2020, accounting for 73.4% of listed medicines for cancer or rare diseases and 97.9% of the cases were finance-based contracts. Meanwhile, outcome-based contracts such as CED accounted for only 2.1%. The application of MEAs differs across countries, resulting in a kappa coefficient of 0.00–0.14 (United Kingdom 0.03, Italy 0.00, Australia 0.14), indicating a lack of consistency compared to South Korea.Conclusion: MEAs, which were introduced as a bypass mechanism, have now superseded the standard process for anticancer agents or orphan drugs. Further studies are needed to evaluate the impact of the confidential agreements and effectiveness of new high-priced medicines with limited clinical data at launch.</p

The schematics of the implemented brain-to-brain interface (BBI).

<p>The implementation consists of steady-state visual evoked potential (SSVEP)-based brain-to-computer interface (BCI: on the left column) and focused ultrasound (FUS)-based computer-to-brain interface (CBI) segments (on the right column).</p

Example of bio-signals obtained from the BBI operation.

<p>(A) Initiation of operator intension (as signaled by the finger movement; top), the raw EEG data (the 2^nd row), the filtered EEG data at 15 Hz (the 3^rd row), and the detected rat tail movement (the last row). The threshold condition for the filtered EEG is shown in dotted line. (B) The time resolved plot of the box shown in (A).</p

An example of raw and filtered SSVEP.

<p>A raw SSVEP (in gray lines) and the signal after the application of the digital filter at the corresponding stimulation frequency (in black lines), obtained from a volunteer from four different stimulation frequencies (5, 10, 15 and 20 Hz). The rectangular box indicates the time the operator intended to engage the task.</p

Distribution of AAC and F1-scores across the participants (n = 7) in various flickering frequencies and peak detection thresholds in terms of standard deviation (SD) of the baseline EEG signal.

<p>Distribution of AAC and F1-scores across the participants (n = 7) in various flickering frequencies and peak detection thresholds in terms of standard deviation (SD) of the baseline EEG signal.</p

Optimization of BCI parameter.

<p>Optimization of BCI parameter.</p

Thermosensitive Structural Changes and Adsorption Properties of Zeolitic Imidazolate Framework‑8 (ZIF-8)

We compared four types of ZIF-8 with varying sizes and shapes to determine their thermal-structural stability and derive appropriate thermal activation conditions and correlation between structural characteristics and adsorption properties. Under air, the ZIF-8 phase for all the samples was converted completely into the zinc oxide phase above ∼300 °C, though thermalgravimetric analysis (TGA) indicated that the original structure was stable to ∼300–350 °C. Longer exposures (∼30 d) suggested that thermal activation at ∼200 °C was appropriate for the removal of guest and/or solvent molecules under air without structural damage. Despite no noticeable change in X-ray diffraction (XRD) patterns after activation at 250 °C under air, the resulting BET surface areas and CO₂ adsorption amounts (at 1 bar and 30 °C) of ZIF-8s were reduced to ∼44–54 and ∼72–87%, respectively, as compared to those of appropriately activated ZIF-8s. It appears that after the activation at 250 °C under air, some Zn and N atoms were dissociated and converted to ZnOH and NOH, respectively, causing the partial structural damage of ZIF-8s