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Background Healthcare workers (HCWs) with latent tuberculosis infection (LTBI) have a high risk of active tuberculosis and need systematic LTBI screening and treatment. However, acceptance and adherence rates of LTBI treatment are low. Aims To examine the specific reasons for the loss at each LTBI treatment-cascade stage: acceptance, continuation and completion of LTBI treatment in HCWs. Methods This retrospective descriptive study was conducted among 61 HCWs with an interferon-gamma release assay-confirmed LTBI diagnosis who were prescribed LTBI treatment at a tertiary hospital in the Republic of Korea. Data were analysed using Pearson’s chi-square, Fisher’s exact, independent t-test and Mann–Whitney U-test. A word cloud analysis was used to describe the perceived meaning of LTBI in HCWs. Results HCWs who refused or discontinued LTBI treatment perceived LTBI as ‘not a big deal’, whereas HCWs who completed LTBI treatment had a high-risk perception of the LTBI prognosis, such as ‘frightened about adverse prognosis’. Determinants of non-adherence to the recommended LTBI treatment included a busy work schedule, side effects of anti-tuberculosis agents and the inconvenience of regularly taking anti-tuberculosis agents. Conclusions To ensure LTBI treatment adherence in HCWs, effective interventions that are customized to each stage of the LTBI treatment should be developed, with due consideration of the stage-specific perceived facilitators and barriers in the LTBI treatment cascade.

First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced NSCLC. We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival.Data were pooled from four studies of first-line nivolumab plus ipilimumab in advanced NSCLC (CheckMate 227 Part 1, 817 cohort A, 568 Part 1, and 012). OS, PFS, ORR, DOR, and safety were assessed. Landmark analyses of OS by response status at 6 months and by tumor-burden reduction in responders to nivolumab plus ipilimumab were also assessed.In the pooled population (N = 1332) with a minimum follow-up of 29.1-58.9 months, median OS was 18.6 months, with a 3-year OS rate of 35%; median PFS was 5.4 months (3-year PFS rate, 17%). ORR was 36%; median DOR was 23.7 months, with 38% of responders having an ongoing response at 3 years. In patients with tumor PD-L11%, ≥1%, 1-49%, or ≥50%, 3-year OS rates were 30%, 38%, 30%, and 48%. Three-year OS rates were 30% and 38% in patients with squamous or non-squamous histology. Efficacy outcomes in patients aged ≥75 years were similar to the overall pooled population (median OS, 20.1 months; 3-year OS rate, 34%). In the pooled population, responders to nivolumab plus ipilimumab at 6 months had longer post-landmark OS than those with stable or progressive disease; 3-year OS rates were 66%, 22%, and 14%, respectively. Greater depth of response was associated with prolonged survival; in patients with tumor-burden reduction ≥80%, 50-80%, or 30-50%, 3-year OS rates were 85%, 72%, and 44%, respectively. No new safety signals were identified in the pooled population.Long-term survival benefit and durable response with nivolumab plus ipilimumab in this large patient population further support this first-line treatment option for advanced NSCLC.

BACKGROUND: Rapid diagnosis of drug-resistant TB is critical for early initiation of effective therapy. YD Diagnostics in South Korea recently developed the MolecuTech® REBA MTB-XMDR test to rapidly detect multidrug-resistant TB (MDR-TB), pre-extensively drug-resistant TB (pre-XDR-TB) and resistance to second-line injectable drugs (SLIDs) simultaneously using a fully automated test platform. This study aimed to evaluate the MolecuTech® test for the detection of MDR- and pre-XDR-TB, as well as SLID resistance.METHODS: A total of 151 clinical Mycobacterium tuberculosis isolates from South Korea were tested using the MolecuTech test, and the results were analysed by comparing these with phenotypic drug susceptibility testing (pDST) and sequencing.RESULTS: Compared to pDST, the MolecuTech test showed a sensitivity and specificity of respectively 97.7% and 100.0% for rifampicin (RIF), 82.4% and 100.0% for isoniazid (INH), 97.5% and 97.2% for fluoroquinolones (FQs), and 94.0% and 98.8% for SLIDs. Concordances with the sequencing results of each resistance determinant were 99.3% for RIF, 96.7% for INH, 98.7% for FQs and 99.3% for SLIDs.CONCLUSION: The MolecuTech test is an efficient and reliable rapid molecular diagnostic tool for the simultaneous screening of MDR- and pre-XDR-TB.

To evaluate the radiological features of isolated posterior inferior cerebellar artery dissection (PICAD) and the feasibility of using high-resolution vessel-wall imaging (HR-VWI) for diagnosing PICAD.Three hundred and nine patients with arterial dissection involving the posterior cerebral circulation, who underwent HR-VWI between March 2012 and July 2019 were reviewed retrospectively. Among them, 44 patients (14.2%) were diagnosed with isolated PICAD in consensus among a neuroradiologist, a neurointerventionist, and a neurologist. Two neuroradiologists reviewed the vessel wall images independently for evidence of dissection (dissection flap, outer diameter enlargement on T2-weighted imaging [WI], mural haematoma). Diagnostic confidence was also scored on a five-point scale. Intra- and interobserver agreement for diagnosing PICAD and detecting evidence of dissection were evaluated.Dissection flaps were seen on T2WI in all cases (100%) and on contrast-enhanced T1WI in 34 patients (79.1%). Outer diameter enlargement of the steno-occlusive lesions on angiography was detected in most cases (97.7%). A mural haematoma was detected on three-dimensional (3D) contrast-enhanced motion-sensitised driven-equilibrium T1WI in 97.1% of the cases. The mean diagnostic confidence score derived by two neuroradiologists was 4.72. The two reviewers showed substantial to almost perfect agreement (weighted kappa coefficient: 0.62-0.97).Use of HR-VWI as a diagnostic tool for PICAD is feasible, and a dissection flap with outer wall enlargement on HR-T2WI allows confident dissection diagnosis. The present data suggest that PICAD might be considered as a stroke aetiology in patients with unexplained ischaemic stroke in the PICA territory, and that PICA evaluation with HR-VWI is both necessary and feasible.

In the work reported in this paper, the converter-level lifetime evaluation of power devices in a railway propulsion inverter is performed to assess and compare operating strategies of a railway vehicle in terms of reliability. Two groups of velocity profiles are considered for the lifetime evaluation, wherein all the velocity profiles have the same running distance and time. The first group consists of three operation velocity profiles with the same acceleration at starting and stopping, but with different cruising ranges. In the second group, three operation velocity profiles with different coasting times and acceleration values are considered. A strategy to improve the lifetimes of power devices in propulsion inverters is proposed for vehicles on a busy railway line.

In this paper, fault diagnosis and tolerant control methods are proposed for an open-switch fault in a Vienna rectifier. The proposed diagnosis method uses only the input currents to detect an open-switch fault without any additional hardware. In the proposed tolerant control, the offset voltage is used to restore the input currents when an open-switch fault occurs in a Vienna rectifier. In addition, the proposed tolerant control considers the balance of the neutral-point voltage. This method can improve the total harmonic distortion of the current and mitigate the DC-link voltage ripple. The effectiveness of the proposed open-switch fault diagnosis and tolerant control method is verified by simulated and experimental results.

The Advanced Mo-based Rare process Experiment (AMoRE)-Pilot experiment is an initial phase of the AMoRE search for neutrinoless double beta decay of $$^{100}$$ 100 Mo, with the purpose of investigating the level and sources of backgrounds. Searches for neutrinoless double beta decay generally require ultimately low backgrounds. Surface $$\alpha $$ α decays on the crystals themselves or nearby materials can deposit a continuum of energies that can be as high as the Q-value of the decay itself and may fall in the region of interest (ROI). To understand these background events, we studied backgrounds from radioactive contaminations internal to and on the surface of the crystals or nearby materials with Geant4-based Monte Carlo simulations. In this study, we report on the measured $$\alpha $$ α energy spectra fitted with the corresponding simulated spectra for six crystal detectors, where sources of background contributions could be identified through high energy $$\alpha $$ α peaks and continuum parts in the energy spectrum for both internal and surface contaminations. We determine the low-energy contributions from internal and surface $$\alpha $$ α contaminations by extrapolating from the $$\alpha $$ α background fitting model.

Stomata open by transporting of osmotic materials to the guard cell vacuole. In the mechanisms of stomatal opening, the transports of osmotic materials between the guard cell cytoplasm and vacuole have not been studied much. There are also important lacks of the understanding about important information regarding tonoplast transport proteins and channels. Tonoplast has many types of channels related to K+ transport, among which are inward-K+ channels/FV, outward-K+ channels/FV, outward-TPK/VK channels and TPC1/SV channels. The two H+ transport enzymes in tonoplast, H+-ATPase and H+-PPase, transport H+ from the cytoplasm to vacuole actively. They serve to create an ideal pH condition for the many metabolisms inside the cytoplasm. K+ is transported from the cytoplasm to the vacuole. However, none of the cytosolic K+ can enter the vacuole because vacuole is too full of positive charges. Therefore, in order to increase the osmotic pressure of the guard cell vacuole, it is necessary to transport solutes that could replace K+. Tonoplast contains sucrose-H+ antiports, an active transport protein that can transport sucrose to the vacuole. Although various solutes including K+ are required for stomatal openings, sucrose is suggested to be the most important substance that may increase the osmotic pressure of the vacuole. In addition, the stomatal openings induced by the blue light-photoreceptor mediated signal transduction pathway are highly likely to reflect the effect of blue light stimulated photosynthesis. This is because numerous results have been published that photosynthesis could be induced even when a single blue light is treated without red light.

Background Aldosterone is an important mediator of hypertension, particularly resistant hypertension, heart failure, and chronic kidney disease. PB6440 is a potent inhibitor of aldosterone synthase (CYP11B2) with high selectivity over the closely related enzyme CYP11B1. In previous studies in cynomolgus monkeys, PB6440 exhibited excellent oral bioavailability and a marked suppression of aldosterone synthesis at doses as low as 1 mg/kg/day. Importantly, no effect was observed on cortisol production nor significant changes noted in plasma concentrations of the steroid precursors 11-deoxycortisol or deoxycorticosterone (DOC), which are dependent on CYP11B1 activity. The purpose of the current study was to assess the safety and pharmacodynamics of higher doses of PB6440 in the cynomolgus monkey in order to determine a therapeutic index prior to initiation of studies in humans. Methods Male and female cynomolgus monkeys (2/sex/dose group) were administered 0, 10, 30 or 100 mg/kg PB6440 once-daily for 14 days by oral gavage. Assessment of safety was based on mortality, clinical observations, body weights, and clinical and anatomic pathology. Blood samples were also collected for pharmacodynamic analysis, including aldosterone, cortisol, 11-deoxycortisol, DOC, and ACTH. Results PB6440 was well tolerated at all doses. There were no deaths and no reports of clinical observations at any dose level. Mild decreases in body weight were observed in PB6440-treated animals, which were likely due to the diuretic effects of the compound. PB6440 caused an increase in adrenal weights which was associated with hypertrophy of the adrenal zona fasciculata, a finding which has previously been observed with other aldosterone synthase inhibitors. PB6440 led to marked declines in basal aldosterone levels of −97%, −97% and −98% from baseline at 10, 30 and 100 mg/kg/day, respectively, at 24-hours following the final dose. Despite these clear declines in circulating aldosterone levels, no meaningful changes in cortisol, 11-deoxycortisol, DOC, or ACTH levels were observed, supporting lack of CYP11B1 inhibition. PB6440 led to expected decreases in plasma sodium (up to 7 nmol/L at the high dose). No effect on plasma potassium levels were observed at any dose level. Conclusions PB6440 was well tolerated in the cynomolgus monkey at doses that are much higher than needed for potent aldosterone suppression based on previous studies. At the highest dose level tested (100 mg/kg), which led to a 98% reduction in basal aldosterone levels, no evidence of significant CYP11B1 inhibition was observed. The absence of an increase in plasma potassium in the presence of a plasma sodium decline merits further study. Thus, PB6440 is a highly selective novel aldosterone synthase inhibitor for the potential treatment of hypertension, heart failure, and chronic kidney disease in humans. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): PhaseBio Pharmaceuticals Inc.

This study proposes route planning considering the characteristics of small ships sailing on coasts. An electronic chart based on the S-57 standard object and attributes catalogue was used. A Quadtree data structure was used for modelling an environment for route planning. The main idea of Hierarchical Pathfinding A* (HPA*) was adapted to our route planning algorithm. The route planning method proposed in this study can find route for small ships within a short time that the users can understand. In addition, it consumes little computer resources so that there is no difficulty in operating it on the computer of the small ships. In addition, the program was verified by conducting route planning tests in various areas along the coastal areas of Korea.

We start with a data set obtained from a study of the CS-M-3 ignitor in a military experiment and is based on the classical up-and-down method of Dixon and Mood (1948). Since the Bruce- ton tests are actively employed in pyrotechnical sensitivity studies, we reexamine this method based on the view that it is designed for data-collection. Two different aspects are addressed: as a design for parameter estimation and as a design for giving clues about the good- ness of fit. Two sets of data are employed to illustrate our points. For the estimation of (µ, σ), the location and the scale parameters, we show that a properly selected up-and-down design is quite infor- mative; for the estimation of xp, the 100p%-th quantile, however, the best selected up-and-down method is only about 50% effective as compared with the corresponding c-optimal design. Although not particularly useful, the up-and-down method does judge the proper selection of underlying model. In any case, all the quantal response models are rather poor in terms goodness of fit.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on weight gain in children and adolescents remains unknown. We aimed to identify an estimated 15-year trend in mean body mass index (BMI) changes and prevalence of obesity and overweight among Korean adolescents from 2005 to 2020, including the period of the COVID-19 pandemic.We analyzed data taken from a nationwide survey (Korea Youth Risk Behavior Survey), between 2005 and 2020. Representative samples of one million Korean adolescents aged 13-18 years (n=1,057,885) were examined. The 15-year trends in mean BMI and proportion of obesity or overweight, and the changes due to the COVID-19 pandemic were analyzed.The data of 1,057,885 Korean adolescents were analyzed (mean age: 14.98 years; females, 48.4%). The estimated weighted mean BMI was 20.5 kg/m2 [95% confidence interval (CI), 20.4-20.5] from 2005 to 2008 and 21.5 kg/m2 (95% CI, 21.4-21.6) in 2020 (during the COVID-19 pandemic). Although the 15-year trend of mean BMI gradually increased, the change in mean BMI before and during the pandemic significantly lessened (βdiff, -0.027; 95% CI, -0.028 to -0.026). The 15-year (2005-2020) trend changes in the prevalence of obesity and overweight were similar (obesity prevalence from 2005-2008, 3.2%; 95% CI, 3.1-3.3 vs. obesity prevalence in 2020, 8.6%; 95% CI, 8.2-9.0; βdiff, -0.309; 95% CI, -0.330 to -0.288).The 15-year trend of overall mean BMI and obesity and overweight prevalence demonstrated a significant increase; however, its slope decreased during the pandemic. These landmark results suggest the need for the development of precise strategies to prevent pediatric obesity and overweight during the COVID-19 pandemic.

To evaluate the clinical efficacy of adding temozolomide (TMZ) to preoperative capecitabine (CAP)-based chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and validate OLARC patients with clinical stage II (cT3-4N0) or III (cTBetween November 2017 and July 2020, 64 patients were randomised. Slow accrual caused early study termination. After excluding four ineligible patients, 60 were included in the full analysis set. The pCR rate was 15.0% (9/60), 0%, 14.3%, 18.8% and 26.7% for the entire cohort, arms A, B, C and D, respectively (P = 0.0498 between arms A and D). The pCR rate was 9.7% in the CAP group (arms A + C), 20.7% in the TMZ + CAP group (arms B + D), 6.9% in the uMGMT group (arms A + B) and 22.6% in the mMGMT group (arms C + D). Grade 1-2 nausea or vomiting was significantly more frequent in the TMZ + CAP treatment groups (arms B + D) than in the CAP treatment groups (arms A + C, P0.001) with no difference in grade 3 adverse events. There were no grade 4 or 5 adverse events.The addition of TMZ to CAP-based chemoradiotherapy tended to improve pCR rates, particularly in those with mMGMT LARC. MGMT status may warrant further investigation as a predictive biomarker for chemotherapeutic agents and radiotherapy.

Superconductivity and charge density waves (CDW) are competitive, yet coexisting orders in cuprate superconductors. To understand their microscopic interdependence, a probe capable of discerning their interaction on its natural length and time scales is necessary. We use ultrafast resonant soft x-ray scattering to track the transient evolution of CDW correlations in YBa$_{2}$Cu$_{3}$O$_{6+x}$ following the quench of superconductivity by an infrared laser pulse. We observe a non-thermal response of the CDW order characterized by a near doubling of the correlation length within $\approx$ 1 picosecond of the superconducting quench. Our results are consistent with a model in which the interaction between superconductivity and CDW manifests inhomogeneously through disruption of spatial coherence, with superconductivity playing the dominant role in stabilizing CDW topological defects, such as discommensurations., Comment: Accepted version. 34 pages, 11 figures, Main text and Supplementary Materials

This essay explores how the term ‘girl,’ or 少女 (sonyŏ), in 1930s colonial Korean society simultaneously created and resisted homogeneity. We analyze the different contexts and cultural forces that shaped the term ‘girl’ in colonial Korea in order to illustrate some phases of the relationships that historical girls of colonial Korea had with their nation and state, the nation, that is, to which they thought they belonged at births and the state for which they were mobilized while they were systematically otherized. In our examination, we scrutinize the ways in which the subjectivities of colonial girls were ideologically forged through educational and institutional interventions and cultural interpellation. The first section discusses the concept of the girl in colonial Korea. The second part analyzes the various ideological functions that school textbooks played in gender-specific inculcation of colonial state ideals. We then read the waysThe Chosŏn Ilbo(Chosŏn Daily) used the term the ‘girl’ in the 1930s, the period when the conceptual distinction between children and adults was further solidified, and the call on children was gender-specific in public. We finally elucidate the colonial processes of which girls of colonial Korea became part, albeit unknowingly.

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Serum amyloid P component (SAP) is a universal constituent of human amyloid deposits including those in Alzheimer's disease. SAP has been observed to be elevated in patients with depression, and higher SAP levels are associated with better response to the antidepressant escitalopram. The mechanisms underlying these clinical observations remain unclear. We examined the effect of SAP on serotonin transporter (SERT) expression and localization using Western blot, confocal microscopy, and positron emission tomography with the radioligand [