Reinforcement Learning-Guided Long-Timescale Simulation of Hydrogen Transport in Metals.

Diffusion in alloys is an important class of atomic processes. However, atomistic simulations of diffusion in chemically complex solids are confronted with the timescale problem: the accessible simulation time is usually far shorter than that of experimental interest. In this work, long-timescale simulation methods are developed using reinforcement learning (RL) that extends simulation capability to match the duration of experimental interest. Two special limits, RL transition kinetics simulator (TKS) and RL low-energy states sampler (LSS), are implemented and explained in detail, while the meaning of general RL are also discussed. As a testbed, hydrogen diffusivity is computed using RL TKS in pure metals and a medium entropy alloy, CrCoNi, and compared with experiments. The algorithm can produce counter-intuitive hydrogen-vacancy cooperative motion. We also demonstrate that RL LSS can accelerate the sampling of low-energy configurations compared to the Metropolis-Hastings algorithm, using hydrogen migration to copper (111) surface as an example.

A nationwide population-based study on therapeutic plasma exchange for 10 years in Korea using Health Insurance Review and Assessment database.

INTRODUCTION: Indications for therapeutic plasma exchange (TPE) have expanded over the years, and the number of procedures is expected to have been increased. Apheresis registries can be difficult to sustain due to workload and privacy issues. This study aimed to analyze national claims data to characterize the use of TPE. MATERIALS AND METHODS: Patients who underwent TPE were retrospectively identified between January 2008 and December 2017 from the Korean Health Insurance Review and Assessment Service database. Data of patients' characteristics, primary diagnosis, hospitalization, treatment, and procedures were analyzed. RESULTS: A total of 9944 patients underwent 62 606 TPE procedures. The median number of TPE procedures performed per patient was 5 (interquartile range, 3-7). Fresh frozen plasma (71.4%) was most commonly used as the replacement fluid. The most common indication was renal diseases (36.8%), followed by hepato-biliary (17.6%) and hematological (15.2%) diseases. Increased frequency of renal diseases was the most remarkable change, which increased from 529 (21.2%) procedures in 2008 to 4107 (44.5%) procedures in 2017, reflecting the widespread implementation of ABO-incompatible kidney transplantation. The top five hospitals conducted 59.6% of the procedures, which showed a centralized distribution. CONCLUSIONS: The most common indication was renal diseases. The number of TPE procedures performed annually increased by approximately 3.7 times from 2008 to 2017. This study shows that other than a registry, claims data can be successfully used to analyze various aspects of TPE procedures on a nationwide scale. This approach could be used by other countries, especially those that have national health insurance.

Flexible Working, Work-Life Balance, and Gender Equality: Introduction.

This special brings together innovative and multidisciplinary research (sociology, economics, and social work) using data from across Europe and the US to examine the potential flexible working has on the gender division of labour and workers' work-life balance. Despite numerous studies on the gendered outcomes of flexible working, it is limited in that the majority is based on qualitative studies based in the US. The papers of this special issue overcome some of the limitations by examining the importance of context, namely, family, organisational and country context, examining the intersection between gender and class, and finally examining the outcomes for different types of flexible working arrangements. The introduction to this special issue provides a review of the existing literature on the gendered outcomes of flexible working on work life balance and other work and family outcomes, before presenting the key findings of the articles of this special issue. The results of the studies show that gender matters in understanding the outcomes of flexible working, but also it matters differently in different contexts. The introduction further provides policy implications drawn from the conclusions of the studies and some thoughts for future studies to consider.

Author Correction: Artificial Intelligence based Models for Screening of Hematologic Malignancies using Cell Population Data.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Automation of Harboe method for the measurement of plasma free hemoglobin.

BACKGROUND: Although plasma free hemoglobin (fHb) test is important for assessing intravascular hemolysis, it is still dependent on the gold standard Harboe method using manual and labor-intensive spectrometric measurements at the wavelength of 380-415-450 nm. We established an automated fHb assay using a routine chemistry autoanalyzer that can be tuned to a wavelength of 380-416-450 nm. METHODS: The linearity, precision, accuracy, correlation, and sample carryover of fHb measurement using TBA200FRneo method and manual Harboe method were evaluated, respectively. fHb values measured by manual Harboe method were compared with those measured by our new automated TBA200FRneo method. RESULTS: fHb measurements were linear in the range of 0.05~38.75 µmol/L by TBA200FRneo and 0.05~9.69 µmol/L by manual Harboe method. Imprecision analysis (%CV) revealed 0.9~2.8% for TBA200FRneo method and 5.3~13.6% for the manual Harboe method. Comparison analysis showed 0.9986 of correlation coefficient (TBA200FRneo = 0.970 × Harboe + 0.12). In analytical accuracy analysis, the manual Harboe method revealed about 4 times higher average total error % (12.2%) than the TBA200FRneo automated method (2.8%). The sample carryover was -0.0016% in TBA200FRneo method and 0.0038% in Harboe method. CONCLUSIONS: In the measurement of fHb, the automated TBA200FRneo method showed better performance than the conventional Harboe method. It is expected that the automated fHb assay using the routine chemistry analyzer can replace the gold standard Harboe method which is labor-intensive and need an independent spectrophotometry equipment.

Artificial Intelligence based Models for Screening of Hematologic Malignancies using Cell Population Data.

Cell Population Data (CPD) provides various blood cell parameters that can be used for differential diagnosis. Data analytics using Machine Learning (ML) have been playing a pivotal role in revolutionizing medical diagnostics. This research presents a novel approach of using ML algorithms for screening hematologic malignancies using CPD. The data collection was done at Konkuk University Medical Center, Seoul. A total of (882 cases: 457 hematologic malignancy and 425 hematologic non-malignancy) were used for analysis. In our study, seven machine learning models, i.e., SGD, SVM, RF, DT, Linear model, Logistic regression, and ANN, were used. In order to measure the performance of our ML models, stratified 10-fold cross validation was performed, and metrics, such as accuracy, precision, recall, and AUC were used. We observed outstanding performance by the ANN model as compared to other ML models. The diagnostic ability of ANN achieved the highest accuracy, precision, recall, and AUC ± Standard Deviation as follows: 82.8%, 82.8%, 84.9%, and 93.5% ± 2.6 respectively. ANN algorithm based on CPD appeared to be an efficient aid for clinical laboratory screening of hematologic malignancies. Our results encourage further work of applying ML to wider field of clinical practice.

Basic auditory processing in the children with autistic features.

This study aimed inhibition mechanisms of auditory processing in the group with autistic features. Thirty-two children (autistic group = 16, typically developing [TD] group = 16) received neuropsychological tests, IQ test and experimental tasks. Both groups showed similar performances except the processing speed index. The results showed that the group with autistic features had less inhibition of return (IOR) than the TD group. However, we did not get a statistically significant group difference in the auditory Go-NoGo task. These results might be attributed to a ceiling effect due to an adjustment failure of a difficulty level instead of showing that the group with autistic features would have intact inhibitory or pitch discriminative function problems. In conclusion, this study showed that the group with autistic features could have an inhibitory processing difficulty in both auditory and visual IOR tasks even when their general cognitive functions are relatively intact. This study presented a possibility that the group with autistic features might have a basic inhibitory function problem, but these findings should be investigated in the further study with enough samples. In addition, we are going to revise the auditory Go-NoGo task and verify the feasibility as a tool to detect ASD in an early stage in the following study.

Benefits of VISION Max automated cross-matching in comparison with manual cross-matching: A multidimensional analysis.

BACKGROUND: VISION Max (Ortho-Clinical Diagnostics, Raritan, NJ, USA) is a newly introduced automated blood bank system. Cross-matching (XM) is an important test confirming safety by simulating reaction between packed Red Blood Cells (RBCs) and patient blood in vitro before transfusion. We assessed the benefits of VISION Max automated XM (A-XM) in comparison with those of manual XM (M-XM) by using multidimensional analysis (cost-effectiveness and quality improvement). MATERIALS AND METHODS: In a total of 327 tests (130 patients), results from A-XM and M-XM were compared. We assessed the concordance rate, risk priority number (RPN), turnaround time, hands-on time, and the costs of both methods. We further simulated their annual effects based on 37,937 XM tests in 2018. RESULTS: The concordance rate between A-XM and M-XM was 97.9% (320/327, kappa = 0.83), and the seven discordant results were incompatible for transfusion in A-XM, while compatible for transfusion in M-XM. None of the results was incompatible for transfusion in A-XM, while compatible for transfusion in M-XM, meaning A-XM detect agglutination more sensitively and consequently provides a more safe result than M-XM. A-XM was estimated to have a 6.3-fold lower risk (229 vs. 1,435 RPN), shorter turnaround time (19.1 vs. 23.3 min, P < 0.0001), shorter hands-on time (1.1 vs. 5.3 min, P < 0.0001), and lower costs per single test than M-XM (1.44 vs. 2.70 USD). A-XM permitted annual savings of 46 million RPN, 15.1 months of daytime workers' labor, and 47,042 USD compared with M-XM. CONCLUSION: This is the first attempt to implement A-XM using VISION Max. VISION Max A-XM appears to be a safe, practical, and reliable alternative for pre-transfusion workflow with the potential to improve quality and cost-effectiveness in the blood bank.

Strategy for performing treponemal tests in reverse-sequence algorithms of syphilis diagnosis.

OBJECTIVES: In South Korea, automated T. pallidum Latex Agglutination (TPLA) based on turbidoimmunoassays and immunochromatographic assay (ICA) are widely used for syphilis diagnosis. However, there is sparse data on the validation of these assays in the reverse-sequence algorithm setting. METHODS: We assessed 551 specimens submitted for syphilis testing. We compared varying reverse-sequence algorithms using combinations of the Cobas Syphilis EIA (Roche Diagnostics, Mannheim, Germany), Mediace TPLA (Sekisui Medical Co., Tokyo, Japan), TPPA (Fujirebio Inc., Tokyo, Japan), and SD Bioline ICA (Standard Diagnostic, Yongin, Korea). We also evaluated modified algorithms incorporating a cut off of high specificity for EIA and TPLA using receiver operating characteristic curves. RESULTS: The agreement was almost perfect between EIA and TPLA (Kappa, 0.953) and strong between TPPA and ICA (Kappa, 0.887). Among TPPA positive and ICA negative specimens, 67% of the specimens were from individuals with syphilis histories. Compared to EIA/RPR/TPPA, the agreement with EIA/RPR/ICA, TPLA/RPR/TPPA and TPLA/RPR/ICA were almost perfect (Kappa, 0.930, 0.995 and 0.914, respectively). When a cut off of 95% specificity was applied, the number of TPPA tests could be reduced by 44% and 40% in EIA and TPLA, respectively. CONCLUSIONS: TPLA showed almost perfect agreement with EIA and that it could be used in the site of EIA in a reverse sequence algorithm. ICA showed a lower detection rate than TPPA as a 2nd treponemal test and should be used with caution. With cut offs of higher specificity, more efficient reverse-sequence algorithms can be made possible.

Experimental fusion of different versions of the total laboratory automation system and improvement of laboratory turnaround time.

BACKGROUND: Use of total laboratory automation (TLA) system has expanded to microbiology and hemostasis and upgraded to second and third generations. We herein report the first successful upgrades and fusion of different versions of the TLA system, thus improving laboratory turnaround time (TAT). METHODS: A 21-day schedule was planned from the time of pre-meeting to installation and clinical sample application. We analyzed the monthly TAT in each menu, distribution of the "out of range for acceptable TAT" samples, and "prolonged time out of acceptable TAT," before and after the upgrade and fusion. RESULTS: We installed and customized hardware, middleware, and software. The one-way CliniLog 2.0 version track, 50.0-m long, was changed to a 23.2-m long one-way 2.0 version and an 18.7-m long two-way 4.0 version. The monthly TAT in the outpatient samples, before and after upgrading the TLA system, were uniformly satisfactory in the chemistry and viral marker menus. However, in the tumor marker menu, the target TAT (98.0% of samples ≤60 minutes) was not satisfied during the familiarization period. There was no significant difference in the proportion of "out of acceptable TAT" samples, before and after the TLA system upgrades (7.4‰ and 8.5‰). However, the mean "prolonged time out of acceptable TAT" in the chemistry samples was significantly shortened to 17.4 (±24.0) minutes after the fusion, from 34.5 (±43.4) minutes. CONCLUSIONS: Despite experimental challenges, a fusion of the TLA system shortened the "prolonged time out of acceptable TAT," indicating a distribution change in overall TAT.

Women's employment patterns after childbirth and the perceived access to and use of flexitime and teleworking.

This article sets out to investigate how flexitime and teleworking can help women maintain their careers after childbirth. Despite the increased number of women in the labour market in the UK, many significantly reduce their working hours or leave the labour market altogether after childbirth. Based on border and boundary management theories, we expect flexitime and teleworking can help mothers stay employed and maintain their working hours. We explore the UK case, where the right to request flexible working has been expanded quickly as a way to address work-life balance issues. The dataset used is Understanding Society (2009-2014), a large household panel survey with data on flexible work. We find some suggestive evidence that flexible working can help women stay in employment after the birth of their first child. More evidence is found that mothers using flexitime and with access to teleworking are less likely to reduce their working hours after childbirth. This contributes to our understanding of flexible working not only as a tool for work-life balance, but also as a tool to enhance and maintain individuals' work capacities in periods of increased family demands. This has major implications for supporting mothers' careers and enhancing gender equality in the labour market.

Harmonization of laboratory results by data adjustment in multicenter clinical trials.

BACKGROUND/AIMS: In multicenter clinical trials, laboratory tests are performed in the laboratory of each center, mostly using different measuring methodologies. The purpose of this study was to evaluate coefficients of variation (CVs) of laboratory results produced by various measuring methods and to determine whether mathematical data adjustment could achieve harmonization between the methods. METHODS: We chose 10 clinical laboratories, including Green Cross Laboratories (GC Labs), the central laboratory, for the measurement of total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), serum triglycerides, creatinine, and glucose. The serum panels made with patient samples referred to GC Labs were sent to the other laboratories. Twenty serum samples for each analyte were prepared, sent frozen, and analyzed by each participating laboratory. RESULTS: All methods used by participating laboratories for the six analytes had traceability by reference materials and methods. When the results from the nine laboratories were compared with those from GC Labs, the mean CVs for total cholesterol, HDL-C, LDL-C, and glucose analyzed using the same method were 1.7%, 3.7%, 4.3%, and 1.7%, respectively; and those for triglycerides and creatinine analyzed using two different methods were 4.5% and 4.48%, respectively. After adjusting data using Deming regression, the mean CV were 0.7%, 1.4%, 1.8%, 1.4%, 1.6%, and 0.8% for total cholesterol, HDL-C, LDL-C, triglyceride, creatinine, and glucose, respectively. CONCLUSION: We found that more comparable results can be produced by laboratory data harmonization using commutable samples. Therefore, harmonization efforts should be undertaken in multicenter trials for accurate data analysis (CRIS number; KCT0001235).

Implementation of biological variation-based analytical performance specifications in the laboratory: Stringent evaluation of Improvacutor blood collection tubes.

Recently, because the quality of laboratory analyses has increased along with the need for quality improvement, several external quality control bodies have adapted performance specifications using the Desirable Biological Variation Database, termed "Ricos goals"; these criteria are more stringent than those presented in CLIA 88. In this study, we aimed to validate newly introduced serum separator tubes, Improvacutor, for routine clinical chemistry testing in accordance with Ricos goals and CLIA 88. Blood samples were collected from 100 volunteers into three types of serum vacuum tubes: Greiner Vacuette, Becton Dickinson (BD) Vacutainer, and Improve Improvacutor. The samples were subjected to 16 routine chemistry tests using a TBA-200fr NEO chemistry autoanalyzer. In the comparison analysis, all 16 test results were acceptable according to CLIA 88. However, in the comparison of Improve and BD tubes, creatinine showed 4.31% (+0.08 µmol/L) bias. This slightly exceeded the Desirable Specification for Inaccuracy Ricos limit of ±3.96%, but still satisfied the CLIS88 limit of ±26.52 µmol/L. The remaining 15 analytes performed acceptably according to the Desirable Specifications of Ricos. The correlation coefficient of 12 analytes was greater than 0.95 in Passing-Bablok regression analysis among the three tubes, but was lower for four analytes: calcium, sodium, potassium, and chloride. In the stability assay, only potassium tested in the Greiner tube revealed a larger positive bias (2.18%) than the Ricos Desirable Specification for Inaccuracy based on biologic variation (1.8%). The BD tube also showed a positive bias of 1.74%, whereas the new Improve tube showed the smallest positive bias of 1.17% in potassium level after 72 h storage. Thus, the results of this study demonstrate that recently introduced analytical performance specifications based on components of biological variation (Rico's goal) could be extended to criterion for performance evaluation and applied.

Nanocomposite versus Mesocomposite for Osteogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells.

Injectable inorganic/organic composite systems consisting of well-defined mesocrystals (4-8 µm) of calcium phosphate and polypeptide thermogel significantly enhance the osteogenic differentiation of the tonsil derived mesenchymal stem cells (TMSCs). Compared to composite systems incorporating nanoparticles (10-100 nm) or pure hydrogel systems, osteogenic biomarkers including alkaline phosphatase (ALP), bone morphogenetic protein 2, and osteocalcin are highly expressed at both the mRNA level and the protein level in the mesocrystal composite systems. ALP activity of differentiated cells is also significantly higher in the mesocomposite systems compared to the nanocomposite systems or the pure hydrogel systems. The mesocomposite systems provide not only hard surfaces for binding the cells/proteins by the inorganic mesocrystals but also a soft matrix for holding the cells by the hydrogel. Through the current research, (1) a novel method of preparing mesocrystals is developed, (2) TMSCs are proved as a new resource of stem cells, and (3) the mesocomposite systems are proved to be a promising tool in controlling stem cell differentiation. (4) Finally, the research emphasizes the significance of mesoscience as a new perspective of science in controlling cell and material interfaces.

Influence of Vitamin C on Urine Dipstick Test Results.

BACKGROUND: Vitamin C is a strong reducing agent found at high levels in various foods, and it may influence the results of urine strip tests even at an ordinary consumption levels. After oral administration, we measured urine vitamin C levels using urine strips and evaluated whether vitamin C interfered with various test items. The utility of a urine strip with a vitamin C indicator was assessed. METHODS: Thirty-three healthy volunteers each ingested 1,000 mg of vitamin C. Their urine samples were tested for vitamin C using a URiSCAN 11 strip (YD Diagnostics, Korea) before and after administration of vitamin C. Standard materials were added to normal pooled urine to generate urine samples with various concentrations of the analytes tested (blood, bilirubin, nitrite, leukocytes, and glucose), and vitamin C was spiked to predetermined levels. These samples were then tested using two urine strips - URiSCAN and Chemstrip test strip (Roche Diagnostics, Germany) - to evaluate interference from vitamin C. In clinical samples with positive vitamin C results, microscopic and chemical analyses were also conducted to examine the differences. RESULTS: Thirteen urine samples from the 33 volunteers were positive for vitamin C before ingestion, and all subjects were positive after ingestion. Vitamin C spiking of urine demonstrated false-negative results at various concentrations. Of 159 specimens with positive results for vitamin C, 14 showed discrepant results after additional confirmatory tests. CONCLUSIONS: Vitamin C in urine can cause significant interference with urine strip tests. A urine strip with a vitamin C indicator is useful to reduce the risk of incorrect results in regard to disease states.

Prediction of fetal lung maturity using the lecithin/sphingomyelin (L/S) ratio analysis with a simplified sample preparation, using a commercial microtip-column combined with mass spectrometric analysis.

Fetal lung maturity is estimated using the lecithin/sphingomyelin ratio (L/S ratio) in amniotic fluid and it is commonly measured with thin-layer chromatography (TLC). The TLC method is time consuming and technically difficult; however, it is widely used because there is no alternative. We evaluated a novel method for measuring the L/S ratio, which involves a tip-column with a cation-exchange resin and mass spectrometry. Phospholipids in the amniotic fluid were extracted using methanol and chloroform. Choline-containing phospholipids such as lecithin and sphingomyelin were purified by passing them through the tip-column. LC-MS/MS and MALDI-TOF were used to directly analyze the purified samples. The L/S ratio by mass spectrometry was calculated from the sum peak intensity of the six lecithin, and that of sphingomyelin 34:1. In 20 samples, the L/S ratio determined with TLC was significantly correlated with that obtained by LC-MS/MS and MALDI-TOF. There was a 100% concordance between the L/S ratio by TLC and that by LC-MS/MS (kappa value=1.0). The concordance between the L/S ratio by TLC and that by MALDI-TOF was also 100% (kappa value=1.0). Our method provides a faster, simpler, and more reliable assessment of fetal lung maturity. The L/S ratio measured by LC-MS/MS and MALDI-TOF offers a compelling alternative method to traditional TLC.

Establishment of trimester-specific reference intervals for thyroid hormones in Korean pregnant women.

BACKGROUND: Establishment of trimester- and assay-specific reference intervals for every population is recommended. The aim of this study was to establish a trimester- and assay-specific reference interval for thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in Korean pregnant women. METHODS: From April 2012 to December 2012, 531 pregnant women receiving prenatal care and 238 age-matched, non-pregnant women were enrolled in this study. After excluding patients with pregnancy-associated complications or thyroid-specific autoantibody, 465 pregnant and 206 non-pregnant women were included. Non-parametric analysis (2.5-97.5th percentile) was performed to determine the reference interval. Levels of TSH and FT4 were determined by electrochemiluminescence immunoassay (Elecsys thyroid tests, Roche Diagnostics, Germany). RESULTS: The TSH reference intervals were 0.01-4.10, 0.01-4.26, and 0.15-4.57 mIU/L for the first, second, and third trimester, respectively. From the first trimester to the third trimester, the median TSH levels showed a significantly increasing trend (P<0.0001). The FT4 reference intervals were 0.83-1.65, 0.71-1.22, and 0.65-1.13 ng/dL for the first, second, and third trimester, respectively, showing a significantly decreasing trend (P<0.0001). CONCLUSIONS: Establishing trimester-specific reference intervals in pregnant women is essential for accurate assessment of thyroid function. Our population-specific and method-specific reference intervals will be useful for screening Korean pregnant women for thyroid disease.