An Evidence-Based Decision Support Framework for Clinician Medical Scheduling

In healthcare management, waiting time for consultation is an important measure that has strong associations with patient's satisfaction (i.e., the longer patients wait for consultation, the less satisfied they are). To this end, it is required to optimize medical scheduling for clinicians. A typical approach for deriving the optimized schedules is to perform experiments using discrete event simulation. The existing work has developed how to build a simulation model based on process mining techniques. However, applying this method for outpatient processes straightforwardly, in particular medical scheduling, is challenging: 1) the collected data from electronic health record system requires a series of processes to acquire simulation parameters from the raw data; and 2) even if the derived simulation model fully reflects the reality, there is no systematic approach to deriving effective improvements for simulation analysis, i.e., experimental scenarios. To overcome these challenges, this paper proposes a novel decision support framework for a clinician's schedule using simulation analysis. In the proposed framework, a data-driven simulation model is constructed based on process mining analysis, which includes process discovery, patient arrival rate analysis, and service time analysis. Also, a series of steps to derive the optimal improvement method from the simulation analysis is included in the framework. To demonstrate the usefulness of our approach, we present the case study results with real-world data in a hospital.11Ysciescopu

Neuroprotective effect of dexmedetomidine on autophagy in mice administered intracerebroventricular injections of Aβ25–35

Alzheimer’s disease (AD), one of the most prevalent neurodegenerative diseases is associated with pathological autophagy-lysosomal pathway dysfunction. Dexmedetomidine (Dex) has been suggested as an adjuvant to general anesthesia with advantages in reducing the incidence of postoperative cognitive dysfunction in Dex-treated patients with AD and older individuals. Several studies reported that Dex improved memory; however, evidence on the effects of Dex on neuronal autophagy dysfunction in the AD model is lacking. We hypothesized that Dex administration would have neuroprotective effects by improving pathological autophagy dysfunction in mice that received an intracerebroventricular (i.c.v.) injection of amyloid β-protein fragment 25–35 (Aβ25–35) and in an autophagy-deficient cellular model. In the Y-maze test, Dex reversed the decreased activity of Aβ25–35 mice. Additionally, it restored the levels of two memory-related proteins, phosphorylated Ca2+/calmodulin-dependent protein kinase II (p-CaMKII) and postsynaptic density-95 (PSD-95) in Aβ25–35 mice and organotypic hippocampal slice culture (OHSC) with Aβ25–35. Dex administration also resulted in decreased expression of the autophagy-related microtubule-associated proteins light chain 3-II (LC3-II), p62, lysosome-associated membrane protein2 (LAMP2), and cathepsin D in Aβ25–35 mice and OHSC with Aβ25–35. Increased numbers of co-localized puncta of LC3-LAMP2 or LC3-cathepsin D, along with dissociated LC3-p62 immunoreactivity following Dex treatment, were observed. These findings were consistent with the results of western blots and the transformation of double-membrane autophagosomes into single-membraned autolysosomes in ultrastructures. It was evident that Dex treatment alleviated impaired autolysosome formation in Aβ mice. Our study demonstrated the improvement of memory impairment caused by Dex and its neuroprotective mechanism by investigating the role of the autophagy-lysosomal pathway in a murine Aβ25–35 model. These findings suggest that Dex could be used as a potential neuroprotective adjuvant in general anesthesia to prevent cognitive decline

Evaluation of gene-environment interactions for colorectal cancer susceptibility loci using case-only and case-control designs

Background Genome-wide association studies (GWAS) have identified more than 40 colorectal cancer susceptibility loci, but only a small fraction of heritability was explained. To account for missing heritability, we investigated gene-environment interactions (G × Es) between GWAS-identified single-nucleotide polymorphisms (SNPs) and established risk or protective factors for colorectal cancer using both case-only and case-control study designs. Methods Data on 703 colorectal cancer cases and 1406 healthy controls from the National Cancer Center in Korea were used. We tested interactions between 31 GWAS-identified SNPs and 13 established risk or protective factors for colorectal cancer (family history, body mass index, history of colorectal polyps, inflammatory bowel disease, and diabetes mellitus, alcohol drinking, smoking, regular exercise, regular aspirin use, postmenopausal hormone replace therapy, red meat and processed meat intake, and dairy consumption). Logistic regression models were used to assess G × Es for colorectal cancer risk. Results The SNP rs4444235 at 14q22.2 interacted with regular exercise in colorectal cancer (pcase-only = 2.4 × 10− 3, pcase-control = 1.5 × 10− 3). The risk allele (C) of rs4444235 increased the risk of colorectal cancer in regularly exercising individuals (OR = 1.47, 95% CI = 1.02–2.10) but decreased the risk in non-exercising individuals (OR = 0.76, 95% CI = 0.62–0.94). Furthermore, the G × E between the SNP rs2423279 at 20p12.3 and regular aspirin use was statistically significant (pcase-only = 7.7 × 10− 3, pcase-control = 1.6 × 10− 3). The additive effect of the risk allele (T) of rs2423279 on colorectal cancer risk was increased among regular aspirin users (OR = 4.62, 95% CI = 1.97–10.80). Conclusion Our results suggest that SNP rs4444235 at 14q22.2 and SNP rs2423279 at 20p12.3 may interact with regular exercise and aspirin use in colorectal carcinogenesis.This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2009–0093820, 2010–0010276, 2016R1D1A1B04935872, 2017R1A2B4009233) and by National Cancer Center (NCC) in Korea (0910220, 1210141). The funding bodies have no role in study design, collection, analysis, interpretation of data or writing the manuscript

Optimal cutoff values for anthropometric indices of obesity as discriminators of metabolic abnormalities in Korea: results from a Health Examinees study

Background Obesity is well known as a risk factor for cardiovascular disease. We aimed to determine the performance of and the optimal cutoff values for obesity indices to discriminate the presence of metabolic abnormalities as a primary risk factor for cardiovascular diseases in a Health Examinees study (HEXA). Methods The current study analyzed 134,195 participants with complete anthropometric and laboratory information in a Health Examinees study, consisting of the Korean population aged 40 to 69 years. The presence of metabolic abnormality was defined as having at least one of the following: hypertension, hyperglycemia, or dyslipidemia. The area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs) were calculated for body mass index, waist to hip ratio, waist to height ratio, waist circumference, and conicity index. Results The AUC of metabolic abnormalities was the highest for waist-to-height ratio (AUC [95% CIs], 0.677 [0.672–0.683] among men; 0.691 [0.687–0.694] among women), and the lowest for the C index (0.616 [0.611–0.622] among men; 0.645 [0.641–0.649] among women) among both men and women. The optimal cutoff values were 24.3 kg/m2 for the body mass index, 0.887 for the waist-to-hip ratio, 0.499 for the waist-to-height ratio, 84.4 cm for waist circumference and 1.20 m3/2/kg1/2 for the conicity index among men, and 23.4 kg/m2 for the body mass index, 0.832 for the waist-to-hip ratio, 0.496 for the waist-to-height ratio, 77.0 cm for the waist circumference and 1.18 m3/2/kg1/2 for the conicity index among women. Conclusion The waist-to-height ratio is the best index to discriminate metabolic abnormalities among middle-aged Koreans. The optimal cutoff of obesity indices is lower than the international guidelines for obesity. It would be appropriate to use the indices for abdominal obesity rather than general obesity and to consider a lower level of body mass index and waist circumference than the current guidelines to determine obesity-related health problems in Koreans.This study was supported by the Korea Centers for Disease Control and Prevention [funding codes 2004-E71004–00, 2007-E71006–00, 2005-E71011–00, 2008-E71006–00, 2005-E71009–00, 2008-E71008–00, 2006-E71001–00, 2009-E71009–00, 2006-E71004–00, 2010-E71006–00, 2006-E71010–00, 2011-E71006–00, 2006-E71003–00, 2012-E71001–00, 2007-E71004–00, and 2013-E71009–00]. The funder had a role in the design of the study and data collection. We declare that the funder had no role in the analysis or writing of the manuscript

Nonlinear Color-Metallicity Relations of Globular Clusters. III. On the Discrepancy in Metallicity between Globular Cluster Systems and their Parent Elliptical Galaxies

One of the conundrums in extragalactic astronomy is the discrepancy in observed metallicity distribution functions (MDFs) between the two prime stellar components of early-type galaxies-globular clusters (GCs) and halo field stars. This is generally taken as evidence of highly decoupled evolutionary histories between GC systems and their parent galaxies. Here we show, however, that new developments in linking the observed GC colors to their intrinsic metallicities suggest nonlinear color-to-metallicity conversions, which translate observed color distributions into strongly-peaked, unimodal MDFs with broad metal-poor tails. Remarkably, the inferred GC MDFs are similar to the MDFs of resolved field stars in nearby elliptical galaxies and those produced by chemical evolution models of galaxies. The GC MDF shape, characterized by a sharp peak with a metal-poor tail, indicates a virtually continuous chemical enrichment with a relatively short timescale. The characteristic shape emerges across three orders of magnitude in the host galaxy mass, suggesting a universal process of chemical enrichment among various GC systems. Given that GCs are bluer than field stars within the same galaxy, it is plausible that the chemical enrichment processes of GCs ceased somewhat earlier than that of field stellar population, and if so, GCs preferentially trace the major, vigorous mode of star formation events in galactic formation. We further suggest a possible systematic age difference among GC systems, in that the GC systems in more luminous galaxies are older. This is consistent with the downsizing paradigm of galaxies and supports additionally the similar nature shared by GCs and field stars. Our findings suggest that GC systems and their parent galaxies have shared a more common origin than previously thought, and hence greatly simplify theories of galaxy formation.Comment: 55 pages, 7 figures, 5 tables; Accepted for publication in Ap

Impact of glycemic control on the progression of aortic stenosis: a single-center cohort study using a common data model

Background Diabetes mellitus (DM) is a well-established risk factor for the progression of degenerative aortic stenosis (AS). However, no study has investigated the impact of glycemic control on the rate of AS progression. We aimed to assess the association between the degree of glycemic control and the AS progression, using an electronic health record-based common data model (CDM). Methods We identified patients with mild AS (aortic valve [AV] maximal velocity [Vpeak] 2.0–3.0 m/sec) or moderate AS (Vpeak 3.0–4.0 m/sec) at baseline, and follow-up echocardiography performed at an interval of ≥ 6 months, using the CDM of a tertiary hospital database. Patients were divided into 3 groups: no DM (n = 1,027), well-controlled DM (mean glycated hemoglobin [HbA1c] < 7.0% during the study period; n = 193), and poorly controlled DM (mean HbA1c ≥ 7.0% during the study period; n = 144). The primary outcome was the AS progression rate, calculated as the annualized change in the Vpeak (△Vpeak/year). Results Among the total study population (n = 1,364), the median age was 74 (IQR 65–80) years, 47% were male, the median HbA1c was 6.1% (IQR 5.6–6.9), and the median Vpeak was 2.5 m/sec (IQR 2.2–2.9). During follow-up (median 18.4 months), 16.1% of the 1,031 patients with mild AS at baseline progressed to moderate AS, and 1.8% progressed to severe AS. Among the 333 patients with moderate AS, 36.3% progressed to severe AS. The mean HbA1c level during follow-up showed a positive relationship with the AS progression rate (β = 2.620; 95% confidence interval [CI] 0.732–4.507; p = 0.007); a 1%-unit increase in HbA1c was associated with a 27% higher risk of accelerated AS progression defined as △Vpeak/year values > 0.2 m/sec/year (adjusted OR = 1.267 per 1%-unit increase in HbA1c; 95% CI 1.106–1.453; p < 0.001), and HbA1c ≥ 7.0% was significantly associated with an accelerated AS progression (adjusted odds ratio = 1.524; 95% CI 1.010–2.285; p = 0.043). This association between the degree of glycemic control and AS progression rate was observed regardless of the baseline AS severity. Conclusion In patients with mild to moderate AS, the presence of DM, as well as the degree of glycemic control, is significantly associated with accelerated AS progression

Lymphohematopoietic cancer mortality among Korean semiconductor manufacturing workers

Abstract Background We aimed to examine the lymphohematopoietic cancer mortality in a cohort of workers at a semiconductor manufacturing company in South Korea according to their jobs. Methods A retrospective cohort was constructed using the personnel records of semiconductor manufacturing workers who were employed in a semiconductor company in South Korea in 1998–2012. Data on their vital status and causes of death were obtained from the National Statistical Office of South Korea. The standardized mortality ratios (SMRs) of lymphohematopoietic cancer were calculated. Results A total of 288 deaths were reported, of which 22 were caused by lymphohematopoietic cancer, among 65,782 workers in 878,325 person-years. The SMRs for lymphohematopoietic cancer were 0.78 (95% confidence interval [CI] = 0.39–1.40; the number of observed cases [Obs] = 11) among male workers and 1.71 (95% CI = 0.85–3.06; Obs = 11) among female workers. Among female operators, excess deaths due to lymphohematopoietic cancer (SMR = 2.59, 95% CI = 1.24–4.76) and leukemia (SMR = 2.92, 95% CI = 1.26–5.76) were observed. However, they were not observed among office workers, facility managers, utility managers, or process managers. Conclusion Female operators involved in the semiconductor wafer fabrication process had higher risk of mortality from lymphohematopoietic cancer

Study on Multi-DOF Actuator for Improving Power Density

This study focuses on improving the power density of a spherical multi-degree-of-freedom (multi-DOF) actuator. A spherical multi-DOF actuator that can operate in three DOFs is designed. The actuator features a double air gap to reduce eddy current loss. However, a multi-DOF actuator driven by a single actuator exhibits low power density. Therefore, a Halbach magnet array is applied to improve the power density of a spherical multi-DOF actuator, and its output characteristics are compared with those of an existing spherical multi-DOF actuator via finite element analysis. Additionally, the output characteristics are analyzed based on changes in the coil pitch angle and magneto-motive force of the rotating winding. Furthermore, it is necessary for a spherical multi-DOF actuator to move to the command position. Hence, a stability analysis is performed to ensure that the spherical multi-DOF actuator is stably driven based on the command position