Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure (HF) cases. The prevalence of HFpEF is increasing due to an aging population with hypertension, diabetes mellitus, and obesity. HFpEF remains a challenging clinical entity due to a lack of effective treatment options. Traditional HF medications have not been shown to reduce mortality of patients with HFpEF, and an implantable cardioverter-defibrillator is not indicated due to normal ejection fraction. Sudden death is the most common mode of death in patients with HFpEF; however, the underlying mechanisms of sudden death are not fully elucidated. Although ventricular arrhythmias are responsible for the majority of sudden deaths in general, their contribution to sudden deaths in HFpEF patients is likely less significant. The mechanisms of ventricular arrhythmias in HFpEF are 1) reduced conduction velocity due to ventricular hypertrophy, 2) delayed repolarization due to potassium current down-regulation, 3) calcium leakage due to altered excitation-contraction coupling, and 4) increased ventricular fibrosis caused by systemic inflammation. Hypertension and subsequent ventricular hypertrophy reduce the conduction velocity in HFpEF hearts via heterogeneous distribution of connexin 43. Delayed repolarization caused by potassium current down-regulation in HFpEF hearts provides a window for early afterdepolarization to trigger ventricular arrhythmias. Altered excitation-contraction coupling in HFpEF can cause calcium to leak and trigger delayed afterdepolarization. Increased systemic inflammation and subsequent ventricular fibrosis provide substrates for re-entry. Further research is warranted to investigate the detailed mechanisms of ventricular arrhythmias in HFpEF.
Jung, Jiwon;Yoo, Ree Nar;Sung, Hungseop;Kim, Mina;Lee, Jina
Pediatric Infection and Vaccine
/
v.26
no.1
/
pp.1-10
/
2019
Purpose: We investigated the distribution and antimicrobial resistance of pneumococcal isolates from hospitalized children at Asan Medical Center for recent 4 years, and aimed to recommend proper choice of empirical antibiotics for pneumococcal infection. Methods: From March 2014 to May 2018, children admitted to Asan Medical Center Childrens' Hospital with pneumococcal infection were subjected for evaluation of minimal inhibitory concentration (MIC) for ${\beta}-lactams$ and macrolide antibiotics. Patient's age, underlying disease, gender were retrospectively collected. Using Monte Carlo simulation model and MIC from our study, we predicted the rate of treatment success with amoxicillin treatment. Results: Sixty-three isolates were analyzed including 20.6% (n=13) of invasive isolates, and 79.4% (n=50) of non-invasive isolates; median age were 3.3 years old, and 87.3% of the pneumococcal infections occurred to children with underlying disease. Overall susceptibility rate was 49.2%, 68.2%, and 74.6% for amoxicillin, parenteral penicillin, and cefotaxime respectively. 23.8% and 9.5% of the isolates showed high resistance for amoxicillin, and cefotaxime. Only 4.8% (n=3) were susceptible to erythromycin. Monte Carlo simulation model revealed the likelihood of treatment success was 46.0% at the dosage of 90 mg/kg/day of amoxicillin. Conclusions: Recent pneumococcal isolates from pediatric patients with underlying disease revealed high resistance for amoxicillin and cefotaxime, and high resistance for erythromycin. Prudent choice of antibiotics based on the local data of resistance cannot be emphasized enough, especially in high risk patients with underlying disease, and timely vaccination should be implemented for prevention of the spread of resistant strains.
Kim, Byung-Sik;Lee, Jung-Ki;Kim, Hung-Soo;Lee, Jin-Won
Journal of Wetlands Research
/
v.13
no.3
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pp.499-514
/
2011
An underlying assumption of traditional hydrologic frequency analysis is that climate, and hence the frequency of hydrologic events, is stationary, or unchanging over time. Under stationary conditions, the distribution of the variable of interest is invariant to temporal translation. Water resources infrastructure planning and design, such as dams, levees, canals, bridges, and culverts, relies on an understanding of past conditions and projection of future conditions. But, Water managers have always known our world is inherently non-stationary, and they routinely deal with this in management and planning. The aim of this paper is to give a brief introduction to non-stationary extreme value analysis methods. In this paper, a non-stationary hydrologic frequency analysis approach is introduced in order to determine probability rainfall consider changing climate. The non-stationary statistical approach is based on the conditional Generalized Extreme Value(GEV) distribution and Maximum Likelihood parameter estimation. This method are applied to the annual maximum 24 hours-rainfall. The results show that the non-stationary GEV approach is suitable for determining probability rainfall for changing climate, sucha sa trend, Moreover, Non-stationary frequency analyzed using SOI(Southern Oscillation Index) of ENSO(El Nino Southern Oscillation).
This study was conducted to derive the optimal regionalization of the precipitation data which can be classified on the basis of climatologically and geographically homogeneous regions all over the regions except Cheju and Ulreung islands in Korea. A total of 65 rain gauges were used to regional analysis of precipitation. Annual maximum series for the consecutive durations of 1, 3, 6, 12, 24, 36, 48 and 72hr were used for various statistical analyses. K-means clustering mettled is used to identify homogeneous regions all over the regions. Five homogeneous regions for the precipitation were classified by the K-means clustering. Using the L-moment ratios and Kolmogorov-Smirnov test, the underlying regional probability distribution was identified to be the generalized extreme value (GEV) distribution among applied distributions. The regional and at-site parameters of the generalized extreme value distribution were estimated by the linear combination of the probability weighted moments, L-moment. The regional and at-site analysis for the design rainfall were tested by Monte Carlo simulation. Relative root-mean-square error (RRMSE), relative bias (RBIAS) and relative reduction (RR) in RRMSE were computed and compared with those resulting from at-site Monte Carlo simulation. All show that the regional analysis procedure can substantially reduce the RRMSE, RBIAS and RR in RRMSE in the prediction of design rainfall. Consequently, optimal design rainfalls following the regions and consecutive durations were derived by the regional frequency analysis.
Background: The discovery that microRNA (miRNA) regulates metastasis provide a principal molecular basis for tumor heterogeneity. A characteristic of solid tumors is their heterogenous distribution of blood vessels, with significant hypoxia occurring in regions (centers of tumor) of low blood flow. It is necessary to discover the mechanism of breast cancer metastasis in relation to the fact that there is a differential distribution of crucial microRNA in tumors from centers to edges. Methods: Breast tissues from 48 patients (32 patients with breast cancer) were classified into the high invasive and metastatic group (HIMG), low invasive and metastatic group (LIMG), and normal group. Samples were collected from both the centers and edges of all tumors. The first six specimens were detected by microRNA array, and the second ten specimens were detected by real-time qRT-PCR and Western blot analyses. Correlation analysis was performed between the miRNAs and target proteins. Results: The relative content of miR-20a and miR-20b was lower in the center of the tumor than at the edge in the LIMG, lower at the edge of the tumor than in the center in the HIMG, and lower in breast cancer tissues than in normal tissues. VEGF-A and HIF-1alpha mRNA levels were higher in the HIMG than in the LIMG, and levels were higher in both groups than in the normal group; there was no difference in mRNA levels between the edge and center of the tumor. VEGF-A and HIF-1alpha protein levels were higher in the HIMG than in the LIMG, and protein levels in both groups were higher than in the normal group; there was a significant difference in protein expression between the edge and center of the tumor. Correlation analysis showed that the key miRNAs (miR-20a and miR-20b) negatively correlated with the target proteins (VEGF-A and HIF-1alpha). Conclusions: Our data suggest that miR-20a and miR-20b are differentially distributed in breast cancer, while VEGF-A and HIF-1alpha mRNA had coincident distributions, and VEGF-A and HIF-1alpha proteins had uneven and opposing distributions to the miRNAs. It appears that one of the most important facets underlying metastatic heterogeneity is the differential distribution of miR-20a and miR-20b and their regulation of target proteins.
Seasonality of hydrologic extreme variable is a significant element from a water resources managemental point of view. It is closely related with various fields such as dam operation, flood control, irrigation water management, and so on. Hydrological frequency analysis conjunction with partial duration series rather than block maxima, offers benefits that include data expansion, analysis of seasonality and occurrence. In this study, nonstationary frequency analysis based on the Bayesian model has been suggested which effectively linked with advantage of POT (peaks over threshold) analysis that contains seasonality information. A selected threshold that the value of upper 98% among the 24 hours duration rainfall was applied to extract POT series at Seoul station, and goodness-fit-test of selected GEV distribution has been examined through graphical representation. Seasonal variation of location and scale parameter ($\mu$ and $\sigma$) of GEV distribution were represented by Fourier series, and the posterior distributions were estimated by Bayesian Markov Chain Monte Carlo simulation. The design rainfall estimated by GEV quantile function and derived posterior distribution for the Fourier coefficients, were illustrated with a wide range of return periods. The nonstationary frequency analysis considering seasonality can reasonably reproduce underlying extreme distribution and simultaneously provide a full annual cycle of the design rainfall as well.
Kang, Wee Saing;Koh, Kyoung Hwan;Ha, Sung Whan;Park, Charn Il
Radiation Oncology Journal
/
v.1
no.1
/
pp.21-24
/
1983
The thickness of the part being irradiated is finite. Percent depth dose tables being used routinely are generally obtained from dosimetry in a phantom much thickner than usual patient. At or close to exit surface, the dose should be less than that obtained from the percent depth dose tables, because of insufficient volume for backscattering. To know the difference between the true absorbed dose and the dose obtained from percent depth dose table, the doses at or close to the exit surface were measured with plate type ionization chamber with volume of 0.5ml. The results are as follows; 1. In the case of $^{60}Co$, percent depth dose at a given depth increases with underlying phantom thickness up to the 5cm. 2. In the case of $^{60}Co$, the dose correction factor at exit surface which is less than 1, increases with part thickness and decreases with field size. 3. Exposure time may not be corrected when the part above 10cm in thickness is treated by $^{60}Co$. 4. In the case of 10MV x-ray, the dose correction factor is nearly 1 and constant for the underlying phantom thickness and field size, so the correction of monitor unit is not necessary for part thickness.
Kim, Hyeung-Il;Kim, Sung-Sook;Chung, Jin-Hong;Lee, Kwan-Ho;Lee, Hyun-Woo
Journal of Yeungnam Medical Science
/
v.10
no.1
/
pp.157-165
/
1993
The authors conducted a clinical observation of 13 cases of pulmonary aspergilloma at Yeungnam University Hospital from March 1983 to March 1992, and the following results were observed : 1) The male to female ratio was 1 : 1.2, and the age distribution was ranged 30 to 67 years old. 2) All cases were symptomatic : hemoptysis, cough, sputum and dyspnea. Especially, hemoptysis was the presenting compliant in 10 patients(77%). 3) The underlying lung disease were pulmonary tuberculosis in 9, COPD in 5 and bronchiectasis in 2, 3 cases were without underlying disease. 4) According to radiographic appearance, 8 cases had the typical crescent sign and 5 cases were seen nodular lesion. And the lesions of 11 cases were located in both upper lung. 5) 10 cases were treated with surgical resection. Among these cases, 8 cases were alieved and 2 cases, died. And other 3 cases were treated with conservative treatment. We suggest that these findings would be helpful for the diagnosis and treatment of pulmonary aspergilloma and further study might be needed to evaluate the prognosis of pulmonary aspergilloma.
Objective: To investigate changes in the invasive capacity of gastric cancer cells in vitro after expression inhibition of T lymphoma invasion and metastasis inducing factor 1 (Tiam 1) and underlying mechanisms. Methods: Using adhesion selection, two subpopulations with high ($M_H$) or low ($M_L$) invasive capacity were separated from the human gastric cancer cell line MKN-45 ($M_0$). Tiam 1 antisense oligodeoxynucleotide (ASODN) was transfected into $M_H$ cells with liposomes, and expression of Tiam 1 mRNA and protein was determined by RT-PCR and quantitative cellular-ELISA. Changes in the cytoskeleton, invasive capacity in vitro and expression of ras-related $C_3$ botulinum toxin substrate 1 (Rac 1), integrin ${\beta}1$ and matrix metalloproteinase 2 (MMP 2) between Tiam 1 ASODN transfected $M_H$ cells and non-transfected cells were observed by HE staining, cytoskeletal protein staining, scanning electron microscopy, Boyden chamber tests and cyto-immunohistochemistry. Results: A positive correlation existed between the expression level of Tiam l mRNA or protein and the invasion capacity of gastric cancer cells. After ASODN treatment ($0.43{\mu}M$ for 48 h), Tiam 1 mRNA transcription and protein expression in $M_H$ cells were decreased by 80% and 24% respectively (P < 0.05), compared with untreated controls, while invasive capacity in vitro was suppressed by 60% (P < 0.05). Morphologic and ultrastructural observation also showed that ASODN-treated $M_H$ cells exhibited smooth surfaces with obviously reduced filopodia and microspikes, which resembled $M_0$ and $M_L$ cells. Additionally, cytoskeletal distribution dramatically altered from disorder to regularity with reduced long filament-like structure, projections, pseudopodia on cell surface, and with decreased acitn-bodies in cytoplasm. After Tiam 1 ASODN treatment, the expression of Rac 1 and Integrin ${\beta}1$ in $M_H$ cells was not affected (P > 0.05), but that of MMP 2 in $M_H$ cells was significantly inhibited compared with untreated cells (P < 0.05). Conclusion: Over-expression of Tiam-1 contributes to the invasive phenotype of gastric cancer cells. Inhibition of Tiam 1 expression could impair the invasive capacity of gastric cancer cells through modulating reconstruction of the cytoskeleton and regulating expression of MMP 2.
Kim, Jin-Young;Kim, Jin-Guk;Cho, Young-Hyun;Kwon, Hyun-Han
Journal of Korea Water Resources Association
/
v.50
no.11
/
pp.745-758
/
2017
The copula-based models have been successfully applied to hydrological modeling including drought frequency analysis and time series modeling. However, uncertainty estimation associated with the parameters of these model is not often properly addressed. In these context, the main purposes of this study are to develop the Bayesian inference scheme for bivariate copula functions. The main applications considered are two-fold: First, this study developed and tested an approach to copula model parameter estimation within a Bayesian framework for drought frequency analysis. The proposed modeling scheme was shown to correctly estimate model parameters and detect the underlying dependence structure of the assumed copula functions in the synthetic dataset. The model was then used to estimate the joint return period of the recent 2013~2015 drought events in the Han River watershed. The joint return period of the drought duration and drought severity was above 100 years for many of stations. The results obtained in the validation process showed that the proposed model could effectively reproduce the underlying distribution of observed extreme rainfalls as well as explicitly account for parameter uncertainty in the bivariate drought frequency analysis.
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