• Communications for Statistical Applications and Methods
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• 제27권6호
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• pp.675-688
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• 2020

In survival analysis of observational data, the inverse probability weighting method and the Cox proportional hazards model are widely used when estimating the causal effects of multiple-valued treatment. In this paper, the two kinds of weights have been examined in the inverse probability weighting method. We explain the reason why the stabilized weight is more appropriate when an inverse probability weighting method using the generalized propensity score is applied. We also emphasize that a marginal hazard ratio and the conditional hazard ratio should be distinguished when defining the hazard ratio as a treatment effect under the Cox proportional hazards model. A simulation study based on real data is conducted to provide concrete numerical evidence.

• 응용통계연구
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• 제32권2호
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• pp.173-185
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• 2019

과학적 연구에서 핵심적인 연구 주제 또는 가설은 대부분 인과적 질문(causal question)을 포함한다. 예를 들어, 전염병 예방을 위한 치료법의 효과 연구, 특정 정책의 시행으로 인한 효용(utility)의 평가에 대한 연구, 특정 사용자를 대상으로 노출된 광고의 종류에 따른 광고의 효과성에 대한 연구는 모두 인과 관계(causal relationship)의 추론이 요구된다. 이러한 인과 관계를 다루는 통계적 인과 추론(statistical causal inference)의 주요 관심사 중 하나는 모집단에 일종의 개입(정책 혹은 처치)을 적용한 후 개입의 효과를 정확하게 추정하는 것이다. 인과 추론은 임상실험과 정책결정에서 주로 이용되었으나, 이른바 빅데이터 시대의 도래로 가용한 관측자료가 폭발적으로 증가하였고 이로 인하여 인과 추론에 대한 잠재적 응용가치와 수요가 지속적으로 증가하고 있다. 하지만 가용한 대부분의 자료는 임의실험 기반의 자료와 달리 개입이 임의로 분배되지 않은 비실험 관측자료이다. 따라서, 본 논문은 비실험 관측자료로부터 개입의 효과를 추정하기 위한 인과 추론의 핵심 개념과 최근의 연구동향을 소개하고자 한다. 이를 위하여 본문에서는 먼저 개입의 효과를 Neyman-Rubin의 잠재 결과(potential outcome) 모형으로 나타내고, 개입의 효과를 추정하는 여러 접근법 중 특히 성향점수(propensity score) 기반 추정법과 회귀모형 기반 추정법을 중점적으로 소개한다. 최근 연구동향으로는 (1) 평균 효과 크기 추정을 넘어선 개인별 효과 크기의 추정, (2) 효과크기 추정에 있어서 자료 규모의 증대로 인한 차원의 저주가 야기하는 난제들과 이에 대한 해결방안들, (3) 복합적 인과관계를 반영하기 위한 Pearl의 구조적 인과 모형(structural causal model) 및 잠재 결과 모형과의 비교의 3가지 주제로 구분하여 소개한다.

• 한국분말재료학회지
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• 제4권3호
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• pp.222-229
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• 1997

A P/M high speed steel of ASP 30 grade was austenitized, gas quenched and tempered at various conditional. The mechanical properties such as hardness, bend strength and fracture toughness were evaluated after heat treatment. The microstructure and the type and volume fraction of carbides were analyzed by an optical microscope, image analyzer and XRD. The primary carbides after the heat treatment were MC and $M_6C$ type. The volume of the total carbide varied from 10 to 15% depending on the austenitizing and tempering temperature. The tempering temperature for maximum hardness was at around 52$0^{\circ}C$. But the maximum bend strength was obtained at about 55$0^{\circ}C$. The fracture toughness was largely affected by the presence of retained austenite after gas quenching and secondary hardening during tempering.

• Communications for Statistical Applications and Methods
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• 제30권6호
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• pp.631-652
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• 2023

In the two-condition within-subject mediation design, pairs of variables such as mediator and outcome are observed under two treatment conditions. The main objective of the design is to investigate the indirect effects of the condition difference (sum) on the outcome difference (sum) through the mediator difference (sum) for comparison of two treatment conditions. The natural condition variables mean the original variables, while the rotated condition variables mean the difference and the sum of two natural variables. The outcome difference (sum) is expressed as a linear model regressed on two natural (rotated) mediators as a parallel two-mediator design in two condition approaches: the natural condition approach uses regressors as the natural condition variables, while the rotated condition approach uses regressors as the rotated condition variables. In each condition approach, the total indirect effect on the outcome difference (sum) can be expressed as the sum of two individual indirect effects: within- and cross-condition indirect effects. The total indirect effects on the outcome difference (sum) for both condition approaches are the same. The invariance of the total indirect effect makes it possible to analyze the nature of two pairs of individual indirect effects induced from the natural conditions and the rotated conditions. The two-condition within-subject design is extended to the addition of a between-subject moderator. Probing of the conditional indirect effects given the moderator values is implemented by plotting the bootstrap confidence intervals of indirect effects against the moderator values. The expected indirect effect with respect to the moderator is derived to provide the overall effect of moderator on the indirect effect. The model coefficients are estimated by the structural equation modeling approach and their statistical significance is tested using the bias-corrected bootstrap confidence intervals. All procedures are evaluated using function lavaan() of package {lavaan} in R.

• Tuberculosis and Respiratory Diseases
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• 제83권1호
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• pp.20-30
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• 2020

Tuberculosis (TB) remains a threat to public health and is the leading cause of death globally. Isoniazid (INH) is an important first-line agent for the treatment of TB considering its early bactericidal activity. Resistance to INH is now the most common type of resistance. Resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other first-line drugs such as rifampicin (RIF), thereby increasing the risk of multidrug-resistant-TB. Studies in the 1970s and 1980s showed high success rates for INH-resistant TB cases receiving regimens comprised of first-line drugs. However, recent data have indicated that INH-resistant TB patients treated with only firs-tline drugs have poor outcomes. Fortunately, based on recent systematic meta-analyses, the World Health Organization published consolidated guidelines on drug-resistant TB in 2019. Their key recommendations are treatment with RIF-ethambutol (EMB)-pyrazinamide (PZA)-levofloxacin (LFX) for 6 months and no addition of injectable agents to the treatment regimen. The guidelines also emphasize the importance of excluding resistance to RIF before starting RIF-EMB-PZA-LFX regimen. Additionally, when the diagnosis of INH-resistant TB is confirmed long after starting the first-line TB treatment, the clinician must decide whether to start a 6-month course of RIF-EMB-PZA-LFX based on the patient's condition. However, these recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty of the effect estimates. Therefore, further work is needed to optimize the treatment of INH-resistant TB.

• 혜화의학회지
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• 제16권2호
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• pp.199-210
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• 2007

Objective & Methods : The case report is to observe 27 case of venesection with negative pressure therapy(buhang) operated at CV17 (Danjuong) on sudden palpitation. We carried out to analyze the distribution and Martin's evaluation and weighted scale by sex & age, patient conditional grade, accompanied symptoms, duration, number of treatments as well. Results : 1. Forties is significantly distributed on sudden palpitation. 2. Depression instance out of many accompanied symptoms is significantly distributed. 3. Mean of operant frequency is significantly resulted on 10 or 11 times. 4. The improvement on the weighted scale is over one grade. 5. Younger is high on the assessment of treatment on Martin's evaluation and weighted scale by age, while older is low. 6. Lesser one year and more three years is some significantly resulted on the assessment of treatment on Martin's evaluation and weighted scale by duration. 7. Pleurodynia, insomnia, distress in the stomach are effective more 90%, and depression, asthma are more 80% on the assessment of treatment on Martin's evaluation by accompanied symptoms, while asthma and pleurodynia are very significantly resulted on the assessment of treatment on weighted scale. 8. The assessment of treatment on Martin's evaluation and weighted scale have no connection with operant frequency. Conclusion : These results suggest that venesection with negative pressure therapy(buhang) operated at CV17 (Danjuong) has a therapeutic effect on on sudden palpitation.

• 한국임상약학회지
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• 제26권4호
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• pp.312-317
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• 2016

Objective: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. Methods: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model ($NONMEM^{(R)}$ 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. Results: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. Conclusion: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.

• Archives of Plastic Surgery
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• 제50권4호
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• pp.432-442
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• 2023

Background Macrophages play a major role in wound healing and prevent infection from the outside. Polarization conversion of macrophages regulates aspects of inflammation, and two macrophages, M1 (classically activated) and M2 (alternatively activated), exist at both ends of broad-spectrum macrophage polarization. Thus, we aimed to investigate whether macrophage polarization can be artificially regulated. To this end, MgSO4 and small-interfering RNA (siRNA) targeting magnesium transport 1 (MAGT1) were used to investigate the effects of intracellular magnesium (Mg2+) concentrations on the differentiation of macrophages in vitro. Methods THP-1 derived macrophages maintained in a culture medium containing 5 mM MgSO4 and siRNA to inhibit the expression of MAGT1. As comparative groups, THP-1 derived macrophages polarized into M1 and M2 macrophages by treatment with M1, M2 inducer cytokine. The polarization status of each group of cells was confirmed by cell surface antigen expression and cytokine secretion. Results We found that MgSO4 treatment increased CD163 and CD206, similar to the effect noted in the M2 group. The expression of CD80 and HLA-DR was increased in the group treated with MAGT1 siRNA, similar to the effect noted in the M1 group. Functional assays demonstrated that the group treated with MgSO4 secreted higher levels of IL-10, whereas the MAGT1 siRNA-treated group secreted higher levels of IL-6 cytokines. Additionally, the conditional medium of the Mg2+ treated group showed enhanced migration of keratinocytes and fibroblasts. Conclusion Mg2+ can help to end the delay in wound healing caused by persistent inflammation in the early stages.

• 응용통계연구
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• 제36권5호
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• pp.381-397
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• 2023

대부분의 임상시험에서 가장 대표적으로 사용되는 실험설계는 무작위화로, 치료 효과를 정확하게 추정하기 위해 이용된다. 그러나 무작위화가 이루어지지 않은 관찰연구의 경우 치료군과 대조군의 비교로 얻는 치료효과에는 환자 간의 특성 등 여러 조정되지 않은 차이로 인해 편향이 발생한다. 성향 점수 가중치는 이러한 문제점을 해결하기 위해 널리쓰이는 방법으로 치료 효과를 추정하는데에 있어 교란요인을 조정하여 편향을 최소화하도록 하는 방법이다. 성향 점수를 이용한 가중치 방법 중 가장 널리 알려진 역확률 가중치는 관찰된 공변량이 주어졌을 때 특정 치료에 할당될 조건부 확률의 역에 비례하는 가중치를 할당한다. 그러나 이 방법은 극단적인 성향 점수에 의해 종종 방해 받아 편향된 추정치와 과도한 분산을 초래한다는 점이 알려져있어 이러한 문제를 완화하기 위해 절사 역확률 가중치, 중복 가중치, 일치 가중치를 포함한 여러 가지 대안 방법이 제안되었다. 본 논문에서는 제한된 중복, 잘못 지정된 성향 점수 모델 및 예측과 반대되는 치료 등 다양한 문제상황에서 여러 성향 점수 가중치 방법의 성능을 비교하는 시뮬레이션 비교연구를 수행하였다. 비교연구의 결과 중복 가중치와 일치 가중치는 편향, 제곱근평균제곱오차 및 포함 확률 측면에서 역확률 가중치와 절사역확률 가중치에 비에 우월한 성능을 보임을 확인하였다.

• 한국가축번식학회지
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• 제27권3호
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• pp.187-195
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• 2003

체외 성숙시킨 M II기 난자의 여러 화학물질간의 중복 및 병용처리를 실시하여 수핵란으로서 적합한 활성화 조건과 활성화 후 자체 탈핵을 유도함으로써 보다 효율적인 탈핵 여건을 확립하고자 본 연구를 실시하였다. 1. Ethanol을 사용하여 6-DMAP 또는 cycloheximide 간의 단독, 중복, 그리고 병용처리를 실시한 결과, 활성화율, 난할율 및 체외 발달율에서 단독처리와 병용처리간의 차이는 없었으나 중복처리시 유의적으로 저하되었다(P<0.05). 2. $Ca^{2+}$ ionophore를 가지고 활성화 조건별로 처리하였을 경우, 6-DMAP와 병용 처리가 활성화율, 난할율 및 체외 발달율에서 각각 80.8%, 78.3%, 40.6%로 단독처리시의 58.0%, 62.9%, 27.0%보다 유의적으로 높았고(P<0.05), 또한 cycloheximide와의 병용처리도 활성화 및 난할율에서 단독처리와의 유의적 차이를 보였다(P<0.05). 그러나 중복처리시에는 효과를 나타내지 못하였다. 3. 탈핵전 수핵란에 미리 활성화 처리를 한 후 핵이식란을 재구성 한 결과 탈핵율 및 세포 융합율에서 90.7%, 71.8%로 활성화 처리하지 않은 것 77.8%, 61.1% 보다 유의적으로 높았다(P<0.05). 그러나 난할율 및 체외 발달율에서는 유의적으로 저하되었다(38.7%, 19.3% vs 68.8%, 30.6%, P<0.05). 또한 변성율도 활성화 처리하지 않은 구에 비해 유의적으로 높게 나타났다(P<0.05). 이상의 결과로 미루어 탈핵전 활성화하여 수핵란으로 이용할 경우 $Ca^{2+}$ ionophore와 6-DMAP를 병용 처리가 가장 효과적이며, 주입되는 체세포와 수핵란 간의 적정한 세포주기의 조절이 효율적인 돼지 복제수정란 생산을 위해 필요할 것이다.