Causal Mediation Analysis for Difference-in-Difference Design and Panel Data

Advantages of panel data, i.e., difference in difference (DID) design data, are a large sample size and easy availability. Therefore, panel data are widely used in epidemiology and in all social science fields. The literatures on causal inferences of panel data setting or DID design are growing, but no theory or mediation analysis method has been proposed for such settings. In this study, we propose a methodology for conducting causal mediation analysis in DID design and panel data setting. We provide formal counterfactual definitions for controlled direct effect and natural direct and indirect effect in panel data setting and DID design, including the identification and required assumptions. We also demonstrate that, under the assumptions of linearity and additivity, controlled direct effects can be estimated by contrasting marginal and conditional DID estimators whereas natural indirect effects can be estimated by calculating the product of the exposure-mediator DID estimator and the mediator-outcome DID estimator. A panel regression-based approach is also proposed. The proposed method is then used to investigate mechanisms of the effects of the Covid 19 pandemic on the mental health status of the population. The results revealed that mobility restrictions mediated approximately 45 % of the causal effect of Covid 19 on mental health status

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

以GARCH相關模型研究台股指數是否具厚尾效應及期貨避險績效

Because of the uncertainty in the stock market, many investors suffered tremendous loss by volatile stock market in recent ten years. How to manage the risk of investment portfolio became an important issue after the financial crisis in 2008. This paper takes advantage of related GARCH models to test the hedge performance in Taiwan index futures from 1998 to 2008. The results are as follows: First, the hedge performance becomes better as the degrees of risk aversion increases. Second, dynamic models have better predictability than static ones. Hence, the dynamic hedge performance is better than static hedge. Third, assuming the error distribution follows t distribution, the hedge performance is superior to the case with normal distribution of error, across the degrees of risk aversion. The results also show that the index has a fat-tailed effect. Forth, simplified GARCH, SGARCH, model can be used to compare GARCH with GJR-GARCH, replaced the original multivariate model with two univariate models. Fifth, assuming error distribution follows t distribution, the hedge performance of SGARCH would improve substantially. In addition, both out-of-sample predictability and hedge performance show that the GARCH model holds preferable results.因股票市場存在許多不確定性，近十年歷經幾次劇烈波動後，許多投資人皆遭受嚴重損失，如何使自己的投資組合風險降到最低更成為大家所關注的焦點。本研究利用GARCH相關模型探討1998年9月至2008年9月台灣加權指數期貨的避險效果，經實證結果發現：1.隨著風險趨避程度的增加，避險績效也跟著提升。2.動態模型比靜態模型更能預測未來走勢，因此動態避險績效比靜態避險績效高。3.在任何風險趨避程度下，各模型在殘差為t分配的假設下，避險績效都顯著較常態分配為佳，顯示台指報酬數列具厚尾現象。4.將GARCH和GJR-GARCH套用至簡化後的模型SGARCH，即能比較GARCH模型績效GJR模型優，與未簡化之模型比較結果相同，如此一來，則可以簡化計算過程取代原始的multivariate model。5.在殘差為t分配的假設下，使SGARCH模型避險績效有大幅的提升。另外，在樣本外預測及避險績效的實證均顯示出GARCH模型的績效較佳。第一章 緒論 1 第一節研究背景與動機 1 第二節 研究流程 2 第二章 文獻探討 4 第一節 避險理論 4 第二節 預測能力 4 第三節 動態避險 v.s.靜態避險 5 第四節 不對稱效果 6 第五節 厚尾效應 7 第三章 研究方法 9 第一節 資料來源與處理 9 第二節 單根檢定 10 第三節 實證模型 11 第四節 避險比率與避險績效的衡量 14 第四章 實證研究 16 第一節 實證資料基本統計量與相關檢定 16 第二節 模擬資料 17 第三節 樣本外預測 20 第四節 實證結果 23 第五章 結論與建議 34 第一節 結論 34 第二節 研究建議 34 參考文獻 3

Functional Properties of Pineapple Plant Stem for Enhanced Glucose Recovery in Amino Acids Production

Pineapples generate large amounts of agricultural wastes during their production. To reduce environmental impacts due to poor handling of these wastes, the underutilised pineapple plant stem (PPS), which has a high starch content, can be explored for its sugar recovery. To achieve this, gelatinisation is a key process in increasing enzymes’ susceptibility. Therefore, this study aimed to enhance glucose recovery from PPS by studying the effects of gelatinisation temperature and time on its functional properties. Afterwards, the fermentable sugar obtained was used for amino acids production by Bacillus subtilis ATCC 6051. PPS has a high gelatinisation temperature (To = 111 °C; Tp = 116 °C; Tc = 161 °C) and enthalpy (ΔH = 263.58 J/g). Both temperature and time showed significant effects on its functional properties, affecting enzymatic hydrolysis. Gelatinisation temperature of 100 °C at 15 min resulted in maximum glucose recovery of 56.81 g/L (0.81 g/g hydrolysis yield) with a 3.53-fold increment over the control. Subsequently, utilisation of PPS hydrolysate in the fermentation by B. subtilis ATCC 6051 resulted in 23.53 mg/mL amino acids being produced with productivity of 0.49 g/L/h. This opens up new opportunities for the applications of PPS as well as B. subtilis ATCC 6051 in the amino acids industry

Metformin regulates oxLDL-facilitated endothelial dysfunction by modulation of SIRT1 through repressing LOX-1-modulated oxidative signaling

[[abstract]]It is suggested that oxLDL is decisive in the initiation and development of atherosclerotic injuries. The up-regulation of oxidative stress and the generation of ROS act as key modulators in developing pro-atherosclerotic and anti-atherosclerotic processes in the human endothelial wall. In this present study, we confirmed that metformin enhanced SIRT1 and AMPK expression in human umbilical vein endothelial cells (HUVECs). Metformin also inhibited oxLDL-increased LOX-1 expression and oxLDL-collapsed AKT/eNOS levels. However, silencing SIRT1 and AMPK diminished the protective function of metformin against oxidative injuries. These results provide a new insight regarding the possible molecular mechanisms of metformin

Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling

Coronary artery disease (CAD) is a critical cardiovascular disease and a cause of high morbidity and mortality in this world. Hyperhomocysteinemia (HHcy) has been suggested as a risk factor for CAD. In addition, SIRT1 (sirtuin 1) has been reported to play a protective role in a variety of diseases, especially in the cardiovascular system. The main purpose of this study was to investigate the effects of exercise training on apoptosis and inflammation in HHcy animals. We also tested whether exercise protected against Hhcy-induced dysfunction of endothelium through modulation of SIRT1. C57BL mice (8 in each group) were fed with or without 1% L-methionine (w/w) in water for 4 months to induce HHcy. We found that Hhcy repressed SIRT1 and AMPK expression and increased NADPH oxidase activity. Plasma MDA, endothelium LOX-1 and p-p38 were up-regulated by Hhcy induction. NF-κB and it downstream molecules were activated under Hhcy situation, thereby promoting pro-inflammatory responses. Moreover, we also reported that Hhcy caused endothelium apoptosis involving Akt inhibition and mitochondria-dependent apoptotic pathways. Exercise training significantly protected against endothelium from Hhcy caused oxidative injuries. In addition, EX527 (SIRT1 inhibitor) reduced the therapeutic effects by exercise. Our results had indicated that exercise training prevent the development of atherosclerosis through SIRT1 activation and oxidative stress inhibition under Hhcy situation. Keywords: Sirtuin 1, Coronary artery disease, Hyperhomocysteinemia, Oxidative stres

Chicoric acid is a potent anti-atherosclerotic ingredient by anti-oxidant action and anti-inflammation capacity

[[abstract]]Atherosclerotic cardiovascular disease is linked to both oxidative stress and endothelial cell dysfunction. Chicoric acid has antioxidant and anti-inflammatory properties. In the present investigation, we demonstrated that chicoric acid inhibits oxidized low-density lipoprotein (oxLDL)-facilitated dysfunction in human umbilical vein endothelial cells (HUVECs). Oxidative injuries were tested by investigating the formation of intracellular reactive oxygen species (ROS) and by examining the activity of antioxidant enzymes and the function of endothelial nitric oxide synthase (eNOS). We also confirmed that chicoric acid mitigates apoptotic features caused by oxLDL, such as the subsequent break down of mitochondrial transmembrane potential and the activation of Bax, which promote DNA strand breaks and activate caspase-3. Moreover, our data revealed that chicoric acid attenuated the oxLDL activation of NF-κB, the attachment of THP-1 cells and the overexpression of adhesion molecules in human endothelial cells. The results of this study suggest a potential molecular mechanism through which chicoric acid inhibits oxLDL-induced human endothelial dysfunction

Exercise intervention attenuates hyperhomocysteinemia- induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling.

[[abstract]]Coronary artery disease (CAD) is a critical cardiovascular disease and a cause of high morbidity and mortality in this world. Hyperhomocysteinemia (HHcy) has been suggested as a risk factor for CAD. In addition, SIRT1 (sirtuin 1) has been reported to play a protective role in a variety of diseases, especially in the cardiovascular system. The main purpose of this study was to investigate the effects of exercise training on apoptosis and inflammation in HHcy animals. We also tested whether exercise protected against Hhcy-induced dysfunction of endothelium through modulation of SIRT1. C57BL mice (8 in each group) were fed with or without 1% L-methionine (w/w) in water for 4 months to induce HHcy. We found that Hhcy repressed SIRT1 and AMPK expression and increased NADPH oxidase activity. Plasma MDA, endothelium LOX-1 and p-p38 were up-regulated by Hhcy induction. NF-κB and it downstream molecules were activated under Hhcy situation, thereby promoting pro-inflammatory responses. Moreover, we also reported that Hhcy caused endothelium apoptosis involving Akt inhibition and mitochondria-dependent apoptotic pathways. Exercise training significantly protected against endothelium from Hhcy caused oxidative injuries. In addition, EX527 (SIRT1 inhibitor) reduced the therapeutic effects by exercise. Our results had indicated that exercise training prevent the development of atherosclerosis through SIRT1 activation and oxidative stress inhibition under Hhcy situation

SIRT1 inhibition causes oxidative stress and inflammation in patients with coronary artery disease

Coronary artery disease (CAD) is the primary critical cardiovascular event. Endothelial cell and monocyte dysfunction with subsequent extravagant inflammation are the main causes of vessel damage in CAD. Thus, strategies that repress cell death and manage unsuitable pro-inflammatory responses in CAD are potential therapeutic strategies for improving the clinical prognosis of patients with CAD. SIRT1 (Sirtuin 1) plays an important role in regulating cellular physiological processes. SIRT1 is also thought to protect the cardiovascular system by means of its antioxidant, anti-inflammation and anti-apoptosis activities. In the present study, we found that the SIRT1 expression levels were repressed and the acetylated p53 expression levels were enhanced in the monocytes of patients with CAD. LOX-1/oxidative stress was also up-regulated in the monocytes of patients with CAD, thereby increasing pro-apoptotic events and pro-inflammatory responses. We also demonstrated that monocytes from CAD patients caused endothelial adhesion molecule activation and the adherence of monocytes and endothelial cells. Our findings may explain why CAD patients remain at an increased risk of long-term recurrent ischemic events and provide new knowledge regarding the management of clinical CAD patients

SIRT1 inhibition causes oxidative stress and inflammation in patients with coronary artery disease

[[abstract]]Coronary artery disease (CAD) is the primary critical cardiovascular event. Endothelial cell and monocyte dysfunction with subsequent extravagant inflammation are the main causes of vessel damage in CAD. Thus, strategies that repress cell death and manage unsuitable pro-inflammatory responses in CAD are potential therapeutic strategies for improving the clinical prognosis of patients with CAD. SIRT1 (Sirtuin 1) plays an important role in regulating cellular physiological processes. SIRT1 is also thought to protect the cardiovascular system by means of its antioxidant, anti-inflammation and anti-apoptosis activities. In the present study, we found that the SIRT1 expression levels were repressed and the acetylated p53 expression levels were enhanced in the monocytes of patients with CAD. LOX-1/oxidative stress was also up-regulated in the monocytes of patients with CAD, thereby increasing pro-apoptotic events and pro-inflammatory responses. We also demonstrated that monocytes from CAD patients caused endothelial adhesion molecule activation and the adherence of monocytes and endothelial cells. Our findings may explain why CAD patients remain at an increased risk of long-term recurrent ischemic events and provide new knowledge regarding the management of clinical CAD patients