Errors of linear multistep methods and Runge-Kutta methods for singular perturbation problems with delays

AbstractThis paper is concerned with the error analysis of linear multistep methods and Runge-Kutta methods applied to some classes of one-parameter stiff singularly perturbed problems with delays. We derive the global error estimates of A(α)-stable linear multistep methods and algebraically and diagonally stable Runge-Kutta methods with Lagrange interpolation procedure. Numerical experiments confirm our theoretical analysis

An Integrated Method for Coding Trees, Measuring Tree Diameter, and Estimating Tree Positions

Accurately measuring tree diameter at breast height (DBH) and estimating tree positions in a sample plot are important in tree mensuration. The main aims of this paper include (1) developing a new, integrated device that can identify trees using the quick response (QR) code technique to record tree identifications, measure DBH, and estimate tree positions concurrently; (2) designing an innovative algorithm to measure DBH using only two angle sensors, which is simple and can reduce the impact of eccentric stems on DBH measures; and (3) designing an algorithm to estimate the position of the tree by combining ultra-wide band (UWB) technology and altitude sensors, which is based on the received signal strength indication (RSSI) algorithm and quadrilateral localization algorithm. This novel device was applied to measure ten 10 × 10 m square plots of diversified environments and various tree species to test its accuracy. Before measuring a plot, a coded sticker was fixed at a height of 1.3 m on each individual tree stem, and four UWB module anchors were set up at the four corners of the plot. All individual trees\u27 DBHs and positions within the plot were then measured. Tree DBH, measured using a tree caliper, and the values of tree positions, measured using tape, angle ruler, and inclinometer, were used as the respective reference values for comparison. Across the plots, the decode rate of QR codes was 100%, with an average response time less than two seconds. The DBH values had a bias of 1.89 mm (1.88% in relative terms) and a root mean square error (RMSE) of 5.38 mm (4.53% in relative terms). The tree positions were accurately estimated; the biases on the x-axis and the y-axis of the tree position were -8.55-14.88 cm and -12.07-24.49 cm, respectively, and the corresponding RMSEs were 12.94-33.96 cm and 17.78-28.43 cm. The average error between the estimated and reference distances was 30.06 cm, with a standard deviation of 13.53 cm. The device is cheap and friendly to use in addition to its high accuracy. Although further studies are needed, our method provides a great alternative to conventional tools for improving the efficiency and accuracy of tree mensuration

The Effect of Volunteer Human Performance Work System on Service Performance: An Empirical Study of Beijing Olympic Volunteers

This study examines the key human resources factors that affect volunteers' service performance from the perspectives of volunteers and managers in the Beijing Summer Olympic Games of 2008.Survey data were collected from 1,727 volunteers and 243 managers at the Beijing Olympics test events held at 10 venues between November 2007 and April 2008.Regression analyses and a moderation test were combined to test the hypotheses.A set of high performance work systems (HPWS) for volunteers in the Beijing Summer Olympic Games were developed which include performance management,training,recognition,teamwork and volunteer participation.Volunteer HPWS were positively related to psychological empowerment,which was in turn positively related to service recovery performance.Moreover,transformational leadership moderates the relationship between volunteer HPWS and psychological empowerment in such a way that the relationship is stronger when transformational leadership is at a higher level than when it is at a lower level.Implications and limitations were also discussed.We acknowledge the support of Fundamental Research Funds for the Central Universities,Jiangsu Philosophy & Social Sciences Research Funding Programme; National Natural Science Foundation of China; CEIBS Research Grant4605-6351

Research progress of coal seam gas content determination technology and equipment

Gas content is an important parameter for the prediction of coal and gas outburst risk, the estimation of coal seam gas resource, and the design of mine gas control engineering. Focusing on how to accurately and quickly determine the gas content of coal seams in large area, and relying on the National Science and Technology Major Project, the National Natural Science Foundation of China, the Joint Fund of Coal Enterprises and other projects to develop scientific and technological research, some progress had been made in sampling and testing, and the main manifestations were as follows. ① The development of sampling for gas content determination in coal seam has gone through four stages, namely, orifice sampling, core tube spot sampling, pressure injection spot sampling, and sealed sampling. The pressure holding capacity of the sealed sampling equipment reached 11.5 MPa, and the diameter of coal core reached 38 mm. ② According to different geological conditions of coal seams, three types of sampling techniques had been developed, including directional long borehole sealed sampling along coal seam, floor cross-layer borehole sealed sampling, and comb-shaped directional long borehole sealed sampling in roof or floor. ③ In the hard coal seams of Jiaozuo mining area in Henan Province and Jincheng mining area in Shanxi Province, the sampling depth of the directional long borehole along the seam reached 516 m, and the gas content of the coal seam measured by the sealed sampling method was increased by an average of 0.44 and 1.04 times compared with the conventional sampling method, respectively. In the broken soft coal seam of the Huainan mining area in Anhui Province, the sealed sampling depth of the cross-layer borehole reached 209 m, and the measured gas content of the coal seam was increased by 0.26 times on average compared with the conventional sampling method. In the broken soft coal seam of the Huaibei mining area in Anhui Province, the comb drilling sealed sampling depth reached 484 m in roof or floor, and the measured coal seam gas content was 0.19 times higher than that of the conventional sampling method. The sealed sampling method was superior than the conventional sampling method in terms of determination accuracy and detection range of coal seam gas content. ④ In terms of gas content testing, in addition to the traditional natural desorption test, a series of coal mine gas content rapid test equipment had been developed, which can measure the gas content of coal seam within 30 min at the earliest, and was generally used for gas content testing in 100-meter hole. It is proposed that the sealed sampling equipment for coal seam gas content determination needs to be developed in the direction of miniaturization and lightweight, and it can realize sealed sampling with the drilling. In the test, a reasonable desorption termination limit should be determined according to the actual situation, and the testing equipment and sealed sampling equipment should be further combined to achieve the rapid and accurate determination of gas content in deep hole. Sealed sampling technology has become the main means of accurate exploration and prediction of coal seam gas content in large areas, and it is an important technical guarantee for the safe and efficient coal mining

Phase I Study of mTORC1/2 Inhibitor Sapanisertib (CB-228/TAK-228) in Combination with Metformin in Patients with mTOR/AKT/PI3K Pathway Alterations and Advanced Solid Malignancies

BACKGROUND: Sapanisertib (CB-228/TAK-228) is a potent, selective ATP-competitive, dual inhibitor of mTORC1/2. Metformin is thought to inhibit the mTOR pathway through upstream activation of 5\u27-AMP-activated protein kinase (AMPK) suggesting combination therapy may enhance antitumor activity of sapanisertib. We report preliminary safety, tolerability, and efficacy from the dose-escalation study of sapanisertib in combination with metformin in patients with advanced solid tumors. METHODS: Patients with advanced metastatic solid tumors resistant or refractory to standard treatment, with and without mTOR/AKT/PI3K pathway alterations, received sapanisertib 3 or 4 mg daily together with metformin once to three times daily (500-1,500 mg). All patients underwent 14-day titration period for metformin in cycle 1. Tumor measurements were performed following cycle 2 and subsequently every 8 weeks. RESULTS: A total of 30 patients were enrolled across four cohorts (3 mg/500 mg; 3 mg/1,000 mg, 4 mg/1,000 mg; 4 mg/1,500 mg). 19 were female (63%), median age was 57 (range: 30-77), all were Eastern Cooperative Oncology Group performance status 1. Tumor types included sarcoma (6), breast (4), ovarian (4), head and neck (3), colorectal (2), lung (2), renal cell (2), endometrial (2), gastroesophageal junction (1), prostate (1), stomach (1), urachus (1), and cervical cancer (1). Median number of prior lines of therapy was 4. Most common genomic alterations included PIK3CA (27%), PTEN (17%), AKT1/2 (10%), mTOR (10%). Of 30 patients evaluable for response, 4 patients achieved partial response (PR); 15 patients achieved stable disease (SD) as best response. Disease control rate (PR+SD) was 63%. Of the responders in PR, 3 of 4 patients had documented PTEN mutations (3/5 patients enrolled with PTEN mutations had PR); 2 of 4 of patients in PR had comutations (patient with leiomyosarcoma had both PTEN and TSC; patient with breast cancer had both PTEN and STK11); 1 of 4 patients in PR had AKT and mTOR mutation; tumor types included leiomyosarcoma (n = 2), breast (n = 1), and endometrial cancer (n = 1). Most common treatment-emergent adverse events included nausea, anorexia, diarrhea, and rash. Grade (G) 3-5 treatment-related adverse events included hyperglycemia (4/30; 13%), fatigue (2/30; 7%), hypertriglyceridemia (1/30; 3%), rash (2/20; 7%), diarrhea (2/30; 7%), creatinine increase (1/30; 3%), acidosis (1/30; 3%). No dose-limiting toxicities (DLT) were reported in the 3 mg/500 mg cohort. One of 6 patient had DLT in the 3 mg/1,000 mg cohort (G3 diarrhea) and 2 of 11 patients had DLTs in the 4 mg/1,500 mg cohort (G3 fatigue, G3 rash). 4 mg/1,000 mg was defined as the MTD. CONCLUSIONS: The safety profile of mTORC1/2 inhibitor sapanisertib in combination with metformin was generally tolerable, with antitumor activity observed in patients with advanced malignancies harboring PTEN mutations and AKT/mTOR pathway alterations. SIGNIFICANCE: Sapanisertib (CB-228/TAK-228) is a potent, selective ATP-competitive, next-generation dual inhibitor of mTORC1/2. Metformin is thought to inhibit the mTOR pathway through upstream activation of AMPK suggesting combination therapy may enhance antitumor activity of sapanisertib. This dose-escalation study of sapanisertib and metformin in advanced solid tumors and mTOR/AKT/PI3K pathway alterations, demonstrates safety, tolerability, and early clinical activity in advanced malignancies harboring PTEN mutations and AKT/mTOR pathway alterations.Clinical trial information: NCT03017833

Spousal concordance in adverse childhood experiences and the association with depressive symptoms in middle-aged and older adults: findings across China, the US, and Europe

BackgroundAdverse childhood experiences (ACEs) are associated with higher depressive risks in adulthood. Whether respondents’ ACEs are associated with their own depressive symptoms in adulthood and whether this association extends to their spouses’ depressive symptoms remain unexplored.MethodsData were from China Health and Retirement Longitudinal Study (CHARLS), the Health and Retirement Study (HRS), and the Survey of Health, Ageing and Retirement in Europe (SHARE). ACEs were categorized into overall, intra-familial, and extra-familial ACEs. Correlations of couples’ ACEs were calculated using Cramer’s V and partial Spearman’s correlation. Associations of respondents’ ACEs with spousal depressive symptoms were assessed using logistic regression, and mediation analyses were conducted to explore the mediating role of respondents’ depressive symptoms.ResultsSignificant associations between husbands’ ACEs and wives’ depressive symptoms, with odds ratios (ORs) and 95% confidence intervals (CIs) of 2.09 (1.36–3.22) for 4 or more ACEs in CHARLS, and 1.25 (1.06–1.48) and 1.38 (1.06–1.79) for 2 or more ACEs in HRS and SHARE. However, wives’ ACEs were associated with husbands’ depressive symptoms only in CHARLS and SHARE. Findings in intra-familial and extra-familial ACEs were consistent with our main results. Additionally, respondents’ depressive symptoms mediated more than 20% of the effect of respondents’ ACEs on spousal depressive symptoms.ConclusionWe found that ACEs were significantly correlated between couples. Respondents’ ACEs were associated with spousal depressive symptoms, with respondents’ depressive symptoms mediating the association. The bidirectional implications of ACEs on depressive symptoms should be considered within household and effective interventions are warranted

First-In-Human Phase I Study of Tinengotinib (TT-00420), a Multiple Kinase Inhibitor, as a Single Agent in Patients With Advanced Solid Tumors

PURPOSE: This first-in-human phase I dose-escalation study evaluated the safety, pharmacokinetics, and efficacy of tinengotinib (TT-00420), a multi-kinase inhibitor targeting fibroblast growth factor receptors 1-3 (FGFRs 1-3), Janus kinase 1/2, vascular endothelial growth factor receptors, and Aurora A/B, in patients with advanced solid tumors. PATIENTS AND METHODS: Patients received tinengotinib orally daily in 28-day cycles. Dose escalation was guided by Bayesian modeling using escalation with overdose control. The primary objective was to assess dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and dose recommended for dose expansion (DRDE). Secondary objectives included pharmacokinetics and efficacy. RESULTS: Forty-eight patients were enrolled (dose escalation, n = 40; dose expansion, n = 8). MTD was not reached; DRDE was 12 mg daily. DLTs were palmar-plantar erythrodysesthesia syndrome (8 mg, n = 1) and hypertension (15 mg, n = 2). The most common treatment-related adverse event was hypertension (50.0%). In 43 response-evaluable patients, 13 (30.2%) achieved partial response (PR; n = 7) or stable disease (SD) ≥ 24 weeks (n = 6), including 4/11 (36.4%) with FGFR2 mutations/fusions and cholangiocarcinoma (PR n = 3; SD ≥ 24 weeks n = 1), 3/3 (100.0%) with hormone receptor (HR)-positive/HER2-negative breast cancer (PR n = 2; SD ≥ 24 weeks n = 1), 2/5 (40.0%) with triple-negative breast cancer (TNBC; PR n = 1; SD ≥ 24 weeks n = 1), and 1/1 (100.0%) with castrate-resistant prostate cancer (CRPC; PR). Four of 12 patients (33.3%; HR-positive/HER2-negative breast cancer, TNBC, prostate cancer, and cholangiocarcinoma) treated at DRDE had PRs. Tinengotinib\u27s half-life was 28-34 hours. CONCLUSIONS: Tinengotinib was well tolerated with favorable pharmacokinetic characteristics. Preliminary findings indicated potential clinical benefit in FGFR inhibitor-refractory cholangiocarcinoma, HER2-negative breast cancer (including TNBC), and CRPC. Continued evaluation of tinengotinib is warranted in phase II trials