Mediation Analysis using Semi-parametric Shape-Restricted Regression with Applications

Often linear regression is used to perform mediation analysis. However, in many instances, the underlying relationships may not be linear, as in the case of placental-fetal hormones and fetal development. Although, the exact functional form of the relationship may be unknown, one may hypothesize the general shape of the relationship. For these reasons, we develop a novel shape-restricted inference-based methodology for conducting mediation analysis. This work is motivated by an application in fetal endocrinology where researchers are interested in understanding the effects of pesticide application on birth weight, with human chorionic gonadotropin (hCG) as the mediator. We assume a practically plausible set of nonlinear effects of hCG on the birth weight and a linear relationship between pesticide exposure and hCG, with both exposure-outcome and exposure-mediator models being linear in the confounding factors. Using the proposed methodology on a population-level prenatal screening program data, with hCG as the mediator, we discovered that, while the natural direct effects suggest a positive association between pesticide application and birth weight, the natural indirect effects were negative

Nonparametric inference on median residual life function

Summary. A simple approach to the estimation of the median residual lifetime is proposed for a single group by inverting a function of the Kaplan-Meier estimators. A test statistic is proposed to compare two median residual lifetimes at any fixed time point. The test statistic does not involve estimation of the underlying probability density function of failure times under censoring. Extensive simulation studies are performed to validate the proposed test statistic in terms of type I error probabilities and powers at various time points. One of the oldest data sets from the National Surgical Adjuvant Breast and Bowel Project (NSABP), which has more than a quarter century of follow-up, is used to illustrate the method. The analysis results indicate that, without systematic post-operative therapy, a significant difference in median residual lifetimes between node-negative and node-positive breast cancer patients persists for about 10 years after surgery. The new estimates of the median residual lifetime could serve as a baseline for physicians to explain any incremental effects of post-operative treatments in terms of delaying breast cancer recurrence or prolonging remaining lifetimes of breast cancer patients

Nonparametric inference on median residual life function

Summary. A simple approach to the estimation of the median residual lifetime is proposed for a single group by inverting a function of the Kaplan-Meier estimators. A test statistic is proposed to compare two median residual lifetimes at any fixed time point. The test statistic does not involve estimation of the underlying probability density function of failure times under censoring. Extensive simulation studies are performed to validate the proposed test statistic in terms of type I error probabilities and powers at various time points. One of the oldest data sets from the National Surgical Adjuvant Breast and Bowel Project (NSABP), which has more than a quarter century of follow-up, is used to illustrate the method. The analysis results indicate that, without systematic post-operative therapy, a significant difference in median residual lifetimes between node-negative and node-positive breast cancer patients persists for about 10 years after surgery. The new estimates of the median residual lifetime could serve as a baseline for physicians to explain any incremental effects of post-operative treatments in terms of delaying breast cancer recurrence or prolonging remaining lifetimes of breast cancer patients

Lung cancer with superior vena cava syndrome diagnosed by intravascular biopsy using EBUS-TBNA

AbstractSince superior vena cava syndrome (SVCS) is a critical condition, immediate diagnostic approach and therapy are imperative to avoid potentially life-threatening complications. Here, we report a case of lung cancer with SVCS, which was diagnosed through intravascular tumor biopsy using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). EBUS-TBNA enabled us to obtain tissue sufficient for diagnosis, without significant complications. Prompt diagnosis was followed by appropriate anticancer treatment and improvement in the symptoms. For patients suspected of SVCS and requiring prompt pathologic diagnosis, we can consider EBUS-TBNA to diagnose intravascular or mediastinal tumors and provide an accurate diagnosis

Age-dependent resistance of a perennial herb, Aristolochia contorta against specialist and generalist leaf-chewing herbivores

Plants need to balance investments in growth and defense throughout their life to increase their fitness. To optimize fitness, levels of defense against herbivores in perennial plants may vary according to plant age and season. However, secondary plant metabolites often have a detrimental effect on generalist herbivores, while many specialists have developed resistance to them. Therefore, varying levels of defensive secondary metabolites depending on plant age and season may have different effects on the performance of specialist and generalist herbivores colonizing the same host plants. In this study, we analyzed concentrations of defensive secondary metabolites (aristolochic acids) and the nutritional value (C/N ratios) of 1st-, 2nd- and 3rd-year Aristolochia contorta in July (the middle of growing season) and September (the end of growing season). We further assessed their effects on the performances of the specialist herbivore Sericinus montela (Lepidoptera: Papilionidae) and the generalist herbivore Spodoptera exigua (Lepidoptera: Noctuidae). Leaves of 1st-year A. contorta contained significantly higher concentrations of aristolochic acids than those of older plants, with concentrations tending to decrease over the first-year season. Therefore, when first year leaves were fed in July, all larvae of S. exigua died and S. montela showed the lowest growth rate compared to older leaves fed in July. However, the nutritional quality of A. contorta leaves was lower in September than July irrespective of plant age, which was reflected in lower larval performance of both herbivores in September. These results suggest that A. contorta invests in the chemical defenses of leaves especially at a young age, while the low nutritional value of leaves seems to limit the performance of leaf-chewing herbivores at the end of the season, regardless of plant age

Does robot-assisted laparoscopic radical prostatectomy enable to obtain adequate oncological and functional outcomes during the learning curve? From the Korean experience

To estimate the short-term results of robot-assisted laparoscopic radical prostatectomy (RALRP) during the learning curve, in terms of surgical, oncological and functional outcomes, we conducted a prospective survey on RALRP. From July 2007, a single surgeon performed 63 robotic prostatectomies using the same operative technique. Perioperative data, including pathological and early functional results of the patient, were collected prospectively and analyzed. Along with the accumulation of the cases, the total operative time, setup time, console time and blood loss were significantly decreased. No major complication was present in any patient. Transfusion was needed in six patients; all of them were within the initial 15 cases. The positive surgical margin rate was 9.8% (5/51) in pT2 disease. The most frequent location of positive margin in this stage was the lateral aspect (60%), but in pT3 disease multiple margins were the most frequent (41.7%). Overall, 53 (84.1%) patients had totally continent status and the median time to continence was 6.56 weeks. Among 17 patients who maintained preoperative sexual activity ( Sexual Health Inventory for Men \u3e = 17), stage below pT2, followed up for \u3e 6 months with minimally one side of neurovascular bundle preservation procedure, 12 (70.6%) were capable of intercourse postoperatively, and the mean time for sexual intercourse after operation was 5.7 months. In this series, robotic prostatectomy was a feasible and reproducible technique, with a short learning curve and low perioperative complication rate. Even during the initial phase of the learning curve, satisfactory results were obtained with regard to functional and oncological outcome