Imprecise Prior for Imprecise Inference on Poisson Sampling Model

Prevalence is a valuable epidemiological measure about the burden of disease in a community for planning health services; however, true prevalence is typically underestimated and there exists no reliable method of confirming the estimate of this prevalence in question. This thesis studies imprecise priors for the development of a statistical reasoning framework regarding this epidemiological decision making problem. The concept of imprecise probabilities introduced by Walley (1991) is adopted for the construction of this inferential framework in order to model prior ignorance and quantify the degree of imprecision associated with the inferential process. The study is restricted to the standard and zero-truncated Poisson sampling models that give an exponential family with a canonical log-link function because of the mechanism involved with the estimation of population size. A three-parameter exponential family of posteriors which includes the normal and log-gamma as limiting cases is introduced by applying normal priors on the canonical parameter of the Poisson sampling models. The canonical parameters simplify dealing with families of priors as Bayesian updating corresponds to a translation of the family in the canonical hyperparameter space. The canonical link function creates a linear relationship between regression coefficients of explanatory variables and the canonical parameters of the sampling distribution. Thus, normal priors on the regression coefficients induce normal priors on the canonical parameters leading to a higher-dimensional exponential family of posteriors whose limiting cases are again normal or log-gamma. All of these implementations are synthesized to build the ipeglim package (Lee, 2013) that provides a convenient method for characterizing imprecise probabilities and visualizing their translation, soft-linearity, and focusing behaviours. A characterization strategy for imprecise priors is introduced for instances when there exists a state of complete ignorance. The learning process of an individual intentional unit, the agreement process between several intentional units, and situations concerning prior-data conflict are graphically illustrated. Finally, the methodology is applied for re-analyzing the data collected from the epidemiological disease surveillance of three specific cases – Cholera epidemic (Dahiya, 1973), Down’s syndrome (Zelterman, 1988), and the female users of methamphetamine and heroin (B ̈ ohning, 2009)

Myrrh Inhibits LPS-Induced Inflammatory Response and Protects from Cecal Ligation and Puncture-Induced Sepsis

Myrrh has been used as an antibacterial and anti-inflammatory agent. However, effect of myrrh on peritoneal macrophages and clinically relevant models of septic shock, such as cecal ligation and puncture (CLP), is not well understood. Here, we investigated the inhibitory effect and mechanism(s) of myrrh on inflammatory responses. Myrrh inhibited LPS-induced productions of inflammatory mediators such as nitric oxide, prostaglandin E2, and tumor necrosis factor-α but not of interleukin (IL)-1β and IL-6 in peritoneal macrophages. In addition, Myrrh inhibited LPS-induced activation of c-jun NH2-terminal kinase (JNK) but not of extracellular signal-regulated kinase (ERK), p38, and nuclear factor-κB. Administration of Myrrh reduced the CLP-induced mortality and bacterial counts and inhibited inflammatory mediators. Furthermore, administration of Myrrh attenuated CLP-induced liver damages, which were mainly evidenced by decreased infiltration of leukocytes and aspartate aminotransferase/alanine aminotransferase level. Taken together, these results provide the evidence for the anti-inflammatory and antibacterial potential of Myrrh in sepsis

Safety and efficacy study of laparoscopic or robotic radical surgery using an endoscopic stapler for inhibiting tumour spillage of cervical malignant neoplasms evaluating survival (SOLUTION): a multi-centre, open-label, single-arm, phase II trial protocol

The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer. This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%. We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery.This study was supported by Johnson & Johnson. The funder has no role in study design, writing of the manuscript and the decision to submit the report for publication

Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study

BackgroundBVAC-C, a B cell– and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV–positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16– or 18–positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy.Patients and methodsPatients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).ResultsOf the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1–not reported), the median PFS was 5.8 months (95% CI 4.2–10.3), and the median OS was 17.7 months (95% CI 12.0–not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses.ConclusionBVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response.Clinical trial registrationClinicalTrials.gov, identifier NCT02866006

Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers

Background Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, progression, and metastasis of gynecologic tumors. However, targeting such alterations has frequently led to treatment failures due to underlying genomic complexity and simultaneous activation of various tumor cell survival pathway molecules. A compilation of molecular characterization of tumors with pharmacological drug response is the next step toward clinical application of patient-tailored treatment regimens. Results Toward this goal, we establish a library of 139 gynecologic tumors including epithelial ovarian cancers (EOCs), cervical, endometrial tumors, and uterine sarcomas that are genomically and/or pharmacologically annotated and explore dynamic pharmacogenomic associations against 37 molecularly targeted drugs. We discover lineage-specific drug sensitivities based on subcategorization of gynecologic tumors and identify TP53 mutation as a molecular determinant that elicits therapeutic response to poly (ADP-Ribose) polymerase (PARP) inhibitor. We further identify transcriptome expression of inhibitor of DNA biding 2 (ID2) as a potential predictive biomarker for treatment response to olaparib. Conclusions Together, our results demonstrate the potential utility of rapid drug screening combined with genomic profiling for precision treatment of gynecologic cancers

SimSST: An R Statistical Software Package to Simulate Stop Signal Task Data

The stop signal task (SST) paradigm with its original roots in 1948 has been proposed to study humans’ response inhibition. Several statistical software codes have been designed by researchers to simulate SST data in order to study various theories of modeling response inhibition and their assumptions. Yet, there has been a missing standalone statistical software package to enable researchers to simulate SST data under generalized scenarios. This paper presents the R statistical software package “SimSST”, available in Comprehensive R Archive Network (CRAN), to simulate stop signal task (SST) data. The package is based on the general non-independent horse race model, the copulas in probability theory, and underlying ExGaussian (ExG) or Shifted Wald (SW) distributional assumption for the involving go and stop processes enabling the researchers to simulate sixteen scenarios of the SST data. A working example for one of the scenarios is presented to evaluate the simulations’ precision on parameter estimations. Package limitations and future work directions for its subsequent extensions are discussed

SimSST: An R Statistical Software Package to Simulate Stop Signal Task Data

The stop signal task (SST) paradigm with its original roots in 1948 has been proposed to study humans’ response inhibition. Several statistical software codes have been designed by researchers to simulate SST data in order to study various theories of modeling response inhibition and their assumptions. Yet, there has been a missing standalone statistical software package to enable researchers to simulate SST data under generalized scenarios. This paper presents the R statistical software package “SimSST”, available in Comprehensive R Archive Network (CRAN), to simulate stop signal task (SST) data. The package is based on the general non-independent horse race model, the copulas in probability theory, and underlying ExGaussian (ExG) or Shifted Wald (SW) distributional assumption for the involving go and stop processes enabling the researchers to simulate sixteen scenarios of the SST data. A working example for one of the scenarios is presented to evaluate the simulations’ precision on parameter estimations. Package limitations and future work directions for its subsequent extensions are discussed

Interrelationships among reproductive hormones and antral follicle count in human menstrual cycles

It is recognised that ovarian factors, including steroid and protein hormones, are critical in the feedback regulation of pituitary gonadotropins; however, their individual contributions are less defined. The aim of this study was to explore the reciprocal relationships between ovarian and pituitary hormones across the normal ovulatory menstrual cycle as women age. FSH, LH, oestradiol, progesterone, inhibin A, inhibin B and anti-mullerian hormone (AMH) were measured in serum collected every 1–3 days across one interovulatory interval (IOI) from 26 healthy women aged 18–50 years. The antral follicle count (AFC) for follicles 2–5 mm, >6 mm and 2–10 mm were tabulated across the IOI. Independent associations between ovarian hormones/AFC vs pituitary follicle-stimulating hormone (FSH) and luteinising hormone (LH) were investigated using multivariate regression analysis. The data were sub-grouped based on the presence or absence luteal phase-dominant follicles (LPDF). Serum oestradiol and AMH were inversely correlated with FSH in both follicular and luteal phases. Inhibin B correlated inversely with FSH and LH in the late follicular phase and directly in the luteal phase. AFC, inhibin A and progesterone were not key predictors of either FSH or LH. The strong association between AMH and FSH with age implies that AMH, as well as oestradiol and inhibin B are important regulators of FSH. The change in feedback response of inhibin B with both FSH and LH across the cycle suggests two phases of the negative feedback