Search

The estimation problem for interval-censored data has been investigated by several authors. The application of conventional methods to interval censored data that has been considered by Lindsey and Ryan (1998) showed misleading results when they tended to underestimate the standard errors of the estimated parameters. In this thesis, we apply the likelihoods in the exponential model in order to estimate the parameters and function of survival when multiple imputation and left imputation methods are used for partly interval censored data. We pay particular attention to the performance of our model. In particular, we present the Likelihood Ratio Test (LRT) with their p-value. We undertake a simulation study with different percentage of exact observations (0%, 25%, 50%, and 75%) in order to quantify and analyze the relative performances of maximum likelihood estimation for exponential model. The numerical evidence suggests that the estimates from multiple imputation are more accurate. We apply the proposed method to a real breast cancer data.

Myasthenia gravis (MG) is an acquired, rare autoimmune disease that occurs due to autoantibodies blocking neuromuscular transmission. Its pathophysiology involves production of antibodies against the nicotinic acetylcholine receptors. Patients with negative anti-acetylcholine receptors (AChR) antibodies results are recognized as seronegative myasthenia gravis. In this review we tried to compare surgical and medical management of MG with each other to find out which is more effective. Different clinical trials and retrospective cohorts comparing these two parameters statistically were searched and studied. Remission rates in both medical and surgical management were compared. We found out that rates of remission were better in post thymectomy patients than patients on various medical treatment options including corticosteroids, immunosuppressants, intravenous immunoglobulins and acetylcholinesterase inhibitors alone. Hence thymectomy is studied to be the superior treatment option than other conservative medical management options alone.

Introduction: Selinexor, an exportin 1(XPO1) inhibitor has demonstrated anti-leukemia activity as a single agent, as well as in combination regimens for the treatment of acute myeloid leukemia (AML). This systematic review aims to explore the efficacy and safety of selinexor based regimens for the treatment of AML. Methods: A systematic literature search was conducted using PubMed, Embase, Cochrane library, ClinicalTrials.gov, ASCO, and ASH meeting websites. The initial databases yielded 698 articles (last updated search until July 20, 2020). After excluding review articles, duplicates, and non-relevant articles, we included data from eight clinical trials (Table 1 and Table 2). Results: Among a total of 286 patients, 259 were evaluated. Selinexor was given as monotherapy to 81 patients and as combination regimens to 178 patients. The total newly diagnosed (ND) AML patients were 48 and relapsed refractory (RR) AML patients were 238. Garzon et al. did a phase I dose-escalation trial (n=81) with selinexor as a single agent in ND-AML and RR-AML patients with a median of three prior lines of therapy. The overall response rate (ORR) was 14%. The median overall survival (OS) was 2.7 months and median progression-free survival (PFS) was 1.7 months. 15% of the patients discontinued the treatment temporarily due to adverse events (AEs). Bhatnagar et al. (n=25) studied selinexor with decitabine, in phase I clinical trial, in ND and RR-AML patients. The ORR was 40% with higher ORR in ND-AML (80%) compared to RR-AML (30%). At a median follow-up of 21.8 months, the median PFS was 5.9 months (95% CI: 2.4-8.7) and median OS was also 5.9 months (95% CI: 3.9-10.4). The PFS was longer for patients who responded to therapy (11.8 months) as compared to those who did not respond to therapy (4.4 months). In phase I/II trial by Daver et al. (n=14) with selinexor and sorafenib in RR-AML patients, the composite complete remission including CR, CR with incomplete blood count recovery (Cri), and CR with incomplete platelet recovery (CRp) was 35.7%. The event-free survival was 1.8 months (0.4-5.0) in FLT3-ITD Inhibitor failure cohort vs 2.1 months (0.7-2.1) in FLT3-ITD inhibitor naive cohort. A single-arm phase I study with selinexor, cytarabine, and daunorubicin was performed testing ND-AML patients by Sweet et al., (n=19). It showed an ORR of 53% and a median OS of 10.3 months (95% CI: 3.74-NR). The early death rate (death ≤ 60 days) was 4.8%. The phase I dose-escalation trial by Weng et al. (n=28) in ND and RR-AML patients with selinexor+cytarabine+mitoxantrone had a better response rate. The ORR was 64% with a higher ORR in ND-AML (87%) compared to RR-AML (38%). The phase I trial by Alexander et al. (n=18) with selinexor+ cytarabine+ fludarabine on RR-AML patients achieved an ORR of 60 % and CR of 33.3%. Fielder et al. (n=38) did a phase II clinical trial on RR-AML patients with selinexor+ cytarabine + idarubicin with 40 mg/m2 selinexor in one cohort (C1) and flat 60 mg dose of selinexor in the second cohort (C2). In C1 37% of patients and C2 40% of patients had previous stem cell transplantation (SCT). The ORR was almost the same in both cohorts, with 55 % in C1 vs 54.5% in C2. The phase I/II trial on RR-AML patients by Abboud et al. (n=40) with selinexor+ cladribine+cytarabine+filgrastim had a total of CR and CRi in 45% of patients with a median overall survival of 7.8 months (95%CI: 5.7-14.1) and median event-free survival of 6.1 months (95% CI: 4.5 - 7.8 months). The main hematological adverse events were pancytopenia and non-hematological adverse events were hypophosphatemia, hyponatremia, gastrointestinal disturbances, and fatigue (Table 2). Conclusion: Selinexor in combination regimens showed superior response rates compared to selinexor alone for the treatment of AML patients. The response rates were better in selinexor based three and four-drug regimens. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

This study introduces a new bowling scoring system and tests its consistency with the current scoring system with respect to preserving player placements. A comprehensive simulation study for different scenarios; two-player, three-player, and four-player games performed. The simulations empirically quantify the likelihood of experiencing concordant results between the two (current and new) systems. The simulation study revealed that the percentage of times that the current and new scoring systems yield the same placements at least 85% when two players compete, at least 66% of the time when three players compete, and at least 43% of the time when four players compete regardless of the ability levels of the players. A comparison study using real bowling data-sets have been done and showed the consistence for the new scoring system with the current one. However, the new scoring system is easy to calculate, understand and to be implemented

Fundus image analysis has emerged as a very useful tool to analyze the structure of retina for detection of different eye-related abnormalities. The detection of these abnormalities requires the segmentation of basic retinal structures including blood vessels and optic disk. The optic disk segmentation becomes a challenging task when the optic disk boundary is degraded due to some deviations including optic disk edema and papilledema. This paper focuses on the segmentation of optic disk in presence of disk blurring. The method proposed makes use of gradient extracted from line profiles that pass through optic disk margin. Initially the optic disk is enhanced using morphological operations and location of optic disk region is detected automatically using vessel density property. Finally, line profiles are extracted at different angles and their gradient is evaluated for the estimation of optic disk boundary. The proposed method has been applied on 28 images taken from Armed Forces Institute of Ophthalmology.