Multicultural futures: The negotiation of identity amongst second generation Iranians of Muslim and Bahái background In Sydney, London and Vancouver

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Combining Exploration and Exploitation in Active Learning

This thesis investigates the active learning in the presence of model bias. State of the art approaches advocate combining exploration and exploitation in active learning. However, they suffer from premature exploitation or unnecessary exploration in the later stages of learning. We propose to combine exploration and exploitation in active learning by discarding instances outside a sampling window that is centered around the estimated decision boundary and uniformly draw sample from this window. Initially the window spans the entire feature space and is gradually constricted, where the rate of constriction models the exploration-exploitation tradeoff. The desired effect of this approach (CExp) is that we get an increasing sampling density in informative regions as active learning progresses, resulting in a continuous and natural transition from exploration to exploitation, limiting both premature exploitation and unnecessary exploration. We show that our approach outperforms state of the art on real world multiclass datasets. We also extend our approach to spatial mapping problems where the standard active learning assumption of uniform costs is violated. We show that we can take advantage of \emph{spatial continuity} in the data by geographically partitioning the instances in the sampling window and choosing a single partition (region) for sampling, as opposed to taking a random sample from the entire window, resulting in a novel spatial active learning algorithm that combines exploration and exploitation. We demonstrate that our approach (CExp-Spatial) can generate cost-effective sampling trajectories over baseline sampling methods. Finally, we present the real world problem of mapping benthic habitats where bathymetry derived features are typically not strong enough to discriminate the fine details between classes identified from high-resolution imagery, increasing the possiblity of model bias in active learning. We demonstrate, under such conditions, that CExp outperforms state of the art and that CExp-Spatial can generate more cost-effective sampling trajectories for an Autonomous Underwater Vehicle in contrast to baseline sampling strategies

LBA36Association of PD-L1 expression and gene expression profiling with clinical response to pembrolizumab in patients with advanced recurrent ovarian cancer: Results from the phase II KEYNOTE-100 study

ispartof: Ann Oncol vol:29 Suppl 8 pages:viii728- ispartof: location:England status: publishe

Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study

BACKGROUND: Advanced recurrent ovarian cancer (ROC) is the leading cause of gynecologic cancer-related death in developed countries and new treatments are needed. Previous studies of immune checkpoint blockade showed low objective response rates (ORR) in ROC with no identified predictive biomarker. PATIENTS AND METHODS: This phase II study of pembrolizumab (NCT02674061) examined two patient cohorts with ROC: cohort A received one to three prior lines of treatment with a platinum-free interval (PFI) or treatment-free interval (TFI) between 3 and 12months and cohort B received four to six prior lines with a PFI/TFI of ≥3months. Pembrolizumab 200mg was administered intravenously every 3weeks until cancer progression, toxicity, or completion of 2years. Primary end points were ORR by Response Evaluation Criteria in Solid Tumors version 1.1 per blinded independent central review by cohort and by PD-L1 expression measured as combined positive score (CPS). Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Cohort A enrolled 285 patients; the first 100 served as the training set for PD-L1 biomarker analysis. Cohort B enrolled 91 patients. ORR was 7.4% for cohort A and 9.9% for cohort B. Median DOR was 8.2months for cohort A and not reached for cohort B. DCR was 37.2% and 37.4%, respectively, in cohorts A and B. Based on the training set analysis, CPS 1 and 10 were selected for evaluation in the confirmation set. In the confirmation set, ORR was 4.1% for CPS<1, 5.7% CPS ≥1, and 10.0% for CPS ≥10. PFS was 2.1months for both cohorts. Median OS was not reached for cohort A and was 17.6months for cohort B. Toxicities were consistent with other single-agent pembrolizumab trials. CONCLUSIONS: Single-agent pembrolizumab showed modest activity in patients with ROC. Higher PD-L1 expression was correlated with higher response. CLINICAL TRIAL NUMBER: Clinicaltrials.gov, NCT02674061. ispartof: Ann Oncol vol:30 issue:7 pages:1080-1087 ispartof: location:England status: publishe

Gastric cancer during pregnancy: A report on 13 cases and review of the literature with focus on chemotherapy during pregnancy

Introduction: Gastric cancer during pregnancy is extremely rare and data on optimal treatment and possible chemotherapeutic regimens are scarce. The aim of this study is to describe the obstetric and maternal outcome of women with gastric cancer during pregnancy and review the literature on antenatal chemotherapy for gastric cancer. Material and methods: Treatment and outcome of patients registered in the International Network on Cancer, Infertility and Pregnancy database with gastric cancer diagnosed during pregnancy were analyzed. Results: In total, 13 women with gastric cancer during pregnancy were registered between 2002 and 2018. Median gestational age at diagnosis was 22 weeks (range 6-30 weeks). Twelve women were diagnosed with advanced disease and died within 2 years after pregnancy, most within 6 months. In total, 8 out of 10 live births ended in a preterm delivery because of preeclampsia, maternal deterioration, or therapy planning. Two out of 6 women who initiated chemotherapy during pregnancy delivered at term. Two neonates prenatally exposed to chemotherapy were growth restricted and 1 of them developed a systemic infection with brain abscess after preterm delivery for preeclampsia 2 weeks after chemotherapy. No malformations were reported. Conclusions: The prognosis of gastric cancer during pregnancy is poor, mainly due to advanced disease at diagnosis, emphasizing the need for early diagnosis. Antenatal chemotherapy can be considered to reach fetal maturity, taking possible complications such as growth restriction, preterm delivery, and hematopoietic suppression at birth into account

Intraperitoneale chemotherapie bij het ovariumcarcinoom: levensverlengend bij geselecteerde patiëntengroepen.,[Intraperitoneal chemotherapy in ovarian carcinoma. Life prolonging in selected patients]

Contains fulltext : 80102.pdf (publisher's version ) (Closed access

Ovarian cancer stem cells more questions than answers

Contains fulltext : 175082.pdf (Publisher’s version ) (Open Access)Epithelial ovarian cancer is a highly lethal disease, which is usually diagnosed at a late stage with extensive metastases in the abdominal cavity. Ovarian cancer either develops from the ovarian surface epithelium (OSE) or from serous intra-epithelial carcinoma (STIC). Primary therapy consists of debulking surgery and platinum based chemotherapy. The success of debulking surgery depends on surgical skills but also on the gene signature of the tumour. Debulking surgery combined with first line platinum based chemotherapy, frequently leads to complete remission. However, most ovarian cancers relapse. Once the disease has relapsed, the interval between subsequent therapies decreases steadily due to rapid progression and therapy resistance. Research on therapy resistance of ovarian cancer is frequently devoted to genetic alterations in cancer cells, leading to drug inactivation, enhanced DNA repair mechanisms and intracellular pathway derangements. However the knowledge of ovarian cancer stem cells (OCSC) and the role they play in the development of cancer and therapy resistance is sparse. In this review current knowledge on the characteristics of OCSCs and the micro environmental mechanisms leading to the development or activation of OCSCs resulting in ovarian cancer is reviewed. Moreover the role of OCSC in both surgical and systemic therapy resistance and the relation with epithelial mesenchymal transformation (EMT) is discussed, as are micro-environmental signals leading to OCSC or EMT activation