Von Neumann-Morgenstern farsightedly stable sets in two-sided matching

We adopt the notion of von Neumann-Morgenstern (vNM) farsightedly stable sets to determine which matchings are possibly stable when agents are farsighted in one-to-one matching problems. We provide the characterization of vNM farsightedly stable sets: a set of matchings is a vNM farsightedly stable set if and only if it is a singleton subset of the core. Thus, contrary to the vNM (myopically) stable sets [Ehlers, J. of Econ. Theory 134 (2007), 537-547], vNM farsightedly stable sets cannot include matchings that are not in the core. Moreover, we show that our main result is robust to many-to-one matching problems with substitutable preferences: a set of matchings is a vNM farsightedly stable set if and only if it is a singleton set and its element is in the strong core.Matching problem, von Neumann-Morgenstern stable sets, farsighted stability

A comparison of experimental and numerical behaviour characteristics of a ship entering a lock using benchmark test data

This paper discusses several papers that were presented at the 3rd International Conference on Ship Manoeuvring in Shallow and Confined Water, which had a non-exclusive focus on Ship Behaviour in Locks. For this conference, experimental model test data obtained at Flanders Hydraulics Research had been made public and researchers were encouraged to compare numerical with experimental results [1]. Data of benchmark tests carried out both with self-propelled and captive models were used by researchers for comparison with various numerical tools. The objective of this paper is to give a selected overview of how accurately numerical tools are presently able to predict the hydrodynamic forces that occur on ships approaching locks. Based on this, the paper concludes that experiments and numerical tools complement each other

Practical guidance for applying the ADNEX model from the IOTA group to discriminate between different subtypes of adnexal tumors.

All gynecologists are faced with ovarian tumors on a regular basis, and the accurate preoperative diagnosis of these masses is important because appropriate management depends on the type of tumor. Recently, the International Ovarian Tumor Analysis (IOTA) consortium published the Assessment of Different NEoplasias in the adneXa (ADNEX) model, the first risk model that differentiates between benign and four types of malignant ovarian tumors: borderline, stage I cancer, stage II-IV cancer, and secondary metastatic cancer. This approach is novel compared to existing tools that only differentiate between benign and malignant tumors, and therefore questions may arise on how ADNEX can be used in clinical practice. In the present paper, we first provide an in-depth discussion about the predictors used in ADNEX and the ability for risk prediction with different tumor histologies. Furthermore, we formulate suggestions about the selection and interpretation of risk cut-offs for patient stratification and choice of appropriate clinical management. This is illustrated with a few example patients. We cannot propose a generally applicable algorithm with fixed cut-offs, because (as with any risk model) this depends on the specific clinical setting in which the model will be used. Nevertheless, this paper provides a guidance on how the ADNEX model may be adopted into clinical practice

Practical application and statistical analysis of titrimetric monitoring of water and sludge samples

Titrimetry offers the possibility of simultaneous measurement at low cost of several (buffering) components. A first step in the study towards practical application of the titrimetric technique was the titrimetric analysis by up- or down-titration of standard solutions, standard mixtures, solids digester samples and water samples coming from autotrophic nitrogen-removal reactors. The resulting raw data were further processed with an Excel-based program. This program first converts the raw data into a buffer curve upon which a linear buffer capacity model is fitted to the experimental data by estimating the (buffer) concentrations and corresponding pKa values. As such the type of component and the concentration can be determined. As a second step the resulting calculated concentrations were analysed statistically to assess the accuracy and precision of the titrimetric technique. For this purpose, the data were paired, i.e. the difference between the concentration obtained with titrimetry and the concentration obtained with another technique such as colorimetry or gas chromatography was calculated. First the normality of the paired data was assessed. Then, a paired t-test (normal data) or a paired Wilcoxon test (normal data) was used to statistically compare the results obtained with the titrimetric technique to either the stock solution concentration or measurements with another method (colorimetry or gas chromatography). The statistical tests showed that, depending on the titrant concentration, concentrations from 50 mg/. to 3 000 mg/. could adequately be measured with the titrimetric technique

Neurodevelopmental outcomes in children with isolated congenital diaphragmatic hernia: A systematic review and meta-analysis

Background: Congenital diaphragmatic hernia (CDH) reportedly has neurologic consequences in childhood however little is known about the impact in isolated CDH. / Aims: Herein we aimed to describe the risk of neurodevelopmental complications in children born with isolated CDH. / Materials & Methods: We systematically reviewed literature for reports on the neurological outcome of infants born with isolated CDH. The primary outcome was neurodevelopmental delay. Secondary outcomes included, motor skills, intelligence, vision, hearing, language and behavior abnormalities. / Results: Thirteen out of 87 (15%) studies reported on isolated CDH, including 2624 out of 24,146 children. Neurodevelopmental delay was investigated in four studies and found to be present in 16% (3‐34%) of children. This was mainly attributed to motor problems in 13% (2‐30%), whereas cognitive dysfunction only in 5% (0‐20%) and hearing in 3% (1‐7%). One study assessed the effect of fetal surgery. When both isolated and non‐isolated children were included, these numbers were higher. / Discussion: This systematic review demonstrates that only a minority of studies focused on isolated CDH, with neurodevelopmental delay present in 16% of children born with CDH. / Conclusion: To accurately counsel patients, more research should focus on isolated CDH cases and examine children that underwent fetal surgery

Dynamics of the intratumoral immune response during progression of high-grade serous ovarian cancer

PURPOSE: Tumor-infiltrating lymphocytes (TILs) have an established impact on the prognosis of high-grade serous ovarian carcinoma (HGSOC), however, their role in recurrent ovarian cancer is largely unknown. We therefore systematically investigated TIL densities and MHC class I and II (MHC1, 2) expression in the progression of HGSOC. EXPERIMENTAL DESIGN: CD3+, CD4+, CD8+ TILs and MHC1, 2 expression were evaluated by immunohistochemistry on tissue microarrays in 113 paired primary and recurrent HGSOC. TILs were quantified by image analysis. All patients had been included to the EU-funded OCTIPS FP7 project. RESULTS: CD3+, CD4+, CD8+ TILs and MHC1 and MHC2 expression showed significant correlations between primary and recurrent tumor levels (Spearman rho 0.427, 0.533, 0.361, 0.456, 0.526 respectively; P<.0001 each). Paired testing revealed higher CD4+ densities and MHC1 expression in recurrent tumors (Wilcoxon P=.034 and P=.018). There was also a shift towards higher CD3+ TILs levels in recurrent carcinomas when analyzing platinum-sensitive tumors only (Wilcoxon P=.026) and in pairs with recurrent tumor tissue from first relapse only (Wilcoxon P=.031). High MHC2 expression was the only parameter to be significantly linked to prolonged progression-free survival after first relapse (PFS2, log-rank P=.012). CONCLUSIONS: This is the first study that analyzed the development of TILs density and MHC expression in paired primary and recurrent HGSOC. The level of the antitumoral immune response in recurrent tumors was clearly dependent on the one in the primary tumor. Our data contribute to the understanding of temporal heterogeneity of HGSOC immune microenvironment and have implications for selection of samples for biomarker testing in the setting of immune-targeting therapeutics

Treatment algorithm in patients with ovarian cancer

Most ovarian cancer patients are diagnosed only at advanced stages when survival outcomes are worse, and when therapeutic decisions might prove challenging. The fundamental treatment for women with ovarian cancer includes debulking surgery whenever possible and appropriate systemic therapy (chemotherapy, targeted and antiangiogenic agents). In the last few years, knowledge about histological and molecular characteristics of ovarian cancer subtypes and stages has increased considerably. This has enabled the development and improvement of several options for the diagnosis and treatment of ovarian cancer in a patient-tailored approach. Accordingly, therapeutic decisions are guided by the characteristics of the patient and the tumour, especially the molecular features of the cancer subtype and disease stage. Particularly relevant are the advances in early genetic testing of germline and somatic mutations involved in DNA repair, and the clinical development of targeted agents. In order to implement the best individual medical strategies, in this article, we present an algorithm of treatment options, including recently developed targeted agents, for primary and recurrent ovarian cancer patients in Belgium

EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer

Chemotherapy; Quality of life; SymptomsQuimioterapia; Calidad de vida; SíntomasQuimioteràpia; Qualitat de vida; SímptomesBackground In a phase III, randomised, active-controlled study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9; R2810-ONC-1676; NCT03257267) and cemiplimab significantly improved survival versus investigator's choice of chemotherapy among patients with recurrent cervical cancer who had progressed on platinum-based therapy. Here we report patient-reported outcomes in this pivotal study. Methods Patients were randomised 1:1 to open-label cemiplimab (350 mg intravenously every 3 weeks) or investigator's choice of chemotherapy in 6-week cycles. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 during cycles 1–16. Least-squares mean changes from baseline in global health status (GHS)/quality of life (QoL) and physical functioning (PF) were secondary end-points in the statistical hierarchy. Results Of 608 patients (304/arm), 77.8% patients had squamous cell carcinoma and 22.2% patients had adenocarcinoma. Questionnaire completion rates were ∼90% throughout. In the squamous cell carcinoma population, overall between-group differences statistically significantly favoured cemiplimab in GHS/QoL (8.49; 95% confidence interval [CI]: 3.77–13.21; P = 0.0003) and PF (8.35; 95% CI: 4.08–12.62; P < 0.0001). Treatment differences favoured cemiplimab in both histologic populations by cycle 2. Overall changes from baseline in most functioning and symptom scales favoured cemiplimab, with clinically meaningful treatment differences in role functioning, appetite loss and pain in both populations. The sensitivity analyses, responder analyses and time to definitive deterioration favoured cemiplimab in both populations. Conclusions Cemiplimab conferred favourable differences in GHS/QoL and PF compared with chemotherapy among patients with recurrent cervical cancer, with benefits in PF by cycle 2, and clinically meaningful differences favouring cemiplimab in role functioning, appetite loss, and pain.This work was supported by Regeneron Pharmaceuticals, Inc., and Sanofi

Opposite macrophage polarization in different subsets of ovarian cancer: observation from a pilot study

The role of the innate immune system in ovarian cancer is gaining importance. The relevance of tumor-associated macrophages (TAM) is insufficiently understood. In this pilot project, comprising the immunofluorescent staining of 30 biopsies taken from 24 patients with ovarian cancer, we evaluated the presence of total TAM (cluster of differentiation (CD) 68 expression), M1 (major histocompatibility complex (MHC) II expression), and M2 (anti-mannose receptor C type 1 (MRC1) expression), and the blood vessel diameter. We observed a high M1/M2 ratio in low-grade ovarian cancer compared to high-grade tumors, more total TAM and M2 in metastatic biopsies, and a further increase in total TAM and M2 at interval debulking, without beneficial effects of bevacizumab. The blood vessel diameter was indicative for M2 tumor infiltration (Spearman correlation coefficient of 0.65). These data mainly reveal an immune beneficial environment in low-grade ovarian cancer in contrast to high-grade serous ovarian cancer, where immune suppression is not altered by neoadjuvant therapy

FORWARD I: a Phase III study of mirvetuximab soravtansine versus chemotherapy in platinum-resistant ovarian cancer

Mirvetuximab soravtansine, an antibody-drug conjugate that binds with high affinity to folate receptor-alpha to provide tumor-directed delivery of the potent microtubule-disrupting agent DM4, has emerged as a promising investigational agent for the treatment of ovarian cancer, particularly in the setting of platinum-resistant disease. Here we describe the rationale and design of FORWARD I (NCT02631876), the first randomized, multicenter Phase III study to compare the safety and efficacy of mirvetuximab soravtansine versus investigator's choice of chemotherapy in women with folate receptor-alpha-positive, platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients will be randomized in a 2:1 ratio. The primary end point is progression-free survival, and key secondary objectives include comparison of overall response rates, overall survival and duration of response