Highly symmetric hypertopes

We study incidence geometries that are thin and residually connected. These geometries generalise abstract polytopes. In this generalised setting, guided by the ideas from the polytopes theory, we introduce the concept of chirality, a property of orderly asymmetry occurring frequently in nature as a natural phenomenon. The main result in this paper is that automorphism groups of regular and chiral thin residually connected geometries need to be C-groups in the regular case and C+-groups in the chiral case

Prostate Cancer: Quo Vadis?

Utility measures are urgently needed for clinical application of new, more sensitive diagnostics to reduce the risk of excessive intervention. © 2019 European Association of Urolog

Future personal health records as a foundation for computational health

Personal Health Records (PHRs) and other emerging health information technologies create the potential for the capture and storage of a much greater quantity and quality of health data in the future. PHRs in particular provide a likely more privacy supporting form of electronic health data storage. This paper discusses how new health information technologies can support richer future health record data and how these records can provide a foundation for current and future applications of computational science approaches, supporting what might be called Computational Health

Enzalutamide in Combination with Abiraterone Acetate in Bone Metastatic Castration-resistant Prostate Cancer Patients

BACKGROUND: It is hypothesised that cotargeting the androgen receptor (AR) and paracrine androgen biosynthesis with enzalutamide and abiraterone acetate in metastatic castration-resistant prostate cancer (mCRPC) will dissipate adaptive feedback loops observed with either agent alone. OBJECTIVE: To assess the safety, efficacy, androgen signalling/metabolome, and drug-drug interactions (DDIs) of enzalutamide with abiraterone acetate in progressive bone mCRPC (bmCRPC). DESIGN, SETTING, AND PARTICIPANTS: This open-label, single-centre interventional study was conducted in bmCRPC patients. INTERVENTION: Enzalutamide 160mg and abiraterone acetate 1000mg once daily; prednisone 5mg twice daily. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adverse events (AEs), prostate-specific antigen (PSA) response, progression-free survival (PFS), tumour biomarker/metabolite expression, and Cmin plasma concentrations were evaluated. RESULTS AND LIMITATIONS: Sixty patients were enrolled. Common AEs independent of grade/causality included fatigue (72%), hyperglycaemia (67%), alkaline phosphatase (ALP) elevation (53%), and hot flush (43%). Grade 3 AEs included hypertension (17%), alanine aminotransferase elevation (12%), ALP elevation (5%), and arthralgia (5%). No treatment-related grade 4 AEs or deaths were reported. Median treatment-discontinuation time was 312d (95% confidence interval [CI] 196.0-483.0). Maximal PSA decline ≥50% and ≥90% occurred in 46 (77%) and 29 (48%) patients, respectively. Median PFS was 251d (95% CI 147-337). At week 9, median tumour microenvironment androgens, precursors, and nuclear AR expression decreased (p<0.001). The baseline tumour AR C/N terminal ratio of ≥80% was associated with treatment benefit. At enzalutamide steady state, abiraterone acetate Cmin was ∼23% lower (range 14.05-200.5ng/ml) than when given alone. CONCLUSIONS: Enzalutamide combined with abiraterone acetate has a manageable safety profile, without a meaningful DDI. Both agents are pharmacodynamically active with no feedback. Efficacy findings do not support significant benefit of combined treatment for unselected bmCRPC. PATIENT SUMMARY: This is the first study combining enzalutamide plus abiraterone in bone metastatic castration-resistant prostate cancer. Results show that this combination is safe. Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved