Survival of veterans treated with enzalutamide and abiraterone for metastatic castrate resistant prostate cancer based on comorbid diseases

BACKGROUND: Comorbid diseases influence patient outcomes, yet little is known about how comorbidities interact with treatments for metastatic castrate-resistant prostate cancer (mCRPC). No head-to-head trials have compared the efficacy of abiraterone and enzalutamide - oral androgen-receptor targeted agents (ARTAs) for mCRPC. In patients with comorbid disease, outcomes with ARTAs may differ due to disparate mechanisms of action, adverse events, and drug interactions. METHODS: Retrospective observational study of US veterans initiating treatment for mCRPC with abiraterone or enzalutamide between September 2014 and June 2017. Treatment duration and overall survival (OS) was compared based on age and comorbid diseases. The association between ARTA and OS was assessed using Cox proportional hazards and propensity-score matched modeling while adjusting for potential confounders. Sensitivity analyses were performed based on patient age, comorbidities, and subsequent treatments for mCRPC. RESULTS: Of 5822 veterans treated for mCRPC, 43.0% initially received enzalutamide and 57.0% abiraterone. Veterans initially treated with enzalutamide versus abiraterone were older (mean 75.8 vs. 75.0 years) with higher mean Charlson comorbidity index (4.4 vs. 4.1), and higher rates of cardiovascular disease or diabetes (74.2% vs. 70.6%). In the entire population, veterans initially treated with enzalutamide had longer median OS compared to those initially treated with abiraterone (24.2 vs. 22.1 months, p = 0.001). In veterans with cardiovascular disease or diabetes, median treatment duration with enzalutamide was longer (11.4 vs. 8.6 months, p \u3c 0.001) with longer median OS compared to abiraterone (23.2 vs. 20.5 months, p \u3c 0.001). In a propensity score matched cohort, enzalutamide was associated with decreased mortality compared to abiraterone (HR 0.90, 95% CI 0.84-0.96). CONCLUSIONS: Veterans with cardiovascular disease or diabetes had longer treatment duration and OS with enzalutamide compared to abiraterone. Further study of ARTA selection may benefit men with metastatic castrate resistant prostate cancer and likely hormone sensitive prostate cancer, especially among patients with comorbid diseases

Magnetic properties in ultrathin 3d transition-metal binary alloys. II. Experimental verification of quantitative theories of damping and spin pumping

A systematic experimental study of Gilbert damping is performed via ferromagnetic resonance for the disordered crystalline binary 3d transition-metal alloys Ni-Co, Ni-Fe, and Co-Fe over the full range of alloy compositions. After accounting for inhomogeneous linewidth broadening, the damping shows clear evidence of both interfacial damping enhancement (by spin pumping) and radiative damping. We quantify these two extrinsic contributions and thereby determine the intrinsic damping. The comparison of the intrinsic damping to multiple theoretical calculations yields good qualitative and quantitative agreement in most cases. Furthermore, the values of the damping obtained in this study are in good agreement with a wide range of published experimental and theoretical values. Additionally, we find a compositional dependence of the spin mixing conductance

Magnetic properties of ultrathin3dtransition-metal binary alloys. I. Spin and orbital moments, anisotropy, and confirmation of Slater-Pauling behavior

The structure and static magnetic properties-saturation magnetization, perpendicular anisotropy, spectroscopic g factor, and orbital magnetization-of thin-film 3d transition metal alloys are determined over the full range of alloy compositions via x-ray diffraction, magnetometry, and ferromagnetic resonance measurements. We determine the interfacial perpendicular magnetic anisotropy by use of samples sets with varying thickness for specific alloy concentrations. The results agreewith prior published data and theoretical predictions. They provide a comprehensive compilation of the magnetic properties of thin-film Ni-x Co1-x, Ni-x Fe1-x, and Co-x Fe1-x alloys that goes well beyond the often-cited Slater-Pauling dependence of magnetic moment on alloy concentration

Anisotropic Polar Magneto-Optic Kerr Effect of Ultrathin Fe/GaAs (001) Layers du to Interfacial Spin-Orbit Interaction

We report the observation of the anisotropic polar magneto-optical Kerr effect in thin layers of epitaxial Fe/GaAs(001) at room temperature. A clear twofold symmetry of the Kerr rotation angle depending on the orientation of the linear polarization of the probing laser beam with respect to the crystallographic directions of the sample is detected for ultrathin magnetic films saturated out of the film plane. The amplitude of the anisotropy decreases with increasing Fe film thickness, suggesting that the interfacial region is the origin of the anisotropy. The twofold symmetry is fully reproduced by model calculations based on an interference of interfacial Bychkov-Rashba and Dresselhaus spin-orbit coupling

Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial

Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient’s liver metastases as surgically removable. Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11⋅9 per cent) and control (25, 11⋅0 per cent) arms (P = 0⋅775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33⋅7 per cent) versus 54 of 472 (11⋅4 per cent) respectively (P = 0⋅001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38⋅1 per cent) versus 66 of 228 (28⋅9 per cent) respectively (P < 0⋅001). Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM

Changes in Employment Uncertainty and the Fertility Intention-Realization Link: An Analysis Based on the Swiss Household Panel.

How do changes in employment uncertainty matter for fertility? Empirical studies on the impact of employment uncertainty on reproductive decision-making offer a variety of conclusions, ranging from gender and socio-economic differences in the effect of employment uncertainty on fertility intentions and behaviour, to the effect of employment on changes in fertility intentions. This article analyses the association between a change in subjective employment uncertainty and fertility intentions and behaviour by distinguishing male and female partners' employment uncertainty, and examines the variation in these associations by education. Using a sample of men and women living in a couple from the Swiss Household Panel (SHP 2002-2011), we examine through multinomial analysis how changes in employment uncertainty and selected socio-demographic factors are related to individual childbearing decisions. Our results show strong gendered effects of changes in employment uncertainty on the revision of reproductive decisions among the highly educated population

University–industry collaboration: using meta-rules to overcome barriers to knowledge transfer

This is the final version of the article. Available from Springer Verlag via the DOI in this record.University–industry knowledge transfer is an important source wealth of creation for all partners; however, the practical management of this activity within universities is often hampered by procedural rigidity either through the absence of decision-making protocols to reconcile conflicting priorities or through the inconsistent implementation of existing policies. This is problematic, since it can impede operational effectiveness, prevent inter-organisational knowledge-creation and hamper organisational learning. This paper addresses this issue by adopting a cross-discipline approach and presenting meta-rules as a solution to aid organisational decision making. It is proposed that meta-rules can help resolve tensions arising from conflicting priorities between academics, knowledge transfer offices and industry and help facilitate strategic alignment of processes and policies within and between organisations. This research contributes to the growing debate on the strategic challenges of managing knowledge transfer and presents meta-rules as a practical solution to facilitate strategic alignment of internal and external stakeholder tensions. Meta-rules has previously only been applied in a computer intelligence context however, this research proves the efficacy of meta rules in a university–industry knowledge transfer context. This research also has practical implications for knowledge transfer office managers who can use meta-rules to help overcome resource limitations, conflicting priorities and goals of diverse internal and external stakeholders