Nonprofit Law: Ten Issues in Search of Resolution

The laws and regulations governing nonprofit organisations in different countries can usefully be assessed in terms of how they address ten basic issues, including everything from eligibility to key trends affecting the sector. The purpose of this paper is to examine these issues more closely, to identify what they are and to understand why they are important. The focus is placed upon the questions that must be addressed in laws related to nonprofit organisations

Experimental investigation of a mach 5 isentropic spike inlet at and below design speed

Zero angle of attack performance of isentropic spike inlet designed for maximum external compression at hypersonic spee

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

A variational principle for stationary, axisymmetric solutions of Einstein's equations

Stationary, axisymmetric, vacuum, solutions of Einstein's equations are obtained as critical points of the total mass among all axisymmetric and $(t,\phi)$ symmetric initial data with fixed angular momentum. In this variational principle the mass is written as a positive definite integral over a spacelike hypersurface. It is also proved that if absolute minimum exists then it is equal to the absolute minimum of the mass among all maximal, axisymmetric, vacuum, initial data with fixed angular momentum. Arguments are given to support the conjecture that this minimum exists and is the extreme Kerr initial data.Comment: 21 page

Area-charge inequality for black holes

The inequality between area and charge $A\geq 4\pi Q^2$ for dynamical black holes is proved. No symmetry assumption is made and charged matter fields are included. Extensions of this inequality are also proved for regions in the spacetime which are not necessarily black hole boundaries.Comment: 21 pages, 2 figure

NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771. Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint. Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SD \u3e 6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SD \u3e 6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Gr ≥ 3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm. Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss

Pre-main sequence stars with disks in the Eagle Nebula observed in scattered light

NGC6611 and its parental cloud, the Eagle Nebula (M16), are well-studied star-forming regions, thanks to their large content of both OB stars and stars with disks and the observed ongoing star formation. We identified 834 disk-bearing stars associated with the cloud, after detecting their excesses in NIR bands from J band to 8.0 micron. In this paper, we study in detail the nature of a subsample of disk-bearing stars that show peculiar characteristics. They appear older than the other members in the V vs. V-I diagram, and/or they have one or more IRAC colors at pure photospheric values, despite showing NIR excesses, when optical and infrared colors are compared. We confirm the membership of these stars to M16 by a spectroscopic analysis. The physical properties of these stars with disks are studied by comparing their spectral energy distributions (SEDs) with the SEDs predicted by models of T-Tauri stars with disks and envelopes. We show that the age of these stars estimated from the V vs. V-I diagram is unreliable since their V-I colors are altered by the light scattered by the disk into the line of sight. Only in a few cases their SEDs are compatible with models with excesses in V band caused by optical veiling. Candidate members with disks and photospheric IRAC colors are selected by the used NIR disk diagnostic, which is sensitive to moderate excesses, such as those produced by disks with low masses. In 1/3 of these cases, scattering of stellar flux by the disks can also be invoked. The photospheric light scattered by the disk grains into the line of sight can affect the derivation of physical parameters of ClassII stars from photometric optical and NIR data. Besides, the disks diagnostic we defined are useful for selecting stars with disks, even those with moderate excesses or whose optical colors are altered by veiling or photospheric scattered light.Comment: Accepted for publication in A&