Courts, Constituencies, and the Enforcement of Fiduciary Duties in the Nonprofit Sector

Directors of nonprofit organizations owe fiduciary duties to their organizations, but the content of these duties—and how and when courts should enforce these duties—has long been debated among scholars and courts. This debate emerges in several areas, including the level of deference to be shown by courts to nonprofit directors (the business judgment rule), who should be allowed to sue to enforce duties (standing), and the type of relief available to prevailing plaintiffs (remedies). Existing literature explores these legal rules in isolation and in abstraction, generally failing to consider how the rules interact with each other and ignoring the empirical reality of the nonprofit sector. Because for-profit and nonprofit corporations evolved from a common ancestor, courts generally apply corporation law principles developed in the context of for-profit corporations to nonprofit corporations as well. But for-profit and nonprofit corporations often differ in key ways, including sources of income, constituencies, and other institutional characteristics. These differences make rote application of corporate law principles to nonprofit corporations a conceptually questionable endeavor. Rather than setting nonprofit rules through strained analogies to for-profit concepts of ownership and profit-maximization, we propose employing an analysis of institutional features that can operate in a whole range of governance contexts, including the nonprofit sector. This approach considers opportunities for voice and exit, impact range, homogeneity, and comparative competence between boards and courts, and it does so among different types of nonprofit actors, like directors, members, employees, donors, customers, and beneficiaries. Using this institutional analysis with for-profit corporation law as the baseline, we compare emerging legal rules in the nonprofit sector against existing empirical literature. We find that, with one exception, institutional characteristics vis-à-vis nonprofit actors are reasonably comparable to their for-profit counterparts, and we therefore place the applicable legal regime with respect to those actors on a more conceptually sound footing. However, beneficiaries of a nonprofit organization tend to lack opportunities for exit or voice, face risk of considerable deprivation, and often differ considerably in relevant aspects from the individuals who manage the organization. We argue that the law should take into account the limited power of beneficiaries in nonprofit governance structures, and we analyze options for reform

Courts, Constituencies, and the Enforcement of Fiduciary Duties in the Nonprofit Sector

Directors of nonprofit organizations owe fiduciary duties to their organizations, but the content of these duties—and how and when courts should enforce these duties—has long been debated among scholars and courts. This debate emerges in several areas, including the level of deference to be shown by courts to nonprofit directors (the business judgment rule), who should be allowed to sue to enforce duties (standing), and the type of relief available to prevailing plaintiffs (remedies). Existing literature explores these legal rules in isolation and in abstraction, generally failing to consider how the rules interact with each other and ignoring the empirical reality of the nonprofit sector. Because for-profit and nonprofit corporations evolved from a common ancestor, courts generally apply corporation law principles developed in the context of for-profit corporations to nonprofit corporations as well. But for-profit and nonprofit corporations often differ in key ways, including sources of income, constituencies, and other institutional characteristics. These differences make rote application of corporate law principles to nonprofit corporations a conceptually questionable endeavor. Rather than setting nonprofit rules through strained analogies to for-profit concepts of ownership and profit-maximization, we propose employing an analysis of institutional features that can operate in a whole range of governance contexts, including the nonprofit sector. This approach considers opportunities for voice and exit, impact range, homogeneity, and comparative competence between boards and courts, and it does so among different types of nonprofit actors, like directors, members, employees, donors, customers, and beneficiaries. Using this institutional analysis with for-profit corporation law as the baseline, we compare emerging legal rules in the nonprofit sector against existing empirical literature. We find that, with one exception, institutional characteristics vis-à-vis nonprofit actors are reasonably comparable to their for-profit counterparts, and we therefore place the applicable legal regime with respect to those actors on a more conceptually sound footing. However, beneficiaries of a nonprofit organization tend to lack opportunities for exit or voice, face risk of considerable deprivation, and often differ considerably in relevant aspects from the individuals who manage the organization. We argue that the law should take into account the limited power of beneficiaries in nonprofit governance structures, and we analyze options for reform

Courts, Constituencies, and the Enforcement of Fiduciary Duties in the Nonprofit Sector

Directors of nonprofit organizations owe fiduciary duties to their organizations, but the content of these duties—and how and when courts should enforce these duties—has long been debated among scholars and courts. This debate emerges in several areas, including the level of deference to be shown by courts to nonprofit directors (the business judgment rule), who should be allowed to sue to enforce duties (standing), and the type of relief available to prevailing plaintiffs (remedies). Existing literature explores these legal rules in isolation and in abstraction, generally failing to consider how the rules interact with each other and ignoring the empirical reality of the nonprofit sector. Because for-profit and nonprofit corporations evolved from a common ancestor, courts generally apply corporation law principles developed in the context of for-profit corporations to nonprofit corporations as well. But for-profit and nonprofit corporations often differ in key ways, including sources of income, constituencies, and other institutional characteristics. These differences make rote application of corporate law principles to nonprofit corporations a conceptually questionable endeavor. Rather than setting nonprofit rules through strained analogies to for-profit concepts of ownership and profit-maximization, we propose employing an analysis of institutional features that can operate in a whole range of governance contexts, including the nonprofit sector. This approach considers opportunities for voice and exit, impact range, homogeneity, and comparative competence between boards and courts, and it does so among different types of nonprofit actors, like directors, members, employees, donors, customers, and beneficiaries. Using this institutional analysis with for-profit corporation law as the baseline, we compare emerging legal rules in the nonprofit sector against existing empirical literature. We find that, with one exception, institutional characteristics vis-à-vis nonprofit actors are reasonably comparable to their for-profit counterparts, and we therefore place the applicable legal regime with respect to those actors on a more conceptually sound footing. However, beneficiaries of a nonprofit organization tend to lack opportunities for exit or voice, face risk of considerable deprivation, and often differ considerably in relevant aspects from the individuals who manage the organization. We argue that the law should take into account the limited power of beneficiaries in nonprofit governance structures, and we analyze options for reform

HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: phase III results from the randomized EPOCH 1 study.

BACKGROUND AND OBJECTIVES: There is a need for local anesthetics that provide consistent analgesia through 72 hours after surgery. This study evaluates the use of HTX-011 (bupivacaine and meloxicam in Biochronomerpolymer technology), an extended-release, dual-acting local anesthetic, in reducing both postoperative pain over 72 hours and postoperative opioid use when compared with bupivacaine hydrochloride (HCl) and saline placebo. Inclusion of low-dose meloxicam in HTX-011 is designed to reduce local inflammation caused by surgery, potentiating the analgesic effect of bupivacaine. Previously, significant synergy has been observed with bupivacaine and meloxicam with both given locally together. METHODS: EPOCH 1 was a randomized, double-blind, placebo-controlled and active-controlled phase III study in subjects undergoing a primary unilateral, distal, first metatarsal bunionectomy in which subjects received either a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl or saline placebo. RESULTS: A total of 412 subjects were dosed. The results for the primary and all four key secondary endpoints were statistically significant in favor of HTX-011. HTX-011 demonstrated superior, sustained pain reduction through 72 hours, significantly reduced opioid consumption and resulted in significantly more opioid-free subjects compared with saline placebo and bupivacaine HCl. Safety was similar across groups with fewer opioid-related adverse events observed in the HTX-011 group. CONCLUSIONS: HTX-011 demonstrated significant reduction in postoperative pain through 72 hours with significant reduction in opioid consumption and a significant increase in the proportion of opioid-free subjects compared with saline placebo and the most widely used local anesthetic, bupivacaine HCl. TRIAL REGISTRATION NUMBER: NCT03295721

DIVERSet JAG compounds inhibit topoisomerase II and are effective against adult and pediatric high-grade gliomas

High-grade gliomas (HGGs) are aggressive primary brain tumors with local invasive growth and poor clinical prognosis in both adult and pediatric patients. Clinical response is compounded by resistance to standard frontline antineoplastic agents, an absence of novel therapeutics, and poor in vitro models to evaluate these. We screened a range of recently identified anticancer compounds in conventional adult, pediatric, and new biopsy-derived HGG models. These in vitro lines showed a range of sensitivity to standard chemotherapeutics, with varying expression levels of the prognostic markers hypoxia-induced factor (HIF) 1α and p53. Our evaluation of lead DIVERSet library compounds identified that JAG-6A, a compound that was significantly more potent than temozolomide or etoposide, was effective against HGG models in two-dimensional and three-dimensional systems; mediated this response by the potent inhibition of topoisomerase Iiα; remained effective under normoxic and hypoxic conditions; and displayed limited toxicity to non-neoplastic astrocytes. These data suggest that JAG-6A could be an alternative topoisomerase IIα inhibitor and used for the treatment of HGG.Funding Agency Brain Tumour Research Ollie Young Foundation Portuguese Foundation for Science and Technology IF/00614/2014 FCT exploratory grant IF/00614/2014/CP12340006 FCT Research Center Grant UID/BIM/04773/2013CBMR1334info:eu-repo/semantics/publishedVersio

Planar digital nanoliter dispensing system based on thermocapillary actuation

We provide guidelines for the design and operation of a planar digital nanodispensing system based on thermocapillary actuation. Thin metallic microheaters embedded within a chemically patterned glass substrate are electronically activated to generate and control 2D surface temperature distributions which either arrest or trigger liquid flow and droplet formation on demand. This flow control is a consequence of the variation of a liquid’s surface tension with temperature, which is used to draw liquid toward cooler regions of the supporting substrate. A liquid sample consisting of several microliters is placed on a flat rectangular supply cell defined by chemical patterning. Thermocapillary switches are then activated to extract a slender fluid filament from the cell and to divide the filament into an array of droplets whose position and volume are digitally controlled. Experimental results for the power required to extract a filament and to divide it into two or more droplets as a function of geometric and operating parameters are in excellent agreement with hydrodynamic simulations. The capability to dispense ultralow volumes onto a 2D substrate extends the functionality of microfluidic devices based on thermocapillary actuation previously shown effective in routing and mixing nanoliter liquid samples on glass or silicon substrates

Dasatinib synergizes with JSI-124 to inhibit growth and migration and induce apoptosis of malignant human glioma cells

Background: Src family kinases (SFK) collectively regulate a variety of cellular functions in many cancer types, including proliferation, invasion, motility, survival, differentiation, and angiogenesis. Although Dasatinib (BMS-354825), an ATP-competitive, small molecule tyrosine kinase inhibitor, suppresses the activity of SFKs at nanomolar concentrations, IC50 values for antiproliferative effects in glioma cell lines were well above the clinically achievable range, suggesting the need to interfere with other components of receptor-induced downstream signaling in order to achieve an optimal therapeutic effect. Materials and Methods: The cytotoxic effects of combining Src and STAT3 inhibition on glioma cell lines were evaluated using assays to measure cell proliferation, apoptosis and migration. Western blotting and immunocytochemistry was used to monitor its effects on cell signaling and morphology. Results: Silencing Src and STAT3 expression each partially inhibited cell proliferation and migration. In addition, JSI - 124 significantly enhanced the efficacy of dasatinib in vitro. Combination of dasatinib and JSI - 124 achieved significant inhibition of migration in all cell lines, which correlated with the inhibition of Src and downstream mediators of adhesion (e.g. focal adhesion kinase). Cells exposed to dasatinib and JSI-124 exhibited morphological changes that were consistent with an upstream role for Src in regulating focal adhesion complexes. Conclusions: Targeting the Src and STAT pathways may contribute to the treatment of cancers that demonstrate increased levels of these signaling mediators, including malignant human glioma. Clinical studies in these tumor types are warranted

Pengembangan Modul Intervensi Untuk Meningkatkan Resiliensi Pada Individu Yang Mengalami Perubahan Fisik Menjadi Penyandang Disabilitas

Penelitian ini bertujuan untuk menindaklanjuti temuan sebelumnya dengan mengembangkan modul intervensi secara terperinci, yang selanjutnya dapat digunakan sebagai panduan dalam membantu meningkatkan resiliensi individu yang mengalami Perubahan kondisi fisik menjadi penyandang disabilitas. Penulis menyusun serta merinci rancangan implementasi awal yang direkomendasikan oleh penelitian sebelumnya kedalam langkah-langkah yang lebih sistematis dan operasional hingga memperoleh hasil akhir berupa modul. Metode yang digunakan berbasis tahapan riset aksi, meskipun proses yang dilakukan hanya sampai pada langkah ketiga, yaitu Perumusan solusi dari persoalan yang diangkat. Partisipan terdiri dari delapan individu yang mengalami Perubahan kondisi menjadi penyandang disabilitas. Selain partisipan, empat orang psikolog juga dilibatkan dalam penelitian ini sebagai penelaah modul. Hasil penelitian ini berupa sebuah paket modul intervensi untuk peningkatan resiliensi melalui penguatan faktor protektif serta pengembangan strategi koping dan adaptasi pada individu yang mengalami Perubahan kondisi fisik menjadi penyandang disabilitas. Paket modul tersebut terdiri dari 5 sub-modul yang telah disusun sedemikian rupa untuk memudahkan pelaksanaannya, terdiri dari modul: (1) memperkuat dukungan keluarga terhadap penyandang disabilitas; (2) pendampingan awal penyandang disabilitas; (3) intervensi lanjut 1 (penguatan faktor protektif internal); (4) intervensi lanjut 2 (pengembangan strategi koping); dan (5) intervensi lanjut 3 (langkah adaptasi positif)