Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease

While the CNS has long been viewed as an immune-privileged environment, a paradigm shift in neuro-immunology has elevated the role of systemic immunotherapy for the treatment of metastatic disease. Increasing knowledge regarding the presence of a CNS lymphatic system and the physical and biochemical alteration of the blood brain barrier (BBB) by the tumor microenvironment suggests immune cell trafficking in and out of the CNS is possible. Emerging clinical data suggest immune checkpoint inhibitors (ICIs) can stimulate T cells peripherally to in turn have anti-tumor effects in the CNS. For example, anti-programmed cell death-1 (PD-1) monotherapy with pembrolizumab has shown intracranial response rates of 20–30% in patients with melanoma or non-small cell lung cancer (NSCLC) brain metastases. The combination of nivolumab and ipilimumab [anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)] showed an intracranial response rate of 55% in patients with melanoma brain metastases. More data are needed to confirm these response rates and to determine mechanisms of efficacy and resistance. While local therapies such as stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT), and surgery remain current mainstays, ICIS offer potential decreased neurotoxicity. This review summarizes the biological rationale for systemic immunotherapy to treat CNS metastatic disease, existing clinical data on ICIs in this setting and ongoing clinical trials exploring areas of unmet need

A QUALITATIVE INVESTIGATION OF TECHNOLOGY TRANSFER* A CASE STUDY

ECHNOLOGY transfer is an issue of national importance and i

Profit and loss analysis for an intensive care unit (ICU) in Japan: a tool for strategic management

BACKGROUND: Accurate cost estimate and a profit and loss analysis are necessary for health care practice. We performed an actual financial analysis for an intensive care unit (ICU) of a university hospital in Japan, and tried to discuss the health care policy and resource allocation decisions that have an impact on critical intensive care. METHODS: The costs were estimated by a department level activity based costing method, and the profit and loss analysis was based on a break-even point analysis. The data used included the monthly number of patients, the revenue, and the direct and indirect costs of the ICU in 2003. RESULTS: The results of this analysis showed that the total costs of US$2,678,052 of the ICU were mainly incurred due to direct costs of 88.8$ 2,295,044. However, it was determined that the ICU required at least 1,986 patient days within one fiscal year based on a break-even point analysis. As a result, an annual deficit of US$ 383,008 has occurred in the ICU. CONCLUSION: These methods are useful for determining the profits or losses for the ICU practice, and how to evaluate and to improve it. In this study, the results indicate that most ICUs in Japanese hospitals may not be profitable at the present time. As a result, in order to increase the income to make up for this deficit, an increase of 437 patient days in the ICU in one fiscal year is needed, and the number of patients admitted to the ICU should thus be increased without increasing the number of beds or staff members. Increasing the number of patients referred from cooperating hospitals and clinics therefore appears to be the best strategy for achieving these goals

Effect of Soil and Foliar Application of Zn and Fe on Nutrient Status of Hybrid Maize (Zea mays L.)

The present experiment was carried out to study the effect of soil and foliar application of zinc and iron on nutrient status of maize at Sardar Vallabhbhai University, Meerut during Kharif season of 2017-18. The present study consists of soil application of eight nutrient treatments namely 100% NPK, NPK+ Zn and Fe each @ 5 kg/ha,@ 10 kg/ha,@ 20 kg/ha, NPK+ Zn and Fe each @10 kg/ha + vermicompost (1.5 t/ha), NPK+Vermicompost @ 1.5 t/ha, NPK+ Zn and Fe each @ 5 kg/ha + foliar spray each @ 0.1% at the tasselling stage and NPK+ Foliar spray Zn and Fe each @ 0.1% at 25 DAS and at tasselling stage. These treatments were tested in RBD with three replications, aiming to know the effect of micro-nutrients (Zinc and Iron) on performance nutrient content and uptake of the maize cultivar, ADV 755. The maximum nitrogen, phosphorus & potassium content and uptake were recorded in the treatment number T5(T1 +soil applied Zn and Fe each @10 kg/ha + vermicompost), the maximum Zn and Fe content and uptake were recorded in the treatment number T7(T1+Soil applied Zn and Fe each @ 5 kg/ha + foliar spray each @ 0.1% at tasseling stage) wherein N,P,K, Zn and Fe were applied with vermicompost.The application of N,P,K and vermicompostwould have also helped in increasing N,P and K content and uptake in plants. The maximum Zn and Fe, content and uptake were recorded in Treatment T7which may have happened due to better soil and foliage application availability of nutrients in it

Fast manipulation of cellular cAMP level by light in vivo

The flagellate Euglena gracilis contains a photoactivated adenylyl cyclase (PAC), consisting of the flavoproteins PACa and PACb. Here we report functional expression of PACs in Xenopus laevis oocytes, HEK293 cells and in Drosophila melanogaster, where neuronal expression yields light-induced changes in behavior. The activity of PACs is strongly and reversibly enhanced by blue light, providing a powerful tool for light-induced manipulation of cAMP in animal cells.Peer Reviewe

Fast manipulation of cellular cAMP level by light in vivo

The flagellate Euglena gracilis contains a photoactivated adenylyl cyclase (PAC), consisting of the flavoproteins PACα and PACβ. Here we report functional expression of PACs in Xenopus laevis oocytes, HEK293 cells and in Drosophila melanogaster, where neuronal expression yields light-induced changes in behavior. The activity of PACs is strongly and reversibly enhanced by blue light, providing a powerful tool for light-induced manipulation of cAMP in animal cells

Fast manipulation of cellular cAMP level by light in vivo

The flagellate Euglena gracilis contains a photoactivated adenylyl cyclase (PAC), consisting of the flavoproteins PACalpha and PACbeta. Here we report functional expression of PACs in Xenopus laevis oocytes, HEK293 cells and in Drosophila melanogaster, where neuronal expression yields light-induced changes in behavior. The activity of PACs is strongly and reversibly enhanced by blue light, providing a powerful tool for light-induced manipulation of cAMP in animal cells