Emerging Therapies for Advanced Clear Cell Renal Cell Carcinoma

Multiple combinational regimens have recently been approved and are now considered the standard of care for patients with advanced clear cell renal cell carcinoma (RCC). Several additional combinational regimens are deep in clinical assessment and are likely to soon join the crowded front-line therapeutic landscape. Most of these regimens are combinations of agents already approved as single-agents in RCC including tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors. While these new front-line regimens are associated with reliably high response rates and prolonged survival, complete and durable remissions remain limited to a small subset of patients and the vast majority of patients continue to require subsequent therapy. The need for the continued development of novel agents in RCC persists and efforts have focused on agents targeting the molecular biology of clear cell RCC and novel immunotherapies including cytokines. In this review, we discuss the progress in the development of these novel therapies in the context of the evolving standard of care for patients with advanced clear cell RCC

The Use of Medicinal Mushroom or Herb as Effective Immunomodulatory Agent

Background: Medicinal mushrooms are mushrooms used with the aim for health enhancement. They have been used in traditional Chinese medicine (TCM) for thousands of years. These mushrooms and some herbal medicines have gain in popularity in recent times, largely due to a growing number of scientific studies that suggest their potential medical benefits. They are found to exert immunomodulatory effects through changes in the quantity of some specific cytokines in blood; as well as numbers and activities of distinct immune cell subsets. This article summarizes the immunomodulatory effects of two commonly consumed medicinal mushrooms (Coriolus versicolor and Ganoderma lucidum) and also three herbal medicines that have been categorized as immunomodulatory in function (Cordyceps sinensis, Astragalus membranaceus and Eleutherococcus senticosus). Methods: A systematic search of published articles of clinical trial studies between 1985 and August 2015 was conducted in four electronic databases (EMBASE, PubMed, Scopus and Web of Science). The outcome measures included changes in the serum cytokines secretion and the number and functional activity of different immune cell populations. Results: After a thorough literature searching of 237 relevant articles, 15 were included. Coriolus versicolor and Ganoderma lucidum showed immunomodulatory effects in both innate and adaptive immunity arms. There are only very few studies in each mushroom or herb, and unequivocal conclusions cannot be drawn. Future larger trials of randomized and placebo controlled clinical studies with laboratory investigation of changes of multiple immune populations and their subsets are needed in consistent with an evidence-based medicine approach

A hybrid method for determining particle masses at the Large Hadron Collider with fully identified cascade decays

A new technique for improving the precision of measurements of SUSY particle masses at the LHC is introduced. The technique involves kinematic fitting of events with two fully identified decay chains. We incorporate both event ETmiss constraints and independent constraints provided by kinematic end-points in experiment invariant mass distributions of SUSY decay products. Incorporation of the event specific information maximises the information used in the fit and is shown to reduce the mass measurement uncertainites by ~30% compared to conventional fitting of experiment end-point constraints for the SPS1a benchmark model.Comment: 10 pages, 2 .eps figures, JHEP3 styl

Podosomes and Invadopodia: Related structures with Common Protein Components that May Promote Breast Cancer Cellular Invasion

A rate-limiting step in breast cancer progression is acquisition of the invasive phenotype, which can precede metastasis. Expression of cell-surface proteases at the leading edge of a migrating cell provides cells with a mechanism to cross tissue barriers. A newly appreciated mechanism that may be relevant for breast cancer cell invasion is the formation of invadopodia, well-defined structures that project from the ventral membrane and promote degradation of the extracellular matrix, allowing the cell to cross a tissue barrier. Recently, there has been some controversy and discussion as to whether invadopodia, which are associated with carcinoma cells, are related to a similar structure called podosomes, which are associated with normal cells. Invadopodia and podosomes share many common characteristics, including a similar size, shape, subcellular localization and an ability to promote invasion. These two structures also share many common protein components, which we outline herein. It has been speculated that podosomes may be precursors to invadopodia and by extension both structures may be relevant to cancer cell invasion. Here, we compare and contrast the protein components of invadopodia and podosomes and discuss a potential role for these proteins and the evidence that supports a role for invadopodia and podosomes in breast cancer invasion

Long-term vascular access ports as a means of sedative administration in a rodent fMRI survival model

The purpose of this study is to develop a rodent functional magnetic resonance imaging (fMRI) survival model with the use of heparin-coated vascular access devices. Such a model would ease the administration of sedative agents, reduce the number of animals required in survival experiments and eliminate animal-to-animal variability seen in previous designs. Seven male Sprague-Dawley rats underwent surgical placement of an MRI-compatible vascular access port, followed by implantable electrode placement on the right median nerve. Functional MRI during nerve stimulation and resting-state functional connectivity MRI (fcMRI) were performed at times 0, 2, 4, 8 and 12 weeks postoperatively using a 9.4 T scanner. Anesthesia was maintained using intravenous dexmedetomidine and reversed using atipamezole. There were no fatalities or infectious complications during this study. All vascular access ports remained patent. Blood oxygen level dependent (BOLD) activation by electrical stimulation of the median nerve using implanted electrodes was seen within the forelimb sensory region (S1FL) for all animals at all time points. The number of activated voxels decreased at time points 4 and 8 weeks, returning to a normal level at 12 weeks, which is attributed to scar tissue formation and resolution around the embedded electrode. The applications of this experiment extend far beyond the scope of peripheral nerve experimentation. These vascular access ports can be applied to any survival MRI study requiring repeated medication administration, intravenous contrast, or blood sampling

Efeitos gerais nos distritos escolares do uso de dados em sala de aula

In the present study, an examination is conducted in three school districts of how data are used to improve classroom practice.  In doing so, we explore the effects that attitudes toward data, principal leadership, and computer data systems have on how data are used to affect classroom practice.  Findings indicate that educators are ambivalent about data: they see how data could support classroom practice, but their data use operates in the presence of numerous barriers.  Many of these barriers are due to principal leadership and computer data systems; these barriers often have negative effects on attitudes toward data and disrupt the progression from using data to inform classroom practice.  It is hypothesized that many of these barriers can be removed through effective district policies to improve structures and supports for using data.En el presente estudio, se examinan como tres distritos escolares usan datos para mejorar la práctica docente. Se exploraron que efectos tienen las actitudes hacia los datos, el liderazgo de los directores/as, y los sistemas de procesamiento de datos para modificar prácticas en el aula. Los resultados indican que los educadores son ambivalentes acerca de los datos: ven cómo los datos podrían apoyar prácticas en el aula, pero el uso de datos funciona en presencia de numerosas barreras. Muchas de estas barreras se deben al liderazgo de directores/as y a los sistemas de procesamiento de datos informáticos. Estas barreras suelen tener efectos negativos en las actitudes hacia los datos e interrumpen la incorporación de datos para mejorar prácticas en el aula. Se formula la hipótesis de que muchas de estas barreras pueden ser removidas a través de políticas distritales eficaces que mejoren las estructuras y brinden apoyos para el uso de datos.Neste estudo, examinamos como três distritos escolares utilizaram dados para melhorar a prática docente. Foram explorados os efeitos de atitudes em relação aos dados, a liderança dos/as diretores/as, e os sistemas de processamento de dados para alterar as práticas de sala de aula. Os resultados indicam que os educadores são ambivalentes respeito a o uso dos dados: observam como os dados podem apoiar as práticas de sala de aula, mas o uso de dados se faz na presença de muitas barreiras. Muitas dessas barreiras são devidas a liderança  dos/as diretores/as e aos sistemas e processamento de dados informáticos. Essas barreiras tendem a ter efeitos negativos nas atitudes com o uso dos dados e interrompem os processos de incorporar dados para melhorar as práticas de sala de aula. Se formula a hipótese de que que muitas dessas barreiras podem ser removidas através de políticas distritais eficazes que melhoram as estruturas e fornecendo suporte para o uso de dados

Deep Thermal Imaging: Proximate Material Type Recognition in the Wild through Deep Learning of Spatial Surface Temperature Patterns

We introduce Deep Thermal Imaging, a new approach for close-range automatic recognition of materials to enhance the understanding of people and ubiquitous technologies of their proximal environment. Our approach uses a low-cost mobile thermal camera integrated into a smartphone to capture thermal textures. A deep neural network classifies these textures into material types. This approach works effectively without the need for ambient light sources or direct contact with materials. Furthermore, the use of a deep learning network removes the need to handcraft the set of features for different materials. We evaluated the performance of the system by training it to recognise 32 material types in both indoor and outdoor environments. Our approach produced recognition accuracies above 98% in 14,860 images of 15 indoor materials and above 89% in 26,584 images of 17 outdoor materials. We conclude by discussing its potentials for real-time use in HCI applications and future directions.Comment: Proceedings of the 2018 CHI Conference on Human Factors in Computing System

Supersymmetric particle mass measurement with the boost-corrected contransverse mass

A modification to the contransverse mass (MCT) technique for measuring the masses of pair-produced semi-invisibly decaying heavy particles is proposed in which MCT is corrected for non-zero boosts of the centre-of-momentum (CoM) frame of the heavy states in the laboratory transverse plane. Lack of knowledge of the mass of the CoM frame prevents exact correction for this boost, however it is shown that a conservative correction can nevertheless be derived which always generates an MCT value which is less than or equal to the true value of MCT in the CoM frame. The new technique is demonstrated with case studies of mass measurement with fully leptonic ttbar events and with SUSY events possessing a similar final state.Comment: 33 pages, 33 .eps figures, JHEP3 styl