Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells

Photodynamic therapy using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) may be applied to the treatment of neoplasms in a variety of organs. In order to enhance existing regimens of photodynamic therapy, we investigated the effects of adding differentiation therapy to photodynamic therapy in human prostate cancer cells in vitro. The objective of differentiation therapy per se is to reverse the lack of differentiation in cancer cells using pharmacological agents. The motivation for this study was to exploit the differentiation-dependent expression of some heme enzymes to enhance tumour cell toxicity of ALA-photodynamic therapy. A short course of differentiation therapy was applied to increase PpIX formation during subsequent ALA exposure. Using the synthetic androgen R1881, isomers of retinoic acid, and analogues of vitamin D for 3 to 4 days, exogenous ALA-dependent PpIX formation in LNCaP cells was increased, along with markers for growth arrest and for differentiation. As a consequence of higher PpIX levels, cytotoxic effects of visible light exposure were also enhanced. Short-term differentiation therapy increased not only the overall PpIX production but also reduced that fraction of cells that contained low PpIX levels as demonstrated by flow cytometry and fluorescence microscopy. This study suggests that it will be feasible to develop protocols combining short-term differentiation therapy with photodynamic therapy for enhanced photosensitisation

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis : APLIOS, a randomized phase-2 study

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Background: An in-depth understanding of the fundamental principles that regulate thyroid hormone homeostasis is critical for the development of new diagnostic and treatment ap-proaches for patients with thyroid disease. Summary: Important clinical practices in use today for the treatment of patients with hypothy-roidism, hyperthyroidism, or thyroid cancer, are the result of laboratory discoveries made by scientists investigating the most basic aspects of thyroid structure and molecular biology. In this document, a panel of experts commissioned by the American Thyroid Association makes a se-ries of recommendations related to the study of thyroid hormone economy and action. These recommendations are intended to promote standardization of study design, which should in turn increase the comparability and reproducibility of experimental findings. Conclusions: It is expected that adherence to these recommendations by investigators in the field will facilitate progress towards a better understanding of the thyroid gland and thyroid hormone dependent processes

Interacting with Microseismic Visualizations: The Video.

Microseismic visualization systems present complex 3D data of small seismic events within oil reservoirs to allow experts to explore and interact with that data. Yet existing systems suffer several problems: 3D spatial navigation and orientation is difficult, and selecting 3D data is challenging due to the problems of occlusion and lack of depth perception. Our work mitigates these problems by applying both proxemic interactions and a spatial input device to simplify how experts navigate through the visualization, and a painting metaphor to simplify how they select that information.Ye

Interacting with Microseismic Visualizations

Microseismic visualization systems present complex 3D data of small seismic events within oil reservoirs to allow experts to explore and interact with that data. Yet existing systems suffer several problems: 3D spatial navigation and orientation is difficult, and selecting 3D data is challenging due to the problems of occlusion and lack of depth perception. Our work mitigates these problems by applying both proxemic interactions and a spatial input device to simplify how experts navigate through the visualization, and a painting metaphor to simplify how they select that information.Ye

PhoneEar

We present PhoneEar, a new approach that enables mobile devices to understand the broadcasted audio and sounds that we hear every day using existing infrastructure. PhoneEar audio streams are embedded with sound-encoded data using nearly inaudible high frequencies. Mobile devices then listen for messages in the sounds around us, taking actions to ensure we don't miss any important info. In this paper, we detail our implementation of PhoneEar, describe a study demonstrating that mobile devices can effectively receive sound-based data, and describe the results of a user study that shows that embedding data in sounds is not detrimental to sound quality. We also exemplify the space of new interactions, through four PhoneEar-enabled applications. Finally, we discuss the challenges to deploying apps that can hear and react to data in the sounds around us.Ye

The evolving field of tangible interaction for children : the challenge of empirical validation

This special issue is devoted to the topic of tangible user interfaces and children. It emphasizes research on tangibility that transcends system descriptions, focusing on the empirical support of theories and design guidance. The papers result from the organization of a workshop at the CHI 2009 ACM conference in Boston, USA. As an introduction to this issue, empirical evidence is discussed for the potential benefits that using TUIs may have for children. In particular, we focus at the impact of tangibility in terms of usability, learning, collaboration and fun. Finally, we suggest directions for future work and outline the papers that are included in this special issue