Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: A multicenter study

The increase of proinflammatory cytokines in vaginal secretions may serve as a surrogate marker of unwanted inflammatory reaction to microbicide products topically applied for the prevention of sexually transmitted diseases, including HIV-1. Interleukin (IL)-1β and IL-6 have been proposed as indicators of inflammation and increased risk of HIV-1 transmission; however, the lack of information regarding detection platforms optimal for vaginal fluids and interlaboratory variation limit their use for microbicide evaluation and other clinical applications. This study examines fluid matrix variants relevant to vaginal sampling techniques and proposes a model for interlaboratory comparisons across current cytokine detection technologies. IL-1β and IL-6 standards were measured by 12 laboratories in four countries, using 14 immunoassays and four detection platforms based on absorbance, chemiluminescence, electrochemiluminescence, and fluorescence. International reference preparations of cytokines with defined biological activity were spiked into (1) a defined medium simulating the composition of human vaginal fluid at pH 4.5 and 7.2, (2) physiologic salt solutions (phosphate-buffered saline and saline) commonly used for vaginal lavage sampling in clinical studies of cytokines, and (3) human blood serum. Assays were assessed for reproducibility, linearity, accuracy, and significantly detectable fold difference in cytokine level. Factors with significant impact on cytokine recovery were determined by Kruskal−Wallis analysis of variance with Dunn’s multiple comparison test and multiple regression models. All assays showed acceptable intra-assay reproducibility; however, most were associated with significant interlaboratory variation. The smallest reliably detectable cytokine differences (P < 0.05) derived from pooled interlaboratory data varied from 1.5- to 26-fold depending on assay, cytokine, and matrix type. IL-6 but not IL-1β determinations were lower in both saline and phosphate-buffered saline as compared to vaginal fluid matrix, with no significant effect of pH. The (electro)chemiluminescence-based assays were most discriminative and consistently detected <2-fold differences within each matrix type. The Luminex-based assays were less discriminative with lower reproducibility between laboratories. These results suggest the need for uniform vaginal sampling techniques and a better understanding of immunoassay platform differences and cross-validation before the biological significance of cytokine variations can be validated in clinical trials. This investigation provides the first standardized analytic approach for assessing differences in mucosal cytokine levels and may improve strategies for monitoring immune responses at the vaginal mucosal interface

Digital Well-Being and Manipulation Online

Social media use is soaring globally. Existing research of its ethical implications predominantly focuses on the relationships amongst human users online, and their effects. The nature of the software-to-human relationship and its impact on digital well-being, however, has not been sufficiently addressed yet. This paper aims to close the gap. I argue that some intelligent software agents, such as newsfeed curator algorithms in social media, manipulate human users because they do not intend their means of influence to reveal the user’s reasons. I support this claim by defending a novel account of manipulation and by showing that some intelligent software agents are manipulative in this sense. Apart from revealing a priori reason for thinking that some intelligent software agents are manipulative, the paper offers a framework for further empirical investigation of manipulation online

Measuring the impact of cancer: a comparison of non-Hodgkin lymphoma and breast cancer survivors

Introduction Self-report instruments such as the Impact of Cancer (IOC) are designed to measure quality of life (QOL) impacts that cancer survivors attribute to their cancer experience. Generalizability of QOL findings across dis-tinct diagnostic categories of survivors is untested. W

Exercise is medicine in oncology: Engaging clinicians to help patients move through cancer

A compelling evidence base supports exercise as a safe, effective intervention to improve many cancer related health outcomes among cancer patients and survivors. Oncology clinicians play a key role in encouraging their patients to move more. Therefore, the oncology clinical care team is urged to do the following at regular intervals: ASSESS exercise levels, ADVISE patients to become more active, and REFER patients to specific exercise programming. It is recommended that a process be developed to incorporate these steps into the standard care of oncology patients. A simple, straightforward approach is recommended to discern whether patients should be referred to outpatient rehabilitation versus community based exercise programming. The exponential growth of exercise oncology research has driven the need for revised cancer exercise guidelines and a roadmap for oncology clinicians to follow to improve physical and psychological outcomes from cancer diagnosis and for the balance of life. This paper serves as a call to action and details pathways for exercise programming (clinical, community and self-directed) tailored to the different levels of support and intervention needed by a given cancer patient or survivor. Preserving activity and functional ability is integral to cancer care and oncology clinicians are key to providing these referrals