In response to infection and trauma, exquisite control of the innate inflammatory response is necessary to promote an anti-microbial response and minimize tissue injury. Over the course of the host response, activated leukocytes are essential for the initial response and can later become unresponsive or undergo apoptosis. Leukocytes, along the continuum of activation to apoptosis, have been shown to generate microvesicles. These vesicles can range in size from 0.1 to 1.0 µm and can retain proteins, RNA and DNA of their parent cells. Importantly, neutrophil-derived microvesicles (NDMV) are robustly increased under inflammatory conditions. The aim of this review is to summarize the research to date upon NDMVs. This will include describing under which disease states NDMVs are increased, mechanisms underlying formation, and the impact of these vesicles upon cellular targets. Altogether, increased awareness of NDMVs during the host innate response may allow for diagnostic tools as well as potential novel therapies during infection and trauma.

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BackgroundSWOG S0421 was a large randomized trial comparing docetaxel/prednisone plus placebo (DPP) to docetaxel/prednisone plus atrasentan over 12 cycles for patients with metastatic castration-resistant prostate cancer (mCRPC). The current report presents the PRO results for this trial, an important secondary endpoint.MethodsThe trial specified two primary PRO endpoints. Palliation of worst pain was based on the Brief Pain Inventory (BPI), where a 2 point difference is defined as clinically meaningful. Improvement of functional status was based on the Functional Assessment of Cancer Therapy – Prostate Cancer Trial Outcome Index (FACT-P TOI); a 5-point difference has been defined as clinically meaningful. We compared rates by arm using chi-square tests. Longitudinal analyses using linear mixed models addressed changes by arm over time.ResultsFour-hundred eighty-nine patients on each arm were evaluable for PRO endpoint data. There were no differences by arm in clinically meaningful pain palliation (41.7% for DPP vs. 44.0% for DPA, p = .70) or functional status (24.2% for DPP vs. 28.7% for DPA, p = .13). Longitudinal comparisons indicated no differences over time by arm for BPI Worst Pain scores (0.13 points, p = .23). Patients on the DPA arm had improved functional status of 1.78 points on average, a statistically significant (p = .02) but not clinically meaningful difference.ConclusionsThe SWOG S0421 PRO data showed little evidence of clinically meaningful differences by arm in either pain palliation or functional status.Electronic supplementary materialThe online version of this article (10.1186/s41687-018-0054-5) contains supplementary material, which is available to authorized users.

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Topology may play an important role in cosmology in several different ways. First, Einstein's field equations tell us about the local geometry of the universe but not about its topology. Therefore, the universe may be multiply connected. Inflation predicts that the fluctuations that made clusters and groups of galaxies arose from random quantum fluctuations in the early universe. These should be Gaussian random phase. This can be tested by quantitatively measuring the topology of large-scale structure in the universe using the genus statistic. If the original fluctuations were Gaussian random phase then the structure we see today should have a spongelike topology. A number of studies by our group and others have shown that this is indeed the case. Future tests using the Sloan Digital Sky Survey should be possible. Microwave background fluctuations should also exhibit a characteristic symmetric pattern of hot and cold spots. The COBE data are consistent with this pattern and the MAP and PLANCK satellites should provide a definitive test. If the original inflationary state was metastable then it should decay by making an infinite number of open inflationary bubble universes. This model makes a specific prediction for the power spectrum of fluctuations in the microwave background which can be checked by the MAP and PLANCK satellites. Finally, Gott and Li have proposed how a multiply connected cosmology with an early epoch of closed timelike curves might allow the universe to be its own mother.

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