A tutorial on pilot studies: the what, why and how

Pilot studies for phase III trials - which are comparative randomized trials designed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas. Also commonly know as "feasibility" or "vanguard" studies, they are designed to assess the safety of treatment or interventions; to assess recruitment potential; to assess the feasibility of international collaboration or coordination for multicentre trials; to increase clinical experience with the study medication or intervention for the phase III trials. They are the best way to assess feasibility of a large, expensive full-scale study, and in fact are an almost essential pre-requisite. Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies. The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including: 1) the general reasons for conducting a pilot study; 2) the relationships between pilot studies, proof-of-concept studies, and adaptive designs; 3) the challenges of and misconceptions about pilot studies; 4) the criteria for evaluating the success of a pilot study; 5) frequently asked questions about pilot studies; 7) some ethical aspects related to pilot studies; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format

Compounds from Silicones Alter Enzyme Activity in Curing Barnacle Glue and Model Enzymes

Background: Attachment strength of fouling organisms on silicone coatings is low. We hypothesized that low attachment strength on silicones is, in part, due to the interaction of surface available components with natural glues. Components could alter curing of glues through bulk changes or specifically through altered enzyme activity. Methodology/Principal Findings: GC-MS analysis of silicone coatings showed surface-available siloxanes when the coatings were gently rubbed with a cotton swab for 15 seconds or given a 30 second rinse with methanol. Mixtures of compounds were found on 2 commercial and 8 model silicone coatings. The hypothesis that silicone components alter glue curing enzymes was tested with curing barnacle glue and with commercial enzymes. In our model, barnacle glue curing involves trypsin-like serine protease(s), which activate enzymes and structural proteins, and a transglutaminase which cross-links glue proteins. Transglutaminase activity was significantly altered upon exposure of curing glue from individual barnacles to silicone eluates. Activity of purified trypsin and, to a greater extent, transglutaminase was significantly altered by relevant concentrations of silicone polymer constituents. Conclusions/Significance: Surface-associated silicone compounds can disrupt glue curing and alter enzyme properties

Search for time-dependent B0s - B0s-bar oscillations using a vertex charge dipole technique

We report a search for B0s - B0s-bar oscillations using a sample of 400,000 hadronic Z0 decays collected by the SLD experiment. The analysis takes advantage of the electron beam polarization as well as information from the hemisphere opposite that of the reconstructed B decay to tag the B production flavor. The excellent resolution provided by the pixel CCD vertex detector is exploited to cleanly reconstruct both B and cascade D decay vertices, and tag the B decay flavor from the charge difference between them. We exclude the following values of the B0s - B0s-bar oscillation frequency: Delta m_s < 4.9 ps-1 and 7.9 < Delta m_s < 10.3 ps-1 at the 95% confidence level.Comment: 18 pages, 3 figures, replaced by version accepted for publication in Phys.Rev.D; results differ slightly from first versio

Saturn satellites as seen by Cassini Mission

In this paper we will summarize some of the most important results of the Cassini mission concerning the satellites of Saturn. Given the long duration of the mission, the complexity of the payload onboard the Cassini Orbiter and the amount of data gathered on the satellites of Saturn, it would be impossible to describe all the new discoveries made, therefore we will describe only some selected, paramount examples showing how Cassini's data confirmed and extended ground-based observations. In particular we will describe the achievements obtained for the satellites Phoebe, Enceladus and Titan. We will also put these examples in the perspective of the overall evolution of the system, stressing out why the selected satellites are representative of the overall evolution of the Saturn system.Comment: 34 pages, 10 figures, to appear on the special issue of Earth, Moon and Planets for the Elba worksho

Dynamic Imaging of the Effector Immune Response to Listeria Infection In Vivo

Host defense against the intracellular pathogen Listeria monocytogenes (Lm) requires innate and adaptive immunity. Here, we directly imaged immune cell dynamics at Lm foci established by dendritic cells in the subcapsular red pulp (scDC) using intravital microscopy. Blood borne Lm rapidly associated with scDC. Myelomonocytic cells (MMC) swarmed around non-motile scDC forming foci from which blood flow was excluded. The depletion of scDC after foci were established resulted in a 10-fold reduction in viable Lm, while graded depletion of MMC resulted in 30–1000 fold increase in viable Lm in foci with enhanced blood flow. Effector CD8+ [CD8 superscript +] T cells at sites of infection displayed a two-tiered reduction in motility with antigen independent and antigen dependent components, including stable interactions with infected and non-infected scDC. Thus, swarming MMC contribute to control of Lm prior to development of T cell immunity by direct killing and sequestration from blood flow, while scDC appear to promote Lm survival while preferentially interacting with CD8+ [CD8 superscript +] T cells in effector sites.National Institutes of Health (U.S.) (Grant P01AI-071195

TESS Hunt for Young and Maturing Exoplanets (THYME): A Planet in the 45 Myr Tucana–Horologium Association

Young exoplanets are snapshots of the planetary evolution process. Planets that orbit stars in young associations are particularly important because the age of the planetary system is well constrained. We present the discovery of a transiting planet larger than Neptune but smaller than Saturn in the 45 Myr Tucana–Horologium young moving group. The host star is a visual binary, and our follow-up observations demonstrate that the planet orbits the G6V primary component, DS Tuc A (HD 222259A, TIC 410214986). We first identified transits using photometry from the Transiting Exoplanet Survey Satellite (TESS; alerted as TOI 200.01). We validated the planet and improved the stellar parameters using a suite of new and archival data, including spectra from Southern Astrophysical Research/Goodman, South African Extremely Large Telescope/High Resolution Spectrograph and Las Cumbres Observatories/Network of Robotic Echelle Spectrographs; transit photometry from Spitzer; and deep adaptive optics imaging from Gemini/Gemini Planet Imager. No additional stellar or planetary signals are seen in the data. We measured the planetary parameters by simultaneously modeling the photometry with a transit model and a Gaussian process to account for stellar variability. We determined that the planetary radius is 5.70 ± 0.17 R ⊕ and that the orbital period is 8.1 days. The inclination angles of the host star’s spin axis, the planet’s orbital axis, and the visual binary’s orbital axis are aligned within 15° to within the uncertainties of the relevant data. DS Tuc Ab is bright enough (V = 8.5) for detailed characterization using radial velocities and transmission spectroscopy

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified