The Green's function for the radial Schramm-Loewner evolution

We prove the existence of the Green's function for radial SLE(k) for k<8. Unlike the chordal case where an explicit formula for the Green's function is known for all values of k<8, we give an explicit formula only for k=4. For other values of k, we give a formula in terms of an expectation with respect to SLE conditioned to go through a point.Comment: v1: 16 pages, 0 figure

Adding a treatment arm to an ongoing clinical trial: a review of methodology and practice

Incorporating an emerging therapy as a new randomisation arm in a clinical trial that is open to recruitment would be desirable to researchers, regulators and patients to ensure that the trial remains current, new treatments are evaluated as quickly as possible, and the time and cost for determining optimal therapies is minimised. It may take many years to run a clinical trial from concept to reporting within a rapidly changing drug development environment; hence, in order for trials to be most useful to inform policy and practice, it is advantageous for them to be able to adapt to emerging therapeutic developments. This paper reports a comprehensive literature review on methodologies for, and practical examples of, amending an ongoing clinical trial by adding a new treatment arm. Relevant methodological literature describing statistical considerations required when making this specific type of amendment is identified, and the key statistical concepts when planning the addition of a new treatment arm are extracted, assessed and summarised. For completeness, this includes an assessment of statistical recommendations within general adaptive design guidance documents. Examples of confirmatory ongoing trials designed within the frequentist framework that have added an arm in practice are reported; and the details of the amendment are reviewed. An assessment is made as to how well the relevant statistical considerations were addressed in practice, and the related implications. The literature review confirmed that there is currently no clear methodological guidance on this topic, but that guidance would be advantageous to help this efficient design amendment to be used more frequently and appropriately in practice. Eight confirmatory trials were identified to have added a treatment arm, suggesting that trials can benefit from this amendment and that it can be practically feasible; however, the trials were not always able to address the key statistical considerations, often leading to uninterpretable or invalid outcomes. If the statistical concepts identified within this review are considered and addressed during the design of a trial amendment, it is possible to effectively assess a new treatment arm within an ongoing trial without compromising the original trial outcomes

An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

Citation: Shi, Z. Z., Chapes, S. K., Ben-Arieh, D., & Wu, C. H. (2016). An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data. Plos One, 11(8), 39. doi:10.1371/journal.pone.0161131We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as "sepsis". Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-a ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

The Ages of Passive Galaxies in a z = 1.62 Protocluster

We present a study of the relation between galaxy stellar age and mass for 14 members of the $z=1.62$ protocluster IRC 0218, using multiband imaging and HST G102 and G141 grism spectroscopy. Using $UVJ$ colors to separate galaxies into star forming and quiescent populations, we find that at stellar masses $M_* \geq 10^{10.85} M_{\odot}$, the quiescent fraction in the protocluster is $f_Q=1.0^{+0.00}_{-0.37}$, consistent with a $\sim 2\times$ enhancement relative to the field value, $f_Q=0.45^{+0.03}_{-0.03}$. At masses $10^{10.2} M_{\odot} \leq M_* \leq 10^{10.85} M_{\odot}$, $f_Q$ in the cluster is $f_Q=0.40^{+0.20}_{-0.18}$, consistent with the field value of $f_Q=0.28^{+0.02}_{-0.02}$. Using galaxy $D_{n}(4000)$ values derived from the G102 spectroscopy, we find no relation between galaxy stellar age and mass. These results may reflect the impact of merger-driven mass redistribution, which is plausible as this cluster is known to host many dry mergers. Alternately, they may imply that the trend in $f_Q$ in IRC 0218 was imprinted over a short timescale in the protocluster's assembly history. Comparing our results with those of other high-redshift studies and studies of clusters at $z\sim 1$, we determine that our observed relation between $f_Q$ and stellar mass only mildly evolves between $z\sim 1.6$ and $z \sim 1$, and only at stellar masses $M_* \leq 10^{10.85} M_{\odot}$. Both the $z\sim 1$ and $z\sim 1.6$ results are in agreement that the red sequence in dense environments was already populated at high redshift, $z \ge 3$, placing constraints on the mechanism(s) responsible for quenching in dense environments at $z\ge 1.5$Comment: 17 pages, 8 figures, 3 tables. Accepted for publication in Ap

The Green function for the radial Schramm–Loewner evolution

We prove the existence of the Green function for radial SLE_κ for κ < 8. Unlike the chordal case where an explicit formula for the Green function is known for all values of κ < 8, we give an explicit formula only for κ = 4. For other values of κ, we give a formula in terms of an expectation with respect to SLE conditioned to go through a point