Planning search and rescue missions for UAV teams

The coordination of multiple Unmanned Aerial Vehicles (UAVs) to carry out aerial surveys is a major challenge for emergency responders. In particular, UAVs have to fly over kilometre-scale areas while trying to discover casualties as quickly as possible. To aid in this process, it is desirable to exploit the increasing availability of data about a disaster from sources such as crowd reports, satellite re- mote sensing, or manned reconnaissance. In particular, such inform- ation can be a valuable resource to drive the planning of UAV flight paths over a space in order to discover people who are in danger. However challenges of computational tractability remain when plan- ning over the very large action spaces that result. To overcome these, we introduce the survivor discovery problem and present as our solu- tion, the first example of a continuous factored coordinated Monte Carlo tree search algorithm. Our evaluation against state of the art benchmarks show that our algorithm, Co-CMCTS, is able to localise more casualties faster than standard approaches by 7% or more on simulations with real-world data

Management of chronic renal allograft dysfunction and when to re-transplant

Despite the advances in renal transplantation over the last decades, chronic allograft dysfunction remains the largest concern for patients, their families, clinicians and other members of the multi-disciplinary team. Although we have made progress in improving patient and renal allograft survival within the first year after transplantation, the rate of transplant failure with requirement for commencement of dialysis or re-transplantation has essentially remained unchanged. It is important that paediatric and adult nephrologists and transplant surgeons, not only manage their patients and their renal transplants but provide the best chronic kidney disease management during the time of decline of renal allograft function. The gold standard for patients with Stage V chronic kidney disease is to have pre-emptive living donor transplants, where possible and the same is true for healthy renal transplant recipients with declining renal allograft function. The consideration for children and young people as they embark on their end-stage kidney disease journey is the risk-benefit profile of giving the best immunologically matched and good quality renal allografts as they may require multiple renal transplantation operations during their lifetime

Comparing breast cancer mortality rates before-and-after a change in availability of screening in different regions: Extension of the paired availability design

BACKGROUND: In recent years there has been increased interest in evaluating breast cancer screening using data from before-and-after studies in multiple geographic regions. One approach, not previously mentioned, is the paired availability design. The paired availability design was developed to evaluate the effect of medical interventions by comparing changes in outcomes before and after a change in the availability of an intervention in various locations. A simple potential outcomes model yields estimates of efficacy, the effect of receiving the intervention, as opposed to effectiveness, the effect of changing the availability of the intervention. By combining estimates of efficacy rather than effectiveness, the paired availability design avoids confounding due to different fractions of subjects receiving the interventions at different locations. The original formulation involved short-term outcomes; the challenge here is accommodating long-term outcomes. METHODS: The outcome is incident breast cancer deaths in a time period, which are breast cancer deaths that were diagnosed in the same time period. We considered the plausibility of the basic five assumptions of the paired availability design and propose a novel analysis to accommodate likely violations of the assumption of stable screening effects. RESULTS: We applied the paired availability design to data on breast cancer screening from six counties in Sweden. The estimated yearly change in incident breast cancer deaths per 100,000 persons ages 40–69 (in most counties) due to receipt of screening (among the relevant type of subject in the potential outcomes model) was -9 with 95% confidence interval (-14, -4) or (-14, -5), depending on the sensitivity analysis. CONCLUSION: In a realistic application, the extended paired availability design yielded reasonably precise confidence intervals for the effect of receiving screening on the rate of incident breast cancer death. Although the assumption of stable preferences may be questionable, its impact will be small if there is little screening in the first time period. However, estimates may be substantially confounded by improvements in systemic therapy over time. Therefore the results should be interpreted with care

Pharmacokinetic analysis of two different docetaxel dose levels in patients with non-small cell lung cancer treated with docetaxel as monotherapy or with concurrent radiotherapy

<p>Abstract</p> <p>Background</p> <p>Previous pharmacokinetic studies with docetaxel have mostly used 3-weekly (75 mg/m²and 100 mg/m²) or weekly regimens (35–40 mg/m²). The pharmacokinetics and radiosensitizing efficacy of weekly 20 mg/m²docetaxel, has however not been well characterized. We examined the pharmacokinetics of weekly docetaxel when administered with concurrent radiotherapy and compared the results with a 3-weekly 100 mg/m²regimen.</p> <p>Methods</p> <p>Thirty-four patients with non small cell lung cancer (NSCLC) were included in this study, 19 receiving 100 mg/m²docetaxel 3-weekly as single therapy, and 15 receiving 20 mg/m²docetaxel weekly with concurrent radiotherapy. A newly developed HPLC method was used for measuring docetaxel levels, capable of quantifying docetaxel in plasma down to the nanomolar level.</p> <p>Results</p> <p>The HPLC method showed detectable concentrations of docetaxel in plasma even after 72 hours. In the present study we have demonstrated that median docetaxel plasma levels of 3 nM can be obtained 72 hours after a dose of 20 mg/m².</p> <p>Conclusion</p> <p>The pharmacokinetics of docetaxel is characterized by great inter-individual variability and at some time points plasma concentrations for 20 mg/m²and 100 mg/m²docetaxel were overlapping. Extrapolation of these results indicates that radio sensitizing docetaxel concentrations may be present for as long as 1 week, thus supporting the use of 20 mg/m²weekly docetaxel.</p

Randomized trials, generalizability, and meta-analysis: Graphical insights for binary outcomes

BACKGROUND: Randomized trials stochastically answer the question. "What would be the effect of treatment on outcome if one turned back the clock and switched treatments in the given population?" Generalizations to other subjects are reliable only if the particular trial is performed on a random sample of the target population. By considering an unobserved binary variable, we graphically investigate how randomized trials can also stochastically answer the question, "What would be the effect of treatment on outcome in a population with a possibly different distribution of an unobserved binary baseline variable that does not interact with treatment in its effect on outcome?" METHOD: For three different outcome measures, absolute difference (DIF), relative risk (RR), and odds ratio (OR), we constructed a modified BK-Plot under the assumption that treatment has the same effect on outcome if either all or no subjects had a given level of the unobserved binary variable. (A BK-Plot shows the effect of an unobserved binary covariate on a binary outcome in two treatment groups; it was originally developed to explain Simpsons's paradox.) RESULTS: For DIF and RR, but not OR, the BK-Plot shows that the estimated treatment effect is invariant to the fraction of subjects with an unobserved binary variable at a given level. CONCLUSION: The BK-Plot provides a simple method to understand generalizability in randomized trials. Meta-analyses of randomized trials with a binary outcome that are based on DIF or RR, but not OR, will avoid bias from an unobserved covariate that does not interact with treatment in its effect on outcome

Liverpool Telescope 2: a new robotic facility for time domain astronomy in 2020

The robotic 2m Liverpool Telescope, based on the Canary island of La Palma, has a diverse instrument suite and a strong track record in time domain science, with highlights including early time photometry and spectra of supernovae, measurements of the polarization of gamma-ray burst afterglows, and high cadence light curves of transiting extrasolar planets. In the next decade the time domain will become an increasingly prominent part of the astronomical agenda with new facilities such as LSST, SKA, CTA and Gaia, and promised detections of astrophysical gravitational wave and neutrino sources opening new windows on the transient universe. To capitalise on this exciting new era we intend to build Liverpool Telescope 2: a new robotic facility on La Palma dedicated to time domain science. The next generation of survey facilities will discover large numbers of new transient sources, but there will be a pressing need for follow-up observations for scientific exploitation, in particular spectroscopic follow-up. Liverpool Telescope 2 will have a 4-metre aperture, enabling optical/infrared spectroscopy of faint objects. Robotic telescopes are capable of rapid reaction to unpredictable phenomena, and for fast-fading transients like gamma-ray burst afterglows. This rapid reaction enables observations which would be impossible on less agile telescopes of much larger aperture. We intend Liverpool Telescope 2 to have a world-leading response time, with the aim that we will be taking data with a few tens of seconds of receipt of a trigger from a ground- or space-based transient detection facility. We outline here our scientific goals and present the results of our preliminary optical design studies. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only

Clinical pharmacodynamic factors in docetaxel toxicity

Neutropenia is the main dose-limiting toxicity occurring in docetaxel treatment. The objective of this study was to identify pharmacodynamic (PD) factors responsible for the neutropaenia caused by docetaxel. Data were obtained from 92 patients treated with docetaxel as a monochemotherapy in two different treatment centres. A semiphysiological population pharmacokinetic–pharmacodynamic (PK/PD) model was applied to describe the time course of neutrophils and the neutropaenic effect of docetaxel. The plasma docetaxel concentration was assumed to inhibit the proliferation of neutrophil precursors through a linear model: Drug effect=Slope × Conc. Slope corresponds to the patients' sensitivity to the neutropaenic effect of docetaxel. Covariate analysis was performed by testing the relationship between the patients' characteristics and Slope using the program NONMEM. The neutropaenic effect of docetaxel showed a high interindividual variability. Three significant PD covariates were identified: serum α1-acid glycoprotein levels (AAG), level of chemotherapy pretreatment, and treatment centre. Extensive pretreatment was associated with an increase in Slope values meaning a higher haematotoxicity. An increase in AAG was associated with a decrease of both Slope and docetaxel plasma clearance. Patients treated in one centre had both higher Slope and docetaxel clearance. The centre effect (most likely due to a bias in the PK part of the study between the two centres) reveals the robustness of the PK/PD model. Individual dosing of docetaxel should be based on previous chemotherapy but not on the AAG level since it has a similar influence on PD and PK docetaxel parameters. This methodology should be applied to further investigate elderly patients and to identify more precisely the characteristics of previous chemotherapy that contribute to the cumulative myelotoxicity

The Response of Electron Pitch Angle Distributions to the Upper Limit on Stably Trapped Particles

We use Van Allen Probes electron data during 70 geomagnetic storms to examine the response of equatorial pitch angle distributions (PADs) at L* = 4.0–4.5 to a theoretical upper limit on stably trapped particle fluxes. Of the energies examined, 54 and 108 keV electron PADs isotropize to a previously assumed level within 6 hr of reaching the limit, near-identically across all 70 storms, consistent with rapid pitch angle scattering due to chorus wave interactions. In around 30% of events, 54 keV electrons completely exceed the KP limit, before being quickly subdued. 470 and 749 keV PADs show clear indications of an upper limit, though less aligned with the calculated limit used here. The consistency of an absolute upper limit shown across all events demonstrates the importance of this phenomena in both the limiting effect on electron flux and consistently influencing electron PAD evolution during geomagnetic storms. These results also highlight the need for further investigation, particularly related to the limiting of higher energy electrons