Novel Missions for Next Generation Microsatellites: The Results of a Joint AFRL/JPL Study

The development of technologies for miniature, low-mass, high density components and of systems that efficiently utilize these teclmologies has enabled a path to the next generation of highly capable microsatellites in the range of 10 - 100-kg. The characteristics and capabilities of this emerging class of satellites are briefly described. These satellites have the potential for revolutionizing space missions owing to their small size, low cost, significant capability, and good return on investment. This paper documents conceptual microsatellite mission scenarios examined in a collaborative effort between the Air Force Research Laboratory (AFRL) and the Jet Propulsion Laboratory of the California Institute of Technology (JPL). Six areas of mutual interest were selected from an initial set of about 30 microsatellite mission areas. Each of the selected areas was examined in more depth. The concepts explored include a remote sensing microsatellite, an on-orbit servicing microsatellite, a micronavigation and communication system, an adjunct microsatellite, and two distributed microsatellite systems; one for surveillance and one for space weather and physics observations. These missions are described briefly. A unique characteristic of these microsatellites, exploited in some of the mission scenarios, is the potential for low cost and rapid launch using non-traditional methods. One method examined involves using air-to-space missile technology

Value of information methods to design a clinical trial in a small population to optimise a health economic utility function

Background: Most confirmatory randomised controlled clinical trials (RCTs) are designed with specified power, usually 80% or 90%, for a hypothesis test conducted at a given significance level, usually 2.5% for a one-sided test. Approval of the experimental treatment by regulatory agencies is then based on the result of such a significance test with other information to balance the risk of adverse events against the benefit of the treatment to future patients. In the setting of a rare disease, recruiting sufficient patients to achieve conventional error rates for clinically reasonable effect sizes may be infeasible, suggesting that the decision-making process should reflect the size of the target population. Methods: We considered the use of a decision-theoretic value of information (VOI) method to obtain the optimal sample size and significance level for confirmatory RCTs in a range of settings. We assume the decision maker represents society. For simplicity we assume the primary endpoint to be normally distributed with unknown mean following some normal prior distribution representing information on the anticipated effectiveness of the therapy available before the trial. The method is illustrated by an application in an RCT in haemophilia A. We explicitly specify the utility in terms of improvement in primary outcome and compare this with the costs of treating patients, both financial and in terms of potential harm, during the trial and in the future. Results: The optimal sample size for the clinical trial decreases as the size of the population decreases. For non-zero cost of treating future patients, either monetary or in terms of potential harmful effects, stronger evidence is required for approval as the population size increases, though this is not the case if the costs of treating future patients are ignored. Conclusions: Decision-theoretic VOI methods offer a flexible approach with both type I error rate and power (or equivalently trial sample size) depending on the size of the future population for whom the treatment under investigation is intended. This might be particularly suitable for small populations when there is considerable information about the patient population

On questions of Fatou and Eremenko

Let $f$ be a transcendental entire function and let $I(f)$ be the set of points whose iterates under $f$ tend to infinity. We show that $I(f)$ has at least one unbounded component. In the case that $f$ has a Baker wandering domain, we show that $I(f)$ is a connected unbounded set

Approaches to sample size calculation for clinical trials in rare diseases

We discuss 3 alternative approaches to sample size calculation: traditional sample size calculation based on power to show a statistically significant effect, sample size calculation based on assurance, and sample size based on a decision-theoretic approach. These approaches are compared head-to-head for clinical trial situations in rare diseases. Specifically, we consider 3 case studies of rare diseases (Lyell disease, adult-onset Still disease, and cystic fibrosis) with the aim to plan the sample size for an upcoming clinical trial. We outline in detail the reasonable choice of parameters for these approaches for each of the 3 case studies and calculate sample sizes. We stress that the influence of the input parameters needs to be investigated in all approaches and recommend investigating different sample size approaches before deciding finally on the trial size. Highly influencing for the sample size are choice of treatment effect parameter in all approaches and the parameter for the additional cost of the new treatment in the decision-theoretic approach. These should therefore be discussed extensively

Trade-offs in the effects of the apolipoprotein E polymorphism on risks of diseases of the heart, cancer, and neurodegenerative disorders: Insights on mechanisms from the long life family study

The lack of evolutionary established mechanisms linking genes to age-related traits makes the problem of genetic susceptibility to health span inherently complex. One complicating factor is genetic trade-off. Here we focused on long-living participants of the Long Life Family Study (LLFS), their offspring, and spouses to: (1) Elucidate whether trade-offs in the effect of the apolipoprotein E e4 allele documented in the Framingham Heart Study (FHS) are a more general phenomenon, and (2) explore potential mechanisms generating age- and gender-specific trade-offs in the effect of the e4 allele on cancer, diseases of the heart, and neurodegenerative disorders assessed retrospectively in the LLFS populations. The e4 allele can diminish risks of cancer and diseases of the heart and confer risks of diseases of the heart in a sex-, age-, and LLFS-population-specific manner. A protective effect against cancer is seen in older long-living men and, potentially, their sons (>75 years, relative risk [RR](>75)=0.48, p=0.086), which resembles our findings in the FHS. The protective effect against diseases of the heart is limited to long-living older men (RR(>76)=0.50, p=0.016), as well. A detrimental effect against diseases of the heart is characteristic for a normal LLFS population of male spouses and is specific for myocardial infarction (RR=3.07, p=2.1×10(−3)). These trade-offs are likely associated with two inherently different mechanisms, including disease-specific (detrimental; characteristic for a normal male population) and systemic, aging-related (protective; characteristic for older long-living men) mechanisms. The e4 allele confers risks of neurological disorders in men and women (RR=1.98, p=0.046). The results highlight the complex role of the e4 allele in genetic susceptibility to health span

Power variability of tidal-stream energy and implications for electricity supply

Temporal variability in renewable energy presents a major challenge for electrical grid systems. Tides are considered predictable due to their regular periodicity; however, the persistence and quality of tidal-stream generated electricity is unknown. This paper is the first study that attempts to address this knowledge gap through direct measurements of rotor-shaft power and shore-side voltage from a 1 MW, rated at grid-connection, tidal turbine (Orkney Islands, UK). Tidal asymmetry in turbulence parameters, flow speed and power variability were observed. Variability in the power at 0.5 Hz, associated with the 10-min running mean, was low (standard deviation 10–12% of rated power), with lower variability associated with higher flow speed and reduced turbulence intensity. Variability of shore-side measured voltage was well within acceptable levels (∼0.3% at 0.5 Hz). Variability in turbine power had <1% difference in energy yield calculation, even with a skewed power variability distribution. Finally, using a “t-location” distribution of observed fine-scale power variability, in combination with an idealised power curve, a synthetic power variability model reliably downscaled 30 min tidal velocity simulations to power at 0.5 Hz (R2 = 85% and ∼14% error). Therefore, the predictability and quality of tidal-stream energy may be undervalued in a future, high-penetration renewable energy, electricity grid

Exogenous exposures shape genetic predisposition to lipids, Alzheimer\u27s, and coronary heart disease in the MLXIPL gene locus

Associations of single nucleotide polymorphisms (SNPs) of th

Experimental evaluation of the wake characteristics of cross flow turbine arrays

One key factor in the exploitation of tidal energy is the study of interactions of turbines when working in tidal turbine farms. The Momentum Reversal and Lift (MRL) turbine is a novel cross flow turbine. The three blades rotate around a common central horizontal axis which is parallel to their own axis and perpendicular to the flow. The novelty of the MRL turbine is that it relies on the combination of both lift and momentum reversal (drag) for energy extraction. Scaled MRL turbine models of 0.164 m in diameter were used to characterise the flow in three different tidal array settings. Detailed maps of axial velocity profiles and velocity deficits downstream of the turbine are presented, enabling the visualisation of characteristic flow patterns. The results show that the MRL generates lower velocity deficits and turbulence intensities in the near wake than those associated with horizontal axis turbines. The downstream wake was not completely symmetrical which was related to the geometry of the device but also due to the flow developed in the flume. Amongst the three array configurations studied, a fence of turbines with the lowest separation provided the highest power output

A population-based audit of surgical practice and outcomes of oncoplastic breast conservations in Scotland – an analysis of 589 patients

Introduction: Current evidence for oncoplastic breast conservation (OBC) is based on single institutional series. Therefore, we carried out a population-based audit of OBC practice and outcomes in Scotland. Methods: A predefined database of patients treated with OBC was completed retrospectively in all breast units practicing OBC in Scotland. Results: 589 patients were included from 11 units. Patients were diagnosed between September 2005 and March 2017. High volume units performed a mean of 19.3 OBCs per year vs. low volume units who did 11.1 (p = 0.012). 23 different surgical techniques were used. High volume units offered a wider range of techniques (8–14) than low volume units (3–6) (p = 0.004). OBC was carried out as a joint operation involving a breast and a plastic surgeon in 389 patients. Immediate contralateral symmetrisation rate was significantly higher when OBC was performed as a joint operation (70.7% vs. not joint operations: 29.8%; p &lt; 0.001). The incomplete excision rate was 10.4% and was significantly higher after surgery for invasive lobular carcinoma (18.9%; p = 0.0292), but was significantly lower after neoadjuvant chemotherapy (3%; p = 0.031). 9.2% of patients developed major complications requiring hospital admission. Overall the complication rate was significantly lower after neoadjuvant chemotherapy (p = 0.035). The 5 year local recurrence rate was 2.7%, which was higher after OBC for DCIS (8.3%) than invasive ductal cancer (1.6%; p = 0.026). 5-year disease-free survival was 91.7%, overall survival was 93.8%, and cancer-specific survival was 96.1%. Conclusion: This study demonstrated that measured outcomes of OBC in a population-based multi-centre setting can be comparable to the outcomes of large volume single centre series

Recent advances in methodology for clinical trials in small populations : the InSPiRe project

Where there are a limited number of patients, such as in a rare disease, clinical trials in these small populations present several challenges, including statistical issues. This led to an EU FP7 call for proposals in 2013. One of the three projects funded was the Innovative Methodology for Small Populations Research (InSPiRe) project. This paper summarizes the main results of the project, which was completed in 2017. The InSPiRe project has led to development of novel statistical methodology for clinical trials in small populations in four areas. We have explored new decision-making methods for small population clinical trials using a Bayesian decision-theoretic framework to compare costs with potential benefits, developed approaches for targeted treatment trials, enabling simultaneous identification of subgroups and confirmation of treatment effect for these patients, worked on early phase clinical trial design and on extrapolation from adult to pediatric studies, developing methods to enable use of pharmacokinetics and pharmacodynamics data, and also developed improved robust meta-analysis methods for a small number of trials to support the planning, analysis and interpretation of a trial as well as enabling extrapolation between patient groups. In addition to scientific publications, we have contributed to regulatory guidance and produced free software in order to facilitate implementation of the novel methods