Boosting and lassoing new prostate cancer SNP risk factors and their connection to selenium

We begin by arguing that the often used algorithm for the discovery and use of disease risk factors, stepwise logistic regression, is unstable. We then argue that there are other algorithms available that are much more stable and reliable (e.g. the lasso and gradient boosting). We then propose a protocol for the discovery and use of risk factors using lasso or boosting variable selection. We then illustrate the use of the protocol with a set of prostate cancer data and show that it recovers known risk factors. Finally, we use the protocol to identify new and important SNP based risk factors for prostate cancer and further seek evidence for or against the hypothesis of an anticancer function for Selenium in prostate cancer. We find that the anticancer effect may depend on the SNP-SNP interaction and, in particular, which alleles are present

Displaced geostationary orbits using hybrid low-thrust propulsion

In this paper, displaced geostationary orbits using hybrid low-thrust propulsion, a complementary combination of Solar Electric Propulsion (SEP) and solar sailing, are investigated to increase the capacity of the geostationary ring that is starting to become congested. The SEP propellant consumption is minimized in order to maximize the mission lifetime by deriving semi-analytical formulae for the optimal steering laws for the SEP and solar sail accelerations. By considering the spacecraft mass budget, the performance is also expressed in terms of payload mass capacity. The analyses are performed both for the use of pure SEP and hybrid low-thrust propulsion to allow for a comparison. It is found that hybrid low-thrust control outperforms the pure SEP case both in terms of payload mass capacity and mission lifetime for all displacements considered. Hybrid low-thrust propulsion enables payloads of 255 to 487 kg to be maintained in a 35 km displaced orbit for 10 to 15 years. Adding the influence of the J2 and J22 terms of the Earth’s gravity field has a small effect on this lifetime, which becomes almost negligible for small values of the sail lightness number. Finally, two SEP transfers that allow for an improvement in the performance of hybrid low-thrust control are optimized for the propellant consumption by solving the accompanying optimal control problem using a direct pseudospectral method. The first type of transfer enables a transit between orbits displaced above and below the equatorial plane, while the second type of transfer enables customized service for which a spacecraft is transferred to a Keplerian parking orbit when geostationary coverage is not needed. While the latter requires a modest propellant budget, the first type of transfer comes at the cost of an almost negligible SEP propellant consumption

The Neurobiology of Fear Generalization

The generalization of fear memories is an adaptive neurobiological process that promotes survival in complex and dynamic environments. When confronted with a potential threat, an animal must select an appropriate defensive response based on previous experiences that are not identical, weighing cues and contextual information that may predict safety or danger. Like other aspects of fear memory, generalization is mediated by the coordinated actions of prefrontal, hippocampal, amygdalar, and thalamic brain areas. In this review article, we describe the current understanding of the behavioral, neural, genetic, and biochemical mechanisms involved in the generalization of fear. Fear generalization is a hallmark of many anxiety and stress-related disorders, and its emergence, severity, and manifestation are sex-dependent. Therefore, to improve the dialog between human and animal studies as well as to accelerate the development of effective therapeutics, we emphasize the need to examine both sex differences and remote timescales in rodent models

Abnormal LDIflare but Normal Quantitative Sensory Testing and Dermal Nerve Fiber Density in Patients with Painful Diabetic Neuropathy

OBJECTIVE—Abnormal small nerve fiber function may be an early feature of diabetic neuropathy and may also underlie painful symptoms. Methods for assessing small-fiber damage include quantitative sensory testing (QST) and determining intraepidermal nerve fiber density. We recently described a reproducible physiological technique, the LDIflare, which assesses small-fiber function and thus may reflect early dysfunction before structural damage. The value of this technique in painful neuropathy was assessed by comparing it with QST and dermal nerve fiber density (NFD)

Designing and Implementing a Novel Graduate Program to Develop Transdisciplinary Leaders in Urban Sustainability

Urban settings, where \u3e50% of the world\u27s population resides, are increasingly faced with environmental challenges that threaten their sustainability. Aging infrastructure, water and air pollution, and increasing recognition of environmental injustices highlight the need for professionals to employ complex scientific reasoning across disciplines where they can effectively address the multifaceted issues of urban sustainability. Here we present an innovative model for preparing the next generation of public, private, and academic leaders to address complex problems in urban sustainability. Specifically, we outline the design and implementation of an integrated, adaptable graduate training program, with the goals of science leadership, curriculum relevancy, community impact, broader applicability, establishing a career development pathway in science, technology, engineering, and mathematics (STEM) programs, and program sustainability. This program addresses human-ecosystem challenges using a transdisciplinary approach to produce scientific products in partnership with local communities, businesses, industries, scientists, and policy makers, while providing a mechanism to understand and overcome contemporary societal and ecological challenges. Students receive rigorous training in their home disciplines, coupled with training across disciplinary lines and developmental experiences, to prepare them to communicate, collaborate, and innovate in a variety of contexts. Training success is evaluated across measurable competency domains including problem definition, research methods, communication, collaboration, and problem-solving. After 3 years the program expanded relationships across fields and professions, successfully established 18 internship opportunities with community partners, created a new dual-title PhD program open to students in five academic departments, and facilitated the coproduction of knowledge with external partners. This model bridges the gaps between research, education, and application, providing an integrated, rigorous graduate training program that fosters collaborative problem-solving between STEM graduate students and the broader community of professionals conducting sustainability work in a postindustrial urban setting

Dawn arrives at Ceres: Exploration of a small, volatile-rich world

On 6 March 2015, Dawn arrived at Ceres to find a dark, desiccated surface punctuated by small, bright areas. Parts of Ceres’ surface are heavily cratered, but the largest expected craters are absent. Ceres appears gravitationally relaxed at only the longest wavelengths, implying a mechanically strong lithosphere with a weaker deep interior. Ceres’ dry exterior displays hydroxylated silicates, including ammoniated clays of endogenous origin. The possibility of abundant volatiles at depth is supported by geomorphologic features such as flat crater floors with pits, lobate flows of materials, and a singular mountain that appears to be an extrusive cryovolcanic dome. On one occasion, Ceres temporarily interacted with the solar wind, producing a bow shock accelerating electrons to energies of tens of kilovolts

Effectiveness of continuous glucose monitoring in pregnant women with diabetes: randomised clinical trial

Objective To evaluate the effectiveness of continuous glucose monitoring during pregnancy on maternal glycaemic control, infant birth weight, and risk of macrosomia in women with type 1 and type 2 diabetes

Sex Differences in Remote Contextual Fear Generalization in Mice

The generalization of fear is adaptive in that it allows an animal to respond appropriately to novel threats that are not identical to previous experiences. In contrast, the overgeneralization of fear is maladaptive and is a hallmark of post-traumatic stress disorder (PTSD), a psychiatric illness that is characterized by chronic symptomatology and a higher incidence in women compared to men. Therefore, understanding the neural basis of fear generalization at remote time-points in female animals is of particular translational relevance. However, our understanding of the neurobiology of fear generalization is largely restricted to studies employing male mice and focusing on recent time-points (i.e., within 24–48 h following conditioning). To address these limitations, we examined how male and female mice generalize contextual fear at remote time intervals (i.e., 3 weeks after conditioning). In agreement with earlier studies of fear generalization at proximal time-points, we find that the test order of training and generalization contexts is a critical determinant of generalization and context discrimination, particularly for female mice. However, tactile elements that are present during fear conditioning are more salient for male mice. Our study highlights long-term sex differences in defensive behavior between male and female mice and may provide insight into sex differences in the processing and retrieval of remote fear memory observed in humans

On the deflection of asteroids with mirrors

This paper presents an analysis of an asteroid deflection method based on multiple solar concentrators. A model of the deflection through the sublimation of the surface material of an asteroid is presented, with simulation results showing the achievable orbital deflection with, and without, accounting for the effects of mirror contamination due to the ejected debris plume. A second model with simulation results is presented analyzing an enhancement of the Yarkovsky effect, which provides a significant deflection even when the surface temperature is not high enough to sublimate. Finally the dynamical model of solar concentrators in the proximity of an irregular celestial body are discussed, together with a Lyapunov-based controller to maintain the spacecraft concentrators at a required distance from the asteroid

Perioperative passport: empowering people with diabetes along their surgical journey

© 2017 Diabetes UK Aim: To determine whether a handheld ‘perioperative passport’ could improve the experience of perioperative care for people with diabetes and overcome some of the communication issues commonly identified in inpatient extracts. Methods: Individuals with diabetes undergoing elective surgery requiring at least an overnight stay were identified via a customized information technology system. Those allocated to the passport group were given the perioperative passport before their hospital admission. A 26-item questionnaire was completed after surgery by 50 participants in the passport group (mean age 69 years) and by 35 participants with diabetes who followed the usual surgical pathway (mean age 70 years). In addition, the former group had a structured interview about their experience of the passport. Results: The prevalence of those who reported having received prior information about their expected diabetes care was 35% in the control group vs 92% in the passport group (