Acceptance Criteria for Critical Software Based on Testability Estimates and Test Results

Testability is defined as the probability that a program will fail a test, conditional on the program containing some fault. In this paper, we show that statements about the testability of a program can be more simply described in terms of assumptions on the probability distribution of the failure intensity of the program. We can thus state general acceptance conditions in clear mathematical terms using Bayesian inference. We develop two scenarios, one for software for which the reliability requirements are that the software must be completely fault-free, and another for requirements stated as an upper bound on the acceptable failure probability

Computational materials design of crystalline solids

The modelling of materials properties and processes from first principles is becoming sufficiently accurate as to facilitate the design and testing of new systems in silico. Computational materials science is both valuable and increasingly necessary for developing novel functional materials and composites that meet the requirements of next-generation technology. A range of simulation techniques are being developed and applied to problems related to materials for energy generation, storage and conversion including solar cells, nuclear reactors, batteries, fuel cells, and catalytic systems. Such techniques may combine crystal-structure prediction (global optimisation), data mining (materials informatics) and high-throughput screening with elements of machine learning. We explore the development process associated with computational materials design, from setting the requirements and descriptors to the development and testing of new materials. As a case study, we critically review progress in the fields of thermoelectrics and photovoltaics, including the simulation of lattice thermal conductivity and the search for Pb-free hybrid halide perovskites. Finally, a number of universal chemical-design principles are advanced

Tissue engineering and ENT surgery

Tissue engineering is the development of biological substitutes for the repair and regeneration of damaged tissues. We explain the principles of this emerging field of biotechology. The present and potential applications of tissue engineering technologies in ENT surgery are then reviewed

The Plant-Derived Chalcone 2,2',5'-Trihydroxychalcone Provides Neuroprotection against Toll-Like Receptor 4 Triggered Inflammation in Microglia

Chalcones are plant metabolites with potential for therapeutic exploitation as antioxidant, anti-inflammatory, and antiproliferative agents. Here we explored the neuroprotective effects of 2,2',5'-trihydroxychalcone (225THC), a potent antioxidant with radical-scavenging properties. 225THC was found to be a potent inhibitor of apoptosis in stimulated primary rat neuronal cultures. This was likely mediated by an anti-inflammatory effect on microglial cells since 225THC inhibited LPS-stimulated TNF-α and IL-6 secretion from primary rat microglia and modulated the cytokine/chemokine profile of BV2 microglial cells. Additionally, 225THC inhibited LPS-evoked inducible nitric oxide synthase expression but did not influence endogenous superoxide generation. Microglial flow cytometric analyses indicated the 225THC treatment induced a shift from an M1-like phenotype to a more downregulated microglial profile. Taken together these data suggest that the chalcone 2,2',5'-trihydroxychalcone can modulate neuroinflammatory activation in brain-derived microglia and holds promise as a therapeutic in neuroinflammatory conditions

Laplace approximation of Lauricella functions F A and F D

The Lauricella functions, which are generalizations of the Gauss hypergeometric function 2 F 1, arise naturally in many areas of mathematics and statistics. So far as we are aware, there is little or nothing in the literature on how to calculate numerical approximations for these functions outside those cases in which a simple one-dimensional integral representation or a one-dimensional series representation is available. In this paper we present first-order and second-order Laplace approximations to the Lauricella functions F(n)A and F(n)D. Our extensive numerical results show that these approximations achieve surprisingly good accuracy in a wide variety of examples, including cases well outside the asymptotic framework within which the approximations were derived. Moreover, it turns out that the second-order Laplace approximations are usually more accurate than their first-order versions. The numerical results are complemented by theoretical investigations which suggest that the approximations have good relative error properties outside the asymptotic regimes within which they were derived, including in certain cases where the dimension n goes to infinity

Could misreporting of condom use explain the observed association between injectable hormonal contraceptives and HIV acquisition risk?

OBJECTIVE: Some observational studies have suggested an association between the use of hormonal contraceptives (HC) and HIV acquisition. One major concern is that differential misreporting of sexual behavior between HC users and nonusers may generate artificially inflated risk estimates. STUDY DESIGN: We developed an individual-based model that simulates the South African HIV serodiscordant couples analyzed for HC-HIV risk by Heffron et al. (2012). We varied the pattern of misreporting condom use between HC users and nonusers and reproduced the trial data under the assumption that HC use is not associated with HIV risk. The simulated data were analyzed using Cox proportional hazards models, adjusting for the reported level of condom use. RESULTS: If HC users overreport condom use more than nonusers, an apparent excess risk could be observed even without any biological effect of HC on HIV acquisition. With 45% overreporting by HC users (i.e., 9 out of every 20 sex acts reported with condoms are actually unprotected) and accurate condom reporting by nonusers, a true null effect can be inflated to give an observed hazard ratio (HR̂) of 2.0. In a different population with lower overall reported condom use, artificially high HR̂s can only be generated if non-HC users underreport condom use. CONCLUSION: Differential condom misreporting can theoretically produce inflated HR̂ values for an association between HC and HIV even without a true association. However, to produce a doubling of HIV risk that is entirely spurious requires substantially different levels of misreporting among HC users and nonusers, which may be unrealistic. IMPLICATIONS: Considerably differential amounts of condom use misreporting by HC users and nonusers would be needed to produce entirely spurious observed levels of excess HIV acquisition risk among HC users when there is actually no true association

A Child's Concept of Pain: An International Survey of Pediatric Pain Experts.

A child's 'concept of pain' refers to how they understand what pain actually is, what function pain serves, and what biological processes are thought to underpin it. We aimed to determine pediatric pain experts' opinions of: (1) the importance and usefulness of assessing a child's concept of pain in clinical and/or research settings; (2) the usefulness of the content of items within currently published adult-targeted resources for assessing a child's concept of pain; and (3) important domains of a child's concept of pain to assess. Forty-nine pediatric pain experts (response rate = 75.4%) completed an online survey. Descriptive statistics and frequency of responses were analyzed. Experts from all included disciplines reported that assessing a child's concept of pain is important and useful both clinically and in a research setting (>80% reported very or extremely useful for each item). Experts considered that the content of 13 items from currently published adult-targeted resources was useful, but the wording was too complex for children aged 8-12 years. Experts considered that all seven of the proposed domains of a child's concept of pain was important to assess. The findings can be used to inform the development of an assessment tool for a child's concept of pain

Demanding stories: television coverage of sustainability, climate change and material demand

This paper explores the past, present and future role of broadcasting, above all via the medium of television, in shaping how societies talk, think about and act on climate change and sustainability issues. The paper explores these broad themes via a focus on the important but relatively neglected issue of material demand and opportunities for its reduction. It takes the outputs and decision-making of one of the world’s most influential broadcasters, the BBC, as its primary focus. The paper considers these themes in terms of stories, touching on some of the broader societal frames of understanding into which they can be grouped. Media decision-makers and producers from a range of genres frequently return to the centrality of ‘story’ in the development, commissioning and production of an idea. With reference to specific examples of programming, and drawing on interviews with media practitioners, the paper considers the challenges of generating broadcast stories that can inspire engagement in issues around climate change, and specifically material demand. The concluding section proposes actions and approaches that might help to establish material demand reduction as a prominent way of thinking about climate change and environmental issues more widely. This article is part of the themed issue ‘Material demand reduction’

Introduction: Interrogating the 'everyday' politics of emotions in international relations

The focus on the everyday in this Special Issue reveals different kinds of emotional practices, their political effects and their political contestation within both micro- and macro-politics in international relations. The articles in this Special Issue address the everyday negotiation of emotions, shifting between the reproduction of hegemonic structures of feelings and emancipation from them. In other words, the everyday politics of emotions allows an exploration of who gets to express emotions, what emotions are perceived as (il)legitimate or (un)desirable, how emotions are circulated and under what circumstances. Consequently, we identify two thematic strands which emerge as central to an interrogation of ‘everyday’ emotions in international relations and which run through each of the contributions: first, an exploration of the relationship between individual and collective emotions and, second, a focus on the role of embodiment within emotions research and its relationship with the dynamics and structures of power

Building an international network for a primary care research program: reflections on challenges and solutions in the set-up and delivery of a prospective observational study of acute cough in 13 European countries

BACKGROUND: Implementing a primary care clinical research study in several countries can make it possible to recruit sufficient patients in a short period of time that allows important clinical questions to be answered. Large multi-country studies in primary care are unusual and are typically associated with challenges requiring innovative solutions. We conducted a multi-country study and through this paper, we share reflections on the challenges we faced and some of the solutions we developed with a special focus on the study set up, structure and development of Primary Care Networks (PCNs).METHOD: GRACE-01 was a multi-European country, investigator-driven prospective observational study implemented by 14 Primary Care Networks (PCNs) within 13 European Countries. General Practitioners (GPs) recruited consecutive patients with an acute cough. GPs completed a case report form (CRF) and the patient completed a daily symptom diary. After study completion, the coordinating team discussed the phases of the study and identified challenges and solutions that they considered might be interesting and helpful to researchers setting up a comparable study.RESULTS: The main challenges fell within three domains as follows:i) selecting, setting up and maintaining PCNs;ii) designing local context-appropriate data collection tools and efficient data management systems; andiii) gaining commitment and trust from all involved and maintaining enthusiasm.The main solutions for each domain were:i) appointing key individuals (National Network Facilitator and Coordinator) with clearly defined tasks, involving PCNs early in the development of study materials and procedures.ii) rigorous back translations of all study materials and the use of information systems to closely monitor each PCNs progress;iii) providing strong central leadership with high level commitment to the value of the study, frequent multi-method communication, establishing a coherent ethos, celebrating achievements, incorporating social events and prizes within meetings, and providing a framework for exploitation of local data.CONCLUSIONS: Many challenges associated with multi-country primary care research can be overcome by engendering strong, effective communication, commitment and involvement of all local researchers. The practical solutions identified and the lessons learned in implementing the GRACE-01 study may assist in establishing other international primary care clinical research platforms