Safety arguments for next generation location aware computing

Concerns over the accuracy, availability, integrity and continuity of Global Navigation Satellite Systems (GNSS) have limited the integration of GPS and GLONASS for safety-critical applications. More recent augmentation systems, such as the European Geostationary Navigation Overlay Service (EGNOS) and the North American Wide Area Augmentation System (WAAS) have begun to address these concerns. Augmentation architectures build on the existing GPS/GLONASS infrastructures to support locationbased services in Safety of Life (SoL) applications. Much of the technical development has been directed by air traffic management requirements, in anticipation of the more extensive support to be offered by GPS III and Galileo. WAAS has already been approved to provide vertical guidance against ICAO safety performance criteria for aviation applications. During the next twelve months, we will see the full certification of EGNOS for SoL applications. This paper identifies strong similarities between the safety assessment techniques used in Europe and North America. Both have relied on hazard analysis techniques to derive estimates of the Probability of Hazardously Misleading Information (PHMI). Later sections identify significant differences between the approaches adopted in application development. Integrated fault trees have been developed by regulatory and commercial organisations to consider both infrastructure hazards and their impact on non-precision RNAV/VNAV approaches using WAAS. In contrast, EUROCONTROL and the European Space Agency have developed a more modular approach to safety-case development for EGNOS. It remains to be seen whether the European or North American strategy offers the greatest support as satellite based augmentation systems are used within a growing range of SoL applications from railway signalling through to Unmanned Airborne Systems. The key contribution of this paper is to focus attention on the safety arguments that might support this wider class of location based services

The Role of Trust and Interaction in GPS Related Accidents: A Human Factors Safety Assessment of the Global Positioning System (GPS)

The Global Positioning System (GPS) uses a network of orbiting and geostationary satellites to calculate the position of a receiver over time. This technology has revolutionised a wide range of safety-critical industries and leisure applications ranging from commercial fisheries through to mountain running. These systems provide diverse benefits; supplementing the users existing navigation skills and reducing the uncertainty that often characterises many route planning tasks. GPS applications can also help to reduce workload by automating tasks that would otherwise require finite cognitive and perceptual resources. However, the operation of these systems has been identified as a contributory factor in a range of recent accidents. Users often come to rely on GPS applications and, therefore, fail to notice when they develop faults or when errors occur in the other systems that use the data from these systems. Further accidents can stem from the ‘over confidence’ that arises when users assume automated warnings will be issued when they stray from an intended route. Unless greater attention is paid to the human factors of GPS applications then there is a danger that we will see an increasing number of these failures as positioning technologies are integrated into increasing numbers of application

Entire solutions of hydrodynamical equations with exponential dissipation

We consider a modification of the three-dimensional Navier--Stokes equations and other hydrodynamical evolution equations with space-periodic initial conditions in which the usual Laplacian of the dissipation operator is replaced by an operator whose Fourier symbol grows exponentially as \ue ^{|k|/\kd} at high wavenumbers $|k|$. Using estimates in suitable classes of analytic functions, we show that the solutions with initially finite energy become immediately entire in the space variables and that the Fourier coefficients decay faster than \ue ^{-C(k/\kd) \ln (|k|/\kd)} for any $C<1/(2\ln 2)$. The same result holds for the one-dimensional Burgers equation with exponential dissipation but can be improved: heuristic arguments and very precise simulations, analyzed by the method of asymptotic extrapolation of van der Hoeven, indicate that the leading-order asymptotics is precisely of the above form with $C= C_\star =1/\ln2$. The same behavior with a universal constant $C_\star$ is conjectured for the Navier--Stokes equations with exponential dissipation in any space dimension. This universality prevents the strong growth of intermittency in the far dissipation range which is obtained for ordinary Navier--Stokes turbulence. Possible applications to improved spectral simulations are briefly discussed.Comment: 29 pages, 3 figures, Comm. Math. Phys., in pres

FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m2, P = 1.9 × 10−105), and all participants (0.30 [0.30, 0.35] kg/m2, P = 3.6 × 10−107). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10−16), and relative weak associations with lower total energy intake (−6.4 [−10.1, −2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (−0.07 [−0.11, −0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10−9) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposit

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4

Functional Annotation of ESR1 Gene Fusions in Estrogen Receptor-Positive Breast Cancer

RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor-positive (ER+) breast cancer, but their role in disease pathogenesis remains unclear. We examined multiple ESR1 fusions and found that two, both identified in advanced endocrine treatment-resistant disease, encoded stable and functional fusion proteins. In both examples, ESR1-e6&gt;YAP1 and ESR1-e6&gt;PCDH11X, ESR1 exons 1–6 were fused in frame to C-terminal sequences from the partner gene. Functional properties include estrogen-independent growth, constitutive expression of ER target genes, and anti-estrogen resistance. Both fusions activate a metastasis-associated transcriptional program, induce cellular motility, and promote the development of lung metastasis. ESR1-e6&gt;YAP1- and ESR1-e6&gt;PCDH11X-induced growth remained sensitive to a CDK4/6 inhibitor, and a patient-derived xenograft (PDX) naturally expressing the ESR1-e6&gt;YAP1 fusion was also responsive. Transcriptionally active ESR1 fusions therefore trigger both endocrine therapy resistance and metastatic progression, explaining the association with fatal disease progression, although CDK4/6 inhibitor treatment is predicted to be effective. Lei et al. show that transcriptionally active estrogen receptor gene (ESR1) fusions identified from late-stage, treatment-refractory estrogen receptor-positive (ER+) breast cancer drive pan-endocrine therapy resistance and metastatic progression. Growth of breast tumors driven by ESR1 fusions at primary and metastatic sties can be suppressed with a CDK4/6 inhibitor