Context Detection, Categorization and Connectivity for Advanced Adaptive Integrated Navigation

Context is the environment that a navigation system operates in and the behaviour of its host vehicle or user. The type and quality of signals and environmental features available for positioning varies with the environment. For example, GNSS provides high-quality positioning in open environments, low-quality positioning in dense urban environments and no solution at all deep indoors. The behaviour of the host vehicle (or pedestrian) is also important. For example, pedestrian, car and train navigation all require different map-matching techniques, different motion constraints to limit inertial navigation error growth, and different dynamic models in a navigation filter [1]. A navigation system design should therefore be matched to its context. However, the context can change, particularly for devices, such as smartphones, which move between indoor and outdoor environments and can be stationary, on a pedestrian, or in a vehicle. For best performance, a navigation system should therefore be able to detect its operating context and adapt accordingly; this is context-adaptive positioning [1]. Previous work on context-adaptive navigation and positioning has focused on individual subsystems. For example, there has been substantial research into determining the motion type and sensor location for pedestrian dead reckoning using step detection [2-4]. Researchers have also begun to investigate context-adaptive (or cognitive) GNSS [5-7]. However, this paper considers context adaptation across an integrated navigation system as a whole. The paper addresses three aspects of context-adaptive integrated navigation: context detection, context categorization and context connectivity. It presents experimental results showing how GNSS C/N0 measurements, frequency-domain MEMS inertial sensor measurements and Wi-Fi signal availability could be used to detect both the environmental and behavioural contexts. It then looks at how context information could be shared across the different components of an integrated navigation system. Finally, the concept of context connectivity is introduced to improve the reliability of context detection. GNSS C/N0 measurement distributions, obtained using a smartphone, and Wi-Fi reception data collected over a range of indoor, urban and open environments will be compared to identify suitable features from which the environmental context may be derived. In an open environment, strong GNSS signals will be received from all directions. In an urban environment, fewer strong signals will be received and only from certain directions. Inside a building, nearly all GNSS signals will be much weaker than outside. Wi-Fi signals essentially vary with the environment in the opposite way to GNSS. Indoors, more access points (APs) can be received at higher signal strengths and there is greater variation in RSS. In urban environments, large numbers of APs can still be received, but at lower signal strengths [6]. Finally, in open environments, few APs, if any, will be received. Behavioural context is studied using an IMU. Although an Xsens MEMS IMU is used in this study, smartphone inertial sensors are also suitable. Pedestrian, car and train data has been collected under a range of different motion types and will be compared to identify context-dependent features. Early indications are that, as well as detecting motion, it is also possible to distinguish nominally-stationary IMUs that are placed in a car, on a person or on a table from the frequency spectra of the sensor measurements. The exchange of context information between subsystems in an integrated navigation system requires agreement on the definitions of those contexts. As different subsystems are often supplied by different organisations, it is desirable to standardize the context definitions across the whole navigation and positioning community. This paper therefore proposes a framework upon which a “context dictionary” could be constructed. Environmental and behavioural contexts are categorized separately and a hierarchy of attributes is proposed to enable some subsystems to work with highly specific context categories and others to work with broader categories. Finally, the concept of context connectivity is introduced. This is analogous to the road link connectivity used in map matching [8]. As context detection involves the matching of measurement data to stored context profiles, there will always be occurrences of false or ambiguous context identification. However, these may be minimized by using the fact that it is only practical to transition directly between certain pairs of contexts. For example, it is not normally possible to move directly from an airborne to an indoor environment as an aircraft must land first. Thus, the air and land contexts are connected, as are the land and indoor contexts, but the air and indoor contexts are not. Thus, by only permitting contexts that are connected to the previous context, false and ambiguous context detection is reduced. Robustness may be further enhanced by considering location-dependent connectivity. For example, people normally board and leave trains at stations and fixed-wing aircraft typically require an airstrip to take off and land. / References [1] Groves, P. D., Principles of GNSS, inertial, and multi-sensor integrated navigation systems, Second Edition, Artech House, 2013. [2] Park, C. G., et al., “Adaptive Step Length Estimation with Awareness of Sensor Equipped Location for PNS,” Proc. ION GNSS 2007. [3] Frank, K., et al., “Reliable Real-Time Recognition of Motion Related Human Activities Using MEMS Inertial Sensors,” Proc. ION GNSS 2010. [4] Pei, L., et al., “Using Motion-Awareness for the 3D Indoor Personal Navigation on a Smartphone,” Proc. ION GNSS 2011. [5] Lin, T., C. O’Driscoll, and G. Lachapelle, “Development of a Context-Aware Vector-Based High-Sensitivity GNSS Software Receiver,” Proc. ION ITM 2011. [6] Shafiee, M., K., O’Keefe, and G. Lachapelle, “Context-aware Adaptive Extended Kalman Filtering Using Wi-Fi Signals for GPS Navigation,” Proc. ION GNSS 2011. [7] Shivaramaiah, N. C., and A. G. Dempster, “Cognitive GNSS Receiver Design: Concept and Challenges,” Proc. ION GNSS 2011. [8] Quddus, M. A., High Integrity Map Matching Algorithms for Advanced Transport Telematics Applications, PhD Thesis, Imperial College London, 2006

Novel Environmental Features for Robust Multisensor Navigation

Many navigation techniques have now become so reliant on GNSS that there is no back up when there is limited or no signal reception. If there is interference, intentional or otherwise, with the signal, navigation could be lost or become misleading [1]. Other navigation techniques harness different technologies such as Wi-Fi [2], eLoran and inertial navigation. However, each of these techniques has its own limitations, such as coverage, degradation in urban areas or solution drift [3]. Therefore there is a need for new navigation and positioning techniques that may be integrated with GNSS to increase the reliability of the system as a whole. This paper presents the results of a feasibility study to identify a set of novel environmental features that could be used for navigation in the temporary absence of GNSS or degradation of the signal. By measuring these features during times of GNSS availability a map can be produced. This can be referred to during times of limited reception, a principle already used for some Wi-Fi positioning techniques [2]. Therefore a “measurable” can be defined as a feature either man-made or natural that is spatially distinct and has limited temporal variation. Possibilities considered include magnetic anomalies [4], light intensity and road signs. Firstly, a brainstorming exercise and a literature study were conducted to generate a list of possible environmental features that was assessed for the viability of each candidate. The features were ranked according to three criteria: practicality, precision and coverage. The definition of practicality for each measurable was that a suitable detector must be installable on a road vehicle, particularly an emergency vehicle, at a reasonable cost with minimal alterations to the vehicle. Precision was defined in terms of the spatial variation of the environmental feature and thus the accuracy with which position information might be derived from it. Coverage was assessed in terms of the availability of the feature over a range of different environments. Continuous coverage is not required because the new measurables may be used in combination and integrated with dead reckoning techniques, such as odometry and inertial navigation [3]. The outcome of the viability study was used to determine which features are to be experimentally tested. Magnetic anomalies, road texture and a dozen other environmental features were found to be worth investigation. Features which were discounted include wind speed and pulsars [5]. The initial experiment was carried out on foot in Central London. The same tests were repeated on two separate days, with a closed loop circuit walked three times on each occasion. This experiment used an Inertial Measurement Unit (IMU), comprising accelerometer and gyro triads, together with a barometer, three-axis magnetometer and GNSS receiver. The experiment was also recorded using a camcorder from the point of view of a pedestrian, enabling visual and audio features of the environment to be assessed. Magnetic anomalies were found to be a promising source of position information. Peaks in the magnetometer data were observed on all rounds at approximately the same positions. There were also similarities seen in the temperature profiles after correcting for the temporal variation of the background temperature. Another potential source of position information was found to be text-based signs. It is relatively simple to extract text from camera images and it is easily stored in a feature database. However, methods of dealing with identically-worded signs in close proximity will need to be developed. Sound levels were analysed in 10s intervals for the mean, minimum and maximum sound volume. There was no clear correlation observed between the different rounds of the experiment. Due to the pedestrian experimental results sound levels of the surroundings will not be used in further experimentation. An alternative area of enquiry for using sound (in the vehicular experiments) is using microphones to indirectly measure road texture based on the noise from the wheel contact with the road [6]. The paper will also present results of road vehicle experiments. Multiple circuits of the same routes will be compared. Different environments will be assessed including rural, dual carriageways, suburban and urban roads. Sensors to be used include the IMU and 3-axis magnetometer from the pedestrian experiment, a barometer, gas sensors, a microphone, an axle-mounted accelerometer, an ambient light sensor and a thermometer. These will be placed either on, inside or under the vehicle as determined by the individual needs of the sensors. The results will be used to determine which of these sensors could be potentially used for a multisensor integrated navigation system and also the environments in which they work optimally. Using the results of the three feasibility study phases (literature review, pedestrian and road experiment) the next project stage will be to produce a demonstration system that uses the most feasible features of the environment and creates a map database during times GNSS is present. This database will then be used for navigation in times of need. In the long term, it is envisaged that this technique will be implemented cooperatively, with a batch of vehicles collecting feature data and contributing it to a common shared database. / References [1] Thomas, M., et al., Global Navigation Space Systems: Reliance and Vulnerabilities, London, UK: Royal Academy of Engineering, 2011. [2] Jones, K., L. Liu, and F. Alizadeh-Shabdiz, “Improving Wireless Positioning with Look-ahead Map-Matching,” Proc. MobiQuitous 2007, Phildaelphia, PA, February 2008, pp. 1-8. [3] Groves, P.D., Principles of GNSS, Inertial, and Multisensor Intergrated Navigation Systems, Second Edition, Artech House, 2013. [4] Judd, T., and T. Vu, “Use of a New Pedometric Dead Reckoning Module in GPS Denied Environments,” Proc. IEEE/ION PLANS, Monterey, CA, May 2008, pp. 120?128. [5] Walter, D. J., "Feasibility study of novel environmental feature mapping to bridge GNSS outage," Young Navigator Conference, London, 2012. [6] Mircea, M., et al., “Strategic mapping of the ambient noise produced by road traffic, accordingly to European regulations,” Proc. IEEE International Conference on Automation, Quality and Testing, Robotics, Cluj Napoca, Romania, May 2008

T1 mapping and T2 mapping at 3T for quantifying the area-at-risk in reperfused STEMI patients

BACKGROUND: Whether T1-mapping cardiovascular magnetic resonance (CMR) can accurately quantify the area-at-risk (AAR) as delineated by T2 mapping and assess myocardial salvage at 3T in reperfused ST-segment elevation myocardial infarction (STEMI) patients is not known and was investigated in this study. METHODS: 18 STEMI patients underwent CMR at 3T (Siemens Bio-graph mMR) at a median of 5 (4–6) days post primary percutaneous coronary intervention using native T1 (MOLLI) and T2 mapping (WIP #699; Siemens Healthcare, UK). Matching short-axis T1 and T2 maps covering the entire left ventricle (LV) were assessed by two independent observers using manual, Otsu and 2 standard deviation thresholds. Inter- and intra-observer variability, correlation and agreement between the T1 and T2 mapping techniques on a per-slice and per patient basis were assessed. RESULTS: A total of 125 matching T1 and T2 mapping short-axis slices were available for analysis from 18 patients. The acquisition times were identical for the T1 maps and T2 maps. 18 slices were excluded due to suboptimal image quality. Both mapping sequences were equally prone to susceptibility artifacts in the lateral wall and were equally likely to be affected by microvascular obstruction requiring manual correction. The Otsu thresholding technique performed best in terms of inter- and intra-observer variability for both T1 and T2 mapping CMR. The mean myocardial infarct size was 18.8 ± 9.4 % of the LV. There was no difference in either the mean AAR (32.3 ± 11.5 % of the LV versus 31.6 ± 11.2 % of the LV, P = 0.25) or myocardial salvage index (0.40 ± 0.26 versus 0.39 ± 0.27, P = 0.20) between the T1 and T2 mapping techniques. On a per-slice analysis, there was an excellent correlation between T1 mapping and T2 mapping in the quantification of the AAR with an R2 of 0.95 (P < 0.001), with no bias (mean ± 2SD: bias 0.0 ± 9.6 %). On a per-patient analysis, the correlation and agreement remained excellent with no bias (R2 0.95, P < 0.0001, bias 0.7 ± 5.1 %). CONCLUSIONS: T1 mapping CMR at 3T performed as well as T2 mapping in quantifying the AAR and assessing myocardial salvage in reperfused STEMI patients, thereby providing an alternative CMR measure of the the AAR

Quantifying the Area at Risk in Reperfused ST-Segment-Elevation Myocardial Infarction Patients Using Hybrid Cardiac Positron Emission Tomography-Magnetic Resonance Imaging

BACKGROUND: Hybrid positron emission tomography and magnetic resonance allows the advantages of magnetic resonance in tissue characterizing the myocardium to be combined with the unique metabolic insights of positron emission tomography. We hypothesized that the area of reduced myocardial glucose uptake would closely match the area at risk delineated by T2 mapping in ST-segment-elevation myocardial infarction patients. METHODS AND RESULTS: Hybrid positron emission tomography and magnetic resonance using (18)F-fluorodeoxyglucose (FDG) for glucose uptake was performed in 21 ST-segment-elevation myocardial infarction patients at a median of 5 days. Follow-up scans were performed in a subset of patients 12 months later. The area of reduced FDG uptake was significantly larger than the infarct size quantified by late gadolinium enhancement (37.2±11.6% versus 22.3±11.7%; P<0.001) and closely matched the area at risk by T2 mapping (37.2±11.6% versus 36.3±12.2%; P=0.10, R=0.98, bias 0.9±4.4%). On the follow-up scans, the area of reduced FDG uptake was significantly smaller in size when compared with the acute scans (19.5 [6.3%-31.8%] versus 44.0 [21.3%-55.3%]; P=0.002) and closely correlated with the areas of late gadolinium enhancement (R 0.98) with a small bias of 2.0±5.6%. An FDG uptake of ≥45% on the acute scans could predict viable myocardium on the follow-up scan. Both transmural extent of late gadolinium enhancement and FDG uptake on the acute scan performed equally well to predict segmental wall motion recovery. CONCLUSIONS: Hybrid positron emission tomography and magnetic resonance in the reperfused ST-segment-elevation myocardial infarction patients showed reduced myocardial glucose uptake within the area at risk and closely matched the area at risk delineated by T2 mapping. FDG uptake, as well as transmural extent of late gadolinium enhancement, acutely can identify viable myocardial segments

Cerebrospinal fluid biomarkers in cerebral amyloid angiopathy

BACKGROUND: There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA). OBJECTIVE: To determine the profile of biomarkers relevant to neurodegenerative disease in the CSF of patients with CAA. METHODS: We performed a detailed comparison of CSF markers, comparing patients with CAA, Alzheimer’s disease (AD), and control (CS) participants, recruited from the Biomarkers and Outcomes in CAA (BOCAA) study, and a Specialist Cognitive Disorders Service. RESULTS: We included 10 CAA, 20 AD, and 10 CS participants (mean age 68.6, 62.5, and 62.2 years, respectively). In unadjusted analyses, CAA patients had a distinctive CSF biomarker profile, with significantly lower (p < 0.01) median concentrations of Aβ_{38}, Aβ_{40}, Aβ_{42}, sAβPPα, and sAβPPβ. CAA patients had higher levels of neurofilament light (NFL) than the CS group (p < 0.01), but there were no significant differences in CSF total tau, phospho-tau, soluble TREM2 (sTREM2), or neurogranin concentrations. AD patients had higher total tau, phospho-tau and neurogranin than CS and CAA groups. In age-adjusted analyses, differences for the CAA group remained for Aβ_{38}, Aβ_{40}, Aβ_{42}, and sAβPPβ. Comparing CAA patients with amyloid-PET positive (n = 5) and negative (n = 5) scans, PET positive individuals had lower (p < 0.05) concentrations of CSF Aβ_{42}, and higher total tau, phospho-tau, NFL, and neurogranin concentrations, consistent with an “AD-like” profile. CONCLUSION: CAA has a characteristic biomarker profile, suggestive of a global, rather than selective, accumulation of amyloid species; we also provide evidence of different phenotypes according to amyloid-PET positivity. Further replication and validation of these preliminary findings in larger cohorts is needed

Promotion of Prescription Drugs to Consumers and Providers, 2001–2010

Background: Pharmaceutical firms heavily promote their products and may have changed marketing strategies in response to reductions in new product approvals, restrictions on some forms of promotion, and the expanding role of biologic therapies. Methods: We used descriptive analyses of annual cross-sectional data from 2001 through 2010 to examine direct-to-consumer advertising (DTCA) (Kantar Media) and provider-targeted promotion (IMS Health and SDI), including: (1) inflation-adjusted total promotion spending ($and percent of sales); (2) distribution by channel (consumer v. provider); and (3) provider specialty both for the industry as a whole and for top-selling biologic and small molecule therapies. Results: Total promotion peaked in 2004 at US$36.1 billion (13.4% of sales). By 2010 it had declined to $27.7B (9.0$370 million (8.8% of sales) spent on promotion, top biologics were promoted less, with only $33 million (1.4% of sales) spent per product. Little change occurred in the composition of promotion between primary care physicians and specialists from 2001–2010. Conclusions: These findings suggest that pharmaceutical companies have reduced promotion following changes in the pharmaceutical pipeline and patent expiry for several blockbuster drugs. Promotional strategies for biologic drugs differ substantially from small molecule therapies

Consumers as tutors – legitimate teachers?

BACKGROUND: The aim of this study was to research the feasibility of training mental health consumers as tutors for 4(th )year medical students in psychiatry. METHODS: A partnership between a consumer network and an academic unit in Psychological Medicine was formed to jointly develop a training package for consumer tutors and a curriculum in interviewing skills for medical students. Student attitudes to mental health consumers were measured pre and post the program. All tutorial evaluation data was analysed using univariate statistics. Both tutors and students evaluated the teaching program using a 4 point rating scale. The mean scores for teaching and content for both students and tutors were compared using an independent samples t-test. RESULTS: Consumer tutors were successfully trained and accredited as tutors and able to sustain delivery of tutorials over a 4 year period. The study found that whilst the medical students started with positive attitudes towards consumers prior to the program, there was a general trend towards improved attitude across all measures. Other outcomes for tutors and students (both positive and negative) are described. CONCLUSIONS: Consumer tutors along with professional tutors have a place in the education of medical students, are an untapped resource and deliver largely positive outcomes for students and themselves. Further possible developments are described

Methodological considerations in the analysis of fecal glucocorticoid metabolites in tufted capuchins (Cebus apella)

Analysis of fecal glucocorticoid (GC) metabolites has recently become the standard method to monitor adrenocortical activity in primates noninvasively. However, given variation in the production, metabolism, and excretion of GCs across species and even between sexes, there are no standard methods that are universally applicable. In particular, it is important to validate assays intended to measure GC production, test extraction and storage procedures, and consider the time course of GC metabolite excretion relative to the production and circulation of the native hormones. This study examines these four methodological aspects of fecal GC metabolite analysis in tufted capuchins (Cebus apella). Specifically, we conducted an adrenocorticotrophic hormone (ACTH) challenge on one male and one female capuchin to test the validity of four GC enzyme immunoassays (EIAs) and document the time course characterizing GC me- tabolite excretion in this species. In addition, we compare a common field-friendly technique for extracting fecal GC metabolites to an established laboratory extraction methodology and test for effects of storing “field extracts” for up to 1 yr. Results suggest that a corticosterone EIA is most sensitive to changes in GC production, provides reliable measures when extracted according to the field method, and measures GC metabolites which remain highly stable after even 12 mo of storage. Further, the time course of GC metabolite excretion is shorter than that described yet for any primate taxa. These results provide guidelines for studies of GCs in tufted capuchins, and underscore the importance of validating methods for fecal hormone analysis for each species of interest

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Myosin IIA Modulates T Cell Receptor Transport and CasL Phosphorylation during Early Immunological Synapse Formation

Activation of T cell receptor (TCR) by antigens occurs in concert with an elaborate multi-scale spatial reorganization of proteins at the immunological synapse, the junction between a T cell and an antigen-presenting cell (APC). The directed movement of molecules, which intrinsically requires physical forces, is known to modulate biochemical signaling. It remains unclear, however, if mechanical forces exert any direct influence on the signaling cascades. We use T cells from AND transgenic mice expressing TCRs specific to the moth cytochrome c 88–103 peptide, and replace the APC with a synthetic supported lipid membrane. Through a series of high spatiotemporal molecular tracking studies in live T cells, we demonstrate that the molecular motor, non-muscle myosin IIA, transiently drives TCR transport during the first one to two minutes of immunological synapse formation. Myosin inhibition reduces calcium influx and colocalization of active ZAP-70 (zeta-chain associated protein kinase 70) with TCR, revealing an influence on signaling activity. More tellingly, its inhibition also significantly reduces phosphorylation of the mechanosensing protein CasL (Crk-associated substrate the lymphocyte type), raising the possibility of a direct mechanical mechanism of signal modulation involving CasL