Concept and evaluation of a hybridization scheme for atom interferometers and inertial measurement units

By measuring accelerations and angular rates with the help of inertial measurement units (IMU), attitude, velocity and position of a mobile platform in motion can be computed. The integration of errors inherent to the signals leads to a drift of the solution over time. In order to reduce this drift while keeping the advantages of an autonomous measurement principle, quantum sensors are a promising concept. In experiments with cold atom interferometers (CAI), great sensitivities and long term stability for the measurement of accelerations and angular rates have been demonstrated. This technology uses wave-particle characteristics of atoms, which are manipulated by a series of light pulses in order to realize different interferometer schemes. In the Mach-Zehnder pulse pattern, the internal states are split, reversed and recombined, making the setup sensitive to accelerations as well as angular rates. Accurate measurement with this technology is limited to a small bandwidth of signals. The preparation of the atomic wave packet needs time in which the assembly is not able to measure. Additionally, the sinusoidal observation equation of the CAI is generally ambiguous. For those reasons, hybridization with high rate, large bandwidth conventional inertial sensors is the proposed scheme for mobile applications. Up to now, this combination has mainly been explored for stationary experiments with accelerometers only. A full quantum inertial navigation system (QINS) demands inclusion of gyroscope measurement as well as experiments in dynamic applications to validate the models and to further understand the behavior of CAI. The final step toward such a QINS consequently has not yet been taken. This thesis pursues an engineering approach to model CAI and QINS. Using methods from the navigation and physics community, a kinematic model for the center of mass of the atom wave packet is developed and applied, the velocity and position of the atoms computed, and the phase shift ambiguity solved. This allows to integrate gyroscope measurements in the formulation, as well as lever arm and misalignment between the sensor frame of the CAI and the IMU, enabling a parametrization of the often unknown transfer function between the systems. The error state kinematics of the wave packets furthermore allow an assessment of the limits of the CAI and the hybridization in the light of dynamic applications. With the help of an extended Kalman filter (EKF), the biases of the classical IMU are estimated. It can be shown that the acceleration biases are always observable, while the observability of the gyroscope biases demands a displacement or velocity of the atoms perpendicular to the sensitive axis. The requirements to observe state vector augmentations like misalignments and lever arms are discussed. The stability analysis results in a steady state formulation of the QINS. Under stationary conditions, the performance gain of the QINS is evaluated. It can be shown that the QINS navigation solution mainly profits from the long term stability of CAI. An additional focus of this study is the optimal configuration of CAI and IMU, supporting future system integrators in designing high performance QINS. Different designs are presented and evaluated, one centered on a complete IMU with high accuracy CAI support, yielding the best overall performance with positioning errors of less than ten meters after one hour of free inertial navigation, the other one centered on the CAI with high rate accelerometer support for applications under stationary conditions which further enhances the sensitivity to accelerations by an order of magnitude. The methods are demonstrated experimentally based on a static, one dimensional CAI data set. Furthermore, noise models for the application in the EKF are derived. The remaining methods under dynamic conditions are verified with the help of dedicated simulations.Durch Erfassung von Beschleunigungen und Drehraten mittels Trägheitssensorik (IMU) lassen sich die Orientierung, Geschwindigkeit und Position einer mobilen Plattform berechnen. Die Integration von Unsicherheiten in den Signalen führt zu einer allmählichen Drift der Lösung. Zur Reduktion dieser Drift bei gleichzeitiger Wahrung der Autonomie des Messprinzips sind Quantensensoren ein vielversprechendes Konzept. Experimente mit Atominterferometrie auf Basis kalter Atome (CAI) lassen auf hohe Genauigkeit und Stabilität der Messung von Beschleunigungen und Winkelgeschwindigkeiten hoffen. Diese Technologie macht sich WelleTeilchen-Eigenschaften der Atome zu Nutze, welche mittels gezielter Lichtpulse manipuliert werden um Informationen über Beschleunigungen und Drehraten zu extrahieren. Akurate Messungen sind jedoch auf kleine Bandbreiten der Signale limitiert. Dies liegt einerseits an der Zeit, die zur Kühlung der Atome benötigt wird und in welcher keine Messung möglich ist. Andererseits ist die sinusförmige Messgleichung des CAI im Allgemeinen mehrdeutig. Aus diesen Gründen ist eine Hybridisierung mit klassischen Inertialsensoren mit hoher Rate und großer Bandbreite ein oft diskutierter Ansatz für mobile Anwendungen. Diese Kombination wurde bisher hauptsächlich in stationären Experimenten unter Nutzung einzelner Beschleunigungsmesser untersucht. Ein vollständiges Quanteninertialnavigationssystem (QINS) erfordert die Einbeziehung von Gyroskopmessungen sowie Experimenten in dynamischen Anwendungen zur Validierung der Modelle und zum besseren Verständnis des Verhaltens von CAI. Die vorliegende Arbeit verfolgt einen ingenieurwissenschaftlichen Ansatz zur Modellierung von CAI und QINS. Unter Verwendung von Methoden aus der Navigations- und PhysikCommunity wird ein kinematisches Modell für den Massenschwerpunkt der Atom-Wellenpakete entwickelt, mit welchem sich die Geschwindigkeit und Position der Atome beschreiben und die Mehrdeutigkeit der Phasenverschiebung lösen lässt. Dadurch können Gyroskopmessungen sowie Hebelarm und Fehlausrichtung zwischen dem Sensorrahmen des CAI und der IMU in die Formulierung integriert werden, was eine Parametrisierung der oft unbekannten Übertragungsfunktion zwischen den Systemen ermöglicht. Die Fehlerzustandskinematik der Wellenpakete ermöglicht darüber hinaus eine Abschätzung der Grenzen des CAI und der Hybridisierung im Hinblick auf dynamische Anwendungen. Ein erweitertes Kalman-Filter (EKF) wird vorgestellt, mit dem sich systematische Fehler der klassischen IMU schätzen lassen. Im Rahmen einer Beobachtbarkeitsanalyse wird gezeigt, dass die Beschleunigungsbias immer beobachtbar sind, während die Schätzung der Drehratenbias eine Positionsverlagerung oder Geschwindigkeit der Atome senkrecht zur Messachse des CAI erfordert. Die Beobachtbarkeit weiterer systematischer Effekte wie Fehlausrichtung und Hebelarm wird diskutiert. Eine Steady-State Formulierung des QINS wird erarbeitet, welche eine Abschätzung des Performance-Gewinns des QINS ermöglicht. Den Ergebnissen zufolge wird die Verbesserung der Navigationslösung insbesondere durch die Langzeitstabilität des CAI erzielt. Ein zusätzlicher Schwerpunkt dieser Arbeit sind die Untersuchungen zu einer optimalen Konfiguration von CAI und IMU, welche Methoden und Formeln für den Entwurf zukünftiger hochperformanter QINS bieten. Es werden unterschiedliche QINS-Designs vorgestellt und bewertet. Eine Positionsgenauigkeit von weniger als zehn Metern nach einer Stunde freier inertialer Navigation scheint möglich, während sich unter stationären Bedingungen eine weitere Genauigkeitssteigerung der Beschleunigungsmessung um eine Größenordnung erzielen lässt. Die Methoden werden experimentell anhand eines statischen, eindimensionalen CAI-Datensatzes demonstriert. Darüber hinaus werden Rauschmodelle für den Einsatz im EKF abgeleitet. Anwendungen der Methodik unter dynamischen Bedingungen werden mit Hilfe dedizierter Simulationen verifiziert

The Effects of the A Matter of Balance Program on Falls and Physical Risk of Falls, Tampa, Florida, 2013

Introduction This study investigated the effects of the A Matter of Balance (MOB) program on falls and physical risk factors of falling among community-dwelling older adults living in Tampa, Florida, in 2013. Methods A total of 110 adults (52 MOB, 58 comparison) were enrolled in this prospective cohort study. Data on falls, physical risk of falling, and other known risk factors of falling were collected at baseline and at the end of the program. Multivariate analysis of covariance with repeated measures and logistic regressions were used to investigate the effects of this program. Results Participants in the MOB group were less likely to have had a fall and had significant improvements in their physical risk of falling compared with adults in the comparison group. No significant effects of the MOB program on recurrent falls or the number of falls reported were found. Conclusion This study contributes to our understanding of the MOB program and its effectiveness in reducing falls and the physical risk of falling among older adults. The findings support extended use of this program to reduce falls and physical risk of falling among older adults

Feasibility of a cognitive behavioural group intervention to reduce fear of falling and associated avoidance of activity in community-living older people: a process evaluation

BACKGROUND: Fear of falling and associated avoidance of activity are common among older people and may have negative consequences in terms of functional decline, quality of life and institutionalisation. We evaluated the effects of a cognitive behavioural group intervention to reduce fear of falling and associated avoidance of activity among older persons. This intervention showed favourable effects on fear of falling, avoidance of activity, daily activity, and several secondary outcomes. The aim of the present study is to assess the feasibility of this cognitive behavioural group intervention for participants and facilitators. METHODS: The intervention consisted of eight weekly group sessions lasting two hours each and a booster session after six months. Self-administered questionnaires, registration forms and interviews were used to collect data from participants (n = 168) and facilitators (n = 6) on the extent to which the intervention was performed according to protocol, participant attendance, participant adherence, and participants' and facilitators' opinion of the intervention. Quantitative data from the questionnaires and registration forms were analysed by means of descriptive statistics. Qualitative data were categorised based on matching contents of the answers. RESULTS: Facilitators reported no major protocol deviations. Twenty-six percent of the participants withdrew before the start of the programme. Of the persons who started the programme, 84% actually completed it. The participants reported their adherence as good, but facilitators had a less favourable opinion of this. The majority of participants still reported substantial benefits from the programme after six and twelve months of follow-up (71% and 61% respectively). Both participants and facilitators provided suggestions for improvement of the intervention. CONCLUSION: Results of this study show that the current cognitive behavioural group intervention is feasible for both participants and facilitators and fits in well with regular care. Minor refinement of the intervention, however, is warranted to further improve intervention effectiveness and efficiency. Based on these positive findings, we recommend implementing a refined version of this effective and feasible intervention in regular care. TRIAL REGISTRATION: ISRCTN43792817

SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia

Loss of cellular polarity is a hallmark of epithelial cancers, raising the possibility that regulators of polarity have a role in suppressing tumorigenesis. The Scribble complex is one of at least three interacting protein complexes that have a critical role in establishing and maintaining epithelial polarity. In human colorectal, breast, and endometrial cancers, expression of the Scribble complex member SCRIB is often mislocalized and deregulated. Here, we report that Scrib is indispensable for prostate homeostasis in mice. Scrib heterozygosity initiated prostate hyperplasia, while targeted biallelic Scrib loss predisposed mice to prostate intraepithelial neoplasia. Mechanistically, Scrib was shown to negatively regulate the MAPK cascade to suppress tumorigenesis. Further analysis revealed that prostate-specific loss of Scrib in mice combined with expression of an oncogenic Kras mutation promoted the progression of prostate cancer that recapitulated the human disease. The clinical significance of the work in mice was highlighted by our observation that SCRIB deregulation strongly correlated with poor survival in human prostate cancer. These data suggest that the polarity network could provide a new avenue for therapeutic intervention

Integration of atom interferometers and inertial measurement units to improve navigation performance

This paper explores a way of combining conventional inertial sensors with cold atom interferometers (CAI) in order to reduce the drift of the navigation solutions in velocity and orientation. Instead of complementing and improving the CAI with conventional sensors, in this approach the conventional IMU will be used as main sensor for a prediction of the kinematic state. The CAI is then used for the correction of systematic errors and offsets in the framework of an extended Kalman Filter. Monte Carlo simulation studies demonstrate an improvement of the navigation solution precision. In addition, most drifts of velocity and orientation can be eliminated and the uncertainty of the velocity solution can further be reduced by a factor of 30 or more compared to the conventional strapdown. The observability of the error states is discussed

Exercise for reducing fear of falling in older people living in the community: Cochrane systematic review and meta-analysis

Objective: To determine the effect of exercise interventions on fear of falling in community-living people aged ≥65 years. Design: Systematic review and meta-analysis. Bibliographic databases, trial registers and other sources were searched for randomised or quasi-randomised trials. Data were independently extracted by pairs of reviewers using a standard form. Results: Thirty trials (2878 participants) reported 36 interventions (Tai Chi and yoga (n=9); balance training (n=19); strength and resistance training (n=8)). The risk of bias was low in few trials. Most studies were from high income countries (Australia=8, USA=7). Intervention periods (26 weeks=7) and exercise frequency (1-3 times/week=32; ≥4 times/week=4) varied between studies. Fear of falling was measured by single-item questions (7) and scales measuring falls efficacy (14), balance confidence (9) and concern or worry about falling (2). Meta-analyses showed a small to moderate effect of exercise interventions on reducing fear of falling immediately post intervention (standardised mean difference (SMD) 0.37, 95% CI 0.18, 0.56; 24 studies; low quality evidence). There was a small, but not statistically significant effect in the longer term (<6 months (SMD 0.17, 95% CI -0.05, 0.38 (four studies) and ≥ 6 months post intervention SMD 0.20, 95% CI -0.01, 0.41 (three studies)). Conclusions: Exercise interventions probably reduce fear of falling to a small to moderate degree immediately post-intervention in community-living older people. The high risk of bias in most included trials suggests findings should be interpreted with caution. High quality trials are needed to strengthen the evidence base in this area

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin