Development and large-scale validation of the Watch Walk wrist-worn digital gait biomarkers

Digital gait biomarkers (including walking speed) indicate functional decline and predict hospitalization and mortality. However, waist or lower-limb devices often used are not designed for continuous life-long use. While wrist devices are ubiquitous and many large research repositories include wrist-sensor data, widely accepted and validated digital gait biomarkers derived from wrist-worn accelerometers are not available yet. Here we describe the development of advanced signal processing algorithms that extract digital gait biomarkers from wrist-worn devices and validation using 1-week data from 78,822 UK Biobank participants. Our gait biomarkers demonstrate good test–retest-reliability, strong agreement with electronic walkway measurements of gait speed and self-reported pace and significantly discriminate individuals with poor self-reported health. With the almost universal uptake of smart-watches, our algorithms offer a new approach to remotely monitor life-long population level walking speed, quality, quantity and distribution, evaluate disease progression, predict risk of adverse events and provide digital gait endpoints for clinical trials

Optimizing probe selection for fault localization

We investigate the use of probing technology for the purpose of problem determination and fault localization in networks. We present a framework for addressing this issue and implement algorithms that exploit interactions between probe paths to find a small collection of probes that can be used to locate faults. Small probe sets are desirable in order to minimize the costs imposed by probing, such as additional network load and data management requirements. Our results show that although finding the optimal collection of probes is expensive for large networks, efficient approximation algorithms can be used to find a nearly-optimal set

Real-time problem determination in distributed systems using active probing

Abstract We describe algorithms and an architecture for a real-time problem determination system that uses online selection of most-informative measurements -the approach called herein active probing. Probes are end-to-end test transactions which gather information about system components. Active probing allows probes to bc selected and sent on-demand, in response to one's belief about the state of the system. At each step the most informative next probe is computed and sent. As probe results are received, belief about the system state is updated using probabilistic inference. This process continues until the problem is diagnosed. We demonstrate through both analysis and simulation that the active probing scheme greatly reduces both the number of probes and the time needed for localizing the problem when compared with non-active probing schemes

Learning Rules from User Behaviour

Accepted versio

The AIMSS Project – III. The Stellar Populations of Compact Stellar Systems

In recent years, a growing zoo of compact stellar systems (CSSs) have been found whose physical properties (mass, size, velocity dispersion) place them between classical globular clusters (GCs) and true galaxies, leading to debates about their nature. Here we present results using a so far underutilized discriminant, their stellar population properties. Based on new spectroscopy from 8–10m telescopes, we derive ages, metallicities, and [α/Fe] of 29 CSSs. These range from GCs with sizes of merely a few parsec to compact ellipticals (cEs) larger than M32. Together with a literature compilation, this provides a panoramic view of the stellar population characteristics of early-type systems. We find that the CSSs are predominantly more metal rich than typical galaxies at the same stellar mass. At high mass, the cEs depart from the mass–metallicity relation of massive early-type galaxies, which forms a continuous sequence with dwarf galaxies. At lower mass, the metallicity distribution of ultracompact dwarfs (UCDs) changes at a few times 107 M⊙, which roughly coincides with the mass where luminosity function arguments previously suggested the GC population ends. The highest metallicities in CSSs are paralleled only by those of dwarf galaxy nuclei and the central parts of massive early types. These findings can be interpreted as CSSs previously being more massive and undergoing tidal interactions to obtain their current mass and compact size. Such an interpretation is supported by CSSs with direct evidence for tidal stripping, and by an examination of the CSS internal escape velocities

Metallicity Estimates for Old Star Clusters in M33

Using the theoretical stellar population synthesis models of BC96, Kong et al. (2003) showed that some BATC colors and color indices could be used to disentangle the age and metallicity effect. They found that there is a very good relation between the flux ratio of L_{8510}/L_{9170} and the metallicity for stellar populations older than 1 Gyr. In this paper, based on the Kong et al. results and on the multicolor spectrophotometry of Ma et al. (2001, 2002a,b,c), we estimate the metallicities of 31 old star clusters in the nearby spiral galaxy M33, 23 of which are ``true'' globular clusters. The results show that most of these old clusters are metal poor. We also find that the ages and metal abundance for these old star clusters of M33 do not vary with deprojected radial position.Comment: Accepted for Publication in A&A, 13 pages, 7 figures (1 figure of jpg

GP88 (PC-Cell Derived Growth Factor, progranulin) stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Aromatase inhibitors (AI) that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER⁺) breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88), also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER⁺breast cancer cells</p> <p>Methods</p> <p>We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined.</p> <p>Results</p> <p>GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole.</p> <p>Conclusion</p> <p>Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER⁺breast cancer.</p

A decade of letrozole: FACE

Third-generation nonsteroidal aromatase inhibitors (AIs), letrozole and anastrozole, are superior to tamoxifen as initial therapy for early breast cancer but have not been directly compared in a head-to-head adjuvant trial. Cumulative evidence suggests that AIs are not equivalent in terms of potency of estrogen suppression and that there may be differences in clinical efficacy. Thus, with no data from head-to-head comparisons of the AIs as adjuvant therapy yet available, the question of whether there are efficacy differences between the AIs remains. To help answer this question, the Femara versus Anastrozole Clinical Evaluation (FACE) is a phase IIIb open-label, randomized, multicenter trial designed to test whether letrozole or anastrozole has superior efficacy as adjuvant treatment of postmenopausal women with hormone receptor (HR)- and lymph node-positive breast cancer. Eligible patients (target accrual, N = 4,000) are randomized to receive either letrozole 2.5 mg or anastrozole 1 mg daily for up to 5 years. The primary objective is to compare disease-free survival at 5 years. Secondary end points include safety, overall survival, time to distant metastases, and time to contralateral breast cancer. The FACE trial will determine whether or not letrozole offers a greater clinical benefit to postmenopausal women with HR+ early breast cancer at increased risk of early recurrence compared with anastrozole

Extragalactic Globular Clusters and Galaxy Formation

Globular cluster (GC) systems have now been studied in galaxies ranging from dwarfs to giants and spanning the full Hubble sequence of morphological types. Imaging and spectroscopy with the Hubble Space Telescope and large ground-based telescopes have together established that most galaxies have bimodal color distributions that reflect two subpopulations of old GCs: metal-poor and metal-rich. The characteristics of both subpopulations are correlated with those of their parent galaxies. We argue that metal-poor GCs formed in low-mass dark matter halos in the early universe and that their properties reflect biased galaxy assembly. The metal-rich GCs were born in the subsequent dissipational buildup of their parent galaxies and their ages and abundances indicate that most massive early-type galaxies formed the bulk of their stars at early times. Detailed studies of both subpopulations offer some of the strongest constraints on hierarchical galaxy formation that can be obtained in the near-field.Comment: 74 pages, including 14 figures. In press for Annual Reviews of Astronomy and Astrophysic

On the nature of the brightest globular cluster in M81

We analyse the photometric, chemical, star formation history and structural properties of the brightest globular cluster (GC) in M81, referred to as GC1 in this work, with the intention of establishing its nature and origin. We find that it is a metal-rich ([Fe/H] = -0.60 +/- 0.10), alpha-enhanced ([alpha/Fe] similar to 0.20 +/- 0.05), core-collapsed (core radius r(c) = 1.2 pc, tidal radius r(t) = 76r(c)), old (&gt; 13 Gyr) cluster. It has an ultraviolet excess equivalent of similar to 2500 blue horizontal branch stars. It is detected in X-rays indicative of the presence of low-mass binaries. With a mass of 1.0 x 10(7) M-circle dot, the cluster is comparable in mass to M31-G1 and is four times more massive than omega Cen. The values of r(c), absolute magnitude and mean surface brightness of GC1 suggest that it could be, like massive GCs in other giant galaxies, the left-over nucleus of a dissolved dwarf galaxy