Nonparametric variable importance for time-to-event outcomes with application to prediction of HIV infection

In survival analysis, complex machine learning algorithms have been increasingly used for predictive modeling. Given a collection of features available for inclusion in a predictive model, it may be of interest to quantify the relative importance of a subset of features for the prediction task at hand. In particular, in HIV vaccine trials, participant baseline characteristics are used to predict the probability of infection over the intended follow-up period, and investigators may wish to understand how much certain types of predictors, such as behavioral factors, contribute toward overall predictiveness. Time-to-event outcomes such as time to infection are often subject to right censoring, and existing methods for assessing variable importance are typically not intended to be used in this setting. We describe a broad class of algorithm-agnostic variable importance measures for prediction in the context of survival data. We propose a nonparametric efficient estimation procedure that incorporates flexible learning of nuisance parameters, yields asymptotically valid inference, and enjoys double-robustness. We assess the performance of our proposed procedure via numerical simulations and analyze data from the HVTN 702 study to inform enrollment strategies for future HIV vaccine trials.Comment: 91 total pages (31 main text, 60 supplementary); 14 total figures (4 main text, 10 supplementary

Enhanced Tissue Integration During Cartilage RepairIn VitroCan Be Achieved by Inhibiting Chondrocyte Death at the Wound Edge

Objective: Experimental wounding of articular cartilage results in cell death at the lesion edge. The objective of this study was to investigate whether inhibition of this cell death results in enhanced integrative cartilage repair. Methods: Bovine articular cartilage discs (6mm) were incubated in media containing inhibitors of necrosis (Necrostatin-1, Nec-1) or apoptosis (Z-VAD-FMK, ZVF) before cutting a 3mm inner core. This core was left in situ to create disc/ring composites, cultured for up to 6 weeks with the inhibitors, and analyzed for cell death, sulfated glycosaminoglycan release, and tissue integration. Results: Creating the disc/ring composites resulted in a significant increase in necrosis. ZVF significantly reduced necrosis and apoptosis at the wound edge. Nec-1 reduced necrosis. Both inhibitors reduced the level of wound-induced sulfated glycosaminoglycan loss. Toluidine blue staining and electron microscopy of cartilage revealed significant integration of the wound edges in disc/ring composites treated with ZVF. Nec-1 improved integration, but to a lesser extent. Push-out testing revealed that ZVF increased adhesive strength compared to control composites. Conclusions: This study shows that treatment of articular cartilage with cell death inhibitors during wound repair increases the number of viable cells at the wound edge, prevents matrix loss, and results in a significant improvement in cartilage-cartilage integration

Staying true with the help of others: doxastic self-control through interpersonal commitment

I explore the possibility and rationality of interpersonal mechanisms of doxastic self-control, that is, ways in which individuals can make use of other people in order to get themselves to stick to their beliefs. I look, in particular, at two ways in which people can make interpersonal epistemic commitments, and thereby willingly undertake accountability to others, in order to get themselves to maintain their beliefs in the face of anticipated “epistemic temptations”. The first way is through the avowal of belief, and the second is through the establishment of collective belief. I argue that both of these forms of interpersonal epistemic commitment can function as effective tools for doxastic self-control, and, moreover, that the control they facilitate should not be dismissed as irrational from an epistemic perspective

Global convergence properties of conjugate gradient methods for optimization

Projet PROMATHWe study the convergence of nonlinear conjugate gradient methods without restarts and with practical line searches. The analysis covers two classes of methods that are globally convergent on smooth, non convex functions. Some properties of the Fletcher-Reeves method play an important role in the first family, whereas the second family shares an important property with the Polak-Ribiere method. Numerical experiments are presented

Perceptual Context in Cognitive Hierarchies

Cognition does not only depend on bottom-up sensor feature abstraction, but also relies on contextual information being passed top-down. Context is higher level information that helps to predict belief states at lower levels. The main contribution of this paper is to provide a formalisation of perceptual context and its integration into a new process model for cognitive hierarchies. Several simple instantiations of a cognitive hierarchy are used to illustrate the role of context. Notably, we demonstrate the use context in a novel approach to visually track the pose of rigid objects with just a 2D camera

The Arclight Ophthalmoscope: A Reliable Low-Cost Alternative to the Standard Direct Ophthalmoscope.

Background. The Arclight ophthalmoscope is a low-cost alternative to standard direct ophthalmoscopes. This study compared the Arclight ophthalmoscope with the Heine K180 direct ophthalmoscope to evaluate its reliability in assessing the vertical cup disc ratio (VCDR) and its ease of use (EOU). Methods. Eight medical students used both the Arclight and the Heine ophthalmoscopes to examine the optic disc in 9 subjects. An EOU score was provided after every examination (a higher score indicating that the ophthalmoscope is easier to use). A consultant ophthalmologist provided the reference standard VCDR. Results. 288 examinations were performed. The number of examinations that yielded an estimation of the VCDR was significantly higher for the Arclight ophthalmoscope (125/144, 85%) compared to the Heine ophthalmoscope (88/144, 61%) (p < 0.001). The mean difference from the reference standard VCDR was similar for both instruments, with a mean of -0.078 (95% CI: -0.10 to -0.056) for the Arclight and -0.072 (95% CI: -0.097 to -0.046) for Heine (p = 0.69). The overall EOU score was significantly higher for the Arclight ophthalmoscope (p < 0.001). Conclusion. The Arclight ophthalmoscope performs as well as, and is easier to use than, a standard direct ophthalmoscope, suggesting it is a reliable, low-cost alternative

The SPLASH Survey: Kinematics of Andromeda's Inner Spheroid

The combination of large size, high stellar density, high metallicity, and Sersic surface brightness profile of the spheroidal component of the Andromeda galaxy (M31) within R_proj ~ 20 kpc suggest that it is unlike any subcomponent of the Milky Way. In this work we capitalize on our proximity to and external view of M31 to probe the kinematical properties of this "inner spheroid." We employ a Markov chain Monte Carlo (MCMC) analysis of resolved stellar kinematics from Keck/DEIMOS spectra of 5651 red giant branch stars to disentangle M31's inner spheroid from its stellar disk. We measure the mean velocity and dispersion of the spheroid in each of five spatial bins after accounting for a locally cold stellar disk as well as the Giant Southern Stream and associated tidal debris. For the first time, we detect significant spheroid rotation (v_rot ~ 50 km/s) beyond R_proj ~ 5 kpc. The velocity dispersion decreases from about 140 km/s at R_proj = 7 kpc to 120 km/s at R_proj = 14 kpc, consistent to 2 sigma with existing measurements and models. We calculate the probability that a given star is a member of the spheroid and find that the spheroid has a significant presence throughout the spatial extent of our sample. Lastly, we show that the flattening of the spheroid is due to velocity anisotropy in addition to rotation. Though this suggests that the inner spheroid of M31 more closely resembles an elliptical galaxy than a typical spiral galaxy bulge, it should be cautioned that our measurements are much farther out (2 - 14 r_eff) than for the comparison samples.Comment: Accepted for publication in Ap

La Differentiation automatique de fonctions representees par des programmes

Projet PROMATHRésumé disponible dans le fichier PD

Evaluation of a Technique to Trap Lemmings Under the Snow

We attempted to live trap lemmings under the snow in their preferred winter habitat at two sites in the Canadian Arctic using chimney-like boxes. Lemmings used the boxes during winter, but we had very low trapping success in April and May. During spring trapping, in contrast to most of the winter, subnivean temperatures became colder than ambient air temperatures. We hypothesize that our low success in spring resulted from lemmings’ leaving the deeper snow areas where our boxes were located and moving to shallower snow or exposed tundra. We suggest that the trapping boxes could be successful if trapping occurred earlier during winter.Nous avons tenté de capturer des lemmings sous la neige dans leur habitat hivernal préféré en utilisant des boîtes en forme de cheminée à deux sites situés dans l’Arctique canadien. Les boîtes ont été utilisées par les lemmings durant l’hiver mais nous avons eu un très faible succès de capture en avril et mai. Contrairement à la majorité de l’hiver, les températures sous-nivales étaient plus froides que les températures de l’air pendant que nous avons trappé au printemps. Nous émettons l’hypothèse que notre faible succès au printemps est dû au déplacement des lemmings des sites de fort enneigement, où nos boîtes étaient installées, vers ceux de faible enneigement ou vers la toundra exposée. Nous suggérons que les boîtes de trappage pourraient être plus utiles si le trappage se faisait plus tôt au courant de l’hiver

Measurement of [OIII] Emission in Lyman Break Galaxies

Measurements of [OIII] emission in Lyman Break galaxies (LBGs) at z>3 are presented. Four galaxies were observed with narrow-band filters using the Near-IR Camera on the Keck I 10-m telescope. A fifth galaxy was observed spectroscopically during the commissioning of NIRSPEC, the new infrared spectrometer on Keck II. The emission-line spectrum is used to place limits on the metallicity. Comparing these new measurements with others available from the literature, we find that strong oxygen emission in LBGs may suggest sub-solar metallicity for these objects. The [OIII]5007 line is also used to estimate the star formation rate (SFR) of the LBGs. The inferred SFRs are higher than those estimated from the UV continuum, and may be evidence for dust extinction.Comment: 25 pages, including 6 figures. Accepted for publication in Ap