Proportional hazards models with continuous marks

For time-to-event data with finitely many competing risks, the proportional hazards model has been a popular tool for relating the cause-specific outcomes to covariates [Prentice et al. Biometrics 34 (1978) 541--554]. This article studies an extension of this approach to allow a continuum of competing risks, in which the cause of failure is replaced by a continuous mark only observed at the failure time. We develop inference for the proportional hazards model in which the regression parameters depend nonparametrically on the mark and the baseline hazard depends nonparametrically on both time and mark. This work is motivated by the need to assess HIV vaccine efficacy, while taking into account the genetic divergence of infecting HIV viruses in trial participants from the HIV strain that is contained in the vaccine, and adjusting for covariate effects. Mark-specific vaccine efficacy is expressed in terms of one of the regression functions in the mark-specific proportional hazards model. The new approach is evaluated in simulations and applied to the first HIV vaccine efficacy trial.Comment: Published in at http://dx.doi.org/10.1214/07-AOS554 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Time course investigation of the dermal leukocyte response to lipoteichoic acid in chickens

Lipoteichoic acid (LTA) is component of the cell wall of Gram-positive bacteria that stimulates inflammation during bacterial infection. However, few studies have investigated the in vivo immune response to LTA, and none of the in vivo studies done have been performed in birds. For this project, the pulp (a skin-derivative) of growing feathers (GFs) of chickens were used as a test site to investigate the in vivo effects of intradermally injected LTA. In Study 1, the pulp of 12 GFs of 11-week-old Light-brown Leghorn (LBL) males were injected with 10 μL of differing concentrations of LTA (0.1, 1.0, 10, 100 or 250 μg LTA/mL; 3 chickens/dose). For each chicken, 2 GF were plucked before injection and at 6, 24, 48, and 72 h post-injection, flash frozen, and stored at -80°C. Frozen pulp sections were stained using immunohistochemistry for visual inspection of leukocyte infiltration in response to LTA. Based on this study, the 10 μg/mL LTA solution was found to be the optimal concentration to stimulate inflammation. In Study 2, GFs of 12, 15-week-old LBL males were then injected with either 10 μL of 10 μg/mL LTA (0.1 μg LTA/GF, 12 GF/bird, n = 8), or 10 μL of PBS (vehicle; n = 4). GFs were collected before injection (0 h) and at 6, 24, 48, and 72 h post-injection. At each time-point, pulp cell suspensions were prepared and immunofluorescently stained with a panel of chicken-leukocyte-specific monoclonal antibodies, and cell population analysis was carried out by flow cytometry. Analyses revealed elevated levels (% pulp cells) in total leukocytes, monocytes/macrophages, and class II MHC expressing cells in GFs injected with LTA when compared to the control. Infiltration of lymphocytes and heterophils was not different between treatment groups. This study suggests that the inflammatory response to LTA in chickens is characterized primarily by recruitment of monocytes/macrophages to the site of inflammation

Trusted execution: applications and verification

Useful security properties arise from sealing data to specific units of code. Modern processors featuring Intel’s TXT and AMD’s SVM achieve this by a process of measured and trusted execution. Only code which has the correct measurement can access the data, and this code runs in an environment trusted from observation and interference. We discuss the history of attempts to provide security for hardware platforms, and review the literature in the field. We propose some applications which would benefit from use of trusted execution, and discuss functionality enabled by trusted execution. We present in more detail a novel variation on Diffie-Hellman key exchange which removes some reliance on random number generation. We present a modelling language with primitives for trusted execution, along with its semantics. We characterise an attacker who has access to all the capabilities of the hardware. In order to achieve automatic analysis of systems using trusted execution without attempting to search a potentially infinite state space, we define transformations that reduce the number of times the attacker needs to use trusted execution to a pre-determined bound. Given reasonable assumptions we prove the soundness of the transformation: no secrecy attacks are lost by applying it. We then describe using the StatVerif extensions to ProVerif to model the bounded invocations of trusted execution. We show the analysis of realistic systems, for which we provide case studies

Target-based drug discovery for human African trypanosomiasis:selection of molecular target and chemical matter

Target-based approaches for human African trypanosomiasis (HAT) and related parasites can be a valuable route for drug discovery for these diseases. However, care needs to be taken in selection of both the actual drug target and the chemical matter that is developed. In this article, potential criteria to aid target selection are described. Then the physiochemical properties of typical oral drugs are discussed and compared to those of known anti-parasitics

Shrinkage and early-age temperature induced cracking and crack control in concrete structures

Cracks occur in reinforced concrete structures wherever and whenever the tensile stress in the concrete reaches the tensile strength of the concrete. After concrete sets and hardens, tensile stress at any location may be caused by factors such as early-age heat of hydration, applied loads, restrained shrinkage, temperature changes, settlement of the supports and so on. This paper deals with the control of cracking caused by restraint to earlyage cooling and shrinkage of concrete. Such cracking is inevitable in many situations and a significant amount of reinforcement crossing each crack is required for crack control. Rational procedures are proposed for determining the effects of internal restraint and external restraint, including restraint provided by embedded reinforcement and both end-restraint and side-restraint that may exist at the supports of beams, slabs and walls. Guidance is also provided for estimating the maximum width and spacing of cracks in a variety of situations

Television in higher education

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