The jurist and philosopher, Jeremy Bentham, and his lesser-known brother, Samuel, equally talented but as a naval architect, engineer and inventor, had a long love affair with Russia. Jeremy hoped to ...assist Empress Catherine II with her legislative projects. Samuel went to St Petersburg to seek his fortune in 1780 and came back with the rank of Brigadier-General and the idea, famously publicised by Jeremy, of the Inspection-House or Panopticon. The Bentham Brothers and Russia chronicles the brothers’ later involvement with the Russian Empire, when Jeremy focused his legislative hopes on Catherine’s grandson Emperor Alexander I (ruled 1801-25) and Samuel found a unique opportunity in 1806 to build a Panopticon in St Petersburg – the only panoptical building ever built by the Benthams themselves. Setting the Benthams’ projects within an in-depth portrayal of the Russian context, Roger Bartlett illuminates an important facet of their later careers and offers insight into their world view and way of thought. He also contributes towards the history of legal codification in Russia, which reached a significant peak in 1830, and towards the demythologising of the Panopticon, made notorious by Michel Foucault: the St Petersburg building, still relatively unknown, is described here in detail on the basis of archival sources. The Benthams’ interactions with Russia under Alexander I constituted a remarkable episode in Anglo-Russian relations; this book fills a significant gap in their history.
Relative to the large literature on upper bounds on complexity of convex optimization, lesser attention has been paid to the fundamental hardn4516420ess of these problems. Given the extensive use of ...convex optimization in machine learning and statistics, gaining an understanding of these complexity-theoretic issues is important. In this paper, we study the complexity of stochastic convex optimization in an oracle model of computation. We introduce a new notion of discrepancy between functions, and use it to reduce problems of stochastic convex optimization to statistical parameter estimation, which can be lower bounded using information-theoretic methods. Using this approach, we improve upon known results and obtain tight minimax complexity estimates for various function classes.
New neurons are continually generated from the resident populations of precursor cells in selective niches of the adult mammalian brain such as the hippocampal dentate gyrus and the olfactory bulb. ...However, whether such cells are present in the adult amygdala, and their neurogenic capacity, is not known. Using the neurosphere assay, we demonstrate that a small number of precursor cells, the majority of which express Achaete-scute complex homolog 1 (Ascl1), are present in the basolateral amygdala (BLA) of the adult mouse. Using neuron-specific Thy1-YFP transgenic mice, we show that YFP+ cells in BLA-derived neurospheres have a neuronal morphology, co-express the neuronal marker βIII-tubulin, and generate action potentials, confirming their neuronal phenotype. In vivo, we demonstrate the presence of newly generated BrdU-labeled cells in the adult BLA, and show that a proportion of these cells co-express the immature neuronal marker doublecortin (DCX). Furthermore, we reveal that a significant proportion of GFP+ neurons (~23%) in the BLA are newly generated (BrdU+) in DCX-GFP mice, and using whole-cell recordings in acute slices we demonstrate that the GFP+ cells display electrophysiological properties that are characteristic of interneurons. Using retrovirus-GFP labeling as well as the Ascl1
mouse line, we further confirm that the precursor cells within the BLA give rise to mature and functional interneurons that persist in the BLA for at least 8 weeks after their birth. Contextual fear conditioning has no effect on the number of neurospheres or BrdU-labeled cells in the BLA, but produces an increase in hippocampal cell proliferation. These results demonstrate that neurogenic precursor cells are present in the adult BLA, and generate functional interneurons, but also show that their activity is not regulated by an amygdala-dependent learning paradigm.
The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) supported an international panel tasked with reviewing the methodology for clinical trials in spinal cord injury (SCI), and ...making recommendations on the conduct of future trials. This is the first of four papers. Here, we examine the spontaneous rate of recovery after SCI and resulting consequences for achieving statistically significant results in clinical trials. We have reanalysed data from the Sygen trial to provide some of this information. Almost all people living with SCI show some recovery of motor function below the initial spinal injury level. While the spontaneous recovery of motor function in patients with motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI patients (American spinal injury Association impairment scale (AIS) C and AIS D) is both more substantial and highly variable. With motor complete lesions (AIS A/AIS B) the majority of functional return is within the zone of partial preservation, and may be sufficient to reclassify the injury level to a lower spinal level. The vast majority of recovery occurs in the first 3 months, but a small amount can persist for up to 18 months or longer. Some sensory recovery occurs after SCI, on roughly the same time course as motor recovery. Based on previous data of the magnitude of spontaneous recovery after SCI, as measured by changes in ASIA motor scores, power calculations suggest that the number of subjects required to achieve a significant result from a trial declines considerably as the start of the study is delayed after SCI. Trials of treatments that are most efficacious when given soon after injury will therefore, require larger patient numbers than trials of treatments that are effective at later time points. As AIS B patients show greater spontaneous recovery than AIS A patients, the number of AIS A patients requiring to be enrolled into a trial is lower. This factor will have to be balanced against the possibility that some treatments will be more effective in incomplete patients. Trials involving motor incomplete SCI patients, or trials where an accurate assessment of AIS grade cannot be made before the start of the trial, will require large subject numbers and/or better objective assessment methods.
The objective of this study was to determine the association between individual cow-level milk production and bovine leukemia virus (BLV) infection as measured by milk BLV-ELISA. Dairy Herd ...Improvement technicians collected milk samples from 10 cows from each of first, second, third, and 4+ parity cows in 105 Holstein herds with ≥120 milking cows. Milk samples were tested for the presence of anti-BLV antibodies by ELISA. Additional data regarding the cows and the herds were collected by farm survey and Dairy Herd Improvement records. A set of mixed-effect models using all cows and only 2+ parity cows were used to investigate the association between BLV ELISA-corrected optical density and 305-d mature equivalents of individual cows. The BLV milk positivity was associated with decreased 305-d mature-equivalent yields, especially among the older cows. Additionally, increasing milk ELISA-corrected optical density was associated with increasing loss of milk production at the cow level. In summary, our results provide evidence that BLV infection is associated with decreased milk production in Michigan dairy cows.
The objective of this study was to determine the herd-level effect of bovine leukemia virus (BLV) infection on dairy production, culling, and cow longevity. During routine herd testing, Dairy Herd ...Improvement Association technicians collected milk samples from about 40 cows from each of 104 randomly selected Michigan dairy herds averaging ≥120 milking cows and 11,686kg of milk/yr. Milk samples were analyzed for the presence of anti-BLV antibodies by ELISA, and herd- and lactation-specific estimates of BLV prevalence were computed to determine which were the most predictive of herd milk production, culling rate, and cow longevity (proportion of cows in their third or greater lactation). On this basis, the herd BLV index (an unweighted mean BLV prevalence rate for lactation number 1, 2, 3, and ≥4) was selected as the measure of BLV prevalence that was the most highly associated with BLV economic impact. Step-down multivariate analysis was used to determine the extent to which any of 19 herd-level management variables may have confounded the association of BLV index and measures of herd economic impact (milk production and cow longevity). The BLV index was not associated with the 12-mo culling rate, but was negatively associated in the final multivariable model with the proportion of cows that were ≥third lactation, and was negatively associated with herd milk production. In summary, increased prevalence of BLV within Michigan dairy herds was found to be associated with decreased herd milk production and decreased cow longevity. Our results provide evidence that BLV infection is associated with herd-level economic impacts in high-performing dairy herds.
Gradient-based approaches to direct policy search in reinforcement learning have received much recent attention as a means to solve problems of partial observability and to avoid some of the problems ...associated with policy degradation in value-function methods. In this paper we introduce GPOMDP, a simulation-based algorithm for generating a biased estimate of the gradient of the average reward in Partially Observable Markov Decision Processes POMDPs controlled by parameterized stochastic policies. A similar algorithm was proposed by (Kimura et al. 1995). The algorithm's chief advantages are that it requires storage of only twice the number of policy parameters, uses one free beta (which has a natural interpretation in terms of bias-variance trade-off), and requires no knowledge of the underlying state. We prove convergence of GPOMDP, and show how the correct choice of the parameter beta is related to the mixing time of the controlled POMDP. We briefly describe extensions of GPOMDP to controlled Markov chains, continuous state, observation and control spaces, multiple-agents, higher-order derivatives, and a version for training stochastic policies with internal states. In a companion paper (Baxter et al., this volume) we show how the gradient estimates generated by GPOMDP can be used in both a traditional stochastic gradient algorithm and a conjugate-gradient procedure to find local optima of the average reward.
Nanostructured metal surfaces comprised of periodically arranged spherical voids are grown by electrochemical deposition through a self-assembled template. Detailed measurements of the angle- and ...orientation-dependent reflectivity reveal the spectral dispersion, from which we identify the presence of both delocalized Bragg and localized Mie plasmons. These couple strongly producing bonding and antibonding mixed plasmons with anomalous dispersion properties. Appropriate plasmon engineering of the void morphology selects the plasmon spatial and spectral positions, allowing these plasmonic crystal films to be optimized for a wide range of sensing applications.
An international panel reviewed the methodology for clinical trials of spinal cord injury (SCI), and provided recommendations for the valid conduct of future trials. This is the second of four ...papers. It examines clinical trial end points that have been used previously, reviews alternative outcome tools and identifies unmet needs for demonstrating the efficacy of an experimental intervention after SCI. The panel focused on outcome measures that are relevant to clinical trials of experimental cell-based and pharmaceutical drug treatments. Outcome measures are of three main classes: (1) those that provide an anatomical or neurological assessment for the connectivity of the spinal cord, (2) those that categorize a subject's functional ability to engage in activities of daily living, and (3) those that measure an individual's quality of life (QoL). The American Spinal Injury Association impairment scale forms the standard basis for measuring neurologic outcomes. Various electrophysiological measures and imaging tools are in development, which may provide more precise information on functional changes following treatment and/or the therapeutic action of experimental agents. When compared to appropriate controls, an improved functional outcome, in response to an experimental treatment, is the necessary goal of a clinical trial program. Several new functional outcome tools are being developed for measuring an individual's ability to engage in activities of daily living. Such clinical end points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures often do not correlate tightly with the above outcome tools, but may need to form part of Phase 3 trial measures.
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