Prioritized Sweeping Neural DynaQ with Multiple Predecessors, and Hippocampal Replays

During sleep and awake rest, the hippocampus replays sequences of place cells that have been activated during prior experiences. These have been interpreted as a memory consolidation process, but recent results suggest a possible interpretation in terms of reinforcement learning. The Dyna reinforcement learning algorithms use off-line replays to improve learning. Under limited replay budget, a prioritized sweeping approach, which requires a model of the transitions to the predecessors, can be used to improve performance. We investigate whether such algorithms can explain the experimentally observed replays. We propose a neural network version of prioritized sweeping Q-learning, for which we developed a growing multiple expert algorithm, able to cope with multiple predecessors. The resulting architecture is able to improve the learning of simulated agents confronted to a navigation task. We predict that, in animals, learning the world model should occur during rest periods, and that the corresponding replays should be shuffled.Comment: Living Machines 2018 (Paris, France

Fluoromycobacteriophages for rapid, specific, and sensitive antibiotic susceptibility testing of Mycobacterium tuberculosis

Rapid antibiotic susceptibility testing of Mycobacterium tuberculosis is of paramount importance as multiple- and extensively- drug resistant strains of M. tuberculosis emerge and spread. We describe here a virus-based assay in which fluoromycobacteriophages are used to deliver a GFP or ZsYellow fluorescent marker gene to M. tuberculosis, which can then be monitored by fluorescent detection approaches including fluorescent microscopy and flow cytometry. Pre-clinical evaluations show that addition of either Rifampicin or Streptomycin at the time of phage addition obliterates fluorescence in susceptible cells but not in isogenic resistant bacteria enabling drug sensitivity determination in less than 24 hours. Detection requires no substrate addition, fewer than 100 cells can be identified, and resistant bacteria can be detected within mixed populations. Fluorescence withstands fixation by paraformaldehyde providing enhanced biosafety for testing MDR-TB and XDR-TB infections. © 2009 Piuri et al

Cross sectional study of performance indicators for English Primary Care Trusts: testing construct validity and identifying explanatory variables

BACKGROUND: The performance of Primary Care Trusts in England is assessed and published using a number of different performance indicators. Our study has two broad purposes. Firstly, to find out whether pairs of indicators that purport to measure similar aspects of quality are correlated (as would be expected if they are both valid measures of the same construct). Secondly, we wanted to find out whether broad (global) indicators correlated with any particular features of Primary Care Trusts, such as expenditure per capita. METHODS: Cross sectional quantitative analysis using data from six 2004/05 PCT performance indicators for 303 English Primary Care Trusts from four sources in the public domain: Star Rating, aggregated Quality and Outcomes Framework scores, Dr Foster mortality index, Dr Foster equity index (heart by-pass and hip replacements), NHS Litigation Authority Risk Management standards and Patient Satisfaction scores from the Star Ratings. Forward stepwise multiple regression analysis to determine the effect of Primary Care Trust characteristics on performance. RESULTS: Star Rating and Quality and Outcomes Framework total, both summary measures of global quality, were not correlated with each other (F = 0.66, p = 0.57). There were however positive correlations between Quality and Outcomes Framework total and patient satisfaction (r = 0.61, p < 0.001) and between screening/'additional services' indicators on the Star Ratings and Quality and Outcomes Framework (F = 24, p < 0.001). There was no correlation between different measures of access to services. Likewise we found no relationship between either Star Rating or Litigation Authority Standards and hospital mortality (F = 0.61, p = 0.61; F = 0.31, p = 0.73). CONCLUSION: Performance assessment in healthcare remains on the Government's agenda, with new core and developmental standards set to replace the Star Ratings in 2006. Yet the results of this analysis provide little evidence that the current indicators have sufficient construct validity to measure the underlying concept of quality, except when the specific area of screening is considered

Medium/Long wavelength sensitive opsin diversity in Pitheciidae

New World primates feature a complex colour vision system. Most species have polymorphic colour vision where males have a dichromatic colour perception and females can be either ichromatic or trichromatic. The adaptive value of high allelic diversity of opsins, a light sensitive protein, found in primates’ eyes remains unknown. Studies revealing the allelic diversity are important as they shed light on our understanding of the adaptive value of differences in the colouration of species and their ecologies. Here we investigate the allelic types found in Pitheciidae, an understudied New World primate family, revealing the diversity of medium/long wavelength sensitive opsins both in cryptic and conspicuous species of this primate family. We found five alleles in Cacajao, six in Callicebinae (i.e. Plecturocebus, Cheracebus, and Callicebus), four in Chiropotes, and three in Pithecia, some of them reported for the first time. Both cryptic and conspicuous species in this group presented high allelic diversity

Facile and inexpensive fabrication of zinc oxide based bio-surfaces for C-reactive protein detection

© 2018, The Author(s). The paper reports a biosensor formed from antibody coated ZnO nano-crystals which has been prepared using a rapid and inexpensive fabrication method which utilises colloidal dispersion enhanced using sonication. This technique was used to prepare highly ordered and uniform nano-crystalline sensor surfaces on polyethylene terephthalate (PET) using 0.5%, 1% and 5% concentrations of zinc oxide nano-crystal suspensions. Impedance spectroscopy was employed to interrogate the sensor surfaces and confirmed high reproducibility of the fabrication process. Changes in impedance values, at a frequency of 138 Hz, were used to establish dose dependent responses for C-reactive protein (CRP) antigen. A limit of detection of less than 1 ng/ml was demonstrated fornano-surfaces fabricated from concentrations of 1% ZnO

Membrane TNF confers protection to acute mycobacterial infection

BACKGROUND: Tumour necrosis factor (TNF) is crucial for the control of mycobacterial infection as TNF deficient (KO) die rapidly of uncontrolled infection with necrotic pneumonia. Here we investigated the role of membrane TNF for host resistance in knock-in mice with a non-cleavable and regulated allele (mem-TNF). METHODS: C57BL/6, TNF KO and mem-TNF mice were infected with M. tuberculosis H37Rv (Mtb at 100 CFU by intranasal administration) and the survival, bacterial load, lung pathology and immunological parameters were investigated. Bone marrow and lymphocytes transfers were used to test the role of membrane TNF to confer resistance to TNF KO mice. RESULTS: While TNF-KO mice succumbed to infection within 4–5 weeks, mem-TNF mice recruited normally T cells and macrophages, developed mature granuloma in the lung and controlled acute Mtb infection. However, during the chronic phase of infection mem-TNF mice succumbed to disseminated infection with necrotic pneumonia at about 150 days. Reconstitution of irradiated TNF-KO mice with mem-TNF derived bone marrow cells, but not with lymphocytes, conferred host resistance to Mtb infection in TNF-KO mice. CONCLUSION: Membrane expressed TNF is sufficient to allow cell-cell signalling and control of acute Mtb infection. Bone marrow cells, but not lymphocytes from mem-TNF mice confer resistance to infection in TNF-KO mice. Long-term infection control with chronic inflammation likely disrupting TNF mediated cell-cell signalling, additionally requires soluble TNF

Mechanisms driving variability in the ocean forcing of Pine Island Glacier

Pine Island Glacier (PIG) terminates in a rapidly melting ice shelf, and ocean circulation and temperature are implicated in the retreat and growing contribution to sea level rise of PIG and nearby glaciers. However, the variability of the ocean forcing of PIG has been poorly constrained due to a lack of multi-year observations. Here we show, using a unique record close to the Pine Island Ice Shelf (PIIS), that there is considerable oceanic variability at seasonal and interannual timescales, including a pronounced cold period from October 2011 to May 2013. This variability can be largely explained by two processes: cumulative ocean surface heat fluxes and sea ice formation close to PIIS; and interannual reversals in ocean currents and associated heat transport within Pine Island Bay, driven by a combination of local and remote forcing. Local atmospheric forcing therefore plays an important role in driving oceanic variability close to PIIS