Event management for large scale event-driven digital hardware spiking neural networks

Abstract : The interest in brain-like computation has led to the design of a plethora of innovative neuromorphic systems. Individually, spiking neural networks (SNNs), event-driven simulation and digital hardware neuromorphic systems get a lot of attention. Despite the popularity of event-driven SNNs in soft- ware, very few digital hardware architectures are found. This is because existing hardware solutions for event management scale badly with the number of events. This paper introduces the structured heap queue, a pipelined digital hardware data structure, and demonstrates its suitability for event management. The structured heap queue scales gracefully with the number of events, allowing the efficient implementation of large scale digital hardware event-driven SNNs. The scaling is linear for memory, logarithmic for logic resources and constant for processing time. The use of the structured heap queue is demonstrated on eld-programmable gate array (FPGA) with an image segmentation experiment and a SNN of 65 536 neurons and 513 184 synapses. Events can be processed at the rate of 1 every 7 clock cycles and a 406 x 158 pixel image is segmented in 200 ms

Impact of reanalysis boundary conditions on downscaled Atlantic hurricane activity

Climate models are capable of producing features similar to tropical cyclones, but typically display strong biases for many of the storm physical characteristics due to their relatively coarse resolution compared to the size of the storms themselves. One strategy that has been adopted to circumvent this limitation is through the use of a hybrid downscaling technique, wherein a large set of synthetic tracks are created by seeding disturbances in the large-scale environment. Here, we evaluate the ability of this technique at reproducing many of the characteristics of the recent North Atlantic hurricane activity as well as its sensitivity to the choice of the reanalysis dataset used as boundary conditions. In particular, we show that the geographical and intensity distributions are well reproduced, but that the technique has difficulty capturing the large difference in activity observed between the most recent active and quiescent phase. Although the signal is somewhat reduced compared to observation, the technique also detects a significant decrease in the intensification rate of hurricanes near the coastal US during the active phase compared to the quiescent phase. Finally, the influence of the El Niño Southern Oscillation on hurricane activity is generally well captured as well, but the technique fails to reproduce the increase in activity over the western part of the basin during Modoki El Niños.We would like to thank NOAA’s National Centers for Environmental Information for making the IBTrACS data available. JPB and LPC would like to acknowledge the financial support from the Ministerio de Economa y Competitividad (MINECO; Project GL2014-55764-R). LPC’s contract is co-financed by the MINECO under Juan de la Cierva Incorporacin postdoctoral fellowship number IJCI-2015-23367. MB would like to acknowledge financial support from the Natural Sciences and Engineering Research Council (NSERC) of Canada. Finally, we are grateful to Kerry Emanuel for providing the data as well as some useful feedback, and two anonymous reviewers for their helpful comments.Peer ReviewedPostprint (published version

Monitoring DNA–Ligand Interactions in Living Human Cells Using NMR Spectroscopy

International audienceStudies on DNA−ligand interactions in the cellular environment are problematic due to the lack of suitable biophysical tools. To address this need, we developed an in-cell NMR-based approach for monitoring DNA−ligand interactions inside the nuclei of living human cells. Our method relies on the acquisition of NMR data from cells electroporated with preformed DNA−ligand complexes. The impact of the intracellular environment on the integrity of the complexes is assessed based on in-cell NMR signals from unbound and ligand-bound forms of a given DNA target. This technique was tested on complexes of two model DNA fragments and four ligands, namely, a representative DNA minor-groove binder (netropsin) and ligands bindin

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status

Lignin biomarkers as tracers of mercury sources in lakes water column

This study presents the role of specific terrigenous organic compounds as important vectors of mercury (Hg) transported from watersheds to lakes of the Canadian boreal forest. In order to differentiate the autochthonous from the allochthonous organic matter (OM), lignin derived biomarker signatures [Lambda, S/V, C/V, P/(V ? S), 3,5-Bd/V and (Ad/Al)v] were used. Since lignin is exclusively produced by terrigenous plants, this approach can give a non equivocal picture of the watershed inputs to the lakes. Moreover, it allows a characterization of the source of OM and its state of degradation. The water column of six lakes from the Canadian Shield was sampled monthly between June and September 2005. Lake total dissolved Hg concentrations and Lambda were positively correlated, meaning that Hg and ligneous inputs are linked (dissolved OM r2 = 0.62, p\0.0001; particulate OM r2 = 0.76, p\0.0001). Ratios of P/(V ? S) and 3,5-Bd/V from both dissolved OM and particulate OM of the water column suggest an inverse relationship between the progressive state of pedogenesis and maturation of the OM in soil before entering the lake, and the Hg concentrations in the water column. No relation was found between Hg levels in the lakes and the watershed flora composition—angiosperm versus gymnosperm or woody versus non-woody compounds. This study has significant implications for watershed management of ecosystems since limiting fresh terrestrial OM inputs should reduce Hg inputs to the aquatic systems. This is particularly the case for largescale land-use impacts, such as deforestation, agriculture and urbanization, associated to large quantities of soil OM being transferred to aquatic systems

Acute bacterial prostatitis: heterogeneity in diagnostic criteria and management. Retrospective multicentric analysis of 371 patients diagnosed with acute prostatitis

<p>Abstract</p> <p>Background</p> <p>There is currently a lack of consensus for the diagnosis, investigations and treatments of acute bacterial prostatitis (AP).</p> <p>Methods</p> <p>The symptoms, investigations and treatments of 371 inpatients diagnosed with AP were analyzed through a retrospective study conducted in four departments – Urology (U), Infectious Diseases (ID), Internal Medicine (IM), Geriatrics (G) – of two French university hospitals.</p> <p>Results</p> <p>The cause of admission, symptoms, investigations and treatments depended markedly on the department of admission but not on the hospital. In U, patients commonly presented with a bladder outlet obstruction, they had a large imaging and functional check-up, and received alpha-blockers and anti-inflammatory drugs. In ID, patients were febrile and received longer and more appropriate antibiotic treatments. In G, patients presented with cognitive disorders and commonly had post-void urine volume measurements. In IM, patients presented with a wide range of symptoms, and had very diverse investigations and antibiotic regimen.</p> <p>Overall, a 3:1 ratio of community-acquired AP (CA-AP) to nosocomial AP (N-AP) was observed. Urine culture isolated mainly <it>E. coli </it>(58% of AP, 68% of CA-AP), with venereal agents constituting less than 1%. The probabilistic antibiotic treatments were similar for N-AP and CA-AP (58% bi-therapy; 63% fluoroquinolone-based regimen). For N-AP, these treatments were more likely to be inadequate (42% <it>vs. </it>8%, p < 0.001) and had a higher rate of bacteriological failure (48% <it>vs. </it>19%, p < 0.001).</p> <p>Clinical failure at follow-up was more common than bacteriological failure (75% versus 24%, p < 0.001). Patients older than 49 had more underlying urinary tract disorders and a higher rate of clinical failure (30% versus 10%, p < 0.0001).</p> <p>Conclusion</p> <p>This study highlights the difficulties encountered on a daily basis by the physicians regarding the diagnosis and management of acute prostatitis.</p

Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial

Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. National Institute of Neurological Disorders and Stroke and Genentech. [Abstract copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Coxiella burnetii, the Agent of Q Fever, Replicates within Trophoblasts and Induces a Unique Transcriptional Response

Q fever is a zoonosis caused by Coxiella burnetii, an obligate intracellular bacterium typically found in myeloid cells. The infection is a source of severe obstetrical complications in humans and cattle and can undergo chronic evolution in a minority of pregnant women. Because C. burnetii is found in the placentas of aborted fetuses, we investigated the possibility that it could infect trophoblasts. Here, we show that C. burnetii infected and replicated in BeWo trophoblasts within phagolysosomes. Using pangenomic microarrays, we found that C. burnetii induced a specific transcriptomic program. This program was associated with the modulation of inflammatory responses that were shared with inflammatory agonists, such as TNF, and more specific responses involving genes related to pregnancy development, including EGR-1 and NDGR1. In addition, C. burnetii stimulated gene networks organized around the IL-6 and IL-13 pathways, which both modulate STAT3. Taken together, these results revealed that trophoblasts represent a protective niche for C. burnetii. The activation program induced by C. burnetii in trophoblasts may allow bacterial replication but seems unable to interfere with the development of normal pregnancy. Such pathophysiologocal processes should require the activation of immune placental cells associated with trophoblasts

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements