Challenges and Opportunities in Near-Threshold DNN Accelerators around Timing Errors

AI evolution is accelerating and Deep Neural Network (DNN) inference accelerators are at the forefront of ad hoc architectures that are evolving to support the immense throughput required for AI computation. However, much more energy efficient design paradigms are inevitable to realize the complete potential of AI evolution and curtail energy consumption. The Near-Threshold Computing (NTC) design paradigm can serve as the best candidate for providing the required energy efficiency. However, NTC operation is plagued with ample performance and reliability concerns arising from the timing errors. In this paper, we dive deep into DNN architecture to uncover some unique challenges and opportunities for operation in the NTC paradigm. By performing rigorous simulations in TPU systolic array, we reveal the severity of timing errors and its impact on inference accuracy at NTC. We analyze various attributes—such as data–delay relationship, delay disparity within arithmetic units, utilization pattern, hardware homogeneity, workload characteristics—and uncover unique localized and global techniques to deal with the timing errors in NTC

Standard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia

Heavy drinkers are at risk for a spectrum of histologic alcohol-related liver injury: steatosis, alcoholic steatohepatitis (ASH), alcohol-related fibrosis, and cirrhosis. Alcoholic hepatitis (AH), the clinical entity associated with severe ASH, has high short-term mortality. The standard-of-care therapy, prednisolone, has limited efficacy and many side effects; no other treatment has consistently shown survival benefit. The National Institute on Alcohol Abuse and Alcoholism (NIAAA)-funded Alcoholic Hepatitis Consortia carry out translational research on pathophysiologic mechanisms, genetic and environmental risk factors, phase II clinical trials, and development of biomarkers. The consortia members were convened by the National Institutes of Health to address diagnostic criteria and practical issues related to clinical AH research, and to develop a set of common data elements to harmonize ongoing and future trials. This was accomplished through 3 face-to-face meetings of the investigators and representatives of the National Institutes of Health, and subsequent electronic communications over the course of 6 months. Evidence for the recommendations was based on published trials and observational data from several of the consortia members. A draft manuscript was iteratively reviewed by members of the consortia. The goal was to reach agreements on recommendations and definitions that could facilitate trial design, and simultaneously be tested by research groups pooling their data. The recommendations made here are specifically directed to achieve better uniformity in clinical trials, rather than serving as clinical practice guidelines

The Lunar Polar Hydrogen Mapper (LunaH-Map) Mission

The Lunar Polar Hydrogen Mapper (LunaH-Map) mission will map hydrogen enrichments within permanently shadowed regions at the lunar south pole using a miniature neutron spectrometer. While hydrogen enrichments have been identified regionally from previous orbital missions, the spatial extent of these regions are often below the resolution of the neutron instruments that have flown on lunar missions. LunaH-Map will enter into an elliptical, low altitude perseline orbit which will enable the mission to spatially isolate and constrain the hydrogen enrichments within permanently shadowed regions. LunaH-Map will use a solid iodine ion propulsion system, X-Band radio communications through the NASA Deep Space Network, star tracker, C&DH and EPS systems from Blue Canyon Technologies, solar arrays from MMA Designs, LLC, mission design and navigation by KinetX. Spacecraft systems design, integration, qualification, test and mission operations are performed by Arizona State University

Selective Caries Removal in Permanent Teeth (SCRiPT) for the treatment of deep carious lesions:a randomised controlled clinical trial in primary care

Background Dental caries is one of the most prevalent non-communicable disease globally and can have serious health sequelae impacting negatively on quality of life. In the UK most adults experience dental caries during their lifetime and the 2009 Adult Dental Health Survey reported that 85% of adults have at least one dental restoration. Conservative removal of tooth tissue for both primary and secondary caries reduces the risk of failure due to tooth-restoration, complex fracture as well as remaining tooth surfaces being less vulnerable to further caries. However, despite its prevalence there is no consensus on how much caries to remove prior to placing a restoration to achieve optimal outcomes. Evidence for selective compared to complete or near-complete caries removal suggests there may be benefits for selective removal in sustaining tooth vitality, therefore avoiding abscess formation and pain, so eliminating the need for more complex and costly treatment or eventual tooth loss. However, the evidence is of low scientific quality and mainly gleaned from studies in primary teeth. Method This is a pragmatic, multi-centre, two-arm patient randomised controlled clinical trial including an internal pilot set in primary dental care in Scotland and England. Dental health professionals will recruit 623 participants over 12-years of age with deep carious lesions in their permanent posterior teeth. Participants will have a single tooth randomised to either the selective caries removal or complete caries removal treatment arm. Baseline measures and outcome data (during the 3-year follow-up period) will be assessed through clinical examination, patient questionnaires and NHS databases. A mixed-method process evaluation will complement the clinical and economic outcome evaluation and examine implementation, mechanisms of impact and context. The primary outcome at three years is sustained tooth vitality. The primary economic outcome is net benefit modelled over a lifetime horizon. Clinical secondary outcomes include pulp exposure, progession of caries, restoration failure; as well as patient-centred and economic outcomes. Discussion SCRiPT will provide evidence for the most clinically effective and cost-beneficial approach to managing deep carious lesions in permanent posterior teeth in primary care. This will support general dental practitioners, patients and policy makers in decision making. Trial Registration Trial registry: ISRCTN. Trial registration number: ISRCTN76503940. Date of Registration: 30.10.2019

LunaH-Map: Revealing Lunar Water with a New Radiation Sensor Array

A new type of neutron and gamma-ray spectrometer called the Miniature Neutron Spectrometer (Mini-NS) has been developed, assembled, qualified and delivered as part of the Lunar Polar Hydrogen Mapper (LunaH-Map) cubesat mission. The LunaH-Map spacecraft is currently manifested as a secondary payload on the Space Launch System (SLS) Artemis-1 rocket. LunaH-Map will deploy from Artemis-1 and enter a low altitude perilune elliptical orbit around the Moon. The Mini-NS will measure the lunar epithermal neutron albedo, and measurements around perilune will be used to produce maps of hydrogen enrichments and depletions across the lunar South Pole region including both within and outside of permanently shadowed regions (PSRs). The Min-NS was designed to achieve twice the epithermal neutron count rate of the Lunar Prospector Neutron Spectrometer (LP-NS). The instrument response was characterized through the collection of pre-flight neutron counting data with a Cf-252 neutron source at Arizona State University across hundreds of power cycles, as well as across the expected temperature range. The instrument spatial response was characterized at the Los Alamos National Laboratories (LANL) Neutron Free In-Air Facility. The LunaH-Map Mini-NS was designed to fit within the cubesat form-factor and uses two detectors with eight sensor heads that can be operated independently. For future missions with different science goals that can be achieved with epithermal neutron detection, the number of Mini-NS sensor heads can easily be modified without requiring a complete re-design and re-qualification

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease

Pulpotomy for the Management of Irreversible Pulpitis in Mature Teeth (PIP) : a feasibility study

Fundings: This study is funded by the National Institute for Health Research (NIHR) Health Technology Assessment Program (project reference NIHR129230). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The funding body has had no role in the design of the study and will have no role in the collection, analysis, and interpretation of the data and in the writing of any future manuscript. Acknowledgements The authors would like to thank all the patients, dentists and dental team members who are participating in the PIP Trial. We would also like to thank the members of the TSC and DMEC. We would like to acknowledge the funding for the project from the National Institute for Health Research Health Technology Assessment Programme (Project Number NIHR129230). The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health. Sponsor: University of Dundee Funder: National Institute for Health Research (NIHR), Health Technology Assessment (HTA) Programme, Project number: NIHR129230 The PIP study group consists of the co-chief investigators, grant holders, project management group and the Trial Management Committee as outlined as follows: Co-chief investigators: Jan E Clarkson (JC) and Craig R Ramsay (CR) Grant holders: Sondos Albradri (SA), Avijit Banerjee (AB), Katie Banister (KB), Dwayne Boyers (DB), David Conway (DC), Chris Deery (CD), Beatriz Goulao (BG), Ekta Gupta (EG), Fadi Jarad (FJ), Thomas Lamont (TL), Graeme MacLennan (GMacL), Francesco Mannocci (FM) Zoe Marshmann (ZM), Tina McGuff (TMcG), David Ricketts (DR), Douglas Robertson (DR) Marjon van der Pol (MvdP) and Linda Young (LY). Trial Management Committee: Sondos Albradri (SA), Avijit Banerjee (AB), Katie Banister (KB), Chris Deery (CD), Rosanne Bell (RB), David Conway (DC), Dwayne Boyers (DB), Lori Brown (LB), Pina Donaldson (PD), Anne Duncan (AD), Katharine Dunn (KD), Patrick Fee (PF), Mark Forrest (MF), Jill Gouick (JG), Beatriz Goulao (BG), Ekta Gupta (EG), Alice Hamilton (AH), Fadi Jarad (FJ), Jennifer Kettle (JK), Thomas Lamont (TL), Graeme MacLennan (GMacL), Lorna Macpherson (LM), Francesco Mannocci (FM), Zoe Marshmann (ZM), Fiona Mitchell (FM), Tina McGuff (TMcG), David Ricketts (DR), Douglas Robertson (DR), Marjon van der Pol (MvdP), Gabriella Wojewodka (GW) and Linda Young (LY)Peer reviewedPublisher PD

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

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.

Phloem sap intricacy and interplay with aphid feeding

Aphididae feed upon the plant sieve elements (SE), where they ingest sugars, nitrogen compounds and other nutrients. For ingestion, aphid stylets penetrate SE, and because of the high hydrostatic pressure in SE, phloem sap exudes out into the stylets. Severing stylets to sample phloem exudates (i.e. stylectomy) has been used extensively for the study of phloem contents. Alternative sampling techniques are spontaneous exudation upon wounding that only works in a few plant species, and the popular EDTA-facilitated exudation technique. These approaches have allowed fundamental advances on the understanding of phloem sap composition and sieve tube physiology, which are surveyed in this review. A more complete picture of metabolites, ions, proteins and RNAs present in phloem sap is now available, which has provided large evidence for the phloem role as a signalling network in addition to its primary role in partitioning of photo-assimilates. Thus, phloem sap sampling methods can have remarkable applications to analyse plant nutrition, physiology and defence responses. Since aphid behaviour is suspected to be affected by phloem sap quality, attempts to manipulate phloem sap content were recently undertaken based on deregulation in mutant plants of genes controlling amino acid or sugar content of phloem sap. This opens up new strategies to control aphid settlement on a plant host