nSharma: Numerical Simulation Heterogeneity Aware Runtime Manager for OpenFOAM

CFD simulations are a fundamental engineering application,implying huge workloads, often with dynamic behaviour due to run-time mesh refinement. Parallel processing over heterogeneous distributedmemory clusters is often used to process such workloads. The executionof dynamic workloads over a set of heterogeneous resources leads to loadimbalances that severely impacts execution time, when static uniformload distribution is used. This paper proposes applying dynamic, het-erogeneity aware, load balancing techniques within CFD simulations.nSharma, a software package that fully integrates with OpenFOAM, ispresented and assessed. Performance gains are demonstrated, achievedby reducing busy times standard deviation among resources, i.e. hetero-geneous computing resources are kept busy with useful work due to aneffective workload distribution. To best of authors’ knowledge, nSharmais the first implementation and integration of heterogeneity aware loadbalancing in OpenFOAM and will be made publicly available in order tofoster its adoption by the large community of OpenFOAM users.The authors would like to thank the financial funding by FEDER through the COMPETE 2020 Program, the National Funds through FCT under the projects UID/CTM/50025/2013. The first author was partially funded by the PT-FLAD Chair on Smart Cities & Smart Governance and also by the School of Engineering, University of Minho within project Performance Portability on Scalable Heterogeneous Computing Systems. The authors also wish to thank Kyle Mooney for making available his code supporting migration of dynamically refined meshes, as well as acknowledge the Texas Advanced Computing Center (TACC) at The University of Texas at Austin for providing HPC resources

Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study

Nicotinic acetylcholine receptors (nAChRs) are involved in a familial form of frontal lobe epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In several ADNFLE families, mutations were identified in the nAChR α4 or β2 subunit, which together compose the main cerebral nAChR. Electrophysiological assessment using in vitro expression systems indicated a gain of function of the mutant receptors. However the precise mechanisms by which they contribute to the pathogenesis of a focal epilepsy remain obscure, especially since α4β2 nAChRs are known to be widely distributed within the entire brain. PET study using [18F]-F-A-85380, a high affinity agonist at the α4β2 nAChRs, allows the determination of the regional distribution and density of the nAChRs in healthy volunteers and in ADNFLE patients, thus offering a unique opportunity to investigate some in vivo consequences of the molecular defect. We have assessed nAChR distribution in eight non-smoking ADNFLE patients (from five families) bearing an identified mutation in nAChRs and in seven age-matched non-smoking healthy volunteers using PET and [18F]-F-A-85380. Parametric images of volume of distribution (Vd) were generated as the ratio of tissue to plasma radioactivities. The images showed a clear difference in the pattern of the nAChR density in the brains of the patients compared to the healthy volunteers. Vd values revealed a significant increase (between 12 and 21%, P < 0.05) in the ADNFLE patients in the mesencephalon, the pons and the cerebellum when compared to control subjects. Statistical parametric mapping (SPM) was then used to better analyse subtle regional differences. This analysis confirmed clear regional differences between patients and controls: patients had increased nAChR density in the epithalamus, ventral mesencephalon and cerebellum, but decreased nAChR density in the right dorsolateral prefrontal region. In five patients who underwent an additional [18F]-fluorodeoxyglucose (FDG) PET experiment, hypometabolism was observed in the neighbouring area of the right orbitofrontal cortex. The demonstration of a regional nAChR density decrease in the prefrontal cortex, despite the known distribution of these receptors throughout the cerebral cortex, is consistent with a focal epilepsy involving the frontal lobe. We also propose that the nAChR density increase in mesencephalon is involved in the pathophysiology of ADNFLE through the role of brainstem ascending cholinergic systems in arousa

Utility and limitations of EEG in the diagnosis and management of ALDH7A1-related pyridoxine-dependent epilepsy. A retrospective observational study

PurposePyridoxine-dependent epilepsy due to ALDH7A1 variants (PDE-ALDH7A1) is a rare disorder, presenting typically with severe neonatal, epileptic encephalopathy. Early diagnosis is imperative to prevent uncontrolled seizures. We have explored the role of EEG in the diagnosis and management of PDE.MethodsA total of 13 Norwegian patients with PDE-ALDH7A1 were identified, of whom five had reached adult age. Altogether 163 EEG recordings were assessed, 101 from the 1st year of life.ResultsMedian age at seizure onset was 9 h (IQR 41), range 1 h-6 days. Median delay from first seizure to first pyridoxine injection was 2 days (IQR 5.5). An EEG burst suppression pattern was seen in eight patients (62%) during the first 5 days of life. Eleven patients had recordings during pyridoxine injections: in three, immediate EEG improvement correlated with seizure control, whereas in six, no change of epileptiform activity occurred. Of these six, one had prompt clinical effect, one had delayed effect (&lt; 1 day), one had no effect, one had uncertain effect, and another had more seizures. A patient without seizures at time of pyridoxine trial remained seizure free for 6 days. Two patients with prompt clinical effect had increased paroxysmal activity, one as a conversion to burst suppression. Autonomic seizures in the form of apnoea appeared to promote respiratory distress and were documented by EEG in one patient. EEG follow-up in adult age did not show signs of progressing encephalopathy.ConclusionA neonatal burst suppression EEG pattern should raise the suspicion of PDE-ALDH7A1. Respiratory distress is common; isolated apnoeic seizures may contribute. EEG responses during pyridoxine trials are diverse, often with poor correlation to immediate clinical effect. Reliance on single trials may lead to under-recognition of this treatable condition. Pyridoxine should be continued until results from biomarkers and genetic testing are available

Sediment transport-based metrics of wetland stability

Despite the importance of sediment availability on wetland stability, vulnerability assessments seldom consider spatiotemporal variability of sediment transport. Models predict that the maximum rate of sea level rise a marsh can survive is proportional to suspended sediment concentration (SSC) and accretion. In contrast, we find that SSC and accretion are higher in an unstable marsh than in an adjacent stable marsh, suggesting that these metrics cannot describe wetland vulnerability. Therefore, we propose the flood/ebb SSC differential and organic-inorganic suspended sediment ratio as better vulnerability metrics. The unstable marsh favors sediment export (18mgL(-1) higher on ebb tides), while the stable marsh imports sediment (12mgL(-1) higher on flood tides). The organic-inorganic SSC ratio is 84% higher in the unstable marsh, and stable isotopes indicate a source consistent with marsh-derived material. These simple metrics scale with sediment fluxes, integrate spatiotemporal variability, and indicate sediment sources

Dynamic Configuration of CUDA Runtime Variables for CDP-based Divide-and-Conquer Algorithms

International audienceCUDA Dynamic Parallelism (CDP) is an extension of the GPGPU programming model proposed to better address irregular applications and recursive patterns of computation. However, processing memory demanding problems by using CDP is not straightforward, because of its particular memory organization. This work presents an algorithm to deal with such an issue. It dynamically calculates and configures the CDP runtime variables and the GPU heap on the basis of an analysis of the partial backtracking tree. The proposed algorithm was implemented for solving permutation combinatorial problems and experimented on two test-cases: N-Queens and the Asymmetric Travelling Salesman Problem. The proposed algorithm allows different CDP-based backtracking from the literature to solve memory demanding problems, adaptively with respect to the number of recursive kernel generations and the presence of dynamic allocations on GPU

The impact of gender, puberty, and pregnancy in patients with POLG disease

Objective To study the impact of gender, puberty, and pregnancy on the expression of POLG disease, one of the most common mitochondrial diseases known. Methods Clinical, laboratory, and genetic data were collected retrospectively from 155 patients with genetically confirmed POLG disease recruited from seven European countries. We used the available data to study the impact of gender, puberty, and pregnancy on disease onset and deterioration. Results We found that disease onset early in life was common in both sexes but there was also a second peak in females around the time of puberty. Further, pregnancy had a negative impact with 10 of 14 women (71%) experiencing disease onset or deterioration during pregnancy. Interpretation Gender clearly influences the expression of POLG disease. While onset very early in life was common in both males and females, puberty in females appeared associated both with disease onset and increased disease activity. Further, both disease onset and deterioration, including seizure aggravation and status epilepticus, appeared to be associated with pregnancy. Thus, whereas disease activity appears maximal early in life with no subsequent peaks in males, both menarche and pregnancy appear associated with disease onset or worsening in females. This suggests that hormonal changes may be a modulating factor.Peer reviewe

Simplifying the clinical classification of polymerase gamma (POLG) disease based on age of onset; studies using a cohort of 155 cases

Background Variants inPOLGare one of the most common causes of inherited mitochondrial disease. Phenotypic classification of POLG disease has evolved haphazardly making it complicated and difficult to implement in everyday clinical practise. The aim of our study was to simplify the classification and facilitate better clinical recognition. Methods A multinational, retrospective study using data from 155 patients withPOLGvariants recruited from seven European countries. Results We describe the spectrum of clinical features associated withPOLGvariants in the largest known cohort of patients. While clinical features clearly form a continuum, stratifying patients simply according to age of onset-onset prior to age 12 years; onset between 12 and 40 years and onset after the age of 40 years, permitted us to identify clear phenotypic and prognostic differences. Prior to 12 years of age, liver involvement (87%), seizures (84%), and feeding difficulties (84%) were the major features. For those with onset between 12 and 40 years, ataxia (90%), peripheral neuropathy (84%), and seizures (71%) predominated, while for those with onset over 40 years, ptosis (95%), progressive external ophthalmoplegia (89%), and ataxia (58%) were the major clinical features. The earlier the onset the worse the prognosis. Patients with epilepsy and those with compound heterozygous variants carried significantly worse prognosis. Conclusion Based on our data, we propose a simplified POLG disease classification, which can be used to guide diagnostic investigations and predict disease course.Peer reviewe

BAKTRAK: Backtracking drifting objects using an iterative algorithm with a forward trajectory model

The task of determining the origin of a drifting object after it has been located is highly complex due to the uncertainties in drift properties and environmental forcing (wind, waves and surface currents). Usually the origin is inferred by running a trajectory model (stochastic or deterministic) in reverse. However, this approach has some severe drawbacks, most notably the fact that many drifting objects go through nonlinear state changes underway (e.g., evaporating oil or a capsizing lifeboat). This makes it difficult to naively construct a reverse-time trajectory model which realistically predicts the earliest possible time the object may have started drifting. We propose instead a different approach where the original (forward) trajectory model is kept unaltered while an iterative seeding and selection process allows us to retain only those particles that end up within a certain time-space radius of the observation. An iterative refinement process named BAKTRAK is employed where those trajectories that do not make it to the goal are rejected and new trajectories are spawned from successful trajectories. This allows the model to be run in the forward direction to determine the point of origin of a drifting object. The method is demonstrated using the Leeway stochastic trajectory model for drifting objects due to its relative simplicity and the practical importance of being able to identify the origin of drifting objects. However, the methodology is general and even more applicable to oil drift trajectories, drifting ships and hazardous material that exhibit non-linear state changes such as evaporation, chemical weathering, capsizing or swamping. The backtracking method is tested against the drift trajectory of a life raft and is shown to predict closely the initial release position of the raft and its subsequent trajectory.Comment: 28 pages, 8 figures, 2 table

Elevated cerebrospinal fluid protein in POLG-related epilepsy : Diagnostic and prognostic implications

Objective: Epilepsy is common in individuals with mutations in POLG, the gene encoding the catalytic subunit of the mitochondrial DNA polymerase gamma. Early recognition and aggressive seizure management are crucial for patient survival. Disruption of the blood-brain barrier (BBB) is implicated in various neurological disorders including epilepsy. The aim of this study was to assess whether POLG-related disease is associated with BBB dysfunction and what clinical implications this has for patients. Methods: Our retrospective study used data from 83 patients with pathogenic POLG mutations from 4 countries-Norway, Sweden, Finland, and the United Kingdom. Data were collected using a structured questionnaire. We used the presence of raised cerebrospinal fluid (CSF) protein and a raised CSF/serum ratio of albumin (Q-alb) to evaluate the integrity of the blood-CSF bather. Results: Raised CSF protein was found in 70% of patients (n = 58/83) and appeared to be associated with the most severe phenotypes. In those in whom it was measured, the Q-alb ratio was markedly elevated (n = 18). The majority of those with epilepsy (n = 50/66, 76%) had raised CSF protein, and this preceded seizure debut in 75% (n = 15/20). The median survival time from symptom onset for those with raised CSF protein was decreased (13 months) compared to those with normal CSF protein (32 months). Significance: Our results indicate that there is disruption of the BBB in POLG-related disease, as evidenced by a raised CSF protein and Q-alb ratio. We also find that raised CSF protein is a common finding in patients with POLG disease. Our data suggest that the presence of BBB dysfunction predicts a poorer outcome, and elevated CSF protein may therefore be an additional biomarker both for early diagnosis and to identify those at high risk of developing epilepsy.Peer reviewe

Safety of Levetiracetam in paediatrics: a systematic review

Objective To identify adverse events (AEs) associated with Levetiracetam (LEV) in children. Methods Databases EMBASE (1974-February 2015) and Medline (1946-February 2015) were searched for articles in which paediatric patients (≤18 years) received LEV treatment for epilepsy. All studies with reports on safety were included. Studies involving adults, mixed age population (i.e. children and adults) in which the paediatric subpopulation was not sufficiently described, were excluded. A meta-analysis of the RCTs was carried out and association between the commonly reported AEs or treatment discontinuation and the type of regimen (polytherapy or monotherapy) was determined using Chi2 analysis. Results Sixty seven articles involving 3,174 paediatric patients were identified. A total of 1,913 AEs were reported across studies. The most common AEs were behavioural problems and somnolence, which accounted for 10.9% and 8.4% of all AEs in prospective studies. 21 prospective studies involving 1120 children stated the number of children experiencing AEs. 47% of these children experienced AEs. Significantly more children experienced AEs with polytherapy (64%) than monotherapy (22%) (p<0.001). Levetiracetam was discontinued in 4.5% of all children on polytherapy and 0.9% on monotherapy (p<0.001), the majority were due to behavioural problems. Conclusion Behavioural problems and somnolence were the most prevalent adverse events to LEV and the most common causes of treatment discontinuation. Children on polytherapy have a greater risk of adverse events than those receiving monotherapy