Search

Despite their essential role in the high‐latitude climate, the representation of mixed‐phase clouds is still a challenge for Global Climate Models (GCMs)'s cloud schemes. In this study we propose a methodology for robustly assessing Arctic mixed‐phase cloud properties in a climate model using airborne measurements. We leverage data collected during the RALI‐THINICE airborne campaign that took place near Svalbard in August 2022 to evaluate the simulation of mid‐level clouds associated with Arctic cyclones. Simulations are carried out with the new limited‐area configuration of the ICOLMDZ model which combines the recent icosahedral dynamical core DYNAMICO and the physics of LMDZ, the atmospheric component of the IPSL‐CM Earth System Model. Airborne radar and microphysical probes measurements are then used to evaluate the simulated clouds. A comparison method has been set‐up to guarantee as much as possible the spatiotemporal co‐location between observed and simulated cloud fields. We mostly focus on the representation of ice and liquid in‐cloud contents and on their vertical distribution. Results show that the model overestimates the amount of cloud condensates and exhibits a poor cloud phase spatial distribution, with too much liquid water far from cloud top and too much ice close to it. The downward gradual increase in snowfall flux is also not captured by the model. This in‐depth model evaluation thereby pinpoints priorities for further improvements in the ICOLMDZ cloud scheme. Plain Language Summary: Mixed‐phase clouds, where ice crystals and supercooled liquid droplets coexist at sub‐zero temperatures, are ubiquitous in the polar regions. Albeit essential for the high‐latitude climate, they are still poorly represented by climate models. In this study, original measurements from the RALI‐THINICE airborne campaign, which took place in the Svalbard region in August 2022, are used to assess how the ICOLMDZ atmospheric model represents Arctic mixed phase clouds. A methodology is developed to make robust and co‐located model‐aircraft observation comparisons. In situ cloud probes and onboard radars are then used to evaluate the simulated amounts of liquid water and ice in clouds as well as the snowfall flux in deep clouds associated with the transit of Arctic cyclones. The results of the model evaluation show an overall overestimation of cloud condensates with too much liquid water far from cloud top and too much ice close to it. Key Points: Airborne RALI‐THINICE observations are used to evaluate Arctic clouds in the new limited area version of the ICOLMDZ modelA methodology has been developed to make robust and co‐located model‐observation comparisonsICOLMDZ simulates overly high amounts of liquid and ice in clouds particularly near cloud top [ABSTRACT FROM AUTHOR]

Despite many years of extensive research, the evolution of Tropical Cyclone (TC) activity in our changing climate remains uncertain. This is partly because the answer to that question relies primarily on climate simulations with horizontal resolutions of a few tens of kilometers. Such simulations have only recently become accessible for most modeling centers, including the Institut Pierre-Simon Laplace (IPSL). Using recent numerical developments in the IPSL model, we perform a series of historical atmospheric-only simulations that follow the HighResMIP protocol. We assess the impact of increasing the resolution from ∼ 200 to 25 km on TC activity. In agreement with previous work, we find a systematic improvement of TC activity with increasing resolution with respect to the observations. However, a clear signature of TC frequencies convergence with resolution is still lacking. Cyclogenesis geographical distributions also improve at the scale of individual basins. This is particularly true of the North Atlantic, where the agreement with the observed distribution is impressive at 25 km. In agreement with the observations, TC activity correlates with the large-scale environment and ENSO in that basin. By contrast, TC frequencies remain too small in the Western North Pacific at 25 km, where significant biases of humidity and vorticity are found compared to the reanalysis. Despite the few minor weaknesses we identified, our results demonstrate that the IPSL model is a suitable tool for studying TCs on climate time scales. This work thus opens the way for further studies contributing to our understanding of TC climatology. [ABSTRACT FROM AUTHOR]

The Coupled Model Intercomparison Project (CMIP) is one of the biggest international efforts aimed at better understanding the past, present, and future of climate changes in a multi-model context. A total of 21 model intercomparison projects (MIPs) were endorsed in its sixth phase (CMIP6), which included 190 different experiments that were used to simulate 40 000 years and produced around 40 PB of data in total. This paper presents the main findings obtained from the CPMIP (the Computational Performance Model Intercomparison Project), a collection of a common set of metrics, specifically designed for assessing climate model performance. These metrics were exclusively collected from the production runs of experiments used in CMIP6 and primarily from institutions within the IS-ENES3 consortium. The document presents the full set of CPMIP metrics per institution and experiment, including a detailed analysis and discussion of each of the measurements. During the analysis, we found a positive correlation between the core hours needed, the complexity of the models, and the resolution used. Likewise, we show that between 5 %–15 % of the execution cost is spent in the coupling between independent components, and it only gets worse by increasing the number of resources. From the data, it is clear that queue times have a great impact on the actual speed achieved and have a huge variability across different institutions, ranging from none to up to 78 % execution overhead. Furthermore, our evaluation shows that the estimated carbon footprint of running such big simulations within the IS-ENES3 consortium is 1692 t of CO 2 equivalent. As a result of the collection, we contribute to the creation of a comprehensive database for future community reference, establishing a benchmark for evaluation and facilitating the multi-model, multi-platform comparisons crucial for understanding climate modelling performance. Given the diverse range of applications, configurations, and hardware utilised, further work is required for the standardisation and formulation of general rules. The paper concludes with recommendations for future exercises aimed at addressing the encountered challenges which will facilitate more collections of a similar nature. [ABSTRACT FROM AUTHOR]

The Coupled Model Intercomparison Project (CMIP) is one of the biggest international efforts to better understand past, present and future climate changes in a multi-model context. A total of 21 Model Intercomparison Projects (MIPs) were endorsed in its 6th phase (CMIP6), which included 190 different experiments that were used to simulate 40000 years and produced around 40 PB of data in total. This paper shows the main results obtained from the collection of performance metrics done for CMIP6 (CPMIP). The document provides the list of partners involved, the CPMIP metrics per institution/model, and the approach used for the collection and the coordination behind this process. Furthermore, a section has been included to analyze the results and prove the usefulness of the metrics for the community. Moreover, we describe the main difficulties faced during the collection and propose recommendations for future exercises. [ABSTRACT FROM AUTHOR]

Background: The enduring presence of COVID-19 and subsequent increasing incidence of COVID-19 reinfection has prompted evaluation of associated risk factors, particularly the role of immunosuppression. Objective: The objective of this study was to characterize cases indicative of COVID-19 reinfection with respect to their reported use of immunosuppressant/immunomodulating agents. Methods: This cross-sectional observational study leveraged the Pfizer global safety database (SDB) containing adverse event data collected in association with use of Pfizer products between 1 October 2019, and 30 June 2022. Selected Medical Dictionary for Drug Regulatory Activities (MedDRA®) Preferred Terms were used to identify COVID-19 cases; the search was further refined to comprise cases that subsequently reported events potentially indicative of COVID-19 reinfection. Results: Of the cumulative total of 218,242 COVID-19 cases reported into the SDB, 4590 cases (2.1%) involving potential COVID-19 reinfection were identified. Of these 4590 cases of potential Covid-19 reinfection, a total of 134 cases reported COVID-19 specifically during treatment with pharmaceutical products, of which approximately 16% (21/134) of cases reported use of immunosuppressant/immunomodulating agents. Likewise, in the overall dataset (213,652 cases; excluding the 4590 cases involving potential COVID-19 recurrence), the percentage of reported immunosuppressant/immunomodulating agents was low (12%). In applying similar parameters to a dataset that excludes COVID-19 vaccine cases, 18% of cases reported use of immunosuppressant/immunomodulating agents (similar to the aforementioned 16% of cases reported from the overall total dataset that was inclusive of vaccine cases). Conclusion: This pharmacovigilance study provides a characterization of cases indicative of COVID-19 reinfection with respect to reported use of immunosuppressant/immunomodulating agents. The observations generated from this cross-sectional observational analysis may prompt further research into the role of immunosuppression in COVID-19 reinfection, in an effort to better inform clinical practice and patient management. [ABSTRACT FROM AUTHOR]

The assessment of current and future risks for natural and human systems associated with climate change largely relies on numerical simulations performed with state‐of‐the‐art climate models. Various steps are involved in the development of such models, from development of individual components of the climate system up to free parameter calibration of the fully coupled model. Here, we describe the final tuning phase for the IPSL‐CM6A‐LR climate model. This phase alone lasted more than 3 years and relied on several pillars: (i) the tuning against present‐day conditions given a small adjustment of the ocean surface albedo to compensate for the current oceanic heat uptake, (ii) the release of successive versions after adjustments of the individual components, implying a systematic and recurrent adjustment of the atmospheric energetics, and (iii) the use of a few metrics based on large scale variables such as near‐global mean temperature, summer Arctic sea‐ice extent, as targets for the tuning. Successes, lessons and prospects of this tuning strategy are discussed. Plain Language Summary: Evaluating current and future risks for natural and human systems associated with climate change is largely based on numerical simulations performed with models of the climate system, which includes the atmosphere, the land, the ocean, the cryosphere, and the oceanic and terrestrial biosphere. Various steps are involved in the development of such models. First, models for individual components are developed and tested. Second, many aspects are represented with parameterizations that summarize the effect of a missing process, such as those happening on scales that are smaller than the model grid sizes. The parameterizations in turn involve many parameters, sometimes poorly estimated from observations, that have to be calibrated. Here, we describe the final tuning phase of the IPSL‐CM6A‐LR climate model, which includes several novel aspects: first, the choice to calibrate the model against present‐day observations, which implies taking into account the transient nature of the observed climate; second, the systematic and recurrent adjustment of the atmospheric radiative budget; third, the use of a few large scale observable variables as targets. Successes, lessons and prospects of this tuning strategy are discussed. Key Points: The tuning process of IPSL‐CM6A‐LR under present‐day control conditions is describedThe associated continuous atmospheric energetics adjustment is presentedSuccesses, lessons and prospects of the IPSL‐CM6A‐LR tuning strategy are discussed [ABSTRACT FROM AUTHOR]

Introduction: Evidence-based clinical data on coronavirus disease 2019 (COVID-19) pharmacotherapies are scarce. Objective: This study documented and characterized COVID-19 cases reported in individuals receiving treatment with Pfizer pharmaceutical products and cases that reported use of Pfizer pharmaceutical products for COVID-19 treatment. Methods: This retrospective observational review leveraged the Pfizer safety database containing adverse event data collected in association with use of Pfizer products between 1 October, 2019, and 25 June, 2020; the database includes worldwide adverse event data from various sources. Selected Medical Dictionary for Drug Regulatory Activities (MedDRA®) Preferred Terms and subsequent clinical review were used to characterize COVID-19 cases. Results: Over 1500 relevant cases were identified over an 8-month period. In cases that reported COVID-19, immunosuppressant/immunomodulating agents, followed by anticoagulant/antithrombic agents and corticosteroids, were the most frequently reported agents. The frequent reporting of immunosuppressant/immunomodulating agents among cases of COVID-19 suggests increased vulnerability to infection among treated patients, either because of immunosuppressive effects of certain agents or the nature of the underlying treated condition. In cases involving off-label pharmacotherapy use for the treatment of COVID-19-related conditions, the most frequently reported therapeutic classes included antibiotics, antimalarial agents, antivirals/antiretroviral agents, immunosuppressant/immunomodulating agents, corticosteroids, anticoagulants, and immunoglobulin/interferons. The most frequently reported pharmacotherapeutic agents were azithromycin and chloroquine/hydroxychloroquine, followed by lopinavir-ritonavir, ceftriaxone, and tofacitinib. The most frequently reported clinical adverse events associated with azithromycin (as sole therapy or combined with chloroquine/hydroxychloroquine) include electrocardiogram QT prolonged, drug interaction, hepatitis, diarrhea, and hepatitis acute. Regarding cardiac-related events, 19% (120/645) of azithromycin cases reported events associated with QT prolongation/torsade de pointes (which included seven fatal cardiac events). The most frequently reported clinical adverse events associated with other commonly used agents are also presented. Conclusions: This pharmacovigilance surveillance study provides a unique characterization of cases in which a broad range of pharmaceutical products was reported in relation to COVID-19. [ABSTRACT FROM AUTHOR]

Purpose There is a need to develop hybrid trial methodology combining the best parts of traditional randomized controlled trials (RCTs) and observational study designs to produce real‐world evidence (RWE) that provides adequate scientific evidence for regulatory decision‐making. Methods: This review explores how hybrid study designs that include features of RCTs and studies with real‐world data (RWD) can combine the advantages of both to generate RWE that is fit for regulatory purposes. Results: Some hybrid designs include randomization and use pragmatic outcomes; other designs use single‐arm trial data supplemented with external comparators derived from RWD or leverage novel data collection approaches to capture long‐term outcomes in a real‐world setting. Some of these approaches have already been successfully used in regulatory decisions, raising the possibility that studies using RWD could increasingly be used to augment or replace traditional RCTs for the demonstration of drug effectiveness in certain contexts. These changes come against a background of long reliance on RCTs for regulatory decision‐making, which are labor‐intensive, costly, and produce data that can have limited applicability in real‐world clinical practice. Conclusions: While RWE from observational studies is well accepted for satisfying postapproval safety monitoring requirements, it has not commonly been used to demonstrate drug effectiveness for regulatory purposes. However, this position is changing as regulatory opinions, guidance frameworks, and RWD methodologies are evolving, with growing recognition of the value of using RWE that is acceptable for regulatory decision‐making. [ABSTRACT FROM AUTHOR]

This study presents the global climate model IPSL‐CM6A‐LR developed at Institut Pierre‐Simon Laplace (IPSL) to study natural climate variability and climate response to natural and anthropogenic forcings as part of the sixth phase of the Coupled Model Intercomparison Project (CMIP6). This article describes the different model components, their coupling, and the simulated climate in comparison to previous model versions. We focus here on the representation of the physical climate along with the main characteristics of the global carbon cycle. The model's climatology, as assessed from a range of metrics (related in particular to radiation, temperature, precipitation, and wind), is strongly improved in comparison to previous model versions. Although they are reduced, a number of known biases and shortcomings (e.g., double Intertropical Convergence Zone [ITCZ], frequency of midlatitude wintertime blockings, and El Niño–Southern Oscillation [ENSO] dynamics) persist. The equilibrium climate sensitivity and transient climate response have both increased from the previous climate model IPSL‐CM5A‐LR used in CMIP5. A large ensemble of more than 30 members for the historical period (1850–2018) and a smaller ensemble for a range of emissions scenarios (until 2100 and 2300) are also presented and discussed. Plain Language Summary: Climate models are unique tools to investigate the characteristics and behavior of the climate system. While climate models and their components are developed gradually over the years, the sixth phase of the Coupled Model Intercomparison Project (CMIP6) has been the opportunity for the Institut Pierre‐Simon Laplace to develop, test, and evaluate a new configuration of its climate model called IPSL‐CM6A‐LR. The characteristics and emerging properties of this new model are presented in this study. The model climatology, as assessed from a range of metrics, is strongly improved, although a number of biases common to many models do persist. The equilibrium climate sensitivity and transient climate response have both increased from the previous climate model IPSL‐CM5A‐LR used in CMIP5. Key Points: The IPSL‐CM6A‐LR model climatology is much improved over the previous version, although some systematic biases and shortcomings persistA long preindustrial control and a large number of historical and scenario simulations have been performed as part of CMIP6The effective climate sensitivity of the IPSL model increases from 4.1 to 4.8 K between IPSL‐CM5A‐LR and IPSL‐CM6A‐LR [ABSTRACT FROM AUTHOR]

Based on the fifth phase of the Coupled Model Intercomparison Project (CMIP5)-generation previous Institut Pierre Simon Laplace (IPSL) Earth system model, we designed a new version, IPSL-CM5A2, aiming at running multi-millennial simulations typical of deep-time paleoclimate studies. Three priorities were followed during the setup of the model: (1) improving the overall model computing performance, (2) overcoming a persistent cold bias depicted in the previous model generation and (3) making the model able to handle the specific continental configurations of the geological past. These developments include the integration of hybrid parallelization Message Passing Interface – Open Multi-Processing (MPI-OpenMP) in the atmospheric model of the Laboratoire de Météorologie Dynamique (LMDZ), the use of a new library to perform parallel asynchronous input/output by using computing cores as "I/O servers" and the use of a parallel coupling library between the ocean and the atmospheric components. The model, which runs with an atmospheric resolution of 3.75∘×1.875∘ and 2 to 0.5 ∘ in the ocean, can now simulate ∼100 years per day, opening new possibilities towards the production of multi-millennial simulations with a full Earth system model. The tuning strategy employed to overcome a persistent cold bias is detailed. The confrontation of a historical simulation to climatological observations shows overall improved ocean meridional overturning circulation, marine productivity and latitudinal position of zonal wind patterns. We also present the numerous steps required to run IPSL-CM5A2 for deep-time paleoclimates through a preliminary case study for the Cretaceous. Namely, specific work on the ocean model grid was required to run the model for specific continental configurations in which continents are relocated according to past paleogeographic reconstructions. By briefly discussing the spin-up of such a simulation, we elaborate on the requirements and challenges awaiting paleoclimate modeling in the next years, namely finding the best trade-off between the level of description of the processes and the computing cost on supercomputers. [ABSTRACT FROM AUTHOR]

Based on the CMIP5-generation previous IPSL earth system model, we designed a new version, IPSL-CM5A2, aiming at running multi-millennial simulations typical of deep-time paleoclimates studies. Three priorities were followed during the set-up of the model: (1) improving the overall model computing performance, (2) overcoming a persistent cold bias depicted in the previous model generation, and (3) making the model able to handle the specific continental configurations of the geological past. Technical developments have been performed on separate components and on the coupling system to speed up the whole coupled model. These developments include the integration of hybrid parallelization MPI-OpenMP in LMDz atmospheric component, the use of a new library to perform parallel asynchronous input/output by using computing cores as "IO servers", the use of a parallel coupling library between the ocean and the atmospheric components. The model can now simulate ~100 years per day, opening new possibilities towards the production of multi-millennial simulations with a full earth system model. The tuning strategy employed to overcome a persistent cold bias is detailed. The confrontation of an historical simulation to climatological observations shows overall improved ocean meridional overturning circulation, marine productivity and latitudinal position of zonal wind patterns. We also present the numerous steps required to run the IPSL-CM5A2 for deep-time paleoclimates through a preliminary case-study for the Cretaceous. Namely, a specific work on the ocean model grid was required to run the model for specific continental configurations in which continents are relocated according to past paleogeographic reconstructions. By briefly discussing the spin-up of such a simulation, we elaborate on the requirements and challenges awaiting paleoclimate modelling in the next years, namely finding the best trade-off between the level of description of the processes and the computing cost on supercomputers. [ABSTRACT FROM AUTHOR]

Particularly dry or wet boreal summer monsoon seasons are major hazards affecting societal vulnerability in India and Africa. Several factors affect monsoon rainfall amount and limit the understanding of possible linkages between monsoon variability and mean climate changes. Here we characterize the multiscale variability of Indian and West African monsoon rain from two simulations of the last 6,000 years. Changes in Earth's orbit cause long‐term monsoon drying trend in India and Africa, but the Indian monsoon is more sensitive to anthropogenic CO2. Variability is characterized by two major ranges of chaotic variability, each related to specific ocean‐atmosphere modes present throughout the period. Combination of random 50‐ to 500‐ and 2‐ to 20‐year variability leads to large events occurring at millennium scale. However, the two regions exhibit opposite trends in rainfall variability due to changes in teleconnection with Pacific sea surface temperature for India and Atlantic sea surface temperature for West Africa at interannual to decadal timescales. Key Points: Indian monsoon rainfall is more sensitive than West African monsoon rainfall to CO2Two major bands of chaotic variability, 2–20 years and 50–500 years, affect Indian and West African monsoon variability of the last 6,000 yearsOpposite Holocene variability trends in Indian and African monsoon are due to interannual and not centennial variability linkages with mean state [ABSTRACT FROM AUTHOR]

Introduction: Drug safety remains a top global public health concern. An increase in the number of data sources available has increased the complexity of pharmacovigilance operations, so the US FDA has created draft guidance focusing on optimizing drug safety data for well-characterized medicines. However, to date, no data demonstrating changes in reports have been presented. Objectives: This study provided data assessing changes in individual case safety reports (ICSRs) and aggregate reports (ARs) for large biopharmaceutical companies from 2007 to 2017. This study also evaluated current trends on the use of advanced machine and deep learning in order to process all data captured for ICSRs as well as opinions from industry thought leaders on creating a sustainable case-processing operation. Methodology: Using data captured from Navitas Life Science's annual pvnet® benchmark, we calculated workload indicators characterizing pharmacovigilance operations for large biopharmaceutical organizations. Workload indicators included the number of ICSRs by organization, the number of ARs, and the number and types of data sources used. We also conducted structured in-depth interviews with seven biopharmaceutical executives to discover the reasons for changes in workload indicators across time as well as current strategies for increasing efficiencies in drug safety reporting. Results: The median number of ICSRs increased from 84,960 cases in 2007 to over 200,000 cases in 2017; this increase was largely attributable to an increase in both nonserious cases and follow-up cases. Member companies reported using 12 ± 3 data sources for case identification. The number of ARs also increased from a median of 70 reports in 2007 to 258 reports in 2017. To address these increases, 61% of the biopharmaceutical organizations we surveyed planned to adopt machine learning for full ICSR processing; however, as of 2018, none of the organizations surveyed had mechanisms in place. Conclusion: This study demonstrated that pharmacovigilance departments are currently burdened by ever-increasing case volumes. With increased guidance from regulatory agencies, as well as improvements in artificial intelligence and natural language processing, biopharmaceutical organizations must determine the most resource-efficient and sustainable methods to process the growing volume of cases. [ABSTRACT FROM AUTHOR]

Automation of pharmaceutical safety case processing represents a significant opportunity to affect the strongest cost driver for a company's overall pharmacovigilance budget. A pilot was undertaken to test the feasibility of using artificial intelligence and robotic process automation to automate processing of adverse event reports. The pilot paradigm was used to simultaneously test proposed solutions of three commercial vendors. The result confirmed the feasibility of using artificial intelligence–based technology to support extraction from adverse event source documents and evaluation of case validity. In addition, the pilot demonstrated viability of the use of safety database data fields as a surrogate for otherwise time‐consuming and costly direct annotation of source documents. Finally, the evaluation and scoring method used in the pilot was able to differentiate vendor capabilities and identify the best candidate to move into the discovery phase. [ABSTRACT FROM AUTHOR]

Low-cost air pollution sensors are emerging and increasingly being deployed in densely distributed wireless networks that provide more spatial resolution than is typical in traditional monitoring of ambient air quality. However, a low-cost option to measure black carbon (BC)—a major component of particulate matter pollution associated with adverse human health risks—is missing. This paper presents a new BC sensor designed to fill this gap, the Aerosol Black Carbon Detector (ABCD), which incorporates a compact weatherproof enclosure, solar-powered rechargeable battery, and cellular communication to enable long-term, remote operation. This paper also demonstrates a data processing methodology that reduces the ABCD’s sensitivity to ambient temperature fluctuations, and therefore improves measurement performance in unconditioned operating environments (e.g., outdoors). A fleet of over 100 ABCDs was operated outdoors in collocation with a commercial BC instrument (Magee Scientific, Model AE33) housed inside a regulatory air quality monitoring station. The measurement performance of the 105 ABCDs is comparable to the AE33. The fleet-average precision and accuracy, expressed in terms of mean absolute percentage error, are 9.2± 0.8% (relative to the fleet average data) and 24.6± 0.9% (relative to the AE33 data), respectively (fleet-average ± 90% confidence interval). [ABSTRACT FROM AUTHOR]

Introduction: Post-marketing drug surveillance is largely based on signals found in spontaneous reports from patients and healthcare providers. Rare adverse drug reactions and adverse events (AEs) that may develop after long-term exposure to a drug or from drug interactions may be missed. The US FDA and others have proposed that web-based data could be mined as a resource to detect latent signals associated with adverse drug reactions.Methods: Recently, a web-based search query method called a query log reaction score (QLRS) was developed to detect whether AEs associated with certain drugs could be found from search engine query data. In this study, we compare the performance of two other algorithms, the proportional query ratio (PQR) and the proportional query rate ratio (Q-PRR) against that of two reference signal-detection algorithms (SDAs) commonly used with the FDA AE Reporting System (FAERS) database.Results: In summary, the web query methods have moderate sensitivity (80%) in detecting signals in web query data compared with reference SDAs in FAERS when the web query data are filtered, but the query metrics generate many false-positives and have low specificity compared with reference SDAs in FAERS.Conclusion: Future research is needed to find better refinements of query data and/or the metrics to improve the specificity of these web query log algorithms. [ABSTRACT FROM AUTHOR]

A climate model represents a multitude of processes on a variety of timescales and space scales: a canonical example of multi-physics multi-scale modeling. The underlying climate system is physically characterized by sensitive dependence on initial conditions, and natural stochastic variability, so very long integrations are needed to extract signals of climate change. Algorithms generally possess weak scaling and can be I/O and/or memory-bound. Such weak-scaling, I/O, and memory-bound multi-physics codes present particular challenges to computational performance. Traditional metrics of computational efficiency such as performance counters and scaling curves do not tell us enough about real sustained performance from climate models on different machines. They also do not provide a satisfactory basis for comparative information across models. codes present particular challenges to computational performance. We introduce a set of metrics that can be used for the study of computational performance of climate (and Earth system) models. These measures do not require specialized software or specific hardware counters, and should be accessible to anyone. They are independent of platform and underlying parallel programming models. We show how these metrics can be used to measure actually attained performance of Earth system models on different machines, and identify the most fruitful areas of research and development for performance engineering. codes present particular challenges to computational performance. We present results for these measures for a diverse suite of models from several modeling centers, and propose to use these measures as a basis for a CPMIP, a computational performance model intercomparison project (MIP). [ABSTRACT FROM AUTHOR]

A climate model represents a multitude of processes on a variety of time and space scales; a canonical example of multi-physics multi-scale modeling. The underlying climate system is physically characterized by sensitive dependence on initial conditions, and natural stochastic variability, so very long integrations are needed to extract signals of climate change. Algorithms generally possess weak scaling and can be I/O and/or memory bound. Such weak-scaling, I/O and memory-bound multi-physics codes present particular challenges to computational performance. Traditional metrics of computational efficiency such as performance counters and scaling curves do not tell us enough about real sustained performance from climate models on different machines. They also do not provide a satisfactory basis for comparative information across models. We introduce a set of metrics that can be used for the study of computational performance of climate (and Earth System) models. These measures do not require specialized software or specific hardware counters, and should be accessible to anyone. They are independent of platform, and underlying parallel programming models. We show how these metrics can be used to measure actually attained performance of Earth system models on different machines, and identify the most fruitful areas of research and development for performance engineering. We present results for these measures for a diverse suite of models from several modeling centres, and propose to use these measures as a basis for a CPMIP, a computational performance MIP. [ABSTRACT FROM AUTHOR]

Objective To obtain perspective on epilepsy in patients referred to tertiary centers in France, and describe etiology, epilepsy syndromes, and identify factors of drug resistance and comorbidities. Methods We performed a cross-sectional analysis of the characteristics of 5,794 pediatric and adult patients with epilepsy included in a collaborative database in France between 2007 and 2013. Comparisons between groups used Student's t-test or Fisher's exact test for binary or categorical variables. Factors associated with drug resistance and intellectual disability were evaluated in multi-adjusted logistic regression models. Results Mean age at inclusion was 17.9 years; children accounted for 67%. Epilepsy was unclassified in 20% of patients, and etiology was unknown in 65%, including those with idiopathic epilepsies. Etiologies differed significantly in adult- when compared to pediatric-onset epilepsy; however, among focal structural epilepsies, mesial temporal lobe epilepsy with hippocampal sclerosis began as often in the pediatric as in adult age range. Drug resistance concerned 53% of 4,210 patients evaluable for seizure control and was highest in progressive myoclonic epilepsy (89%), metabolic diseases (84%), focal cortical dysplasia (70%), other cortical malformations (69%), and mesial temporal lobe epilepsy with hippocampal sclerosis (67%). Fifty-nine percent of patients with focal structural epilepsy and 69% with epileptic encephalopathies were drug resistant; however, 40-50% of patients with West syndrome and epileptic encephalopathy with continuous spike-and-waves during sleep were seizure-free. Ages at onset in infancy and in young adults shared the highest risk of drug resistance. Epilepsy onset in infancy comprised the highest risk of intellectual disability, whereas specific cognitive impairment affected 36% of children with idiopathic focal epilepsy. Significance Our study provides a snapshot on epilepsy in patients referred to tertiary centers and discloses needs for diagnosis and treatment. Large databases help identify patients with rare conditions that could benefit from specific prospective studies. [ABSTRACT FROM AUTHOR]

Studies show that if we retrofit all the lighting systems in the buildings of California with dimming ballasts, then it would be possible to obtain a 450 MW of regulation, 2.5 GW of nonspinning reserve, and 380 MW of contingency reserve from participation of lighting loads in the energy market. However, in order to guarantee participation, it will be important to monitor and model lighting demand and supply in buildings. To this end, wireless sensor and actuator networks have proven to bear a great potential for personalized intelligent lighting with reduced energy use at 50%-70%. Closed-loop control of these lighting systems relies upon instantaneous and dense sensing. Such systems can be expensive to install and commission. In this paper, we present a sensor-based intelligent lighting system for future grid-integrated buildings. The system is intended to guarantee participation of lighting loads in the energy market, based on predictive models of indoor light distribution, developed using sparse sensing. We deployed ~92 % fewer sensors compared with state-of-art systems using one photosensor per luminaire. The sensor modules contained small solar panels that were powered by ambient light. Reduction in sensor deployments is achieved using piecewise linear predictive models of indoor light, discretized by clustering for sky conditions and sun positions. Day-ahead daylight is predicted from forecasts of temperature, humidity, and cloud cover. With two weeks of daylight and artificial light training data acquired at the sustainability base at NASA Ames, our model was able to predict the illuminance at seven monitored workstations with 80%-95% accuracy. Moreover, our support vector regression model was able to predict day-ahead daylight at ~92% accuracy. [ABSTRACT FROM PUBLISHER]

The climates of the mid-Holocene (MH), 6,000 years ago, and of the Last Glacial Maximum (LGM), 21,000 years ago, have extensively been simulated, in particular in the framework of the Palaeoclimate Modelling Intercomparion Project. These periods are well documented by paleo-records, which can be used for evaluating model results for climates different from the present one. Here, we present new simulations of the MH and the LGM climates obtained with the IPSL_CM5A model and compare them to our previous results obtained with the IPSL_CM4 model. Compared to IPSL_CM4, IPSL_CM5A includes two new features: the interactive representation of the plant phenology and marine biogeochemistry. But one of the most important differences between these models is the latitudinal resolution and vertical domain of their atmospheric component, which have been improved in IPSL_CM5A and results in a better representation of the mid-latitude jet-streams. The Asian monsoon's representation is also substantially improved. The global average mean annual temperature simulated for the pre-industrial (PI) period is colder in IPSL_CM5A than in IPSL_CM4 but their climate sensitivity to a CO doubling is similar. Here we show that these differences in the simulated PI climate have an impact on the simulated MH and LGM climatic anomalies. The larger cooling response to LGM boundary conditions in IPSL_CM5A appears to be mainly due to differences between the PMIP3 and PMIP2 boundary conditions, as shown by a short wave radiative forcing/feedback analysis based on a simplified perturbation method. It is found that the sensitivity computed from the LGM climate is lower than that computed from 2 × CO simulations, confirming previous studies based on different models. For the MH, the Asian monsoon, stronger in the IPSL_CM5A PI simulation, is also more sensitive to the insolation changes. The African monsoon is also further amplified in IPSL_CM5A due to the impact of the interactive phenology. Finally the changes in variability for both models and for MH and LGM are presented taking the example of the El-Niño Southern Oscillation (ENSO), which is very different in the PI simulations. ENSO variability is damped in both model versions at the MH, whereas inconsistent responses are found between the two versions for the LGM. Part 2 of this paper examines whether these differences between IPSL_CM4 and IPSL_CM5A can be distinguished when comparing those results to palaeo-climatic reconstructions and investigates new approaches for model-data comparisons made possible by the inclusion of new components in IPSL_CM5A. [ABSTRACT FROM AUTHOR]

We present the global general circulation model IPSL-CM5 developed to study the long-term response of the climate system to natural and anthropogenic forcings as part of the 5th Phase of the Coupled Model Intercomparison Project (CMIP5). This model includes an interactive carbon cycle, a representation of tropospheric and stratospheric chemistry, and a comprehensive representation of aerosols. As it represents the principal dynamical, physical, and bio-geochemical processes relevant to the climate system, it may be referred to as an Earth System Model. However, the IPSL-CM5 model may be used in a multitude of configurations associated with different boundary conditions and with a range of complexities in terms of processes and interactions. This paper presents an overview of the different model components and explains how they were coupled and used to simulate historical climate changes over the past 150 years and different scenarios of future climate change. A single version of the IPSL-CM5 model (IPSL-CM5A-LR) was used to provide climate projections associated with different socio-economic scenarios, including the different Representative Concentration Pathways considered by CMIP5 and several scenarios from the Special Report on Emission Scenarios considered by CMIP3. Results suggest that the magnitude of global warming projections primarily depends on the socio-economic scenario considered, that there is potential for an aggressive mitigation policy to limit global warming to about two degrees, and that the behavior of some components of the climate system such as the Arctic sea ice and the Atlantic Meridional Overturning Circulation may change drastically by the end of the twenty-first century in the case of a no climate policy scenario. Although the magnitude of regional temperature and precipitation changes depends fairly linearly on the magnitude of the projected global warming (and thus on the scenario considered), the geographical pattern of these changes is strikingly similar for the different scenarios. The representation of atmospheric physical processes in the model is shown to strongly influence the simulated climate variability and both the magnitude and pattern of the projected climate changes. [ABSTRACT FROM AUTHOR]

The climates of the mid-Holocene (MH, 6,000 years ago) and the Last Glacial Maximum (LGM, 21,000 years ago) have been extensively documented and as such, have become targets for the evaluation of climate models for climate contexts very different from the present. In Part 1 of the present work, we have studied the MH and LGM simulations performed with the last two versions of the IPSL model: IPSL_CM4, run for the PMIP2/CMIP3 (Coupled Model Intercomparion Project) projects and IPSL_CM5A, run for the most recent PMIP3/CMIP5 projets. We have shown that not only are these models different in their simulations of the PI climate, but also in their simulations of the climatic anomalies for the MH and LGM. In the Part 2 of this paper, we first examine whether palaeo-data can help discriminate between the model performances. This is indeed the case for the African monsoon for the MH or for North America south of the Laurentide ice sheet, the South Atlantic or the southern Indian ocean for the LGM. For the LGM, off-line vegetation modelling appears to offer good opportunities to distinguish climate model results because glacial vegetation proves to be very sensitive to even small differences in LGM climate. For other cases such as the LGM North Atlantic or the LGM equatorial Pacific, the large uncertainty on the SST reconstructions, prevents model discrimination. We have examined the use of other proxy-data for model evaluation, which has become possible with the inclusion of the biogeochemistry morel PISCES in the IPSL_CM5A model. We show a broad agreement of the LGM-PI export production changes with reconstructions. These changes are related to the mixed layer depth in most regions and to sea-ice variations in the high latitudes. We have also modelled foraminifer abundances with the FORAMCLIM model and shown that the changes in foraminifer abundance in the equatorial Pacific are mainly forced by changes in SSTs, hence confirming the SST-foraminifer abundance relationship. Yet, this is not the case in all regions in the North Atlantic, where food availability can have a strong impact of foraminifer abundances. Further work will be needed to exhaustively examine the role of factors other than climate in piloting changes in palaeo-indicators. [ABSTRACT FROM AUTHOR]

In urban conditions, the widescale availability of organic matter to be recycled and the necessity for soil reconstitution (Technosol) has led to the input of very large quantities of organic matter (up to 50% v/v). The long-term degradation of these large quantities of organic matter in the soil is not well known. We monitored, over a 60-month period, the total carbon (C) content and the particulate and biochemical fractions of reconstituted soils placed in 600-litre boxes under natural conditions. The top layer was a sandy loam amended with 20 or 40% of sphagnum peat or organic compost (sewage sludge, wood chip compost or green waste compost) lying on a layer of sandy loam. We measured C mineralization over time under controlled conditions and built a long-term model to simulate carbon dynamics where exogenous organic carbon (EOC) was divided into two biodegradable compartments. The model yielded the proportions of EOC that either resisted degradation or contributed to soil organic C storage by mineralization and/or humification. Organic matter degradation was linked to its maturity and to its contents in certain particulate and biochemical fractions but was independent of how much of a given organic matter was introduced. We found a good correlation between the degradable organic compartment and the lignin and cutin-like, hemicellulose and cellulose-like fractions larger than 1 mm. The model showed that a large part of initial EOC was still present in the soil after 5 years in a potentially biodegradable but resistant compartment. The degradation of that compartment by mineralization or humification is therefore expected to take longer. [ABSTRACT FROM AUTHOR]

Background Benign hereditary chorea (BHC) is a rare autosomal dominant disorder characterised by childhood onset that tends to improve in adulthood. The associated gene, NKX2-1 (previously called TITF1), is essential for organogenesis of the basal ganglia, thyroid and lungs. The aim of the study was to refine the movement disorders phenotype. We also studied disease course and response to therapy in a large series of genetically proven patients. Methods We analysed clinical, genetic findings and follow-up data in 28 NKX2-1 mutated BHC patients from 13 families. Results All patients had private mutations, including seven new mutations, three previously reported mutations and three sporadic deletions encompassing the NKX2-1 gene. Hypotonia and chorea were present in early infancy, with delayed walking ability (25/28); dystonia, myoclonus and tics were often associated. Attention deficit hyperactivity disorder (ADHD) was present in seven. Among the 14 patients followed-up until adulthood, nine had persistent mild chorea, two had near total resolution of chorea but persistent disabling prominent myoclonus and three recovered completely. Learning difficulties were observed in 20/28 patients, and three had mental cretardation. Various combinations of BHC, thyroid (67%) and lung (46%) features were noted. We found no genotypeephenotype correlation. A rapid and sustained beneficial effect on chorea was obtained in 5/8 patients treated with tetrabenazine. Conclusion Early onset chorea preceded by hypotonia is suggestive of BHC. Associated thyroid or respiratory disorders further support the diagnosis and call for genetic studies. Tetrabenazine may be an interesting option to treat disabling chorea. [ABSTRACT FROM AUTHOR]

This paper presents the major characteristics of the Institut Pierre Simon Laplace (IPSL) coupled ocean–atmosphere general circulation model. The model components and the coupling methodology are described, as well as the main characteristics of the climatology and interannual variability. The model results of the standard version used for IPCC climate projections, and for intercomparison projects like the Paleoclimate Modeling Intercomparison Project (PMIP 2) are compared to those with a higher resolution in the atmosphere. A focus on the North Atlantic and on the tropics is used to address the impact of the atmosphere resolution on processes and feedbacks. In the North Atlantic, the resolution change leads to an improved representation of the storm-tracks and the North Atlantic oscillation. The better representation of the wind structure increases the northward salt transports, the deep-water formation and the Atlantic meridional overturning circulation. In the tropics, the ocean–atmosphere dynamical coupling, or Bjerknes feedback, improves with the resolution. The amplitude of ENSO (El Niño-Southern oscillation) consequently increases, as the damping processes are left unchanged. [ABSTRACT FROM AUTHOR]

This article discusses soil-water movement and the transpiration and root water uptake of hedgerow trees. The authors used a simulation model to quantify water balance components including soil water content and spatio-temporal variation in boundary conditions. They found that the shallow water table below the hedgerow trees was mainly responsible for the high transpiration rate. They concluded that the impacts of hedges have been underestimated due to their effects related to the vadose zone and water table.

The aim of the present study is to evaluate the possible extent of modal shifts from car use to ‘alternative modes’ (public transport, cycling, walking) without any change in individual patterns of activity. Its approach is based on a transfer procedure that allows the simulation of the maximal potential market for transport modes other than the private car. The method is based on repeated iterations of a simulation model that assigns journeys to transport modes other than the automobile based on a number of improved public transport scenarios. Demand is channelled towards individual modes (walking, cycling), public transport, and a combination of individual and public modes, based on their relative time and distance performance. The modal transfer procedure is applied to several transport supply scenarios, which provide a picture of what is possible in the sphere of modal split. Each simulation entails a potential transfer of private vehicle‐km to each of the other modes. Even where different public transport scenarios are simulated, the transfer is evaluated for round trips in both the Paris and Lyon surveys. There is therefore no modification in the activity pattern of the people surveyed nor trips induced by improvements in transport supply. The aim is not to predict what would be the modal split in other circumstances, but the upper limit of the shifts. This paper presents our methodology and the principal results obtained through numerical simulations based on figures for the Paris and Lyon conurbations. This approach demonstrates that a policy focused on modal shifts has the potential to reduce car use, but that this potential is limited. Any aspiration to reduce car use further would mean changes in the patterns and loci of activity. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between body mass index (BMI) and mortality in adult intensive care unit (ICU) patients. DESIGN. A prospective multi-center study.Interventions: None.Methods: A cohort study (yielding the OUTCOMEREA database) was conducted over 2 years in 6 medical-surgical ICUs. In each participating ICU, the following were collected daily: demographic information, admission height and weight, comorbidities, severity scores (SAPS II, LOD, and SOFA), ICU and hospital lengths of stay, and ICU and hospital mortality rates.Results: A total of 1,698 patients were examined and divided into 4 groups based on BMI: <18.5, 18.5-24.9, 25-29.9, and >30 kg/m(2). These groups differed significantly for age, gender, admission category (medical, scheduled surgery, unscheduled surgery), ICU and hospital lengths of stay, and comorbidities. Severity at admission and within the first 2 days was similar in the 4 groups, except for the SOFA score. Overall hospital mortality was 31.3% (532 out of 1,698 patients). By multivariate analysis, a BMI below 18.5 kg/m(2) was independently associated with increased mortality (odds ratio 1.63; 95% confidence intervals 1.11-2.39). None of the other BMI categories were associated with higher mortality and even a BMI>30 kg/m(2) was protective of mortality (odds ratio 0.60, 95% confidence intervals 0.40-0.88).Conclusions: A low BMI was independently associated with higher mortality and a high BMI with lower mortality in this large cohort of critically ill patients. Since BMI is absent from currently available scoring systems, further studies are needed to determine whether adding BMI would improve the effectiveness of scores in predicting mortality. [ABSTRACT FROM AUTHOR]

Copyright of Genome is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The influence of a hedge surrounding bottomland on soil-water movement along the hillslope was studied on a plot scale for 28 months. The study was based on the comparison of two transects, one with a hedge, the other without, using mainly a dense grid of tensiometers. The influence of the bottomland hedge was located in the area where tree roots were developed, several metres upslope from the hedge, and could be observed both in the saturated and non-saturated zone, from May to December. The hedge induced a high rate of soil drying, because of the high evaporative capacity of the trees. We evaluated that water uptake by the hedge during the growing season was at least 100 mm higher than without a hedge. This increased drying rate led to a delayed rewetting of the soils upslope from the hedge in autumn, of about 1 month compared with the situation without a hedge. Several consequences of this delayed rewetting are expected: a delay in the return of subsurface transfer from the hillslope to the riparian zone, a buffering effect of hedges on floods, already observed at the catchment scale, and an increased residence time of pollutants. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We define the contact boundary of a complex polynomial f : [double-struck C]n → [double-struck C] as the intersection of some generic fiber with a large sphere. We show that, up to contact isotopy, this does not depend on the choice of the fiber (provided it is generic) and is invariant under polynomial automorphism of [double-struck C]n. We next prove that the formal homotopy class of this contact boundary is invariant in a large family of deformations of polynomials, which are not necessarily topologically trivial. [ABSTRACT FROM AUTHOR]

Background: To decrease exposure to progestin during hormone replacement therapy (HRT), a novel oral regimen consisting of constant 17beta-estradiol (E2) daily plus intermittent norgestimate (NGM) has been developed.Methods: A multicenter study compared the safety and efficacy of E2 1 mg daily plus intermittent NGM 90 micro g (3 days off, 3 days on) (n = 150) vs. a continuous oral dose of E2 2 mg plus norethisterone acetate (NETA) 1 mg (n = 172) daily, for a period of 2 years. Endometrial biopsies were performed at 1 and 2 years. Subjects recorded the occurrence of vasomotor symptoms, uterine bleeding, and adverse events on diary cards.Results: At 2 years' follow-up, no subject had developed endometrial hyperplasia or cancer. Endometrial atrophy was seen in 75% of subjects using the intermittent NGM regimen and in 78% of women using the constant NETA regimen. Both groups maintained a 96% reduction in vasomotor symptoms up to 2 years. The rates of bleeding and/or spotting showed no difference between the groups, and at 2 years' follow-up, 73% of women in the intermittent NGM group and 83% of subjects in the constant NETA group were amenorrheic. There was a lower incidence of progestin-associated side-effects, such as abdominal discomfort, edema, painful bleeding episodes, and breast symptoms, with the intermittent progestin regimen vs. the constant progestin regimen. Intermittent NGM use was associated with an elevation in HDL- and HDL2-cholesterol, whereas constant NETA reduced these lipoproteins.Conclusions: The intermittent administration of a progestin, such as NGM, provides a new, well-tolerated regimen to achieve endometrial safety, an adequate rate of amenorrhea, and effective reduction of vasomotor symptoms in postmenopausal women. [ABSTRACT FROM AUTHOR]

Presents a study that determined whether, over daytime, one or several hyperglycemic excursions exist that can be general failures in the glycemic control of patients with type 2 diabetes. Protocol of the study and analytical procedures; Comparison of plasma glucose and insulin concentrations at the different time points of the day; Respective contributions of fasting and postprandial glucose increment to the overall diabetic control over the diurnal period.

Let $\Phi=(f,g):({\mathbb C}^{n+1},{\bf 0}) \to({\mathbb C}^2,{\bf 0})$ be a pair of holomorphic germs with no blowing up in codimension 0. (Two examples are the following: $\Phi$ defines an isolated complete intersection singularity; $g=\ell^N$ where $\ell$ is a generic linear form with respect to $f$ and $N>0$.) We study how the Milnor fibrations of the germs $\varphi_{(\alpha:\beta)}=\alpha g-\beta f$ are related to each other when $(\alpha:\beta)$ varies in ${\mathbb P}^1$. More precisely, we construct isotopic subfibrations or subfibres of the Milnor fibrations of any two such germs. The proofs are based on the precise study of the subdiscs of complex lines meeting a fixed complex plane curve germ transversally, generalizing Lê's work on the Cerf diagram.2000 Mathematical Subject Classification: 32S55, 32S15, 32S30. [ABSTRACT FROM AUTHOR]

Summary Objective: To compare substrates oxidative patterns in type 2 diabetic patients treated with sulphonylurea alone or in combination with metformin. Methods: Plasma glucose (PG), plasma insulin (PI) and substrates oxidation rates measured by indirect calorimetry were compared during a test day at 8.00 a.m. (before breakfast), 11.00 a.m. (before the lunch), 2.00 p.m. (2 h after the lunch) and at 5.00 p.m. in 56 diabetic patients treated with diet (group C, n = 14), sulphonylurea (group S, n = 14) or with a sulphonylurea-metformin combination (group SM, n = 28). Results: The three groups were comparable for age, body mass index (b.m.i.), body composition and PG levels. Mean glucose oxidation (Gox) was increased since mean lipid oxidation (Lox) was decreased in group S in comparison both with group C (3.02 ± 0.08 vs. 2.62 ± 0.08 g/min/kg/103, p < 0.05; 0.53 ± 0.04 vs. 0.88 ± 0.09 g/min/kg/103, p < 0.01). Mean Lox was also decreased in group S in comparison with group SM (0.88 ± 0.06 vs. 0.53 ± 0.04 g/min1/kg1/103, p< 0.0001) whereas the difference in Gox between these latter two groups was only significant in the basal state (1.94 ± 0.17 vs. 2.47 ± 0.17 g/min1/kg1/103, p< 0.05). Mean respiratory quotient (RQ) was increased in group S (0.90 ± 0.01) in comparison both with group C (0.86 ± 0.01, p < 0.001) and with group SM (0.86 ± 0.01, p < 0.001). Mean energy expenditure was lower in group S than in group SM (21.4 ± 0.6 vs. 23.6 ± 0.6 kcal/min/kg/103, p < 0.05). Substrates oxidative patterns, RQ values and energy expenditure were similar in group C and in group SM. Conclusions: When compared to patients treated with a sulphonylurea-metformin bitherapy, patients treated with a sulphonylurea monotherapy have a shift in their ratio of fat to carbohydrate oxidation that could make body weight loss more... [ABSTRACT FROM AUTHOR]

The correct name of the second author should be "Moritz Fehrle", and not "Mortiz Fehrle" as given in the original publication of the article. [ABSTRACT FROM AUTHOR]