We describe the Geophysical Fluid Dynamics Laboratory's CM4.0 physical climate model, with emphasis on those aspects that may be of particular importance to users of this model and its simulations. ...The model is built with the AM4.0/LM4.0 atmosphere/land model and OM4.0 ocean model. Topics include the rationale for key choices made in the model formulation, the stability as well as drift of the preindustrial control simulation, and comparison of key aspects of the historical simulations with observations from recent decades. Notable achievements include the relatively small biases in seasonal spatial patterns of top‐of‐atmosphere fluxes, surface temperature, and precipitation; reduced double Intertropical Convergence Zone bias; dramatically improved representation of ocean boundary currents; a high‐quality simulation of climatological Arctic sea ice extent and its recent decline; and excellent simulation of the El Niño‐Southern Oscillation spectrum and structure. Areas of concern include inadequate deep convection in the Nordic Seas; an inaccurate Antarctic sea ice simulation; precipitation and wind composites still affected by the equatorial cold tongue bias; muted variability in the Atlantic Meridional Overturning Circulation; strong 100 year quasiperiodicity in Southern Ocean ventilation; and a lack of historical warming before 1990 and too rapid warming thereafter due to high climate sensitivity and strong aerosol forcing, in contrast to the observational record. Overall, CM4.0 scores very well in its fidelity against observations compared to the Coupled Model Intercomparison Project Phase 5 generation in terms of both mean state and modes of variability and should prove a valuable new addition for analysis across a broad array of applications.
Plain Language Summary
The Geophysical Fluid Dynamics Laboratory (GFDL) of the National Oceanic and Atmospheric Administration participates along with a number of model centers around the world in constructing state‐of‐the‐art climate models for use in studies for climate change and prediction. GFDL's latest multipurpose atmosphere‐ocean coupled climate model, CM4.0, is described here. It consists of GFDL's latest atmosphere and land models at about 100 km horizontal resolution and ocean and sea ice models at roughly 25 km horizontal resolution. A handful of standard experiments have been conducted with CM4.0 for participation in the Coupled Model Intercomparison Project Phase 6, an archive of climate model results utilized by the Intergovernmental Panel on Climate Change and the climate research community more generally. The model results have been extensively evaluated against observations. This paper makes the case that CM4.0 ranks high among state‐of‐the‐art coupled climate models by many measures of bias in the simulated climatology and in its ability to capture modes of climate variability such as the El Niño‐Southern Oscillation and Madden‐Julian Oscillation. The paper also discusses some potential weaknesses, including unrealistically large internal variability in the Southern Ocean and insufficient warming before 1990 in the simulation of the twentieth century.
Key Points
A team at GFDL has developed a new model of the physical climate system referred to as CM4.0
Strengths of model include ENSO simulation and small biases in TOA fluxes, precipitation, Arctic sea ice extent, and sea surface temperature
Problematic aspects include large variability in Southern Ocean and historical simulation with little warming prior to 1990
To define the types and numbers of inpatient clinical decision support alerts, measure the frequency with which they are overridden, and describe providers' reasons for overriding them and the ...appropriateness of those reasons.
We conducted a cross-sectional study of medication-related clinical decision support alerts over a 3-year period at a 793-bed tertiary-care teaching institution. We measured the rate of alert overrides, the rate of overrides by alert type, the reasons cited for overrides, and the appropriateness of those reasons.
Overall, 73.3% of patient allergy, drug-drug interaction, and duplicate drug alerts were overridden, though the rate of overrides varied by alert type (P < .0001). About 60% of overrides were appropriate, and that proportion also varied by alert type (P < .0001). Few overrides of renal- (2.2%) or age-based (26.4%) medication substitutions were appropriate, while most duplicate drug (98%), patient allergy (96.5%), and formulary substitution (82.5%) alerts were appropriate.
Despite warnings of potential significant harm, certain categories of alert overrides were inappropriate >75% of the time. The vast majority of duplicate drug, patient allergy, and formulary substitution alerts were appropriate, suggesting that these categories of alerts might be good targets for refinement to reduce alert fatigue.
Almost three-quarters of alerts were overridden, and 40% of the overrides were not appropriate. Future research should optimize alert types and frequencies to increase their clinical relevance, reducing alert fatigue so that important alerts are not inappropriately overridden.
In October 2017, the International Olympic Committee hosted an international expert group of physiotherapists and orthopaedic surgeons who specialise in treating and researching paediatric anterior ...cruciate ligament (ACL) injuries. Representatives from the American Orthopaedic Society for Sports Medicine, European Paediatric Orthopaedic Society, European Society for Sports Traumatology, Knee Surgery and Arthroscopy, International Society of Arthroscopy Knee Surgery and Orthopaedic Sports Medicine, Pediatric Orthopaedic Society of North America, and Sociedad Latinoamericana de Artroscopia, Rodilla y Deporte attended. Physiotherapists and orthopaedic surgeons with clinical and research experience in the field, and an ethics expert with substantial experience in the area of sports injuries also participated. Injury management is challenging in the current landscape of clinical uncertainty and limited scientific knowledge. Injury management decisions also occur against the backdrop of the complexity of shared decision-making with children and the potential long-term ramifications of the injury. This consensus statement addresses six fundamental clinical questions regarding the prevention, diagnosis, and management of paediatric ACL injuries. The aim of this consensus statement is to provide a comprehensive, evidence-informed summary to support the clinician, and help children with ACL injury and their parents/guardians make the best possible decisions.
Therapeutic drugs that block DNA repair, including poly(ADP-ribose) polymerase (PARP) inhibitors, fail due to lack of tumor-selectivity. When PARP inhibitors and β-lapachone are combined, synergistic ...antitumor activity results from sustained NAD(P)H levels that refuel NQO1-dependent futile redox drug recycling. Significant oxygen-consumption-rate/reactive oxygen species cause dramatic DNA lesion increases that are not repaired due to PARP inhibition. In NQO1+ cancers, such as non-small-cell lung, pancreatic, and breast cancers, cell death mechanism switches from PARP1 hyperactivation-mediated programmed necrosis with β-lapachone monotherapy to synergistic tumor-selective, caspase-dependent apoptosis with PARP inhibitors and β-lapachone. Synergistic antitumor efficacy and prolonged survival were noted in human orthotopic pancreatic and non-small-cell lung xenograft models, expanding use and efficacy of PARP inhibitors for human cancer therapy.
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•Solid cancers overexpress NQO1, with low catalase levels, reverse of normal tissue•β-Lapachone kills independent of oncogenic driver or passenger mutations•Synergy with PARP inhibitors and β-lapachone is NQO1 dependent•PARP inhibitors + β-lap induce DNA lesions, block repair, and cause apoptosis
Huang et al. show that combination treatment with NQO1 bioactivatible β-lapachone and a PARP inhibitor causes unrepaired DNA damage and induces apoptosis, and that the combination treatment has a synergistic therapeutic effect in orthotopic pancreatic and non-small-cell lung cancer models.
In Part 2 of this two‐part paper, documentation is provided of key aspects of a version of the AM4.0/LM4.0 atmosphere/land model that will serve as a base for a new set of climate and Earth system ...models (CM4 and ESM4) under development at NOAA's Geophysical Fluid Dynamics Laboratory (GFDL). The quality of the simulation in AMIP (Atmospheric Model Intercomparison Project) mode has been provided in Part 1. Part 2 provides documentation of key components and some sensitivities to choices of model formulation and values of parameters, highlighting the convection parameterization and orographic gravity wave drag. The approach taken to tune the model's clouds to observations is a particular focal point. Care is taken to describe the extent to which aerosol effective forcing and Cess sensitivity have been tuned through the model development process, both of which are relevant to the ability of the model to simulate the evolution of temperatures over the last century when coupled to an ocean model.
Key Points
Part 2 of the AM4.0/LM4.0 paper provides documentation of key changes in individual components from previous GFDL models
Some sensitivities to choices of model formulation and parameter values are presented with emphasis on convection and tuning of clouds
We describe the extent to which the effect on aerosol forcing and Cess sensitivity has been taken into account during model development
Does size matter for dispersal distance? Jenkins, David G.; Brescacin, Camille R.; Duxbury, Craig V. ...
Global ecology and biogeography,
July 2007, Letnik:
16, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Aim: The aim of this study is to answer the questions: (1) do small organisms disperse farther than large, or vice versa; and (2) does the observed pattern differ for passive and active dispersers? ...These questions are central to several themes in biogeography (including microbial biogeography), macroecology, metacommunity ecology and conservation biology. Location: The meta-analysis was conducted using published data collected worldwide. Methods: We collected and analysed 795 data values in the peer-reviewed literature for direct observations of both maximal dispersal distance and mass of the dispersing organisms (e.g. seeds, not trees). Analysed taxa ranged in size from bacteria to whales. We applied macroecology analyses based on null models (using Monte Carlo randomizations) to test patterns relative to specific hypotheses. Results: Collected dispersal distance and mass data spanned 9 and 21 orders of magnitude, respectively. Active dispersers dispersed significantly farther (P < 0.001) and were significantly greater in mass (P < 0.001) than passive dispersers. Overall, size matters: larger active dispersers attained greater maximum observed dispersal distances than smaller active dispersers. In contrast, passive-disperser distances were random with respect to propagule mass, but not uniformly random, in part due to sparse data available for tiny propagules. Conclusions: Size is important to maximal dispersal distance for active dispersers, but not for passive dispersers. Claims that microbes disperse widely cannot be tested by current data based on direct observations of dispersal: indirect approaches will need to be applied. Distance-mass relationships should contribute to a resolution of neutral and niche-based metacommunity theories by helping scale expectations for dispersal limitation. Also, distance-mass relationships should inform analyses of latitudinal species richness and conservation biology topics such as fragmentation, umbrella species and taxonomic homogenization.
In this two‐part paper, a description is provided of a version of the AM4.0/LM4.0 atmosphere/land model that will serve as a base for a new set of climate and Earth system models (CM4 and ESM4) under ...development at NOAA's Geophysical Fluid Dynamics Laboratory (GFDL). This version, with roughly 100 km horizontal resolution and 33 levels in the vertical, contains an aerosol model that generates aerosol fields from emissions and a “light” chemistry mechanism designed to support the aerosol model but with prescribed ozone. In Part 1, the quality of the simulation in AMIP (Atmospheric Model Intercomparison Project) mode—with prescribed sea surface temperatures (SSTs) and sea‐ice distribution—is described and compared with previous GFDL models and with the CMIP5 archive of AMIP simulations. The model's Cess sensitivity (response in the top‐of‐atmosphere radiative flux to uniform warming of SSTs) and effective radiative forcing are also presented. In Part 2, the model formulation is described more fully and key sensitivities to aspects of the model formulation are discussed, along with the approach to model tuning.
Key Points
A description is provided of the AM4.0/LM4.0 model that will serve as a base for a new set of GFDL/NOAA climate and Earth system models
The simulation quality in AMIP mode is described and compared with previous GFDL models and with the CMIP5 archive of AMIP simulations
The model's Cess sensitivity and effective radiative forcing are presented
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