507 research outputs found
Statin associated necrotizing autoimmune myopathies in the Indigenous population: a case series from North Queensland
Aim: To describe clinical and histopathological features of statin associated necrotizing autoimmune myopathies (NAM) in Indigenous Australians and increase awareness of this condition amongst treating physicians.
Methods: Cases were collected through the Rheumatology Department at The Townsville Hospital between March 2012 and January 2015. A chart review was performed to obtain retrospective information about each case. We detail patient demographics, presenting features, histopathological findings, autoimmune profile, treatment and outcomes.
Results: 4 Indigenous Australians were identified as having a biopsy confirmed statin associated NAM. All patients had been on atorvastatin for at least 2 years and had significant proximal weakness with average CK level on presentation 16,820 U/L. Predisposing factors for myopathy included vitamin D deficiency and diabetes mellitus (all cases), with primary hypothyroidism and liver cirrhosis identified in two other cases. Two individuals were positive for the auto-antibody anti-HMGCR. Histopathological findings included muscle necrosis with varying degrees of inflammation, membrane attack complex (MAC) deposition and MHC-1 upregulation. Treatment involved various combinations of prednisolone, IVIG, methotrexate and mycophenolate. Recovery was slow but favourable in all cases with an average length of inpatient stay of 54 days. There was a significant delay in diagnosis of 1â3 months in two of the cases.
Conclusions: The statin associated necrotizing autoimmune myopathies are rare but important disorders that cause significant morbidity to affected individuals. Given the prevalence of cardiovascular disease in Indigenous Australians, further research is required to facilitate earlier diagnosis and improved treatment outcomes
Statin associated necrotizing autoimmune myopathies in the Indigenous population: a case series from North Queensland
Aim: To describe clinical and histopathological features of statin associated necrotizing autoimmune myopathies (NAM) in Indigenous Australians and increase awareness of this condition amongst treating physicians.
Methods: Cases were collected through the Rheumatology Department at The Townsville Hospital between March 2012 and January 2015. A chart review was performed to obtain retrospective information about each case. We detail patient demographics, presenting features, histopathological findings, autoimmune profile, treatment and outcomes.
Results: 4 Indigenous Australians were identified as having a biopsy confirmed statin associated NAM. All patients had been on atorvastatin for at least 2 years and had significant proximal weakness with average CK level on presentation 16,820 U/L. Predisposing factors for myopathy included vitamin D deficiency and diabetes mellitus (all cases), with primary hypothyroidism and liver cirrhosis identified in two other cases. Two individuals were positive for the auto-antibody anti-HMGCR. Histopathological findings included muscle necrosis with varying degrees of inflammation, membrane attack complex (MAC) deposition and MHC-1 upregulation. Treatment involved various combinations of prednisolone, IVIG, methotrexate and mycophenolate. Recovery was slow but favourable in all cases with an average length of inpatient stay of 54 days. There was a significant delay in diagnosis of 1â3 months in two of the cases.
Conclusions: The statin associated necrotizing autoimmune myopathies are rare but important disorders that cause significant morbidity to affected individuals. Given the prevalence of cardiovascular disease in Indigenous Australians, further research is required to facilitate earlier diagnosis and improved treatment outcomes
Generative technologies for model animation in the TopCased platform
International audienceDomain Specific Modeling Languages (DSML) are more and more used to handle high level concepts, and thus bring complex software development under control. The increasingly recurring definition of new languages raises the problem of the definition of support tools such as editor, simulator, compiler, etc. In this paper we propose generative technologies that have been designed to ease the development of model animation tools inside the TopCased platform. These tools rely on the automatically generated graphical editors of TopCased and provide additional generators for building model animator graphical interface. We also rely on an architecture for executable metamodel (i.e., the TopCased model execution metamodeling pattern) to bind the behavioral semantics of the modeling language. These tools were designed in a pragmatic manner by abstracting the various model animators that had been hand-coded in the TopCased project, and then validated by refactoring these animators
Global mean cloud feedbacks in idealized climate change experiments
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94978/1/grl21109.pd
Helping education undergraduates to use appropriate criteria for evaluating accounts of motivation
The aim of the study was to compare students in a control group with those in a treatment group with respect to evaluative comments on psychological accounts of motivation. The treatment group systematically scrutinized the nature and interpretation of evidence that supported different accounts, and the assumptions, logic, coherence and clarity of accounts. Content analysis of 74 scripts (using three categories) showed that the control group students made more assertions than either evidential or evaluative points, whereas the treatment group used evaluative statements as often as they used assertion. The findings provide support for privileging activities that develop understanding of how knowledge might be contested, and suggest a need for further research on pedagogies to serve this end. The idea is considered that such understanding has a pivotal role in the development of critical thinking
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Radiative forcing of climate: the historical evolution of the radiative forcing concept, the forcing agents and their quantification, and applications
We describe the historical evolution of the conceptualization, formulation, quantification, application and utilization of âradiative forcing (RF, see e.g., IPCC, 1990)â of Earthâs climate.
Basic theories of shortwave and long wave radiation were developed through the 19th and 20th centuries, and established the analytical framework for defining and quantifying the perturbations to the Earthâs radiative energy balance by natural and anthropogenic influences. The insight that the Earthâs climate could be radiatively forced by changes in carbon dioxide, first introduced in the 19th century, gained empirical support with sustained observations of the atmospheric concentrations of the gas beginning in 1957. Advances in laboratory and field measurements, theory, instrumentation, computational technology, data and analysis of well-mixed greenhouse gases and the global climate system through the 20th Century enabled the development and formalism of RF; this allowed RF to be related to changes in global-mean surface temperature with the aid of increasingly sophisticated models. This in turn led to RF becoming firmly established as a principal concept in climate science by 1990.
The linkage with surface temperature has proven to be the most important application of the RF concept, enabling a simple metric to evaluate the relative climate impacts of different agents. The late 1970s and 1980s saw accelerated developments in quantification including the first assessment of the effect of the forcing due to doubling of carbon dioxide on climate (the âCharneyâ report, National Research Council, 1979). The concept was subsequently extended to a wide variety of agents beyond well-mixed greenhouse gases (WMGHGs: carbon dioxide, methane, nitrous oxide, and halocarbons) to short-lived species such as ozone. The WMO (1986) and IPCC (1990) international assessments began the important sequence of periodic evaluations and quantifications of the forcings by natural (solar irradiance changes and stratospheric aerosols resulting from volcanic eruptions) and a growing set of anthropogenic agents (WMGHGs, ozone, aerosols, land surface changes, contrails). From 1990s to the present, knowledge and scientific confidence in the radiative agents acting on the climate system has proliferated. The conceptual basis of RF has also evolved as both our understanding of the way radiative forcing drives climate change, and the diversity of the forcing mechanisms, have grown. This has led to the current situation where âEffective Radiative Forcing (ERF, e.g., IPCC, 2013)â is regarded as the preferred practical definition of radiative forcing in order to better capture the link between forcing and global-mean surface temperature change. The use of ERF, however, comes with its own attendant issues, including challenges in its diagnosis from climate models, its applications to small forcings, and blurring of the distinction between rapid climate adjustments (fast responses) and climate feedbacks; this will necessitate further elaboration of its utility in the future. Global climate model simulations of radiative perturbations by various agents have established how the forcings affect other climate variables besides temperature e.g., precipitation. The forcing-response linkage as simulated by models, including the diversity in the spatial distribution of forcings by the different agents, has provided a practical demonstration of the effectiveness of agents in perturbing the radiative energy balance and causing climate changes.
The significant advances over the past half-century have established, with very high confidence, that the global-mean ERF due to human activity since preindustrial times is positive (the 2013 IPCC assessment gives a best estimate of 2.3 W m-2, with a range from 1.1 to 3.3 W m-2; 90% confidence interval). Further, except in the immediate aftermath of climatically-significant volcanic eruptions, the net anthropogenic forcing dominates over natural radiative forcing mechanisms. Nevertheless, the substantial remaining uncertainty in the net anthropogenic ERF leads to large uncertainties in estimates of climate sensitivity from observations and in predicting future climate impacts. The uncertainty in the ERF arises principally from the incorporation of the rapid climate adjustments in the formulation, the well-recognized difficulties in characterizing the preindustrial state of the atmosphere, and the incomplete knowledge of the interactions of aerosols with clouds. This uncertainty impairs the quantitative evaluation of climate adaptation and mitigation pathways in the future. A grand challenge in Earth System science lies in continuing to sustain the relatively simple essence of the radiative forcing concept in a form similar to that originally devised, and at the same time improving the quantification of the forcing. This, in turn, demands an accurate, yet increasingly complex and comprehensive, accounting of the relevant processes in the climate system
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Effects on focused ion beam irradiation on MOS transistors
The effects of irradiation from a focused ion beam (FIB) system on MOS transistors are reported systematically for the first time. Three MOS transistor technologies, with 0.5, 1, and 3 {mu}m minimum feature sizes and with gate oxide thicknesses ranging from 11 to 50 nm, were analyzed. Significant shifts in transistor parameters (such as threshold voltage, transconductance, and mobility) were observed following irradiation with a 30 keV Ga{sup +} focused ion beam with ion doses varying by over 5 orders of magnitude. The apparent damage mechanism (which involved the creation of interface traps, oxide trapped charge, or both) and extent of damage were different for each of the three technologies investigated
Pragmatics of Yes/No Indirect-responses (YNIRs)
AbstractHow do people transmit information with âquestion-answerâ structures? What happens when a speaker utters a meaningful question and the hearer understands it? The present paper focuses on YNIRs in terms of (a) a radical lack of consensus about their potential in production of messages in interpersonal communication; (b) the ways in which they are used to establish and maintain coherent conversation, and (c) to what extent commentary, and supplementary indirect responses can invoke goal (in) compatibility, and how this kind of conflict can prevent stagnation, stimulate interest, and finally contribute to âescalationâ of mutual understanding. Although the functional horizons of general questions and the answers to them vary from context to context, the addressee can âcontrolâ his judgements and attitudes (apology, ignorance, consent, or refusal) by his deeper exposure to the situation, what, in the end, enables his affiliation with others. The other major concern of the paper is to specify the cases when the pragmatic interpretation of questionless responses is defined as unification of the semantic representation and the internal utterance context
The vertical distribution of ozone instantaneous radiative forcing from satellite and chemistry climate models
We evaluate the instantaneous radiative forcing (IRF) of tropospheric ozone predicted by four state-of-the-art global chemistry climate models (AM2-Chem, CAM-Chem, ECHAM5-MOZ, and GISS-PUCCINI) against ozone distribution observed from the NASA Tropospheric Emission Spectrometer (TES) during August 2006. The IRF is computed through the application of an observationally constrained instantaneous radiative forcing kernels (IRFK) to the difference between TES and model-predicted ozone. The IRFK represent the sensitivity of outgoing longwave radiation to the vertical and spatial distribution of ozone under all-sky condition. Through this technique, we find total tropospheric IRF biases from -0.4 to + 0.7 W/m(2) over large regions within the tropics and midlatitudes, due to ozone differences over the region in the lower and middle troposphere, enhanced by persistent bias in the upper troposphere-lower stratospheric region. The zonal mean biases also range from -30 to + 50 mW/m(2) for the models. However, the ensemble mean total tropospheric IRF bias is less than 0.2 W/m(2) within the entire troposphere
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