Nearly seven decades have passed since Barach described the first cases of asthma managed with he... more Nearly seven decades have passed since Barach described the first cases of asthma managed with heliox, and Fuchs reported the therapeutic use of general anesthesia for severe asthmatics. Since then, IV anesthetics, BAL and ECLS have been added to the list of salvage therapies for patients with refractory asthma. Furtunately, most patients will respond to conventional therapies, but for those who don't, we lack good evidence to guide us in our choice of further treatments. Heliox has been demonstrated in some but not all studies to improve airflow and other parameters among patients with asthma, without any significant side effects. It is reasonable to give a therapeutic trial of heliox in patients with severe airflow obstruction who are felt to be at risk of respiratory muscle fatigue and respiratory failure. For intubated patients on mechanical ventilatory, support, heliox may be given through the ventilator circuit, but the potential issues with inaccuracy of flow meters for this low-density gas must be considered. Limited evidence supports the use of propofol in refractory SA; given its ready availability and ease of administration, it is worth trying in the hemodynamically stable asthmatic patients. Extreme caution should be exercised in administering this drug to a nonintubated patient. Inhalational anesthesia should be left for cases in which propofol has failed or cannot be tolerated, given the difficulties in its therapeutic administration. Therapeutic BAL may be of benefit in selected patients with mucous plugging, but criteria for selecting patients for this aggressive and potentially dangerous intervention are not clear. ECLS may be considered as a last ditch effort for the patient with SA who has inadequate gas exchange despite all other available therapies.
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since t... more In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
We introduce a new probabilistic model for transliteration that performs significantly better tha... more We introduce a new probabilistic model for transliteration that performs significantly better than previous approaches, is language-agnostic, requiring no knowledge of the source or target languages, and is capable of both generation (creating the most likely transliteration of a source word) and discovery (selecting the most likely transliteration from a list of candidate words). Our experimental results demonstrate improved accuracy
Journal of Experimental Psychology-human Perception and Performance, 2001
In 4 experiments, participants alternated between different tasks or performed the same task repe... more In 4 experiments, participants alternated between different tasks or performed the same task repeatedly. The tasks for 2 of the experiments required responding to geometric objects in terms of alternative classification rules, and the tasks for the other 2 experiments required solving arithmetic problems in terms of alternative numerical operations. Performance was measured as a function of whether the tasks were familiar or unfamiliar, the rules were simple or complex, and visual cues were present or absent about which tasks should be performed. Task alternation yielded switching-time costs that increased with rule complexity but decreased with task cuing. These factor effects were additive, supporting a model of executive control that has goal-shifting and rule-activation stages for task switching. It appears that rule activation takes more time for switching from familiar to unfamiliar tasks than for switching in the opposite direction.
Nearly seven decades have passed since Barach described the first cases of asthma managed with he... more Nearly seven decades have passed since Barach described the first cases of asthma managed with heliox, and Fuchs reported the therapeutic use of general anesthesia for severe asthmatics. Since then, IV anesthetics, BAL and ECLS have been added to the list of salvage therapies for patients with refractory asthma. Furtunately, most patients will respond to conventional therapies, but for those who don't, we lack good evidence to guide us in our choice of further treatments. Heliox has been demonstrated in some but not all studies to improve airflow and other parameters among patients with asthma, without any significant side effects. It is reasonable to give a therapeutic trial of heliox in patients with severe airflow obstruction who are felt to be at risk of respiratory muscle fatigue and respiratory failure. For intubated patients on mechanical ventilatory, support, heliox may be given through the ventilator circuit, but the potential issues with inaccuracy of flow meters for this low-density gas must be considered. Limited evidence supports the use of propofol in refractory SA; given its ready availability and ease of administration, it is worth trying in the hemodynamically stable asthmatic patients. Extreme caution should be exercised in administering this drug to a nonintubated patient. Inhalational anesthesia should be left for cases in which propofol has failed or cannot be tolerated, given the difficulties in its therapeutic administration. Therapeutic BAL may be of benefit in selected patients with mucous plugging, but criteria for selecting patients for this aggressive and potentially dangerous intervention are not clear. ECLS may be considered as a last ditch effort for the patient with SA who has inadequate gas exchange despite all other available therapies.
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since t... more In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
We introduce a new probabilistic model for transliteration that performs significantly better tha... more We introduce a new probabilistic model for transliteration that performs significantly better than previous approaches, is language-agnostic, requiring no knowledge of the source or target languages, and is capable of both generation (creating the most likely transliteration of a source word) and discovery (selecting the most likely transliteration from a list of candidate words). Our experimental results demonstrate improved accuracy
Journal of Experimental Psychology-human Perception and Performance, 2001
In 4 experiments, participants alternated between different tasks or performed the same task repe... more In 4 experiments, participants alternated between different tasks or performed the same task repeatedly. The tasks for 2 of the experiments required responding to geometric objects in terms of alternative classification rules, and the tasks for the other 2 experiments required solving arithmetic problems in terms of alternative numerical operations. Performance was measured as a function of whether the tasks were familiar or unfamiliar, the rules were simple or complex, and visual cues were present or absent about which tasks should be performed. Task alternation yielded switching-time costs that increased with rule complexity but decreased with task cuing. These factor effects were additive, supporting a model of executive control that has goal-shifting and rule-activation stages for task switching. It appears that rule activation takes more time for switching from familiar to unfamiliar tasks than for switching in the opposite direction.
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