Search

Background and Purpose: The discovery of DP2 as a second receptor for PGD2 has prompted the search for antagonists as potential novel therapies based on the associations between PGD2 and disease. Here we describe the biochemical and pharmacological properties of 4-(acetylamino)-3-[(4-chlorophenyl)thio]-2-methyl-1H-indole-1-acetic acid (AZD1981), a novel DP2 receptor antagonist.Experimental Approach: Binding to DP2 , functional receptor pharmacology and selectivity were studied in both human and animal systems.Key Results: AZD1981 displaced radio-labelled PGD2 from human recombinant DP2 with high potency (pIC50 = 8.4). Binding was reversible, non-competitive and highly selective against a panel of more than 340 other enzymes and receptors, including DP1 (>1000-fold selective). AZD1981 inhibited DP2 -mediated shape change and CD11b up-regulation in human eosinophils, shape change in basophils and chemotaxis of human eosinophils and Th2 cells with similar potency. AZD1981 exhibited good cross-species binding activity against mouse, rat, guinea pig, rabbit and dog DP2 . Evaluation in mouse, rat or rabbit cell systems was not possible as they did not respond to DP2 agonists. Agonist responses were seen in guinea pig and dog, and AZD1981 blocked DP2 -mediated eosinophil shape change. Such responses were more robust in the guinea pig, where AZD1981 also blocked DP2 -dependent eosinophil emigration from bone marrow.Conclusions and Implications: AZD1981 is a DP2 antagonist that blocks functional responses in eosinophils, Th2 cells and basophils. It exhibited similar potency irrespective of the cell type, DP2 agonist or species used. This selective orally active agent is currently under clinical evaluation as a potential therapeutic agent in respiratory diseases including asthma. [ABSTRACT FROM AUTHOR]

Background and Purpose The discovery of DP2 as a second receptor for PGD2 has prompted the search for antagonists as potential novel therapies based on the associations between PGD2 and disease. Here we describe the biochemical and pharmacological properties of 4-(acetylamino)-3-[(4-chlorophenyl)thio]-2-methyl- 1 H-indole-1-acetic acid ( AZD1981), a novel DP2 receptor antagonist. Experimental Approach Binding to DP2, functional receptor pharmacology and selectivity were studied in both human and animal systems. Key Results AZD1981 displaced radio-labelled PGD2 from human recombinant DP2 with high potency ( pIC50 = 8.4). Binding was reversible, non-competitive and highly selective against a panel of more than 340 other enzymes and receptors, including DP1 (>1000-fold selective). AZD1981 inhibited DP2-mediated shape change and CD11b up-regulation in human eosinophils, shape change in basophils and chemotaxis of human eosinophils and Th2 cells with similar potency. AZD1981 exhibited good cross-species binding activity against mouse, rat, guinea pig, rabbit and dog DP2. Evaluation in mouse, rat or rabbit cell systems was not possible as they did not respond to DP2 agonists. Agonist responses were seen in guinea pig and dog, and AZD1981 blocked DP2-mediated eosinophil shape change. Such responses were more robust in the guinea pig, where AZD1981 also blocked DP2-dependent eosinophil emigration from bone marrow. Conclusions and Implications AZD1981 is a DP2 antagonist that blocks functional responses in eosinophils, Th2 cells and basophils. It exhibited similar potency irrespective of the cell type, DP2 agonist or species used. This selective orally active agent is currently under clinical evaluation as a potential therapeutic agent in respiratory diseases including asthma. [ABSTRACT FROM AUTHOR]

The study aimed to examine physiological responses of firefighters performing a firefighting simulation test (FST) and to determine the relationship between physical fitness parameters and FST performance. Aerobic fitness, muscular strength, muscular endurance, and anaerobic capabilities were evaluated in 37 firefighters (21-profesionals and 16-volunteers firefighters). Furthermore, participants carried out the FST during which we measured performance, respiratory gas exchange, heart rate (HR), perceived exertion and blood lactate concentrations. Males were significantly faster than females for all tasks of the FST ( p  < 0.01); however, final performance score (16.5 ± 2.9 and 14.5 ± 2.6 points for males and females, respectively), HR (94.0 ± 2.0% and 93.7 ± 2.3% of HR max ) and perceived exertion (8.1 ± 0.9 and 7.1 ± 1.3) were not significantly different. Prediction of FST performance by LASSO regression revealed a model that included mainly aerobic capacity and maximal strength. In conclusion, FST challenged both aerobic and anaerobic energy metabolisms for both males and females and requires various physiological abilities to perform. Practitioner Summary: For the safety of firefighters and victims, firefighters must meet minimum physical requirements. 37 firefighters performed physical tests and a new firefighting test implemented for the recruitment of firefighters in France. The results revealed that this test is strenuous and that performance is associated with cardiorespiratory fitness and muscular strength. Abbreviations : V̇O 2 : oxygen consumption; V̇CO 2 : carbon dioxyde production; V̇ E : expired ventilation; RER: respiratory exchange ratio; FST: firefighting simulation test; MAS: maximal aerobic speed; HR: heart rate; RPE: rating of perceived exertion; MVC: maximum voluntary contraction; IMTP: isometric mid-thigh pull; TTE: time to exhaustion; P peak : peak power; P mean : mean power; LASSO: least absolute shrinkage and selection operator; La-: blood lactate concentration.

The COVID-19 pandemic has amplified existing injustices in the United States, which is exemplified in Ypsilanti, Michigan. However, the pandemic also provides an opportunity to re-imagine existing ways of being in the world, and mutual aid networks that have provided for people's basic needs during multiple crises while also working towards more radical change provide an opportunity for social workers to examine their relationship to "helping." The author uses their personal experience with a local mutual aid network to examine the power and possibility of mutual aid, particularly in times of crisis, as well as sources of social work resistance to decentralized and non-professional forms of helping and caring. These lessons are carried beyond the COVID-19 pandemic to their consequences for the looming climate crisis., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Indigenous women in North America have traditionally had reciprocal relationships with and responsibilities to the Earth. The process of colonization violently transformed both the treatment of the Earth and of Indigenous women. Current environmental crises highlight not only the vulnerability of Indigenous women, but also their long-standing leadership in resisting environmental injustices affecting their families, relationships, and nations. In this article, authors focus on the resistance of Dakota water protectors with the #NoDAPL movement in the United States and Anishinaabe water protectors in Mother Earth Water Walks in Canada. Recommendations for social workers in supporting Indigenous women in a thoughtful and effective way include incorporating a definition of a "social" response to more-than-human world relationships and responsibilities, supporting direct action as a necessary social response to environmental issues, and acting in solidarity with Indigenous women in these movements., (© 2020 National Association of Social Workers.)

Theoretical and practical advances in time-frequency analysis, in general, and the continuous wavelet transform (CWT), in particular, have increased over the last two decades. Although the Morlet wavelet has been the default choice for wavelet analysis, a new family of analytic wavelets, known as generalized Morse wavelets, which subsume several other analytic wavelet families, have been increasingly employed due to their time and frequency localization benefits and their utility in isolating and extracting quantifiable features in the time-frequency domain. The current paper describes two practical applications of analysing the features obtained from the generalized Morse CWT: (i) electromyography, for isolating important features in muscle bursts during skating, and (ii) electrocardiography, for assessing heart rate variability, which is represented as the ridge of the main transform frequency band. These features are subsequently quantified to facilitate exploration of the underlying physiological processes from which the signals were generated.This article is part of the theme issue 'Redundancy rules: the continuous wavelet transform comes of age'., (© 2017 The Author(s).)

Background: The severity of wildland fires is increasing due to continually hotter and drier summers. Firefighters are required to make life altering decisions on the fireground, which requires analytical thinking, problem solving, and situational awareness. This study aimed to determine the effects of very hot (45°C; HOT) conditions on cognitive function following periods of simulated wildfire suppression work when compared to a temperate environment (18°C; CON). Methods: Ten male volunteer firefighters intermittently performed a simulated fireground task for 3 h in both the CON and HOT environments, with cognitive function tests (paired associates learning and spatial span) assessed at baseline (cog 1) and during the final 20-min of each hour (cog 2, 3, and 4). Reaction time was also assessed at cog 1 and cog 4. Pre- and post- body mass were recorded, and core and skin temperature were measured continuously throughout the protocol. Results: There were no differences between the CON and HOT trials for any of the cognitive assessments, regardless of complexity. While core temperature reached 38.7°C in the HOT (compared to only 37.5°C in the CON; p < 0.01), core temperature declined during the cognitive assessments in both conditions (at a rate of -0.15 ± 0.20°C·hr -1 and -0.63 ± 0.12°C·hr -1 in the HOT and CON trial respectively). Firefighters also maintained their pre-exercise body mass in both conditions, indicating euhydration. Conclusions: It is likely that this maintenance of euhydration and the relative drop in core temperature experienced between physical work bouts was responsible for the preservation of firefighters' cognitive function in the present study.

Professional firefighters (33 men, 3 women), ranging in age from 30 to 53 years, participated in a simulation of a subway system search and rescue while breathing from their self-contained breathing apparatus (SCBA). We tested the hypothesis that during this task, established by expert firefighters to be of moderate intensity, the rate of air consumption would exceed the capacity of a nominal 30-min cylinder. Oxygen uptake, carbon dioxide output, and air consumption were measured with a portable breath-by-breath gas exchange analysis system, which was fully integrated with the expired port of the SCBA. The task involved descending a flight of stairs, walking, performing a search and rescue, retreat walking, then ascending a single flight of stairs to a safe exit. This scenario required between 9:56 and 13:24 min:s (mean, 12:10 ± 1:10 min:s) to complete, with an average oxygen uptake of 24.3 ± 4.5 mL kg(-1) min(-1) (47 ± 10 % peak oxygen uptake) and heart rate of 76% ± 7% of maximum. The highest energy requirement was during the final single-flight stair climb (30.4 ± 5.4 mL kg(-1) min(-1)). The average respiratory exchange ratio (carbon dioxide output/oxygen uptake) throughout the scenario was 0.95 ± 0.08, indicating a high carbon dioxide output for a relatively moderate average energy requirement. Air consumption from the nominal "30-min" cylinder averaged 51% (range, 26%-68%); however, extrapolation of these rates of consumption suggested that the low-air alarm, signalling that only 25% of the air remains, would have occurred as early as 11 min for an individual with the highest rate of air consumption, and at 16 min for the group average. These data suggest that even the moderate physical demands of walking combined with search and rescue while wearing full protective gear and breathing through the SCBA impose considerable physiological strain on professional firefighters. As well, the rate of air consumption in these tasks classed as moderate, compared with high-rise firefighting, would have depleted the air supply well before the nominal time used to describe the cylinders.

Air consumption, oxygen uptake (VO(2)), carbon dioxide output (VCO(2)) and respiratory exchange ratio (RER=VCO(2)/VO(2)) were measured directly from the self-contained breathing apparatus (SCBA) as 36 professional firefighters (three women) completed scenarios of high-rise stair climbing and fifth floor search and rescue. During stair climbing VO(2) was 75+/-8% VO(2max) (mean+/-SD), RER=1.10+/-0.10, and heart rate=91+/-3% maximum (based on maximum treadmill data). Firefighters stopped climbing on consuming 55% of the air cylinder then descended. In the fifth floor search and rescue VO(2) was slightly lower than stair climbing but RER remained elevated (1.13+/-0.12) reflecting high anaerobic metabolism. The first low air alarm sounded, indicating 25% of the air remaining in a "30-min cylinder", during the stair climb at 8 min with 19 of 36 sounding before 12 min. Aggressive air management strategies are required for safety in high-rise firefighting.

Purpose: The Candidate Physical Ability Test (CPAT) is used by fire departments across North America to screen for minimal physical capabilities in potential candidates, but its physiological demands are unknown., Methods and Results: We examined oxygen uptake and carbon dioxide output (V x O2, V x CO2) and heart rate (HR) responses with the portable system in 57 subjects (23 females) who were familiarized before completing the CPAT in times similar to those of actual candidates. Two men and nine women failed to complete the circuit because of fatigue. Thirty-two men (91%) and four women (15%) completed the circuit under the criterion time (10 min 20 s) with mean completion times for men (8 min 32 s +/- 51 s) and women (11 min 16 s +/- 1 min 28 s, P < 0.05). For all finishers, V x O2 during the test was 38.5 and 36.6 mL x kg(-1) x min(-1), corresponding to 73% and 71% of V x O 2max for men and women, and HR was 90% and 91% of maximum (P > 0.05). RER averaged 1.02 for men and 0.97 for women suggesting elevated anaerobic metabolism. Women had a drop in RER after the second event, and they were significantly slower at each event after the step mill than the men. Prediction of circuit completion time by backward stepwise regression yielded models with absolute V x O 2max alone or relative V x O 2max plus body mass and handgrip strength accounting for more than 67% of the variance but with large errors of estimation exceeding 75 s., Conclusion: The CPAT challenged both the aerobic and anaerobic energy supply systems, and the average V x O2 and HR were similar to reported values during firefighting simulations with incumbent firefighters.

Starting with the weak agonist indomethacin, a series of potent, selective CRTh2 (DP(2)) antagonists have been discovered as potential treatments for asthma, allergic rhinitis and other inflammatory diseases.