444 resultados para Swift, Jonathan, 1667-1745.
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Based on regional-scale studies, aboveground production and litter decomposition are thought to positively covary, because they are driven by shared biotic and climatic factors. Until now we have been unable to test whether production and decomposition are generally coupled across climatically dissimilar regions, because we lacked replicated data collected within a single vegetation type across multiple regions, obfuscating the drivers and generality of the association between production and decomposition. Furthermore, our understanding of the relationships between production and decomposition rests heavily on separate meta-analyses of each response, because no studies have simultaneously measured production and the accumulation or decomposition of litter using consistent methods at globally relevant scales. Here, we use a multi-country grassland dataset collected using a standardized protocol to show that live plant biomass (an estimate of aboveground net primary production) and litter disappearance (represented by mass loss of aboveground litter) do not strongly covary. Live biomass and litter disappearance varied at different spatial scales. There was substantial variation in live biomass among continents, sites and plots whereas among continent differences accounted for most of the variation in litter disappearance rates. Although there were strong associations among aboveground biomass, litter disappearance and climatic factors in some regions (e.g. U.S. Great Plains), these relationships were inconsistent within and among the regions represented by this study. These results highlight the importance of replication among regions and continents when characterizing the correlations between ecosystem processes and interpreting their global-scale implications for carbon flux. We must exercise caution in parameterizing litter decomposition and aboveground production in future regional and global carbon models as their relationship is complex.
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Rail operators recognize a need to increase ridership in order to improve the economic viability of rail service, and to magnify the role that rail travel plays in making cities feel liveable. This study extends previous research that used cluster analysis with a small sample of rail passengers to identify five salient perspectives of rail access (Zuniga et al, 2013). In this project stage, we used correlation techniques to determine how those perspectives would resonate with two larger study populations, including a relatively homogeneous sample of university students in Brisbane, Australia and a diverse sample of rail passengers in Melbourne, Australia. Findings from Zuniga et al. (2013) described a complex typology of current passengers that was based on respondents’ subjective attitudes and perceptions rather than socio-demographic or travel behaviour characteristics commonly used for segmentation analysis. The typology included five qualitative perspectives of rail travel. Based on the transport accessibility literature, we expected to find that perspectives from that study emphasizing physical access to rail stations would be shared by current and potential rail passengers who live further from rail stations. Other perspectives might be shared among respondents who live nearby, since the relevance of distance would be diminished. The population living nearby would thus represent an important target group for increasing ridership, since making rail travel accessible to them does not require expansion of costly infrastructure such as new lines or stations. By measuring the prevalence of each perspective in a larger respondent pool, results from this study provide insight into the typical socio-demographic and travel behaviour characteristics that correspond to each perspective of intra-urban rail travel. In several instances, our quantitative findings reinforced Zuniga et al.’s (2013) qualitative descriptions of passenger types, further validating the original research. This work may directly inform rail operators’ approach to increasing ridership through marketing and improvements to service quality and station experience. Operators in other parts of Australia and internationally may also choose to replicate the study locally, to fine-tune understanding of diverse customer bases. Developing regional and international collaboration would provide additional opportunities to evaluate and benchmark service and station amenities as they address the various access dimensions.
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The objective of exercise training is to initiate desirable physiological adaptations that ultimately enhance physical work capacity. Optimal training prescription requires an individualized approach, with an appropriate balance of training stimulus and recovery and optimal periodization. Recovery from exercise involves integrated physiological responses. The cardiovascular system plays a fundamental role in facilitating many of these responses, including thermoregulation and delivery/removal of nutrients and waste products. As a marker of cardiovascular recovery, cardiac parasympathetic reactivation following a training session is highly individualized. It appears to parallel the acute/intermediate recovery of the thermoregulatory and vascular systems, as described by the supercompensation theory. The physiological mechanisms underlying cardiac parasympathetic reactivation are not completely understood. However, changes in cardiac autonomic activity may provide a proxy measure of the changes in autonomic input into organs and (by default) the blood flow requirements to restore homeostasis. Metaboreflex stimulation (e.g. muscle and blood acidosis) is likely a key determinant of parasympathetic reactivation in the short term (0–90 min post-exercise), whereas baroreflex stimulation (e.g. exercise-induced changes in plasma volume) probably mediates parasympathetic reactivation in the intermediate term (1–48 h post-exercise). Cardiac parasympathetic reactivation does not appear to coincide with the recovery of all physiological systems (e.g. energy stores or the neuromuscular system). However, this may reflect the limited data currently available on parasympathetic reactivation following strength/resistance-based exercise of variable intensity. In this review, we quantitatively analyse post-exercise cardiac parasympathetic reactivation in athletes and healthy individuals following aerobic exercise, with respect to exercise intensity and duration, and fitness/training status. Our results demonstrate that the time required for complete cardiac autonomic recovery after a single aerobic-based training session is up to 24 h following low-intensity exercise, 24–48 h following threshold-intensity exercise and at least 48 h following high-intensity exercise. Based on limited data, exercise duration is unlikely to be the greatest determinant of cardiac parasympathetic reactivation. Cardiac autonomic recovery occurs more rapidly in individuals with greater aerobic fitness. Our data lend support to the concept that in conjunction with daily training logs, data on cardiac parasympathetic activity are useful for individualizing training programmes. In the final sections of this review, we provide recommendations for structuring training microcycles with reference to cardiac parasympathetic recovery kinetics. Ultimately, coaches should structure training programmes tailored to the unique recovery kinetics of each individual.
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This paper aims to address the knowledge gap in regards to the potential intermediary role tertiary institutions can play in developing generic design thinking/design led innovation capabilities in non-designers. Specifically, it investigates the value derived from the contribution of postgraduate design students as facilitators/educators for undergraduate non-design student cohorts. It examines a design immersion workshop designed to encourage the use of design thinking capabilities for project brief development for undergraduate multi-disciplinary student teams involved in a community service learning project for a social enterprise. The workshop was facilitated by design led innovation masters students embedded in industry organisations to research the integration of design led innovation capabilities in business. Data was collected from participating non-design students and postgraduate facilitators’ in the form of reflective journals and semi-structured interviews. The thematic analysis provided insight into the value of design thinking/design led innovation immersion programs for both the postgraduate facilitators and the undergraduate non-design students. The research results will inform a tentative foundation prototype framework to allow for ongoing program developments and research in design thinking/design led innovation integration in higher education, facilitating the development of generic capabilities required to empower future generations for business innovation and active citizenship in the 21st century knowledge economy.
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Recent evidence indicates that the estrogen receptor-a-negative, androgen receptor (AR)- positive molecular apocrine subtype of breast cancer is driven by AR signaling. The MDA-MB-453 cell line is the prototypical model of this breast cancer subtype; its proliferation is stimulated by androgens such as 5a-dihydrotestosterone (DHT) but inhibited by the progestin medroxyprogesterone acetate (MPA) via AR-mediated mechanisms. We report here that the AR gene in MDAMB- 453 cells contains a G-T transversion in exon 7, resulting in a receptor variant with a glutamine to histidine substitution at amino acid 865 (Q865H) in the ligand binding domain. Compared with wild-type AR, the Q865H variant exhibited reduced sensitivity to DHT and MPA in transactivation assays in MDA-MB-453 and PC-3 cells but did not respond to non-androgenic ligands or receptor antagonists. Ligand binding, molecular modeling, mammalian two-hybrid and immunoblot assays revealed effects of the Q865H mutation on ligand dissociation, AR intramolecular interactions, and receptor stability. Microarray expression profiling demonstrated that DHT and MPA regulate distinct transcriptional programs in MDA-MB-453 cells. Gene Set Enrichment Analysis revealed that DHT- but not MPA-regulated genes were associated with estrogen-responsive transcriptomes from MCF-7 cells and the Wnt signaling pathway. These findings suggest that the divergent proliferative responses of MDA-MB-453 cells to DHT and MPA result from the different genetic programs elicited by these two ligands through the AR-Q865H variant. This work highlights the necessity to characterize additional models of molecular apocrine breast cancer to determine the precise role of AR signaling in this breast cancer subtype. Endocrine-Related Cancer (2012) 19 599–613
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There is a rapidly growing appreciation of the important physiological roles played by kallikreins and kallikrein-related peptidases (KLKs). Recent studies have revealed that these enzymes control key events in processes as diverse as inflammation and skin desquamation. Accordingly, there is considerable interest in developing tools to further dissect kallikrein activity, and a burgeoning effort aimed at producing lead inhibitors for therapeutic development. Indeed, several candidate inhibitors are already in clinical trials. This chapter surveys the naturally occurring kallikrein inhibitors, together with strategies for employing these molecules as bioscaffolds, as well as current progress in the development of small-molecule kallikrein inhibitors.
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Plasmin is the primary enzyme responsible for dissolution of fibrin in the circulatory system. Plasminogen, the zymogen of plasmin is expressed ubiquitously in the human body [1], with the predominant source being the liver [2, 3]. Plasminogen is produced as an 810 amino acid protein with a 19 amino acid leader peptide, which is cleaved during secretion to produce the mature 791 amino acid one-chain zymogen. This is converted to plasmin by cleavage of the Arg561 - Val562 scissile bond [4], resulting in an active protease consisting of two disulfide linked chains. The amino-terminal heavy chain (residues Glu1-Arg561) is comprised of a plasminogen/apple/nematode (PAN) domain [5] and five kringle domains of approximately equal size [6] while the light chain (residues Val562-Asn791) contains a serine protease domain homologous to trypsin with a catalytic triad comprising His603, Asp646 and Ser741 [7]. Both plasmin and plasminogen occur in two forms, full length and a Lys77-Lys78 activated variant produced through self catalysis (Figure 1). The former exists in a tight conformation through binding of Lys50 and/or Lys62 to kringle domain 5 [8, 9] while Lys78-plasminogen assumes a more relaxed conformation rendering it more susceptible to plasmin conversion [10, 11].
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Weather is one of the most significant elements affecting transit ridership on a daily basis. Until now, there has been limited focus in the literature investigating this issue. Adverse weather conditions impact travellers in choosing travel mode and route, travel schedule, and trip making itself. This paper explores the relationship between adverse weather and transit ridership by analysing the correlation between daily bus ridership and daily precipitation for a three-year period from 2010 to 2012. It is observed from the analysis that wet weather has varying impacts on daily bus ridership. Overall, rainfall negatively affects the daily bus ridership in this region. Morning peak-hours and weekend ridership were found more sensitive to rain than entire day’s ridership and weekdays. The study also found a negative correlation between the morning-peak precipitation level and the daily bus ridership, which suggests that a small amount of morning peak-hours rain reduces a significant amount bus ridership for the whole day. The analysis also confirms that summer rain has the most significant effect on ridership compared with the other three seasons. The study findings will contribute to enhancing the fundamental understanding of traveller behaviours, particularly mode choice behaviour under adverse weather conditions.
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Purpose To observe the incidence rates of hamstring strain injuries (HSIs) across different competition levels and ages during the Penn Relays Carnival. Methods Over a 3-year period all injuries treated by the medical staff were recorded. The type of injury, anatomic location, event in which the injury occurred, competition level and demographic data were documented. Absolute and relative HSI (per 1000 participants) were determined and odds ratios (OR) were calculated between genders, competition levels and events. Results Throughout the study period 48,473 athletes registered to participate in the Penn Relays Carnival, with 118 HSIs treated by the medical team. High school females displayed lesser risk of HSI than high school males (OR = 0.55, p = 0.021), and masters athletes were more likely than high school (OR = 4.26, p < 0.001) and college (OR = 3.55, p = 0.001) level athletes to suffer a HSI. The 4x400m relay displayed a greater likelihood of HSI compared to the 4x100m relay (OR = 1.77, p = 0.008). Conclusions High school males and masters levels athletes are most likely to suffer HSI, and there is higher risk in 400m events compared to 100m events.
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To the Editor: The Victorian Health Records Act 2001 became operational on 1 July 2002. This legislation provides important protection for the individual against misuse of health information through the establishment of Health Privacy Principles. We support the spirit of this legislation, but would like to draw attention to its potential effects on multicentre research and disease surveillance...
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Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland). In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management of exacerbations in people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs) in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel.
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Background Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. Discussion Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879