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Search Results: 1 - 10 of 307507 matches for " Patrick J Graham "
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A note on the use of sensitivity analysis to explore the potential impact of declining institutional care utilisation on disability prevalence
Patrick J Graham
Population Health Metrics , 2004, DOI: 10.1186/1478-7954-2-3
Abstract: Prevalence measures of disability, functional limitation and other health states are important descriptive statistics for assessing population health and are integral to the construction of summary measures such as health expectancy [1]. Commonly used health and disability survey sampling frames exclude individuals living in institutions such as hospitals or retirement homes. For example, reports based on the United States National Health Interview Survey [2], the French Health and Medical Care Survey [3], the Finnish and Norwegian Surveys of Living Conditions [4] and the New-Zealand Household Health Survey [5] all note that the survey data refer to the non-institutionalised population. Because the prevalence of limiting and disabling conditions is likely to be higher among the population in institutional care, prevalence estimates based solely on the non-institutionalised population are likely to underestimate prevalence for the full population, particularly at older ages. In the context of health expectancy calculations, one response to this situation has been to define institutional care as a distinct health state and to produce estimates of the expectation of life in institutional care, not in institutional care but with functional limitations or disability and not in institutional care and free of limitations or disabilities [2,6]. Surveys of the non-institutionalised population produce estimates of the conditional prevalence, Pr(limitation|non-institutionalised), which is exactly what is required to compute the expectation of life with non-institutionalised disability in a health expectancy calculation, partitioned as just discussed.The strategy of defining institutional care as a distinct health state yields a coherent set of point-in-time health state prevalences and health expectancy estimates, covering the entire population. However changes in the prevalence of institutionalisation complicate the interpretation of changes in non-institutionalised health st
Robust Bayesian detection of unmodelled bursts
Antony C Searle,Patrick J Sutton,Massimo Tinto,Graham Woan
Physics , 2007, DOI: 10.1088/0264-9381/25/11/114038
Abstract: A Bayesian treatment of the problem of detecting an unmodelled gravitational wave burst with a global network of gravitational wave observatories reveals that several previously proposed statistics have implicit biases that render them sub-optimal for realistic signal populations.
Vision and Foraging in Cormorants: More like Herons than Hawks?
Craig R. White, Norman Day, Patrick J. Butler, Graham R. Martin
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000639
Abstract: Background Great cormorants (Phalacrocorax carbo L.) show the highest known foraging yield for a marine predator and they are often perceived to be in conflict with human economic interests. They are generally regarded as visually-guided, pursuit-dive foragers, so it would be expected that cormorants have excellent vision much like aerial predators, such as hawks which detect and pursue prey from a distance. Indeed cormorant eyes appear to show some specific adaptations to the amphibious life style. They are reported to have a highly pliable lens and powerful intraocular muscles which are thought to accommodate for the loss of corneal refractive power that accompanies immersion and ensures a well focussed image on the retina. However, nothing is known of the visual performance of these birds and how this might influence their prey capture technique. Methodology/Principal Findings We measured the aquatic visual acuity of great cormorants under a range of viewing conditions (illuminance, target contrast, viewing distance) and found it to be unexpectedly poor. Cormorant visual acuity under a range of viewing conditions is in fact comparable to unaided humans under water, and very inferior to that of aerial predators. We present a prey detectability model based upon the known acuity of cormorants at different illuminances, target contrasts and viewing distances. This shows that cormorants are able to detect individual prey only at close range (less than 1 m). Conclusions/Significance We conclude that cormorants are not the aquatic equivalent of hawks. Their efficient hunting involves the use of specialised foraging techniques which employ brief short-distance pursuit and/or rapid neck extension to capture prey that is visually detected or flushed only at short range. This technique appears to be driven proximately by the cormorant's limited visual capacities, and is analogous to the foraging techniques employed by herons.
Biofuels and biodiversity in South Africa
Ryan Blanchard,David M. Richardson,Patrick J. O’Farrell,Graham P. von Maltitz
South African Journal of Science , 2011, DOI: 10.4102/sajs.v107i5/6.186
Abstract: The South African government, as part of its efforts to mitigate the effects of the ongoing energy crisis, has proposed that biofuels should form an important part of the country’s energy supply. The contribution of liquid biofuels to the national fuel supply is expected to be at least 2% by 2013. The Biofuels Industrial Strategy of the Republic of South Africa of 2007 outlines key incentives for reaching this target and promoting the development of a sustainable biofuels industry. This paper discusses issues relating to this strategy as well as key drivers in biofuel processing with reference to potential impacts on South Africa’s rich biological heritage. Our understanding of many of the broader aspects of biofuels needs to be enhanced. We identify key areas where challenges exist, such as the link between technology, conversion processes and feedstock selection. The available and proposed processing technologies have important implications for land use and the use of different non-native plant species as desired feedstocks. South Africa has a long history of planting non-native plant species for commercial purposes, notably for commercial forestry. Valuable lessons can be drawn from this experience on mitigation against potential impacts by considering plausible scenarios and the appropriate management framework and policies. We conceptualise key issues embodied in the biofuels strategy, adapting a framework developed for assessing and quantifying impacts of invasive alien species. In so doing, we provide guidelines for minimising the potential impacts of biofuel projects on biodiversity.
Dopamine Receptor-Interacting Protein 78 Acts as a Molecular Chaperone for CCR5 Chemokine Receptor Signaling Complex Organization
Yi-Qun Kuang, Nicholle Charette, Jennifer Frazer, Patrick J. Holland, Kathleen M. Attwood, Graham Dellaire, Denis J. Dupré
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040522
Abstract: Chemokine receptors are members of the G protein-coupled receptor (GPCR) family. CCR5 and CXCR4 act as co-receptors for human immunodeficiency virus (HIV) and several efforts have been made to develop ligands to inhibit HIV infection by blocking those receptors. Removal of chemokine receptors from the cell surface using polymorphisms or other means confers some levels of immunity against HIV infection. Up to now, very limited success has been obtained using ligand therapies so we explored potential avenues to regulate chemokine receptor expression at the plasma membrane. We identified a molecular chaperone, DRiP78, that interacts with both CXCR4 and CCR5, but not the heterodimer formed by these receptors. We further characterized the effects of DRiP78 on CCR5 function. We show that the molecular chaperone inhibits CCR5 localization to the plasma membrane. We identified the interaction region on the receptor, the F(x)6LL motif, and show that upon mutation of this motif the chaperone cannot interact with the receptor. We also show that DRiP78 is involved in the assembly of CCR5 chemokine signaling complex as a homodimer, as well as with the Gαi protein. Finally, modulation of DRiP78 levels will affect receptor functions, such as cell migration in cells that endogenously express CCR5. Our results demonstrate that modulation of the functions of a chaperone can affect signal transduction at the cell surface.
Subsonic critical velocity at finite temperature
Patrick Navez,Robert Graham
Physics , 2005,
Abstract: Based on the dielectric formalism in the generalised random phase approximation, we generalise the description of a Bose condensed gas to allow for a relative velocity between the superfluid and normal fluid. In this model, we determine the critical velocity dynamically as the transition point between stable and unstable dynamics. Unlike the zero temperature case, at finite temperature the relative critical velocity of a dilute Bose gas is lower than the sound velocity. This result illustrates one relevant difference that exists between a conserving and gapless approximation and other approaches.
Maximum Running Speed of Captive Bar-Headed Geese Is Unaffected by Severe Hypoxia
Lucy A. Hawkes, Patrick J. Butler, Peter B. Frappell, Jessica U. Meir, William K. Milsom, Graham R. Scott, Charles M. Bishop
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0094015
Abstract: While bar-headed geese are renowned for migration at high altitude over the Himalayas, previous work on captive birds suggested that these geese are unable to maintain rates of oxygen consumption while running in severely hypoxic conditions. To investigate this paradox, we re-examined the running performance and heart rates of bar-headed geese and barnacle geese (a low altitude species) during exercise in hypoxia. Bar-headed geese (n = 7) were able to run at maximum speeds (determined in normoxia) for 15 minutes in severe hypoxia (7% O2; simulating the hypoxia at 8500 m) with mean heart rates of 466±8 beats min?1. Barnacle geese (n = 10), on the other hand, were unable to complete similar trials in severe hypoxia and their mean heart rate (316 beats.min?1) was significantly lower than bar-headed geese. In bar-headed geese, partial pressures of oxygen and carbon dioxide in both arterial and mixed venous blood were significantly lower during hypoxia than normoxia, both at rest and while running. However, measurements of blood lactate in bar-headed geese suggested that anaerobic metabolism was not a major energy source during running in hypoxia. We combined these data with values taken from the literature to estimate (i) oxygen supply, using the Fick equation and (ii) oxygen demand using aerodynamic theory for bar-headed geese flying aerobically, and under their own power, at altitude. This analysis predicts that the maximum altitude at which geese can transport enough oxygen to fly without environmental assistance ranges from 6,800 m to 8,900 m altitude, depending on the parameters used in the model but that such flights should be rare.
Forward Genetic Screening Identifies a Small Molecule That Blocks Toxoplasma gondii Growth by Inhibiting Both Host- and Parasite-Encoded Kinases
Kevin M. Brown,Elena Suvorova,Andrew Farrell,Aaron McLain,Ashley Dittmar,Graham B. Wiley,Gabor Marth,Patrick M. Gaffney,Marc Jan Gubbels,Michael White,Ira J. Blader
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004180
Abstract: The simultaneous targeting of host and pathogen processes represents an untapped approach for the treatment of intracellular infections. Hypoxia-inducible factor-1 (HIF-1) is a host cell transcription factor that is activated by and required for the growth of the intracellular protozoan parasite Toxoplasma gondii at physiological oxygen levels. Parasite activation of HIF-1 is blocked by inhibiting the family of closely related Activin-Like Kinase (ALK) host cell receptors ALK4, ALK5, and ALK7, which was determined in part by use of an ALK4,5,7 inhibitor named SB505124. Besides inhibiting HIF-1 activation, SB505124 also potently blocks parasite replication under normoxic conditions. To determine whether SB505124 inhibition of parasite growth was exclusively due to inhibition of ALK4,5,7 or because the drug inhibited a second kinase, SB505124-resistant parasites were isolated by chemical mutagenesis. Whole-genome sequencing of these mutants revealed mutations in the Toxoplasma MAP kinase, TgMAPK1. Allelic replacement of mutant TgMAPK1 alleles into wild-type parasites was sufficient to confer SB505124 resistance. SB505124 independently impacts TgMAPK1 and ALK4,5,7 signaling since drug resistant parasites could not activate HIF-1 in the presence of SB505124 or grow in HIF-1 deficient cells. In addition, TgMAPK1 kinase activity is inhibited by SB505124. Finally, mice treated with SB505124 had significantly lower tissue burdens following Toxoplasma infection. These data therefore identify SB505124 as a novel small molecule inhibitor that acts by inhibiting two distinct targets, host HIF-1 and TgMAPK1.
Cell Cycle Control by the Master Regulator CtrA in Sinorhizobium meliloti
Francesco Pini?,Nicole J. De Nisco?,Lorenzo Ferri?,Jon Penterman?,Antonella Fioravanti?,Matteo Brilli?,Alessio Mengoni?,Marco Bazzicalupo?,Patrick H. Viollier?,Graham C. Walker
PLOS Genetics , 2015, DOI: 10.1371/journal.pgen.1005232
Abstract: In all domains of life, proper regulation of the cell cycle is critical to coordinate genome replication, segregation and cell division. In some groups of bacteria, e.g. Alphaproteobacteria, tight regulation of the cell cycle is also necessary for the morphological and functional differentiation of cells. Sinorhizobium meliloti is an alphaproteobacterium that forms an economically and ecologically important nitrogen-fixing symbiosis with specific legume hosts. During this symbiosis S. meliloti undergoes an elaborate cellular differentiation within host root cells. The differentiation of S. meliloti results in massive amplification of the genome, cell branching and/or elongation, and loss of reproductive capacity. In Caulobacter crescentus, cellular differentiation is tightly linked to the cell cycle via the activity of the master regulator CtrA, and recent research in S. meliloti suggests that CtrA might also be key to cellular differentiation during symbiosis. However, the regulatory circuit driving cell cycle progression in S. meliloti is not well characterized in both the free-living and symbiotic state. Here, we investigated the regulation and function of CtrA in S. meliloti. We demonstrated that depletion of CtrA cause cell elongation, branching and genome amplification, similar to that observed in nitrogen-fixing bacteroids. We also showed that the cell cycle regulated proteolytic degradation of CtrA is essential in S. meliloti, suggesting a possible mechanism of CtrA depletion in differentiated bacteroids. Using a combination of ChIP-Seq and gene expression microarray analysis we found that although S. meliloti CtrA regulates similar processes as C. crescentus CtrA, it does so through different target genes. For example, our data suggest that CtrA does not control the expression of the Fts complex to control the timing of cell division during the cell cycle, but instead it negatively regulates the septum-inhibiting Min system. Our findings provide valuable insight into how highly conserved genetic networks can evolve, possibly to fit the diverse lifestyles of different bacteria.
Constraints on the Progenitor System of the Type Ia Supernova 2014J from Pre-Explosion Hubble Space Telescope Imaging
Patrick L. Kelly,Ori D. Fox,Alexei V. Filippenko,S. Bradley Cenko,Lisa Prato,Gail Schaefer,Ken J. Shen,WeiKang Zheng,Melissa L. Graham,Brad E. Tucker
Physics , 2014, DOI: 10.1088/0004-637X/790/1/3
Abstract: We constrain the properties of the progenitor system of the highly reddened Type Ia supernova (SN) 2014J in Messier 82 (M82; d ~ 3.5 Mpc). We determine the SN location using Keck-II K-band adaptive optics images, and we find no evidence for flux from a progenitor system in pre-explosion near-ultraviolet through near-infrared Hubble Space Telescope (HST) images. Our upper limits exclude systems having a bright red giant companion, including symbiotic novae with luminosities comparable to that of RS Ophiuchi. While the flux constraints are also inconsistent with predictions for comparatively cool He-donor systems (T < ~35,000 K), we cannot preclude a system similar to V445 Puppis. The progenitor constraints are robust across a wide range of R_V and A_V values, but significantly greater values than those inferred from the SN light curve and spectrum would yield proportionally brighter luminosity limits. The comparatively faint flux expected from a binary progenitor system consisting of white dwarf stars would not have been detected in the pre-explosion HST imaging. Infrared HST exposures yield more stringent constraints on the luminosities of very cool (T < 3000 K) companion stars than was possible in the case of SN Ia 2011fe.
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