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Search Results: 1 - 10 of 141979 matches for " Ann K Goodchild "
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Role of ionotropic GABA, glutamate and glycine receptors in the tonic and reflex control of cardiac vagal outflow in the rat
Cara M Hildreth, Ann K Goodchild
BMC Neuroscience , 2010, DOI: 10.1186/1471-2202-11-128
Abstract: Microinjection of the GABAA antagonist picrotoxin into CVPN decreased HR but did not affect baroreflex bradycardia. The glycine antagonist strychnine did not alter HR or baroreflex bradycardia. Combined microinjection of the NMDA antagonist, MK801, and AMPA antagonist, CNQX, into CVPN evoked a small bradycardia and abolished baroreflex bradycardia. MK801 attenuated whereas CNQX abolished baroreceptor bradycardia. Control intravenous injections of the 5-HT1A agonist 8-OH-DPAT evoked a small bradycardia and potentiated baroreflex bradycardia. These effects were still observed following microinjection of picrotoxin but not strychnine into CVPN.We conclude that activation of GABAA receptors set the level of HR whereas AMPA to a greater extent than NMDA receptors elicit baroreflex changes in HR. Furthermore, activation of 5-HT1A receptors evokes bradycardia and enhances baroreflex changes in HR due to interactions with glycinergic neurons involving strychnine receptors. This study provides reference for future studies investigating how diseases alter neurochemical inputs to CVPN.Cardiac vagal preganglionic neurons (CVPN) are found predominantly in the nucleus ambiguus (NA) as well as dorsal motor nucleus of the vagus (DMNV) and in the intermediate zone (IZ) between these two nuclei [1-3]. Activation of CVPN has negative chronotropic, dromotropic and ionotropic effects on the heart [4-6] and the activity of these neurons is increased in response to baroreceptor stimulation [7-9] and inhibited during inspiration [10,11].Surprisingly little is known about the functional significance of inputs to CVPN mediated by either ionotropic or g-protein coupled receptors (GPCR). CVPN receive substantial inputs from ionotropic receptors. Microinjection of the GABAA receptor antagonist bicuculline into the NA evokes a profound decrease in HR [12] demonstrating that there is a large GABAergic input to CVPN that plays a role in setting the tonic level of heart rate (HR). GABAergic inputs
Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats
Margery C. Pardey,Natasha N. Kumar,Ann K. Goodchild,Kelly J. Clemens,Judi Homewood,Jennifer L. Cornish
Brain Sciences , 2012, DOI: 10.3390/brainsci2030375
Abstract: The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin ?). With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed “normal” (Wistar Kyoto, WKY) rats and in Spontaneously Hypertensive Rats (SHR), a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin ? (2 × 2 mg/kg/day) or distilled water (dH 2O). The effect of chronic treatment on delayed reinforcement tasks (DRT) and tyrosine hydroxylase immunoreactivity (TH-ir) in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH 2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in “normal” WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls.
Tyrosine Hydroxylase Phosphorylation in Catecholaminergic Brain Regions: A Marker of Activation following Acute Hypotension and Glucoprivation
Hanafi A. Damanhuri, Peter G. R. Burke, Lin K. Ong, Larisa Bobrovskaya, Phillip W. Dickson, Peter R. Dunkley, Ann K. Goodchild
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0050535
Abstract: The expression of c-Fos defines brain regions activated by the stressors hypotension and glucoprivation however, whether this identifies all brain sites involved is unknown. Furthermore, the neurochemicals that delineate these regions, or are utilized in them when responding to these stressors remain undefined. Conscious rats were subjected to hypotension, glucoprivation or vehicle for 30, 60 or 120 min and changes in the phosphorylation of serine residues 19, 31 and 40 in the biosynthetic enzyme, tyrosine hydroxylase (TH), the activity of TH and/or, the expression of c-Fos were determined, in up to ten brain regions simultaneously that contain catecholaminergic cell bodies and/or terminals: A1, A2, caudal C1, rostral C1, A6, A8/9, A10, nucleus accumbens, dorsal striatum and medial prefrontal cortex. Glucoprivation evoked phosphorylation changes in A1, caudal C1, rostral C1 and nucleus accumbens whereas hypotension evoked changes A1, caudal C1, rostral C1, A6, A8/9, A10 and medial prefrontal cortex 30 min post stimulus whereas few changes were evident at 60 min. Although increases in pSer19, indicative of depolarization, were seen in sites where c-Fos was evoked, phosphorylation changes were a sensitive measure of activation in A8/9 and A10 regions that did not express c-Fos and in the prefrontal cortex that contains only catecholaminergic terminals. Specific patterns of serine residue phosphorylation were detected, dependent upon the stimulus and brain region, suggesting activation of distinct signaling cascades. Hypotension evoked a reduction in phosphorylation in A1 suggestive of reduced kinase activity. TH activity was increased, indicating synthesis of TH, in regions where pSer31 alone was increased (prefrontal cortex) or in conjunction with pSer40 (caudal C1). Thus, changes in phosphorylation of serine residues in TH provide a highly sensitive measure of activity, cellular signaling and catecholamine utilization in catecholaminergic brain regions, in the short term, in response to hypotension and glucoprivation.
Revolt, She Said
Goodchild, Philip
Ars Disputandi : the Online Journal for Philosophy of Religion , 2003,
Positive attitudes towards priority setting in clinical guidelines among Danish general practitioners: A web based survey  [PDF]
Ann Nielsen, Benedicte Carlsen, Pia K. Kjellberg
Health (Health) , 2013, DOI: 10.4236/health.2013.52026

Aims: Increasing focus on improvement and optimisation of the treatment in primary care and reduction of healthcare costs emphasize the need to understand which factors determines adherence and non-adherence to clinical guidelines. In the present study, we examined attitudes towards clinical guidelines in Danish general practitioners (GPs). Methods: We conducted a survey among Danish GPs from all five regions of Denmark. In total, 443 GPs answered the web-based questionnaire that contained questions about attitudes and barriers to clinical guidelines. Results: More than 90% of the GPs reported that they have good knowledge of the guidelines and in general follows the guidelines. A majority of the GPs (81%) found it acceptable that economic considerations are part of the guidelines. The most important factors for non- adherence to guidelines were “need of adjustment to clinical practice” and “lack of confidence in guidelines”. The attitudes to clinical guidelines were not significantly associated with practice characteristics such as gender, years of experience, practice organisation and localisation. Conclusions: Our findings show that clinical guidelines are an integrated or internalised part of everyday practice among GPs in Denmark. Furthermore, the findings indicate that Danish GPs are positive towards applying priority setting in their practice. This is decisive in the light of rising healthcare costs due to development of new expensive technologies and ageing populations that puts pressure on the healthcare system in general and primary healthcare in particular.

Pharmacogenomics of anticoagulants: steps toward personal dosage
Ann K Daly
Genome Medicine , 2009, DOI: 10.1186/gm10
Abstract: Coumarin anticoagulants, including warfarin, are among the most widely prescribed drugs in modern medicine. A difficulty with their use is that dosage needs to be individually determined for each patient, usually by following a standard initial dosing protocol, measuring the coagulation rate regularly (using the international normalized ratio, INR, which is a measure of prothrombin time. A high INR value indicates overcoagulation) and then adjusting the dose until the required rate of coagulation is obtained. Overcoagulation places the patient at risk of potentially fatal hemorrhage, so improving protocols for initiation of anticoagulant treatment remains an important issue. In particular, warfarin has been shown to be frequently implicated in emergency admissions relating to adverse drug reactions in a survey of two UK hospitals [1]. Approximately 10% of Europeans require an unusually low dose of warfarin (1.5 mg/day or less) and these patients could be at increased risk of developing serious bleeds and undesirably high levels of anticoagulation, especially during the initial weeks of treatment [2]. Although the current oral coumarin anticoagulants, such as warfarin, acenocoumarol and phenprocoumon, are likely to be replaced eventually by other drugs under development, such as the specific thrombin inhibitors, the current drugs will probably continue to be the main oral anticoagulants prescribed in the short to medium term.The metabolism of warfarin and the other coumarin anticoagulants is well understood, with the cytochrome P450 enzyme CYP2C9 having a major role in their phase I metabolism (reviewed in [3]). CYP2C9 is subject to a genetic polymorphism affecting its activity, and the fact that this polymorphism contributes to individual anticoagulant dose requirement is now well established, although its effect on phenprocoumon metabolism is less pronounced than that on either warfarin or acenocoumarol [2,4-7]. Coumarin anticoagulants exert their effect by inhibit
The Alexandria Digital Library Project Review, Assessment, and Prospects
Michael F Goodchild
Trends in Information Management , 2005,
Abstract: The Alexandria Digital Library (ADL) was established in the late 1990s as a response to several perceived problems of traditional map libraries, notably access and organization. By 1999 it had evolved into an operational digital library, offering a well-defined set of services to a broad user community, based on an extensive collection of georeferenced information objects. The vision of ADL continues to evolve, as technology makes new services possible, as its users become more sophisticated and demanding, and as the broader field of geographic information science (GlScience) identifies new avenues for research and application.
Twenty years of progress: GIScience in 2010
Michael F Goodchild
Journal of Spatial Information Science , 2010, DOI: 10.5311/josis.2010.1.2
Abstract: It is 20 years since the term “geographic information science” was suggested to encompass the set of fundamental research issues that surround GIS. Two decades of GIScience have produced a range of accomplishments, in an expanding literature of research results as well as in the infrastructure of research. Several themes are suggested for future research, based both on gaps in what has been accomplished thus far, and on technology trends that will themselves raise research questions.
Local Well-posedness of A Non-local Burgers Equation
Hang Yang,Sam Goodchild
Mathematics , 2013,
Abstract: In this paper, we explore a nonlocal inviscid Burgers equation. Fixing a parameter $h$, we prove existence and uniqueness of the local solution of the equation $\InviscidBurgersNonlocal{u}$ with periodic initial condition. We also explore the blow up properties of solutions to these kinds of equations with given periodic initial data, and show that there exists solutions that blow up in finite time and solutions that are globally regular. This contrasts with the classical inviscid Burgers equation, for which all non-constant smooth periodic initial data lead to finite time blow up. Finally, we present results of simulations to illustrate our findings.
Drosophila PRL-1 Is a Growth Inhibitor That Counteracts the Function of the Src Oncogene
Krystle T. Pagarigan, Bryce W. Bunn, Jake Goodchild, Travis K. Rahe, Julie F. Weis, Leslie J. Saucedo
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0061084
Abstract: Phosphatase of Regenerating Liver (PRL) family members have emerged as molecular markers that significantly correlate to the ability of many cancers to metastasize. However, contradictory cellular responses to PRL expression have been reported, including the inhibition of cell cycle progression. An obvious culprit for the discrepancy is the use of dozens of different cell lines, including many isolated from tumors or cultured cells selected for immortalization which may have missing or mutated modulators of PRL function. We created transgenic Drosophila to study the effects of PRL overexpression in a genetically controlled, organismal model. Our data support the paradigm that the normal cellular response to high levels of PRL is growth suppression and furthermore, that PRL can counter oncogenic activity of Src. The ability of PRL to inhibit growth under normal conditions is dependent on a CAAX motif that is required to localize PRL to the apical edge of the lateral membrane. However, PRL lacking the CAAX motif can still associate indiscriminately with the plasma membrane and retains its ability to inhibit Src function. We propose that PRL binds to other membrane-localized proteins that are effectors of Src or to Src itself. This first examination of PRL in a model organism demonstrates that PRL performs as a tumor suppressor and underscores the necessity of identifying the conditions that enable it to transform into an oncogene in cancer.
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