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D Parker

Publications and source records attributed to D Parker.

At least 19 recordsLinked to original sources
PubMed2007

Developmental differences in neuromodulation and synaptic properties in the lamprey spinal cord.

Functional properties in the spinal cord change during development to adapt motor outputs to differing behavioral requirements. Here, we have examined whether there are also developmental differences in spinal cord plasticity by comparing the neuromodulatory effects of substance P in the larval lamprey spinal cord with its previously characterized effects in premigratory adults. The premigratory adult effects of substance P were all significantly reduced in larvae. As the adult effects of substance P depend on the N-methyl-d-aspartate (NMDA)-dependent potentiation of glutamatergic synaptic transmission, we examined if the developmental differences in neuromodulation were associated with differences in synaptic properties. We found that the amplitude, rise time, and half-width of excitatory postsynaptic potentials (EPSPs) from excitatory network interneurons were all significantly reduced in larvae compared with adults. These differences were associated with a reduction in the NMDA component of larval EPSPs, an effect that could have contributed to the reduced modulatory effects of substance P in larvae. In contrast to glutamatergic inputs, the amplitude, rise time, and half-width of inhibitory postsynaptic potentials (IPSPs) from ipsilateral inhibitory interneurons were all significantly increased in larvae compared with adults. Substance P also potentiated larval IPSP amplitudes, an effect not seen in adults. This increase in inhibition contributed to the reduced effects of substance P in larvae, as premigratory adult-like modulation could be evoked when inhibition was blocked with strychnine. These results suggest that opposite developmental changes in excitatory and inhibitory synaptic transmission and their modulation are associated with developmental differences in spinal cord neuromodulation.

Age Factors↗
PubMed2006

Pressure dependence of the Fulde-Ferrell-Larkin-Ovchinnikov state in CeCoIn5.

Pressure studies of the thermodynamics of CeCoIn5 under magnetic fields H parallel to c and H parallel to ab have been made up to P = 1.34 GPa. We recorded the signature of the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state for all pressures when H parallel to ab. Also remarkably, the FFLO regime suddenly expands for P = 1.34 GPa. With the help of a microscopic theory for d-wave superconductivity, we have extracted the gyromagnetic ratio g and the Fermi velocities nu(a) and nu(c). Our study is the first evidence for the existence of the FFLO state away from the influence of the antiferromagnetic fluctuations. We find a close parallel between the T-P phase diagram of CeCoIn5 and the T-x phase diagram of the high-Tc cuprates, where x is the hole concentration.

Journal Article↗
PubMed2006

Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness.

There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids. A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 mug b.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment separated by a 4-week washout period. The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second. In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.

Acetates↗
PubMed2006

Likelihood of reporting adverse events in community pharmacy: an experimental study.

BACKGROUND: In the UK the National Reporting and Learning System (NRLS) is designed to coordinate the reporting of patient safety incidents nationally and to improve the ability of the health service to learn from the analysis of these events. Little is known about levels of engagement with the NRLS. OBJECTIVE: To examine the likelihood of community pharmacists and support staff reporting patient safety incidents which occur in community pharmacies. METHODS: Questionnaire survey containing nine incident scenarios. In the scenarios two factors were orthogonally manipulated: the outcome for the patient was reported as good, bad or poor, and the behaviour of the pharmacist was described as either complying with a protocol, not being aware of a protocol (error), or violating a protocol. Respondents were asked to rate whether they would report the incident (1) locally within the pharmacy and (2) nationally to the National Patient Safety Agency (NPSA). RESULTS: 275 questionnaires were returned (79% response rate) from 223 community pharmacists and 52 members of support staff. There were significant main effects for both patient outcome (F(2,520) = 18.19, p<0.001) and behaviour type (F(2,520) = 93.98, p<0.001), indicating that pharmacists and support staff would take into account both the outcome of the behaviour and whether or not it follows a protocol when considering to report an incident within the pharmacy. Likewise, both pharmacists and support staff considered patient outcome (F(2,524) = 12.59, p<0.001) and behaviour type (F(2,524) = 34.82, p<0.001) when considering to report to the NPSA. Both locally and nationally, the likelihood of reporting any incident was low, and judgements on whether to report were more affected by the behaviour of the pharmacist in relation to protocols than the resulting outcome for the patient. CONCLUSIONS: Community pharmacists and their support staff would be unlikely to report adverse incidents if they witnessed them occurring in a community pharmacy. They remain to be convinced that the advantages to them and their patients outweigh the consequences of blame.

Analysis of Variance↗
PubMed2006

A collaborative hit-to-lead investigation leveraging medicinal chemistry expertise with high throughput library design, synthesis and purification capabilities.

High throughput screening (HTS) campaigns, where laboratory automation is used to expose biological targets to large numbers of materials from corporate compound collections, have become commonplace within the lead generation phase of pharmaceutical discovery. Advances in genomics and related fields have afforded a wealth of targets such that screening facilities at larger organizations routinely execute over 100 hit-finding campaigns per year. Often, 10(5) or 10(6) molecules will be tested within a campaign/cycle to locate a large number of actives requiring follow-up investigation. Due to resource constraints at every organization, traditional chemistry methods for validating hits and developing structure activity relationships (SAR) become untenable when challenged with hundreds of hits in multiple chemical families per target. To compound the issue, comparison and prioritization of hits versus multiple screens, or physical chemical property criteria, is made more complex by the informatics issues associated with handling large data sets. This article describes a collaborative research project designed to simultaneously leverage the medicinal chemistry and drug development expertise of the Novartis Institutes for Biomedical Research Inc. (NIBRI) and ArQule Inc.'s high throughput library design, synthesis and purification capabilities. The work processes developed by the team to efficiently design, prepare, purify, assess and prioritize multiple chemical classes that were identified during high throughput screening, cheminformatics and molecular modeling activities will be detailed.

Chemistry, Pharmaceutical↗
PubMed2005

Sputum eosinophilia in idiopathic pulmonary fibrosis.

OBJECTIVES AND DESIGN: Cough is a common symptom in idiopathic pulmonary fibrosis that is difficult to treat and has a major impact on quality of life. We tested the hypothesis that the cough and increased cough reflex sensitivity seen in patients with idiopathic pulmonary fibrosis may be due to airway inflammation in a prospective, cross-sectional study. SUBJECTS AND METHODS: We measured the induced sputum inflammatory cell profile and cell-free supernatant inflammatory mediator concentrations in 15 patients with idiopathic pulmonary fibrosis, 17 healthy controls and 15 patients with chronic obstructive pulmonary disease. RESULTS: Both the geometric mean sputum differential eosinophil cell count and median eosinophilic-cationic-protein concentration were significantly higher in patients with idiopathic pulmonary fibrosis than controls (2.1% vs 0.3%; p <0.001 and 1.1 mg/ml versus 0.2 mg/ml; p=0.03 respectively). There were no significant differences in sputum eosinophil counts and eosinophilic-cationic-protein concentrations between patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. Sputum leukotriene-B4 concentrations were significantly lower in patients with idiopathic pulmonary fibrosis (p=0.03) and chronic obstructive pulmonary disease (p=0.008) compared to controls. CONCLUSIONS: Idiopathic pulmonary fibrosis is characterised by the presence of active eosinophilic airway inflammation raising the possibility that airway inflammation may contribute to symptoms such as cough.

Aged↗
PubMed2005

Single-photon emission computed tomography perfusion imaging in the differential diagnosis of dementia: a retrospective regional audit.

A retrospective audit of (99m)Tc-HMPAO SPECT scans was undertaken to assess the utility of brain perfusion imaging in a cohort of young cognitively impaired patients in whom diagnostic uncertainty remained after standard clinical and neuropsychological assessment and structural brain imaging. SPECT scans were assessed by five raters (two neurologists and three nuclear medicine specialists) on two occasions 6 months apart, first without any clinical data and second with brief pertinent clinical information. SPECT diagnoses were compared with criterion diagnoses subsequently established by the two neurologists with access to all clinical, neuropsychological and neuroimaging data. Despite reasonable intra- and interrater reliability, diagnostic accuracy ranged from 32 to 58%. SPECT scan normality or abnormality in blind and informed viewings gave respective sensitivities of 77 and 71%, specificities of 44 and 38%, positive predictive values of 88 and 87% and negative predictive values of 27 and 18%. Calculating pairwise disease group comparisons, likelihood ratios suggested some diagnostic gain in differentiating AD from 'not AD' and from FTD/focal syndromes. SPECT scanning was of little help in establishing diagnoses in this cohort of patients, a finding which supports the conclusion of the American Academy of Neurology evidence-based review that SPECT imaging cannot be recommended for either the initial or the differential diagnosis of suspected dementia because it has not demonstrated superiority to clinical criteria.

Adult↗
PubMed2005

Is ultrasound useful for evaluating paediatric inflammatory neck masses?

OBJECTIVE: To determine the accuracy of ultrasound in detecting the presence of pus in a neck mass in children. DESIGN: Retrospective case sheet review. SETTING: A district general hospital. PARTICIPANTS: Children admitted from January 2000 to January 2004 with an acute cervical mass who were investigated by ultrasonography. MAIN OUTCOME MEASURES: The presence of a clinically relevant abscess that did not respond to clinical management was used to determine the accuracy of the ultrasound result. RESULTS: The sensitivity of ultrasound in the detection of an abscess was 65% and the specificity 88%. The predictive value of a positive ultrasound result was 81% and the predictive value of a negative test 77%. CONCLUSIONS: Ultrasound is a useful modality in the evaluation of acute cervical masses but is observer dependent and has a relatively low sensitivity in detecting whether or not pus is present. The clinical indicators for the presence of an abscess are discussed and clinicians should combine clinical findings with the ultrasound findings in order to determine treatment.

Abscess↗
PubMed2005

Making psychological theory useful for implementing evidence based practice: a consensus approach.

BACKGROUND: Evidence-based guidelines are often not implemented effectively with the result that best health outcomes are not achieved. This may be due to a lack of theoretical understanding of the processes involved in changing the behaviour of healthcare professionals. This paper reports the development of a consensus on a theoretical framework that could be used in implementation research. The objectives were to identify an agreed set of key theoretical constructs for use in (1) studying the implementation of evidence based practice and (2) developing strategies for effective implementation, and to communicate these constructs to an interdisciplinary audience. METHODS: Six phases of work were conducted to develop a consensus: (1) identifying theoretical constructs; (2) simplifying into construct domains; (3) evaluating the importance of the construct domains; (4) interdisciplinary evaluation; (5) validating the domain list; and (6) piloting interview questions. The contributors were a "psychological theory" group (n = 18), a "health services research" group (n = 13), and a "health psychology" group (n = 30). RESULTS: Twelve domains were identified to explain behaviour change: (1) knowledge, (2) skills, (3) social/professional role and identity, (4) beliefs about capabilities, (5) beliefs about consequences, (6) motivation and goals, (7) memory, attention and decision processes, (8) environmental context and resources, (9) social influences, (10) emotion regulation, (11) behavioural regulation, and (12) nature of the behaviour. CONCLUSIONS: A set of behaviour change domains agreed by a consensus of experts is available for use in implementation research. Applications of this domain list will enhance understanding of the behaviour change processes inherent in implementation of evidence-based practice and will also test the validity of these proposed domains.

Evidence-Based Medicine↗
PubMed2005

Safety culture assessment in community pharmacy: development, face validity, and feasibility of the Manchester Patient Safety Assessment Framework.

OBJECTIVE: To develop a framework that could be used by community pharmacies to self-assess their current level of safety culture maturity, which has high face validity and is both acceptable and feasible for use in this setting. DESIGN: An iterative review process in which the framework was developed and evaluated through a series of 10 focus groups with a purposive sample of 67 community pharmacists and support staff in the UK. MAIN OUTCOME MEASURES: Development of the framework and qualitative process feedback on its acceptability, face validity, and feasibility for use in community pharmacies. RESULTS: Using this process, a version of the Manchester Patient Safety Assessment Framework (MaPSAF) was developed that is suitable for application to community pharmacies. The participants were able to understand the concepts, recognised differences between the five stages of safety culture maturity, and concurred with the descriptions from personal experience. They also indicated that they would be willing to use the framework but recognised that staff would require protected time in order to complete the assessment. CONCLUSIONS: In practice the MaPSAF is likely to have a number of uses including raising awareness about patient safety and illustrating any differences in perception between staff, stimulating discussion about the strengths and weaknesses of patient safety culture within the pharmacy, identifying areas for improvement, and evaluating patient safety interventions and tracking changes over time. This will support the development of a mature safety culture in community pharmacies.

England↗
PubMed2005

Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease.

BACKGROUND: An association between the sputum eosinophil count and the response to a 2 week course of prednisolone has previously been reported in patients with chronic obstructive pulmonary disease (COPD). Whether the response to inhaled corticosteroids is related to the presence of eosinophilic inflammation is unclear. METHODS: A randomised, double blind, crossover trial of placebo and mometasone furoate (800 microg/day), each given for 6 weeks with a 4 week washout period, was performed in subjects with COPD treated with bronchodilator therapy only. Spirometric tests, symptom scores, chronic respiratory disease questionnaire (CRQ), and induced sputum were performed before and after each treatment phase. RESULTS: Ninety five patients were recruited of which 60 were randomised. Overall there were no treatment associated changes in forced expiratory volume in 1 second (FEV(1)), total CRQ, or sputum characteristics. After stratification into tertiles by baseline eosinophil count, the net improvement in post-bronchodilator FEV(1) increased with mometasone compared with placebo progressively from the least to the most eosinophilic tertile. The mean change in post-bronchodilator FEV(1) with mometasone compared with placebo in the highest tertile was 0.11 l (95% CI 0.03 to 0.19). This improvement was not associated with a fall in the sputum eosinophil count. CONCLUSIONS: An increased sputum eosinophil count is related to an improvement in post-bronchodilator FEV(1) following treatment with inhaled mometasone in COPD, but the improvement is not associated with a reduction in the sputum eosinophil count.

Administration, Inhalation↗
PubMed2005

Airway function and markers of airway inflammation in patients with treated hypothyroidism.

BACKGROUND: There is increasing evidence of an association between organ specific autoimmune diseases, particularly autoimmune thyroid disease and respiratory morbidity. A study was undertaken to determine whether patients with autoimmune thyroid disease have objective evidence of airway inflammation and dysfunction. METHODS: Twenty six non-smoking women with treated hypothyroidism and 19 non-smoking controls completed a symptom questionnaire and underwent full lung function tests, capsaicin cough reflex sensitivity measurement, methacholine challenge test, and sputum induction over two visits. RESULTS: Symptoms of cough (p = 0.01), dyspnoea (p = 0.01), sputum production (p = 0.004), and wheeze (p = 0.04) were reported more commonly in patients than controls. Patients with hypothyroidism had heightened cough reflex sensitivity compared with controls (geometric mean concentration of capsaicin causing five coughs: 40 v 108 mmol/l; mean difference 1.4 doubling doses; 95% confidence interval of difference 0.4 to 2.5; p = 0.008) and a significantly higher proportion of patients had airway hyperresponsiveness (methacholine provocative concentration (PC(20)) <8 mg/ml: 38% v 0%; p = 0.016). Patients with hypothyroidism also had a significantly higher induced sputum total neutrophil cell count (p = 0.01), total lymphocyte count (p = 0.02), and sputum supernatant interleukin-8 concentrations (p = 0.048). CONCLUSION: Patients with treated hypothyroidism report more respiratory symptoms and have objective evidence of airway dysfunction and inflammation.

Biomarkers↗
PubMed2004

Modification of soft drinks with xanthan gum to minimise erosion: a study in situ.

OBJECTIVE: To compare the erosive effect of a new blackcurrant/calcium drink with xanthan gum, on enamel in situ, with a low erosive product, a conventional fruit beverage and water. DESIGN: The study was single centre, randomised, single blind, 4 treatment crossover design. SETTING: This study, conducted in 2000, employed volunteers working at the Bristol Dental Hospital, UK. SUBJECTS, MATERIALS AND METHODS: 16 subjects (>or=18 years) wore two enamel samples in a removable acrylic appliance. The drinks tested were (A) New blackcurrant/calcium/gum drink (test product), (B) Original blackcurrant/calcium drink, (C) Conventional blackcurrant drink (positive control) and (D) Water (negative control), for 15 day study periods. Drinking was supervised, with 250 ml imbibed four times/day between 9.00am-5.00pm. Profile measurements of specimens were made at baseline, 5, 10 and 15 days. MAIN OUTCOME MEASURES: Paired t-tests compared erosion by surfometry with selected pairs of formulations. RESULTS: Of 16 screened subjects (3 male, 13 female), mean age 34.2 years, 1 subject failed to complete the study. A caused significantly less enamel loss than C, with no statistically significant differences from B at any time points measured. Of 43 treatment emergent adverse events, none were considered related to the study formulations. CONCLUSIONS: A retained low erosive properties similar to B, with additional benefits of taste flexibility and beverage stability.

Adolescent↗
PubMed2004

North American performance experience with anoxic and anaerobic selectors for activated sludge bulking control.

Obtaining reliably high compaction characteristics and low SVI values has enormous economic consequences on activated sludge plant design and operation. Now that use of selectors has become more common for achieving low SVI values, the assessment of the full-scale performance characteristics of activated sludge plants incorporating selectors has high value for the design and operation of future plants. Treatment plant effluent quality is seldom analyzed solely on an average basis and the impact peak events have on effluent quality must be considered in design and operation. Descriptive statistics should also be used to assess selector performance, so that the influence of infrequently occurring values on plant design and operation can be assessed. The performance of 21 activated sludge plants incorporating selectors was evaluated. All the selector plants for which post installation data were available showed that the operating SVI values were significantly improved. One plant studied in detail showed that final effluent quality was significantly better after the selector installation. As a group, activated sludge plants with anaerobic selectors outperform those with anoxic selectors. Dissolved oxygen control is just as important in activated sludge plants with selectors as in conventional activated sludge plants.

Bacteria, Aerobic↗
PubMed2003

Energy metabolism in Bardet-Biedl syndrome.

INTRODUCTION: Obesity is a consistent presenting feature of the Bardet-Biedl syndrome (BBS), a hereditary disorder caused by a single gene defect. This contrasts sharply with general obesity which, despite a strong hereditary component, has a multifactorial aetiology. For BBS, the phenotypic characterisation of the components of energy balance and the implications for their management remains relatively uninvestigated. OBJECTIVE: A case-control study to determine whether energy metabolism in subjects with BBS differs from matched obese controls and to inform the clinical management of these patients. METHODS: A total of 20 overweight and obese subjects with BBS (11 females, 9 males) matched for age, gender and BMI to 20 subjects without BBS. Resting metabolic rate (RMR) was measured by indirect calorimetry, physical activity by CSA accelerometry, body composition by the deuterium dilution technique and dietary intake by 7-day food records. RESULTS: There was no significant difference between BBS and control subjects in body fat (male: % fat=38, s.d. 2.8 vs 34, s.d. 9.1, female: % fat=45, s.d. 5.9 vs 44, s.d. 8.1; P=0.46] or absolute RMR (male: 6.95, s.d. 1.55 MJ/day vs 7.19, s.d. 1.28 MJ/day; P=0.6). After adjustment for gender, age, fat-free mass and fat mass, there was no significant difference in RMR between BBS and control subjects (F(1, 30)=0.91; P=0.35). A lower level of physical activity was observed in BBS subjects (median cnts/min 259, IQR=153) compared to controls (median cnts/min=306, IQR=119, P=0.02). Reported energy intake, macronutrient composition and magnitude of under-reporting were comparable in both groups. CONCLUSION: This study reveals no evidence for systematic differences in energy metabolism in subjects with BBS relative to other obese individuals, suggesting that the genetic basis of BBS is not associated with specific abnormalities in energy metabolism. This is an important finding for clinical management and supports the use of energy prescriptions based on RMR for the general obese population plus an appropriate allowance for energy expended via physical activity. Further research is needed on physical activity in BBS.

Adult↗