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Biomedical subjects

P McDonald

Publications and source records attributed to P McDonald.

At least 19 recordsLinked to original sources
PubMed2006

Cost-effectiveness of pharmacotherapies for nicotine dependence in primary care settings: a multinational comparison.

OBJECTIVE: To estimate the incremental cost-effectiveness of the first-line pharmacotherapies (nicotine gum, patch, spray, inhaler, and bupropion) for smoking cessation across six Western countries-Canada, France, Spain, Switzerland, the United States, and the United Kingdom. DESIGN AND STUDY POPULATION: A Markov-chain cohort model to simulate two cohorts of smokers: (1) a reference cohort given brief cessation counselling by a general practitioner (GP); (2) a treatment cohort given counselling plus pharmacotherapy. Effectiveness expressed as odds ratios for quitting associated with pharmacotherapies. Costs based on the additional physician time required and retail prices of the medications. INTERVENTIONS: Addition of each first-line pharmacotherapy to GP cessation counselling. MAIN OUTCOME MEASURES: Cost per life-year saved associated with pharmacotherapies. RESULTS: The cost per life-year saved for counselling only ranged from US190 dollars in Spain to 773 dollars in the UK for men, and from 288 dollars in Spain to 1168 dollars in the UK for women. The incremental cost per life-year saved for gum ranged from 2230 dollars for men in Spain to 7643 dollars for women in the US; for patch from 1758 dollars for men in Spain to 5131 dollars for women in the UK; for spray from 1935 dollars for men in Spain to 7969 dollars for women in the US; for inhaler from 3480 dollars for men in Switzerland to 8700 dollars for women in France; and for bupropion from 792 dollars for men in Canada to 2922 dollars for women in the US. In sensitivity analysis, changes in discount rate, treatment effectiveness, and natural quit rate had the strongest influences on cost-effectiveness. CONCLUSIONS: The cost-effectiveness of the pharmacotherapies varied significantly across the six study countries, however, in each case, the results would be considered favourable as compared to other common preventive pharmacotherapies.

Adult↗
PubMed2005

Field and model investigations of external gamma dose rates along the Cumbrian coast, NW England.

A survey of the contribution to external dose from gamma rays originating from intertidal sediments in the vicinity of the British Nuclear Group Sellafield site showed that the major anthropogenic contributions were due to (137)Cs and (60)Co. At some sites, traces of other anthropogenic radionuclides were detected, namely (106)Ru, (125)Sb, and (154)Eu. The proportions of fine grained material (<63 microm) were used to improve model predictions of dose contribution due to external exposure to gamma rays, using the CUMBRIA77/DOSE77 model. Model dose predictions were compared to those directly measured in the field. Using the new proportions of fine grained material (1-17.5%) in conjunction with field gamma-ray spectra, model predictions were improved considerably for most sites. Exceptions were at Drigg Barn Scar and Whitehaven Coal Sands sites, which had their own unique characteristics. The highest (60)Co activity concentrations in this study were detected at Drigg Barn Scar. These relatively high activity concentrations of (60)Co were due to the presence of (60)Co in mussels and barnacles, hence upsetting the fine sediment relationships used in previous dose calculations. Whitehaven Coal Sands was unusual in that it contained higher levels of radionuclides than would be expected in sandy sediment. The mineralogy of these sediments was the controlling factor on (137)Cs binding, rather than the proportion of fine grained material. By adjusting the effective fine grained sediment proportions for calculations involving (60)Co and (137)Cs at Drigg Barn Scar and Whitehaven Coal Sands respectively, the CUMBRIA77/DOSE77 model predictions could be improved upon significantly for these sites. This work highlights the influence of particle size and sediment composition on external dose rate calculations, as well as the potential for external dose contributions from biota.

Animals↗
PubMed2005

Ceramide induces mitochondrial abnormalities in insulin-secreting INS-1 cells: potential mechanisms underlying ceramide-mediated metabolic dysfunction of the beta cell.

C2-ceramide, a cell permeable analogue of ceramide [CER] markedly reduced mitochondrial membrane potential [MMP] in insulin-secreting INS cells, which was followed by a significant accumulation of cytochrome c [Cyt c] into the cytosolic compartment. In a manner akin to CER, exposure of these cells to interleukin-1beta [IL-1beta] also resulted in reduction in MMP and cytosolic accumulation of Cyt c. Further, long-term exposure of these cells to either CER [but not its inactive analogue] or IL-1beta caused a marked reduction in their metabolic viability. However, unlike IL-1beta, which increased nitric oxide [NO] release, CER-treatment of INS cells had no effects of CER on NO release were demonstrable. Together, these findings suggest that CER-induced mitochondrial effects may not be mediated via iNOS gene expression and NO production. CER also activated an okadaic acid -sensitive protein phosphatase [CAPP] in the purified mitochondrial fraction, suggesting that CAPP might represent one of the target proteins for CER in the beta cell mitochondria. Together, our findings suggest direct detrimental effects of CER on mitochondrial function in beta cells leading to their dysfunction and demise via apoptosis. Moreover, our findings provide evidence for a potential difference in the mechanisms underlying CER- and IL-1beta-induced mitochondrial defects and apoptotic demise of the effete beta cell.

Animals↗
PubMed2005

Uptake and depuration of 131I by the edible periwinkle Littorina littorea: uptake from seawater.

Uptake and depuration experiments for the edible periwinkle Littorina littorea have been performed using 131I-labelled seawater. Throughout the experimental phase the winkles were fed on unlabelled Chondrus crispus. 131I concentrations in winkles during uptake followed linear first-order kinetics with an uptake half-time of 11 days, whereas for depuration a triphasic sequence with biological half-lives of 4, 23 and 56 days was determined. In general, iodine turnover in winkles via labelled seawater appears to be slower than observed for other molluscs (2-3 days). Most of the activity prior to and after depuration is found to be in the shell, with indications that shell and soft parts accumulate and depurate 131I at a similar rate. The operculum displays the highest specific activity of all fractions with a concentration factor of 750 l kg(-1). Concentration factors for whole winkle, shell, soft parts and digestive gland are in the order of 40-60 l kg(-1), higher than the IAEA recommended CF value for iodine in molluscs of 10 l kg(-1). The 131I CF in winkles is closer to that of the conservative radionuclides 99Tc and 137Cs than the CF of the particle reactive radionuclides (239,240)Pu and 241Am.

Animals↗
PubMed2004

Uptake and depuration of 131I by the edible periwinkle Littorina littorea: uptake from labelled seaweed (Chondrus crispus).

Uptake and depuration experiments of (131)I from labelled seaweed (Chondrus crispus) by the edible periwinkle Littorina littorea have been performed. Radioiodine concentrations in winkles during uptake followed first-order kinetics with an uptake half-time of 1 day, and a calculated equilibrium concentration (C(infinity)) of 21 000 Bq kg(-1) resulting in a transfer factor of 0.07 with respect to the labelled seaweed used as food. For depuration, a biphasic sequence with biological half-lives of 1 and 24 days was determined. The results suggest that in general, iodine turnover in periwinkles is slower than observed for other molluscs (monophasic biological half-lives in the order of 2-3 days). Both environmental media, food and seawater, can be significant sources of radioiodine for the winkle.

Animals↗
PubMed2004

14C and delta13C characteristics of organic matter and carbonate in saltmarsh sediments from south west Scotland.

The distribution of contaminant radionuclides from the Sellafield nuclear fuel reprocessing plant was used to establish chronologies for three saltmarsh sediment cores from south west Scotland. delta(13)C and (14)C analyses indicated that the cores provided a useful archive record of variations in input of organic matter and carbonate. The results imply that prior to major releases of contaminant (14)C from Sellafield, the (14)C specific activity of organic matter in Irish Sea offshore sediments was about 24 Bq kg(-1) C, while that of the carbonate component was below the limit of detection. These results provide baseline data for modelling the uptake of contaminant (14)C by the Irish Sea sediment system. The study confirmed that small(13)C analyses provide a sensitive means of apportioning the origin of saltmarsh organic matter between C(3) terrigenous plants, C(4) terrigenous plants and suspended particulate marine organic matter. For the <2 mm fraction of sediment, a clear pattern of decreasing marine organic input was observed in response to increasing elevation of the marsh surface as a result of sediment accumulation. Bulk sediment, including detrital vegetation, had a dominant input from terrigenous plants. The combined use of delta(13)C and (14)C data revealed that organic matter in the marine organic component of the <2 mm fraction of contemporary surface sediments of the saltmarshes is dominated by recycled old organic material.

Carbon Radioisotopes↗
PubMed2004

Seasonal variations in activity concentrations of 99Tc and 137Cs in the edible meat fraction of crabs and lobsters from the central Irish Sea.

Discharges of most radionuclides into the Irish Sea from the BNFL site at Sellafield have decreased over the past 20 years or so. For a few radionuclides, however, discharges have peaked more recently. Notably, operation of the Enhanced Actinide Removal Plant (EARP) since 1994 has led to an increase in discharges of (99)Tc, as a result of the treatment of previously stored waste, with consequent increases in (99)Tc activity concentrations in a number of marine species, particularly in crustaceans such as lobsters. Previous research has considered the significance of factors such as sex and body weight on radionuclide concentrations. The current project set out to investigate whether seasonal variations in radionuclide concentrations in crabs and lobsters occur, with particular emphasis on the dynamics of (99)Tc and (137)Cs. Organisms were obtained from a site off the Isle of Man, where radionuclide concentrations were measurable but the site was sufficiently distant from Sellafield that the radionuclides were well mixed in the water column and not likely to be influenced by the pulsed nature of discharges of (99)Tc. Crab and lobster samples were collected monthly, between February 2000 and February 2001. Fifteen or 16 individuals (evenly split as male and female) of each species were collected on each occasion. Seawater samples were also collected over the 12-month period. Activity concentrations of (99)Tc in the edible meat fraction (both brown and white meat) ranged from 0.23 to 2.46 Bq kg(-1) (fresh weight (fw)) in crabs and 124 to 216 Bq kg(-1) (fw) in lobsters, with no observed seasonal variations. Activity concentrations of (137)Cs in both crab and lobster were lower, ranging from <0.16 to 0.85 Bq kg(-1) for crab meat (fw) and <0.3 to 3.3 Bq kg(-1) for lobster meat (fw). A statistically significant increase in activity concentrations of (137)Cs in the meat was observed in the summer months for both crab and lobster. The cause has not been investigated but may be related to the laying down of energy reserves during the active feeding period over the summer. At all times, uptake of (99)Tc is higher in the brown meat fraction of both crabs and lobsters, whilst (137)Cs is more uniformly distributed. These results are used to discuss the implications for sampling and monitoring programmes.

Animals↗
PubMed2004

Comparison between the predictions of a Gaussian plume model and a Lagrangian particle dispersion model for annual average calculations of long-range dispersion of radionuclides.

This study attempts to validate the applicability of a simple Gaussian dispersion model for predicting long-range dispersion of continuous releases from an industrial site, by comparison with a Lagrangian particle dispersion model. The United Kingdom Meteorological Office model NAME has been used to predict annual average concentrations of radionuclides over Western Europe, resulting from discharges from the British Nuclear Fuels (BNFL) site at Sellafield, UK. The results are compared here to calculations performed using a conventional Gaussian type of dispersion model, PLUME. The results of the Gaussian model were compared at 14 locations within Western Europe at long range (up to 1700 km). The differences in predictions between the models were explained readily by differences in the way dispersion and deposition processes are represented in the two models. However, differences are generally small compared to the expected precision of the models. The implementation of environmental processes in NAME is more complete and realistic than in PLUME, and as such the results from this model may be considered more realistic. However, given that PLUME is much simpler to use, and appears to over-estimate, rather than under-estimate, environmental concentrations, its use for radiological assessments appears appropriate.

Air Movements↗
PubMed2004

Incidental neurodevelopmental episodes in the etiology of schizophrenia: an expanded model involving epigenetics and development.

Epidemiological data favors genetic predisposition for schizophrenia, a common and complex mental disorder in most populations. Search for the genes involved using candidate genes, positional cloning, and chromosomal aberrations including triplet repeat expansions have established a number of susceptibility loci and genomic sites but no causal gene(s) with a proven mechanism of action. Recent genome-wide gene expression studies on brains from schizophrenia patients and their matched controls have identified a number of genes that show an alteration in expression in the diseased brains. Although it is not possible to offer a cause and effect association between altered gene expression and disease, such observations support a neurodevelopmental model in schizophrenia. Here, we offer a mechanism of this disease, which takes into account the role of developmental noise and diversions of the neural system. It suggests that the final outcome of a neural developmental process is not fixed and exact. Rather it develops with a variation around the mean. More important, the phenotypic consequence may cross the norm as a result of fortuitous and/or epigenetic events. As a result, a normal genotype may develop as abnormal with a disease phenotype. More important, susceptible genotypes may have reduced penetrance and develop as a normal phenocopy. The incidental episodes in neurodevelopment will explain the frequency of schizophrenia in most populations and high discordance of monozygotic twins.

Brain↗
PubMed2003

Epidemiology of MRSA: the North/South study of MRSA in Ireland 1999.

The North/South Study of methicillin-resistant Staphylococcus aureus (MRSA) in Ireland, 1999, includes a joint review of the epidemiology of MRSA across both jurisdictions on the island of Ireland. Data were gathered on all MRSA cases identified in laboratories in Northern Ireland (the North) and in the Republic of Ireland (the South) over a two-week period. The prevalence rate per 100000 population was 11.4 in the North and 14.0 in the South, with a marked variation across geographical regions. MRSA cases were located throughout hospitals and the community, were slightly more common in males than females, and occurred in all age groups, especially in the elderly. The majority of cases were inpatients in acute hospitals and were distributed across all types of wards. Most cases were colonized with MRSA but 5% of cases in the North and 10% in the South had invasive infection. Invasive infection was associated with intravascular lines and invasive procedures/surgery. Continuous surveillance is recommended to monitor the epidemiology of MRSA and the effectiveness of control measures.

Adolescent↗
PubMed2003

MEAD (part I)--a mathematical model of the long-term dispersion of radioactivity in shelf sea environments.

A mathematical model (MEAD) that simulates the transport of radioactivity in shelf-sea environments is presented. In the model it is assumed that the radioactivity can be present in three phases and transport both within and between the phases is captured. The set-up of the model for the Irish Sea is described and results from a simple discharge scenario are presented for (137)Cs and (239)Pu. From these results it appears that MEAD provides a good representation of the transport of radionuclides in the Irish Sea.

Forecasting↗
PubMed2003

MEAD (part II)-Predictions of radioactivity concentrations in the Irish Sea.

The predictions from MEAD, a model that simulates the transport of radionuclides in the marine environment, are presented for the Irish Sea. MEAD predictions for (137)Cs and Pu(alpha) are presented following discharges from BNFL Sellafield and the predictions compared to measured data from near the discharge location and further a field in the Irish Sea. The model performs well in most circumstances given the uncertainties involved in both modelling and data collection although some inconsistencies in the predictions are found. MEAD is also compared to other models of radionuclide transport in the Irish Sea.

Cesium Radioisotopes↗
PubMed2003

Control and the prevention of methicillin-resistant Staphylococcus aureus in hospitals in Ireland: North/South Study of MRSA in Ireland 1999.

As part of an all-island survey of methicillin-resistant Staphylococcus aureus (MRSA) in the Republic of Ireland (the South), where there is a mixed public and private healthcare system, and Northern Ireland (the North), where the healthcare system is part of the UK National Health Service, a questionnaire was circulated to all participating hospitals on measures routinely taken to control MRSA. Response rates were 100% in the North and 89% in the South. Over 70% of hospitals screened particular groups of patients on admission to hospital. Ninety-five percent of hospitals in the North and 88% in the South attempted to eradicate MRSA from carriage sites. Most hospitals attempted to isolate or cohort positive patients. About a quarter of hospitals in both parts of Ireland screened new healthcare workers for the presence of MRSA. Terminal decontamination of the environment after the discharge of a patient positive for MRSA was the norm in over 90% of hospitals, however, 6% of hospitals in the South used inappropriate disinfectants for MRSA. All hospitals in the North, but a minority (41%) in the South, had written antibiotic prescribing policies, but only 65% of hospitals in the South had access to an infection control committee, acute hospitals having greater access than district hospitals. The prevention and control of spread of MRSA remains a major challenge in the North and in the South. Although most hospitals in the North and in the South implemented current recommended guidelines on the control of MRSA in hospitals, there was some variability that may be resource related. Policies need to be reviewed in the light of the changing epidemiology of MRSA.

Cross Infection↗
PubMed2003

MMR vaccine uptake rates: a data validation study.

As part of our investigation into the decrease in the measles, mumps and rubella (MMR) vaccine uptake rates, we validated MMR vaccination records of all children born between 01/09/1998 and 31/08/1999 in our area (North Cheshire, South Cheshire, and Wirral). A significant number of children had received their MMR vaccine but were not recorded as such by the Child Health Computer System (CHCS). Reported COVER (cover of vaccination evaluated rapidly) data uptake (combined) for North Cheshire, South Cheshire, and Wirral Health Authorities for the period covered by the data validation study was 90.5%, the corrected uptake following the validation was 92.6%, 2.1% higher than the reported coverage. If the coverage data were to continue to form part of the NHS indicators of PCT performance, action by all PCTs to improve accuracy of immunisation data would be highly desirable. Electronic transfer of information from practices to the CHCS and between CHCSs, i.e. across boundaries, could improve data accuracy.

Child↗