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Biomedical subjects

J A Jones

Publications and source records attributed to J A Jones.

At least 19 recordsLinked to original sources

Sphingolipid-binding proteins.

Emerging information on sphingolipid metabolism and signaling is leading to a better understanding of cellular processes such as apoptosis, cancer, cell survival and aging. In this review, we discuss the involvement of sphingolipids in these processes and focus on underlying mechanisms based on sphingolipid:protein interactions. Due to the inherent difficulty of studying lipids, we discuss techniques that are useful in the elucidation of these interactions. We classify sphingolipid-binding proteins into four main classes: receptor, effector, enzyme, and transporter. Known structures of sphingolipid-binding proteins are surveyed, and sphingolipid-binding characteristics are described, acknowledging the limitations that there are presently insufficient protein:sphingolipid complexes for more definitive conclusions on this topic. Finally we summarize relevant literature to better inform the reader about sphingolipid:protein interactions.

Animals↗

No increase in human cases of Mycobacterium bovis disease despite resurgence of infections in cattle in the United Kingdom.

A resurgence of Mycobacterium bovis infections in cattle in the United Kingdom since the 1980s has raised concern about risks to human health. Enhanced surveillance data for England, Wales and Northern Ireland between 1993 and 2003 of culture-positive human M. bovis cases identified 315 M. bovis infections; the mean annual number of cases was 28 (range 12-41). The most frequently reported exposures were consumption of unpasteurized dairy products 41/83 (49%) and exposure to cattle 45/123 (37%). Of all cases, 249 (83%) were born before 1960. Of 50 cases born after 1960, only 14 were born in the United Kingdom. Over the same time period the annual number of new herd infections increased from 332 to 1749 as derived from the UK State Veterinary Service database. In conclusion, despite a more than fivefold increase in cattle herd infections during the 1990s, there was no increase in reported human cases.

Adult↗

Application of a generic biosphere model for dose assessments to five European sites.

The BIOMOSA (BIOsphere MOdels for Safety Assessment of radioactive waste disposal) project was part of the EC fifth framework research programme. The main goal of this project was to improve the scientific basis for the application of biosphere models in the framework of long-term safety studies of radioactive waste disposal facilities and to enhance the confidence in using biosphere models for performance assessments. The study focused on the development and application of a generic biosphere tool BIOGEM (BIOsphere GEneric Model) using the IAEA BIOMASS reference biosphere methodology, and the comparison between BIOGEM and five site-specific biosphere models. The site-specific models and the generic model were applied to five typical locations in Europe, resulting in estimates of the annual effective individual doses to the critical groups and the ranking of the importance of the exposure pathways for each of the sites. Uncertainty in the results was also estimated by means of stochastic calculations based on variation of the site-specific parameter values. This paper describes the generic model and the deterministic and stochastic results obtained when it was applied to the five sites. Details of the site-specific models and the corresponding results are described in two companion papers. This paper also presents a comparison of the results between the generic model and site-specific models. In general, there was an acceptable agreement of the BIOGEM for both the deterministic and stochastic results with the results from the site-specific models.

Body Burden↗

The EXPURT model for calculating external gamma doses from deposited material in inhabited areas.

EXPURT, NRPB's model for calculating external gamma doses in inhabited areas, was originally developed in the mid-1980s. Deposition on surfaces in the area, the subsequent transfer of material between different surfaces or its removal from the system, and dose rates in various locations from material on the different surfaces are modelled. The model has been updated to take account of more recent experimental data on the transfer rates between surfaces and to make it more flexible for use in assessing dose rates following an accidental release. EXPURT is a compartmental model and models the transfer of material between the surfaces using a set of first order differential equations. It enables the impact of the decontamination of surfaces on doses and dose rates to be explored. The paper describes the EXPURT model and presents some preliminary results obtained using it.

Air Pollutants, Radioactive↗

Requirements of future models for inhabited areas.

Models for inhabited areas are used in a variety of applications for accidental or continuous releases of radioactivity to atmosphere. Pathways of interest are external exposure from radioactive material in the cloud or deposited on indoor and outdoor surfaces and people, inhalation from the plume and from material resuspended from the ground. In developing a model for inhabited areas it is necessary to consider what the end users may need and ensure that the model is appropriate for the application; different levels of detail may be appropriate for different applications. This paper considers the main processes governing exposure in inhabited areas, commenting on the extent to which we understand them and how well current models reflect this understanding. It also identifies where the authors believe future modelling is needed and the key areas where the current inhabited area models could be improved.

Air Pollution, Indoor↗

Generation and interrogation of a pure nuclear spin state by parahydrogen-enhanced NMR spectroscopy: a defined initial state for quantum computation.

We describe a number of studies used to establish that parahydrogen can be used to prepare a two-spin system in a pure state, which is suitable for implementing NMR quantum computation. States are generated by pulsed and continuous-wave (CW) UV laser initiation of a chemical reaction between Ru(CO)(3)(L(2)) [where L(2) = dppe = 1,2-bis(diphenylphosphino)ethane or L(2) = dpae = 1,2-bis(diphenylarsino)ethane] with pure parahydrogen (generated at 18 K). This process forms Ru(CO)(2)(dppe)(H)(2) and Ru(CO)(2)(dpae)(H)(2) on a sub-microsecond time-scale. With the pulsed laser, the spin state of the hydride nuclei in Ru(CO)(2)(dppe)(H)(2) has a purity of 89.8 +/- 2.6% (from 12 measurements). To achieve comparable results by cooling would require a temperature of 6.6 mK, which is unmanageable in the liquid state, or an impractical magnetic field of 0.44 MT at room temperature. In the case of CW initiation, reduced state purities are observed due to natural signal relaxation even when a spin-lock is used to prevent dephasing. When Ru(CO)(3)(dpae) and pulsed laser excitation are utilized, the corresponding dihydride product spin state purity was determined as 106 +/- 4% of the theoretical maximum. In other words, the state prepared using Ru(CO)(3)(dpae) as the precursor is indistinguishable from a pure state.

Bicarbonates↗

Genitourinary issues during spaceflight: a review.

The genitourinary (GU) system is not uncommonly affected during previous spaceflights. GU issues that have been observed during spaceflight include urinary calculi, infections, retention, waste management, and reproductive. In-flight countermeasures for each of these issues are being developed to reduce the likelihood of adverse sequelae, due to GU issues during exploration-class spaceflight, to begin in 2018 with flights back to the Moon and on to Mars, according to the February 2004 Presendent's Vision for US Space Exploration. With implementation of a robust countermeasures program, GU issues should not have a significant threat for mission impact during future spaceflights.

Aerospace Medicine↗

Does periodontal treatment improve glycemic control in diabetic patients? A meta-analysis of intervention studies.

Previous analyses regarding effects of periodontal treatment on glycemic control included studies where causal association might not be assumed, or the results were reported non-quantitatively. We initiated this meta-analysis of 10 intervention studies to quantify the effects of periodontal treatment on HbA1c level among diabetic patients, to explore possible causes for the discrepant reports, and to make recommendations for future studies. Data sources were MEDLINE (January, 1980, to January, 2005), the EBMR, Cochrane Register, and bibliographies of the published articles. Three investigators extracted data regarding intervention, outcomes, and effect size. A total of 456 patients was included in this analysis, with periodontal treatment as predictor and the actual change in hemoglobin A1c level as the outcome. The weighted average decrease in actual HbA1c level was 0.38% for all studies, 0.66% when restricted to type 2 diabetic patients, and 0.71% if antibiotics were given to them. However, none was statistically significant.

Anti-Bacterial Agents↗

Rural GPs' ratings of initiatives designed to improve rural medical workforce recruitment and retention.

INTRODUCTION: Since the early 1990s, Australian governments have recognised the problems of rural medical workforce recruitment and retention and have implemented a range of programs and incentives designed to improve the supply of, and access to, doctors in rural and remote areas. Some incentives involve differential payments according to degree of rurality or remoteness. Since these programs involve considerable costs to governments, some assessment of their impact on recruitment or retention is warranted. The objective of this study is to examine the effectiveness of different recruitment and retention incentives from the perspective of the rural GP. Doctors practising in rural and remote communities were, therefore, asked to rank the relative importance of different interventions in terms of their impact on recruitment to and retention of GPs in their communities. METHODS: Six possible interventions were selected to cover the major objectives underpinning rural workforce programs most relevant to doctors currently in rural practice. Respondents assigned a rank to indicate the relative importance of each item with respect to each of the two questions: "What would help most to attract more GPs to this community?" and "What would help most to retain GPs in this community?" The data were collected as part of a national study into the viability of rural general practice undertaken jointly by the Rural Doctors Association of Australia and Monash University School of Rural Health Bendigo. The Rural, Remote and Metropolitan Areas (RRMA) classification was used as the rurality indicator. Analysis involved the calculation of mean ranks for each item. Item means were then ranked to indicate most to least important items in total, and within each RRMA category. RESULTS: Thirty-five percent of all GPs practising in rural and remote Australia responded to the national survey, representing 53% of all practices in those areas. Of these, 1050 doctors who nominated themselves as a principal, partner or associate in their practice were eligible for inclusion in this analysis. The results showed a high degree of agreement in the responses to both questions, with the possible interventions being ranked in the same overall order. 'Better remuneration for Medicare consultations' and 'Improved after-hours and on-call arrangements' were ranked as the most important interventions for both attracting and retaining GPs, whereas 'Better education and professional support activity' and 'Improved availability of allied health professional services' were ranked as least important of the options presented. 'Better locum availability' and 'Capital funding to improve practice infrastructure/enable GPs to set up practice' ranked in between. Results within each RRMA category were very similar to the overall rankings, confirming the significance of the improved remuneration and workload arrangements, regardless of geographical location. CONCLUSIONS: Ensuring professional support, workforce supply, income and infrastructure support are all relevant to the recruitment and retention of GPs in rural and remote areas. However, from the perspective of GPs practising in such areas, specific initiatives that increase the core income of rural practices, and which address those medical workforce supply issues which impact most on workload, are considered those which are most likely to assist in the recruitment and retention of GPs to Australia's rural and remote communities.

Journal Article↗

Preparing high purity initial states for nuclear magnetic resonance quantum computing.

Here we demonstrate how parahydrogen can be used to prepare a two-spin system in an almost pure state which is suitable for implementing nuclear magnetic resonance quantum computation. A 12 ns laser pulse is used to initiate a chemical reaction involving pure parahydrogen (the nuclear spin singlet of H2). The product, formed on the micros time scale, contains a hydrogen-derived two-spin system with an effective spin-state purity of 0.916. To achieve a comparable result by direct cooling would require an unmanageable (in the liquid state) temperature of 6.4 mK or an impractical magnetic field of 0.45 MT at room temperature. The resulting spin state has an entanglement of formation of 0.822 and cannot be described by local hidden variable models.

Journal Article↗

Doctors' perspectives on the viability of rural practice.

INTRODUCTION: Private practitioners play a vital role in meeting the health needs of rural communities. However, the prospect of operating a private practice business in rural Australia seems to be increasingly unattractive, because many communities are forced to recruit salaried or overseas-trained doctors. This study focuses on rural practices as businesses whose viability influences their attractiveness for the recruitment and retention of practitioners. The specific objectives are to ascertain which factors contribute to or threaten practice viability in rural areas, and whether they vary according to the degree of rurality or geographical remoteness. METHODS: This study is based on data collected from a national study into the viability of rural general practice undertaken jointly by the Rural Doctors Association of Australia and Monash University School of Rural Health Bendigo. The Rural Remote and Metropolitan Area (RRMA) classification was used as the indicator of rurality. The study surveyed all general practitioners practising in rural or remote regions of Australia (RRMAs 3 to 7). Only practitioners with some financial interest in the practice were selected for this analysis. Free-text responses to the two questions 'What are the key factors contributing to the viability of your practice?' and 'What factors would put the viability of your practice at risk?' were analysed using qualitative content analysis. Factors were derived iteratively through higher-level aggregation of responses. Chi-square tests were used to make comparisons across the RRMA categories. RESULTS: The national survey achieved a response rate of 35% of the entire population of GPs practising in RRMA 3 to 7 regions. Of these, 1050 respondents were relevant to this analysis. Seven major factors were identified by practitioners as the main contributors to practice viability. 'Practice characteristics' was nominated by 59% of respondents, followed by 'Income' (31%), 'Personal circumstances', 'Workforce' and 'Community characteristics' (all approximately 23%), 'GP activities and workload' (16%) and 'Professional support' (12%). Eight main factors were identified by practitioners as threats to viability. 'Workforce' was nominated by 57% of respondents, followed by 'Financial' (44%), 'Medico-legal' (33%), 'Administration-political' (16%), 'Community characteristics' (15%), 'GP-practice characteristics' and 'Personal circumstances' (10%) and 'Family circumstances' (3%). Across RRMA 3 to 5 the order of the percentage of respondents identifying each factor was generally consistent, with significant differences in the magnitude of the percentages for three contributing factors and four risk factors. While respondent numbers in RRMA 6 and 7 communities were low, significance testing did reveal differences between them and the rural communities on two contributing and one risk factor. CONCLUSIONS: Practice viability is a major factor affecting the attractiveness of rural and remote practice for intending and existing GPs. Initiatives designed to contribute to viability will not be successful unless measures are also adopted to address perceived threats. This study highlights the systemic nature of the factors which contribute to and threaten practice viability. Although a primary component of practice viability is economic, with income from consultations being critical, the importance of the interrelationships between the main viability factors should not be underestimated. Clearly a multifaceted systemic response is required to overcome problems associated with rural workforce recruitment of future and burnout of current rural GPs.

Journal Article↗

Too hot to trot? Exploring potential links between climate change, physical activity and health.

Based on an analysis of existing literature, this paper explores the links between climate change, physical activity and health. It highlights the importance of physical activity for health, explores current understandings of factors influencing participation in sport and physical activity, and develops some hypotheses about the ways in which climate change may impact on the factors influencing physical activity and thereby on the level of participation in physical activity. The paper argues that climate change has the potential to be a barrier to participation in physical activity, particularly in areas where temperatures are already relatively high, and that a reduction in physical activity across the population is likely to have detrimental health impacts. The need for research to clarify the nature and extent of the threat posed to physical activity participation is highlighted, as is the need to take into account the direct and indirect costs of any changes or reductions in physical activity in any assessment of the costs of climate change and/or its mitigation.

Australia↗

Overlap between genitourinary medicine and public health in the surveillance and control of sexually transmitted infection in England, Wales and Northern Ireland.

The control of sexually transmitted infections (STI), and in particular outbreaks and other acute incidents of STI, often requires resources outside the genitourinary medicine (GUM) clinic. This study of Consultants in Communicable Disease Control (CsCDC) in England, Wales and Northern Ireland, explored the level of collaboration between district public health departments and GUM clinics and the usefulness at local level of STI surveillance data. The results show an inconsistent working relationship between GUM and public health throughout the country and highlight deficiencies in current surveillance systems. Participants in the survey suggested potential remedies to the problems identified including enhanced surveillance of STI and formalised relationships between GUM and local public health departments. Enactment of these suggested remedies may contribute to meeting the challenge of reversing current disease trends.

Communicable Disease Control↗

Uncertainties on predicted concentrations of radionuclides in terrestrial foods and ingestion doses.

Models are routinely used to calculate doses following routine releases and potential accidental releases of radionuclides. These models contain a number of parameters. Values for many of these are not accurately known. The primary aim of this study was to determine the level of uncertainty on predicted concentrations of radionuclides in foods, and doses to individuals consuming those foods, arising from uncertainties on the model input parameter values. A secondary objective was to identify those input parameters whose uncertainty makes a major contribution to the overall uncertainty on the predicted endpoints. The methodology adopted and results obtained are presented for the following radionuclides: 90Sr, 131I, 137Cs and 239Pu. The estimated uncertainty ratios (the ratio of the 95th to the 5th percentile) are frequently very large, often two to three orders of magnitude. The results of this study may be used to identify areas where further research could improve assessment capabilities.

Accidents↗

An outbreak of serious illness and death among injecting drug users in England during 2000.

An outbreak of serious illness and death occurred in injecting drug users during 2000 in Scotland, Ireland and England. National and international collaboration was necessary for the investigation and management of this outbreak. In England and Wales active case-finding was initiated, coupled with standardised data collection and microbiological investigation of cases. Twenty-six definite or probable cases were identified in England between 1 April and 31 Aug. 2000; 17 of these occurred in the North. The overall case fatality was 50% (13/26). The principal apparent risk factor was a history of intramuscular or subcutaneous injection of heroin and the limited duration of the outbreak suggested that the problem might have been related to a particular supply of heroin. Clostridium novyi was isolated from two English cases. Taken in conjunction with contemporaneous microbiological and epidemiological results from Scottish and Irish cases, the probable aetiology for this outbreak was infection with C. novyi associated with both a particular supply of heroin and the method of preparation and injection used. A 'toolkit' was distributed in Sept. 2000 to all Consultants for Communicable Disease Control in England and Wales to assist them with the ongoing surveillance, investigation and management of this condition. Lessons learned have been used to produce guidance for the investigation and management of outbreaks of unexplained serious illness of possible infective aetiology.

Adult↗

SALSA: a pattern recognition algorithm to detect electrophile-adducted peptides by automated evaluation of CID spectra in LC-MS-MS analyses.

A pattern recognition algorithm called SALSA (scoring algorithm for spectral analysis) has been developed to rapidly screen large numbers of peptide MS-MS spectra for fragmentation characteristics indicative of specific peptide modifications. The algorithm facilitates sensitive and specific detection of modified peptides at low abundance in an enzymatic protein digest. SALSA can simultaneously score multiple user-specified search criteria, including product ions, neutral losses, charged losses, and ion pairs that are diagnostic of specific peptide modifications. Application of SALSA to the detection of peptide adducts of the electrophiles dehydromonocrotaline, benzoquinone, and iodoacetic acid permitted their detection in a complex tryptic peptide digest mixture. SALSA provides superior detection of adducted peptides compared to conventional tandem MS precursor ion or neutral loss scans.

Algorithms↗

A phase II trial of estramustine and etoposide in hormone refractory prostate cancer: A Southwest Oncology Group trial (SWOG 9407).

BACKGROUND: The combination of oral estramustine and oral etoposide has generated response rates of 40-50% in patients with hormone refractory prostate cancer in single institution trials. This study tested this regimen in a multi-institutional setting. METHODS: Fifty-five patients were accrued over a period of 4 months between 1 March 1996 and 1 July 1996. Two patients were not analyzable and two patients were ineligible. They were given an oral regimen consisting of estramustine 15 mg/kg/day (capped at 1120 mg per day) and etoposide 50 mg/M(2)/day, days 1-21 every 28 days. Patients received a median of two cycles of therapy. RESULTS: Toxicities included 11 patients (20%) with grades 3 or 4 granulocytopenia, 5 patients (10%) with grades 3 or 4 edema, and 3 patients (6%) with a thrombotic event. There were two treatment-related deaths, one as a result of anemia and the other as a result of a myocardial infarction. Of the 32 men who received at least 2 cycles of therapy, 7 men (22%) demonstrated a partial response to this regimen as measured by prostate-specific antigen (PSA) criteria of a 50% decline from pretreatment values. CONCLUSIONS: This trial demonstrates the toxicity of estramustine delivered in high dose. It also illustrates the difficulty of conducting phase II trials in prostate cancer in the cooperative group setting where the experience and comfort level of oncologists with new agents is less than that of the physicians at the institution where the therapy was developed. As the activity of this regimen with low-dose estramustine is defined, further multi-institutional studies may be warranted.

Administration, Oral↗

Resonance offset tailored composite pulses.

We describe novel composite pulse sequences which act as general rotors and thus are particularly suitable for nuclear magnetic resonance quantum computation. The resonance offset tailoring to enhance nutations approach permits perfect compensation of off-resonance errors at two selected frequencies placed symmetrically around the frequency of the radiofrequency source.

Journal Article↗