Search PubMed⌕ Search

Biomedical subjects

R J Smith

Publications and source records attributed to R J Smith.

At least 19 recordsLinked to original sources
PubMed2006

Spheromak formation by steady inductive helicity injection.

A spheromak is formed for the first time using a new steady state inductive helicity injection method. Using two inductive injectors with odd symmetry and oscillating at 5.8 kHz, a steady state spheromak with even symmetry is formed and sustained through nonlinear relaxation. A spheromak with about 13 kA of toroidal current is formed and sustained using about 3 MW of power. This is a much lower power threshold for spheromak production than required for electrode-based helicity injection. Internal magnetic probe data, including oscillations driven by the injectors, agree with the plasma being in the Taylor state. The agreement is remarkable considering the only fitting parameter is the amplitude of the spheromak component of the state.

Journal Article↗
PubMed2006

Adherence to antiretroviral HIV drugs: how many doses can you miss before resistance emerges?

The question of determining how many doses may be skipped before HIV treatment response is adversely affected by the emergence of drug-resistance is addressed. Impulsive differential equations are used to develop a prescription to minimize the emergence of drug-resistance for protease-sparing regimens. A threshold for the maximal number of missable doses is determined. If the number of missed doses is below this threshold, then resistance levels are negligible and dissipate quickly, assuming perfect adherence subsequently. If the number of missed doses exceeds this threshold, even for 24h, resistance levels are extremely high and will not dissipate for weeks, even assuming perfect adherence subsequently. After this interruption, the minimum number of successive doses that should be taken is determined. Estimates are provided for all protease-sparing drugs approved by the US Food and Drug Administration. Estimates for the basic reproductive ratios for the wild-type and mutant strains of the virus are also calculated, for a long-term average fractional degree of adherence. There are regions within this fraction of adherence where the outcome is not predictable and may depend on a patient's entire history of drug-taking.

Anti-HIV Agents↗
PubMed2005

Perspectives on the basic reproductive ratio.

The basic reproductive ratio, R0, is defined as the expected number of secondary infections arising from a single individual during his or her entire infectious period, in a population of susceptibles. This concept is fundamental to the study of epidemiology and within-host pathogen dynamics. Most importantly, R0 often serves as a threshold parameter that predicts whether an infection will spread. Related parameters which share this threshold behaviour, however, may or may not give the true value of R0. In this paper we give a brief overview of common methods of formulating R0 and surrogate threshold parameters from deterministic, non-structured models. We also review common means of estimating R0 from epidemiological data. Finally, we survey the recent use of R0 in assessing emerging diseases, such as severe acute respiratory syndrome and avian influenza, a number of recent livestock diseases, and vector-borne diseases malaria, dengue and West Nile virus.

Animals↗
PubMed2005

Datura contamination of hay as the suspected cause of an extensive outbreak of impaction colic in horses.

Datura poisoning of horses is extensively reviewed. An outbreak of intractable impaction colic affecting 18 of 83 horses was stopped by withdrawing dried tef hay contaminated with young Datura plants. The dried, botanically identified Datura stramonium and D. ferox contained respectively 0.15% mass/mass (m/m) hyoscyamine as well as 0.16% m/m hyoscine (scopolamine) and only hyoscine at a concentration of 0.11% m/m. Immature, unidentifiable plants resembling D. stramonium, contained 0.14% m/m and 0.12% m/m of the 2 respective tropane alkaloids. The outbreak was characterised by protracted and repeated colic attacks due to impaction of the large colon and/or caecum without any other anti-muscarinic signs. Comparative analyses of single specimens of dried seed of the 2 species collected from both fertilised and waste areas revealed that young South African Datura spp. had levels of tropane alkaloids comparable to those in the well-known toxic seed and were, consequently, equally toxic. The inherent danger of tef hay being contaminated with Datura is emphasised. To our knowledge this is the 1st field case of poisoning in horses ascribed to the vegetative parts of Datura spp.

Animals↗
PubMed2004

Drug resistance in an immunological model of HIV-1 infection with impulsive drug effects.

We consider an SIR-type model of immunological behaviour for HIV dynamics, including the effects of reverse transcriptase inhibitors and other drugs which prevent cellular infection. We use impulsive differential equations to model drug behaviour. We classify different regimes according to whether the drug efficacy is negligible, intermediate or high. We consider two strains of the virus: a wild-type strain that can be controlled by both intermediate and high drug concentrations, and a mutant strain that can only be controlled by high drug concentrations. Drug regimes may take trajectories through one, two or all three regimes, depending on the dosage and the dosing schedule. We demonstrate that drug resistance arises at both intermediate and high drug levels. At low drug levels resistance does not emerge, but the total T cell count is proven to be significantly lower than in the disease-free state. At intermediate drug levels, drug resistance is guaranteed to emerge. At high drug levels, either the drug-resistant strain will dominate or, in the absence of longer-lived reservoirs of infected cells, both viral sub-populations will be cleared. In the latter case the immune system is maintained by a population of T cells which have absorbed sufficient quantities of the drug to prevent infection by even the drug-resistant strain. We provide estimates of a range of dosages and dosing schedules which would, if physiologically tolerable, theoretically eliminate free virus in this system. Our results predict that to control viral load, decreasing the interval between doses is more effective than increasing the dose.

Anti-HIV Agents↗
PubMed2004

Identification of genes differentially expressed in T cells following stimulation with the chemokines CXCL12 and CXCL10.

BACKGROUND: Chemokines are involved in many biological activities ranging from leukocyte differentiation to neuronal morphogenesis. Despite numerous reports describing chemokine function, little is known about the molecular changes induced by cytokines. METHODS: We have isolated and identified by differential display analysis 182 differentially expressed cDNAs from CXCR3-transfected Jurkat T cells following treatment with CXCL12 or CXCL10. These chemokine-modulated genes were further verified using quantitative RT-PCR and Western blot analysis. RESULTS: One hundred and forty-six of the cDNAs were successfully cloned, sequenced, and identified by BLAST. Following removal of redundant and non-informative clones, seventeen mRNAs were found to be differentially expressed post treatment with either chemokine ligand with several representing known genes with established functions. Twenty-one genes were upregulated in these transfected Jurkat cells following both CXCL12 and CXCL10, four genes displayed a discordant response and seven genes were downregulated upon treatment with either chemokine. Identified genes include geminin (GEM), thioredoxin (TXN), DEAD/H box polypeptide 1 (DDX1), growth hormone inducible transmembrane protein (GHITM), and transcription elongation regulator 1 (TCERG1). Subsequent analysis of several of these genes using semi-quantitative PCR and western blot analysis confirmed their differential expression post ligand treatment. CONCLUSIONS: Together, these results provide insight into chemokine-induced gene activation and identify potentially novel functions for known genes in chemokine biology.

Blotting, Western↗
PubMed2004

Monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 are involved in both excitotoxin-induced neurodegeneration and regeneration.

Intrahippocamal injections of kainic acid (KA) significantly increase the expression of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) in the ipsilateral hippocampus at 2-4 h and 21-45 days post-administration, suggesting the possible involvement of these chemokines in both neurodegenerative and regenerative processes. To examine the possible role of these chemokines on neuronal cell death, hippocampal neurons were incubated with either MCP-1 or MIP-2 in vitro and examined to assess the effects on neuronal cell viability. These treatments resulted in significant neuronal apoptosis that could be abrogated by prior treatment with the caspase-1 inhibitor, Z-VAD-FMK, the caspase-3 inhibitor, Z-DEVD-FMK, the Galphai inhibitor, pertussis toxin, or the MAO-B inhibitor, (-)deprenyl. Furthermore, this chemokine apoptotic effect could also be observed in vivo as intrahippocampal injections of MCP-1 or MIP-2 resulted in the apoptosis of hippocampal neurons, thus supporting a direct role of these chemokines in neuronal death. In contrast, immunohistological analysis of kainic acid lesions on days 21-45 revealed significant expression of MCP-1 and MIP-2 associated with reactive astrocytes and macrophages, respectively, with no apoptotic populations being observed. These results suggested that these chemokines might also mediate distinct biological effects on local microenvironmental cell populations at various stages post truama and during cellular repair. To address this possibility, astrocyte were cultured in the presence or absence of these chemokines and examined by microarray analysis for effects on astrocytes gene expression. A number of genes encoding proteins associated with inflammation, cellular signaling, differentiation, and repair were directly modulated by chemokine treatment. More specifically, the RNA and protein expression of the neurotrophic factor, basic fibroblast growth factor (bFGF), was found to be significantly increased upon culture with MCP-1 and MIP-2. Conditioned media derived from chemokine-stimulated astrocytes also facilitated bFGF-dependent neuronal cell differentiation and promoted survival of H19-7 neurons in vitro, suggesting a possible role for chemokine-activated astrocytes as a source of trophic support. Taken together, these data support possible autocrine and paracrine roles for MCP-1 and MIP-2 in both the "death and life" of hippocampal neurons following CNS injury.

Animals↗
PubMed2004

Refinement of the DFNA4 locus to a 1.44 Mb region in 19q13.33.

Many forms of autosomal dominant non-syndromic hearing impairment are known. While the underlying gene defects and causative mutations have been discovered for some forms, the gene responsible for DFNA4 has remained elusive to date. Examination of a German four-generation kindred led to the identification of a 1.44 Mb map segment in contig NT_011109 as being the most likely DFNA4 candidate region in 19q13.33. The recombination breakpoints in this family and the intervals of two previously reported DFNA4 families allowed us to delineate a minimum consensus region between the markers D19S879 and D19S246. In our family, a maximum two-point LOD score of 4.5 was obtained at theta = 0 for the marker D19S867. Within the refined DFNA4 interval the public databases list more than 50 genes, from which several appear to be promising DFNA4 candidates due to similarities with animal models and with other causative genes involved in hearing disability.

Adult↗
PubMed2004

Distinct effects of protease and reverse transcriptase inhibition in an immunological model of HIV-1 infection with impulsive drug effects.

We present an immunological model that considers the dynamics of CD4+ T cells interacting with free virions, reverse transcriptase inhibiting drugs and protease inhibiting drugs. We divide the T cells into multiple classes and use impulsive differential equations to describe the drug activity. As expected, we find that insufficient dosing of either drug corresponds to high viral load and a large population of infectious T cells. The model further predicts that, in the absence of physiological limits on tolerable drug concentrations, sufficiently frequent dosing with the reverse transcriptase inhibitor alone could theoretically maintain the CD4+ T cell count arbitrarily close to the T cell count in the uninfected immune system. However, for frequent dosing of the protease inhibitor alone, the limiting T cell populations may not be enough to maintain the immune system. Furthermore, frequent dosing of both drugs has the same net effect on the T cell population as frequent dosing of the reverse transcriptase inhibitor only. Thus, the two drug classes can have fundamentally different effects on the long-term dynamics and the reverse transcriptase inhibitor, in particular, plays a crucial role in maintaining the immune system. We also provide estimates for the dosing intervals of each drug that could theoretically sustain the T cell population at a desired level.

CD4 Lymphocyte Count↗
PubMed2004

Design and acceptability of patient-oriented computerized diabetes care reminders for use at the point of care.

Despite the widespread availability of guidelines for caring for patients with diabetes and decades of research on computerized reminder systems, large gaps in quality remain in diabetes care remain and computerized reminder systems are rarely used for patients with diabetes. We set out to develop and test the feasibility of a system that would overcome many of the barriers preventing the widespread use of point-of-care computerized reminders to improve diabetes care. Five primary care physicians and 32 patients with type 2 diabetes pilot tested the system. We set out to design and measure the preliminary acceptability of patient-oriented point of care computerized diabetes care reminders. The main findings of our study were that (1) the reports were well accepted by both patients and providers and (2) survey and audiotape data suggest that they may be helpful at improving the quality of outpatient care for patients with diabetes.

Ambulatory Care↗
PubMed2004

Identification and properties of imprinted genes and their control elements.

Imprinted genes have the unusual characteristic that the copy from one parent is destined to remain inactive. Though few in number they nonetheless constitute a functionally important part of the mammalian genome. With their memory of parental origin, imprinted genes represent an important model for the epigenetic regulation of gene function and will provide invaluable paradigms to test whether we can predict epigenetic state from DNA sequence. Since their first discovery, systematic screens and some good fortune have led to identification of over seventy imprinted genes in the mouse and human: recent microarray analysis may reveal many more. With a significant number of imprinted genes now identified and completion of key mammalian genome sequences, we are able systematically to examine the organization of imprinted loci, properties of their control elements and begin to recognize common themes in imprinted gene regulation.

Alleles↗
PubMed2003

Governance and the loss of biodiversity.

Most of the world's biodiversity occurs within developing countries that require donor support to build their conservation capacity. Unfortunately, some of these countries experience high levels of political corruption, which may limit the success of conservation projects by reducing effective funding levels and distorting priorities. We investigated whether changes in three well surveyed and widespread components of biodiversity were associated with national governance scores and other socio-economic measures. Here we show that governance scores were correlated with changes in total forest cover, but not with changes in natural forest cover. We found strong associations between governance scores and changes in the numbers of African elephants and black rhinoceroses, and these socio-economic factors explained observed patterns better than any others. Finally, we show that countries rich in species and identified as containing priority areas for conservation have lower governance scores than other nations. These results stress the need for conservationists to develop and implement policies that reduce the effects of political corruption and, in this regard, we question the universal applicability of an influential approach to conservation that seeks to ban international trade in endangered species.

Animals↗
PubMed2003

Field sports and conservation in the United Kingdom.

Many natural habitats exist on privately owned land outside protected areas, but few governments can afford to enforce or subsidize conservation of this biodiversity. Even in some developed countries, conservation subsidy schemes have only achieved limited success. Fortunately, some landowners may be willing to accept management costs in return for other benefits, although this remains controversial when it involves the killing of charismatic species. For example, participants in British field sports, such as fox hunting and game-bird shooting, may voluntarily conserve important habitats that are required by quarry species. Here we report results from a multidisciplinary study that addressed this issue by focusing on three sites across central England. We found that landowners participating in field sports maintained the most established woodland and planted more new woodland and hedgerows than those who did not, despite the equal availability of subsidies. Therefore, voluntary habitat management appears to be important for biodiversity conservation in Britain. Current debates on the future of field sports in Britain, and similar activities globally, may benefit from considering their utility as incentives to conserve additional habitat on private land.

Conservation of Natural Resources↗
PubMed2003

Demonstration of plasma startup by coaxial helicity injection.

The first successful results on the transfer of a coaxial helicity injection (CHI) produced discharge to inductive operation are reported. CHI-assisted plasma startup is more robust than inductive only operation. After hand off for inductive operation, the initial 90 kA of CHI-produced current drops to 40 kA, then ramps up to 170 kA, using only 30 mV s, more than 30% higher than that produced by induction alone. These significant performance enhancing results were obtained on the HIT-II spherical torus experiment (major/minor radius of 0.3/0.2 m).

Journal Article↗
PubMed2003

Using metallic interlayers to stabilize abrupt, epitaxial metal-metal interfaces.

An approach is described for stabilizing metal-metal epitaxial interfaces using a thin metallic interlayer. Rutherford backscattering and channeling techniques along with low-energy electron diffraction and keV He+ ion backscattering are used to demonstrate that an atomically thin layer of Ti deposited at the Fe-Al interface, a system well known for considerable intermixing at room temperature, forms a thin interface alloy that prevents interdiffusion and improves epitaxial growth of Fe on Al(100). The structure is stable up to about 200 degrees C.

Journal Article↗
PubMed2003

Pulmonary inflammation and crystalline silica in respirable coal mine dust: dose-response.

This study describes the quantitative relationships between early pulmonary responses and the estimated lung-burden or cumulative exposure of respirable-quartz or coal mine dust. Data from a previous bronchoalveolar lavage (BAL) study in coal miners (n = 20) and nonminers (n = 16) were used including cell counts of alveolar macrophages (AMs) and polymorphonuclear leukocytes (PMNs), and the antioxidant superoxide dismutase (SOD) levels. Miners' individual working lifetime particulate exposures were estimated from work histories and mine air sampling data, and quartz lung-burdens were estimated using a lung dosimetry model. Results show that quartz, as either cumulative exposure or estimated lung-burden, was a highly statistically significant predictor of PMN response (P < 0.0001); however cumulative coal dust exposure did not significantly add to the prediction of PMNs (P = 0.2) above that predicted by cumulative quartz exposure (P < 0.0001). Despite the small study size, radiographic category was also significantly related to increasing levels of both PMNs and quartz lung burden (P-values < 0.04). SOD in BAL fluid rose linearly with quartz lung burden (P < 0.01), but AM count in BAL fluid did not (P > 0.4). This study demonstrates dose-response relationships between respirable crystalline silica in coal mine dust and pulmonary inflammation, antioxidant production, and radiographic small opacities.

Adult↗
PubMed2003

Why I am optimistic.

Explore the source record for details and available documents.

Delivery of Health Care↗