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Biomedical subjects

P J White

Publications and source records attributed to P J White.

At least 19 recordsLinked to original sources

Local frequency dependence in transcranial ultrasound transmission.

The development of large-aperture multiple-source transducer arrays for ultrasound transmission through the human skull has demonstrated the possibility of controlled and substantial acoustic energy delivery into the brain parenchyma without the necessitation of a craniotomy. The individual control of acoustic parameters from each ultrasound source allows for the correction of distortions arising from transmission through the skull bone and also opens up the possibility for electronic steering of the acoustic focus within the brain. In addition, the capability to adjust the frequency of insonation at different locations on the skull can have an effect on ultrasound transmission. To determine the efficacy and applicability of a multiple-frequency approach with such a device, this study examined the frequency dependence of ultrasound transmission in the range of 0.6-1.4 MHz through a series of 17 points on four ex vivo human skulls. Effects beyond those that are characteristic of frequency-dependent attenuation were examined. Using broadband pulses, it was shown that the reflected spectra from the skull revealed information regarding ultrasound transmission at specific frequencies. A multiple-frequency insonation with optimized frequencies over the entirety of five skull specimens was found to yield on average a temporally brief 230% increase in the transmitted intensity with an 88% decrease in time-averaged intensity transmission within the focal volume. This finding demonstrates a potential applicability of a multiple-frequency approach in transcranial ultrasound transmission.

Cadaver↗

Longitudinal and shear mode ultrasound propagation in human skull bone.

Recent studies have attempted to dispel the idea of the longitudinal mode being the only significant mode of ultrasound energy transport through the skull bone. The inclusion of shear waves in propagation models has been largely ignored because of an assumption that shear mode conversions from the skull interfaces to the surrounding media rendered the resulting acoustic field insignificant in amplitude and overly distorted. Experimental investigations with isotropic phantom materials and ex vivo human skulls demonstrated that, in certain cases, a shear mode propagation scenario not only can be less distorted, but at times allowed for a substantial (as much as 36% of the longitudinal pressure amplitude) transmission of energy. The phase speed of 1.0-MHz shear mode propagation through ex vivo human skull specimens has been measured to be nearly half of that of the longitudinal mode (shear sound speed = 1500 +/- 140 m/s, longitudinal sound speed = 2820 +/- 40 m/s), demonstrating that a closer match in impedance can be achieved between the skull and surrounding soft tissues with shear mode transmission. By comparing propagation model results with measurements of transcranial ultrasound transmission obtained by a radiation force method, the attenuation coefficient for the longitudinal mode of propagation was determined to between 14 Np/m and 70 Np/m for the frequency range studied, while the same for shear waves was found to be between 94 Np/m and 213 Np/m. This study was performed within the frequency range of 0.2 to 0.9 MHz.

Acoustics↗

Short term estimates of adult HIV incidence by mode of transmission: Kenya and Thailand as examples.

OBJECTIVE: Patterns of transmission of HIV are different among different regions of the world and change over time within regions. In order to adapt prevention strategies to changing patterns of risk, we need to understand the behaviours that put people at risk of infection and how new infections are distributed among risk groups. METHODS: A model is described to calculate the expected incidence of HIV infections in the adult population by mode of exposure using the current distribution of prevalent infections and the patterns of risk within different populations. For illustration the model is applied to Thailand and Kenya. RESULTS: New infections in Kenya were mainly transmitted through heterosexual contact (90%), while a small but significant number were related to injecting drug use (4.8%) and men who have sex with men (4.5%). In Thailand, the epidemic has spread over time to the sexual partners of vulnerable groups and in 2005 the majority of new infections occurred among the low risk heterosexual population (43%). Men having sex with men accounted for 21% and sex work (including sex workers, clients, and partners of clients) for 18% of new infections. Medical interventions did not contribute significantly to new infections in either Kenya or Thailand. CONCLUSIONS: The model provides a simple tool to inform the planning of effective, appropriately targeted, country specific intervention programmes. However, better surveillance systems are needed in countries to obtain more reliable biological and behavioural data in order to improve the estimates of incidence by risk group.

Adolescent↗

Temporal variability in winter travel patterns of Yellowstone bison: the effects of road grooming.

The influence of winter recreation on wildlife in Yellowstone National Park (YNP), Wyoming and Montana, USA, is a controversial issue. In particular, the effects of road grooming, done to facilitate snowmobile and snowcoach travel, on bison (Bison bison) ecology are under debate. We collected data during winters, from 1997 to 2005, on bison road use, off-road travel, and activity budgets to quantify temporal trends in the amount of bison road and off-road travel and to identify the ecological factors affecting bison movements and use of the groomed road system in the Madison-Gibbon-Firehole (MGF) area of YNP. Using model comparison techniques, we found bison travel patterns to be influenced by multiple, interacting effects. Road travel was negatively correlated with road grooming, and we found no evidence that bison preferentially used groomed roads during winter. Snow water equivalent, bison density, and the springtime melt period were positively correlated with both bison road and off-road travel. From behavioral scans on 68,791 bison, we found that travel is only a small percentage (11%) of all bison activity, with foraging comprising 67% of observations. Also, only 7% of traveling bison and 30% of foraging bison were displacing snow, and we suggest foraging, rather than traveling, is likely the major energetic cost to bison in winter. Bison utilize their own trail network, connecting foraging areas using stream corridors, geothermal pathways, and self-groomed travel routes. Our results indicate that temporal patterns in bison road travel are a manifestation of general travel behavior and that groomed roads in the MGF do not appear to be a major factor influencing bison ecology and spatial redistribution. We suggest that the changes in bison spatial dynamics during the past three decades have likely been the result of the natural phenomenon of density-dependent range expansion, rather than having been caused by the anthropogenic influence of road grooming.

Animals↗

Behavioral responses of bison and elk in Yellowstone to snowmobiles and snow coaches.

Managers of public lands are charged with protecting some of our most important natural resources and ecosystems, while providing for their use and enjoyment by visitors. Almost one million visitors entered Yellowstone National Park by motorized means on snowmobiles (87%) or snow coaches (13%) during 1992-2003. Most vehicles toured the central portion of the park where bison (Bison bison) and elk (Cervus elaphus) concentrate in geothermal areas. We sampled >6500 interactions between groups of these species and groups of snowmobiles and snow coaches (collectively, OSV, over-snow vehicles) during five winters (1999-2000, 2002-2004). Multinomial logits models were used to identify conditions leading to behavioral responses. Elk responded three times as often (52%) as bison (19%) during interactions with groups of snowmobiles and snow coaches due to increased vigilance responses (elk, 44%; bison, 10%). However, the frequency of higher-intensity movement responses by bison and elk were similar (6-7% travel, 1-2% flight, <1% defense) and relatively low compared to other studies of ungulates and snowmobile disturbance. The likelihood of active responses by bison and elk increased significantly if animals were on or near roads, groups were smaller, or humans approached. The likelihood of an active response by bison decreased within winters having the largest visitation, suggesting some habituation to snowmobiles and snow coaches. There was no evidence that snowmobile use during the past 35 years affected the population dynamics or demography of bison or elk. Thus, we suggest that regulations restricting levels and travel routes of over-snow vehicles (OSVs) were effective at reducing disturbances to bison and elk below a level that would cause measurable fitness effects. We recommend park managers consider maintaining OSV traffic levels at or below those observed during our study. Regardless, differing interpretations of the behavioral and physiological response data will continue to exist because of the diverse values and beliefs of the many constituencies of Yellowstone.

Animals↗

Comparison of opioid receptor distributions in the rat ileum.

The cellular expression patterns of mu-, delta- and kappa-opioid receptors in the rat ileum were examined using fluorescence immunohistochemistry. Double-labelling was used to examine cellular receptor co-localisation as a pre-requisite for intracellular molecular interactions, such as heterodimerisation. Tissues were stained as whole-mount preparations. Strong, broadly distributed immunoreactivity (ir) was observed for each receptor in the myenteric and submucous plexuses. Although intracellular mu- and delta-ir patterns differed in ganglion neurons, mu/delta co-expression was extensive in these cells. mu/delta co-expression was also observed in interstitial cells, which were diffusely distributed in submucous plexus preparations but generally located adjacent to myenteric plexus structures. Punctate kappa-ir was seen broadly in nerve fibres in both plexuses, suggesting localisation in varicosities. Neuronal mu/kappa co-localisation was not apparent, although kappa-ir fibres were often apposed against mu-ir cells. mu/kappa co-localisation was detected in interstitial cells in submucous plexus preparations. Similarities in mu and delta expression patterns might reflect similar functional properties previously detected for these receptors. This study indicates that the rat gastrointestinal tract might provide a useful tool for the future study of molecular interactions between opioid receptor types.

Animals↗

Phylogenetic variation in the silicon composition of plants.

BACKGROUND AND AIMS: Silicon (Si) in plants provides structural support and improves tolerance to diseases, drought and metal toxicity. Shoot Si concentrations are generally considered to be greater in monocotyledonous than in non-monocot plant species. The phylogenetic variation in the shoot Si concentration of plants reported in the primary literature has been quantified. METHODS: Studies were identified which reported Si concentrations in leaf or non-woody shoot tissues from at least two plant species growing in the same environment. Each study contained at least one species in common with another study. KEY RESULTS: Meta-analysis of the data revealed that, in general, ferns, gymnosperms and angiosperms accumulated less Si in their shoots than non-vascular plant species and horsetails. Within angiosperms and ferns, differences in shoot Si concentration between species grouped by their higher-level phylogenetic position were identified. Within the angiosperms, species from the commelinoid monocot orders Poales and Arecales accumulated substantially more Si in their shoots than species from other monocot clades. CONCLUSIONS: A high shoot Si concentration is not a general feature of monocot species. Information on the phylogenetic variation in shoot Si concentration may provide useful palaeoecological and archaeological information, and inform studies of the biogeochemical cycling of Si and those of the molecular genetics of Si uptake and transport in plants.

Biological Evolution↗

Biological costs and benefits to plant-microbe interactions in the rhizosphere.

This review looks briefly at plants and their rhizosphere microbes, the chemical communications that exist, and the biological processes they sustain. Primarily it is the loss of carbon compounds from roots that drives the development of enhanced microbial populations in the rhizosphere when compared with the bulk soil, or that sustains specific mycorrhizal or legume associations. The benefits to the plant from this carbon loss are discussed. Overall the general rhizosphere effect could help the plant by maintaining the recycling of nutrients, through the production of hormones, helping to provide resistance to microbial diseases and to aid tolerance to toxic compounds. When plants lack essential mineral elements such as P or N, symbiotic relationships can be beneficial and promote plant growth. However, this benefit may be lost in well-fertilized (agricultural) soils where nutrients are readily available to plants and symbionts reduce growth. Since these rhizosphere associations are commonplace and offer key benefits to plants, these interactions would appear to be essential to their overall success.

Ecosystem↗

Interactions between selenium and sulphur nutrition in Arabidopsis thaliana.

Selenium (Se) is an essential plant micronutrient, but is toxic at high tissue concentrations. It is chemically similar to sulphur (S), an essential plant macronutrient. The interactions between Se and S nutrition were investigated in the model plant Arabidopsis thaliana (L.) Heynh. Arabidopsis plants were grown on agar containing a complete mineral complement and various concentrations of selenate and sulphate. The Se/S concentration ratio in the shoot ([Se](shoot)/[S](shoot)) showed a complex dependence on the ratio of selenate to sulphate concentration in the agar ([Se](agar)/[S](agar)). Increasing [S](agar) increased shoot fresh weight (FW) and [S](shoot), but decreased [Se](shoot). Increasing [Se](agar) increased both [Se](shoot) and [S](shoot), but reduced shoot FW. The reduction in shoot FW in the presence of Se was linearly related to the shoot Se/S concentration ratio. These data suggest (i) that Se and S enter Arabidopsis through multiple transport pathways with contrasting sulphate/selenate selectivities, whose activities vary between plants of contrasting nutritional status, (ii) that rhizosphere sulphate inhibits selenate uptake, (iii) that rhizosphere selenate promotes sulphate uptake, possibly by preventing the reduction in the abundance and/or activity of sulphate transporters by sulphate and/or its metabolites, and (iv) that Se toxicity occurs because Se and S compete for a biochemical process, such as assimilation into amino acids of essential proteins.

Arabidopsis↗

Methodological concerns when designing trials for the efficacy of acupuncture for the treatment of pain.

The aim of all clinical research must surely be to assess an intervention or process or relationship between variables, ultimately in order to be able to improve clinical practice and healthcare for patients/consumers. As such, evidence gathered must have external validity (generalisability) and it must be relevant to clinical practice. It can be seen therefore that research into acupuncture for pain relief is an inherently difficult task, which requires much sensitivity and careful planning in order to minimise error when drawing conclusions. The researcher needs to adequately address problems such as sample size, blinding, randomisation and appropriate use of control and treatment. It is also most important to be able to clarify that the placebo (if used) is credible to the patient. The field of acupuncture has been overwhelmed with hundreds of sub-standard trials and much doubt still surrounds the issue of efficacy. Few good quality rigorous trials exist to support the use of acupuncture for pain relief in general. It has also been noted that the question of long-term efficacy has not been assessed by the many trials and this needs to be addressed prior to its acceptance. Further well conducted rigorous trials are therefore needed, utilising the lessons learnt through the substantial number of previous trials, in order to adequately assess the efficacy of acupuncture for painful conditions. Such trials must therefore: Utilise a placebo control. Be randomised and stratified. Ensure patient blinding. Use self completed outcome measures and blinded assessors. Have sufficient and well validated outcome measures. Check credibility of treatment. Have a well defined entry criteria which includes a single condition only. Have a long term follow up. Enrol sufficient subjects, the number to be determined by a power calculation. Provide adequate acupuncture treatment as would be found in clinical practice. Be group comparative so as to negate any carry-over effects. In this way good quality trials can be undertaken which will yield reliable results and therefore add meaningful data to the body of knowledge appertaining to the effectiveness of acupuncture.

Acupuncture↗

Epidemiology of rabbit haemorrhagic disease virus in the United Kingdom: evidence for seasonal transmission by both virulent and avirulent modes of infection.

Rabbit haemorrhagic disease virus (RHDV) has killed many millions of wild rabbits in Europe and Australia, but has had little impact in the United Kingdom, despite outbreaks having occurred since 1994. High seroprevalence detected in the absence of associated mortality had suggested the presence of an endemic non-pathogenic strain which may be 'protecting' UK populations. Following the first detailed field study of RHDV epidemiology in the United Kingdom, using mark-recapture with serum sampling, we report that RHDV caused highly prevalent persistent infection in seropositive rabbits in the absence of associated mortality. Furthermore the virus strains responsible could not be distinguished phylogenetically from known pathogenic isolates, and were clearly very different from the only previously identified non-pathogenic strain of RHDV. These findings suggest that many--perhaps most--strains of RHDV may be propagated through both 'pathogenic' and 'non-pathogenic' modes of behaviour. Transmission occurred predominantly during and just after the breeding season.

Animals↗

Estimating radionuclide transfer to wild species--data requirements and availability for terrestrial ecosystems.

Assessment of the transfer of radionuclides to wild species is an important component in the estimation of predicted doses to biota. Reviews of available data for the many potential radionuclide-biota combinations which may be required for environmental assessments highlight many data gaps for terrestrial species. Here, we discuss different approaches which have been suggested to compensate for these data gaps. All of the reviewed approaches have merit; however, there is a requirement for transparency in methodology and data provenance which in some instances is currently missing. Furthermore, there is a need to validate the various methodologies to enable their use with confidence. The requirements of improving our ability to predict radionuclide transfer to wild species are discussed and recommendations made.

Animals↗

Enhanced ultrasound transmission through the human skull using shear mode conversion.

A new transskull propagation technique, which deliberately induces a shear mode in the skull bone, is investigated. Incident waves beyond Snell's critical angle experience a mode conversion from an incident longitudinal wave into a shear wave in the bone layers and then back to a longitudinal wave in the brain. The skull's shear speed provides a better impedance match, less refraction, and less phase alteration than its longitudinal counterpart. Therefore, the idea of utilizing a shear wave for focusing ultrasound in the brain is examined. Demonstrations of the phenomena, and numerical predictions are first studied with plastic phantoms and then using an ex vivo human skull. It is shown that at a frequency of 0.74 MHz the transskull shear method produces an amplitude on the order of--and sometimes higher than--longitudinal propagation. Furthermore, since the shear wave experiences a reduced overall phase shift, this indicates that it is plausible for an existing noninvasive transskull focusing method [Clement, Phys. Med. Biol. 47(8), 1219-1236 (2002)] to be simplified and extended to a larger region in the brain.

Absorption↗

Informal confidential voting interview methods and temporal changes in reported sexual risk behaviour for HIV transmission in sub-Saharan Africa.

OBJECTIVES: Reliable data on sexual behaviour trends are needed to evaluate HIV interventions in sub-Saharan Africa but are difficult to obtain due inter alia to social desirability bias. The objective of this paper is to assess whether the use of informal confidential voting interviews (ICVI) was associated with greater reporting of socially proscribed behavioural risk factors for HIV infection than were conventional interviewing methods. METHODS: Comparison of changes in reports of risk behaviours for HIV infection in ICVI versus face to face interviews (FTFIs) between the first two rounds of a large scale, longitudinal, population based survey in Manicaland, Zimbabwe. Examination of factors that could contribute to observed changes in the effect of ICVI, including temporal changes in response error and social desirability, and factors affecting statistical power to detect differences between methods-that is, reductions in the prevalence of risk behaviours and sample size. RESULTS: Enhanced reporting of HIV associated risk behaviours in ICVI interviews was not so apparent in the second round as in the first round of the survey, particularly for less frequently reported behaviours. Levels of reported HIV associated risk behaviour and sample sizes both declined between the two survey rounds. The level of response error was higher in ICVI interviews than in FTFI interviews but did not alter over time. CONCLUSION: ICVI interviews can reduce social desirability bias in data on HIV associated risk behaviours. The extent and direction of change in net reduction in bias over time remains uncertain and will depend on local circumstances.

Adult↗

Antisense oligonucleotide treatments for psoriasis.

Antisense oligonucleotides are emerging as an exciting therapeutic strategy for treating skin diseases such as psoriasis. Potential antisense targets are proteins upregulated in psoriatic skin, in particular those associated with inflammation (intercellular adhesion molecule [ICAM]-1, IL-2 and -8), proliferation (insulin-like growth factor type I receptor [IGF-IR], epidermal growth factor) and hyperangiogenesis (vascular endothelial growth factor [VEGF]). Whereas topical application and subsequent penetration of large oligonucleotides into normal skin is problematic, the impaired barrier function of psoriatic lesions permits the uptake of antisense drugs. Studies to date indicate that topically applied antisense molecules can be delivered to target cells in the epidermis and dermis of psoriatic skin. Antisense-mediated suppression of target mRNA and protein has been demonstrated in models of human skin grafted to immunosuppressed mice and in hairless mouse models of skin inflammation. In a xenograft model of human psoriasis, treatment with repeated intradermal injections of IGF-IR antisense caused a normalisation of the epidermal hyperproliferation. This class of drug, therefore, holds much potential for the successful treatment of psoriasis in the clinical setting.

Animals↗

Long-term survival of New Zealand rabbit haemorrhagic disease virus RNA in wild rabbits, revealed by RT-PCR and phylogenetic analysis.

Because Rabbit haemorrhagic disease virus (RHDV) is highly pathogenic for rabbits, farmers illegally introduced it as a bio-control agent onto New Zealand farms in 1997. The virus was dispersed rapidly, initially causing high fatality rates in rabbits. Nevertheless, many survived and these surviving rabbits have been investigated for evidence of infection by RHDV. Livers from healthy rabbits contained RHDV-specific RNA, as shown by nested RT-PCR sequencing. The sequences of the viral capsids were related closely to the released Czech strain of RHDV, although the sequence from one rabbit was related most closely to a Spanish strain of RHDV. Phylogenetic analysis of the capsid sequences of 38 samples implied that there have been at least two introductions of the Czech virus into New Zealand, probably corresponding firstly to the original illegal introduction by farmers and secondly to the introduction of the same virus under governmental control. Genomic length sequence of two samples was obtained, suggesting that they may have retained the potential to be infectious, although this has not yet been demonstrated. The detection of genomic-length RNA in the liver of healthy rabbits suggests that even though a highly virulent virus was introduced into New Zealand, it rapidly established persistent or latent infections in a proportion of rabbits. This might account for their ability to survive in the face of virulent released virus. Moreover, the co-circulation of other strains of RHDV in the same rabbit population, such as the Spanish strain, might also impact on their susceptibility to the bio-control agent.

Animals↗

Epidemiological consequences of a pathogen having both virulent and avirulent modes of transmission: the case of rabbit haemorrhagic disease virus.

A number of pathogens cause chronic infection in survivors of acute disease and this is believed to be a common means of persistence, including for highly virulent agents. We present a model in which transmission from chronically infected hosts causes chronic infection in naive individuals, without causing acute disease--indeed 'protecting' against it. Thus the pathogen obtains the benefit of virulence (high transmission rate), but mitigates against the cost (high host mortality). Recent findings suggest that rabbit haemorrhagic disease virus (RHDV), a highly contagious and virulent pathogen, may also utilize this alternative, 'avirulent', mode of transmission. The model may resolve the paradox of how RHDV can be highly prevalent in some populations, in the absence of mortality. Differences in host demography determine whether avirulent transmission prevents large-scale mortality (as in most UK populations) or not. Other pathogens may exhibit similar behaviour and the implications for emerging diseases in general are discussed.

Acute Disease↗