Showing papers by "University of Nottingham published in 1999"

Polymeric Systems for Controlled Drug Release

Abstract: s, and 360 patents, and edited 12 books. He has also received over 80 major awards including the Gairdner Foundation International Award, Lemelson-MIT prize, ACS’s Applied Polymer Science and Polymer Chemistry Awards, AICHE’s Professional Progress, Bioengineering, Walker and Stine Materials Science and Engineering Awards. In 1989, Dr. Langer was elected to the Institute of Medicine of the National Academy of Sciences, and in 1992 he was elected to both the National Academy of Engineering and the National Academy of Sciences. He is the only active member of all three National Academies. Kevin Shakesheff was born in Ashington, Northumberland, U.K., in 1969. He received his Bacheclor of Pharmacy degree from the University of Nottingham in 1991 and a Ph.D. from the same institution in 1995. In 1996 he became a NATO Postdoctoral Fellow at MIT, Department of Chemical Engineering. He is currently an EPSRC Advanced Fellow at the School of Pharmaceutical Sciences, The University of Nottingham. His research group investigates new methods of engineering polymer surfaces and the application of these engineered materials in drug delivery and tissue engineering. 3182 Chemical Reviews, 1999, Vol. 99, No. 11 Uhrich et al.

Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes

Abstract: The human AIDS viruses human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) represent cross-species (zoonotic) infections. Although the primate reservoir of HIV-2 has been clearly identified as the sooty mangabey (Cercocebus atys), the origin of HIV-1 remains uncertain. Viruses related to HIV-1 have been isolated from the common chimpanzee (Pan troglodytes), but only three such SIVcpz infections have been documented, one of which involved a virus so divergent that it might represent a different primate lentiviral lineage. In a search for the HIV-1 reservoir, we have now sequenced the genome of a new SIVcpzstrain (SIVcpzUS) and have determined, by mitochondrial DNA analysis, the subspecies identity of all known SIVcpz-infected chimpanzees. We find that two chimpanzee subspecies in Africa, the central P. t. troglodytes and the eastern P. t. schweinfurthii, harbour SIVcpz and that their respective viruses form two highly divergent (but subspecies-specific) phylogenetic lineages. All HIV-1 strains known to infect man, including HIV-1 groups M, N and O, are closely related to just one of these SIVcpz lineages, that found in P. t. troglodytes. Moreover, we find that HIV-1 group N is a mosaic of SIVcpzUS- and HIV-1-related sequences, indicating an ancestral recombination event in a chimpanzee host. These results, together with the observation that the natural range of P. t. troglodytes coincides uniquely with areas of HIV-1 group M, N and O endemicity, indicate that P. t. troglodytes is the primary reservoir for HIV-1 and has been the source of at least three independent introductions of SIVcpz into the human population.

The functions of multiple representations

Abstract: Multiple representations and multi-media can support learning in many diAerent ways. In this paper, it is claimed that by identifying the functions that they can serve, many of the conflicting findings arising out of the existing evaluations of multi-representational learning environments can be explained. This will lead to more systematic design principles. To this end, this paper describes a functional taxonomy of MERs. This taxonomy is used to ask how translation across representations should be supported to maximise learning outcomes and what information should be gathered from empirical evaluation in order to determine the eAectiveness of multi-representational learning environments. # 2000 Elsevier Science Ltd. All rights reserved.

Evolutionary relationships among diverse bacteriophages and prophages: All the world’s a phage

Abstract: We report DNA and predicted protein sequence similarities, implying homology, among genes of double-stranded DNA (dsDNA) bacteriophages and prophages spanning a broad phylogenetic range of host bacteria. The sequence matches reported here establish genetic connections, not always direct, among the lambdoid phages of Escherichia coli, phage phiC31 of Streptomyces, phages of Mycobacterium, a previously unrecognized cryptic prophage, phiflu, in the Haemophilus influenzae genome, and two small prophage-like elements, phiRv1 and phiRv2, in the genome of Mycobacterium tuberculosis. The results imply that these phage genes, and very possibly all of the dsDNA tailed phages, share common ancestry. We propose a model for the genetic structure and dynamics of the global phage population in which all dsDNA phage genomes are mosaics with access, by horizontal exchange, to a large common genetic pool but in which access to the gene pool is not uniform for all phage.

"Sparse" temporal sampling in auditory fMRI.

Abstract: The use of functional magnetic resonance imaging (fMRI) to explore central auditory function may be compromised by the intense bursts of stray acoustic noise produced by the scanner whenever the magnetic resonance signal is read out. We present results evaluating the use of one method to reduce the effect of the scanner noise: "sparse" temporal sampling. Using this technique, single volumes of brain images are acquired at the end of stimulus and baseline conditions. To optimize detection of the activation, images are taken near to the maxima and minima of the hemodynamic response during the experimental cycle. Thus, the effective auditory stimulus for the activation is not masked by the scanner noise. In experiment 1, the course of the hemodynamic response to auditory stimulation was mapped during continuous task performance. The mean peak of the response was at 10.5 sec after stimulus onset, with little further change until stimulus offset. In experiment 2, sparse imaging was used to acquire activation images. Despite the fewer samples with sparse imaging, this method successfully delimited broadly the same regions of activation as conventional continuous imaging. However, the mean percentage MR signal change within the region of interest was greater using sparse imaging. Auditory experiments that use continuous imaging methods may measure activation that is a result of an interaction between the stimulus and task factors (e.g., attentive effort) induced by the intense background noise. We suggest that sparse imaging is advantageous in auditory experiments as it ensures that the obtained activation depends on the stimulus alone.

Choosing between Small, Likely Rewards and Large, Unlikely Rewards Activates Inferior and Orbital Prefrontal Cortex

Abstract: Patients sustaining lesions of the orbital prefrontal cortex (PFC) exhibit marked impairments in the performance of laboratory-based gambling, or risk-taking, tasks, suggesting that this part of the human PFC contributes to decision-making cognition. However, to date, little is known about the particular regions of the orbital cortex that participate in this function. In the present study, eight healthy volunteers were scanned, using H2150 PET technology, while performing a novel computerized risk-taking task. The task involved predicting which of two mutually exclusive outcomes would occur, but critically, the larger reward (and penalty) was associated with choice of the least likely outcome, whereas the smallest reward (and penalty) was associated with choice of the most likely outcome. Resolving these “conflicting” decisions was associated with three distinct foci of regional cerebral blood flow increase within the right inferior and orbital PFC: laterally, in the anterior part of the middle frontal gyrus [Brodmann area 10 (BA 10)], medially, in the orbital gyrus (BA 11), and posteriorly, in the anterior portion of the inferior frontal gyrus (BA 47). By contrast, increases in the degree of conflict inherent in these decisions was associated with only limited changes in activity within orbital PFC and the anterior cingulate cortex. These results suggest that decision making recruits neural activity from multiple regions of the inferior PFC that receive information from a diverse set of cortical and limbic inputs, and that the contribution of the orbitofrontal regions may involve processing changes in reward-related information.

AUX1 regulates root gravitropism in Arabidopsis by facilitating auxin uptake within root apical tissues

Abstract: Plants employ a specialized transport system composed of separate influx and efflux carriers to mobilize the plant hormone auxin between its site(s) of synthesis and action. Mutations within the permease-like AUX1 protein significantly reduce the rate of carrier-mediated auxin uptake within Arabidopsis roots, conferring an agravitropic phenotype. We are able to bypass the defect within auxin uptake and restore the gravitropic root phenotype of aux1 by growing mutant seedlings in the presence of the membrane-permeable synthetic auxin, 1-naphthaleneacetic acid. We illustrate that AUX1 expression overlaps that previously described for the auxin efflux carrier, AtPIN2, using transgenic lines expressing an AUX1 promoter::uidA (GUS) gene. Finally, we demonstrate that AUX1 regulates gravitropic curvature by acting in unison with the auxin efflux carrier to co-ordinate the localized redistribution of auxin within the Arabidopsis root apex. Our results provide the first example of a developmental role for the auxin influx carrier within higher plants and supply new insight into the molecular basis of gravitropic signalling.

Amniotic membrane transplantation for ocular surface reconstruction

Abstract: Aims—To evaluate the eYcacy of amniotic membrane transplantation (AMT) for ocular surface reconstruction. Methods—10 consecutive patients who underwent AMT were included. The indications were: group A, cases with persistent epithelial defect after corneal abscess (n=1), radiation (n=1), or chemical burn (n=3); group B, cases with epithelial defect and severe stromal thinning and impending or recent perforation, due to chemical burn (two patients, three eyes) or corneal abscess (n=2); group C, to promote corneal epithelium healing and prevent scarring after symblepharon surgery with extensive corneo-conjunctival adhesion (n=1). Under sterile conditions amniotic membrane was prepared from a fresh placenta of a seronegative pregnant woman and stored at ˛70°C. This technique involved the use of amniotic membrane to cover the entire cornea and perilimbal area in groups A and B, and the epithelial defect only in group C. Results—The cornea healed satisfactorily in four of five patients in group A, but the epithelial defect recurred in one of these patients. After AMT three patients underwent limbal transplantation and one penetrating keratoplasty and cataract extraction. In group B amniotic membrane transplantation was not helpful, and all cases underwent an urgent tectonic corneal graft. Surgery successfully released the symblepharon, promoted epithelialisation and prevented adhesions in the case of group C. Conclusion—AMT was eVective to promote corneal healing in patients with persistent epithelial defect, and appeared to be helpful after surgery to release corneoconjunctival adhesion. Most cases required further surgery for visual and ocular surface rehabilitation. Amniotic membrane used as a patch was not eVective to prevent tectonic corneal graft in cases with severe stromal thinning and impending or recent perforation. (Br J Ophthalmol 1999;83:399‐402)

Effectiveness of home exercise on pain and disability from osteoarthritis of the knee: a randomised controlled trial

Abstract: Objective—To assess the eVect of a home based exercise programme, designed to improve quadriceps strength, on knee pain and disability. Methods—191 men and women with knee pain aged 40‐80 were recruited from the community and randomised to exercise (n=113) or no intervention (n=78). The exercise group performed strengthening exercises daily for six months. The primary outcome measure was change in knee pain (Western Ontario McMaster Osteoarthritis index (WOMAC)). Secondary measures included visual analogue scales (VAS) for pain on stairs and walking and WOMAC physical function scores. Results—WOMAC pain score reduced by 22.5% in the exercise group and by 6.2% in the control group (between group diVerence p<0.05, unpaired t test).VAS scores for pain also reduced in the exercise group compared with the control group (p<0.05). Physical function scores reduced by 17.4% in the exercise group and were unchanged in controls (p<0.05). Conclusion—A simple programme of home quadriceps exercises can significantly improve self reported knee pain and function. (Ann Rheum Dis 1999;58:15‐19)

Processing of cellular ceramics by foaming and in situ polymerisation of organic monomers

Abstract: This paper describes studies on a new processing route for fabricating highly porous ceramics. The method is based on the generation of a foam from an aqueous suspension of ceramic powder and the subsequent stabilisation of the structure by in situ polymerisation of organic monomers. The influence of the slip viscosity on the foam volume and stability was determined using concentrated alumina suspensions containing dispersing agents and two commercial foaming agents. The in situ polymerisation of organic monomers led to fast solidification, resulting in strong, porous bodies which could withstand machining. The resulting ceramic foams consisted of a highly interconnected network of spherical cells with densities as low as 6% of theoretical. The distribution of cell size was dependent both on the density of the specimen produced and on the time for polymerisation onset. The size ranged from approximately 30 to 600 μm. Enlargement of cell size to achieve materials of higher permeability was possible through expansion of the foam via pressure reduction before polymerisation. The creation of highly densified struts between the cells led to flexural strengths as high as 26 MPa. ©

Virtual Reality-Induced Symptoms and Effects (VRISE)

Abstract: An experimental program of research was carried out to assess the potential health and safety effects of participating in virtual environments (VEs) via head-mounted displays (HMDs) This paper presents the results obtained from nine experiments examining the effects experienced during and after participation in a variety of VR systems, VE designs, and task requirements, for a total participant sample of 148 individuals A combination of methods including self-report scales, performance measures, physiological indicators, observation, interview, and user attitude/opinion questionnaires were used to measure simulator (VE) sickness, postural instability, psychomotor control, perceptual judgment, concentration, stress, and ergonomics effects Greatest effects across the different systems, VEs, and exposure times were found for sickness symptoms and physiological measures, with some concern over postural instability and physical ergonomics, also Although many of the effects were relatively minor and short lived, they were serious for five percent of participants and irritating for a considerable percentage more The aetiology of the effects is sufficiently different to that for simulators or transport systems to justify us using a new term, virtual reality-induced symptoms and effects (VRISE) Implications are drawn for VR system design, VE specification, and the ways in which industrial use of VR/VE should be planned and supported

Hf-Nd Element and Isotope Perspective on the Nature and Provenance of Mantle and Subduction Components in Western Pacific Arc-Basin Systems

Abstract: This paper develops methods for using the integrated study of Hf-Nd element and isotope covariations to define the nature and provenance of the mantle and subduction inputs to subduction systems. In particular, it can be demonstrated that (1) Hf-Nd isotope space permits discrimination between mantle of Pacific and Indian provenance, (2) displacements from mantle arrays on Hf-Nd isotope and trace element projections can be related to the magnitude, source and composition of the subduction input, and (3) Hf-Nd isotope and trace element covariations can be used to interpret high field strength element (HFSE) anomalies [specifically, Hf anomalies on extended rare earth element (REE) patterns] in subduction-related magmas. These methods are tested using published volcanic arc data coupled with new data from the many components of the Izu-Bonin-Mariana (IBM) subduction system, namely the pre-subduction marginal basins, the Eocene to Recent volcanic arcs, and the crust, volcanogenic sediments and pelagic sediments of the subducting Pacific plate. The results of the IBM study show that the mantle that fed the IBM system was always of Indian provenance and that Pacific volcanogenic sediments make the most significant, though variable, contribution to the subduction component. Modelling demonstrates that the Nd/Hf ratio of the subduction component probably lay between 40 and infinity and thus was probably the main cause of the negative HFSE anomalies that characterize much of the Recent arc. This result may further indicate that the subducting sediment lost elements to the mantle wedge mostly by dehydration rather than fusion. In contrast, the data also show that the positive Hf anomalies that characterize much of the Protoarc cannot be attributed directly to subduction. One option consistent with Hf-Nd systematics is that the positive Hf anomalies in the Protoarc boninites were caused by fusion of mafic veins in their shallow mantle sources. Comparison with published data on other arcs shows significant inter-arc variations. For example, the subduction components in near-continent arcs (Banda, Lesser Antilles) appear to have lower Nd/Hf ratios more consistent with sediment fusion, and at least one arc (Tonga-Fiji) carries evidence of temporal variations in mantle provenance.

Clinical features and outcome of septic arthritis in a single UK Health District 1982-1991

Abstract: AIMS To determine the clinical features of a large number of unselected UK hospital patients with confirmed septic arthritis and to determine those features associated with a poor outcome. STUDY DESIGN Retrospective, case-note survey. SETTING A single English Health District. PATIENTS All patients admitted to hospital in Nottingham during the period 1 January 1982 to 31 December 1991 with confirmed septic arthritis were included. OUTCOME MEASURES Death, osteomyelitis and recorded functional impairment. RESULTS The spectrum of causative organisms remains similar to that seen in previous studies with the Gram positive organisms Staphylococcus aureus and Streptococci responsible for 74% of cases, gonococcal infections though were less common. Culture of joint aspirates and or blood were positive in 82% of cases, with the Gram stain demonstrating the causative organism in 50% of cases. Pre-existing joint disease was evident in 35% of cases. The mortality remains high at 11.5% with a significant additional morbidity of 31.6%. Multivariate analysis suggests that important predictors of death are: confusion at presentation, age ⩾65 years, multiple joint sepsis or involvement of the elbow joint, and of morbidity are: age ⩾ 65 years, diabetes mellitus, open surgical drainage, and Gram positive infections other than S aureus. CONCLUSIONS Septic arthritis continues to be associated with a considerable degree of morbidity and mortality. These results confirm the importance of obtaining synovial fluid and blood for culture before starting antimicrobial treatment. The apparent poorer outcome found with surgical intervention is in line with some previous suggestions but should be interpreted with caution in light of the retrospective nature of this study.

Low Body Mass Index Is an Important Risk Factor for Low Bone Mass and Increased Bone Loss in Early Postmenopausal Women

Abstract: Thinness (low percentage of body fat, low body mass index [BMI], or low body weight) was evaluated as a risk factor for low bone mineral density (BMD) or increased bone loss in a randomized trial of alendronate for prevention of osteoporosis in recently postmenopausal women with normal bone mass (n = 1609). The 2-year data from the placebo group were used (n = 417). Percentage of body fat, BMI, and body weight were correlated with baseline BMD (r = −0.13 to −0.43, p < 0.01) and 2-year bone loss (r = −0.14 to −0.19, p < 0.01). Women in the lowest tertiles of percentage of body fat or BMI had up to 12% lower BMD at baseline and a more than 2-fold higher 2-year bone loss as compared with women in the highest tertiles (p ≤ 0.004). Women with a lower percentage of body fat or BMI had higher baseline levels of urine N-telopeptide cross-links (r = −0.24 to −0.31, p < 0.0001) and serum osteocalcin (r = −0.12 to −0.15, p < 0.01). To determine if the magnitude of treatment effect of alendronate was dependent on these risk factors, the group treated with 5 mg of alendronate was included (n = 403). There were no associations between fat mass parameters and response to alendronate treatment, which indicated that risk of low bone mass and increased bone loss caused by thinness could be compensated by alendronate treatment. In conclusion, thinness is an important risk factor for low bone mass and increased bone loss in postmenopausal women. Because the response to alendronate treatment is independent of fat mass parameters, prevention of postmenopausal osteoporosis can be equally achieved in thinner and heavier women.

The representation of pleasant touch in the brain and its relationship with taste and olfactory areas.

Abstract: Although there has been much investigation of brain pathways involved in pain, little is known about the brain mechanisms involved in processing somatosensory stimuli which feel pleasant. Employing fMRI it was shown that pleasant touch to the hand with velvet produced stronger activation of the orbitofrontal cortex than affectively neutral touch of the hand with wood. In contrast, the affectively neutral but more intense touch produced more activation of the primary somatosensory cortex than the pleasant stimulus. This indicates that part of the orbitofrontal cortex is concerned with representing the positively affective aspects of somatosensory stimuli, and in further experiments it was shown that this orbitofrontal area is different from that activated by taste and smell. The finding that three different primary or unlearned types of reinforcer (touch, taste, and smell) are represented in the orbitofrontal cortex helps to provide a firm foundation for understanding the neural basis of emotions, which can be understood in terms of states elicited by stimuli which are rewarding or punishing.

Interdependence of peat and vegetation in a tropical peat swamp forest

Abstract: The visual uniformity of tropical peat swamp forest masks the considerable variation in forest structure that has evolved in response to differences and changes in peat characteristics over many millennia. Details are presented of forest structure and tree composition of the principal peat swamp forest types in the upper catchment of Sungai Sebangau, Central Kalimantan, Indonesia, in relation to thickness and hydrology of the peat. Consideration is given to data on peat geochemistry and age of peat that provide evidence of the ombrotrophic nature of this vast peatland and its mode of formation. The future sustainability of this ecosystem is predicted from information available on climate change and human impact in this region.

Amniotic membrane transplantation

Abstract: In 1910 Davis was the first to report the use of fetal membranes as surgical material in skin transplantation.1Since then the use of amniotic membrane in surgery has been expanded.1-9 It is now utilised as a biological dressing for burned skin, skin wounds, and chronic ulcers of the leg,9-16 as an adjunctive tissue in surgical reconstruction of artificial vagina,9 17-19 and for repairing omphaloceles.9 20 It has also been used to prevent tissue adhesion in surgical procedures of the abdomen, head, and pelvis.9 21 22 In the 1940s several authors reported the beneficial role of amniotic membrane in treating a variety of ocular surface disorders.5-7 23 However, its use was abandoned for decades until recently, when it was reintroduced to ophthalmologists. Several studies have addressed this subject and the scope of the application of amniotic membrane transplantation (AMT) in the management of ocular surface disorders is ever increasing. Certain characteristics make the amniotic membrane ideally suited to its application in ocular surface reconstruction. It can be easily obtained and its availability is nearly unlimited. The tissue can be preserved at −80°C for several months, allowing sufficient time to plan surgery or consider a trial of other options. Amniotic membrane does not express HLA-A, B, or DR antigens and hence immunological rejection after its transplantation does not occur.24-26It is also believed to have antimicrobial properties, reducing the risks of postoperative infection.27 Antifibroblastic activity28-30 and cell migration/growth promoting activity31-33 have also been demonstrated with regard to the amniotic membrane. The purpose of this paper is to review the characteristics of amniotic membrane that make it potentially useful to treat ocular surface abnormalities and to discuss the current indications, the surgical technique, and the outcome of AMT. Mammalian embryos lie …