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Biomedical subjects

M Wilson

Publications and source records attributed to M Wilson.

At least 37 records · Page 2Linked to original sources

Prevention of coordinated eye movements and steering impairs driving performance.

When approaching a bend in the road, a driver looks across to the inside kerb before turning the steering wheel. Eye movements and steering are tightly linked, with the eyes leading, which means that the oculomotor controller can assist the neural centres controlling steering. This optimum coordination is observed for all drivers; but despite being the preferred solution to the motor-control problem of successfully steering along a winding road, the question remains as to how crucial such coordinated eye and steering movements are for driving performance. Twenty subjects repeatedly drove a simulated stage of the World Rally Championship, aiming to complete the course in the fastest possible time. For the first six repetitions they used the usual coordination of eye movements and steering; for drives 7--12 they were instructed to fixate on a small spot in the centre of the screen (centre gaze). Prevention of coordination in this way impaired their performance (drives 6 and 7 compared), dramatically increasing their time taken to complete the course, equivalent to slipping 19 places down the leader board in the actual rally stage. This indicates that the usual pattern of eye movements correlated with steering is crucial for driving performance. Further experiments are suggested to reveal whether any attentional demand associated with keeping the eyes still contributes to the loss in performance.

Adult↗

Uncertainty and power at low levels of incurred radiation dose.

It is common practice when calculating dose to exposed populations to average the variables that go into the dose calculation (e.g. environmental concentrations, air kerma, consumption rates, occupancy rates). This approach is simple and can be useful where data are obtained over different periods (weekly, monthly, quarterly), where samples may be bulked for some analyses but not others and where gaps in the data are present. However, such an approach does not yield information on the degree of uncertainty around the average dose calculated. An alternative approach is to estimate the dose to each individual and to obtain an average from this data set, which can then also be used to derive a measure of uncertainty around the central dose estimate. In this study, we demonstrate the variability in dose estimates using a hypothetical data set and consider the implications for sample size to achieve fixed confidence or resolving power. We recommend calculating the dose to every individual sampled, in order both to obtain the average dose and to estimate its variability. We argue that it is best practice to obtain information as complete as possible from the available sample of individuals.

Animals↗

X-ray and neutron diffraction studies and MD simulation of atomic configurations in polyamorphic Y2O3-Al2O3 systems.

Supercooled liquids in the Y(2)O(3)-Al(2)O(3) system undergo a liquid-liquid phase transition between a high-temperature, high-density amorphous (HDA) polymorph form and one with lower density (LDA form) that is stable at lower temperature. The two amorphous polymorphs have the same chemical composition, but they differ in their density (ca. 4% difference) and in their heat content (enthalpy) and entropy determined by calorimetry. Here we present new results of structural studies using neutron and high-energy X-ray diffraction to study the structural differences between HDA and LDA polyamorphs. The combined datasets show no large differences in the average nearest-neighbour Al-O or Y-O bond lengths or coordination numbers between the low- and high-density liquids. However, the data indicate that substantial changes occur among the packing geometries and clustering of the Al-O and Y-O coordination polyhedra, i.e. within the second-nearest-neighbour shell defined by the metal-metal (i.e. Y-Y, Y-Al, Al-Al) interactions. Polarizable ion model molecular dynamics simulations of Y(2)O(3)-Al(2)O(3) liquids are used to help interpret the pair-correlation functions obtained from X-ray and neutron scattering data. Unexpectedly large density fluctuations are observed to occur during the simulation of nominally equilibrated systems. These are interpreted as being due to dynamic sampling of high- and low-density configurations within the single-phase liquid at temperatures above the critical point or phase transition line. Calculated partial radial distribution functions indicate that the primary differences between HDA and LDA configurations occur among the Y-Y correlations.

Aluminum Oxide↗

OPA3 mutation screening in patients with unexplained 3-methylglutaconic aciduria.

We have screened 13 patients with neurological abnormalities and 3-methylglutaconic aciduria (3MGA) for mutations in the OPA3 gene, which are known to be the cause of Costeff syndrome (optic atrophy, chorea and spasticity; type III 3MGA). We aimed to explore whether mutations in the OPA3 gene are present in patients with 3MGA but without classic Costeff syndrome. OPA3 mutations (IVS1-1G>C) were identified in 2 patients with the classic phenotype of type III 3MGA, but not in the other 11 patients with differing non-Costeff phenotypes associated with developmental delay and neurological signs and symptoms as described. We identified a previously described sequence variation in the OPA3 gene (c.231T>C) in 12/13 patients. The alteration was homozygous in 8/12 and heterozygous in 4/12. This alteration was also found in 60 of 98 normal control alleles. In a single patient, a novel sequence variation in the 5' UTR was identified, (c.-38A>G). Our studies suggest that the c.231T>C sequence variation is of no clinical significance, whereas the significance of the 5' UTR sequence variation remains open to speculation. Our study of the OPA3 gene in patients with 3MGA without Costeff syndrome suggests that mutations in OPA3 are not a common cause of 3MGA in the absence of signs of Costeff syndrome.

5' Untranslated Regions↗

Assessment of a low-fidelity human patient simulator for the acquisition of nursing skills.

AIM: Assess the user-friendliness of a low-fidelity human patient simulator as a precursor to developing and evaluating nurses' health assessment knowledge and skills. METHOD: An assessment tool was developed to assess nurse perceptions about the components and functions of the Nursing Anne Complete manikin in terms of its realism, perceived suitability for teaching purposes (rated on five-point scales from disagree to agree), and how it compared with other teaching tools (e.g., better than text book). The manikin was placed on hospital wards to assume patient realism and data was collected from two hospital sites over one month. RESULTS: Nurses (N=70) reported that most of the components and functions (appearance, movement, procedures and sounds) of Nursing Anne Complete were realistic, better than existing training products, and suitable for teaching purposes. Additional comments included suggestions for improvement. CONCLUSIONS: Overall, the results indicated that this manikin is a very useful training product for nursing education. IMPLICATIONS: Low-fidelity simulators may facilitate experiential learning concomitant with behaviour modification and improved health assessment competence of nurses. Moreover, utilising human simulators in nurse education has the potential to reduce the risk of adverse events and facilitate increased positive patient outcomes.

Adult↗

Enzyme replacement therapy for Gaucher disease in Australia.

AIM: To study the effectiveness of a specific national programme of enzyme replacement therapy (ERT) for patients with severe forms of Gaucher disease, a disorder of sphingolipid metabolism resulting from an inherited deficiency of the lysosomal enzyme beta-Glucocerebrosidase. METHODS: Prospective analysis of data submitted at entry and every 6 months on therapy. The responses of haemoglobin (Hb) and platelet (plt) concentrations, liver and spleen volumes were assessed. PATIENTS: Forty-eight patients were treated with ERT for a minimum of 6 months. Forty patients had Type 1 disease and eight had Type 3B. The age range was 1-70 years (median 24 years). Duration of therapy at the time of analysis was 6-114 months. RESULTS: Thirty-six per cent of patients started with a normal Hb increasing to 76% after 6 months. The mean improvement in Hb from baseline to the end of study period was 20 g/L, when the Hb was normal in 85% (41 patients). Thirty per cent of patients had a normal plt count at the start of therapy, with a more gradual increase in the count at 6 monthly intervals of 50, 91, 108 and 142% of starting value. Seventy-five per cent of patients had a normal plt count at the end of study. Spleen volumes reduced by a mean of 56% in 33 evaluable patients, and the liver by 27% in 30 of 38 evaluable patients. Eight patients had an increase in liver volume of 28%. CONCLUSION: Enzyme replacement therapy produced a spectrum of beneficial responses in patients with Gaucher disease, but all had some evidence of reversal of haematological complications and/or reduction in visceromegaly. Future analyses will examine the effect of therapy on bone disease, prepubertal growth and quality of life.

Adolescent↗

Efficacy of removal of sucrose-supplemented interproximal plaque by electric toothbrushes in an in vitro model.

Electric toothbrushes were evaluated using a model of plaque removal by fluid shear forces. Sucrose supplementation during plaque development did not affect the removal of bacteria from biofilm exposed to low-energy shear but did increase their resistance to high-energy shear. The toothbrush supplying high-energy shear forces removed significantly more viable bacteria.

Bacteria↗

Type III secretion of the Salmonella effector protein SopE is mediated via an N-terminal amino acid signal and not an mRNA sequence.

Type III secretion systems (TTSS) are virulence-associated components of many gram-negative bacteria that translocate bacterial proteins directly from the bacterial cytoplasm into the host cell. The Salmonella translocated effector protein SopE has no consensus cleavable amino-terminal secretion sequence, and the mechanism leading to its secretion through the Salmonella pathogenicity island 1 (SPI-1) TTSS is still not fully understood. There is evidence from other bacteria which suggests that the TTSS signal may reside within the 5' untranslated region (UTR) of the mRNA of secreted effectors. We investigated the role of the 5' UTR in the SPI-1 TTSS-mediated secretion of SopE using promoter fusions and obtained data indicating that the mRNA sequence is not involved in the secretion process. To clarify the proteinaceous versus RNA nature of the signal, we constructed frameshift mutations in the amino-terminal region of SopE of Salmonella enterica serovar Typhimurium SL1344. Only constructs with the native amino acid sequence were secreted, highlighting the importance of the amino acid sequence versus the mRNA sequence for secretion. Additionally, we obtained frameshift mutation data suggesting that the first 15 amino acids are important for secretion of SopE independent of the presence of the chaperone binding site. These data shed light on the nature of the signal for SopE secretion and highlight the importance of the amino-terminal amino acids for correct targeting and secretion of SopE via the SPI-1-encoded TTSS during host cell invasion.

Amino Acid Motifs↗

Pitfalls in the clinical diagnosis of vertebral fractures: a case series in which posterior midline tenderness was absent.

OBJECTIVE: There is widespread belief among doctors that posterior midline tenderness is virtually a prerequisite for spinal fracture in alert, sober patients without any painful distracting injury or neurological deficit. This paper examines and challenges this belief. METHODS AND RESULTS: We present three patients in whom significant thoracic and lumbar vertebral fractures were missed, or were thought to be "old", because of lack of posterior midline tenderness. We also present two further patients, one with a lumbar spine fracture and one with a cervical spine fracture, in whom posterior midline tenderness was absent but in whom the correct diagnosis was made. All these patients were sober and fully alert and none had a neurological deficit or a painful distracting injury. CONCLUSION: The absence of posterior midline tenderness does not exclude significant spinal injury. We suggest that patients should satisfy both the Canadian and British guidelines before it is decided that imaging of the cervical spine is unnecessary.

Adult↗

Effectiveness of outpatient geriatric assessment programs: exploring caregiver needs, goals, and outcomes.

In this study, the authors examined the goals and outcomes of 141 caregivers of older adults with cognitive impairment who attended a comprehensive geriatric assessment program (CGA). The vast majority of caregivers expressed at least one assessment goal, suggesting that the concept was relevant to them. Most caregiver goals focused on patient needs, with only 10% expressing goals specifically related to their own coping needs. At follow up, more than two-thirds of caregiver goals were attained. The findings confirm the great potential of CGA programs in promoting positive outcomes and point to the opportunities for nurses to improve the process of care.

Aged↗

Syndromic surveillance at hospital emergency departments--southeastern Virginia.

Hospital emergency department (ED) syndromic surveillance has been proposed for early detection of a large-scale biologic terrorist attack. However, questions remain regarding its usefulness. The authors examined the use of active syndromic surveillance at hospital EDs in Virginia for early detection of disease events and analyzed the effectiveness of the cumulative sum (CUSUM) algorithm in identifying disease events from syndromic data. Daily chief-complaint data were collected for 10 months at seven hospital EDs in southeastern Virginia. Data were categorized into seven syndromes (fever, respiratory distress, vomiting, diarrhea, rash, disorientation, and sepsis), and the CUSUM algorithm was used to detect anomalies in each of the seven syndromes at each hospital. Fever and respiratory distress syndromes exhibited monthly and ambient-temperature-specific trends consistent with southeastern Virginia's influenza season. Furthermore, preliminary frequencies of hospital ED patient chief complaints in southeastern Virginia during a 10-month period were produced by using syndromic data. This system represents an example of a local syndromic surveillance program serving multiple cities in a limited geographic region.

Algorithms↗

In vitro modeling of dental water line contamination and decontamination.

The contamination of dental unit water lines (DUWL) is an emerging concern in dentistry. The aim of this study was to use an in vitro DUWL to model microbial contamination and evaluate the decontamination efficacy of tetraacetylethylenediamine (TAED) solutions. A DUWL biofilm model used to simulate clinical conditions was used to generate a range of biofilms in DUWL. Three distinct biofilms were generated: (1) biofilm from water, (2) biofilm from a mix of water + contaminating human commensal bacteria, (3) biofilm from water with contaminating oral bacteria added after biofilm formed. The contaminating oral species used were Streptococcus oralis, Enterococcus faecalis and Staphylococcus aureus. Decontamination by simple water flushing or flushing with TAED was evaluated (2, 5 and 10 min intervals). The DUWL tubes were split and samples were plated onto a range of media, incubated and bacteria enumerated. Water flushing did not reduce the number of microorganisms detected. Bacteria were not detected from any of the TAED sampling points for any of the biofilm types tested. Interestingly, if contamination was introduced to new DUWL along with the waterborne species a biofilm was formed containing only the waterborne species. If however, an existing biofilm was present before the introduction of "contaminating" bacteria then these could be detected in the biofilm. This implies that if the DUWL are new or satisfactorily cleaned on a regular basis then the associated cross-contamination aspects are reduced. In conclusion, TAED provides effective control for DUWL biofilms.

Biofilms↗

Cocaine- and amphetamine-regulated transcript peptide levels in blood exhibit a diurnal rhythm: regulation by glucocorticoids.

Cocaine- and amphetamine-regulated transcript (CART) peptides are novel neurotransmitters that are implicated in several physiological functions such as control of feeding behavior, drug reward, sensory processing, stress, and development. Although a majority of studies have examined the role of CART in the brain, less is known about its function in the periphery. Therefore, the goals of this study were to examine the levels and species of CART peptides in blood, to determine whether they undergo diurnal rhythms, and to elucidate their sources and regulatory factors. RIA showed that CART peptides are present in the blood of rats and monkeys and that they exhibit a diurnal variation. Western blotting confirmed the pattern of diurnal variation in rats and, additionally, showed that CART immunoreactivity was due to a single predominant fragment with an apparent molecular weight in the range of the active CART 55-102 peptide. Adrenalectomy caused a 70% reduction in CART peptide levels in rat blood, and this was reversed by corticosterone replacement. CART levels paralleled glucocorticoid levels in rat and monkey blood. Control of CART levels by corticosterone suggests the possibility that CART peptides in blood may be influenced by hypothalamic-pituitary-adrenal interactions and that they may play a role in glucocorticoid-related processes such as stress.

Adrenalectomy↗

Maternal adaptation to high-altitude pregnancy: an experiment of nature--a review.

A long and productive history of studies at high altitude has demonstrated that chronic hypoxia plays a key role in the aetiology of intrauterine growth restriction (IUGR) and pre-eclampsia. Susceptibility to altitude-associated IUGR varies among high-altitude populations in relation to their duration of altitude exposure, with multigenerational residents demonstrating one-third the birth weight fall present in shorter-resident groups. Higher uteroplacental blood flow during pregnancy in multigenerational high-altitude residents suggests that such population differences are due, at least in part, to differences in maternal vascular responses to pregnancy. We hypothesize that natural selection acting on hypoxia-inducible factor (HIF)-targeted or -regulatory genes has enabled maternal vascular adaptation to pregnancy in long-resident high-altitude groups. Preliminary evidence in support of this hypothesis demonstrates that the potent HIF-targeted vasoconstrictor, endothelin-1 (ET-1), is differentially regulated by pregnancy and chronic hypoxia in Andean vs European residents of high altitude. Andeans show the normal, pregnancy-associated fall in ET-1 levels previously reported at low altitude, whereas Europeans have higher ET-1 levels and little pregnancy-associated change, like pre-eclamptic women. Single nucleotide polymorphisms (SNPs) in the ET-1 gene also differ in Andeans compared with low-altitude populations. We conclude that high altitude serves as an experiment of nature for elucidating genetic factors underlying susceptibility to complications of pregnancy and fetal life. Such studies may be important for identifying persons at risk for these complications at any altitude.

Acclimatization↗

Bystander help within a polyepitope DNA vaccine improves immune responses to influenza antigens.

A polyepitope DNA vaccine has the potential to generate protective immune responses to a range of antigens in a single construct. We investigated whether it was possible to obtain responses to individual epitopes from different antigens, directly linked in a string, and whether the response to a given epitope was enhanced by adjacent epitopes within the construct. A polyepitope plasmid was created, which included three Th epitopes (influenza haemagglutinin, moth cytochrome c and ovalbumin), a Tc epitope (ovalbumin) and two B cell epitopes (haemagglutinin and ovalbumin). Mice were immunized with DNA by using a gene gun. Responses to the polyepitope DNA vaccine were compared with those to DNA vaccine comprising only the haemagglutinin Th and B epitopes (HAT(h)B) or with responses to the recombinant protein. These experiments showed that the polyepitope DNA vaccine induced greater antigen-specific responses to HAT(h)B peptide than the HAT(h)B DNA vaccine. Antigen-specific in vivo cytotoxic responses following polyepitope DNA vaccination were also clearly demonstrable. We conclude that a 'naked DNA' polyepitope vaccine generates specific responses to constituent epitopes and that adjacent irrelevant epitopes may enhance these responses.

Animals↗

Oral health and caries related microflora in children during the first three months following renal transplantation.

UNLABELLED: There is little information on the oral health of children undergoing renal transplantation during the early transplant period. METHODS: Twenty-four children undergoing renal transplantation aged 4-13.2 years and their matched controls were recruited. The dmfs, dmft, DMFS and DMFT, plaque, gingivitis and gingival enlargement scores were recorded. The oral microflora was sampled and cultured for S. mutans, Lactobacllus species and Candida species. RESULTS: There was a significantly lower mean dmfs (0.3 +/- 0.9; P = 0.03), dmft (0.3 +/- 0.9; P = 0.03), DMFS (2.3 +/- 5.3; P = 0.01) and DMFT (1.5 +/- 2.6; P = 0.02), respectively, in the transplant group. There was a significantly greater mean plaque score (14.7 +/- 11) for the permanent dentition, at baseline only, compared with 90 days post-transplantation (9.4 +/- 10.4; P = 0.02). There was a significantly greater gingival enlargement score (1.8 +/- 1.4; P = 0.04) 90 days post-transplantation compared with baseline. The S. mutans and Lactobacillus counts were significantly lower both at baseline (P = 0.0001 and P = 0.004) and 90 days post-transplantation (P = 0.02; and P = 0.05), respectively, compared with the controls. CONCLUSIONS: The transplant children had less active dental disease than the controls although gingival enlargement needs careful monitoring.

Adolescent↗