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Biomedical subjects

A D Smith

Publications and source records attributed to A D Smith.

At least 19 recordsLinked to original sources

Appetitive flight patterns of male Agrotis segetum moths over landscape scales.

An analysis is presented of the first harmonic radar studies of pheromone-plume locating flights of male Agrotis segetum moths over distances of up to 500 m. Upon release most moths flew in a direction having a downwind component. The first significant changes in flight orientations occur in the immediate vicinity of a pheromone source. Moths that were initially flying downwind change course and start flying crosswind whilst those that initially flew crosswind change course and start flying upwind. It is shown that such behaviour is consistent with the adoption of an effective plume-location strategy, and conditions are identified when downwind flights would be more advantageous than crosswind ones. Additionally, some of the complex flight patterns that can arise at later times are shown to be compatible with the adoption of an optimal biased scale-free (Lévy-flight) searching strategy. It is found that disruptive doses of sex pheromone can have a marked influence upon male moth flight patterns.

Animals↗

Apolipoprotein E epsilon4 and impaired episodic memory in community-dwelling elderly people: a marked sex difference. The Hordaland Health Study.

BACKGROUND: Among elderly people without dementia, the apolipoprotein E epsilon4 allele (APOE4) has been associated with cognitive deficit, particularly in episodic memory, but few reports are available on whether this association differs by sex. METHODS: In a community-dwelling Norwegian cohort of 2181 elderly people (55% women), aged 70-74 years, episodic memory was examined in relation to sex and APOE4 zygosity, with the Kendrick Object Learning Test (KOLT). RESULTS: Possession of at least one APOE4 allele had a modest, detrimental effect on episodic memory in women, whereas in men, heterozygotes were unaffected and homozygotes had markedly lower scores across the distribution of KOLT scores. This sex difference was found consistently in all analyses: on comparing means and medians, examining trends across quintiles, and studying the distribution of scores and the risk of cognitive impairment. Results were broadly similar when adjusted for known determinants of cognition and also when severely impaired participants were excluded. The adjusted odds ratio (OR) of cognitive impairment in women was shown to be 1.8 (95% confidence interval (CI): 1.1 to 2.8) for heterozygotes and 1.1 (0.3 to 3.7) for homozygotes; the adjusted OR in men was observed to be 1.1 (0.6 to 2.1) for heterozygotes and 10.7 (4.7 to 24) for homozygotes. CONCLUSIONS: Although the harmful effect of APOE4 on episodic memory was modest in women, the risk was found to occur in about 30%. APOE4 was observed to have a dramatic effect on episodic memory in men, but only in homozygotes, who comprised about 3% of men: the whole male homozygous group showed a marked shift to lower memory scores.

Aged↗

Iron genes, iron load and risk of Alzheimer's disease.

BACKGROUND: Compound heterozygotes of the haemochromatosis gene (HFE) variants, H63D and C282Y, have raised transferrin saturation compared with that in the wild type. In the cohort of the Oxford Project To Investigate Memory and Ageing (OPTIMA), bicarriers of the HFE C282Y and the transferrin C2 gene variants are at five times greater risk of developing Alzheimer's disease; the addition of HFE H63D may raise the risk still further. OBJECTIVE: To investigate transferrin saturation by HFE and transferrin genotype among people without dementia-that is, controls and those with mild cognitive impairment (MCI)-and also among those with Alzheimer's disease. METHODS: Serum iron status and genotype were examined of 177 patients with Alzheimer's disease, 69 patients with MCI and 197 controls from the OPTIMA cohort. RESULTS: Although each of these variants alone had relatively little effect on iron status, the combination of either HFE C282Y and HFE H63D or of HFE C282Y and transferrin C2 markedly raised transferrin saturation in those without dementia, but had little effect in those with mature Alzheimer's disease. CONCLUSIONS: These combinations may raise the risk for Alzheimer's disease, owing to higher iron loads and therefore oxidative stress in the preclinical phase. If replicated, these findings will have implications for the prevention of Alzheimer's disease.

Aged↗

Around the clock surveillance: simple graphic disturbance in patients with hemispatial neglect carries implications for the clock drawing task.

BACKGROUND: Drawing, and the clock drawing task in particular, is widely used as a diagnostic tool in the study of hemispatial neglect. It is generally assumed that the errors in graphic production, such as the misplacement of numbers, reflect a visuospatial deficit, and that drawing production itself (for example, producing the circle) is unimpaired. OBJECTIVES: To test this assumption by examining whether the production of simple circles is affected by neglect. METHODS: 16 right hemisphere stroke patients copied circles of various sizes and their drawings were measured for size accuracy. RESULTS: Patients with more severe neglect produced greater scaling errors, consistently drawing the circle smaller than the original. Errors were not in the horizontal axis alone--shrinkage occurred equally in both height and width axes. CONCLUSIONS: Neglect can co-occur with constructional difficulties that serve to exacerbate the symptoms presented. This should be taken into account in the assessment of even apparently simple drawing tasks.

Aged↗

Exhaled nitric oxide measurements: clinical application and interpretation.

The use of exhaled nitric oxide measurements (F(E)NO) in clinical practice is now coming of age. There are a number of theoretical and practical factors which have brought this about. Firstly, F(E)NO is a good surrogate marker for eosinophilic airway inflammation. High F(E)NO levels may be used to distinguish eosinophilic from non-eosinophilic pathologies. This information complements conventional pulmonary function testing in the assessment of patients with non-specific respiratory symptoms. Secondly, eosinophilic airway inflammation is steroid responsive. There are now sufficient data to justify the claim that F(E)NO measurements may be used successfully to identify and monitor steroid response as well as steroid requirements in the diagnosis and management of airways disease. F(E)NO measurements are also helpful in identifying patients who do/do not require ongoing treatment with inhaled steroids. Thirdly, portable nitric oxide analysers are now available, making routine testing a practical possibility. However, a number of issues still need to be resolved, including the diagnostic role of F(E)NO in preschool children and the use of reference values versus individual F(E)NO profiles in managing patients with difficult or severe asthma.

Asthma↗

Effect of physical restraint on oxidative stress in mice fed a selenium and vitamin E deficient diet.

Physical restraint has been associated with increased oxidative damage to lipid, protein, and DNA. The purpose of this experiment was to determine whether physical restraint would further exacerbate oxidative stress in mice fed a selenium (Se) and vitamin E (VE) deficient diet. Three-week- old mice were fed a Torula yeast diet containing adequate or deficient Se and VE. Menhaden oil was added to the deficient diet to impose an additional oxidative stress. After 4 wk feeding, half the mice in each group were restrained for 5 d in well-ventilated conical tubes for 8 h daily. Mice fed the Se and VE deficient diets had increased liver thiobarbituric acid-reactive substance (TBARS) levels and decreased liver glutathione peroxidase (GPX1) activity and alpha-tocopherol levels. Plasma corticosterone levels were elevated in restrained mice fed the deficient diet compared to unrestrained mice fed the adequate diet. Restraint had no effect on liver TBARS or alpha-tocopherol levels. Liver GPX1 activity, however, was lower in restrained mice fed the adequate diet. In addition, liver superoxide dismutase (SOD) activity was lower in the restrained mice fed the adequate or deficient diet. Thus, under our conditions, Se and VE deficient diet, but not restraint, increased lipid peroxidation in mice. Restraint, however, decreased antioxidant protection in mice due to decreased activities of GPX1 and SOD enzymes.

Animals↗

Application notes on the use of softer X-rays for anomalous powder diffraction.

An in-vacuum diffractometer has been modified to collect powder diffraction data from a sample of promazine hydrochloride. Strong anomalous contrast has been observed at, or close to, the sulphur edge. Based on the data collected, a bespoke diffractometer has been designed that, together with minor changes to the geometry of the experiment, will enable the routine collection of powder data at absorption edges below 5.5 keV.

Equipment Design↗

Levels of CSF prostaglandin E2, cognitive decline, and survival in Alzheimer's disease.

BACKGROUND: Although epidemiological, clinical, and experimental evidence indicates that the inducible isoform of cyclo-oxygenase (COX-2) may be involved in the pathogenesis of several neurodegenerative disorders, the mechanisms whereby COX-2 contributes to Alzheimer's disease are largely unknown. OBJECTIVE: To undertake a longitudinal study of CSF levels of a major product of COX activity, prostaglandin E2 (PGE2), in relation to cognitive decline and survival in patients with Alzheimer's disease. METHODS: CSF PGE2 was measured on at least three annual visits in 35 controls and 33 Alzheimer patients (26 necropsy confirmed) who completed the Cambridge cognitive assessment (CAMCOG). RESULTS: Compared with controls, CSF PGE2 was higher in patients with mild memory impairment, but lower in those with more advanced Alzheimer's disease. The median survival time of patients with higher initial PGE2 levels was five years longer than those with lower levels. CONCLUSIONS: COX activity in Alzheimer's disease varies with stage of the disease. PGE2 levels correlate positively with patient survival. These findings suggest that inhibition of COX activity does not represent a major target for the pharmacological treatment of Alzheimer's disease.

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The flight paths of honeybees recruited by the waggle dance.

In the 'dance language' of honeybees, the dancer generates a specific, coded message that describes the direction and distance from the hive of a new food source, and this message is displaced in both space and time from the dancer's discovery of that source. Karl von Frisch concluded that bees 'recruited' by this dance used the information encoded in it to guide them directly to the remote food source, and this Nobel Prize-winning discovery revealed the most sophisticated example of non-primate communication that we know of. In spite of some initial scepticism, almost all biologists are now convinced that von Frisch was correct, but what has hitherto been lacking is a quantitative description of how effectively recruits translate the code in the dance into flight to their destinations. Using harmonic radar to record the actual flight paths of recruited bees, we now provide that description.

Animal Communication↗

Tracking butterfly flight paths across the landscape with harmonic radar.

For the first time, the flight paths of five butterfly species were successfully tracked using harmonic radar within an agricultural landscape. Until now, butterfly mobility has been predominantly studied using visual observations and mark-recapture experiments. Attachment of a light-weight radar transponder to the butterfly's thorax did not significantly affect behaviour or mobility. Tracks were analysed for straightness, duration, displacement, ground speed, foraging and the influence of linear landscape features on flight direction. Two main styles of track were identified: (A) fast linear flight and (B) slower nonlinear flights involving a period of foraging and/or looped sections of flight. These loops potentially perform an orientation function, and were often associated with areas of forage. In the absence of forage, linear features did not provide a guiding effect on flight direction, and only dense treelines were perceived as barriers. The results provide tentative support for non-random dispersal and a perceptual range of 100-200 m for these species. This study has demonstrated a methodology of significant value for future investigation of butterfly mobility and dispersal.

Animals↗

Effect of AdGDNF on dopaminergic neurotransmission in the striatum of 6-OHDA-treated rats.

We have previously observed that the delivery of an adenoviral vector encoding for glial cell line-derived neurotrophic factor (AdGDNF) into the substantia nigra (SN) 7 days after intrastriatal administration of 6-hydroxydopamine (6-OHDA) protects dopamine (DA)-dependent behaviors, tyrosine hydroxylase immunoreactive (TH+) cells in SN, and amphetamine-induced c-fos induction in striatum. In the present study, we sought to determine if the behavioral protection observed in 6-OHDA-treated rats receiving AdGDNF was associated with an increase in DA availability in the striatum as measured by microdialysis. Rats received intrastriatal 6-OHDA (16 microg/2.8 microl) or vehicle followed 7 days later by intranigral AdGDNF (3.2x10(7) pfu/2 microl), AdLacZ (3.2 x 10(7) pfu/2 microl), or phosphate buffered saline (PBS). Three weeks later, microdialysis samples were collected from the same striatal region under basal conditions, following KCl (100 mM) or amphetamine (250 microM) administered via the striatal microdialysis probe, or amphetamine administered systemically (6.8 mg/kg i.p). Animals given 6-OHDA followed by either PBS or AdLacZ showed a decrease in basal extracellular striatal DA levels to 24% of control. In contrast, basal extracellular DA in 6-OHDA-lesioned rats with a nigral injection of AdGDNF was almost 3-fold higher than 6-OHDA-vehicle treated animals, 65% of control DA levels. Moreover, although KCl and amphetamine produced no increase in striatal DA release in 6-OHDA-treated rats that subsequently were given either PBS or AdLacZ, these manipulations increased DA levels significantly in 6-OHDA-treated rats later given AdGDNF. Thus, DA neurotransmission within the striatum of 6-OHDA treated rats appears to be enhanced by increased expression of GDNF in the nigra.

3,4-Dihydroxyphenylacetic Acid↗

Radar studies of the vertical distribution of insects migrating over southern Britain: the influence of temperature inversions on nocturnal layer concentrations.

Insects migrating over two sites in southern UK (Malvern in Worcestershire, and Harpenden in Hertfordshire) have been monitored continuously with nutating vertical-looking radars (VLRs) equipped with powerful control and analysis software. These observations make possible, for the first time, a systematic investigation of the vertical distribution of insect aerial density in the atmosphere, over temporal scales ranging from the short (instantaneous vertical profiles updated every 15 min) to the very long (profiles aggregated over whole seasons or even years). In the present paper, an outline is given of some general features of insect stratification as revealed by the radars, followed by a description of occasions during warm nights in the summer months when intense insect layers developed. Some of these nocturnal layers were due to the insects flying preferentially at the top of strong surface temperature inversions, and in other cases, layering was associated with higher-altitude temperature maxima, such as those due to subsidence inversions. The layers were formed from insects of a great variety of sizes, but peaks in the mass distributions pointed to a preponderance of medium-sized noctuid moths on certain occasions.

Altitude↗

The CT-based radial width of the temporal horn: pathological validation in AD without cerebrovascular disease.

BACKGROUND: Medial temporal lobe atrophy is one of the most accurate markers of Alzheimer's disease (AD). Given the wide availability of the CT in the routine diagnostic assessment of patients with cognitive disturbances, a CT-based marker of AD might be clinically useful. OBJECTIVE: To test the accuracy of a simple CT-based measure, the radial width of the temporal horn (rWTH). METHOD: The rWTH was taken in a group of 20 pathologically confirmed AD patients and 23 non demented persons enrolled in the Oxford Project to Investigate Memory and Aging (OPTIMA project). RESULTS: The rWTH was significantly larger in AD patients than controls. Using a cutoff value between 3.9 at 50 and 8.1 at 90 years, the rWTH was able to correctly classify 16/20 and 19/23 subjects with a sensitivity and a specificity of 80% and 83%. The overall accuracy was 81%. CONCLUSION: The CT measurement of the rWTH is a simple and reasonably sensitive marker of regional brain atrophy in AD.

Aged↗

Presynaptic dopaminergic properties of differentiated mouse embryonic stem cells.

This study characterized the presynaptic dopaminergic properties of neuronally differentiated mouse embryonic stem (ES) cells. Approximately 30% of the ES cells expressed tyrosine hydroxylase (TH) immunoreactivity when co-cultured with PA6 cells. These cultures expressed high affinity, sodium-dependent dopamine uptake as well as depolarization-induced and calcium-dependent dopamine release of this transmitter. These and other important dopaminergic genes found expressed in these cultures by RT-PCR included Nurr1, vesicular monoamine transporter 2 (VMAT2), TH, dopamine transporter (DAT), and glial cell line-derived neurotrophic factor (GDNF) receptors c-Ret and GFRalpha1. These results demonstrate that differentiated ES cells have the presynaptic functions for maintaining dopaminergic homeostasis, which may be essential for their long-term use in restoring CNS levels of this transmitter.

Animals↗

An aerial netting study of insects migrating at high altitude over England.

Day and night sampling of windborne arthropods at a height of 200 m above ground was undertaken at Cardington, Bedfordshire, UK, during July 1999, 2000 and 2002, using a net supported by a tethered balloon. The results from this study are compared with those from the classic aerial sampling programmes carried out by Hardy, Freeman and colleagues over the UK and North Sea in the 1930s. In the present study, aerial netting was undertaken at night as well as daytime, and so the diel periodicity of migration could be investigated, and comparisons made with the results from Lewis and Taylor's extensive survey of flight periodicity near ground level. In some taxa with day-time emigration, quite large populations could continue in high-altitude flight after dark, perhaps to a previously underrated extent, and this would greatly increase their potential migratory range. Any trend towards increases in night temperatures, associated with global warming, would facilitate movements of this type in the UK. Observations on the windborne migration of a variety of species, particularly those of economic significance or of radar-detectable size, are briefly discussed.

Altitude↗

No panacea for drainage after percutaneous nephrolithotomy.

BACKGROUND AND PURPOSE: The optimal postoperative drainage system for patients undergoing percutaneous nephrolithotomy (PCNL) has not yet been determined. Each of the different tubes available has theoretical advantages and disadvantages. The objective of this study was to determine if any one system of post-PCNL drainage has any significant advantage over the others. PATIENTS AND METHODS: Sixty patients were randomized to either a 24F Re-entry tube (Group 1), an 8F pigtail catheter (Group 2), or a double-J stent (Group 3) (N = 20 for all groups). The double-J stent patients also had an 18F Councill catheter as a nephrostomy tube, which was removed on the morning of postoperative day 1. The three groups were well-matched for age, stone size, operative time, and mean number of percutaneous tracts (P > 0.05 for all). Data collected included intraoperative findings, postoperative analog pain scores and narcotic usage, presence of extravasation on postoperative nephrostogram, presence of perinephric fluid on postoperative ultrasound scans, length of stay, and whether leakage from the nephrostomy site persisted more than 48 hours after tube removal. RESULTS: There were no statistically significant differences among the three groups in terms of change in hematocrit or number of patients requiring blood transfusion; in the incidence of tube blockage, extravasation, or presence of perinephritic fluid; or in complication rates, length of hospital stay, or persistent leakage after tube removal. There was a strong trend to less postoperative leakage with the 8F pigtail than the Reentry tube (P = 0.05). Postoperative analog pain scores and narcotic usage were equivalent for all three groups. Patients Groups 1 and 2 were free of all tubes sooner than patients in Group 3 (P < 0.001). CONCLUSIONS: This study did not demonstrate an overwhelming advantage of any one drainage system over the others. All three systems were equally tolerated by patients. There may be less chance of prolonged nephrostomy-site leakage with an 8F pigtail catheter.

Catheterization↗

Are new-generation flexible ureteroscopes better than their predecessors?

OBJECTIVE: To compare two newly designed flexible ureteroscopes with their respective predecessors, to determine whether design advances have overcome the limitation of tip deflection, which may interfere with diagnosis and treatment of lower pole renal pathology. MATERIALS AND METHODS: Two new-generation flexible ureteroscopes, the DUR-8 Elite (ACMI, Southborough, MA, USA) and 11278AU (Karl Storz Endoscopy, Culver City, CA, USA) were compared with their previous models, the ACMI DUR-8 and the Storz 11274AAU. Active tip deflection and irrigation flow rates with and without various endoscopic tools were assessed. Specifications, purchase prices and repair costs were obtained from each manufacturer. The field of view and screen image size of each ureteroscope were also compared. RESULTS: The ACMI DUR-8 Elite and the Storz 11278AU had improvements of 79 degrees and 144 degrees, respectively, from their respective older models. Although the tip deflection of all ureteroscopes was compromised by inserting different endoscopic tools, these new instruments were less affected. With a 3 F basket inside the working channel, the ACMI DUR-8 Elite and the Storz 11278AU had only 0.7% and 2.8% loss of upward tip deflection, compared with their older models, at 9.6% and 5.0%, respectively. However, the flow rates of these new instruments were decreased. CONCLUSION: The new flexible ureteroscopes have significantly better active tip deflection than previous models, both with and without endoscopic instrumentation inserted. However, improved flexibility is at the expense of decreased flow rates and higher purchase costs.

Equipment Design↗