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Biomedical subjects

S Grant

Publications and source records attributed to S Grant.

At least 19 recordsLinked to original sources

Using functional data analysis to summarise and interpret lactate curves.

John Tukey used the term exploratory data analysis (EDA) to describe a philosophy for analyzing data where graphical and numerical summaries are used to uncover interesting structures. The applied statistician today has a much more sophisticated set of methods to use when applying the EDA philosophy. One such collection of methods is functional data analysis (FDA), which was used to explore the structure of lactate curves. A principal components analysis and plots of the second derivatives provide new intuitive endurance markers which correlates highly with other numerical summaries of lactate curves that have been suggested in the literature.

Humans↗

Herpetiform cutaneous metastases from transitional cell carcinoma of the urinary bladder: immunohistochemical analysis.

The case of an 83-year-old woman with an uncommon presentation of cutaneous metastases from muscle-invasive transitional cell carcinoma of the urinary bladder is reported. The band-like eruption of the metastatic lesion can often be misdiagnosed and treated initially as herpes zoster. A detailed immunohistochemical analysis is also described to differentiate metastatic lesions from other sources.

Aged, 80 and over↗

Incidence of injury in elite Gaelic footballers.

The purpose of this study was to undertake a comprehensive prospective epidemiological study of injuries sustained by elite Gaelic Football players over one season. The pattern of injury is strikingly similar across all teams with 47% of all injuries occurring in the final quarter of games and training. Injuries to the lower limb, particularly the hamstrings muscles accounted for the majority of injuries. 65% of players were unable to participate fully in Gaelic Football activity for between one and three weeks as a result of injury. The high incidence of injury especially hamstrings injuries in the latter stages of training and games warrants further investigation.

Adolescent↗

Comparison of stimulation patterns for FES-cycling using measures of oxygen cost and stimulation cost.

AIM: The energy efficiency of FES-cycling in spinal cord injured subjects is very much lower than that of normal cycling, and efficiency is dependent upon the parameters of muscle stimulation. We investigated measures which can be used to evaluate the effect on cycling performance of changes in stimulation parameters, and which might therefore be used to optimise them. We aimed to determine whether oxygen cost and stimulation cost measurements are sensitive enough to allow discrimination between the efficacy of different activation ranges for stimulation of each muscle group during constant-power cycling. METHODS: We employed a custom FES-cycling ergometer system, with accurate control of cadence and stimulated exercise workrate. Two sets of muscle activation angles ("stimulation patterns"), denoted "P1" and "P2", were applied repeatedly (eight times each) during constant-power cycling, in a repeated measures design with a single paraplegic subject. Pulmonary oxygen uptake was measured in real time and used to determine the oxygen cost of the exercise. A new measure of stimulation cost of the exercise is proposed, which represents the total rate of stimulation charge applied to the stimulated muscle groups during cycling. A number of energy-efficiency measures were also estimated. RESULTS: Average oxygen cost and stimulation cost of P1 were found to be significantly lower than those for P2 (paired t-test, p<0.05): oxygen costs were 0.56+/-0.03l min-1 and 0.61+/-0.04l min-1 (mean+/-S.D.), respectively; stimulation costs were 74.91+/-12.15 mC min-1 and 100.30+/-14.78 mC min-1 (mean+/-S.D.), respectively. Correspondingly, all efficiency estimates for P1 were greater than those for P2. CONCLUSION: Oxygen cost and stimulation cost measures both allow discrimination between the efficacy of different muscle activation patterns during constant-power FES-cycling. However, stimulation cost is more easily determined in real time, and responds more rapidly and with greatly improved signal-to-noise properties than the ventilatory oxygen uptake measurements required for estimation of oxygen cost. These measures may find utility in the adjustment of stimulation patterns for achievement of optimal cycling performance.

Biomedical Engineering↗

Intermolecular multiple quantum coherences at high magnetic field: the nonlinear regime.

Experiments have been carried at magnetic-field strengths of 9.4, 14.1, and 17.6 T to explore the evolution of intermolecular multiple quantum coherences in the nonlinear regime where the system evolves for times that are much greater than the characteristic time of action of the long-range dipolar field, tau(d). The results show the expected Bessel function form of the recorded signal as a function of time of evolution, with evident zeros and sign changes. As expected, the rate of signal evolution increases at higher-field strengths as a result of the increased equilibrium magnetization. A numerical method for calculating the evolution of magnetization under the action of the distant dipolar field, relaxation, and diffusion that is based on Fourier analysis of the magnetization distribution has been applied to the correlated two-dimensional spectroscopy revamped by asymmetric z-gradient echo detection sequence in the nonlinear regime and shown to produce results that are in good agreement with experimental data acquired at different magnetic fields and rates of spatial modulation. Experiments and simulations have also been used to explore the evolution of magnetization in a mixture of two interacting spin species in the nonlinear regime.

Algorithms↗

Effect of socioeconomic status on objectively measured physical activity.

BACKGROUND: A socioeconomic gradient in childhood obesity is known to be present by the age of school entry in the UK. The origin of this gradient is unclear at present, but must lie in socioeconomic differences in habitual physical activity, sedentary behaviour, or dietary intake. AIMS: To test the hypothesis that habitual physical activity and/or sedentary behaviour are associated with socioeconomic status (SES) in young Scottish children. METHODS: Observational study of 339 children (mean age 4.2 years, SD 0.3) in which habitual physical activity and sedentary behaviour were measured by accelerometry over six days (study 1). In a second study, 39 pairs of children of distinctly different SES (mean age 5.6 years, SD 0.3) were tested for differences in habitual physical activity and sedentary behaviour by accelerometry over seven days. RESULTS: In study 1, SES was not a significant factor in explaining the amount of time spent in physical activity or sedentary behaviour once gender and month of measurement were taken into account. In study 2, there were no significant differences in time spent in physical activity or sedentary behaviour between affluent and deprived groups. CONCLUSION: Results do not support the hypothesis that low SES in young Scottish children is associated with lower habitual physical activity or higher engagement in sedentary behaviour.

Body Mass Index↗

Factors affecting a climber's ability to ascend Mont Blanc.

The aim of the study was to determine the factors affecting a climber's ability to ascend Mont Blanc using a number of variables collected at the Gouter Hut (3,817 m) before and after an attempted ascent on the Mont Blanc summit. Subjects (n=285) were tested at 3,817 m prior to their ascent of Mont Blanc. Maximum height ascended in the last 14 days was recorded. End tidal CO2, arterial oxygen saturation (SaO2), heart rate and respiratory rate were measured using a Capnograph (Nellcor Patrick NPB75). Acute mountain sickness (AMS) was assessed using the Lake Louise scoring system. Summit information is available for 216 subjects. None of the subjects who attained 4,000 m in the previous 14 days failed to reach the summit (P=0.04). Previous recent exposure to an altitude of 4,000 m resulted in faster ascent times to the summit than those who had not been above 3,000 m in the previous 14 days (4.02+/-0.6 vs. 4.46+/-0.8 h, P=0.009), higher SaO2 on arrival at the Gouter Hut on day 1 (88.6+/-5 vs. 86.3+/-6%, P=0.004) and lower AMS scores upon arrival at the Gouter Hut after the attempted ascent to the summit 2.5+/-1.8 versus 4.7+/-2.5 U (P=0.001), respectively. It is concluded that recent exposure to 4,000 m confers an advantage to those who wish to ascend a 4,800 m peak.

Adolescent↗

A screening procedure for identifying acid-sensitive lakes from catchment characteristics.

Monitoring of Wilderness lakes for potential acidification requires information on lake sensitivity to acidification. Catchment properties can be used to estimate the acid neutralizing capacity (ANC) of lakes. Conceptual and general linear models were developed to predict the ANC of lakes in high-elevation (> or = 2170 m) Wilderness Areas in California's Sierra Nevada mountains. Catchment-to-lake area ratio, lake perimeter-to-area ratio, bedrock lithology, vegetation cover, and lake headwater location are significant variables explaining ANC. The general linear models were validated against independently collected water chemistry data and were used as part of a first stage screen to identify Wilderness lakes with low ANC. Expanded monitoring of atmospheric deposition is essential for improving the predictability of lake ANC.

Acid Rain↗

Synergistic interactions between MEK1/2 and histone deacetylase inhibitors in BCR/ABL+ human leukemia cells.

Interactions between the histone deacetylase inhibitor SAHA and the pharmacologic MEK1/2 inhibitor PD184352 were examined in Bcr/Abl+ human leukemia cells. Coadministration of minimally toxic concentrations of SAHA (or sodium butyrate) and PD184352 (or U0126) resulted in a synergistic increase in mitochondrial damage, caspase activation, and apoptosis in K562 and LAMA 84 cells. Similar interactions were observed in CD34+ cells from two patients with CML and in imatinib mesylate-resistant K562 cells but not in normal human CD34+ bone marrow cells. These events were associated with a marked increase in ROS generation, inactivation of ERK and Akt, downregulation of p21CIP1, Bcr/Abl, and cyclin D1, and activation of JNK. Of these events, ROS generation, ERK inactivation, and cytochrome c/AIF release were largely caspase-independent, whereas the other phenomena displayed varying degrees of caspase-dependence. Using pharmacologic and genetic approaches, generation of ROS, p21CIP1 downregulation, and inactivation of Akt and MEK were found to play significant functional roles in SAHA/PD184352-mediated lethality, whereas JNK activation and Raf-1 downregulation were determined to represent secondary events. These findings indicate that interruption of the MEK/ERK pathway substantially lowers the threshold for HDAC inhibitor-mediated oxidative injury, mitochondrial dysfunction, and apoptosis, suggesting that this approach warrants further examination in Bcr/Abl+-related malignancies.

Antigens, CD34↗

The effect of towing a range of relative resistances on sprint performance.

The aim of this study was to compare sprint performance over 10 and 20 m when participants ran while towing resistances, weighing between 0 and 30% of body mass. The sample of 33 participants consisted of male rugby and soccer players (age 21.1 +/- 1.8 years, body mass 83.6 +/- 13.1 kg, height 1.82 +/- 0.1 m; mean +/- s). Each participant performed two sets of seven sprints over 20 m using a Latin rectangular design. The times were recorded at 10 and 20 m using electronic speed gates. The sprints of 13 players were video-recorded to allow calculation of stride length and frequency. For both sprints, a quadratic relationship was observed between sprint time and resistance as sprint time increased from 2.94 s to 3.80 s from 0 to 30% resistance. This relationship was statistically significant but considered not to be meaningful for performance because, over the range of resistances used in this study, the quadratic model was never more than 1% (in terms of sprint time) from the linear model. As resistance increased, the stride length shortened, with mean values of 1.63 +/- 0.13 m at 0% body mass and 1.33 +/- 0.13 m at 30% of body mass. There was no significant change in stride frequency with increasing resistance. The results show that in general there is an increase in sprint time with an increase in resistance. No particular resistance in the range tested (0 - 30%) can be recommended for practice.

Adult↗

Low physical activity levels and high levels of sedentary behaviour are characteristic of rural Irish primary school children.

There is increasing public health concern that levels of physical activity in children are extremely low. This study aimed to describe objectively levels of physical activity and sedentary behaviour during the waking hours in a sample of 4-5 year old (median 5.4 years range 4.3, 6.0) rural Irish children (n=41) and to test for gender differences in patterns of physical activity and sedentary behaviour. There were significant gender differences in physical activity (Boys (median) 834 accelerometer counts per minute (cpm), girls (median) 628cpm; p = 0.0015), sedentary behaviour (Boys 74% of waking time, girls 81% of waking time, p=0.0011) and moderate-vigorous physical activity (Boys 4% of waking time, girls 2% of waking time; p=0.0175). This study that suggests young rural Irish children lead sedentary lifestyles.

Anthropometry↗

Performance at altitude and angiotensin I-converting enzyme genotype.

The "insertion" (I) rather than "deletion" (D) variant of the human angiotensin-converting enzyme (ACE) gene is associated with both lower tissue ACE activity and elite performance at high altitude. We examined whether the onset of acute mountain sickness (AMS), and further performance on reaching the summit of Mt. Blanc are influenced by the ACE I/D polymorphism. Two hundred and eighty-four climbers (235 males, [37.0 (11.0 years], (86 DD, 142 ID, 56 II)) had assessment of their AMS status upon arrival to the Gouter hut (3,807 m) on day 1, and again on day 2 after an attempted ascent to the summit of Mt. Blanc (4,807 m). Success in reaching the summit was genotype dependent (87.7% of DD, 94.9% of ID and 100% of II individuals; P=0.048); I allele frequency for those reaching the summit was 0.47 compared to 0.21 for those who did not (P=0.01). The onset of AMS on day 1 appeared to be dependent on genotype (P=0.003), but with those heterozygous being less affected. ACE genotype was not associated either with AMS onset or severity on day 2. Thus, ACE I/D genotype is associated with successful high altitude ascent in this prospective study-an association not explicable by genotype-dependence of AMS onset or severity. Values are given as mean (SD) unless otherwise stated.

Adult↗

Robot-assisted minimally invasive Kasai portoenterostomy: a survival porcine study.

BACKGROUND: Major enhancements offered by robotic surgery for minimally invasive procedure include tremor filtration, motion scaling, and the addition of a wrist to the instrument. Minor enhancements include indexing as well as safe and rapid instrument exchange. A benefit associated with any endoscopic procedure is magnification. It was hypothesized that these enhancements would allow the performance of complex gastrointestinal surgery. METHODS: Eight survival pigs (weight, 2.5-8 kg) underwent a robotically assisted minimally invasive portoenterostomy. The procedure was analogous to the Kasai portoenterostomy for biliary atresia usually performed for human patients at the age of 4 to 12 weeks. RESULTS: Five of the eight animals survived for more than 1 month after the operation, returning to normal eating and bowel habits in 2 to 3 days. None were jaundiced. All laboratory values were normal. At 1 month, the animals were killed. There was no anastomotic stenosis at either the end-to-side enteroenterostomy or the portoenterostomy. Histologically, the anastomoses were well healed. CONCLUSION: Computer-assisted robot-enhanced technology allows complex gastrointestinal surgery to be performed using minimally invasive techniques.

Animals↗

Total energy expenditure and physical activity in young Scottish children: mixed longitudinal study.

Childhood obesity has been attributed to a decline in total energy expenditure (TEE). We measured TEE, physical activity, and sedentary behaviour in a representative sample of young children from Glasgow, UK, at age 3 years (n=78), and we did a follow-up study at age 5 years (n=72). Mean physical activity level (TEE/resting energy expenditure) was 1.56 (SD 0.39) at age 3 years and 1.61 (0.22) at age 5 years. Median time in sedentary behaviour was 79% of monitored hours at age 3 years (IQR 74-84) and 76% (71-80) at age 5 years. Median time spent in moderate to vigorous physical activity represented only 2% of monitored hours at age 3 years (IQR 1-4) and 4% at age 5 years (2-6). Modern British children establish a sedentary lifestyle at an early age.

Age Factors↗

The effects of a 12-week group exercise programme on physiological and psychological variables and function in overweight women.

OBJECTIVES: The aim of this study was to investigate the effect of a 12-week functional exercise programme on overweight women. METHODS: Twenty-six subjects (n=13 exercisers, n=13 controls) aged (mean+/-SD) 63 (+/-4) years completed the study. The exercise sessions were carried out twice each week for 12 weeks. The variables measured were body mass, body mass index, skin-fold thickness, resting blood pressure, total blood cholesterol, chair rise, timed 'up and go' test, 20-m walk,lifting a 1- and a 2-kg bag on to a shelf, stair walking, 'sit and reach' flexibility test, Life Satisfaction Index and Physical Self-perception Profile for Older Adults. The exercise sessions consisted of 40-min sessions during which the subjects performed aerobic and strength exercises. RESULTS: Paired analyses showed that body mass, body mass index, blood pressure (systolic and diastolic values), 'up and go' time, time to complete a 20-m walk, time to lift a 1- and a 2-kg bag with both the right and left arms onto a shelf, and stair climbing-total time and ascent time-decreased significantly in the exercise group. Also, the exercise group improved their Life Satisfaction Index score significantly compared with the control group. CONCLUSIONS: The results indicate that a functional exercise programme has the potential to improve performance in a number of physiological variables and functional activities in overweight women. The exercise programme enhanced life satisfaction.

Aged↗

Potent antileukemic interactions between flavopiridol and TRAIL/Apo2L involve flavopiridol-mediated XIAP downregulation.

Interactions between the cyclin-dependent kinase inhibitor flavopiridol (FP) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L), were examined in human leukemia cells (U937 and Jurkat). Coexposure of cells to marginally toxic concentrations of TRAIL and FP (24 h) synergistically increased mitochondrial injury (eg, cytochrome c, AIF, Smac/DIABLO release), cytoplasmic depletion of Bax, activation of Bid as well as caspase-8 and -3, PARP cleavage, and apoptosis. Coadministration of TRAIL markedly increased FP-induced apoptosis in leukemic cells ectopically expressing Bcl-2, Bcl-x(L), or a phosphorylation loop-deleted form of Bcl-2 (DeltaBcl-2), whereas lethality was substantially attenuated in cells ectopically expressing CrmA, dominant-negative-FADD, or dominant-negative-caspase-8. TRAIL/FP induced no discernible changes in FLIP, DR4, DR5, Mcl-1, or survivin expression, modest declines in levels of DcR2 and c-IAP, but resulted in the marked transcriptional downregulation of XIAP. Moreover, cells stably expressing an XIAP-antisense construct exhibited a pronounced increase in TRAIL sensitivity comparable to degrees of apoptosis achieved with TRAIL/FP. Conversely, enforced XIAP expression significantly attenuated caspase activation and TRAIL/FP lethality. Together, these findings suggest that simultaneous activation of the intrinsic and extrinsic apoptotic pathways by TRAIL and FP synergistically induces apoptosis in human leukemia cells through a mechanism that involves FP-mediated XIAP downregulation.

Apoptosis↗